title: Chemoradionuclide therapy with 186Re-labeled liposomal doxorubicin in combination with radiofrequency ablation for effective treatment of head and neck cancer in a nude rat tumor xenograft model.

text: PURPOSE To determine the therapeutic efficacy of rhenium 186 ((186)Re)-labeled PEGylated liposomal doxorubicin ((186)Re-liposomal doxorubicin) in combination with radiofrequency (RF) ablation of human head and neck squamous cell carcinoma (HNSCC) xenograft in nude rats. MATERIALS AND METHODS This investigation was approved by the animal care committee. Sixty nude rats with subcutaneously implanted HNSCC xenografts (six per group) were treated with (a) RF ablation (70 °C for 5 minutes), (b) PEGylated liposomes, (c) liposomal doxorubicin, (d) (186)Re-PEGylated liposomes (1295 MBq/kg), (e) (186)Re-liposomal doxorubicin (555 MBq/kg), (f) PEGylated liposomes plus RF ablation, (g) liposomal doxorubicin plus RF ablation, (h) (186)Re-PEGylated liposomes plus RF ablation, or (i) (186)Re-liposomal doxorubicin plus RF ablation. Six rats did not receive any treatment (control group). Tumor uptake in (186)Re therapy groups was monitored with small-animal single photon emission computed tomography for 5 days. Therapeutic efficacy was monitored for 6 weeks with measurement of tumor volume, calculation of the percentage injected dose of fluorine 18 fluorodeoxyglucose (FDG) in tumor from small-animal positron emission tomography (PET) images, and determination of viable tumor volume at histopathologic examination. Significant differences between groups were determined with analysis of variance. RESULTS The average tumor volume (± standard deviation) on the day of therapy was 1.32 cm(3) ± 0.17. At 6 weeks after therapy, control of tumor growth was better with (186)Re-liposomal doxorubicin than with liposomal doxorubicin alone (tumor volume, 2.26 cm(3) ± 0.89 vs 5.43 cm(3) ± 0.93, respectively; P < .01). The use of RF ablation with liposomal doxorubicin and (186)Re-liposomal doxorubicin further improved tumor control (tumor volume, 2.05 cm(3) ± 1.36 and 1.49 cm(3) ± 1.47, respectively). The tumor growth trend correlated with change in percentage of injected dose of FDG in tumor for all groups (R(2) = 0.85, P < .001). Viable tumor volume was significantly decreased in the group treated with (186)Re-liposomal doxorubicin plus RF ablation (0.54 cm(3) ± 0.38; P < .001 vs all groups except (186)Re-liposomal doxorubicin alone). CONCLUSION Triple and dual therapies had an observable trend ((186)Re-liposomal doxorubicin plus RF ablation > (186)Re-liposomal doxorubicin > liposomal doxorubicin plus RF ablation > liposomal doxorubicin) of improved tumor growth control and decreased viable tumor compared with other therapies. FDG PET could be used as a noninvasive surrogate marker for tumor growth and viability in this tumor model.


title: Design and Psychometric Analysis of the COVID-19 Prevention, Recognition and Home-Management Self-Efficacy Scale.

text: In order to control the spread of COVID-19, people must adopt preventive behaviours that can affect their day-to-day life. People's self-efficacy to adopt preventive behaviours to avoid COVID-19 contagion and spread should be studied. The aim of this study was to develop and psychometrically test the COVID-19 prevention, detection, and home-management self-efficacy scale (COVID-19-SES). We conducted an observational cross-sectional study. Six-hundred and seventy-eight people participated in the study. Data were collected between March and May 2020. The COVID-19-SES' validity (content, criterion, and construct), reliability (internal consistency and test-retest reliability), and legibility were studied. The COVID-19-SES' reliability was high (Cronbach's alpha = 0.906; intraclass correlation coefficient = 0.754). The COVID-19-SES showed good content validity (scale's content validity index = 0.92) and good criterion validity when the participants' results on the COVID-19-SES were compared to their general self-efficacy (r = 0.38; p < 0.001). Construct validity analysis revealed that the COVID-19-SES' three-factor structure explained 52.12% of the variance found and it was congruent with the World Health Organisation's recommendations to prevent COVID-19 contagion and spread. Legibility analysis showed that the COVID-19-SES is easy to read and understand by laypeople. The COVID-19-SES is a psychometrically robust instrument that allows for a valid and reliable assessment of people's self-efficacy in preventing, detecting symptoms, and home-managing COVID-19.


title: Characteristics and risk factors for 28-day mortality of hospital acquired fungemias in ICUs: data from the EUROBACT study.

text: BACKGROUND To characterize and identify prognostic factors for 28-day mortality among patients with hospital-acquired fungemia (HAF) in the Intensive Care Unit (ICU). METHODS A sub-analysis of a prospective, multicenter non-representative cohort study conducted in 162 ICUs in 24 countries. RESULTS Of the 1156 patients with hospital-acquired bloodstream infections (HA-BSI) included in the EUROBACT study, 96 patients had a HAF. Median time to its diagnosis was 20 days (IQR 10.5-30.5) and 9 days (IQR 3-15.5) after hospital and ICU admission, respectively. Median time to positivity of blood culture was longer in fungemia than in bacteremia (48.7 h vs. 38.1 h; p = 0.0004). Candida albicans was the most frequent fungus isolated (57.1%), followed by Candida glabrata (15.3%) and Candida parapsilosis (10.2%). No clear source of HAF was detected in 33.3% of the episodes and it was catheter-related in 21.9% of them. Compared to patients with bacteremia, HAF patients had a higher rate of septic shock (39.6% vs. 21.6%; p = 0.0003) and renal dysfunction (25% vs. 12.4%; p = 0.0023) on admission and a higher rate of renal failure (26% vs. 16.2%; p = 0.0273) at diagnosis. Adequate treatment started within 24 h after blood culture collection was less frequent in HAF patients (22.9% vs. 55.3%; p < 0.001). The 28-day all cause fatality was 40.6%. According to multivariate analysis, only liver failure (OR 14.35; 95% CI 1.17-175.6; p = 0.037), need for mechanical ventilation (OR 8.86; 95% CI 1.2-65.24; p = 0.032) and ICU admission for medical reason (OR 3.87; 95% CI 1.25-11.99; p = 0.020) were independent predictors of 28-day mortality in HAF patients. CONCLUSIONS Fungi are an important cause of hospital-acquired BSI in the ICU. Patients with HAF present more frequently with septic shock and renal dysfunction on ICU admission and have a higher rate of renal failure at diagnosis. HAF are associated with a significant 28-day mortality rate (40%), but delayed adequate antifungal therapy was not an independent risk factor for death. Liver failure, need for mechanical ventilation and ICU admission for medical reason were the only independent predictors of 28-day mortality.


Coronavirus 2020.


title: Nutraceuticals and nutritional supplements for the treatment of bipolar disorder: protocol for a systematic review.

text: INTRODUCTION First line pharmacological treatments for bipolar disorder (BD) can leave shortfalls in recovery leading to patients seeking alternative and adjunctive treatments such as nutraceuticals. This protocol for a systematic review and proposed meta-analysis aims to answer the research question: in patients with BD, how does use of nutraceutical treatments compare with placebo in reducing depressive and mania symptoms? METHODS AND ANALYSIS Clinical trials will be identified through database searches using PubMed via PubMed, EMBASE via embase.com, Cochrane Central Register of Controlled Clinical Trials (CENTRAL) via cochranelibrary.com and CINAHL Complete via EBSCO. Search terms for BD and specific nutraceuticals (75 total search terms) will be used. Double-blind, randomised, controlled, clinical trials of adults with BD will be included in the review. Risk of bias will be assessed using the Cochrane Collaboration's tool for assessing risk of bias in randomised trials. ETHICS AND DISSEMINATION This review will only look at published data (already reviewed for ethical compliance); therefore, ethical approval is not required. We aim to publish the systematic review in a peer-reviewed journal and present at conferences. PROSPERO REGISTRATION NUMBER CRD42019100745.


title: Hyperoxic resuscitation after hypoxia-ischemia induces cerebral inflammation that is attenuated by tempol in a reporter mouse model with very young mice.

text: BACKGROUND Oxygen supplementation is still part of international resuscitation protocols for premature children. Mechanisms for tissue damage by hypoxia/ischemia in the extreme premature involve inflammation. AIM AND METHOD To study cerebral inflammation after hypoxia/ischemia and oxygen treatment in the premature, we measured NF-κB activity in 5-day-old transgenic reporter mice in response to experimental hypoxia/ischemia. results were correlated to cerebral histological evaluation and plasma cytokine levels. A treatment strategy with the antioxidant tempol was tested. RESULTS One day after hypoxia/ischemia NF-κB activation was increased compared to controls [mean difference: 10.6±4.6% (P=0.03)]. Exposure to 100% oxygen after hypoxia/ischemia further increased NF-κB activation compared to hypoxia/ischemia alone [mean difference: 15.0±5.5% (P=0.01)]. Histological changes in the brain were positively correlated with NF-κB activity (P<0.001), but we found no significant difference in tissue damage between resuscitation with air and resuscitation with pure oxygen. Administration of tempol reduced NF-κB activation [mean difference: 14.6±5.0% (P=0.01)] and the plasma level of cytokines; however, the histological damage score was not affected. CONCLUSION Cerebral inflammatory response after hypoxia/ischemia in a mouse model with immature brain development corresponding to human prematurity prior to 32 weeks' gestation was influenced by administration of oxygen. Tempol treatment attenuated inflammation but did not reduce the extent of histological cerebral damage.


title: Role of perforin secretion from CD8+ T-cells in neuronal cytotoxicity in multiple sclerosis.

text: OBJECTIVES Multiple sclerosis (MS) is the most prevalent autoimmune disease of the central nervous system, and is characterized by inflammation and myelin damage. The immune system initiates the autoimmune response, although the mechanisms of neuronal damage have not been elucidated. The purpose of the present study was to investigate autoreactive CD4+ and CD8+ T lymphocytes, in conjunction with other inflammatory cells and cytokines in active MS lesions. METHODS EAE animal models was established by plantar injections of MBP (200 μg per rat). Purified CD4+ or CD8+ T-cells were isolated from heparinized peripheral blood (EAE animals and control animals) via negative selection. To examine effects of presence of autoreactive CD4+ and CD8+ T lymphocytes, we carried out ELISA, Western blot analysis and TUNEL. In addition, we examined the direct effects of various factors on neuronal cell death using MTT assay. RESULTS The data revealed that CD8+ T-cells were more toxic to neurons compared to CD4+ T-cells, in both the MBP and EAE conditions. Bax was greater increased when neurons were co-cultured with CD8+ T-cells in the MBP group. There is a significant increase in IL-17 secretion by CD4+ T-cells in both the MBP group and EAE group. Neuronal viability were affected by Perforin (1.5 μg/mL). CONCLUSION The present study extends previous research by demonstrating the role of CD8+ T-cells in MS and supports perforin secretion by CD8+ T-cells as a potential therapeutic factor. Furthermore, we determined that CD4+ T-cells can enhance CD8+ T-cell neuronal cytotoxicity via induction of intense inflammation.


