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Retrospective performance evaluation of a computer-aided detection (CAD) system on standard posteroanterior (PA) chest radiographs (PA-CXR) in detection of pulmonary nodules, infectious consolidation, pneumothorax, pleural effusion, aortic calcification, cardiomegaly and rib fractures compared to radiologists analyzing PA-CXR including dual-energy subtraction radiography (further termed as DESR).PA-CXR/DESR images of 197 patients were included. All patients underwent chest CT (gold standard) within a short interval (mean 28 hours). All images were evaluated by three blinded readers for the presence of pulmonary nodules, infectious consolidation, pneumothorax, pleural effusion, aortic calcification, cardiomegaly, and rib fractures. Meanwhile PA-CXR were analyzed by a CAD software. CAD results were compared to the majority result of the three readers. Sensitivity and specificity were calculated. McNemar's test was applied to test for significant differences. Interobserver agreement was defined using Cohen's kappa (κ).Sensitivity of the CAD software was significantly higher (p0.05) for detection of infectious consolidation and pulmonary nodules (67.9% vs 26.8% and 54% vs 35.6%, respectively; p0.001) compared to radiologists analyzing DESR images. For the residual evaluated pathologies no statistical significant differences could be found. Overall, mean inter observer agreement between the three radiologists was moderate (k = 0.534). The best interobserver agreement could be reached for pneumothorax (k = 0.708) and pleural effusion (k = 0.699), while the worst was obtained for rib fractures (k = 0.412).The CAD system has the potential to improve the detection of infectious consolidation and pulmonary nodules on CXR images.

Background Bariatric surgery can influence the presentation, diagnosis, and management of gastrointestinal cancers. Oesophago-Gastric (OG) malignancies in patients who have had a prior bariatric procedure have not been fully characterised. Objective To characterise OG malignancies after bariatric procedures. Setting University Hospital, United Kingdom. Methods We performed a retrospective, multi-centre observational study of patients with OG malignancies after bariatric surgery to characterise this condition. Results This study includes 170 patients from 75 centres in 25 countries who underwent bariatric procedures between 1985 and 2020. At the time of the bariatric procedure, the mean age was 50.2 ± 10 years and the mean weight 128.8 ± 28.9 kg. Females comprised 57.3% (n=98) of the population. Most (n=64) patients underwent a Roux-en-Y Gastric Bypass (RYGB) followed by Adjustable Gastric Band (AGB) (n = 46) and Sleeve Gastrectomy (SG) (n = 43). Time to cancer diagnosis after bariatric surgery was 9.5 ± 7.4 years and mean weight at diagnosis was 87.4 ± 21.9 kg. The time lag was 5.9 ± 4.1 years after SG compared to 9.4 ± 7.1 years after RYGB and 10.5 ± 5.7 years after AGB. One-third of patients presented with metastatic disease. The majority of tumours were adenocarcinoma (82.9%). Approximately 1 in 5 patients underwent palliative treatment from the outset. Time from diagnosis to mortality was under one year for most patients who died over the intervening period. Conclusions The OGMOS (Oesophago-Gastric Malignancies after Obesity/ Bariatric Surgery) study presents the largest series to date of patients developing OG malignancies after bariatric surgery and attempts to characterise this condition.

Background: Prospective data collection for perioperative outcomes might increase awareness of surgical results obtained for patients with prostate cancer (PCa) undergoing robot-assisted radical prostatectomy (RARP). This would prompt the implementation of measures aimed at reducing the risk of adverse outcomes. Objective: To assess the efficacy of an audit and feedback process aimed at identifying the most common complications after RARP and at implementing measures to improve outcomes. Design, setting, and participants: Overall, 415 patients treated with RARP by a high-volume surgeon were included. Perioperative outcomes for 187 patients treated between September 2016 and December 2017 were prospectively collected at 30 d according to the European Association of Urology guideline recommendations (group 1). An audit and feedback process was implemented in January 2018 whereby the most common complication (anastomotic leak) was identified and measures aimed at improving outcomes (changes in the anastomotic technique) were implemented. The outcomes for group 1 were then compared to 228 patients treated after implementation of the modified surgical technique (group 2). Surgical procedure: A novel technique for posterior reconstruction and urethrovesical anastomosis was introduced. Measurements: Perioperative outcomes included blood loss, operative time, length of stay, and 30-d postoperative complications. Logistic regression models tested the effect of the novel surgical technique on anastomotic leaks. Results and limitations: Overall, 97 patients (23%) experienced postoperative complications at 30 d. The rate of anastomotic leaks was significantly lower in group 2 compared to group 1 (3.1% vs 9.6%; p < 0.01). Similarly, overall and Clavien-Dindo grade ≥2 complication rates were lower in group 2 versus group 1 (17% vs 31%, and 6% vs 20%; both p ≤ 0.001). In multivariable analyses, treatment after implementation of changes in the anastomotic technique independently predicted a lower risk of complications (odds ratio [OR] 0.58, 95% confidence interval [CI] 0.38–0.89) and of anastomotic leaks (OR 0.43, 95% CI 0.17–0.97). The lack of randomization represents the main limitation. Conclusions: Implementation of changes in the urethrovesical anastomosis technique arising from increased awareness of surgical outcomes reduced the risk of anastomotic leaks. These findings highlight the importance of audit and feedback processes using a standardized method for reporting surgical morbidity. Patient summary: Increased awareness of surgical outcomes prompted us to change our technique for connecting the bladder to the urethra during robot-assisted surgery to remove the prostate in patients with prostate cancer. These changes resulted in significant improvements in surgical outcomes.

BACKGROUND To investigate associations between exposure to various trajectories of severe hypoglycemic events and risk of dementia in patients with type 2 diabetes. METHODS In 2002-2003, 677618 patients in Taiwan were newly diagnosed as having type 2 diabetes. Among them, 35720 (5.3%) experienced severe hypoglycemic events during the 3-year baseline period following diagnosis. All patients were followed from the first day after baseline period to the date of dementia diagnosis, death, or the end of 2011. A group-based trajectory model was used to classify individuals with severe hypoglycemic events during the baseline period. Cox proportional hazard models with the competing risk method were used to relate dementia risk to various severe hypoglycemia trajectories. RESULTS After a median follow-up 6.70 and 6.10 years for patients with and without severe hypoglycemia at baseline, respectively, 1952 (5.5%) individuals with severe hypoglycemia and 23492 (3.7%) without developed dementia during follow-up, for incidence rates of 109.80 and 61.88 per 10000 person-years, respectively. Four groups of severe hypoglycemia trajectory were identified with a proportion of 18.06%, 33.19%, 43.25%, and 5.50%, respectively for Groups 1 to 4. Groups 3 (early manifestation but with later decrease) and 4 (early and sustained manifestation) were associated with a significantly increased risk of dementia diagnosis, with a covariate-adjusted subdistribution hazard ratio of 1.22 (95% confidence interval, 1.14-1.31) and 1.25 (95% confidence interval, 1.02-1.54), respectively. CONCLUSIONS Our analysis highlighted that early manifestation of severe hypoglycemic events may contribute more than does late manifestation to the risk of dementia among individuals newly diagnosed as having type 2 diabetes.

Funder: Alma Mater Studiorum - Università di Bologna, Patent ductus arteriosus (PDA) is common among extremely preterm infants. In selected cases, surgical PDA ligation may be required. The timing for PDA ligation may depend upon a variety of factors, with potential clinical implications. We aimed to investigate the impact of different surgical PDA managements on ligation timing and neonatal outcomes. Inborn infants < 32 weeks of gestation and < 1500 g admitted at two tertiary Neonatal Intensive Care Units that underwent PDA ligation between 2007 and 2018 were enrolled in this retrospective cohort study and split into the following groups based on their surgical management: on-site bedside PDA ligation (ONS) vs. referral to an off-site pediatric cardiac surgery (OFS). Neonatal characteristics, surgical timing, and clinical outcomes of the enrolled infants were compared between the groups. Multivariate analysis was performed to evaluate the impact of PDA ligation timing on significantly different outcomes. Seventy-eight neonates (ONS, n = 39; OFS, n = 39) were included. Infants in the ONS group underwent PDA ligation significantly earlier than those in the OFS group (median age 12 vs. 36 days, p < 0.001) with no increase in postoperative mortality and complications. The multivariate analysis revealed a significant association between PDA ligation timing, late-onset sepsis prevalence (OR 1.045, 0.032), and oxygen need at discharge (OR 1.037, p = 0.025).Conclusions: Compared with off-site surgery, on-site bedside ligation allows an earlier surgical closure of PDA, with no apparent increase in mortality or complications. Earlier PDA ligation may contribute to reduced rates of late-onset sepsis and post-discharge home oxygen therapy, with possible cost-benefit implications. What is known: • Ineffective or contraindicated pharmacological closure of a hemodynamically significant PDA may require a surgical ligation. • Available literature comparing the effect of early vs. late PDA ligation on the main neonatal morbidities has yield contrasting results. What is new: • The availability of a cardiac surgery service performing bedside PDA ligation allows an earlier intervention compared to patient referral to an off-site center, with no difference in postoperative mortality and complications compared to off-site surgery. • Earlier PDA ligation was associated with a lower prevalence of late-onset sepsis and of oxygen need at discharge, with possible cost-benefit implications.

