CEN Case Reports

Correction to: Oliguria due to extensive subcapsular hematoma in renal graft: does surgical intervention ensure better outcomes? In the original publication of the article, the author name "Nadeem Iqbal" has appeared twice. The corrected author group and affiliations are given in this Correction. The original article has been corrected.

A case of secondary IgA nephropathy accompanied by psoriasis treated with secukinumab Abstract A 60-year-old man was diagnosed with psoriasis 4 years ago. Treatment with adalimumab (a monoclonal anti-TNF-α antibody) became ineffective 1 year ago, and proteinuria and urinary occult blood were detected. Treatment with topical medicine, ultraviolet therapy, and etretinate resulted in remission of psoriasis, and proteinuria and hematuria also improved. For maintenance of remission, treatment with secukinumab (a human anti-interleukin-17A monoclonal antibody) was initiated. After the induction phase, treatment was changed from once a week to once every 4 weeks. After 5 months, he developed nephritis with kidney dysfunction, hematuria, and severe proteinuria (14 g/g Cr) accompanied by pitting edema. After admission, treatment with secukinumab was continued. Kidney biopsy revealed IgA nephropathy with fibrocellular crescents, and immunofluorescence analysis did not detect galactose-deficient IgA1. With these findings, he was diagnosed as secondary IgA nephropathy associated with psoriasis. Tonsillectomy followed by steroid pulse therapy prevented proteinuria and kidney function. In this case, treatment of refractory psoriasis with secukinumab and tonsillectomy was effective, leading to remission of relapsing secondary IgA nephropathy. Therefore, secukinumab might play an immunological role in the treatment of nephropathy.

A case of posterior reversible encephalopathy syndrome in a patient undergoing automated peritoneal dialysis Abstract A 44-year-old man undergoing automated peritoneal dialysis (PD) developed headache and dizziness with truncal ataxia and ataxic gait. Severe hypertension (systolic blood pressure/diastolic pressure: 193/83 mm Hg) and lower extremity edema were present, and his PD efficiency (weekly KT/V: 1.49) was inadequate. Magnetic resonance imaging revealed diffuse hyperintensities in the brain stem and bilateral cerebellar hemispheres on fluid-attenuated inversion recovery and apparent diffusion coefficient mapping imaging. Based on these findings, the patient was diagnosed with posterior reversible encephalopathy syndrome due to hypertension and uremia. He was treated with antihypertensive agents, and we changed the PD prescription to improve PD efficiency. Thereafter, his symptoms gradually improved, and abnormal findings on brain magnetic resonance imaging disappeared in accordance with lowering blood pressure.

Oliguria due to extensive subcapsular hematoma in renal graft: does surgical intervention ensure better outcomes? Abstract A 58-year-old male patient, with end-stage renal disease secondary to hypertension, underwent living-related kidney transplant at our transplant unit. The transplant surgery went uneventful and brisk urine output was recorded. Four hours after the transplant, the output suddenly dropped despite normal central venous pressure. Doppler scan revealed an extensive peri-allograft hematoma and high renal arterial resistive indices (RI). The patient was taken to the operating room where capsulotomy of the subcapsular hematoma was done. Postoperatively, the urine output restored to normal and the patient was sent home on the 5th post-operative day with adequately functioning renal graft. Surgical capsulotomy seems to be a valid approach in the management of such cases.

Successful peritoneal dialysis for the end-stage kidney disease associated with Prader–Willi syndrome: a case report Abstract Prader–Willi Syndrome (PWS) is characterized by hyperphagia, severe obesity, and mental retardation from early childhood and occurs 1/10,000 to 1/15,000 live births in Japan. There is high prevalence of diabetes mellitus because of hyperphagia. The patient may sometimes face the necessity of renal replacement therapy (RRT) because of end-stage kidney disease (ESKD) caused by diabetes-associated kidney disease (DKD). Since mental retardation and extreme obesity usually prevent to introduce peritoneal dialysis (PD), hemodialysis (HD) has been the first choice of RRT. In this report, we experienced one case of patient with PWS suffering from ESKD due to DKD who started PD as an initial RRT and succeeded to continue for total of 40 months. The patient was 37-year-old man at the time of initiation of dialysis. PD was chosen for RRT because we suspected that he might have more technical difficulties for continuing HD. After several episodes of peritonitis, he successfully continues PD without peritonitis for next 27 months until the present time with good support by his family member. To our best knowledge, this is the first reported case of ESKD associated with PWS who was successfully treated with PD for long period.

A case of biopsy-proven oxaliplatin-induced acute tubulointerstitial nephritis with thrombocytopenia and anemia Abstract Oxaliplatin, a third-generation platinum agent, has been used for the treatment of colon, pancreatic, and stomach cancers in recent years. It carries a reduced risk of acute kidney injury (AKI) compared to the previous platinum agents, including cisplatin and carboplatin. Several cases of oxaliplatin-induced acute tubular necrosis (ATN) have been reported; however, only one case has been reported as acute tubulointerstitial nephritis (ATIN) histopathologically. Here, we present a case of biopsy-proven and dialysis-dependent ATIN, which dramatically resolved with steroid therapy. The patient was a 67-year-old male who had undergone chemotherapy for colon adenocarcinoma. He suddenly developed shaking chills, fever, and hot flashes at the end of the 18th 5-fluorouracil (5-FU)/l-leucovorin/oxaliplatin administration, and was admitted to our hospital. On the 4th day of hospitalization, severe renal dysfunction (creatinine 6.5 mg/dL) was observed. As oliguria continued, we initiated hemodialysis therapy on the 6th day of hospitalization. Drug-induced ATIN was strongly suspected due to the history of multiple exposures to oxaliplatin with allergic reaction and sterile pyuria. We began steroid therapy on the 8th day of hospitalization. Subsequently, renal biopsy was performed and the diagnosis of ATIN was made. The patient's renal function gradually improved, and 6 months later, it had returned to baseline. Our case demonstrates that we should consider not only ATN, but also ATIN, as potential presentations of oxaliplatin-induced AKI.

A case of acute kidney injury secondary to black cherry concentrate in a patient with chronic kidney disease secondary to type 2 diabetes mellitus Abstract There are many herbal products which are accessible to patients, and they may provide with many health benefits. Nevertheless, some of these supplements can lead to significant morbidity as they can also have important side effects and impact patient's organ systems. In this case report, we present a patient with chronic kidney disease secondary to type II diabetes mellitus who develops acute kidney injury and metabolic disturbances secondary to consuming black cherry concentrate as a mean to self-manage his gout flare. The most likely mechanism of injury was cyclooxygenase inhibition by anthocyanins, molecular compounds found in cherries that have a similar mechanism of action to nonsteroidal anti-inflammatory medications. Patient's kidney injury and metabolic disturbances improved after the discontinuation of black cherry concentrate. This is the second case report that presents a correlation between consumption of cherry concentrate in a patient with chronic kidney disease and acute kidney injury.

Chronological change of renal pathological findings in the proliferative glomerulonephritis with monoclonal IgG deposits considered to have recurred early after kidney transplantation Abstract Proliferative glomerulonephritis with monoclonal immunoglobulin G (IgG) deposits (PGNMID) is a rare disease that recently became recognized. Its pathological findings are characterized by the deposition of a single heavy chain subclass and a single light chain isotype. PGNMID has been proven to recur in renal allografts. Herein, the authors describe the case of a 46-year-old man who presented with nephrotic syndrome and progressive kidney injury following kidney transplantation. One month after transplantation, his clinical condition stabilized; however, the protocol biopsy showed depositions of IgG and complement on the glomeruli by immunofluorescence staining. Electron microscopy (EM) revealed granular electron-dense deposits (EDD) in the mesangium. Thereafter, renal biopsy was repeated because his proteinuria level increased. Proliferative glomerulonephritis, mainly in the mesangium, with IgG and complement deposits and mesangial and subendothelial EDD were observed; however, the pathological diagnosis was difficult. Renal dysfunction then became apparent, and renal biopsy was performed again 4 years and 10 months after kidney transplantation. Glomerular deposits on a single IgG subclass and a single light chain isotype (IgG3 kappa) with membranoproliferative features were observed. Abundant subendothelial EDD were detected on EM. Finally, the patient was diagnosed with PGNMID. Since it seemed that PGNMID had already developed at 1 month after transplantation, we considered recurrent PGNMID case in the allograft. The treatment for PGNMID has not been established yet, and even in this case, the graft function was eventually lost. For improving renal prognosis, early diagnosis and further investigation on the treatment are necessary.

