Δευτέρα 10 Δεκεμβρίου 2018
Predictive factors for complications associated with penetrated fish bones outside the upper gastrointestinal tract
Abstract
Purpose
To investigate predictive risk factors for complications associated with migrating fish bones in the surrounding tissue of upper gastrointestinal tract.
Methods
A retrospective analysis over 12 years was conducted of 45 cases of buried fish bones in the surrounding tissue of upper gastrointestinal tract with complications. Meanwhile, a control group, including 39 cases of prolonged buried fish bones in the surrounding tissue of upper gastrointestinal tract without complications, was set. Patient clinical data were collected and analyzed to predict the risk factors for complications.
Results
The results of Chi-square test and univariate analysis both showed a significant difference in length of fish bone (> 2 cm), a history of concurrent medical illness (diabetes mellitus and renal hypofunction), symptoms (medium or heavy pain and dysphagia), and duration of significant symptoms (> 7 days) between the complication group and non-complication group. Multivariate analysis further identified length (> 2 cm), diabetes mellitus, medium or heavy pain, dysphagia, and duration of significant symptoms (> 7 days) as independent risk factors for complications.
Conclusions
The consequences of fish bones migrating outside the upper gastrointestinal tract are various in different people. Awareness should be raised when encountering a patient ingesting a long fish bone, having a history of diabetes mellitus, presenting with significant discomforts, or these discomforts lasting for a long time. This study will help practitioners counsel their patients on the risks and `benefits of surgery versus observation of this condition.
https://ift.tt/2BaGklJ
Two Cases of Cartilaginous Choristoma—Not Chondroma of the Bony External Auditory Canal
The presence of a cartilaginous mass on the bony external auditory canal is an unusual finding. Currently, two different diagnoses have been used to describe this type of mass: chondroma and cartilaginous choristoma. There is currently no consensus on which diagnosis is appropriate for this type of lesion. Choristoma is defined as a tumor-like growth of normal tissue occurring in an abnormal location. Histological examination alone cannot be used to distinguish between cartilaginous choristoma and chondroma, as both lesions comprise normal mature hyaline cartilage. To diagnose a mass as cartilaginous choristoma on the bony external auditory canal, it is necessary to confirm that it does not originate from the underlying periosteum. Here, we present the cases of two patients with typical cartilaginous masses on the bony external auditory canal, in which the surgical findings showed that the masses were not in contact with the underlying periosteum, indicating that cartilaginous choristoma—not chondroma—is an appropriate diagnosis for these mass lesions. The clinical findings (characteristic appearance and location) reported here may aid clinicians in the diagnostic and surgical management of these cartilaginous masses.
https://ift.tt/2EpoShl
Classic pseudoxanthoma elasticum in a girl with sickle cell disease
Abstract
A pseudoxanthoma elasticum (PXE)–like phenotype develops in a subset of patients with inherited hemoglobinopathies. Although PXE tissue changes are thought to develop in the absence of ABCC6 mutations in patients with beta‐thalassemia, ABCC6 mutations have not been well evaluated among sickle cell disease patients with PXE‐like disease. To our knowledge, we describe the first patient with sickle cell disease, PXE skin findings, and two confirmed pathogenic ABCC6 mutations. This case suggests that ABCC6 testing is warranted for sickle cell disease patients with the PXE‐like phenotype and that the pathogenesis of PXE manifestations in beta‐thalassemia and sickle cell disease may differ.
https://ift.tt/2QG3ni7
ENT Doctors at UT Physicians Provide Comprehensive ENT Care in Southeast Houston
The Department of Otorhinolaryngology-Head & Neck Surgery at McGovern Medical School at UTHealth now offers comprehensive care in southeast Houston....https://ift.tt/2ruUvgQ
When It Isn’t Tonsillitis
Repeated bouts of strep throat and suspected tonsillitis led Shelby Boatwright's primary care physician to refer her to William Yao,...https://ift.tt/2rwRywy
UT Physicians Sinus Surgeons Use Augmented Reality Technology During Minimally Invasive Sinus Procedures.
"Augmented reality, which uses 3-D mapping and imagery, enhances our understanding of complex anatomy so surgical procedures are more precise,"...https://ift.tt/2GbhgRn
Disseminated Histoplasmosis with Miliary Histoplasmosis, Neurohistoplasmosis, and Histoplasma capsulatum Bacteremia in Probable Neurosarcoidosis
Introduction. Neurosarcoidosis, either isolated or as part of systemic sarcoidosis, is an uncommon entity and has diagnostic uncertainty. Treatment for neurosarcoidosis can increase the risk of infections, including fungal infections such as disseminated histoplasmosis. Neurosarcoidosis may further predispose patients to infections of the central nervous system. Case Presentation. A 54-year-old male with a history of probable neurosarcoidosis on methotrexate and infliximab presented with encephalopathy, hypoxia, and reported fevers. The patient was found to have disseminated histoplasmosis involving the lungs (miliary histoplasmosis), central nervous system (neurohistoplasmosis), and bloodstream. The Histoplasma capsulatum infection was treated with amphotericin and then voriconazole. Discussion. Patients with neurosarcoidosis are suspected to have blood-brain barrier dysfunction. Lumbar puncture should be considered as part of initial investigative studies for infection. Empiric antimicrobial therapy for a patient with neurosarcoidosis on immunosuppressive agents may need to include antifungal agents.
https://ift.tt/2QIOATF
Thrombosis of the internal jugular vein in the ENT-department — Prevalence, causes and therapy: A retrospective analysis
Less than 5% of deep vein thrombosis is due to thrombosis of the internal jugular vein. Genetic, malignant or inflammatory underlying diseases as well as insertion of venous catheters can be responsible for this pathology. Due to its rare occurrence, it is difficult to find systematic research about thrombosis of the internal jugular vein.
https://ift.tt/2Qp1WoZ
Sinonasal inverted papilloma associated with small cell neuroendocrine carcinoma: A case report and literature review of rare malignancies associated with inverted papilloma
We report a rare case of sinonasal inverted papilloma (IP) associated with small cell neuroendocrine carcinoma (SNEC). To our knowledge, this is the first report to describe SNEC found during the treatment of sinonasal IP. Surgery and five cycles of cisplatin plus etoposide with concurrent intensity modulated radiation therapy were performed. Neither local recurrence nor distant metastasis was noted during 6 years of post-diagnostic follow-up. The prognosis of SNEC is very poor. Treatment planning for sinonasal IP should consider a possible association with this rare but aggressive malignancy, whose treatment is completely different from that of squamous cell carcinoma, a malignancy which is commonly associated with IP.
https://ift.tt/2RPOmrk
Factors associated with suspected nonmelanoma skin cancers, dysplastic nevus, and cutaneous melanoma among first-time SPOTme screening program participants (2009-2010)
No study of the SPOTme program to date has comprehensively analyzed the risk factors associated with suspected non-melanoma skin cancers, dysplastic nevi, and cutaneous melanoma. This research underscores key shared risk factors that can be meaningful for earlier detection of cutaneous malignancies.
https://ift.tt/2L7raSI
Diagnosis and Management of Delusional Parasitosis
Delusional parasitosis can be effectively managed with second generation antipsychotic agents. Extrapyramidal and metabolic side effects are major limiting factors in the choice of therapy.Based on the published data on efficacy, incidence of side effects and attributable risk, risperidone (.5-4mg/day) is a reasonable first-line choice for pharmacotherapy.
https://ift.tt/2C42CHp
Gasdermin D Promotes AIM2 Inflammasome Activation and Is Required for Host Protection against Francisella novicida [INNATE IMMUNITY AND INFLAMMATION]
The DNA sensor absent in melanoma 2 (AIM2) forms an inflammasome complex with ASC and caspase-1 in response to Francisella tularensis subspecies novicida infection, leading to maturation of IL-1β and IL-18 and pyroptosis. AIM2 is critical for host protection against F. novicida infection in vivo; however, the role of pyroptosis downstream of the AIM2 inflammasome is unknown. Recent studies have identified gasdermin D (GSDMD) as the molecule executing pyroptosis by forming pores on the plasma membrane following activation by inflammatory caspase-1 and -11. In this study, we report that GSDMD-deficient mice were susceptible to F. novicida infection compared with wild type mice. Interestingly, we observed that GSDMD is required for optimal caspase-1 activation and pyroptotic cell death in F. novicida–infected bone marrow–derived macrophages. Furthermore, caspase-1 activation was compromised in bone marrow–derived macrophages lacking GSDMD stimulated with other AIM2 inflammasome triggers, including poly(dA:dT) transfection and mouse CMV infection. Overall, our study highlights a function, to our knowledge previously unknown, for GSDMD in promoting caspase-1 activation by AIM2 inflammasome.
https://ift.tt/2RQDqth
Filtering Next-Generation Sequencing of the Ig Gene Repertoire Data Using Antibody Structural Information [SYSTEMS IMMUNOLOGY]
Next-generation sequencing of the Ig gene repertoire (Ig-seq) produces large volumes of information at the nucleotide sequence level. Such data have improved our understanding of immune systems across numerous species and have already been successfully applied in vaccine development and drug discovery. However, the high-throughput nature of Ig-seq means that it is afflicted by high error rates. This has led to the development of error-correction approaches. Computational error-correction methods use sequence information alone, primarily designating sequences as likely to be correct if they are observed frequently. In this work, we describe an orthogonal method for filtering Ig-seq data, which considers the structural viability of each sequence. A typical natural Ab structure requires the presence of a disulfide bridge within each of its variable chains to maintain the fold. Our Ab Sequence Selector (ABOSS) uses the presence/absence of this bridge as a way of both identifying structurally viable sequences and estimating the sequencing error rate. On simulated Ig-seq datasets, ABOSS is able to identify more than 99% of structurally viable sequences. Applying our method to six independent Ig-seq datasets (one mouse and five human), we show that our error calculations are in line with previous experimental and computational error estimates. We also show how ABOSS is able to identify structurally impossible sequences missed by other error-correction methods.
