title: Balloon-assisted osteoplasty of periacetabular tumors following percutaneous cryoablation.

text: PURPOSE To describe the feasibility, safety, and effectiveness of a technique using vertebral augmentation balloons to promote delivery of cement into periacetabular tumors after cryoablation for fracture prevention. MATERIALS AND METHODS A retrospective review was performed of seven consecutive patients (six men and one woman; mean age, 64 y ± 8) with unilateral periacetabular tumors (mean size, 4.2 cm ± 1.4) treated with cryoablation and balloon-assisted osteoplasty for fracture prevention. Cortical defects were seen in six (86%) tumors, and additional pathologic fractures occurred in five (71%) tumors before treatment. The cohort included six (86%) Harrington class I defects and one (14%) class II defect. Procedures were performed with computed tomography fluoroscopic guidance and general anesthesia. Vertebral augmentation balloons (mean, 2; range, 1-4) were inflated within the ablation cavity immediately before or during cement injection. RESULTS All procedures were technically successful. Median percentage tumor fill was 63% (range, 17%-96%). Minor cement leakage occurred in two (29%) patients with no symptomatic or intraarticular extravasation. A new nondisplaced fracture occurred in one patient and was conservatively managed. No major complications occurred. Local tumor progression occurred in one (20%) of five patients with imaging follow-up. CONCLUSIONS Balloon-assisted osteoplasty after cryoablation of periacetabular tumors appears feasible, safe, and effective for fracture prevention. This technique directs cement instillation into ablation defects with a high degree of filling and minimal leakage.


Hematologic parameters in patients with COVID-19 infection.


title: Swinging the pendulum: lessons learned from public discourse concerning hydroxychloroquine and COVID-19.

text: INTRODUCTION Several months into the COVID-19 pandemic, safe and effective treatments against this global health disaster have yet to be identified. Clinical research trials around the world are underway testing a wide array of possible medications. In particular, the off-label use of hydroxychloroquine for COVID-19 prophylaxis and treatment has created many unprecedented challenges for the scientific community and the public. AREAS COVERED We critically assessed major events from February - May 2020 that contributed to widespread use of hydroxychloroquine for the treatment and prophylaxis of COVID-19. We aimed to explore how opinions towards hydroxychloroquine may shift from early enthusiasm (based on in vitro and preliminary clinical data) to the hope for a miracle cure (through communication and promotion of questionable results) and, finally, to a rise of skepticism as more in-depth analyses are emerging. EXPERT OPINION Mindful and rigorous acquisition of data, as well as its interpretation, are essential to an effective pandemic response. The rapid and premature promotion of results has had major implications for global crisis management, even creating distrust among the public. It is crucial for the medical and scientific community to incorporate the lessons learned from this situation.


title: FTIR microscopy contribution for comprehension of degradation mechanisms in PLA-based implantable medical devices.

text: The integration and evolution of implantable medical devices made of bioresorbable polymers and used for temporary biomedical applications are crucial criteria in the success of a therapy and means of follow-up after implantation are needed. The objective of this work is to develop and evaluate a method based on microscopic Fourier Transform InfraRed spectroscopy (FTIR) mappings to monitor the degradation of such polymers on tissue explant sections, after implantation. This technique provided information on their location and on both their composition and crystallinity, which is directly linked to their state of degradation induced predominantly by chain scissions. An in vitro study was first performed on poly(L-lactic acid) (PLLA) meshes to validate the procedure and the assumption that changes observed on FTIR spectra are indeed a consequence of degradation. Then, mappings of in vivo degraded PLLA meshes were realized to follow up their degradation and to better visualize their degradation mechanisms. This work further warrants its translation to medical implants made of copolymers of lactic acid and to other polyesters.


title: Impaired cerebral autoregulation and elevation in plasma glial fibrillary acidic protein level during cardiopulmonary bypass surgery for CHD.

text: BACKGROUND Cerebrovascular reactivity monitoring has been used to identify the lower limit of pressure autoregulation in adult patients with brain injury. We hypothesise that impaired cerebrovascular reactivity and time spent below the lower limit of autoregulation during cardiopulmonary bypass will result in hypoperfusion injuries to the brain detectable by elevation in serum glial fibrillary acidic protein level. METHODS We designed a multicentre observational pilot study combining concurrent cerebrovascular reactivity and biomarker monitoring during cardiopulmonary bypass. All children undergoing bypass for CHD were eligible. Autoregulation was monitored with the haemoglobin volume index, a moving correlation coefficient between the mean arterial blood pressure and the near-infrared spectroscopy-based trend of cerebral blood volume. Both haemoglobin volume index and glial fibrillary acidic protein data were analysed by phases of bypass. Each patient's autoregulation curve was analysed to identify the lower limit of autoregulation and optimal arterial blood pressure. RESULTS A total of 57 children had autoregulation and biomarker data for all phases of bypass. The mean baseline haemoglobin volume index was 0.084. Haemoglobin volume index increased with lowering of pressure with 82% demonstrating a lower limit of autoregulation (41±9 mmHg), whereas 100% demonstrated optimal blood pressure (48±11 mmHg). There was a significant association between an individual's peak autoregulation and biomarker values (p=0.01). CONCLUSIONS Individual, dynamic non-invasive cerebrovascular reactivity monitoring demonstrated transient periods of impairment related to possible silent brain injury. The association between an impaired autoregulation burden and elevation in the serum brain biomarker may identify brain perfusion risk that could result in injury.


title: Navigating Coronavirus Disease 2019 (Covid-19) in Physiatry: A CAN report for Inpatient Rehabilitation Facilities.

text: We are facing a global pandemic in relation to coronavirus disease 2019 (Covid-19). Emergency preparedness plans often do not consider issues specific to inpatient rehabilitation facilities. The CAN model can be used to prepare for natural disasters, including the COVID-19 pandemic. This report was created to aid specialists in acute Inpatient Rehabilitation Facilities. This article is protected by copyright. All rights reserved.


title: Effect of Tracheostomy on Weaning Parameters in Difficult-to-Wean Mechanically Ventilated Patients: A Prospective Observational Study.

text: BACKGROUND AND OBJECTIVE Weaning parameters are commonly measured through an endotracheal tube in mechanically ventilated patients recovering from acute respiratory failure, however this practice has rarely been evaluated in tracheostomized patients. This study aimed to investigate changes in weaning parameters measured before and after tracheostomy, and to explore whether the data measured after tracheostomy were associated with weaning outcomes in difficult-to-wean patients. METHODS In a two-year study period, we enrolled orotracheally intubated patients who were prepared for tracheostomy due to difficult weaning. Weaning parameters were measured before and after the conversion to tracheostomy and compared, and the post-tracheostomy data were tested for associations with weaning outcomes. RESULTS A total of 86 patients were included. After tracheostomy, maximum inspiratory pressure (mean difference (Δ) = 4.4, 95% CI, 2.7 to 6.1, P<0.001), maximum expiratory pressure (Δ = 5.4, 95% CI, 2.9 to 8.0, P<0.001) and tidal volume (Δ = 33.7, 95% CI, 9.0 to 58.5, P<0.008) significantly increased, and rapid shallow breathing index (Δ = -14.6, 95% CI, -25.4 to -3.7, P<0.009) and airway resistance (Δ = -4.9, 95% CI, -5.8 to -4.0, P<0.001) significantly decreased. The patients who were successfully weaned within 90 days of the initiation of mechanical ventilation had greater increments in maximum inspiratory pressure (5.9 vs. 2.4, P = 0.04) and maximum expiratory pressure (8.0 vs. 2.0, P = 0.02) after tracheostomy than those who were unsuccessfully weaned. CONCLUSIONS In conclusion, the conversion from endotracheal tube to tracheostomy significantly improved the measured values of weaning parameters in difficult-to-wean patients who subsequently weaned successfully from the mechanical ventilator. The change was significant only for airway resistance in patients who failed weaning. TRIAL REGISTRATION ClinicalTrials.gov NCT01312142.


Coronavirus R number hides raised risk for minority ethnic groups.


title: Phylogeny and S1 Gene Variation of Infectious Bronchitis Virus Detected in Broilers and Layers in Turkey.

text: The avian coronavirus infectious bronchitis virus (AvCoV-IBV) is recognized as an important global pathogen because new variants are a continuous threat to the poultry industry worldwide. This study investigates the genetic origin and diversity of AvCoV-IBV by analysis of the S1 sequence derived from 49 broiler flocks and 14 layer flocks in different regions of Turkey. AvCoV-IBV RNA was detected in 41 (83.6%) broiler flocks and nine (64.2%) of the layer flocks by TaqMan real-time RT-PCR. In addition, AvCoV-IBV RNA was detected in the tracheas 27/30 (90%), lungs 31/49 (62.2%), caecal tonsils 7/22 (31.8%), and kidneys 4/49 (8.1%) of broiler flocks examined. Pathologic lesions, hemorrhages, and mononuclear infiltrations were predominantly observed in tracheas and to a lesser extent in the lungs and a few in kidneys. A phylogenetic tree based on partial S1 sequences of the detected AvCoV-IBVs (including isolates) revealed that 1) viruses detected in five broiler flocks were similar to the IBV vaccines Ma5, H120, M41; 2) viruses detected in 24 broiler flocks were similar to those previously reported from Turkey and to Israel variant-2 strains; 3) viruses detected in seven layer flocks were different from those found in any of the broiler flocks but similar to viruses previously reported from Iran, India, and China (similar to Israel variant-1 and 4/91 serotypes); and 4) that the AVCoV-IBV, Israeli variant-2 strain, found to be circulating in Turkey appears to be undergoing molecular evolution. In conclusion, genetically different AvCoV-IBV strains, including vaccine-like strains, based on their partial S1 sequence, are circulating in broiler and layer chicken flocks in Turkey and the Israeli variant-2 strain is undergoing evolution.


title: Comparative Assessment of Guidewire and Microcatheter vs a Crossing Device-Based Strategy to Traverse Infrainguinal Peripheral Artery Chronic Total Occlusions.