title: Selective approach for upper rectal cancer treatment: total mesorectal excision and preoperative chemoradiation are seldom necessary.

text: BACKGROUND The implementation of preoperative chemoradiation combined with total mesorectal excision has reduced local recurrence rates in rectal cancer. However, the use of both types of treatment in upper rectal cancer is controversial. OBJECTIVE The purpose of this work was to assess oncological results after radical resection of upper rectal cancers compared with sigmoid, middle, and lower rectal cancers and to determine risk factors for local recurrence in upper rectal cancer. DESIGN This was a retrospective analysis of prospectively collected data. SETTINGS This study was conducted in a tertiary care referral hospital in Valencia, Spain. PATIENTS Analysis included 1145 patients who underwent colorectal resection with primary curative intent for primary sigmoid (n = 450), rectosigmoid (n = 70), upper rectal (n = 178), middle rectal (n = 186), or lower rectal (n = 261) cancer. MAIN OUTCOME MEASURES Oncological results, including local recurrence, disease-free survival, and cancer-specific survival, were compared between the different tumor locations. Univariate and multivariate analyses were performed to identify risk factors for local recurrence in upper rectal cancer. RESULTS A total of 147 patients (82.6%) with upper rectal tumors underwent partial mesorectal excision, and only 10 patients (5.6%) of that group received preoperative chemoradiation. The 5-year actuarial local recurrence, disease-free survival, and cancer-specific survival rates for upper rectal tumors were 4.9%, 82.0%, and 91.6%. Local recurrence rates showed no differences when compared among all of the locations (p = 0.20), whereas disease-free survival and cancer-specific survival were shorter for lower rectal tumors (p = 0.006; p = 0.003). The only independent risk factor for local recurrence in upper rectal cancer was an involved circumferential resection margin at pathologic analysis (HR, 14.23 (95% CI, 2.75-73.71); p = 0.002). LIMITATIONS This was a single-institution, retrospective study. CONCLUSIONS Most upper rectal tumors can be treated with partial mesorectal excision without the systematic use of preoperative chemoradiation. Involvement of the mesorectal fascia was the only independent risk factor for local recurrence in these tumors.


title: Cardiopulmonary changes induced by retroperitoneal insufflation in healthy dogs in sternal recumbency with the abdomen unsupported.

text: This study assessed the effects of retroperitoneal carbon dioxide (CO2) insufflation on cardiopulmonary variables and intra-abdominal pressure (IAP) in mechanically ventilated dogs in sternal recumbency with the abdomen unsupported, following placement of a positioning kit and towels under the pectoral and pelvic regions. General anesthesia was induced in eight healthy adult male Beagles. A Swan-Ganz catheter was placed in the pulmonary artery via the jugular vein for cardiac output measurements. A Foley urethral catheter was placed to monitor transvesical IAP. A 10 mm balloon blunt-tip trocar was inserted into the retroperitoneal space. With a fixed respiratory rate and tidal volume by mechanical ventilation, insufflation pressure was sequentially increased from 0 to 10 mmHg in 5 mmHg increments, followed by desufflation. All variables were measured before insufflation, 5 min after the establishment of each insufflation pressure, and after desufflation. At 10 mmHg, the IAP was nearly equal to insufflation pressure. Cardiopulmonary function was not compromised at any point, although the cardiac index (CI), heart rate, mean arterial pressure (MAP), and mean pulmonary arterial pressure increased within normal ranges. End-tidal CO2 concentration, arterial CO2 partial pressure, and oxygen delivery index (DO2I) increased, whereas pH decreased, at 10 mmHg. CI, MAP, and DO2I did not recover to baseline after decompression. Thus, retroperitoneal CO2 insufflation up to 10 mmHg is well tolerated by mechanically ventilated dogs positioned in sternal recumbency with the abdomen unsupported, although sympathetic changes may occur with an insufflation pressure increase.


title: Thoracoscopic purse string technique for minimally invasive Ivor Lewis esophagectomy.

text: OBJECTIVE Thoracolaparoscopic esophagectomy with chest anastomosis (TLE-chest) is increasingly performed for middle and lower esophageal cancer; however, gastroesophageal anastomosis for this surgery remains both challenging and inefficient. To address this issue, we previously reported our MIE technique with Ivor-Lewis anastomosis. Here we present the video to introduce our TLE-chest operation procedures. METHODS TLE-chest with a combined thoracoscopic and laparoscopic technique was performed by one group of surgeons. From October 2011 to September 2013, 80 esophageal cancer patients were treated with TLE-chest using this improved anastomotic technique. RESULTS The surgery was successful for all patients, although the anastomosis in one patient required intraoperative manual repair. No patients required open conversion. In this video, dissociation of stomach, and dissection of lymph nodes, creation of gastric tube and staple line embedding, jejunostomy were carried out by laparoscopic surgery. Dissection of esophageal cancer and mediastinal lymph nodes were done through rib 3 or 4 by a 3-4 cm video-assisted right anterior minithoracotomy, then esophago-gastric anastomosis was performed in right thoracic cavity This video shows the R0 resection of T3N0M0 esophageal cancer. Totally, 36 lymph nodes were dissected, including 21 mediastinal lymph nodes and 15 abdominal lymph nodes. The patient recovered well and was discharged on day 8 after the surgery, with good short term outcomes. CONCLUSIONS A safe, cost effective purse string stapled anastomotic technique has been presented for TLE-chest in our video. It is consistent with the oncology principles.


title: The Effect of Perioperative Ischemia and Reperfusion on Multiorgan Dysfunction following Abdominal Aortic Aneurysm Repair.

text: Abdominal aortic aneurysms (AAAs) are relatively common and are potentially life-threatening medical problems. The aim of this review is to provide an overview of the effect of I/R injury on multiorgan failure following AAA repair. The PubMed, CINAHL, EMBASE, Medline, Cochrane Review, and Scopus databases were comprehensively searched for articles concerning the pathophysiology of I/R and its systemic effects. Cross-referencing was performed using the bibliographies from the articles obtained. Articles retrieved were restricted to those published in English. One of the most prominent characteristics of AAA open repair is the double physiological phenomenon of ischemia-reperfusion (I/R) that happens either at the time of clamping or following the aortic clamp removal. Ischemia-reperfusion injury causes significant pathophysiological disturbances to distant organs, increasing the possibility for postoperative multiorgan failure. Although tissue injury is mediated by diverse mechanisms, microvascular dysfunction seems to be the final outcome of I/R.


Covid-19 pandemic has derailed progress on sustainable development goals, says WHO.


title: Effectiveness and Safety of Intrathecal Ziconotide: Interim Analysis of the Patient Registry of Intrathecal Ziconotide Management (PRIZM).

text: BACKGROUND The Patient Registry of Intrathecal Ziconotide Management (PRIZM) evaluated long-term effectiveness, safety, and tolerability of intrathecal ziconotide treatment in clinical practice. METHODS Patient Registry of Intrathecal Ziconotide Management was an open-label, long-term, multicenter, observational study of adult patients with severe chronic pain. This interim analysis (data through July 10, 2015) of ziconotide as the first vs. not first intrathecal agent in pump included change from baseline in the Numeric Pain Rating Scale (NPRS; primary efficacy measure) and Patient Global Impression of Change (PGIC) scores. RESULTS Enrollment closed at 93 patients; data collection was ongoing at the time of this interim analysis. Fifty-one patients (54.8%) received ziconotide as the first agent in pump (FIP+), whereas 42 (45.2%) did not (FIP-). Mean (SD) baseline NPRS scores were 7.4 (1.9) and 7.9 (1.6) in FIP+ and FIP- patients, respectively. Mean (SEM) percentage changes in NPRS scores were -29.4% (5.5%) in FIP+ patients (n = 26) and +6.4% (7.7%) in FIP- patients (n = 17) at month 6 and -34.4% (9.1%) in FIP+ patients (n = 14) and -3.4% (10.2%) in FIP- patients (n = 9) at month 12. Improvement from baseline, measured by PGIC score, was reported in 69.2% of FIP+ (n = 26) and 35.7% of FIP- (n = 14) patients at month 6 and 85.7% of FIP+ (n = 7) and 71.4% of FIP- (n = 7) patients at month 12. The most common adverse events (≥ 10% of patients overall as of the data cut) were nausea (19.6% vs. 7.1% of FIP+ vs. FIP- patients, respectively), confusional state (9.8% vs. 11.9%), and dizziness (13.7% vs. 7.1%). CONCLUSIONS Greater improvements in efficacy outcomes were observed when ziconotide was initiated as first-line intrathecal therapy vs. not first intrathecal agent in pump. The adverse event profile was consistent with the ziconotide prescribing information.


title: Comparison of diclofenac with apigenin-glycosides rich Clinacanthus nutans extract for amending inflammation and catabolic protease regulations in osteoporotic-osteoarthritis rat model.

text: BACKGROUND Osteoporotic-osteoarthritis is an incapacitating musculoskeletal illness of the aged. OBJECTIVES The anti-inflammatory and anti-catabolic actions of Diclofenac were compared with apigenin-C-glycosides rich Clinacanthus nutans (CN) leaf extract in osteoporotic-osteoarthritis rats. METHODS Female Sprague Dawley rats were randomized into five groups (n = 6). Four groups were bilateral ovariectomised for osteoporosis development, and osteoarthritis were induced by intra-articular injection of monosodium iodoacetate (MIA) into the right knee joints. The Sham group was sham-operated, received saline injection and deionized drinking water. The treatment groups were orally given 200 or 400 mg extract/kg body weight or 5 mg diclofenac /kg body weight daily for 28 days. Articular cartilage and bone changes were monitored by gross and histological structures, micro-CT analysis, serum protein biomarkers, and mRNA expressions for inflammation and catabolic protease genes. RESULTS HPLC analysis confirmed that apigenin-C-glycosides (shaftoside, vitexin, and isovitexin) were the major compounds in the extract. The extract significantly and dose-dependently reduced cartilage erosion, bone loss, cartilage catabolic changes, serum osteoporotic-osteoarthritis biomarkers (procollagen-type-II-N-terminal-propeptide PIINP; procollagen-type-I-N-terminal-propeptide PINP; osteocalcin), inflammation (IL-1β) and mRNA expressions for nuclear-factor-kappa-beta NF-κβ, interleukin-1-beta IL-1β, cyclooxygenase-2; and matrix-metalloproteinase-13 MMP13 activities, in osteoporotic-osteoarthritis rats comparable to Diclofenac. CONCLUSION This study demonstrates that apigenin-C-glycosides at 400 mg CN extract/kg (about 0.2 mg apigenin-equivalent/kg) is comparable to diclofenac in suppressing inflammation and catabolic proteases for osteoporotic-osteoarthritis prevention. Graphical abstract.


