title: Clinical management of an ectopic egg in a Timneh African grey parrot (Psittacus erithacus timneh).

text: CASE DESCRIPTION A 13-year-old female Timneh African grey parrot (Psittacus erithacus timneh) was evaluated because of the presence of a bald patch of skin caudal to the sternum and increased territorial and nesting behavior of 2 weeks' duration. CLINICAL FINDINGS Whole-body radiography revealed a mineralized egg of normal size and shape. However, no oviposition occurred, and the bird had no signs consistent with dystocia. After 7 days, repeated radiography revealed that the egg had rotated by approximately 180° along its short axis, leading to a diagnosis of ectopic egg retention, which was supported by the results of ultrasonography. TREATMENT AND OUTCOME Surgical removal of the ectopic egg was performed by means of a ventral midline approach 14 days after administration of leuprolide acetate (800 μg/kg [364 μg/lb], IM). No intracoelomic abnormalities, such as coelomitis or oviductal disease, were diagnosed, and the bird recovered without complications. Physical examination and whole-body radiography at 8 months and a follow-up phone call with the owner at 16 months after surgical treatment revealed no evidence of ectopic egg recurrence or reproductive behavior. CLINICAL RELEVANCE Clinical management of ectopic egg retention differs considerably from treatment of intraoviductal egg binding. Therefore, careful evaluation of avian patients with radiographic evidence of egg binding should be performed to avoid possible iatrogenic deterioration of the patient's condition, secondary to inappropriate treatment attempts such as hormonal induction of oviposition or attempts to remove the retained egg via the cloaca. Repeated radiography and ultrasonography and close monitoring of the patient's general condition as well as the lack of clinical signs consistent with dystocia will facilitate the diagnosis of ectopic egg retention.


title: The role of viruses in the clinical presentation of chronic rhinosinusitis.

text: BACKGROUND The role of viruses in chronic rhinosinusitis (CRS) is poorly understood. In part, this is secondary to difficulty in isolating viruses. Although traditional detection methods for respiratory viruses have had little clinical utility, modern viral screening techniques that use molecular sequencing are now both rapid and feasible, which makes analysis of the paranasal sinus microbiome more accessible. OBJECTIVE To detect respiratory viruses in the paranasal sinuses of patients with CRS and of healthy controls as well as to correlate clinical and radiographic measures of CRS with viral presence. METHODS In this prospective study, 13 patients with CRS with nasal polyposis (CRSwNP) and 8 patients without nasal polyposis (CRSsNP) were enrolled and compared with 14 healthy controls. Samples were obtained from the paranasal sinuses and were screened for viral DNA with polymerase chain reaction--based sequencing techniques. Typical symptoms of CRS, the Sinonasal Questionnaire, and objective measures, including the modified Lund-Mackay and modified Lund-Kennedy scores were obtained. RESULTS Eighty percent of the positive screens (4/5) were found in patients with CRSsNP, whereas 20% of the positive tests (1/5) were in the CRSwNP group, and none of the controls tested positive (p = 0.0029). Coronavirus was the most common virus detected. Sinonasal Questionnaire scores of the patients with CRS who tested positive for viruses were higher but not statistically different than those without a positive screen (p = 0.31). Radiographic and endoscopic measures of disease were not significantly different in the setting of a positive viral screen (p = 0.12 and 0.11 respectively). CONCLUSION Although traditionally difficult, advances in molecular sequencing enhance detection of viruses in the sinonasal tract. In this study, respiratory viruses were more commonly isolated from patients with CRS compared with healthy controls. Moreover, viral infection may play a greater role in symptom exacerbation in CRSsNP than in CRSwNP. These findings warrant further investigation into the role of the viral microbiome in CRS.


title: Simple classification and clinical outcomes of angiographic dissection after balloon angioplasty for femoropopliteal disease.

text: OBJECTIVE Angiographic dissection is considered to be associated with restenosis. However, little is known about the impact of the severity of angiographic dissection on future restenosis. METHODS A total of 319 consecutive de novo femoropopliteal lesions were treated by balloon angioplasty alone. All of these lesions were divided into three groups: group A, no angiographic dissection; group B, mild dissection, the width of the dissection was less than one-third of the lumen; and group C, severe dissection, the width of the dissection was more than one-third of the lumen. Kaplan-Meier analysis estimated the primary patency rate at 3 years between the groups. RESULTS The primary patency rates at 3 years were 66.0% in group A, 63.8% in group B, and 32.5% in group C (log-rank, P < .001). Cox proportional hazards analysis revealed that a lesion length >100 mm (hazard ratio, 1.734; 95% confidence interval, 1.099-2.735; P = .018) and severe angiographic dissection (hazard ratio, 1.956; 95% confidence interval, 1.276-2.997; P = .002) were predictors of primary patency loss at 3 years. When the lesions were divided into two groups according to the lesion length >100 mm or not, angiographic dissection had a larger impact on restenosis in a long lesion >100 mm (≤100 mm: 65.5% in group A, 75.6% in group B, and 48.0% in group C [log-rank, P = .015]; >100 mm: 68.8% in group A, 42.5% in group B, and 24.2% in group C [log-rank, P = .017]). CONCLUSIONS Severe angiographic dissection was associated with future restenosis after balloon angioplasty for femoropopliteal lesions, but mild angiographic dissection was not. Angiographic dissection had more impact on future restenosis particularly in treated long lesions. Stents might not be necessary in short lesions with mild dissection.


title: COVID-19 Pandemic: Hopes from Proteomics and Multiomics Research.

text: The successful sequencing of the novel coronavirus SARS-CoV-2 nucleic acid paved the way for exploration of omics systems science and integrative biology research approaches for combating this unprecedented planetary health challenge. Omics-scale studies on this viral infection are emerging rapidly and offer a tremendous potential to unravel the puzzles of the SARS-CoV-2 pathobiology, and ways forward for diagnostic and therapeutic innovation.


title: Development of a loop-mediated isothermal amplification targeting a gene within the pyruvate dehydrogenase complex, the pdhA gene, for rapid detection of Mycoplasma gallisepticum.

text: Mycoplasma gallisepticum infections impose a significant economic burden on the poultry industry. In the current study, a loop-mediated isothermal amplification (LAMP) assay was developed and optimized to detect M. gallisepticum based on a gene within the pyruvate dehydrogenase complex, the pdhA gene, which codes for the major subunit (E1α) in the complex. The reaction conditions were optimized, and the specificity was confirmed by successful amplification of several M. gallisepticum strains, while no amplification was detected with 20 other major bacterial and viral pathogens of poultry. Additionally, the LAMP assay achieved 10-fold higher sensitivity than an existing polymerase chain reaction (PCR) method. The LAMP assay was applied to swab samples collected from poultry farms and compared with PCR. The positive detection rate was 20.2% (37/183) by LAMP and 13.1% (24/183) by PCR. The LAMP assay could provide a cost-effective, quick, and sensitive method for the detection of M. gallisepticum.


title: Novel Totally Laparoscopic Endolumenal Rectal Resection With Transanal Natural Orifice Specimen Extraction (NOSE) Without Rectal Stump Opening: A Modification of Our Recently Published Clean Surgical Technique in a Porcine Model.

text: Our group has recently described a novel technique for clean endolumenal bowel resection, in which abdominal and transanal approaches were used. In the current study, 2 modifications of this procedure were tested for feasibility in a porcine model. A laparoscopic approach to the peritoneal cavity was employed in rectal mobilization; this was followed by a transanal rectorectal intussusception and pull-through (IPT). IPT was established in a stepwise fashion. First, the proximal margin of resection was attached to the shaft of the anvil of an end-to-end circular stapler with a ligature around the rectum. Second, this complex was pulled transanally to produce IPT. Once IPT was established, a second ligature was placed around the rectum approximating the proximal and distal resection margins. This was followed by a purse string suture through 2 bowel walls, encircling the shaft of the anvil just proximal to the ligatures. The specimen was resected and extracted by making a full-thickness incision through the 2 bowel walls distal to the previously placed purse string suture and ligatures. The anastomosis was achieved by applying the stapler. The technique was found to be feasible. Peritoneal samples, collected after transanal specimen extraction, did not demonstrate bacterial growth. Although, this is a novel and evolving procedure, its minimally invasive nature, as well as aseptic bowel manipulation during endolumenal rectal resection, has the potential to limit the complications associated with abdominal wall incision and surgical site infection.


title: Disastrous events and political failures.

text: Response to the Ebola crisis (ongoing event) has been less than efficient. It has been monitored less than adequately by the international community and has been coordinated poorly in the USA. The event is used as a platform to examine deficiencies in public health infrastructure, the limits of its political and financial support, and how political outcomes can be affected. The need to tease out the political determinants implicit in policy failure and disaster management is argued in this Editorial. Failures mentioned include in the Balkans and in Greece with ongoing austerity. Comments on the real heroes of Ebola on the ground in Africa and the need for a charismatic role for political leaders in public health are also included.


title: Laparoscopic versus open parenchymal preserving liver resections in the posterosuperior segments: a case-matched study.

text: BACKGROUND Patients with lesions in the posterosuperior (PS) segments of the liver have been considered poor candidates for laparoscopic liver resection (LLR). This study aims to compare short-term outcomes of LLR and open liver resections (OLR) in the PS segments. METHODS This multicenter study consisted of all patients who underwent LLR in the PS segments and all patients who underwent OLR in the PS segments between October 2011 and July 2016. Laparoscopic cases were case-matched with those who had an identical open procedure during the same period based on tumor location (same segment) and the Brisbane classification of the resection. Demographics, comorbid factors, perioperative outcomes, short-term outcomes, necessity of adjuvant chemotherapy, and the interval between surgery and initiation of adjuvant chemotherapy were compared between the two groups. Data were retrieved from a prospectively maintained electronic database. RESULTS Both groups were comparable for age, sex, ASA score, maximum tumor diameter, and number of patients with additional liver resections outside the posterior segments. Operative time was similar in both groups (median 140 min; p = 0.92). Blood loss was less in the LLR-group (median: 150 vs. 300 ml in OLR-group). Median hospital stay was 6 days in both groups. There was no significant difference in postoperative complications (OLR-group: 31.4% vs. LLR-group: 25.7%; p = 0.60). There was no significant difference in R0 resections (LLR: 97.2 vs. 100% in OLR; p = 1.00). Tumor-free margins were less in the LLR group (LLR: 5 vs. 9.5 mm in OLR; p = 0.012). Patients undergoing LLR were treated with chemotherapy sooner compared to those undergoing OLR (41 vs. 56 days, p = 0.02). CONCLUSION This study suggests that laparoscopic parenchymal preserving liver resections in the PS segments can be performed with comparable short-term outcomes as similar OLR. The shorter interval to chemotherapy might provide long-term oncologic benefits in patients who underwent LLR.


title: Challenges facing coronavirus disease 2019: Psychiatric services for patients with mental disorders.

