title: A prospective study of preoperative computed tomographic angiography for head and neck reconstruction with anterolateral thigh flaps.

text: BACKGROUND During anterolateral thigh flap harvest, inadequate perforators may necessitate modification of the flap design, exploration of the contralateral thigh, or additional flap harvest. Computed tomographic angiography may facilitate perforator mapping and optimize flap design. The authors performed this pilot study to determine the predictive power of computed tomographic angiography in anterolateral thigh flap planning and execution. METHODS : Sixteen consecutive computed tomographic angiography-mapped anterolateral thigh flaps for head and neck reconstruction were studied. Perforator location, origin, caliber, and course were compared between computed tomographic angiography and intraoperative findings. The relationship of patient characteristics, imaging studies, and intraoperative factors to flap design and surgical outcomes was analyzed. RESULTS : Among the 16 anterolateral thigh flaps, 40 of 54 perforators identified intraoperatively were visible on computed tomographic angiography, resulting in 74 percent sensitivity. Intraoperative perforator location averaged 0.35 cm from the computed tomographic angiography-predicted location. The overall ability of computed tomographic angiography to predict perforator size was 67.5 percent. Its overall accuracy in predicting whether a perforator took a septocutaneous or intramuscular course before perforating the deep fascia was 77.5 percent. Preoperative angiography resulted in surgeons modifying the operative plan in 37 percent of cases and 57 percent of double-island flap cases. All flaps were elevated successfully and survived. CONCLUSIONS : Computed tomographic angiography identified larger perforators better than smaller ones and proximal perforators better than distal ones. It accurately predicted the location and origin of visible perforators and less accurately predicted the size and course of visible perforators. Most importantly, the information it provided influenced surgeons to modify their reconstructive strategy, resulting in a higher level of recipient-site specificity.


title: COVID-19 pandemic and uro-oncology follow-up: A "virtual" multidisciplinary team strategy and patients' satisfaction assessment.

text: COVID-19 pandemic strongly modified the organizations of our clinical practice. Strict containment measures have been adopted to limit the disease diffusion. In particular, hospital face-to-face post discharge and follow up visits have been reduced. Although cancelling or deferring appointments seems to be a pragmatic approach, this solution may have a devasting long-term impact on health medical care and on patients. In this context, telemedicine and remote consultations may have the potential to provide healthcare minimizing virus exposure. In this paper we describe how Multidisciplinary team (MDT) reorganized genitourinary cancer care delivery at our Institute (AO SS Antonio e Biagio e Cesare Arrigo, Alessandria), taking advantage of telematic means. Furthermore, we present our preliminary results regarding patients' satisfaction.


Infusion pumps: constantly evolving.


title: Stent Retriever Thrombectomy in Different Thrombus Locations of Anterior Cerebral Circulation.

text: BACKGROUND Mechanical thrombectomy (MT) is a safe and efficient treatment for acute ischemic stroke in patients with proximal anterior occlusion and large penumbra. We evaluated the technical and clinical success of MT in relation to the location of the occlusion (internal carotid artery, M1 and M2 segments of the middle cerebral artery). METHODS We prospectively reviewed 130 patients of whom 105 met the inclusion criteria. Baseline clinical, procedural and imaging variables, technical outcome (TICI, thrombolysis in cerebral infarction), 24 h imaging outcome and three-month clinical outcome (mRS, modified Rankin Scale) were recorded. Differences between the groups were studied with statistical tests according to the type of the variable. RESULTS There were 37, 46 and 22 patients in the internal carotid artery (ICA), M1 and M2 groups, respectively. TICI 2b or 3 was achieved in 92 cases (88 %) with a non-significant trend towards a better recanalization outcome in the ICA and M1 groups. Overall, 57 of the 105 patients (55 %) experienced favorable clinical outcome (mRS ≤ 2) with no significant differences between the groups. Excellent outcome (mRS ≤ 1) was seen in 40 patients (39 %) and there proportionally more patients with excellent outcome in the ICA and M1 groups (ICA: 44 %, M1: 41 %, M2: 23 % of patients, p = 0.22). CONCLUSIONS There were no statistically significant differences in the technical or clinical outcomes between the different sites of occlusion (ICA, M1 or M2). There was a non-significant trend towards achieving excellent clinical outcome (3-month mRS ≤ 1) more often and better recanalization results in the two more proximal locations.


Too much guidance.


title: Flow dynamics and characterization of a cough.

text: UNLABELLED Airborne disease transmission has always been a topic of wide interests in various fields for decades. Cough is found to be one of the prime sources of airborne diseases as it has high velocity and large quantity of droplets. To understand and characterize the flow dynamics of a cough can help to control the airborne disease transmission. This study has measured flow dynamics of coughs with human subjects. The flow rate variation of a cough with time can be represented as a combination of gamma-probability-distribution functions. The variables needed to define the gamma-probability-distribution functions can be represented by some medical parameters. A robust multiple linear regression analysis indicated that these medical parameters can be obtained from the physiological details of a person. However, the jet direction and mouth opening area during a cough seemed not related to the physiological parameters of the human subjects. Combining the flow characteristics reported in this study with appropriate virus and droplet distribution information, the infectious source strength by coughing can be evaluated. PRACTICAL IMPLICATIONS There is a clear need for the scientific community to accurately predict and control the transmission of airborne diseases. Transportation of airborne viruses is often predicted using Computational Fluid Dynamics (CFD) simulations. CFD simulations are inexpensive but need accurate source boundary conditions for the precise prediction of disease transmission. Cough is found to be the prime source for generating infectious viruses. The present study was designed to develop an accurate source model to define thermo-fluid boundary conditions for a cough. The model can aid in accurately predicting the disease transmission in various indoor environments, such as aircraft cabins, office spaces and hospitals.


Free tissue transfer in the obese patient: an outcome and cost analysis in 1258 consecutive abdominally based reconstructions.


Possible consequences of the COVID-19 pandemic on the use of biospecimens from cancer biobanks for research in academia and bioindustry.


Behind This Face Shield, I See You.


title: Vaginal cuff dehiscence after robotic total laparoscopic hysterectomy.

text: BACKGROUND Vaginal cuff dehiscence with small bowel evisceration after hysterectomy is a rare event that may be occurring more frequently with the advent of robotic laparoscopic hysterectomies. CASES Two women underwent robotic total laparoscopic hysterectomy for menorrhagia and stage I endocervical adenocarcinoma, respectively. Each presented 7-8 weeks postoperatively with abdominal pain and vaginal pressure after intercourse. The small bowel protruded into the vagina through the dehisced vaginal cuff. Both cuffs were repaired vaginally with delayed absorbable suture. One repair required revision 7 weeks after the initial repair. CONCLUSION Robotic total laparoscopic hysterectomy may be associated with increased risk of vaginal cuff dehiscence and small bowel evisceration. This observation may be because of thermal spread and cuff tissue damage from electrosurgery used for colpotomy.


title: Robotic and laparoscopic high extended pelvic lymph node dissection during radical cystectomy: technique and outcomes.

text: BACKGROUND With the increasing use of laparoscopic and robotic radical cystectomy (RC), there are perceived concerns about the adequacy of lymph node dissection (LND). OBJECTIVE Describe the robotic and laparoscopic technique and the short-term outcomes of high extended pelvic LND (PLND) up to the inferior mesenteric artery (IMA) during RC. DESIGN, SETTING, AND PARTICIPANTS From January 2007 through September 2009, we performed high extended PLND with proximal extent up to the IMA (n=10) or aortic bifurcation (n=5) in 15 patients undergoing robotic RC (n=4) or laparoscopic RC (n=11) at two institutions. SURGICAL PROCEDURE We performed robotic extended PLND with the proximal extent up to the IMA or aortic bifurcation. The LND was performed starting from the right external iliac, obturator, internal iliac, common iliac, preaortic and para-aortic, precaval, and presacral and then proceeding to the left side. The accompanying video highlights our detailed technique. MEASUREMENTS Median age was 69 yr, body mass index was 26, and American Society of Anesthesiologists class ≥ 3 was present in 40% of patients. All urinary diversions, including orthotopic neobladder (n=5) and ileal conduit (n=10), were performed extracorporeally. RESULTS AND LIMITATIONS All 15 procedures were technically successful without need for conversion to open surgery. Median operative time was 6.7h, estimated blood loss was 500 ml, and three patients (21%) required blood transfusion. Median nodal yield in the entire cohort was 31 (range: 15-78). The IMA group had more nodes retrieved (median: 42.5) compared with the aortic bifurcation group (median: 20.5). Histopathology confirmed nodal metastases in four patients (27%), including three patients in the IMA group and one patient in the aortic bifurcation group. Perioperative complications were recorded in six cases (40%). During a median follow-up of 13 mo, no patient developed local or systemic recurrence. Limitations of the study include its retrospective design and small cohort of patients. CONCLUSIONS High extended PLND during laparoscopic or robotic RC is technically feasible. Longer survival data in a larger cohort of patients are necessary to determine the proper place for robotic and laparoscopic surgery in patients undergoing RC for high-risk bladder cancer.


Should neutering be classed as essential?


title: The nucleocapsid protein of severe acute respiratory syndrome coronavirus inhibits cell cytokinesis and proliferation by interacting with translation elongation factor 1alpha.

text: Severe acute respiratory syndrome coronavirus (SARS-CoV) is the etiological agent of SARS, an emerging disease characterized by atypical pneumonia. Using a yeast two-hybrid screen with the nucleocapsid (N) protein of SARS-CoV as a bait, the C terminus (amino acids 251 to 422) of the N protein was found to interact with human elongation factor 1-alpha (EF1alpha), an essential component of the translational machinery with an important role in cytokinesis, promoting the bundling of filamentous actin (F-actin). In vitro and in vivo interaction was then confirmed by immuno-coprecipitation, far-Western blotting, and surface plasmon resonance. It was demonstrated that the N protein of SARS-CoV induces aggregation of EF1alpha, inhibiting protein translation and cytokinesis by blocking F-actin bundling. Proliferation of human peripheral blood lymphocytes and other human cell lines was significantly inhibited by the infection of recombinant retrovirus expressing SARS-CoV N protein.


title: Searching for primaries in patients with neuroendocrine tumors (NET) of unknown primary and clinically suspected NET: Evaluation of Ga-68 DOTATOC PET/CT and In-111 DTPA octreotide SPECT/CT.

