title: Initial experience of complete laparoscopic radical nephroureterectomy combined with transvesical laparoscopic excision of distal ureter in patients with upper urinary tract cancer.

text: BACKGROUND Selecting the treatment procedure for cancer patients is a challenging task. We report our initial experience of complete laparoscopic radical nephroureterectomy (RNU) for patients with upper urinary tract urothelial cancer (UTUC). METHODS A total of four patients with UTUC underwent complete laparoscopic RNU combined with transvesical laparoscopic excision of the distal ureter using three 5-mm ports. Transvaginal specimen extraction was applied in female patients to reduce incisional pain and improve cosmesis. Peri-operative complications were evaluated using the Clavien-Dindo classification system. Postoperative pain was evaluated during hospitalization using a numeric pain rating scale (scales of 1 to 10). Patients who underwent retroperitoneal laparoscopic surgery combined with open excision of the distal ureter during the same period were included as a control group (conventional RNU, consisting of laparoscopic nephrectomy combined with open bladder cuff excision) for pain scale evaluation. RESULTS The novel surgery was successfully completed for all four patients (two males and two females). The mean pneumoperitoneum time for retroperitoneoscopic nephroureterectomy and specimen extraction was 174 min, while the mean pneumovesicum time for the ureteral orifice excision was 88 min. One male patient had bladder leakage at the suture site of the bladder wall, which lasted for 2 weeks. No patient experienced recurrent disease during the follow-up period (median, 10 months). Mild to moderate pain lasted for 5 or 6 days after RNU. A couple of days after surgery, the numeric pain rating scale of complete laparoscopic RNU and conventional RNU group reached its peak level at 3.0 ± 1.8 and 5.3 ± 2.8, respectively. There was no statistical difference in the degree of postoperative pain (P = 0.31). CONCLUSIONS We described our initial experience and outcome of complete laparoscopic RNU for UTUC. Further experience and research are required to determine whether this advanced laparoscopic technique yields better outcomes and has true clinical value.


title: Knot integrity using different suture types and different knot-tying techniques for reconstructive pelvic floor procedures.

text: INTRODUCTION AND HYPOTHESIS Surgeons use a variety of sutures and knot-tying methods during pelvic reconstructive procedures. We hypothesized that knot-strength integrity will be similar with regards to type of knot, type of suture, and the knot-tying process. METHODS Using six different suture materials, flat square knots and slip knots were tied robotically and by hand by two surgeons. Knot integrity was evaluated using an Instron 5544 machine. We measured force and elongation at suture failure or knot slippage (whichever came first) as well as force at 3-mm displacement. RESULTS Four hundred and thirty-two knots were tie; one unraveled before the analysis, and 431 were tested. Three hundred and ninety-two knots reached or surpassed tensile strength of 30 N, the force at which tissue itself will fail. Knots tied with polyglyconate suture achieved the greatest tensile strength and those with OO-polydioxanone had the lowest. Hand-tied knots, regardless of technique and suture material, had greater tensile strength but greater elongation than robotically tied knots. Slip knots and flat square knots have similar integrity regardless of the tying technique. CONCLUSION Hand-tied knots had greater tensile strength than robotic knots, but the strength to break all knots required supraphysiological conditions. The decision to use a specific type of suture based on strength is not supported by our results, suggesting that surgeons may choose sutures based on other characteristics and personal comfort.


COVID-19, Renin-angiotensin System and Hematopoiesis.


title: Iatrogenic intestinal and mesenteric injuries with small bowel volvulus following use of barbed suture during laparoscopic myomectomy.

text: This is a case report of a patient who developed major intestinal complications after the utilization of barbed sutures for an off-label indication. The report serves as a warning for patients and surgeons of the potential injuries that may be caused by the use of new products in unapproved indications.


title: Implementation of an Effective Strategy for Teaching Nontechnical Skills in the Operating Room: A Single-blinded Nonrandomized Trial.

text: OBJECTIVE To evaluate the effectiveness of debriefing and feedback on intraoperative nontechnical performance as an instructional strategy in surgical training. BACKGROUND Regulatory authorities for accreditation in North America have included nontechnical skills such as communication and teamwork in the competencies to be acquired by surgical residents before graduation. Concrete recommendations regarding the training and assessment of these competencies, however, are lacking. METHODS Nonrandomized, single-blinded study using an interrupted time-series design. Eleven senior surgical residents were observed during routine cases in the operating room (OR) at baseline and post-training. The Non-Technical Skills for Surgeons (NOTSS) rating system was used. Observers were trained in NOTSS and blinded to the study purpose. Independent of the blinded observations, a surgeon educator conducted intraoperative observations, which served as the basis for the structured debriefing and feedback intervention. The intervention was administered to participants after a set of (blinded) baseline observations had been completed. Primary outcome was nontechnical performance in the OR as measured by the NOTSS system. Secondary outcome was perceived utility as assessed by a post-training questionnaire. RESULTS Twelve senior trainees were recruited, 11 completed the study. Average NOTSS scores improved significantly from 3.2 (SD 0.37) at baseline to 3.5 (SD 0.43) post-training [t(10) = -2.55, P = 0.29]. All participants felt the intervention was useful, and the majority thought that debriefing and feedback on nontechnical skills should be integrated in surgical training. CONCLUSIONS Debriefing and feedback in the OR may represent an effective strategy to ensure development of nontechnical skills in competency-based education.


title: Creating a High-Frequency Electronic Database in the PICU: The Perpetual Patient.

text: OBJECTIVE Our objective was to construct a prospective high-quality and high-frequency database combining patient therapeutics and clinical variables in real time, automatically fed by the information system and network architecture available through fully electronic charting in our PICU. The purpose of this article is to describe the data acquisition process from bedside to the research electronic database. DESIGN Descriptive report and analysis of a prospective database. SETTING A 24-bed PICU, medical ICU, surgical ICU, and cardiac ICU in a tertiary care free-standing maternal child health center in Canada. PATIENTS All patients less than 18 years old were included at admission to the PICU. INTERVENTIONS None. MEASUREMENTS AND MAIN RESULTS Between May 21, 2015, and December 31, 2016, 1,386 consecutive PICU stays from 1,194 patients were recorded in the database. Data were prospectively collected from admission to discharge, every 5 seconds from monitors and every 30 seconds from mechanical ventilators and infusion pumps. These data were linked to the patient's electronic medical record. The database total volume was 241 GB. The patients' median age was 2.0 years (interquartile range, 0.0-9.0). Data were available for all mechanically ventilated patients (n = 511; recorded duration, 77,678 hr), and respiratory failure was the most frequent reason for admission (n = 360). The complete pharmacologic profile was synched to database for all PICU stays. Following this implementation, a validation phase is in process and several research projects are ongoing using this high-fidelity database. CONCLUSIONS Using the existing bedside information system and network architecture of our PICU, we implemented an ongoing high-fidelity prospectively collected electronic database, preventing the continuous loss of scientific information. This offers the opportunity to develop research on clinical decision support systems and computational models of cardiorespiratory physiology for example.


title: Interferon-β and mycophenolic acid are potent inhibitors of Middle East respiratory syndrome coronavirus in cell-based assays.

text: The Middle East respiratory syndrome coronavirus (MERS-CoV) presents a novel emerging threat to public health worldwide. Several treatments for infected individuals have been suggested including IFN, ribavirin and passive immunotherapy with convalescent plasma. Administration of IFN-α2b and ribavirin has improved outcomes of MERS-CoV infection in rhesus macaques when administered within 8 h post-challenge. However, detailed and systematic evidence on the activity of other clinically available drugs is limited. Here we compared the susceptibility of MERS-CoV with different IFN products (IFN-α2b, IFN-γ, IFN-universal, IFN-α2a and IFN-β), as well as with two antivirals, ribavirin and mycophenolic acid (MPA), against MERS-CoV (Hu/Jordan-N3/2012) in vitro. Of all the IFNs tested, IFN-β showed the strongst inhibition of MERS-CoV in vitro, with an IC₅₀ of 1.37 U ml(-1), 41 times lower than the previously reported IC₅₀ (56.08 U ml(-1)) of IFN-α2b. IFN-β inhibition was confirmed in the virus yield reduction assay, with an IC90 of 38.8 U ml(-1). Ribavirin did not inhibit viral replication in vitro at a dose that would be applicable to current treatment protocols in humans. In contrast, MPA showed strong inhibition, with an IC₅₀ of 2.87 µM. This drug has not been previously tested against MERS-CoV and may provide an alternative to ribavirin for treatment of MERS-CoV. In conclusion, IFN-β, MPA or a combination of the two may be beneficial in the treatment of MERS-CoV or as a post-exposure intervention in high-risk patients with known exposures to MERS-CoV.


title: The Effectiveness of Multiple Electrode Radiofrequency Ablation in Patients with Hepatocellular Carcinoma with Lesions More than 3 cm in Size and Barcelona Clinic Liver Cancer Stage A to B2.

text: Outcomes of hepatocellular carcinoma (HCC) lesions >3.0 cm in size including Barcelona Clinic Liver Cancer (BCLC) stage B after radiofrequency ablation (RFA) with a single electrode remain unsatisfactory. This study aimed to investigate the outcomes of RFA with multiple electrodes (ME-RFA) for HCC tumors 3.1-7.0 cm in size and BCLC stage B. This retrospective study included 70 consecutive patients with 58 medium- (3.1-5.0 cm) and 17 large- (5.1-7.0 cm) sized HCCs after ME-RFA using a controller. Outcomes in terms of complete response, primary technique effectiveness, local tumor progression, and overall survival were investigated. After 1-4 applications of ME-RFA, the rates of complete response and PTE in medium-sized tumors were 79.3% and 91.4%, respectively, and in large tumors were 76.5% and 94.1%, respectively. Overall, the major complication rate was 5.7%. After a median 21-month follow-up period, both two- and three-year estimated overall survival rates were above 80%. There were no significant differences in overall survival and local tumor progression rates between medium- and large-size tumors and among BCLC stages A, B1 and B2. A complete response to ME-RFA was the only significant factor associated with improved survival (p=0.008). In conclusion, ME-RFA can effectively treat 3.1-7.0-cm sized HCCs with a comparable outcome between medium- and large-size tumors and among BCLA stages A to B2.


title: Parathyroid function after open thyroidectomy: A prospective randomized study for ligasure precise versus harmonic FOCUS.

text: BACKGROUND Options for controlling hemostasis during thyroidectomy include bipolar vessel sealing system and ultrasonic technology. The purpose of this study was to compare these energy-based devices on the performance of open thyroidectomy for benign disease with emphasis given to postoperative parathyroid function. METHODS Among the available energy-based devices, the LigaSure Precise (LP; Valleylab, Boulder, CO) and FOCUS Shears (FS; Ethicon Endo-Surgery, Cincinnati, OH) were evaluated. One hundred ninety-nine consecutive patients scheduled for open thyroidectomy were prospectively randomized into 2 similar-sized groups. Operative time, morbidity, incision length, postoperative pain, and hospital stay were analyzed. Postoperative hypoparathyroidism was monitored with serial determinations of intact parathyroid hormone (iPTH) and serum calcium. RESULTS Early postoperative measurement of iPTH plasma level, although within the reference range, was significantly lower in the FS group (p < .001). Oral calcium supplementation was significantly higher and prolonged in the FS group. CONCLUSION The present study demonstrates a significant difference of the rates for postoperative parathyroid malfunction when using different energy-based devices.