Unlocking towns and cities: COVID-19 exit strategy.


title: A novel surgical technique: single-incision transumbilical laparoscopic Roux-en-Y gastric bypass.

text: Conventional laparoscopic Roux-en-Y gastric bypass (LRYGB) is a gold standard for bariatric surgery, but the procedure requires five to seven incisions for placement of multiple trocars and thus may produce less-than-ideal cosmetic results. We have developed a new approach, single-incision transumbilical LRYGB (SITU-LRYGB) to treat morbid obesity. We compared the surgical results and patient satisfaction in a study of five-port LRYGB and SITU-LRYGB. Fifty morbidly obese patients (14 males, 36 females) underwent either Roux-en-Y gastric bypass with five-port LRYGB or the SITU-LRYGB approach. During the operation, we used a novel intraoperative liver traction method with a "liver suspension tape" that we specifically designed for SITU-LRYGB. Compared to five-port surgery with SITU-LRYGB, there were no intraoperative complications, wound healing was excellent, and there was no abdominal scarring. SITU surgical time was longer than that with five-port LRYGB (99.8 vs. 67.6 min, P < 0.001). Patients treated with the five-port method were more obese than those in the SITU group (127.9 vs. 112.4 kg, P = 0.016). After the bariatric surgery, no difference in comorbidity was found in both groups. Patient satisfaction was greater with SITU than with the five-port method (4.48 vs. 3.96, P = 0.006). Roux-en-Y gastric bypass can be successfully achieved via a single umbilical incision, a method that provides a short operative time and good recovery and eliminates abdominal scarring.


COVID-19: Perspective of a Dean of Dentistry.


Non-steroidal anti-inflammatory drugs and covid-19.


Viropathic multinuclear syncytial giant cells in bronchial fluid from a patient with COVID-19.


title: Endovascular approach and technique for treatment of transverse-sigmoid dural arteriovenous fistula with cortical reflux: the importance of venous sinus sacrifice.

text: BACKGROUND Treatment of dural arteriovenous fistula involving the transverse-sigmoid region with cortical reflux is complex and treatment options may require sacrifice of the fistulous segment of the sinus. OBJECTIVE To review our results in this subset of patients and describe current endovascular decision-making and approaches. METHODS We reviewed cases of endovascular sinus sacrifice for dural fistulas at our institution from 2007 to 2012. Demographic, decision-making, technical and outcome data were collected. RESULTS Seven patients were identified who underwent endovascular sinus sacrifice for treatment of dural fistula during this 4-year period. Determination of the fistulous sinus segment was based on the pattern of cortical drainage. Endovascular access to the sinus was achieved by transarterial, transvenous or via open surgery in one case. Complete cure of the target fistula was obtained in all cases. One patient had transient post-procedure headache. There were no hemorrhages, new neurological deficits or signs of increased intracranial pressure. Six of the seven patients had angiographic follow-up at least 6 months after treatment with no recurrence. CONCLUSIONS Fistulas of the transverse-sigmoid sinuses with cortical reflux may require sacrifice of the parent sinus for cure. Defining the fistulous segment and occluding this segment deliberately, completely and precisely is essential for cure. Several modalities and approaches can be used to achieve this. For properly selected patients, cure of the lesions can be achieved with this method with low risk of morbidity.


title: Increased serum autotaxin levels in hepatocellular carcinoma patients were caused by background liver fibrosis but not by carcinoma.

text: BACKGROUND Controversy exists as to whether autotaxin (ATX) may be importantly associated with pathophysiology of hepatocellular carcinoma (HCC). METHODS We evaluated serum ATX levels and its mRNA expression in consecutive 148 HCC patients treated with radiofrequency ablation (RFA) and 30 patients with hepatic resection. RESULTS Although increased serum ATX levels were observed in almost all the patients treated with RFA, they were not reduced after RFA. Furthermore, serum ATX levels were associated not with tumor burden but with the parameters predicting for liver fibrosis, such as liver stiffness values. Then, in surgically-treated patients, there was no significant correlation between serum ATX levels and ATX mRNA expression levels in HCC tissues. Notably, ATX mRNA expression levels in HCC tissues were not higher than those in peri-tumorous tissues. Finally, serum ATX levels in surgically-treated HCC patients were rather correlated with ATX mRNA expression levels in peri-tumorous tissues as well as with liver fibrosis stage. CONCLUSION The increase in serum ATX levels in HCC patients may not be caused by abundant ATX production in HCC tissues but by fibrosis in the background livers.


title: Combined low-dose contrast-enhanced MR angiography and perfusion for acute ischemic stroke at 3T: A more efficient stroke protocol.

text: BACKGROUND AND PURPOSE There is need to improve image acquisition speed for MR imaging in evaluation of patients with acute ischemic stroke. The purpose of this study was to evaluate the feasibility of a 3T MR stroke protocol that combines low-dose contrast-enhanced MRA and dynamic susceptibility contrast perfusion, without additional contrast. METHODS Thirty patients with acute stroke who underwent 3T MR imaging followed by DSA were retrospectively enrolled. TOF-MRA of the neck and brain and 3D contrast-enhanced MRA of the craniocervical arteries were obtained. A total of 0.1 mmol/kg of gadolinium was used for both contrast-enhanced MRA (0.05 mmol/kg) and dynamic susceptibility contrast perfusion (0.05 mmol/kg) (referred to as half-dose). An age-matched control stroke population underwent TOF-MRA and full-dose (0.1 mmol/kg) dynamic susceptibility contrast perfusion. The cervicocranial arteries were divided into 25 segments. Degree of arterial stenosis on contrast-enhanced MRA and TOF-MRA was compared with DSA. Time-to-maximum maps (>6 seconds) were evaluated for image quality and hypoperfusion. Quantitative analysis of arterial input function curves, SNR, and maximum T2* effects were compared between half- and full-dose groups. RESULTS The intermodality agreements (k) for arterial stenosis were 0.89 for DSA/contrast-enhanced MRA and 0.63 for DSA/TOF-MRA. Detection specificity of >50% arterial stenosis was lower for TOF-MRA (89%) versus contrast-enhanced MRA (97%) as the result of overestimation of 10% (39/410) of segments by TOF-MRA. The DWI-perfusion mismatch was identified in both groups with high interobserver agreement (r = 1). There was no significant difference between full width at half maximum of the arterial input function curves (P = .14) or the SNR values (0.6) between the half-dose and full-dose groups. CONCLUSIONS In patients with acute stroke, combined low-dose contrast-enhanced MRA and dynamic susceptibility contrast perfusion at 3T is feasible and results in significant scan time and contrast dose reductions.


title: In Vivo Impedance Characterization of Cortical Recording Electrodes Shows Dependence on Electrode Location and Size.

text: OBJECTIVE Neural prostheses are improving the quality of life for those suffering from neurological impairments. Electrocorticography electrodes located in subdural, epidural, and intravascular positions show promise as long-term neural prostheses. However, chronic implantation affects the electrochemical environments of these arrays. METHODS In the present work, the effect of electrode location on the electrochemical properties of the interface was compared. The impedances of the electrode arrays were measured using electrochemical impedance spectroscopy in vitro in saline and in vivo four-week postimplantation. RESULTS There was not a significant effect of electrode location (subdural, intravascular, or epidural) on the impedance magnitude, and the effect of the electrode size on the impedance magnitude was frequency dependent. There was a frequency-dependent statistically significant effect of electrode location and electrode size on the phase angles of the three arrays. The subdural and epidural arrays showed phase shifts closer to -90° indicating the capacitive nature of the interface in these locations. The impact of placing electrodes within a blood vessel and adjacent to the blood vessel wall was most obvious when looking at the phase responses at frequencies below 10 kHz. CONCLUSION Our results show that intravascular electrodes, like those in subdural and epidural positions, show electrical properties that are suitable for recording. These results provide support for the use of intravascular arrays in clinically relevant neural prostheses and diagnostic devices. SIGNIFICANCE Comparison of electrochemical impedance of the epidural, intravascular, and subdural electrode array showed that all three locations are possible placement options, since impedances are in comparable ranges.


title: Safety and efficacy of a novel linear staple device with bioabsorbable polyglicolic acid felt in laparoscopic colorectal surgery.

text: INTRODUCTION Laparoscopic surgery is widely used for the treatment of colorectal cancer, but it is often associated with postoperative anastomotic complications. Generally, gastrointestinal anastomosis for colorectal surgery is performed using mechanical anastomosis with a double stapling technique. Using the automatic suture device with bioabsorbable polyglycolic acid (PGA) felt is expected to adequately reinforce staple lines on fragile tissue, helping to prevent anastomotic complications, including leakage. METHODS This study included 17 patients who underwent laparoscopic surgery after a diagnosis of colorectal cancer. The rectosigmoidal colon was resected toward the dentate line with a novel automatic PGA-felt suture device. RESULTS None of the patients had any postoperative bleeding, and none developed grade III or higher postoperative complications based on the Clavien-Dindo classification. When the sigmoid colon, rectosigmoid, or rectum was anastomosed, holding the excess portion of the PGA felt, stapled with the automatic PGA-felt suture device, allowed us to adequately maneuver the part of the colon or rectum to be anastomosed. With this technique, we could easily and safely insert and remove the automatic anastomotic device. When the lower rectum was resected in a planned, two-step operation, the orientation of the PGA felt helped to determine the direction in which the automatic suture device was to be inserted in the second step. Thus, the resected rectum could easily be stapled in a straight line. CONCLUSION The automatic PGA-felt suture device is safe and effective for colorectal resections and anastomoses.


title: Intraparenchymal Hyperattenuations on Flat-Panel CT Directly After Mechanical Thrombectomy are Restricted to the Initial Infarct Core on Diffusion-Weighted Imaging.

text: PURPOSE The presence of intraparenchymal hyperattenuations (IPH) on flat-panel computed tomography (FP-CT) after endovascular recanalization in stroke patients is a common phenomenon. They are thought to occur in ischemic areas with breakdown of the blood-brain barrier but previous studies that investigated a mutual interaction are scarce. We aimed to assess the relationship of IPH localization with prethrombectomy diffusion-weighted imaging (DWI) lesions. METHODS This retrospective multicenter study included 27 acute stroke patients who underwent DWI prior to FP-CT following mechanical thrombectomy. After software-based coregistration of DWI and FP-CT, lesion volumetry was conducted and overlapping was analyzed. RESULTS Two different patterns were observed: IPH corresponding to the DWI lesion and IPH exceeding the DWI lesion. The latter showed demarcated infarction of DWI exceeding IPH at 24 h. No major hemorrhage following IPH was observed. Most IPH were manifested within the basal ganglia and insular cortex. CONCLUSION The IPH primarily appeared within the initial ischemic core and secondarily within the penumbral tissue that progressed to infarction. The IPH represent the minimum final infarct volume, which may help in periinterventional decision making.


title: Neonatal Pneumothorax Pressures Surpass Higher Threshold in Lung Recruitment Maneuvers: An In Vivo Interventional Study.

