Circulating integrin alpha4/beta7+ lymphocytes targeted by vedolizumab have a pro-inflammatory phenotype

Publication date: Available online 26 May 2018
Source:Clinical Immunology
Author(s): James D. Lord, S. Alice Long, Donna M. Shows, Jerill Thorpe, Katherine Schwedhelm, Janice Chen, Mariko Kita, Jane H. Buckner
Integrin alpha4/beta7 on circulating lymphocytes identifies them as gut-tropic, and can be targeted by the humanized antibody vedolizumab to treat inflammatory bowel disease (IBD). We found lymphocytes expressing alpha4/beta7 were significantly more responsive to the pro-inflammatory cytokines IL-6, IL-7, and IL-21, and less responsive to the regulatory T cell (Treg)-supporting cytokine IL-2. Alpha4/beta7 was expressed by a smaller percent of FOXP3 + Helios+ thymically-derived Tregs (tTregs) than FOXP3 + Helios- peripherally-derived Tregs (pTregs) or FOXP3- effector T cells. Integrin alpha4/beta7+ CD4 T cells were also rare among cells expressing the Th2 marker CRTh2, but enriched in cells bearing the circulating T follicular helper cell marker CXCR5. Thus the effect of this anti-integrin therapy on the mucosal immune system may be more qualitative than quantitative, and selectively replace pro-inflammatory effector cells with Tregs and Th2 cells to facilitate immune tolerance in the mucosa without globally depleting lymphocytes from the intestinal mucosa.



https://ift.tt/2IQ6BfG

Combination of anti-citrullinated protein antibodies and rheumatoid factor is associated with increased systemic inflammatory mediators and more rapid progression from preclinical to clinical rheumatoid arthritis

Publication date: Available online 26 May 2018
Source:Clinical Immunology
Author(s): Nithya Lingampalli, Jeremy Sokolove, Lauren J. Lahey, Jess D. Edison, William R. Gilliland, V. Michael Holers, Kevin D. Deane, William H. Robinson
The development of rheumatoid factor (RF) and/or anti-citrullinated protein antibodies (ACPAs) can be observed years prior to clinical diagnosis of rheumatoid arthritis (RA). Nevertheless, the interaction between these two autoantibodies and their combined effect on development of RA is unclear. We measured RF, cytokines, and ACPA subtypes in serial pre-clinical serum samples collected from 83 US veterans who all developed RA. Levels of cytokines and ACPAs were compared between the following groups: anti-cyclic citrullinated peptide (anti-CCP)-/RF- (double negative), anti-CCP+/RF-, anti-CCP-/RF+, or anti-CCP+/RF+ (double-positive). The double-positive subgroup had significantly higher levels of 20 inflammatory cytokines and 29 ACPA reactivities, and the shortest interval, 1.3 years, between the preclinical sample timepoint and diagnosis of RA. Thus, the combined presence of ACPAs and RF is associated with a more rapid progression to RA, suggesting that anti-CCP+/RF+ individuals have a more advanced preclinical disease state and that the onset of RA may be imminent.



https://ift.tt/2GQNYCB

Role of Cervical Vestibular Evoked Myogenic Potentials (cVEMP) as Outcome-Measure of Glycerol Test

Abstract

Diagnosis of Meniere's disease is mainly clinical although many tests have been studied for efficacy in diagnosis of Meniere's disease. Glycerol test is a functional test to identify hydrops in Meniere's disease and can be done with PTA, Speech audiometry, otoacoustic emission, EcochG and cVEMP as its outcome measures. The study aimed to compare two outcome measures of glycerol test to identify Meniere's disease; to determine whether the stage of Meniere's disease affected glycerol outcomes; and to attempt to identify independent variables that could predict outcomes of glycerol test. 26 ears of 20 Meniere's disease participants were evaluated using PTA-based and cVEMP-based glycerol tests. Each test identified ten of 26 ears with Meniere's disease; and high agreement was noted in the two outcome measures. The stage of Meniere's disease based on four frequency hearing threshold average was not associated with outcome of glycerol test, but staging of Meniere's disease based on symptom duration was associated with glycerol test results. As the duration of symptoms increased there was lesser chance of positive outcomes on glycerol test; but intermediate stages of Meniere's disease showed positive outcomes. Variables such as age, gender, severity of hearing loss, duration of symptoms and pre-glycerol cVEMP measurements could not predict glycerol test outcomes. PTA-based and cVEMP- based glycerol tests hold promise in the test battery for identification of Meniere's disease. Positive findings on the test lead to confirmatory diagnosis but a negative glycerol test does not rule out Meniere's disease.

https://ift.tt/2GTMibh

Predicted miRNA-mRNA-mediated posttranscriptional control associated with differences in cervical and thoracic thymus function

Publication date: July 2018
Source:Molecular Immunology, Volume 99
Author(s): Amanda F. Assis, Jie Li, Paula B. Donate, Janaína A. Dernowsek, Nancy R. Manley, Geraldo A. Passos
A secondary cervical thymus (CT) is present in the neck region in about 50% of human and mice. CT in mice is an independent and functional organ, which can be colonized by T lymphocyte progenitors and generate thymocytes that are selected by the T cell receptor repertoire following the positive and negative selection. However, CT and the main thoracic thymus (TT) have been shown in mice to have significant functional differences. In this study, we use transcriptional profiling to compare mRNA or miRNAs expression patterns in murine CT and TT. We used these data to perform functional enrichment of the expression signatures and reconstruction of posttranscriptional miRNA-mRNA interaction networks. For this purpose, we compared the transcriptome profiling of paired RNA samples of whole CTs, TTs and parathyroid gland (PT), which was used as an external group, from Foxn1-GFP;Pth-Cre;R26dTomato transgenic mice that differentially label CT and TT. As expected, CT and TT featured comprehensive transcriptome similarity and this suggests that these organs are subjected to correlated transcriptional control. Nevertheless, significant differences were also observed between TT and CT, characterized by 107 differentially expressed (DE) mRNAs, and in 13 DE miRNAs, that in turn established interactions. These results suggest that functional similarity between TT and CT is reflected in their transcriptional activity and that CT functional uniqueness might be under posttranscriptional control.



https://ift.tt/2LzHvQ0

Genomic organization and adaptive evolution of IGHC genes in marine mammals

Publication date: July 2018
Source:Molecular Immunology, Volume 99
Author(s): Lili Li, Xinghua Rong, Guiting Li, Yingying Wang, Bingyao Chen, Wenhua Ren, Guang Yang, Shixia Xu
Immunoglobulins are important elements of the adaptive immune system that bind to an immense variety of microbial antigens to neutralize infectivity and specify effector functions. In the present study, the immunoglobulin heavy chain constant region (IGHC) genes from marine mammals were identified and compared with those of their terrestrial relatives to explore their genomic organization and evolutionary characteristics. The genomic organization of marine mammal IGHC genes was shown to be conservative with other eutherian mammals. Stronger signals of positive selection on IGHC were revealed in terrestrial mammals than that in marine mammals with the branch-site model, displaying different selective pressure, which might suggest their divergent adaptations to contrasted environments.



https://ift.tt/2KX4Olx

Pirfenidone ameliorates lipopolysaccharide-induced pulmonary inflammation and fibrosis by blocking NLRP3 inflammasome activation