https://ift.tt/2RNSdVO
The Goldilocks Zone of Type I IFNs: Lessons from Human Genetics [BRIEF REVIEWS]
Type I IFNs (IFN-Is) are powerful cytokines. They provide remarkable protection against viral infections, but their indiscriminate production causes severe self-inflicted damage that can be lethal, particularly in early development. In humans, inappropriately high IFN-I levels caused by defects in the regulatory mechanisms that control IFN-I production and response result in clinical conditions known as type I interferonopathies. In essence, type I interferonopathies define the upper limit of safe, IFN-related inflammation in vivo. Conversely, the loss of IFN-I responsiveness increases susceptibility to viral infections, but, surprisingly, most affected individuals survive despite these inborn errors of immunity. These findings suggest that too much IFN-I early in life is toxic, but that insensitivity to IFN-I is perhaps not the death sentence it was initially thought to be. Human genetic analyses have suggested that seemingly insignificant levels of IFN-regulated gene activity may be sufficient for most of the antiviral defenses used by humans in natura.
https://ift.tt/2Qq2ACm
High Fc{gamma}R Expression on Intratumoral Macrophages Enhances Tumor-Targeting Antibody Therapy [TUMOR IMMUNOLOGY]
Therapy with tumor-specific Abs is common in the clinic but has limited success against solid malignancies. We aimed at improving the efficacy of this therapy by combining a tumor-specific Ab with immune-activating compounds. In this study, we demonstrate in the aggressive B16F10 mouse melanoma model that concomitant application of the anti-TRP1 Ab (clone TA99) with TLR3-7/8 or -9 ligands, and IL-2 strongly enhanced tumor control in a therapeutic setting. Depletion of NK cells, macrophages, or CD8+ T cells all mitigated the therapeutic response, showing a coordinated immune rejection by innate and adaptive immune cells. FcRs were essential for the therapeutic effect, with a dominant role for FcRI and a minor role for FcRIII and FcRIV. FcR expression on NK cells and granulocytes was dispensable, indicating that other tumoricidal functions of NK cells were involved and implicating that FcRI, -III, and -IV exerted their activity on macrophages. Indeed, F4/80+Ly-6C+ inflammatory macrophages in the tumor microenvironment displayed high levels of these receptors. Whereas administration of the anti-TRP1 Ab alone reduced the frequency of these macrophages, the combination with a TLR agonist retained these cells in the tumor microenvironment. Thus, the addition of innate stimulatory compounds, such as TLR ligands, to tumor-specific Ab therapy could greatly enhance its efficacy in solid cancers via optimal exploitation of FcRs.
https://ift.tt/2RRjYNa
Complement Inhibitor CRIg/FH Ameliorates Renal Ischemia Reperfusion Injury via Activation of PI3K/AKT Signaling [TRANSPLANTATION]
Complement activation is involved in the pathogenesis of ischemia reperfusion injury (IRI), which is an inevitable process during kidney transplantation. Therefore, complement-targeted therapeutics hold great potential in protecting the allografts from IRI. We observed universal deposition of C3d and membrane attack complex in human renal allografts with delayed graft function or biopsy-proved rejection, which confirmed the involvement of complement in IRI. Using FB-, C3-, C4-, C5-, C5aR1-, C5aR2-, and C6-deficient mice, we found that all components, except C5aR2 deficiency, significantly alleviated renal IRI to varying degrees. These gene deficiencies reduced local (deposition of C3d and membrane attack complex) and systemic (serum levels of C3a and C5a) complement activation, attenuated pathological damage, suppressed apoptosis, and restored the levels of multiple local cytokines (e.g., reduced IL-1β, IL-9, and IL-12p40 and increased IL-4, IL-5, IL-10, and IL-13) in various gene-deficient mice, which resulted in the eventual recovery of renal function. In addition, we demonstrated that CRIg/FH, which is a targeted complement inhibitor for the classical and primarily alternative pathways, exerted a robust renoprotective effect that was comparable to gene deficiency using similar mechanisms. Further, we revealed that PI3K/AKT activation, predominantly in glomeruli that was remarkably inhibited by IRI, played an essential role in the CRIg/FH renoprotective effect. The specific PI3K antagonist duvelisib almost completely abrogated AKT phosphorylation, thus abolishing the renoprotective role of CRIg/FH. Our findings suggested that complement activation at multiple stages induced renal IRI, and CRIg/FH and/or PI3K/AKT agonists may hold the potential in ameliorating renal IRI.
https://ift.tt/2RMsKvO
Blocking Matrix Metalloproteinase-9 Abrogates Collagen-Induced Arthritis via Inhibiting Dendritic Cell Migration [AUTOIMMUNITY]
Trafficking of dendritic cells (DCs) to lymph nodes (LNs) to present Ags is a crucial step in the pathogenesis of rheumatoid arthritis (RA). Matrix metalloproteinase-9 (MMP-9) is the key molecule for DC migration. Thus, blocking MMP-9 to inhibit DC migration may be a novel strategy to treat RA. In this study, we used anti–MMP-9 Ab to treat collagen-induced arthritis (CIA) in DBA/1J mice and demonstrated that anti–MMP-9 Ab treatment significantly suppressed the development of CIA via the modulation of DC trafficking. In anti–MMP-9 Ab–treated CIA mice, the number of DCs in draining LNs was obviously decreased. In vitro, anti–MMP-9 Ab and MMP-9 inhibitor restrained the migration of mature bone marrow–derived DCs in Matrigel in response to CCR7 ligand CCL21. In addition, blocking MMP-9 decreased T and B cell numbers in LNs of CIA mice but had no direct influence on the T cell response to collagen II by CD4+ T cells purified from LNs or spleen. Besides, anti–MMP-9 Ab did not impact on the expression of MHC class II, CD40, CD80, CD86, and chemokine receptors (CCR5 and CCR7) of DCs both in vivo and in vitro. Furthermore, we discovered the number of MMP-9–/– DCs trafficking from footpads to popliteal LNs was dramatically reduced as compared with wild type DCs in both MMP-9–/– mice and wild type mice. Taken together, these results indicated that DC-derived MMP-9 is the crucial factor for DC migration, and blocking MMP-9 to inhibit DC migration may constitute a novel strategy of future therapy for RA and other similar autoimmune diseases.
https://ift.tt/2QnuG17
Predicting Humoral Alloimmunity from Differences in Donor and Recipient HLA Surface Electrostatic Potential [NOVEL IMMUNOLOGICAL METHODS]
In transplantation, development of humoral alloimmunity against donor HLA is a major cause of organ transplant failure, but our ability to assess the immunological risk associated with a potential donor–recipient HLA combination is limited. We hypothesized that the capacity of donor HLA to induce a specific alloantibody response depends on their structural and physicochemical dissimilarity compared with recipient HLA. To test this hypothesis, we first developed a novel computational scoring system that enables quantitative assessment of surface electrostatic potential differences between donor and recipient HLA molecules at the tertiary structure level [three-dimensional electrostatic mismatch score (EMS-3D)]. We then examined humoral alloimmune responses in healthy females subjected to a standardized injection of donor lymphocytes from their male partner. This analysis showed a strong association between the EMS-3D of donor HLA and donor-specific alloantibody development; this relationship was strongest for HLA-DQ alloantigens. In the clinical transplantation setting, the immunogenic potential of HLA-DRB1 and -DQ mismatches expressed on donor kidneys, as assessed by their EMS-3D, was an independent predictor of development of donor-specific alloantibody after graft failure. Collectively, these findings demonstrate the translational potential of our approach to improve immunological risk assessment and to decrease the burden of humoral alloimmunity in organ transplantation.
https://ift.tt/2RWiAbW
CD8{alpha}+ Dendritic Cells Dictate Leukemia-Specific CD8+ T Cell Fates [TUMOR IMMUNOLOGY]
APCs are essential for the orchestration of antitumor T cell responses. Batf3-lineage CD8α+ and CD103+ dendritic cells (DCs), in particular, are required for the spontaneous initiation of CD8+ T cell priming against solid tumors. In contrast, little is known about the APCs that regulate CD8+ T cell responses against hematological malignancies. Using an unbiased approach, we aimed to characterize the APCs responsible for regulating CD8+ T cell responses in a syngeneic murine leukemia model. We show with single-cell resolution that CD8α+ DCs alone acquire and cross-present leukemia Ags in vivo, culminating in the induction of leukemia-specific CD8+ T cell tolerance. Furthermore, we demonstrate that the mere acquisition of leukemia cell cargo is associated with a unique transcriptional program that may be important in regulating tolerogenic CD8α+ DC functions in mice with leukemia. Finally, we show that systemic CD8α+ DC activation with a TLR3 agonist completely prevents their ability to generate leukemia-specific CD8+ T cell tolerance in vivo, resulting instead in the induction of potent antileukemia T cell immunity and prolonged survival of leukemia-bearing mice. Together, our data reveal that Batf3-lineage DCs imprint disparate CD8+ T cell fates in hosts with solid tumors versus systemic leukemia.
https://ift.tt/2RPLjPE
Cutting Edge: Transcriptional Profiling Reveals Multifunctional and Cytotoxic Antiviral Responses of Zika Virus-Specific CD8+ T Cells [CUTTING EDGE]
Zika virus (ZIKV) constitutes an increasing public health problem. Previous studies have shown that CD8+ T cells play an important role in ZIKV-specific protective immunity. We have previously defined antigenic targets of the ZIKV-specific CD8+ T cell response in humans. In this study, we characterized the quality and phenotypes of these responses by a combined use of flow cytometry and transcriptomic methods, using PBMCs from donors deriving from different geographical locations collected in the convalescent phase of infection. We show that ZIKV-specific CD8+ T cells are characterized by a polyfunctional IFN- signature with upregulation of TNF-α, TNF receptors, and related activation markers, such as CD69, as well as a cytotoxic signature characterized by strong upregulation of GZMB and CRTAM. The signature is stable and not influenced by previous dengue virus exposure, geographical location, or time of sample collection postinfection. To our knowledge, this work elucidates the first in-depth characterization of human CD8+ T cells responding to ZIKV infection.
