title: Prolapse and continence surgery in countries of the Organization for Economic Cooperation and Development in 2012.

text: OBJECTIVE The purpose of this study was to report the rates and types of pelvic organ prolapse (POP) and female continence surgery performed in member countries of the Organization for Economic Co-operation and Development (OECD) in 2012. STUDY DESIGN The published health outcome data sources of the 34 OECD countries were contacted for data on POP and female continence interventions from 2010-2012. In nonresponding countries, data were sought from national or insurer databases. Extracted data were entered into an age-specific International Classification of Disease, edition 10 (ICD-10)-compliant Excel spreadsheet by 2 authors independently in English-speaking countries and a single author in non-English-speaking countries. Data were collated centrally and discrepancies were resolved by mutual agreement. RESULTS We report on 684,250 POP and 410,352 continence procedures that were performed in 15 OECD countries in 2012. POP procedures (median rate, 1.38/1000 women; range, 0.51-2.55 prolapse procedures/1000 women) were performed 1.8 times more frequently than continence procedures (median rate, 0.75/1000 women; range, 0.46-1.65 continence procedures/1000 women). Repairs of the anterior vaginal compartment represented 54% of POP procedures; posterior repairs represented 43% of the procedures, and apical compartment repairs represented 20% of POP procedures. Median rate of graft usage was 15.7% of anterior vaginal repairs (range, 3.3-25.6%) and 8.5% (range, 3.2-17%) of posterior vaginal repairs. Apical compartment repairs were repaired vaginally at a median rate of 70% (range, 35-95%). Sacral colpopexy represented a median rate of 17% (range, 5-65%) of apical repairs; 61% of sacral colpopexies were performed minimally invasively. Between 2010 and 2012, there was a 3.7% median reduction in transvaginal grafts, a 4.0% reduction in midurethral slings, and a 25% increase in sacral colpopexies that were performed per 1000 women. Midurethral slings represented 82% of female continence surgeries. CONCLUSION The 5-fold variation in the rate of prolapse interventions within OECD countries needs further evaluation. The significant heterogeneity (>10 times) in the rates at which individual POP procedures are performed indicates a lack of uniformity in the delivery of care to women with POP and demands the development of uniform guidelines for the surgical management of prolapse. In contrast, the midurethral slings were the standard female continence surgery performed throughout OECD countries in 2012.


title: Bipolar thermofusion vessel sealing system (TVS) versus conventional vessel ligation (CVL) in thyroid surgery--results of a prospective study.

text: INTRODUCTION One of the keystones in surgery of the thyroid gland is accurate hemostasis. This can be achieved by conventional ligations or new instruments as harmonic scissors or bipolar devices. In the present study, we report our experience with a new bipolar thermofusion vessel sealing system (TVS) compared to conventional vessel ligation (CVL). METHODS This prospective non-randomized study included 186 patients operated on by two surgeons between April and November 2007. Age, gender, preoperative diagnosis, type of surgery, operative time, and complications were prospectively collected. TVS was used in 93 patients (29 M, 64 F; mean age 50+/-14 years, range 11-83) and CVL in 93 patients (27 M, 66 F; mean age 49+/-14 years, range 16-82). Results and postoperative complications were registered. RESULTS Postoperative complications included two cases of transient hypocalcaemia in both groups 1 (TVS group) and 2 (CVL group) hemorrhages requiring reoperation (p = ns). No recurrent laryngeal nerve palsy was observed in both groups. A drain was used in 25 cases in the TVS group and in 47 patients in the CVL group (p<0.008). Mean operative time for total thyroidectomy was significantly shorter in the TVS group (73+/-18 min, range=35-110) than in the CVL group (18+/-20 min, range = 40 -130; p<0.01). No differences were found for lobectomies or subtotal thyroidectomies. CONCLUSION TVS is safe with a similar complication rate as CVL. Mean operative time for total thyroidectomy is shortened with TVS.


title: Comparison of strength of sacrocolpopexy mesh attachment using barbed and nonbarbed sutures.

text: INTRODUCTION AND HYPOTHESIS We aimed to assess the pull-out strength of barbed and nonbarbed sutures used in sacrocolpopexy mesh fixation. We hypothesized there are no differences in the force needed to dislodge mesh from tissue using barbed and nonbarbed sutures of similar size. METHODS Using the rectus fascia of three unembalmed cadavers, a 6 × 3 cm strip of polypropylene mesh was anchored to the fascia with sutures. The barbed sutures investigated were 2-0 V-Loc 180 (nine trials) and 3-0 bidirectional Quill™ SRS PDO (five trials). The nonbarbed sutures included 2-0 PDS (nine trials), CV-2 GORE-TEX (nine trials) and 2-0 Prolene (nine trials). The free-end of the mesh was anchored to a pulley system fixed to a tensiometer to measure the peak force applied at the moment of mesh dislodgement (termed the pull-out force). The pull-out force was recorded. Continuous variables are presented as medians and interquartile ranges (IQR). Analysis of variance was used to compare the forces across the suture types. RESULTS The highest pull-out force observed was with GORE-TEX (median 65.14 N, IQR 53.37-68.77 N) followed by Prolene (median 58.98 N, IQR 54.64-62.59 N), V-Loc (median 55.23 N, IQR 51.60-58.57 N), PDS (53.96 N, IQR 51.60-57.88 N), and Quill (44.44 N, IQR 17.27-47.38 N). All 2-0 and CV-2 caliber sutures had greater pull-out forces than 3-0 Quill sutures (p < 0.01). No significant differences in pull-out forces were observed between 2-0 and CV-2 caliber sutures (p > 0.05). In 35 of the 41 trials (85%), the mesh sheared from the tissue. CONCLUSION CV-2 ad 2-0 barbed and nonbarbed sutures had similar pull-out forces in an assessment of mesh fixation strength.


title: Single-incision laparoscopic resection of Bismuth I hilar cholangiocarcinoma.

text: INTRODUCTION Laparoscopic hilar cholangiocarcinoma is rarely performed because of its aggressive growth and complicated anatomy. The authors successfully performed single-incision laparoscopic resection of Bismuth I hilar cholangiocarcinoma in 2 cases. METHOD Two cases with Bismuth I cholangiocarcinoma were chosen for the laparoscopic surgery. Segmental bile duct resection and hepatoduodenal ligament lymphadenectomy were performed using single-incision laparoscopic technique with conventional instruments. RESULTS Two operations were successfully performed without conversion. The operation time was 300 and 350 minutes, respectively. The margins of proximal and distal bile ducts were negative. The hospital stay was 6 and 9 days, respectively. One dosage of analgesic was administered after surgery. The abdominal wound recovered very well with good cosmesis. CONCLUSION Single-incision laparoscopic surgery cholangiocarcinoma resection can be optional in strictly selected patients with Bismuth I cholangiocarcinoma. Long-term follow-up and more data are needed to evaluate its benefits.


title: Ultra-protective tidal volume: how low should we go?

text: Applying tidal volumes of less than 6 mL/kg might improve lung protection in patients with acute respiratory distress syndrome. In a recent article, Retamal and colleagues showed that such a reduction is feasible with conventional mechanical ventilation and leads to less tidal recruitment and overdistension without causing carbon dioxide retention or auto-positive end-expiratory pressure. However, whether the compensatory increase in the respiratory rate blunts the lung protection remains unestablished.


title: Innovating in the medical device industry - challenges & opportunities ESB 2015 translational research symposium.

text: The European Society for Biomaterials 2015 Translational Research Symposium focused on 'Innovating in the Medical Device Industry - Challenges & Opportunities' from different perspectives, i.e., from a non-profit research organisation to a syndicate of small and medium-sized companies and large companies. Lecturers from regulatory consultants, industry and research institutions described the innovation process and regulatory processes (e.g., 510K, PMA, combination product) towards market approval. The aim of the present article is to summarise and explain the main statements made during the symposium, in terms of challenges and opportunities for medical device industries, in a constantly changing customer and regulatory environment.


title: Effectiveness of pneumococcal conjugate vaccines against invasive pneumococcal disease among children under five years of age in Africa: A systematic review.

text: BACKGROUND Despite the widespread implementation of the pneumococcal conjugate vaccine, Streptococcus pneumoniae remains the leading cause of severe pneumonia associated with mortality among children less than 5 years of age worldwide, with the highest mortality rates recorded in Africa and Asia. However, information on the effectiveness and prevalence of vaccine serotypes post-roll out remains scarce in most African countries. Hence, this systematic review aimed to describe what is known about the decline of childhood invasive pneumococcal disease post-introduction of the pneumococcal conjugate vaccine in Africa. METHODS This systematic review included articles published between 2009 and 2018 on the implementation of the pneumococcal conjugate vaccine in Africa. We searched PubMed, Scopus and African Index Medicus for articles in English. Studies on implementation programmes of pneumococcal conjugate vaccine 10/13, with before and after data from different African countries, were considered eligible. The review followed the procedures published in PROSPERO (ID = CRD42016049192). RESULTS In total, 2,280 studies were identified through electronic database research, and only 8 studies were eligible for inclusion in the final analysis. Approximately half (n = 3) of these studies were from South Africa. The overall decline in invasive pneumococcal disease ranged from 31.7 to 80.1%. Invasive pneumococcal diseases caused by vaccine serotypes declined significantly, the decline ranged from 35.0 to 92.0%. A much higher decline (55.0-89.0%) was found in children below 24 months of age. Of all vaccine serotypes, the relative proportions of serotypes 1, 5 and 19A doubled following vaccine roll out. INTERPRETATION Following the introduction of the pneumococcal conjugate vaccine, a significant decline was observed in invasive pneumococcal disease caused by vaccine serotypes. However, data on the effectiveness in this region remain scarce, meriting continued surveillance to assess the effectiveness of pneumococcal vaccination to improve protection against invasive pneumococcal disease.


title: Telemedicine During the COVID-19 Pandemic: A Pediatric Otolaryngology Perspective.

text: The COVID-19 pandemic has created a situation unparalleled in our lifetime. As the medical community has attempted to navigate a sea of ever-changing information and policies, this uncertainty has instead bred creativity, community, and evolution. Necessity is the mother of invention, and one of the by-products of our rapidly changing environment is the increased reliance on telemedicine. Here, we discuss our experience with incorporating telemedicine into an urban academic pediatric otolaryngology practice, the challenges that we have encountered, and the principles unique to this population.


title: A novel approach to dual excitation ratiometric optical mapping of cardiac action potentials with di-4-ANEPPS using pulsed LED excitation.