Guiding ventilation with transpulmonary pressure.


title: Adipose Tissue-Preserved Skin Graft: Applicability and Long-Term Results.

text: BACKGROUND Composite grafts consisting of adipose tissue and skin have been reported in the literature but have been restricted to areas smaller than 4 to 5 cm. The senior author (D.T.W.C.) has developed a technique of adipose tissue-preserved full-thickness skin grafts for larger areas with success similar to that achieved with conventional full-thickness skin grafts. METHODS All cases of the senior author involving a full-thickness skin graft were identified and reviewed to identify cases in which adipose tissue-preserved full-thickness skin grafts were used. Indication for skin grafting, anatomical location of recipient and donor sites, size of graft, total number of grafts received by each patient, and percentage take were extracted from patient charts. Graft take was measured between days 5 and 14. RESULTS A total of 72 adipose tissue-preserved skin grafts on 47 patients were identified from 1994 to 2009, with a median follow-up of 8 years. The size of defect ranged from 0.7 to 210 cm, with a median area of 6 cm (interquartile range, 2.5 to 15 cm). Only six of 72 grafts were found to have less than 100 percent take. The lowest take percentage was 85 percent in a graft with an area of 2.6 cm. There were no graft failures. CONCLUSIONS This study confirms the proof-of-concept that both larger and distant donor- site adipose tissue-preserved skin grafts are a viable alternative to conventional defatted full-thickness skin grafting. It appears that there is a low complication rate with respect to graft failure or incomplete graft take. CLINICAL QUESTION/LEVEL OF EVIDENCE Therapeutic, IV.


Retraction: Melioidosis: Clinical impact and public health threat in the tropics.


title: Isolation and Cellular Phenotyping of Mesenchymal Stem Cells Derived from Synovial Fluid and Bone Marrow of Minipigs.

text: Mesenchymal stem cells (MSCs) have been established after isolation from various tissue sources, including bone marrow and synovial fluid. Recently, synovial-fluid-derived MSCs were reported to have multi-lineage differentiation potential and immunomodulatory features, which indicates that these cells can be used for tissue engineering and systemic treatments. This study presents a protocol for simple and non-invasive isolation of MSCs derived from the bone marrow and synovial fluid of minipigs to analyze cell surface markers for cell phenotyping and in vitro culturing. Using sexually mature six-month-old minipigs, bone marrow was extracted from the iliac crest bone using a bone marrow extractor, and the synovial fluid was aspirated from the femorotibial joint. Procedures for the collection of samples from both sources were non-invasive. The protocols for effective isolation of MSCs from harvested cell sources and for creating in vitro culture conditions to expand stable MSCs from minipigs and the application of systemic autologous treatments are provided. For cell phenotyping, the cell surface markers of both cells were analyzed using flow cytometry. In the results, the MSCs were isolated from the synovial fluid of the minipigs and showed that synovial-fluid-derived MSCs have a similar morphology and cell phenotype to bone-marrow-derived MSCs. Therefore, non-invasively obtained synovial fluid is a valuable source of MSCs.


title: Stem-Cell Therapy as a Potential Strategy for Radiation-Induced Brain Injury.

text: Radiation therapy is a standard and effective non-surgical treatment for primary brain tumors and metastases. However, this strategy inevitably results in damage of normal brain tissue, causing severe complications, especially the late-delayed cognitive impairment. Due to the multifactorial and complex pathological effects of radiation, there is a lack of effective preventative and restorative treatments for the irradiated brain. Stem-cell therapy has held considerable promise for decades in the treatment of central nervous system (CNS) disorders because of its unique capacity for tissue repair and functional integrity. Currently, there is growing interest in using stem cells as a novel option to attenuate the adverse effects of irradiation. In the present review, we discuss recent studies evaluating stem-cell therapies for the irradiated brain and their therapeutic effects on ameliorating radiation-related brain injury as well as their potential challenges in clinical applications. We discuss these works in context of the pathogenesis of radiation-induced injury to CNS tissue in an attempt to elucidate the potential mechanisms of engrafted stem cells to reverse radiation-induced degenerative processes.


title: Host tissue response by the expression of collagen to cyanoacrylate adhesives used in implant fixation for abdominal hernia repair.

text: The less traumatic use of surgical adhesives rather than sutures for mesh fixation in hernia repair has started to gain popularity because they induce less host tissue damage and provoke less postoperative pain. This study examines the host tissue response to a new cyanoacrylate (CA) adhesive (n-octyl, OCA). Partial defects (3 × 5 cm) created in the rabbit anterior abdominal wall were repaired by mesh fixation using OCA, Glubran2®(n-butyl-CA), Ifabond®(n-hexyl-CA) or sutures. Samples were obtained at 14/90 days for morphology, collagens qRT-PCR/immunofluorescence and biomechanical studies. All meshes were successfully fixed. Seroma was detected mainly in the Glubran group at 14 days. Meshes fixed using all methods showed good host tissue incorporation. No signs of degradation of any of the adhesives were observed. At 14 days, collagen 1 and 3 mRNA expression levels were greater in the suture and OCA groups, and lower in Ifabond, with levels varying significantly in the latter group with respect to the others. By 90 days, expression levels had fallen in all groups, except for collagen 3 mRNA in Ifabond. Collagen I and III protein expression was marked in the suture and OCA groups at 90 days, but lower in Ifabond at both time points. Tensile strengths were similar across groups. Our findings indicate the similar behavior of the adhesives to sutures in terms of good tissue incorporation of the meshes and optimal repair zone strength. The lower seroma rate and similar collagenization to controls induced by OCA suggests its improved behavior over the other two glues. This article deals with a preclinical study to examine different aspects of the repair process in the host of three alkyl cyanoacrylates (n-butyl (GLUBRAN 2), n-hexyl (IFABOND), and n-octyl cyanoacrylate (EVOBOND)) compared to sutures (control), in the fixation of surgical meshes for hernia repair. It goes into detail about collagen deposition in the repair zone at short and medium term. The results obtained demonstrate lower seroma rate and similar collagenization to sutures induced by the n-octyl suggesting better behavior than the other two cyanoacrylates.


title: Laparoscopic repair of post-abdominoperineal resection hernia: biological mesh and augmentation technique.

text: Perineal hernias are infrequent complications following abdominoperineal surgeries. These hernias require surgical repair when they become symptomatic by several conventional or reconstructive techniques. The benefits of a full laparoscopic approach and/or the combined approach of a perineal repair of the pelvic floor associated to the laparoscopic placement of a traditional synthetic mesh have been previously demonstrated. In this article, we present the case of a perineal incisional hernia, post-abdominoperineal resection of the rectum after radio chemotherapy, in the neoadjuvant treatment of a rectal adenocarcinoma tumor. An alternative approach, not previously described for the surgical repair of this type of hernia, is presented to assess the feasibility of the suturing repair, and efficacy of a biological acellular porcine collagen implant Permacol(®). A full laparoscopic suturing for the closure of the perineal defect associated to biological mesh reinforcement was successfully undertaken, with good short-term outcomes.


title: Comparison of stricture rates using three different gastrojejunostomy anastomotic techniques in laparoscopic Roux-en-Y gastric bypass.

text: INTRODUCTION No single gastrojejunostomy anastomosis technique (GJA) in Laparoscopic Roux-en-Y gastric bypass (LRYGB) is currently preferred over another. Bendewald et al. confirmed that there was no difference in anastomotic stricture rates when comparing hand-sewn (HS), linear-stapled (LS), and circular-stapled (CS) GJA techniques. We present and analyze our own institutional data to readdress stricture rates. METHODS From January 2010 to January 2013, 860 consecutive patients underwent LRYGB using HS, LS, and CS anastomotic techniques at a single institution. All patients in this study were followed to see if they had a complication of a stricture within this time period. Hospital records were retrospectively reviewed and those who had stricture complications shown on endoscopy requiring intervention were compiled and compared using univariate analysis. RESULTS Patient demographics did not differ substantially between the three groups. The most common technique employed was LS (n = 429, 49.8%), followed by CS (n = 254, 29.5%) and HS (n = 177, 20.6%), respectively. Using multivariate analysis, there was a significant difference in the rate of strictures between the anastomotic techniques (LS 4.42%, HS 2.82%, CS 1.18%, p = 0.0163). CONCLUSIONS Our data show that the discussion of which anastomotic technique is superior should be reopened given the statistically significant low rate of strictures in patients who underwent LRYGB with a CS anastomosis in comparison with LS and HS anastomoses.


title: Bilateral medial iliac lymph node excision by a ventral laparoscopic approach: technique description.

text: The aim of this study was to describe a ventral laparoscopic technique for bilateral medial iliac lymphadenectomy in dogs. Twelve intact male purpose-bred research dogs, weighing less than 15 kg, were positioned in dorsal recumbency, and a 3-portal technique was used. Bilateral dissection was performed with vessel-sealing devices while tilting the surgical table by up to 30° towards the contralateral side of the target medial iliac lymph node (MILN) without changing the surgeon's position. Using a ventral laparoscopic approach, bilateral MILNs were identified and excised in all dogs. The mean times for unilateral and bilateral MILN dissections were 9.7 ± 3.8 and 21.0 ± 6.0 min, respectively. The mean times for the right and left MILN dissections were 10.8 ± 4.3 and 9.8 ± 2.5 min, respectively. The mean total surgery time was 43.7 ± 7.7 min. In total, 26 MILNs were dissected. Several complications, including mild to moderate capillary hemorrhage from perinodal fat and vessels (controlled laparoscopically), mild spleen trauma caused by the first trocar insertion and capsular damage of MILNs, were observed. However, there were no other major complications. All MILN samples were evaluated and deemed suitable for histopathologic diagnosis. Laparoscopic excision of MILNs is a useful method of excisional biopsy for histopathologic diagnosis. Using this ventral laparoscopic approach with the 3-portal technique, bilateral MILN dissection suitable for obtaining histopathologic samples could be achieved in a short time in dogs weighing less than 15 kg.