https://ift.tt/2Qmre7d
Cutting Edge: B Cells Expressing Cyclic Citrullinated Peptide-Specific Antigen Receptor Are Tolerized in Normal Conditions [CUTTING EDGE]
Generation of neoantigens by citrullination is implicated in the production of anti–citrullinated protein Abs in rheumatoid arthritis, but citrullination is also a physiological process. To verify whether citrullin-specific B cells are immunologically ignorant or tolerant in normal conditions, transgenic (Tg) mice expressing IgM with the V region of an anti–cyclic citrullinated peptide (CCP) mAb cloned from a rheumatoid arthritis patient were generated. CCP-specific B cells developed in the anti-CCP IgM Tg mice with an alteration of bone marrow B cell fractions, and the number of mature B cells decreased compared with wild-type or the control anti–influenza nucleoprotein–specific IgM Tg mice. In addition, B cells in anti-CCP IgM Tg mice are functionally anergic. Thus, tolerance is induced in CCP-specific B cells in vivo, suggesting that the immune systems are naturally exposed to citrullinated Ags, and anti-CCP Ab production requires additional steps beyond the generation of neoantigens by citrullination.
https://ift.tt/2Qs2hqL
Programming of CD8 T Cell Quantity and Polyfunctionality by Direct IL-1 Signals [INFECTIOUS DISEASE AND HOST RESPONSE]
IL-1, generally considered an amplifier of adaptive immune responses, has been proposed for use as adjuvant during immunization with weak immunogens. However, its effects on memory T cell function remain largely undefined. Using the murine model of acute viral infection, in this paper, we show that in addition to augmenting the size of the Ag-specific pool, IL-1 signals act directly on CD8 T cells to promote the quality of effector and memory responses. Ablation of IL-1R1 or MyD88 signaling in T cells led to functional impairment; both the ability to produce multiple cytokines on a per cell basis (polyfunctionality) and the potential for recall proliferation in response to antigenic restimulation were compromised. IL-1 supplementation during priming augmented the expansion of Ag-specific CD8 T cells through the MyD88–IRAK1/4 axis, resulting in a larger memory pool capable of robust secondary expansion in response to rechallange. Together, these findings demonstrate a critical role of the IL-1–MyD88 axis in programming the quantity and quality of memory CD8 T cell responses and support the notion that IL-1 supplementation may be exploited to enhance adoptive T cell therapies against cancers and chronic infections.
https://ift.tt/2RJZENv
Cutting Edge: FHR-1 Binding Impairs Factor H-Mediated Complement Evasion by the Malaria Parasite Plasmodium falciparum [CUTTING EDGE]
Human complement is the first line of defense against invading pathogens, including the malaria parasite Plasmodium falciparum. We previously demonstrated that human complement represents a particular threat for the clinically relevant blood stages of the parasite. To evade complement-mediated destruction, the parasites acquire factor H (FH) via specific receptors. We now report that the FH-related protein FHR-1 competes with FH for binding to the parasites. FHR-1, which is composed of five complement control protein domains with variable homology to FH but lacks C3b regulatory activity, accumulates on the surfaces of intraerythrocytic schizonts and free merozoites. Although binding of FH to schizont-infected RBCs and merozoites is increased in FHR-1–deficient human serum, the addition of recombinant FHR-1 decreases FH binding. The presence of FHR-1 consequently impairs C3b inactivation and parasite viability. We conclude that FHR-1 acts as a protective factor in human immunity by counteracting FH-mediated microbial complement evasion.
https://ift.tt/2Qnv7sh
TLR-7 Stress Signaling in Differentiating and Mature Eosinophils Is Mediated by the Prolyl Isomerase Pin1 [ALLERGY AND OTHER HYPERSENSITIVITIES]
The response of eosinophils (Eos) to respiratory virus has emerged as an important link between pulmonary infection and allergic asthmatic exacerbations. Eos activate innate immune responses through TLR signaling. In this study, using mouse and human Eos and mice lacking the prolyl isomerase Pin1 selectively in Eos, we show that Pin1 is indispensable for eosinophilopoiesis in the bone marrow (BM) and mature cell function in the presence of TLR7 activation. Unbiased in vivo analysis of mouse models of allergic airway inflammation revealed that TLR7 activation in knockout mice resulted in systemic loss of Eos, reduced IFN production, and an inability to clear respiratory viruses. Consistent with this finding, BM mouse Eos progenitors lacking Pin1 showed markedly reduced cell proliferation and survival after TLR7 activation. Mechanistically, unlike wild-type cells, Pin1 null mouse Eos were defective in the activation of the endoplasmic reticulum stress-induced unfolded protein response. We observed significant reductions in the expression of unfolded protein response components and target genes, aberrant TLR7 cleavage and trafficking, and reduced granule protein production in knockout Eos. Our data strongly suggest that Pin1 is required for BM Eos generation and function during concurrent allergen challenge and viral infection.
https://ift.tt/2QqfSic
The Transcription Factors PU.1 and IRF4 Determine Dendritic Cell-Specific Expression of RALDH2 [MOLECULAR AND STRUCTURAL IMMUNOLOGY]
RALDH2 expressed in dendritic cells (DCs) plays a critical role in the development of regulatory T cells in mesenteric lymph nodes. Despite the importance of RALDH2 in intestinal immunity, little is known about the mechanism of DC-specific expression of RALDH2. In the current study, we focused on the hematopoietic cell–specific transcription factors PU.1 and IRF4 as the determinants of Aldh1a2 gene expression. The mRNA level of Aldh1a2, and subsequently the enzyme activity, were decreased by knockdown of PU.1 and IRF4 in bone marrow–derived DCs (BMDCs) of BALB/c mice. Chromatin immunoprecipitation assays showed that PU.1 and IRF4 bound to the Aldh1a2 gene ~2 kb upstream from the transcription start site in BMDCs. A reporter assay and an EMSA revealed that the Aldh1a2 promoter was synergistically transactivated by a heterodimer composed with PU.1 and IRF4 via the EICE motif at –1961/–1952 of the gene. The effect of small interfering RNAs for Spi1 and Irf4 and specific binding of PU.1 and IRF4 on the Aldh1a2 gene were also observed in DCs freshly isolated from spleen and mesenteric lymph nodes, respectively. GM-CSF stimulation upregulated the Aldh1a2 transcription in Flt3 ligand–generated BMDCs, in which the IRF4 expression and the PU.1 recruitment to the Aldh1a2 promoter were enhanced. We conclude that PU.1 and IRF4 are transactivators of the Aldh1a2 gene in vitro and ex vivo.
https://ift.tt/2RQ1QmI
DRB4*01:01 Has a Distinct Motif and Presents a Proinsulin Epitope That Is Recognized in Subjects with Type 1 Diabetes [AUTOIMMUNITY]
DRB4*01:01 (DRB4) is a secondary HLA-DR product that is part of the high-risk DR4/DQ8 haplotype that is associated with type 1 diabetes (T1D). DRB4 shares considerable homology with HLA-DR4 alleles that predispose to autoimmunity, including DRB1*04:01 and DRB1*04:04. However, the DRB4 protein sequence includes distinct residues that would be expected to alter the characteristics of its binding pockets. To identify high-affinity peptides that are recognized in the context of DRB4, we used an HLA class II tetramer-based approach to identify epitopes within multiple viral Ags. We applied a similar approach to identify antigenic sequences within glutamic acid decarboxylase 65 and pre-proinsulin that are recognized in the context of DRB4. Seven sequences were immunogenic, eliciting high-affinity T cell responses in DRB4+ subjects. DRB1*04:01-restricted responses toward many of these peptides have been previously described, but responses to a novel pre-proinsulin 9–28 peptide were commonly observed in subjects with T1D. Furthermore, T cells that recognized this peptide in the context of DRB4 were present at significantly higher frequencies in patients with T1D than in healthy controls, implicating this as a disease-relevant specificity that may contribute to the breakdown of β cell tolerance in genetically susceptible individuals. We then deduced a DRB4 motif and confirmed its key features through structural modeling. This modeling suggested that the core epitope within the pre-proinsulin 9–28 peptide has a somewhat unusual binding motif, with tryptophan in the fourth binding pocket of DRB4, perhaps influencing the availability of this complex for T cell selection.
https://ift.tt/2QqCoYw
Colitis Promotes a Pathological Condition of the Liver in the Absence of Foxp3+ Regulatory T Cells [IMMUNE REGULATION]
Inflammatory bowel disease is associated with extraintestinal diseases such as primary sclerosing cholangitis in the liver. Interestingly, it is known that an imbalance between Foxp3+ regulatory T cells (Treg) and Th17 cells is involved in inflammatory bowel disease and also in primary sclerosing cholangitis. To explain these associations, one hypothesis is that intestinal inflammation and barrier defects promote liver disease because of the influx of bacteria and inflammatory cells to the liver. However, whether and how this is linked to the Treg and Th17 cell imbalance is unclear. To address this, we used dextran sodium sulfate (DSS) and T cell transfer colitis mouse models. We analyzed the pathological conditions of the intestine and liver on histological, cellular, and molecular levels. We observed bacterial translocation and an influx of inflammatory cells, in particular Th17 cells, to the liver during colitis. In the DSS colitis model, in which Treg were concomitantly increased in the liver, we did not observe an overt pathological condition of the liver. In contrast, the T cell–mediated colitis model, in which Treg are not abundant, was associated with marked liver inflammation and a pathological condition. Of note, upon depletion of Treg in DEREG mice, DSS colitis promotes accumulation of Th17 cells and a pathological condition of the liver. Finally, we studied immune cell migration using KAEDE mice and found that some of these cells had migrated directly from the inflamed intestine into the liver. Overall, these data indicate that colitis can promote a pathological condition of the liver and highlight an important role of Treg in controlling colitis-associated liver inflammation.