text: We developed a new method for ratiometric optical mapping of transmembrane potential (V(m)) in cardiac preparations stained with di-4-ANEPPS. V(m)-dependent shifts of excitation and emission spectra establish two excitation bands (<481 and >481 nm) that produce fluorescence changes of opposite polarity within a single emission band (575-620 nm). The ratio of these positive and negative fluorescence signals (excitation ratiometry) increases V(m) sensitivity and removes artifacts common to both signals. We pulsed blue (450 ± 10 nm) and cyan (505 ± 15 nm) light emitting diodes (LEDs) at 375 Hz in alternating phase synchronized to a camera (750 frames-per-second). Fluorescence was bandpass filtered (585 ± 20 nm). This produced signals with upright (blue) and inverted (cyan) action potentials (APs) interleaved in sequential frames. In four whole swine hearts with motion chemically arrested, fractional fluorescence for blue, cyan, and ratio signals was 1.2 ± 0.3%, 1.2 ± 0.3%, and 2.4 ± 0.6%, respectively. Signal-to-noise ratios were 4.3 ± 1.4, 4.0 ± 1.2, and 5.8 ± 1.9, respectively. After washing out the electromechanical uncoupling agent, we characterized motion artifact by cross-correlating blue, cyan, and ratio signals with a signal with normal AP morphology. Ratiometry improved cross-correlation coefficients from 0.50 ± 0.48 to 0.81 ± 0.25, but did not cancel all motion artifacts. These findings demonstrate the feasibility of pulsed LED excitation ratiometry in myocardium.


title: Swine enteric alphacoronavirus (swine acute diarrhea syndrome coronavirus): an update three years after its discovery

text: Discovered in 2017, swine enteric alphacoronavirus (SeACoV), also known as swine acute diarrhea syndrome coronavirus (SADS-CoV) or porcine enteric alphacoronavirus (PEAV), is the fifth porcine CoV identified in diarrheal piglets. The presumed name “SADS-CoV” may not be appropriate since current studies have not provided strong evidence for high pathogenicity of the virus. SeACoV was the most recently recognized CoV of potential bat origin prior to the novel human severe acute respiratory syndrome CoV 2 (SARS-CoV-2), associated with the pandemic CoV disease 2019 (COVID-19). Although SeACoV is recognized as a regional epizootic virus currently, it possesses the most extensive cell species tropism in vitro among known CoVs. This review summarizes the emergence of SeACoV and updates the research progress made from 2017 to early 2020, mainly focusing on the etiology, epidemiology, evolutionary perspective, potential for interspecies transmission, pathogenesis and diagnosis.


Saliva testing for COVID-19?


title: Sensitive targeted quantification of ERK phosphorylation dynamics and stoichiometry in human cells without affinity enrichment.

text: Targeted mass spectrometry is a promising technology for site-specific quantification of posttranslational modifications. However, a major constraint is the limited sensitivity for quantifying low-abundance PTMs, requiring the use of affinity reagents for enrichment. Herein, we demonstrate the direct site-specific quantification of ERK phosphorylation isoforms (pT, pY, pTpY) and their relative stoichiometry using a sensitive targeted MS approach termed high-pressure, high-resolution separations with intelligent selection, and multiplexing (PRISM). PRISM provides effective enrichment of target peptides into a given fraction from complex mixture, followed by selected reaction monitoring quantification. Direct quantification of ERK phosphorylation in human mammary epithelial cells (HMEC) was demonstrated from as little as 25 μg tryptic peptides from whole cell lysates. Compared to immobilized metal-ion affinity chromatography, PRISM provided ∼10-fold higher signal intensities, presumably due to the better peptide recovery of PRISM. This approach was applied to quantify ERK phosphorylation dynamics in HMEC treated by different doses of epidermal growth factor at both the peak activation (10 min) and steady state (2 h). The maximal ERK activation was observed with 0.3 and 3 ng/mL doses for 10 min and 2 h time points, respectively. The dose-response profiles of individual phosphorylated isoforms showed that singly phosphorylated pT-ERK never increases significantly, while the increase of pY-ERK paralleled that of pTpY-ERK. This data supports for a processive, rather than distributed model of ERK phosphorylation. The PRISM-SRM quantification of protein phosphorylation illustrates the potential for simultaneous quantification of multiple PTMs.


title: Gender differences in the frequency of gastrointestinal symptoms and olfactory or taste disorders among 1,942 non-hospitalized patients with COVID-19.

text: INTRODUCTION The Coronavirus Disease 2019 (COVID 19) is a communicable disease caused by novel coronavirus. OBJECTIVES This study aimed to assess self-reported frequency of gastrointestinal symptoms and olfactory or taste disorders in non-hospitalized patients with COVID-19 in Poland. PATIENTS AND METHODS This cross-sectional survey was conducted between April 17 and 18, 2020, among 4,516 non-hospitalized patients with COVID-19 in Poland. The questionnaire included eight questions related to the health status, symptoms of COVID-19, comorbidities, and smoking status. RESULTS Completed questionnaires were obtained from 1,942 patients with COVID-19, a response rate of 43%. The median age of the respondents was 50 years; 60.2% were women. Among non-hospitalized patients with COVID-19, 21.3% had hypertension, 4.5% had diabetes, and 3.1% of COVID-19 cases had chronic respiratory disease. Regular tobacco use was declared by 11.2% of patients with COVID-19. At least one gastrointestinal symptom was reported by 53.6% of patients. Almost half of patients (47%) with COVID-19 reported lack of appetite and 24.2% reported diarrhea. Among 1,942 interviewed patients, 54.2% reported at least one olfactory or taste disorder and 42.5% reported both alterations. Self-reported olfactory and taste disorders were 49.2% and 47.5%, respectively. Self-reported frequency of gastrointestinal symptoms and olfactory or taste disorders during COVID-19 course was significantly higher (p<0.001) among women than men. CONCLUSIONS In conclusion, this study demonstrated that olfactory and taste disorders are frequent symptoms in mild-to-moderate COVID-19 patients. Moreover, our study indicates gender differences in the frequency of gastrointestinal symptoms and olfactory or taste disorders among non-hospitalized patients with COVID-19.


Surviving influenza: lived experiences of health inequity and pandemic disease in Canada.


title: Cyclophilin and NS5A inhibitors, but not other anti-hepatitis C virus (HCV) agents, preclude HCV-mediated formation of double-membrane-vesicle viral factories.

text: Although the mechanisms of action (MoA) of nonstructural protein 3 inhibitors (NS3i) and NS5B inhibitors (NS5Bi) are well understood, the MoA of cyclophilin inhibitors (CypI) and NS5A inhibitors (NS5Ai) are not fully defined. In this study, we examined whether CypI and NS5Ai interfere with hepatitis C virus (HCV) RNA synthesis of replication complexes (RCs) or with an earlier step of HCV RNA replication, the creation of double-membrane vesicles (DMVs) essential for HCV RNA replication. In contrast to NS5Bi, both CypI and NS5Ai do not block HCV RNA synthesis by way of RCs, suggesting that they exert their antiviral activity prior to the establishment of enzymatically active RCs. We found that viral replication is not a precondition for DMV formation, since the NS3-NS5B polyprotein or NS5A suffices to create DMVs. Importantly, only CypI and NS5Ai, but not NS5Bi, mir-122, or phosphatidylinositol-4 kinase IIIα (PI4KIIIα) inhibitors, prevent NS3-NS5B-mediated DMV formation. NS3-NS5B was unable to create DMVs in cyclophilin A (CypA) knockdown (KD) cells. We also found that the isomerase activity of CypA is absolutely required for DMV formation. This not only suggests that NS5A and CypA act in concert to build membranous viral factories but that CypI and NS5Ai mediate their early anti-HCV effects by preventing the formation of organelles, where HCV replication is normally initiated. This is the first investigation to examine the effect of a large panel of anti-HCV agents on DMV formation, and the results reveal that CypI and NS5Ai act at the same membranous web biogenesis step of HCV RNA replication, thus indicating a new therapeutic target of chronic hepatitis C.


title: Transfemoral endovascular treatment of atherosclerotic stenotic lesions of the left common carotid artery ostium: case series and review of the literature.

text: OBJECTIVE Endovascular treatment of atherosclerotic stenosis of the left common carotid artery ostium (LCCAO) represents a technical challenge. Unlike stenting of other supra-aortic trunk lesions, LCCAO stenting is not able to be performed from a retrograde approach through the brachial artery. Stenting may be performed via a retrograde approach with a carotid artery cut-down or with total endovascular technique via a transfemoral approach. A consecutive case series is presented to demonstrate the feasibility and safety of the endovascular transfemoral LCCAO stenting technique. METHODS Our prospectively maintained database of elective neuroendovascular procedures was searched for cases of LCCAO angioplasty and stenting for atherosclerotic stenosis performed between January 2003 and April 2012. Cases identified were isolated and analyzed for clinical and anatomic data. The primary outcome of interest was the incidence of periprocedural (30-day) neurological or cardiopulmonary complications. RESULTS Fourteen patients were treated with a transfemoral approach (mean arterial stenosis 72%; symptomatic lesions 86%). Six (43%) had tandem stenosis of the proximal left internal carotid artery. In these cases, embolic protection was used. Stent revascularization was a technical success in all 14 patients, resulting in <20% residual stenosis in each. One intraprocedural complication (transient ischemic attack) was noted in a patient with symptomatic stenosis. One additional patient was identified who was treated with retrograde stenting due to bilateral leg amputations and no femoral access, with no periprocedural complication. CONCLUSIONS In our experience, transfemoral stenting of stenotic LCCAO lesions is feasible and no permanent neurological or cardiopulmonary sequelae occurred in 14 patients treated with this technique.


title: Alpha blockers for treatment of ureteric stones: systematic review and meta-analysis.