Publication date: July 2018
Source:Molecular Immunology, Volume 99
Author(s): Yi Li, Haitao Li, Shuai Liu, Pinhua Pan, Xiaoli Su, Hongyi Tan, Dongdong Wu, Lemeng Zhang, Chao Song, Minhui Dai, Qian Li, Zhi Mao, Yuan Long, Yongbin Hu, Chengping Hu
Acute respiratory distress syndrome(ARDS)is a severe clinical disorder characterized by its acute onset, diffuse alveolar damage, intractable hypoxemia, and non-cardiogenic pulmonary edema.Acute lung injury(ALI) can trigger persistent lung inflammation and fibrosis through activation of the NLRP3 inflammasome and subsequent secretion of mature IL-1β, suggesting that the NLRP3 inflammasome is a potential therapeutic target for ALI, for which new therapeutic approaches are needed. Our present study aims to assess whether pirfenidone,with anti-fibrotic and anti-inflammatory properties, can improve LPS-induced inflammation and fibrosis by inhibiting NLRP3 inflammasome activation. Male C57BL/6 J mice were intratracheally injected with LPS to induce ALI. Mice were administered pirfenidone by oral gavage throughout the entire experimental course. The mouse macrophage cell line (J774 A.1) was incubated with LPS and ATP, with or without PFD pre-treatment. We demonstrated that PFD remarkably ameliorated LPS-induced pulmonary inflammation and fibrosis and reduced IL-1β and TGF-β1 levels in bronchoalveolar lavage fluid(BALF). Pirfenidone substantially reduced NLRP3 and ASC expression and inhibited caspase-1 activation and IL-1β maturation in lung tissues. In vitro, the experiments revealed that PFD significantly suppressed LPS/ATP-induced production of reactive oxygen species (ROS) and decreased caspase-1 activation and the level of IL-1β in J774 A.1 cells. Taken together, the administration of PFD reduced LPS-induced lung inflammation and fibrosis by blocking NLRP3 inflammasome activation and subsequent IL-1β secretion. These findings indicated that PFD can down-regulate NLRP3 inflammasome activation and that it may offer a promising therapeutic approach for ARDS patients.



https://ift.tt/2LA7whZ

TLR2/4 ligand-amplified liver inflammation promotes initiation of autoimmune hepatitis due to sustained IL-6/IL-12/IL-4/IL-25 expression

Publication date: July 2018
Source:Molecular Immunology, Volume 99
Author(s): Gang Chi, Xin-Xia Feng, Ying-Xia Ru, Ting Xiong, Yuan Gao, Han Wang, Zhen-Long Luo, Ran Mo, Fang Guo, Yong-Pei He, Gui-Mei Zhang, De-An Tian, Zuo-Hua Feng
Autoimmune hepatitis (AIH), a serious autoimmune liver disease, can be a lifelong illness, leading to fibrosis, cirrhosis, and hepatocellular carcinoma (HCC). So far the mechanisms for disease initiation are largely unknown. Here we report that the amplified non-AIH liver inflammation could promote the initiation of AIH due to the sustained increase of IL-6, IL-12, IL-4, and IL-25 in the liver. The liver injury resulting from virus (adenovirus) or chemicals (CCl4) could induce an amplified (stronger/long-lasting) hepatic inflammation by releasing the ligands for TLR2/TLR4. The amplified inflammation resulted in the increase of multiple cytokines and chemokines in the liver. Among them, the sustained increase of IL-6/IL-12 resulted in the activation of STAT3 and STAT4 in hepatic CD4⁺CD25⁺ Treg cells, thus suppressing Foxp3 gene expression to reduce the suppressive function of Treg cells in the liver, but not those in the spleen. The increase of IL-12 and the impairment of Treg function promoted Th1 response in presence of self-mimicking antigen (human CYP2D6). Intriguingly, the amplified inflammation resulted in the increase of IL-4 and IL-25 in the liver. The moderate increase of IL-4 was sufficient for cooperating with IL-25 to initiate Th2 response, but inefficient in suppressing Th1 response, favoring the initiation of autoimmune response. Consequently, either adenovirus/CYP2D6 or CCl4/CYP2D6 could induce the autoimmune response and AIH in the mice, leading to hepatic fibrosis. The findings in this study suggest that the amplified non-AIH inflammation in the liver could be a driving force for the initiation of autoimmune response and AIH.



https://ift.tt/2KVtNpw

Polyglutamine binding protein 1 (PQBP1) inhibits innate immune responses to cytosolic DNA

Publication date: July 2018
Source:Molecular Immunology, Volume 99
Author(s): Jessica L. Shannon, Molly S. Murphy, Uma Kantheti, Jordan M. Burnett, Marina G. Hahn, Tyler J. Dorrity, Constantinos J. Bacas, Ethan B. Mattice, Kathryna D. Corpuz, Brianne R. Barker
Recent studies have highlighted the importance of immune sensing of cytosolic DNA of both pathogen and host origin. We aimed to examine the role of DNA sensors interferon-γ-inducible protein 16 (IFI16) and cyclic GMP-AMP synthase (cGAS) in responding to cytosolic DNA. We show IFI16 and cGAS can synergistically induce IFNb transcriptional activity in response to cytoplasmic DNA. We also examined the role of polyglutamine binding protein 1 (PQBP1), a protein predominantly expressed in lymphoid and myeloid cells that has been shown to lead to type I interferon production in response to retroviral infection. We show PQBP1 associates with cGAS and IFI16 in THP-1 cells. Unexpectedly, knockout of PQBP1 in THP-1 cells causes significantly increased type I IFN production in response to transfected cytosolic nucleic acids or DNA damage, unlike what is seen in response to retroviral infection. Overexpression of PQBP1 in HEK293 T cells impairs IFI16/cGAS-induced IFNb transcriptional activity. In human cancer patients, low expression of PQBP1 is correlated with improved survival, the opposite correlation of that seen with cGAS or IFI16 expression. Our findings suggest that PQBP1 inhibits IFI16/cGAS-induced signaling in response to cytosolic DNA, in contrast to the role of this protein in response to retroviral infection.

Graphical abstract

https://ift.tt/2LA7iHF

Notch1 primes CD4 T cells for T helper type I differentiation through its early effects on miR-29

Publication date: July 2018
Source:Molecular Immunology, Volume 99
Author(s): Karthik Chandiran, Rebecca Lawlor, Antonio Pannuti, Gabriela Gonzalez Perez, Janani Srinivasan, Todd E. Golde, Lucio Miele, Barbara A. Osborne, Lisa M. Minter
The transmembrane receptor, Notch1 plays an important role during the differentiation of CD4 T cells into T helper (Th) subsets in the presence of appropriate cytokines, including differentiation into Th1 cells. MicroRNAs have also been shown to be important regulators of immune responses, including negatively regulating cytokine production by Th1 cells. The miR-29 family of microRNAs can act to inhibit tbx21 and ifng transcription, two important pro-inflammatory genes that are abundantly expressed in Th1 cells. Here we show that Notch1 may prime CD4 T cells to be responsive to Th1-polarizing cues through its early repressive effects on the miR-29 family of microRNAs. Using a combination of cell lines and primary cells, we demonstrate that Notch1 can repress miR-29a, miR-29b, and miR-29c transcription through a mechanism that is independent of NF-κB. We further show that this repression is mediated by canonical Notch signaling and requires active Mastermind like (MAML) 1, but this process is superseded by positive regulation of miR-29 in response to IFNγ at later stages of CD4 T cell activation and differentiation. Collectively, our data suggest an additional mechanism by which Notch1 signaling may fine-tune Th1 cell differentiation.