Collapsing glomerulopathy in a child with LCHAD deficiency: a rare association Abstract Metabolic disorders, although rare, can involve multiple organ systems and have a varied presentation. Renal involvement has been reported in several metabolic disorders in the pediatric age group. We report a rare metabolic disorder, long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency, in a child who developed steroid-resistant nephrotic syndrome at the age of 5 years. Renal biopsy showed features of collapsing glomerulopathy. The child had progressive chronic kidney disease. Alternative immunosuppressants including tacrolimus failed to show any clinical improvement. There have been no reports of children with long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency developing steroid-resistant nephrotic syndrome and collapsing glomerulopathy. This case highlights the need to monitor renal function and proteinuria among this group of children.

Effectiveness of cryofiltration and mizoribine combination with oral steroid therapy in a patient with membranoproliferative glomerulonephritis due to essential cryoglobulinemia Abstract A 65-year-old male patient with nephrotic syndrome was admitted to our hospital due to worsening systemic edema and purpura on the limbs. He had an impaired renal function, low serum complement level, and elevated rheumatoid factor level. He was positive for cryoglobulin (monoclonal IgM-κ and polyclonal mixed-type IgG), and the results of his kidney biopsy showed a tissue profile of membranoproliferative glomerulonephritis (MPGN). Due to the fact that the secondary cause was unclear, he was diagnosed with MPGN due to essential mixed cryoglobulinemia. On hospital day 20, he was initiated on 50 mg/day prednisolone (PSL). On hospital day 43, oral mizoribine (MZR) at a dose of 150 mg/day was prescribed. On hospital day 49, cryofiltration was performed because the disease was steroid resistant. The treatment promptly decreased urine protein levels. Serum albumin and serum complement levels increased, and complete remission was achieved approximately three months after the initiation of treatment. The PSL and MZR doses were gradually reduced to 2 mg/day and 100 mg/day, respectively, without any reemergence of the symptoms of cryoglobulinemia or relapse of the nephrotic syndrome for three years. Here, we report this case with essential mixed cryoglobulinemia in whom we could achieve complete remission of the disease by adding cryofiltration to the oral corticosteroid and immunosuppressant therapy with mizoribine and could maintain for a long time.

Alexandros Sfakianakis
Anapafseos 5 . Agios Nikolaos
Crete.Greece.72100
2841026182

6948891480

alsfakia@gmail.com

Genetics

How do cells count multi-copy genes?: "Musical Chair" model for preserving the number of rDNA copies Abstract To supply abundant ribosomes, multiple copies of ribosomal RNA genes (rDNA) are conserved from bacterial to human cells. In eukaryotic genomes, clusters of tandemly repeated rDNA units are present, and their number is stably maintained. Due to high level of transcription of rRNA genes, the repetitive structure is prone to rearrangement. In budding yeast, rDNA homeostasis can compensate for this by the regulation of recombination events that will change the copy number. The histone deacetylase Sir2 plays a key role in rDNA copy maintenance and its expression level determines a state of "maintenance" or "amplification" of rDNA copy number. We recently showed that Upstream Activating Factors (UAF) for RNA polymerase I act as a RNA polymerase II repressor of SIR2 transcription in response to rDNA copy loss. Furthermore, the amount of UAF, which is limited in the cell, determines the stable copy number of rDNA and is a molecular switch for rDNA recovery. In this mini-review, we propose a "Musical Chair" model for rDNA copy counting as mediated by UAF and Sir2. The model describes how a straightforward molecular mechanism can account for the "cellular memory" of the proper rDNA copy number.

Towards understanding mRNA-binding protein specificity: lessons from post-transcriptional regulation of ATG mRNA during nitrogen starvation-induced autophagy Abstract In this report, we discuss recent discoveries concerning the effects and specificity of different RNA-binding proteins (RBPs) as they pertain to macroautophagy/autophagy. Autophagy is a fundamental cellular degradation and recycling pathway, which has attracted substantial attention because defects in this process are associated with a wide range of human disorders including cancer, neurodegeneration, and metabolic diseases. Autophagy must be tightly controlled—either too much or too little can be deleterious. Therefore, understanding the complex regulation of autophagy is critical to achieve the goal of modulating the process for therapeutic purposes. Autophagy occurs constitutively, but is upregulated in response to stress. Here, we highlight a role for various RBPs in regulating particular autophagy-related (ATG) mRNAs. We briefly summarize recent publications, which focus on the RBPs Dhh1, Pat1, Lsm1–Lsm7 and Dcp2 in the post-transcriptional regulation of certain mRNAs that encode key components of the autophagy machinery. Finally, we consider how the established role of these and other RBPs in enhancing decapping and downregulating mRNAs is not their only function when it comes to regulating stress-related transcripts. Most ATG genes are downregulated during growth, in contrast to the vast majority of the genome; we discuss how certain regulatory factors play a key role in maintaining autophagy at a basal level during growth, while allowing for a rapid increase when cells encounter various stress conditions.

CreA-independent carbon catabolite repression of cellulase genes by trimeric G-protein and protein kinase A in Aspergillus nidulans Abstract Cellulase production in filamentous fungi is repressed by various carbon sources. In our preliminary survey in Aspergillus nidulans, degree of de-repression differed depending on carbon sources in a mutant of creA, encoding the transcriptional repressor for carbon catabolite repression (CCR). To further understand mechanisms of CCR of cellulase production, we compared the effects of creA deletion with deletion of protein kinase A (pkaA) and G (ganB) genes, which constitute a nutrient sensing and signaling pathway. In plate culture with carboxymethyl cellulose and d-glucose, deletion of pkaA and ganB, but not creA, led to significant de-repression of cellulase production. In submerged culture with cellobiose and d-glucose or 2-deoxyglucose, both creA or pkaA single deletion led to partial de-repression of cellulase genes with the highest level by their double deletion, while ganB deletion caused de-repression comparable to that of the creA/pkaA double deletion. With ball-milled cellulose and d-glucose, partial de-repression was detected by deletion of creA but not of pkaA or ganB. The creA/pkaA or creA/ganB double deletion led to earlier expression than the creA deletion. Furthermore, the effect of each deletion with d-xylose or L-arabinose as the repressing carbon source was significantly different from that with d-glucose, d-fructose, and d-mannose. Consequently, this study revealed that PkaA and GanB participate in CreA-independent CCR and that contribution of CreA, PkaA, and GanB in CCR differs depending on the inducers, repressing carbon sources, and culture conditions (plate or submerged). Further study of CreA-independent mechanisms is needed to fully understand CCR in filamentous fungi.

High-energy guanine nucleotides as a signal capable of linking growth to cellular energy status via the control of gene transcription Abstract This mini-review considers the idea that guanylate nucleotide energy charge acts as an integrative signal for the regulation of gene expression in eukaryotic cells and discusses possible routes for that signal's transduction. Gene expression is intimately linked with cell nutrition and diverse signaling systems serve to coordinate the synthesis of proteins required for growth and proliferation with the prevailing cellular nutritional status. Using short pathways for the inducible and futile consumption of ATP or GTP in engineered cells of Saccharomyces cerevisiae, we have recently shown that GTP levels can also play a role in determining how genes act to respond to changes in cellular energy supply. This review aims to interpret the importance of GTP as an integrative signal in the context of an increasing body of evidence indicating the spatio-temporal complexity of cellular de novo purine nucleotide biosynthesis.