Objective The primary aim of this article was to describe SARS‐CoV‐2 infection among pregnant women during the wild‐type and Alpha‐variant periods in Italy. The secondary aim was to compare the impact of the virus variants on the severity of maternal and perinatal outcomes. Design National population‐based prospective cohort study. Setting A total of 315 Italian maternity hospitals. Sample A cohort of 3306 women with SARS‐CoV‐2 infection confirmed within 7 days of hospital admission. Methods Cases were prospectively reported by trained clinicians for each participating maternity unit. Data were described by univariate and multivariate analyses. Main outcome measures COVID‐19 pneumonia, ventilatory support, intensive care unit (ICU) admission, mode of delivery, preterm birth, stillbirth, and maternal and neonatal mortality. Results We found that 64.3% of the cohort was asymptomatic, 12.8% developed COVID‐19 pneumonia and 3.3% required ventilatory support and/or ICU admission. Maternal age of 30–34 years (OR 1.43, 95% CI 1.09–1.87) and ≥35 years (OR 1.62, 95% CI 1.23–2.13), citizenship of countries with high migration pressure (OR 1.75, 95% CI 1.36–2.25), previous comorbidities (OR 1.49, 95% CI 1.13–1.98) and obesity (OR 1.72, 95% CI 1.29–2.27) were all associated with a higher occurrence of pneumonia. The preterm birth rate was 11.1%. In comparison with the pre‐pandemic period, stillbirths and maternal and neonatal deaths remained stable. The need for ventilatory support and/or ICU admission among women with pneumonia increased during the Alpha‐variant period compared with the wild‐type period (OR 3.24, 95% CI 1.99–5.28). Conclusions Our results are consistent with a low risk of severe COVID‐19 disease among pregnant women and with rare adverse perinatal outcomes. During the Alpha‐variant period there was a significant increase of severe COVID‐19 illness. Further research is needed to describe the impact of different SARS‐CoV‐2 viral strains on maternal and perinatal outcomes., Tweetable abstract The rate of severe COVID‐19 disease increased during the Alpha‐variant period compared with the wild‐type period.

Background: Despite the low spatial resolution of 2D-multisegment late gadolinium enhancement (2D-MSLGE) sequences, it may be useful in uncooperative patients instead of standard 2D single segmented inversion recovery gradient echo late gadolinium enhancement sequences (2D-SSLGE). The aim of the study is to assess the feasibility and comparison of 2D-MSLGE reconstructed with artificial intelligence reconstruction deep learning noise reduction (NR) algorithm compared to standard 2D-SSLGE in consecutive patients with ischemic cardiomyopathy (ICM). Methods: Fifty-seven patients with known ICM referred for a clinically indicated CMR were enrolled in this study. 2D-MSLGE were reconstructed using a growing level of NR (0%,25%,50%,75%and 100%). Subjective image quality, signal to noise ratio (SNR) and contrast to noise ratio (CNR) were evaluated in each dataset and compared to standard 2D-SSLGE. Moreover, diagnostic accuracy, LGE mass and scan time were compared between 2D-MSLGE with NR and 2D-SSLGE. Results: The application of NR reconstruction ≥50% to 2D-MSLGE provided better subjective image quality, CNR and SNR compared to 2D-SSLGE (p < 0.01). The best compromise in terms of subjective and objective image quality was observed for values of 2D-MSLGE 75%, while no differences were found in terms of LGE quantification between 2D-MSLGE versus 2D-SSLGE, regardless the NR applied. The sensitivity, specificity, negative predictive value, positive predictive value and accuracy of 2D-MSLGE NR 75% were 87.77%,96.27%,96.13%,88.16% and 94.22%, respectively. Time of acquisition of 2D-MSLGE was significantly shorter compared to 2D-SSLGE (p < 0.01). Conclusion: When compared to standard 2D-SSLGE, the application of NR reconstruction to 2D-MSLGE provides superior image quality with similar diagnostic accuracy.

Presently, major guidelines do not provide specific recommendations on oncologic surveillance for patients who harbor variant histology (VH) bladder cancer (BCa) at radical cystectomy. We aimed to create a personalized followup scheme that dynamically weighs other cause mortality (OCM) vs the risk of recurrence for VH BCa, and to compare it with a similar one for pure urothelial carcinoma (pUC).Within a multi-institutional registry, 528 and 1,894 patients with VH BCa and pUC, respectively, were identified. The Weibull regression was used to detect the time points after which the risk of OCM exceeded the risk of recurrence during followup. The risk of OCM over time was stratified based on age and comorbidities, and the risk of recurrence on pathological stage and recurrence site.Individuals with VH had a higher risk of recurrence (recurrence-free survival 30% vs 51% at 10 years, p0.001) and shorter median time to recurrence (88 vs 123 months, p0.01) relative to pUC. Among VH, micropapillary variant conferred the greatest risk of recurrence on the abdomen and lungs, and mixed variants carried the greatest risk of metastasizing to bones and other sites compared to pUC. Overall, surveillance should be continued for a longer time for individuals with VH BCa. Notably, patients younger than 60 years with VH and pT0/Ta/T1/N0 at radical cystectomy should continue oncologic surveillance after 10 years vs 6.5 years for pUC individuals.VH BCa is associated with greater recurrence risk than pUC. A followup scheme that is valid for pUC should not be applied to individuals with VH. Herein, we present a personalized approach for surveillance that may allow an improved shared decision.

Objectives: The aim of this study was to assess the incidence of being overweight and metabolic syndrome (MS) among people living with HIV (PHIV) in three different cross-sectional studies conducted over three different periods: 2005, 2011 and 2015. Methods: This was a multi-centre, nationwide study. Data were collected in three studies from the CISAI group - SIMOne, HIV-HY and STOPSHIV - and included a total of 3014 PHIV. Logistic regression [odds ratio (OR), 95% confidence interval (CI)] was used to account for age and gender difference among three groups when comparing MS prevalence and being overweight; potential confounders were accounted for by including them in the regression equation. Results: Overall, the mean age was 46.9±10.2years, and men comprised 73.3% of participants. Comparing 2005, 2011 and 2015, MS was present in 34.5%, 33.0% and 29.3% of PHIV, respectively. Adjusted OR for MS was 0.64 (95% CI: 0.52-0.78) in 2011 and 0.56 (95% CI: 0.46-0.69) in 2015 compared with 2005, while BMI (kg/m2 ) increased from 23.6 in 2005, 24.5 in 2011 and 24.5 in 2015, with a concomitant increase of being overweight from 29.4% to 39.5% to 39.6% (p&nbsp

Food insecurity, defined as the lack of physical or economic access to safe, nutritious and sufficient food, remains one of the main challenges included in the 2030 Agenda for Sustainable Development. Near real-time data on the food insecurity situation collected by international organizations such as the World Food Programme can be crucial to monitor and forecast time trends of insufficient food consumption levels in countries at risk. Here, using food consumption observations in combination with secondary data on conflict, extreme weather events and economic shocks, we build a forecasting model based on gradient boosted regression trees to create predictions on the evolution of insufficient food consumption trends up to 30 days in to the future in 6 countries (Burkina Faso, Cameroon, Mali, Nigeria, Syria and Yemen). Results show that the number of available historical observations is a key element for the forecasting model performance. Among the 6 countries studied in this work, for those with the longest food insecurity time series, that is Syria and Yemen, the proposed forecasting model allows to forecast the prevalence of people with insufficient food consumption up to 30 days into the future with higher accuracy than a naive approach based on the last measured prevalence only. The framework developed in this work could provide decision makers with a tool to assess how the food insecurity situation will evolve in the near future in countries at risk. Results clearly point to the added value of continuous near real-time data collection at sub-national level.