text: OBJECTIVE To investigate the efficacy and safety of alpha blockers in the treatment of patients with ureteric stones. DESIGN Systematic review and meta-analysis. DATA SOURCES Cochrane Central Register of Controlled Trials, Web of Science, Embase, LILACS, and Medline databases and scientific meeting abstracts to July 2016. REVIEW METHODS Randomized controlled trials of alpha blockers compared with placebo or control for treatment of ureteric stones were eligible. : Two team members independently extracted data from each included study. The primary outcome was the proportion of patients who passed their stone. Secondary outcomes were the time to passage; the number of pain episodes; and the proportions of patients who underwent surgery, required admission to hospital, and experienced an adverse event. Pooled risk ratios and 95% confidence intervals were calculated for the primary outcome with profile likelihood random effects models. Cochrane Collaboration's tool for assessing risk of bias and the GRADE approach were used to evaluate the quality of evidence and summarize conclusions. RESULTS 55 randomized controlled trials were included. There was moderate quality evidence that alpha blockers facilitate passage of ureteric stones (risk ratio 1.49, 95% confidence interval 1.39 to 1.61). Based on a priori subgroup analysis, there seemed to be no benefit to treatment with alpha blocker among patients with smaller ureteric stones (1.19, 1.00 to 1.48). Patients with larger stones treated with an alpha blocker, however, had a 57% higher risk of stone passage compared with controls (1.57, 1.17 to 2.27). The effect of alpha blockers was independent of stone location (1.48 (1.05 to 2.10) for upper or middle stones; 1.49 (1.38 to 1.63) for lower stones). Compared with controls, patients who received alpha blockers had significantly shorter times to stone passage (mean difference -3.79 days, -4.45 to -3.14; moderate quality evidence), fewer episodes of pain (-0.74 episodes, -1.28 to -0.21; low quality evidence), lower risks of surgical intervention (risk ratio 0.44, 0.37 to 0.52; moderate quality evidence), and lower risks of admission to hospital (0.37, 0.22 to 0.64; moderate quality evidence). The risk of a serious adverse event was similar between treatment and control groups (1.49, 0.24 to 9.35; low quality evidence). CONCLUSIONS Alpha blockers seem efficacious in the treatment of patients with ureteric stones who are amenable to conservative management. The greatest benefit might be among those with larger stones. These results support current guideline recommendations advocating a role for alpha blockers in patients with ureteric stones. SYSTEMATIC REVIEW REGISTRATION PROSPERO registration No CRD42015024169.


title: Validation of contrast-enhanced magnetic resonance imaging to monitor regenerative efficacy after cell therapy in a porcine model of convalescent myocardial infarction.

text: BACKGROUND Magnetic resonance imaging (MRI) in the CArdiosphere-Derived aUtologous stem CElls to reverse ventricUlar dySfunction (CADUCEUS) trial revealed that cardiosphere-derived cells (CDCs) decrease scar size and increase viable myocardium after myocardial infarction (MI), but MRI has not been validated as an index of regeneration after cell therapy. We tested the validity of contrast-enhanced MRI in quantifying scarred and viable myocardium after cell therapy in a porcine model of convalescent MI. METHODS AND RESULTS Yucatan minipigs underwent induction of MI and 2-3 weeks later were randomized to receive intracoronary infusion of 12.5×10(6) mismatched allogeneic CDCs or vehicle. Allogeneic CDCs induced mild local mononuclear infiltration but no systemic immunogenicity. MRI revealed that allogeneic CDCs attenuated remodeling, improved global and regional function, decreased scar size, and increased viable myocardium compared with placebo 2 months post-treatment. Extensive histological analysis validated quantitatively the MRI measurements of scar size, scar mass, and viable mass. CDCs neither altered gadolinium contrast myocardial kinetics nor induced changes in vascular density or architecture in viable and scarred myocardium. Histology demonstrated that CDCs lead to cardiomyocyte hyperplasia in the border zone, consistent with the observed stimulation of endogenous regenerative mechanisms (cardiomyocyte cycling, upregulation of endogenous progenitors, angiogenesis). CONCLUSIONS Contrast-enhanced MRI accurately measures scarred and viable myocardium after cell therapy in a porcine model of convalescent MI. MRI represents a useful tool for assessing dynamic changes in the infarct and monitoring regenerative efficacy.


title: Increase in fluorodeoxyglucose positron emission tomography activity following complete radiofrequency ablation of lung tumors.

text: OBJECTIVE The objective of this study was to evaluate the F-fluorodeoxyglucose positron emission tomography (F-FDG-PET) findings following complete radiofrequency ablation (RFA) treatment of malignant lung tumors. METHODS Follow-up PET and computed tomography examinations in 18 patients (mean age, 67 ± 16 years [range, 30-91 years]; 10 males, 8 females) who underwent 19 RFA sessions for the treatment of primary (n = 14) and metastatic (n = 5) lung tumors with mean follow-up of 18 months (range, 12-24 months) were retrospectively reviewed by 2 thoracic radiologists. All tumors were completely ablated. The maximum standardized uptake value (SUV) of the tumor and surrounding lung at baseline and at 1, 6, 12 and 24 months after RFA was measured. In addition, the size, histology, location of the tumor, presence of underlying emphysema, electrode type, and complications from RFA were recorded. Data were analyzed using Fisher exact test. RESULTS Baseline tumor SUV was variable (mean, 1.8 ± 1.5 [range, 0.7-7]). The post-RFA F-FDG-PET appearances could be divided into 2 groups. A ring of peripheral activity and central photopenia was seen following 13 (68%) of 19 of ablations, and no ring was noted following 6 (32%) of 19 of ablations. The ring of F-FDG-PET activity was present at 1 month in 62%, at 6 months in 69% and at both 1 and 6 months in 31%. In all cases, central photopenia at 1 or 6 months was replaced by increased activity as the ring resolved at 6 or 12 months, mimicking local tumor progression. The presence of a ring of activity was associated with the use of a cluster electrode (P = 0.01). Lesion size, histology, location, baseline SUV, electrode type, or development of cavitation following RFA were not significantly associated with a post-RFA ring (P > 0.05) on PET scans. At 12 or 24 months, the SUV in the center of the lesion was equal to or greater than the SUV at baseline in 9 (47%) of 19 cases. CONCLUSIONS Recognition of the normal FDG-PET appearances after RFA is important to prevent misdiagnosis of local tumor progression.


title: Minimally Invasive Surgery for Resection of Parapharyngeal Space Tumors.

text: Background Surgical removal of parapharyngeal space tumors (PPST) poses challenges due to the complex anatomy of the region. PPSTs are routinely resected by a transcervical approach using blind finger dissection. Large PPSTs or those located high at the skull base, often require transmandibular or infratemporal fossa approaches, associated with considerable morbidity. Objective Here, we describe an approach for PPST removal that comprises transcervical endoscopic, with or without transoral robotic technique. Materials and Methods We retrospectively studied the demographic, clinical, surgical, and outcome data of 11 consecutive patients who underwent PPST excision between June 2013 and July 2017 at our center. Patients either underwent a transcervical endoscopic procedure ( n = 4), a transoral robotic procedure ( n = 2) or a combination of the two procedures ( n = 5). Results Complete tumor excision was achieved in all cases, with no intra-, peri-, or postoperative complications. Final histopathologic findings demonstrated pleomorphic adenoma for seven patients, cavernous hemangioma for one patient, and malignant tumors for three patients. The average tumor size was 44.22 ± 31.9 cm 3 (range: 7.5-111 cm 3 ). At follow-up (range: 3-42 months), there was no evidence of recurrence. Conclusions The approach described provides improved visualization and safe vascular control with minimum tumor stress, preventing the need for blind finger dissection, and allowing complete tumor removal while minimizing tumor spillage, nerve injury, and blood loss, maintaining excellent cosmetic and functional results. This approach could be utilized for the removal of large benign PPST, or small PPST located high.


The old-style public health measures and the novel coronavirus outbreak.


title: The trauma and acute care surgeon in the COVID-19 pandemic era.

text: The World Health Organization recognized in March 2020 the existence of a pandemic for the new coronavirus that appeared in China, in late 2019, and whose disease was named COVID-19. In this context, the SBAIT (Brazilian Society of Integrated Care for Traumatized Patients) conducted a survey with 219 trauma and emergency surgeons regarding the availability of personal protective equipment (PPE) and the role of the surgeon in this pandemic by means of an electronic survey. It was observed that surgeons have been acting under inadequate conditions, with a lack of basic supplies as well as more specific equipment such as N95 masks and facial shields for the care of potential victims who may be contaminated. The latter increases the risk of contamination of professionals, resulting in potential losses in the working teams. Immediate measures must be taken to guarantee access to safety equipment throughout the country, since all trauma victims and/or patients with emergency surgical conditions must be treated as potential carriers of COVID-19.


title: Influence of mesh materials on the expression of mediators involved in wound healing.

text: The use of synthetic mesh for ventral hernia repair is widely accepted, but mesh-induced inflammatory responses may lead to postoperative complications. Molecular mechanisms that direct the extent of the foreign body reaction to implanted materials are poorly understood. This study compares the influence of three macroporous meshes on the expression of genes critical for wound healing and extracellular matrix remodeling in a rat model. Full thickness abdominal wall defects were corrected with polypropylene, polyester, polytetrafluoroethylene (PTFE), or suture repair with no mesh. Explants were harvested 7 or 90 days after repair and were divided for histological, immunohistochemical, and mRNA analyses. Real-time quantitative polymerase chain reaction arrays were used to profile the expression of 84 genes involved in angiogenesis at the tissue-mesh interface. Evaluation of gene expression profiles and histologic specimens revealed that polypropylene and polyester induced a greater and more persistent inflammatory response than PTFE, which elicited a response most similar to that induced by suture repair. Mesh implantation induced the differential expression (>3-fold change and p < .01) of genes encoding inflammatory cytokines, growth factors, and extracellular matrix proteins relative to suture repair without mesh. Genes most markedly upregulated included the neutrophil chemoattractant CXCL2 and matrix metalloproteinases 3 and 9. Polyester induced the greatest number of differentially expressed genes relative to suture repair both at 7 and 90 days after implantation. Results from this study suggest that the particular type of mesh used in a hernia repair may affect the patient's wound healing response and clinical outcome.


title: Resection of esophageal diverticulum through uniportal video-assisted thoracoscopic surgery.

text: Open surgery remains the standard strategy for management of esophageal diverticulum in symptomatic patients. However, in the last years an increasing number of minimally invasive approaches have been proposed for this issue in order to reduce the surgical trauma and favor a fast return to daily activity. Herein, we describe a novel technique as uniportal video-assisted thoracoscopic surgery (VATS) for performing resection of esophageal diverticulum. This procedure was successfully carried out in three consecutive patients with giant mid-esophageal diverticulum (mean size: 6.5±0.5 cm). The mean post-operative time was 121±10 minutes. The chest drain was removed 48 hours later in all cases and the mean length of hospital stay was 9±1 days. No intraoperative neither postoperative complications were found in all patients but one. He had a small fistula 15 days later that was successfully treated with stent insertion. No recurrence of diverticulum was seen in all cases. Uniportal VATS is a feasible procedure that in theory could reduce the surgical trauma compared to standard open approach. However, future prospective studies should corroborate our impression before it can be recommended as acceptable therapy.