ESCRT-III accessory proteins regulate fungal development and plant infection in Fusarium graminearum Abstract Ubiquitinated biosynthetic and surface proteins destined for degradation are sorted into the lysosome/vacuole via the multivesicular body sorting pathway, which depends on the function of ESCRT machinery. Fusarium head blight (FHB) caused by Fusarium graminearum is one of the most devastating diseases for wheat and barley worldwide. To better understand the role of ESCRT machinery in F. graminearum, we investigated the function of ESCRT-III accessory proteins FgVps60, FgDid2 and FgIst1 in this study. FgVps60–GFP, FgDid2–GFP and FgIst1–GFP are localized to punctate structures adjacent to the vacuolar membrane except for FgIst1–GFP that is also found in the nucleus. Then, the gene deletion mutants ΔFgvps60, ΔFgdid2 and ΔFgist1 displayed defective growth to a different extent. ΔFgvps60 and ΔFgdid2 but not ΔFgist1 also showed significant reduction in hydrophobicity on cell surface, conidiation, perithecia production and virulence. Interestingly, ΔFgist1 mutant produced a significantly higher level of DON while showing a minor reduction in pathogenicity. Microscopic analyses revealed that FgVps60 but not FgIst1 and FgDid2 is necessary for endocytosis. Moreover, spontaneous mutations were identified in the ΔFgvps60 mutant that partially rescued its defects in growth and conidiation. Taken together, we conclude that ESCRT-III accessory proteins play critical roles in growth, reproduction and plant infection in F. graminearum.

A brief review of bioluminescent systems (2019) Abstract Despite being widely used in reporter technologies, bioluminescent systems are largely understudied. Of at least forty different bioluminescent systems thought to exist in nature, molecular components of only seven light-emitting reactions are known, and the full biochemical pathway leading to light emission is only understood for two of them. Here, we provide a succinct overview of currently known bioluminescent systems highlighting available tools for research and discussing future applications.

Stress-induced protein aggregates shape population heterogeneity in bacteria Abstract The concept of phenotypic heterogeneity preparing a subpopulation of isogenic cells to better cope with anticipated stresses has been well established. However, less is known about how stress itself can drive subsequent cellular individualization in clonal populations. In this perspective, we focus on the impact of stress-induced cellular protein aggregates, and how their segregation and disaggregation can act as a deterministic incentive for heterogeneity in the population emerging from a stressed ancestor.

Impaired GCR1 transcription resulted in defective inositol levels, vacuolar structure and autophagy in Saccharomyces cerevisiae Abstract In yeast, the GCR1 transcription factor is involved in the regulation of glycolysis and its deletion exhibited growth defect, reduced inositol and phosphatidylinositol (PI) levels compared to WT cells. We observed a down regulation of the INO1 and PIS1 expression in gcr1∆ cells under both I− and I+ conditions and the over expression of GCR1 in gcr1∆ cells restored the growth, retrieved the expression of INO1, and PIS1 comparable to WT cells. In the gel shift assay, the Gcr1p binds to its consensus sequence CTTCC in PIS1 promoter and regulates its expression but not in INO1 transcription. The WT cells, under I− significantly reduced the expression of GCR1 and PIS1, but increased the expression of KCS1 and de-repressed INO1. The Kcs1p expression was reduced in gcr1∆ cells; this reduced INO1 expression resulting in abnormal vacuolar structure and reduced autophagy in Saccharomyces cerevisiae.

Meiotic prophase-like pathway for cleavage-independent removal of cohesin for chromosome morphogenesis Abstract Sister chromatid cohesion is essential for chromosome segregation both in mitosis and meiosis. Cohesion between two chromatids is mediated by a protein complex called cohesin. The loading and unloading of the cohesin are tightly regulated during the cell cycle. In vertebrate cells, cohesin is released from chromosomes by two distinct pathways. The best characterized pathway occurs at the onset of anaphase, when the kleisin component of the cohesin is destroyed by a protease, separase. The cleavage of the cohesin by separase releases entrapped sister chromatids allowing anaphase to commence. In addition, prior to the metaphase–anaphase transition, most of cohesin is removed from chromosomes in a cleavage-independent manner. This cohesin release is referred to as the prophase pathway. In meiotic cells, sister chromatid cohesion is essential for the segregation of homologous chromosomes during meiosis I. Thus, it was assumed that the prophase pathway for cohesin removal from chromosome arms would be suppressed during meiosis to avoid errors in chromosome segregation. However, recent studies revealed the presence of a meiosis-specific prophase-like pathway for cleavage-independent removal of cohesin during late prophase I in different organisms. In budding yeast, the cleavage-independent removal of cohesin is mediated through meiosis-specific phosphorylation of cohesin subunits, Rec8, the meiosis-specific kleisin, and the yeast Wapl ortholog, Rad61/Wpl1. This pathway plays a role in chromosome morphogenesis during late prophase I, promoting chromosome compaction. In this review, we give an overview of the prophase pathway for cohesin dynamics during meiosis, which has a complex regulation leading to differentially localized populations of cohesin along meiotic chromosomes.

Mdivi-1 and mitochondrial fission: recent insights from fungal pathogens Abstract Mitochondrial fission shows potential as a therapeutic target in non-infectious human diseases. The compound mdivi-1 was identified as a mitochondrial fission inhibitor that acts against the evolutionarily conserved mitochondrial fission GTPase Dnm1/Drp1, and shows promising data in pre-clinical models of human pathologies. Two recent studies, however, found no evidence that mdivi-1 acts as a mitochondrial fission inhibitor and proposed other mechanisms. In mammalian cells, Bordt et al. showed that mdivi-1 inhibits complex I in mitochondria (Dev Cell 40:583, 2017). In a second study, we have recently demonstrated that mdivi-1 does not trigger a mitochondrial morphology change in the human yeast pathogen Candida albicans, but impacts on endogenous nitric oxide (NO) levels and inhibits the key virulence property of hyphal formation (Koch et al., Cell Rep 25:2244, 2018). Here we discuss recent insights into mdivi-1's action in pathogenic fungi and the potential and challenges for repurposing it as an anti-infective. We also outline recent findings on the roles of mitochondrial fission in human and plant fungal pathogens, with the goal of starting the conversation on whether the research field of fungal pathogenesis can benefit from efforts in other disease areas aimed at developing therapeutic inhibitors of mitochondrial division.

Alexandros Sfakianakis
Anapafseos 5 . Agios Nikolaos
Crete.Greece.72100
2841026182

6948891480

alsfakia@gmail.com

Heart and Vessels

Correction to: Cell salvage processing of residual cardiopulmonary bypass volume in minimally invasive cardiac surgery In the article "Cell salvage processing of residual cardiopulmonary bypass volume in minimally invasive cardiac surgery" published in Heart and Vessels, there were several errors in numerical values.

Edoxaban suppresses the progression of atrial fibrosis and atrial fibrillation in a canine congestive heart failure model Abstract Coagulation factor Xa activates the protease-activated receptor 2 (PAR2) and causes tissue fibrosis; however, the effects of Xa inhibitor edoxaban on atrial fibrosis and atrial fibrillation (AF) have not been investigated. We examined the effect of edoxaban on the progression of atrial fibrosis in a canine congestive heart failure (CHF) model. Beagle dogs were assigned to sham, placebo, and edoxaban groups (n = 6/group). Dogs of the placebo or edoxaban groups received 19 days of medication with daily oral placebo or edoxaban, respectively, followed by 14 days of ventricular tachypacing. Dogs of the sham group had no medication or pacing. Ventricular tachypacing prolonged AF duration in dogs of the placebo group (159 ± 41 s, p < 0.01 vs. sham); however, this effect was suppressed by edoxaban treatment. Compared with the sham group, tachypacing alone also significantly increased the atrial fibrotic area (2.9 ± 0.1% vs. 7.8 ± 0.4%, p < 0.01), PAR2 expression (1.0 ± 0.1 vs. 1.8 ± 0.3, p < 0.05), and atrial fibronectin expression (1.0 ± 0.2 vs. 2.0 ± 0.2, p < 0.01). These responses were suppressed by edoxaban treatment (area 5.9 ± 0.4%, p < 0.01; PAR2 1.1 ± 0.1, p < 0.05; fibronectin 1.2 ± 0.2, p < 0.05 vs. placebo). Edoxaban showed suppressive effects on atrial remodeling, AF progression, and excessive expressions of PAR2 and fibronectin in a canine CHF model. The suppression of the Xa/PAR2 pathway might be a potential pharmacological target of edoxaban.