text: As a Public Health Emergency of International Concern declared by WHO, the current outbreak of coronavirus disease (COVID-19) in China has captured the world's attention.1.


title: Acute heart failure in multisystem inflammatory syndrome in children (MIS-C) in the context of global SARS-CoV-2 pandemic.

text: Background: Cardiac injury and myocarditis have been described in adults with COVID-19. SARS-CoV-2 infection in children is typically minimally symptomatic. We report a series of febrile pediatric patients with acute heart failure potentially associated with SARS-CoV-2 infection and the multisystem inflammatory syndrome in children (MIS-C) as defined by the US Centers for Disease Control. Methods: Over a two-month period contemporary with the SARS-CoV-2 pandemic in France and Switzerland, we retrospectively collected clinical, biological, therapeutic, and early outcomes data in children who were admitted to pediatric intensive care units in 14 centers for cardiogenic shock, left ventricular dysfunction and severe inflammatory state. Results: Thirty-five children were identified and included in the study. Median age at admission was 10 years (range 2-16 years). Co-morbidities were present in 28% including asthma and overweight. Gastrointestinal symptoms were prominent. Left ventricular ejection fraction was <30% in one third; 80% required inotropic support with 28% treated with ECMO. Inflammation markers were suggestive of cytokine storm (interleukin 6 median 135 pg/mL) and macrophage activation (D-dimer median 5284 ng/mL). Mean brain natriuretic peptide was elevated (5743 pg/mL). Thirty-one/35 (88%) patients tested positive for SARS-CoV-2 infection by PCR of nasopharyngeal swab or serology. All patients received intravenous immune globulin, with adjunctive steroid therapy used in one third. Left ventricular function was restored in the 25/35 of those discharged from the intensive care unit. No patient died, and all patients treated with ECMO were successfully weaned. Conclusion: Children may experience an acute cardiac decompensation due to severe inflammatory state following SARS-CoV-2 infection (multisystem inflammatory syndrome in children - MIS-C). Treatment with immune globulin appears to be associated with recovery of left ventricular systolic function.


title: Laryngeal injuries following endotracheal intubation in ENT surgery: predictive value of anatomical scores.

text: Endotracheal intubation has been associated with a threefold higher incidence of laryngopharyngeal complaints following anesthesia in comparison to laryngeal mask airway. Such complaints, including hoarseness and sore throat, have been reported in up to 90% of patients within 24 h of extubation. The purpose of this study was to determine which preoperatively documented clinical and anatomic parameters are predictive of laryngo-pharyngeal trauma resulting from elective endotracheal intubation. Fifty-three patients undergoing ENT procedures requiring general anesthesia with endotracheal intubation were recruited. Pre and postoperative laryngostroboscopic examination was performed and findings correlated to preoperative clinical and anatomic parameters. Readily assessed anatomic parameters including height (>180 cm) and weight (>80 kg) correlated significantly to the Eckerbom grade of intubation-associated acute laryngeal injury (rs = 0.374; p = 0.006 and rs = 0.278; p = 0.044, respectively). The mandibular protrusion test also correlated significantly to the Eckerbom grade (rs = 0.462, p = 0.001) while the upper-lip-bite test showed significant correlation to impaired vocal fold oscillation (rs = 0.288, p = 0.036), with injury prediction sensitivities of 37.5 and 39.4%, respectively. No parameters correlated to subjective complaints (n = 5, 9.2%). This study provides suggestions on how to improve the classification of intubation-associated laryngeal injuries as well as providing the basis for larger clinical trials in other surgical subspecialties.


title: Development of Snake Fungal Disease after Experimental Challenge with Ophidiomyces ophiodiicola in Cottonmouths (Agkistrodon piscivorous).

text: Snake fungal disease (SFD) is a clinical syndrome associated with dermatitis, myositis, osteomyelitis, and pneumonia in several species of free-ranging snakes in the US. The causative agent has been suggested as Ophidiomyces ophiodiicola, but other agents may contribute to the syndrome and the pathogenesis is not understood. To understand the role of O. ophiodiicola in SFD, a cottonmouth snake model of SFD was designed. Five cottonmouths (Agkistrodon piscivorous) were experimentally challenged by nasolabial pit inoculation with a pure culture of O. ophiodiicola. Development of skin lesions or facial swelling at the site of inoculation was observed in all snakes. Twice weekly swabs of the inoculation site revealed variable presence of O. ophiodiicola DNA by qPCR in all five inoculated snakes for 3 to 58 days post-inoculation; nasolabial flushes were not a useful sampling method for detection. Inoculated snakes had a 40% mortality rate. All inoculated snakes had microscopic lesions unilaterally on the side of the swabbed nasolabial pit, including erosions to ulcerations and heterophilic dermatitis. All signs were consistent with SFD; however, the severity of lesions varied in individual snakes, and fungal hyphae were only observed in 3 of 5 inoculated snakes. These three snakes correlated with post-mortem tissue qPCR evidence of O. ophiodiicola. The findings of this study conclude that O. ophiodiicola inoculation in a cottonmouth snake model leads to disease similar to SFD, although lesion severity and the fungal load are quite variable within the model. Future studies may utilize this model to further understand the pathogenesis of this disease and develop management strategies that mitigate disease effects, but investigation of other models with less variability may be warranted.


Outcomes of the 10th International Conference on Pediatric Mechanical Circulatory Support Systems and Pediatric Cardiopulmonary Perfusion.


title: Kinetic characterization and molecular docking of a novel, potent, and selective slow-binding inhibitor of human cathepsin L.

text: A novel small molecule thiocarbazate (PubChem SID 26681509), a potent inhibitor of human cathepsin L (EC 3.4.22.15) with an IC(50) of 56 nM, was developed after a 57,821-compound screen of the National Institutes of Health Molecular Libraries Small Molecule Repository. After a 4-h preincubation with cathepsin L, this compound became even more potent, demonstrating an IC(50) of 1.0 nM. The thiocarbazate was determined to be a slow-binding and slowly reversible competitive inhibitor. Through a transient kinetic analysis for single-step reversibility, inhibition rate constants were k(on) = 24,000 M(-1)s(-1) and k(off) = 2.2 x 10(-5) s(-1) (K(i) = 0.89 nM). Molecular docking studies were undertaken using the experimentally derived X-ray crystal structure of papain/CLIK-148 (1cvz. pdb). These studies revealed critical hydrogen bonding patterns of the thiocarbazate with key active site residues in papain. The thiocarbazate displayed 7- to 151-fold greater selectivity toward cathepsin L than papain and cathepsins B, K, V, and S with no activity against cathepsin G. The inhibitor demonstrated a lack of toxicity in human aortic endothelial cells and zebrafish. In addition, the thiocarbazate inhibited in vitro propagation of malaria parasite Plasmodium falciparum with an IC(50) of 15.4 microM and inhibited Leishmania major with an IC(50) of 12.5 microM.


title: Transcaval access for TAVR across a polyester aortic graft.

text: Transcaval access to the aorta allows transcatheter aortic valve replacement in patients without other good access options. The resulting aorto-caval fistula is closed with a nitinol cardiac occluder device. There is no experience traversing a synthetic aortic graft to perform transcaval access and closure. We describe a patient who underwent successful traversal of a polyester aortic graft using radiofrequency energy applied from the tip of a guidewire, to allow retrograde transcatheter aortic valve replacement from a femoral vein, along with details of our technique. The patient did well and was discharged home after 3 days. There was residual aorto-caval fistulous flow immediately after implantation of a polyester-seeded nitinol muscular ventricular septal defect occluder device, but this fistula spontaneously occluded within one month.


title: Factors predicting chronic pain after open inguinal hernia repair: a regression analysis of randomized trial comparing three different meshes with three fixation methods (FinnMesh Study).

text: BACKGROUND Chronic pain after inguinal hernioplasty is the foremost side-effect up to 10-30% of patients. Mesh fixation may influence on the incidence of chronic pain after open anterior mesh repairs. METHODS Some 625 patients who underwent open anterior mesh repairs were randomized to receive one of the three meshes and fixations: cyanoacrylate glue with low-weight polypropylene mesh (n = 216), non-absorbable sutures with partially absorbable mesh (n = 207) or self-gripping polyesther mesh (n = 202). Factors related to chronic pain (visual analogue scores; VAS ≥ 30, range 0-100) at 1 year postoperatively were analyzed using logistic regression method. A second analysis using telephone interview and patient records was performed 2 years after the index surgery. RESULTS At index operation, all patient characteristics were similar in the three study groups. After 1 year, chronic inguinal pain was found in 52 patients and after 2 years in only 16 patients with no difference between the study groups. During 2 years' follow-up, three (0.48%) patients with recurrences and five (0.8%) patients with chronic pain were re-operated. Multivariate regression analysis indicated that only new recurrent hernias and high pain scores at day 7 were predictive factors for longstanding groin pain (p = 0.001). Type of mesh or fixation, gender, pre-operative VAS, age, body mass index or duration of operation did not predict chronic pain. CONCLUSION Only the presence of recurrent hernia and early severe pain after index operation seemed to predict longstanding inguinal pain.


title: Influence of DOTA chelator position on biodistribution and targeting properties of (111)In-labeled synthetic anti-HER2 affibody molecules.

text: Affibody molecules are a class of affinity proteins. Their small size (7 kDa) in combination with the high (subnanomolar) affinity for a number of cancer-associated molecular targets makes them suitable for molecular imaging. Earlier studies demonstrated that the selection of radionuclide and chelator may substantially influence the tumor-targeting properties of affibody molecules. Moreover, the placement of chelators for labeling of affibody molecules with (99m)Tc at different positions in affibody molecules influenced both blood clearance rate and uptake in healthy tissues. This introduces an opportunity to improve the contrast of affibody-mediated imaging. In this comparative study, 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) was conjugated to the synthetic affibody molecule Z(HER2:S1) at three different positions: DOTA-A1-Z(HER2:S1) (N-terminus), DOTA-K58-Z(HER2:S1) (C-terminus), and DOTA-K50-Z(HER2:S1) (middle of helix 3). The affinity for HER2 differed slightly among the variants and the K(D) values were determined to be 133 pM, 107 pM and 94 pM for DOTA-A1-Z(HER2:S1), DOTA-K50-Z(HER2:S1), and DOTA-K58-Z(HER2:S1), respectively. Z(HER2:S1)-K50-DOTA showed a slightly lower melting point (57 °C) compared to DOTA-A1-Z(HER2:S1) (64 °C) and DOTA-K58-Z(HER2:S1) (62 °C), but all variants showed good refolding properties after heat treatment. All conjugates were successfully labeled with (111)In resulting in a radiochemical yield of 99% with preserved binding capacity. In vitro specificity studies using SKOV-3 and LS174T cell lines showed that the binding of the radiolabeled compounds was HER2 receptor-mediated, which also was verified in vivo using BALB/C nu/nu mice with LS174T and Ramos lymphoma xenografts. The three conjugates all showed specific uptake in LS174T xenografts in nude mice, where DOTA-A1-Z(HER2:S1)and DOTA-K58-Z(HER2:S1) showed the highest uptake. Overall, DOTA-K58-Z(HER2:S1) provided the highest tumor-to-blood ratio, which is important for a high-contrast imaging. In conclusion, the positioning of the DOTA chelator influences the cellular processing and the biodistribution pattern of radiolabeled affibody molecules, creating preconditions for imaging optimization.