title: Poor Results of Flow Diversion as Salvage Treatment for Intracranial Aneurysm Rerupture After Surgical Clip Reconstruction.

text: Rebleeding episodes after a ruptured intracranial aneurysm has been secured are considered a significant source of patient morbidity and mortality. Theoretically, acute treatment with a flow-diversion device may offer a reasonable treatment option to prevent future bleeding and to remodel the diseased vessel segment. The authors identified two patients who underwent emergent treatment with the placement of a Pipeline Embolization Device (PED) in the setting of an acute rebleeding of a ruptured intracranial aneurysm previously treated with clip reconstruction. The first patient was a 50-year-old woman who underwent clip reconstruction for a broad-based right anterior choroidal artery aneurysm measuring approximately 2×8 mm. Clip reconstruction was achieved with a single fenestrated clip. On day 14, the patient experienced a rebleeding episode. She underwent emergent treatment with a single PED but experienced another rebleeding and died. The second patient was a 53-year-old woman who presented with a ruptured dorsal variant blister aneurysm, which was treated with clip reconstruction. On day 22, she experienced a rebleeding episode and underwent emergent treatment using two PEDs in a duplicative fashion. After the procedure, she experienced another acute rebleeding episode and died. The treatment of reruptured intracranial aneurysms in a salvage fashion with emergent placement of PEDs in two patients resulted in good technical placement of the device covering the neck of the aneurysm, yet both patients experienced additional rebleeding and did not survive. Future generations of flow diverters may have more appropriate properties that would allow their use as salvage treatment in the setting of acutely ruptured aneurysms.


title: Siting epidemic disease: 3 centuries of American history.

text: Epidemics of infectious disease have always played a role in American history, and such epidemics are sited in time and place and configured in terms of ecology and demography, available medical knowledge, and cultural values and collective experience. The mix of these variables has changed dramatically since the theocratic world of 17th-century New England, but the relevance of each remains. Avian influenza already exists virtually in Western society in terms of planning, global networks, laboratory research, social expectations, media representations, and a specific shared history based on the memory of the 1918 influenza pandemic.


title: Haloperidol for delirium in critically ill patients - protocol for a systematic review.

text: BACKGROUND In the intensive care unit, the prevalence of delirium is high. Delirium has been associated with morbidity and mortality including more ventilator days, longer intensive care unit stay, increased long-term mortality, and cognitive impairment. Thus, the burden of delirium for patients, relatives, and societies is considerable. The objective of this systematic review was to critically access the evidence of randomised clinical trials on the effects of haloperidol vs. placebo or any other agents for delirium in critically ill patients. METHODS We will search for randomised clinical trials in the following databases: Cochrane Library, MEDLINE, EMBASE, Science Citation Index, BIOSIS, Cumulative Index to Nursing and Allied Health Literature, Latin American and Caribbean Health Sciences Literature, and Allied and Complementary Medicine Database. Two authors will independently screen and select references for inclusion using Covidence, extract data and assess the methodological quality of the included randomised clinical trials using the Cochrane risk of bias tool. Any disagreement will be resolved by consensus. We will analyse the extracted data using Review Manager, STATA 15, and Trial Sequential. ANALYSIS The aim of this study was to assess the quality of the evidence, we will create a 'Summary of Findings' table containing our primary and secondary outcomes using the GRADE assessment. DISCUSSION Our ambition with this systematic review is to provide reliable and powered evidence to better inform decision makers on the use of or future trials with haloperidol for the management of delirium in critically ill patients.


Personalized approach to revascularization of critical limb ischemia.


title: [Airborne spreading for patients suffering severe coronavirus disease-2019 with different oxygen therapies].

text: 根据COVID-19诊疗方案（试行第七版），目前新型冠状病毒的主要传播途径是呼吸道飞沫和密切接触。然而在相对封闭环境如重症监护病房中，长时间暴露于高浓度气溶胶环境中，亦存在经气溶胶传播的可能。就ICU而言，不同氧疗方式对新型冠状病毒传播的影响，主要基于不同氧疗方式对气溶胶或飞沫的产生以及扩散范围。本文比较了三种氧疗方式过程中，新型冠状病毒经空气传播的风险差异，以进一步减少院内感染发生。.


Platelet inhibition with cangrelor during PCI.


title: Successful laparoscopic resection of a sacrococcygeal teratoma in an adult: report of a case.

text: Sacrococcygeal teratoma is a relatively rare congenital retroperitoneal tumor in adults. The standard treatment is a complete tumor resection. This report describes the successful laparoscopic resection of a sacrococcygeal teratoma. The patient was a 27-year-old woman with a well-demarcated cystic mass, 6 cm in diameter, in the retroperitoneum overlying the anterior surface of the sacrum. The mass was resected laparoscopically. A histopathological examination showed a mature teratoma. The magnifying function of the laparoscope allowed an en bloc resection in the narrow pelvic cavity, without damaging the tumor. The aesthetic outcome was excellent. The patient remains relapse-free at 1 year 6 months after surgery.


title: Successful laparoscopic management of combined traumatic diaphragmatic rupture and abdominal wall hernia: a case report.

text: BACKGROUND Traumatic diaphragmatic rupture and traumatic abdominal wall hernia are two well-described but rare clinical entities associated with blunt thoracoabdominal injuries. To the best of our knowledge, the combination of these two clinical entities as a result of a motor vehicle accident has not been previously reported. CASE PRESENTATION A 32-year-old Indian man was brought to our emergency department after being involved in a road traffic accident. He described a temporary loss of consciousness and had multiple tender bruises at his right upper anterior abdominal wall and left lumbar region. An initial examination revealed blood pressure of 99/63 mmHg, heart rate of 107 beats/minute, and oxygen saturation of 93 % on room air. His clinical parameters stabilized after initial resuscitation. A computed tomographic scan revealed a rupture of the left diaphragm as well as extensive disruptions of the left upper anterior abdominal wall. We performed exploratory laparoscopic surgery with the intention of primary repair. The diaphragmatic and abdominal wall defect was primarily closed, followed by reinforcement with PROLENE onlay mesh. The patient's postoperative recovery was complicated by infected hematomas over both flanks that were managed with ultrasound-guided percutaneous drainage. He was discharged well despite a prolonged hospital stay. CONCLUSIONS We present a complex form of injuries managed successfully via a laparoscopic approach. Meticulous attention to potential complications in both the acute and convalescent phases is important for achieving a successful outcome following surgery.


title: Nanoceramics for blood-borne virus removal.

text: The development of nanoscience and nanotechnology in the field of ceramics has brought new opportunities for the development of virus-removal techniques. A number of nanoceramics, including nanostructured alumina, titania and zirconia, have been introduced for the applications in virus removal or separation. Filtration or adsorption of viruses, and thus the removal of viruses through nanoceramics, such as nanoporous/mesoporous ceramic membranes, ceramic nanofibers and ceramic nanoparticles, will make it possible to produce an efficient system for virus removal from blood and one with excellent chemical/thermal stability. Currently, nanoceramic membranes and filters based on sol-gel alumina membranes and NanoCeram nanofiber filters have been commercialized and applied to remove viruses from the blood. Nevertheless, filtration using nanoporous filters is limited to the removal of only free viruses in the bloodstream.


COVID-19 (Coronavirus Disease 2019): Opportunities and Challenges for Digital Health and the Internet of Medical Things in China.


title: New Normal Terminology.

text: The COVID-19 pandemic has required us to recognize a new normal and other additions to our general and clinical vocabulary. Some were preexisting terms that now have been broadened or changed during these unprecedented times. Others have helped to bring to light some of the issues or difficulties that healthcare professionals faced prior to this pandemic.


title: Thoracoscopy with Concurrent Esophagoscopy for Persistent Right Aortic Arch in 9 Dogs.

text: OBJECTIVE To report the diagnosis, treatment, and short-term outcome in dogs with suspected persistent right aortic arch (PRAA) undergoing thoracoscopy with concurrent esophagoscopy. STUDY DESIGN Multi-institutional retrospective case series. ANIMALS Dogs with suspected PRAA (n=9). METHODS Medical records were reviewed from 2012 to 2016. Dogs undergoing thoracoscopy for PRAA at 3 referral hospitals were included. Signalment, clinical signs, diagnostic imaging, anesthesia protocol (including the use of one-lung ventilation), surgical approach, complications, and short-term outcome were recorded. Dogs underwent a left-sided intercostal thoracoscopic approach with concurrent intraoperative esophagoscopy. The ligamentum arteriosum (LA) and constricting fibers were divided using a vessel-sealing device using a 3 or 4 port thoracoscopy technique. Visualization and dissection of the LA was aided by transesophageal illumination by esophagoscopy. RESULTS Thoracoscopy confirmed PRAA in 9 dogs, with an aberrant left subclavian artery (LS) identified in 5 dogs. Major complications occurred in 2 dogs: postoperative hemorrhage from the LS and esophageal perforation, which resulted in euthanasia. Median follow-up was 250 days (range, 56-1,595). Regurgitation resolved in 4 of 8 surviving dogs. One dog had recurrence of regurgitation 1,450 days postoperatively, esophageal compression by the LS was identified, and regurgitation resolved following LS transection. CONCLUSION Esophagoscopy aided identification and dissection of the LA in all cases. Due to the potential for the LS to cause clinical esophageal constriction postoperatively, a recommendation for LS transection may be warranted. Vascular clips can also be considered as an alternative for vessel ligation to avoid complications associated with vessel-sealing device use.


title: Transanal Approach to Rectal Polyps and Cancer.

text: A transanal approach to rectal polyp and cancer excision is often an appropriate alternative to conventional rectal resection, and has a lower associated morbidity. There has been a steady evolution in the techniques of transanal surgery over the past 30 years. It started with traditional transanal excision and was revolutionized by introduction of transanal endoscopic microsurgery in early 1980s. Introduction of transanal minimally invasive surgery made it more accessible to surgeons around the world. Now robotic platforms are being tried in certain institutions. Concerns have been raised about recurrence rates of cancers with transanal approach and success of subsequent salvage operations.


title: Single incision laparoscopic myomectomy.

text: Single port laparoscopic surgery (SPLS), also called SILS is the natural extension of multi-incisional laparoscopic surgery, in the quest for reduction of traumatic insult and residual scarring to the patient. Today with the evolution of newer instruments, bidirectional self-retaining sutures, and surgical experience we are able to perform many surgeries in gynecology.