Assessment of strut coverage of everolimus-eluting platinum chromium stent 2 weeks after implantation by optical coherence tomography Abstract The SYNERGY coronary stent is new-generation drug-eluting stents, which has a thin-strut platinum–chromium platform with everolimus in a biodegradable polymer applied to the abluminal surface. It would be speculated that favorable arterial healing with early strut coverage could be achieved. The present study investigated the degree of strut coverage using optical coherence tomography (OCT) 2 weeks after SYNERGY implantation and clinical factors contributing to strut coverage. A total of 29 patients who underwent staged percutaneous coronary intervention (PCI) to residual lesions 2 weeks after the index PCI with SYNERGY stent implantation were enrolled. At the time of staged PCI, OCT examinations of the SYNERGY stent were performed for conventional OCT analysis on both cross-sectional and strut level. SYNERGY stent showed a high level of strut coverage and apposition, and the percentage was 82.4 ± 12.4% and 96.2 ± 5.0%, respectively. The lesion complexity was significantly related to greater strut coverage on univariate analysis; however, it was found to be insignificant in multivariate analysis. Our findings suggest early arterial healing after SYNERGY stent implantation.

Cell salvage processing of residual cardiopulmonary bypass volume in minimally invasive cardiac surgery Abstract Several reports demonstrated positive effects of processing residual cardiopulmonary bypass volume using a cell salvage device in conventional open heart surgery via sternotomy on hemostasis. The present study aimed to investigate whether cell salvage processing has the same effects on postoperative blood loss and transfusion in minimally invasive cardiac surgery. Between July 2015 and April 2018, 80 consecutive patients undergoing minimally invasive aortic valve replacement via right anterolateral minithoracotomy were enrolled in the present study. Perioperative outcomes and coagulation data of 40 patients who were retransfused with processed cardiopulmonary bypass volumes were compared with those of 40 patients receiving unprocessed residual blood (control group). Postoperative blood loss in patients receiving processed residual blood was significantly less than that in the control group at 6 h (115 ± 50 vs. 73 ± 33 ml, p < 0.001) and 12 h (167 ± 70 vs. 125 ± 67 ml, p = 0.009) after surgery, and the rate of fresh frozen plasma use after surgery was significantly reduced in patients receiving processed residual blood (18 vs. 0%, p = 0.012). In conclusion, processing of residual cardiopulmonary bypass volume reduced postoperative blood loss and postoperative use of fresh frozen plasma and could be useful for hemostasis in minimally invasive cardiac surgery.

Liraglutide suppresses atrial electrophysiological changes Abstract We have shown that a dipeptidyl peptidase 4 (DPP-4) inhibitor suppresses atrial remodeling in a canine atrial fibrillation (AF) model. Glucagon-like peptide-1 (GLP-1) is increased by DPP-4 inhibitors. However, it is not clear whether GLP-1 is involved in the suppression of atrial remodeling. In this study, we evaluated the effect of liraglutide (a GLP-1 analog) on atrial electrophysiological changes using the same canine AF model. We established a canine AF model using continuous 3-week rapid atrial stimulation in seven beagle dogs divided into two groups: a liraglutide group with four dogs (3-week atrial pacing with liraglutide (150 µg/kg/day) administration) and a pacing control group with three dogs (3-week pacing without any medicine). We evaluated the atrial effective refractory period (AERP), conduction velocity (CV), and AF inducibility every week during the protocol using implanted epicardial wires against the surfaces of both atria. In the pacing control group, the AERP was gradually shortened and the CV was decreased along the time course. In the liraglutide group, the AERP was similarly shortened as in the pacing control group (94 ± 4% versus 85 ± 2%, respectively; p = 0.5926), but the CV became significantly higher than that in the pacing control group after 2 and 3 weeks (95 ± 4 versus 83 ± 5%, respectively; p = 0.0339). The AF inducibility was gradually increased in the pacing control group, but it was suppressed in the liraglutide group (5 ± 9% versus 73 ± 5%; p = 0.0262). Liraglutide suppressed electrophysiological changes such as AF inducibility and CV decrease in our canine AF model.

Randomized comparison between 2-link cell design biolimus A9-eluting stent and 3-link cell design everolimus-eluting stent in patients with de novo true coronary bifurcation lesions: the BEGIN trial Abstract The appropriate stent platform for treating coronary bifurcation lesions (CBLs) remains controversial. Previous bench tests have demonstrated the superiority of a 2-link cell design to 3-link cell design for creating inter-strut dilation at the side branch ostium. This randomized multicenter prospective BEGIN trial compared the biodegradable polymer-based biolimus A9-eluting stent (2-link BES) with the durable polymer-based cobalt chromium everolimus-eluting stent (3-link EES) in 226 patients with de novo CBLs. Patients with true bifurcations, defined as > 50% stenosis in the main vessel and side branch (SB) and an SB diameter > 2.25 mm, were enrolled. Guide wire re-crossing to the distal cell (near the carina) in the jailed SB and final kissing inflation were recommended. The SB angiographic endpoint was < 50% stenosis diameter. Left-main CBLs (13.5% vs. 13.0%) and 2-stent technique (30.6% vs. 22.6%) rates were similar. The primary endpoints (minimum lumen diameter at the SB ostium measured at an independent core laboratory at the 8-month follow-up) were comparable (1.64 ± 0.50 mm vs. 1.63 ± 0.51 mm, p = 0.976). There was no significant difference in composite outcomes of cardiac death, myocardial infarction, or target vascular revascularization at 12 months (7.4% vs. 8.0%, p = 0.894). Two-link BES and 3-link EES showed similar 8-month angiographic and 1-year clinical outcomes for true CBLs.

Linc00299/miR-490-3p/AURKA axis regulates cell growth and migration in atherosclerosis Abstract Long non-coding RNA (lncRNA) plays a crucial role in regulating various cellular processes in atherosclerosis. The present study identified the regulation of Linc00299, via miR-490-3p targeting Aurora kinase A (AURKA), on migration and proliferation of endothelial cells and vascular smooth muscle cells (VSMCs) during atherosclerosis. The expression of RNAs was assessed by real-time PCR. The proliferation, apoptosis and migration were detected using MTT assay, Annexin V/PI staining and Transwell system, respectively. Bindings of Linc00299/miR-490-3p and subsequent miR-490-3p/AURKA were verified by luciferase and biotin pull-down assays. The protein expression of AURKA was detected by Western blotting. Expressions of Linc00299 and miR-490-3p were upregulated and downregulated in atherosclerosis patients, respectively. Both Linc00299 knockdown and miR-490-3p overexpression suppressed cell proliferation, increased apoptosis and inhibited migration of VSMCs and HUVECs. Linc00299 directly bound to miR-490-3p which targeted AURKA. The regulation of Linc00299 on expression of AURKA and proliferation and migration of VSMCs were dependent on miR-490-3p. Atherosclerosis-increased Linc00299 acts as a sponge of miR-490-3p to upregulate AURKA, and as a result increases proliferation and migration in VSMCs and HUVECs. Our study reveals an important effect of Linc00299/miR-490-3p/AURKA axis on regulating cell proliferation and migration in atherosclerosis.