Background Current European Association of Urology, American Urological Association, and National Comprehensive Cancer Network guidelines recommend active surveillance (AS) for selected intermediate-risk prostate cancer (PCa) patients. However, limited evidence exists regarding which men can be selected safely. Objective To externally validate the Gandaglia risk calculator (Gandaglia-RC), designed to predict adverse pathology (AP) at radical prostatectomy (RP) and thus able to improve selection of intermediate-risk PCa patients suitable for AS, and to assess whether addition of magnetic resonance imaging (MRI) findings (MAP model) improves the predictive ability of Gandaglia-RC. Design, setting, and participants This is a retrospective analysis of a single-center cohort of 1284 consecutive men with low- and intermediate-risk PCa treated with RP between 2013 and 2019. Outcome measurements and statistical analysis AP was defined as non–organ-confined disease and/or lymph node invasion and/or pathological grade group ≥ 3 at RP. Logistic regression was used to calculate the predictors of AP; calculated coefficients were used to develop a risk score. Receiver operating characteristic curve analysis and decision curve analysis were performed to evaluate the net benefit within models. Results and limitations At multivariable analysis, age at surgery, prostate-specific antigen, systematic and targeted biopsy Gleason grade group, MRI prostate volume, Prostate Imaging Reporting and Data System score, and MRI extraprostatic extension were significantly associated with AP. The model significantly improved the ability of Gandaglia-RC to predict AP (area under the curve 0.71 vs 0.63 [p Conclusions Compared with Gandaglia-RC, the MAP model significantly increased the number of patients eligible for AS without significantly increasing the risk of AP at RP. Patient summary In this report, we have developed a risk prediction tool to select men for conservative treatment of prostate cancer. Using the novel tool, more men could safely be allocated to conservative treatment rather than surgery or radiation.

Objective To assess efficacy and safety of a treatment regimen based on rectal administration of Boswellia resin extract and propolis derived polyphenols in patients with type IIIa/IIIb chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS). Methods Patients with IIIa/IIIb CP/CPPS received one rectal suppository a day for 15 days per month for 3 consecutive months. Participants were evaluated with National Institutes of Health-Chronic Prostatitis Symptom Index (NIH–CPSI), the International Prostate Symptom Scores (IPSS), International Index of Erectile Function (IIEF), four-glass test, uroflowmetry, and prostate-specific antigen (PSA) assessments at baseline and at weeks 4, and 12. Primary endpoints were improvement in pain domain of NIH–CPSI and improvement of NIH–CPSI total score. Secondary outcomes included improvement of micturition and quality of life (QoL) domains of NIH–CPSI questionnaire. Results A total of 61 males have been enrolled. No adverse events have been reported. Significant improvements from baseline to Day 30 have been reported for NIH–CPSI total score (mean difference: −9.2; p Conclusion Rectal administration of Boswellia resin extract and propolis derived polyphenols is well tolerated and delivers a significant symptomatic improvement in most patients with IIIa/IIIb CP/CPPS.

Background The aim of this survey was to assess practices regarding pain management, fluid therapy and thromboprophylaxis in patients undergoing pancreatoduodenectomy on a global basis. Methods This survey study among surgeons from eight (inter)national scientific societies was performed according to the CHERRIES guideline. Results Overall, 236 surgeons completed the survey. ERAS protocols are used by 61% of surgeons and respectively 82%, 93%, 57% believed there is a relationship between pain management, fluid therapy, and thromboprophylaxis and clinical outcomes. Epidural analgesia (50%) was most popular followed by intravenous morphine (24%). A restrictive fluid therapy was used by 58% of surgeons. Chemical thromboprophylaxis was used by 88% of surgeons. Variations were observed between continents, most interesting being the choice for analgesic technique (transversus abdominis plane block was popular in North America), restrictive fluid therapy (little use in Asia and Oceania) and duration of chemical thromboprophylaxis (large variation). Conclusion The results of this international survey showed that only 61% of surgeons practice ERAS protocols. Although the majority of surgeons presume a relationship between pain management, fluid therapy and thromboprophylaxis and clinical outcomes, variations in practices were observed. Additional studies are needed to further optimize, standardize and implement ERAS protocols after pancreatic surgery.

Traumatic brain injury (TBI) and blunt thoracic aortic injury (BTAI) are the top two leading causes of death after blunt force trauma. Patients presenting with concomitant BTAI and TBI pose a specific challenge with respect to management strategy, because the optimal hemodynamic parameters are conflicting between the two pathologies. Early thoracic endovascular aortic repair (TEVAR) is often performed, even for minimal aortic injuries, to allow for the higher blood pressure parameters required for TBI management. However, the optimal timing of TEVAR for the treatment of BTAI in patients with concomitant TBI remains an active matter of controversy.The Aortic Trauma Foundation international prospective multicenter registry was used to identify all patients who had undergone TEVAR for BTAI in the setting of TBI from 2015 to 2020. The primary outcomes included delayed ischemic or hemorrhagic stroke, in-hospital mortality, and aortic-related mortality. The outcomes were examined among patients who had undergone TEVAR at emergent (6 vs ≥6 hours) or urgent (24 vs ≥24 hours) intervals.A total of 100 patients (median age, 43 years; 79% men; median injury severity score, 41) with BTAI (Society for Vascular Surgery BTAI grade 1, 3%; grade 2, 10%; grade 3, 78%; grade 4, 9%) and concomitant TBI who had undergone TEVAR were identified. Emergent repair was performed for 51 patients (51%). Comparing emergent repair (6 hours) to urgent repair (≥6 hours), no difference was found in delayed cerebral ischemic events (2.0% vs 4.1%; P = .614), in-hospital mortality (15.7% vs 22.4%; P = .389), or aortic-related mortality (2.0% vs 2.0%; P = .996) and no patient had experienced delayed hemorrhagic stroke. Likewise, repairs conducted in an urgent (24 hours) setting showed no differences compared with those completed in an emergent (≥24 hours) setting regarding delayed ischemic stroke (2.6% vs 4.3%; P = .548), in-hospital mortality (18.2% vs 21.7%; P = .764), or aortic-related mortality (1.3% vs 4.3%; P = .654), and no patient had experienced delayed hemorrhagic stroke.In contrast to prior retrospective efforts, results from the Aortic Trauma Foundation international prospective multicenter registry have demonstrated that neither emergent nor urgent TEVAR for patients with concomitant BTAI and TBI was associated with delayed stroke, in-hospital mortality, or aortic-related mortality. In these patients, the timing of TEVAR did not have an effect on the outcomes. Therefore, the decision to intervene should be guided by individual patient factors rather than surgical timing.

PURPOSE To evaluate the effectiveness and safety of the Preserflo MicroShunt implant (Santen) in patients with primary open-angle glaucoma (POAG) and pseudoexfoliation glaucoma (PXG). DESIGN Retrospective, open-label, multicenter study. PARTICIPANTS Patients with insufficiently controlled primary POAG or PXG who underwent a standalone MicroShunt implantation procedure. METHODS Consecutive patients with POAG and PXG who underwent surgery with the ab externo minimally invasive glaucoma surgery device Preserflo MicroShunt with mitomycin C. MAIN OUTCOME MEASURES Primary end points were mean change in intraocular pressure (IOP) and number of hypotensive medications from baseline through month 12. Success was defined as an IOP of 18 mmHg or less and an IOP reduction of 20% or more, with (qualified) or without (complete) any hypotensive medication. RESULTS Among the 130 patients who underwent MicroShunt implantation, 104 fulfilled the inclusion and exclusion criteria and were included in the analysis. Eighty-one eyes (77.9%) were diagnosed with POAG and 23 eyes (22.1%) were diagnosed with PXG. The mean age was 71.4 ± 12.6 years, and 45 patients (43.3%) were women. Mean IOP was lowered significantly from 25.1 ± 6.5 mmHg at baseline to 14.1 ± 3.4 mmHg at month 12 (P < 0.0001). At month 12, 27 eyes (26.0%) were categorized as complete successes and 61 eyes (58.7%) were categorized as qualified successes. The mean number of hypotensive medications was reduced significantly from 3.0 ± 1.0 medications at the preoperative visit to 0.77 ± 0.95 medication at month 12 (P < 0.001). Throughout the study, 19 eyes (18.3%) required needling and 14 eyes (13.5%) underwent surgical revision. Eight eyes (7.7%) showed hyphema and 5 eyes (4.8%) showed choroidal detachment. These were resolved with medical therapy without sequelae. Four patients underwent subsequent surgeries, and 2 patients underwent trabeculectomy (at months 3 and 6): One patient underwent transscleral cyclophotocoagulation at month 3 and 1 patient underwent MicroPulse cyclophotocoagulation at month 4. CONCLUSIONS In this retrospective study, the MicroShunt effectively lowered IOP and the need for IOP-lowering medications.

