title: Pepscan mapping of viral hemorrhagic septicemia virus glycoprotein G major lineal determinants implicated in triggering host cell antiviral responses mediated by type I interferon.

text: Surface glycoproteins of enveloped virus are potent elicitors of type I interferon (IFN)-mediated antiviral responses in a way that may be independent of the well-studied genome-mediated route. However, the viral glycoprotein determinants responsible for initiating the IFN response remain unidentified. In this study, we have used a collection of 60 synthetic 20-mer overlapping peptides (pepscan) spanning the full length of glycoprotein G (gpG) of viral hemorrhagic septicemia virus (VHSV) to investigate what regions of this protein are implicated in triggering the type I IFN-associated immune responses. Briefly, two regions with ability to increase severalfold the basal expression level of the IFN-stimulated mx gene and to restrict the spread of virus among responder cells were mapped to amino acid residues 280 to 310 and 340 to 370 of the gpG protein of VHSV. In addition, the results obtained suggest that an interaction between VHSV gpG and integrins might trigger the host IFN-mediated antiviral response after VHSV infection. Since it is known that type I IFN plays an important role in determining/modulating the protective-antigen-specific immune responses, the identification of viral glycoprotein determinants directly implicated in the type I IFN induction might be of special interest for designing new adjuvants and/or more-efficient and cost-effective viral vaccines as well as for improving our knowledge on how to stimulate the innate immune system.


title: Synthesis, biodistribution and PET studies in rats of (18)F-Labeled bridgehead fluoromethyl analogues of WAY-100635.

text: INTRODUCTION In vitro screening of fluoromethyl bridge-fused ring (BFR) analogues of WAY-100635 (5a, 5b and 5c) has shown a high binding affinity and a good selectivity for the 5-HT(1A) receptor. As these compounds were designed to provide PET ligands with high metabolic stability, they are now radiolabeled with fluorine-18 and investigated in vivo. METHODS BFR precursors were synthesized and reacted with fluorine-18 in dry MeCN in the presence of 2,2,2-kryptofix and K(2)CO(3). In rats, biodistribution and PET studies were performed using [(18)F]5a, [(18)F]5b and [(18)F]5c. The binding specificity was determined by administration of non-labeled WAY-100635 prior to the radiolabeled ligands. RESULTS [(18)F]5 ligands were synthesized in overall radiochemical yields of 24%-45%, respectively with a radiochemical purity of >98%. Relatively good hippocampus to cerebellum ratios of 5.55, 4.79 and 5.45, respectively were reached at 45 min pi. However, PET studies indicated defluorination of the radioligands by showing high accumulation of radioactivity in the bones in the order of [(18)F]5a≈[(18)F]5b>[(18)F]5c. CONCLUSION Also in vivo, the radioligands bind preferentially to the 5-HT(1A) receptor. Unfortunately, no metabolic stability with regard to defluorination was observed in rats.


Covid-19: Racism may be linked to ethnic minorities' raised death risk, says PHE.


title: Migration of engrafted neural stem cells is mediated by CXCL12 signaling through CXCR4 in a viral model of multiple sclerosis.

text: Multiple sclerosis (MS) is a human demyelinating disease characterized by multifocal regions of inflammation, progressive myelin loss within the central nervous system (CNS), and eventual failure to remyelinate damaged axons. These problems suggest deficiencies in recruiting and/or maturation of oligodendrocyte progentior cells (OPCs) and highlight cell replacement therapies to promote remyelination. We have used a model of viral-induced demyelination to characterize signaling cues associated with positional migration of transplanted remyelination-competent cells. Although successful transplantation of rodent-derived glial cell types into models of MS has been performed, the mechanisms by which these cells navigate within an inflammatory environment created by a persistent virus has not been defined. Infection of the mouse CNS with the neurotropic JHM strain of mouse hepatitis virus (JHMV) results in an immune-mediated demyelinating disease with clinical and histologic similarities to MS. Surgical engraftment of GFP+ neural stem cells (NSCs) into spinal cords of JHMV-infected mice with established demyelination results in migration, proliferation, and differentiation of the cells into OPCs and mature oligodendrocytes that is associated with increased axonal remyelination. Treatment with anti-CXCL12 [stromal derived factor-1alpha, (SDF-1alpha)] blocking serum resulted in a marked impairment in migration and proliferation of engrafted stem cells. Moreover, small molecule-mediated antagonism of CXCR4, but not CXCR7, impaired migration and proliferation, to an extent similar to that with anti-CXCL12 treatment. These data highlight the importance of the CXCL12:CXCR4 pathway in regulating homing of engrafted stem cells to sites of tissue damage within the CNS of mice persistently infected with a neurotropic virus undergoing immune-mediated demyelination.


title: Endovascular procedures in the management of DVT.

text: The post-thrombotic syndrome (PTS) develops in 25%-50% of patients with proximal lower extremity deep vein thrombosis (DVT) despite the use of standard anticoagulant therapy and elastic compression stockings. PTS is a major cause of quality of life impairment in DVT patients and often leads to limiting venous claudication, work disability, and venous ulcers. Endovascular thrombolytic procedures that eliminate venous thrombus, restore venous flow, and show strong potential to prevent PTS are now under study in multicenter randomized clinical trials. In addition, endovascular procedures can be used to treat valvular reflux and venous obstruction and thereby provide symptom improvement to patients with chronic established PTS.


COVID-19 and Racial/Ethnic Disparities.


title: Microlobectomy: A Novel Form of Endoscopic Lobectomy.

text: OBJECTIVE Microlobectomy is a novel form of videoscopic-assisted thoracic surgery lobectomy. Strict inclusion criteria consist of the following: no intercostal incisions greater than 5 mm, 12 mm subxiphoid port, subxiphoid removal of the specimen, total endoscopic technique with CO2 insufflation, vision through a 5-mm camera, stapling via the subxiphoid port, or with 5-mm stapling devices. METHODS The combined early experiences of six hospitals from three countries were combined from September 2014 to May 2016. During that time, the study represents a consecutive cohort study of this technique. RESULTS Seventy-two patients underwent microlobectomy. The median (range) age was 66 (27-82). Half of the patients were female. There were 48 right-sided resections and 24 on the left. There were four segmental resections and there was one right pneumonectomy. Four operations were performed robotically (with 8-mm intercostal incisions). The median (range) operative time was 180 (94-285) minutes and the blood loss was 118 (5-800) mL. There were three conversions to thoracotomy and two conversions to videoscopic-assisted thoracic surgery by means of an intercostal utility incision to complete the operation. The median (range) length of stay was 3 (1-44) days and 30 patients (42%) when home by day 2 and 16 patients (22%) were discharged on day 1. There were no deaths. Five patients (7%) had a prolonged airleak. There were no wound infections and there was one incisional hernia. CONCLUSIONS We believe that microlobectomy is an interesting novel form of videoscopic-assisted thoracic surgery lobectomy and has several theoretical advantages. We have presented our early results and hope that this will stimulate others to investigate this type of videoscopic-assisted thoracic surgery lobectomy further.


title: Outcome impact of goal directed fluid therapy during high risk abdominal surgery in low to moderate risk patients: a randomized controlled trial.

text: Intraoperative goal directed fluid therapy (GDT) guided by an arterial pressure-based cardiac output system has been reported to improve gastrointestinal (GI) recovery in high-risk patients. This study evaluates the impact of this approach on GI recovery in low to moderate risk patients undergoing major abdominal surgery. IRB approved randomized controlled trial in low to moderate risk adults scheduled for major surgery. Patients were randomized to standard (n = 20) or GDT (n = 18) groups, whose fluids were managed to maintain stroke volume variation (SVV) <12 %. The primary outcome measure was GI recovery. Additional measures included quality of recovery score. Continuous, non-normally distributed by Mann-Whitney test; ordinal and nominal by Chi square analysis. GDT patients had lower average intraoperative SVV. The GDT group had faster return of GI function (p = 0.004) and higher quality of recovery scores. In low to moderate risk patients undergoing major abdominal surgery, intraoperative GDT guided by SVV optimization was associated with faster restoration of GI recovery and higher quality of recovery scores. These results suggest that outcome benefits related to the use of an intraoperative goal directed fluid protocol guided by SVV are not limited to high-risk patients.


title: COVID-19's Impact on Italian Urology.

text: The COVID-19 pandemic has impacted our lives, our habits and our healthcare system. Italy is one of the countries affected first and more aggressively from the outbreak. Our rapidity has been guide for other healthcare systems from around the World. We describe the impact of COVID-19 on Urology, how the Urological scientific community responded to the emergency and our experience in a high-volume Roman University hospital. The aim of our work is to share our experience providing suggestions for other global hospitals on how to manage the COVID-19 emergency.


title: Laparoscopic transabdominal preperitoneal inguinal hernia repair using needlescopic instruments: a 15-year, single-center experience in 317 patients.

text: BACKGROUND Laparoscopic inguinal hernia repair is associated with a decrease in postoperative pain, shortened hospital stay, earlier return to normal activity, and decrease in chronic pain. Moreover, laparoscopic surgery performed with needlescopic instruments has more advantages than conventional laparoscopic surgery. However, there are few reports of large-scale laparoscopic transabdominal preperitoneal inguinal hernia repair using needlescopic instruments (nTAPP). This report reviews our experiences with 352 nTAPP in 317 patients during the 15-year period from April 1996 to April 2011. METHODS We performed nTAPP as the method of choice in 88.5% of all patients presenting with inguinal hernia. To perform the nTAPP, 3-mm instruments were used. A 5-mm laparoscope was inserted from the umbilicus, and surgical instruments were inserted through 5- and 3-mm trocars. After reduction of the hernia sac and dissection of the preperitoneal space, we placed polyester mesh or polypropylene soft mesh with staple fixation. The peritoneum was closed with 3-0 silk interrupted sutures. RESULTS The mean operative time was 102.9 min for unilateral hernias and 155.8 min for bilateral hernias. There was no conversion to open repair. Forty-three patients (13.6%) used postoperative analgesics, and the mean frequency of use was 0.5 times. Regarding intraoperative complications, we observed one bladder injury, but no bowel injuries or major vessel injuries. Postoperative complications occurred in 32 patients (10.1%). One patient with a retained lipoma required reoperation. There was no incidence of chronic pain or mesh infection. The operative time for experienced surgeons (≥ 20 repairs) was significantly shorter than that of inexperienced surgeons (< 20 repairs; P < 0.05). CONCLUSIONS The nTAPP was a safe and useful technique for inguinal hernia repair. Large prospective, randomized controlled trials will be required to establish the benefit of nTAPP.


Salivary Glands: Potential Reservoirs for COVID-19 Asymptomatic Infection.