title: Billroth II with Braun Enteroenterostomy Is a Good Alternative Reconstruction to Roux-en-Y Gastrojejunostomy in Laparoscopic Distal Gastrectomy.

text: Background. Although Billroth II (BII) reconstruction is simpler and faster than Billroth I or Roux-en-Y (RY) reconstruction in patients undergoing totally laparoscopic distal gastrectomy (TLDG), BII reconstruction is associated with several complications, including more severe bile reflux. BII Braun anastomosis may be a better alternative to RY reconstruction. Methods. This retrospective study included 56 consecutive patients who underwent TLDG for gastric cancer, followed by BII Braun or RY reconstruction, between January 2013 and December 2015. Surgical outcomes, including length of operation, quantity of blood lost, and postoperative complications, were compared in the two groups. Results. Clinicopathological characteristics did not differ between the BII Braun and RY groups. Mean length of operation was significantly longer in the RY than the BII Braun group (157.3 min versus 134.6 min, p < 0.010), but length of hospital stay, blood loss, and complication rate did not differ between the two groups. Ileus occurred in three patients (10.0%) in the RY group. Endoscopic findings 6 months after surgery showed bile reflux in seven (28%) patients in the BII Braun group and five (17.2%) in the RY group (p = 0.343), but no significant differences in rate of gastric residue or degree of gastritis in the remnant stomach in the two groups. Conclusions. B-II Braun anastomosis is a good alternative to RY reconstruction, reducing length of operation and ileus after TLDG.


COVID-19 and Cancer: Lessons From a Pooled Meta-Analysis.


title: Coronavirus: Update Related to the Current Outbreak of COVID-19.

text: In December 2019, some cases of viral pneumonia were epidemiologically related to a new coronavirus in the province of Hubei, China. Subsequently, there has been an increase in infections attributable to this virus throughout China and worldwide. The World Health Organization (WHO) has officially named the infection coronavirus disease 2019 (COVID-19), and the virus has been classified as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This appears to be a virus from Rhinolophus bats, but the intermediate host has not yet been identified. The mechanism of infection of SARS-CoV-2 is not yet known; it appears to have affinity for cells located in the lower airways, where it replicates. The interhuman transmission of coronaviruses mainly occurs through saliva droplets and direct and indirect contact via surfaces. As of March 10, 2020, the number of cases worldwide was 113,702. Along with severe acute respiratory syndrome (SARS) and Middle Eastern respiratory syndrome (MERS), COVID-19 appears to cause a severe clinical picture in humans, ranging from mild malaise to death by sepsis/acute respiratory distress syndrome. The prognosis is worse in elderly patients with comorbidities. To date, there is no specific therapy for COVID-19. Prevention of SARS-CoV-2 infection implies strategies that limit the spread of the virus. WHO and other international and national bodies have developed continuously updated strategic objectives and provisions to contain the spread of the virus and infection.


The medical biochemistry of poverty and neglect.


title: Assessing the Detection of Middle East Respiratory Syndrome Coronavirus IgG in Suspected and Proven Cases of Middle East Respiratory Syndrome Coronavirus Infection.

text: Middle East respiratory syndrome coronavirus (MERS-CoV) causes severe respiratory disease with significant mortality. Two testing methods are currently used for MERS-CoV diagnostics: nucleic acid detection (the gold standard) and serological analysis. In this study, we evaluated the detection of MERS-CoV-IgG in suspected and proven cases of MERS-CoV infection. We enrolled 174 patients: 113 had respiratory symptoms/suspected MERS-CoV infection, 31 had confirmed influenza A or B infection, 23 had a recent confirmed MERS-CoV infection, and 7 had confirmed MERS-CoV infection 1 year before. All underwent MERS-CoV RNA and MERS-CoV-IgG testing. Thirty patients were found to be MERS-CoV RNA positive; however, during serological analysis, only 6 (3.4%) patients were positive for MERS-CoV-IgG, 1 (0.6%) patient was equivocal, and 167 (96%) patients were negative. Among the serological positives, four were recently MERS-CoV RNA positive and two were MERS-CoV RNA negative. No cross-reactivity to influenza A or B was detected. Based on the lack of correlation between nucleic acid and serological analysis, we conclude that MERS-CoV-IgG testing may not be suitable for diagnosing acute infection or estimating its prevalence during an outbreak. In addition, our findings show that MERS-CoV-IgG may not have significant value in determining disease severity or prognosis.


title: Negative prognostic impact of renal replacement therapy in adult living-donor liver transplant recipients: preoperative recipient condition and donor factors.

text: BACKGROUND In deceased-donor liver transplantation settings, post-transplantation acute renal failure with the induction of renal replacement therapy (RRT) is known to have negative effects on graft and patient survivals. However, the impact of RRT in living-donor liver transplantation (LDLT) has not been well investigated. The aim of this study was to elucidate risk factors requiring RRT and prognostic factors after its induction. METHODS Clinical data on the consecutive 113 adult patients who underwent LDLT from March 2002 to May 2013 were retrospectively reviewed. They were divided into 2 groups: RRT (n = 33) and Non-RRT (n = 80). The primary reasons for receiving RRT were hepatorenal syndrome (n = 17), sepsis (n = 12), and renal hypoperfusion (n = 4). RESULTS Although there were no significant differences in age or sex, the Model for End-Stage Liver Disease (MELD) score was significantly higher in the RRT group than in the Non-RRT group (23 ± 13 vs 16 ± 7; P = .002). The graft-recipient weight ratio (GRWR) was significantly lower in the RRT group (0.86 ± 0.3 vs 0.99 ± 0.2; P = .025). The 1- and 5-year patient survival rates were significantly higher in the Non-RRT group than in the RRT group (respectively, 91.3% and 84.3% vs 42.9% and 25.5%; P < .001). In multivariate analysis, independent risk factors for receiving RRT were MELD score >20 (P = .044) and GRWR <0.7 (P = .039). In the RRT group, donor age >50 years (P = .042) and preoperative serum creatinine level >1.5 mg/dL (P = .049) were significant prognostic risk factors. CONCLUSIONS In adult LDLT patients, the induction of RRT after LDLT was a negative predictor of survival. In addition to the preoperative recipient's condition, donor factors including graft size and donor age influenced prognosis after the induction of RRT.


COVID-19-New Insights on a Rapidly Changing Epidemic.


title: Evolution of the sequence composition of Flaviviruses.

text: The adaption of pathogens to their host(s) is a major factor in the emergence of infectious disease and the persistent survival of many of the infectious diseases within the population. Since many of the smaller viral pathogens are entirely dependent upon host machinery, it has been postulated that they are under selection for a composition similar to that of their host. Analyses of sequence composition have been conducted for numerous small viral species including the Flavivirus genus. Examination of the species within this particular genus that infect vertebrate hosts revealed that sequence composition proclivities do not correspond with vector transmission as the evolutionary history of this species suggests. Recent sequencing efforts have generated complete genomes for many viral species including members of the Flavivirus genus. A thorough comparison of the sequence composition was conducted for all of the available Flaviviruses for which the complete genome is publicly available. This effort expands the work of previous studies to include new vector-borne species as well as members of the insect-specific group which previously have not been explored. Metrics, including mono-, di-, and tri-nucleotide abundances as well as N(C) values and codon usage preferences, were explored both for the entire polyprotein sequence as well as for each individual coding region. Preferences for compositions correspond to host-range rather than evolutionary history; species which infect vertebrate hosts exhibited particular preferences similar to each other as well as in correspondence with their host's preferences. Flaviviruses which do not infect vertebrate hosts, however, did not show these proclivities, with the exception of the Kamiti River virus suggesting its recent (either past or present) infectivity of an unknown vertebrate host.


Illness Schema Activation and the Effects of Illness Seasonality on Accessibility of Implicit Illness-Related Information.


title: Upregulation of epidermal gap junctional proteins in patients with venous disease.

text: BACKGROUND Leg ulceration is a feared complication of venous insufficiency. It is not known whether varicose veins predispose skin to poor wound healing. The expression pattern of gap junctional protein connexin, a known marker of poor wound healing, was investigated across various stages of venous disease. METHODS Patients undergoing intervention for varicose veins were assessed according to the Clinical Etiologic Anatomic Pathophysiologic (CEAP) classification of varicose veins. Paired 4-mm punch biopsies were taken from above the ankle (pathological) and above the knee (control). Tissues were stained with haematoxylin and eosin, and for connexin 43, connexin 30 and connexin 26. RESULTS Forty-eight paired biopsies were taken (12 each for CEAP class C0, C2, C4 and C6). The pathological skin showed progressive epithelial hyperthickening, an increase in the number and depth of rete ridges, increased inflammation and loss of dermal architecture with disease progression from C4 onwards. The overall absolute connexin expression and mean connexin expression per cell in the pathological skin similarly increased across the CEAP classes from as early as C2. Increasing levels of connexin in control skin were also noted, indicating progression of the disease proximally. Connexin 43 expression showed the strongest positive correlation between pathological and control skin. CONCLUSION Connexins were overexpressed in patients with simple varicose veins, with a stepwise increased expression through venous eczema to ulceration. Connexin 43 is a potential biomarker for venous disease. This finding suggests that varicose veins predispose skin to poor wound healing. Surgical relevance The overexpression of connexins, a family of gap junctional proteins, is known to cause poor healing in venous leg ulceration. It is not known whether there is any association with superficial venous disease. Here, connexin proteins were overexpressed in patients with uncomplicated varicose veins, before histological skin changes. Connexin could be a biomarker of venous disease progression.


title: Flow and airway pressure analysis for detecting ineffective effort during mechanical ventilation in neuromuscular patients.

text: Ineffective efforts (IEs) are among the most common types of patient-ventilator asynchrony. The objective of this study is to validate IE detection during expiration using pressure and flow signals, with respiratory effort detection by esophageal pressure (Pes) measurement as the reference, in patients with neuromuscular diseases (NMDs). We included 10 patients diagnosed with chronic respiratory failure related to NMD. Twenty-eight 5-minute recordings of daytime ventilation were studied for IE detection. Standard formulas were used to calculate sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of IE detection using pressure and flow signals compared to Pes measurement. Mean sensitivity and specificity of flow and pressure signal-based IE detection versus Pes measurement were 97.5% ± 5.3% and 91.4% ± 13.7%, respectively. NPV was 98.1% ± 8.2% and PPV was 67.6% ± 33.8%. Spearman's rank correlation coefficient indicated a moderately significant correlation between frequencies of IEs and controlled cycles ( ρ = 0.50 and p = 0.01). Among respiratory cycles, 311 (11.2%) were false-positive IEs overall. Separating false-positive IEs according to their mechanisms, we observed premature cycling in 1.2% of cycles, delayed ventilator triggering in 0.1%, cardiac contraction in 9.2%, and upper airway instability during expiration in 0.3%. Using flow and pressure signals to detect IEs is a simple and rapid method that produces adequate data to support clinical decisions.