Obstructive sleep apnea is associated with increased coronary plaque instability: an optical frequency domain imaging study Abstract Obstructive sleep apnea (OSA) is associated with coronary artery disease (CAD) and with an increased risk for myocardial infarction, stroke or death due to cardiovascular disease. Optical frequency-domain imaging (OFDI) is a useful modality for evaluating the characteristics of atherosclerotic plaque. The purpose of the study was to use OFDI to investigate the association of OSA with coronary plaque characteristics in patients undergoing percutaneous coronary intervention (PCI). We retrospectively analyzed OFDI data for coronary artery plaques from 15 patients with OSA and 35 non–OSA patients treated between October 2015 and October 2018. Plaque morphology was evaluated for 70 lesions, including 21 from patients with OSA and 49 from non–OSA patients. Compared with the non–OSA group, patients with OSA had significantly higher prevalences of thinned cap fibroatheroma (TCFA) (67% vs. 35%, P = 0.014) and microchannels (86% vs. 55%, P = 0.014); a significantly higher mean lipid index (1392 ± 982 vs. 817 ± 699, P = 0.021), macrophage grade (8.4 ± 6.4 vs. 4.8 ± 4.5, P = 0.030), and maximum number of microchannels (1.5 ± 1.0 vs. 0.7 ± 0.7, P = 0.001); and a significantly lower mean minimum fibrous cap thickness (69.4 ± 28.7 vs. 96.1 ± 51.8 μm, P = 0.008). This OFDI analysis suggests that OSA is associated with unstable plaque characteristics in patients with CAD. More intensive medical management for stabilization of coronary atherosclerotic plaque is required in patients with OSA.

Importance of sympathetic nervous system activity during left ventricular functional recovery and its association with in-hospital complications in Takotsubo syndrome Abstract The relationship between activation of the sympathetic nervous system (SNS) and improvement of left ventricular (LV) function and how this correlates with clinical outcomes are not fully explored in Takotsubo syndrome (TS). The purpose of this study is to evaluate the relationship between activation of the SNS and LV function improvement and how this correlates with clinical outcomes in TS. Patients with TS were retrospectively identified. Patients were divided into two groups according to the timing of LV function improvement: < 1 month (S group) and ≥ 1 month (L group). Activation of the SNS was assessed by plasma catecholamine measurement and Iodine-123 meta-iodobenzylguanidine (I123-MIBG) scintigraphy. In-hospital complications included heart failure, cardiogenic shock, the use of invasive or noninvasive ventilation, life-threatening arrhythmia, cerebrovascular event and all-cause death. A total of 90 patients with TS were enrolled. Of these, 39 patients were in the S group and 51 in the L group. There were no significant differences between the two groups in clinical demographics. The L group was characterized by enhanced SNS activation, including higher levels of catecholamines and lower late heart–mediastinum ratio followed by higher washout rate in I123-MIBG scintigraphy, compared with the S group. In-hospital complications were increased in the L group (56% vs. 33.3%, p = 0.03), including higher rates of heart failure (45% vs. 23%, p = 0.03) and in-hospital death (8.0% vs. 0%, p = 0.03). In patients with TS, high activity of the SNS was observed in patients with delayed LV function recovery, which was associated with in-hospital adverse outcomes.

Regional layer-specific longitudinal peak systolic strain using exercise stress two-dimensional speckle-tracking echocardiography for the detection of functionally significant coronary artery disease Abstract The present study aimed to investigate whether layer-specific regional peak-systolic longitudinal strain (LS) measurement on transthoracic echocardiogram (TTE) with exercise stress can be useful for the detection of functionally significant coronary artery disease as confirmed by invasive fractional flow reserve (FFR) in stable patients. This is a prospective analysis of 88 coronary arteries in 30 stable patients undergoing invasive FFR measurement and ergometer exercise stress TTE. Regional LS in the mid, endocardial and epicardial layers was calculated at rest, peak stress and early and late recovery phases after the exercise stress test. The endocardial-to-epicardial LS ratio was calculated as an indicator of endocardial-layer dependency of the left ventricular myocardium. Ischemic FFR defined as FFR ≤ 0.80 was observed in 33 of 88 coronary arteries. The mid-, endocardial- and epicardial-layer LS at early recovery (− 15.4 ± 5.2 vs. −  13.0 ± 4.4%, P = 0.040;  − 15.7 ± 5.1 vs.  − 13.2 ± 4.5%, P = 0.029;  − 14.6 ± 5.1 vs.  − 12.4 ± 4.0%, P = 0.038, respectively) and the percent change in the endocardial-to-epicardial LS ratio from baseline to peak stress, early recovery, and late recovery phases (1.5 ± 11.2% vs. 6.6 ± 10.5%, P = 0.009; 2.8 ± 8.9% vs. 7.1 ± 12.6%, P = 0.002; 5.2 ± 8.8% vs. 8.5 ± 13.7%, P = 0.026; respectively) were significantly more impaired in the ischemic territories (FFR ≤ 0.80) compared with the non-ischemic territories (FFR > 0.80). According to the receiver operating characteristic curve analysis, a combination of endocardial LS and percent change in the endocardial-to-epicardial LS ratio at early recovery phase plus visual evaluation of LV wall motion had incremental diagnostic value for the detection of the ischemic territory compared with visual evaluation alone (area under the curve = 0.752 and 0.618, P = 0.006). The results of this study suggested that assessing layer-specific LS and the endocardial-to-epicardial LS ratio after exercise stress on speckle-tracking TTE may have potential for objective and quantitative evaluation in the assessment of myocardial ischemia. Further studies in a larger population are needed to confirm these findings.

Alexandros Sfakianakis
Anapafseos 5 . Agios Nikolaos
Crete.Greece.72100
2841026182

6948891480

alsfakia@gmail.com

Medical Ultrasonics

Clinical application of stress echocardiography for valvular heart disease Abstract Stress echocardiography is widely used to assess several cardiovascular diseases, including ischemic heart disease, valvular heart disease (VHD), heart failure, congenital heart disease, and pulmonary hypertension. In valvular heart disease with asymptomatic severe or symptomatic non-severe status, stress echocardiography plays a central role in the management. As of 2017, the updated American College of Cardiology/American Heart Association and European Society of Cardiology/European Association for Cardio-Thoracic Surgery VHD guidelines recommended stress testing to (1) confirm symptoms and (2) evaluate the hemodynamic response to exercise. In patients with undetermined VHD severity in the presence of low-flow status, it can also be helpful to determine whether the VHD is severe based on flow-dependent changes in response to stress. The clinical indications of stress echocardiography in VHD have expanded with growing evidence for prognosis and being an early marker for interventions. As a result, demand has increased in major cardiology societies for the standardization of stress echocardiography in VHD. Echocardiographic centers should be aware of the clinical potential of stress echocardiography to ensure its optimal application and performance in VHD. This article reviews the clinical application of stress echocardiography, including dobutamine, semisupine bicycle, treadmill, and leg-positive pressure for VHD patient management, and focuses on the current consensus regarding the use of stress echocardiography in VHD. Stress echocardiography is safe and should be encouraged, especially in heart valve clinics, to understand the complex mechanism in asymptomatic patients.

Expectations for contrast-enhanced ultrasonography

Cross-sectional understanding/research across clinical disciplines and integration of basic and clinical research

Ultrasound-guided injection and the pie crust technique for the treatment of symptomatic bipartite patella Abstract Purpose This study aimed to investigate the results of a new treatment procedure (ultrasound-guided injection and the "pie crust" technique for lengthening of capsular tendon structures) for symptomatic bipartite patella. Methods We retrospectively investigated patient outcomes following the treatment of symptomatic type III bipartite patella with our new technique. Fifteen knees in 14 boys (mean age, 13.0 ± 1.7 years) were included. The procedure involved the injection of 1% lidocaine (2 mL) and triamcinolone acetonide (5 mg) between the patella and fragment. We then punctured 10 sites from one skin puncture to extend lateral capsular tendon structures. The patients were clinically assessed using the Victorian Institute of Sports Assessment (VISA) score before and 1 week, 1 month, and 3 months after the procedure. Patients were also evaluated for complications. Results The average VISA score was 45.7 ± 4.7 before treatment, 70.6 ± 7.3 at 1 week post-treatment, 84.4 ± 16.6 at 1 month post-treatment, and 88.6 ± 18.3 at 3 months post-treatment. The VISA score improvement from before the procedure to 1 week after the procedure was significant (P < 0.01). There were no complications in any of the patients, who returned to sports at a mean of 4.2 ± 2.1 weeks after the procedure. However, two patients (three knees) had poor results and could not return to action; thus, they underwent surgical treatment 4 months after the ultrasonographic procedure. Conclusions This novel method is a potential treatment option for the management of symptomatic bipartite patella in outpatient clinics.