text: PURPOSE To compare success rates of a guidewire and microcatheter strategy vs the use of specialized crossing devices to traverse infrainguinal peripheral artery chronic total occlusions (CTOs). METHODS For this analysis, data on 438 consecutive infrainguinal CTO interventions in 438 patients (mean age 63.2 years; 402 men) performed between August 2006 and May 2014 were extracted from the multicenter Excellence in Peripheral Artery Disease (XLPAD) database (ClinicalTrials.gov; identifier NCT01904851). Primary technical success constituted placement of a guidewire in the true lumen, past the distal CTO cap, with the initial crossing strategy. RESULTS A wire-catheter strategy was used in 295 (67.4%) and a specialized CTO crossing device in 143 (32.6%) patients (p<0.001). Primary crossing technical success was higher with CTO devices (72.1% vs 51.9%, p<0.001). The primary wire-catheter arm used significantly more secondary CTO devices (28.1% vs 17.5%) and/or provisional re-entry devices (26.7% vs 4.9%) compared with the primary CTO device arm (both p<0.001). Secondary crossing technical success (defined as crossing with an alternate strategy: 67.5% vs 71.4%, p=1.000), provisional crossing technical success (defined as use of a re-entry device: 84.2% vs 87.5%, p=0.768), and procedure success (93.6% vs 90.9%, p=0.332) were similar between the wire-catheter and CTO device strategies, respectively. No differences were observed in periprocedural complications or 30-day adverse events; however, at 12 months, there was a significantly higher surgical revascularization rate in the primary wire-catheter arm (8.8% vs 2.8%, p=0.025). CONCLUSION Infrainguinal peripheral artery CTO crossing is frequently attempted with a wire-catheter technique; however, an initial CTO crossing device approach is associated with higher primary technical success. Overall procedure success is similar with both strategies.


title: The road less traveled: transarterial embolization of dural arteriovenous fistulas via the ascending pharyngeal artery.

text: BACKGROUND With the introduction of Onyx, transarterial embolization has become the most common endovascular approach to treating dural arteriovenous fistulas (dAVFs), often via the middle meningeal or occipital arteries. The ascending pharyngeal artery (APA) is a less frequently explored transarterial route because of its small caliber, potential anastomoses to the internal carotid and vertebral arteries, and vital supply to lower cranial nerves. OBJECTIVE To review our institutional experience and highlight the prevalence of APA supply to dAVFs and cases where it is a safe and effective pedicle for embolization. METHODS We reviewed our endovascular database (January 1, 1996 to March 1, 2016) for cranial dAVFs, evaluating dAVF characteristics and embolization results for those treated transarterially via the APA. RESULTS Of 267 endovascularly treated dAVFs, 68 had APA supply (25%). Of these 68 dAVFs, embolization was carried out via this pedicle in 8 (12%) and 7 were ultimately occluded. No complications, including post-treatment cranial neuropathies or radiographic evidence of non-target embolization, were found. For 5 dAVFs, the APA was selected as the initial pedicle for embolization (two marginal sinus, one distal sigmoid, one cavernous, one tentorial). In four of these five cases, dAVF occlusion was achieved via the initial APA feeding artery pedicle. In one case, near-complete, stagnant occlusion was achieved after APA embolization; complete occlusion was achieved after adjunctive embolization of a single additional middle meningeal artery pedicle. In three other cases of complex transverse/sigmoid dAVFs, the APA was used after multiple attempts via middle meningeal and occipital artery pedicles. Occlusion was not achieved transarterially; two of these three dAVFs were ultimately occluded transvenously. CONCLUSIONS In rare, select cases, the APA is an excellent route for transarterial embolization of cranial dAVFs.


title: Is hand, foot and mouth disease associated with meteorological parameters?

text: We examined the relationship between meteorological parameters and hand, foot and mouth disease (HFMD) activity. Meteorological data collected from 2000 to 2004 were tested for correlation with HFMD consultation rates calculated through the sentinel surveillance system in Hong Kong. The regression model constructed was used to predict HFMD consultation rates for 2005-2009. After adjusting for the effect of collinearity, mean temperature, diurnal difference in temperature, relative humidity, and wind speed were positively associated with HFMD consultation rates, and explained HFMD consultation rates well with 2 weeks' lag time (R²=0·119, P=0·010). The predicted HFMD consultation rates were also also well matched with the observed rates (Spearman's correlation coefficient=0·276, P=0·000) in 2005-2009. Sensitivity analysis showed that HFMD consultation rates were mostly affected by relative humidity and least affected by wind speed. Our model demonstrated that climate parameters help in predicting HFMD activity, which could assist in explaining the winter peak detected in recent years and in issuing early warning.


Case 18-2020: A 73-Year-Old Man with Hypoxemic Respiratory Failure and Cardiac Dysfunction.


title: Mini-laparoscopic sacrocolpopexy for apical and posterior female pelvic organ prolapse.

text: AIM OF THE VIDEO Mini-laparoscopic surgery is the future for most laparoscopic procedures. Although already applied in some gynaecological surgical interventions, this video is to our knowledge the first publication on the use of the mini-laparoscopic approach to sacrocolpopexy for apical and posterior pelvic organ prolapse following total hysterectomy. METHODS The concept of mini-laparoscopic sacrocolpopexy presented in this video article was performed on 12 women with post-hysterectomy apical and posterior pelvic organ prolapse using mini-laparoscopic instruments and ports of 3 mm in diameter combined with a 12-mm umbilical port. Surgery was performed with the same principles as for the conventional laparoscopic procedure. RESULTS The mean operating time was 70 min (SD ± 12). The tensile strength of the mini-laparoscopic instruments allowed appropriate manipulation of tissue consistent with that of conventional instruments. No difficulties or complications were experienced in comparison to a conventional technique. All patients were discharged from hospital on day 1 postoperatively. CONCLUSIONS The effectiveness, safety and feasibility of the mini-laparoscopic surgical technique was applied to sacrocolpopexy. Because of the initial favourable experience, the mini-laparoscopic sacrocolpopexy could become more widely used in the future.


title: May-Thurner syndrome and iliac arteriovenous fistula in an elderly woman.

text: May-Thurner syndrome most commonly involves compression of the left common iliac vein by the right common iliac artery and can result in leg pain and swelling as well as potentially precipitate deep venous thrombosis. These symptoms can be exacerbated by additional vascular abnormalities. This is a case report of a 91-year-old woman with intractable massive left lower extremity edema that interfered with walking. She was diagnosed with concurrent May-Thurner syndrome and pelvic arteriovenous fistula. Treatment with embolization of the fistula and stenting of the left common iliac vein relieved her symptoms and allowed her to walk again.


title: Valuing the impact of health and social care programs using social return on investment analysis: how have academics advanced the methodology? A systematic review.

text: OBJECTIVES To identify how social return on investment (SROI) analysis-traditionally used by business consultants-has been interpreted, used and innovated by academics in the health and social care sector and to assess the quality of peer-reviewed SROI studies in this sector. DESIGN Systematic review. SETTINGS Community and residential settings. PARTICIPANTS A wide range of demographic groups and age groups. RESULTS The following databases were searched: Web of Science, Scopus, CINAHL, Econlit, Medline, PsychINFO, Embase, Emerald, Social Care Online and the National Institute for Health and Care Excellence. Limited uptake of SROI methodology by academics was found in the health and social care sector. From 868 papers screened, 8 studies met the criteria for inclusion in this systematic review. Study quality was found to be highly variable, ranging from 38% to 90% based on scores from a purpose-designed quality assessment tool. In general, relatively high consistency and clarity was observed in the reporting of the research question, reasons for using this methodology and justifying the need for the study. However, weaknesses were observed in other areas including justifying stakeholders, reporting sample sizes, undertaking sensitivity analysis and reporting unexpected or negative outcomes. Most papers cited links to additional materials to aid in reporting. There was little evidence that academics had innovated or advanced the methodology beyond that outlined in a much-cited SROI guide. CONCLUSION Academics have thus far been slow to adopt SROI methodology in the evaluation of health and social care interventions, and there is little evidence of innovation and development of the methodology. The word count requirements of peer-reviewed journals may make it difficult for authors to be fully transparent about the details of their studies, potentially impacting the quality of reporting in those studies published in these journals. PROSPERO REGISTRATION NUMBER CRD42018080195.


title: Disruptive technology will transform what we think of as robotic surgery in under ten years.

text: What is currently described as 'robotic surgery' will undergo a transformation as rapid as the transformation from Kodak film cameras to digital cameras, from Nokia phones to iPhones, from listening to music on tape to CD then to digital downloading, and the transformation that is shortly to come from petrol cars into electric cars. We are only at the very infancy of what is currently termed robotic surgery, but in reality, is in fact just computer-assisted, instrument-controlled surgery. This article will describe the current state of robotic surgery and will then go on to look at why we will hardly recognize the surgical world in ten years' time, as novel, disruptive technology transforms our specialty.


title: Effective cerebrovascular thrombectomy requires well-organized structures : Real world experiences of a regional stroke network between 2012-2015.

text: BACKGROUND The objective of this study was to analyse the Neurothrombectomy Network registry of the Neuromed Campus (NMC) of the Kepler University Hospital in Linz (Austria). The data were compared to the results of recently published thrombectomy trials (MR CLEAN, ESCAPE, EXTEND-IA, SWIFT-PRIME, REVASCAT and THRACE). METHODS We retrospectively studied 246 patients with acute ischemic stroke who underwent thrombectomy between January 2012 and December 2015 at the NMC in Upper Austria. The main outcome measures were modified Rankin scale (mRS) score 0-2 at 90 days, all-cause mortality and stroke or thrombectomy-related mortality at discharge, as well as 90 days postdischarge. RESULTS The median age was 70.4 years (IQR 59.9-76.9) and the median NIHSS at admission 16 (IQR 13-20). The thrombolysis in cerebral infarction (TICI) scale 2b-3 recanalization was achieved in 87.4%, 11.0% of the patients died in hospital and an additional 6.1% within 90 days after discharge. After 90 days, 56.5% had a mRS score 0-2. CONCLUSIONS These data suggest that the positive results of thrombectomy reported in several randomized controlled studies can be achieved in routine clinical practice; therefore, the setting of an organized, regional stroke network proved an effective and appropriate method for delivering regional thrombectomy stroke treatment.


title: 3-Trifluoromethylpyrazolones derived nucleosides: Synthesis and antiviral evaluation.

text: Dengue (DENV) viral infection is a global public health problem that infrequently develops life threatening diseases such as dengue hemorrhagic fever (DFS) and dengue shock syndrome (DSS). Middle East respiratory syndrome coronavirus (MERS-CoV) is a highly pathogenic human corona virus with 38% fatality rate of infected patients. A series of 4-arylhydrazono-5-trifluoromethyl-pyrazolones, their ribofuranosyl, and 5'-deoxyribofuranosyl nucleosides were synthesized, geometry optimized using Density functional theory (DFT), and evaluated for their antiviral activity. 2-Nitrophenylhydrazonopyra-zolone derivative 5 showed significant activity against MERS-CoV (EC50 = 4.6 μM). The nucleoside analog 8 showed moderate activity against DENV-2 (EC50 = 10 μM), while the activity was abolished with the corresponding 5'-deoxyribonucleoside analogs. The identified hits in this study set this category of compounds for further future optimizations.