https://ift.tt/2QrCtLB
Placenta Specific 8 Suppresses IL-18 Production through Regulation of Autophagy and Is Associated with Adult Still Disease [CLINICAL AND HUMAN IMMUNOLOGY]
Adult Still disease (ASD) is a systemic disorder of unknown etiology characterized by high spiking fever, rash, and arthritis. The purpose of this study was to identify genes specifically associated with the active phase of the disease. In this study, we have reported that placenta specific 8 (PLAC8) was a newly specific gene involved in ASD. DNA microarray and validation analysis using human monocytes revealed that the expression of PLAC8 was significantly higher in active-ASD patients than in inactive-ASD patients and healthy controls. In ASD, PLAC8 expression level correlated with serum levels of CRP, ferritin, IL-1β, and IL-18. Stimulation of monocytes with LPS results in PLAC8 upregulation. LPS or nigericin stimulation of PLAC8-overexpressing human monocytic cell line (THP-1), but not mock THP-1 cells, was associated with a significant decrease in IL-1β and IL-18 production. PLAC8 overexpression in THP-1 cells was associated with enhanced autophagy and suppression of IL-1β and IL-18 production. Therefore, we found that PLAC8 was upregulated in activated monocytes, as was IL-1β and IL-18. The upregulated PLAC8 acts on the synthesis of inactive precursors of IL-1β and IL-18 and seemed to suppress the production of IL-1β and IL-18 by negative feedback through enhanced autophagy, resulting in the suppression of ASD. The results highlight the role of PLAC8 in the pathogenesis of ASD and suggest its potential suitability as an activity marker and therapeutic target in ASD.
https://ift.tt/2QrCxuP
Multiplexed FluoroSpot for the Analysis of Dengue Virus- and Zika Virus-Specific and Cross-Reactive Memory B Cells [NOVEL IMMUNOLOGICAL METHODS]
Dengue virus (DENV) and Zika virus (ZIKV) are mosquito-borne pathogens that have a significant impact on human health. Immune sera, mAbs, and memory B cells (MBCs) isolated from patients infected with one DENV type can be cross-reactive with the other three DENV serotypes and even more distantly related flaviviruses such as ZIKV. Conventional ELISPOTs effectively measure Ab-secreting B cells but because they are limited to the assessment of a single Ag at a time, it is challenging to distinguish serotype-specific and cross-reactive MBCs in the same well. We developed a novel multifunction FluoroSpot assay using fluorescently labeled DENV and ZIKV (FLVs) that measures the cross-reactivity of Abs secreted by single B cells. Conjugation efficiency and recognition of FLVs by virus-specific Abs were confirmed by flow cytometry. Using a panel of DENV immune, ZIKV immune, and naive PBMC, FLVs were able to simultaneously detect DENV serotype-specific, ZIKV-specific, DENV serotype cross-reactive, and DENV/ZIKV cross-reactive Abs secreted by individual MBCs. Our findings indicate that the FLVs are sensitive and specific tools to detect specific and cross-reactive MBCs. These reagents will allow the assessment of the breadth as well as the durability of DENV/ZIKV B cell responses following vaccination or natural infection. This novel approach using FLVs in a FluoroSpot assay can be applied to other diseases such as influenza in which prior immunity with homosubtype- or heterosubtype-specific MBCs may influence subsequent infections.
https://ift.tt/2RNSb08
Surveillance of Myelodysplastic Syndrome via Migration Analyses of Blood Neutrophils: A Potential Prognostic Tool [CLINICAL AND HUMAN IMMUNOLOGY]
Autonomous migration is a central characteristic of immune cells, and changes in this function have been correlated to the progression and severity of diseases. Hence, the identification of pathologically altered leukocyte migration patterns might be a promising approach for disease surveillance and prognostic scoring. However, because of the lack of standardized and robust assays, migration patterns have not been clinically exploited so far. In this study, we introduce an easy-to-use and cross-laboratory, standardized two-dimensional migration assay for neutrophil granulocytes from peripheral blood. By combining time-lapse video microscopy and automated cell tracking, we calculated the average migration of neutrophils from 111 individual participants of the German Heinz Nixdorf Recall MultiGeneration study under steady-state, formyl-methionyl-leucyl-phenylalanine–, CXCL1-, and CXCL8-stimulated conditions. Comparable values were obtained in an independent laboratory from a cohort in Belgium, demonstrating the robustness and transferability of the assay. In a double-blinded retrospective clinical analysis, we found that neutrophil migration strongly correlated with the Revised International Prognostic Scoring System scoring and risk category of myelodysplastic syndrome (MDS) patients. In fact, patients suffering from high-risk subtypes MDS with excess blasts I or II displayed highly significantly reduced neutrophil migration. Hence, the determination of neutrophil migration patterns might represent a useful tool in the surveillance of MDS. Taken together, we suggest that standardized migration assays of neutrophils and other leukocyte subtypes might be broadly applicable as prognostic and surveillance tools for MDS and potentially for other diseases.
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Talin1 Methylation Is Required for Neutrophil Infiltration and Lipopolysaccharide-Induced Lethality [INNATE IMMUNITY AND INFLAMMATION]
Talin1, a well-established integrin coactivator, is critical for the transmigration of neutrophils across the vascular endothelium into various organs and the peritoneal cavity during inflammation. Several posttranslational modifications of talin1 have been proposed to play a role in this process. In this study, we show that trimethylation of talin1 at Lys2454 by cytosolic Ezh2 is substantially increased in murine peritoneal neutrophils upon induction of peritonitis. By reconstituting talin1-deficient mouse myeloid cells with wild-type, methyl-mimicking, or unmethylatable talin1 variants, we demonstrate that methylation of talin1 at Lys2454 is important for integrin-dependent neutrophil infiltration into the peritoneal cavity. Furthermore, we show that treatment with an Ezh2 inhibitor or reconstitution of talin1-deficient myeloid cells with unmethylatable talin1 significantly reduces the number of organ-infiltrating neutrophils and protects mice from LPS-induced mortality.
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Association of Meniere disease with human leukocyte antigen in Taiwanese population
Kai-Chieh Chan, MD; Che-Ming Wu, MD; Wan-Ling Ho, MD, PhD; Ping-Chin Lai, MD, PhD
Abstract
The etiology of Ménière disease (MD) is multifactorial; genetic factors seem to play an important role. The associations between MD and human leukocyte antigen (HLA) status have been studied previously in several populations and have shown that the HLA alleles imparting susceptibility varied. In the present study, we explored HLA status in Taiwanese patients with definitive MD. HLA was typed via polymerase chain reaction, sequence-specific oligonucleotide genotyping in 35 patients with MD diagnosed using the criteria of the American Academy of Otolaryngology-Head and Neck Surgery and 70 unrelated healthy controls. HLA allele association tests were used to evaluate differences in allelic frequencies between the patients and controls. The allelic frequency of HLA-A*11 was significantly greater in MD patients than in controls (52.9 vs. 31.4%, odds ratio: 2.45, 95% confidence interval: 1.4 to 4.4, p = 0.004, p corrected = 0.03). Thus, A*11 may be a useful HLA biomarker in Taiwanese patients with MD. Further larger-scale studies are required.
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Destructive lesion of the temporomandibular joint: A case of tophaceous pseudogout
Jessica B. Howell, MD; Yula A. Indeyeva, MD; Stephanie E. Ambrose, MD; Evan R. Reiter, MD
Abstract
Tophaceous pseudogout of the temporomandibular joint is a rare entity that clinically and radiographically mimics neoplastic or infectious conditions. Diagnosis requires histopathologic examination. Given the rarity of this condition, there is a paucity of information pertaining to the surgical approach, reconstructive options, and postoperative outcomes.
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The root cause of physician burnout cannot be solved with resilience efforts
Michael M. Johns, MD, III
The burnout problem can be traced largely to loss of physician autonomy and marginalization of physicians in decision making.
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Evaluation of bendable surgical suction devices made of shape-memory alloy for the endonasal transsphenoid removal of pituitary tumors
Ronny Grunert, PhD; Sandra Klietz, BEng; Paul A. Gardner, MD; Juan C. Fernandez-Miranda, MD; Carl H. Snyderman, MD, MBA
Abstract
In minimally invasive surgeries, it can be difficult to reach desired anatomic areas with rigid instruments, especially when obstacles are present in the surgical corridor (e.g., during transnasal pituitary surgery). We developed a new kind of suction device constructed of the shape-memory alloy Nitinol (nickel titanium), which is adaptable to a patient's specific anatomy. Use of this device minimizes surgical risks by allowing physicians to use an endonasal transsphenoid approach. The suction device, which is equipped with a cannula made of the shape-memory alloy, was planned and manufactured with three different handpiece designs. Experienced pituitary surgeons tested the prototypes in human cadaver skulls and rated the devices on specific questionnaires. The results of their evaluation indicate that this device is a suitable tool for improving the surgical procedure. Its potential benefits include a more effective surgery and reductions in the risk of injury, the duration of surgery, and costs.
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A fistulating oropharyngeal lesion
Richard Heyes, MBChB (Hons), MRCS DO-HNS; Courtney M. Tomblinson, MD; David G. Lott, MD
Abstract
Post-transplant lymphoproliferative disorder (PTLD) is a unifying term for a spectrum of lymphoid expansion entities brought about by immunosuppression. It can present throughout the head and neck, and tonsillar involvement is not limited to children. We report the case of a 67-year-old woman who developed odynophagia associated with putrid halitosis 4 months after she had undergone renal transplantation. Direct visualization of the oropharynx revealed multiple sites of severe ulceration and erythema, with erosion of both the anterior and posterior right tonsillar pillars and a necrotic ulceration fistulating deeply. Biopsy analysis led to a diagnosis of PTLD. The patient underwent rituximab monotherapy and responded well. However, after the cessation of therapy, she experienced a recurrence that necessitated chemotherapy, which resulted in a lasting remission. At follow-up 5 years later, she remained PTLD-free with stable stage 4 chronic kidney disease.
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Laryngeal hereditary hemorrhagic telangiectasia
Jerome R. Lechien, PHD, MS; Camille Finck, MD, PhD
Laryngeal telengiectasia involving the vocal folds is known to cause hemorrhages, which are often difficult to control given the vascular wall fragility.
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Stapes footplate defect as a source of CSF leak and otogenic meningitis in a patient with a cochlear implant
Maria Vartanyan, MD; Fiona Hill, MBBS; Kumiko Orimoto, MD, PhD; Stephen O'Leary, PhD, FRACS, FAHMS
Clinicians should be proactive in ensuring that cochlear implant patients have received comprehensive immunization.