The role of ultrasound imaging in adult patients with testicular torsion: a systematic review and meta-analysis Abstract Purpose Our aim was to determine the accuracy of ultrasound (US) examination-based testicular torsion diagnosis in adult patients with acute scrotal pain. Methods A comprehensive electronic search was performed using internet retrieval systems up to 5 August 2018 in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. The quality of eligible studies was assessed using Quality Assessment for Studies of Diagnostic Accuracy (QUADAS-2). The diagnostic value of ultrasound in patients with testicular torsion was evaluated using pooled estimates of sensitivity, specificity, likelihood ratio, and diagnostic odds ratio, as well as the summary receiver operating characteristics curve. Results Twenty-six studies with 2116 patients were included in the study. Overall diagnostic sensitivity was 0.86 [95% confidence interval (CI) 0.79–0.91] and specificity was 0.95 (95% CI: 0.92–0.97). Subgroup analysis of prospective studies showed pooled sensitivity of ultrasound for testicular torsion was 0.94 (95% CI 0.83–0.98), and pooled specificity was 0.98 (95% CI 0.94–1.00). Recent studies after 2010 showed diagnostic sensitivity of 0.95 (95% CI 0.84–0.99) and specificity of 0.98 (95% CI 0.93–0.99). Conclusions This meta-analysis demonstrated that ultrasound represents an effective imaging modality for diagnosing testicular torsion in adult patients with acute scrotal pain.

Echocardiography and cancer therapeutics-related cardiac dysfunction Abstract Cancer therapeutics-related cardiac dysfunction (CTRCD) has become a leading cause of morbidity and mortality for cancer survivors, with the mortality rate for patients with CTRCD reportedly being as high as 60% by 2 years after treatment. Although early detection of subclinical left ventricular (LV) dysfunction is essential for delaying progression to heart failure (HF) in patients with a history of using cardiotoxins, assessment of such dysfunction can be challenging. CTRCD may present initially as asymptomatic LV dysfunction and ultimately as symptomatic HF, which can occur even decades after discontinuation of the treatment. Once CTRCD has developed, the mortality rate is very high, because CTRCD is believed to be refractory to conventional pharmacological therapy and to be associated with a poor prognosis. Thus, there has been a growing interest in early detection of CTRCD by means of global longitudinal strain (GLS) assessed by two-dimensional speckle-tracking echocardiography, because it is a more sensitive and robust parameter for detecting subclinical LV dysfunction than other conventional LV functional parameters such as LV ejection fraction. This article reviews the utility of GLS for early detection of cardiotoxicity in patients during and after cancer chemotherapy, and future perspectives for the management of such patients.

Fast adaptive beamforming through a cascade structure for ultrasound imaging Abstract Purpose A major limiting factor for applying a minimum variance (MV) beamformer in medical ultrasound imaging is its high computational complexity. This paper introduces a new fast MV beamforming method with almost the same capabilities as the standard MV. Methods The fast beamformer is implemented using a cascade structure. At the first stage, the echo signals received from the points far from the main axis are strongly suppressed using a fixed-weight beamformer. At the second stage, after spatially decimating the output of the first stage, an MV-based adaptive beamformer is used to eliminate the echo signals from the points adjacent to the focal point. The greatest advantage of the proposed method is that the second beamformer can be a low-complexity implementation of MV such as beamspace (BS) MV to further reduce the complexity, resulting in a superfast MV. Results The resulting beamformers were evaluated through both simulation and experimental data, and it was verified that the method was competitive with standard MV and BS methods at a lower computational cost. Conclusion The new fast and superfast MV methods are capable of obtaining the same results as the MV and BS-MV, at a significantly lower computational cost.

Investigating the minimum distance between the finger flexor tendons and distal radius during wrist and finger positions in healthy people Abstract Purpose Rupture of the flexor pollicis longus (FPL) and index flexor digitorum profundus (FDP2) tendons often occurs after locking plate fixation for distal radius fracture. This study aimed to determine the shortest tendon-radius distances of different hand positions. Methods Fifty-nine hands of 30 healthy volunteers were studied. Distances between the FPL or FDP2 and distal radius were calculated in six wrist positions: 30° palmar flexion, neutral, 30° dorsiflexion, 60° dorsiflexion, maximum dorsiflexion, and 40° ulnar deviation with three finger positions (full extension and flexion of fingers, full flexion of the thumb or index finger, and full extension of the other four fingers). The shortest distance between the FPL or FDP2 and distal radius was noted. Results The shortest distance between the FPL and distal radius was during maximum wrist dorsiflexion with isolated thumb flexion. The distance between the FDP2 and distal radius was shortest with all-finger flexion in 30° wrist dorsiflexion. Conclusions It is necessary to measure the distance between the FPL and distal radius in maximal wrist dorsiflexion with full flexion of the isolated thumb, as the shortest distance was observed with flexion of the isolated thumb. On the contrary, we recommend measuring the distance between the FDP2 and distal radius in 30° wrist dorsiflexion with flexion of all fingers.

Range-ambiguity artifact in abdominal ultrasound Abstract Range-ambiguity artifacts (RAAs) are an erroneous mapping of returning echoes into a composite picture. The purpose of this review was to illustrate the mechanism of RAAs and to present the diagnostic problems caused by RAAs. RAA features differ slightly from organ to organ. At the level of the urinary bladder, RAAs take the form of a cloud-like, ill-demarcated, immobile, echogenic area, and the depth of the echogenic area differs depending on the pulse repetition frequency (PRF). This form is referred to as "static RAA" in this review. There are two key ultrasound characteristics of RAAs at the level of the liver: (a) the depth of RAAs change according to the PRF, and (b) RAAs move in accordance with the cardiac cycle. This form is referred to as "mobile RAA" in this review. At the level of the gallbladder, RAAs take the form of fine echogenic lines in the gallbladder. This phenomenon is actually a combination of two phenomena: a ring-down artifact and RAA. This form is referred to as "complex RAA (searchlight phenomenon)" in this review. The easiest way to reduce RAAs is to change the image depth. Sufficient knowledge of RAAs can prevent misdiagnosis of erroneously displayed returning echoes as real pathologic changes.

Diagnosis of anomalous origin of the right coronary artery from the pulmonary artery by echocardiography Abstract Purpose To review the imaging characteristics and evaluate the diagnostic value of echocardiography for diagnosing anomalous origin of the right coronary artery from the pulmonary artery (ARCAPA). Methods We retrospectively reviewed the echocardiographic records and compared these images with operative findings in six children with ARCAPA. Results ARCAPA was characterized by dilation of the left coronary artery, inappropriate origin of the right coronary artery from the pulmonary artery, and collaterals within the interventricular septum. The associated malformations included atrial septal defect in four cases. Four of six cases were diagnosed correctly, while the remaining two cases were misdiagnosed: one of fistula between the pulmonary artery and the left coronary artery and another of ARCAPA diagnosed intraoperatively in one case of atrial septal defect. Conclusion ARCAPA can be diagnosed by echocardiography but is prone to misdiagnosis. This malformation should be distinguished from coronary artery fistula.

Alexandros Sfakianakis
Anapafseos 5 . Agios Nikolaos
Crete.Greece.72100
2841026182

6948891480

alsfakia@gmail.com

NeuroRadiology

European Society of Neuroradiology (ESNR)

Response to letter regarding "Combined aspiration thrombectomy and continuous intrasinus thrombolysis for cerebral venous sinus thrombosis: technical note and case series"

Correction to: European multicentre study on technical success and long-term clinical outcome of radiofrequency ablation for the treatment of spinal osteoid osteomas and osteoblastomas The original version of this paper contained an error: the Acknowledgements were dropped during early manuscript editing.