title: Laparoscopic Sleeve Gastrectomy for Morbid Obesity in 3003 Patients: Results at a High-Volume Bariatric Center.

text: BACKGROUND Laparoscopic sleeve gastrectomy (LSG) is gaining wide acceptance as a single surgical treatment for obesity. The reported morbidity and mortality rates are low. We herein report the results of LSG performed in a high-volume center by an experienced team. METHODS Retrospective analysis of a prospectively maintained database of all bariatric surgery (BS) was performed between May 2006 and December 2014. Data inspected included operative time, length of hospital stay (LOS), comorbidity resolution, re-operation, percent excess weight loss (%EWL), and 30-day morbidity and mortality. RESULTS In the study period, 3003 patients underwent BS (1901 (63 %) female). Mean age and body mass index (BMI) were 43 years (range 14-73) and 42.8 kg/m(2) (range 35-73), respectively. %EWL at 1 year was 72 % (n = 937; 57 % follow-up rate). There was 1 perioperative mortality due to bleeding (0.03 %). Comorbidity improvement and resolution were 98 % for obstructive sleep apnea, 79 % for diabetes mellitus, 87 % for dyslipidemia, and 85 % for hypertension. Mean operative time and LOS were 50 min (range 32-94) and 2.2 days (range 1-38), respectively. Of the patients, 132 had complications (4.4 %), 25 leaks (0.83 %), 63 bleeding (2.1 %), 1 intra-abdominal abscesses (0.03 %), 3 sleeve strictures (0.1 %), 2 mesenteric vein thromboses (0.06 %), 10 trocar site hernias (0.3 %), and 78 symptomatic cholelithiasis (2.6 %). Re-operation was needed in 13 patients (0.43 %). CONCLUSION In a high-volume center with an experienced team, LSG can be performed with low morbidity and mortality.


title: Electrothermal bipolar vessel sealing system (LigaSure) for hemostasis during thyroid surgery: a comprehensive review.

text: Conventional hemostatic technologies utilized in thyroid surgery include clamp-and-tie, clips and monopolar and bipolar diathermy. Over the last decade, there has been a major shift towards utilizing newer hemostatic technologies, most notably the electrothermal bipolar vessel sealing systems (EBVS) and the Harmonic Scalpel (Ethicon Endosurgery, OH, USA), for thyroid surgery. Since the first report of EBVS thyroidectomy in 2003, more than 50 studies have been published evaluating EBVS utilization for thyroid surgery. In addition to providing a historical perspective and exploring the principles of EBVS technology, this review aims to evaluate the current published data regarding EBVS utilization for thyroid surgery. In particular, a focus is given to LigaSure (Covidien, Dublin, Ireland) technology because it has been studied most thoroughly in the literature. This review will also evaluate studies comparing the EBVS with Harmonic Scalpel technology for thyroid surgery.


title: Safety and efficacy of microsurgical treatment of previously coiled aneurysms: a systematic review and meta-analysis.

text: BACKGROUND We conducted a systematic review of the literature to evaluate the safety and efficacy of surgical treatment of previously coiled aneurysms. METHODS A comprehensive review of the literature for studies on surgical treatment of previously coiled aneurysms was conducted. For each study, the following data were extracted: patient demographics, initial clinical status, location and size of aneurysms, time interval between initial/last endovascular procedure and surgery, surgical indications, and microsurgical technique. We performed subgroup analyses to compare direct clipping versus coil removal and clipping versus parent vessel occlusion, early (<4 weeks post-coiling) versus late surgery and anterior versus posterior circulation. RESULTS Twenty-six studies with 466 patients and 471 intracranial aneurysms were included. All of the studies were retrospective and non-comparative case-series. Patients undergoing direct clipping had lower perioperative morbidity (5.0 %, 95 % CI = 2.6-7.4 %) when compared to those undergoing coil removal and clipping (11.1 %, 95 % CI = 5.3-17.0 %) or parent vessel occlusion (13.1 %, 95 % CI = 4.6-21.6 %) (p = 0.05). Patients receiving early surgery (<4 weeks post-coiling) had significantly lower rates of good neurological outcome (77.1 %, 95 % CI = 69.3-84.8 %) when compared to those undergoing late surgery (92.1 %, 95 % CI = 89.0-95.2 %) (p < 0.01). There were higher rates of long-term neurological morbidity in the posterior circulation group (23.1 vs. 4.7 %, p < 0.01) as well as long-term neurological mortality (4.4 vs. 2.8 %, p < 0.01). CONCLUSIONS Our meta-analysis suggests that surgical treatment is safe and effective. Our data indicate that aneurysms that are amenable to direct clipping have superior outcomes. Late surgery was also associated with better clinical outcomes. Surgery of recurrent posterior circulation aneurysms was associated with high rates of morbidity and mortality. Given the characteristics of the included studies, the quality of evidence of this meta-analysis is limited.


title: Does the impact of biodiversity differ between emerging and endemic pathogens? The need to separate the concepts of hazard and risk.

text: Biodiversity is of critical value to human societies, but recent evidence that biodiversity may mitigate infectious-disease risk has sparked controversy among researchers. The majority of work on this topic has focused on direct assessments of the relationship between biodiversity and endemic-pathogen prevalence, without disentangling intervening mechanisms; thus study outcomes often differ, fuelling more debate. Here, we suggest two critical changes to the approach researchers take to understanding relationships between infectious disease, both endemic and emerging, and biodiversity that may help clarify sources of controversy. First, the distinct concepts of hazards versus risks need to be separated to determine how biodiversity and its drivers may act differently on each. This distinction is particularly important since it illustrates that disease emergence drivers in humans could be quite different to the general relationship between biodiversity and transmission of endemic pathogens. Second, the interactive relationship among biodiversity, anthropogenic change and zoonotic disease risk, including both direct and indirect effects, needs to be recognized and accounted for. By carefully disentangling these interactions between humans' activities and pathogen circulation in wildlife, we suggest that conservation efforts could mitigate disease risks and hazards in novel ways that complement more typical disease control efforts.This article is part of the themed issue 'Conservation, biodiversity and infectious disease: scientific evidence and policy implications'.


title: Alternative molecular formats and therapeutic applications for bispecific antibodies.

text: Bispecific antibodies are on the cusp of coming of age as therapeutics more than half a century after they were first described. Two bispecific antibodies, catumaxomab (Removab(®), anti-EpCAM×anti-CD3) and blinatumomab (Blincyto(®), anti-CD19×anti-CD3) are approved for therapy, and >30 additional bispecific antibodies are currently in clinical development. Many of these investigational bispecific antibody drugs are designed to retarget T cells to kill tumor cells, whereas most others are intended to interact with two different disease mediators such as cell surface receptors, soluble ligands and other proteins. The modular architecture of antibodies has been exploited to create more than 60 different bispecific antibody formats. These formats vary in many ways including their molecular weight, number of antigen-binding sites, spatial relationship between different binding sites, valency for each antigen, ability to support secondary immune functions and pharmacokinetic half-life. These diverse formats provide great opportunity to tailor the design of bispecific antibodies to match the proposed mechanisms of action and the intended clinical application.


title: Hydroxychloroquine/ chloroquine as a treatment choice or prophylaxis for Covid-19 at the primary care level in developing countries: A Primum non Nocere dilemma.

text: The Food and Drug Administration (FDA) warned against the use of Hydroxychloroquine or chloroquine for Covid-19 outside of a hospital or a clinical trial setting due to the risk of QT interval prolongation, ventricular tachycardia and the increased risk of these complications when combined with some antibiotics such as azithromycin. Several studies have reported no benefit of Hydroxychloroquine or chloroquine, when used alone or with a macrolide in COVID-19 hospitalized patients. Despite these warnings, in several developing countries the official guidelines for treatment of Covid-19 patients at the primary care level recommend Hydroxychloroquine and azithromycin, among other treatments, as the first-choice for mild symptomatic Covid-19 patients, asymptomatic contacts or for prophylaxis. In our opinion there is a primum non nocere dilemma during this Covid-19 pandemic. In order to solve this bioethical problem, we strongly recommend that a randomized controlled trial in a primary care setting be carried out as a matter of urgency in these areas of the world.


title: Investigations of selected historically important syndromic outbreaks: impact and lessons learned for public health preparedness and response.

text: Public health readiness has increased at all jurisdictional levels because of increased sensitivity to threats. Since 2001, with billions of dollars invested to bolster the public health system's capacity, the public expects that public health will identify the etiology of and respond to events more rapidly. However, when etiologies are unknown at the onset of the investigation but interventions must be implemented, public health practitioners must benefit from past investigations' lessons to strengthen preparedness for emerging threats. We have identified such potentially actionable lessons learned from historically important public health events that occurred primarily as syndromes for which the etiological agent initially was unknown. Ongoing analysis of investigations can advance our capability to recognize and investigate syndromes and other problems and implement the most appropriate interventions.


title: Into the eye of the cytokine storm.

text: The cytokine storm has captured the attention of the public and the scientific community alike, and while the general notion of an excessive or uncontrolled release of proinflammatory cytokines is well known, the concept of a cytokine storm and the biological consequences of cytokine overproduction are not clearly defined. Cytokine storms are associated with a wide variety of infectious and noninfectious diseases. The term was popularized largely in the context of avian H5N1 influenza virus infection, bringing the term into popular media. In this review, we focus on the cytokine storm in the context of virus infection, and we highlight how high-throughput genomic methods are revealing the importance of the kinetics of cytokine gene expression and the remarkable degree of redundancy and overlap in cytokine signaling. We also address evidence for and against the role of the cytokine storm in the pathology of clinical and infectious disease and discuss why it has been so difficult to use knowledge of the cytokine storm and immunomodulatory therapies to improve the clinical outcomes for patients with severe acute infections.


title: Advances in endovascular aneurysm management: coiling and adjunctive devices.

text: Endovascular coil embolisation continues to evolve and remains a valid modality in managing ruptured and unruptured cerebral aneurysms. Technological advances in coil properties, adjunctive devices and interventional techniques continue to improve long-term aneurysm occlusion rates. This review elaborates on the latest advances in next-generation endovascular coils and adjunctive coiling techniques for treating cerebral aneurysms.


title: Single-port laparoscopic adrenalectomy for a right-sided aldosterone-producing adenoma: a case report.

text: INTRODUCTION Single-port laparoscopic adrenalectomy is one of the most interesting surgical advances. Here, we evaluate the safety and feasibility of single-port laparoscopic adrenalectomy as treatment for a right-sided aldosterone-producing adenoma. CASE PRESENTATION A 39-year-old Japanese woman presented with hypertension and hypokalemia. Abdominal computed tomography and an endocrinological workup revealed a 19mm right adrenal tumor with primary aldosteronism. Our patient was informed of the details of the surgical procedure and our efforts to reduce the number of incisions needed - ideally, to a single incision - when removing her adrenal gland. A single-port laparoscopic adrenalectomy was attempted. A multichannel port was inserted through a 2.5cm umbilical incision. A 5mm flexible laparoscope, articulating laparoscopic dissector and tissue sealing device were the primary tools used in the operation. The right liver lobe was evaluated using a percutaneous instrument, providing good visualization of the operative field surrounding her right adrenal gland. The single-port laparoscopic adrenalectomy was successfully completed without any intraoperative complications. The operating time was 76 minutes, and her blood loss was 5mL. Oral intake was resumed on the first postoperative day, and the length of her hospital stay was three days. Her postoperative course was uneventful with no morbidity within one month of follow-up, and our patient had excellent cosmetic results. CONCLUSIONS Single-port laparoscopic adrenalectomy is a safe and feasible procedure for patients with a right-sided adrenal tumor when performed by a surgeon experienced in laparoscopic and adrenal surgery. However, more surgical experience using this technique is required to confirm our initial impressions.