Objectives: The purposes of this study are to describe the epidemiology of pericardial and tunica vaginalis testis mesothelioma and assess the role of asbestos exposure for these rare diseases. Methods: Based on incident pericardial and tunica vaginalis testis mesothelioma cases collected from the Italian national mesothelioma registry (ReNaM) in the period 1993–2015, incidence rates, survival median period and prognostic factors have been evaluated. A case–control study has been performed to analyze the association with asbestos exposure (occupational and non-occupational) for these diseases. Results: Between 1993 and 2015, 58 pericardial (20 women and 38 men) and 80 tunica vaginalis testis mesothelioma cases have been registered with a mean annual standardized (world standard population as reference) incidence rates of 0.049 (per million) in men and 0.023 in women for the pericardial site, and 0.095 for tunica vaginalis testis mesothelioma. Occupational exposure to asbestos was significantly associated with the risk of the diseases [odds ratio (OR) 3.68, 95% confidence interval (CI) 1.85–7.31 and OR 3.42, 95% CI 1.93–6.04 in pericardial and tunica vaginalis testis mesothelioma, respectively]. The median survival was 2.5 months for pericardial and 33.0 months for tunica vaginalis testis mesotheliomas. Age was the main predictive factor for survival for both anatomical sites. Conclusions: For the first time in an analytical study, asbestos exposure was associated with pericardial and tunica vaginalis testis mesothelioma risk, supporting the causal role of asbestos for all anatomical sites. The extreme rarity of the diseases, the poor survival and the prognostic role of age have been confirmed based on population and nationwide mesothelioma registry data.

We aimed to evaluate the reliability of lung ultrasound (LU) to predict admission to the neonatal intensive care unit (NICU) for transient neonatal tachypnoea or respiratory distress syndrome in infants born by caesarean section (CS). A prospective, observational, single-centre study was performed in the delivery room and NICU of Sant’Orsola-Malpighi Hospital in Bologna, Italy. Term and late-preterm infants born by CS were included. LU was performed at 30’ and 4 h after birth. LU appearance was graded according to a previously validated three-point scoring system (3P-LUS: type-1, white lung; type-2, black/white lung; type-3, normal lung). Full LUS was also calculated. One hundred infants were enrolled, and seven were admitted to the NICU. The 5 infants with bilateral type-1 lung at birth were all admitted to the NICU. Infants with type-2 and/or type-3 lung were unlikely to be admitted to the NICU. Mean full-LUS was 17 in infants admitted to the NICU, and 8 in infants not admitted. In two separate binary logistic regression models, both the 3P- and the full LUS proved to be independently associated with NICU admission (OR [95% CI] 0.001 [0.000–0.058], P = .001, and 2.890 [1.472–5.672], P = .002, respectively). The ROC analysis for the 3P-LUS yielded an AUC of 0.942 (95%CI, 0.876–0.979; PPp = .261).Conclusion: the 3P-LUS performed 30 min after birth proved to be a reliable tool to identify, among term and late preterm infants born to CS, those who will require NICU admission for transient neonatal tachypnoea or respiratory distress syndrome. What is known• Lung ultrasound (LU) has become an attractive diagnostic tool in neonatal settings, and guidelines on point-of-care LU in the neonatal intensive care unit (NICU) have been recently issued.• LU is currently used for diagnosing several neonatal respiratory morbidities and has been also proposed for predicting further intervention, such as NICU admission, need for surfactant treatment or mechanical ventilation in preterm infants. What is new• LU performed 30′ after birth and evaluated through a simple three-point scoring system represents a reliable tool to identify, among term and late preterm infants born to caesarean section, those with transient neonatal tachypnoea or respiratory distress syndrome who will require NICU admission.• LU performed in the neonatal period confirms its potential role in ameliorating routine neonatal clinical management.

Background: Hip fracture (HF) is a burdening health problem in older people. The orthogeriatric approach has been shown to favour functional recovery and reduce mortality, but its implementation in clinical practice cannot rely upon shared management protocols and greatly varies among different healthcare systems. Here, we present the rationale and design of the Italian consensus document on the management of HF in older people. Methods: A panel of multidisciplinary experts from ten Italian scientific societies involved in the care of HF and including geriatricians, orthopaedics, anaesthesiologists, physiatrists and general practitioners, will join to establish the content validity of a list of statements. A Delphi consensus methodology will be applied to obtain the opinions of the panel and to provide the final recommendations. Objectives: The document will include indications on the following relevant topics: (1) optimal care path of older subjects with HF; (2) management of comorbidities and pre-operative alteration of physiological parameters; (3) management of selected categories of patients at expected increased risk of adverse outcomes; (4) continuity of care out of hospital; (5) screening and correction of risk factors for HF in older subjects; (6) information and divulgation of shared management strategies. The objective of the consensus will be to inform clinicians, patients, researchers, and health policy makers about the best management strategies for HF in older people and their inherent limitations, thus facilitating communication between stakeholders and promoting the most cost/effective models of care.

Background and aims To investigate diabetes treatment initiation and continuation in the next sixth months in newly diagnosed Italian subjects. Methods and results We analyzed administrative claims of 11,300,750 Italian residents. Subjects with incident diabetes were identified by glucose lowering drug prescriptions, disease-specific co-payment exemptions and hospital discharge codes occurring in 2018 but not in 2017. Incident cases were 65,932 of whom 91.4% received the prescription of a glucose lowering drug. Among the latter, those receiving a prescription of a noninsulin medication but no insulin were 84.8%, those receiving a prescription of insulin only were 9.4%, and those receiving prescriptions of both insulin and noninsulin drugs were 5.8%. Metformin was the most frequently drug initially prescribed in noninsulin treated subjects (~85%) and sulphonylurea receptor (SUR) agonists collectively ranked as second (~13%). Lispro (35%) and glargine (34%) were the most frequently prescribed molecules in subjects who were insulin treated. Differences in prescriptions were found in age categories, with increased use of SUR agonists across decades. In the first six months, as many as 50% of noninsulin treated patients continued with the initial drug, ~15% added a second agent, ~5% switched to another medication, and ~30% discontinued any glucose lowering treatment. Conclusions These data document that current guidelines are often neglected because prescriptions of SUR agonists as first agent are still quite common and insulin is prescribed more than expected. They point out the urgent need to improve the dissemination and implementations of guidelines in diabetes care.

Single photon detectors (SPD) are largely used when the signal to be measured is particularly low or if high accuracy, timing resolution and low noise are required. About twenty years ago, a new type of SPD based on superconducting materials appeared, and today these devices present the best performances in terms of efficiency, noise, counting rate, detectable wavelength, dead time, and timing jitter. In this work, we first describe the working principle of Superconducting Nanostrips Single Photon Detectors (SNSPDs) and provide a brief overview of the main properties and applications. Then, we present the results of the fabrication and characterization of Molybdenum Silicide SNSPDs with a cover layer of a thin Aluminium film (MoSi/Al). MoSi has already been adopted to fabricate SNSPDs, and in this work, we prove that the additional Al layer enhances the operating conditions without compromising the detection likelihood and leaving unaltered the properties of the device, even over a temporal window of two years and after several thermal cycles.

Background We compared cardiovascular magnetic resonance segmental native T1 against T2* values for the detection of myocardial iron overload (MIO) in thalassaemia major and we evaluated the clinical correlates of native T1 measurements. Methods We considered 146 patients (87 females, 38.7 ± 11.1 years) consecutively enrolled in the Extension-Myocardial Iron Overload in Thalassaemia Network. T1 and T2* values were obtained in the 16 left ventricular (LV) segments. LV function parameters were quantified by cine images. Post-contrast late gadolinium enhancement (LGE) and T1 images were acquired. Results 64.1% of segments had normal T2* and T1 values while 10.1% had pathologic T2* and T1 values. In 526 (23.0%) segments, there was a pathologic T1 and a normal T2* value while 65 (2.8%) segments had a pathologic T2* value but a normal T1 and an extracellular volume (ECV) ≥ 25% was detected in 16 of 19 segments where ECV was quantified. Global native T1 was independent from gender or LV function but decreased with increasing age. Patients with replacement myocardial fibrosis had significantly lower native global T1. Patients with cardiac complications had significantly lower native global T1. Conclusions The combined use of both segmental native T1 and T2* values could improve the sensitivity for detecting MIO. Native T1 is associated with cardiac complications in thalassaemia major.