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Aggressive fibromatosis of the parotid gland
Vishaal Patel, MD; Virginia Falvello, MD; Marion Hughes, MD; Barry Schaitkin, MD
Abstract
Extra-abdominal fibromatosis (EAF) is a rare, locally aggressive tumor that originates in fascial structures. It accounts for less than 0.3% of all tumors diagnosed. Head and neck tumors account for only 7% of those, and only a few cases occurring in the parotid gland have been previously reported. We describe the case of a 34-year-old woman who presented with a painful parotid mass. She was found to have an EAF of her right parotid gland. Medical management with antibiotics and immunosuppression therapy was unsuccessful. Surgical resection was required for both a definitive diagnosis and management. Preoperative findings on computed tomography, magnetic resonance imaging, and both fine-needle aspiration biopsy and surgical biopsy were nonspecific, as is typical in EAF cases.
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An unusual presentation of papillary thyroid carcinoma in a pediatric patient: A case report
Matthew G. Cravens, BS, BA; Tyson J. Nielsen, MD; Erynne A. Faucett, MD; Audrey B. Erman, MD
Abstract
Cystic neck masses in the pediatric population are common but rarely concerning for malignancy. Given this typically benign nature, they are frequently managed conservatively. Here we present an unusual case of a waxing and waning cystic neck mass in a pediatric patient. After surgical removal, the mass was found to be metastatic papillary thyroid cancer. This is a unique presentation in the pediatric age group that has not yet been described. Based on this case, we suggest an expanded differential in any workup for a cystic neck mass to include papillary thyroid carcinoma, regardless of the patient's age.
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Huge neck lymphangioma removed in toto with minimal access
Vikas Malhotra, MBBS, MS(ENT), DNB; Nikhil Arora, MBBS, MS(ENT), DNB; Pankhuri Mittal, MBBS, MS(ENT), DNB
Treatment selection should be based on the size, depth, and location of the lesion, as well as potential morbidity and surgical complications.
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Epidemiologie primärer Hirntumoren bei Kindern und Erwachsenen in Deutschland
Zusammenfassung
Der Artikel gibt einen Überblick über die Epidemiologie primärer Hirntumoren in Deutschland, basierend auf den Daten der bevölkerungsbezogenen Krebsregister der Bundesländer, Krebsregistern und dem deutschen Kinderkrebsregister. Etwa 6700 Personen erkrankten im Jahr 2014 in Deutschland an einem bösartigen Hirntumor, davon 229 Kinder. 5770 Menschen starben im Jahr 2015 an dieser Erkrankung. Die alterststandardisierten Erkrankungs- und Sterberaten zeigen seit 1999 keine wesentlichen Veränderungen. Bei Erwachsenen machen die hochmalignen Glioblastome (Astrozytome WHO-Grad IV) mehr als zwei Drittel aller Erkrankungen aus, während bei Kindern die embryonalen Tumoren mit etwa einem Drittel der Fälle die häufigste Form darstellen. Die Prognose ist abhängig von der Histologie; relative Fünfjahresüberlebensraten liegen zwischen Werten deutlich unter 10 % (Astrozytom IV) und um 80 % (Ependymome und Keimzelltumoren). Nichtmaligne Tumoren des hirneigenen Gewebes (ohne Tumoren der Hirnnerven und -häute) sind mit geschätzten rund 850 Neuerkrankungen pro Jahr vergleichsweise selten.
https://ift.tt/2C3zkZD
Microneedling by dermapen and glycolic acid peel for the treatment of acne scars: Comparative study
Summary
Background
Many methods have been performed to achieve a satisfying outcome in acne scars but some of them were high cost and also were associated with low results and some complications.
Objectives
To evaluate and compare the efficacy and safety therapy of glycolic acid (GA) peel, microneedling with dermapen and a combination of both procedures in treatment of atrophic acne scars.
Patents and methods
This study was conducted on 30 patients suffering from acne scars. They were randomly assigned into three groups, each group included 10 patients; group I was treated with GA peel, group II treated was with microneedling. Group III received a combination of both procedures. All patients received six sessions with 2‐week intervals. The clinical assessment was based on the qualitative global scar grading system before and after treatment, quartile grading scale, and degree of patient satisfaction.
Results
There was a statistically significant decrease in acne scars grade after treatment among the studied groups (P = 0.04) but it was higher in group III. There was improvement in boxcar, ice pick, and rolling scars in all groups, respectively (P = 0.03, P = 0.04, P = 0.04). Patients' satisfaction was higher in group III (P = 0.04).
Conclusion
The combination of dermapen and GA peel is more effective than monotherapy.
https://ift.tt/2zRIDdn
Six years of experience using an advanced algorithm for botulinum toxin application
Summary
Background
Botulinum toxin (BTX) products continue to be widely used for facial rejuvenation. Variables to consider prior to BTX treatment include the anatomical area to be treated, gender, muscle mass, ethnicity, skin thickness, and the effects of aging.
Objective
To describe a treatment algorithm which has been developed for facial rejuvenation to help physicians to easily and systematically customize BTX treatment, and to describe its use in a large number of patients.
Methods and Materials
Prior to treatment, digital images of patients were obtained while relaxed and while forming different facial expressions. This information was used to plan the depth, dose, and location of BTX injections (onabotulinumtoxinA; Botox®; Allergan, Inc). Dilution was 100 U of BTX to 1 mL 0.9% preserved saline. Injections were performed with 30 U insulin syringes and 30 gauge needles.
Results
The treatment algorithm described here has been used by the author for facial rejuvenation for more than 5 years. It was originally based on published guidelines; however, by carefully noting treatment outcomes, the number and location of injection points and the dose of BTX used have been modified to create the current treatment system.
Conclusion
Published guidelines for the use of BTX are an excellent starting point for clinicians with little experience; however, each practitioner is likely to develop their own algorithm for achieving good facial rejuvenation outcomes.
https://ift.tt/2PvN2YH
Evaluation of oral tranexamic acid in the treatment of melasma
Summary
Background
Melasma is an acquired, chronic, recurrent hypermelanosis that occurs exclusively in areas exposed to the sun. Its treatment can be very challenging. Tranexamic acid (TA) is an inhibitor of plasmin, and it is a synthetic derivative of the amino acid lysine that reversibly blocks binding sites on the plasminogen molecule, inhibiting the plasminogen activator from converting plasminogen to plasmin.
Aims
This study evaluated the efficacy of oral TA in the treatment of melasma in patients from a philanthropic dermatological clinic.
Patients/Methods
This was a monocentric, randomized, double‐blind, controlled clinical trial. Patients with facial melasma were randomly divided into the following two groups: A (TA 250 mg orally twice daily) or B (oral placebo twice daily). Evaluations were performed before and after 12 weeks of treatment with photographs, colorimetry, MELASQoL, and MASI. All patients were instructed to use tinted sunscreen (SPF 50).
Results
Of the 47 patients selected, 37 completed the study, with 20 in group A and 17 in group B; the patients consisted of one male and 36 females, and the mean age was 43.97 years old. Based on the four methods of evaluation, the melasma in 50% of patients in group A improved versus only 5.9% of patients in group B (P < 0.005). There was an improvement according to all evaluation methods in the treatment group. No patient had severe side effects.
Conclusions
We conclude that tranexamic acid was effective in 50% of patients according to four methods of evaluation when compared to the placebo.
https://ift.tt/2PvkVZt
Difficult-to-diagnose diabetes in a patient treated with cyclophosphamide – the contradictory roles of immunosuppressant agents: a case report
Cyclophosphamide may induce autoimmune diabetes through a decrease in suppressor T cells and increase of proinflammatory T helper type 1 response in animal models. In humans, this association is not as clear d...
https://ift.tt/2zTlYgX
A modified method of local infiltration for endoscopic stapes surgery: how I do it
Abstract
Purpose
To present a modified method of local infiltration (MMLI) for endoscopic stapes surgery to reduce surgical time, bleeding and complications.
Materials and methods
This study involved 70 patients who underwent stapes surgery for otosclerosis by endoscopic and microscopic approaches. The MMLI was applied as follows: local infiltration was performed with one hand while the other hand inserted the endoscope into the ear canal to observe vasoconstriction signs on the monitor; the single site of infiltration was located at the center of the anterior conchal cartilage. Operative time, intraoperative blood loss, preservation of anatomical structures, postoperative hearing and complications were evaluated.
Results
The MMLI allowed for quick bleeding control and a clear and dry operative field. Operative time, intraoperative blood loss and preservation of anatomical structures were significantly reduced in the endoscopic group (P < 0.00) versus the microscopic group. The scutum was removed less frequent in the endoscopic group 7.1% versus 53.6% of the microscopic group (P < 0.00). The chorda tympani was preserved in all cases but it was more manipulated in the microscopic group 39.3% versus 9.5% of the endoscopic group (P < 0.00). No complications were observed and the hearing outcomes were significantly better than the preoperative thresholds.
Conclusions
This is the first report on the use of a MMLI for endoscopic stapes surgery. Using this method, the surgeon performs the infiltration at one site and concurrently observes the vasoconstriction signs without the use of a microscope, frontal lamp or speculum. This method provides benefits in terms of operative time and complications.
https://ift.tt/2EchRiW
A Trial to Evaluate the Efficacy of Poziotinib, Pan HER Inhibitor in Recurrent/Metastatic Esophageal Cancer (R/M ESCC)
Condition: Inoperable or Recurrent or Metastatic Esophageal Squamous Carcinoma
Intervention: Drug: Treatment with Poziotinib
Sponsor: Yonsei University
Not yet recruiting
https://ift.tt/2EdtTJ6
Intervention: Drug: Treatment with Poziotinib
Sponsor: Yonsei University
Not yet recruiting
https://ift.tt/2EdtTJ6
Laparoscopic Appendectomy Performed by Junior SUrgeonS: Impact of 3D Visualization on Surgical Outcome
Conditions: Appendicolith; Appendicitis; Appendicitis With Perforation; Appendicitis Peritonitis; Appendiceal Abscess; Appendicitis Acute
Interventions: Procedure: 3D Laparoscopic Appendectomy; Procedure: 2D Laparoscopic Appendectomy
Sponsor: Azienda Ospedaliera Spedali Civili di Brescia
Recruiting
https://ift.tt/2Enj4F2
Interventions: Procedure: 3D Laparoscopic Appendectomy; Procedure: 2D Laparoscopic Appendectomy
Sponsor: Azienda Ospedaliera Spedali Civili di Brescia
Recruiting
https://ift.tt/2Enj4F2
Dual exposure to smoking and household air pollution is associated with an increased risk of severe asthma in adults in Brazil
The relationship between smoking, household pollution, dual exposure and severity of asthma in adults has not been sufficiently studied. We examined and compared the effects of cigarette smoking, domestic wood...