title: Right-sided transperitoneal hand-assisted laparoscopic donor nephrectomy: is there an issue with the renal vessels?

text: OBJECTIVE Short right renal vessels might complicate kidney transplantation, thus causing traction and difficulties during anastomosis. Single-center prospective comparison of right- and left-sided transperitoneal hand-assisted laparoscopic donor nephrectomy (HALDN) is presented. PATIENTS AND METHODS Eighty-two living kidney donors underwent HALDN between 2003 and 2008. Right-sided HALDN was performed in 46 living kidney donors. The operative technique of right-sided HALDN was modified to obtain the maximum length of right renal vessels. Outcome data in donors including quality of life as well as graft outcome in recipients were prospectively collected. RESULTS All procedures were laparoscopically completed with no conversion. Mean operative time was 127 minutes (vs. 138 minutes in left HALDN, p = 0.08). The mean warm ischemia time was 41 seconds (vs. 39 seconds in left HALDN, p = 0.23). There was no renal artery or vein thrombosis in any of the grafts. Mean blood loss was 81 mL (vs. 92 mL in left HALDN, p = 0.09). Hospital discharge was on an average of 3.6 days postoperative. Delayed graft function occurred in two recipients: one in the left group and the other in the right group. One-year graft survival rate was 95% in the left group versus 96.9% in the right group (p = 0.08). Further, no statistically significant difference in serum levels of creatinine was seen between the groups 1 year after the transplantation. CONCLUSIONS Right HALDN is technically safe and feasible and results in convenient extension of right renal vessels to full length with no increased incidence of vascular thrombosis.


Check-ins not check-ups.


title: Examining the Ethical Implications of Health Care Technology Described in US and Swedish PhD Dissertations: Protocol for a Scoping Review.

text: BACKGROUND The development of new biomedical technologies is accelerating at an unprecedented speed. These new technologies will undoubtedly bring solutions to long-standing problems and health conditions. However, they will likely also have unintended effects or ethical implications accompanying them. It may be presumed that the research behind new technologies has been evaluated from an ethical perspective; however, the evidence that this has been done is scant. OBJECTIVE This study aims to understand whether and in what manner PhD dissertations focused on health technologies describe actual or possible ethical issues resulting from their research. METHODS The purpose of scoping reviews is to map a topic in the literature comprehensively and systematically to identify gaps in the literature or identify key evidence. The search strategy for this protocol will include electronic databases (eg, ProQuest, PubMed, Diva, SwePub, and LIBRIS). Searches will be limited to PhD dissertations published in the United States and Sweden in the last 10 years. The study will be mapped in 5 stages: (1) identifying the research question, (2) identifying relevant studies, (3) study selection, (4) retrieving and charting the data, and (5) collating, summarizing, and reporting the results. RESULTS The findings of this study will indicate if and how researchers, PhD students, and their supervisors are considering ethics in their studies, including both research ethics and the ethical implications of their work. The findings can guide researchers in determining gaps and shortcomings in current doctoral education and offer a foundation to adjusting doctoral research education. CONCLUSIONS In a society where technology and research are advancing at speeds unknown to us before, we need to find new and more efficient ways to consider ethical issues and address them in a timely manner. This study will offer an understanding of how ethics is currently being integrated into US and Swedish PhD dissertations and inform the future direction of ethics education at a doctoral level. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID) PRR1-10.2196/14157.


title: A Review of Simulators with Haptic Devices for Medical Training.

text: Medical procedures often involve the use of the tactile sense to manipulate organs or tissues by using special tools. Doctors require extensive preparation in order to perform them successfully; for example, research shows that a minimum of 750 operations are needed to acquire sufficient experience to perform medical procedures correctly. Haptic devices have become an important training alternative and they have been considered to improve medical training because they let users interact with virtual environments by adding the sense of touch to the simulation. Previous articles in the field state that haptic devices enhance the learning of surgeons compared to current training environments used in medical schools (corpses, animals, or synthetic skin and organs). Consequently, virtual environments use haptic devices to improve realism. The goal of this paper is to provide a state of the art review of recent medical simulators that use haptic devices. In particular we focus on stitching, palpation, dental procedures, endoscopy, laparoscopy, and orthopaedics. These simulators are reviewed and compared from the viewpoint of used technology, the number of degrees of freedom, degrees of force feedback, perceived realism, immersion, and feedback provided to the user. In the conclusion, several observations per area and suggestions for future work are provided.


title: How Indians responded to the Arogya Setu app?

text: The mHealth app Arogya Setu can substantially contribute to the containment and management of COVID-19. This study explores the experiences and expectations of Arogya Setu app users by conducting a combined content analysis of their reviews. Five hundred and three most relevant reviews were analyzed using the descriptive statistics and thematic analysis. The reviews are primarily posted in the areas of user acceptance (80%), app usefulness (72.8%), and app features (62.2%). The thematic analysis resulted in four themes: user acceptance, app usefulness, promptness of the Indian Government in bringing the app on time, and concerns and cautions raised by the users. These help in strengthening the app features enabling the real-time data capture and analytics and providing timely information to authorities for better decision-making.


title: Preliminary application of a single-port access technique for laparoscopic ovariohysterectomy in dogs.

text: Laparoscopic ovariohysterectomy using single-portal access was performed in nine selected owned dogs admitted for elective ovariohysterectomy and the surgical technique and outcomes were detailed. A multiport device (SILS Port, Covidien, USA) was placed at the umbilical area through a single 3 cm incision. Three cannulae were introduced in the multiport device through the access channels and laparoscopic ovariohysterectomy was performed using a 5-mm sealing device, a 5-mm articulating grasper and a 5-mm 30° laparoscope. The mean total operative time was 52.66±15.20 minutes and the mean skin incision during surgery was 3.09±0.20 cm. Of the nine cases examined, in the one with an ovarian tumour, the technique was converted to multiport laparoscopy introducing an additional 5-mm trocar. No surgical complications were encountered and intraoperative blood loss was minimum in all animals. Clashing of the instruments and reduced triangulation were the main limitations of this technique. The combination of articulated and straight instruments facilitated triangulation towards the surgical field and dissection capability. One month after surgery a complete wound healing was observed in all animals. The present data showed that ovariohysterectomy performed with a single-port access is technically feasible in dogs. The unique abdominal incision minimises the abdominal trauma with good cosmetic results.


title: Oncology practice during COVID-19 pandemic: a fast response is the best response.

text: The first confirmed case of coronavirus disease 2019 (COVID-19) in Brasil was reported on February 25th, 2020, and by April 3rd, 8076 were confirmed in the country. As COVID-19 disease incidence escalates in Brasil, management of cancer patients requires immediate action and oncology clinics are urged to establish a contingency plan. We have installed a COVID-19 Management Committee to elaborate and implement best practices to assist cancer outpatients as well as to provide a safe environment for clinical staff and other employees at the outpatient clinics. The challenges of cancer treatment in the midst of COVID-19 global pandemic highlight the importance of a rapid response by institutions, where organizational structure, strategic planning, agility in guidelines implementation and alternative ways to protect and support clinical staff, employees and patients may be the key to mitigate pandemic effects.


title: Effect of a hypertonic balanced ketone solution on plasma, CSF and brain beta-hydroxybutyrate levels and acid-base status.

text: PURPOSE Although glucose is the main source of energy for the human brain, ketones play an important role during starvation or injury. The purpose of our study was to investigate the metabolic effects of a novel hypertonic sodium ketone solution in normal animals. METHODS Adult Sprague-Dawley rats (420-570 g) were divided into three groups of five, one control and two study arms. The control group received an intravenous infusion of 3 % NaCl at 5 ml/kg/h. The animals in the two study arms were assigned to receive one of the two formulations of ketone solutions, containing hypertonic saline with 40 and 120 mmol/l beta-hydroxybutyrate, respectively. This was infused for 6 h and then the animal was euthanized and brains removed and frozen. RESULTS Both blood and cerebrospinal fluid (CSF) levels of beta-hydroxybutyrate (BHB) demonstrated strong evidence of a change over time (p < 0.0001). There was also strong evidence of a difference between groups (p < 0.0001). Multiple comparisons showed all these means were statistically different (p < 0.05). Measurement of BHB levels in brain tissue found strong evidence of a difference between groups (p < 0.0001) with control: 0.15 mmol/l (0.01), BHB 40: 0.19 mmol/l (0.01), and BHB 120: 0.28 mmol/l (0.01). Multiple comparisons showed all these means were statistically different (p < 0.05). There were no differences over time (p = 0.31) or between groups (p = 0.33) or an interaction between groups and time (p = 0.47) for base excess. CONCLUSION The IV infusions of hypertonic saline/BHB are feasible and lead to increased plasma, CSF and brain levels of BHB without significant acid/base effects.


Impact of COVID-19 mitigation measures on patients with spine disease in Friuli Venezia Giulia.


title: Outcomes of robot-assisted versus laparoscopic repair of small-sized ventral hernias.

text: INTRODUCTION The aim of the study is to investigate the outcomes of the da Vinci robot-assisted laparoscopic hernia repair of small-sized ventral hernias with circumferential suturing of the mesh compared to the traditional laparoscopic repair with trans-fascial suturing. METHODS A retrospective review was conducted of all robot-assisted umbilical, epigastric and incisional hernia repairs performed at our institution between 2013 and 2015 compared to laparoscopic umbilical or epigastric hernia repairs. Patient characteristics, operative details and postoperative complications were collected and analyzed using univariate analysis. Three primary minimally invasive fellowship trained surgeons performed all of the procedures included in the analysis. RESULTS 72 patients were identified during the study period. 39 patients underwent robot- assisted repair (21 umbilical, 14 epigastric, 4 incisional), and 33 patients laparoscopic repair (27 umbilical, 6 epigastric). Seven had recurrent hernias (robot: 4, laparoscopic: 3). There were no significant differences in preoperative characteristics between the two groups. Average operative time was 156 min for robot-assisted repair and 65 min for laparoscopic repair (p < 0.0001). The average defect size was significantly larger for the robot group [3.07 cm (1-9 cm)] than that for the laparoscopic group [2.02 cm (0.5-5 cm)] (p < 0.0001), although there was no significant difference in the average size of mesh used (13 vs. 13 cm). There was no difference in patients requiring postoperative admission or length of stay between the two groups. The mean duration of follow-up was 47 days. There was no difference in complication rate during this time, and no recurrences were reported. CONCLUSION There are no significant differences in terms of safety and early efficacy when comparing small-sized ventral hernias repaired using the robot-assisted technique versus the standard laparoscopic repair.