Objective The objective of this study was to use real-world data to evaluate the effectiveness and safety of canakinumab in Italian patients with systemic JIA (sJIA). Methods A retrospective multicentre study of children with sJIA was performed. Clinical features, laboratory parameters and adverse events were collected at baseline, and 6 and 12 months after starting canakinumab. The primary outcome measure of effectiveness was clinically inactive disease (CID) off glucocorticoids (GCs) treatment at 6 months. Results A total of 80 children from 15 Italian centres were analysed. Of the 12 patients who started canakinumab in CID while receiving anakinra, all maintained CID. Of the 68 with active disease at baseline, 57.4% achieved CID off GCs at 6 months and 63.8% at 12 months. In univariate analysis, the variables significantly related to non-response were number of active joints (NAJs) ≥5, history of macrophage activation syndrome (MAS) and disease duration. Multivariate analysis confirmed the association between non-response and NAJs ≥5 [odds ratio (OR) 6.37 (95% CI: 1.69, 24.02), P = 0.006] and between non-response and history of MAS [OR 3.53 (95% CI: 1.06, 11.70), P = 0.039]. No serious adverse events were recorded in this series. There were two cases of MAS during canakinumab, leading to a rate of 2.9 episodes per 100 patient years. Conclusion We have confirmed, using real-world data, the efficacy of canakinumab in sJIA in a multicentric cohort. History of MAS and higher NAJ were associated with lower probability of achieving CID.

Background : Full dose cabozantinib for metastatic renal cell carcinoma (mRCC) is 60mg, but adverse events (AEs) may require dose reductions. Limited data exist comparing efficacy among cabozantinib doses. We compared AEs and clinical outcomes in mRCC patients treated with full versus reduced starting cabozantinib dose. Methods : We performed a retrospective analysis of 87 mRCC patients treated with cabozantinib at Winship Cancer Institute from 2016-2019. Overall survival (OS), progression-free survival (PFS), and objective response (OR) rate measured clinical outcomes. AEs were collected from clinic notes and the most common were hypertension, mucositis/hand-foot skin reaction (HFSR), or gastrointestinal toxicity. Univariate analysis (UVA) between starting doses and AEs with clinical outcomes was performed using logistic regression model. Multivariable analysis (MVA) was also performed using Cox proportional hazard model. Results : Most patients were male (71%) with clear-cell RCC (72%). The majority were IMDC intermediate (58%) or poor (35%) risk. One third received first-line cabozantinib and 64% had ≥3 baseline metastatic sites. Most patients (68%) required dose reduction from 60mg or started at reduced dose without escalation. Reduced dose patients were more likely to have ≥3 distant metastatic sites (70% vs 58%) and ≥ 2 prior lines of systemic therapy (50% vs 40%) compared to full dose patients. UVA revealed a trend towards shorter OS (HR: 1.78, p=0.095), PFS (HR: 1.50, p=0.107), and lower chance of OR (HR:0.42, p=0.149) among reduced dose patients. This trend did not hold in MVA (OS HR: 1.20, p=0.636; PFS HR: 1.23, p=0.4662). Mucositis/HFSR and hypertension were significantly associated with improved outcomes in UVA. Conclusions : Although we found a trend favoring full dose cabozantinib, this is likely due to worse baseline disease characteristics among patients starting on a reduced dose. Hypertension and mucositis/HFSR may be associated with improved outcomes. Larger studies are warranted to validate these findings.

Metasurfaces (MTSs) have emerged in the last years as a promising platform for next generation planar devices in a broad range of frequencies, thanks to their unique field manipulation capability. In particular, in the microwave range this solution is characterized by low-cost, lightweight, and simple integration with electronic circuits, since MTSs can be realized in PCB technology by printing electrically small patches over a dielectric slab. The MTS behavior can then be conveniently described in terms of homogenized boundary conditions of impedance type. Spatial modulation of these boundary conditions allows one to implement a broad class of functionalities, involving space wave or surface wave control, as well as conversion from surface waves to leaky waves. This paper reviews numerical and analytical models, design procedures and microwave applications of modulated MTSs, with particular emphasis on surface wave manipulation, and it discusses expected future developments of this technology.

Commuterline plays an important role for transportation planning in Indonesia, and it is essential to learn more on how to motivate people to actively use this public transportation facility. This paper presents an empirical investigation to explore different factors influencing the use of this publica transportation facility. The proposed study develops a questionnaire in Likert scale and distributes it among 374 people who had good experience of using commuterline in their daily lives. The questionnaire is designed to learn the effects of environmental, individual, consumer resources and psychological factors. Using some statistical techniques, the study has determined that psychological factors are the most important elements influencing consumer behavior to use this public transportation followed by consumer resources, product knowledge and individual characteristics.

The purpose of this study was to determine the effect of ease of use, transaction success rate, and technological system capability on trust and to determine the effect of ease of use, transaction success rate, technology system capability and interest in transaction using mobile banking. This research was conducted at PT Bank NIAGA which is located in Denpasar. The data collection technique used a questionnaire to 160 PT Bank NIAGA customers who were selected as samples. Data were analyzed by Structural Equation Modeling (SEM) with AMOS program. Ease of use, transaction success rate, and technology system capability have a positive and significant influence on trust and interest in transacting using mobile banking. This means that the better the ease of use, the success rate of transactions, and the capability of the technology system, the higher the customer trust and interest in transactions using mobile banking.

About two-thirds of patients with major depressive disorder (MDD) fail to achieve symptom remission after the initial antidepressant treatment. Despite a role of genetic factors was proven, the specific underpinnings are not fully understood yet. Polygenic risk scores (PRSs), which summarise the additive effect of multiple risk variants across the genome, might provide insights into the underlying genetics. This study aims to investigate the possible association of PRSs for bipolar disorder, MDD, neuroticism, and schizophrenia (SCZ) with antidepressant non-response or non-remission in patients with MDD. PRSs were calculated at eight genome-wide P-thresholds based on publicly available summary statistics of the largest genome-wide association studies. Logistic regressions were performed between PRSs and non-response or non-remission in six European clinical samples, adjusting for age, sex, baseline symptom severity, recruitment sites, and population stratification. Results were meta-analysed across samples, including up to 3,637 individuals. Bonferroni correction was applied. In the meta-analysis, no result was significant after Bonferroni correction. The top result was found for MDD-PRS and non-remission (p = 0.004), with patients in the highest vs. lowest PRS quintile being more likely not to achieve remission (OR=1.5, 95% CI=1.11–1.98, p = 0.007). Nominal associations were also found between MDD-PRS and non-response (p = 0.013), as well as between SCZ-PRS and non-remission (p = 0.035). Although PRSs are still not able to predict non-response or non-remission, our results are in line with previous works; methodological improvements in PRSs calculation may improve their predictive performance and have a meaningful role in precision psychiatry.

Central Pattern Generators (CPGs) have several properties desirable for locomotion: they generate smooth trajectories, are robust to perturbations and are simple to implement. Although conceptually promising, we argue that the full potential of CPGs has so far been limited by insufficient sensory-feedback information. This paper proposes a new methodology that allows tuning CPG controllers through gradient-based optimization in a Reinforcement Learning (RL) setting. To the best of our knowledge, this is the first time CPGs have been trained in conjunction with a MultilayerPerceptron (MLP) network in a Deep-RL context. In particular, we show how CPGs can directly be integrated as the Actor in an Actor-Critic formulation. Additionally, we demonstrate how this change permits us to integrate highly non-linear feedback directly from sensory perception to reshape the oscillators' dynamics. Our results on a locomotion task using a single-leg hopper demonstrate that explicitly using the CPG as the Actor rather than as part of the environment results in a significant increase in the reward gained over time (6x more) compared with previous approaches. Furthermore, we show that our method without feedback reproduces results similar to prior work with feedback. Finally, we demonstrate how our closed-loop CPG progressively improves the hopping behaviour for longer training epochs relying only on basic reward functions.