text: BACKGROUND Causing pneumothorax is one of the main concerns of lung recruitment maneuvers in pediatric patients, especially newborns. Therefore, these maneuvers are not performed routinely during anesthesia. Our objective was to determine the pressures that cause pneumothorax in healthy newborns by a prospective experimental study of 10 newborn piglets (<48 h old) with healthy lungs under general anesthesia. METHODS The primary outcome was peak inspiratory pressure (PIP) causing pneumothorax. Animals under anesthesia and bilateral chest tube catheterization were randomly allocated to 2 groups: one with PEEP and fixed inspiratory driving pressure of 15 cm H2O (PEEP group) and the second one with PEEP = 0 cm H2O and non-fixed inspiratory driving pressure (zero PEEP group). In both groups, the ventilation mode was pressure-controlled, and PIP was raised at 2-min intervals, with steps of 5 cm H2O until air leak was observed through the chest tubes. The PEEP group raised PIP through 5-cm H2O PEEP increments, and the zero PEEP group raised PIP through 5-cm H2O inspiratory driving pressure increments. RESULTS Pneumothorax was observed with a PIP of 90.5 ± 15.7 cm H2O with no statistically significant differences between the PEEP group (92 ± 14.8 cm H2O) and the zero PEEP group (89 ± 18.2 cm H2O). The zero PEEP group had hypotension, with a PIP of 35 cm H2O; the PEEP group had hypotension, with a PIP of 60 cm H2O (P = .01). The zero PEEP group presented bradycardia, with PIP of 40 cm H2O; the PEEP group presented bradycardia, with PIP of 70 cm H2O (P = .002). CONCLUSIONS Performing recruitment maneuvers in newborns without lung disease is a safe procedure in terms of pneumothorax. Pneumothorax does not seem to occur in the clinically relevant PIPs of <50 cm H2O. Hemodynamic impairment may occur with high driving pressures. More studies are needed to determine the exact hemodynamic impact of these procedures and pneumothorax PIP in poorly compliant lungs.


title: SARS-like WIV1-CoV poised for human emergence.

text: Outbreaks from zoonotic sources represent a threat to both human disease as well as the global economy. Despite a wealth of metagenomics studies, methods to leverage these datasets to identify future threats are underdeveloped. In this study, we describe an approach that combines existing metagenomics data with reverse genetics to engineer reagents to evaluate emergence and pathogenic potential of circulating zoonotic viruses. Focusing on the severe acute respiratory syndrome (SARS)-like viruses, the results indicate that the WIV1-coronavirus (CoV) cluster has the ability to directly infect and may undergo limited transmission in human populations. However, in vivo attenuation suggests additional adaptation is required for epidemic disease. Importantly, available SARS monoclonal antibodies offered success in limiting viral infection absent from available vaccine approaches. Together, the data highlight the utility of a platform to identify and prioritize prepandemic strains harbored in animal reservoirs and document the threat posed by WIV1-CoV for emergence in human populations.


title: Unerupted teeth associated with dentigerous cysts and treated with coronectomy: mini case series.

text: There is a resurgence of interest in coronectomy, but its appropriate application in the management of third molar teeth has yet to be defined. Dentigerous cysts associated with unerupted teeth are most commonly associated with mandibular third molars. In this case series we evaluate outcome after coronectomy of teeth with associated dentigerous cysts in cases where the inferior dental nerve was thought to be at risk, or there was an increased risk of mandibular fracture. We retrospectively studied 21 consecutive patients treated by coronectomy for dentigerous cysts at the Oral Surgery Department at Guy's Hospital. The most commonly affected teeth were mandibular third molars (20/21). One patient had permanent injury to the inferior dental nerve, but no mandibular fracture or recurrence of cyst was reported. One patient required secondary retrieval of the retained root because of eruption. Coronectomy of unerupted teeth associated with dentigerous cysts is an effective treatment when there is high risk of injury to the inferior dental nerve injury or potential for mandibular fracture. Further work with larger numbers and longer follow-up is required to discover the long-term outcome of the electively retained root.


How to Deal with COVID-19 Pandemic: A Radiologic Approach.


title: Amicus or Adversary Revisited: Platelets in Acute Lung Injury and Acute Respiratory Distress Syndrome.

text: Platelets are essential cellular effectors of hemostasis and contribute to disease as circulating effectors of pathologic thrombosis. These are their most widely known biologic activities. Nevertheless, recent observations demonstrate that platelets have a much more intricate repertoire beyond these traditional functions and that they are specialized for contributions to vascular barrier integrity, organ repair, antimicrobial host defense, inflammation, and activities across the immune continuum. Paradoxically, on the basis of clinical investigations and animal models of disease, some of these newly discovered activities of platelets appear to contribute to tissue injury. Studies in the last decade indicate unique interactions of platelets and their precursor, the megakaryocyte, in the lung and implicate platelets as essential effectors in experimental acute lung injury and clinical acute respiratory distress syndrome. Additional discoveries derived from evolving work will be required to precisely define the contributions of platelets to complex subphenotypes of acute lung injury and to determine if these remarkable and versatile blood cells are therapeutic targets in acute respiratory distress syndrome.


title: Inhibiting the Physiological Stress Effects of a Sustained Attention Task on Shoulder Muscle Activity.

text: OBJECTIVE The objective of this study was to investigate if a breathing technique could counteract the effects of hyperventilation due to a sustained attention task on shoulder muscle activity. BACKGROUND The trend towards higher levels of automation in industry is increasing. Consequently, manufacturing operators often monitor automated process for long periods of their work shift. Prolonged monitoring work requires sustained attention, which is a cognitive process that humans are typically poor at and find stressful. As sustained attention becomes an increasing requirement of manufacturing operators' job content, the resulting stress experienced could contribute to the onset of many health problems, including work related musculoskeletal disorders (WRMSDs). METHODS The SART attention test was completed by a group of participants before and after a breathing intervention exercise. The effects of the abdominal breathing intervention on breathing rate, upper trapezius muscle activity and end-tidal CO₂ were evaluated. RESULTS The breathing intervention reduced the moderation effect of end-tidal CO₂ on upper trapezius muscle activity. CONCLUSIONS Abdominal breathing could be a useful technique in reducing the effects of sustained attention work on muscular activity. APPLICATION This research can be applied to highly-automated manufacturing industries, where prolonged monitoring of work is widespread and could, in its role as a stressor, be a potential contributor to WRMSDs.


title: Results of the ALSTER BP real-world registry on renal denervation employing the Symplicity system.

text: AIMS To prove the efficacy and safety of renal sympathetic denervation as a new treatment option for patients suffering from resistant hypertension in a real-world setting. METHODS AND RESULTS This single-centre real-world registry included 93 patients who underwent renal denervation employing the Symplicity system. Patients were followed for six months. The patient cohort was divided into early responders with a reduction of office systolic blood pressure >10 mmHg three months after the procedure (n=53, 57%), late responders (six months after the procedure, n=16, 17%) and non-responders (n=24, 26%). After six months, systolic blood pressure was lowered by 46±2.9 mmHg (mean±SEM, p<0.001), 31±3.4 mmHg (p<0.001) and 7.1±3.3 mmHg (p=0.79, ns), respectively. Ambulatory blood pressure monitoring also showed a significant reduction in the early responder group (20±5.7 mmHg, p=0.002). We subjected eight patients to a re-do procedure which led to a significant reduction of blood pressure in another five patients after six months (63%). One patient in this cohort developed a one-sided renal artery stenosis associated with an increase in blood pressure. CONCLUSIONS This real-world analysis of renal sympathetic denervation confirms the procedure to be safe and efficient in the majority of patients. Non-responders may profit from a second ablation, arguing in favour of the hypothesis that the procedure did not destroy sufficient amounts of sympathetic innervation in these patients. However, repeated denervations may also increase side effects.


title: Psychological impact of COVID-19 on ophthalmologists-in-training and practising ophthalmologists in India.

text: Purpose To evaluate the psychological impact of the COVID 19 crisis on ophthalmologists-in-training and practising ophthalmologists during lockdown in India. Methods An online survey was completed by ophthalmologists and ophthalmology trainees during the lockdown. The information collected included demographics (age, gender), domicile (state, union territory), current professional status (in training or practising), type of practice (solo, group, institutional, governmental, non-governmental), marital status (married, single), impact of COVID-19 on their training or practice, and impact on income and ability to meet living expenses. Psychological distress was assessed using the Patient Health Questionnaire-9 (PHQ-9). Results In all, 2,355 ophthalmologists responded. Mean age was 42.5 (range, 25-82 years; SD, 12.05) years. Of these, 1,332 (56.7%) were males; 475 (20.2%) were still not in practice; 366 (15.5%) were single; 1,244 (52.8%) felt that COVID-19 would impact on their training or professional work; and 869 (37%) had difficulty in meeting their living expenses. The mean PHQ-9 score was 3.98 (range, 0-27; SD, 4.65). In terms of psychological impact, 768 (32.6%) had some degree of depression; mild in 504 (21.4%), moderate in 163 (6.9%), and severe in 101 (4.3%). Multivariable analysis showed that depression was significantly higher at younger age. The odds of depression decreased by 3% with 1 year increase in age. It was higher in non-practicing ophthalmologists, especially those who were considerably worried about their training or professional growth, and those with difficulty in meeting living expenses. Conclusion A strikingly high proportion of ophthalmologists are psychologically affected and may require personalized mental health care.


title: Proposal of a formal gynecologic endoscopy curriculum.

text: As minimally invasive surgery becomes the standard of care in the United States and around the world, the formal training of endoscopic surgeons is an issue of growing concern. With the implementation of the American Association of Gynecologic Laparoscopists/Society of Reproductive Surgeons (AAGL/SRS)-sponsored fellowship training in gynecologic endoscopy and a growing number of hands-on courses, we have the challenge of credentialing and certifying future gynecologic endoscopists. The objective of this article is to propose and to illustrate a uniform standardized core curriculum for obstetrics and gynecology residents, fellows in AAGL/SRS-sponsored fellowship programs, and participants in postgraduate courses. Consisting of 3 discrete parts, this proposal addresses formal laparoscopic training for gynecologists, already implemented and available to general surgeons, and a novel proposition for core training in hysteroscopy. The curriculum is distributed in a quarterly system with specific educational objectives in each quarter. After quarters 1 and 2, an online examination is given; after quarter 3, participants are required to take and pass a hands-on examination at a specified testing facility; and at the end of quarter 4, participants must demonstrate leadership skills in the operating room and in a teaching capacity, and promote the principles of the AAGL.


title: Arthroscopic Superior Capsular Reconstruction With a Minimally Invasive Harvested Fascia Lata Autograft Produces Good Clinical Results.