Association between Numbers of "Imported Cases" and "Reported Cases in a Source Country" of COVID-19: January to April 2020 in Japan.


title: Prognostic Hemostasis Biomarkers in Acute Ischemic Stroke.

text: Objectives- The prediction of patients at risk for poor clinical outcome after acute ischemic stroke remains challenging. An imbalance of coagulation factors may play an important role in progression and prognosis of these patients. In this systematic review, we assessed the current literature on hemostasis biomarkers and the association with poor clinical outcome in acute ischemic stroke. Approach and Results- A systematic search of Embase, Medline, Cochrane Library, Web of Science, and Google Scholar was performed on studies reporting on hemostasis biomarkers and clinical outcome after acute ischemic stroke. Studies were considered eligible if blood samples were collected within 72 hours after symptom onset. Additionally, clinical outcome should be assessed using a disability score (Barthel Index or modified Rankin scale). Methodological quality of included studies was assessed with an adapted version of the Quality Assessment of Diagnostic Accuracy Studies questionnaire. A total of 80 articles were read full text, and 41 studies were considered eligible for inclusion, reporting on 37 different hemostasis biomarkers. No single biomarker appeared to be effective in predicting poor clinical outcome in acute ischemic stroke patients. Conclusions- Based on current literature, no clear recommendations can be provided on which hemostasis biomarkers are a predictor of clinical outcome after acute ischemic stroke. However, some biomarkers show promising results and need to be further investigated and validated in large populations with clear defined study designs.


title: Emerging studies of human HIV-specific antibody repertoires.

text: There has been an explosion of interest in the human B cell response to HIV infection of late. Recent advances in techniques for isolation of human antibodies and antibody secreting cell lines have facilitated a rapid expansion in the number of antibodies available for study. Early analysis of these repertoires reveals interesting features of the HIV-specific antibody response. HIV-specific repertoires exhibit a high level of clonality in circulating cells, and high levels of somatic mutations within the antibody variable gene segments. It appears that many if not most antibodies in circulation bind to virus envelope conformations that are found only in complex oligomeric structures on virion particles or virus-like particles. The rapid isolation of large panels of novel human neutralizing antibodies promises to reveal new insights into the fundamental principles underlying antibody-mediated neutralization of HIV.


title: Electrical stimulation induces differentiation of human cardiosphere-derived cells (hCDCs) to committed cardiomyocyte.

text: Logistic complexities of heart transplantation embossed the necessity of utilizing novel methods, which enable heart regeneration. Human cardiosphere-derived cells (hCDCs) are taken into consideration as a promising cell resource in cell therapy in recent years. In this study, we designed an electrochemical stimulation system, which sends square pulses to the hCDCs and records their electrical response. Morphology, viability and differentiation of hCDCs are monitored at certain time courses of the treatment. Differentiating hCDCs aligned perpendicularly with respect to the direction of applied electric current, and obtained a spindle-like morphology, while they remained viable. At the same time, specific cardiac marker genes including GATA4, cTnT and α-MHC showed a considerable up-regulation. Our findings confirm that hCDCs differentiate to committed cardiomyocytes when hCDCs receive an electrical energy of 0.06 - 0.12 Wh. This amount of electrical energy could be applied to the stem cells using versatile electrical stimulation patterns via commercially available devices.


title: Management of neonates after postpartum discharge and all children in the ambulatory setting during the coronavirus disease 2019 pandemic.

text: PURPOSE OF REVIEW The present coronavirus disease 2019 (COVID-19) pandemic has created additional challenges with an increased number of presumed healthy, full-term newborns being discharged at 24 h after delivery. Short lengths of stay raise the possibility of mother-infant dyads being less ready for discharge, defined as at least one of the three informants (i.e., mother, pediatrician, and obstetrician) believing that either the mother and/or infant should stay longer than the proposed time of discharge. This public health crisis has reduced the number of in-person well child visits, negatively impacting vaccine receipt, and anticipatory guidance. RECENT FINDINGS Extra precautions should be taken during the transition period between postpartum discharge and follow-up in the ambulatory setting to ensure the safety of all patients and practice team members. This should include restructuring office flow by visit type and location, limiting in-person visits during well infant exams, instituting proper procedures for personal protective equipment and for cleaning of the office, expanding telehealth capabilities for care and education, and prioritizing universal vaccinations and routine screenings. SUMMARY Based on current limited evidence, this report provides guidance for the postdischarge management of newborns born to mothers with confirmed or suspected disease in the ambulatory setting as well as prioritizing universal immunizations and routine screenings during the COVID-19 pandemic.


title: MicroRNA-126 Regulates Angiogenesis and Neurogenesis in a Mouse Model of Focal Cerebral Ischemia.

text: Studies demonstrate that microRNA-126 plays a critical role in promoting angiogenesis. However, its effects on angiogenesis following ischemic stroke are unclear. Here, we explored the effect of microRNA-126-3p and microRNA-126-5p on angiogenesis and neurogenesis after brain ischemia. We demonstrated that both microRNA (miRNA)-126-3p and microRNA-126-5p increased the proliferation, migration, and tube formation of human umbilical vein endothelial cells (HUVECs) compared with the scrambled miRNA control (p < 0.05). Transferring microRNA-126 into a mouse middle cerebral artery occlusion model via lentivirus, we found that microRNA-126 overexpression increased the number of CD31+/BrdU+ (5-bromo-2'-deoxyuridine-positive) proliferating endothelial cells and DCX+/BrdU+ neuroblasts in the ischemic mouse brain, improved neurobehavioral outcomes (p < 0.05), and reduced brain atrophy volume (p < 0.05) compared with control mice. Western blot results showed that AKT and ERK signaling pathways were activated in the lentiviral-microRNA-126-treated group (p < 0.05). Both PCR and western blot results demonstrated that tyrosine-protein phosphatase non-receptor type 9 (PTPN9) was decreased in the lentiviral-microRNA-126-treated group (p < 0.05). Dual-luciferase gene reporter assay also showed that PTPN9 was the direct target of microRNA-126-3p and microRNA-126-5p in the ischemic brain. We demonstrated that microRNA-126-3p and microRNA-126-5p promoted angiogenesis and neurogenesis in ischemic mouse brain, and further improved neurobehavioral outcomes. Our mechanistic study further showed that microRNA-126 mediated angiogenesis through directly inhibiting its target PTPN9 and activating AKT and ERK signaling pathways.


title: A multidisciplinary, minimally invasive approach combining lacrimoscopy and fluoroscopically guided stenting for management of nasolacrimal apparatus obstruction in dogs.

text: OBJECTIVE To describe and evaluate outcomes of a multidisciplinary, minimally invasive approach combining lacrimoscopy and fluoroscopically guided stenting for management of nasolacrimal apparatus (NLA) obstruction in dogs. DESIGN Prospective, nonrandomized clinical trial. ANIMALS 16 client-owned dogs with confirmed NLA obstruction. PROCEDURES Dogs underwent CT contrast dacryocystorhinography, rhinoscopy, and lacrimoscopy. Whenever possible, the NLA was stented, typically with fluoroscopic guidance. RESULTS Median duration of clinical signs prior to treatment was 3.2 months (range, 0.2 to 14 months). Causes of NLA obstruction were a foreign body (n = 5), dacryocystitis (4), stenosis secondary to fibrosis (3), granulation tissue (1), or granulation tissue in association with a small foreign body (1); a cause was not identified in 2 dogs. Stents were placed in 14 of 16 (88%) dogs for a median duration of 5.6 weeks (range, 1.3 to 9.4 weeks). Stenting was not possible in 2 dogs with stenosis of the NLA secondary to granulation tissue or fibrosis. Owners of all 16 dogs reported at least 60% clinical improvement with median improvement rated as 95%, and owners of 8 dogs reporting complete resolution of signs. Two dogs required antimicrobial administration because of dacryocystitis that persisted after stent removal; a foreign body was not found in either dog. CONCLUSIONS AND CLINICAL RELEVANCE Overall clinical response and owner-rated improvement for dogs with NLA obstruction that underwent lacrimoscopy and fluoroscopically guided stenting were high, especially given that these dogs had failed to respond to conventional treatment.


title: Mechanism of PM2.5-induced human bronchial epithelial cell toxicity in central China.

text: Exposure to PM2.5 has been linked to respiratory disorders, yet knowledge of the molecular mechanism is limited. Here, PM2.5 was monitored and collected in central China, and its cytotoxicity mechanism on human bronchial epithelial cells (BEAS-2B) was investigated. With the average concentration of 109 ± 69 μg/m3, PM2.5 was rich in heavy metals and organic pollutants. After exposure to PM2.5, the viability of BEAS-2B cells decreased, where 510 dysregulated genes were predicted to induce necroptosis via inhibiting ATP synthesis through the oxidative phosphorylation signaling pathway. Cellular experiments demonstrated that the content of ATP was downregulated, while the expression of RIP3, a necroptosis indicator, was upregulated. Besides, four enzymes in charge of ATP synthesis were downregulated, including ATP5F, NDUF, COX7A, and UQCR, while two genes of RELA and CAPN1 responsible for necroptosis were upregulated. Furthermore, N-acetylcysteine was applied as an enhancer for ATP synthesis, which reversed the downregulation of ATP5F, NDUF, and COX7A, and consequently alleviated the elevation of RELA, CAPN1, and RIP3. In conclusion, PM2.5 exposure downregulates ATP5F, NDUF, COX7A, and UQCR, and that inhibits ATP synthesis via the oxidative phosphorylation signaling pathway, which subsequently upregulates RELA and CAPN1 and ultimately leads to necroptosis of BEAS-2B cells.