text: BACKGROUND To evaluate the clinical efficacy of In-111 DTPA octreotide SPECT/CT and Ga-68 DOTATOC PET/CT for detection of primary tumors in patients with either neuroendocrine tumor of unknown primary (NETUP) or clinically suspected primary NET (SNET). PATIENTS AND METHODS A total of 123 patients were included from 2006 to 2009, 52 received Ga-68 DOTATOC PET/CT (NETUP, 33; SNET, 19) and 71 underwent In-111 DTPA octreotide SPECT/CT (50; 21). The standard of reference included histopathology or clinical verification based on follow-up examinations. RESULTS In the NETUP group Ga-68 DOTATOC detected primaries in 15 patients (45.5%) and In-111 DTPA octreotide in 4 patients (8%) (p < 0.001); in the SNET group, only 2 primaries could be detected, all by Ga-68 DOTATOC. In patients with NETUP, primary tumors could be found significantly more often than in patients with SNET (p = 0.01). Out of these 21 patients 14 patients were operated. CONCLUSION Ga-68 DOTATOC PET/CT is preferable to In-111 DTPA octreotide SPECT/CT when searching for primary NETs in patients with NETUP but should be used with caution in patients with SNET.


title: Myd88 Initiates Early Innate Immune Responses and Promotes CD4 T Cells during Coronavirus Encephalomyelitis.

text: UNLABELLED Myd88 signaling is critical to the control of numerous central nervous system (CNS) infections by promoting both innate and adaptive immune responses. Nevertheless, the extent to which Myd88 regulates type I interferon (IFN) versus proinflammatory factors and T cell function, as well as the anatomical site of action, varies extensively with the pathogen. CNS infection by neurotropic coronavirus with replication confined to the brain and spinal cord induces protective IFN-α/β via Myd88-independent activation of melanoma differentiation-associated gene 5 (MDA5). However, a contribution of Myd88-dependent signals to CNS pathogenesis has not been assessed. Infected Myd88(-/-) mice failed to control virus, exhibited enhanced clinical disease coincident with increased demyelination, and succumbed to infection within 3 weeks. The induction of IFN-α/β, as well as of proinflammatory cytokines and chemokines, was impaired early during infection. However, defects in both IFN-α/β and select proinflammatory factors were rapidly overcome prior to T cell recruitment. Myd88 deficiency also specifically blunted myeloid and CD4 T cell recruitment into the CNS without affecting CD8 T cells. Moreover, CD4 T cells but not CD8 T cells were impaired in IFN-γ production. Ineffective virus control indeed correlated most prominently with reduced antiviral IFN-γ in the CNS of Myd88(-/-) mice. The results demonstrate a crucial role for Myd88 both in early induction of innate immune responses during coronavirus-induced encephalomyelitis and in specifically promoting protective CD4 T cell activation. In the absence of these responses, functional CD8 T cells are insufficient to control viral spread within the CNS, resulting in severe demyelination. IMPORTANCE During central nervous system (CNS) infections, signaling through the adaptor protein Myd88 promotes both innate and adaptive immune responses. The extent to which Myd88 regulates antiviral type I IFN, proinflammatory factors, adaptive immunity, and pathology is pathogen dependent. These results reveal that Myd88 protects from lethal neurotropic coronavirus-induced encephalomyelitis by accelerating but not enhancing the induction of IFN-α/β, as well as by promoting peripheral activation and CNS accumulation of virus-specific CD4 T cells secreting IFN-γ. By controlling both early innate immune responses and CD4 T cell-mediated antiviral IFN-γ, Myd88 signaling limits the initial viral dissemination and is vital for T cell-mediated control of viral loads. Uncontrolled viral replication in the absence of Myd88 leads to severe demyelination and pathology despite overall reduced inflammatory responses. These data support a vital role of Myd88 signaling in protective antimicrobial functions in the CNS by promoting proinflammatory mediators and T cell-mediated IFN-γ production.


title: Acute stroke and obstruction of the extracranial carotid artery combined with intracranial tandem occlusion: results of interventional revascularization.

text: PURPOSE Due to high thrombus load, acute stroke patients with tandem obstructions of the extra- and intracranial carotid arteries or the middle cerebral artery show a very limited response to systemic thrombolysis. Interventional treatment with mechanical thrombectomy-often in combination with acute stenting of underlying atherosclerotic stenosis or dissection-is increasingly used. It has been shown that such complex interventions are technically feasible. The lack of optimal management strategies and clinical data encouraged us to review our acute stroke interventions in patient with anterior circulation tandem lesions to determine lesion patterns, interventional approaches, and angiographic or clinical outcomes. PATIENTS AND METHODS We retrospectively analyzed a series of 39 consecutive patients with intracranial vessel occlusion of the anterior circulation simultaneously presenting with high-grade cervical internal carotid artery (ICA) stenosis or occlusion. RESULTS Emergency ICA stent implantation was technically feasible in all patients, and intracranial recanalization with TICI ≥ 2b was reached in a large number of patients (64 %). Good clinical outcomes (mRS ≤ 2 at 3 months) were achieved in one third of the patients (36 %). Symptomatic hemorrhages occurred in four patients (10 %). Mortality was 10 %. CONCLUSION Endovascular recanalization of acute cervical carotid artery occlusion was technically feasible in all patients, and resulted in high extra- and intracranial revascularization rates. A trend for favorable clinical outcome was seen in a higher TICI score, younger age, good collateral status, and combined IV rTPA and endovascular therapy.


title: The impact of stigma on somatic treatment and care for people with comorbid mental and somatic disorders.

text: PURPOSE OF REVIEW The problems associated with high rates of medical comorbidities among people with mental disorders have multidimensional consequences, including the challenge of their management. The stigma on the treatment of these complex situations is the focus of this review. The time span and context of the review are set to cover the period from 2006 to the present; the review includes related themes of stigma. RECENT FINDINGS The stigma attached to the management of somatic illnesses of patients with mental disorders is considered as a more recent issue of concern. Few relevant studies could be found. Medical comorbidities among people with mental disorders along with the treatment gap constitute a public-health problem. SUMMARY The stigma attached to mental disorders in general forms the basis of the stigma towards the physical health problems of these patient groups. The impact of stigma on somatic treatment and care for people with comorbid mental and somatic disorders is discussed in its context as a public-health problem. Integrative services, and optimism and hope in health professionals are essential factors in reducing such stigma, and hence in enhancing better healthcare.


title: Risk factors for early mortality following modern total hip arthroplasty.

text: The aim of this study was to evaluate the incidence of early mortality and identify risk factors for early death following modern uncemented THA. Between 2000 and 2006, we identified patients who died within 90days of THA. Demographics, comorbidities, laboratory studies, and complications were analyzed as risk factors for mortality. 38 of 8261 patients undergoing THA (0.46%) died within 90days postoperatively. Of these, 26% were due to myocardial infarction. Multivariate analysis revealed Charlson index >3, peripheral vascular disease, elevated postoperative glucose, and abnormal postoperative cardiac studies as independent predictors of early mortality following THA. Caution should be taken in patients with increased comorbidities, PVD, perioperative hyperglycemia, and impaired renal function in order to reduce mortality following THA.


title: Osteoarthritis guidelines: a progressive role for topical nonsteroidal anti-inflammatory drugs.

text: Current treatment guidelines for the treatment of chronic pain associated with osteoarthritis reflect the collective clinical knowledge of international experts in weighing the benefits of pharmacologic therapy options while striving to minimize the negative effects associated with them. Consideration of disease progression, pattern of flares, level of functional impairment or disability, response to treatment, coexisting conditions such as cardiovascular disease or gastrointestinal disorders, and concomitant prescription medication use should be considered when creating a therapeutic plan for a patient with osteoarthritis. Although topical nonsteroidal anti-inflammatory drugs historically have not been prevalent in many of the guidelines for osteoarthritis treatment, recent evidence-based medicine and new guidelines now support their use as a viable option for the clinician seeking alternatives to typical oral formulations. This article provides a qualitative review of these treatment guidelines and the emerging role of topical nonsteroidal anti-inflammatory drugs as a therapy option for patients with localized symptoms of osteoarthritis who may be at risk for oral nonsteroidal anti-inflammatory drug-related serious adverse events.


title: How we do it: repair of large perineal hernia after abdominoperineal resection.

text: BACKGROUND Symptomatic perineal hernia is a rare complication after abdominoperineal resection (APR). Management of these hernias is challenging. The recurrence rate after surgical repair is high because of the difficulty of prosthetic material fixation; there is no consensus regarding the best method of repair. METHODS We introduced a novel combined laparoscopic-perineal dual fixation technique in the repair of perineal hernias after APR. This technique begins with a perineal approach under laparoscopic vision. After excision of the hernia sac, the mesh is introduced and fixed anteriorly to the urogenital diaphragm and laterally to the sacrotuberous ligament and the surrounding scar tissue. The perineal incision is then closed. Next, the mesh is fixed to the sacrum with ProTack® and is fixed again to the sacrotuberous ligament via a laparoscopic approach. RESULTS The dual fixation repair method is successful and without difficulties, with no recurrence at 13-month follow-up. CONCLUSION Our laparoscopic-perineal dual fixation method is a good alternative method for large perineal hernia repair after APR.


title: Antethoracic pedicled jejunum reconstruction with the supercharge technique for esophageal cancer.

text: BACKGROUND Gastric tube is the first choice as an esophageal substitute for reconstruction after esophagectomy. Colon or jejunum is selected for patients in whom stomach cannot be used. Colon interposition is reported to have a high incidence of anastomotic leakage and mortality. For safer surgical treatment, the authors adopted supercharged pedicle jejunum reconstruction as the operation of choice in patients with esophageal cancer who had no stomach to use as an esophageal substitute. The aim of this study was to review our experience with this technique. METHODS From 2003 to 2009, esophagectomy and antethoracic pedicled jejunum reconstruction with the supercharge technique was performed in 27 patients with esophageal cancer at the Department of Gastroenterological Surgery (Surgery II), Nagoya University Hospital. Medical records of these 27 patients were retrospectively reviewed to determine demographic data, diagnosis, functional results, and perioperative course. RESULTS Median operating time, blood loss, hospital stay, and duration of enteral feeding were 636 min (range 454-856 min), 580 ml (range 208-1959 ml), 27 days (range 16-72 days), and 80 days (range 26-1740 days), respectively. There were no in-hospital deaths. Anastomotic leakage occurred in two patients and was successfully managed conservatively. In 2 of 27 patients, the pedicled jejunum was of insufficient length, and additional procedures were needed to complete the anastomosis. CONCLUSIONS Although antethoracic pedicled jejunum reconstruction with the supercharge technique is technically demanding, it is a reliable technique and contributes to successful reconstruction after esophagectomy for patients in whom stomach is not available for reconstruction.


title: Vaccines and Therapies in Development for SARS-CoV-2 Infections.