Background and Purpose: Clinical trials on stroke prevention in patients with atrial fibrillation have consistently shown clinical benefit from either warfarin or non–vitamin K antagonist oral anticoagulants (NOACs). NOAC-treated patients have consistently reported to be at lower risk for intracerebral hemorrhage (ICH) than warfarin-treated patients. The aims of this prospective, multicenter, multinational, unmatched, case-control study were (1) to investigate for risk factors that could predict ICH occurring in patients with atrial fibrillation during NOAC treatment and (2) to evaluate the role of CHA 2 DS 2 -VASc and HAS-BLED scores in the same setting. Methods: Cases were consecutive patients with atrial fibrillation who had ICH during NOAC treatment. Controls were consecutive patients with atrial fibrillation who did not have ICH during NOAC treatment. As within the CHA 2 DS 2 -VASc and HAS-BLED scores there are some risk factors in common, several multivariable logistic regression models were performed to identify independent prespecified predictors for ICH events. Results: Four hundred nineteen cases (mean age, 78.8±8.1 years) and 1526 controls (mean age, 76.0±10.3 years) were included in the study. From the different models performed, independent predictors of ICH were increasing age, concomitant use of antiplatelet agents, active malignancy, high risk of fall, hyperlipidemia, low clearance of creatinine, peripheral artery disease, and white matter changes. Low doses of NOACs (given according to label or not) and congestive heart failure were inversely associated with the risk of ICH. HAS-BLED and CHA 2 DS 2 -VASc scores performed poorly in predicting ICH with areas under the curves of 0.496 (95% CI, 0.468–0.525) and 0.530 (95% CI, 0.500–0.560), respectively. Conclusions: Several risk factors were associated to ICH in patients treated with NOACs for stroke prevention but not HAS-BLED and CHA 2 DS 2 -VASc scores.

Population screening; Liver fibrosis; Early diagnosis Cribratge de població; Fibrosi hepàtica; Diagnòstic precoç Cribado de población; Fibrosis hepática; Diagnóstico precoz Cirrhosis, highly prevalent worldwide, develops after years of hepatic inflammation triggering progressive fibrosis. Currently, the main etiologies of cirrhosis are non-alcoholic fatty liver disease and alcohol-related liver disease, although chronic hepatitis B and C infections are still major etiological factors in some areas of the world. Recent studies have shown that liver fibrosis can be assessed with relatively high accuracy noninvasively by serological tests, transient elastography, and radiological methods. These modalities may be utilized for screening for liver fibrosis in at-risk populations. Thus far, a limited number of population-based studies using noninvasive tests in different areas of the world indicate that a significant percentage of subjects without known liver disease (around 5% in general populations and a higher rate −18% to 27%-in populations with risk factors for liver disease) have significant undetected liver fibrosis or established cirrhosis. Larger international studies are required to show the harms and benefits before concluding that screening for liver fibrosis should be applied to populations at risk for chronic liver diseases. Screening for liver fibrosis has the potential for changing the current approach from diagnosing chronic liver diseases late when patients have already developed complications of cirrhosis to diagnosing liver fibrosis in asymptomatic subjects providing the opportunity of preventing disease progression. LiverScreen Consortium and the European Commission under the H20/20 program (847989); AGAUR (2017SGR-01281); Centro de Investigacion Biomedica en Enfermedades Hepaticas y Digestivas; Fundación de Investigación Sanitaria, cofunded by Instituto Carlos III–Subdirección General de Evaluación and the European Regional Development Fund (PI18/01330, PI18/00662, and PI18/00862); and Gilead’s Investigator–sponsored research program (IN-ES-989-5309)

Objectives To assess the antibody response to BNT162b2 mRNA COVID-19 vaccine in a cohort of health-care workers (HCW), comparing individuals with previous severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and SARS-CoV-2-naive individuals. Methods HCW were tested at T0 (day of first dose), T1 (day of second dose) and T2 (2–3weeks after second dose) for IgG anti-nucleocapsid protein, IgM anti-spike protein and IgG anti-receptor binding domain (IgG-RBD-S). The antibody response was compared between four main groups: group A, individuals with previous infection and positive antibodies at baseline; group B, individuals with the same history but negative antibodies; group C, individuals with no infection history but positive antibodies; group D, naive individuals. Repeated measures analysis was used to compare results over time-points. Results A total of 1935 HCW were included. Median IgG-RBD-S titre was significantly higher for group A (232 individuals) than for group B (56 individuals) both at T1 (A: 22763 AU/mL, interquartile range (IQR) 14222–37 204 AU/mL; B: 1373 AU/mL, IQR 783–3078 AU/mL, p 0.0003) and T2 (A: 30765 AU/mL, IQR 19841–42 813 AU/mL; B: 13171 AU/mL, IQR 2324–22 688 AU/mL, p 0.0038) and for group D (1563 individuals; 796 AU/mL, IQR 379–1510 AU/mL at T1; 15494 AU/mL, IQR 9122–23 916 AU/mL at T2, p Conclusions Individuals with past SARS-CoV-2 infection had a strong antibody response after one single vaccine shot. A single dose might be sufficient for this group, regardless of the time elapsed since infection; however, the clinical correlation with antibody response needs to be studied.

Background Salvage treatment for local recurrence after prior partial nephrectomy (PN) or local tumor ablation (LTA) for kidney cancer is, as of yet, poorly investigated. Objective To classify the treatments and standardize the nomenclature of salvage robot-assisted renal surgery, to describe the surgical technique for each scenario, and to investigate complications, renal function, and oncologic outcomes. Design, setting, and participants Sixty-seven patients underwent salvage robot-assisted renal surgery from October 2010 to December 2020 at nine tertiary referral centers. Surgical procedure Salvage robot-assisted renal surgery classified according to treatment type as salvage robot-assisted partial or radical nephrectomy (sRAPN or sRARN) and according to previous primary treatment (PN or LTA). Measurements Postoperative complications, renal function, and oncologic outcomes were assessed. Results and limitations A total of 32 and 35 patients underwent salvage robotic surgery following PN and LTA, respectively. After prior PN, two patients underwent sRAPN, while ten underwent sRARN for a metachronous recurrence in the same kidney. No intra- or perioperative complication occurred. For local recurrence in the resection bed, six patients underwent sRAPN, while 14 underwent sRARN. For sRAPN, the intraoperative complication rate was 33%; there was no postoperative complication. For sRARN, there was no intraoperative complication and the postoperative complication rate was 7%. At 3 yr, the local recurrence-free rates were 64% and 82% for sRAPN and sRARN, respectively, while the 3-yr metastasis-free rates were 80% and 79%, respectively. At 33 mo, the median estimated glomerular filtration rates (eGFRs) were 57 and 45 ml/min/1.73 m2 for sRAPN and sRARN, respectively. After prior LTA, 35 patients underwent sRAPN and no patient underwent sRARN. There was no intraoperative complication; the overall postoperative complications rate was 20%. No local recurrence occurred. The 3-yr metastasis-free rate was 90%. At 43 mo, the median eGFR was 38 ml/min/1.73 m2. The main limitations are the relatively small population and the noncomparative design of the study. Conclusions Salvage robot-assisted surgery has a safe complication profile in the hands of experienced surgeons at high-volume institutions, but the risk of local recurrence in this setting is non-negligible. Patient summary Patients with local recurrence after partial nephrectomy or local tumor ablation should be aware that further treatment with robot-assisted surgery is not associated with a worrisome complication profile, but also that they are at risk of further recurrence.