Malpositioning of supraglottic airway devices: preventive and corrective strategies.


title: Development of a research-oriented system for collecting mechanical ventilator waveform data.

text: Lack of access to high-frequency, high-volume patient-derived data, such as mechanical ventilator waveform data, has limited the secondary use of these data for research, quality improvement, and decision support. Existing methods for collecting these data are obtrusive, require high levels of technical expertise, and are often cost-prohibitive, limiting their use and scalability for research applications. We describe here the development of an unobtrusive, open-source, scalable, and user-friendly architecture for collecting, transmitting, and storing mechanical ventilator waveform data that is generalizable to other patient care devices. The system implements a software framework that automates and enforces end-to-end data collection and transmission. A web-based data management application facilitates nontechnical end users' abilities to manage data acquisition devices, mitigates data loss and misattribution, and automates data storage. Using this integrated system, we have been able to collect ventilator waveform data from >450 patients as part of an ongoing clinical study.


title: Are ADHD medications under or over prescribed worldwide?: Protocol for a systematic review and meta-analysis.

text: INTRODUCTION Attention-Deficit/Hyperactivity Disorder (ADHD) is a common neurodevelopmental disorder, characterized by age inappropriate and impairing levels of inattention and/or hyperactivity/impulsivity. Pharmacotherapy is an important part of the ADHD multimodal treatment. The extent to which ADHD is pharmacologically over or under treated worldwide is controversial. We aimed to estimate the pooled worldwide rate of ADHD pharmacological treatment in individuals with and without the disorder. METHOD AND ANALYSIS We will include published or unpublished studies reporting the rates of ADHD pharmacological treatment in participants with and without ADHD of any age group. Population-based, cohort, or follow-up studies, as well as data from insurance health system and third-party reimbursements will be eligible. Searches will be performed in a large number of electronic databases, including Medline, Embase, CINAHL, Cochrane, PsycINFO, Web of Science, and Scopus. The primary outcome will be the prevalence of ADHD pharmacological treatment in individuals with ADHD and without ADHD. Two independent reviewers will perform the screening, and data extraction process. Study quality/bias will be assessed with the Newcastle-Ottawa scale by 2 independent reviewers. To test the robustness of the findings, we will perform a series of sensitivity and meta-regression analysis. Analyses will be performed with R and STATA software. ETHICS AND DISSEMINATION No IRB approval will be necessary. The results of this systematic review and meta-analysis will be presented at international conferences and published in peer-reviewed journals. REGISTRATION AND STATUS PROSPERO 2018 CRD42018085233.


title: Assessment of distal access catheter performance during neuroendovascular procedures: measuring force in three-dimensional patient specific phantoms.

text: BACKGROUND The amount of force applied on a device is an important measure to evaluate the endovascular and surgical device manipulations. The measure has not been evaluated for neuroenodvascular procedures. PURPOSE We aimed to study the use of force measure as a novel approach to test distal access catheter (DAC) performance during catheterization of cervical and intracranial vessels using patient specific 3-dimentional (3D) phantoms. METHODS Using patient specific 3D phantoms of the cervical and intracranial circulation, we recorded measure of force required to deliver three types of DACs beyond the ophthalmic segment of the internal carotid artery. Six different combinations of DAC-microcatheter-guidewire were tested. We intentionally included what we considered suboptimal combinations of DACs, microcatheters, and guidewires during our experiments to test the feasibility of measuring force under different conditions. A six axis force sensor was secured to the DAC with an adjustable torque used to track axially directed push and pull forces required to navigate the DAC to the target site. RESULTS In a total of 55 experiments, we found a significant difference in the amount of force used between different DACs (mean force for DAC A, 1.887±0.531N; for DAC B, 2.153±1.280 N; and for DAC C, 1.194±0.521 N, P=0.007). There was also a significant difference in force measures among the six different catheter systems (P=0.035). CONCLUSIONS Significant difference in the amount of force used between different DACs and catheter systems were recorded. Use of force measure in neuroendovascular procedures on 3D printed phantoms is feasible.


title: The efficacy of fall-risk-increasing drug (FRID) withdrawal for the prevention of falls and fall-related complications: protocol for a systematic review and meta-analysis.

text: BACKGROUND Despite limited evidence of effectiveness, withdrawal (discontinuation or dose reduction) of high risk medications known as "fall-risk increasing drugs" (FRIDs) is typically conducted as a fall prevention strategy based on presumptive benefit. Our objective is to determine the efficacy of fall-risk increasing drugs (FRIDs) withdrawal on the prevention of falls and fall-related complications. METHODS/DESIGN We will search for all published and unpublished randomized controlled trials evaluating the effect of FRID withdrawal compared to usual care on the rate of falls, incidence of falls, fall-related injuries, fall-related fractures, fall-related hospitalizations, or adverse effects related to the intervention in adults aged 65 years or older. Electronic database searches will be conducted in MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials (CENTRAL), and CINAHL. A grey literature search will be conducted including clinical trial registries and conference proceedings and abstracts. Two reviewers will independently perform in duplicate citation screening, full-text review, data abstraction, and risk of bias assessment. Conflicts will be resolved through team discussion or by a third reviewer if no consensus can be reached. The Grades of Recommendation, Assessment, Development and Evaluation (GRADE) criteria will be used to independently rate overall confidence in effect estimates for each outcome. Results will be synthesized descriptively, and a random effects meta-analysis will be conducted for each outcome if studies are deemed similar methodologically, clinically, and statistically. DISCUSSION We will attempt to determine whether a FRID withdrawal strategy alone is effective at preventing falls in older adults. Our results will be used to optimize and focus fall prevention strategies and initiatives internationally with a goal of improving the health of older adults. SYSTEMATIC REVIEW REGISTRATION PROSPERO CRD42016040203.


title: Semiautomated motion correction of tumors in lung CT-perfusion studies.

text: RATIONALE AND OBJECTIVES To compare the relative performance of one-dimensional (1D) manual, rigid-translational, and nonrigid registration techniques to correct misalignment of lung tumor anatomy acquired from computed tomography perfusion (CTp) datasets. MATERIALS AND METHODS Twenty-five datasets in patients with lung tumors who had undergone a CTp protocol were evaluated. Each dataset consisted of one reference CT image from an initial cine slab and six subsequent breathhold helical volumes (16-row multi-detector CT), acquired during intravenous contrast administration. Each helical volume was registered to the reference image using two semiautomated intensity-based registration methods (rigid-translational and nonrigid), and 1D manual registration (the only registration method available in the relevant application software). The performance of each technique to align tumor regions was assessed quantitatively (percent overlap and distance of center of mass), and by a visual validation study (using a 5-point scale). The registration methods were statistically compared using linear mixed and ordinal probit regression models. RESULTS Quantitatively, tumor alignment with the nonrigid method compared to rigid-translation was borderline significant, which in turn was significantly better than the 1D manual method: average (± SD) percent overlap, 91.8 ± 2.3%, 87.7 ± 5.5%, and 77.6 ± 5.9%, respectively; and average (± SD) DCOM, 0.41 ± 0.16 mm, 1.08 ± 1.13 mm, and 2.99 ± 2.93 mm, respectively (all P < .0001). Visual validation confirmed these findings. CONCLUSION Semiautomated registration methods achieved superior alignment of lung tumors compared to the 1D manual method. This will hopefully translate into more reliable CTp analyses.


title: Thioredoxin System Protein Expression Is Associated with Poor Clinical Outcome in Adult and Paediatric Gliomas and Medulloblastomas.

text: The thioredoxin (Trx) system is an important enzyme family that regulates cellular redox homeostasis. Protein expression of Trx system family members has been assessed in various cancers and linked to various clinicopathological variables, disease progression, treatment response and survival outcomes but information is lacking in brain tumours. Expression of the system was therefore examined, by immunohistochemistry in different brain tumour types, adult and paediatric cases, to determine if expression was of importance to clinical outcome. Trx system proteins were expressed, to variable levels, across all brain tumour types with significant variations in expression between different tumour types/grades/regions. High Trx reductase (TrxR) expression was linked to worse prognosis across all cohorts. High cytoplasmic TrxR expression was significantly associated with adverse overall survival (OS) in adult glioblastoma (P = 0.027) and paediatric low-grade glioma (LGG) patients (P = 0.012). High expression of nuclear TrxR, cytoplasmic and nuclear Trx and Trx-interacting protein (TxNIP) was associated with improved OS in paediatric LGGs (P = 0.031, P < 0.001, P = 0.044 and P = 0.018, respectively). For patients with high-grade gliomas, both high cytoplasmic TrxR and Trx expression were associated with poor OS (P = 0.002 and P = 0.007, respectively). In medulloblastoma, high expression of cytoplasmic TrxR and Trx and nuclear Trx was associated with worse prognosis (P = 0.013, P = 0.033 and P = 0.007, respectively); with cytoplasmic TrxR and nuclear Trx remaining so in multivariate analysis (P = 0.009 and P = 0.013, respectively). The consistent finding that high levels of cytoplasmic TrxR are associated with a worse prognosis across all cohorts suggests that TrxR is an important therapeutic target in brain cancers.


title: Time and diffusion lesion size in major anterior circulation ischemic strokes.

text: BACKGROUND AND PURPOSE Major anterior circulation ischemic strokes caused by occlusion of the distal internal carotid artery or proximal middle cerebral artery or both account for about one third of ischemic strokes with mostly poor outcomes. These strokes are treatable by intravenous tissue-type plasminogen activator and endovascular methods. However, dynamics of infarct growth in these strokes are poorly documented. The purpose was to help understand infarct growth dynamics by measuring acute infarct size with diffusion-weighted imaging (DWI) at known times after stroke onset in patients with documented internal carotid artery/middle cerebral artery occlusions. METHODS Retrospectively, we included 47 consecutive patients with documented internal carotid artery/middle cerebral artery occlusions who underwent DWI within 30 hours of stroke onset. Prospectively, 139 patients were identified using the same inclusion criteria. DWI lesion volumes were measured and correlated to time since stroke onset. Perfusion data were reviewed in those who underwent perfusion imaging. RESULTS Acute infarct volumes ranged from 0.41 to 318.3 mL. Infarct size and time did not correlate (R2=0.001). The majority of patients had DWI lesions that were <25% the territory at risk (<70 mL) whether they were imaged <8 or >8 hours after stroke onset. DWI lesions corresponded to areas of greatly reduced perfusion. CONCLUSIONS Poor correlation between infarct volume and time after stroke onset suggests that there are factors more powerful than time in determining infarct size within the first 30 hours. The observations suggest that highly variable cerebral perfusion via the collateral circulation may primarily determine infarct growth dynamics. If verified, clinical implications include the possibility of treating many patients outside traditional time windows.


Faced with 2019-nCoV outbreak, we have learned our lessons from SARS of 2003.