title: Enhanced colonic delivery of ciclosporin A self-emulsifying drug delivery system encapsulated in coated minispheres.

text: OBJECTIVES Investigate the potential of coated minispheres (SmPill®) to enhance localized Ciclosporin A (CsA) delivery to the colon. METHODS CsA self-emulsifying drug delivery systems (SEDDS) were encapsulated into SmPill® minispheres. Varying degrees of coating thickness (low, medium and high) were applied using ethylcellulose and pectin (E:P) polymers. In vitro CsA release was evaluated in simulated gastric and intestinal media. Bioavailability of CsA in vivo following oral administration to pigs of SmPill® minispheres was compared to Neoral® po and Sandimmun® iv in a pig model. CsA concentrations in blood and intestinal tissue were determined by HPLC-UV. RESULTS In vitro CsA release from coated minispheres decreased with increasing coating thickness. A linear relationship was observed between in vitro CsA release and in vivo bioavailability (r(2) = 0.98). CsA concentrations in the proximal, transverse and distal colon were significantly higher following administration of SmPill®, compared to Neoral® po and Sandimmun® iv (p < 0.05). Analysis of transverse colon tissue subsections also revealed significantly higher CsA concentrations in the mucosa and submucosa using SmPill® minispheres (p < 0.05). CONCLUSIONS Modulating E:P coating thickness controls release of CsA from SmPill® minispheres. Coated minispheres limited CsA release in the small intestine and enhanced delivery and uptake in the colon. These findings demonstrate clinical advantages of an oral coated minisphere-enabled CsA formulation in the treatment of inflammatory conditions of the large intestine.


title: Novel defect in phosphatidylinositol 4-kinase type 2-alpha (PI4K2A) at the membrane-enzyme interface is associated with metabolic cutis laxa.

text: BACKGROUND Inherited cutis laxa, or inelastic, sagging skin is a genetic condition of premature and generalized connective tissue aging, affecting various elastic components of the extracellular matrix. Several cutis laxa syndromes are inborn errors of metabolism and lead to severe neurological symptoms. PATIENT AND METHODS In a patient with cutis laxa, a choreoathetoid movement disorder, dysmorphic features and intellectual disability we performed exome sequencing to elucidate the underlying genetic defect. We identified the amino acid substitution R275W in phosphatidylinositol 4-kinase type IIα, caused by a homozygous missense mutation in the PI4K2A gene. We used lipidomics, complexome profiling and functional studies to measure phosphatidylinositol 4-phosphate synthesis in the patient and evaluated PI4K2A deficient mice to define a novel metabolic disorder. RESULTS The R275W residue, located on the surface of the protein, is involved in forming electrostatic interactions with the membrane. The catalytic activity of PI4K2A in patient fibroblasts was severely reduced and lipid mass spectrometry showed that particular acyl-chain pools of PI4P and PI(4,5)P2 were decreased. CONCLUSIONS Phosphoinositide lipids play a major role in intracellular signalling and trafficking and regulate the balance between proliferation and apoptosis. Phosphatidylinositol 4-kinases such as PI4K2A mediate the first step in the main metabolic pathway that generates PI4P, PI(4,5)P2 and PI(3,4,5)P3 . Although neurologic involvement is common, cutis laxa has not been reported previously in metabolic defects affecting signalling. Here we describe a patient with a complex neurological phenotype, premature aging and a mutation in PI4K2A, illustrating the importance of this enzyme in the generation of inositol lipids with particular acylation characteristics. This article is protected by copyright. All rights reserved.


Surgery: the coming of age of metabolic surgery.


title: Motivational interviewing to improve adherence behaviours for the prevention of diabetic foot ulceration.

text: Diabetic foot ulceration is a major complication associated with high morbidity. Little evidence exists on which interventions are effective at preventing ulceration. Participants who are adherent to self-care behaviours have significantly better outcomes. Motivational interviewing is an intervention that has been used successfully for conditions where adherence is important, such as reduction of obesity and HbA1c levels. A systematic review was conducted to determine whether motivational interviewing is effective at improving adherence for the prevention of Diabetic Foot Ulceration. Electronic searches were run without date or language restrictions in MEDLINE (viaEBSCOhost), CINAHL (viaEBSCOhost), ProQuest (Health and Medical Collection, Nursing and Allied Health Database, PsycINFO, Psychology, PsychArticles), AMED, EMBASE, Cochrane Central Register of Controlled Trials, ScienceDirect, and Web of Science Core Collections. Papers were included if participants had or were at risk of diabetic foot ulceration. Studies required motivational interviewing or a motivational approach as the sole intervention or as a component. Randomised controlled trials and quasi-experimental studies were included if ulceration and/or at least one behavioural outcome was measured before and after the intervention. Five studies met the inclusion criteria. Heterogeneity prevented the pooling of data. One study used motivational interviewing as the sole intervention. This study found a short-term positive effect on footwear adherence. The remaining four studies had a motivational component within their interventions. Two of these studies showed the intervention to be effective but both were at a high risk of bias. This review demonstrates an evidence gap. More research is needed.


title: Relationships between brain metabolite levels, functional connectivity, and negative mood in urologic chronic pelvic pain syndrome patients compared to controls: A MAPP research network study.

text: Until recently, the predominant pathology of chronic pelvic pain conditions was thought to reside in the peripheral tissues. However, mounting evidence from neuroimaging studies suggests an important role of the central nervous system in the pathogenesis of these conditions. In the present cross-sectional study, proton magnetic resonance spectroscopy (1H-MRS) of the brain was conducted in female patients with urologic chronic pelvic pain syndrome (UCPPS) to determine if they exhibit abnormal concentrations of brain metabolites (e.g. those indicative of heightened excitatory tone) in regions involved in the processing and modulation of pain, including the anterior cingulate cortex (ACC) and the anterior and posterior insular cortices. Compared to a group of age-matched healthy subjects, there were significantly higher levels of choline (p = 0.006, uncorrected) in the ACC of UCPPS patients. ACC choline levels were therefore compared with the region's resting functional connectivity to the rest of the brain. Higher choline was associated with greater ACC-to-limbic system connectivity in UCPPS patients, contrasted with lower connectivity in controls (i.e. an interaction). In patients, ACC choline levels were also positively correlated with negative mood. ACC γ-aminobutyric acid (GABA) levels were lower in UCPPS patients compared with controls (p = 0.02, uncorrected), but this did not meet statistical correction for the 4 separate regional comparisons of metabolites. These results are the first to uncover abnormal GABA and choline levels in the brain of UCPPS patients compared to controls. Low GABA levels have been identified in other pain syndromes and might contribute to CNS hyper-excitability in these conditions. The relationships between increased ACC choline levels, ACC-to-limbic connectivity, and negative mood in UCPPS patients suggest that this metabolite could be related to the affective symptomatology of this syndrome.


title: [Surgical treatment strategy for digestive system malignancies during the outbreak of novel coronavirus pneumonia].

text: The outbreak of novel coronavirus pneumonia occurred in Wuhan, Hubei province of China, at the end of 2019, and spread rapidly across the country. After the outbreak of this disease, the overwhelming majority of cities have launched the "first level response" and the regular diagnosis and treatment of cancer patients are greatly affected. The digestive systemic cancer is the most common malignancy. Most patients are diagnosed in the advanced stage with poor prognosis. The epidemic of novel coronavirus pneumonia poses new challenges to diagnosis and treatment of the patients with digestive system malignancies. Based on the fully understanding of the characteristics of digestive system tumors, we should change the treatment strategy and adopt more reasonable treatment strategy timely during the epidemic period to minimize the adverse effects of the epidemic of novel coronavirus pneumonia on the treatment.


Impact of the COVID-19 pandemic in the paediatric emergency department attendances in Argentina.


title: Electrocardiographic changes after successful recanalization of a chronic total coronary occlusion. A systematic review and meta-analysis.

text: BACKGROUND Observational studies suggest that in patients with a CTO successful recanalization is associated with better clinical outcome. This could be related to a reduction in the occurrence of arrhythmias, which may result from modifications of the hibernating myocardium in a CTO region. METHODS AND RESULTS We aimed to evaluate the effect of CTO PCI on electrophysiological parameters, and conducted a systematic review and meta-analysis according to the PRISMA guidelines. MEDLINE and EMBASE were searched. Titles and abstracts identified by the search strategy were independently screened by two investigators. Data were extracted and used for meta-analyses where possible. In total, eight studies incorporating 467 patients were included in this review, evaluating the effect of successful CTO PCI on various ECG parameters. Three studies showed a significant decrease in mean QT dispersion of 17.46ms [95% CI 10.62-24.30] after successful CTO PCI. QTc dispersion also decreased significantly, with a mean decrease of 18.74ms [95% CI 11.53-25.94]. In one trial a significant decrease in Tp-e interval in leads V2 and V5, and a significant decrease in Tp-e/QT ratio in leads V2 and V5 post-CTO PCI were observed. CONCLUSIONS This first systematic review and meta-analysis suggests that successful CTO PCI is associated with an immediate decrease in ECG parameters that reflect heterogeneity in depolarization and repolarization, which could lead to a reduction in the risk for ventricular arrhythmias and sudden cardiac death. We raise the hypothesis that hibernating myocardium in a CTO region may not be as deeply "in sleep" as one would assume.


title: Identification and management of the ilio-inguinal and ilio-hypogastric nerves in open inguinal hernia repair: benefits of self-gripping mesh.

text: PURPOSE A large randomized, multicenter European study recently reported a reduction in early pain after open inguinal surgery when self-gripping mesh was used compared with sutured Lichtenstein repair. This secondary exploratory study is focused on the influence of nerve identification and handling on post-operative pain. METHODS Post-operative VAS pain data and Surgical Pain Scores (SPS) from 507 patients included in this study were analyzed according to whether inguinal nerves were preserved or resected during surgery to investigate whether identification and peri-operative nerve handling impact post-operative pain. RESULTS Preservation of the ilio-hypogastric nerve during Lichtenstein mesh repair with suture fixation was associated with significantly more post-operative pain compared with resection at each follow-up (p ≤ 0.003). This difference was not significant with self-gripping mesh repair. The decrease from baseline in post-operative VAS and SPS scores were significantly greater after self-gripping mesh repair compared to Lichtenstein repair at 1 year, but only when the ilio-hypogastric nerve was preserved (VAS scores, p = 0.009; SPS scores, p = 0.015). No such difference was observed with the ilio-inguinal nerve. When self-gripping mesh was used, preservation of the ilio-hypogastric nerve was associated with significantly greater decreases in post-operative pain (change in VAS score from baseline) compared with Lichtenstein repair at each follow-up (p ≤ 0.018). CONCLUSIONS The ilio-hypogastric nerve is in danger of being traumatized during Lichtenstein mesh repair with suture fixation. The use of self-gripping mesh was shown to reduce the level of post-operative pain when the ilio-hypogastric nerve was preserved. Resection of the ilio-hypogastric nerve during Lichtenstein repair eliminates this difference.