text: Background Painful dysfunctional shoulders with irreparable rotator cuff tears (IRCTs) in active patients are a challenge. Arthroscopic superior capsular reconstruction (ASCR) is a new treatment option originally described using a fascia lata autograft harvested through an open approach. However, concerns about donor site morbidity have discouraged surgeons from using this type of graft. Hypothesis ASCR using a minimally invasive harvested fascia lata autograft produces good 6-month and 2-year shoulder outcomes in IRCTs, with low-impact thigh morbidity at 2 years. Study Design Case series; Level of evidence, 4. Methods From 2015 to 2016, a total of 22 consecutive patients (mean age, 64.8 ± 8.6 years) with chronic IRCTs (Hamada grade 1-2; Goutallier cumulative grade ≥3; Patte stage 1: 2 patients; Patte stage 2: 6 patients; Patte stage 3: 14 patients) underwent ASCR using a minimally invasive harvested fascia lata autograft. All patients completed preoperative and 6-month evaluations consisting of the Simple Shoulder Test (SST), subjective shoulder value (SSV), Constant score (CS), range of motion (ROM), acromiohumeral interval (AHI), and magnetic resonance imaging. Twenty-one patients completed the 2-year shoulder and donor site morbidity assessments. Results The mean active ROMs improved significantly (P < .001): elevation, from 74.8° ± 55.5° to 104.5° ± 41.9° (6 months) and 143.8° ± 31.7° (2 years); abduction, from 53.2° ± 43.3° to 86.6° ± 32.9° (6 months) and 120.7° ± 37.7° (2 years); external rotation, from 13.2° ± 18.4° to 27.0° ± 16.1° (6 months) and 35.6° ± 17.3° (2 years); and internal rotation, from 1.2 ± 1.5 points to 2.6 ± 1.5 points (6 months) and 3.8 ± 1.2 points (2 years). The mean functional shoulder scores improved significantly (P < .001): SST, from 2.1 ± 2.9 to 6.8 ± 3.5 (6 months) and 8.6 ± 3.5 (2 years); SSV, from 33.0% ± 17.4% to 55.7% ± 25.6% (6 months) and 70.0% ± 23.0% (2 years); CS, from 17.5 ± 13.4 to 42.5 ± 14.9 (6 months) and 64.9 ± 18.0 (2 years). The mean shoulder abduction strength improved significantly (P < .001) from 0.0 to 1.1 ± 1.4 kg (6 months) and 2.8 ± 2.6 kg (2 years). The mean AHI improved from 6.4 ± 3.3 mm to 8.0 ± 2.5 mm (6 months) and decreased to 7.1 ± 2.5 mm (2 years). This 0.7 ± 1.5-mm overall decrease was statistically significant (P = .042). At 6 months, 20 of 22 patients (90.9%) had no graft tears. At 2 years, 12 of 21 patients (57.1%) were bothered by their harvested thigh, 16 (76.2%) noticed donor site changes, 16 (76.2%) considered that the shoulder surgery's end result compensated for the thigh's changes, and 18 (85.7%) would undergo the same surgery again. Conclusion ASCR using a minimally invasive harvested fascia lata autograft produced good 6-month and 2-year shoulder outcomes in IRCTs, with low-impact thigh morbidity at 2 years.


Implementing a structured digital-based online pathology curriculum for trainees at the time of COVID-19.


title: 10 pearls for safe endoscopic skull base surgery.

text: The introduction of the endoscopic endonasal approach for the management of lesions of the skull base has produced a paradigm shift in the way complicated lesions of this complex anatomic location are managed. The endonasal approach provides the most direct route to the anterior cranial base and adjacent skull base locations. This article presents the 10 most important tenets that have proved useful to the authors regarding postoperative patient management and surgical practice.


Immunomodulation and infection: back to the future.


Ebola Virus in Breast Milk in an Ebola Virus-Positive Mother with Twin Babies, Guinea, 2015.


title: Chimeric feline coronaviruses that encode type II spike protein on type I genetic background display accelerated viral growth and altered receptor usage.

text: Persistent infection of domestic cats with feline coronaviruses (FCoVs) can lead to a highly lethal, immunopathological disease termed feline infectious peritonitis (FIP). Interestingly, there are two serotypes, type I and type II FCoVs, that can cause both persistent infection and FIP, even though their main determinant of host cell tropism, the spike (S) protein, is of different phylogeny and displays limited sequence identity. In cell culture, however, there are apparent differences. Type II FCoVs can be propagated to high titers by employing feline aminopeptidase N (fAPN) as a cellular receptor, whereas the propagation of type I FCoVs is usually difficult, and the involvement of fAPN as a receptor is controversial. In this study we have analyzed the phenotypes of recombinant FCoVs that are based on the genetic background of type I FCoV strain Black but encode the type II FCoV strain 79-1146 S protein. Our data demonstrate that recombinant FCoVs expressing a type II FCoV S protein acquire the ability to efficiently use fAPN for host cell entry and corroborate the notion that type I FCoVs use another main host cell receptor. We also observed that recombinant FCoVs display a large-plaque phenotype and, unexpectedly, accelerated growth kinetics indistinguishable from that of type II FCoV strain 79-1146. Thus, the main phenotypic differences for type I and type II FCoVs in cell culture, namely, the growth kinetics and the efficient usage of fAPN as a cellular receptor, can be attributed solely to the FCoV S protein.


title: The associations of acceptance with quality of life and mental health following spinal cord injury: a systematic review.

text: STUDY DESIGN Systematic review. OBJECTIVES To identify, critically appraise, and synthesize research findings on the associations between acceptance, quality of life (QOL), and mental health outcomes in individuals living with spinal cord injury (SCI). METHODS Five databases (PubMed, PsycINFO, Embase, Web of Science, and Scopus) were systematically searched. Studies were included if they provided findings on the association between acceptance and QOL, mental health outcomes, or both in an SCI population aged 16 years or older. Only peer-reviewed original quantitative and qualitative studies were included. Screening, quality assessment, and data extraction were conducted independently by two researchers. Findings were tabulated and synthesized by outcome. RESULTS Forty-one studies were included. Greater acceptance was consistently associated with greater global and psychological QOL, life satisfaction, sense of well-being, mental health, and with lower levels of depression and anxiety. Inconsistent evidence was found with regards to social QOL and post-traumatic stress disorder. Acceptance was generally not associated with adjustment outcomes further than 2 years into the future. Study quality of the quantitative studies was mostly fair (n = 17) followed by good (n = 13), and poor (n = 9). CONCLUSION Health-care professionals may regard acceptance as a psychological resource they can aim to support in improving QOL and mental health following SCI. A range of methodological and conceptual limitations were present in the research. Future studies should prioritize longitudinal designs, consider dyadic effects, explore subjective meaning(s) of acceptance, and investigate the effectiveness of therapeutic approaches that stimulate the acceptance process.


title: Apixaban compared with warfarin in patients with atrial fibrillation and previous stroke or transient ischaemic attack: a subgroup analysis of the ARISTOTLE trial.

text: BACKGROUND In the ARISTOTLE trial, the rate of stroke or systemic embolism was reduced by apixaban compared with warfarin in patients with atrial fibrillation (AF). Patients with AF and previous stroke or transient ischaemic attack (TIA) have a high risk of stroke. We therefore aimed to assess the efficacy and safety of apixaban compared with warfarin in prespecified subgroups of patients with and without previous stroke or TIA. METHODS Between Dec 19, 2006, and April 2, 2010, patients were enrolled in the ARISTOTLE trial at 1034 clinical sites in 39 countries. 18,201 patients with AF or atrial flutter were randomly assigned to receive apixaban 5 mg twice daily or warfarin (target international normalised ratio 2·0-3·0). The median duration of follow-up was 1·8 years (IQR 1·4-2·3). The primary efficacy outcome was stroke or systemic embolism, analysed by intention to treat. The primary safety outcome was major bleeding in the on-treatment population. All participants, investigators, and sponsors were masked to treatment assignments. In this subgroup analysis, we estimated event rates and used Cox models to compare outcomes in patients with and without previous stroke or TIA. The ARISTOTLE trial is registered with ClinicalTrials.gov, number NTC00412984. FINDINGS Of the trial population, 3436 (19%) had a previous stroke or TIA. In the subgroup of patients with previous stroke or TIA, the rate of stroke or systemic embolism was 2·46 per 100 patient-years of follow-up in the apixaban group and 3·24 in the warfarin group (hazard ratio [HR] 0·76, 95% CI 0·56 to 1·03); in the subgroup of patients without previous stroke or TIA, the rate of stroke or systemic embolism was 1·01 per 100 patient-years of follow-up with apixaban and 1·23 with warfarin (HR 0·82, 95% CI 0·65 to 1·03; p for interaction=0·71). The absolute reduction in the rate of stroke and systemic embolism with apixaban versus warfarin was 0·77 per 100 patient-years of follow-up (95% CI -0·08 to 1·63) in patients with and 0·22 (-0·03 to 0·47) in those without previous stroke or TIA. The difference in major bleeding with apixaban compared with warfarin was 1·07 per 100 patient-years (95% CI 0·09-2·04) in patients with and 0·93 (0·54-1·32) in those without previous stroke or TIA. INTERPRETATION The effects of apixaban versus warfarin were consistent in patients with AF with and without previous stroke or TIA. Owing to the higher risk of these outcomes in patients with previous stroke or TIA, the absolute benefits of apixaban might be greater in this population. FUNDING Bristol-Myers Squibb and Pfizer.


title: Qualitative systematic review of barriers and facilitators to patient-involved antipsychotic prescribing.

text: BACKGROUND Despite policy and practice mandates for patient involvement, people with serious mental illness often feel marginalised in decisions about antipsychotic medication. Aims To examine stakeholder perspectives of barriers and facilitators to involving people with serious mental illness in antipsychotic prescribing decisions. METHOD Systematic thematic synthesis. RESULTS Synthesis of 29 studies identified the following key influences on involvement: patient's capability, desire and expectation for involvement, organisational context, and the consultation setting and processes. CONCLUSIONS Optimal patient involvement in antipsychotic decisions demands that individual and contextual barriers are addressed. There was divergence in perceived barriers to involvement identified by patients and prescribers. For example, patients felt that lack of time in consultations was a barrier to involvement, something seldom raised by prescribers, who identified organisational barriers. Patients must understand their rights to involvement and the value of their expertise. Organisational initiatives should mandate prescriber responsibility to overcome barriers to involvement. Declaration of interest None.


title: Livestock infectious diseases and zoonoses.

text: Infectious diseases of livestock are a major threat to global animal health and welfare and their effective control is crucial for agronomic health, for safeguarding and securing national and international food supplies and for alleviating rural poverty in developing countries. Some devastating livestock diseases are endemic in many parts of the world and threats from old and new pathogens continue to emerge, with changes to global climate, agricultural practices and demography presenting conditions that are especially favourable for the spread of arthropod-borne diseases into new geographical areas. Zoonotic infections that are transmissible either directly or indirectly between animals and humans are on the increase and pose significant additional threats to human health and the current pandemic status of new influenza A (H1N1) is a topical example of the challenge presented by zoonotic viruses. In this article, we provide a brief overview of some of the issues relating to infectious diseases of livestock, which will be discussed in more detail in the papers that follow.


title: Catheter entrapment due to severe radial artery spasm during transradial approach.