Icarus and Sports After COVID 19: Too Close to the Sun?


title: COVID-19: lessons for junior doctors redeployed to critical care.

text: Approximately 4% of patients with coronavirus disease 2019 (COVID-19) will require admission to an intensive care unit (ICU). Governments have cancelled elective procedures, ordered new ventilators and built new hospitals to meet this unprecedented challenge. However, intensive care ultimately relies on human resources. To enhance surge capacity, many junior doctors have been redeployed to ICU despite a relative lack of training and experience. The COVID-19 pandemic poses additional challenges to new ICU recruits, from the practicalities of using personal protective equipment to higher risks of burnout and moral injury. In this article, we describe lessons for junior doctors responsible for managing patients who are critically ill with COVID-19 based on our experiences at an urban teaching hospital.


title: Burnout-depression overlap: a review.

text: Whether burnout is a form of depression or a distinct phenomenon is an object of controversy. The aim of the present article was to provide an up-to-date review of the literature dedicated to the question of burnout-depression overlap. A systematic literature search was carried out in PubMed, PsycINFO, and IngentaConnect. A total of 92 studies were identified as informing the issue of burnout-depression overlap. The current state of the art suggests that the distinction between burnout and depression is conceptually fragile. It is notably unclear how the state of burnout (i.e., the end stage of the burnout process) is conceived to differ from clinical depression. Empirically, evidence for the distinctiveness of the burnout phenomenon has been inconsistent, with the most recent studies casting doubt on that distinctiveness. The absence of consensual diagnostic criteria for burnout and burnout research's insufficient consideration of the heterogeneity of depressive disorders constitute major obstacles to the resolution of the raised issue. In conclusion, the epistemic status of the seminal, field-dominating definition of burnout is questioned. It is suggested that systematic clinical observation should be given a central place in future research on burnout-depression overlap.


title: Knotless choledochorraphy with barbed suture, safe and feasible.

text: PURPOSE To describe the safety and feasibility of a running continuous unidirectional barbed suture (V-Loc, Covidien, Mansfield, MA) for primary common bile duct closure while performing laparoscopic common bile duct exploration (LCBDE). INTRODUCTION LCBDE is nowadays the best approach for treating complex common bile duct lithiasis or cases where the endoscopic retrograde cholangiopancreatography has failed. It is clear that the primary closure of the common bile duct must be preferred over the T-tube drainage. The actual technical aspects offer room for improvement. We present our experience with barbed suture, for which recently, various fields of surgery have become interested in and which now has a series of studies that support it for several uses. METHODS Between July 2012 and July 2014, 54 consecutive patients with bile duct stones underwent LCBDE by a single surgeon. Perioperative outcomes and 30-day complications were recorded. RESULTS Upon the completion of the exploration, 50 patients had primary common bile duct closure using knotless unidirectional barbed 3-0 V-Loc 90 suture, and 4 patients were excluded. All of the sutures were performed without knot tying. The procedure in all patients was successfully performed with no intraoperative complications. There were no bile leaks in the 50 patients or other postoperative complications such as infection, need for reintervention or death. CONCLUSION The use of unidirectional knotless barbed suture (V-Loc 90) is safe, feasible and effective on LCBDE for primary common bile duct closure. The biliary leak rate is acceptably low and comparable to the rate reported in the literature. This report is our initial experience that needs further clinical trials.


title: Quantitative measurements in capsule endoscopy.

text: This review summarizes several approaches for quantitative measurement in capsule endoscopy. Video capsule endoscopy (VCE) typically provides wireless imaging of small bowel. Currently, a variety of quantitative measurements are implemented in commercially available hardware/software. The majority is proprietary and hence undisclosed algorithms. Measurement of amount of luminal contamination allows calculating scores from whole VCE studies. Other scores express the severity of small bowel lesions in Crohn׳s disease or the degree of villous atrophy in celiac disease. Image processing with numerous algorithms of textural and color feature extraction is further in the research focuses for automated image analysis. These tools aim to select single images with relevant lesions as blood, ulcers, polyps and tumors or to omit images showing only luminal contamination. Analysis of motility pattern, size measurement and determination of capsule localization are additional topics. Non-visual wireless capsules transmitting data acquired with specific sensors from the gastrointestinal (GI) tract are available for clinical routine. This includes pH measurement in the esophagus for the diagnosis of acid gastro-esophageal reflux. A wireless motility capsule provides GI motility analysis on the basis of pH, pressure, and temperature measurement. Electromagnetically tracking of another motility capsule allows visualization of motility. However, measurement of substances by GI capsules is of great interest but still at an early stage of development.


title: Corticosteroids as standalone or add-on treatment for sore throat.

text: BACKGROUND Sore throat is a common condition associated with a high rate of antibiotic prescriptions, despite limited evidence for the effectiveness of antibiotics. Corticosteroids may improve symptoms of sore throat by reducing inflammation of the upper respiratory tract. OBJECTIVES To assess the clinical benefit and safety of corticosteroids for symptoms of sore throat in adults and children. SEARCH METHODS We searched The Cochrane Library, the Cochrane Central Register of Controlled Trials (CENTRAL 2012, Issue 5) which includes the Acute Respiratory Infections (ARI) Group's Specialised Register, the Database of Reviews of Effects and the NHS Health Economics Database, MEDLINE (1966 to November Week 4, 2012) and EMBASE (1974 to June 2012). SELECTION CRITERIA We included randomised controlled trials that compared steroids to either placebo or standard care in adults and children (older than three years of age) with sore throat. We excluded studies of hospitalised participants, those with infectious mononucleosis, sore throat following tonsillectomy or intubation, or peritonsillar abscess. DATA COLLECTION AND ANALYSIS Two review authors independently reviewed and selected trials from searches, assessed and rated study quality, and extracted relevant data. MAIN RESULTS We included eight trials involving 743 participants (369 children and 374 adults). All trials gave antibiotics to both placebo and corticosteroid groups; no trials assessed corticosteroids as standalone treatment for sore throat. In addition to any effect of antibiotics and analgesia, corticosteroids increased the likelihood of complete resolution of pain at 24 hours by more than three times (risk ratio (RR) 3.2, 95% confidence interval (CI) 2.0 to 5.1, P < 0.001, I(2) statistic 44%) and at 48 hours by 1.7 times. Fewer than four people need to be treated to prevent one person continuing to experience pain at 24 hours. Corticosteroids also reduced the mean time to onset of pain relief and the mean time to complete resolution of pain by 6 and 14 hours, respectively, although significant heterogeneity was present. At 24 hours, pain (assessed by visual analogue scores) was reduced by an additional 14% by corticosteroids. No difference in rates of recurrence, relapse or adverse events were reported for participants taking corticosteroids compared to placebo, although reporting of adverse events was poor. AUTHORS' CONCLUSIONS Oral or intramuscular corticosteroids, in addition to antibiotics, increase the likelihood of both resolution and improvement of pain in participants with sore throat. Further trials assessing corticosteroids in the absence of antibiotics and in children are warranted.


Vascular Changes Detected With Thoracic CT in Coronavirus Disease (COVID-19) Might Be Significant Determinants for Accurate Diagnosis and Optimal Patient Management.


title: Social Capital in the Response to COVID-19.

text: Social capital provides a number of benefits during crisis scenarios, and high social capital communities respond more efficaciously than those with low social capital. With this in mind, we argue that the response to and recovery from the COVID-19 pandemic may be hampered in many American communities by deficiencies or disruptions in social capital brought about by physical distancing. Drawing on evidence from past crises, we recommend individuals, communities, and government institutions work to strengthen and expand social networks. A failure to do so will exact a toll in terms of human morbidity and mortality and exacerbate the current disaster.


title: Laparoscopic resection of hepatoblastoma: report of a case.

text: Despite the increasing number of recent reports on laparoscopic resection of malignant liver tumors in adults, there have been few reports involving children. In this paper we discuss the laparoscopic resection of a hepatoblastoma in a 1-year-old boy. The CT scan revealed an exophytic hepatic tumor on S5 measuring 6 × 5 × 4 cm after preoperative chemotherapy. The operation time was 225 min with an estimated blood loss of about 38 mL; intraoperative transfusion was not required. Radiofrequency-assisted precoagulation was performed. The patient had an uncomplicated recovery and started postoperative chemotherapy on postoperative day 12. Our literature search revealed only five reported cases of laparoscopic resection of hepatoblastoma in which there was no postoperative complication or recurrence. Laparoscopic resection of a hepatoblastoma in a selected subgroup of patients can be safe and feasible.


title: S1 gene sequence analysis of new variant isolates of avian infectious bronchitis virus in Tunisia.

text: Purpose Tissue samples were collected from suspected broiler flocks showing respiratory signs to identify infectious bronchitis virus (IBV), characterize emerging field strains, and study their relationships with the Massachusetts H120 strain, the only IB vaccine used in Tunisia. Samples and methods Several IBV isolates were identified from field samples collected from flocks located in different regions in the northeast of Tunisia. The IBV isolates were characterized and compared to commonly used vaccine strains (including 793B, D274, and H120 types), other reference IBV strains from Europe, and the recently characterized Tunisian field variants TN20/00, TN200/01, and TN335/01. Reverse transcription-polymerase chain reaction and nucleotide sequencing analyses of the hypervariable regions of the S1 gene were carried out. Results Four new IBV variants were isolated during the period 2007-10 and were designated TN295/07, TN296/07, TN556/07, and TN557/07. The amino acid sequence data showed 100% similarity between TN295/07 and TN296/07, suggesting that these two isolates are identical and belong to the same genotype. Similar results were demonstrated for TN556/07 and TN557/07. Sequence identity values indicated that TN296/07 and TN556/07 share 55% amino acid homologies between each other, but are very different from the reference IBV serotypes, in particular the H120 strain. It was also shown that they have 50%-77% similarities with the Tunisian virus isolated between 2000 and 2001. Phylogenetic clustering allowed classification of these Tunisian isolates as new genotypes that are closer to TN200/01, TN335/01 Tunisian field variants, and Italy02 variant than MassH120 vaccine strain. Conclusion S1 sequence analyses confirmed the cocirculation of H120 vaccine strain with novel IBV variants isolated from Tunisian field.


title: Target lesion failure with BRS? good old DES to the rescue.

text: Target lesion revascularization (TLR) for BRS failure is burdened with a high rate of adverse events. DES implantation appears to be the safest treatment option following BRS failure. A real world observational study with a minimum of 2-year follow-up would be required to investigate the long-term clinical outcomes in patients with a BRS failure and to assess the best treatment option in case of TLR.


title: Use of pioglitazone in people with type 2 diabetes mellitus with coronavirus disease 2019 (COVID-19): Boon or bane?

text: BACKGROUND AND AIMS People with type 2 diabetes mellitus (T2DM) have increased morbidity and mortality due to coronavirus disease-19(COVID-19). It has been speculated that use of pioglitazone might increase such risk. The aim of our brief commentary is to review the safety of pioglitazone in people with T2DM and mild/moderate COVID-19. METHODS We searched PubMed database using specific keywords related to our aims till May 15, 2020. Full text of relevant articles published in English language were retrieved and reviewed. RESULTS Medications, including pioglitazone, that upregulate tissue expression of angiotensin converting enzyme 2 (ACE2), might have a dual role in COVID-19; on the one hand they might increase risk of infection as SARS-CoV2 uses ACE2 as a coreceptor to enter alveolar cells, but on the other hand, by reducing angiotensin II levels, they can protect against acute lung injury. There is no evidence to date that pioglitazone upregulates ACE2 in the alveolar cells; rather, there is evidence from animal studies of upregulation of ACE2 in insulin sensitive tissues, which might have a protective effect on lung injury. Moreover by moderating the exaggerated host proinflammatory response, pioglitazone can potentially reduce SARS-CoV-2 driven hyperinflammation. CONCLUSIONS Pioglitazone has more potential for benefit than harm, and can be continued in people with T2DM and mild/moderate COVID-19, unless there are specific contraindications for its use. There is an urgent need to assess clinically relevant outcomes in people with diabetes and COVID-19 based upon baseline antidiabetes therapy, in particular pioglitazone.