Graphical abstract

https://ift.tt/2KWhx88

Editorial Board/Reviewing Committee

https://ift.tt/2ktNUzG

Asymptomatic Pulmonary Artery Intimal Sarcoma with Chest Wall Metastasis as an Initial Manifestation: An Autopsy Case

Pulmonary artery intimal sarcoma (PAIS) is a rare mesenchymal malignancy arising in the pulmonary trunk or proximal pulmonary artery and shows intraluminal growth. Clinical manifestations in PAIS are predominantly related to the pulmonary artery embolism, so cases with initial symptoms related to an extrapulmonary metastasis are unusual. The present report describes an 82-year-old man without any cardiopulmonary symptoms who was detected with an abnormal shadow on chest radiography during a routine health checkup. Contrast medium-enhanced chest computed tomography revealed an enhancing mass in the right pulmonary artery, pulmonary nodules, and a chest wall tumor corresponding to the abnormal shadow observed using chest radiography. A core needle biopsy for the chest wall tumor determined a pathological diagnosis of unclassified sarcoma. The patient was diagnosed with PAIS on the basis of clinical, radiological, and pathological correlations. He was scheduled to receive supportive care, but died of respiratory failure 1 year from the first visit. An autopsy revealed the pleomorphic sarcoma occupying the entire lumen of the right pulmonary artery with the only site of extrapulmonary metastasis in the chest wall. We should be aware of rare cases of asymptomatic PAIS found through routine health checkups.

https://ift.tt/2IOpgbV

Sublingual gland excision for the surgical management of plunging ranula

A plunging ranula is a pseudocystic collection of mucin extravasated from the sublingual gland into the floor of mouth and through the mylohyoid muscle into the neck. While the lining of a ranula is non-secreting and resection of the sublingual gland is adequate for simple sublingual mucoceles, many surgeons attempt to address plunging ranulas with extensive transoral and transcervical dissections. We review our experience managing plunging ranulas with intraoral sublingual gland excision and ranula drainage alone.

https://ift.tt/2sde9Pe

Adherence to Continuous Positive Airway Pressure therapy in Singaporean patients with Obstructive Sleep Apnea

To investigate the rates of Continuous Positive Airway Pressure (CPAP) uptake and adherence amongst Singaporean patients diagnosed with Obstructive Sleep Apnea (OSA), and to evaluate factors correlated with CPAP uptake and adherence.

https://ift.tt/2IPzFjg

The impact of nasal airflow on sinus mucosa: A radiographic review

Chronic rhinosinusitis (CRS) is a disease of widespread prevalence and high morbidity. Many suggest that the introduction of toxins and allergens via nasal airflow plays a significant role in the development of CRS. In patients who have undergone total laryngectomy, nasal airflow is disrupted, providing an opportunity to examine the role of nasal airflow in sinonasal pathology.

https://ift.tt/2sbyCEe

Risks and benefits of local anesthesia versus general anesthesia in tonsillectomy

Tonsillectomy is one of the most common surgical procedures in otorhinolaryngology. Modern general anesthetic techniques have reduced surgical risks, but performing the procedure under local anesthesia may still offer significant benefit for both the patient and surgeon. This study analyzed the risks and benefits of performing tonsillectomies under local anesthesia.

https://ift.tt/2IU61ta

Treatment of intravitreal bevacizumab combined with focal laser photocoagulation in the case of macular telangiectasia type 2 with retinal arterial macroaneurysm

Abstract

Macular telangiectasia type 2 (Mac Tel 2) is a bilateral disease of unknown cause with characteristic changes of the retinal vasculature. To the best of our knowledge, we could not find any reported cases of Mac Tel 2 with retinal arterial macroaneurysm (RAM). Our aim is to report a case of Mac Tel 2 with RAM.

https://ift.tt/2IQen5n

Clinicopathological and prognostic significance of preoperative serum epidermal growth factor levels in patients with oral squamous cell carcinoma

Epidermal growth factor (EGF) promotes tumourigenesis and tissue repair of epithelial and mesenchymal cells and has a role in chemotaxis, mitogenesis, cell motility, and cytoprotection. It also enhances the growth of cancers. EGF may therefore have a role in the initiation or promotion of oral carcinogenesis. The cases of 152 patients with oral squamous cell carcinoma whose preoperative serum EGF level was determined by enzyme-linked immunosorbent assay were analyzed retrospectively, along with those of 40 age- and sex-matched controls.

https://ift.tt/2krxAj5

Comparison of osseous healing after sagittal split ramus osteotomy and intraoral vertical ramus osteotomy

The sagittal split ramus osteotomy (SSRO) is generally associated with greater postoperative stability than the intraoral vertical ramus osteotomy (IVRO); however, it entails a risk of inferior alveolar nerve damage. In contrast, IVRO has the disadvantages of slow postoperative osseous healing and projection of the antegonial notch, but inferior alveolar nerve damage is believed to be less likely. The purposes of this study were to compare the osseous healing processes associated with SSRO and IVRO and to investigate changes in mandibular width after IVRO in 29 patients undergoing mandibular setback.

https://ift.tt/2sgZBxb

Man as a living bioreactor: Long-term histological aspects of a mandibular replacement engineered in the patient’s own body

In 2016, we reported the world's first reconstruction of a mandibular discontinuity defect using a custom-made bone transplant that had been prefabricated in the gastrocolic omentum using tissue engineering strategies. However, the tissue of an engineered human neomandible has not been evaluated histologically until now. The current study assessed the long-term histological characteristics of biopsies of the neomandible 9months after transplantation. Histological analysis showed an increased amount of vital mineralized bone tissue after 10months, in comparison to biopsies obtained earlier.

https://ift.tt/2krYgQI

Short implants versus bone augmentation in combination with standard-length implants in posterior atrophic partially edentulous mandibles: systematic review and meta-analysis with the Bayesian approach

The use of short implants as an alternative to bone reconstruction techniques for the placement of standard-length dental implants is a debated topic. The aim of this study was to perform a systematic review and meta-analysis in order to assist in the clinical decision making about the most appropriate approach for the fixed rehabilitation of the posterior atrophic partially edentulous lower jaws. Only randomized trials with at least 1-year follow-up were included. Of the 1024 studies initially retrieved, 14 articles were selected and independently evaluated by two reviewers.

https://ift.tt/2sgZvFP

Sandwich osteotomy for the reconstruction of deficient alveolar bone

Alveolar bone deficiency is a very common problem encountered by the practitioner when planning dental implants. The severity of the deficiency is variable. Many practitioners perform augmentation using the method they feel comfortable with and do not necessarily use the most appropriate method. This is a retrospective study on 21 patients between the ages of 25 and 63 years exhibiting moderate vertical alveolar bone deficiency and treated by the sandwich technique. Mean vertical bone gain was 7.5mm.

https://ift.tt/2IJDJ8O

Jugular foramen tumour resulting in hypoglossal denervation pseudohypertrophy: a rare and significant cause for tongue asymmetry

Paragangliomas of the jugular foramen are rare. They may present with symptoms of compression of the glossopharyngeal or vagus nerves, or due to secretion of catecholamines from chromaffin cells within the tumour. This case describes a rare presentation of glomus tumour. A 67-year-old patient presented with a 2-month history of right-sided tongue swelling. She was found to have an obvious swelling on the right side of the tongue but no obvious weakness or fasciculation on initial examination. Ultrasound confirmed diffuse muscle swelling, but no lesion within the tongue.

https://ift.tt/2shcFCX

MicroRNA-4497 functions as a tumor suppressor in laryngeal squamous cell carcinoma via negatively modulation the GBX2

MicroRNAs (miRNAs) are aberrantly expressed in various tumors and play a critical role in the progression and development of tumors. However, there is little information about the role of miR-4497 in laryngeal squamous cell carcinoma (LSCC). The aim of this study is to investigate the role of miR-4497 in LSCC.

https://ift.tt/2GSqxbX

Rare presentation of rickettsial infection as purpura fulminans: a case report

Purpura fulminans is an acute life-threatening disorder characterized by intravascular thrombosis and hemorrhagic infarction of the skin complicated with disseminated intravascular coagulation. It is commonly ...

https://ift.tt/2saYKPC

Systemic therapy in non-conventional cancers of the larynx

Publication date: July 2018
Source:Oral Oncology, Volume 82
Author(s): Elaine Tan, Mayur D. Mody, Nabil F. Saba
Laryngeal cancer (LC) remains a challenging disease to treat. The majority of LCs diagnosed worldwide are squamous cell carcinomas (SCC), and current treatment guidelines are designed to address conventional laryngeal SCC. However, several histologically rare tumor types can originate in the larynx. There is a lack of guidelines regarding the best therapeutic approaches to these tumors and their treatment is often modeled after their recommended management at non-laryngeal sites. Understanding the role for systemic therapy in these rare tumors is important, especially for patients with advanced disease or those who are not surgical candidates. We provide in this manuscript a detailed and comprehensive overview of systemic therapy considerations for the following histologic tumor types of the larynx: verrucous carcinoma (VC), HPV-related SCC, basaloid SCC (BSCC), lymphoepithelial carcinoma (LEC), adenosquamous carcinoma (ASC), typical and atypical carcinoid, small cell neuroendocrine carcinoma (SCNC), large cell neuroendocrine carcinoma (LCNC), NUT midline carcinomas (NUTMC), melanoma, adenoid cystic carcinoma, rhabdomyosarcoma (RMS), malignant fibrous histiocytoma (MFH), lymphoma, mucoepidermoid carcinoma (MEC), acinic cell carcinoma, and spindle cell carcinoma (SpCC).