An alternative COVID-19 checklist.


title: Discovery of dihydropyrrolidones as novel inhibitors against influenza A virus.

text: More effective prophylactic and therapeutic strategies to combat influenza viruses are urgently required worldwide because the conventional anti-influenza drugs are facing drug resistance. Here, dihydropyrrolidones (DHPs), the products of an efficient multi-components reaction, were found to possess good activities against influenza A virus (IAV). Primary structure-activity relationship indicated that the activities of DHPs were greatly influenced by substituents and four of them had IC50 values lower than 10 μM (DHPs 5-2, 8, 14 and 19: IC50 = 3.11-9.23 μM). The activities against multiple IAV strains and mechanism of DHPs were further investigated by using 5-2 (IC50 = 3.11 μM). It was found that 5-2 possessed antiviral effects against all the investigated subtypes of IAVs with the IC50 values from 3.11 to 7.13 μM. Moreover, 5-2 showed very low cytotoxicity with CC50 > 400 μM. Results of mechanism study indicated that 5-2 could efficiently inhibit replication of IAV, up-regulate the expression of key antiviral cytokines IFN-β and antiviral protein MxA, and suppress the production of the NDAPH oxidase NOX1 in MDCK cells. These results indicated that 5-2 could be used as a potential inhibitor against wide subtypes of IAVs.


Stretch-resistant coils for intracranial aneurysms: one step forward or two steps back?


title: Laparoscopic procurement of single versus multiple artery kidney allografts: is long-term graft survival affected?

text: BACKGROUND Living donor kidneys with multiple arteries (MA) are increasingly procured laparoscopically for transplant. METHODS We compare long-term graft function and survival of kidneys with single arteries (SA) and MA over a 10-year period. RESULTS There were a total of 218 grafts with SA and 60 grafts with MA. The MA group had longer operative and ischemic times than SA group. There was a small increase in ureteral complication (8.3% vs. 2.3% P=0.06) and a significantly higher incidence of rejection (23.3% vs. 10.1%, P=0.01) in MA group than in SA group. Graft function was lower in MA group than SA group. The 5-year graft survival by Kaplan Meier analysis was better in SA group than in MA group (P=0.023). The estimated graft survivals at 1, 3, and 5 year were 94.4%, 90.6%, and 86% for SA group and 89.6%, 83.2%, and 71.8% for MA group. There was a higher percentage of graft loss from chronic allograft nephropathy in MA group than in SA group (16.7% vs. 5.5%, P=0.01). The presence of MA (vs. SA) was an independent risk for acute rejection (OR 3.60, 95% CI 1.59-8.14, P=0.002) and for graft loss (HR 2.31, 95% CI 1.05-5.09, P=0.038). CONCLUSION Laparoscopic procurement of living donor kidneys with SA may be associated with a lower risk of rejection, better function, and superior long-term survival when compared with kidneys with MA.


title: Pilot study using telemedicine video-consultation for vascular patients' care during the COVID-19 period.

text: INTRODUCTION The aim of this pilot study was to evaluate the effectiveness and patients satisfaction of using telemedicine virtual communications to provide remote health care to vascular patients during the coronavirus disease 2019 (COVID-19) period in China. METHODS Video-calls using Wechat software (Tencent, Shenzhen, China) between patients and vascular surgeons were conducted in a period when there were restrictions and limitations for people' travels in China. At the end of each video-call, a short questionnaire was used to evaluate the patient satisfaction level. RESULTS During the COVID-19 period from 19 February to 16 March 2020, a sample of 114 from 165 (69%) patients were reached after one phone call attempt. One hundred and forty-two telemedicine remote communications were made between the two vascular surgeons and 114 patients. The mean age of this cohort of patients were 60±15.2 (range 25 to 90) years old, and 74 (65%) were male. Twenty-five patients (22%) were outside of our province when they received the video-call. The mean duration of the video-call was 11.0±8.9 minutes. All of the patients thought telemedicine was a good substitute for coming to hospital, and 95% (108/114) of them preferred to have remote telemedicine rather than postpone the appointment. All the patients agreed with the advantages of telemedicine including no infection risks, no need to travel and no need to wait for long time. All the patients were 'satisfied' or 'highly satisfied' with the video-call and they would like to use telemedicine for follow-up in the future. CONCLUSION Telemedicine virtual communications was effective to provide remote healthcare with a high patient satisfaction during the COVID-19 period. Telemedicine offers support to vulnerable vascular patients without the need for travel and face-to-face hospital consultation, and so avoided transmission and infection.


title: Disparities Based on Race, Ethnicity, and Socioeconomic Status Over the Transition to Adulthood Among Adolescents and Young Adults on the Autism Spectrum: a Systematic Review.

text: PURPOSE OF REVIEW Few studies have examined disparities in autism services and functional outcomes over the life course. Transition to adulthood is an especially important developmental period, as it sets up trajectories of adult functioning. This systematic review summarizes patterns of service use and transition outcomes according to race, ethnicity, and socioeconomic characteristics over the transition to adulthood. RECENT FINDINGS Forty studies were included. Low-income and racial/ethnic minority youth on the autism spectrum were less likely to participate in transition planning meetings, enroll in postsecondary education, find competitive employment after high school, live independently, participate in social activities, and receive health care transition services than their White and higher income peers on the autism spectrum. Racial/ethnic minority and low-income youth on the autism spectrum were more likely to be disconnected from educational, occupational, and social activities upon entering adulthood. Future research should explore the mechanisms underlying these disparities as a first step to addressing them.


title: Endovascular coil retrieval using a TrevoProVue stentriever.

text: A 65-year-old man with a left cavernous internal carotid artery cerebral aneurysm experienced a premature detachment of the first framing coil (10 mm × 40 cm Penumbra Complex Standard) during a coil embolization procedure. The coil herniated into the anterior cerebral artery and pericallosal artery. Multiple attempts to retrieve the coil using both a 2 and 4 mm Microsnare (Amplatz GooseNeck) failed. A Trevo ProVue retrievable stent was then used to retrieve the coil without any adverse events. This case report highlights a novel use of a stent for the removal of a foreign body from the cerebrovascular system.


Association of Uneven MitraClip Application and Leaflet Stress in a Finite Element Model.


Know your ventilator to beat the leak.


title: Overview of Covid-19 regarding the cardiovascular situation in the light of current reports.

text: Nowadays coronavirus disease 2019 (Covid-19) is increasing mortality all over the world mercilessly. We are learning almost every day about its new symptoms and that it mutates quickly. This disease ties us up and leaves us desperate. Death from this disease has increased in patients who had with pre-existing medical conditions, especially cardiovascular ones, by eliminating the angiotensin-converting enzyme (ACE)-2 receptor in the lungs. Also, ACE1 and angiotensin receptor blockers (ARB) may stimulate ACE2 expression and worse the prognosis. Intravenous infusions of ACEIs and ARBs in experimental animals increase the numbers of ACE2 receptors. So, it may be one of the reasons that COVID-19 infects the cells of patients treating hypertension. However, most of the congress of cardiology do not recommend discontinue of these anti-hypertensive drugs. Therefore, this brief report evaluates Covid-19 in the view of cardiovascular diseases taking into account current reports and suggests some possible solutions to keep the virus under control.


title: Anterior Cruciate Ligament Re-tear and Revision Reconstruction in the Skeletally Immature Athlete.

text: PURPOSE OF REVIEW With an increase in high-demand sporting activity, the rate of pediatric and adolescent anterior cruciate ligament (ACL) reconstruction is increasing. Yet, the failure rates after reconstruction are much higher than the adult population. The purpose of this paper is to understand failure rates, reasons for graft failure, and strategies for successful revision surgery. RECENT FINDINGS A complete understanding of the failure etiology is essential for the clinician treating this population prior to revision. This begins with an assessment of post-operative patient compliance and sporting activity. Surgical technique must then be scrutinized for non-anatomic tunnel placement and poor graft size/type. Concurrent bony deformity must also be addressed including lower extremity valgus alignment and tibial slope abnormalities. Meniscus and chondral injury must be aggressively treated. Furthermore, imaging must be examined to look for missed posterolateral corner injury. Lateral extra-articular tenodesis (in the setting of ligamentous laxity or rotational instability) may be also indicated as well. The surgeon can then choose a graft type and surgical technique that optimizes outcome and respects skeletal growth. Prior to surgical intervention, the clinician must also counsel patients in regard to the guarded prognosis and outcomes in this setting. Prolonged rehabilitation protocols/return-to-play timing as well as sporting activity modification in the post-operative period after revision are critical. There is limited literature on revision ACL reconstruction in the skeletally immature athlete. An understanding of all the risk factors for failure is essential in order to achieve treatment success.


Guidelines for sedation and anesthesia in GI endoscopy.


Covid-19: UK records first death, as world's cases exceed 100 000.