text: The current COVID-19 pandemic is caused by the novel coronavirus SARS-CoV-2. The virus causes severe respiratory symptoms which manifest disproportionately in the elderly. Currently, there are over 6.5 million cases and 380,000 deaths reported. Given the current severity of the outbreak, there is a great need for antiviral therapies and vaccines to treat and prevent COVID-19. In this review, we provide an overview of SARS-CoV-2 and discuss the emerging therapies and vaccines that show promise in combating COVID-19. We also highlight potential viral targets that could be exploited by researchers and drug manufacturers.


title: Development and evaluation of a novel multiplex PCR technology for molecular differential detection of bacterial respiratory disease pathogens.

text: The ResPlex I assay (Qiagen) was designed to amplify and detect DNA of six bacterial respiratory pathogens. This assay was compared with real-time PCR assays based upon the same target sequences for the ability detect the target bacteria by use of both stock strains and specimens from respiratory disease patients. The ResPlex I assay is somewhat less sensitive than real-time PCR assays but offers the advantage of multiple assays in a single reaction.


title: Safety and feasibility of a novel non-thermal device for tissue dissection: A preliminary study of the DD1 differential dissector.

text: Energy devices can cause significant thermal damage to surrounding tissues causing unanticipated organ trauma. To evaluate the safety and feasibility of a novel electric device (DD1) for soft tissue dissection. Three series of measurements were performed in a pig model. First, macro- and microscopic tissue damage was compared between the DD1 and an electric scalpel (ES). Second, the time course of tissue temperature was measured for the DD1 and three other energy devices (ES, Harmonic and LigaSure). Third, the time required for mobilization of a peripheral artery of the intestine was compared between the DD1 and manual, non-energized forceps. First, the tissue damage area caused by ES was significantly larger compared to that in the DD1 at all time points (p < 0.0001). The number of damaged cells due to thermal damage was significantly larger for ES than for DD1, even when the DD1 was applied to a single point at maximum power for 60 sec (p < 0.0001). Second, the maximum temperature of Harmonic was 160°C 3 sec after use and dropped to 68°C after 10 sec. At the same time points after use, we observed: ES (84°C, 45°C), LigaSure (61°C, 49°C), and DD1 (30.5°C, 29°C). Third, the median dissection time for the artery using DD1 was significantly shorter than that for dissecting forceps (DD1: 100 sec, range 70-205 sec vs. forceps: 130 sec, range 90-210 sec, p = 0.0325). DD1 was a safe non-thermal device which causes less tissue damage while also providing shorter dissection times than manual dissection.


Covid-19: The doctors turned YouTubers.


title: Internal Carotid Artery Dissection in Brazilian Jiu-Jitsu.

text: Carotid artery dissection is a significant cause of stroke in young patients. It may be asymptomatic and go undiagnosed, or minimal transient manifestations may follow, commanding a higher index of suspicion than ordinarily exists to avoid misdiagnosis. Reported herein is a 27-year-old man who suffered extracranial internal carotid artery dissection while practicing a Brazilian Jiu-Jitsu submission maneuver. The patient's condition suddenly deteriorated one week later due to distal embolization and stroke. Despite endovascular treatment, with stenting of the cervical carotid artery, neurologic deficits remained. Of note, the objective in martial arts, which is to kill or incapacitate, has yet to be fully tempered in transitioning to sport. Brazilian Jiu-jitsu, a relatively new and fast-growing form of martial art, places emphasis on submission maneuvers. Related injuries are not common knowledge and are poorly described in the literature. This account is intended to shed light on the risk of this discipline. Through education and improved supervision, vascular injuries of this nature and the potentially lethal or disabling consequences may thus be prevented in young athletes.


title: Bio-electrical impedance analysis for perioperative fluid evaluation in open major abdominal surgery.

text: Water retention and intercompartmental redistribution occur frequently in association with adverse postoperative outcomes, yet the available strategies for non-invasive assessment are limited. One such approach for evaluating body water composition in various circumstances is bio-electrical impedance analysis (BIA). This study aims to appraise the usefulness of the Body Composition Monitor (BCM, Fresenius Medical Care, Germany) in assessing body fluid composition and intercompartmental shifts before and after open major abdominal surgery. This prospective, clinician blinded observational study enrolled all the patients scheduled consecutively for elective major open abdominal surgery during a 1-year period starting from January 1st, 2016. BIA parameters-total body water (TBW), extracellular water (ECW), intracellular water (ICW), absolute fluid overload (AFO), and relative fluid overload (RFO) were measured before and after surgery. The results were compared with fluid balance and outcome parameters such as organ dysfunction, ICU-and hospital length of stay (-LOS). The study population included 71 patients aged 60.2 ± 12 of whom 60.6% men and with a BMI of 26.3 ± 5.1 kg/m2. Postoperative acute kidney injury, respiratory dysfunction, and infections occurred in 14.0%, 19.7% and 28.1% of cases, respectively. The median LOS in ICU was 20 h and the hospital-LOS was 10 days. Positive intraoperative fluid balance (2.4 ± 1.0 L) resulted in a significant increase of TBW (1.4 ± 2.4 L) and of ECW (1.4 ± 1.2 L). Intraoperative fluid balance significantly correlated with TBW change (r = 0.23, p = 0.04) and with AFO change (r = 0.31, p < 0.01). A significant correlation was found between pre- and postoperative AFO and RFO on one hand, and ICU-LOS on the other. BIA may be a useful tool for the perioperative assessment of volume status.


title: Quantitative proteomics analysis reveals BAG3 as a potential target to suppress severe acute respiratory syndrome coronavirus replication.

text: The discovery of a novel coronavirus (CoV) as the causative agent of severe acute respiratory syndrome (SARS) has highlighted the need for a better understanding of CoV replication. The replication of SARS-CoV is highly dependent on host cell factors. However, relatively little is known about the cellular proteome changes that occur during SARS-CoV replication. Recently, we developed a cell line expressing a SARS-CoV subgenomic replicon and used it to screen inhibitors of SARS-CoV replication. To identify host proteins important for SARS-CoV RNA replication, the protein profiles of the SARS-CoV replicon cells and parental BHK21 cells were compared using a quantitative proteomic strategy termed "stable-isotope labeling by amino acids in cell culture-mass spectrometry" (SILAC-MS). Our results revealed that, among the 1,081 host proteins quantified in both forward and reverse SILAC measurements, 74 had significantly altered levels of expression. Of these, significantly upregulated BCL2-associated athanogene 3 (BAG3) was selected for further functional studies. BAG3 is involved in a wide variety of cellular processes, including cell survival, cellular stress response, proliferation, migration, and apoptosis. Our results show that inhibition of BAG3 expression by RNA interference led to significant suppression of SARS-CoV replication, suggesting the possibility that upregulation of BAG3 may be part of the machinery that SARS-CoV relies on for replication. By correlating the proteomic data with these functional studies, the findings of this study provide important information for understanding SARS-CoV replication.


title: Systematic review of definitions and outcome measures for return of bowel function after gastrointestinal surgery.

text: Background Ileus is common after gastrointestinal surgery and has been identified as a research priority. Several issues have limited previous research, including a widely accepted definition and agreed outcome measure. This review is the first stage in the development of a core outcome set for the return of bowel function after gastrointestinal surgery. It aims to characterize the extent of variation in current outcome reporting. Methods A systematic search of MEDLINE, Embase, CINAHL (Cumulative Index to Nursing and Allied Health Literature) and the Cochrane Library was performed for 1990-2017. RCTs of adults undergoing gastrointestinal surgery, including at least one reported measure relating to return of bowel function, were eligible. Trial registries were searched across the same period for ongoing and completed (but not published) RCTs. Definitions of ileus and outcome measures describing the return of bowel function were extracted. Results Of 5670 manuscripts screened, 215 (reporting 217 RCTs) were eligible. Most RCTs involved patients undergoing colorectal surgery (161 of 217, 74·2 per cent). A total of 784 outcomes were identified across all published RCTs, comprising 73 measures (clinical: 63, 86 per cent; radiological: 6, 8 per cent; physiological: 4, 5 per cent). The most commonly reported outcome measure was 'time to first passage of flatus' (140 of 217, 64·5 per cent). The outcomes 'ileus' and 'prolonged ileus' were defined infrequently and variably. Conclusion Outcome reporting for the return of bowel function after gastrointestinal surgery is variable and not fit for purpose. An agreed core outcome set will improve the consistency, reliability and clinical value of future studies.


title: Systemic inflammatory response after hernia repair: a systematic review.

text: PURPOSE All surgical procedures elicit a complex systemic inflammatory response effectuated and modulated by cytokines. The purpose of this systematic review was to present an overview of the inflammatory response and the serum markers associated with hernia repair and to compare the response between patients treated with and without mesh. METHODS The review was conducted in line with PRISMA guidelines. The outcomes of interest were serum concentration of leukocytes, cytokines, and acute phase proteins before and after hernia repair with or without mesh reinforcement. The risk of bias was assessed using the Cochrane ROBINS-I tool for non-randomized studies of intervention. RESULTS A total of 31 studies were included in the systematic review including 1326 patients with a mean age ranging from 33 to 67 years. The studies predominantly included males (95.0% males, 5.0% female) with inguinal hernias (98.5% inguinal hernias, 1.5% incisional hernias). The inflammatory response after hernia repair was characterized by an increase in CRP, IL-6, leukocytes, neutrophils, IL-1, IL-10, fibrinogen, and α1-antitrypsin and a decrease in lymphocytes and albumin within the first 24 postoperative hours. The systemic inflammatory response was normalized before or on the seventh postoperative day. A higher CRP and IL-6 serum concentration was found in patients treated with mesh compared with sutured repairs. CONCLUSIONS Hernia repair elicits a systemic inflammatory response characterized by an increase in CRP, IL-6, leukocytes, neutrophils, IL-1, IL-10, fibrinogen, and α1-antitrypsin and a decrease in lymphocytes and albumin. A higher inflammatory response was found after mesh repair compared with non-mesh repair and after open mesh repair compared with laparoscopic mesh repair.


title: Supine Versus Standing Radiographs for Detecting Ischiofemoral Impingement: A Propensity Score-Matched Analysis.