https://ift.tt/2J86oE1

Dysfunction of HPV16-specific CD8+ T cells derived from oropharyngeal tumors is related to the expression of Tim-3 but not PD-1

Publication date: July 2018
Source:Oral Oncology, Volume 82
Author(s): Kamila Hladíková, Simona Partlová, Vladimír Koucký, Jan Bouček, Jean-Francois Fonteneau, Michal Zábrodský, Ruth Tachezy, Marek Grega, Radek Špíšek, Anna Fialová
BackgroundHuman papillomavirus (HPV) type 16 infection is one of the most important etiological agents of oropharyngeal squamous cell carcinoma. Patients with HPV-associated carcinomas of the head and neck were reported to have a better clinical outcome than patients with HPV-negative tumors. Because HPV16 E6 and E7 oncoproteins are highly immunogenic and constitutively expressed, HPV-specific T cell immunity may play the key role in improving the prognosis of these patients.MethodsTumor-derived T cells were expanded in high levels of IL-2 and stimulated with HPV16 E6/E7 peptides in the presence or absence of anti-PD-1 monoclonal antibody nivolumab and soluble Tim-3.ResultsHPV16-specific tumor-infiltrating T cells were present in 73.1% of HPV-associated oropharyngeal tumors. HPV16 specific CD8+ TILs were able to produce IFNγ upon specific stimulation and predominantly expressed PD-1 but not Tim-3. Specific IFNγ production was further enhanced after a blockade of both PD-1 and Tim-3 pathways but not after a PD-1 blockade alone. Additionally, the specific stimulation of anti-HPV16 CD8+ T cells suppressed Tim-3 upregulation after the PD-1 blockade.ConclusionOur data provide the rationale for combination cancer immunotherapy approaches, including the dual blockade of PD-1 and Tim-3 and, potentially, the use of HPV16-directed therapeutic vaccines.



https://ift.tt/2seU3Dy

National treatment times in oropharyngeal cancer treated with primary radiation or chemoradiation

Publication date: July 2018
Source:Oral Oncology, Volume 82
Author(s): Elliot Morse, Benjamin Judson, Zain Husain, Barbara Burtness, Wendell Yarbrough, Clarence Sasaki, Shayan Cheraghlou, Saral Mehra
ObjectiveTo characterize treatment delays in oropharyngeal cancer treated with radiation in a national sample, identify factors associated with delays, and associate treatment delays with survival.Materials and MethodsWe included adults in the National Cancer Database treated for oropharyngeal cancer with primary radiation or chemoradiation 2010–2013. We characterized diagnosis-to-treatment initiation, radiation treatment duration, and diagnosis-to-treatment end intervals as medians. We examined delays for association with patient, tumor, and treatment characteristics and with overall survival with multivariable logistic and Cox proportional hazards regression, respectively.Results4089 patients were included; 12% received radiation alone and 88% chemoradiation. The incidence of human papilloma virus-associated tumors was 64%. Median durations of diagnosis-to-treatment initiation, radiation duration, and diagnosis-to-treatment end were 35, 50, and 87 days, respectively. Human papilloma virus-positive tumors were linked to decreased delays in radiation treatment duration and diagnosis-to-treatment end (OR = 0.72 (0.60–0.85), p < 0.001 and OR = 0.79 (0.66–0.95), p = 0.010, respectively). Delays in radiation treatment duration and diagnosis-to-treatment end were negatively associated with overall survival (HR = 1.23 (1.03–1.47), p = 0.024 and 1.24 (1.04–1.48), p = 0.017, respectively). When examined separately, radiation duration remained associated with decreased overall survival in patients with human papilloma virus-negative (HR = 1.29 (1.03–1.63), p = 0.030) but not human papilloma virus-positive tumors (HR = 1.17 (0.89–1.54), p = 0.257).ConclusionThese median durations can serve as national benchmarks. Diagnosis-to-treatment end interval is associated with overall survival in all patients, and radiation treatment duration in patients with human papilloma virus-negative tumors. These intervals could be considered quality indicators for oropharyngeal squamous cell carcinoma treated with primary radiation or chemoradiation.



https://ift.tt/2Jb0dPE

Smoking impact on HPV driven head and neck cancer’s oncological outcomes?

Publication date: July 2018
Source:Oral Oncology, Volume 82
Author(s): Haitham Mirghani, Charlotte Leroy, Younes Chekourry, Odile Casiraghi, Anne Aupérin, Yungan Tao, France Nguyen, Even Caroline, Ingrid Breuskin, Antoine Moya Plana, Dana Hartl, François Janot, Stéphane Temam, Philippe Gorphe, Pierre Blanchard
IntroductionHPV-driven oropharyngeal cancer (OPC) patients have a better prognosis than their HPV-negative counterparts but several studies have suggested that among HPV-positive patients those with a smoking history had worse oncological outcomes. The aim of our study is to characterize the interplay between tobacco consumption, patient and disease characteristics, and disease control.Materials and methodsAll patients diagnosed with HPV-driven OPC and treated with curative intent between 2007 and 2009 and 2011–2016 at Gustave Roussy cancer center were included (n = 282). Demographic, clinical, morphological and tobacco consumption were correlated with oncologic outcomes.Results157 (56%) patients had a positive smoking history, including 23.8% who were smoking at the time of diagnosis and 37.6% who had a tobacco consumption exceeding 20 pack-years. In multivariate analysis, the strongest prognostic factor for survival was smoking status at cancer diagnosis, with a hazard ratio (HR) for non-smokers compared to smokers of 0.25 ([0.12, 0.50], p = 0.0001). Smoking history, either more than 20 pack-years or smoking at diagnosis, was associated with local relapse and distant relapse. There was no difference in terms of comorbidity (p = 0.32) and radiotherapy duration (p = 0.93) according to tobacco consumption.DiscussionSmoking is frequent among patients with HPV-driven OPC and increases the risk of death and oncologic failure.



https://ift.tt/2GTbheP

Jugular dominance is unrelated to isolated unilateral congenital aural atresia in children

Publication date: July 2018
Source:International Journal of Pediatric Otorhinolaryngology, Volume 110
Author(s): Tyler R. Halle, Amanda S. Corey, N. Wendell Todd
ObjectivesThe right jugular foramen is usually larger than the left in Homo sapiens, but it is unknown if right-sided jugular dominance is also more common amongst those with unilateral congenital aural atresia. We hypothesized that the dominant (i.e. larger) jugular foramen in children with isolated, non-syndromic, unilateral congenital aural atresia would be contralateral to the atretic ear.MethodsWe reviewed high-resolution computed tomography scans of the temporal bones of 70 children with isolated, non-syndromic, unilateral congenital aural atresia. Images were viewed in the transverse (axial) plane by a board-certified neuroradiologist and a board-certified otolaryngologist. Consensus opinion was recorded. Multiple logistic regression was used to assess the impact of age, sex, and side of aural atresia on jugular dominance.ResultsJugular foramen dominance was not associated with the side of aural atresia (P = 0.20), age (P = 0.50) or sex (P = 0.76). Right-sided jugular dominance (46/70, 65.7%) was more common in both left- and right-sided unilateral aural atresia (P = 0.004).ConclusionsThe side of jugular foramen dominance is not associated with the side of aural atresia in children with isolated, non-syndromic, unilateral congenital aural atresia. Right-sided jugular dominance is more common irrespective of unilateral aural atresia.