Background Regularly updated data on stroke and its pathological types, including data on their incidence, prevalence, mortality, disability, risk factors, and epidemiological trends, are important for evidence-based stroke care planning and resource allocation. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) aims to provide a standardised and comprehensive measurement of these metrics at global, regional, and national levels. Methods We applied GBD 2019 analytical tools to calculate stroke incidence, prevalence, mortality, disability-adjusted life-years (DALYs), and the population attributable fraction (PAF) of DALYs (with corresponding 95% uncertainty intervals [UIs]) associated with 19 risk factors, for 204 countries and territories from 1990 to 2019. These estimates were provided for ischaemic stroke, intracerebral haemorrhage, subarachnoid haemorrhage, and all strokes combined, and stratified by sex, age group, and World Bank country income level. Findings In 2019, there were 12·2 million (95% UI 11·0–13·6) incident cases of stroke, 101 million (93·2–111) prevalent cases of stroke, 143 million (133–153) DALYs due to stroke, and 6·55 million (6·00–7·02) deaths from stroke. Globally, stroke remained the second-leading cause of death (11·6% [10·8–12·2] of total deaths) and the third-leading cause of death and disability combined (5·7% [5·1–6·2] of total DALYs) in 2019. From 1990 to 2019, the absolute number of incident strokes increased by 70·0% (67·0–73·0), prevalent strokes increased by 85·0% (83·0–88·0), deaths from stroke increased by 43·0% (31·0–55·0), and DALYs due to stroke increased by 32·0% (22·0–42·0). During the same period, age-standardised rates of stroke incidence decreased by 17·0% (15·0–18·0), mortality decreased by 36·0% (31·0–42·0), prevalence decreased by 6·0% (5·0–7·0), and DALYs decreased by 36·0% (31·0–42·0). However, among people younger than 70 years, prevalence rates increased by 22·0% (21·0–24·0) and incidence rates increased by 15·0% (12·0–18·0). In 2019, the age-standardised stroke-related mortality rate was 3·6 (3·5–3·8) times higher in the World Bank low-income group than in the World Bank high-income group, and the age-standardised stroke-related DALY rate was 3·7 (3·5–3·9) times higher in the low-income group than the high-income group. Ischaemic stroke constituted 62·4% of all incident strokes in 2019 (7·63 million [6·57–8·96]), while intracerebral haemorrhage constituted 27·9% (3·41 million [2·97–3·91]) and subarachnoid haemorrhage constituted 9·7% (1·18 million [1·01–1·39]). In 2019, the five leading risk factors for stroke were high systolic blood pressure (contributing to 79·6 million [67·7–90·8] DALYs or 55·5% [48·2–62·0] of total stroke DALYs), high body-mass index (34·9 million [22·3–48·6] DALYs or 24·3% [15·7–33·2]), high fasting plasma glucose (28·9 million [19·8–41·5] DALYs or 20·2% [13·8–29·1]), ambient particulate matter pollution (28·7 million [23·4–33·4] DALYs or 20·1% [16·6–23·0]), and smoking (25·3 million [22·6–28·2] DALYs or 17·6% [16·4–19·0]). Interpretation The annual number of strokes and deaths due to stroke increased substantially from 1990 to 2019, despite substantial reductions in age-standardised rates, particularly among people older than 70 years. The highest age-standardised stroke-related mortality and DALY rates were in the World Bank low-income group. The fastest-growing risk factor for stroke between 1990 and 2019 was high body-mass index. Without urgent implementation of effective primary prevention strategies, the stroke burden will probably continue to grow across the world, particularly in low-income countries. Funding Bill & Melinda Gates Foundation.

Objective: To compare the incidence of dyslipidemia in people with HIV receiving integrase inhibitors (INSTI) versus boosted protease inhibitors (PI/b) and nonnucleoside reverse transcriptase inhibitors (NNRTI) within RESPOND consortium of prospective cohorts. Methods: Participants were eligible if they were at least 18 years, without dyslipidemia and initiated or switched to a three-drug antiretroviral therapy (ART)-regimen consisting of either INSTI, NNRTI, or PI/b for the first time, between 1 January 2012 and 31 December 2018. Dyslipidemia was defined as random total cholesterol more than 240 mg/dl, HDL less than 35 mg/dl, triglyceride more than 200 mg/dl, or initiation of lipid-lowering therapy. Poisson regression was used to determine the adjusted incidence rate ratios. Follow-up was censored after 3 years or upon ART-regimen discontinuation or last lipid measurement or 31 December 2019, whichever occurred first. Results: Overall, 4577 people with HIV were eligible (INSTI = 66.9%, PI/b = 12.5%, and NNRTI = 20.6%), 1938 (42.3%) of whom were ART-naive. During 1.7 (interquartile range, 0.6 - 3.0) median years of follow-up, 1460 participants developed dyslipidemia [incidence rate: 191.6 per 1000 person-years, 95% confidence interval (CI) 182.0 - 201.7]. Participants taking INSTI had a lower incidence of dyslipidemia compared with those on PI/b (adjusted incidence rate ratio 0.71; CI 0.59 - 0.85), but higher rate compared with those on NNRTI (1.35; CI 1.15 - 1.58). Compared with dolutegravir, the incidence of dyslipidemia was higher with elvitegravir/cobicistat (1.20; CI 1.00 - 1.43) and raltegravir (1.24; CI 1.02 - 1.51), but lower with rilpivirine (0.77; CI 0.63 - 0.94). Conclusion: In this large consortium of heterogeneous cohorts, dyslipidemia was less common with INSTI than with PI/b. Compared with dolutegravir, dyslipidemia was more common with elvitegravir/cobicistat and raltegravir, but less common with rilpivirine.

Objective: The treatment landscape for renal cell carcinoma (RCC) is rapidly evolving. The aim of this review is to summarize the randomized-controlled trials evaluating the role of immunotherapy in neoadjuvant or adjuvant setting. Materials and methods: We searched PubMed, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov for studies including neoadjuvant or adjuvant immunotherapy, and provided a brief overview of the pharmacodynamics of immunotherapy for RCC. Results: Several drugs are currently under investigation. In the neoadjuvant setting, four studies are evaluating the role of single-agent immunotherapy, one of dual-agent immunotherapy, and four studies the role of immunotherapy in combination with tyrosine kinase inhibitors or anti-interleukin-1 beta. In the adjuvant setting, two studies are evaluating the role of single-agent immunotherapy and two of dual-agent immunotherapy. Conclusions: The approval of immune checkpoint inhibition as a front-line therapeutic strategy for advanced RCC has also ultimately led to the investigation of these agents first in the adjuvant and then in the neoadjuvant setting. Currently, there are nine studies aimed to evaluate the role of immunotherapy in the neoadjuvant setting and four studies in the adjuvant setting.

The aim of this systematic review is to collect clinical trials conducted using essential oils (EOs) in obstetric symptoms by evaluating if and in which context the aromatherapy practice is effective in obstetrics. The research was conducted by using the databases of EMBASE, Medline, Biosis and Toxcenter, PubMed, and Google Scholar search engine, selecting articles from January 2004 to July 2020. This study was performed according to the MOOSE and PRISMA guidelines. Only the randomized clinical trials were considered, and in cases of multiple publications, it was considered the most up to date information. Biases were highlighted. In the presence of homogeneous data, pooling statistics and meta-analysis were applied. The research led to 71 articles, 17 of which were eligible. Among the trials selected, eight investigated the effectiveness of EOs on anxiety, depression, and stress. Two concerned the treatment of nausea and vomiting, six evaluated the application of EOs on labor for pain treatment, and two showed the effectiveness in the treatment of episiotomy. The heterogeneity of works carried out so far has made it possible to develop a meta-analysis only in the field of pain treatment during childbirth, identifying the effectiveness of the EOs Lavandula spp. and Rosa damascena.

Background The prognostic role of multiparametric magnetic resonance imaging (mpMRI) and systematic biopsy in predicting biochemical recurrence (BCR) after radical prostatectomy (RP) in prostate cancer (PCa) patients has not been addressed yet. Objective To develop a risk tool predicting BCR after RP in patients diagnosed with magnetic resonance imaging (MRI)-targeted biopsy. Design, setting, and participants A total of 804 patients with a clinical suspicion of PCa and positive mpMRI diagnosed with MRI-targeted plus concomitant systematic biopsy treated with RP were identified. Outcome measurements and statistical analyses The outcome was represented by BCR defined as two prostate-specific antigen (PSA) values ≥0.2 ng/ml after surgery. Multivariable Cox regression analyses assessed the predictors of BCR. A risk tool model based on imaging and biopsy parameters was developed and validated internally. The c-index, calibration plot, and decision curve analyses were used to assess discrimination, calibration, and the net benefit associated with its use in predicting BCR at 36 mo. Results and limitations Median (interquartile range) follow-up was 28 (25–29) mo, and 89 patients experienced BCR. The 36-mo BCR-free survival rate was 89%. The maximum diameter of the index lesion and seminal vesicle invasion (SVI) at mpMRI as well as the presence of clinically significant PCa at systematic biopsy (defined as a grade group of >2) were associated with BCR (all p ≤ 0.03). A model based on PSA, Prostate Imaging Reporting and Data System score, SVI at mpMRI, diameter of the index lesion, grade group at MRI-targeted biopsy, and clinically significant PCa at systematic biopsy achieved the highest discrimination (77%) among all clinical models, as well as the European Association of Urology risk groups (62%) and the Cancer of the Prostate Risk Assessment (CAPRA) score (60%). This tool was characterized by excellent calibration at internal validation and the highest net benefit when predicting BCR for the threshold risk between 0% and 30%. Conclusions The adoption of predictive models accounting for mpMRI and MRI-targeted biopsy-derived variables and concomitant systematic biopsy would improve clinicians’ ability to identify patients at a higher risk of early recurrence after surgery. Patient summary The use of information obtained at multiparametric magnetic resonance imaging (mpMRI), and MRI-targeted and concomitant systematic biopsy would improve clinicians’ ability to identify prostate cancer patients at a higher risk of experiencing early biochemical recurrence after surgery.