title: Ethics Lessons From Seattle's Early Experience With COVID-19.

text: Ethics consultants and critical care clinicians reflect on Seattle's early experience as the United States' first epicenter of COVID-19. We discuss ethically salient issues confronted at UW Medicine's hospitals and provide lessons for other health care institutions that may soon face what we have faced.


title: Deep learning-based image reconstruction and motion estimation from undersampled radial k-space for real-time MRI-guided radiotherapy.

text: Purpose: To enable magnetic resonance imaging (MRI)-guided radiotherapy with real-time adaptation, motion must be quickly estimated with low latency. The motion estimate is used to adapt the radiation beam to the current anatomy, yielding a more conformal dose distribution. As the MR acquisition is the largest component of latency, deep learning (DL) may reduce the total latency by enabling much higher undersampling factors compared to conventional reconstruction and motion estimation methods. The benefit of DL on image reconstruction and motion estimation was investigated for obtaining accurate deformation vector fields (DVFs) with high temporal resolution and minimal latency.Methods: 2D cine MRI acquired at 1.5T from 135 abdominal cancer patients were retrospectively included in this study. Undersampled radial golden angle acquisitions were retrospectively simulated. DVFs were computed using different combinations of conventional- and DL-based methods for image reconstruction and motion estimation, allowing a comparison of four approaches to achieve real-time motion estimation. The four approaches were evaluated based on the end-point-error and root-mean-square error compared to a ground-truth optical flow estimate on fully-sampled images, the structural similarity (SSIM) after registration and time necessary to acquire k-space, reconstruct an image and estimate motion.Results: The lowest DVF error and highest SSIM were obtained using conventional methods up to R≤10. For undersampling factors R>10, the lowest DVF error and highest SSIM were obtained using conventional image reconstruction and DL-based motion estimation. We have found that, with this combination, accurate DVFs can be obtained up to R=25 with an average root-mean-square error up to 1 millimeter and an SSIM greater than 0.8 after registration, taking 60 milliseconds.Conclusion: High-quality 2D DVFs from highly undersampled k-space can be obtained with a high temporal resolution with conventional image reconstruction and a deep learning-based motion estimation approach for real-time adaptive MRI-guided radiotherapy.


Continuing care and COVID-19: a Canadian tragedy that must not be allowed to happen again.


title: Complications of Stamey percutaneous loop cystostomy catheters in three cats.

text: Complications associated with the Stamey percutaneous loop cystostomy catheter (Cook Medical), including exposure of the most proximal side-hole and leakage of urine from the bladder, were encountered following percutaneous placement in three cats. In all cats, surgical exploration for removal of the catheter was performed.


title: Renal denervation: unde venis et quo vadis?

text: OBJECTIVE AND METHODS Renal denervation is a minimally invasive, catheter-based option for the treatment of refractory hypertension. Indications and contraindications for renal denervation have been defined in an interdisciplinary manner. The efficacy and safety of the procedure were evaluated. RESULTS Currently, indication for renal denervation is limited to patients with primary hypertension and a systolic blood pressure of ≥ 160 mm Hg (or ≥ 150 mm Hg in diabetes type 2) despite optimal medical therapy with ≥ 3 different antihypertensive drugs. In this specific patient population, an average blood pressure reduction of 32/14 mmHg was observed in non-randomized/-controlled trials after renal denervation. These results were not confirmed in the first randomized controlled trial with a non-significantly superior blood pressure reduction of 14.1 ± 23.9 mm Hg compared to controls (-11.74 ± 25.94 mm Hg, difference -2.39 mm Hg p = 0.26 for superiority with a margin of 5 mm Hg) who underwent a sham procedure. CONCLUSION The efficacy and long-term effects of renal denervation need to be re-evaluated in light of the HTN3 study results. To date, renal denervation should not be performed outside of clinical trials. Future trials should also assess if renal denervation can be performed with sufficient safety and efficacy in patients with hypertension-associated diseases. The use of renal denervation as an alternative therapy (e. g. in patients with drug intolerance) can currently not be advocated. KEY POINTS The indication for renal denervation should be assessed in an interdisciplinary fashion and according to current guidelines with a special focus on ruling out secondary causes for arterial hypertension. 5 - 10 % of patients with hypertension suffer from refractory hypertension, but only about 1 % of patients meet the criteria for a renal denervation. Renal denervation leads to a significant decrease in office blood pressure; however, the impact on 24-hour blood pressure measurements remains unclear. In the first randomized controlled trial on renal denervation with a control group undergoing a sham procedure, blood pressure reduction failed to reach the anticipated level of superiority over best medical treatment. Periprocedural complications are rare, but long-term safety can currently not be appraised due to the limited data available.


title: A multicenter, randomized, controlled clinical trial of LigaSure small jaw vessel sealing system versus conventional technique in thyroidectomy.

text: The objective of this work was to compare efficacy and adverse effects between vessel sealing system thyroid lobectomy (VSSL) with the new LigaSure™ Small Jaw Instrument and conventional thyroid lobectomy (CTL). This is a multicenter, randomized and controlled study, conducted in the Department of Otolaryngology, King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Faculty of Medicine, Chulalongkorn University, Bangkok and Division of Otolaryngology, Sukhothai General Hospital, Sukhothai, Thailand. Forty subjects with solitary thyroid nodule planned for thyroid lobectomy were enrolled consecutively in both centers. Intervention was randomized by block randomization into two groups (VSSL, CTL). Primary outcomes were operative time and intraoperative blood loss. Secondary outcomes were postoperative blood loss and recurrent laryngeal nerve paralysis. There was clinically significant less operative time (VSSL/CTL = 62.4 ± 15.9/83.3 ± 16.1 min, p < 0.001) and less intraoperative blood loss (VSSL/CTL = 40.5 ± 19.1/63.3 ± 22.4 mL, p = 0.001) in VSSL group compared with CTL group. There was no significant difference of postoperative blood loss (VSSL/CTL = 58.8 ± 30.6/76.0 ± 36.9 mL, p = 0.116) between both the groups. There was one case of permanent recurrent laryngeal nerve injury found in both groups. VSSL with the new LigaSure™ Small Jaw Instrument was better than conventional technique in terms of shortening operative time. It was also better in reducing intraoperative hemorrhage, but this effect did not exceed clinically significant levels. Postoperative blood loss and recurrent laryngeal nerve injury were not significantly different between both the groups.


Sourcing Personal Protective Equipment During the COVID-19 Pandemic.


title: Disaster Ergonomics: Human Factors in COVID-19 Pandemic Emergency Management.

text: OBJECTIVE We aimed to identify opportunities for application of human factors knowledge base to mitigate disaster management (DM) challenges associated with the unique characteristics of the COVID-19 pandemic. BACKGROUND The role of DM is to minimize and prevent further spread of the contagion over an extended period of time. This requires addressing large-scale logistics, coordination, and specialized training needs. However, DM-related challenges during the pandemic response and recovery are significantly different than with other kinds of disasters. METHOD An expert review was conducted to document issues relevant to human factors and ergonomics (HFE) in DM. RESULTS The response to the COVID-19 crisis has presented complex and unique challenges to DM and public health practitioners. Compared to other disasters and previous pandemics, the COVID-19 outbreak has had an unprecedented scale, magnitude, and propagation rate. The high technical complexity of response and DM coupled with lack of mental model and expertise to respond to such a unique disaster has seriously challenged the response work systems. Recent research has investigated the role of HFE in modeling DM systems' characteristics to improve resilience, accelerating emergency management expertise, developing agile training methods to facilitate dynamically changing response, improving communication and coordination among system elements, mitigating occupational hazards including guidelines for the design of personal protective equipment, and improving procedures to enhance efficiency and effectiveness of response efforts. CONCLUSION This short review highlights the potential for the field's contribution to proactive and resilient DM for the ongoing and future pandemics.


Coronavirus Disease 2019 (COVID-19) and Immune-Engaging Cancer Treatment.


title: Detection of Hepatozoon felis in Ticks Collected from Free-Ranging Amur Tigers ( Panthera tigris altaica), Russian Far East, 2002-12.

text: We collected 69 ticks from nine, free-ranging Amur tigers ( Panthera tigris altaica) between 2002 and 2011 and investigated them for tick-borne pathogens. DNA was extracted using alkaline digestion and PCR was performed to detect apicomplexan organisms. Partial 18S rDNA amplification products were obtained from 14 ticks from four tigers, of which 13 yielded unambiguous nucleotide sequence data. Comparative sequence analysis revealed all 13 partial 18S rDNA sequences were most similar to those belonging to strains of Hepatozoon felis (>564/572 base-pair identity, >99% sequence similarity). Although this tick-borne protozoon pathogen has been detected in wild felids from many parts of the world, this is the first record from the Russian Far East.


title: Identification of the toxic constituents in Rhizoma Coptidis.

text: AIM OF THE STUDY Rhizoma Coptidis (Huanglian) is a widely used Traditional Chinese Medicine. However, it causes human as well as animal toxicities. In this study, we aimed to ascertain the toxic constituents in Rhizoma Coptidis. MATERIALS AND METHODS The acute toxicity of both the total extract and the alkaloid-rich extract of Rhizoma Coptidis were tested in mice. The dose related tissue concentration of the Rhizoma Coptidis alkaloids in mice was determined using high performance liquid chromatography with ultraviolet detection. The influence of phenobarbital sodium [a non-selective hepatic enzyme (P450) inducer] on the acute toxicity of Rhizoma Coptidis as well as the tissue concentration of the alkaloids was investigated. The cytotoxicity of the Rhizoma Coptidis alkaloids was tested in six cell lines using the MTT assay. RESULTS The median acute oral lethal dose of the total extract of Rhizoma Coptidis was 2.95g/kg in mice. The alkaloid-rich extract was much more toxic than the total extract of Rhizoma Coptidis. Four Rhizoma Coptidis alkaloids were detected in brain, heart, and lung tissues of mice that received the oral total extract of Rhizoma Coptidis. Tissue concentration increased nonlinearly with higher doses. Phenobarbital sodium decreased the tissue concentration of every alkaloid as well as the toxicity of Rhizoma Coptidis. All alkaloids, especially berberine, showed dose and time dependent cytotoxicity. CONCLUSIONS The toxic constituents of Rhizoma Coptidis were the alkaloids, mainly berberine.