https://ift.tt/2IOsA2w

Dichotic training in children with auditory processing disorder

Publication date: July 2018
Source:International Journal of Pediatric Otorhinolaryngology, Volume 110
Author(s): Maryam Delphi, Farzaneh Zamiri Abdollahi
ObjectivesSeveral test batteries have been suggested for auditory processing disorder (APD) diagnosis. One of the important tests is dichotic listening tests. Significant ear asymmetry (usually right ear advantage) can be indicative of (APD). Two main trainings have been suggested for dichotic listening disorders: Differential Interaural Intensity Difference (DIID) and Dichotic Offset Training (DOT). The aim of the present study was comparing the efficacy of these two trainings in resolving dichotic listening disorders.Methods12 children in the age range of 8 to 9 years old with APD were included (mean age 8.41 years old±0.51). They all had abnormal right ear advantage based on established age-appropriate norms for Farsi dichotic digit test. Then subjects were randomly divided into two groups (each contained 6 subjects): group 1 received DIID training (8.33 years old ±0.51) and group 2 received DOT training (8.50 years old±0.54).ResultsBoth trainings were effective in improvement of dichotic listening. There was a significant difference between two trainings with respect to the length of treatment (P-value≤0.001). DOT needed more training sessions (12.83±0.98 sessions) than DIID (21.16±0.75 sessions) to achieve the same amount of performance improvement.ConclusionBased on the present study it can be assumed that DOT might be a good replacement for DIID training in cases that DIID is not applicable and DIID candidacy conditions are not met. To generalize the results, studies with larger sample sizes are recommended.



https://ift.tt/2s9IwpH

Intracranial complications of acute sinusitis in children: The role of endoscopic sinus surgery

Publication date: July 2018
Source:International Journal of Pediatric Otorhinolaryngology, Volume 110
Author(s): Yann-Fuu Kou, Daniel Killeen, Brett Whittemore, Zainab Farzal, Tim Booth, Dale Swift, Eric Berg, Ron Mitchell, Gopi Shah
ObjectiveTo study the role of endoscopic sinus surgery (ESS) in the management of intracranial complications of children with acute rhinosinusitisMethodsRetrospective chart review at a tertiary care pediatric hospitalMain outcomesDemographics, intracranial complications, length of hospital stay (LOS), neurological sequelae, ESS, neurosurgical proceduresResultsTwenty-four children with a mean age (SD) of 12.9 years (+/-3.2) with an intracranial complication(s) of acute rhinosinusitis were identified between 2005-2016. A total of 22 were included and 15 (68%) of these were males. The most common complications were: subdural abscess (n=10), epidural abscess (n=10), meningitis (n=5), intraparenchymal abscess (n=5), and cavernous sinus thrombosis (n= 2). Neurologic symptoms included headache (n=12), hemiparesis (n=5) and aphasia (n=3). Average length of stay was 16 (+/- 9.2) days. Average follow up was 7 (+/-5.6) months. One patient had residual seizures and 1 had recurrent rhinosinusitis. Aphasia and hemiparesis resolved in all patients within 1 year. Nineteen (86%) patients had ESS within 4 days of admission. Fourteen patients (63%) had a neurosurgical procedure, 6 (27%) required more than 1 neurosurgical procedure. Six patients (27%) had concurrent neurosurgical drainage and ESS. Four patients (17%) had neurosurgical procedure followed by ESS and 3 patients (13%) were treated only by a neurosurgical procedure. Patients who underwent ESS prior to a neurosurgical procedure had significantly less risk of needing a neurosurgical intervention (OR = .02, p < .01). There was a significantly higher proportion of neurosurgical patients with positive Strep anginosus cultures compared to the ESS only group (85.7% vs 37.5%, p = .02). Studies with larger patient populations are needed to determine the role of ESS in the management of intracranial complications of children with acute rhinosinusitis.DiscussionEarly ESS may be associated with less need for neurosurgical procedures.



https://ift.tt/2xfIKRo

Primary gastric melanoma: a rare presentation

Description

A man in his early 50s presented to the emergency department with complaints of abdominal pain and dark tarry stools. He reported 3/10 burning left upper quadrant abdominal pain that started 2 days before. The pain radiated to the epigastric region and the patient was unsure what exacerbates or relieves the pain. Starting around the same time, the patient had 8 to 10 black tarry stools daily, which were loose in consistency, which were coming out of his ostomy bag. Review of systems was positive for weakness, fatigue, nausea, abdominal pain and change in stools. The patient has a history of T4 caecal adenocarcinoma with metastasis to bladder diagnosed in 2014, for which he underwent right hemicolectomy, low anterior resection, radical cystectomy and colostomy with urostomy that was reversed 2 years later. He also underwent chemotherapy/radiation therapy with (FIFLORI) leucovorin calcium (folinic acid), fluorouracil and irinotecan hydrochloride. Vitals showed a temperature of 97.5°F, pulse...

https://ift.tt/2KWmv4Z

Coronary artery fistula and mid-cavitary obstructive hypertrophic cardiomyopathy: a rare association

We report a case of a 60-year-old man with a history of angina on exertion (New York Heart Association Class II) who was found to have mid-cavitary obstructive hypertrophic cardiomyopathy on two-dimensional echocardiography and whose coronary angiogram showed right coronary artery–left ventricular fistula, with no significant coronary atherosclerosis suggestive of ischaemic heart disease. The patient was started on beta-blocker therapy, and on follow-up his angina improved. The patient had a benign course and did not have any progressive heart failure or acute coronary syndrome on follow-up. This case report highlights a rare association of mid-cavitary obstructive hypertrophic cardiomyopathy with coronary artery fistula.

https://ift.tt/2LzwFt4

Personalised 3D-printed model of a chest-wall chondrosarcoma to enhance patient understanding of complex cardiothoracic surgery

Description

Novel technologies, such as additive manufacturing (also termed three-dimensional (3D) printing), play an important role in surgical planning. Their role in enhancing a patient's understanding of their medical condition and increasing their satisfaction with their treatment is also gaining increased attention in medicine and surgery. As an illustration, we describe the case of a 65-year-old Caucasian man who presented with left-sided anterior chest-wall pain which was associated with a visible palpable lump. He had a body mass index of 27 kg/m², and CT of the thorax demonstrated a 62 mm x 60 mm x 48 mm tumour involving multiple structures, including the left fourth to sixth ribs, costal cartilages and the pericardium overlaying the right ventricle (figure 1). Transthoracic echocardiography showed normal ventricular function without any indication of tumour infiltration into the myocardium.

Figure 1

Axial (right) and sagittal (left) CT slices of the thorax demonstrating a large chondrosarcoma...

https://ift.tt/2KW5YxD

Neisseria meningitidis sepsis in a patient with acute epiglottitis and respiratory failure

A 78-year-old female patient presented to our emergency department with a 5-day history of throat pain, hoarseness and a progressive and dolorous submandibular swelling. Due to non-conclusive clinical examination and the stable but visibly affected patient, we performed a neck CT scan with intravenous contrast, which showed the thumbprint sign typical for acute epiglottitis. Within minutes, the patient's condition deteriorated and the patient was close to respiratory exhaustion. As intubation was severely complicated by massive swelling of the supraglottic soft tissue, the patient went into hypoxaemia and eventually cardiac arrest. After initiating reanimation protocol, eventually the airway was secured and Return of spontaneous circulation (ROSC) achieved after around 5 min. The initially sampled blood cultures revealed Neisseria meningitidis bactera emia and the patient was successfully treated accordingly. In patients with swelling of the upper airway, rapid clinical deterioration is possible. Diagnostics should not delay therapy, including administration of empiric antibiotics, steroids and intubation.

https://ift.tt/2JcomFD

Right-sided hydrothorax: a peritoneal dialysis dilemma

We present a 23-year-old female patient with a chief complaint of progressively worsening dyspnoea of 2 days duration. Her medical history was significant for end stage renal disease secondary to membranoproliferative glomerulonephritis. A peritoneal dialysis (PD) catheter was placed 8 weeks prior to admission. She did not miss any of the PD sessions prior to this admission. Vital signs were significant for hypoxemia. Physical examination was remarkable for right-sided basilar crackles with no other signs of fluid overload. A chest X-ray demonstrated the presence of a large right-sided pleural effusion. Right-sided thoracentesis was performed, with subsequent pleural fluid analysis concerning for a pleuroperitoneal leak. CT peritoneography performed confirming the diagnosis as contrast material leaked through the inferior vena cava (IVC) diaphragmatic foramen into the right pleural space. Surgical intervention was deferred in light of the close proximity of the defect to the IVC. The patient was transitioned to haemodialysis for temporary cessation of PD.