text: OBJECTIVE The purpose of this study was to assess parameters of ischiofemoral impingement on supine and standing anteroposterior hip radiographs and to suggest optimal cutoff points for detection of ischiofemoral impingement. MATERIALS AND METHODS A retrospective study included patients with a clinical history of hip pain. All hip joints with evidence of quadratus femoris muscle edema on MR images were included in the ischiofemoral impingement patient group. An age- and sex-matched control group was derived from the same cohort by propensity score matching. On radiographs, two readers independently measured the following parameters: ischiofemoral space, quadratus femoris space, hamstring tendon area, ischiofemoral distance on supine radiograph, ischiofemoral distance on standing radiograph, and femoral neck-shaft angle. Group differences in parameters were assessed by Mann-Whitney U test. The intraclass correlation coefficient and the ROC AUC were obtained. Correlations between radiographic and MRI measures were assessed with Pearson correlation and Bland-Altman plot analyses. The Youden J index was used to select optimum cutoff points for each parameter. RESULTS There were 30 patients (44 hip joints; mean age, 54.8 ± 11 years) in the ischiofemoral impingement group and 88 patients (88 hip joints; mean age, 51.8 ± 13.4 years) in the control group. There were significant group differences in ischiofemoral space, quadratus femoris space, ischiofemoral distance on supine radiograph, ischiofemoral distance on standing radiograph, and neck-shaft angle (p < 0.05). Ischiofemoral distance on supine and standing radiographs exhibited good discriminative ability (AUC > 0.80). The optimal cutoff points for ischiofemoral distances on supine and standing radiographs were 19.9 and 19.1 mm for reader 1 and 21.1 and 17.0 mm for reader 2. Ischiofemoral space, quadratus femoris space, ischiofemoral distance on supine radiograph, and ischiofemoral distance on standing radiograph exhibited nearly perfect interobserver agreement (r > 0.8). CONCLUSION Ischiofemoral distances on supine and standing hip radiographs had good diagnostic performance and can be used as a screening tool, with optimal cutoff points.


title: Comparison of SLA® or SLActive® implants placed in the maxillary sinus with or without synthetic bone graft materials--an animal study in sheep.

text: AIMS To assess the influence of an activated implant surface and a synthetic graft material in the maxillary sinus in combination with sinus floor elevation on bone-to-implant contact (BIC) as compared to implants with conventional surfaces. MATERIAL AND METHODS In 16 sheep, sinus bone augmentation was performed using a synthetic bone graft material according to the methods described by Haas et al (Clinical Oral Implants Research, 9, 1998, 107; Clinical Oral Implants Research, 13, 2002, 396). Another 16 sheep received a sinus floor elevation procedure without graft material. Using a paired design, in one sinus of each animal, a conventional implant was placed, whereas an implant with activated surface was placed in the other. Eight animals of each group were sacrificed at 12 weeks and the others at 26 weeks after surgery. Histological analysis was performed to analyse BIC. Results were statistically compared at a significance level of P < 0.05. RESULTS After 12 weeks, the BIC for conventional and activated implants with or without graft showed comparable results, with mean values of 14.8%, 16.5%, 21.5% and 20.1% (P > 0.05). For ungrafted sinuses after 26 weeks, no increase in BIC was recorded (12.1% conventional surface, 15.8% activated surface; P > 0.05). In grafted sinuses after 26 weeks, mean values increased to 28.7% for conventional and 34.1% for activated implants (P = 0.014; P = 0.015). However, only BIC of the latter was statistically significantly higher compared with ungrafted sinuses (P = 0.038). CONCLUSION After 12 weeks of healing, neither grafting nor implant type seemed to influence BIC. Use of an activated implant surface did not increase BIC when compared with a conventional implant. The synthetic graft seemed to improve BIC values after 26 weeks.


title: A randomized trial of intraarterial treatment for acute ischemic stroke.

text: BACKGROUND In patients with acute ischemic stroke caused by a proximal intracranial arterial occlusion, intraarterial treatment is highly effective for emergency revascularization. However, proof of a beneficial effect on functional outcome is lacking. METHODS We randomly assigned eligible patients to either intraarterial treatment plus usual care or usual care alone. Eligible patients had a proximal arterial occlusion in the anterior cerebral circulation that was confirmed on vessel imaging and that could be treated intraarterially within 6 hours after symptom onset. The primary outcome was the modified Rankin scale score at 90 days; this categorical scale measures functional outcome, with scores ranging from 0 (no symptoms) to 6 (death). The treatment effect was estimated with ordinal logistic regression as a common odds ratio, adjusted for prespecified prognostic factors. The adjusted common odds ratio measured the likelihood that intraarterial treatment would lead to lower modified Rankin scores, as compared with usual care alone (shift analysis). RESULTS We enrolled 500 patients at 16 medical centers in The Netherlands (233 assigned to intraarterial treatment and 267 to usual care alone). The mean age was 65 years (range, 23 to 96), and 445 patients (89.0%) were treated with intravenous alteplase before randomization. Retrievable stents were used in 190 of the 233 patients (81.5%) assigned to intraarterial treatment. The adjusted common odds ratio was 1.67 (95% confidence interval [CI], 1.21 to 2.30). There was an absolute difference of 13.5 percentage points (95% CI, 5.9 to 21.2) in the rate of functional independence (modified Rankin score, 0 to 2) in favor of the intervention (32.6% vs. 19.1%). There were no significant differences in mortality or the occurrence of symptomatic intracerebral hemorrhage. CONCLUSIONS In patients with acute ischemic stroke caused by a proximal intracranial occlusion of the anterior circulation, intraarterial treatment administered within 6 hours after stroke onset was effective and safe. (Funded by the Dutch Heart Foundation and others; MR CLEAN Netherlands Trial Registry number, NTR1804, and Current Controlled Trials number, ISRCTN10888758.).


title: Seroprevalence of influenza D virus in bulls in Argentina.

text: Influenza D virus (IDV) is considered a new agent involved in bovine respiratory disease (BRD). Based on seroprevalence studies or isolation from clinical samples, this virus has been detected on several continents and in several animal species, including cattle, pigs, camel, horses, and goats. We used an indirect in-house ELISA to detect anti-IDV antibodies in 165 serum samples from bulls on 116 farms in the province of La Pampa, Argentina. Eighty-five of 116 (73%) farms had at least 1 positive animal, and 112 of 165 (68%) of the analyzed samples were positive. There were no significant differences in the proportion of seropositive samples depending on the geographic region in which the samples were taken. Our results suggest that IDV infection is endemic in La Pampa; the clinical importance of IDV in Argentina remains to be investigated.


title: Gnotobiotic Rats Reveal that Gut Microbiota Regulates Colonic mRNA of Ace2, the Receptor for SARS-CoV-2 Infectivity.

text: N/A.


title: A 7% decrease in the differential renal uptake of MAG3 implies a loss in renal function.

text: OBJECTIVES To address the fact that a decrease in the relative renal uptake of 99mTc-mercaptoacetyltriglycine (MAG3) on serial MAG3 scans may indicate a loss of function and require a change in management by providing guidance as to what constitutes a meaningful change in serial relative function measurements as well determining the normal variation of other common MAG3 renogram parameters. METHODS A prospective study was conducted in 24 male urology patients with stable renal function. The mean age was 66.5 ± 7.9 (SD) years; the mean serum creatinine was 1.38 ± 0.57 (SD) mg/dL, and the MAG3 renal scans were performed a mean of 11 ± 8 days apart. Each MAG3 scan included a measurement of relative function as well as the time to maximum counts and 20 minutes to maximum count ratios for both cortical and whole kidney regions of interest. RESULTS The Pearson and intraclass correlations for the baseline and repeat measurements of relative renal function were both 0.98. Bland-Altman plots showed no bias between the baseline and repeat relative uptake measurements. The mean difference between 2 repeated measurements of the relative MAG3 uptake was 0.04 ± 2.88% (SD) for the left kidney and 0.08 ± 3.07% (SD) for the right kidney. Comparable results were obtained for the other renogram parameters. CONCLUSIONS Measurements of relative renal uptake of MAG3 and common renogram parameters are highly reproducible; a decrease in relative uptake ≥7% (ie, 50%-43%) implies a loss in renal function.


title: Cerebral Blood Flow Autoregulation in Sepsis for the Intensivist: Why Its Monitoring May Be the Future of Individualized Care.

text: Cerebral blood flow (CBF) autoregulation maintains consistent blood flow across a range of blood pressures (BPs). Sepsis is a common cause of systemic hypotension and cerebral dysfunction. Guidelines for BP management in sepsis are based on historical concepts of CBF autoregulation that have now evolved with the availability of more precise technology for its measurement. In this article, we provide a narrative review of methods of monitoring CBF autoregulation, the cerebral effects of sepsis, and the current knowledge of CBF autoregulation in sepsis. Current guidelines for BP management in sepsis are based on a goal of maintaining mean arterial pressure (MAP) above the lower limit of CBF autoregulation. Bedside tools are now available to monitor CBF autoregulation continuously. These data reveal that individual BP goals determined from CBF autoregulation monitoring are more variable than previously expected. In patients undergoing cardiac surgery with cardiopulmonary bypass, for example, the lower limit of autoregulation varied between a MAP of 40 to 90 mm Hg. Studies of CBF autoregulation in sepsis suggest patients frequently manifest impaired CBF autoregulation, possibly a result of BP below the lower limit of autoregulation, particularly in early sepsis or with sepsis-associated encephalopathy. This suggests that the present consensus guidelines for BP management in sepsis may expose some patients to both cerebral hypoperfusion and cerebral hyperperfusion, potentially resulting in damage to brain parenchyma. The future use of novel techniques to study and clinically monitor CBF autoregulation could provide insight into the cerebral pathophysiology of sepsis and offer more precise treatments that may improve functional and cognitive outcomes for survivors of sepsis.


title: Caveolin-1: a critical regulator of lung injury.

text: Caveolin-1 (cav-1), a 22-kDa transmembrane scaffolding protein, is the principal structural component of caveolae. Cav-1 regulates critical cell functions including proliferation, apoptosis, cell differentiation, and transcytosis via diverse signaling pathways. Abundant in almost every cell type in the lung, including type I epithelial cells, endothelial cells, smooth muscle cells, fibroblasts, macrophages, and neutrophils, cav-1 plays a crucial role in the pathogenesis of acute lung injury (ALI). ALI and its severe form, acute respiratory distress syndrome (ARDS), are responsible for significant morbidity and mortality in intensive care units, despite improvement in ventilation strategies. The pathogenesis of ARDS is still poorly understood, and therapeutic options remain limited. In this article, we summarize recent data regarding the regulation and function of cav-1 in lung biology and pathology, in particular as it relates to ALI. We further discuss the potential molecular and cellular mechanisms by which cav-1 expression contributes to ALI. Investigating the cellular functions of cav-1 may provide new insights for understanding the pathogenesis of ALI and provide novel targets for therapeutic interventions in the future.


Crisis Standards of Care: A Systems Framework for Catastrophic Disaster Response.