This study investigates the effect of fintech on financial inclusion, and financial literacy, it was able to influence financial literacy on financial inclusion in Lubuklinggau. The research was conducted by distributing questionnaires to eight districts in the city of Lubuklinggau with a total sample of 401 people who use fintech as the main requirement. Data analysis was carried out with WarpPLS to identify direct and indirect effects on the tested variables. Based on the results, the perception of the ease and effectiveness of using fintech does not affect financial inclusion in Lubuklinggau. People are still not familiar with fintech and consider fintech as a new financial system and not easy to use. The level of risk and interest in using fintech has a significant influence on the financial inclusion variable in the Lubuklinggau. The indirect analysis explains it proves that financial literacy is able to moderate perceptions of the ease of using fintech and reduce the risk of fintech itself on financial inclusion. However, financial literacy is not able to moderate the effectiveness of using fintech and interest in financial inclusion to use of fintech after understanding financial literacy, people become more selective in using fintech.

BACKGROUND Anterior cruciate ligament (ACL) injuries represent detrimental injuries in the National Football League (NFL). A significant portion of these injuries often occur in preseason exhibitions. The Coronavirus disease 2019 pandemic presented a unique disruption to preseason NFL football with the cancelation of all preseason games. AIM To compare the incidence of ACL tears through the first eight weeks of the NFL season in 2020 to the mean incidence over the previous 5 seasons (2015-2019) and determine if there was any change in incidence with the elimination of the preseason. METHODS NFL players who suffered ACL tears during the preseason and first eight weeks of the NFL season from 2015-2020 were identified. The number of ACL injuries for the 2015-2019 seasons was compared to the 2020 season for four different timeframes. For each analysis, the cumulative number of ACL injuries to that time point was used to calculate the percent difference for descriptive analysis. Additionally, the number of teams with at least one player suffering an ACL tear were identified and compared using Chi-Squared testing. Finally, a cumulative relative risk was calculated for each week played. RESULTS There were 14 ACL tears through the first four games of the 2020 season, a 118.8% (14 vs 6.4) increase in comparison to the 5-year average over the first 4 regular season weeks of 2015-2019. However, when accounting for injuries occurring during the preseason from 2015-2019, there were 18.6% (14 vs 17.2) fewer total ACL injuries through regular season week 4 with no significant difference in percentage of teams impacted when these preseason injuries were accounted for P = 0.394. Results were similar (19 vs 17.2) over 8 total games played (whether regular season or preseason), and over 8 regular season games (P = 0.196, P = 0.600). CONCLUSION The elimination of the NFL preseason resulted in a higher rate of injuries during the first 4 games of the regular season. However, these increases are offset by the injuries typically sustained during the preseason. This suggests there may be front-loading of injuries over the course of an NFL season, such that players may be more prone to injury when the intensity of play suddenly increases, whether in the preseason or regular season.

AIMS The introduction of immunotherapy for patients with head and neck squamous cell carcinoma (HNSCC) raises the need for harmonisation between different types of antibody and immunohistochemistry platform for evaluating the expression of PD-L1 by use of the combined positive score (CPS) in this tumour. The aim of this study was to compare the expression of PD-L1 as determined with the CPS and two widely used assays (the 22C3 PharmDx assay and the SP263 assay) in a cohort of HNSCCs. METHODS AND RESULTS We analysed 43 whole sections of HNSCC with two different anti-PD-L1 antibodies, 22C3 and SP263. The results, expressed as the CPS, were evaluated by 10 trained pathologists and statistical analyses were performed. We found a very similar results for PD-L1 expression between the 22C3 PharmDx assay and the SP263 assay in our cohort, and a strong and significant correlation between the two assays for all specimens (P

Remote sensing has long been used to study wildlife; however, manual methods of detecting wildlife in aerial imagery are often time-consuming and prone to human error, and newer computer vision tec...

The locus coeruleus is the main noradrenergic nucleus of the brain and is often affected in neurodegenerative diseases. Recently, magnetic resonance imaging with specific T1-weighted sequences for neuromelanin has been used to evaluate locus coeruleus integrity in patients with these conditions. In some of these studies, abnormalities in locus coeruleus signal have also been found in healthy controls and related to ageing. However, this would be at variance with recent post-mortem studies showing that the nucleus is not affected during normal ageing. The present study aimed at evaluating locus coeruleus features in a well-defined cohort of cognitively healthy subjects who remained cognitively intact on a one-year follow-up. An ad-hoc semiautomatic analysis of locus coeruleus magnetic resonance was applied. Sixty-two cognitively intact subjects aged 60–80 years, without significant comorbidities, underwent 3 T magnetic resonance with specific sequences for locus coeruleus. A semi-automatic tool was used to estimate the number of voxels belonging to locus coeruleus and its intensity was obtained for each subject. Each subject underwent extensive neuropsychological testing at baseline and 12 months after magnetic resonance scan. Based on neuropsychological testing 53 subjects were cognitively normal at baseline and follow up. No significant age-related differences in locus coeruleus parameters were found in this cohort. In line with recent post-mortem studies, our in vivo study confirms that locus coeruleus magnetic resonance features are not statistically significantly affected by age between 60 and 80 years, the age range usually evaluated in studies on neurodegenerative diseases. A significant alteration of locus coeruleus features in a cognitively intact elderly subject might be an early sign of pathology.

The purpose of this study was to describe demographic, toxicological, criminal, and medicolegal characteristics of suicides of young people aged up to 24 years examined by the Porto Alegre Medicolegal Office, from 2010 to 2016. This cross-sectional study collected data from the Porto Alegre Medicolegal Office and the Rio Grande do Sul State Police Department. The information was obtained from death certificates, toxicological analyses and police reports. Rates were calculated according to sex and age range (under 15 years old, 15 to 19 years old, and 20 to 24 years old) for comparing local with national data. There were 143 people who died by suicide in the period, 120 males and 23 females. Hanging was the most frequently used method, but in the range of 10 to 14 years old, firearm use was the predominant method. Fifty percent of male victims and 30% of female victims had some criminal history. Suicide rates in the study groups generally followed national trends. The relative frequency of suicide by firearm in this study diverged from international findings, as it was relatively more frequent in children under 15 years old and less frequent in older ranges. If confirmed, the finding draws attention to access to firearms in this age range. In older age ranges, adolescents and young adults were frequently involved in the criminal system. This finding may be useful for planning interventions involving both mental health education and screening for problems that may be associated with criminal involvement.

The hospital is one of the health service units for the community that functions health services, the hospital must pay attention to employee motivation so that good work discipline is realized, thereby creating work harmony that will later have an impact on productivity. The research objectives are to find out 1) The Effect of Motivation on Work Discipline at Udayana University Hospital; 2) The Effect of Motivation on Employee Productivity at Udayana University Hospital; 3) The Effect of Work Motivation and Discipline on Employee Productivity at Udayana University Hospital. This research uses quantitative methods with SEM PLS analysis techniques. This study shows the results of 1) The significant positive effect of motivation on employee discipline of 0.573 with a t-statistic value of 6.615; 2) The significant positive effect of motivation on productivity is 0.307 with a t-statistic value of 3.730; 3) The significant positive effect of employee discipline on productivity is 0.621 with a t-statistic value of 8.875.

Delivering increasingly complex software-reliant systems demands better ways to manage the long-term effects of short-term expedients. The technical debt (TD) metaphor has gained significant traction as a way to understand and communicate such issues. Almost 25 years after the term was coined in 1992 by Ward Cunningham, and more than 10 years after the first edition of the TechDebt workshop/conference series, we take a brief look at the past, present, and future of TD.

BACKGROUND The effects of adrenaline on cerebral blood vessels during cardiopulmonary resuscitation (CPR) are not well understood. We developed an extracorporeal CPR model that maintains constant low systemic blood flow while allowing adrenaline-associated effects on cerebral vasculature to be assessed at different mean arterial pressure (MAP) levels independently of the effects on systemic blood flow. METHODS After eight minutes of cardiac arrest, low-flow extracorporeal life support (ECLS) (30 ml/kg/min) was started in fourteen pigs. After ten minutes, continuous adrenaline administration was started to achieve MAP values of 40 (n = 7) or 60 mmHg (n = 7). Measurements included intracranial pressure (ICP), cerebral perfusion pressure (CePP), laser-Doppler-derived regional cerebral blood flow (CBF), cerebral regional oxygen saturation (rSO2), brain tissue oxygen tension (PbtO2) and extracellular cerebral metabolites assessed by cerebral microdialysis. RESULTS During ECLS without adrenaline, regional CBF increased by only 5% (25th to 75th percentile: -3 to 14; p = 0.2642) and PbtO2 by 6% (0-15; p = 0.0073) despite a significant increase in MAP to 28 mmHg (25-30; p