text: BACKGROUND Catheter entrapment due to severe radial artery spasm (RAS) during transradial coronary catheterization has been rarely reported and its management is not precisely defined. The aim of this study was to determine the incidence, predictors and management of catheter entrapment due to severe RAS. METHODS A total of 723 patients undergoing transradial coronary catheterization at a single center were retrospectively enrolled in the present study. Patients were divided into two groups: those with catheter entrapment due to severe RAS and those without. RESULTS The incidence of catheter entrapment was 0.8%. Height (161.2 ± 9.1 cm vs. 169.6 ± ± 10 cm, p = 0.047) and body surface area (1.86 ± 0.04 vs. 1.95 ± 0.18, p = 0.002) were found to be lower, and total procedure time 33.2 ± 13.4 min vs. 15.2 ± 12.3 min, p < 0.001) was longer in the entrapment group. Multivariate logistic regression analysis demonstrated that total procedure time independently predicted catheter entrapment (odds ratio: 1.057, 95% confidence interval [CI] 1.004-1.114, p = 0.035). Receiver-operating characteristic curve demonstrated good diagnostic accuracy for prolonged total procedure time in predicting catheter entrapment (area under curve = 0.8, 95% CI 0.63-0.97, p = 0.01). Patients were effectively treated with stepwise administration of systemic vasodilators, forearm heating, sedation and as a last resort general anesthesia with no significant complication. CONCLUSIONS Catheter entrapment due to severe RAS during transradial approach was rare and prolonged total procedure time is an independent predictor of catheter entrapment. Treatment with stepwise administration of different treatment modalities is possible with no significant complication.


title: Two head positions for orotracheal intubation with the trachway videolight intubating stylet with manual in-line stabilization: A randomized controlled trial.

text: BACKGROUND The Trachway Videolight Intubating Stylet is a video-assisted system with a rigid but malleable intubating stylet that facilitates endotracheal intubation. Minimizing cervical spine movement with manual in-line stabilization is essential for patients with cervical spine injuries such as multiple trauma. However, the intubation time of the Trachway Videolight Intubating Stylet and complications associated with intubation in patients with manual in-line stabilization in the neutral-head and head-lift positions remain unclear. METHODS Patients (20-80 years old) who were scheduled to undergo surgery that required general anesthesia with tracheal intubation were randomly allocated to either a neutral-head (n = 62) or a head-lift position (n = 62) group. Manual in-line stabilization was performed to limit cervical spine mobility. We aimed to evaluate orotracheal intubation time and success rate in these 2 positions with the Trachway Videolight Intubating Stylet. RESULTS Intubation was faster in the head-lift than in the neutral-head position (20 ± 10 and 25 ± 13 seconds, respectively, P = .000); intubation was equally successful in the 2 positions (96.8% vs 96.8%). Responses to intubation did not differ between positions (heart rate, P = .142; visual analog scale scores for throat soreness, P = .54). The only significant predictor of intubation time was the body mass index in the head-lift position group (P = .005). CONCLUSIONS Intubation using the Trachway Videolight Intubating Stylet with manual in-line stabilization is faster in the head-lift position, and therefore preferable. However, if the head-lift position is not suitable, the neutral-head position is a sensible alternative, with comparable intubation success rate, heart rate change, and postoperative throat soreness.


title: Survival study of natural orifice translumenal endoscopic surgery for rectosigmoid resection using transanal endoscopic microsurgery with or without transgastric endoscopic assistance in a swine model.

text: BACKGROUND The feasibility of transanal rectosigmoid resection with transanal endoscopic microsurgery (TEM) was previously demonstrated in a swine nonsurvival model in which transgastric endoscopic assistance also was shown to extend the length of colon mobilized transanally. METHODS A 2-week survival study evaluating transanal endoscopic rectosigmoid resection with stapled colorectal anastomosis was conducted with swine using the transanal approach alone (TEM group, n = 10) or a transanal approach combined with transgastric endoscopic assistance (TEM + TG group, n = 10). Gastrotomies were created using a needleknife and balloon dilation, then closed using prototype T-tags. Outcomes were evaluated and compared between the groups using Student's t-test and Fisher's exact test. RESULTS Relative to the TEM group, the average length of rectosigmoid mobilized in the TEM + TG group was 15.6 versus 10.5 cm (p < 0.0005), the length of the resected specimen was 9 versus 6.2 cm (p < 0.0005), and the mean operative time was 254.5 versus 97.5 min (p < 0.0005). Intraoperatively, no organ injury or major bleeding was noted. Two T-tag misfires occurred during gastrotomy closure and four small staple line defects requiring transanal repair including one in the TEM group and three in the TEM + TG group (p = 0.2). Postoperatively, there was no mortality, and the animals gained an average of 3.4 lb. Two major complications (10%) were identified at necropsy in the TEM + TG group including an intraabdominal abscess and an abdominal wall hematoma related to T-tag misfire. Gastrotomy closure sites and colorectal anastomoses were all grossly healed, with adhesions noted in 60 and 70% and microabscesses in 50 and 20% of the gastrotomy sites and colorectal anastomoses, respectively. CONCLUSIONS Natural orifice translumenal endoscopic surgery (NOTES) for rectosigmoid resection using TEM with or without transgastric endoscopic assistance is feasible and associated with low morbidity in a porcine survival model. Transgastric assistance significantly prolongs the operative time but extends the length of the rectosigmoid mobilized transanally, with a nonsignificant increase in complication rates related to gastrotomy creation.


title: Lassa Fever-associated Stigmatization among Staff and Students of the University of Benin, Nigeria.

text: Lassa Fever (LF) remains a health burden in several endemic areas of Nigeria, and its toll remains unabated over several decades. Although most studies have focused on virological and clinical considerations, few studies have attempted to address the perceived psychosocial component of LF disease in Nigeria. Evaluation of stigmatization and discrimination faced by LF survivors is an important step in improving individual health and protecting public health. This study aimed to assess LF-associated stigmatization associated among staff and students of the University of Benin. Descriptive analyses of 600 consenting respondents (300 staff and 300 students) sampled using pretested questionnaires was conducted, and the Chi-square test was used to test for significant association between perceived LF stigmatization and predefined variables. LF was a potential cause of stigmatization in a higher proportion of student (n = 162, 57.9%) than staff (n = 112, 39.9%). LF-associated stigmatization among students was significantly associated with sex (p = 0.012) and poor knowledge (p = 0.013) of LF transmission and prevention. A greater tendency for stigmatization was observed among females than males. A comprehensive emergency response plan incorporating accurate knowledge dissemination about the disease may be a first step toward tackling perceived LF stigmatization.


title: Conservative Management of Invasive Placentation: Two Cases with Different Surgical Approaches.

text: Background When placenta accreta complicates a delivery, the typical management is to perform a cesarean hysterectomy. Other management strategies, including leaving the placenta in situ, have been attempted and supported in some cases. This may allow for an interval hysterectomy, which can potentially decrease average blood loss and/or allow a minimally invasive approach to the hysterectomy. Cases We present two cases of women with invasive placentation managed conservatively with interval hysterectomy. One woman was managed with robotic-assisted laparoscopic surgery and the other with an open surgical approach. Conclusion These cases highlight the successful use of conservative management for invasive placentation in two stable patients and showcase the novel use of a robotic-assisted laparoscopic surgery for management of invasive placentation.


COVID-19 associated central nervous system vasculopathy.


title: Acellular Hydrogels for Regenerative Burn Wound Healing: Translation from a Porcine Model.

text: Currently available skin grafts and skin substitutes for healing following third-degree burn injuries are fraught with complications, often resulting in long-term physical and psychological sequelae. Synthetic treatment that can promote wound healing in a regenerative manner would provide an off-the-shelf, non-immunogenic strategy to improve clinical care of severe burn wounds. Here, we demonstrate the vulnerary efficacy and accelerated healing mechanism of a dextran-based hydrogel in a third-degree porcine burn model. The model was optimized to allow examination of the hydrogel treatment for clinical translation and its regenerative response mechanisms. Hydrogel treatment accelerated third-degree burn wound healing by rapid wound closure, improved re-epithelialization, enhanced extracellular matrix remodeling, and greater nerve reinnervation, compared with the dressing-treated group. These effects appear to be mediated through the ability of the hydrogel to facilitate a rapid but brief initial inflammatory response that coherently stimulates neovascularization within the granulation tissue during the first week of treatment, followed by an efficient vascular regression to promote a regenerative healing process. Our results suggest that the dextran-based hydrogels may substantially improve healing quality and reduce skin grafting incidents and thus pave the way for clinical studies to improve the care of severe burn injury patients.


The Role of Lung Ultrasound in Diagnosis and Follow-Up of Children With Coronavirus Disease 2019.


title: Triterpene functional genomics in licorice for identification of CYP72A154 involved in the biosynthesis of glycyrrhizin.

text: Glycyrrhizin, a triterpenoid saponin derived from the underground parts of Glycyrrhiza plants (licorice), has several pharmacological activities and is also used worldwide as a natural sweetener. The biosynthesis of glycyrrhizin involves the initial cyclization of 2,3-oxidosqualene to the triterpene skeleton β-amyrin, followed by a series of oxidative reactions at positions C-11 and C-30, and glycosyl transfers to the C-3 hydroxyl group. We previously reported the identification of a cytochrome P450 monooxygenase (P450) gene encoding β-amyrin 11-oxidase (CYP88D6) as the initial P450 gene in glycyrrhizin biosynthesis. In this study, a second relevant P450 (CYP72A154) was identified and shown to be responsible for C-30 oxidation in the glycyrrhizin pathway. CYP72A154 expressed in an engineered yeast strain that endogenously produces 11-oxo-β-amyrin (a possible biosynthetic intermediate between β-amyrin and glycyrrhizin) catalyzed three sequential oxidation steps at C-30 of 11-oxo-β-amyrin supplied in situ to produce glycyrrhetinic acid, a glycyrrhizin aglycone. Furthermore, CYP72A63 of Medicago truncatula, which has high sequence similarity to CYP72A154, was able to catalyze C-30 oxidation of β-amyrin. These results reveal a function of CYP72A subfamily proteins as triterpene-oxidizing enzymes and provide a genetic tool for engineering the production of glycyrrhizin.