title: Psychological sequelae of social isolation and loneliness might be a larger problem in young adults than older adults.

text: As the spread of COVID-19 has led to global efforts to social distance, concerns about the negative psychological effects of social isolation and loneliness have grown. The purpose of this commentary is to draw attention to 2 populations across the life span at risk for the psychological sequelae of social isolation and loneliness: young adults and old-old adults. We present data from three population-based longitudinal studies from two nations (United States and Sweden) to support this view. We then provide recommendations for the prevention of loneliness during social distancing as well as after social distancing measures are eased through implementation of programs that match young adults with older adults to foster intergenerational connection and group-based psychotherapy. (PsycInfo Database Record (c) 2020 APA, all rights reserved).


title: A systematic review of the anal fistula plug for patients with Crohn's and non-Crohn's related fistula-in-ano.

text: BACKGROUND The management of fistula-in-ano is a balance between fistula cure and preservation of continence. OBJECTIVE The aim of this study is to summarize the anal fistula plug literature for Crohn's and non-Crohn's fistula-in-ano in a homogenous patient population. DATA SOURCES PubMed, MEDLINE, Embase, and Cochrane medical databases were searched from 1995 to 2011. Abstracts from The American Society of Colon and Rectal Surgeons, The Society for Surgery of the Alimentary Tract, The European Society of Coloproctology, and the Association of Coloproctology of Great Britain and Ireland meetings between 2007 and 2010 were also evaluated. STUDY SELECTION Studies were included if results for patients with and without Crohn's disease could be differentiated. Patients with rectovaginal, anovaginal, rectourethral, or ileal-pouch vaginal fistulas were excluded as were studies where the mean or median follow-up was less than 3 months. Two researchers independently selected studies matching the inclusion criteria. INTERVENTION Anal fistula plug insertion was performed. MAIN OUTCOME MEASURES The primary outcomes measured were the overall fistula closure rates and length of follow-up. RESULTS Seventy-six articles or abstracts were identified from the title as being of relevance. Twenty studies (2 abstracts, 18 articles) were finally included. Study sample size ranged from 4 to 60 patients; 530 patients were included in all studies (488 non-Crohn's and 42 Crohn's patients). The plug extrusion rate was 8.7% (46 patients). The proportion of patients achieving fistula closure varied widely between studies for non-Crohn's, ranging from 0.2 (95% CI 0.04-0.48) to 0.86 (95% CI 0.64-0.97). The pooled proportion of patients achieving fistula closure in patients with non-Crohn's fistula-in-ano was 0.54 (95% CI 0.50-0.59). The proportion achieving closure in patients with Crohn's disease was similar (0.55, 95% CI 0.39-0.70). LIMITATIONS This study was limited by the variability of operative technique and perioperative care between studies. CONCLUSIONS Fistula closure is achieved by using the anal fistula plug in approximately 54% of patients without Crohn's disease. The anal fistula plug has not been adequately evaluated in the Crohn's population.


title: Review of seven cases of granulosa cell tumour of the equine ovary.

text: This paper reviews the equine granulosa cell tumour (GCT) and describes the clinicopathological features, treatment and outcome in seven cases of GCT in mares. Mares were presented with unilateral ovarian enlargement during the 2007 to 2010 breeding seasons. The mean (sd) age of the mares was 11.7 (5.96) years. Three mares were multiparous barren, three were nulliparous and one was primigravida. Behaviour at presentation was 57 per cent anoestrus, 28 per cent with stallion-like behaviour and 14 per cent with persistent oestrus. All mares had unilateral ovarian enlargement. Six non-pregnant mares had a small and inactive contralateral ovary; the pregnant mare had a single small corpus luteum on the contralateral ovary and was at three-and-a-half months' gestation. Enlarged ovaries measured 7 cm to an estimated 30 cm in diameter. 28 per cent had a multicystic ultrasound appearance, 57 per cent were dense structures and 14 per cent were of mixed appearance. Mean concentrations of progesterone were <1 ng/ml, oestrone sulphate 3.06 (2.32) ng/ml and testosterone 0.58 (0.64) nmol/l in non-pregnant mares. Inhibin was elevated in all non-pregnant cases at 7.6 (12.45) ng/ml. The pregnant mare had concentrations of progesterone 2.5 ng/ml, oestrone sulphate 81.0 ng/ml, testosterone 1.9 nmol/l and inhibin 1.31 ng/ml. Mares demonstrating stallion-like behaviour had a significantly higher (P<0.001) testosterone concentration (1.85 [0.07] nmol/l) than those that did not (0.34 [0.26] nmol/l). Three mares underwent unilateral ovariectomy and resumed cyclic ovarian activity within nine months of surgery.


title: Perioperative aspirin and clonidine and risk of acute kidney injury: a randomized clinical trial.

text: IMPORTANCE Acute kidney injury, a common complication of surgery, is associated with poor outcomes and high health care costs. Some studies suggest aspirin or clonidine administered during the perioperative period reduces the risk of acute kidney injury; however, these effects are uncertain and each intervention has the potential for harm. OBJECTIVE To determine whether aspirin compared with placebo, and clonidine compared with placebo, alters the risk of perioperative acute kidney injury. DESIGN, SETTING, AND PARTICIPANTS A 2 × 2 factorial randomized, blinded, clinical trial of 6905 patients undergoing noncardiac surgery from 88 centers in 22 countries with consecutive patients enrolled between January 2011 and December 2013. INTERVENTIONS Patients were assigned to take aspirin (200 mg) or placebo 2 to 4 hours before surgery and then aspirin (100 mg) or placebo daily up to 30 days after surgery, and were assigned to take oral clonidine (0.2 mg) or placebo 2 to 4 hours before surgery, and then a transdermal clonidine patch (which provided clonidine at 0.2 mg/d) or placebo patch that remained until 72 hours after surgery. MAIN OUTCOMES AND MEASURES Acute kidney injury was primarily defined as an increase in serum creatinine concentration from the preoperative concentration by either an increase of 0.3 mg/dL or greater (≥26.5 μmol/L) within 48 hours of surgery or an increase of 50% or greater within 7 days of surgery. RESULTS Aspirin (n = 3443) vs placebo (n = 3462) did not alter the risk of acute kidney injury (13.4% vs 12.3%, respectively; adjusted relative risk, 1.10; 95% CI, 0.96-1.25). Clonidine (n = 3453) vs placebo (n = 3452) did not alter the risk of acute kidney injury (13.0% vs 12.7%, respectively; adjusted relative risk, 1.03; 95% CI, 0.90-1.18). Aspirin increased the risk of major bleeding. In a post hoc analysis, major bleeding was associated with a greater risk of subsequent acute kidney injury (23.3% when bleeding was present vs 12.3% when bleeding was absent; adjusted hazard ratio, 2.20; 95% CI, 1.72-2.83). Similarly, clonidine increased the risk of clinically important hypotension. In a post hoc analysis, clinically important hypotension was associated with a greater risk of subsequent acute kidney injury (14.3% when hypotension was present vs 11.8% when hypotension was absent; adjusted hazard ratio, 1.34; 95% CI, 1.14-1.58). CONCLUSIONS AND RELEVANCE Among patients undergoing major noncardiac surgery, neither aspirin nor clonidine administered perioperatively reduced the risk of acute kidney injury. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT01082874.


title: Evolution of approaches to viral safety issues for biological products.

text: CONFERENCE PROCEEDING Proceedings of the PDA/FDA Adventitious Viruses in Biologics: Detection and Mitigation Strategies Workshop in Bethesda, MD, USA; December 1-3, 2010 Guest Editors: Arifa Khan (Bethesda, MD), Patricia Hughes (Bethesda, MD) and Michael Wiebe (San Francisco, CA) Approaches to viral safety issues for biological products have evolved during the past 50+ years. The first cell culture products (viral vaccines) relied largely on the use of in vitro and in vivo virus screening assays that were based upon infectivity of adventitious viral agents. The use of Cohn fractionation and pasteurization by manufacturers of plasma derivatives introduced the concepts that purification and treatment with physical and chemical agents could greatly reduce the risk of viral contamination of human albumin and immunoglobulin products. But the limitations of such approaches became clear for thermolabile products that were removed early in fractionation such as antihemophilic factors, which transmitted hepatitis viruses and HIV-1 to some product recipients. These successes and limitations were taken into account by the early developers of recombinant DNA (rDNA)-derived cell culture products and by regulatory agencies, leading to the utilization of cloning technology to reduce/eliminate contamination due to human viruses and purification technologies to physically remove and inactivate adventitious and endogenous viruses, along with cell banking and cell bank characterization for adventitious and endogenous viruses, viral screening of biological raw materials, and testing of cell culture harvests, to ensure virus safety. Later development and incorporation of nanofiltration technology in the manufacturing process provided additional assurance of viral clearance for safety of biotechnology products. These measures have proven very effective at preventing iatrogenic infection of recipients of biotechnology products; however, viral contamination of production cell cultures has occasionally occurred. Screening tests for viral contamination in raw materials have not proven practical by themselves to prevent contamination of cell cultures, but they can be made more effective by coupling with treatment using physical or chemical agents to further reduce the hypothetical viral loads present in cell culture raw materials. Recent advances in polymerase chain reaction (PCR) technology have allowed preharvest testing for specific viral agents to reduce the risk of cell culture contamination by specific viruses in the harvest material. Examples of each of these stages in the evolution of virus detection methods are described and assessed in this paper.


title: Perforin inhibition protects from lethal endothelial damage during fulminant viral hepatitis.

text: CD8 T cells protect the liver against viral infection, but can also cause severe liver damage that may even lead to organ failure. Given the lack of mechanistic insights and specific treatment options in patients with acute fulminant hepatitis, we develop a mouse model reflecting a severe acute virus-induced CD8 T cell-mediated hepatitis. Here we show that antigen-specific CD8 T cells induce liver damage in a perforin-dependent manner, yet liver failure is not caused by effector responses targeting virus-infected hepatocytes alone. Additionally, CD8 T cell mediated elimination of cross-presenting liver sinusoidal endothelial cells causes endothelial damage that leads to a dramatically impaired sinusoidal perfusion and indirectly to hepatocyte death. With the identification of perforin-mediated killing as a critical pathophysiologic mechanism of liver failure and the protective function of a new class of perforin inhibitor, our study opens new potential therapeutic angles for fulminant viral hepatitis.


title: Cleft-lift operation for pilonidal sinuses under tumescent local anesthesia: a prospective cohort study of peri- and postoperative pain.

text: BACKGROUND The use of tumescent local anesthesia in the Bascom cleft-lift procedure has not been described before. OBJECTIVE This study aimed to find whether moderate to complex pilonidal sinuses could be treated using the cleft-lift procedure with local anesthesia, with only minor postoperative pain and brief sick leave. DESIGN This is a prospective cohort study. SETTING The study was conducted in a day-surgical department. PATIENTS Eighty-three consecutive cleft-lift operations for pilonidal sinus were performed with tumescent local anesthesia. INTERVENTIONS Tumescent local anesthesia with a saline water solution of 0.8 mg/mL mepivacaine and 0.001 mg/mL adrenalin buffered with sodium bicarbonate to pH 7.2 was infused subcutaneously. Seventy-five patients were interviewed daily by phone for 1 week to register their ability to return to work and to score their pain on a Numerical Rating Scale pain score from 0 (no pain) to 10. MAIN OUTCOME MEASURES Outcome measures were the rate of conversion to general anesthesia, peri- and postoperative pain, and the times to discharge and to return to work. RESULTS Eighty-two (99%) of the 83 procedures were performed with local anesthesia. In one patient, local was converted to general anesthesia. The mean maximum pain score experienced during the infusion was 3.7 (CI: 3.3-4.1), and during surgery, the score was 1.9 (CI: 1.4-2.3). Sixty-three (76%) of the patients were discharged directly from the operating room and 90% in less than an hour after the last stitch. The maximum pain after 2 days was none or mild (pain score ≤3) in 80% of the patients. Work could be resumed the next day by 35%, and after 4 days by 87% of the patients with a mean time of 3.0 (CI: 2.2-3.7) days. LIMITATIONS This study might be limited by its noncomparative design. CONCLUSION Most patients with moderate to complex pilonidal sinuses can be treated under local anesthesia without notable pain, and discharged minutes after the operation. The Bascom cleft-lift procedure causes only mild postoperative pain, and patients can resume work a few days later.