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Incidental findings on 18-FDG PET–CT in head and neck cancer. A retrospective case-control study of incidental findings on 18-FDG PET–CT in patients with head and neck cancer
Abstract
Purpose
Use of 18-FDG PET–CT is increasing in patients with head and neck cancer, enabling the identification of metastases or synchronous malignancies, but also 'incidental' disease. We aimed to establish the rate of 'incidental' findings resulting from 18-FDG PET-specific imaging, that would not have been otherwise identified on other imaging, in patients with head and neck cancer undergoing staging or surveillance of disease.
Methods
18-FDG PET–CT was performed for investigation or surveillance. Case notes were reviewed retrospectively. Unexpected findings identifiable on CT imaging alone, or by FDG-PET were recorded. For those only identifiable with FDG-PET, findings were divided into either 'incidental' or 'intentional', and benign or malignant.
Results
93 patients underwent 18- FDG PET–CT. 86.0% had new pathology identified. 3.2% had a new malignancy identified. 37.6% had new findings on FDG-PET that would not have been identified on CT alone: 5.4% had 'intentional findings' (metastasis), and 32.3% had 'incidental findings' (synchronous malignancy or benign). 1.1% had a new malignancy on FDG-PET alone.
Conclusions
Intentional and incidental findings are likely on 18-FDG PET–CT. Whilst important for patient management, there is an associated emotional and financial cost, which needs acknowledgement and further investigation.
https://ift.tt/2UAHMa3
Nachsorge und Lebensqualität nach Therapie eines Ovarialkarzinoms
Zusammenfassung
Hintergrund
Die leitliniengerechte Therapie des Ovarialkarzinoms beinhaltet meist eine Kombination aus operativem und systemtherapeutischem Ansatz; für viele Patientinnen schließt sich eine Erhaltungstherapie an. Nach Abschluss von OP und Chemotherapie beginnt für die Betroffenen die Nachsorgephase. Nach der initialen Konfrontation mit der Diagnosestellung und den beeinträchtigenden Therapien, kommt bei den meisten Betroffenen der Wunsch auf, in ein „normales" Leben zurückzukehren. Erkrankungs- und therapieassoziierte Folgen können diesem Wunsch jedoch konträr gegenüberstehen.
Ergebnisse
Die standardisierte Nachsorge erfolgt über 5 Jahre. Sie umfasst in den ersten 3 Jahren ein 3‑monatiges Intervall, anschließend ist eine halbjährliche Untersuchung für die folgenden 2 Jahre vorgesehen. Der Nachsorge schließen sich regelmäßige Kontrollen im Rahmen der Krebsfrüherkennungsprogramme an. In den letzten Jahren hat sich die symptomgesteuerte Nachsorge etabliert, sodass bildgebende Verfahren nur bei klinischem Verdacht auf ein Rezidiv oder möglichen therapeutischen Konsequenzen eingesetzt werden sollen. Ein routinemäßiger Einsatz von Tumormarkerkontrollen (CA125) bei fehlender klinischer Symptomatik ist laut S3-Leitlinie nicht indiziert.
Schlussfolgerung
Das Erreichen individueller Lebensqualität, einschließlich sexueller Bedürfnisse, ist ein essenzielles Thema der Nachsorge. Der Bedarf der Betroffenen an professioneller Unterstützung ist sehr unterschiedlich. Dies verlangt von den betreuenden Ärzten Erfahrung, eine hohe kommunikative Kompetenz und besonderes Einfühlungsvermögen.
https://ift.tt/2rv4ouZ
Etiology of subjective taste loss
Background
Taste complaints are commonly encountered in clinical practice. Although changes in taste function may arise from varied etiologies, numerous other factors may impact patients' taste perceptions, the most common of which is olfactory dysfunction. Thus, patients with taste complaints may or may not have measurable deficits in taste function. This poses a challenge to providers faced with evaluation of patients with taste disorders, and may delay diagnosis and management.
Methods
We retrospectively examined records of 1108 patients evaluated at the Virginia Commonwealth University Health System Smell and Taste Clinic and compared patients' subjective taste complaints with results of objective testing of the senses of taste and smell.
Results
A total of 358 patients had a subjective taste complaint and results from both gustatory and olfactory function tests. Patients were grouped by subjective complaint as "taste only" (n = 63) or "taste and smell" (n = 295). Of patients reporting a "taste‐only" complaint, 25.4% had abnormal gustatory function, whereas 44.4% had abnormal olfactory function. For those reporting taste‐and‐smell complaints, only 9.5% had abnormal gustatory function, whereas 86.8% had abnormal olfactory function.
Conclusion
This study supports the hypothesis that patients who present with a taste complaint are more likely to have an underlying olfactory than gustatory impairment. However, those with a taste‐only complaint are more likely to have objective gustatory deficits than those with a taste‐and‐smell complaint. These findings may prove useful to healthcare providers who evaluate patients presenting with complaints of taste loss.
https://ift.tt/2Qpg9Sw
A large screen for paraneoplastic neurological autoantibodies; diagnosis and predictive values
Publication date: Available online 10 December 2018
Source: Clinical Immunology
Author(s): Lior Seluk, Alisa Taliansky, Hagith Yonath, Boris Gilburd, Howard Amital, Yehuda Shoenfeld, Shaye Kivity
Abstract
Background
Paraneoplastic neurological syndromes (PNS) are a group of syndromes that affect the central and peripheral neuromuscular system in association with cancer. Specific antibodies may assist in the diagnosis of PNS. The antibodies tested can be classified into those directed against intracellular neuronal proteins ("well characterized" PNS: Hu, Yo, RI, CV2, amphiphysin, Ma1, Ma2) and those directed against neural surface antigens (autoimmune encephalitis syndromes: NMDA, AMPA, LGI1, CASPR2, GABAR). We aimed to characterize patients with unexplained neuropsychiatric symptoms, in whom positive PNS antibodies were detected in the Sheba medical center, a large referral hospital.
Methods
Clinical and demographic data of patients with positive PNS antibodies were collected during the years 2002–2016. Antibodies were tested by either Line immunoassay or by cell-based indirect immunofluorscent assay.
Results
During the follow up of 14 years, 4010 PNS tests were performed in patients with unexplained neuropsychiatric symptoms. Seventy-two were found to be positive; among them we had full clinical data access to 44. The most frequent antibodies were anti-Hu (31.8%), anti-Yo (18.2%), anti-CV2 (13.6%), and anti-NMDA (9.1%), and the most common cancers were small-cell lung (SCLC) and ovarian cancers. In the well characterized paraneoplastic group, cancer was diagnosed in 55.9% of the patients, and in the autoimmune encephalitis group, 40.0% were diagnosed with cancer. A positive correlation between antibody titer and the presence of cancer was found. Ninety percent of the tests in patients who were found positive were ordered by a neurologist or neuro-oncologist.
Conclusions
The titers of PNS auto-antibodies can predict cancer in patients whom anti-PNS antibodies are tested. In addition, consultation with a specialist should be considered before this test is ordered.
https://ift.tt/2Pvcz40
Central compartment revision surgery for persistent or recurrent thyroid carcinoma: analysis of survival and complication rate
Abstract
Purpose
Locoregional recurrence of thyroid carcinoma is relatively common and reported rate are between 5 and 20%. Cervical nodes are usually involved, especially at the central compartment. The management of recurrent thyroid carcinoma at central compartment still remains challenging because of higher incidence of complication rate. The aim of the study is to evaluate the survival and complications rate after revision surgery.
Methods
Retrospective cohort study on a group of patients that underwent revision surgery for persistent or recurrent thyroid carcinoma from January 1, 2003 to December 31, 2017. Survival outcomes were calculated using Kaplan–Meier method. Significant variables on univariate analysis were subjected to a Cox proportional hazards regression multivariate model.
Results
Fifty-two patients involved, 22 male (40%) and 30 female (60%). Mean age was 54 years old (range 24–85). Mean follow-up was 79 months, median follow-up was 85 months, with a range between 8 and 153 months. The 5-year overall survival was 90.8% while at 10 years it was 69.8%. The 5-year disease-specific survival was 93.5%, while at 10 years it dropped to 77.9%. The rate of recurrent laryngeal nerve paralysis and persistent hypocalcemia in our series were 1.3% and 5.9%, respectively. No evidence of thoracic duct, esophageal or laryngeal and tracheal injury was found in this case series. Regarding prognostic factors, univariate and multivariate analysis highlighted as statistically significant: the aggressive histological variants, the presence extranodal extension or soft-tissue metastasis.
Conclusion
The surgical option remains the gold standard in locoregional recurrences of thyroid carcinoma and should be performed by experienced surgeons to reduce postoperative complications.
https://ift.tt/2C1VeMS
Palatine Tonsil Stenting of the Airway as Determined by Drug-Induced Sleep Endoscopy
Objective. To demonstrate lateral pharyngeal wall collapse and increased apnea-hypopnea index in a child posttonsillectomy. Background. Some children have worsening of their sleep symptoms after tonsillectomy for obstructive sleep apnea. This case report demonstrates an open airway on drug-induced sleep endoscopy (DISE) in a child with tonsillar hypertrophy followed by more pronounced airway obstruction related to lateral pharyngeal wall collapse after tonsillectomy. Case Presentation. A 7-year-old boy presented with obstructive sleep apnea and underwent workup with DISE. Following adenotonsillectomy and subsequent lingual tonsillectomy with epiglottopexy, the patient's sleep apnea symptoms and polysomnogram results worsened. Subsequent DISE showed a more narrowed oropharyngeal airway space as compared to his preoperative DISE. Discussion. Palatine tonsillar tissue may splint open the airway and prevent airway obstruction in a subset of pediatric patients. Further clinical studies are necessary to determine which children experience this phenomenon. Clinical examination using DISE can be useful in making clinical decisions prior to tonsillectomy.
https://ift.tt/2Gb2ZEa
Effects of crystalloids and colloids on microcirculation, central venous oxygen saturation, and central venous-to-arterial carbon dioxide gap in a rabbit model of hemorrhagic shock
Abstract
Objective
The effects of hydroxyethyl starch (HES) on microcirculation, central venous oxygen saturation (ScvO2), and the central venous-to-arterial carbon dioxide gap (dCO2) are studied in a rabbit model of hemorrhagic shock for elucidating the advantages and drawbacks of resuscitation with HES compared with crystalloids.