[Characteristics, causes, diagnosis and treatment of coagulation dysfunction in patients with COVID-19].


title: Effect of Synthetic Vitamin A and Probiotics Supplementation for Prevention of Morbidity and Mortality during the Neonatal Period. A Systematic Review and Meta-Analysis of Studies from Low- and Middle-Income Countries.

text: Background: Suboptimal nutritional status of a newborn is a risk factor for short- and long-term morbidity and mortality. The objectives of this review were to assess the efficacy and effectiveness of neonatal synthetic vitamin A supplementation, dextrose gel and probiotic supplementation for prevention of morbidity and mortality during infancy in low and middle-income countries. Methods: We included randomized trials. Primary outcome was all-cause mortality. We conducted electronic searches on multiple databases. Data were meta-analyzed to obtain relative risk (RR) and 95% confidence interval (CI). Studies for vitamin A and Probiotics were analyzed separately. No studies were found for dextrose gel supplementation during neonatal period. The overall rating of evidence was determined by Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. Results: Sixteen studies assessed the effect of vitamin A supplementation during the neonatal period. Based on pooled data from community-based studies only, there was no significant effect of vitamin A on all-cause mortality at age 1 month (RR 0.99, 95% CI 0.90, 1.08), 6 months (RR 0.98; 95% CI 0.89-1.08) and 12 months (RR 1.04, 95% CI 0.94, 1.14) but increased risk of bulging fontanelle (RR 1.53, 95% CI 1.12, 2.09). The overall quality of evidence was high for the above outcomes. Thirty-three studies assessed the effect of probiotic supplementation during the neonatal period and were mostly conducted in the hospital setting. Probiotics reduced the risk of all-cause mortality (RR 0.80, 95% CI 0.66, 0.96), necrotizing enterocolitis (RR 0.46, 95% CI 0.35, 0.59) and neonatal sepsis (RR 0.78, 95% CI 0.70, 0.86). The grade ratings for the above three outcomes were high. Conclusions: Vitamin A supplementation during the neonatal period does not reduce all-cause neonatal or infant mortality in low and middle-income countries in the community setting. Probiotic supplementation during the neonatal period seems to reduce all-cause mortality, NEC, and sepsis in babies born low birth weight and/or preterm in the hospital setting.


title: Noninvasive ventilation as acute therapy.

text: PURPOSE OF REVIEW Noninvasive ventilation (NIV) is widely used in ICU patients to treat or to prevent acute respiratory failure. Whereas its physiological effects are clearly beneficial in hypercapnic patients, it could be deleterious in hypoxemic patients without hypercapnia. RECENT FINDINGS NIV should be cautiously used in patients with de-novo respiratory failure, the vast majority of whom meet the criteria for acute respiratory distress syndrome. Spontaneous breathing with high tidal volumes may worsen lung injury in these patients, and recent findings suggest that NIV may increase the risk of mortality. Even though high-flow oxygen therapy is increasingly applied in this context, NIV remains recommended for management of immunocompromised patients with acute respiratory failure. NIV should be the first-line oxygenation strategy in patients with acute hypercapnic respiratory failure when pH is equal to or below 7.35. Prophylactic NIV prevents respiratory failure after extubation of patients at high risk of reintubation. SUMMARY Most previous studies have compared NIV with standard oxygen, and recent recommendations have been established from these findings. Given the growing use of high-flow oxygen therapy, new studies are needed to compare NIV versus high-flow oxygen therapy so as to better define the appropriate indications for each treatment.


To the editor.


title: Mechanical Ventilation Boot Camp: A Simulation-Based Pilot Study.

text: Objectives. Management of mechanically ventilated patients may pose a challenge to novice residents, many of which may not have received formal dedicated critical care instruction prior to starting their residency training. There is a paucity of data regarding simulation and mechanical ventilation training in the medical education literature. The purpose of this study was to develop a curriculum to educate first-year residents on addressing and troubleshooting ventilator alarms. Methods. Prospective evaluation was conducted of seventeen residents undergoing a twelve-hour three-day curriculum. Residents were assessed using a predetermined critical action checklist for each case, as well as pre- and postcurriculum multiple-choice cognitive knowledge questionnaires and confidence surveys. Results. Significant improvements in cognitive knowledge, critical actions, and self-reported confidence were demonstrated. The mean change in test score from before to after intervention was +26.8%, and a median score increase of 25% was noted. The ARDS and the mucus plugging cases had statistically significant improvements in critical actions, p < 0.001. A mean increase in self-reported confidence was realized (1.55 to 3.64), p = 0.049. Conclusions. A three-day simulation curriculum for residents was effective in increasing competency, knowledge, and confidence with ventilator management.


title: Low Abdominal NIRS Values and Elevated Plasma Intestinal Fatty Acid-Binding Protein in a Premature Piglet Model of Necrotizing Enterocolitis.

text: To identify early markers of necrotizing enterocolitis (NEC), we hypothesized that continuous abdominal near-infrared spectroscopy (A-NIRS) measurement of splanchnic tissue oxygen saturation and intermittent plasma intestinal fatty-acid binding protein (pI-FABP) measured every 6 hours can detect NEC prior to onset of clinical symptoms. Premature piglets received parenteral nutrition for 48-hours after delivery, followed by enteral feeds every three hours until death or euthanasia at 96-hours. Continuous A-NIRS, systemic oxygen saturation (SpO2), and heart rate were measured while monitoring for clinical signs of NEC. Blood samples obtained at 6-hour intervals were used to determine pI-FABP levels by ELISA. Piglets were classified as fulminant-NEC (f-NEC), non-fulminant-NEC (nf-NEC) and No-NEC according to severity of clinical and histologic features. Of 38 piglets, 37% (n=14) developed nf-NEC, 18% (n=7) developed f-NEC and 45% (n=17) had No-NEC. There were significant differences in baseline heart rate (p=0.008), SpO2 (p<0.001) and A-NIRS (p<0.001) among the three groups. A-NIRS values of NEC piglets remained lower throughout the study with mean for f-NEC of 69±3.8%, 71.9±4.04% for nf-NEC, and 78.4±1.8% for No-NEC piglets (p<0.001). A-NIRS <75% predicted NEC with 97% sensitivity and 97% specificity. NEC piglets demonstrated greater variability from baseline in A-NIRS than healthy piglets (10.1% vs. 6.3%; p=0.04). Mean pI-FABP levels were higher in animals that developed NEC compared to No-NEC piglets (0.66 vs. 0.09 ng/mL;p<0.001). In f-NEC piglets, pI-FABP increased precipitously after feeds (0.04 to 1.87 ng/mL;p<0.001). pI-FABP levels increased in parallel with disease progression and a value >0.25ng/mL identified animals with NEC (68% sensitivity and 90% specificity). NIRS is a real-time, non-invasive tool that can serve as a diagnostic modality for NEC. In premature piglets, low A-NIRS in the early neonatal period and increased variability during initial feeds are highly predictive of NEC, which is then confirmed by rising plasma I-FABP levels. These modalities may help identify neonates with NEC prior to clinical manifestations of disease.


title: A stakeholder co-design approach for developing a community pharmacy service to enhance screening and management of atrial fibrillation.

text: BACKGROUND Community pharmacies provide a suitable setting to promote self-screening programs aimed at enhancing the early detection of atrial fibrillation (AF). Developing and implementing novel community pharmacy services (CPSs) is a complex and acknowledged challenge, which requires comprehensive planning and the participation of relevant stakeholders. Co-design processes are participatory research approaches that can enhance the development, evaluation and implementation of health services. The aim of this study was to co-design a pharmacist-led CPS aimed at enhancing self-monitoring/screening of AF. METHODS A 3-step co-design process was conducted using qualitative methods: (1) interviews and focus group with potential service users (n = 8) to identify key needs and concerns; (2) focus group with a mixed group of stakeholders (n = 8) to generate a preliminary model of the service; and (3) focus group with community pharmacy owners and managers (n = 4) to explore the feasibility and appropriateness of the model. Data were analysed qualitatively to identify themes and intersections between themes. The JeMa2 model to conceptualize pharmacy-based health programs was used to build a theoretical model of the service. RESULTS Stakeholders delineated: a clear target population (i.e., individuals ≥65 years old, with hypertension, with or without previous AF or stroke); the components of the service (i.e., patient education; self-monitoring at home; results evaluation, referral and follow-up); and a set of circumstances that may influence the implementation of the service (e.g., quality of the service, competency of the pharmacist, inter-professional relationships, etc.). A number of strategies were recommended to enable implementation (e.g.,. endorsement by leading cardiovascular organizations, appropriate communication methods and channels between the pharmacy and the general medical practice settings, etc.). CONCLUSION A novel and preliminary model of a CPS aimed at enhancing the management of AF was generated from this participatory process. This model can be used to inform decision making processes aimed at adopting and piloting of the service. It is expected the co-designed service has been adapted to suit existing needs of patients and current care practices, which, in turn, may increase the feasibility and acceptance of the service when it is implemented into a real setting.


title: Report of Positive Placental Swabs for SARS-CoV-2 in an Asymptomatic Pregnant Woman with COVID-19.

text: Currently, limited data on maternal and neonatal outcomes of pregnant women with infection and pneumonia related to SARS coronavirus 2 (SARS-CoV-2) are available. Our report aims to describe a case of placental swabs positive for the molecular research on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2 RNA in an asymptomatic woman with positive rhino-pharyngeal swab for SARS-CoV-2 who underwent an urgent cesarean section in our obstetrics unit. Sample collection, processing, and laboratory testing were conducted in accordance with the World Health Organization (WHO) guidance. In the next months, conclusive data on obstetrical outcomes concerning the gestational age and pregnancy comorbidity as well as the eventual maternal-fetal transmission are needed.


title: Respiratory depression detected by capnography among children in the postanesthesia care unit: a cross-sectional study.

text: BACKGROUND Children are at risk for respiratory depression while recovering from anesthesia. Currently, monitoring children in the postanesthesia care unit (PACU) with pulse oximetry is recommended. However, pulse oximetry does not reliably recognize hypoventilation or apnea, particularly in the presence of supplemental oxygen. Capnography is a sensitive monitor of ventilation that is not often used in the PACU. AIM To determine the frequency of hypoventilation and apnea as detected by capnography among children in the PACU. METHODS In a cross-sectional study, capnography monitoring was applied to healthy children of age 1-17 years in the PACU of a tertiary care hospital. Staff was blinded to the capnography monitor; alarms were disabled. Staff provided routine care and monitoring with pulse oximetry to all patients. Vital signs, patient interventions, and medication administration were recorded by a research assistant every 30 s until all monitoring was discontinued by staff. Outcome measures included frequency of hypoventilation and apnea as measured by capnography and oxygen desaturations as measured by pulse oximetry, as well as staff interventions for these events. RESULTS Data from 194 children were analyzed. Capnography detected hypoventilation or apnea in 45.5% (95% CI 38.5%, 52.5%) of patients. Oxygen desaturations occurred in 19% (95% CI 13%, 24%) of patients. Interventions occurred in 9% (95% CI 5%, 13%) of patients. Patients who received narcotic medications were more likely to experience hypoventilation (OR 2.3, 95% CI 1.02, 5.3) and apnea (OR 2.7, 95% CI 1.1, 7). Hypoventilation was seen more often among children who received supplemental oxygen (OR 3.1, 95% CI 1.1, 12). CONCLUSIONS Hypoventilation and apnea are common among children in the PACU; however, few interventions occur to address these events. Routine monitoring with capnography may improve recognition of respiratory depression and enhance patient safety in the PACU.