title: ECG-based gating in ultra high field cardiovascular magnetic resonance using an independent component analysis approach.

text: BACKGROUND In Cardiovascular Magnetic Resonance (CMR), the synchronization of image acquisition with heart motion is performed in clinical practice by processing the electrocardiogram (ECG). The ECG-based synchronization is well established for MR scanners with magnetic fields up to 3 T. However, this technique is prone to errors in ultra high field environments, e.g. in 7 T MR scanners as used in research applications. The high magnetic fields cause severe magnetohydrodynamic (MHD) effects which disturb the ECG signal. Image synchronization is thus less reliable and yields artefacts in CMR images. METHODS A strategy based on Independent Component Analysis (ICA) was pursued in this work to enhance the ECG contribution and attenuate the MHD effect. ICA was applied to 12-lead ECG signals recorded inside a 7 T MR scanner. An automatic source identification procedure was proposed to identify an independent component (IC) dominated by the ECG signal. The identified IC was then used for detecting the R-peaks. The presented ICA-based method was compared to other R-peak detection methods using 1) the raw ECG signal, 2) the raw vectorcardiogram (VCG), 3) the state-of-the-art gating technique based on the VCG, 4) an updated version of the VCG-based approach and 5) the ICA of the VCG. RESULTS ECG signals from eight volunteers were recorded inside the MR scanner. Recordings with an overall length of 87 min accounting for 5457 QRS complexes were available for the analysis. The records were divided into a training and a test dataset. In terms of R-peak detection within the test dataset, the proposed ICA-based algorithm achieved a detection performance with an average sensitivity (Se) of 99.2%, a positive predictive value (+P) of 99.1%, with an average trigger delay and jitter of 5.8 ms and 5.0 ms, respectively. Long term stability of the demixing matrix was shown based on two measurements of the same subject, each being separated by one year, whereas an averaged detection performance of Se = 99.4% and +P = 99.7% was achieved.Compared to the state-of-the-art VCG-based gating technique at 7 T, the proposed method increased the sensitivity and positive predictive value within the test dataset by 27.1% and 42.7%, respectively. CONCLUSIONS The presented ICA-based method allows the estimation and identification of an IC dominated by the ECG signal. R-peak detection based on this IC outperforms the state-of-the-art VCG-based technique in a 7 T MR scanner environment.


title: Comparison of skin-sparing mastectomy using LigaSure™ Small Jaw and electrocautery.

text: BACKGROUND Skin-sparing mastectomy (SSM) is increasingly used in patients with breast cancer. We compared the differences between use of electrocautery and LigaSure™ Small Jaw in patients with breast cancer who underwent SSM. METHODS Between January 2012 and December 2015, 81 patients with breast cancer who underwent SSM were selected and were divided into the electrocautery group and the LigaSure™ Small Jaw group based on the devices that were used. Clinicopathological characteristics, body mass index, operative time, and weight of removed breast were obtained from medical records. Total amount and days of drain use, until removal, and postoperative skin necrosis, requiring debridement, were also analyzed. RESULTS The study population consisted of 50 patients in the electrocautery group and 31 in the LigaSure™ Small Jaw group. The latter group has significantly shorter operative time (117.5 ± 16.9 vs. 104.0 ± 23.6 min, P = 0.004). The mean total volume of drainage was less (805 ± 278 vs. 694 ± 131 mL, P = 0.017) and mean duration of drainage was also significantly shorter in the LigaSure™ Small Jaw group (11.3 ± 2.5 vs. 10.1 ± 2.0 days, P = 0.029). CONCLUSIONS The use of LigaSure™ Small Jaw during skin-sparing mastectomy shortened the operative time and duration of drainage and reduced the total volume of drainage.


title: Transcatheter stenting of the systemic-to-pulmonary artery shunt: A 7-year experience from a single tertiary center.

text: BACKGROUND Systemic-to-pulmonary artery shunt (SPS) dysfunction can be deleterious in shunt dependent patients and traditionally have undergone surgical revision. Data on transcatheter stenting of SPS is limited. We sought to evaluate feasibility, safety and outcomes of stenting SPS. METHODS Retrospective review of all patients who underwent transcatheter SPS stenting from 1/2006 to 12/2013. RESULTS Of 229 surgically implanted SPS, 25 transcatheter stent interventions were performed in 22 patients. The majority had pulmonary atresia (n = 9) or HLHS (n = 10). Their median age was 4 ms (range 10 days to 4 years) and median weight 4.9 kg (range 3-14). Nine had a central and 15 had a BT shunt with a median shunt size of 3.75 mm (range 3-6). The interval from shunt placement to intervention was 1.9 ms (range 4 days-3.8 years). The indication for intervention was increasing cyanosis in10 patients and delaying final repair in 9. Two patients were on ECMO at the time of intervention. The median shunt diameter increased from 2.3 to 4.1 mm and oxygen saturation from 72 to 85% (P < 0.001). No intra-procedural complications were encountered. One patient died from aspiration (autopsy demonstrated a patent shunt), 13 progressed to repair or next stage, 6 remain palliated with shunts as they are deemed unfit for the next stage and 2 are awaiting surgery. CONCLUSIONS Stenting of systemic to pulmonary artery shunt is a safe and effective procedure and avoids surgical re-intervention. It can be performed both as a rescue procedure in patients with acute shunt occlusion and as an elective procedure to palliate patients not yet suitable for subsequent corrective or staged repair.


title: Rotator cuff repair: a biomechanical ex vivo ovine study.

text: The purpose of this study was to assess load to failure of sutures, suturing techniques, and suture anchors used in rotator cuff surgery in order to explore their weaknesses. Ten types of sutures (absorbable and nonabsorbable), four types of suturing techniques, and eight types of suture anchors (bioabsorbable and metallic) were tested. Material Testing Machine and attached load cell were used to test the biomaterials in ex vivo ovine tissues. The results show that the mean load to failure and stiffness were higher in nonabsorbable sutures. Massive cuff tear and modified Mason-Allen suturing techniques had higher failure strength and stiffness when compared to simple and mattress techniques, but there was no substantial difference between them. Metallic suture anchors had higher failure strength when compared to bioabsorbable ones. Often either in metallic or in bioabsorbable anchors, the eyelet fails first. The failure sequence in ovine tissues is found to be in the following order: simple and mattress suturing techniques, nonabsorbable sutures, massive cuff tear and modified Mason-Allen suturing techniques, bioabsorbable anchors, and metallic anchors. Thus, it is concluded that metallic anchors mounted with modern nonabsorbable sutures will fail last. If we use simple and mattress techniques, the tendon-suture level will fail first, but it will improve substantially using more sophisticated suturing techniques (massive cuff tear or modified Mason-Allen).


title: Stress urinary incontinence after transvaginal mesh surgery for anterior and apical prolapse: preoperative risk factors.

text: INTRODUCTION AND HYPOTHESIS Debate persists over whether surgery to correct pelvic organ prolapse (POP) should be combined with midurethral sling (MUS) insertion. The aim of this study was to evaluate the incidence of stress urinary incontinence (SUI) up to 12 months after transvaginal mesh surgery, with or without MUS, and to identify risk factors for postoperative SUI. METHODS This retrospective single-center study included patients who underwent transvaginal mesh surgery with Uphold™ between October 2010 and December 2017. The primary outcome was the prevalence of SUI at 12 months postoperatively. Univariate and multivariate logistic regression was used to identify risks factors for postoperative SUI. RESULTS Of the 308 women included, 123 (40%) were continent (no SUI), 108 (35%) had SUI, and 76 (25%) had occult SUI. Forty-nine patients (15.9%) had a concomitant MUS procedure. At 12 months after surgery, 35.9% of patients without concomitant MUS had SUI vs 14.3% with (p = 0.003). Thirty-five patients (29%) developed de novo SUI. Postoperative complications were more common in patients with concomitant MUS (30.6% vs 17%; p = 0.003). The best predictor of postoperative SUI was the presence of preoperative SUI (OR 2.52 (1.25-5.09). Concomitant MUS (p < 0.001), and prior POP surgery (p = 0.034) were protective factors for postoperative SUI. CONCLUSION Preoperative SUI is the most important risk factor for postoperative SUI. However, given the higher risk of postoperative complications with concomitant MUS and the acceptable rate of de novo SUI rate without it, two-stage surgery seems preferable for patients with preoperative SUI.


title: Robotic extended pancreatectomy with vascular resection for locally advanced pancreatic tumors.

text: OBJECTIVES Limited involvement of the major peripancreatic vessels is no longer considered a contraindication for resection in cases of locally advanced pancreatic cancer. Extended open pancreatectomies associated with vascular resection are performed in experienced centers with mortality and morbidity rates comparable to standard pancreatic resection. We evaluate the safety, feasibility, and outcomes of robotic extended pancreatectomy with vascular resection. METHODS We reviewed data of 5 patients with a median age of 60 years (range, 52-74 years) who underwent robotic surgery for pancreatic tumors with vascular involvement between May 2007 and March 2010 at our institution. The types of resection included 2 left-sided splenopancreatectomy with celiac axis resection, 1 left-sided splenopancreatectomy with portal vein resection, and 2 pancreaticoduodenectomy with portal vein resection. RESULTS No conversions occurred. The overall mean operating time was 392 ± 66 minutes (range, 310-460 min). The overall mean blood loss was 200 ± 61 mL (range, 150-300 mL) with no transfusions. No mortalities occurred. At a median follow-up of 6 months (range, 3-20 months), 4 patients were alive and disease free. CONCLUSIONS This early series by a single surgeon supports the feasibility and safety of robotic pancreatectomy with vascular resection for selected patients with locally advanced pancreatic tumor.