COVID-19 pandemic: stringent measures of Malaysia and implications for other countries.


title: COVID-19 in Correctional and Detention Facilities - United States, February-April 2020.

text: An estimated 2.1 million U.S. adults are housed within approximately 5,000 correctional and detention facilities† on any given day (1). Many facilities face significant challenges in controlling the spread of highly infectious pathogens such as SARS-CoV-2, the virus that causes coronavirus disease 2019 (COVID-19). Such challenges include crowded dormitories, shared lavatories, limited medical and isolation resources, daily entry and exit of staff members and visitors, continual introduction of newly incarcerated or detained persons, and transport of incarcerated or detained persons in multiperson vehicles for court-related, medical, or security reasons (2,3). During April 22-28, 2020, aggregate data on COVID-19 cases were reported to CDC by 37 of 54 state and territorial health department jurisdictions. Thirty-two (86%) jurisdictions reported at least one laboratory-confirmed case from a total of 420 correctional and detention facilities. Among these facilities, COVID-19 was diagnosed in 4,893 incarcerated or detained persons and 2,778 facility staff members, resulting in 88 deaths in incarcerated or detained persons and 15 deaths among staff members. Prompt identification of COVID-19 cases and consistent application of prevention measures, such as symptom screening and quarantine, are critical to protecting incarcerated and detained persons and staff members.


title: Outcome of overlap anastomosis using a linear stapler after laparoscopic total and proximal gastrectomy.

text: BACKGROUND Recently, novel intracorporeal esophagojejunostomy using a linear stapler after laparoscopic total gastrectomy (LTG) was reported and termed as the overlap method. In this study, we evaluated the feasibility and safety of the overlap method for esophagojejunostomy or esophagogastrostomy after LTG or laparoscopic proximal gastrectomy (LPG), respectively. METHODS Twenty-five patients underwent anastomosis using a linear stapler during esophagojejunostomy and esophagogastrostomy after LTG and LPG, respectively. Clinicopathological data and surgical outcomes were evaluated. RESULTS The average surgical duration for LTG was 236.8 min compared with 224.1 min for LPG. Postoperative complications were observed in four patients (16.0%); these included a wound infection, an intestinal obstruction, an afferent loop syndrome, and a reflux symptom. The average postoperative hospital stay of the patients was 12.5 days. There was no case of conversion to open surgery, anastomotic leakage or stenosis, or mortality. CONCLUSIONS The overlap method for esophagojejunostomy or esophagogastrostomy after LTG or LPG is safe and feasible and does not require an additional minilaparotomy, which may result in less pain and favorable cosmetic outcomes.


Coronavirus diaries: We'll meet again.


Severe pneumonia among Kenyan infants and children.


title: COVID-19 Associated Hepatitis Complicating Recent Living Donor Liver Transplantation.

text: We present a case of COVID-19 hepatitis in a living donor liver allograft recipient whose donor subsequently tested positive for COVID-19. The patient is a female infant with biliary atresia (failed Kasai procedure). She recovered well, with improving liver function tests for 4 days. On post-operative day (POD) 4 the patient developed respiratory distress and fever. COVID-19 testing (polymerase chain reaction) was positive. Liver function tests increased approximately 5-fold. Liver biopsy showed moderate acute hepatitis with prominent clusters of apoptotic hepatocytes and associated cellular debris. Lobular lymphohistiocytic inflammation was noted. Typical portal features of mild to moderate acute cellular rejection were also noted.


title: [Prospective randomised study: robotic-assisted versus conventional laparoscopic surgery in colorectal cancer resection].

text: INTRODUCTION Robotic-assisted surgery is playing an increasingly important role in the last few years in the treatment of colorectal oncological disease. However, there are still no studies that objectively demonstrate the advantages of this type of surgery. We present a prospective randomised study in order to compare the short-term results between colorectal robotic surgery and laparoscopic surgery. MATERIAL AND METHOD A total of 56 patients diagnosed with colorectal cancer between January 2008 and January 2009, were randomised and assigned to the robotic or laparoscopic group. Age, body mass index, tumour location, conversions in each group, complications during and after surgery, and histological characteristics of the specimens obtained, were all compared. RESULTS There were no significant differences between age (P=.055), body mass index (P=.12), or tumour location (P=.91). Only one patient in the robotic group required a transfusion and none in the laparoscopic group. The percentage of conversions was the same in both groups, however, the preparation times and operating times were significantly longer in patients intervened using the robotic device (P=.0001 and P=.017, respectively). There were no differences as regards the rate of complications or in the percentage of re-interventions (14.2% and 7.1%). The mean hospital stay of the patients was 9.3 (8.1) days in the robotic group and 9.2 (6.8) days in the laparoscopic (P=.79). The distal resection margin was greater in the specimen obtained using robotic surgery (P =.003) as well as the number of lymph nodes obtained in the specimen (P =.23). CONCLUSION Robotic colorectal was performed safely and effectively, and with similar clinical results. International Trial Number for this study is: ISRCTN60866560.


title: Intratumoral coagulation by radiofrequency ablation facilitated the laparoscopic resection of giant hepatic hemangioma: a surgical technique report of two cases.

text: BACKGROUND Traditionally, open hepatic resection is the first choice of treatment for symptomatic enlarging hepatic hemangiomas, which requires a large abdominal incision and is associated with substantial recovery time and morbidity. Minimally invasive laparoscopic resection has been used recently in liver surgery for treating selected hepatic hemangiomas. However, laparoscopic liver surgery poses the significant technical challenges and high rate of conversion. Radiofrequency (RF) ablation has been proved feasible in the treatment of hepatic hemangiomas with a size range of 5.0-9.9 cm. It is controversial to treat giant hepatic hemangiomas (≥10.0 cm) by means of RF ablation, due to the low technique success rate and high incidence of ablation-related complications. We aimed to assess the safety and efficacy of combined laparoscopic resection with intratumoral RF-induced coagulation for giant hepatic hemangiomas. METHODS We treated 2 patients with giant subcapsular hepatic hemangioma (12.0 cm and 13.1 cm in diameters respectively) by laparoscopic resection following intratumoral coagulation of the tumor with RF ablation. RESULTS Blood loss during resection was 100 ml (case 1) and 300ml (case 2) respectively. No blood transfusion and dialysis were needed during perioperative period. The two patients were discharged 6 days (case 1) and 12 days (case 2) after surgery without any complications, respectively. Postoperative contrast-enhanced CT follow up showed there was no residual tumor. CONCLUSIONS It is feasible to treat giant subcapsular hepatic hemangioma by laparoscopic tumor resection boosted by intratumoral coagulation using RF ablation, which may open a new avenue for treating giant hemangioma.


title: A pilot prospective randomized, controlled trial comparing LigaSure™ tissue fusion technology with the ForceTriad™ energy platform to the electrosurgical pencil on rates of atrial fibrillation after pulmonary lobectomy and mediastinal lymphadenectomy.

text: OBJECTIVES The use of bipolar sealing devices during pulmonary resection is particularly useful in thoracoscopic surgery. Theoretically, a bipolar device, which contains the current in a smaller area and completes the current cycle only through the tissue between the electrodes, may reduce the proportion of patients experiencing atrial fibrillation compared with monopolar devices such as the electrosurgical pencil using which the current completes the cycle through the patient. We investigated the impact of the LigaSure™ (LS) tissue fusion technology with the ForceTriad™ energy platform device on the incidence of postoperative atrial fibrillation and on the reduction of postoperative chest tube output and hospital length of stay after open pulmonary lobectomy. METHODS A pilot prospective randomized, controlled trial comparing LS tissue fusion technology with the ForceTriad™ energy platform to the conventional electrosurgical pencil. Overall, 146 patients with resectable lung cancer were recruited at the Division of Thoracic Surgery of the Istituto Nazionale Tumori, Fondazione Pascale, IRCCS, between January 2011 and July 2013. Of these, 119 candidates to open lobectomy for non-small-cell lung cancer were randomized to either LS tissue fusion technology with the ForceTriad™ energy platform (LS: 57 patients) or standard haemostatic procedure (standard treatment, ST: 62 patients) for hilar and mediastinal nodal dissection. The primary end-point was to compare the incidence of postoperative atrial fibrillation of LS compared with ST. The secondary end-point was to compare the efficacy of LS compared with ST in terms of total chest tube drainage, daily chest tube drainage and chest tube duration. RESULTS There was no statistically significant difference between LS and ST in terms of postoperative atrial fibrillation (P=0.31). However, LS was associated to significant reduction of duration of both mediastinal nodal dissection (P=0.017) and the cumulative chest tube drainage (P=0.025). CONCLUSIONS The incidence of atrial fibrillation with LS tissue fusion technology with the ForceTriad™ energy platform is not reduced as compared with conventional electrosurgical pencil. However, the use of LS during mediastinal nodal dissection is associated to shorter duration of lymphadenectomy and duration of chest tube drainage.


title: Trends in diverticulitis management in the United States from 2002 to 2007.

text: OBJECTIVE To demonstrate the recent trends of admission and surgical management for diverticulitis in the United States. DESIGN Retrospective database analysis. SETTING The National Inpatient Sample database. PATIENTS Patients admitted to the hospital for diverticulitis from 2002 to 2007. MAIN OUTCOME MEASURES Patient characteristics, surgical approach, and mortality were evaluated for elective or emergent admission. RESULTS A total of 1,073,397 patients were admitted with diverticulitis (emergent: 78.3%, elective: 21.7%). The emergent admission rate increased by 9.5% over the study period. For emergent patients, 12.2% underwent urgent surgical resection and 87.8% were treated with nonoperative methods (percutaneous abscess drainage: 1.88% and medical treatment: 85.92%). There was only a 4.3% increase in urgent surgical resections, while elective surgical resections increased by 38.7.%. The overall rate of elective laparoscopic colon resection was 10.5%. Elective laparoscopic surgery nearly doubled from 6.9% in 2002 to 13.5% in 2007 (P < .001). Primary anastomosis rates increased for elective resections over time (92.1% in 2002 to 94.5% in 2007; P < .001). For urgent open operation, use of colostomy decreased significantly from 61.2% in 2002 to 54.0% in 2007 (P < .001). In-hospital mortality significantly decreased in both elective and urgent surgery (elective: 0.53% in 2002 to 0.44% in 2007; P = .001; urgent: 4.5% in 2002 to 2.5% in 2007; P < .001). CONCLUSION Diverticulitis continues to be a source of significant morbidity in the United States. However, our data show a trend toward increased use of laparoscopic techniques for elective operations and primary anastomosis for urgent operations.


title: Perioperative complications of robot-assisted laparoscopic surgery using three robotic arms at a single institution.