MedEdPublish.


title: Establishment of conventional PCR and real-time PCR assays for accurate, rapid and quantitative authentication of four mistletoe species.

text: Adulterants in processed food and herbal medicines reduce their safety, quality control, or pharmacological efficacy. Four mistletoe species, including Viscum coloratum, inhabit Korea. Leaves and branches of V. coloratum, defined as edible or medicinal mistletoe species in Korean, are used to prepare Korean herbal medicines as well as leached tea. However, other mistletoe species including Taxillus sutchuenensis var. duclouxii, Korthalsella japonica, and Loranthus tanakae are frequently distributed as authentic V. coloratum in Korean markets because of similarities in the branches morphology and Korean names of these species with V. coloratum. Although herbal medicines and food products prepared from the other mistletoe species are inauthentic, they are sold at high prices because of the rarity of these species. Thus, it is important to distinguish between authentic and inauthentic adulterant mistletoe species. In this study, we developed species-specific primer, based on matK sequences, suitable for both conventional PCR and real time PCR (qPCR) assay. These assays allowed rapid discrimination among all four mistletoe species. Moreover, qPCR assay enabled the detection of trace amounts of adulterant mistletoe species in V. coloratum samples. Furthermore, we used these assays to monitor commercial mistletoe products distributed in Korean markets. Our data suggest that these methods would serve as a reliable genetic tool to prevent adulteration and standardize the quality of commercial V. coloratum products.


title: Persistent posterior seroma after laparoscopic repair of ventral abdominal wall hernias with expanded polytetrafluoroethylene mesh: prevalence, independent predictors and detached tacks : Retrospective review.

text: PURPOSE A persistent seroma located posterior to a mesh (PPS) remains a little known complication after laparoscopic ventral hernia repair (LVHR). The aim of this large case series was to analyse the prevalence and clinical course as well as identify related factors and independent predictors of PPS. METHODS All 1288 adult patients who underwent a LVHR with an expanded polytetrafluoroethylene mesh (ePTFE) between January 2003 and July 2014 were reviewed. Those who underwent an abdominal computed tomography (CT) scan more than 3 months afterwards (n = 166) were included and their scans were analysed. The primary outcome measure was the prevalence of a PPS and its characteristics. The secondary outcome measures were identification of significantly related factors and independent predictors of PPS. RESULTS A PPS was observed in 14 of 166 analysed CT scans (8.4%). Eleven patients were symptomatic; conservative treatment (wait-and-see policy) was successful in eight. Three underwent relaparoscopy with removal of a thick neoperitoneum. Several instances of tack and/or mesh detachment were identified on CT scans and during relaparoscopy. Independent predictors were: > 3 trocars (RR 5.0, 95% CI 1.6-15.8) and use of a mesh larger than > 300 cm2 (RR 9.9, 95% CI 1.9-51.2). CONCLUSIONS A PPS is a relatively common complication after LVHR with an ePTFE mesh of usually larger hernias. A "wait-and-see" approach seems justified in most cases. Some require laparoscopic excision of the thick neoperitoneum. A PPS can cause tack and mesh detachment but the clinical consequences are unclear. Recurrences have not been observed in this series.


title: MicroRNA transcriptome analysis in chicken kidneys in response to differing virulent infectious bronchitis virus infections.

text: Infectious bronchitis virus (IBV) can cause a highly contagious and acute respiratory disease in poultry. MicroRNAs (miRNAs) have emerged as a class of crucial regulators for gene expression and are involved in the regulation of virus defence and immunological processes. To understand miRNA regulation in chickens in response to IBV infection, high-throughput sequencing was performed to compare the small RNA libraries from the kidneys of chicken infected with SCK2, SCDY2 and LDT3-A. By comparing these data to healthy chickens, a total of 58 differentially expressed (DE) miRNAs were identified. The DE miRNAs were further classified into five miRNA expression patterns (up or down regulation compared to control). Using Gene Ontology (GO) enrichment prediction, the DE miRNAs were shown to be mostly associated with metabolic processes, catalytic activities, gene expression, binding activities and immune responses. Seven highly expressed miRNAs (gga-miR-30d, gga-miR-1454, gga-miR-7b, gga-miR-215-5p, gga-miR-1a-3p, gga-miR-3538 and gga-miR-2954) were selected for miRNA-mRNA conjoint analysis. Furthermore, the miRNAs inversely correlated with the corresponding target gene mRNAs. These seven miRNAs were considered to play an important role in IBV-host interactions and the differing virulence of IBV strains. This is the first demonstration that infection with different virulent IBVs elicits different expression of miRNAs in chicken kidneys; this expression also seems to be associated with the virulence of IBV. These results are significant for the study of immune responses to infection with different virulent IBVs mediated by miRNAs as well as the interaction between the chicken host and IBV.


title: Use of stapling devices for safe cholecystectomy in acute cholecystitis.

text: Many techniques are described for the ligation of a difficult cystic duct (CD). The aim of this study is to assess the effectiveness and safety of stapling of a difficult CD in acute cholecystitis using Endo-GIA. From January 2008 to June 2012, 1441 patients with cholelithiasis underwent laparoscopic cholecystectomy (LC) at the Department of General Surgery, Haydarpasa Numune Education and Research Hospital. Of these, 19 (0.62%) were identified as having a difficult CD and were ligated using an Endo-GIA stapler. All patients were successfully treated with a laparoscopic approach. The length of hospital stay was 3.4 days. There were umbilical wound infections in 4 patients (21%). The length of follow-up ranged from 1.0 to 50.4 months. In conclusion, Endo-GIA is a safe and easy treatment method for patients with a dilated and difficult CD. The cystic artery should be isolated and ligated if possible before firing the Endo-GIA stapler. If isolation and stapling are not possible, fibrin sealant can be applied to avoid bleeding. The vascular Endo-GIA can be applied in a large CD, but for acute cholecystitis with an edematous CD, the Endo-GIA roticulator 4.8 or 3.5 stapler is preferred.


title: Training in neurology: Flexibility and adaptability of a neurology training program at the epicenter of COVID-19.

text: OBJECTIVE To outline changes made to a neurology residency program in response to coronavirus disease 2019 (COVID-19). METHODS In early March 2020, the first cases of COVID-19 were announced in the United States. New York City quickly became the epicenter of a global pandemic, and our training program needed to rapidly adapt to the increasing number of inpatient cases while being mindful of protecting providers and continuing education. Many of these changes unfolded over days, including removing residents from outpatient services, minimizing the number of residents on inpatient services, deploying residents to medicine services and medical intensive care units, converting continuity clinic patient visits to virtual options, transforming didactics to online platforms only, and maintaining connectedness in an era of social distancing. We have been able to accomplish this through daily virtual meetings among leadership, faculty, and residents. RESULTS Over time, our program has successfully rolled out initiatives to service the growing number of COVID-related inpatients while maintaining neurologic care for those in need and continuing our neurologic education curriculum. CONCLUSION It has been necessary and feasible for our residency training program to undergo rapid structural changes to adapt to a medical crisis. The key ingredients in doing this successfully have been flexibility and teamwork. We suspect that many of the implemented changes will persist long after the COVID-19 crisis has passed and will change the approach to neurologic and medical training.


Managing clinical trials for covid-19: the importance of ethics committees.


title: Open tension-free hernioplasty using a novel lightweight self-gripping mesh: medium-term experience from two institutions.

text: PURPOSE The process of mesh fixation and the potential risk of associated chronic pain are always surgeon's main concerns in hernia surgery. A wide variety of lightweight mesh models are currently available on the market to overcome some of these problems showing good preliminary results, but no data representing the medium- or long-term results. The present study aims to report the clinical outcomes of two institutional series of patients who underwent hernia repair using a partially absorbable auto adherent mesh (Parietene™ Progrip™--PP). METHODS A prospective analysis was performed including unselected patients with primary groin hernia who underwent a standardized Lichtenstein procedure using the PP mesh at two tertiary institutions. RESULTS During the 2-year study period, 181 patients (167 males; 14 females) with a median age of 63 years (19-85 years) were operated on at both centers. Short-term complications occurred in 27 patients (15%), the most commonly seen being urinary retention (6%) followed by hematoma (5%) and acute orchitis (2%). With a median follow-up of 17 months (12-29 months), 4 patients (2%) had a feeling of a foreign body in the groin, and 7 (4%) developed chronic pain. A total of four patients (2%) developed recurrence. CONCLUSIONS In our experience, the use of the PP mesh for hernioplasties offers a potential benefit not only in the short-term period but also in a medium-term follow-up with low recurrence and late chronic pain rates. However, this particular mesh does not fully prevent all complications and chronic pain and recurrent hernias have been reported for the first time.


title: Insights from COVID-19 cluster containment in Bhilwara District, Rajasthan.

text: Background In March 2020, a healthcare professional from a renowned private hospital, in the textile city of Bhilwara, Rajasthan, reported clustering of cases of pneumonia amongst doctors and paramedical staff suspected to be due to COVID-19. The basis of suspicion was clinico-eco-epidemiologic-radiological findings as, by that time, about 20 COVID19 cases were reported from the state of Rajasthan including a big Italian group of tourists who travelled extensively in Rajasthan, including Udaipur city. Objectives The current study presents the field experience of the Central and the State Rapid Response Teams (RRTs) in the cluster containment at Bhilwara. Methods: The information regarding the sociodemographic profile of the cases was provided by the Senior Medical Officer In-charge. The containment strategy was modeled under 6 pillars. Google Maps was used for preparing spot map. Results Immediate public health actions of cluster containment including contact tracing, quarantine, and isolation were initiated using epidemiological approach of mapping the cluster and taking care of reservoir of infection by the District Public Health Team supported by Multidisciplinary Rapid Response Team. This was supplemented by strict enforcement of lock down in the District taking care of daily need of the community by the leadership of administration with very strong intersectoral co-ordination (locally called "ruthless containment"). Conclusion The forthcoming challenge resides in re-establishment of inter-district and inter-state travel, which can become a risk of re-entry of the new cases, which needs to be taken care of, with the help of stringent administrative measures and screening at all points of entry. The team in Bhilwara needs to remain vigilant to pick up any imported cases early before local transmission establishes.