Dissecting racial disparities in multiple myeloma-clues from differential immunoglobulin levels.


title: Comparative study of talc poudrage versus pleural abrasion for the treatment of primary spontaneous pneumothorax.

text: Primary spontaneous pneumothorax is a pathology mainly affecting healthy young patients. Clinical guidelines do not specify the type of pleurodesis that should be conducted, due to the lack of comparative studies on the different techniques. The aim of this study was to compare talc poudrage and pleural abrasion in the treatment of spontaneous pneumothorax. A retrospective comparative study was performed, including 787 patients with primary spontaneous pneumothorax. The 787 patients were classified into two groups: Group A (pleural abrasion) n = 399 and Group B (talc pleurodesis) n = 388. The variables studied were recurrence, surgical time, morbidity and in-hospital length of stay. Statistical analysis was done by an unpaired t-test and Fisher's exact test (SSPS 18.0). Statistically significant differences were observed in the variables: surgical time (A: 46 ± 12.3; B: 37 ± 11.8 min; P < 0.001); length of stay (A: 4.7 ± 2.5; B: 4.3 ± 1.8 days; P = 0.01); apical air camera (A: 25; B: 4; P < 0.001); pleural effusion (A: 6; B: 0; P = 0.05). Talc poudrage shows shorter surgical times and length of stay, and lower re-intervention rates. Morbidity is lower in patients with talc poudrage. Statistically significant differences were not observed in recurrence, persistent air leaks, atelectasis and haemothorax.


title: Work of breathing for cuffed and uncuffed pediatric endotracheal tubes in an in vitro lung model setting.

text: BACKGROUND Over the last decade, cuffed endotracheal tubes are increasingly used in pediatric anesthesia and also in pediatric intensive care. However, the smaller inner diameter of cuffed endotracheal tubes and, implicitly, the increased endotracheal tube resistance is still a matter of debate. AIMS This in vitro study investigated work of breathing and inspiratory airway pressures in cuffed and uncuffed endotracheal tubes and the impact of pressure support ventilation and automatic tube compensation. METHODS In 5 simulated neonatal and pediatric lung models, the Active Servo Lung 5000 and an intensive care ventilator were used to quantify the differences in work of breathing under spontaneous breathing (with and without pressure support ventilation and automatic tube compensation) between cuffed and uncuffed endotracheal tubes. Additionally, differences in inspiratory airway pressures, measured either proximal or distal of the endotracheal tube, between cuffed and uncuffed endotracheal tubes under mechanical ventilation were investigated. RESULTS Work of breathing was overall 10.27% [95% confidence interval 9.01-11.94] higher with cuffed than with uncuffed endotracheal tubes and was dramatically reduced by 34.19% [95% confidence interval 31.61-35.25] with the application of pressure support. Automatic tube compensation almost diminished work of breathing differences between the 2 endotracheal tube types in nearly all pediatric lung models. Peak inspiratory and mean airway pressures measured at the proximal endotracheal tube end revealed significantly higher values in cuffed than in uncuffed endotracheal tubes. However, these differences measured at the distal end of the endotracheal tube became minimal. CONCLUSION This in vitro study confirmed significant differences in work of breathing and inspiratory pressures between cuffed and uncuffed endotracheal tubes. Work of breathing, however, is almost neutralized by pressure support ventilation with automatic tube compensation and distal inspiratory airway pressures that, from a clinical perspective, are not significantly increased.


title: Face validity of the pulsatile organ perfusion trainer for laparoscopic cholecystectomy.

text: BACKGROUND The pulsatile organ perfusion (POP) trainer provides training of minimally invasive surgery (MIS) with real instruments and cadaveric organs. It provides training of full procedures with simulation of bleeding. Although widely used, the face validity has not yet been evaluated. This study aimed to establish face validity of the POP trainer for laparoscopic cholecystectomy (LC) and its usefulness compared with other training modalities. MATERIALS AND METHODS During MIS courses, the participants (n = 52) used the POP trainer to perform LC. Face validity was assessed with questionnaires for realism and usefulness on a five-point Likert scale. Participants were divided into two groups: experts (n = 15) who had performed more than 50 laparoscopic procedures and novices (n = 37) with less than 50 procedures. Secondary aims included the ranking of training modalities, as well as exploration of their specific advantages and disadvantages. RESULTS The POP trainer was found to be realistic (3.8 ± 0.9) and useful (4.6 ± 0.9). Differences between experts and novices were only found for "The training modality resembles reality" (3.1 ± 0.8 vs. 3.8 ± 0.7; p = 0.010), "The operation on the POP trainer is realistic" (3.4 ± 1.1 vs. 4.5 ± 0.8; p = 0.003), and "It would be desirable to have a POP trainer at my own hospital" (4.2 ± 1.1 vs. 4.8 ± 0.8; p = 0.040). In the ranking, the animal training (1.1 ± 0.3) placed first, the POP trainer (2.3 ± 0.9) second, and the VR trainer (2.8 ± 0.9) and box trainer (2.8 ± 1.1) third. The realistic simulation of animal training was named as an advantage most often, while the unrealistic simulation of the VR trainer was the most often named disadvantage. CONCLUSIONS The POP trainer was rated a highly realistic and useful training modality with face validity for LC. Differences between experts and novices existed concerning realism and desirability. Future studies should evaluate the POP trainer for more advanced surgical procedures. The POP trainer widens the spectrum of modalities for training of MIS in a safe environment outside the operating room.


title: [Individualized treatment recommendations for lung cancer patients at different stages of treatment during the outbreak of 2019 novel coronavirus disease].

text: In order to achieve the overall victory over 2019 novel coronavirus disease epidemic, especially to prevent the disease recurrence from rebounding during the resumption of labor, the government has not loosened any control of personnel mobility, which has obviously affected the normal examination and treatment of lung cancer patients under the influence of this epidemic. During the epidemic period, cancer patients with low immunity levels face the double ordeals of disease and epidemic situation. Compared with the general population, they are more likely to be infected with the new coronavirus. Among the infected cancer patients, lung cancer is the most common type. It is necessary to provide more appropriate individualized treatment recommendations for patients with lung cancer based on the epidemic situation of the patient's location and in combination with the patient's own condition. Through active prevention of infection, timely conversion of treatment strategies, online and offline joint control, and positive psychological counseling, we do our best to help patients with lung cancer to survive this difficult period.


title: Pharmacological inhibition of RORC2 enhances human Th17-Treg stability and function.

text: Inflammatory bowel diseases (IBD) are chronic conditions that result from uncontrolled intestinal inflammation. Pathogenic Th17 cells, characterised by production of IL-17A in the absence of IL-10, are thought to contribute to this inflammation, but in humans, antibody-mediated blockade of IL-17A is an ineffective IBD therapy whereas IL-23 blockade is effective. Here, we investigated the effects of pharmacological inhibition of RORC2, the Th17 cell lineage-defining transcription factor, on in vivo-differentiated human Th17 cells and Th17-like regulatory T cells (Th17-Tregs). BMS-336, a small molecule RORC2 inverse agonist, inhibited expression of RORC2-regulated genes in peripheral Th17 cells (CD4+ CD25- CD127+ CXCR3- CCR4+ CCR6+ ) in a dose-dependent manner, with similar inhibitory effects on laminar propria mononuclear cells from IBD and non-IBD subjects. Exposure of peripheral Th17-Tregs (CD4+ CD25hi CD127lo CXCR3- CCR4+ CCR6+ ) to BMS-336 also inhibited IL-17A production and prevented inflammatory cytokine-induced destabilisation, as evidenced by preserved FOXP3 expression and epigenetic status of the Treg-specific demethylation region. In parallel, RORC2 inhibition increased the production of IL-10 in Th17-Tregs, resulting in enhanced suppression of inflammatory cytokines from myeloid cells. Thus, via its ability to simultaneously inhibit Th17 cells and enhance the stability and function of Th17-Tregs, pharmacological inhibition of RORC2 is a promising approach to suppress inflammation and promote immune regulation in IBD. This article is protected by copyright. All rights reserved.


title: Newcastle disease virus expressing human immunodeficiency virus type 1 envelope glycoprotein induces strong mucosal and serum antibody responses in Guinea pigs.

text: Human immunodeficiency virus type 1 (HIV-1) is transmitted mainly through mucosal sites. Optimum strategies to elicit both systemic and mucosal immunity are critical for the development of vaccines against HIV-1. We therefore sought to evaluate the induction of systemic and mucosal immune responses by the use of Newcastle disease virus (NDV) as a vaccine vector. We generated a recombinant NDV, designated rLaSota/gp160, expressing the gp160 envelope (Env) protein of HIV-1 from an added gene. The gp160 protein expressed by rLaSota/gp160 virus was detected on an infected cell surface and was incorporated into the NDV virion. Biochemical studies showed that gp160 present in infected cells and in the virion formed a higher-order oligomer that retained recognition by conformationally sensitive monoclonal antibodies. Expression of gp160 did not increase the virulence of recombinant NDV (rNDV) strain LaSota. Guinea pigs were administered rLaSota/gp160 via the intranasal (i.n.) or intramuscular (i.m.) route in different prime-boost combinations. Systemic and mucosal antibody responses specific to the HIV-1 envelope protein were assessed in serum and vaginal washes, respectively. Two or three immunizations via the i.n. or i.m. route induced a more potent systemic and mucosal immune response than a single immunization by either route. Priming by the i.n. route was more immunogenic than by the i.m. route, and the same was true for the boosts. Furthermore, immunization with rLaSota/gp160 by any route or combination of routes induced a Th1-type response, as reflected by the induction of stronger antigen-specific IgG2a than IgG1 antibody responses. Additionally, i.n. immunization elicited a stronger neutralizing serum antibody response to laboratory-adapted HIV-1 strain MN.3. These data illustrate that it is feasible to use NDV as a vaccine vector to elicit potent humoral and mucosal responses to the HIV-1 envelope protein.