Factors associated with COVID-19 outbreak-related suicides in India.


title: Survival after Endoscopic Valve Therapy in Patients with Severe Emphysema.

text: BACKGROUND Endoscopic valve therapy leads to an improvement of lung function, exercise tolerance, and quality of life in a selected cohort of patients with advanced emphysema. So far, only few data exist on the long-term outcome. OBJECTIVES This analysis evaluated the impact of valve therapy on the survival of emphysema patients. METHODS Survival rates of emphysema patients who underwent valve therapy were assessed according to their radiological outcome following valve placement. RESULTS From 2005 to 2013, 449 emphysema patients (mean age 64 ± 7 years) underwent valve therapy and were followed for a mean time of 37.3 ± 21.3 months. A total of 128 patients (29%) developed complete lobar atelectasis, 34 out of these also experienced a pneumothorax; 50 patients (11%) developed pneumothorax without lobar atelectasis, and 261 patients (58%) target lobe volume reduction or no volume change. Patients with atelectasis showed significantly better baseline forced expiratory volume in 1 second (%), residual volume (L), total lung capacity (L), and transfer factor for carbon monoxide (%; all p < 0.05), but there was no significant difference in the BODE score (p = 0.195). Patients with valve-induced lobar atelectasis had a significant survival benefit compared to patients without atelectasis (p = 0.009; 5-year survival rate 65.3 vs. 43.9%). The advent of pneumothorax in 84 patients did not influence survival (p = 0.52). CONCLUSIONS Lobar atelectasis following endoscopic valve therapy is associated with a survival benefit.


title: Analysis of endovascular treatment of ruptured microaneurysms compared with ruptured larger aneurysms.

text: OBJECTIVE To retrospectively analyze the complications and outcome of the endovascular treatment of ruptured microaneurysms compared with the treatment of ruptured larger aneurysms. METHODS 40 ruptured cerebral microaneurysms treated by endovascular techniques were selected retrospectively and compared with 207 larger ruptured cerebral aneurysms treated by endovascular techniques during the same time period. Medical charts and imaging studies were reviewed to analyze baseline clinical and epidemiologic characteristics, procedural complications, and clinical outcomes RESULTS: Cerebral microaneurysms had a higher incidence of intraoperative technical ruptures (13.5% vs 2.9%, p<0.005). The number of thromboembolic complications was not increased. Patient prognosis was similar for the two groups (mean modified Rankin Scale score 1.81 vs 2.09, p>0.1). CONCLUSIONS Coiling of cerebral microaneurysms has a reasonable safety profile with good clinical outcomes, similar to coiling of larger aneurysms. In our experience, the systematic use of remodeling balloons, operator experience, and the ability to manage complications are the reasons for the satisfactory results.


title: Y90 Radioembolization in chemo-refractory metastastic, liver dominant colorectal cancer patients: outcome assessment applying a predictive scoring system.

text: BACKGROUND In treatment-refractory liver dominant metastatic colorectal cancer, the role of liver directed therapies still is unclear. We sought to determine a prognostic score for Y90 radioembolization in these patients. METHODS We analyzed 106 patients with refractory liver dominant mCRC who had undergone a total of 178 Y90 radioembolizations with resin microspheres was collected. Potential factors influencing survival were analyzed using a Cox regression. The Log rank test served to establish prognostic factors and to form a clinical score for outcome prediction after Y90 radioembolization. RESULTS Median survival of all patients was 6.7 months. Neither age nor prior surgical or systemic therapy nor metastatic spread had an effect on survival. In contrast, hepatic tumor load, Karnofsky index as well as CEA and CA19-9 serums level had a significant influence (p < 0.001, p = 0.037, p = 0.023 and p < 0.001, respectively). These three factors formed a score with 1 point each for tumor load >20 %, CEA >130 ng/ml or CA19-9 > 200U/ml and Karnofsky index <80 %. Patients with a score of 0 and 1 displayed a median OS of 10.4 months. Patients with a score of 2 and 3 demonstrated a median OS of 5.1 months only (p < 0.001). CONCLUSION Overaggressive patient selection for Y90 radioembolization of liver dominant chemorefractory mCRC is of questionable benefit. A scoring system comprising hepatic tumor load, CEA and CA19-9 serum levels and Karnofsky index (TuCK-score) may support an improved patient selection. In our cohort of liver only versus liver dominant disease, extrahepatic lung or lymphatic metastases did not significantly alter the prognosis.


The COVID-19 pandemonium pandemic.


title: Endocrine vigilance in COVID-19.

text: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a novel coronavirus responsible for a pandemic that emerged in December 2019. Heterogeneous clinical forms are described from asymptomatic to severe hypoxaemic acute respiratory syndrome with multisystem organ failure. The impact of this coronavirus disease 2019 on the endocrine glands remains unknown. However, the results of previous studies on viruses from the same family allow us to write proposals for patients followed for chronic endocrine diseases. Currently, if these subjects are infected with SARS-CoV-2, they must not stop their treatment. In some cases, hormone replacement doses have to be increased. In case of worsening clinical signs, hormonal biological monitoring must be done. This article will be helpful for improving the management of chronic endocrine diseases that could affect thyroid, adrenals, gonads and pituitary gland functions. Proposals could be applied in COVID-19 infected subjects or in those who have been in contact with COVID-19 infected people.


title: Impact of coronary lesion complexity on drug-eluting stent outcomes in patients with and without diabetes mellitus: analysis from 18 pooled randomized trials.

text: OBJECTIVES The aim of this study was to investigate whether baseline lesion complexity affects drug-eluting stent (DES) outcomes according to diabetic status. BACKGROUND Previous studies have reported conflicting results regarding DES safety and efficacy in patients with and without diabetes mellitus (DM). METHODS Patient-level data from 18 prospective randomized trials were pooled. DES treatment outcomes in patients with versus without DM were analyzed in 2 propensity score-matched groups further stratified according to lesion complexity (American College of Cardiology and American Heart Association class A/B1 vs. B2/C). Remaining baseline differences were adjusted for by multivariate analysis. RESULTS DM was present in 3,467 of 18,441 patients (18.8%). DM was a predictor of 1-year repeat revascularization (target lesion revascularization: hazard ratio: 1.34; 95% confidence interval: 1.05 to 1.70; target vessel revascularization: hazard ratio: 1.40; 95% confidence interval: 1.15 to 1.72) and cardiac death or myocardial infarction (hazard ratio: 1.40; 95% confidence interval: 1.09 to 1.81). Rates of target lesion and target vessel revascularization were significantly higher in patients with versus those without DM with type B2/C lesions (8.0% vs. 4.5% and 10.6% vs. 5.9%, respectively, p < 0.0001 for both), but not in patients with only type A/B1 lesions (4.6% vs. 4.8%, p = 0.87, and 7.4% vs. 6.8%, p = 0.47, respectively), with a significant interaction between DM and lesion type observed for both endpoints (p = 0.01 and p = 0.02, respectively). No interaction was observed for death or myocardial infarction (p = 0.28). CONCLUSIONS In the DES era, patients with DM remain at increased risk for cardiac death or myocardial infarction. However, DM is a risk factor for repeat revascularization only in those patients with complex lesions; patients with DM and noncomplex lesions have similar rates of 1-year freedom from repeat revascularization as do patients without DM.


Age matters for cardiac arrests? No meaningful interpretation of results is possible without understanding context.


title: Utilization of antidepressants in Taiwan: a nationwide population-based survey from 2000 to 2009.

text: OBJECTIVE This study examined trends in antidepressant utilization in Taiwan between 2000 and 2009. METHODS We collected data from the National Health Insurance Research Database of all incident antidepressant use. We described the incidence, prevalence, and therapeutic indications of antidepressant use. We tested the trends by using logistic regression analyses with adjustment for age and sex. RESULTS Overall, the prevalence of antidepressant use per 1000 persons increased from 32.1 in 2000 to 46.3 in 2009; however, the incidence per 1000 persons declined from 20.8 in 2000 to 16.5 in 2009. For antidepressant classes, the prescriptions of selective serotonin reuptake inhibitors and other new agents increased during the study periods; however, the use of tricyclic antidepressants, trazodone, and monoamine oxidase inhibitors declined. For therapeutic indications, we found increasing trends of antidepressant use for sleep and adjustment disorders; however, the rates of antidepressant use for mood disorder, anxiety disorders, and non-psychiatric conditions decreased. CONCLUSIONS Regarding the new use of antidepressants in Taiwan between 2000 and 2009, we found that the decreased incidence of antidepressant use might be attributed mainly to the decreased use of tricyclic antidepressants and monoamine oxidase inhibitors. Decreased use among middle-aged and older persons and fewer antidepressant prescriptions for non-psychiatric conditions were also noted.