Preventing a Parallel Pandemic - A National Strategy to Protect Clinicians' Well-Being.


title: Physically Distant, Educationally Connected: Interactive Conferencing in the Era of COVID-19.

text: During the coronavirus outbreak, physical distancing restrictions led to the cancellation of live, large-group events worldwide. This included weekly educational conferences required of Emergency Medicine (EM) residency programs in the United States. Specifically, the Residency Review Committee in EM under the Accreditation Council for Graduate Medical Education has mandated that there be at least four hours per week of synchronous conference didactics.


Could it be COVID-19? Atypical presentations in a pandemic.


title: Evaluation of a novel cricothyroidotomy introducer in a simulated obese porcine model: a randomised crossover comparison with scalpel cricothyroidotomy.

text: The Difficult Airway Society 2015 guidelines for management of unanticipated difficulties in tracheal intubation in adults have generated much discussion regarding Plan D: emergency front-of-neck access with a scalpel-bougie cricothyroidotomy technique. There is concern that this technique may not provide an adequate pathway for the bougie and subsequently the tracheal tube, especially in obese patients with deeper airway structures. This could lead to the formation of a false passage, trauma and failure. A novel cricothyroidotomy introducer, 8 mm wide and 170 mm long, with a sharp leading edge and guiding channel to pass a bougie into the trachea, has been designed to complement the scalpel cricothyroidotomy technique. A comparison study of the use of this novel introducer with the scalpel technique in a simulated obese porcine laryngeal model demonstrated shorter insertion times (median (IQR [range]) 85 (65-123 [48-224]) s vs. 84 (72-184 [46-377]) s, p = 0.030). All 26 (100%) participants successfully performed cricothyroidotomy in the introducer group, whereas only 24 (92%) participants were successful in the scalpel group. The introducer group required fewer attempts to access the trachea compared with the scalpel group (p = 0.046). False passages occurred eight (31%) times in the introducer group compared with 17 (65%) times in the scalpel group (p = 0.022). There were no statistical differences in tracheal trauma (p = 0.490), ease of use (p = 0.220) and device preference (p = 0.240). This novel cricothyroidotomy introducer has shown promising results in securing the airway in an emergency front-of-neck access situation. With robust training, this introducer could potentially be complementary to the scalpel-bougie cricothyroidotomy technique.


title: The development of a non-contact screening system for rapid medical inspection at a quarantine depot using a laser Doppler blood-flow meter, microwave radar and infrared thermography.

text: In order to conduct fast screening of passengers with infections such as severe acute respiratory syndrome (SARS) or pandemic influenza at a quarantine depot, we developed a non-contact screening system with self-produced program to conduct a human screening within five seconds, via a linear discriminant function from non-contact derived variables, i.e. palmer pulse derived from a laser Doppler blood-flow meter, respiration rate determined by a 10-GHz microwave radar, and facial temperature measured by thermography. The system evaluation was conducted on seven healthy male subjects (23 +/- 1 years). In order to achieve a pseudo-infection condition, the subjects maintained an ergometer exercise load (100 W, 10 minutes). Before (normal condition) and after (pseudo-infection condition) exercise, a significant linear discriminant function (p < 0.001) was determined to distinguish pseudo-infection condition from normal condition (Mahalanobis D-square = 20.3, classification error rate <5%). The proposed system appears promising for future application in fast screening of infection at a quarantine depot.


title: Role of penumbra mechanical thrombectomy device in acute dural sinus thrombosis.

text: BACKGROUND In dural venous sinus thrombosis (DVST), the mortality ranges 5-30%. Deep venous system involvement and septic dural sinus thrombosis have a higher mortality rate. In acute occlusion, collateral flow may not be established, which may result in significant edema and mass effect. Endovascular interventions may be considered as a treatment option in appropriate high-risk patients with DVST. MATERIALS AND METHODS Eight patients with magnetic resonance imaging (MRI)-confirmed dural sinus thrombosis, who did not respond to the conventional standard medical treatment, were subsequently treated with mechanical thrombectomy using the Penumbra System®. In all cases, medical treatment including anticoagulants were continued following the procedure for a minimum period of 1 year. RESULTS Recanalization of the dural sinus thrombosis was achieved in all 8 cases. There were no immediate or late endovascular-related complications. One death occurred due to an unrelated medical event. At 6 months, there was notable improvement in the modified Rankin Score (mRS), with 5/8 (62%) patients achieving mRS of 2 or less. The follow-up ranged between 3 months and 26 months (mean: 14.5 months), and there were no new neurological events during the follow-up period. CONCLUSION Cerebral venous sinus thrombosis is a rare but life-threatening condition that demands timely diagnosis and therapy. In cases of rapidly declining neurological status despite standard therapy with systemic anticoagulation and anti-edema measures, mechanical thrombectomy could be a lifesaving and effective option. In this study, good outcomes were observed in the majority of patients at long-term follow up.


Peruvian Guideline to Care the Mental Health of Health Providers During COVID-19 Pandemic.


Covid-19: trainee healthcare scientists are crucial to surviving the long road ahead.


COVID-19 in Padua, Italy: not just an economic and health issue.


title: Silk fibroin-Pellethane® cardiovascular patches: Effect of silk fibroin concentration on vascular remodeling in rat model.

text: Life-threatening cardiovascular anomalies require surgery for structural repair with cardiovascular patches. The biomaterial patch, derived from Bombyx mori silk fibroin (SF), is used as an alternative material due to its excellent tissue affinity and biocompatibility. However, SF lacks the elastomeric characteristics required for a cardiovascular patch. In order to overcome this shortcoming, we combined the thermoplastic polyurethane, Pellethane® (PU) with SF to develop an elastic biocompatible patch. Therefore, the purpose of this study was to investigate the feasibility of the blended SF/PU patch in a vascular model. Additionally, we focused on the effects of different SF concentrations in the SF/PU patch on its biological and physical properties. Three patches of different compositions (SF, SF7PU3 and SF4PU6) were created using an electrospinning method. Each patch type (n = 18) was implanted into rat abdominal aorta and histopathology was assessed at 1, 3, and 6 months post-implantation. The results showed that with increasing SF content the tensile strength and elasticity decreased. Histological evaluation revealed that inflammation gradually decreased in the SF7PU3 and SF patches throughout the study period. At 6 months post-implantation, the SF7PU3 patch demonstrated progressive remodeling, including significantly higher tissue infiltration, elastogenesis and endothelialization compared with SF4PU6. In conclusion, an increase of SF concentration in the SF/PU patch had effects on vascular remodeling and physical properties. Moreover, our blended patch might be an attractive alternative material that could induce the growth of a neo-artery composed of tissue present in native artery.


Rapid roll out of SARS-CoV-2 antibody testing-a concern.


title: Nursing Students' Spiritual Orientations and Their Attitudes Toward the Principles of Dying with Dignity: A Sample from Turkey.

text: Nurses' attitudes toward spiritual care and death are influenced by their personal belief systems and world-views. The aim of this study is to reveal the attitudes of nursing students toward spiritual orientation and principles of dying with dignity. The study was conducted with the participation of 478 nursing students. As a result of the study, it was found that the average score of the students' spiritual orientation scale was high and the average score of the assessment scale of attitudes toward the principles of dying with dignity was found to be moderate.


title: Lactoferrin-modified poly(ethylene glycol)-grafted BSA nanoparticles as a dual-targeting carrier for treating brain gliomas.

text: In this study, a dual-targeting drug delivery system based on bovine serum albumin nanoparticles (BSA-NPs) modified with both lactoferrin (Lf) and mPEG2000 loading doxorubicin (DOX) was designed, and its blood-brain barrier (BBB) penetration and brain glioma cells targeting properties were explored. BSA-NPs were prepared by a desolvation technique, and mPEG2000 was incorporated onto the surface of BSA-NPs by reacting with the free amino-group of BSA to form mPEG2000-modified BSA-NPs (P2000-NPs). Finally, Lf-modified P2000-NPs (Lf-NPs) was obtained by absorbing Lf onto the surface of P2000-NPs via the positive and negative charges interaction at physiological pH. Three levels of mPEG2000 and Lf-modified NPs were prepared and characterized, respectively. The uptake and potential cytotoxicity of different DOX preparations in vitro by the primary brain capillary endothelial cells (BCECs) and glioma cells (C6) were investigated. The dual-targeting effects were studied on the BBB model in vitro, BCECs/C6 glioma coculture model in vitro, and C6 glioma-bearing rats in vivo, respectively. The results exhibited that, with the increase of the amount of both mPEG2000 and Lf, the particle size of NPs increased and its zeta potential decreased. The in vivo pharmacokinetics study in healthy rats exhibited that P2000-NPs with a high level of mPEG2000 (P2000H-NPs) had longer circulation time in vivo. Compared to other NPs, Lf-NPs with high level of both Lf and mPEG2000 (LfH-NPs) showed the strongest cytotoxicity and the highest effectiveness in the uptake both in BCECs and C6 as well as improved the dual-targeting effects. Body distribution of DOX in different formulations revealed that LfH-NPs could significantly increase the accumulation of DOX in the brain, especially at 2 h postinjection (P < 0.05). In conclusion, Lf-NPs were a prospective dual-targeting drug delivery system for effective targeting therapy of brain gliomas.


Airway issues in anaplastic thyroid carcinoma.