title: Rapid COVID-19 vaccine development.

text: Finding the fastest pathway to vaccine availability includes the avoidance of safety pitfalls.


title: Duplex real-time reverse transcriptase PCR assays for rapid detection and identification of pandemic (H1N1) 2009 and seasonal influenza A/H1, A/H3, and B viruses.

text: Reports of a novel influenza virus type A (H1N1), now designated by the World Health Organization as pandemic (H1N1) 2009, emerged from the United States and Mexico in April 2009. The management of the pandemic in Australia required rapid and reliable testing of large numbers of specimens for the novel influenza strain and differentiation from seasonal influenza strains. A real-time reverse transcriptase PCR (RT-PCR) assay for the detection of pandemic (H1N1) 2009 was designed and used with existing real-time RT-PCR assays for seasonal influenza viruses A and B. MS2 coliphage was added to all samples and amplified as a quality control. Three duplex RT-PCR assays, each containing two primer pairs and corresponding 5' nuclease probes, were initially evaluated on control material and stored samples and showed high sensitivity and specificity. More than 11,000 clinical samples were then tested for influenza A and B matrix gene targets and specific hemagglutinin gene targets for seasonal influenza A/H1, A/H3, and pandemic A (H1N1) 2009. Minimum sensitivities and specificities were 98.8% and 100%, respectively, for pandemic (H1N1) 2009, 81.5% and 98.9% for seasonal A/H1, and 96.3% and 99.6% for A/H3. Automated sample extraction facilitated the rapid processing of samples so that the assays allowed accurate, rapid, and cost-effective screening of large numbers of clinical samples.


title: Does Helicobacter pylori infection influence the major postoperative complication rate after sleeve gastrectomy? A retrospective cohort study in an endemic region.

text: BACKGROUND/AIMS Helicobacter pylori infection is very common in Eastern countries. Little is known about the impact this infection has on bariatric surgery outcomes. This retrospective cohort study conducted on obese Turkish adults who underwent sleeve gastrectomy at a single center aimed to determine the prevalence of H. pylori infection and the effect of this infection on the rate of early major postoperative complications. MATERIALS AND METHODS All consecutive patients who underwent sleeve gastrectomy for obesity between 2014 and 2015 and who had complete data were enrolled. A single surgeon performed all procedures. All resected specimens were sent to pathology for analysis. RESULTS Of the 460 patients who met the eligibility criteria, 326 (71%) were female. The average (±standard deviation) age and body mass index were 37.5±10.0 years and 42.7±7.7 kg/m2, respectively. Histology revealed that 150 (33%) patients had H. pylori infection. The H. pylori-infected group developed two complications (leakage and intra-abdominal collection). The uninfected group developed three complications (all bleeding related). The two groups did not differ significantly regarding postoperative complication rates (1.3% vs. 1.0%; p=0.717). CONCLUSION H. pylori infection did not affect the rate of early complications after sleeve gastrectomy. This suggests that H. pylori screening or eradication policy is not essential for asymptomatic candidates who have undergone sleeve gastrectomy.


title: Intrahepatic Cholangiocarcinoma and Thermal Ablation: Long-term Results of An Italian Retrospective Multicenter Study.

text: Background and Aims: Despite resection being considered the treatment of choice for intrahepatic cholangiocarcinoma (ICC), percutaneous thermal ablation can be an alternative treatment for patients unfit for surgery. Our aim was to compare long-term results of percutaneous sonographically-guided radiofrequency ablation (RFA) with high-powered microwave ablation (MWSA) in treatment of ICC. Methods: Results of 71 ICC patients with 98 nodules treated with RFA (36 patients) or MWSA (35 patients) between January 2008 and June 2018 in 5 Interventional Ultrasound centers of Southern Italy were retrospectively reviewed. Cumulative overall survival curves were calculated with the Kaplan-Meyer method and differences with the log-rank test. Eleven possible factors affecting survival were analyzed. Results: Overall survival of the entire series was 88%, 65%, 45% and 34% at 12, 36, 60 and 80 months, respectively. Patients treated with MWSA survived longer than patients treated with RFA (p < 0.005). The MWSA group with ICC nodules ≤3 cm or nodules up to 4 cm survived longer than the RFA group (p < 0.0005). In patients with nodules >4 cm, no significant difference was found. Disease-free survival and progression-free survival were better in the MWSA group compared to the RFA group (p < 0.005). Diameter of nodules and MWSA were independent factors predicting a better survival. No major complications were observed. Conclusions: MWSA is superior to RFA in treating ICC unfit for surgery, achieving better long-term survival in small (≤3 cm) ICC nodules as well as nodules up to 4 cm of neoplastic tumors and should replace RFA.


title: The impacts of vulnerability, perceived risk, and fear on preventive behaviours against COVID-19.

text: The world has been under the negative effect of the COVID-19 pandemic for the last few months. While people may take many preventive behaviours to minimize the risk, very little is known about the factors that can increase preventive behaviours during the COVID-19 pandemic. This study examined the effects of vulnerability, perceived risk, and fear on preventive behaviours of COVID-19. The study used a sample of 4,536 Turkish adults (M = 30.33 ± 10.95 years) recruited from 17 March through 1 April 2020. Vulnerability, perceived risk, fear, and preventive behaviours were measured with self-rating scales. Participants mostly engaged in avoidance of public transportation and frequent handwashing as preventive behaviours. Women had a significantly higher vulnerability to, perceived risk, and fear of new coronavirus compared to men. Correlation results indicated that age, gender, education level, vulnerability, perceived risk, and fear were related to preventive behaviours. Regression results demonstrated that vulnerability, perceived risk, and fear accounted for a significant amount of variance in preventive behaviours over and above the effects of demographic variables. The results suggest that vulnerability, perceived risk, and fear can significantly increase engagement in preventive behaviours during the novel coronavirus pandemic. The results have important implications for research and practice.


title: The Quality of Care for Gastroesophageal Reflux Disease.

text: Improving the quality of healthcare delivery is a cornerstone of modern medical care shared between all stakeholders. However, effectively improving quality requires both an understanding of the tenets of healthcare quality and how they relate to an individual disease process. This is especially important for common diseases, such as gastroesophageal reflux disease (GERD), where wide variations in practice exist. The high prevalence of GERD coupled with wide variation in clinical approach results in significant economic burden and poor quality of care. Thus, GERD serves as a useful framework to highlight the opportunities and current challenges of delivering high-quality care. In this article, we identify quality metrics in GERD and the areas in need of research to improve the quality of the management of GERD. Additionally, we suggest strategies for improvement as it relates to the proper diagnostic testing utilization and the decision-making process.


Mechanical Thrombectomy for Acute Middle Cerebral Artery Occlusion Caused by a Giant, Thrombosed, Extracranial Internal Carotid Artery Aneurysm.


title: Complex bilobular, bisaccular, and broad-neck microsurgical aneurysm formation in the rabbit bifurcation model for the study of upcoming endovascular techniques.

text: BACKGROUND AND PURPOSE Despite rapid advances in the development of materials and techniques for endovascular intracranial aneurysm treatment, occlusion of large broad-neck aneurysms remains a challenge. Animal models featuring complex aneurysm architecture are needed to test endovascular innovations and train interventionalists. MATERIALS AND METHODS Eleven adult female New Zealand rabbits were assigned to 3 experimental groups. Complex bilobular, bisaccular, and broad-neck venous pouch aneurysms were surgically formed at an artificially created bifurcation of both CCAs. Three and 5 weeks postoperatively, the rabbits underwent 2D-DSA and CE-3D-MRA, respectively. RESULTS Mortality was 0%. We observed no neurologic, respiratory, or gastrointestinal complications. The aneurysm patency rate was 91% (1 aneurysm thrombosis). There was 1 postoperative aneurysm hemorrhage (9% morbidity). The mean aneurysm volumes were 176.9 ± 63.6 mm(3), 298.6 ± 75.2 mm(3), and 183.4 ± 72.4 mm(3) in bilobular, bisaccular, and broad-neck aneurysms, respectively. The mean operation time was 245 minutes (range, 175-290 minutes). An average of 27 ± 4 interrupted sutures (range, 21-32) were needed to create the aneurysms. CONCLUSIONS This study demonstrates the feasibility of creating complex venous pouch bifurcation aneurysms in the rabbit with low morbidity, mortality, and high short-term aneurysm patency. The necks, domes, and volumes of the bilobular, bisaccular, and broad-neck aneurysms created are larger than those previously described. These new complex aneurysm formations are a promising tool for in vivo animal testing of new endovascular devices.


title: Ethylene glycol toxicity: a retrospective pathological study in cats.

text: Ethylene glycol (EG) is a well known toxic compound, the assumption of which can be fatal to pet animals as well as to humans. Limited information is available on the pathological features of EG poisoning in pet animals, with special emphasis on cats. Twenty-five cats with histologically confirmed EG intoxication were retrospectively investigated, in order to define more precisely the gross pathological findings and improve the diagnostic process. Furthermore, a brief comparison with the lesions reported in EG-poisoned human patients and dogs was also made.


title: Interleukin-6 blockade with sarilumab in severe COVID-19 pneumonia with systemic hyperinflammation: an open-label cohort study.

text: OBJECTIVES To assess the safety and efficacy of interleukin (IL)-6 blockade with sarilumab in patients with severe COVID-19 pneumonia and systemic hyperinflammation. METHODS We conducted an open-label study of sarilumab in severe COVID-19 pneumonia (PaO2/FiO2 <300 mm Hg) with hyperinflammation (elevated inflammatory markers and serum IL-6 levels). Sarilumab 400 mg was administered intravenously in addition to standard of care and results were compared with contemporary matched patients treated with standard of care alone. Clinical improvement, mortality, safety and predictors of response were assessed at 28 days. RESULTS Twenty-eight patients were treated with sarilumab and 28 contemporary patients receiving standard of care alone were used as controls. At day 28 of follow-up, 61% of patients treated with sarilumab experienced clinical improvement and 7% died. These findings were not significantly different from the comparison group (clinical improvement 64%, mortality 18%; p=NS). Baseline PaO2/FiO2 ratio >100 mm Hg and lung consolidation <17% at CT scan predicted clinical improvement in patients treated with sarilumab. Median time to clinical improvement in patients with lung consolidation <17% was shorter after sarilumab (10 days) than after standard treatment (24 days; p=0.01). The rate of infection and pulmonary thrombosis was similar between the two groups. CONCLUSIONS At day 28, overall clinical improvement and mortality in patients with severe COVID-19 were not significantly different between sarilumab and standard of care. Sarilumab was associated with faster recovery in a subset of patients showing minor lung consolidation at baseline.