text: PURPOSE The aim of this study was to evaluate perioperative complications of robot-assisted laparoscopic surgery in gynecology. MATERIALS AND METHODS Patients who underwent elective robot-assisted laparoscopic surgery between February 2006 and December 2013 were identified. Robotic procedures were performed using the da Vinci robotic system. Patient demographic data and operative outcomes were prospectively collected in a computerized database and extracted for this study. RESULTS Two hundred and ninety eight patients were identified during the study period. One case was converted to conventional laparoscopy due to mechanical failure of the robot system before the procedure and excluded from review. The median age and body mass index of patients were 48 years and 23.0 kg/m², respectively. The majority (n=130, 43.6%) of operative procedures was radical hysterectomy, followed by endometrial cancer staging (n=112, 37.6%), total hysterectomy (n=39, 13.1%), and myomectomy (n=17, 5.7%). The median operative time, estimated blood loss, and postoperative hospital stay were 208.5 min, 184.8 mL, and 8.9 days, respectively. The overall complication rate was 18.8% and that for only oncologic cases was 16.1%. Intraoperative complications (n=5, 1.7%) consisted of three vessel injuries, one bowel content leakage during an appendectomy during endometrial cancer staging and one case of bladder injury during radical hysterectomy. Early and late postoperative complications were 14.4% and 2.7%, respectively. Five patients (1.7%) experienced grade 3 complications according to Clavien-Dindo classification and therefore needed further intervention. CONCLUSION Robot-assisted laparoscopic surgery is a feasible approach in gynecology with acceptable complications.


title: Effect of Endotracheal Tube Size, Respiratory System Mechanics, and Ventilator Settings on Driving Pressure.

text: OBJECTIVES We sought to investigate factors that affect the difference between the peak inspiratory pressure measured at the Y-piece under dynamic flow conditions and plateau pressure measured under zero-flow conditions (resistive pressure) during pressure controlled ventilation across a range of endotracheal tube sizes, respiratory mechanics, and ventilator settings. DESIGN In vitro study. SETTING Research laboratory. PATIENTS None. INTERVENTIONS An in vitro bench model of the intubated respiratory system during pressure controlled ventilation was used to obtain the difference between peak inspiratory pressure measured at the Y-piece under dynamic flow conditions and plateau pressure measured under zero-flow conditions across a range of endotracheal tubes sizes (3.0-8.0 mm). Measurements were taken at combinations of pressure above positive end-expiratory pressure (10, 15, and 20 cm H2O), airway resistance (no, low, high), respiratory system compliance (ranging from normal to extremely severe), and inspiratory time at constant positive end-expiratory pressure (5 cm H2O). Multiple regression analysis was used to construct models predicting resistive pressure stratified by endotracheal tube size. MEASUREMENTS AND MAIN RESULTS On univariate regression analysis, respiratory system compliance (β -1.5; 95% CI, -1.7 to -1.4; p < 0.001), respiratory system resistance (β 1.7; 95% CI, 1.5-2.0; p < 0.001), pressure above positive end-expiratory pressure (β 1.7; 95% CI, 1.4-2.0; p < 0.001), and inspiratory time (β -0.7; 95% CI, -1.0 to -0.4; p < 0.001) were associated with resistive pressure. Multiple linear regression analysis showed the independent association between increasing respiratory system compliance, increasing airway resistance, increasing pressure above positive end-expiratory pressure, and decreasing inspiratory time and resistive pressure across all endotracheal tube sizes. Inspiratory time was the strongest variable associated with a proportional increase in resistive pressure. The contribution of airway resistance became more prominent with increasing endotracheal tube size. CONCLUSIONS Peak inspiratory pressures measured during pressure controlled ventilation overestimated plateau pressure irrespective of endotracheal tube size, especially with decreased inspiratory time or increased airway resistance.


title: The Heart and COVID-19: What Cardiologists Need to Know.

text: In face of the pandemic of the novel coronavirus disease 2019 (COVID-19), the management of patients with cardiovascular risk factors and/or disease is challenging. The cardiovascular complications evidenced in patients with COVID-19 derive from several mechanisms, ranging from direct viral injury to complications secondary to the inflammatory and thrombotic responses to the infection. The proper care of patients with COVID-19 requires special attention to the cardiovascular system aimed at better outcomes.


title: The role of occlusal support and lower third molars in mandibular angle and condylar fractures

text: INTRODUCTION AND AIM The aim of our study was to investigate the influence of the occlusal support, and mandibular third molars on mandibular angle and condylar fractures. METHOD AND RESULTS Patients with unilateral and isolated angle or condylar fractures were included in this retrospective, cross-sectional study. Data was collected from patient records and panoramic x-rays. The predictor variables included the type of occlusal support and the presence or absence of third molars. The outcome variable was angle or condylar fracture, while other predictor variables included demographic factors. Bivariate (χ2 test) and logistic regression analyses were conducted to investigate the associations between variables and the outcome. 43 angle (mean age: 29.9 ± 12.8 years; 98.4% male) and 37 condylar (mean age: 46.8 ± 20.2 years; 62.2% male) fracture cases were included in this study. Bilateral occlusal support was present in 81.4% of angle fracture group and in 51.3% of condylar fracture group (p<0.001). In the case of bilateral occlusal support, an odds ratio (OR) of 4.2 was found for angle fractures (p<0.006). A third molar was present in 86% of the angle fracture group and in 43.2% of the condylar fracture group (p<0.001). The presence of a third molar exhibited an odds ratio of 8.1 for the angle fractures (p<0.001). When bilateral occlusal support and third molar were present simultaneously, the risk was 15.9 times higher for an angle fracture (p<0.001). CONCLUSION The presence of occlusal support and/or third molars was significantly associated with angle fractures, however, the absence of occlusal support and/or third molars significantly correlated with condylar fractures. Orv Hetil. 2020; 161(28): 1166-1174.


title: Propagation, Inactivation, and Safety Testing of SARS-CoV-2.

text: In late 2019, a novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in Wuhan, the capital of the Chinese province Hubei. Since then, SARS-CoV-2 has been responsible for a worldwide pandemic resulting in over 4 million infections and over 250,000 deaths. The pandemic has instigated widespread research related to SARS-CoV-2 and the disease that it causes, COVID-19. Research into this new virus will be facilitated by the availability of clearly described and effective procedures that enable the propagation and quantification of infectious virus. As work with the virus is recommended to be performed at biosafety level 3, validated methods to effectively inactivate the virus to enable the safe study of RNA, DNA, and protein from infected cells are also needed. Here, we report methods used to grow SARS-CoV-2 in multiple cell lines and to measure virus infectivity by plaque assay using either agarose or microcrystalline cellulose as an overlay as well as a SARS-CoV-2 specific focus forming assay. We also demonstrate effective inactivation by TRIzol, 10% neutral buffered formalin, beta propiolactone, and heat.


title: Early experience with single-incision laparoscopic surgery for the placement of a gastrostomy in a 10-year-old girl: a case report.

text: UNLABELLED INTRODUCTION Access procedures for alimentation have been performed both endoscopically and surgically. In patients in whom endoscopic gastrostomy feeding tubes cannot be placed, single-incision laparoscopic surgery gastrostomy is an alternative method. This minimally invasive approach is a new technique performed through a single umbilical incision and without the need for additional laparoscopic ports. CASE PRESENTATION In this article we present a case of single-incision laparoscopic surgery gastrostomy performed with conventional laparoscopic instruments in a 10-year-old girl of Caucasian ethnicity who was not a candidate for a percutaneous endoscopic gastrostomy tube because of esophageal varices due to her advanced-stage cystic fibrosis with liver cirrhosis and portal hypertension. She also had an umbilical hernia, which was repaired during the same procedure through the same incision. Access and pneumoperitoneum were obtained through the umbilicus with the single-incision laparoscopic surgery port. The selected site for the feeding tube in the stomach was exteriorized through this incision and a feeding tube was placed. The stomach was returned into the abdomen. The fascial defect, and thus also the hernia, was repaired, and the 2cm umbilical incision was closed with endocutaneous sutures. The total operative time was 25 minutes. Our patient's intra-operative and post-operative course was uneventful. We were able to use the feeding tube on the first post-operative day with good intestinal function. Our patient and her parents were pleased with the cosmetic result. CONCLUSIONS The single-incision laparoscopic surgery procedure seems to be a less invasive alternative to open placement of gastrostomy. This approach has the possible advantages of reduced post-operative pain, faster return to normal function, reduced port site complications, improved cosmesis and better patient satisfaction.


title: Differentiation between human coronaviruses NL63 and 229E using a novel double-antibody sandwich enzyme-linked immunosorbent assay based on specific monoclonal antibodies.

text: Human coronaviruses (HCoVs) are responsible for respiratory tract infections ranging from common colds to severe acute respiratory syndrome. HCoV-NL63 and HCoV-229E are two of the four HCoVs that circulate worldwide and are close phylogenetic relatives. HCoV infections can lead to hospitalization of children, elderly individuals, and immunocompromised patients. Globally, approximately 5% of all upper and lower respiratory tract infections in hospitalized children are caused by HCoV-229E and HCoV-NL63. The latter virus has recently been associated with the childhood disease croup. Thus, differentiation between the two viruses is relevant for epidemiology studies. The aim of this study was to develop a double-antibody sandwich enzyme-linked immunosorbent assay (DAS-ELISA) as a potential tool for identification and differentiation between HCoV-NL63 and HCoV-229E. The nucleocapsid (N) proteins of HCoV-NL63 and HCoV-229E were expressed in an Escherichia coli system and used to immunize mice in order to obtain monoclonal antibodies (MAbs) specific for each virus. Three specific MAbs to HCoV-NL63, one MAb specific to HCoV-229E, and four MAbs that recognized both viruses were obtained. After their characterization, three MAbs were selected in order to develop a differential DAS-ELISA. The described assay could detect up to 3 ng/ml of N protein and 50 50% tissue culture infective doses/ml of virus stock. No cross-reactivity with other human coronaviruses or closely related animal coronaviruses was found. The newly developed DAS-ELISA was species specific, and therefore, it could be considered a potential tool for detection and differentiation of HCoV-NL63 and HCoV-229E infections.


title: Optimizing reperfusion in patients with STEMI: a critical evaluation of pharmacologic and non-pharmacologic strategies.

text: Among patients with ST-elevation myocardial infarction (STEMI), rapidly re-establishing normal coronary blood flow is of paramount importance. More than 25 % of hospitals in the USA do not have access to timely primary percutaneous coronary intervention, highlighting the need for clinicians to understand both pharmacologic and non-pharmacologic strategies for STEMI. This manuscript reviews the current state of the art in STEMI care, describing both pharmacologic and non-pharmacologic strategies for reperfusion.


title: Directed evolution of adeno-associated virus to an infectious respiratory virus.

text: Respiratory viruses evolve to maintain infectivity levels that permit spread yet prevent host and virus extinction, resulting in surprisingly low infection rates. Respiratory viruses harnessed as gene therapy vectors have illustrated this limitation. We used directed evolution in an organotypic human airway model to generate a highly infectious adeno-associated virus. This virus mediated gene transfer more than 100-fold better than parental strains and corrected the cystic fibrosis epithelial Cl(-) transport defect. Thus, under appropriate selective pressures, viruses can evolve to be more infectious than observed in nature, a finding that holds significant implications for designing vectors for gene therapy and for understanding emerging pathogens.