Topic: Abdominal Wall Hernia - Abdominal wall closure.


title: Molecular cloning, characterization, and bioactivity analysis of interleukin 18 in giant panda (Ailuropoda melanoleuca).

text: Interleukin 18 (IL-18), as a member of IL-1 superfamily, is an important pleiotropic cytokine that modulates Th1 immune responses. In this report, we cloned and identified a homolog of IL-18 in giant panda (Ailuropoda melanoleuca) (designated as AmIL-18) from peripheral blood mononuclear cells stimulated with lipopolysaccharide. The open readin g frame of AmIL-18 cDNA is 579 bp encoding a deduced protein of 192 amino acids. AmIL-18 gDNA fragments contained 5 exons and 4 introns. The amino acid sequence of AmIL-18 shared 23.9 to 87.0% identity with other species. To evaluate the effects of AmIL-18 on the immune response, we expressed the recombinant AmIL-18 in Escherichia coli BL21 (DE3). The fusion protein PET-AmIL-18 was purified by nickel affinity column chromatography and verified by sodium dodecyl sulfate polyacrylamide gel electrophoresis and Western blot analysis. The biological function of purified PET-AmIL-18 was determined on mouse splenocytes by quantitative real-time polymerase chain reaction. INF-γ and other cytokines were increased when stimulated by PET-AmIL-18, particularly when combined with recombinant human interleukin 12, while a Th2-type cytokine, interleukin-4, was strikingly suppressed. These results will provide information for the potential use of recombinant proteins to manipulate the immune response in giant pandas and facilitate the study to protect this treasured species.


title: Detection of feline coronavirus spike gene mutations as a tool to diagnose feline infectious peritonitis.

text: Objectives Feline infectious peritonitis (FIP) is an important cause of death in the cat population worldwide. The ante-mortem diagnosis of FIP in clinical cases is still challenging. In cats without effusion, a definitive diagnosis can only be achieved post mortem or with invasive methods. The aim of this study was to evaluate the use of a combined reverse transcriptase nested polymerase chain reaction (RT-nPCR) and sequencing approach in the diagnosis of FIP, detecting mutations at two different nucleotide positions within the spike (S) gene. Methods The study population consisted of 64 cats with confirmed FIP and 63 cats in which FIP was initially suspected due to similar clinical or laboratory signs, but that were definitively diagnosed with another disease. Serum/plasma and/or effusion samples of these cats were examined for feline coronavirus (FCoV) RNA by RT-nPCR and, if positive, PCR products were sequenced for nucleotide transitions within the S gene. Results Specificity of RT-nPCR was 100% in all materials (95% confidence interval [CI] in serum/plasma 83.9-100.0; 95% CI in effusion 93.0-100.0). The specificity of the sequencing step could not be determined as none of the cats of the control group tested positive for FCoV RNA. Sensitivity of the 'combined RT-nPCR and sequencing approach' was 6.5% (95% CI 0.8-21.4) in serum/plasma and 65.3% (95% CI 50.4-78.3) in effusion. Conclusions and relevance A positive result is highly indicative of the presence of FIP, but as none of the control cats tested positive by RT-nPCR, it was not possible to confirm that the FCoV mutant described can only be found in cats with FIP. Further studies are necessary to evaluate the usefulness of the sequencing step including FCoV-RNA-positive cats with and without FIP. A negative result cannot be used to exclude the disease, especially when only serum/plasma samples are available.


Five legal preparedness challenges for responding to future public health emergencies.


title: Totally extraperitoneal inguinal hernia repair with or without fixation leads to similar results. Outcome of randomized prospective trial.

text: Introduction The use of implants in inguinal hernia repair has reduced its recurrence rate. However, postoperative groin pain still remains an unresolved problem. There are suggestions that in totally extraperitoneal inguinal hernia repair (TEP-IHR) two of the likely factors responsible for pain are use of fixation and the type of fixation used. Aim To evaluate the impact of mesh fixation on the incidence of postoperative pain, restriction of physical activities, hernia recurrence risk, return to normal activities and demand for analgesics in patients after unilateral TEP-IHR. Material and methods Unilateral TEP-IHR was performed in 139 male patients randomized to three groups: self-gripping mesh (SG), lightweight mesh (L) and lightweight mesh with fixation (LF). Full study-inclusion criteria were met by 110 patients; 43, 18 and 49 in groups SG, L and LF respectively. Follow-up occurred on the 1st, 2nd, and 7th day and 3, 6, 12 months postoperatively. The numeric rating scale (NRS) was used to assess pain and the EuraHS-QoL (European Registry for Abdominal Wall Hernias Quality of Life Score) questionnaire to compare quality of life (QoL) prior to surgery and one year later. Results No statistically significant differences were observed between study groups with regard to the incidence rate and intensity of acute post-operative pain, chronic pain, analgesic demand, return to normal activity, hernia recurrence rate and post-operative QoL. Conclusions Lack of fixation in TEP-IHR does not increase the risk of hernia recurrence, and its presence does not significantly worsen the treatment results; especially it does not increase the incidence of chronic pain.


Postpartum exacerbation of antenatal COVID-19 pneumonia in 3 women.


title: Local management of rectal neoplasia.

text: The treatment of rectal neoplasia, whether benign or malignant, challenges the surgeon. The challenge in treating rectal cancer is selecting the proper approach for the appropriate patient. In a small number of rectal cancer patients local excision may be the best approach. In an attempt to achieve two goals-cure of disease with a low rate of local failure and maintenance of function and quality of life-multiple approaches can be utilized. The key to obtaining a good outcome for any one patient is balancing the competing factors that impact on these goals. Any effective treatment aimed at controlling rectal cancer in the pelvis must take into account the disease in the bowel wall itself and the disease, or potential disease, in the mesorectum. The major downside of local excision techniques is the potential of leaving untreated disease in the mesorectum. Local management techniques avoid the potential morbidity, mortality, and functional consequences of a major abdominal radical resection and are thus quite effective in achieving the maintenance of function and quality of life goal. The issue for the transanal techniques is how they fare in achieving the first goal-cure of the cancer while keeping local recurrence rates to an absolute minimum. Without removing both the rectum and the mesorectum there is no completely accurate way to determine whether a rectal cancer has moved outside the bowel wall, so any decision on local management of a rectal neoplasm is a calculated risk. For benign neoplasia, the challenge is removing the lesion without having to resort to a major abdominal procedure.


title: Extended Lifetime In Vivo Pulse Stimulated Ultrasound Imaging.

text: An on-demand long-lived ultrasound contrast agent that can be activated with single pulse stimulated imaging (SPSI) has been developed using hard shell liquid perfluoropentane filled silica 500-nm nanoparticles for tumor ultrasound imaging. SPSI was tested on LnCAP prostate tumor models in mice; tumor localization was observed after intravenous (IV) injection of the contrast agent. Consistent with enhanced permeability and retention, the silica nanoparticles displayed an extended imaging lifetime of 3.3±1 days (mean±standard deviation). With added tumor specific folate functionalization, the useful lifetime was extended to 12 ± 2 days; in contrast to ligand-based tumor targeting, the effect of the ligands in this application is enhanced nanoparticle retention by the tumor. This paper demonstrates for the first time that IV injected functionalized silica contrast agents can be imaged with an in vivo lifetime ~500 times longer than current microbubble-based contrast agents. Such functionalized long-lived contrast agents may lead to new applications in tumor monitoring and therapy.


Are we aware of potential interactions between drugs used in lung cancer and drugs used in the treatment of COVID-19?


Reply: Research and Therapeutic Nihilisms in Chronic Kidney Disease.


title: Ca2+ ions promote fusion of Middle East respiratory syndrome coronavirus with host cells and increase infectivity.

text: Fusion with, and subsequent entry into, the host cell is one of the critical steps in the life cycle of enveloped viruses. For Middle East respiratory syndrome coronavirus (MERS-CoV), the spike protein (S) is the main determinant of viral entry. Proteolytic cleavage of S exposes its fusion peptide (FP), which initiates the process of membrane fusion. Previous studies on the related severe acute respiratory syndrome coronavirus (SARS-CoV) FP have shown that calcium ions (Ca2+) play an important role for fusogenic activity via a Ca2+ binding pocket with conserved glutamic acid (E) and aspartic acid (D) residues. SARS-CoV and MERS-CoV FP share a high sequence homology and here, we investigated whether Ca2+ is required for MERS-CoV fusion by screening a mutant array in which E and D residues in the MERS-CoV FP were substituted with neutrally charged alanines (A). Upon verifying mutant cell surface expression and proteolytic cleavage, we tested their ability to mediate infection of pseudo-particles (PPs) on host cells in modulating Ca2+ environments. Our results demonstrate that intracellular Ca2+ enhances MERS-CoV WT PPs infection by approximately two-fold and that E891 is a crucial residue for Ca2+ interaction. Subsequent electron spin resonance (ESR) experiments revealed that this enhancement could be attributed to Ca2+ increasing MERS-CoV FP fusion-relevant membrane ordering. Intriguingly, isothermal calorimetry showed an approximate 1:1 MERS-CoV FP to Ca2+ ratio, as opposed to an 1:2 SARS-CoV FP to Ca2+ ratio, suggesting significant differences in FP Ca2+ interactions of MERS-CoV and SARS-CoV FP despite their high sequence similarity.SignificanceMERS-CoV is a major emerging infectious disease with zoonotic potential and a reservoir in dromedary camels and bats. Since its first outbreak in 2012, the virus has repeatedly transmitted from camels to humans with 2,468 confirmed cases causing 851 deaths. To date, there are no efficacious drugs and vaccines against MERS-CoV, increasing its potential to cause a public health emergency. In order to develop novel drugs and vaccines, it is important to understand the molecular mechanisms that enable the virus to infect host cells. Our data has found that calcium is an important regulator of viral fusion by interacting with negatively charged residues in the MERS-CoV FP region. This can guide therapeutic solutions to either block this calcium interaction and also repurpose already approved drugs for this use for a fast response to MERS-CoV outbreaks.


title: Single-incision laparoscopic sleeve gastrectomy versus conventional multiport laparoscopic sleeve gastrectomy: technical considerations and strategic modifications.

text: BACKGROUND Since its inception, minimal access surgery has been a dynamic field, experiencing successive leaps in technique and instrumental design. Each improvement in minimal access surgery must demonstrate that patients benefit from the change in approach, without compromising the outcome. The present study presents the technical considerations and strategic modifications for single-incision laparoscopic sleeve gastrectomy. We also compared the newly adopted single-incision laparoscopic approach with conventional multiport laparoscopic sleeve gastrectomy. METHODS Of the 26 patients included in the present study, 14 underwent single-incision laparoscopic sleeve gastrectomy and 12 underwent conventional multiport sleeve gastrectomy. All procedures were performed by the same surgeon (A.A.S.) during a 12-month period from September 2008 to August 2009 at Michigan State University Kalamazoo Center for Medical Studies. RESULTS The Mann-Whitney U tests showed with 95% confidence that the difference in pain scores and length of hospital stay in the single-incision laparoscopic sleeve gastrectomy group were statistically significant. A modest increase occurred in the operative time in the single-incision laparoscopic sleeve gastrectomy group. This difference was the least statistically significant of all variables (P = .055). CONCLUSION Single-incision laparoscopic sleeve gastrectomy was associated with less postoperative pain, a lower need for analgesia, and a decreased length of hospital stay compared with conventional multiport laparoscopic sleeve gastrectomy. This was achieved without decreasing the quality of surgery or the outcomes offered by the conventional multiport counterpart.


title: COVID-19: A Review for the Pediatric Neurologist.

text: Children are susceptible to infection with the novel coronavirus SARS-CoV-2. In this time of uncertainty, this review attempts to compile information that may be helpful to pediatric neurologists. This review consolidates current data on the disease associated with SARS-CoV-2, called COVID-19, and information from past coronavirus epidemics, to discuss diseases of pediatric neurology including Guillain-Barre syndrome (acute inflammatory demyelinating polyradiculoneuropathy); central demyelinating diseases like multiple sclerosis and acute disseminated encephalomyelitis; infantile spasms; febrile seizures; and maternal-fetal transmission of virus.