Methods
An ear chamber and sublingual mucosa were used to examine blood vessels by intravital microscopy. Hemorrhagic shock was induced by removing nearly half of the blood volume. Twenty-two rabbits received 20 mL of HES by intravenous infusion immediately after bloodletting. Additional HES was then administered intravenously to a total volume of 100 mL. The other 22 rabbits (control) were intravenously given 40 mL of normal saline solution (NSS), followed by additional NSS to a total volume of 200 mL, administered under the same conditions as HES.
Results
After the infusion, the vessel density and perfusion rate of the sublingual microcirculation recovered in the HES group. The arteriolar diameter, blood flow velocity, and blood flow rate of the ear microcirculation were maintained in this group, and microcirculatory failure did not develop. In the NSS group, however, all 5 of the aforementioned measured variables were significantly smaller than those in the HES group after the completion of infusion. The recovery of ScvO2 and dCO2 to the respective baseline values was significantly better in the HES group than in the NSS group.
Conclusion
Intravenous infusion of HES effectively maintains adequate tissue oxygenation and perfusion in hemorrhagic shock.
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Establishment of a novel and effective reflux laryngitis model in rabbits: a preliminary study
Abstract
Purpose
To establish a novel and effective reflux model with a modified nasogastric aspiration tube and to investigate the association between different types of nasogastric aspiration tubes and reflux laryngitis, we conducted this study.
Methods
Thirty-eight healthy New Zealand albino rabbits (2.5–3.5 kg) were divided into three groups: control (CTR, n = 6)—non-intubated; normal nasogastric intubation (NNI, n = 16)—intubated with 4#, 6#, 8#, and 10# normal nasogastric aspiration tubes; and modified nasogastric intubation (MNI, n = 16)—intubated with 4#, 6#, 8#, and 10# modified nasogastric aspiration tubes. The laryngoscopy, body weight, and pH values at the esophageal entrance were recorded before and 1, 2, and 4 weeks after intubation. After the final laryngoscopy, the animals in groups with a pH below 4 were sacrificed to obtain histological and gene expression analysis results.
Results
The reflux finding score (RFS) after 4 weeks showed that there was a statistically significant difference in the 8# NNI group (7 ± 0.816, P < 0.001), the 8# MNI group (11.5 ± 2.517, P < 0.001) and the 10# MNI (12.75 ± 1.893, P < 0.001) group compared with the control group (1.83 ± 1.602). The pH values of these three groups were lower than 4. However, the weight loss of the rabbits in the 10# NNI and 10# MNI groups was more obvious. Submucous gland hyperplasia and inflammation were significantly increased in the 8# NNI group, 8# MNI group and the 10# MNI group, but in the level of some pro-inflammatory cytokines and COX-2, the MNI group was significantly higher than the NNI group (8# NNI × 8# MNI, P < 0.01; 8# MNI × 10# MNI, P < 0.01).
Conclusion
This study showed that 8# modified nasogastric intubation (MNI) produces effective reflux laryngitis in the rabbits.
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Family Caregiving and Cancer Pain Management
Family caregivers are centrally involved in cancer pain management, especially for patients with advanced disease. This issue is becoming ever more important as care shifts to the outpatient setting and home care and as the aging population creates more patients who have multiple illnesses and family caregivers who often live with serious illnesses. This narrative review evaluated current knowledge and literature regarding family caregivers' involvement in cancer pain management and identified areas for future research and clinical practice. There is a need for additional research in this area and for clinical models of support for family caregivers as they provide pain management for patients with cancer. Accepted for publication October 10, 2018. Funding: None. The author declares no conflicts of interest. Reprints will not be available from the authors. Address correspondence to Betty R. Ferrell, PhD, CHPN, FAAN, FPCN, Division of Nursing Research and Education, City of Hope Comprehensive Cancer Center, 1500 E Duarte Rd, Pop Sci Bldg 173, Duarte, CA 91010. Address e-mail to bferrell@coh.org. © 2018 International Anesthesia Research Society
https://ift.tt/2zNJVWL
https://ift.tt/2zNJVWL
Weeding Out the Problem: The Impact of Preoperative Cannabinoid Use on Pain in the Perioperative Period
BACKGROUND: The recreational and medical use of cannabinoids has been increasing. While most studies and reviews have focused on the role of cannabinoids in the management of acute pain, no study has examined the postoperative outcomes of surgical candidates who are on cannabinoids preoperatively. This retrospective cohort study examined the impact of preoperative cannabinoid use on postoperative pain scores and pain-related outcomes in patients undergoing major orthopedic surgery. METHODS: Outcomes of patients who had major orthopedic surgery at our hospital between April 1, 2015 and June 30, 2017 were reviewed. Data were obtained from Networked Online Processing of Acute Pain Information, a locally developed database for our Acute Pain Service. Propensity score matching was used to balance baselines variables including age, sex, type of surgery, history of depression or anxiety, and perioperative use of regional anesthesia between patients who reported use of cannabinoids and those not on this substance. Intensity of pain with movement in the early postoperative period (defined as up to 36 hours after surgery) was the primary outcome of this study. The secondary outcomes (all in early postoperative period) were pain at rest, opioid consumption, incidence of pruritus, nausea and vomiting, sedation, delirium, constipation, impairment of sleep and physical activity, patient satisfaction with analgesia, and the length of Acute Pain Service follow-up. RESULTS: A total of 3793 patients were included in the study. Of these, 155 patients were identified as being on cannabinoids for recreational or medical indications in the preoperative period. After propensity score matching, we compared data from 155 patients who were on cannabinoids and 155 patients who were not on cannabinoids. Patients who were on preoperative cannabinoids had higher pain numerical rating score (median [25th, 75th percentiles]) at rest (5.0 [3.0, 6.1] vs 3.0 [2.0, 5.5], P = .010) and with movement (8.0 [6.0, 9.0] vs 7.0 [3.5, 8.5], P = .003), and a higher incidence of moderate-to-severe pain at rest (62.3% vs 45.5%, respectively, P = .004; odds ratio, 1.98; 95% CI, 1.25–3.14) and with movement (85.7% vs 75.2% respectively, P = .021; odds ratio, 1.98; 95% CI, 1.10–3.57) in the early postoperative period compared to patients who were not on cannabinoids. There was also a higher incidence of sleep interruption in the early postoperative period for patients who used cannabinoids. CONCLUSIONS: This retrospective study with propensity-matched cohorts showed that cannabinoid use was associated with higher pain scores and a poorer quality of sleep in the early postoperative period in patients undergoing major orthopedic surgery. Accepted for publication October 29, 2018. Funding: This work was supported by internal departmental funding from the Department of Anesthesia and Pain Medicine at University Health Network, Toronto Western Hospital. Conflicts of Interest: See Disclosures at the end of the article. Reprints will not be available from the authors. Address correspondence to Anuj Bhatia, MBBS, MD, FRCA, FRCPC, FIPP, FFPMRCA, EDRA, Department of Anesthesia and Pain Medicine, Toronto Western Hospital, McL 2-405, 399 Bathurst St, Toronto, ON M5T 2S8, Canada. Address e-mail to anuj.bhatia@uhn.ca. © 2018 International Anesthesia Research Society
https://ift.tt/2zMFv2w
https://ift.tt/2zMFv2w
Evidence Review Conducted for the Agency for Healthcare Research and Quality Safety Program for Improving Surgical Care and Recovery: Focus on Anesthesiology for Hip Fracture Surgery
Enhanced recovery after surgery (ERAS) protocols represent patient-centered, evidence-based, multidisciplinary care of the surgical patient. Although these patterns have been validated in numerous surgical specialities, ERAS has not been widely described for patients undergoing hip fracture (HFx) repair. As part of the Agency for Healthcare Research and Quality Safety Program for Improving Surgical Care and Recovery, we have conducted a full evidence review of interventions that form the basis of the anesthesia components of the ERAS HFx pathway. A literature search was performed for each protocol component, and the highest levels of evidence available were selected for review. Anesthesiology components of care were identified and evaluated across the perioperative continuum. For the preoperative phase, the use of regional analgesia and nonopioid multimodal analgesic agents is suggested. For the intraoperative phase, a standardized anesthetic with postoperative nausea and vomiting prophylaxis is suggested. For the postoperative phase, a multimodal (primarily nonopioid) analgesic regimen is suggested. A summary of the best available evidence and recommendations for inclusion in ERAS protocols for HFx repair are provided. Accepted for publication September 19, 2018. Funding: This project was funded under contract number HHSP233201500020I from the Agency for Healthcare Research and Quality, US Department of Health and Human Services. Conflicts of Interest: See Disclosures at the end of the article. The opinions expressed in this document are those of the authors and do not reflect the official position of the Agency for Healthcare Research and Quality or the US Department of Health and Human Services. Reprints will not be available from the authors. Address correspondence to Ellen M. Soffin, MD, PhD, Department of Anesthesiology, The Hospital for Special Surgery, 535 E 70th St, New York, NY 10021. Address e-mail to soffine@hss.edu. © 2018 International Anesthesia Research Society
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https://ift.tt/2PuSWJm
Validation of a Simple Tool for Electronic Documentation of Behavioral Responses to Anesthesia Induction
BACKGROUND: Anxiety and distress behaviors during anesthesia induction are associated with negative postoperative outcomes for pediatric patients. Documenting behavioral responses to induction is useful to evaluate induction quality at hospitals and to optimize future anesthetics for returning patients, but we lack a simple tool for clinical documentation. The Induction Compliance Checklist is a tool for grading induction behaviors that is well validated for research purposes, but it is not practical for routine documentation in busy clinical practice settings. The Child Induction Behavioral Assessment tool was developed to provide a simple and easy to use electronic tool for clinical documentation of induction behaviors. The aim of this study was to test the Child Induction Behavioral Assessment tool's concurrent validity with the Induction Compliance Checklist and the interrater reliability. METHODS: This prospective, observational study included 384 pediatric patients undergoing anesthesia inhalation induction. Concurrent validity with the Induction Compliance Checklist and interrater reliability of the Child Induction Behavioral Assessment were evaluated. Two researchers alternated scoring the Induction Compliance Checklist. The 2 researchers independently scored the Child Induction Behavioral Assessment. The anesthesia clinician caring for the patient also independently scored the Child Induction Behavioral Assessment by completing their routine documentation in the patient's medical record. Two age groups were evaluated (ages 1–3 and 4–12 years old). RESULTS: Clinicians' and researchers' Child Induction Behavioral Assessment scores demonstrated a strong correlation with the Induction Compliance Checklist (P