title: Structure and function of the complete internal fusion loop from Ebolavirus glycoprotein 2.

text: Ebolavirus (Ebov), an enveloped virus of the family Filoviridae, causes hemorrhagic fever in humans and nonhuman primates. The viral glycoprotein (GP) is solely responsible for virus-host membrane fusion, but how it does so remains elusive. Fusion occurs after virions reach an endosomal compartment where GP is proteolytically primed by cathepsins. Fusion by primed GP is governed by an internal fusion loop found in GP2, the fusion subunit. This fusion loop contains a stretch of hydrophobic residues, some of which have been shown to be critical for GP-mediated infection. Here we present liposome fusion data and NMR structures for a complete (54-residue) disulfide-bonded internal fusion loop (Ebov FL) in a membrane mimetic. The Ebov FL induced rapid fusion of liposomes of varying compositions at pH values at or below 5.5. Consistently, circular dichroism experiments indicated that the α-helical content of the Ebov FL in the presence of either lipid-mimetic micelles or small liposomes increases in samples exposed to pH ≤5.5. NMR structures in dodecylphosphocholine micelles at pH 7.0 and 5.5 revealed a conformational change from a relatively flat extended loop structure at pH 7.0 to a structure with an ∼90° bend at pH 5.5. Induction of the bend at low pH reorients and compacts the hydrophobic patch at the tip of the FL. We propose that these changes facilitate disruption of lipids at the site of virus-host cell membrane contact and, hence, initiate Ebov fusion.


title: Cyclovirus in nasopharyngeal aspirates of Chilean children with respiratory infections.

text: Some respiratory tract infections remain unexplained despite extensive testing for common pathogens. Nasopharyngeal aspirates (NPAs) from 120 Chilean infants from Santiago with acute lower respiratory tract infections were analysed by viral metagenomics, revealing the presence of nucleic acids from anelloviruses, adenovirus-associated virus and 12 known respiratory viral pathogens. A single sequence read showed translated protein similarity to cycloviruses. We used inverse PCR to amplify the complete circular ssDNA genome of a novel cyclovirus we named CyCV-ChileNPA1. Closely related variants were detected using PCR in the NPAs of three other affected children that also contained anelloviruses. This report increases the current knowledge of the genetic diversity of cycloviruses whose detection in multiple NPAs may reflect a tropism for human respiratory tissues.


title: Roles of Capsule Endoscopy and Single-Balloon Enteroscopy in Diagnosing Unexplained Gastrointestinal Bleeding.

text: BACKGROUND/AIMS The diagnostic algorithms used for selecting patients with obscure gastrointestinal bleeding (OGIB) for capsule endoscopy (CE) or balloon-assisted enteroscopy (BE) vary among facilities. We aimed to demonstrate the appropriate selection criteria of CE and single balloon-assisted enteroscopy (SBE) for patients with OGIB according to their conditions, by retrospectively comparing the diagnostic performances of CE and BE for detecting the source of the OGIB. METHODS We investigated 194 patients who underwent CE and/or BE. The rate of positive findings, details of the findings, accidental symptoms, and hemostasis methods were examined and analyzed. RESULTS CE and SBE were performed in 103 and 91 patients, respectively, and 26 patients underwent both examinations. The rate of positive findings was significantly higher with SBE (73.6%) than with CE (47.5%, p<0.01). The rate of positive findings was higher in overt bleeding cases than in occult bleeding cases for both BE and SBE. Among the overt bleeding cases, the rate was significantly higher in ongoing bleeding cases than in previous bleeding cases. CONCLUSIONS Both CE and SBE are useful to diagnose OGIB. For overt bleeding cases and ongoing bleeding cases, SBE may be more appropriate than CE because endoscopic diagnosis and treatment can be completed simultaneously.


title: Inclusion Body Fusion of Human Parainfluenza Virus Type 3 Regulated by Acetylated α-Tubulin Enhances Viral Replication.

text: Viral inclusion bodies (IBs), or replication factories, are unique structures generated by viral proteins together with some cellular proteins as a platform for efficient viral replication, but little is known about the mechanism underlying IB formation and fusion. Our previous study demonstrated that the interaction between the nucleoprotein (N) and phosphoprotein (P) of human parainfluenza virus type 3 (HPIV3), an enveloped virus with great medical impact, can form IBs. In this study, we found that small IBs can fuse with each other to form large IBs that enhance viral replication. Furthermore, we found that acetylated α-tubulin interacts with the N-P complex and colocalizes with IBs of HPIV3 but does not interact with the N-P complex of human respiratory syncytial virus or vesicular stomatitis virus and does not colocalize with IBs of human respiratory syncytial virus. Most importantly, enhancement of α-tubulin acetylation using the pharmacological inhibitor trichostatin A (TSA), RNA interference (RNAi) knockdown of the deacetylase enzymes histone deacetylase 6 (HDAC6) and sirtuin 2 (SIRT2), or expression of α-tubulin acetyltransferase 1 (α-TAT1) resulted in the fusion of small IBs into large IBs and effective viral replication. In contrast, suppression of acetylation of α-tubulin by overexpressing HDAC6 and SIRT2 profoundly inhibited the fusion of small IBs and viral replication. Our findings offer previously unidentified mechanistic insights into the regulation of viral IB fusion by acetylated α-tubulin, which is critical for viral replication. IMPORTANCE Inclusion bodies (IBs) are unique structures generated by viral proteins and some cellular proteins as a platform for efficient viral replication. Human parainfluenza virus type 3 (HPIV3) is a nonsegmented single-stranded RNA virus that mainly causes lower respiratory tract disease in infants and young children. However, no vaccines or antiviral drugs for HPIV3 are available. Therefore, understanding virus-host interactions and developing new antiviral strategies are increasingly important. Acetylation on lysine (K) 40 of α-tubulin is an evolutionarily conserved modification and plays an important role in many cellular processes, but its role in viral IB dynamics has not been fully explored. To our knowledge, our findings are the first to show that acetylated α-tubulin enhances viral replication by regulating HPIV3 IB fusion.


title: Characteristics and Outcomes of Middle East Respiratory Syndrome Coronavirus Patients Admitted to an Intensive Care Unit in Jeddah, Saudi Arabia.

text: BACKGROUND An increasing number of patients are being infected with Middle East respiratory syndrome coronavirus (MERS-CoV) since the first case was identified in September 2012. We report the characteristics and outcomes of MERS-CoV-confirmed patients who developed critical illness requiring admission to an intensive care unit (ICU). METHODS We conducted a prospective cohort study of all MERS-CoV-confirmed cases who were admitted to our ICU from March 20, 2014, till June 1, 2014. Presenting symptoms, comorbid conditions, and details of their ICU stay were recorded. RESULTS Eight patients were admitted to the ICU with MERS-CoV infection. All had signs of respiratory distress with 7 requiring mechanical ventilation. Three patients were health care workers. In all, 6 patients had comorbid conditions and 5 patients developed multiorgan system failure (MOSF). In all, 5 patients expired, 2 were discharged alive, and 1 remained intubated at the end of the study period. CONCLUSIONS Middle East respiratory syndrome coronavirus carries a high mortality rate in patients who require ICU admission, with a significant number of patients developing MOSF. Further investigation is needed to determine optimal management guidelines for these patients.


title: Early application of airway pressure release ventilation may reduce the duration of mechanical ventilation in acute respiratory distress syndrome.

text: PURPOSE Experimental animal models of acute respiratory distress syndrome (ARDS) have shown that the updated airway pressure release ventilation (APRV) methodologies may significantly improve oxygenation, maximize lung recruitment, and attenuate lung injury, without circulatory depression. This led us to hypothesize that early application of APRV in patients with ARDS would allow pulmonary function to recover faster and would reduce the duration of mechanical ventilation as compared with low tidal volume lung protective ventilation (LTV). METHODS A total of 138 patients with ARDS who received mechanical ventilation for <48 h between May 2015 to October 2016 while in the critical care medicine unit (ICU) of the West China Hospital of Sichuan University were enrolled in the study. Patients were randomly assigned to receive APRV (n = 71) or LTV (n = 67). The settings for APRV were: high airway pressure (Phigh) set at the last plateau airway pressure (Pplat), not to exceed 30 cmH2O) and low airway pressure ( Plow) set at 5 cmH2O; the release phase (Tlow) setting adjusted to terminate the peak expiratory flow rate to ≥ 50%; release frequency of 10-14 cycles/min. The settings for LTV were: target tidal volume of 6 mL/kg of predicted body weight; Pplat not exceeding 30 cmH2O; positive end-expiratory pressure (PEEP) guided by the PEEP-FiO2 table according to the ARDSnet protocol. The primary outcome was the number of days without mechanical ventilation from enrollment to day 28. The secondary endpoints included oxygenation, Pplat, respiratory system compliance, and patient outcomes. RESULTS Compared with the LTV group, patients in the APRV group had a higher median number of ventilator-free days {19 [interquartile range (IQR) 8-22] vs. 2 (IQR 0-15); P < 0.001}. This finding was independent of the coexisting differences in chronic disease. The APRV group had a shorter stay in the ICU (P = 0.003). The ICU mortality rate was 19.7% in the APRV group versus 34.3% in the LTV group (P = 0.053) and was associated with better oxygenation and respiratory system compliance, lower Pplat, and less sedation requirement during the first week following enrollment (P < 0.05, repeated-measures analysis of variance). CONCLUSIONS Compared with LTV, early application of APRV in patients with ARDS improved oxygenation and respiratory system compliance, decreased Pplat and reduced the duration of both mechanical ventilation and ICU stay.


title: Body composition after allogeneic haematopoietic cell transplantation/total body irradiation in children and young people: a restricted systematic review.