title: Effect of Axonal Trauma on Nerve Regeneration in Side-to-side Neurorrhaphy: An Experimental Study.

text: BACKGROUND Side-to-side (STS) neurorrhaphy can be performed distally to ensure timely end-organ innervation. It leaves the distal end of the injured nerve intact for further reconstruction. Despite encouraging clinical results, only few experimental studies have been published to enhance the regeneration results of the procedure. We examined the influence of different size epineural windows and degree of axonal injury of STS repair on nerve regeneration and donor nerve morbidity. METHODS Three clinically relevant repair techniques of the transected common peroneal nerve (CPN) were compared. Group A: 10-mm long epineural STS windows; group B: 2-mm long windows and partial axotomy to the donor tibial nerve; and group C: 2-mm long windows with axotomies to both nerves. Regeneration was followed by the walk track analysis, nerve morphometry, histology, and wet muscle mass calculations. RESULTS The results of the walk track analysis were significantly better in groups B and C compared with group A. The nerve fiber count, total fiber area, fiber density, and percentage of the fiber area values of CPN of the group C were significantly higher when compared with group A. The wet mass ratio of the CPN-innervated anterior tibial muscle was significantly higher in group C compared with group A. The wet mass ratio of the tibial nerve-innervated gastrocnemial muscle was higher in group A compared with the other groups. CONCLUSIONS All three variations of the STS repair technique showed nerve regeneration. Deliberate donor nerve axotomy enhanced nerve regeneration. A larger epineural window did not compensate the effect of axonal trauma on nerve regeneration.


title: Selective laser trabeculoplasty (SLT) performed by optometrists for patients with glaucoma and ocular hypertension: a scoping review protocol.

text: Introduction In the UK, the National Institute for Health and Clinical Excellence are amending guidelines to support use of selective laser trabeculoplasty (SLT) as a first-line treatment for patients with glaucoma and ocular hypertension. The procedure is quick, effective in lowering intraocular pressure, cost-effective for the National Health Service and offers an equivalent safety profile to other therapies. The procedure is typically performed by an ophthalmologist; however, there is potential for suitably trained non-medical professionals to deliver the therapy. This scoping review will identify service delivery models where SLT is delivered by non-medical professionals worldwide, with a focus on optometrists. Methods and analysis A systematic search of the following databases will be conducted: CINAHL; MEDLINE Complete; Embase; HMIC and Ovid Emcare. For inclusion, studies must examine healthcare models of SLT delivery by optometrists and describe one of the following outcomes: training procedures; clinical effectiveness; safety and cost-effectiveness. A search of grey literature will be conducted via professional societies; national health departments; medicine regulatory bodies; charities and conference proceedings. Two reviewers will independently screen titles, abstracts and full-texts articles, followed by charting of data. This evidence synthesis will summarise findings narratively, supplemented with tables and descriptive statistics. Ethics and dissemination The review focuses on published articles and therefore ethical approval is not required. The findings will be relevant to key stakeholders including health service managers, policymakers, clinicians and patients. The findings of this review will be disseminated through peer-reviewed publications, conference presentations and summary reports for key stakeholders.


title: Robotic cylindrical abdominoperineal resection with transabdominal levator transection.

text: PURPOSE The extralevator approach to abdominoperineal resection is an emerging surgical option for patients with low rectal cancer. This technique involves a wide excision of the levator muscles that could reduce the high incidence of circumferential margin positivity associated with conventional abdominoperineal resections. We present our technique of robotic cylindrical abdominoperineal resection where the daVinci robot is used to perform a controlled transection of the levator muscles transabdominally under direct visualization. METHODS Five patients with rectal adenocarcinoma within 5 cm of the anal verge underwent robot-assisted cylindrical abdominoperineal resection. Safety, feasibility, immediate postoperative outcomes, and pathological adequacy of the specimen were assessed. RESULTS The procedure was successfully completed in all 5 patients without any intraoperative complications, robot-associated morbidity, or conversion to the open approach. The mean operative time and length of hospital stay were 343 minutes and 5.8 days. An intact mesorectal envelope and negative circumferential margin was achieved in all cases. All specimens had a cylindrical shape. CONCLUSIONS Robotic assistance enables the transabdominal transection of the levator muscles in cylindrical abdominoperineal resection, with acceptable perioperative and pathological outcomes. Further studies are essential to objectively define the safety, efficacy, and long-term results of this new technique.


title: Inhibition of Human Metapneumovirus Binding to Heparan Sulfate Blocks Infection in Human Lung Cells and Airway Tissues.

text: UNLABELLED Human metapneumovirus (HMPV), a recently discovered paramyxovirus, infects nearly 100% of the world population and causes severe respiratory disease in infants, the elderly, and immunocompromised patients. We previously showed that HMPV binds heparan sulfate proteoglycans (HSPGs) and that HMPV binding requires only the viral fusion (F) protein. To characterize the features of this interaction critical for HMPV binding and the role of this interaction in infection in relevant models, we utilized sulfated polysaccharides, heparan sulfate mimetics, and occluding compounds. Iota-carrageenan demonstrated potent anti-HMPV activity by inhibiting binding to lung cells mediated by the F protein. Furthermore, analysis of a minilibrary of variably sulfated derivatives of Escherichia coli K5 polysaccharide mimicking the HS structure revealed that the highly O-sulfated K5 polysaccharides inhibited HMPV infection, identifying a potential feature of HS critical for HMPV binding. The peptide dendrimer SB105-A10, which binds HS, reduced binding and infection in an F-dependent manner, suggesting that occlusion of HS at the target cell surface is sufficient to prevent infection. HMPV infection was also inhibited by these compounds during apical infection of polarized airway tissues, suggesting that these interactions take place during HMPV infection in a physiologically relevant model. These results reveal key features of the interaction between HMPV and HS, supporting the hypothesis that apical HS in the airway serves as a binding factor during infection, and HS modulating compounds may serve as a platform for potential antiviral development. IMPORTANCE Human metapneumovirus (HMPV) is a paramyxovirus that causes respiratory disease worldwide. It has been previously shown that HMPV requires binding to heparan sulfate on the surfaces of target cells for attachment and infection. In this study, we characterize the key features of this binding interaction using heparan sulfate mimetics, identify an important sulfate modification, and demonstrate that these interactions occur at the apical surface of polarized airway tissues. These findings provide insights into the initial binding step of HMPV infection that has potential for antiviral development.


title: The Role of Punctuated Evolution in the Pathogenicity of Influenza Viruses.

text: Influenza is an acute respiratory disease caused by influenza viruses. Evolutionarily, all influenza viruses are zoonoses, arising in the animal reservoir and spilling over into the human population. Several times a century, one of these zoonotic events results in a new influenza virus lineage becoming established in humans and circulating for years or decades as an endemic strain. The worldwide pandemic that occurs shortly after the nascent virus becomes established can have a profound impact on morbidity and mortality. Because influenza viruses continually evolve and the illness they engender can vary considerably based on characteristics of the strain, the weather, other circulating or endemic pathogens, as well as the number of susceptible hosts, the impact of each season on human health is unpredictable. Over time, the general pattern is for pandemic strains to adapt and gradually take on characteristics of seasonal strains with lower virulence and a diminished synergism with bacterial pathogens. Study of this punctuated evolution yields a number of insights into the overall pathogenicity of influenza viruses.


title: A critical role for proinflammatory behavior of smooth muscle cells in hemodynamic initiation of intracranial aneurysm.

text: BACKGROUND Intracranial aneurysm initiation is poorly understood, although hemodynamic insult is believed to play an important role in triggering the pathology. It has recently been found in a rabbit model that while macrophages are absent during hemodynamic aneurysm initiation, matrix metalloproteinases (MMPs) are elevated and co-localize with smooth muscle cells (SMCs). This study investigates whether SMCs play a mechanistic role in aneurysm initiation triggered by hemodynamics. METHODS Aneurysmal damage was induced at the basilar terminus via bilateral common carotid artery ligation in rabbits (n = 45, plus 7 sham controls). 16 ligated rabbits were treated with doxycycline to inhibit MMPs, 7 received clodronate liposomes to deplete circulating monocytes, and the rest received no drug. Effects of the treatments on aneurysm development were assessed histologically 5 days and 6 months after ligation. MMP production and expression of inflammatory markers by SMCs was monitored by immunohistochemistry and in situ hybridization. RESULTS Treatment with doxycycline attenuated aneurysmal development examined at 5 days and 6 months, suggesting that MMPs contribute to aneurysm initiation. However, systemic depletion of macrophages did not decrease MMPs or suppress aneurysmal development. Immunofluorescence showed that during aneurysm initiation MMP-2 and MMP-9 were distributed in SMCs, and in situ hybridization indicated that they were transcribed by SMCs. In regions of early aneurysmal lesion, SMCs exhibited decreased expression of smooth muscle actin and increased NF-κB and MCP-1 expressions. CONCLUSIONS During aneurysm initiation triggered by hemodynamics, SMCs rather than macrophages are responsible for MMP production that is critical for aneurysmal lesion development. These SMCs exhibit proinflammatory behavior.


title: Prioritizing candidate disease genes by network-based boosting of genome-wide association data.

text: Network "guilt by association" (GBA) is a proven approach for identifying novel disease genes based on the observation that similar mutational phenotypes arise from functionally related genes. In principle, this approach could account even for nonadditive genetic interactions, which underlie the synergistic combinations of mutations often linked to complex diseases. Here, we analyze a large-scale, human gene functional interaction network (dubbed HumanNet). We show that candidate disease genes can be effectively identified by GBA in cross-validated tests using label propagation algorithms related to Google's PageRank. However, GBA has been shown to work poorly in genome-wide association studies (GWAS), where many genes are somewhat implicated, but few are known with very high certainty. Here, we resolve this by explicitly modeling the uncertainty of the associations and incorporating the uncertainty for the seed set into the GBA framework. We observe a significant boost in the power to detect validated candidate genes for Crohn's disease and type 2 diabetes by comparing our predictions to results from follow-up meta-analyses, with incorporation of the network serving to highlight the JAK-STAT pathway and associated adaptors GRB2/SHC1 in Crohn's disease and BACH2 in type 2 diabetes. Consideration of the network during GWAS thus conveys some of the benefits of enrolling more participants in the GWAS study. More generally, we demonstrate that a functional network of human genes provides a valuable statistical framework for prioritizing candidate disease genes, both for candidate gene-based and GWAS-based studies.