https://ift.tt/2KWKgd2

Successful pregnancies and reduced treatment requirement while breast feeding in a patient with congenital hypoparathyroidism due to homozygous c.68C>A null parathyroid hormone gene mutation

A female patient with consanguineous parents presented at the age of 4 with isolated hypoparathyroidism due to a parathyroid hormone (PTH) gene mutation. She was managed with alfacalcidol and calcium supplements, and developed normally. Her consanguineous parents described symptoms suggestive of hypocalcaemia but had normal serum calcium and low normal PTH levels. A molecular diagnosis obtained in her adulthood revealed the presence of homozygous point mutation (c.68C>A) in exon 2 introducing a premature stop codon resulting in a non-functional precursor protein. This mutation has been reported only once before. Our patient remained on stable doses of alfacalcidol during pregnancy, but stopped all supplementation while breast feeding. This case confirms that alternative mechanisms (likely breast-derived parathyroid hormone-related protein) contribute to calcium homeostasis during breast feeding. Heterozygotes for the c.68C>A mutation may have latent hypoparathyroidism and maintain calcium homeostasis except during prolonged hypocalcaemia. This would suggest incomplete dominance, or a dose effect of the wild-type PTH allele.

https://ift.tt/2LvmE0g

Chronic pancreatitis with Bochdalek hernia causing right-sided pleural effusion in a previously asymptomatic adult

A 41-year-old man with a medical history of chronic back pain, seizure disorder, alcohol and tobacco abuse presented with acute shortness of breath. Chest X-ray showed a large right-sided pleural effusion. Pleural fluid analysis was significant for an elevated amylase level, suggestive of pleural effusion secondary to pancreatitis. Magnetic resonance cholangiopancreatography (MRCP) revealed a persistent right-sided pleural effusion in connection with a right pararenal space fluid collection via a Bochdalek hernia. An endoscopic ultrasound found hyperechoic strands and foci, and pancreatic parenchyma consistent with chronic pancreatitis, as well as a pseudocyst in the pancreatic head. A chest tube was ultimately placed to continuously drain the pleural effusion. The patient was discharged and was referred to gastroenterology for outpatient follow-up. This case illustrates a rare presentation of chronic pancreatitis with a Bochdalek hernia as a right-sided pleural effusion in a patient who was previously asymptomatic.

https://ift.tt/2KSAhp5

Thromboatheromatous coarctation of the aorta diagnosed with intraoperative TOE during emergent open aneurysm clipping

A woman in her 50s presenting for emergent intracranial surgery was discovered to have a large incongruity in blood pressure between her right arm and her other extremities. Intraoperative rescue transoesophageal echocardiography (TOE) revealed a large thromboatheromatous burden in her descending aorta resulting in a functional coarctation. Usually diagnosed via CT imaging, we present what we believe to be the first published case diagnosed intraoperatively using TOE. After the diagnosis was made, blood pressure goals were adjusted to provide sufficient perfusion distally and her surgery was completed otherwise uneventfully.

https://ift.tt/2LxRHIU

Synchronous oesophageal and gastric sarcomatoid carcinoma: first reported case in Australia

A 75-year-old retired teacher presents with dysphagia and weight loss for a duration of 6 months. Her gastroscopy showed two synchronous submucosal masses. A 7 cm polypoid mass was seen at the distal oesophagus, arising from a thick stalk and a 4 cm mass seen at the cardia. The biopsies showed high-grade sarcomatoid cancer. Staging CT scan and Positron Emission Tomography scan did not show any distant metastasis except a lesion in the rectum that was subsequently found to be tubulovillous adenoma on transanal excision. The patient was managed with Ivor Lewis oesophagectomy. The biopsies of resection specimen showed spindle cell/sarcomatoid carcinoma with a component of poorly differentiated neuroendocrine carcinoma in oesophageal tumour and a small component of conventional invasive squamous cell carcinoma in tumour at cardia. The patient recovered well after surgery. Since then, she has completed adjuvant chemoradiotherapy. No recurrence has been noted in 10 months follow-up.

https://ift.tt/2KYfi4n

Spinal tophaceous gout presenting in a young adult without pain

A 26-year-old man with a medical history of gout and morbid obesity presented with a 7-day history of decreased sensation to light touch and temperature from the feet to the level of the nipples. He also noted incomplete voiding. Laboratory investigations showed an elevated serum uric acid level (10.4 mg/dL, reference range: 3.8–8.7 mg/dL) as well as negative rapid plasma reagin and rheumatoid factor. MRI showed inflammatory changes on multiple spinal levels. Laminectomy was performed, with follow-up biopsy revealing multiple multinucleated giant cells and monosodium urate (MSU) crystals. He was ultimately diagnosed with spinal gout. Patient's symptoms did not resolve immediately after surgery. Yet with the administration of intravenous glucocorticoids and a course of non-steroidal anti-inflammatory drugs, he slowly regained sensation, leaving the hospital with complete resolution of symptoms.

https://ift.tt/2KWLzsi

Bronchiolitis obliterans organising pneumonia as an initial manifestation in a patient with systemic lupus erythematosus: a rare presentation

Bronchiolitis obliterans organising pneumonia as an initial manifestation of systemic lupus erythematosus (SLE) is a rare and uncommon presentation. We describe a case of SLE presenting with shortness of breath, found to have pneumothorax, bilateral nodular infiltrates along with pleural effusions and pericardial effusion. Work-up suggested a diagnosis of active SLE with anaemia, thrombocytopenia, positive antinuclear antibodies (ANAs) and positive anti-double-stranded DNA. On retrospective review of patient records, from 8 years prior to presentation, lung biopsy histology consistent with bronchiolitis obliterans organising pneumonia with positive ANA serology was found, without any further autoimmune work-up. In our opinion, bronchiolitis obliterans organising pneumonia was the index presentation of SLE. Treatment with steroids and subsequent management with immunosuppressive therapy could have prevented subsequent hospitalisations. Prompt work-up for autoimmune diseases should be considered in patients with positive ANA and histological evidence of bronchiolitis obliterans organising pneumonia.

https://ift.tt/2LyS1qO

Metastatic ductal carcinoma of the breast to colonic mucosa

Breast cancer is the most common malignancy among women, while invasive ductal carcinoma is the most common type of invasive breast cancer. Metastatic spread to the colon and rectum in breast cancer is rare. This report describes a case of a 69-year-old woman with metastatic ductal breast cancer to the rectosigmoid, presenting as an incidental finding on screening colonoscopy. The breast carcinoma was first diagnosed 2 years prior. Colonic biopsies from colonoscopy confirmed metastatic adenocarcinoma consistent with a breast primary. Ultimately her clinical condition worsened as she developed malignant ascites, a small bowel obstruction, and new bone metastases, and the patient succumbed to her illness. Cases of metastatic breast cancer to the gastrointestinal tract have predominantly been lobular breast carcinoma. Increased awareness of colonic metastasis may lead to more accurate diagnosis and earlier systemic treatment.

https://ift.tt/2LxvcU9

Foreign body urethra misdiagnosed as stricture leading to inadequate management and prolonged treatment duration: a lesson to learn

Misdiagnosis of a urethral foreign body (FB) as urethral stricture leads to inadequate management and prolonged treatment duration. A 55-year-old male patient was referred with complaints of difficulty in voiding and poor urinary stream for 2 months. He initially presented at a primary healthcare centre and was misdiagnosed as urethral stricture and was scheduled for urethroplasty. Surprisingly, intraoperative cystourethroscopy performed by us revealed that the urethra had been obstructed by an FB. The FB was gently pushed into the bladder and retrieved. The postoperative course was uneventful. The present case represents a rare occurrence of polyembolokoilamania or insertion of a FB into any bodily orifice for sexual gratification.