title: Synthetic, biological and composite scaffolds for abdominal wall reconstruction.

text: The reconstruction of abdominal wall defects remains a huge surgical challenge. Tension-free repair is proven to be superior to suture repair in abdominal wall reconstruction. Scaffolds are essential for tension-free repair. They are used to bridge a defect or reinforce the abdominal wall. A huge variety of scaffolds are now commercially available. Most of the synthetic scaffolds are composed of polypropylene. They provide strong tissue reinforcement, but cause a foreign body reaction, which can result in serious complications. Absorbable synthetic scaffolds, such as Dexon™ (polyglycolic acid) and Vicryl™ (polyglactin 910), are not suitable for abdominal wall reconstruction as they usually require subsequent surgeries to repair recurrent hernias. Composite scaffolds combine the strength of nonabsorbable synthetic scaffolds with the antiadhesive properties of the absorbable scaffold, but require long-term follow-up. Biological scaffolds, such as Permacol™, Surgisis(®) and Alloderm(®), are derived from acellular mammalian tissues. Non-cross-linked biological scaffolds show excellent biocompatibility and degrade slowly over time. However, remnant DNA has been found in several products and the degradation leads to recurrence. Randomized controlled trials with long-term follow-up studies are lacking for all of the available scaffolds, particularly those derived from animal tissue. This article provides an overview of the different types of scaffolds available, and presents the key clinical studies of the commercially available synthetic, composite and biological scaffolds for abdominal wall reconstruction.


title: Reactive Polymer Targeting dsRNA as Universal Virus Detection Platform with Enhanced Sensitivity.

text: Reactive poly(pentafluorophenyl acrylate) (PPFPA) grafted surfaces offer a versatile platform to immobilize biomolecules. Here, we utilize PPFPA grafted surface and double-stranded RNA (dsRNA) recognizing J2 antibody to construct a universal virus detection platform with enhanced sensitivity. PPFPA on silicon substrates are prepared, and surface hydrophilicity is modulated by partial substitution of the pentafluorophenyl units with poly(ethylene glycol). Following dsRNA antibody immobilization, the prepared surfaces can distinguish long dsRNAs from single-stranded RNAs of the same length and short dsRNAs. As long dsRNAs are common byproducts of viral transcription/replication, these surfaces can detect the presence of different kinds of viruses without prior knowledge of their genomic sequences. To increase dsRNA detection sensitivity, a two-step method is devised where the captured dsRNAs are visualized with multiple fluorophore-tagged J2 antibodies. We show that the developed platform can differentiate foreign long dsRNAs from cellular dsRNAs and other biomolecules present in the cell lysate. Moreover, when tested against cells infected with hepatitis A or C viruses, both viruses are successfully detected using a single platform. Our study shows that the developed PPFPA platform immobilized with J2 antibody can serve as a primary diagnostic tool to determine the infection status for a wide range of viruses.


title: Laparoscopy-assisted D2 radical distal gastrectomy for gastric cancer (Billroth II anastomosis).

text: Laparoscopic radical gastrectomy has been increasingly applied in China. However, how to reduce surgery-related trauma, shorten operative time and achieve the long-term prognosis equal to the conventional open surgery is still hot research topics. Along with the change in learning curve and the optimization of endoscopic techniques, laparoscopic lymph node dissection can achieve or even exceed the extent that can be achieved in open surgery. Therefore, it has gradually replaced the conventional digestive tract reconstruction using an auxiliary incision. By completing the laparoscopic digestive tract reconstruction with EndoGIA, we describe the laparoscopy-assisted D2 radical distal gastrectomy for gastric cancer (Billroth II anastomosis).


title: Type III Interferons in Viral Infection and Antiviral Immunity.

text: Interferons (IFNs) can serve as the first line of immune defense against viral infection. The identification of IFN-λs 1, 2, 3 & 4 (termed as type III IFNs) has revealed that the antiviral immune response to viruses contains more components than the type I IFNs that have been known for more than 50 years. IFN-λs are IFN-λ1 (IL-29), IFN-λ2 (IL-28a), IFN-λ3 (IL-28b) and IFN-λ4, which resembles IFN-λ3. IFN-λs have type I-IFN-like immune responses and biological activities, but our knowledge of these novel players in the antiviral response is not well established. In this review, we try to describe the current information on the expression and function of IFN-λs in the innate antiviral immune defense and IFN-λ2's role in regulating and shaping the adaptive immune response. We suggest that IFN-λs are key antiviral cytokines, directly performing an antiviral immune response at epithelial surfaces in the early stages of viral infection, and that these cytokines also skew the balance of Th1 and Th2 cells to Th1 phenotype. In addition, genetic polymorphisms in IFN-λ genes can impair antiviral immune responses in clinical treatment.


title: Clinical and Imaging Determinants of Collateral Status in Patients With Acute Ischemic Stroke in MR CLEAN Trial and Registry.

text: Background and Purpose- Collateral circulation status at baseline is associated with functional outcome after ischemic stroke and effect of endovascular treatment. We aimed to identify clinical and imaging determinants that are associated with collateral grade on baseline computed tomography angiography in patients with acute ischemic stroke due to an anterior circulation large vessel occlusion. Methods- Patients included in the MR CLEAN trial (Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands; n=500) and MR CLEAN Registry (n=1488) were studied. Collateral status on baseline computed tomography angiography was scored from 0 (absent) to 3 (good). Multivariable ordinal logistic regression analyses were used to test the association of selected determinants with collateral status. Results- In total, 1988 patients were analyzed. Distribution of the collateral status was as follows: absent (7%, n=123), poor (32%, n=596), moderate (39%, n=735), and good (23%, n=422). Associations for a poor collateral status in a multivariable model existed for age (adjusted common odds ratio, 0.92 per 10 years [95% CI, 0.886-0.98]), male (adjusted common odds ratio, 0.64 [95% CI, 0.53-0.76]), blood glucose level (adjusted common odds ratio, 0.97 [95% CI, 0.95-1.00]), and occlusion of the intracranial segment of the internal carotid artery with occlusion of the terminus (adjusted common odds ratio 0.50 [95% CI, 0.41-0.61]). In contrast to previous studies, we did not find an association between cardiovascular risk factors and collateral status. Conclusions- Older age, male sex, high glucose levels, and intracranial internal carotid artery with occlusion of the terminus occlusions are associated with poor computed tomography angiography collateral grades in patients with acute ischemic stroke eligible for endovascular treatment.


title: Single-access laparoscopic surgery for ileal disease.

text: Aim. Single-access laparoscopic surgery (SALS) can be effective for benign and malignant diseases of the ileum in both the elective and urgent setting. Methods. Ten consecutive, nonselected patients with ileal disease requiring surgery over a twelve month period were included. All had a preoperative abdominopelvic computerized tomogram. Peritoneal access was achieved via a single transumbilical incision and a "surgical glove port" utilized as our preferred access device. With the pneumoperitoneum established, the relevant ileal loop was located using standard rigid instruments. For ileal resection, anastomosis, or enterotomy, the site of pathology was delivered and addressed extracorporeally. Result. The median (range) age of the patients was 42.5 (22-78) years, and the median body mass index was 22 (20.2-28) kg/m(2). Procedures included tru-cut biopsy of an ileal mesenteric mass, loop ileostomy and ileotomy for impacted gallstone extraction as well as ileal (n = 3) and ileocaecal resection (n = 4). Mean (range) incision length was 2.5 (2-5) cm. All convalescences were uncomplicated. Conclusions. These preliminary results show that SALS is an efficient and safe modality for the surgical management of ileal disease with all the advantages of minimal access surgery and without requiring a significant increase in theatre resource or cost or incurring extra patient morbidity.


title: Atherosclerotic renal artery stenosis and renal artery stenting: an evolving therapeutic option.

text: Atherosclerotic renal artery stenosis is a common clinical problem for which the optimal therapeutic strategy remains to be defined. However, renal artery stenting procedures have significantly increased as one approach to treat this clinical problem. Despite improvements in device design and technical performance of the procedure, the benefits and results of randomized clinical trials of renal artery stenting as a therapy remain confusing. Understanding the epidemiology, pathophysiology and natural history of renal artery stenosis are central to improving the outcomes of renal artery stenting. Developing both noninvasive and invasive predictive tools to better identify which patient will respond to renal revascularization will also be beneficial. In this article, we will present an overview of atherosclerotic renal artery disease. The results of renal artery stenting will be discussed and from this, the available noninvasive and invasive tools available to assess the clinical and hemodynamic significance of renal artery stenosis will be presented.


title: Transcatheter Embolisation of Proximal Type 1 Endoleaks Following Endovascular Aneurysm Sealing (EVAS) Using the Nellix Device: Technique and Outcomes.

text: AIM To evaluate the technical success and mid-term outcomes following transcatheter embolisation of type 1a endoleak after Nellix endovascular aneurysm sealing (EVAS). MATERIALS AND METHODS Seven patients (5 men; mean age 83; range 79-90) underwent transcatheter embolisation between July 2013 and August 2014. The average time from EVAS to embolisation was 136 days (range 6-301) and from endoleak diagnosis to embolisation was 20 days (range 2-50). Embolisation was performed with coils and Onyx in six cases and Onyx only in one case. Technical success, imaging and clinical outcomes of embolisation were reviewed. Technical success was defined as elimination of the endoleak on completion angiography and first imaging follow-up. Clinical success was defined as unchanged or decreased aneurysm sac size on subsequent follow-up (average 8 months; range 103-471 days). RESULTS All cases were technically successful. One patient required a second endovascular procedure following Onyx reflux into the Nellix endograft and another patient required surgical closure of a brachial puncture site. All patients are endoleak free with stable sac size on the latest available follow-up imaging. CONCLUSION If a type 1 endoleak occurs after EVAS, embolisation using Onyx with or without coils is feasible and effective with high technical success and freedom from endoleak recurrence at mid-term follow-up.


title: The renin-angiotensin system - a therapeutic target in COVID-19?

text: COVID-19, caused by infection with SARS-CoV-2, is a disease characterised by cough, fever and fatigue, which progresses to life-threatening lung injury in approximately 5% of patients. The SARS-CoV-2 virus enters the cell via ACE2. ACE2 is a component of the renin-angiotensin system (RAS) which has an important counterregulatory effect on the classical ACE-dependent pathway. Several antihypertensives increase ACE2 expression or activity, leading to concern that this may facilitate SARS-CoV-2 entry and worsen COVID-19 disease. However, ACE2 is protective against lung injury while ANG II (which is catabolised by ACE2) is associated with lung injury both in mice and humans. We propose that medications which inhibit the RAS ACE-dependent pathway may be beneficial in treating COVID-19 and should be explored in animal models and clinical trials. Here we give an overview of the RAS pathway with respect to COVID-19 and argue that strategies which manipulate this pathway might reduce the destructive lung manifestations of COVID-19 and improve patient outcomes.