COVID-19: An unprecedented pandemia with a potential arrhythmic undertone.


Long-term risk of adenocarcinoma post-ileal pouch-anal anastomosis for ulcerative colitis: report of two cases and review of the literature.


Three cases of small bowel obstruction after laparoscopic ventral rectopexy using the V-Loc(®) suture.


title: 18F-FDG PET/CT for detection of metastatic infection in gram-positive bacteremia.

text: UNLABELLED The timely detection of metastatic infectious foci in gram-positive bacteremia is crucial, because these foci often require prolonged antibiotic treatment or drainage. The diagnosis of metastatic infectious foci is difficult because localizing symptoms are often absent. We investigated whether (18)F-FDG PET/CT was able to detect such foci and whether detection influenced clinical outcome. METHODS One hundred fifteen nonneutropenic patients with gram-positive bacteremia were prospectively included. Patients with positive blood cultures growing Staphylococcus aureus, Streptococcus species, or Enterococcus species were eligible when a risk factor for developing metastatic infectious foci was present. (18)F-FDG PET/CT was performed within 2 wk after the first positive blood culture. Abnormal (18)F-FDG uptake had to be confirmed by radiologic, microbiologic, or pathologic studies. Results were compared with a matched historical control group of 230 patients in whom no (18)F-FDG PET/CT was performed. RESULTS Significantly more patients were diagnosed with metastatic foci in the study group (67.8% vs. 35.7%). Of the imaging investigations performed, (18)F-FDG PET/CT was the first to delineate infectious foci in 35 patients (30%). In the remaining 70%, either symptoms on physical examination or other imaging techniques first revealed infectious foci. The sensitivity, specificity, negative predictive value, and positive predictive value of (18)F-FDG PET/CT were 100%, 87%, 100%, and 89%, respectively. Relapse rates decreased from 7.4% to 2.6% among study patients (P = 0.09) and from 8.9% to 1.4% in patients with S. aureus (P = 0.04). Overall mortality after 6 mo decreased from 32.2% to 19.1% in the (18)F-FDG PET/CT group (P = 0.014). CONCLUSION In the diagnostic work-up of high-risk patients with gram-positive bacteremia, (18)F-FDG PET/CT is a valuable technique that results in lower mortality rates. In patients with S. aureus bacteremia, relapse rates decreased significantly after the addition of (18)F-FDG PET/CT.


title: Robotic kidney transplantation with intraoperative regional hypothermia.

text: OBJECTIVE To describe a novel and reproducible technique of robotic kidney transplantation (RKT) that requires no repositioning, and permits intraoperative regional hypothermia. PATIENTS AND METHODS A GelPOINT™ (Applied Medical, Santa Ranchero, CA, USA) access port was used for delivery of ice-slush and introduction of the graft kidney. The new RKT technique using ice-slush has been performed in 39 patients. RESULTS At a mean follow-up of 3 months all of the grafts functioned. There was a marked reduction in pain and analgesic requirement compared with patients undergoing open KT, with a propensity towards quicker graft recovery and lower complication rate. CONCLUSION RKT has been shown to be safe and feasible in patients undergoing living-donor related KT. A prospective trial is underway to assess outcomes definitively.


title: Prospective Analysis Regarding Health-Related Quality of Life (HR-QOL) between Morbid Obese Patients Following Bariatric Surgery Versus on a Waiting List.

text: BACKGROUND Major impairment of health-related quality of life (HRQoL) is one of the main reasons why obese patients request surgical treatment. OBJECTIVE To prospectively analyze the impact of HRQoL between obese patients who underwent surgery and those who were wait-listed. METHODS Between April 2017 and March 2018, 70 surgical and 69 wait-listed patients were interviewed twice, at baseline and at the 12-month follow-up. Quality of life was measured by the SF-12v2 and the Impact of Weight on Quality of Life-Lite (IWQoL-Lite) questionnaires. Sociodemographic-, clinical-, and surgical-related variables were collected. RESULTS One hundred thirty-nine patients were analyzed, showing similar baseline characteristics but differences in HRQoL. Performing more qualified work improved scores on some aspects of the SF-12 survey. In contrast, women scored worse on the self-esteem domain, and men scored worse on the mental health domain. By group, at the 12-month follow-up, statistically significant differences were found among all aspects of the questionnaires between both groups (P < 0.001) and between baseline and postoperative 12-month follow-up in the surgical group (P < 0.001). Furthermore, scores were lower in all domains in the evolution of wait-listed patients, with statistically significant differences among the Bodily Pain, Emotional Role, Mental Health, and Mental Component Summary Domains (P < 0.05). CONCLUSION HRQoL is a multimodal concept that allows the identification of factors impacting obese patients' quality of life. It promotes the benefit of surgery against waiting list delays, which can take up to 4 years in our hospital. Therefore, HRQoL is an important pillar to justify more resources for reducing unacceptable surgical delays.


title: Bartonella quintana and Typhus Group Rickettsiae Exposure among Homeless Persons, Bogotá, Colombia.

text: In 2015, we investigated Bartonella quintana and typhus group rickettsiae in body lice from homeless persons in Bogotá, Colombia. We found B. quintana-infected body lice and seroprevalence of this microorganism in 19% of homeless persons and typhus group rickettsiae in 56%. Public health professionals should start preemptive measures and active vector control.


title: Endothelial dysfunction and specific inflammation in obesity hypoventilation syndrome.

text: BACKGROUND Obesity hypoventilation syndrome (OHS) is associated with increased cardiovascular morbidity. What moderate chronic hypoventilation adds to obesity on systemic inflammation and endothelial dysfunction remains unknown. QUESTION To compare inflammatory status and endothelial function in OHS versus eucapnic obese patients. METHODOLOGY 14 OHS and 39 eucapnic obese patients matched for BMI and age were compared. Diurnal blood gazes, overnight polysomnography and endothelial function, measured by reactive hyperemia peripheral arterial tonometry (RH-PAT), were assessed. Inflammatory (Leptin, RANTES, MCP-1, IL-6, IL-8, TNFalpha, Resistin) and anti-inflammatory (adiponectin, IL-1Ra) cytokines were measured by multiplex beads immunoassays. PRINCIPAL FINDINGS OHS exhibited a higher PaCO(2), a lower forced vital capacity (FVC) and tended to have a lower PaO(2) than eucapnic obese patients. (HS)-CRP, RANTES levels and glycated haemoglobin (HbA1c) were significantly increased in OHS (respectively 11.1+/-10.9 vs. 5.7+/-5.5 mg x l(-1) for (HS)-CRP, 55.9+/-55.3 vs 23.3+/-15.8 ng/ml for RANTES and 7.3+/-4.3 vs 6.1+/-1.7 for HbA1c). Serum adiponectin was reduced in OHS (7606+/-2977 vs 13,660+/-7854 ng/ml). Endothelial function was significantly more impaired in OHS (RH-PAT index: 0.22+/-0.06 vs 0.51+/-0.11). CONCLUSIONS Compared to eucapnic obesity, OHS is associated with a specific increase in the pro-atherosclerotic RANTES chemokine, a decrease in the anti-inflammatory adipokine adiponectin and impaired endothelial function. These three conditions are known to be strongly associated with an increased cardiovascular risk. TRIAL REGISTRATION ClinicalTrials.gov NCT00603096.


title: The outbreak that was always here: Racial trauma in the context of COVID-19 and implications for mental health providers.

text: The present commentary offers a timely exploration of the racial trauma experienced by Asian, Black, and Latinx communities as it relates to COVID-19. Instances of individual, cultural, and structural racism and implications for mental health are discussed. Evidence-based strategies are identified for mental health professionals in order to support healing and mitigate the risk of further racial traumas. (PsycInfo Database Record (c) 2020 APA, all rights reserved).


title: Silodosin for the treatment of lower urinary tract symptoms in men with benign prostatic hyperplasia.

text: BACKGROUND A variety of alpha-blockers are used for treating lower urinary tract symptoms (LUTS) in men with benign prostatic hyperplasia (BPH). Silodosin is a novel, more selective alpha-blocker, which is specific to the lower urinary tract and may have fewer side effects than other alpha-blockers. OBJECTIVES To assess the effects of silodosin for the treatment of LUTS in men with BPH. SEARCH METHODS We performed a comprehensive search using multiple databases (Cochrane Library, MEDLINE, EMBASE, Scopus, Google Scholar, and Web of Science), trials registries, other sources of grey literature, and conference proceedings with no restrictions on the language of publication or publication status up until 13 June 2017. SELECTION CRITERIA We included all parallel, randomized controlled trials. We also included cross-over designs. DATA COLLECTION AND ANALYSIS Two review authors independently classified studies and abstracted data from the included studies. We performed statistical analyses using a random-effects model and interpreted them according to the Cochrane Handbook for Systematic Reviews of Interventions. We rated the quality of evidence according to the GRADE approach. MAIN RESULTS We included 19 unique studies with 4295 randomized participants across four comparisons for short-term follow-up. The mean age, prostate volume, and International Prostate Symptom Score were 66.5 years, 38.2 mL, and 19.1, respectively. Silodosin versus placeboBased on four studies with a total of 1968 randomized participants, silodosin may reduce urologic symptom scores in an appreciable number of men (mean difference (MD) -2.65, 95% confidence interval (CI) -3.23 to -2.08; low-quality evidence). Silodosin likely does not result in a clinically important reduction in quality of life (MD -0.42, 95% CI -0.71 to -0.13; moderate-quality evidence). It may not increase rates of treatment withdrawal for any reason (relative risk (RR) 1.08, 95% CI 0.70 to 1.66; low-quality evidence). We are uncertain about the effect of silodosin on cardiovascular adverse events (RR 1.28, 95% CI 0.67 to 2.45; very low-quality evidence). Silodosin likely increases sexual adverse events (RR 26.07, 95% CI 12.36 to 54.97; moderate-quality evidence); this would result in 180 more sexual adverse events per 1000 men (95% CI 82 more to 388 more). Silodosin versus tamsulosinBased on 13 studies with a total of 2129 randomized participants, silodosin may result in little to no difference in urologic symptom scores (MD -0.04, 95% CI -1.31 to 1.24; low-quality evidence) and quality of life (MD -0.15, 95% CI -0.53 to 0.22; low-quality evidence). We are uncertain about treatment withdrawals for any reason (RR 1.02, 95% CI 0.62 to 1.69; very low-quality evidence). Silodosin may result in little to no difference in cardiovascular adverse events (RR 0.77, 95% CI 0.53 to 1.12; low-quality evidence). Silodosin likely increases sexual adverse events (RR 6.05, 95% CI 3.55 to 10.31; moderate-quality evidence); this would result in 141 more sexual adverse events per 1000 men (95% CI 71 more to 261 more). Silodosin versus naftopidilBased on five studies with a total of 763 randomized participants, silodosin may result in little to no differences in urologic symptom scores (MD -0.85, 95% CI -2.57 to 0.87; low-quality evidence), quality of life (MD -0.17, 95% CI -0.60 to 0.27; low-quality evidence), treatment withdrawal for any reason (RR 1.25, 95% CI 0.81 to 1.93; low-quality evidence), and cardiovascular adverse events (RR 1.02, 95% CI 0.41 to 2.56; low-quality evidence). Silodosin likely increases sexual adverse events (RR 5.93, 95% CI 2.16 to 16.29; moderate-quality evidence); this would result in 74 more sexual adverse events per 1000 men (95% CI 17 more to 231 more). Silodosin versus alfuzosinBased on two studies with a total of 155 randomized participants, silodosin may or may not result in a clinically important increase in urologic symptom scores (MD 3.83, 95% CI 0.12 to 7.54; low-quality evidence). Silodosin likely results in little to no difference in quality of life (MD 0.14, 95% CI -0.46 to 0.74; moderate-quality evidence). We found no event of treatment withdrawal for any reason. Silodosin may not reduce cardiovascular adverse events (RR 0.67, 95% CI 0.36 to 1.24; low-quality evidence) but likely increases sexual adverse events (RR 37.21, 95% CI 5.32 to 260.07; moderate-quality evidence); this would result in 217 more sexual adverse events per 1000 men (95% CI 26 more to 1000 more). AUTHORS' CONCLUSIONS Silodosin may reduce urologic symptom scores in an appreciable number of men compared to placebo. Quality of life and treatment withdrawals for any reason appears similar. Its efficacy appears similar to that of other alpha blockers (tamsulosin, naftopidil and alfuzosin) but the rate of sexual side effects is likely higher. Our certainty in the estimates of effect was lowered due to study limitations, inconsistency and imprecision.