https://ift.tt/2KSsOGD

Approach to rectal foreign body: an unusual presentation

Foreign bodies in the rectum are commonly confronted worldwide in the surgical emergency. Such a situation arises either accidentally or for autoerotic purposes. A wide variety of foreign objects have been reported in the literature and this usual object would add to the reports for its unusual location. We report a case of a 26-year-old young man with accidental insertion of hand shower in the rectum and no signs of any active bleed or peritonism. Extraction was done successfully in the operating room under general anaesthesia, with an uneventful postprocedure period and the patient was discharged after 48 hours of observation. Rectal foreign bodies can be of wide variety and can lead to life-threatening conditions. An orderly approach is required for diagnosis, management and evaluation in the postprocedure period.

https://ift.tt/2Lwfo40

Mycobacterium avium intracellulare infection complicated by allergic bronchopulmonary aspergillosis in a non-asthmatic patient

Allergic bronchopulmonary aspergillosis (ABPA) most often develops in patients with asthma or cystic fibrosis. We present a 91-year-old non-asthmatic patient with pre-existing Mycobacteriumavium complex (MAC) infection who got diagnosed with ABPA. Treatment of the two conditions can be challenging as immunosuppression with steroids for treatment of ABPA may exacerbate the underlying MAC infection. Treatment with steroids and antibiotics resulted in significant improvement in the patient's condition.

https://ift.tt/2KUT17m

Uterine torsion and subsequent rupture in a gravid bicornuate uterus associated with an elevated alpha-fetoprotein

Uterine torsion is a rare obstetric complication with a non-specific presentation. We describe a patient with a bicornuate uterus and a pregnancy complicated by a markedly elevated second-trimester maternal serum alpha-fetoprotein (MSAFP), intermittent pelvic pain and fetal growth restriction. At 24 weeks gestational age, she presented to labour and delivery with an acute abdomen. A subsequent exploratory laparotomy revealed torsion and rupture of her right uterine horn. Uterine torsion can be difficult to diagnose because it is not associated with specific symptoms or characteristic imaging findings. In patients with a bicornuate uterus who present with abdominal pain, an elevated mid-trimester MSAFP may be a harbinger of placental ischaemia as a result of uterine torsion.

https://ift.tt/2LxuZQR

Disseminated coccidioidomycosis masquerading as recurrent lymphoma

Description

Infection with Coccidioides immitis, a soil-dwelling fungus endemic to the American Southwest, may have protean manifestations in immunocompromised patients who reside in1 2 or who have travelled to3 that region. We report a patient whose abnormal PET/CT scan raised concern for recurrent lymphoma but instead was due to disseminated coccidioidomycosis.

A 62-year-old woman was diagnosed with ileocaecal marginal zone lymphoma (MZL) after presenting with iron-deficiency anaemia and faecal occult blood. Ten years earlier, she underwent allogeneic haematopoietic cell transplantation for acute myeloid leukaemia (AML). She had recurrent cutaneous chronic graft-versus-host-disease (CGVHD); 50 months before the diagnosis of MZL, she completed a 9-month course of prednisone (50 mg every other day) and did not receive any further corticosteroid therapy. At the time of diagnosis of MZL, the patient was receiving twice-monthly extracorporeal photopheresis (ECP), which had been initiated 1 year earlier for the most...

https://ift.tt/2KX3UWq

Seronegative enteropathy and malnutrition: a diagnostic challenge

A 21-year-old woman presented with a 2-week history of vomiting, diarrhoea and epigastric pain, with 9 kg weight loss over the last two months. Laboratory tests were normal with negative coeliac serology. Duodenal biopsies revealed total villous atrophy, crypt hypertrophy and intraepithelial lymphocytosis. A diagnosis of seronegative coeliac disease was made, and she started a gluten-free diet. However, she did not respond and her weight fell to 30.6 kg (body mass index 11), becoming dependent on parenteral nutrition. Her diagnosis was reconsidered and the histology reviewed. The histopathological features were of severe active chronic duodenitis. By diagnosis of exclusion, with the absence of other clear pathology, she was treated as Crohn's disease. She responded to third-line therapy with biologics. In this case, the patient had refractory villous atrophy and the mucosal features, in addition to response with anti-tumour necrosis factor therapy, suggest inflammatory bowel disease, although not with complete diagnostic certainty.

https://ift.tt/2LxuNkB

Renal ultrasound imaging in a preterm infant with a persistently elevated C reactive protein

Description 

A preterm infant born at 25+5 weeks gestation was being treated for late onset sepsis on day 30. She had just recovered from an episode of necrotising enterocolitis, requiring a 14-day course of intravenous antibiotics. She was on biphasic non-invasive respiratory support and fully enterally fed on expressed breast milk. During this time, she was noted to have a rising C reactive protein (to maximum of 114 mg/L), high white cell count (highest count 26.2x10⁹/L) and thrombocytopaenia (lowest count 63x10⁹/L), in spite of being treated with second-line intravenous broad-spectrum antibiotics (meropenem and vancomycin) for 14 days. She did not receive antifungal prophylaxis during her admission. Blood and cerebrospinal fluid cultures showed no growth. Urinalysis showed no growth on bacterial and fungal culture and no filamentous fungi were noted on microscopy. She remained clinically well. A cranial and abdominal ultrasound scan was  undertaken on day 35. The abdominal ultrasound revealed a...

https://ift.tt/2KYhmJD

Anomalous origin of the coronary artery from the pulmonary artery in a 33-year-old man

Description 

A 33-year-old man, without prior history of coronary artery disease, was referred to a catheterisation laboratory with a diagnosis of non-ST elevation myocardial infarction. Coronary angiogram showed a dilated, dominant right coronary artery of normal origin with multiple collaterals draining to the left coronary system (figure 1A,B) and a coronary 'steal' phenomenon into the pulmonary artery (PA). Left main coronary artery (LMA) was not visualised on contrast injection into the aortic root (figure 1B). Ventriculogram showed ejection fraction of 40%–45% and anterior wall hypokinesis. Subsequent three-dimensional heart computer tomogram revealed anomalous origin of the LMA from PA, (figure 1C), confirming the diagnosis of anomalous origin of the coronary artery from the pulmonary artery (ALCAPA).

Figure 1

(A) Left anterior oblique (LAO) view. Large dominating RCA with extensive collaterals to the left coronary system. (B) Failure to visualise left coronary artery...

https://ift.tt/2LweYdW

Blood loss mitigation and replacement in facial surgery: a review

Purpose of review To provide a comprehensive overview of the predisposing factors that contribute to a risk of excess bleeding for surgical therapy in the head and neck regions, provide a thorough overview of techniques and tools for managing blood loss complications, and provide intervention algorithms to help guide clinical decision making. Recent findings With the current landscape of medications and reversal agents, protocols for intervention in a variety of situations, and new tools for blood loss management all rapidly changing and being developed it is critical to stay up to date to provide patients the best care in the most critical of situations. Summary With the risk of blood loss complications in head and neck surgery ranging from minimal to extreme surgeons require a comprehensive understanding risk factors, patient evaluation tools, and proper management algorithms. The first opportunity to prevent unnecessary blood loss and blood loss complications is the health history and physical appointment where a clinician can identify any medications, conditions, or other predisposing factors that would elevate a patient's risk of excess bleeding and the necessity for treatment augmentation. Although not all complications can be prevented because of the natural physiological variation that occurs from patient to patient, despite proper and proper diagnostics, a full working knowledge of most likely complications, hemostatic tools, and concise communication with team members can prevent a lot of blood loss and the complications associated. Correspondence to Dr Alan Herford, DDS, MD, OMFS, FACS, Loma Linda University OMFS Chair, Loma Linda, California, USA. Tel: +1-909-558-4222; fax: +1-909-558-0285; e-mail: aherford@llu.edu Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

https://ift.tt/2xdPtey

Sedation for gastrointestinal endoscopy in Australia: what is the same and what is different?