Hydrothermal duodenal mucosal resurfacing: a novel procedural therapy for metabolic disease.


title: Fundamental Use of Surgical Energy (FUSE) certification: validation and predictors of success.

text: INTRODUCTION The Fundamental Use of Surgical Energy (FUSE) program includes a Web-based didactic curriculum and a high-stakes multiple-choice question examination with the goal to provide certification of knowledge on the safe use of surgical energy-based devices. The purpose of this study was (1) to set a passing score through a psychometrically sound process and (2) to determine what pretest factors predicted passing the FUSE examination. METHODS Beta-testing of multiple-choice questions on 62 topics of importance to the safe use of surgical energy-based devices was performed. Eligible test takers were physicians with a minimum of 1 year of surgical training who were recruited by FUSE task force members. A pretest survey collected baseline information. RESULTS A total of 227 individuals completed the FUSE beta-test, and 208 completed the pretest survey. The passing/cut score for the first test form of the FUSE multiple-choice examination was determined using the modified Angoff methodology and for the second test form was determined using a linear equating methodology. The overall passing rate across the two examination forms was 81.5%. Self-reported time studying the FUSE Web-based curriculum for a minimum of >2 h was associated with a passing examination score (p < 0.001). Performance was not different based on increased years of surgical practice (p = 0.363), self-reported expertise on one or more types of energy-based devices (p = 0.683), participation in the FUSE postgraduate course (p = 0.426), or having reviewed the FUSE manual (p = 0.428). Logistic regression found that studying the FUSE didactics for >2 h predicted a passing score (OR 3.61; 95% CI 1.44-9.05; p = 0.006) independent of the other baseline characteristics recorded. CONCLUSION(S) The development of the FUSE examination, including the passing score, followed a psychometrically sound process. Self-reported time studying the FUSE curriculum predicted a passing score independent of other pretest characteristics such as years in practice and self-reported expertise.


title: Predictors for Symptomatic Intracranial Hemorrhage After Endovascular Treatment of Acute Ischemic Stroke.

text: BACKGROUND AND PURPOSE Symptomatic intracranial hemorrhage (SICH) pose a major safety concern for endovascular treatment of acute ischemic stroke. This study aimed to evaluate the risk and related factors of SICH after endovascular treatment in a real-world practice. METHODS Patients with stroke treated with stent-like retrievers for recanalizing a blocked artery in anterior circulation were enrolled from 21 stroke centers in China. Intracranial hemorrhage was classified as symptomatic and asymptomatic ones according to Heidelberg Bleeding Classification. Logistic regression was used to identify predictors for SICH. RESULTS Of the 632 enrolled patients, 101 (16.0%) were diagnosed with SICH within 72 hours after endovascular treatment. Ninety-day mortality was higher in patients with SICH than in patients without SICH (65.3% versus 18.8%; P<0.001). On multivariate analysis, baseline neutrophil ratio >0.83 (odds ratio [OR], 2.07; 95% confidence interval [CI], 1.24-3.46), pretreatment Alberta Stroke Program Early Computed Tomography Score of <6 (OR, 2.27; 95% CI, 1.24-4.14), stroke of cardioembolism type (OR, 1.91; 95% CI, 1.13-3.25), poor collateral circulation (OR, 1.97; 95% CI, 1.16-3.36), delay from symptoms onset to groin puncture >270 minutes (OR, 1.70; 95% CI, 1.03-2.80), >3 passes with retriever (OR, 2.55; 95% CI, 1.40-4.65) were associated with SICH after endovascular treatment. CONCLUSIONS Incidence of SICH after thrombectomy is higher in Asian patients with acute ischemic stroke. Cardioembolic stroke, poor collateral circulation, delayed endovascular treatment, multiple passes with stent retriever device, lower pretreatment Alberta Stroke Program Early Computed Tomography Score, higher baseline neutrophil ratio may increase the risk of SICH.


title: Conserved baculoviral ORFs 10 and 14 from Bombyx mori multiple nucleopolyhedrovirus.

text: ORFs 10 and 14 from Bombyx mori multiple nucleopolyhedrovirus (BmMNPV) were amplified, cloned and sequenced. Nucleotide analysis of these genes and those of other baculoviruses showed that these genes are highly conserved. The p10 protein from BmMNPV ORF10 has 70 amino acid residues similar to that of the four other known BmNPV strains. The BmMNPV ORF14 alignment showed a higher identity with the nucleopolyhedrovirus ORF14 from the baculovirus BmNPV and from Autographa californica multiple nucleopolyhedrovirus. The BmMNPV ORF14 protein has a putative transmembrane domain in the C-terminal region, which is similar to that of other baculoviruses. A phylogenetic analysis showed that BmMNPV ORF14 protein has higher similarity with BmNPV ORF14 and ORF23 of A. californica multicapsid nucleopolyhedrovirus (Ac23). We conclude that proteins produced by ORFs 10 and 14 from BmNPV and BmMNPV are highly conserved in NPVs and MNPVs. The high degree of conservation among members of these genera indicates the importance of these proteins, which could mean an important function that is active throughout the infection cycle.


title: Computed tomography lymphography for the detection of sentinel nodes in patients with gastric carcinoma.

text: The sentinel node (SN) concept has been found to be feasible in gastric cancer. However, the lymphatic network of gastric cancer may be more complex, and it may be difficult to visualize all the SN distributed in unexpected areas by conventional modalities. In this study, we evaluate the feasibility and efficacy of CT lymphography for the detection of SN in gastric cancer. A total 24 patients with early gastric cancer were enrolled in the study. Three modalities (CT lymphography, dye and radioisotope [RI] methods) were used for the detection of SN. The images of CT lymphography were obtained at 10 min after injection of contrast agents. The SN were successfully identified by CT lymphography in 83.3% of patients; detection rates by the dye and RI methods were 95% and 100%, respectively. Most patients, in whom SN were successfully detected by CT lymphography, had positive results at 5 min after injection of the contrast material. The SN stations detected by CT lymphography were consistent with or included those detected by dye and/or RI methods. In conclusion, CT lymphography for the detection of SN in gastric cancer is feasible and has several advantages. However, based on this initial experience, CT lymphography had a relatively low detection rate compared with conventional methods, and further efforts will be necessary to improve the detection rate and widen the clinical application of CT lymphography for the detection of SN in gastric cancer.


title: Combined cranionasal surgery for spheno-orbital meningiomas invading the paranasal sinuses, pterygopalatine, and infratemporal fossa.

text: OBJECTIVE To evaluate the efficacy of combining an endonasal endoscopic skull-base approach and repair with a transcranial orbitozygomatic approach for spheno-orbital meningiomas (SOMs). METHODS Three patients with recurrent SOMs underwent combined orbitozygomatic and endonasal endoscopic surgery. In 2 patients both procedures were done in 1 operation and in 1 patient the endonasal surgery was done 2.5 months after the craniotomy. Extent of resection, complications, morbidity, and mortality were evaluated. RESULTS Gross total resection was achieved in 1 patient and near total resection in the other 2 patients with tumor left in the cavernous sinus and parapharyngeal space. Two patients suffered cranial neuropathy from the transcranial surgery and the other developed a pseudomeningocele. There were no complications from the endonasal surgery. Patients having combined single setting cranionasal surgery were discharged on day 6 and 8, whereas the patient having only the endonasal component on a later date was discharged on day 2. CONCLUSIONS A combined cranionasal approach involving transcranial orbitozygomatic and endonasal endoscopic approaches is an effective 2-stage surgery for resecting SOMs invading into the sinuses and paranasal compartments. The ability to perform a multilayer closure involving a vascularized nasoseptal flap additionally decreases the risk of postoperative cerebrospinal fluid leak.


title: Diagnostic role of chest computed tomography in coronavirus disease 2019.

text: Coronavirus disease 2019 (COVID-19) is an infectious disease caused by a novel strain of coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), that appeared in China in December 2019 and spread globally, evolving into the currently observed pandemic. The laboratory diagnosis of SARS-CoV-2 infection is currently based on real-time reverse transcriptase-polymerase chain reaction (RT-PCR) testing, and imaging cannot replace genetic testing in patients suspected of COVID-19. However, with predominant respiratory manifestations of COVID-19, particularly in more severe cases, chest imaging using computed tomography (CT) plays a major role in detecting viral lung infection, evaluating the nature and extent of pulmonary lesions, and monitoring the disease activity. The role of chest CT as a diagnostic tool may be increased when the laboratory testing capacities using RT-PCR prove inaccurate or insufficient during a major outbreak of the disease. In these settings, a rapid presumptive diagnosis of COVID-19 potentially offered by CT might be an advantage, in addition to obvious benefits of delineating the nature and extent of pulmonary changes. In the present paper, we reviewed the diagnostic role of chest CT in COVID-19 patients.


The role of the medicine student in COVID-19 pandemic. A shared responsibility.


title: Antimicrobial Resistance in Escherichia coli.

text: Multidrug resistance in Escherichia coli has become a worrying issue that is increasingly observed in human but also in veterinary medicine worldwide. E. coli is intrinsically susceptible to almost all clinically relevant antimicrobial agents, but this bacterial species has a great capacity to accumulate resistance genes, mostly through horizontal gene transfer. The most problematic mechanisms in E. coli correspond to the acquisition of genes coding for extended-spectrum β-lactamases (conferring resistance to broad-spectrum cephalosporins), carbapenemases (conferring resistance to carbapenems), 16S rRNA methylases (conferring pan-resistance to aminoglycosides), plasmid-mediated quinolone resistance (PMQR) genes (conferring resistance to [fluoro]quinolones), and mcr genes (conferring resistance to polymyxins). Although the spread of carbapenemase genes has been mainly recognized in the human sector but poorly recognized in animals, colistin resistance in E. coli seems rather to be related to the use of colistin in veterinary medicine on a global scale. For the other resistance traits, their cross-transfer between the human and animal sectors still remains controversial even though genomic investigations indicate that extended-spectrum β-lactamase producers encountered in animals are distinct from those affecting humans. In addition, E. coli of animal origin often also show resistances to other-mostly older-antimicrobial agents, including tetracyclines, phenicols, sulfonamides, trimethoprim, and fosfomycin. Plasmids, especially multiresistance plasmids, but also other mobile genetic elements, such as transposons and gene cassettes in class 1 and class 2 integrons, seem to play a major role in the dissemination of resistance genes. Of note, coselection and persistence of resistances to critically important antimicrobial agents in human medicine also occurs through the massive use of antimicrobial agents in veterinary medicine, such as tetracyclines or sulfonamides, as long as all those determinants are located on the same genetic elements.


title: Obituary: Pietro Cugini (13 December 1936 - 6 April 2020).

text: Chronobiology lost a great and distinguished physician-scientist, Pietro Cugini (Figure 1). He will be dearly missed by his family, his friends, and the field he helped shape and guide as he remained active until the end of his life at 83 years of age. In the middle of the worst pandemic the world has known in recent times, but not from COVID-19, Pietro passed away unexpectedly in front of his Rome apartment, on Via Latina, the same street where he was born and where he spent most of his life. He was buried shortly afterward in the Monumental cemetery of Marino. There was no formal ceremony as funerals were suspended because of the coronavirus. A proper ceremony will take place as soon as travel and congregation are possible. Pietro is survived by his three children, Silvia, Raffaella and Riccardo Cugini.


title: Survival after radiofrequency ablation and salvage transplantation in patients with hepatocellular carcinoma and Child-Pugh A cirrhosis.

text: BACKGROUND & AIMS In patients with hepatocellular carcinoma (HCC) within the Milan criteria, liver transplantation (LT) may be the best therapeutic option. However, the shortage of grafts, leads to attempt liver resection (LR) or radiofrequency ablation (RFA) as a first-line treatment for patients with Child-Pugh A cirrhosis. METHODS We report results, obtained between 2000 and 2007 from a single center, involving 67 patients (mean age: 57 years) eligible for LT, who were treated with RFA, followed by LT if there was recurrence or liver failure. RESULTS Eighty three tumors were treated (mean size: 29±9 mm; 16 binodular forms). RFA achieved complete ablation in 96% of nodules. No mortality occurred. During a post-RFA median follow-up of 48 months, 38 patients experienced recurrence, corresponding to a 5-year recurrence rate of 58%. Of these, 14 patients did not receive a transplant because they fell outside the Milan criteria, 21 were transplanted, and 3 were treated by RFA after refusing LT. Binodularity (95% CI HR=2, 1.0-4.0; p=0.049) was the unique risk factor for recurrence. By the study's end-point, 24 patients had undergone LT (21 for HCC recurrence and three for liver failure). No HCC recurrence occurred after LT. Among the 43 non-transplant patients, 12 died due to HCC progression, and 27 were alive without detectable viable tumor. The probability rates for 5-year overall and tumor-free survival were 74% and 69%, respectively. CONCLUSIONS First line RFA followed by salvage LT allows survival figures that are at least as good as a first-line LT, while limiting the number of grafts.