https://ift.tt/2PuSKK8
https://ift.tt/2PuSKK8
New Strategies to Expand and Optimize Heart Donor Pool: Ex Vivo Heart Perfusion and Donation After Circulatory Death A Review of Current Research and Future Trends
Heart transplantation remains the definitive management for end-stage heart failure refractory to medical therapy. While heart transplantation cases are increasing annually worldwide, there remains a deficiency in organ availability with significant patient mortality while on the waiting list. Attempts have therefore been made to expand the donor pool and improve access to available organs by recruiting donors who may not satisfy the standard criteria for organ donation because of donor pathology, anticipated organ ischemic time, or donation after circulatory death. "Ex vivo" heart perfusion (EVHP) is an emerging technique for the procurement of heart allografts. This technique provides mechanically supported warm circulation to a beating heart once removed from the donor and before implantation into the recipient. EVHP can be sustained for several hours, facilitate extended travel time, and enable administration of pharmacological agents to optimize cardiac recovery and function, as well as allow assessment of allograft function before implantation. In this article, we review recent advances in expanding the donor pool for cardiac transplantation. Current limitations of conventional donor criteria are outlined, including the determinants of organ suitability and assessment, involving transplantation of donation after circulatory death hearts, extended criteria donors, and EVHP-associated assessment, optimization, and transportation. Finally, ongoing research relating to organ optimization and functional ex vivo allograft assessment are reviewed. Accepted for publication October 8, 2018. Funding: None. The authors declare no conflicts of interest. Reprints will not be available from the authors. Address correspondence to Massimiliano Meineri, MD, FASE, Department of Anesthesia, Toronto General Hospital, 200 Elizabeth St, EN 3–442, Toronto, ON M5G 2C4, Canada. Address e-mail to Massimiliano.Meineri@uhn.ca. © 2018 International Anesthesia Research Society
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https://ift.tt/2zPOO1P
Development and Validation of an Electronic Postoperative Morbidity Score
BACKGROUND: Electronic health records are being adopted due to numerous potential benefits. This requires the development of objective metrics to characterize morbidity, comparable to studies performed in centers without an electronic health record. We outline the development of an electronic version of the postoperative morbidity score for integration into our electronic health record. METHODS: Two hundred and three frail patients who underwent elective surgery were reviewed. We retrospectively defined postoperative morbidity score on postoperative day 3. We also recorded potential electronic surrogates for morbidities that could not be easily extracted in an objective format. We compared discriminative capability (area under the receiver operator curve) for patients having prolonged length of stay or complex discharge requirements. RESULTS: One hundred thirty-nine patients (68%) had morbidity in ≥1 postoperative morbidity score domain. Initial electronic surrogates were overly sensitive, identifying 173 patients (84%) as having morbidity. We refined our definitions using backward logistic regression against "gold-standard" postoperative morbidity score. The final electronic postoperative morbidity score differed from the initial version in its definition of cardiac and neurological morbidity. There was no significant difference in the discriminative capability between electronic postoperative morbidity score and postoperative morbidity score for either outcome (area under the receiver operator curve: 0.66 vs 0.66 for complex discharge requirement, area under the receiver operator curve: 0.66 vs 0.67 for a prolonged length of stay; P> .05 for both). Patients with postoperative morbidity score or electronic postoperative morbidity score–defined morbidity on day 3 had increased risk of prolonged length of stay (P
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https://ift.tt/2PuVNCj
Association of Preoperative Serum Chloride Levels With Mortality and Morbidity After Noncardiac Surgery: A Retrospective Cohort Study
BACKGROUND: Postoperative hyperchloremia is known to be related to increases in mortality and morbidity after surgery. However, the relationship between preoperative hyperchloremia and hypochloremia and postoperative mortality and morbidity is not well established. Our aim was to evaluate the relationship between preoperative hyperchloremia or hypochloremia, as assessed using preoperative serum chloride tests, and 90-day mortality and morbidity after noncardiac surgery. METHODS: In this retrospective cohort study, we reviewed the medical records of patients >20 years of age who underwent noncardiac surgery between January 2010 and December 2016. Patients were categorized into one of the following groups on the basis of the results of serum chloride testing performed within 1 month before surgery: normochloremia, 97–110 mmol·L−1; hyperchloremia, >110 mmol·L−1; and hypochloremia,
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https://ift.tt/2PuSPNW
Statistical Process Control: No Hits, No Runs, No Errors?
A novel intervention or new clinical program must achieve and sustain its operational and clinical goals. To demonstrate successfully optimizing health care value, providers and other stakeholders must longitudinally measure and report these tracked relevant associated outcomes. This includes clinicians and perioperative health services researchers who chose to participate in these process improvement and quality improvement efforts ("play in this space"). Statistical process control is a branch of statistics that combines rigorous sequential, time-based analysis methods with graphical presentation of performance and quality data. Statistical process control and its primary tool—the control chart—provide researchers and practitioners with a method of better understanding and communicating data from health care performance and quality improvement efforts. Statistical process control presents performance and quality data in a format that is typically more understandable to practicing clinicians, administrators, and health care decision makers and often more readily generates actionable insights and conclusions. Health care quality improvement is predicated on statistical process control. Undertaking, achieving, and reporting continuous quality improvement in anesthesiology, critical care, perioperative medicine, and acute and chronic pain management all fundamentally rely on applying statistical process control methods and tools. Thus, the present basic statistical tutorial focuses on the germane topic of statistical process control, including random (common) causes of variation versus assignable (special) causes of variation: Six Sigma versus Lean versus Lean Six Sigma, levels of quality management, run chart, control charts, selecting the applicable type of control chart, and analyzing a control chart. Specific attention is focused on quasi-experimental study designs, which are particularly applicable to process improvement and quality improvement efforts. Accepted for publication November 6, 2018. Funding: None. The authors declare no conflicts of interest. Reprints will not be available from the author. Address correspondence to Thomas R. Vetter, MD, MPH, Department of Surgery and Perioperative Care, Dell Medical School at the University of Texas at Austin, Health Discovery Bldg, Room 6.812, 1701 Trinity St, Austin, TX 78712. Address e-mail to thomas.vetter@austin.utexas.edu. © 2018 International Anesthesia Research Society
https://ift.tt/2zPKOhO
https://ift.tt/2zPKOhO
Impact of Anesthetics on Human Neutrophil Function
Anesthetics are widely used drugs administered in a multitude of clinical settings. Their impacts on various functions of the immune system have been studied but are still not fully understood. Neutrophil granulocytes are a critical first-line host defense mechanism against infections and contribute to the inflammatory phase of wound healing, but dysregulated neutrophil activation can also precipitate perioperative organ injury. A better understanding of the interactions between common anesthetics and neutrophils may reveal considerations toward optimizing treatment of our most vulnerable patients in the intensive care unit and in the perioperative setting. Accepted for publication October 12, 2018. Funding: A.M. is supported by the mentored research training grant of the International Anesthesia Research Society and is supported by the International Anesthesia Research Society Mentored Research Award. V.N. is supported by National Institutes of Health grant U54 HD090259. Conflicts of Interest: See Disclosures at the end of the article. Reprints will not be available from the authors. Address correspondence to Angela Meier, MD, PhD, Department of Anesthesiology, Division of Critical Care, 200 W Arbor Dr, San Diego, CA. Address e-mail to anmeier@ucsd.edu. © 2018 International Anesthesia Research Society
https://ift.tt/2zSBLwo
https://ift.tt/2zSBLwo
Ryanodine Receptor to Mitochondrial Reactive Oxygen Species Pathway Plays an Important Role in Chronic Human Immunodeficiency Virus gp120MN-Induced Neuropathic Pain in Rats
BACKGROUND: Chronic pain is one of the most common complaints in patients with human immunodeficiency virus (HIV)–associated sensory neuropathy. Ryanodine receptor (RyR) and mitochondrial oxidative stress are involved in neuropathic pain induced by nerve injury. Here, we investigated the role of RyR and mitochondrial superoxide in neuropathic pain induced by repeated intrathecal HIV glycoprotein 120 (gp120) injection. METHODS: Recombinant HIV glycoprotein gp120MN was intrathecally administered to induce neuropathic pain. Mechanical threshold was tested using von Frey filaments. Peripheral nerve fiber was assessed by the quantification of the intraepidermal nerve fiber density in the skin of the hindpaw. The expression of spinal RyR was examined using Western blots. Colocalization of RyR with neuronal nuclei (NeuN; neuron marker), glial fibrillary acidic protein (GFAP; astrocyte marker), or ionizing calcium-binding adaptor molecule 1 (Iba1; microglia marker) in the spinal cord was examined using immunohistochemistry. MitoSox-positive profiles (a mitochondrial-targeted fluorescent superoxide indicator) were examined. The antiallodynic effects of intrathecal administration of RyR antagonist, dantrolene (a clinical drug for malignant hyperthermia management), or selective mitochondrial superoxide scavenger, Mito-Tempol, were evaluated in the model. RESULTS: We found that repeated but not single intrathecal injection of recombinant protein gp120 induced persistent mechanical allodynia. Intraepidermal nerve fibers in repeated gp120 group was lower than that in sham at 2 weeks, and the difference in means (95% confidence interval) was 8.495 (4.79–12.20), P = .0014. Repeated gp120 increased expression of RyR, and the difference in means (95% confidence interval) was 1.50 (0.504–2.495), P = .007. Repeated gp120 also increased mitochondrial superoxide cell number in the spinal cord, and the difference in means (95% confidence interval) was 6.99 (5.99–8.00), P
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https://ift.tt/2zSrgtf
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