COVID-19: how will this impact children with cancer, now and in the future?


title: Endovascular Therapy in Ischemic Stroke With Acute Large-Vessel Occlusion: Recovery by Endovascular Salvage for Cerebral Ultra-Acute Embolism Japan Registry 2.

text: BACKGROUND Endovascular therapy has been shown to be effective in patients with acute cerebral large-vessel occlusion, but real-world efficacies are unknown. METHODS AND RESULTS We conducted a prospective registry at 46 centers between October 2014 and January 2017. Eligible patients were those who were aged 20 years or older, with acute cerebral large-vessel occlusion, and who were hospitalized within 24 hours of the onset. We enrolled both consecutive patients who were treated with or without endovascular therapy. Endovascular therapy included thrombectomy, balloon angioplasty, stenting, local fibrinolysis, and piercing. The primary outcome was a favorable outcome as defined by a modified Rankin Scale of 0 to 2 at 90 days after onset. Secondary outcomes were modified Rankin Scale of 0 to 1 and mortality. Safety outcomes were intracerebral hemorrhage or a recurrence of ischemic stroke. We constructed the 2242 (1121 each) propensity score-matched patients cohort based on a propensity score for endovascular therapy and estimated the adjusted odds ratio, followed by sensitivity analyses on original 2399 (1278 in endovascular therapy versus 1121 in no endovascular therapy) patients. In the propensity score-matched cohort, favorable outcomes were observed in 35.3% and 30.7% of patients in the endovascular therapy and no endovascular therapy groups, respectively (P=0.02). The adjusted odds ratio for the favorable outcome was 1.44 (95% confidence interval, 1.10-1.86, P=0.007). The efficacy of endovascular therapy in achieving favorable outcomes did not differ between our subgroups and in the sensitivity analyses. CONCLUSIONS Endovascular therapy decreased disabilities at 90 days in real-world patients with acute cerebral large-vessel occlusion. CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique identifier: NCT02419794.


title: Slowing down with age: lung DCs do it too.

text: Decline in immune function with age has been attributed to defects or alterations in both the innate and the adaptive immune system. In this issue of the JCI, Zhao and coworkers provide evidence for a novel mechanism of immune dysfunction in aging mice. They show that migration of respiratory DCs from the site of virus replication to the draining lymph nodes in response to infection with several different respiratory viruses is markedly diminished with increasing age. The impaired DC migration was a result of increased levels of the lipid mediator prostaglandin D(2) (PGD(2)) in the respiratory tract with age and could be partially reversed by blockade of PGD(2) synthesis or action.


title: Dexamethasone attenuated endotoxin-induced acute lung injury through inhibiting expression of inducible nitric oxide synthase.

text: Application of glucocorticoids in sepsis or severe infection is disputable in clinic. In this experiment, we studied the effect of dexamethasone on nitric oxide synthases and whether dexamethasone could attenuate endotoxin-induced acute lung injury (ALI). SD rats received 5 mg/kg lipopolisaccharide (LPS) injection. Then arterial oxygen partial pressure (PaO2), lung histology, lung tissue nitric oxide (NO) production and expression of nitric oxide synthases (NOS) were detected at 0.5, 1, 2, 3 or 4 h after LPS injection. PaO2 and lung injury deteriorated upon time. Production of NO in lung tissue increased significantly particularly in the first two hours, and this change was mainly due to the over-expression of inducible NOS (iNOS), but not endothelial NOS (eNOS). Furthermore, a tight positive correlation was observed between lung injury score (LIS) and NO production level in lung tissue. Dexamethasone could ameliorate PaO2 and lung damage evidently, which were paralleled by significant decreases in the production of NO and in the expression of iNOS mRNA. In conclusion, dexamethasone could effectively attenuate endotoxin-induced lung injury through inhibiting iNOS expression and activation in the very early stage of ALI.


title: Short-Term Outcomes of Laparoscopic Total Gastrectomy Performed by a Single Surgeon Experienced in Open Gastrectomy: Review of Initial Experience.

text: PURPOSE Laparoscopic total gastrectomy (LTG) is more complicated than laparoscopic distal gastrectomy, especially during a surgeon's initial experience with the technique. In this study, we evaluated the short-term outcomes of and learning curve for LTG during the initial cases of a single surgeon compared with those of open total gastrectomy (OTG). MATERIALS AND METHODS Between 2009 and 2013, 134 OTG and 74 LTG procedures were performed by a single surgeon who was experienced with OTG but new to performing LTG. Clinical characteristics, operative parameters, and short-term postoperative outcomes were compared between groups. RESULTS Advanced gastric cancer and D2 lymph node dissection were more common in the OTG than LTG group. Although the operation time was significantly longer for LTG than for OTG (175.7±43.1 minutes vs. 217.5±63.4 minutes), LTG seems to be slightly superior or similar to OTG in terms of postoperative recovery measures. The operation time moving average of 15 cases in the LTG group decreased gradually, and the curve flattened at 54 cases. The postoperative complication rate was similar for the two groups (11.9% vs. 13.5%). No anastomotic or stump leaks occurred. CONCLUSIONS Although LTG is technically difficult and operation time is longer for surgeons experienced in open surgery, it can be performed safely, even during a surgeon's early experience with the technique. Considering the benefits of minimally invasive surgery, LTG is recommended for early gastric cancer.


title: Development and validation of a risk prediction model to diagnose Barrett's oesophagus (MARK-BE): a case-control machine learning approach.

text: Background Screening for Barrett's Oesophagus (BE) relies on endoscopy which is invasive and has a low yield. This study aimed to develop and externally validate a simple symptom and risk-factor questionnaire to screen for patients with BE. Methods Questionnaires from 1299 patients in the BEST2 case-controlled study were analysed: 880 had BE including 40 with invasive oesophageal adenocarcinoma (OAC) and 419 were controls. This was randomly split into a training cohort of 776 patients and an internal validation cohort of 523 patients. External validation included 398 patients from the BOOST case-controlled study: 198 with BE (23 with OAC) and 200 controls. Identification of independently important diagnostic features was undertaken using machine learning techniques information gain (IG) and correlation based feature selection (CFS). Multiple classification tools were assessed to create a multi-variable risk prediction model. Internal validation was followed by external validation in the independent dataset. Findings The BEST2 study included 40 features. Of these, 24 added IG but following CFS, only 8 demonstrated independent diagnostic value including age, gender, smoking, waist circumference, frequency of stomach pain, duration of heartburn and acid taste and taking of acid suppression medicines. Logistic regression offered the highest prediction quality with AUC (area under the receiver operator curve) of 0.87. In the internal validation set, AUC was 0.86. In the BOOST external validation set, AUC was 0.81. Interpretation The diagnostic model offers valid predictions of diagnosis of BE in patients with symptomatic gastroesophageal reflux, assisting in identifying who should go forward to invasive testing. Overweight men who have been taking stomach medicines for a long time may merit particular consideration for further testing. The risk prediction tool is quick and simple to administer but will need further calibration and validation in a prospective study in primary care. Funding Charles Wolfson Trust and Guts UK.


title: Rotavirus infection as a frequent cause of neonatal fever.

text: BACKGROUND Fever rather than diarrhea or vomiting was the most common symptom of neonatal rotavirus (RV) infection in our previous study. We investigated whether RV infection is a major cause of neonatal fever and compared the clinical characteristics of bacterial infection, viral infection and unknown causes of neonatal fever. METHOD We reviewed the electronic medical records of 48 newborns aged ≤28 days who were admitted to the Special Care Nursery of Hanyang University Guri Hospital for fever (≥38°C) from 2005 to 2009. All the newborns underwent complete blood count, urinalysis, C-reactive protein, cultures of blood, urine, and cerebrospinal fluid as well as stool RV enzyme-linked immunosorbent assay. Respiratory virus polymerase chain reaction for cough or rhinorrhea, and stool culture for diarrhea were also done. RESULTS All the babies were term, with mean age 13 ± 8 days and peak body temperature 38.5 ± 0.5°C. The causes of neonatal fever were viral (44%), bacterial (10%) and unknown (46%). The viral infections included RV (n = 12), enterovirus (n = 6), respiratory syncytial virus (n = 2), and rhinovirus (n = 1). All the rotavirus genotypes were G4P[6]. Only three of 12 RV-infected febrile newborns had diarrhea. The bacterial infections included three cases of urinary tract infection (Escherichia coli, n = 2; Klebsiella pneumoniae, n = 1), and two cases of sepsis complicated with meningitis (all Streptococcus agalactiae). CONCLUSIONS RV infection is the most common single cause of neonatal fever. It may be necessary to include stool RV tests for febrile newborns.


title: Bowel preparation in "real-life" small bowel capsule endoscopy: a two-center experience.

text: BACKGROUND Video capsule endoscopy (VCE) is an established diagnostic tool for the investigation of small bowel (SB) pathology. Bowel preparation prior to VCE may improve visualization, transit time, and diagnostic yield. We aimed to evaluate the "real-life" experience comparing two different preparation protocols in patients undergoing SB VCE. METHODS We performed a retrospective analysis of prospectively collected data from SB VCE procedures, performed in two tertiary care medical centers in Israel. VCE procedures performed at "Sheba Medical Center" used a 2-L polyethylene glycol (PEG) bowel preparation (n=360) while VCEs performed at "Rambam Health Care campus" used a clear liquid diet plus 12-h fast protocol (n=500). A dichotomous preparation scale (adequate, inadequate) was used to classify cleansing quality. Data collection included patient and procedural details. The proportion of VCE procedures with adequate bowel preparation and the overall positive SB findings in the two different bowel preparation protocols were evaluated. RESULTS SB completion rates were higher in the PEG protocol (96% vs. 83%, P<0.001) and SB passage time was significantly faster in the PEG protocol (mean 217±73 vs. 238±77 min, P<0.001). Bowel preparation quality was similar between groups (8% vs. 7% inadequate preparation, P=0.591). Overall positive SB findings were similar between the two groups (57% clear liquid fasting only vs. 51% PEG protocol, P=0.119). CONCLUSION In this large cohort, a 2-L PEG protocol had similar preparation quality and diagnostic yield compared with clear liquid fasting.


title: The Pipeline Embolization Device for the treatment of posterior circulation fusiform aneurysms: lessons learned at a single institution.

text: OBJECT Vertebrobasilar fusiform aneurysms (VFAs) are rare lesions characterized by abnormal dilation and tortuosity of the vertebral and/or basilar arteries. Untreated, these aneurysms have a tendency to progress, often resulting in neurological symptoms or rupture leading to subarachnoid hemorrhage. The microsurgical treatment of these lesions can be difficult due to their location and the circumferential involvement of the arteries. These features make microsurgical treatment prone to high morbidity. The Pipeline Embolization Device (PED) has gained popularity for the treatment of aneurysms of the internal carotid artery. Its use in the posterior circulation has been limited, likely due to a fear of perforating artery occlusion. METHODS The authors retrospectively reviewed their database of patients treated with the PED and identified 12 patients who had VFAs. The clinical features, complications, and outcomes of these patients were analyzed. RESULTS At an average follow-up of 11 months, the mean modified Rankin Scale score was 1.9. Complete aneurysm occlusion was seen in 90% of the patients with radiographic follow-up. Three patients suffered new neurological deficits postoperatively. One of these patients died, while the remaining 2 demonstrated significant clinical improvement at follow-up. CONCLUSIONS With attention to the anatomy of perforating arteries, staged contralateral vertebral artery sacrifice, and adequate platelet inhibition, PED may be an effective treatment option-alone or in a hybrid construct with stents of less coverage for VFAs-with an acceptable complication rate.


title: Pseudoaneurysm in the Internal Maxillary Artery Occurring After Endoscopic Sinus Surgery.

text: Pseudoaneurysm is defined as blood leaking out of a vessel that does not have true 3 arterial walls like a true aneurysm, and is susceptible to rupture. Only 4 patients of pseudoaneurysm after endoscopic sinus surgery have been reported so far in English literature. Recently, the authors encountered a pseudoaneurysm in the internal maxillary artery after endoscopic sinus surgery, which was immediately and successfully managed with endovascular embolization. There was no bleeding or complications 6 months after the embolization.