Air Hunger and Psychological Trauma in Ventilated COVID-19 Patients: An Urgent Problem.


Chloroquine and hydroxychloroquine repositioning in times of COVID-19 pandemics, all that glitters is not gold.


title: Closure of bronchopleural fistula with porcine dermal collagen and fibrin glue in an infant.

text: The management of an 11-month-old infant who developed a bronchopleural fistula (BPF) 3 weeks after video-assisted thoracic surgery for congenital cystic adenomatoid malformation of the right lower pulmonary lobe is presented. Being refractory to treatment with chest tubes, the BPF was managed using a bronchoscopic approach using porcine dermal collagen (PDC) combined with a fibrin glue plug. The single session was sufficient to manage the BPF and the postoperative course was uneventful. This case highlights the novelty in the successful management of BPF in infants after pulmonary surgery using PDC and fibrin glue using the minimal access bronchoscopic approach.


News and Views.


title: Nurses' perception of disaster: implications for disaster nursing curriculum.

text: AIMS AND OBJECTIVES The aims of the study were to identify nurses' perception of disaster, whether they considered some of the events that have occurred in Hong Kong to be disasters and the types of disastrous events that they considered likely in Hong Kong. BACKGROUND The frequent occurrence of disasters has caused concern internationally. When disaster strikes, the demands on nursing staff are much higher than those on other healthcare professionals. There is little understanding of the concept of disaster among nurses in Hong Kong. DESIGN This was a descriptive study. A questionnaire was used to explore nurses' perception of disaster. METHOD The questionnaire was distributed to all registered nurses studying in a master's degree programme in a university in Hong Kong. FINDINGS Only 123 out of the 164 respondents (75%) gave a description of disaster in the open-ended question. Sixty-one per cent of them described unfortunate events with large numbers of victims as disasters. The 'Lan Kwai Fong tragedy--stampede caused by over-crowdedness' (90.9%) and the severe acute respiratory syndrome outbreak (89.6%) were commonly referred to as disasters in Hong Kong. Fires in tall buildings (61.6%), infectious disease outbreaks (61%) and stampedes caused by overcrowding (48.8%) were rated as the events most likely to happen in Hong Kong. CONCLUSION Understanding how nurses perceive disaster and the likelihood of disastrous events is the initial step for disaster planning and the development of a disaster nursing curriculum in Hong Kong. RELEVANCE TO CLINICAL PRACTICE All nurses around the world should be equipped with knowledge and skills for disaster care. This study provides information and implications for related research and the development of a disaster nursing curriculum to meet the global demand for disaster preparedness.


title: Ski Boots Do Not Impair Standing Balance by Restricting Ankle-Joint Mobility.

text: OBJECTIVE This study was undertaken in order to provide new insight into sensorimotor control of posture when wearing high-shaft (HS) boots as ski boots. BACKGROUND Previous studies into the effects of HS boots on postural control have produced controversial results. Some studies reported postural control impairments with ski boots in bipedal postural tasks due to ankle movement restrictions without quantifying the actual restrictive effect of these boots and specifying the adaptations of the postural control system. METHOD Eighteen young healthy subjects took part in the experiment. Bilateral postural control was assessed on stable and unstable surfaces, while standing barefoot or wearing ski boots. Center of pressure (COP) parameters, ankle, knee, and hip joints movements were calculated and EMG activity from main postural muscles was recorded. RESULTS Ski boots did not restrict the amplitude of ankle angular movements and largely impacted COP parameters and EMG activity on stable ground. In conditions of mediolateral instability, COP data illustrated an enhanced postural control in the frontal plane when wearing ski boots. CONCLUSIONS Ski boots do not affect bipedal postural balance by restricting the ankle angular motions but induce complex adaptations of the postural control system which combine factors of a mechanical, motor, and sensorial nature. They impede postural control mainly when standing on stable ground without producing similar deleterious effects on unstable surfaces. APPLICATION Our results show that HS boots as ski boots can improve lateral balance on unstable surfaces, which can contribute to prevent fall risk and ankle sprain.


title: Human coronaviruses OC43 and HKU1 bind to 9-O-acetylated sialic acids via a conserved receptor-binding site in spike protein domain A.

text: Human betacoronaviruses OC43 and HKU1 are endemic respiratory pathogens and, while related, originated from independent zoonotic introductions. OC43 is in fact a host-range variant of the species Betacoronavirus-1, and more closely related to bovine coronavirus (BCoV)-its presumptive ancestor-and porcine hemagglutinating encephalomyelitis virus (PHEV). The β1-coronaviruses (β1CoVs) and HKU1 employ glycan-based receptors carrying 9-O-acetylated sialic acid (9-O-Ac-Sia). Receptor binding is mediated by spike protein S, the main determinant of coronavirus host specificity. For BCoV, a crystal structure for the receptor-binding domain S1A is available and for HKU1 a cryoelectron microscopy structure of the complete S ectodomain. However, the location of the receptor-binding site (RBS), arguably the single-most important piece of information, is unknown. Here we solved the 3.0-Å crystal structure of PHEV S1A We then took a comparative structural analysis approach to map the β1CoV S RBS, using the general design of 9-O-Ac-Sia-binding sites as blueprint, backed-up by automated ligand docking, structure-guided mutagenesis of OC43, BCoV, and PHEV S1A, and infectivity assays with BCoV-S-pseudotyped vesicular stomatitis viruses. The RBS is not exclusive to OC43 and related animal viruses, but is apparently conserved and functional also in HKU1 S1A The binding affinity of the HKU1 S RBS toward short sialoglycans is significantly lower than that of OC43, which we attribute to differences in local architecture and accessibility, and which may be indicative for differences between the two viruses in receptor fine-specificity. Our findings challenge reports that would map the OC43 RBS elsewhere in S1A and that of HKU1 in domain S1B.


title: Prognostic impact of microscopic vessel invasion and visceral pleural invasion in non-small cell lung cancer: a retrospective analysis of 2657 patients.

text: OBJECTIVE We aimed to assess the prognostic significance of microscopic vessel invasion (MVI) and visceral pleural invasion (VPI) in non-small cell lung cancer (NSCLC). BACKGROUND VPI is included in the current tumor-node-metastasis (TNM) classification in NSCLC; however, MVI is not incorporated in TNM classification. METHODS From August 1992 to December 2009, 2657 consecutive patients with pathological T1-4N0-2M0 NSCLC underwent complete resection. In addition to conventional staging factors, we evaluated MVI histologically and analyzed its significance in NSCLC recurrence prognosis. The recurrence-free period in several NSCLC subgroups was analyzed using the Kaplan-Meier method and Cox regression analysis. RESULTS The proportion of patients with a 5-year recurrence-free period was 52.6% and 87.5%, respectively, in those with and without MVI (P < 0.001). Multivariate analysis showed that MVI, similarly to VPI, was found to be an independently significant predictor of recurrence [hazard ratio (HR): 2.78]. In particular, MVI and VPI were the 2 strongest significant independent predictors of recurrence in 1601 patients with pathological stage I disease treated without adjuvant chemotherapy (HR: 2.74 and 1.84, respectively). In each T subgroup analysis, evident and significant separation of the recurrence-free proportion curves were observed among the 3 groups (VPI and MVI absent, VPI or MVI present, and VPI and MVI present). CONCLUSIONS This study demonstrated that MVI was a significant independent risk factor for recurrence in patients with a resected T1-4N0-2M0 NSCLC. Further data on MVI prognostic impact should be collected for the next revision of the TNM staging system.


title: An ex vivo comparison of cuffed endotracheal tubes and self-sealing baffled endotracheal tubes.

text: AIMS To compare cuffed silicone endotracheal tubes with self-sealing baffled silicone endotracheal tubes in an ex vivo canine tracheal model, to determine whether the tubes differed in their maintenance of a seal and their effectiveness in removing fluid from the tracheal lumen, and whether the self-sealing endotracheal tubes would release pressure when a closed anaesthetic circuit reached ≥30 cm H2O. METHODS Twelve cadaver tracheae were randomly selected to be intubated with either cuffed or self-sealing baffled endotracheal tubes. To test tracheal seal efficacy, the tracheae were positioned vertically, 5 mL of water was instilled proximal to the tube cuff or baffles and they were monitored for leakage at 0, 15, 30, 45, and 60 minutes, recording the total volume leaked. To test fluid removal at extubation, the tracheae were intubated, then 5.6 g of 60% barium sulphate suspension was instilled proximal to the seal and left undisturbed for 5 minutes. The tubes were then extubated, with the cuffed endotracheal tubes being partially deflated before extubation, and the amount of barium recovered was weighed. These procedures were repeated on the same tracheae using the other endotracheal tubes. To test whether self-sealing baffled endotracheal tubes would release pressure at ≥30 cm H2O, the tracheae were intubated, connected to an anaesthetic machine and pressurised to 30 cm H2O for 5 minutes and then 50 cm H2O for 5 minutes. Release of pressure was defined as a decrease in pressure within the closed anaesthetic circuit. RESULTS More cuffed (7/12) than baffled (0/12) endotracheal tubes leaked water after 60 minutes (p=0.016). The mean amount of barium removed by the self-sealing baffled endotracheal tubes (4.9 (95% CI=3.8-4.4) g) was greater than that removed by the partially deflated cuffed endotracheal tubes (0.4 (95% CI=0.14-0.66) g) (p<0.001). None of the self-sealing baffled endotracheal tubes released pressure at ≥30 cm H2O in a closed anaesthetic circuit. CONCLUSIONS AND CLINICAL RELEVANCE Self-sealing baffled endotracheal tubes were more effective than cuffed endotracheal tubes at both preventing fluid leakage at the tracheal seal and removing fluid from the lumen of the trachea in cadaver tracheae. However they did not release pressure when the closed-circuit system was at ≥30 cm H2O in a canine cadaver model. The self-sealing baffled endotracheal tubes may be a suitable substitute for cuffed endotracheal tubes.