title: MDCT of giant gastric folds: differential diagnosis.

text: OBJECTIVE The purpose of this study was to evaluate the efficacy of MDCT in the differentiation of diseases involving giant gastric folds and to identify the features most useful for predicting the presence of malignant gastric disease. MATERIALS AND METHODS Blinded reviewers retrospectively analyzed 16-MDCT scans of 64 patients who had endoscopic findings of giant gastric folds. Thirty of these patients had histopathologic results showing scirrhous carcinoma; 15, large B-cell lymphoma; 14, acute gastric mucosal lesions; and five, Ménétrier disease. Unenhanced transparent volume-rendered images were assessed to determine the morphologic features of the whole stomach. Contrast-enhanced images were used to analyze wall thickness, stratification, enhancement pattern, and perigastric conditions. We used the Cramer phi-prime correlation coefficient to calculate the overall diagnostic accuracy of MDCT in several gastric disorders. Scatterplot analysis was used for overall diagnostic score, and analysis of the receiver operator characteristic curves of the neighboring two diseases was used to locate the cutoff values for best diagnostic accuracy. We used exact logistic regression to identify which MDCT image features were most predictive of the presence of malignant gastric disease. RESULTS The gastric wall was found to be significantly thicker in large B-cell lymphoma than in other disorders (p < 0.001). The overall diagnostic accuracy of MDCT in the four diseases was 100%. Loss of wall stratification was deemed the best MDCT predictor of the presence of malignancy. CONCLUSION MDCT may be a reliable means of noninvasive diagnosis in the care of patients with endoscopically detected giant gastric folds and may be useful for differentiating benign from malignant disease.


title: Laparoscopic versus open surgery for rectal cancer: long-term oncologic results.

text: OBJECTIVE The goal was to assess long-term oncologic outcome after laparoscopic versus open surgery for rectal cancer and to evaluate the impact of conversion. SUMMARY BACKGROUND DATA Laparoscopic resection of rectal cancer is technically feasible, but there are no data to evaluate the long-term outcome between laparoscopic and open approach. Moreover, the long-term impact of conversion is not known. METHODS Between 1994 and 2006, patients treated by open (1994-1999) and laparoscopic (2000-2006) curative resection for rectal cancer were included in a retrospective comparative study. Patients with fixed tumors or metastatic disease were excluded. Those with T3-T4 or N+ disease received long course preoperative radiotherapy. Surgical technique and follow-up were standardized. Survival were analyzed by Kaplan Meier method and compared with the Log Rank test. RESULTS Some 471 patients had rectal excision for invasive rectal carcinoma: 238 were treated by laparoscopy and 233 by open procedure. Postoperative mortality (0.8% vs. 2.6%; P = 0.17), morbidity (22.7% vs. 20.2%; P = 0.51), and quality of surgery (92.0% vs. 94.8% R0 resection; P = 0.22) were similar in the 2 groups. At 5 years, there was no difference of local recurrence (3.9% vs. 5.5%; P = 0.371) and cancer-free survival (82% vs. 79%; P = 0.52) between laparoscopic and open surgery. Multivariate analysis confirmed that type of surgery did not influence cancer outcome. Conversion (36/238, 15%) had no negative impact on postoperative mortality, local recurrence, and survival. CONCLUSIONS The efficacy of laparoscopic surgery in a team specialized in rectal excision for cancer (open and laparoscopic surgery) is suggested with similar long-term local control and cancer-free survival than open surgery. Moreover, conversion had no negative impact on survival.


title: Laparoscopic esophagojejunostomy using the EndoStitch and a circular stapler under a direct view created by the ENDOCAMELEON.

text: Laparoscopic esophagojejunostomy using a circular stapler is associated with technical difficulties in the purse-string sutures used to insert the anvil head and in obtaining an adequate visual field to prevent rolling the mesentery and the wall of the jejunum on the mesenteric side into the anastomosis. To overcome these difficulties, we used the EndoStitch to create the purse-string suture and the ENDOCAMELEON to create the visual field to stretch the jejunum. After resecting the esophagus, purse-string sutures were placed using the EndoStitch. A total of five to six needle deliveries were performed. Next, the anvil head was inserted into the esophagus. The main unit of the EEA was inserted from the end of the resected jejunum. Then, the scope was changed to the ENDOCAMELEON. The main unit was slowly moved toward the anvil head. After making sure that the mesentery and the wall of the jejunum on the mesenteric side were not rolled into the anastomosis under the visual field created by the ENDOCAMELEON, the main unit was then fired. Thereafter, esophagojejunostomy was successfully completed. This technique was applied in 20 patients between April 2010 and May 2012. Laparoscopic esophagojejunostomy after total gastrectomy for gastric cancer was completed in all 20 patients. No case required conversion to open surgery. Neither anastomotic leakage nor stenosis was observed. This method is simple and useful for laparoscopic esophagojejunostomy after total gastrectomy for gastric cancer.


title: Putative Roles for Peptidylarginine Deiminases in COVID-19.

text: Peptidylarginine deiminases (PADs) are a family of calcium-regulated enzymes that are phylogenetically conserved and cause post-translational deimination/citrullination, contributing to protein moonlighting in health and disease. PADs are implicated in a range of inflammatory and autoimmune conditions, in the regulation of extracellular vesicle (EV) release, and their roles in infection and immunomodulation are known to some extent, including in viral infections. In the current study we describe putative roles for PADs in COVID-19, based on in silico analysis of BioProject transcriptome data (PRJNA615032 BioProject), including lung biopsies from healthy volunteers and SARS-CoV-2-infected patients, as well as SARS-CoV-2-infected, and mock human bronchial epithelial NHBE and adenocarcinoma alveolar basal epithelial A549 cell lines. In addition, BioProject Data PRJNA631753, analysing patients tissue biopsy data (n = 5), was utilised. We report a high individual variation observed for all PADI isozymes in the patients' tissue biopsies, including lung, in response to SARS-CoV-2 infection, while PADI2 and PADI4 mRNA showed most variability in lung tissue specifically. The other tissues assessed were heart, kidney, marrow, bowel, jejunum, skin and fat, which all varied with respect to mRNA levels for the different PADI isozymes. In vitro lung epithelial and adenocarcinoma alveolar cell models revealed that PADI1, PADI2 and PADI4 mRNA levels were elevated, but PADI3 and PADI6 mRNA levels were reduced in SARS-CoV-2-infected NHBE cells. In A549 cells, PADI2 mRNA was elevated, PADI3 and PADI6 mRNA was downregulated, and no effect was observed on the PADI4 or PADI6 mRNA levels in infected cells, compared with control mock cells. Our findings indicate a link between PADI expression changes, including modulation of PADI2 and PADI4, particularly in lung tissue, in response to SARS-CoV-2 infection. PADI isozyme 1-6 expression in other organ biopsies also reveals putative links to COVID-19 symptoms, including vascular, cardiac and cutaneous responses, kidney injury and stroke. KEGG and GO pathway analysis furthermore identified links between PADs and inflammatory pathways, in particular between PAD4 and viral infections, as well as identifying links for PADs with a range of comorbidities. The analysis presented here highlights roles for PADs in-host responses to SARS-CoV-2, and their potential as therapeutic targets in COVID-19.


The Guyana Diabetes and Foot Care Project: a complex quality improvement intervention to decrease diabetes-related major lower extremity amputations and improve diabetes care in a lower-middle-income country.


Ethics of reallocating ventilators in the covid-19 pandemic.


title: Short-term results for laparoscopic repair of large paraesophageal hiatal hernias with Gore Bio A® mesh.

text: BACKGROUND The application of mesh-reinforced hiatal closure has resulted in a significant reduction in recurrence rates in comparison with primary suture repair. One of the most debated issues is the risk of complications related to the use of the prosthesis, such as esophageal erosion and postoperative dysphagia. The aim of this study is to present our short-terms results in the treatment of laparoscopic paraesophageal hiatal hernia (LPHH) with a synthetic polyglycolic acid:trimethylene carbonate mesh (Gore Bio A(®)). METHODS From January 2011 to December 2012, 10 patients with large paraesophageal hiatal hernias and hiatal defect over 5 cm were included. Primary simple suture of the crura and additional reinforcement with a Gore Bio A(®) mesh was performed. Hiatal hernia or gastroesophageal reflux disease (GERD) symptoms recurrence, dysphagia and mesh-related complications were investigated. RESULTS Of the 10 patients undergoing mesh repair, there were 7 women and 3 men with a mean age of 65.5 years. All operations were completed laparoscopically. Median postoperative stay was 3 days. After a median follow-up of 20.3 months, one patient developed a recurrent hiatal hernia (10%). There were no mesh-related complications. CONCLUSIONS The use of Gore Bio A(®) mesh for the laparoscopic repair of large paraesophageal hiatal hernias is safe and with a reasonably low recurrence rate in this short-term study. Additional long-term studies with ample numbers carried out for years will be necessary to see if this synthetic mesh is not only safe but also successful in the prevention of recurrences.


title: Effects of two training curricula on basic laparoscopic skills and surgical performance among veterinarians.

text: OBJECTIVE To compare laparoscopic skills among veterinarians before and after undertaking 1 of 2 programs of simulation training. DESIGN Evaluation study. SAMPLE POPULATION 17 veterinarians at 1 institution. PROCEDURES Basic skills were tested by use of the McGill inanimate system for training and evaluation of laparoscopic skills (MISTELS). Surgical performance was assessed through an objective structured assessment of technical skills (OSATS). Both tests were performed prior to and after a 12-session training program, consisting of MISTELS exercises (curriculum A) or a variety of exercises (curriculum B). RESULTS Curriculum B led to improvement of scores obtained with both the MISTELS and the OSATS. Curriculum A did not result in higher scores obtained with the MISTELS, compared with curriculum B. Curriculum A did not lead to an improvement of scores obtained with the OSATS. Participant-perceived value of the training program was correlated positively with the improvement of scores for MISTELS suturing tasks and scores obtained with the OSATS. Time spent in clinical laparoscopic surgery and curriculum B training were both positively correlated with the post-training OSATS scores but not with post-training MISTELS scores. Conversely, simulation training time correlated with an increase in MISTELS scores but not OSATS scores. CONCLUSIONS AND CLINICAL RELEVANCE MISTELS training resulted in significant improvement of basic laparoscopic skills but not in the assessment used for surgical performance. This may have been due to the small number of study participants, the assessment tool, or the method of training. A varied curriculum may be advantageous when training veterinarians for clinical laparoscopic practice.