COVID-19 Research in Brief: 9 May to 15 May, 2020.


title: [Application of pulmonary ultrasound in the diagnosis of COVID-19 pneumonia in neonates].

text: Objective: To investigate the application of pulmonary ultrasound in the diagnosis of neonatal COVID-19. Methods: In this retrospective study, the clinical data of 5 infants, who were admitted to the Department of Neonatology in Wuhan Children's Hospital from 31(st) January to 25(th) February 2020, were collected. Bedsides pulmondary ultrasound was conducted on admission, during the hospitalization, and before discharge, the result were compared with the chest X-ray or CT done at the same time. Results: Among the 5 cases who aged 1-18 days, 3 were male. The main clinical manifestations were respiratory and gastrointestinal symptoms. The pulmonary ultrasonography on admission showed abnormal pleural line and pulmonary edema of different severity in all 5 cases, presented as increase and fusion of B-line, and pulmonary interstitial syndrome; among them, one case also had a small-range consolidation. The chest CT on admission showed no obvious parenchymal infiltration in 2 cases, small strip or patchy high-density shadow in 2 cases, and ground glass change in one case. The re-examination of ultrosound during the hospitalization and at discharge showed improvement in all cases and were consistent with the chest X-ray taken at the same time. Conclusions: The main changes on the pulmonary ultrasonography in neonates with COVID-19 pneumonia are increase and fusion of B-line, abnormal pleural line, and alveolar interstitial syndrome, and may coexist with small range of pulmonary consolidation. The sensitivity of pulmonary ultrasound is higher than that of chest X-ray and CT in the diagnosis of pulmonary edema, and could be used in monitoring and evaluation of the disease.


title: Development of reverse transcription recombinase polymerase amplification assay for avian influenza H5N1 HA gene detection.

text: The 2006 outbreaks of H5N1 avian influenza in Egypt interrupted poultry production and caused staggering economic damage. In addition, H5N1 avian influenza viruses represent a significant threat to public health. Therefore, the rapid detection of H5 viruses is very important in order to control the disease. In this study, a qualitative reverse transcription recombinase polymerase amplification (RT-RPA) assay for the detection of hemagglutinin gene of H5 subtype influenza viruses was developed. The results were compared to the real-time reverse transcription polymerase chain reaction (RT-PCR). An in vitro transcribed RNA standard of 970 nucleotides of the hemagglutinin gene was developed and used to determine the assay sensitivity. The developed H5 RT-RPA assay was able to detect one RNA molecule within 7 min, while in real-time RT-PCR, at least 90 min was required. H5 RT-RPA assay did not detect nucleic acid extracted from H5 negative samples or from other pathogens producing respiratory manifestation in poultry. The clinical performance of the H5 RT-RPA assay was tested in 30 samples collected between 2014 and 2015; the sensitivity of H5 RT-RPA and real-time RT-PCR was 100%. In conclusion, H5 RT-RPA was faster than real-time RT-PCR and easily operable in a portable device. Moreover, it had an equivalent sensitivity and specificity.


Intermittent high dosage oxygen treats COVID-19 infection: the Chinese studies.


title: Clinical trial design principles and endpoint definitions for transcatheter mitral valve repair and replacement: part 2: endpoint definitions: A consensus document from the Mitral Valve Academic Research Consortium.

text: Mitral regurgitation (MR) is one of the most prevalent valve disorders and has numerous aetiologies, including primary (organic) MR, due to underlying degenerative/structural mitral valve (MV) pathology, and secondary (functional) MR, which is principally caused by global or regional left ventricular remodelling and/or severe left atrial dilation. Diagnosis and optimal management of MR requires integration of valve disease and heart failure specialists, MV cardiac surgeons, interventional cardiologists with expertise in structural heart disease, and imaging experts. The introduction of trans- catheter MV therapies has highlighted the need for a consensus approach to pragmatic clinical trial design and uniform endpoint definitions to evaluate outcomes in patients with MR. The Mitral Valve Academic Research Consortium is a collaboration between leading academic research organizations and physician-scientists specializing in MV disease from the United States and Europe. Three in-person meetings were held in Virginia and New York during which 44 heart failure, valve, and imaging experts, MV surgeons and interventional cardiologists, clinical trial specialists and statisticians, and representatives from the U.S. Food and Drug Administration considered all aspects of MV pathophysiology, prognosis, and therapies, culminating in a 2-part document describing consensus recommendations for clinical trial design (Part 1) and endpoint definitions (Part 2) to guide evaluation of transcatheter and surgical therapies for MR. The adoption of these recommendations will afford robustness and consistency in the comparative effectiveness evaluation of new devices and approaches to treat MR. These principles may be useful for regulatory assessment of new transcatheter MV devices, as well as for monitoring local and regional outcomes to guide quality improvement initiatives.


title: Prospective analysis of the pattern and risk for severe vital sign changes during percutaneous radiofrequency ablation of the liver under opioid analgesia.

text: OBJECTIVE The aims of this study were to evaluate the pattern of vital sign changes and to elucidate significant risk factors for severe cardiovascular inhibition caused by percutaneous hepatic radiofrequency ablation (RFA). SUBJECTS AND METHODS A total of 102 patients (male-to-female ratio, 73:29; age range, 35-85 years; mean age, 58.1 years) with 119 malignant hepatic tumors were enrolled and analyzed prospectively. The patients underwent percutaneous RFA with IV infusion of opioid analgesics. Changes in blood pressure (BP) and heart rate (HR) and the occurrence of significant cardiovascular inhibition (BP or HR < 70% of baseline) were monitored during the procedure. Respiratory rate and skin body temperature were recorded before and after the procedure. RESULTS Whereas the mean BP was elevated (36%, 43/119) or depressed (36%, 43/119) with a similar frequency, the HR was predominantly depressed (56%, 66/119) during the procedure. The BP and HR were stable in only 18% cases (21/119), respectively. The respiratory rate showed no significant change (p = 0.521) after RFA; however, body temperature decreased (p < 0.001) after RFA. Although significant cardiovascular inhibition occurred in 41 cases (35%), all of the cases could be managed successfully and the technical success rate was 100% (119/119). Among the risk factors analyzed, old age (B = -0.003, p = 0.019) was significant for systolic BP depression, and contact of the RFA zone with the central portal vein (B = -0.096, p = 0.014) and female sex (B = -0.078, p = 0.033) were significant risk factors for HR depression as determined by multivariate analysis. CONCLUSION Changes in BP and HR, especially bradycardia, are common during percutaneous RFA of hepatic lesions. Significant risk factors for severe cardiovascular inhibition include contact of the RFA zone with the branches of the central portal vein, old age, and female sex.


title: Assay sensitivity and study features in neuropathic pain trials: an ACTTION meta-analysis.

text: OBJECTIVE Our objective was to identify patient, study, and site factors associated with assay sensitivity in placebo-controlled neuropathic pain trials. METHODS We examined the associations between study characteristics and standardized effect size (SES) in a database of 200 publicly available randomized clinical trials of pharmacologic treatments for neuropathic pain. RESULTS There was considerable heterogeneity in the SESs among the examined trials. Univariate meta-regression analyses indicated that larger SESs were significantly associated with trials that had 1) greater minimum baseline pain inclusion criteria, 2) greater mean subject age, 3) a larger percentage of Caucasian subjects, and 4) a smaller total number of subjects. In a multiple meta-regression analysis, the associations between SES and minimum baseline pain inclusion criterion and age remained significant. CONCLUSIONS Our analyses have examined potentially modifiable correlates of study SES and shown that a minimum pain inclusion criterion of 40 or above on a 0 to 100 scale is associated with a larger SES. These data provide a foundation for investigating strategies to improve assay sensitivity and thereby decrease the likelihood of falsely negative outcomes in clinical trials of efficacious treatments for neuropathic pain.


Testing strategy for SARS-CoV-2 in the paediatric emergency department.


title: A Prospective Blinded Study of Endoscopic Ultrasound Elastography in Liver Disease: Towards a Virtual Biopsy.

text: BACKGROUND/AIMS Liver biopsy has traditionally been used for determining the degree of fibrosis, however there are several limitations. Endoscopic ultrasound (EUS) real-time elastography (RTE) is a novel technology that uses image enhancement to display differences in tissue compressibility. We sought to assess whether liver fibrosis index (LFI) can distinguish normal, fatty, and cirrhotic liver tissue. METHODS A total of 50 patients undergoing EUS were prospectively enrolled. RTE of the liver was performed to synthesize the LFI in each patient. Univariate and multivariable analyses were performed. Chi-square and t-tests were performed for categorical and continuous variables, respectively. A p-value of <0.05 was considered significant. RESULTS Abdominal imaging prior to endoscopic evaluation suggested normal tissue, fatty liver, and cirrhosis in 26, 16, and 8 patients, respectively. Patients with cirrhosis had significantly increased mean LFI compared to the fatty liver (3.2 vs. 1.7, p<0.001) and normal (3.2 vs. 0.8, p<0.001) groups. The fatty liver group showed significantly increased LFI compared to the normal group (3.8 vs. 1.4, p<0.001). Multivariable regression analysis suggested that LFI was an independent predictor of group features (p<0.001). CONCLUSIONS LFI computed from RTE images significantly correlates with abdominal imaging and can distinguish normal, fatty, and cirrhotic-appearing livers; therefore, LFI may play an important role in patients with chronic liver disease.


title: Treatment of Intra- and Extracranial Aneurysms Using the Flow-Redirection Endoluminal Device: Multicenter Experience and Follow-Up Results.

text: BACKGROUND AND PURPOSE Flow diversion emerged as a crucial treatment option for intracranial aneurysms. We report a multicenter retrospective analysis of the safety and efficacy in the treatment of intracranial aneurysms with the Flow-Redirection Endoluminal Device (FRED) flow diverter, a dual-layer flow-modulation device. MATERIALS AND METHODS All intracranial aneurysms treated with the FRED between March 2013 and February 2016 at 4 neurovascular centers were included. Angiographic and clinical results were retrospectively analyzed, including all follow-up examinations. Aneurysms were unruptured in 44 cases, whereas 8 treatments were due to an acute SAH from the target aneurysm. RESULTS Successful implantation of the FRED was possible in 96.2% (50/52) of cases. At 3-month follow-up, complete occlusion was determined in 58.1% (25/43) and near-complete in 25.6% (11/43). At 12-month follow-up, aneurysm occlusion was complete in 75.0% (27/36) and near-complete in 22.2% (8/36). The overall acute and late thromboembolic and hemorrhagic complication rate was 17.3% (9/52), with a permanent treatment-related morbidity and mortality of 4.0% (2/50) and 2.0% (1/50), respectively, to date. CONCLUSIONS The FRED device offers an effective tool in the treatment of intracranial aneurysms. The dual-layer design promotes contemporary and stable long-term occlusion rates. Sufficient device expansion should be documented by angiographic CT. Further studies might help to identify a more optimal antiplatelet regimen to avoid thromboembolic complications during the follow-up period.