title: Why continuing uncertainties are no reason to postpone challenge trials for coronavirus vaccines.

text: To counter the pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), some have proposed accelerating SARS-CoV-2 vaccine development through controlled human infection (or 'challenge') trials. These trials would involve the deliberate exposure of relatively few young, healthy volunteers to SARS-CoV-2. We defend this proposal against the charge that there is still too much uncertainty surrounding the risks of COVID-19 to responsibly run such a trial.


title: Imaging Features of Radiofrequency Ablation with Heat-Deployed Liposomal Doxorubicin in Hepatic Tumors.

text: INTRODUCTION The imaging features of unresectable hepatic malignancies in patients who underwent radiofrequency ablation (RFA) in combination with lyso-thermosensitive liposomal doxorubicin (LTLD) were determined. MATERIALS AND METHODS A phase I dose escalation study combining RFA with LTLD was performed with peri- and post- procedural CT and MRI. Imaging features were analyzed and measured in terms of ablative zone size and surrounding penumbra size. The dynamic imaging appearance was described qualitatively immediately following the procedure and at 1-month follow-up. The control group receiving liver RFA without LTLD was compared to the study group in terms of imaging features and post-ablative zone size dynamics at follow-up. RESULTS Post-treatment scans of hepatic lesions treated with RFA and LTLD have distinctive imaging characteristics when compared to those treated with RFA alone. The addition of LTLD resulted in a regular or smooth enhancing rim on T1W MRI which often correlated with increased attenuation on CT. The LTLD-treated ablation zones were stable or enlarged at follow-up four weeks later in 69% of study subjects as opposed to conventional RFA where the ablation zone underwent involution compared to imaging acquired immediately after the procedure. CONCLUSION The imaging features following RFA with LTLD were different from those after standard RFA and can mimic residual or recurrent tumor. Knowledge of the subtle findings between the two groups can help avoid misinterpretation and proper identification of treatment failure in this setting. Increased size of the LTLD-treated ablation zone after RFA suggests the ongoing drug-induced biological effects.


Impact of the COVID-19 pandemic on interventional cardiology practice: results of the EAPCI survey.


title: Effectiveness and safety of n-butyl-2-cyanoacrylate medical adhesive for noninvasive patch fixation in laparoscopic inguinal hernia repair.

text: BACKGROUND Our purpose was to compare the recurrence rate and other clinical outcomes of laparoscopic (LS) transabdominal preperitoneal (TAPP) inguinal hernia repair using n-butyl-2-cyanoacrylate (NBCA) for mesh fixation with those of no mesh fixation and mesh fixation with titanium spiral tacks (ST). METHODS The medical records of patients who received LS TAPP inguinal hernia repair between 2009 and 2012 at our institution were reviewed. Patients were included if the received LS TAPP with either no mesh fixation, mesh fixation with NBCA only, fixation with ST only, or fixation with NBCA + ST. Outcome measures were operation time, postoperative length of stay, visual analogue scale (VAS) pain score 24 h after surgery, postoperative complications, and hernia recurrence. RESULTS A total of 1,027 TAPP cases were included. In 552 cases, meshes were fixed with NBCA only, in 89 cases only ST were used, in 47 cases ST and NBCA were used, and in 339 cases meshes were not fixed. The groups were comparable with respect to demographic and clinical characteristics. No surgical complications occurred in any group. VAS pain scores were significantly lower in the nonfixation and NBCA only groups (1.4 ± 0.6 and 1.3 ± 0.6, respectively) than in the ST and NBCA + ST groups (2.2 ± 0.9 and 2.2 ± 0.7, respectively; P = 0.001). The mean follow-up duration was ~19 months. At the final follow-up, no wound infections or hernia recurrences had occurred in any of the groups. No occurrence of chronic pain was noted in the nonfixation and NBCA only groups, whereas two cases (2.2%) were noted in the ST group and one case (2.1%) in the NBCA + ST group (P = 0.005). CONCLUSIONS The use of NBCA medical adhesive for noninvasive patch fixation in laparoscopic hernia repair (TAPP) is effective and safe.


Endoloop-assisted alignment--a simple, effective, cheap, and safe technique to aid specimen extraction following sleeve gastrectomy.


title: Rupture of the spleen following thoracoscopic spine surgery in a patient with chronic pancreatitis.

text: PURPOSE To highlight the perioperative risk of intracapsular haematoma of the spleen or splenic ruptures during thoracoscopic spine surgery in patients with chronic pancreatitis. METHODS A 38-year-old patient with an L1 burst fracture (AO A3.3) underwent a standard thoracoscopic corpectomy and replacement of the vertebral body with an extendable vertebral body replacement 10 days after posterior instrumentation of T12-L2. In patients history chronic abusive alcoholism with related diseases such as pancreatitis, followed by hemipancreatectomy was found. Six hours after the surgery, the patient became hemodynamically unstable. An emergency CT scan revealed a splenic rupture. Emergent splenectomy was performed. RESULTS After surgical treatment of the L1 burst fracture, a rupture of the spleen was detected. An immediate splenectomy was performed. At the 18-month follow-up, an unchanged stable position of the cage was observed on CT. CONCLUSIONS Due to its proximity to the thoracolumbar junction, the spleen is vulnerable to injury during spine surgery. If the patient has undergone previous intra-abdominal operations or chronic inflammation of the pancreas is found, special care of the spleen during the operation is necessary.


title: In Vivo Stabilized SB3, an Attractive GRPR Antagonist, for Pre- and Intra-Operative Imaging for Prostate Cancer.

text: PURPOSE The gastrin-releasing peptide receptor (GRPR), overexpressed on various tumor types, is an attractive target for receptor-mediated imaging and therapy. Another interesting approach would be the use of GRPR radioligands for pre-operative imaging and subsequent radio-guided surgery, with the goal to improve surgical outcome. GRPR radioligands were successfully implemented in clinical studies, especially Sarabesin 3 (SB3) is an appealing GRPR antagonist with high receptor affinity. Gallium-68 labeled SB3 has good in vivo stability, after labeling with Indium-111; however, the molecule shows poor in vivo stability, which negatively impacts tumor-targeting capacity. A novel approach to increase in vivo stability of radiopeptides is by co-administration of the neutral endopeptidase (NEP) inhibitor, phosphoramidon (PA). We studied in vivo stability and biodistribution of [111In]SB3 without/with (-/+) PA in mice. Furthermore, SPECT/MRI on a novel, state-of-the-art platform was performed. PROCEDURES GRPR affinity of SB3 was determined on PC295 xenograft sections using [125I]Tyr4-bombesin with tracer only or with increasing concentrations of SB3. For in vivo stability, mice were injected with 200/2000 pmol [111In]SB3 -/+ 300 μg PA. Blood was collected and analyzed. Biodistribution and SPECT/MRI studies were performed at 1, 4, and 24 h postinjection (p.i.) of 2.5 MBq/200 pmol or 25 MBq/200 pmol [111In]SB3 -/+ 300 μg PA in PC-3-xenografted mice. RESULTS SB3 showed high affinity for GRPR (IC50 3.5 nM). Co-administration of PA resulted in twice higher intact peptide in vivo vs [111In]SB3 alone. Biodistribution studies at 1, 4, and 24 h p.i. show higher tumor uptake values with PA co-administration (19.7 ± 3.5 vs 10.2 ± 1.5, 17.6 ± 5.1 vs 8.3 ± 1.1, 6.5 ± 3.3 vs 3.1 ± 1.9 % ID/g tissue (P < 0.0001)). Tumor imaging with SPECT/MRI clearly improved after co-injection of PA. CONCLUSIONS Co-administration of PA increased in vivo tumor targeting capacity of [111In]SB3, making this an attractive combination for GRPR-targeted tumor imaging.


title: Breath diagnostics in the era of SARS-CoV-2 - in clinical and research arena.

text: The emergence of the SARS-CoV-2 pandemic has transformed not just healthcare, but also the economic systems on a global scale. Despite significant efforts to contain the infection, it continues to spread. Stringent infection control measures have been taken to minimise the transmission between individuals and healthcare workers, especially those undertaking aerosols generating medical procedures. The uncertainties surrounding infection transmission through breath tests in particular, and to some extent faecal testing, will invariably cause concerns among both the patients and the healthcare workers. It is therefore pertinent that all of the necessary measures are adopted to minimise this risk of spreading. In this article, we summarise the physiology and virulence of SARS-CoV-2 and discuss the implications for breath testing (in both the clinical and research arena) as well as outlining methods to mitigate these risks.


title: Systematic review of the use of Google Street View in health research: Major themes, strengths, weaknesses and possibilities for future research.

text: We systematically reviewed the current use of Google Street View (GSV) in health research and characterized major themes, strengths and weaknesses in order to highlight possibilities for future research. Of 54 qualifying studies, we found that most used GSV to assess the neighborhood built environment, followed by health policy compliance, study site selection, and disaster preparedness. Most studies were conducted in urban areas of North America, Europe, or New Zealand, with few studies from South America or Asia and none from Africa or rural areas. Health behaviors and outcomes of interest in these studies included injury, alcohol and tobacco use, physical activity and mental health. Major strengths of using GSV imagery included low cost, ease of use, and time saved. Identified weaknesses were image resolution and spatial and temporal availability, largely in developing regions of the world. Despite important limitations, GSV is a promising tool for automated environmental assessment for health research. Currently untapped areas of health research using GSV include identification of sources of air, soil or water pollution, park design and usage, amenity design and longitudinal research on neighborhood conditions.