Letter regarding "Artery of Adamkiewicz: a meta-analysis of anatomical characteristics"

Hypothalamic malformations in patients with X-linked deafness and incomplete partition type 3 Abstract Patients with X-linked deafness carry mutations in the POU3F4 gene and have pathognomonic inner ear malformations characterised by symmetrical incomplete partition type 3 (absent modiolus and lamina spiralis but preserved interscalar septum in a normal-sized cochlea) and large internal auditory meatus (IAM) with an increased risk of gusher during stapes surgery. We describe a range of fairly characteristic malformations in the hypothalamus of some patients with this rare condition, ranging from subtle asymmetric appearance and thickening of the tuber cinereum to more marked hypothalamic enlargement. We discuss the role of POU3F4 in the normal development of both the inner ear and hypothalamus and the proposed pathophysiology of incomplete partition type 3.

Improving resolution of head and neck CTA using the small x-ray tube focal spot Abstract CT-resolution depends on tube focal spot size. To investigate the effect of reducing focal spot on vessel wall clarity, 22 patients underwent head and neck CTA acquisition with large and small focal spot size. Hounsfield density profile was assessed for each head and neck vessel separately, and significantly sharper density increase at vessel borders was observed using smaller tube focus by an average of 9.9% to 82° angle degrees (p < .05). In conclusion, spatial resolution of CTA of head and neck vessels can be improved by using the small x-ray tube focal spot.

Haemosiderin cap sign in cervical intramedullary schwannoma mimicking ependymoma: how to differentiate? Abstract A 37-year-old female presented with gradually progressive asymmetric ascending paraesthesia and weakness involving bilateral upper and lower limbs. The MRI spine images revealed expansile intramedullary, solid cystic, peripherally enhancing lesion with a haemosiderin cap along the lower margin. The lesion extended into the left C5 and C6 nerve root exit zones, along with thickening and enhancement of the nerve roots. She underwent excision of the lesion, which revealed intramedullary schwannoma on histopathological examination. Presence of the cap, an extension of the lesion into the nerve root exit zone, with associated thickening and enhancement of the dorsal nerve roots should alert the radiologist to consider the possibility of intramedullary schwannoma rather than ependymoma. Schwannoma showing compact Antoni A area with Schwannian whorls and nuclear palisades (A,B) and loose Antoni B area with haemosiderin pigment (C). The tumour exhibits diffuse positivity for S-100 protein (D) and negativity for GFAP (E). [Stain: A-C: Haematoxylin and Eosin; D,E: Immunoperoxidase. Magnification = Scale Bar, A-E: 100μm]

Reply by Tomaszewski et al. to the letter by Jiang et al. regarding "Artery of Adamkiewicz: a meta-analysis of anatomical characteristics"

Letter regarding "Combined aspiration thrombectomy and continuous intrasinus thrombolysis for cerebral venous sinus thrombosis: technical note and case series"

Artery of Adamkiewicz: a meta-analysis of anatomical characteristics Abstract Purpose The artery of Adamkiewicz (AKA) provides the major blood supply to the anterior thoracolumbar spinal cord and iatrogenic injury or inadequate reconstruction of this vessel during vascular and endovascular surgery can result in postoperative neurological deficit due to spinal cord ischemia. The aim of this study was to provide comprehensive data on the prevalence and anatomical characteristics of the AKA. Methods An extensive search was conducted through the major electronic databases to identify eligible articles. Data extracted included study type, prevalence of the AKA, gender, number of AKA per patient, laterality, origin based on vertebral level, side of origin, morphometric data, and ethnicity subgroups. Results A total of 60 studies (n = 5437 subjects) were included in the meta-analysis. Our main findings revealed that the AKA was present in 84.6% of the population, and patients most frequently had a single AKA (87.4%) on the left side (76.6%) originating between T8 and L1 (89%). Conclusion As an AKA is present in the majority of the population, caution should be taken during vascular and endovascular surgical procedures to avoid injury or ensure proper reconstruction. All surgeons operating in the thoracolumbar spinal cord should have a thorough understanding of the anatomical characteristics and surgical implications of an AKA.

Alexandros Sfakianakis
Anapafseos 5 . Agios Nikolaos
Crete.Greece.72100
2841026182

6948891480

alsfakia@gmail.com

Drugs & Therapy Perspectives

First reports of adverse drug reactions

Management and evaluation of treatment adherence and effectiveness in chronic venous disorders: results of the international study VEIN Act Program Abstract Objective The aim of this study was to examine worldwide chronic venous disease (CVD) burden and evaluate effectiveness, adherence and satisfaction with conservative treatment. Materials and methods The VEIN Act Program (VAP) was an international, prospective, observational study that enrolled adult outpatients with lower-limb pain consulting for any CVD-related clinical presentation. Patients' CVD symptoms, Clinical Etiological Anatomic Pathophysiologic (CEAP) classification, and symptom intensity were recorded. After prescribing conservative treatments, patients returned for a follow-up visit. Result A total of 567 physicians enrolled 7987 patients, 7397 of whom were included in the analysis. Patients were mainly female (79.3%), mean age was 54.0 ± 15.1 years and mean body mass index was 26.8 ± 4.8 kg/m2. CEAP clinical classifications were C0s (3.6%), C1 (19.4%), C2 (21.8%), C3 (32.0%) and C4–C6 (23.2%). Symptoms were reported by 89.6% of patients and were present across all CEAP classes. Mean intensity (10 cm visual analog scale) was > 5 cm for all symptoms. Only 30.7% of patients had previously consulted for leg problems, and 24.3% had previously received treatment. Conservative treatment alone was prescribed to 78.3% of patients, and in association with operative treatment in 21.6% of patients, and consisted mostly of venoactive drugs (VADs) [99.6%, mostly micronized purified flavonoid fraction] and compression therapy (63.4%) in combination with lifestyle changes such as weight loss. Adherence to prescribed duration was 65.2% for VADs, but only 29.1% wore compression therapy as prescribed. Symptom relief was high with VADs and compression therapy (> 96%), and the majority of patients were satisfied (94.1%). Conclusion Conservative treatments were beneficial across the spectrum of CVD, highlighting the importance of identifying patients early in the disease course.

Ertugliflozin in type 2 diabetes: a profile of its use Abstract Oral ertugliflozin (Steglatro™), a selective sodium-glucose cotransporter 2 (SGLT2) inhibitor, is approved in numerous countries as an adjunct to diet and exercise to improve glycaemic control in adults with type 2 diabetes (T2D), either as monotherapy or add-on therapy to other antihyperglycaemic agents; specific indications may vary between individual countries. In numerous well-designed VERTIS trials and extension studies in adults with inadequately controlled T2D, ertugliflozin monotherapy, initial combination therapy to sitagliptin and add-on therapy to metformin or to metformin plus sitagliptin consistently provided effective and durable glycaemic control, and reduced bodyweight and blood pressure. Ertugliflozin is generally well tolerated, with a good benefit/risk profile. The availability of ertugliflozin/metformin (Segluromet™) and ertugliflozin/sitagliptin (Steglujan™) fixed-dose combinations (FDCs) may potentially improve compliance/adherence in patients requiring intensification of antihyperglycaemic treatment with combination therapy to achieve adequate glycaemic control. Given the proven benefits of other SGLT2 inhibitors on cardiovascular (CV) and renal outcomes, results from the ongoing VERTIS CV outcome trial are awaited with interest.

When managing ulcerative colitis in older patients, understanding their overall health profile is key Abstract Ulcerative colitis (UC) in patients aged > 60 years is increasingly common. The treatment of UC aims to induce and maintain clinical remission, with 5-aminosalicylates the mainstay for mild UC. In moderate-to-severe or refractory UC, oral corticosteroids, thiopurines, anti-TNF agents, vedolizumab and tofacitinib are treatment options to induce and/or maintain remission. To facilitate compliance and minimize adverse drug events, treatment should be tailored to patients' general health status, comorbidities and existing medications.