Coronavirus diaries: hello from home.


title: Bat Biology, Genomes, and the Bat1K Project: To Generate Chromosome-Level Genomes for All Living Bat Species.

text: Bats are unique among mammals, possessing some of the rarest mammalian adaptations, including true self-powered flight, laryngeal echolocation, exceptional longevity, unique immunity, contracted genomes, and vocal learning. They provide key ecosystem services, pollinating tropical plants, dispersing seeds, and controlling insect pest populations, thus driving healthy ecosystems. They account for more than 20% of all living mammalian diversity, and their crown-group evolutionary history dates back to the Eocene. Despite their great numbers and diversity, many species are threatened and endangered. Here we announce Bat1K, an initiative to sequence the genomes of all living bat species (n∼1,300) to chromosome-level assembly. The Bat1K genome consortium unites bat biologists (>148 members as of writing), computational scientists, conservation organizations, genome technologists, and any interested individuals committed to a better understanding of the genetic and evolutionary mechanisms that underlie the unique adaptations of bats. Our aim is to catalog the unique genetic diversity present in all living bats to better understand the molecular basis of their unique adaptations; uncover their evolutionary history; link genotype with phenotype; and ultimately better understand, promote, and conserve bats. Here we review the unique adaptations of bats and highlight how chromosome-level genome assemblies can uncover the molecular basis of these traits. We present a novel sequencing and assembly strategy and review the striking societal and scientific benefits that will result from the Bat1K initiative.


title: Comparison of Mesh Fixation Techniques in Elective Laparoscopic Repair of Incisional Hernia-ReliaTack™ v ProTack™ (TACKoMesh) - A double-blind randomised controlled trial.

text: BACKGROUND Minimally invasive incisional hernia repair has been established as a safe and efficient surgical option in most centres worldwide. Laparoscopic technique includes the placement of an intraperitoneal onlay mesh with fixation achieved using spiral tacks or sutures. An additional step is the closure of the fascial defect depending upon its size. Key outcomes in the evaluation of ventral abdominal hernia surgery include postoperative pain, the presence of infection, seroma formation and hernia recurrence. TACKoMESH is a randomised controlled trial that will provide important information on the laparoscopic repair of an incisional hernia; 1) with fascial closure, 2) with an IPOM mesh and 3) comparing the use of an articulating mesh-fixation device that deploys absorbable tacks with a straight-arm mesh-fixation device that deploys non-absorbable tacks. METHODS A prospective, single-centre, double-blinded randomised trial, TACKoMESH, will establish whether the use of absorbable compared to non-absorbable tacks in adult patients undergoing elective incisional hernia repair produces a lower rate of pain both immediately and long-term. Eligible and consenting patients will be randomized to surgery with one of two tack-fixation devices and followed up for a minimum one year. Secondary outcomes to be explored include wound infection, seroma formation, hernia recurrence, length of postoperative hospital stay, reoperation rate, operation time, health related quality of life and time to return to normal daily activity. DISCUSSION With ongoing debate around the best management of incisional hernia, continued trials that will add substance are both necessary and important. Laparoscopic techniques have become established in reducing hospital stay and rates of infection and report improvement in some patient centered outcomes whilst achieving similarly low rates of recurrence as open surgical techniques. The laparoscopic method with tack fixation has developed a reputation for its tendency to cause post-operative pain. Novel additions to technique, such as intraoperative-sutured closure of a fascial defect, and developments in surgical technology, such as the evolution of composite mesh design and mesh-fixation devices, have brought about new considerations for patient and surgeon. This study will evaluate the efficacy of several new technical considerations in the setting of elective laparoscopic incisional hernia repair. TRIAL REGISTRATION Name of registry - ClinicalTrials.gov Registration number: NCT03434301 . Retrospectively registered on 15th February 2018.


title: Destruction of microbial collections in response to select agent and toxin list regulations.

text: In this study we have followed up on anecdotal and hearsay evidence that microbial collections were destroyed in the United States following the imposition of the regulations associated with the Select Agents and Toxins List, to validate or refute that information. Using a questionnaire, we documented 13 episodes of microbial collection destruction involving viral, bacterial, and fungal strains, which we believe is almost certainly an underestimate of the number of collections destroyed. In every case, the motivation for the destruction of the collection was a desire to avoid the perceived burdens of the regulatory environment associated with operating under the Select Agent Regulations. Some institutions that destroyed isolates considered, and in some cases tried, transferring their collections to registered institutions prior to collection destruction but desisted when confronted with transport regulations. Destruction of microbial collections represents a loss of strains and biological diversity available for biomedical research and future mechanistic, forensic, and epidemiologic investigations. Given the rapid evolution of microbial strains, the destruction of archival collections is a potentially irretrievable loss that was an unintended consequence of regulations to protect society against the nefarious use of biological agents. Furthermore, unregistered institutions continue to destroy newly acquired clinical isolates, thus preventing the establishment of new repository collections. We recommend that government agencies develop plans to ensure that microbial collections are preserved when considering future additions to microbial threat lists under which the possession of certain microbes is criminalized.


title: Anti-severe acute respiratory syndrome coronavirus spike antibodies trigger infection of human immune cells via a pH- and cysteine protease-independent FcγR pathway.

text: Public health measures successfully contained outbreaks of the severe acute respiratory syndrome coronavirus (SARS-CoV) infection. However, the precursor of the SARS-CoV remains in its natural bat reservoir, and reemergence of a human-adapted SARS-like coronavirus remains a plausible public health concern. Vaccination is a major strategy for containing resurgence of SARS in humans, and a number of vaccine candidates have been tested in experimental animal models. We previously reported that antibody elicited by a SARS-CoV vaccine candidate based on recombinant full-length Spike-protein trimers potentiated infection of human B cell lines despite eliciting in vivo a neutralizing and protective immune response in rodents. These observations prompted us to investigate the mechanisms underlying antibody-dependent enhancement (ADE) of SARS-CoV infection in vitro. We demonstrate here that anti-Spike immune serum, while inhibiting viral entry in a permissive cell line, potentiated infection of immune cells by SARS-CoV Spike-pseudotyped lentiviral particles, as well as replication-competent SARS coronavirus. Antibody-mediated infection was dependent on Fcγ receptor II but did not use the endosomal/lysosomal pathway utilized by angiotensin I converting enzyme 2 (ACE2), the accepted receptor for SARS-CoV. This suggests that ADE of SARS-CoV utilizes a novel cell entry mechanism into immune cells. Different SARS vaccine candidates elicit sera that differ in their capacity to induce ADE in immune cells despite their comparable potency to neutralize infection in ACE2-bearing cells. Our results suggest a novel mechanism by which SARS-CoV can enter target cells and illustrate the potential pitfalls associated with immunization against it. These findings should prompt further investigations into SARS pathogenesis.


title: Averting epidemics of extensively drug-resistant tuberculosis.

text: Extensively drug-resistant tuberculosis (XDR TB) has been detected in most provinces of South Africa, particularly in the KwaZulu-Natal province where several hundred cases have been reported since 2004. We analyzed the transmission dynamics of XDR TB in the region using mathematical models, and observed that nosocomial transmission clusters of XDR TB may emerge into community-based epidemics under the public health conditions of many South African communities. The effective reproductive number of XDR TB in KwaZulu-Natal may be around 2. Intensified community-based case finding and therapy appears critical to curtailing transmission. In the setting of delayed disease presentation and high system demand, improved diagnostic approaches may need to be employed in community-based programs rather than exclusively at tertiary hospitals. Using branching process mathematics, we observed that early, community-based drug-susceptibility testing and effective XDR therapy could help curtail ongoing transmission and reduce the probability of XDR TB epidemics in neighboring territories.


title: Use of CT angiography and digital subtraction angiography in patients with ruptured cerebral aneurysm: evaluation of a large multihospital data base.

text: BACKGROUND AND PURPOSE Both CT angiography and digital subtraction angiography are used to detect aneurysms in patients with subarachnoid hemorrhage. We examined a large multihospital data base to determine how practice is evolving with regard to the use of CT angiography and DSA in patients with ruptured cerebral aneurysm. MATERIALS AND METHODS The Premier Perspective data base was used to identify hospitalizations of patients treated with clipping or coiling of ruptured cerebral aneurysms from 2006-2011. Billing information was used to determine pretreatment and posttreatment use of DSA and CT angiography during hospitalization. RESULTS A total of 4972 patients (1022 clipping, 3950 coiling) at 116 hospitals were identified. The percentage of patients with SAH who underwent pretreatment CT angiography significantly increased from 20% in 2006 to 44% in 2011 (P < .0001), whereas the percentage of patients who underwent DSA remained unchanged from 96-94% (P = .28). This CT angiography trend was observed in coiling patients (17-42%, P < .0001) and clipping patients (32-54%, P < .0001). There was a significant increase in the percentage of patients who underwent posttreatment imaging from 41% in 2006 to 48% in 2011 (P = .0037). This trend was observed in clipping patients (33-65%, P < .0001) but not coiling patients (43-45%, P = .62). CONCLUSIONS For the pretreatment evaluation of ruptured aneurysms, the use of CT angiography increased from 2006-2011 without a corresponding decrease in the use of DSA. These results raise the question of potential redundancy without added clinical value of the second test.


title: Novel pH1N1 viral cardiomyopathy requiring veno-venous extracorporeal membrane oxygenation.

text: OBJECTIVE To report a case of pH1N1 viral infection presenting as heart failure requiring mechanical extracorporeal life support. DESIGN Case report. SETTING Pediatric intensive care unit at a regional children's hospital. PATIENT Obese 15-yr-old boy who presented with pH1N1-related cardiomyopathy and respiratory failure that required extracorporeal membrane oxygenation. INTERVENTIONS Extracorporeal membrane oxygenation, echocardiography, high-frequency oscillating ventilation. MEASUREMENTS AND MAIN RESULTS Discovery of severe dilated cardiomyopathy and respiratory failure. CONCLUSIONS Patients with pH1N1 may present in profound heart failure in addition to respiratory failure. Extracorporeal membrane oxygenation may play an important role in managing these complex patients.


Letter to the Editor: Addressing test security issues pertaining to reuse of closed-book summative assessment items possibly compromised during the COVID-19 pandemic.


title: Multiple Barriers to the Evolution of Alternative Gene Orders in a Positive-Strand RNA Virus.

text: The order in which genes are organized within a genome is generally not conserved between distantly related species. However, within virus orders and families, strong conservation of gene order is observed. The factors that constrain or promote gene-order diversity are largely unknown, although the regulation of gene expression is one important constraint for viruses. Here we investigate why gene order is conserved for a positive-strand RNA virus encoding a single polyprotein in the context of its authentic multicellular host. Initially, we identified the most plausible trajectory by which alternative gene orders could evolve. Subsequently, we studied the accessibility of key steps along this evolutionary trajectory by constructing two virus intermediates: (1) duplication of a gene followed by (2) loss of the ancestral gene. We identified five barriers to the evolution of alternative gene orders. First, the number of viable positions for reordering is limited. Second, the within-host fitness of viruses with gene duplications is low compared to the wild-type virus. Third, after duplication, the ancestral gene copy is always maintained and never the duplicated one. Fourth, viruses with an alternative gene order have even lower fitness than viruses with gene duplications. Fifth, after more than half a year of evolution in isolation, viruses with an alternative gene order are still vastly inferior to the wild-type virus. Our results show that all steps along plausible evolutionary trajectories to alternative gene orders are highly unlikely. Hence, the inaccessibility of these trajectories probably contributes to the conservation of gene order in present-day viruses.