text: PURPOSE To collate evidence of changes in body composition following treatment of leukaemia in children, teenagers and young adults (CTYA, 0-24 years) with allogeneic haematopoietic stem cell transplant and total body irradiation (HSCT+TBI). METHODS Papers were identified by searching Medline and Google Scholar, reference lists/citations and contacting key authors, with no date or language restrictions. Inclusion criteria were as follows: leukaemia, HSCT+TBI, aged ≤ 24 years at HSCT and changes in body composition (total fat, central adiposity, adipose tissue function, muscle mass, muscle function). Quality was assessed using a brief Newcastle-Ottawa scale. RESULTS Of 900 papers, 20 were included: seven controlled, five uncontrolled studies and eight case reports. Study quality appeared good. There was little evidence of differences in total fat/weight for HSCT + TBI groups (compared to healthy controls/population norms/short stature controls). There was some evidence of significantly higher central adiposity and differences in adipose tissue function (compared to leukaemic/non-leukaemic controls). Muscle mass was significantly lower (compared to healthy/obese controls). Muscle function results were inconclusive but suggested impairment. Case reports confirmed a lipodystrophic phenotype. CONCLUSIONS Early remodelling of adipose tissue and loss of skeletal muscle are evident following HSCT + TBI for CTYA leukaemia, with extreme phenotype of overt lipodystrophy. There is some evidence for reduced muscle effectiveness. IMPLICATIONS FOR CANCER SURVIVORS Body composition changes in patients after HSCT + TBI are apparent by early adult life and link with the risk of excess cardiometabolic morbidity seen in adult survivors. Interventions to improve muscle and/or adipose function, perhaps utilizing nutritional manipulation and/or targeted activity, should be investigated.


title: Pharmacokinetics-Based Adjusted Versus Standard Dose of Ribavirin Does Not Improve Virologic Response Rates in Chronic Hepatitis C Genotype 4 Patients: A Randomized Controlled Trial.

text: Optimal doses of Ribavirin (RBV) for hepatitis C virus (HCV) treatment are not known. To assess the safety and efficacy of PegIFNalfa-2a in combination with an adjusted (ADJ) RBV dose based on early pharmacokinetics versus a fixed standard (STD) dose of RBV in chronic HCV genotype (GT) 4-naive patients in a randomized trial. One hundred eighty-one patients were randomized. The baseline variables were similar in both arms and females were 50.3% of the patients, 76.5% had minimal-moderate fibrosis (F0-2). Sustained virologic response (SVR) was achieved in 99 (54.7%) subjects. SVR was seen in 50/90 (55.6%) of ADJ dose of RBV and 49/91 (53.9%) of STD dose subjects. Prematurely withdrawal or discontinuation of treatment prematurely in the ADJ RBV arm occurred in 11/90 patients (12.2%) compared with 6/91 subjects (6.6%) in the STD arm (P = 0.214). Similarly, virologic relapse was seen in 14/90 (15.6%) patients of the ADJ arm and 12/91 (13.2%) of the STD arm. Anemia grade 3-4 was seen in 36.7% in ADJ versus 17.6% in STD arm (P = 0.003). Occurrence of rapid virologic response and absences of F4 fibrosis predicted SVR in a univariate analysis. However, age, gender, weight, presence of diabetes, baseline alanine aminotransferase, and vitamin D levels were not significantly different in patients achieving SVR. ADJ higher doses of RBV based on its early pharmacokinetics-based RBV do not improve SVR rates in HCV GT4 treated in combination with peg-IFN alpha-2-a versus STD therapy. Patients on ADJ higher doses of RBV experienced higher rates of anemia and require more erythropoietin without increasing SVR.


title: Isolation and characterization of porcine epidemic diarrhea viruses associated with the 2013 disease outbreak among swine in the United States.

text: Porcine epidemic diarrhea virus (PEDV) was detected in May 2013 for the first time in U.S. swine and has since caused significant economic loss. Obtaining a U.S. PEDV isolate that can grow efficiently in cell culture is critical for investigating pathogenesis and developing diagnostic assays and for vaccine development. An additional objective was to determine which gene(s) of PEDV is most suitable for studying the genetic relatedness of the virus. Here we describe two PEDV isolates (ISU13-19338E and ISU13-22038) successfully obtained from the small intestines of piglets from sow farms in Indiana and Iowa, respectively. The two isolates have been serially propagated in cell culture for over 30 passages and were characterized for the first 10 passages. Virus production in cell culture was confirmed by PEDV-specific real-time reverse-transcription PCR (RT-PCR), immunofluorescence assays, and electron microscopy. The infectious titers of the viruses during the first 10 passages ranged from 6 × 10(2) to 2 × 10(5) 50% tissue culture infective doses (TCID50)/ml. In addition, the full-length genome sequences of six viruses (ISU13-19338E homogenate, P3, and P9; ISU13-22038 homogenate, P3, and P9) were determined. Genetically, the two PEDV isolates were relatively stable during the first 10 passages in cell culture. Sequences were also compared to those of 4 additional U.S. PEDV strains and 23 non-U.S. strains. All U.S. PEDV strains were genetically closely related to each other (≥99.7% nucleotide identity) and were most genetically similar to Chinese strains reported in 2011 to 2012. Phylogenetic analyses using different genes of PEDV suggested that the full-length spike gene or the S1 portion is appropriate for sequencing to study the genetic relatedness of these viruses.


Cancer Treatment Adaptations in the COVID-19 Era.


title: Bats host diverse parvoviruses as possible origin of mammalian dependoparvoviruses and source for bat-swine interspecies transmission.

text: Compared to the enormous species diversity of bats, relatively few parvoviruses have been reported. We detected diverse and potentially novel parvoviruses from bats in Hong Kong and mainland China. Parvoviruses belonging to Amdoparvovirus, Bocaparvovirus and Dependoparvovirus were detected in alimentary, liver and spleen samples from 16 different chiropteran species of five families by PCR. Phylogenetic analysis of partial helicase sequences showed that they potentially belonged to 25 bocaparvovirus, three dependoparvovirus and one amdoparvovirus species. Nearly complete genome sequencing confirmed the existence of at least four novel bat bocaparvovirus species (Rp-BtBoV1 and Rp-BtBoV2 from Rhinolophus pusillus, Rs-BtBoV2 from Rhinolophus sinicus and Rol-BtBoV1 from Rousettus leschenaultii) and two novel bat dependoparvovirus species (Rp-BtAAV1 from Rhinolophus pusillus and Rs-BtAAV1 from Rhinolophus sinicus). Rs-BtBoV2 was closely related to Ungulate bocaparvovirus 5 with 93, 72.1 and 78.7 % amino acid identities in the NS1, NP1 and VP1/VP2 genes, respectively. The detection of bat bocaparvoviruses, including Rs-BtBoV2, closely related to porcine bocaparvoviruses, suggests recent interspecies transmission of bocaparvoviruses between bats and swine. Moreover, Rp-BtAAV1 and Rs-BtAAV1 were most closely related to human AAV1 with 48.7 and 57.5 % amino acid identities in the rep gene. The phylogenetic relationship between BtAAVs and other mammalian AAVs suggests bats as the ancestral origin of mammalian AAVs. Furthermore, parvoviruses of the same species were detected from multiple bat species or families, supporting the ability of bat parvoviruses to cross species barriers. The results extend our knowledge on the diversity of bat parvoviruses and the role of bats in parvovirus evolution and emergence in humans and animals.


title: Radiofrequency ablation plus drug-eluting beads transcatheter arterial chemoembolization for the treatment of single large hepatocellular carcinoma.

text: BACKGROUND Our aim was to evaluate the effectiveness of the single-step combined therapy with radiofrequency ablation and drug-eluting beads transarterial chemoembolization in single hepatocellular carcinoma (HCC) larger than 3cm. Secondary aim was to compare the results with those obtained in a matched population treated with drug-eluting beads transarterial chemoembolization alone. METHODS 40 consecutive cirrhotic patients with single HCC were prospectively enrolled and treated. Twenty-three patients had tumours between 3 and 5cm (Group A), and 17 larger than 5cm (Group B). Twenty cirrhotic patients with single HCC treated only with chemoembolization formed the control group. RESULTS Complete response at 1 month was achieved in 32/40 tumours (80%). During follow-up, complete response was maintained in 25 patients (25/40, 62.5%), and this rate was higher in Group A (69.6% vs 53%, p=0.008). The group treated with combined therapy showed a significantly lower 2-year recurrence (48.1% vs 78.2%, p<0.001) and significantly higher survival (91.1% vs 60.6%, p=0.004) than the group treated with chemoembolization alone. CONCLUSIONS Balloon-occluded-radiofrequency ablation plus drug-eluting beads transarterial chemoembolization is an effective treatment of HCC larger than 3cm not amenable to surgical resection, providing better results than transarterial chemoembolization alone. The best results are achieved in tumours up to 5cm.


Changes in SARS-CoV-2 Positivity Rate in Outpatients in Seattle and Washington State, March 1-April 16, 2020.


Response to letter to the editor.


Cocirculation of Influenza C Viruses with Distinct Internal Genome Constellations in Iwate Prefecture, Japan, in 2016.


Choosing Wisely in the COVID-19 Era: Preventing Harm to Healthcare Workers.


title: Conformational changes in the capsid of a calicivirus upon interaction with its functional receptor.

text: Nonenveloped viral capsids are metastable structures that undergo conformational changes during virus entry that lead to interactions of the capsid or capsid fragments with the cell membrane. For members of the Caliciviridae, neither the nature of these structural changes in the capsid nor the factor(s) responsible for inducing these changes is known. Feline junctional adhesion molecule A (fJAM-A) mediates the attachment and infectious viral entry of feline calicivirus (FCV). Here, we show that the infectivity of some FCV isolates is neutralized following incubation with the soluble receptor at 37 degrees C. We used this property to select mutants resistant to preincubation with the soluble receptor. We isolated and sequenced 24 soluble receptor-resistant (srr) mutants and characterized the growth properties and receptor-binding activities of eight mutants. The location of the mutations within the capsid structure of FCV was mapped using a new 3.6-A structure of native FCV. The srr mutations mapped to the surface of the P2 domain were buried at the protruding domain dimer interface or were present in inaccessible regions of the capsid protein. Coupled with data showing that both the parental FCV and the srr mutants underwent increases in hydrophobicity upon incubation with the soluble receptor at 37 degrees C, these findings indicate that FCV likely undergoes conformational change upon interaction with its receptor. Changes in FCV capsid conformation following its interaction with fJAM-A may be important for subsequent interactions of the capsid with cellular membranes, membrane penetration, and genome delivery.


title: Acute subarachnoid hemorrhage in posterior condylar canal dural arteriovenous fistula: imaging features with endovascular management.

text: A 43-year-old man presented with acute subarachnoid hemorrhage. He was investigated and found to have a rare posterior condylar canal dural arteriovenous fistula (DAVF). DAVFs of the posterior condylar canal are rare. Venous drainage of the DAVF was through a long, tortuous, and aneurysmal bridging vein. We describe the clinical presentation, cross sectional imaging, angiographic features, and endovascular management of this patient. The patient was treated by transarterial embolization of the fistula through the ascending pharyngeal artery. This is the first report of an acutely bled posterior condylar canal DAVF treated by transarterial Onyx embolization with balloon protection in the vertebral artery. The patient recovered without any neurological deficit and had an excellent outcome. On 6 month follow-up angiogram, there was stable occlusion of the dural fistula.


The Importance of Proper Death Certification During the COVID-19 Pandemic.