The off-label use of medicines in pediatric outpatients in Bulgaria based on an analysis of their prescription data Abstract Background The off-label use of medicines is a common practice that occurs over a wide range of therapeutic areas in both adults and children, but occurs much more frequently in pediatric population. So far, the extent of off-label use among children in Bulgaria has not been studied. Objective The aim of this nested, retrospective, non-interventional, single-center study is to provide data on the frequency, type, and the most common situations in which off-label medicines are prescribed in daily pediatric practice in Bulgaria. Methods The data on prescriptions of 360 pediatric outpatients, treated during a 1-year period, were recorded and provided for analysis. The summaries of product characteristics (SmPC) were used as reference documents for the assessment of prescriptions. Descriptive statistics, with absolute frequencies, means, and standard deviation, were used to analyze the processed data. Results The results from this study show that most pediatric patients (78%) were exposed to off-label use. Half of the medicines prescribed off-label were used for a therapeutic indication other than the one listed in the SmPC. We found that certain medicines were used 100% off-label, and certain diseases were also 100% treated with off-label medications. Conclusion Although the study was limited to one center, it deserves attention as it reveals many different aspects of the off-label use of medications in pediatric patients in Bulgaria. Further studies involving a larger number of medical centers are needed to establish more accurate data on off-label prescribing in pediatric patients at a national level.

Intravenous medication errors in Selangor, Malaysia: prevalence, contributing factors and potential clinical outcomes Abstract Introduction Medication errors may have serious implications to both the patient and the healthcare system, and may also compromise patient safety and significantly impact healthcare costs. Therefore, assessing the prevalence and factors associated with intravenous medication errors will significantly improve the quality of care and hospital services. Objective The aim of this study was to determine the prevalence of intravenous medication errors and their potential clinical outcomes. Additionally, this study evaluates the relationship between medication errors and the factors associated with their occurrences. Methods This prospective study was conducted using a direct observation technique and medication record reviews in a secondary hospital in Malaysia. The preparation and administration of intravenous drugs were observed for a total of 213 doses using a checklist supplemented with a review of medication charts. Results Medication administration errors were detected in 85% (181/213) of the doses observed. Overall, 307 errors were identified. After excluding the 39 wrong-time errors, 66.7% (142/213) remained erroneous. More errors were detected during the drug administration stage (62.5%) than in the drug preparation stage (37.5%). Central nervous system drugs recorded the highest error rate at 94.1%. Overall, a total of 43 errors (14.3%) were found to be potentially severe. In a bivariate analysis, the occurrence of errors was significantly associated with nurses' experience and level of education. Conclusion Intravenous preparation and administration errors were highly prevalent in a resource-restricted secondary hospital in Malaysia. Targeted and prompt remedial actions such as training and enforcing existing standard operating procedures to reduce medication errors should be implemented.

Human α 1 -proteinase inhibitor (Respreeza ® ) in α 1 -antitrypsin deficiency emphysema: a profile of its use in the EU Abstract Augmentation therapy with human α1-proteinase inhibitor (Respreeza®) is an effective and generally well tolerated treatment option for patients with severe α1-antitrypsin deficiency. In the 2-year RAPID trial, intravenous Respreeza 60 mg/kg once weekly was associated with a trend towards reduced mean annual rate of lung density loss (as measured by computed tomography) at total lung capacity (TLC) and functional residual capacity (FRC) combined, and at FRC alone, with a significant reduction seen at TLC alone. The continued efficacy of Respreeza in slowing the progression of emphysema was demonstrated in a 2-year open-label extension of the RAPID trial. Although lung density loss was slowed when treatment was initiated later in the disease course, lung density loss prior to treatment was not recovered.

Identify potentially inappropriate medications in older adults with chronic kidney disease and deprescribe when possible Abstract Older adults with chronic kidney disease (CKD) often receive treatment with multiple medications and are vulnerable to adverse treatment-related outcomes. Although specific guidelines for deprescribing (defined as the process of eliminating or reducing the use of unnecessary and/or inappropriate medications) in older patients with CKD are lacking, a systemic process should be used to assess the individual patient, identify the use of potentially inappropriate medications (PIMs), and deprescribe such medications when possible. Dosage tapering is needed when some commonly used PIMs (e.g. proton pump inhibitors and oral antidiabetic drugs) are deprescribed, but not when others (e.g. statins) are discontinued. Patient involvement and a collaborative approach are important factors in the success of the deprescribing process.

The use of fluoroquinolones and macrolides for sinusitis: a retrospective cross-sectional study Abstract Background and objective β-Lactam antibiotics are the recommended first-line treatment for acute bacterial sinusitis. Fluoroquinolones are recommended in patients with hypersensitivity reactions to penicillins, and macrolide antibiotics are no longer recommended. The objectives of this study were to understand whether outpatient antibiotic prescribing practices adhere to treatment guidelines and to describe rates of fluoroquinolone and macrolide antibiotic prescribing for the treatment of sinusitis. Methods This was a retrospective cross-sectional study using US National Ambulatory Medical Care Survey (NAMCS) data. The prevalence of antibiotic prescribing for sinusitis was estimated, and the antibiotic prescribing pattern was measured. Additionally, significant factors associated with various antibiotic prescribing during the visits related to sinusitis were identified. Results Among physician visits related to sinusitis from 2013 to 2016 (n = 2739), 66.4% involved antibiotic prescribing. Visits with antibiotic prescribing showed greater proportions of patients aged < 18 years (21.7 vs 11.1%, p < 0.001), patients reporting fever (79.8 vs 50.7%, p < 0.001), and patients seeing family physicians or internal medicine specialists (68.4 vs 44.8%, p < 0.001) than those without antibiotic prescribing. Penicillins, macrolides, cephalosporins, and fluoroquinolones were prescribed in 42.2%, 30.6%, 15.2%, and 9.5% of the visits involving antibiotic prescribing for sinusitis, respectively. The odds of fluoroquinolone/macrolide prescribing were reduced by 73% if patients visited pediatricians and by 59% with otolaryngologists. Conclusions Macrolides were the most common inappropriate antibiotic class prescribed for sinusitis. This study identifies a need for more focused attention to improve prescribing for sinusitis and adherence to the treatment guidelines.

Outcome measures in pediatric polypharmacy research: a scoping review Abstract Introduction Various methods have been used to interpret the reports of pediatric polypharmacy across the literature. This is the first scoping review that explores outcome measures in pediatric polypharmacy research. Objectives The aim of our study was to describe outcome measures assessed in pediatric polypharmacy research. Methods A search of electronic databases was conducted in July 2017, including Ovid Medline, PubMed, Elsevier Embase, Wiley Cochrane Central Register of Controlled Trials (CENTRAL), EBSCO CINAHL, Ovid PsycINFO, Web of Science Core Collection, ProQuest Dissertations and Thesis A&I. Data were extracted about study characteristics and outcome measures, and also synthesized by harms or benefits mentioned. Results The search strategy initially identified 8169 titles and screened 4398 using the inclusion criteria after de-duplicating. After the primary screening, a total of 363 studies were extracted for the data analysis. Polypharmacy (prevalence) was identified as an outcome in 31.4% of the studies, prognosis-related outcomes in 25.6%, and adverse drug reactions in 16.5%. A total of 265 articles (73.0%) mentioned harms, including adverse drug reactions (26.4%), side effects (24.2%), and drug–drug interactions (20.9%). A total of 83 studies (22.9%) mentioned any benefit, 48.2% of which identified combination for efficacy, 24.1% combination for treatment of complex diseases, and 19.3% combination for treatment augmentation. Thirty-eight studies reported adverse drug reaction as an outcome, where polypharmacy was a predictor, with various designs. Conclusions Most studies of pediatric polypharmacy evaluate prevalence, prognosis, or adverse drug reaction-related outcomes, and underscore harms related to polypharmacy. Clinicians should carefully weigh benefits and harms when introducing medications to treatment regimens.

Alexandros Sfakianakis
Anapafseos 5 . Agios Nikolaos
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6948891480

alsfakia@gmail.com