title: Pretargeted 177Lu radioimmunotherapy of carcinoembryonic antigen-expressing human colonic tumors in mice.

text: UNLABELLED Pretargeted radioimmunotherapy (PRIT) with bispecific antibodies in combination with a radiolabeled peptide reduces the radiation dose to normal tissues, especially the bone marrow. In this study, the optimization, therapeutic efficacy, and toxicity of PRIT of colon cancer with a (177)Lu-labeled peptide was determined in mice with carcinoembryonic antigen (CEA)-expressing human tumors. METHODS To obtain the optimal therapeutic efficacy, several strategies were evaluated to increase the total amount of radioactivity targeted to subcutaneous LS174T colon cancer tumors in BALB/c nude mice. First, the maximum amount of bispecific anti-CEA and antihapten antibody TF2 and the peptide IMP288 that could be targeted was determined. Second, the tumor targeting of repeated administrations of radiolabeled IMP288 was investigated. Mice received 1 TF2 injection, followed by multiple IMP288 injections (3-h interval) or multiple cycles, with each IMP288 administration preceded by a new TF2 injection (72-h interval). PRIT was administered at maximum doses of TF2 and (177)Lu-labeled IMP288 in groups of 9 mice with subcutaneous LS174T tumors. Mice received 1, 2, or 3 successive cycles of treatment (26 MBq/mouse/cycle) or carrier only. The primary endpoint was survival; secondary endpoints were tumor growth, body weight, bone marrow, and renal toxicity. RESULTS The highest amount of radioactivity delivered to a subcutaneous colon tumor was achieved by the administration of 5.0 nmol of TF2 and 0.28 nmol of IMP288 in 3 successive cycles, with each IMP288 preceded by a new TF2 injection (72-h interval). PRIT effectively delayed tumor growth and prolonged survival significantly. Higher activity doses, administered in successive cycles, correlated with longer survival: the median survival of untreated mice was 13 d (range, 6-20 d), whereas that of mice treated with 1, 2, or 3 cycles of PRIT was 24 (range, 24-31 d), 45 (range, 38 ≥ 130 d), and 65 (range, 48 ≥ 130 d) days, respectively. Toxicity was limited: no significant changes in mean body weight were measured. Minimal changes in leukocyte counts were measured at 2 and 3 wk after injection, with full recovery within 7 wk after treatment. Platelet counts were unaffected. Serum creatinine levels were not increased significantly; thus, there was no indication of acute renal toxicity. CONCLUSION This study indicates that PRIT in mice is an effective treatment modality against colon cancer, with limited toxicity.


title: Clinical significance of mediastinoscope-assisted transhiatal esophagectomy in patients with esophageal cancer.

text: PURPOSE Mediastinoscope-assisted transhiatal esophagectomy (MATHE) is a useful surgical procedure in esophageal cancer patients who have limited indications for transthoracic operations due to preoperative complications. METHODS In the last 10 years, 63 patients underwent MATHE at our department. We examined the clinical data of these patients and assessed the indications, postoperative outcomes, and prognostic factors of MATHE. RESULTS The 5-year overall survival (OS) rate was 53.4 %, and disease-free survival (DFS) rate was 66.0 %. Postoperative complications were observed in 22 cases (34.9 %), and recurrent disease occurred in 17 cases (27.0 %). On univariate analyses of OS, location of the tumor, tumor depth, lymph node metastasis, clinical stage, simultaneous resection of other organs, postoperative pneumonia, and blood loss were significant prognostic factors. On multivariate analyses, location of the tumor and lymph node metastasis were independent prognostic factors of OS. On univariate analyses, location of the tumor, tumor depth, lymph node metastasis, clinical stage, and blood loss were significant prognostic factors of DFS, while on multivariate analyses of DFS, lymph node metastasis and blood loss were independent prognostic factors. CONCLUSION MATHE is a useful procedure for the middle to lower thoracic esophageal cancer patients without clinical lymph node metastasis with serious complications who were unable to undergo thoracotomy.


Disaster Response to the COVID-19 Pandemic for Patients with Kidney Disease in New York City.


title: A cluster of tertiary transmissions of 2019 novel coronavirus (SARS-CoV-2) in the community from infectors with common cold symptoms.

text: Background/Aims As the global impact of the novel coronavirus disease 2019 (COVID-19) has been severe, many countries have intensified containment activities to eliminate virus transmission, through early detection and isolation strategies. To establish a proper quarantine strategy, it is essential to understand how easily the virus can spread in the communities. Methods In this study, we collected detailed information on the circumstances in which human-to-human transmission occurred in the tertiary transmission cases of COVID-19 in the community. Results On January 26, 2020, an imported case of COVID-19 was confirmed, and by February 10, 2020, one secondary transmission and three tertiary transmissions were identified. Secondary transmission occurred on the first day of illness of the infector, and his symptoms were suggestive of a common cold. The transmission occurred during a 90-minute long meal together in a restaurant. The people were sitting within one meter of each other, and had no direct contact. The tertiary transmission also occurred on the first-day illness of the other infector, and his only symptom was slight chills. The transmission occurred at a church during 2-hour-long worship, and two rows separated them. Conclusions Our findings suggest that mildly symptomatic patients with COVID-19 could transmit the virus from the first day of illness through daily activities in the community. Early detection and isolation of patients with COVID-19 may be challenging.


title: Sex and gender considerations in transplantation research: protocol for a scoping review.

text: BACKGROUND Despite the growing appreciation of the importance of sex and gender considerations in transplantation research, there is currently no framework or good practice guidelines for the appropriate handling of sex and gender issues in human allotransplantation research. METHODS We will conduct a scoping review to synthesize the evidence on how matters of sex and gender have been handled in human allotransplantation research. We will survey the literature discussing sex and gender in relation to transplantation, including adult and pediatric patients, hematopoietic and solid organ transplant recipients as well as organ donors. We will search MEDLINE and Embase for literature discussing sex and gender in relation to transplantation. Two reviewers will independently evaluate the eligibility of all identified titles and abstracts for inclusion in the full text review, as well as data extraction. Descriptive data and information on how sex and gender have been considered in human transplantation research will be reported. DISCUSSION This scoping review will be an important stepping stone towards the development of good practice guidelines on study design and analysis considerations when handling sex and gender issues in human transplantation research. This scoping review can also help identify methodological issues that restrict the translation of transplantation research findings into clinical practice related to underestimation of sex/gender differences. This review will ultimately identify major gaps, inform donor-recipient selection, guide personalized interventions, and prioritize research recommendations in human transplantation research.


A third of covid-19 patients admitted to UK hospitals die.


Pandemic preparedness and protective clothing: priorities of health care workers in a Canadian teaching hospital.


title: Bladder outlet procedures in the setting of anticoagulation therapy.

text: PURPOSE OF REVIEW To assess the safety and bleeding risk in men on chronic oral anticoagulation, including antiplatelet therapies, undergoing bladder outlet procedures for the treatment of benign prostatic hyperplasia (BPH). RECENT FINDINGS There are conflicting findings; however, most recent series show that when treating bladder outlet obstruction from BPH in patients on chronic anticoagulants, there is an increased risk of hemorrhagic complications for these men. There is also an increased risk of cardiovascular and cerebrovascular complications, especially when antithrombotic therapy is used for secondary prevention and is withdrawn perioperatively. Some have found bipolar electrosurgical vaporization of the prostate, laser vaporization, and enucleation of the prostate to provide superior hemostatic outcomes compared to classic monopolar transurethral resection of the prostate. SUMMARY Extra caution should always be given to patients on chronic anticoagulation undergoing surgical procedures, given increased risk of bleeding and cardiovascular and cerebrovascular complications. For men with BPH undergoing bladder outlet procedures, photoselective vaporization of the prostate, Holmium laser enucleation of the prostate, and vaporization of the prostate with bipolar electrosurgical instruments may result in less bleeding complications. Further prospective randomized studies are needed to elucidate which methods provide better hemostasis and lower postoperative bleeding to best manage men with BPH on chronic antithrombotic therapy, especially when the anticoagulation therapy cannot be discontinued prior to therapy.


title: Efficient induction of a Her2-specific anti-tumor response by dendritic cells pulsed with a Hsp70L1-Her2(341-456) fusion protein.

text: Heat shock proteins (HSPs) have been shown to interact with antigen-presenting cells (APCs), especially dendritic cells (DCs). HSPs act as potent adjuvants, inducing a Th1 response, as well as antigen-specific CD8(+) cytotoxic T lymphocytes (CTL) via cross-presentation. Our previous work has demonstrated that Hsp70-like protein 1 (Hsp70L1), a new member of the Hsp70 subfamily, can act as a powerful Th1 adjuvant in a DC-based vaccine. Here we report the efficient induction of tumor antigen-specific T cell immune response by DCs pulsed with recombinant fusion protein of Hsp70L1 and Her2(341-456), the latter of which is a fragment of Her2/neu (Her2) containing E75 (a HLA-A2 restricted CTL epitope). The fusion protein Hsp70L1-Her2(341-456) promotes the maturation of DCs and activates them to produce cytokines, such as IL-12 and TNF-α, and chemokines, such as MIP-1α, MIP-1β and RANTES. Taken together, these results indicate that the adjuvant activity of Hsp70L1 is maintained in the fusion protein. Her2-specific HLA-A2.1-restricted CD8(+) CTLs can be generated efficiently either from the Peripheral blood lymphocytes (PBL) of healthy donors or from the splenocytes of immunized HLA-A2.1/K(b) transgenic mice by in vitro stimulation or immunization with DCs pulsed with the Hsp70L1-Her2(341-456) fusion protein. This results in more potent target cell killing in an antigen-specific and HLA-A2.1-restricted manner. Adoptive transfer of splenocytes from transgenic mice immunized with Hsp70L1-Her2(341-456)-pulsed DCs can markedly inhibit tumor growth and prolong the survival of nude mice with Her2(+)/HLA-A2.1(+) human carcinomas. These results suggest that Hsp70L1-Her2(341-456)-pulsed DCs could be a new therapeutic vaccine for patients with Her2(+) cancer.


Reflections on the evolution of cardiac biomarkers.


COVID-19 Emergency and the Need to Speed Up the Adoption of Electronic Patient-Reported Outcomes in Cancer Clinical Practice.


Still early to define a clear role of antimalarial drugs for COVID-19 in patients with rheumatic disease. Response to: 'Hydroxychloroquine reduces the risk of covid-19 in patients with rheumatic diseases: myth or reality?' by Xie et al.