title: Comparison of combination therapies in the management of hepatocellular carcinoma: transarterial chemoembolization with radiofrequency ablation versus microwave ablation.

text: PURPOSE To compare retrospectively the outcomes and complications of transcatheter arterial chemoembolization with drug-eluting embolic agents combined with radiofrequency (RF) ablation or microwave (MW) ablation in treatment of hepatocellular carcinoma (HCC). MATERIALS AND METHODS From 2003-2011, 89 patients with HCC received a combination therapy-transcatheter arterial chemoembolization plus RF ablation in 38 patients and transcatheter arterial chemoembolization plus MW ablation in 51 patients. Local tumor response, tumor progression-free survival (PFS), overall PFS, overall survival (OS), and complications were compared. Overall PFS and OS were compared between the two treatment groups in multivariate analysis controlling for Child-Pugh class, Barcelona Clinic Liver Classification stage, and index tumor size. RESULTS Complete local tumor response was achieved in 37 (80.4%) of the tumors treated with transcatheter arterial chemoembolization plus RF ablation and 49 (76.6%) of the tumors treated with transcatheter arterial chemoembolization plus MW ablation (P = .67). The median tumor PFS and overall PFS were 20.8 months and 9.3 months (P = .72) for transarterial chemoembolization plus RF ablation and 21.8 months and 9.2 months for transarterial chemoembolization plus MW ablation (P = .32). The median OS of the transcatheter arterial chemoembolization plus RF ablation group was 23.3 months, and the median OS of the transcatheter arterial chemoembolization plus MW ablation group was 42.6 months, with no significant difference in the survival experience between the two groups (log-rank test, P = .10). In the multivariate analysis, Barcelona Clinic Liver Classification stage was the only factor associated with overall PFS and OS. One patient in the transcatheter arterial chemoembolization plus RF ablation cohort (3%) and two patients in the transcatheter arterial chemoembolization plus MW ablation cohort (4%) required prolonged hospitalization (< 48 h) for pain management after the procedure (P = 1.00). CONCLUSIONS Based on similar safety and efficacy outcomes, both combination therapies, transcatheter arterial chemoembolization plus RF ablation and transcatheter arterial chemoembolization plus MW ablation, are effective treatments for HCC.


title: A Teenager with Congenital Heart Defect and Covid-19.

text: A 16 year-old girl with history of treated congenital mitral valve disease and signs of respiratory infection was admitted to our pediatric cardiology department. She was tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Despite her severe preexisting cardiac conditions with pulmonary hypertension, atrial arrhythmias and mitral valve stenosis, the infection did not lead to any cardiac or pulmonary deterioration. In adults, cardiac comorbidities are known risk-factors for a severe course of Covid-19 infections. This case illustrates that in children even severe cardiac disease is not necessarily associated with a severe course of Covid-19.


title: The wire anchor loop traction (WALT) maneuver.

text: Crossing the neck of large complex intracranial aneurysms for the purposes of stent deployment can be challenging using standard over the wire techniques. We describe a novel yet simple technique for straightening out the loop formed within a large intracranial aneurysm, which is often required in order to cross the aneurysm neck into the distal branch. Both the microcatheter and microwire are initially introduced into the distal vasculature, followed by withdrawal of the microwire to a point parallel to the distal exiting branch. The microcatheter and microwire are then gently withdrawn and a series of maneuvers to gradually reduce the loop is performed, obviating the need for distal purchase in the form of a stent, balloon, or coil, which have previously been described to maintain distal purchase.


title: From SARS-CoV to SARS-CoV-2: The response and challenge of forensic infectious disease autopsy.

text: Abstract


title: Human small intestine is capable of restoring barrier function after short ischemic periods.

text: AIM To assess intestinal barrier function during human intestinal ischemia and reperfusion (IR). METHODS In a human experimental model, 6 cm of jejunum was selectively exposed to 30 min of ischemia (I) followed by 30 and 120 min of reperfusion (R). A sham procedure was also performed. Blood and tissue was sampled at all-time points. Functional barrier function was assessed using dual-sugar absorption tests with lactulose (L) and rhamnose (R). Plasma concentrations of citrulline, an amino acid described as marker for enterocyte function were measured as marker of metabolic enterocytes restoration. Damage to the epithelial lining was assessed by immunohistochemistry for tight junctions (TJs), by plasma marker for enterocytes damage (I-FABP) and analyzed by electron microscopy (EM) using lanthanum nitrate as an electrondense marker. RESULTS Plasma L/R ratio's were significantly increased after 30 min of ischemia (30I) followed by 30 min of reperfusion (30R) compared to control (0.75 ± 0.10 vs 0.20 ± 0.09, P < 0.05). At 120 min of reperfusion (120R), ratio's normalized (0.17 ± 0.06) and were not significantly different from control. Plasma levels of I-FABP correlated with plasma L/R ratios measured at the same time points (correlation: 0.467, P < 0.01). TJs staining shows distortion of staining at 30I. An intact lining of TJs was again observed at 30I120R. Electron microscopy analysis revealed disrupted TJs after 30I with paracellular leakage of lanthanum nitrate, which restored after 30I120R. Furthermore, citrulline concentrations closely paralleled the histological perturbations during intestinal IR. CONCLUSION This study directly correlates histological data with intestinal permeability tests, revealing that the human gut has the ability of to withstand short episodes of ischemia, with morphological and functional recovery of the intestinal barrier within 120 min of reperfusion.


title: A novel design for steerable instruments based on laser-cut nitinol.

text: OBJECTIVE Omnidirectional articulated instruments enhance dexterity. In neurosurgery, for example, the simultaneous use of 2 instruments through the same endoscopic shaft remains a difficult feat. It is, however, very challenging to manufacture steerable instruments of the requisite small diameter. We present a new technique to produce such instruments by means of laser cutting. Only 3 coaxial tubes are used. The middle tube has a cutting pattern that allows the steering forces to be transmitted from the proximal to the distal end. In this way the steering part is concealed in the wall of the tube. Large diameter articulated instruments such as for laparoscopy might benefit from the excellent tip stability provided by the same economical technology. METHOD Coaxial nitinol tubes are laser-cut with a Rofin Stent Cutter in a specific pattern. The 3 tubes are assembled by sliding them over one another, forming a single composite tube. In a surgical simulator, the neurosurgical microinstruments and laparoscopic needle drivers were evaluated on surgical convenience. RESULTS Simultaneous use of 2 neurosurgical instruments (1.5 mm diameter) through the same endoscopic shaft proved to be very intuitive. The tip of the steerable laparoscopic instruments (10 mm diameter) could resist a lateral force of more than 20 N. The angle of motion for either instrument was at least 70° in any direction. CONCLUSIONS A new design for steerable endoscopic instruments is presented. It allows the construction in a range from microinstruments to 10-mm laparoscopic devices with excellent tip stability.


Regional coordination and bottom-up response of general practitioners in Belgium and the Netherlands.


title: Multi-modal Framework for Image-guided Trans-oral Surgery with Intraoperative Imaging and Deformation Modeling.

text: Treatment of throat cancers have improved due to minimally-invasive trans-oral approaches. Surgeons rely on preoperative imaging to guide their resection; however, large tissue deformations occur during trans-oral procedures due to placement of necessary retractors and laryngoscopes which hinders the surgeon's ability to accurately assess tumor extent and location of critical structures. We propose an image-guided framework utilizing intraoperative imaging and deformation modeling to improve surgeon accuracy and confidence. A CT-compatible laryngoscopy system previously developed was evaluated in this framework. Intraoperative images were acquired during laryngoscopy; force-sensing capabilities were enabled in the laryngoscope; and tracking of the scope and anatomic features was trialed. Tissue deformation and displacement were quantified and determined to be extensive, with values <; 4.6 cm in the tongue, <; 1.8 cm in bony structures, and <; 108.9 cm3 in airway volume change. Surgical navigation using intraoperative imaging and tracking was evaluated. Preliminary assessment of deformation modeling showed potential to supplement intraoperative imaging. Future work will involve streamlined integration of the components of this framework.


title: Virus and Immune-Mediated Encephalitides: Epidemiology, Diagnosis, Treatment, and Prevention.

text: Virus encephalitis remains a major cause of acute neurological dysfunction and permanent disability among children worldwide. Although some disorders, such as measles encephalomyelitis, subacute sclerosing panencephalitis, and varicella-zoster virus-associated neurological conditions, have largely disappeared in resource-rich regions because of widespread immunization programs, other disorders, such as herpes simplex virus encephalitis, West Nile virus-associated neuroinvasive disease, and nonpolio enterovirus-induced disorders of the nervous system, cannot be prevented. Moreover, emerging viral disorders pose new, potential threats to the child's nervous system. This review summarizes current information regarding the epidemiology of virus encephalitis, the diagnostic methods available to detect central nervous system infection and identify viral pathogens, and the available treatments. The review also describes immune-mediated disorders, including acute disseminated encephalomyelitis and N-methyl-D-aspartate receptor antibody encephalitis, conditions that mimic virus encephalitis and account for a substantial proportion of childhood encephalitis.


title: A review of antibody-based therapeutics targeting G protein-coupled receptors: an update.

text: Introduction: G protein-coupled receptors (GPCRs) play key roles in many biological functions and are linked to many diseases across all therapeutic areas. As such, GPCRs represent a significant opportunity for antibody-based therapeutics.Areas covered: The structure of the major GPCR families is summarized in the context of choice of antigen source employed in the drug discovery process and receptor biology considerations which may impact on targeting strategies. An overview of the therapeutic GPCR-antibody target landscape and the diversity of current therapeutic programs is provided along with summary case studies for marketed antibody drugs or those in advanced clinical studies. Antibodies in early clinical studies and the emergence of next-generation modalities are also highlighted.Expert opinion: The GPCR-antibody pipeline has progressed significantly with a number of technical developments enabling the successful resolution of some of the challenges previously encountered and this has contributed to the growing interest in antibody-based therapeutics addressing this target class.