[COVID-19. The only certainty is the uncertainty].


title: Respiratory pathogens and acute chest syndrome in children with sickle cell disease.

text: BACKGROUND Acute chest syndromes (ACS) may be associated with upper respiratory tract infections, but the epidemiology of viral and intracellular respiratory pathogens in children with sickle cell disease (SCD) is not precisely known. The aim of this study was to describe the epidemiology of viral and intracellular respiratory pathogens in children with SCD presenting with fever and/or ACS. MATERIALS AND METHODS An observational, prospective, single-centre cohort study with nested case-control analysis was conducted on children with SCD admitted from October 2016 to October 2017 for fever and/or ACS to the paediatric department of Robert Debré university hospital, Paris, France. They were screened for 20 respiratory pathogens by a multiplex PCR in the nasopharynx (FilmArray). RESULTS We included 101 children. M/F sex ratio of 0.45. The median age was 3.2 years (IQR: 1.4-8.2). At least one pathogen was isolated in 67 patients (67%). The most frequent viruses were as follows: rhinovirus (n=33), adenovirus (n=14), respiratory syncytial virus (n=13) and parainfluenza viruses (n=11). Mycoplasma pneumoniae was detected in one case. Twenty-three (23%) presented with or developed ACS. A nested case-control analysis was performed, after pairing ACS with non-ACS children for age and inclusion period. There was no statistical association between any viral detection or multiple viral infection, and ACS (p=0.51) even though parainfluenza viruses were twice as common in ACS. CONCLUSIONS Viral detection in febrile children with SCD is frequent, but its association with ACS was not demonstrated. In this study, M. pneumoniae was rare in young children with SCD experiencing ACS.


title: Adverse drug reactions associated with amitriptyline - protocol for a systematic multiple-indication review and meta-analysis.

text: BACKGROUND Unwanted anticholinergic effects are both underestimated and frequently overlooked. Failure to identify adverse drug reactions (ADRs) can lead to prescribing cascades and the unnecessary use of over-the-counter products. The objective of this systematic review and meta-analysis is to explore and quantify the frequency and severity of ADRs associated with amitriptyline vs. placebo in randomized controlled trials (RCTs) involving adults with any indication, as well as healthy individuals. METHODS A systematic search in six electronic databases, forward/backward searches, manual searches, and searches for Food and Drug Administration (FDA) and European Medicines Agency (EMA) approval studies, will be performed. Placebo-controlled RCTs evaluating amitriptyline in any dosage, regardless of indication and without restrictions on the time and language of publication, will be included, as will healthy individuals. Studies of topical amitriptyline, combination therapies, or including < 100 participants, will be excluded. Two investigators will screen the studies independently, assess methodological quality, and extract data on design, population, intervention, and outcomes ((non-)anticholinergic ADRs, e.g., symptoms, test results, and adverse drug events (ADEs) such as falls). The primary outcome will be the frequency of anticholinergic ADRs as a binary outcome (absolute number of patients with/without anticholinergic ADRs) in amitriptyline vs. placebo groups. Anticholinergic ADRs will be defined by an experienced clinical pharmacologist, based on literature and data from Martindale: The Complete Drug Reference. Secondary outcomes will be frequency and severity of (non-)anticholinergic ADRs and ADEs. The information will be synthesized in meta-analyses and narratives. We intend to assess heterogeneity using meta-regression (for indication, outcome, and time points) and I2 statistics. Binary outcomes will be expressed as odds ratios, and continuous outcomes as standardized mean differences. Effect measures will be provided using 95% confidence intervals. We plan sensitivity analyses to assess methodological quality, outcome reporting etc., and subgroup analyses on age, dosage, and duration of treatment. DISCUSSION We will quantify the frequency of anticholinergic and other ADRs/ADEs in adults taking amitriptyline for any indication by comparing rates for amitriptyline vs. placebo, hence, preventing bias from disease symptoms and nocebo effects. As no standardized instrument exists to measure it, our overall estimate of anticholinergic ADRs may have limitations. SYSTEMATIC REVIEW REGISTRATION Submitted to PROSPERO; assignment is in progress.


title: Results of stent-assisted vs non-stent-assisted endovascular therapies in 489 cerebral aneurysms: single-center experience.

text: BACKGROUND Whether the addition of stenting to intracranial aneurysm coil embolization results in benefit in terms of occlusion rates or additional risk in terms of periprocedural adverse events is not clear. OBJECTIVE To report retrospectively analyzed results of endovascular aneurysm treatment comparing stent-assisted coiling with coiling without stents at our hospital from 2005 to 2009. METHODS In this retrospectively reviewed case series, aneurysms were grouped as intent-to-treat or initially treated with stent-assisted coiling (A) vs coiling alone (B) or as-treated-those that ultimately received a stent (C) or not (D). Complication and occlusion rates were compared between groups. Some patients crossed from group B to C after receiving stent placement at a later treatment following the initial therapeutic modality (without a stent). RESULTS In 459 patients, 489 aneurysms were treated by group as follows: A = 181, B = 308, C = 225, and D = 264. In stent groups (A and C), there were significantly lower frequencies of ruptured aneurysms (A vs B = 11% vs 62%, P < .001; C vs D = 20.4% vs 62.5%, P < .001) and more giant aneurysms (A vs B = 7.3% vs 1.0%, P = .001; C vs D = 5.9% vs 1.1%, P < .001). There was no statistically significant difference in permanent event-related morbidity (A vs B = 4.4% vs 4.2%, P = 1.0; C vs D = 4.4% vs 4.2%, P = 1.0). Average angiographic follow-up after last treatment was 18.2 ± 15 months (median = 14). Higher rates of complete occlusion at last angiographic follow-up were observed in stented aneurysms (A vs B = 64.6% vs 49.7%, P = .001; C vs D = 62.7% vs 48.9%, P = .003). CONCLUSION Stent-assisted aneurysm treatment resulted in higher total occlusion rates than non-stent-assisted treatment, with acceptable, comparable periprocedural event rates.


title: Mapping Antigenic Epitopes on the Human Bocavirus Capsid.

text: UNLABELLED Human bocaviruses (HBoV1 to -4) are emerging pathogens associated with pneumonia and/or diarrhea in young children. Currently, there is no treatment or vaccination, so there is a need to study these pathogens to understand their disease mechanisms on a molecular and structural level for the development of control strategies. Here, we report the structures of six HBoV monoclonal antibody (MAb) fragment complexes, HBoV1-15C6, HBoV2-15C6, HBoV4-15C6, HBoV1-4C2, HBoV1-9G12, and HBoV1-12C1, determined by cryo-electron microscopy and three-dimensional image reconstruction to 18.0- to 8.5-Å resolution. Of these, the 15C6 MAb cross-reacted with HBoV1, HBoV2, and HBoV4, while the 4C2, 12C1, and 9G12 MAbs recognized only HBoV1. Pseudoatomic modeling mapped the 15C6 footprint to the capsid surface DE and HI loops, at the 5-fold axis and the depression surrounding it, respectively, which are conserved motifs in Parvoviridae The footprints for 4C2, 12C1, and 9G12 span the surface loops that assemble portions of the 2-/5-fold wall (a raised surface feature between the 2-fold and 5-fold axes of symmetry) and the shoulder of the 3-fold protrusions. The MAb footprints, cross reactive and strain specific, coincide with regions with high and low sequence/structural identities, respectively, on the capsid surfaces of the HBoVs and identify potential regions for the development of peptide vaccines for these viruses. IMPORTANCE Human bocaviruses (HBoVs) may cause severe respiratory and gastrointestinal infections in young children. The nonenveloped parvovirus capsid carries determinants of host and tissue tropism, pathogenicity, genome packaging, assembly, and antigenicity important for virus infection. This information is currently unavailable for the HBoVs and other bocaparvoviruses. This study identifies three strain-specific antigenic epitopes on the HBoV1 capsid and a cross-reactive epitope on the HBoV1, HBoV2, and HBoV4 capsids using structures of capsid-antibody complexes determined using cryo-electron microscopy and image reconstruction. This is the first study to report the highly conserved parvovirus DE loop at the 5-fold axis as a determinant of antigenicity. Additionally, knowledge of the strain-specific and conserved antigenic epitopes of the bocaviruses can be instrumental in characterization of the virus life cycle, development of peptide vaccines, and generation of gene delivery vectors for cystic fibrosis given the strict tropism of HBoV1 for human airway epithelial cells.


title: Modeling the impact of simulated educational interventions on the use and abuse of pharmaceutical opioids in the United States: a report on initial efforts.

text: Three educational interventions were simulated in a system dynamics model of the medical use, trafficking, and nonmedical use of pharmaceutical opioids. The study relied on secondary data obtained in the literature for the period of 1995 to 2008 as well as expert panel recommendations regarding model parameters and structure. The behavior of the resulting systems-level model was tested for fit against reference behavior data. After the base model was tested, logic to represent three educational interventions was added and the impact of each intervention on simulated overdose deaths was evaluated over a 7-year evaluation period, 2008 to 2015. Principal findings were that a prescriber education intervention not only reduced total overdose deaths in the model but also reduced the total number of persons who receive opioid analgesic therapy, medical user education not only reduced overdose deaths among medical users but also resulted in increased deaths from nonmedical use, and a "popularity" intervention sharply reduced overdose deaths among nonmedical users while having no effect on medical use. System dynamics modeling shows promise for evaluating potential interventions to ameliorate the adverse outcomes associated with the complex system surrounding the use of opioid analgesics to treat pain.