Purpose of review The purpose of this article is to review the practice of sedation for adults having gastrointestinal endoscopy in Australia and to compare it with practice in other countries. Recent findings The practice of sedation for endoscopy in Australia is dominated by anaesthesiologists, who have a preference for deep propofol-based sedation. The recent literature includes a number of guidelines for sedation developed by multidisciplinary groups, anaesthesiologists and gastroenterologists in Australia and other countries. The appropriate health practitioner to provide deep sedation and general anaesthesia, to use propofol for sedation and to manage higher risk patients remains controversial. The estimated risks associated with endoscopy vary by provider, sedation technique and study design (prospective or retrospective, single- or multicentre). New airway management techniques are being investigated that may be useful in patients at high risk of hypoventilation and hypoxia. Summary Endoscopy sedation is safe but more high-quality, multicentre observer-blinded randomized controlled trials are required. Correspondence to Kate Leslie, AO, FAHMS, Department of Anaesthesia and Pain Management, Royal Melbourne Hospital, Parkville, VIC 3050, Australia. Tel: +61 3 93427540; e-mail: kate.leslie@mh.org.au Copyright © 2018 YEAR Wolters Kluwer Health, Inc. All rights reserved.

https://ift.tt/2KYobuB

Measuring quality of recovery in perioperative clinical trials

Purpose of review Perioperative studies increasingly report patient-centered outcomes, but few provide a valid, global measure of a patient's health status after surgery and anesthesia. This review considers three quality of recovery (QoR) scales. Recent findings The 9-item (QoR Score), 15-item (QoR-15), and 40-item (QoR-40) QoR scales have been extensively validated in perioperative settings, and have also been used as outcome measures in numerous surgery and anesthesia studies. A range of clinical trials are presented to illustrate the value of the QoR scales in perioperative medicine research. Summary The QoR Score, QoR-15, and QoR-40 are valid and recommended endpoints for perioperative clinical trials, and there is guidance as to what constitutes a minimal clinically important difference. These recovery scales are sensitive to a change in health status and, as numerical data, optimize statistical power when used in the design of a clinical trial. They are closely correlated with conventional measures of outcome such as analgesic consumption, pain scores, nausea and vomiting, and hospital stay. Although conventional measures may be considered patient-centered, each are incomplete by themselves. QoR scores provide a meaningful overall evaluation of a patient's recovery after surgery and anesthesia. Correspondence to Paul S. Myles, Department of Anaesthesia and Perioperative Medicine, Alfred Hospital, Commercial Road, Melbourne 3004, VIC, Australia. Tel: +61 39076 2000; fax: +61 39076 2813; e-mail: p.myles@alfred.org.au Copyright © 2018 YEAR Wolters Kluwer Health, Inc. All rights reserved.

https://ift.tt/2J5wsiZ

Blood loss mitigation and replacement in facial surgery: a review

Purpose of review To provide a comprehensive overview of the predisposing factors that contribute to a risk of excess bleeding for surgical therapy in the head and neck regions, provide a thorough overview of techniques and tools for managing blood loss complications, and provide intervention algorithms to help guide clinical decision making. Recent findings With the current landscape of medications and reversal agents, protocols for intervention in a variety of situations, and new tools for blood loss management all rapidly changing and being developed it is critical to stay up to date to provide patients the best care in the most critical of situations. Summary With the risk of blood loss complications in head and neck surgery ranging from minimal to extreme surgeons require a comprehensive understanding risk factors, patient evaluation tools, and proper management algorithms. The first opportunity to prevent unnecessary blood loss and blood loss complications is the health history and physical appointment where a clinician can identify any medications, conditions, or other predisposing factors that would elevate a patient's risk of excess bleeding and the necessity for treatment augmentation. Although not all complications can be prevented because of the natural physiological variation that occurs from patient to patient, despite proper and proper diagnostics, a full working knowledge of most likely complications, hemostatic tools, and concise communication with team members can prevent a lot of blood loss and the complications associated. Correspondence to Dr Alan Herford, DDS, MD, OMFS, FACS, Loma Linda University OMFS Chair, Loma Linda, California, USA. Tel: +1-909-558-4222; fax: +1-909-558-0285; e-mail: aherford@llu.edu Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

https://ift.tt/2xdPtey

Hepatocellular nodules in vascular liver diseases

Abstract

Hepatocellular nodules have been recognized in vascular liver diseases for a long time and mostly described and studied in the imaging literature. Some confusions in their identification and overlap in their definitions exist, especially in this specific clinical context. Pathology descriptions report the development of nodular regenerative hyperplasia, large regenerative nodule, and focal nodular hyperplasia, as adaptive responses of the liver parenchyma to the modified blood flow. True neoplastic hepatocellular nodules such as hepatocellular adenoma and hepatocellular carcinoma can also appear, mainly in Budd-Chiari syndrome, and have to be correctly diagnosed. This is more difficult for the radiologist in these diseased livers, leading more frequently to perform liver biopsies. We describe the histology of each type of well-differentiated hepatocellular nodules and provide some clues for their differential diagnosis. A review of the literature gives an historical perspective of the problem and enlightens the frequency and the subtypes of hepatocellular nodules found in the most common vascular liver diseases.

https://ift.tt/2ktVuum

Atraumatic splenic rupture secondary to abscess in a hemodialysis patient: a rare and fatal cause of acute abdomen diagnosed late

Abstract

Splenic abscess is a very rare condition in the general population. It is more likely to develop in association with underlying comorbidities and trauma. More attention should be paid in patients with immunosuppression, diabetes mellitus, and congenital or acquired immunocompromise. Splenic rupture secondary to nontraumatic abscess causing acute abdomen is a rarer condition. Herein, we report a 55-year-old hemodialysis patient who presented with signs and symptoms of late generalized peritonitis. The patient was operated under emergency conditions and diagnosed with splenic abscess rupture, for which splenectomy with drainage procedure was performed. In such patients, the morbidity and mortality rates vary depending on the intraoperative and postoperative risks.

https://ift.tt/2GTdAP5

Gastric hibernoma: a novel location and presentation of a rare tumor

Abstract

We present a case of gastric hibernoma, an unusual tumor with a location novel to the literature. A 39-year-old female presented with one year of upper gastrointestinal bleeding and dysphagia. Gastroenterology performed an esophagogastroduodenoscopy with ultrasound and identified a 6 cm mass within the muscularis propria of the antrum. Computed tomography demonstrated a 9.7 × 7.8 × 4.8 cm³ heterogeneous antral mass with internal septa. A distal gastrectomy with Bilroth I gastroduodenostomy was performed with 4 cm proximal and 2 cm distal margins. Excision was appropriate to make the diagnosis, exclude malignancy, and remove a symptomatic mass. Hibernoma was confirmed by histopathology. These are rare tumors of brown fat named for their resemblance to the thermogenic tissue found in hibernating animals. They typically present as a slowly enlarging mass of the thigh or shoulder. To our knowledge, this is the first presentation of a hibernoma as a submucosal gastric mass.

https://ift.tt/2koMXsy

Phosphaturic mesenchymal tumor, an unusual localization in head and neck

Abstract

Phosphaturic mesenchymal tumor (PMT) is a rare mesenchymal neoplasm associated with tumor-induced osteomalacia involving bone and soft tissue that produces paraneoplastic hypophosphatemic osteomalacia. The common physiologic defect in this conditions involves an impairment in renal tubular phosphate reabsorption with a downregulation of renal 1α-hydroxylase activity, while calcium metabolism remains essentially unaffected. Microscopic features consist of spindle cells, multinucleated giant cells and calcifications embedded in a chondromyxoid matrix with variable cellularity and prominent vascularity. Approximately 95% of PMTs involve the extremities and appendicular skeleton, with only 5% occurring in the head and neck region. Localization in the head and neck is pretty uncommon, nose and paranasal sinuses are preferentially affected. Due to its rarity, the purpose of the study was to report a new case of PMT whose locations in temporomandibular joint was never reported in literature.

https://ift.tt/2sdwkne