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ImportanceGiven that mycosis fungoides−cutaneous T-cell lymphoma (MF/CTCL) is chronic, there is a need for additional therapies with minimal short- and long-term adverse effects. Topical synthetic hypericin ointment, 0.25%, activated with visible light is a novel, nonmutagenic photodynamic therapy (PDT).ObjectivesTo determine the efficacy and safety of topical synthetic hypericin ointment, 0.25%, activated with visible light as a nonmutagenic PDT in early-stage MF/CTCL.Design, Settings, and ParticipantsThis was a multicenter, placebo-controlled, double-blinded, phase 3 randomized clinical trial (FLASH study) conducted from December 2015 to November 2020 at 39 academic and community-based US medical centers. Participants were adults (≥18 years) with early-stage (IA-IIA) MF/CTCL.InterventionsIn cycle 1, patients were randomized 2:1 to receive hypericin or placebo to 3 index lesions twice weekly for 6 weeks. In cycle 2, all patients received the active drug for 6 weeks to index lesions. In cycle 3 (optional), both index and additional lesions received active drug for 6 weeks.Main Outcomes and MeasuresThe primary end point was index lesion response rate (ILRR), defined as 50% or greater improvement in modified Composite Assessment of Index Lesion Severity (mCAILS) score from baseline after 6 weeks of therapy for cycle 1. For cycles 2 and 3, open label response rates were secondary end points. Adverse events (AEs) were assessed at each treatment visit, after each cycle, and then monthly for 6 months. Data analyses were performed on December 21, 2020.ResultsThe study population comprised 169 patients (mean [SD] age, 58.4 [16.0] years; 96 [57.8%] men; 120 [72.3%] White individuals) with early-stage MF/CTCL. After 6 weeks of treatment, hypericin PDT was more effective than placebo (cycle 1 ILRR, 16% vs 4%; P = .04). The ILRR increased to 40% in patients who received 2 cycles of hypericin PDT (P P Conclusion and RelevanceThe findings of this randomized clinical trial indicate that synthetic hypericin PDT is effective in early-stage patch and plaque MF/CTCL and has a favorable safety profile.Trial RegistrationClinicalTrials.gov Identifier: NCT02448381

Osteoporosis is a risk factor for instrumentation failure in spine surgery. Bone strength is commonly assessed by bone mineral density (BMD) as a surrogate marker. However, BMD represents only a portion of bone strength and does not capture the qualitative dimensions of bone. Recently, the magnetic resonance imaging (MRI)-based vertebral bone quality (VBQ) score was introduced as a novel marker of bone quality. However, it is still unclear if the VBQ score correlates with in-vivo bone microstructure.The aims of the study were (1) to demonstrate differences in MRI-based (VBQ) and in-vivo (microcomputed tomography; μCT) bone quality between osteopenic/osteoporotic and normal bone, (2) to show the correlation between VBQ, bone microstructure and volumetric BMD (vBMD), and (3) to determine the predictive value of the VBQ score for the prevalence of osteopenia/osteoporosis.Retrospective cross-sectional study.267 patients who underwent posterior lumbar fusion surgery from 2014 to 2021 at a single academic institution. Bone biopsies were harvested intraoperatively in 118 patients.VBMD, VBQ score, and bone microstructure parameters derived from μCT.Quantitative computed tomography (QCT) measurements were performed at the lumbar spine and the L1/L2 average was used to categorize patients with a vBMD ≤120mg/cm267 patients (55.8% female, age 63.3 years, BMI 29.7 kg/mThis study demonstrated for the first time that the VBQ score is associated with trabecular microstructure determined by μCT. The bone microstructure and VBQ score were significantly different in patients with impaired vBMD. However, the ability to predict osteopenia/osteoporosis with the VBQ score was moderate. The VBQ score appears to reflect additional bone quality characteristics and might have a complementary role to vBMD. This enhances our understanding of the biological background of the radiographic VBQ score and might be a take-off point to evaluate the clinical utility of it as non-invasive screening tool for bone quality.

The aim of this study was to assess temporal trends in disability benefits for breast cancer awarded to women by Brazil's National Social Security Institute. We conducted a time-series analysis of disability benefit incidence rates between 2007 and 2018 using joinpoint regression and data from the Unified Benefits Information System (SUIBE) and open access social security system database. The age-adjusted incidence rate increased by 6.7% per year between 2015 and 2018 after a period of stability between 2007 and 2014. The number of benefits granted to women aged 20-49 increased, on average, by 3.4% per year, showing a marked rise from 2015 to 2018 (10.4% per year). The findings highlight that breast cancer is an important cause of sick leave among female workers and that the incidence of the disease is growing in younger economically active women, reinforcing the importance of early referral to the Social Security Professional Rehabilitation Program to help workers return to work and readapt to working life.O objetivo deste estudo foi avaliar a tendência temporal dos benefícios previdenciários concedidos pelo Instituto Nacional do Seguro Social a mulheres por câncer de mama. Foi realizado um estudo de tendência temporal das taxas de incidência dos auxílios por incapacidade temporária de espécie previdenciária concedidos por câncer de mama em mulheres entre 2007 e 2018 no Brasil, utilizando o Sistema Único de Informações de Benefícios e a base de dados abertos da Previdência Social. As análises de tendência foram realizadas através de regressão segmentada joinpoint. As taxas de incidência dos benefícios ajustadas por idade apresentaram estabilidade entre 2007 e 2015, seguida de elevação anual de 6,7% de 2015 a 2018. Houve aumento anual médio de 3,4% do número de benefícios concedidos a mulheres entre 20 e 49 anos, sendo mais evidente entre 2015 e 2018, com elevação de 10,4% ao ano. Este estudo demonstrou a importância do câncer de mama como causa de afastamento do trabalho em mulheres, com acometimento crescente das faixas etárias mais jovens e economicamente ativas, o que reforça a necessidade de abordagem precoce do Programa de Reabilitação Profissional da Previdência Social para a readaptação destas trabalhadoras em suas atividades ou a reinserção no mercado de trabalho.

BACKGROUND: Immediate initiation of antiretroviral therapy (ART) regardless of CD4 cell count reduces risk for AIDS and non-AIDS-related events in asymptomatic, HIV-positive persons and is the standard of care. However, most HIV-positive persons initiate ART when their CD4 count decreases below 500 × 10 9 cells/L. Consequences of delayed ART on risk for non-AIDS-defining and AIDS-defining cancer, one of the most common reasons for death in HIV, are unclear. OBJECTIVE: To estimate the long-term risk difference for cancer with the immediate ART strategy.DESIGN: Multinational prospective cohort study.SETTING: The D:A:D (Data collection on Adverse events of anti-HIV Drugs) study, which included HIV-positive persons from Europe, Australia, and the United States.PARTICIPANTS: 8318 HIV-positive persons with at least 1 measurement each of CD4 cell count and viral load while ART-naive (study period, 2006 to 2016).MEASUREMENTS: The parametric g-formula was used, with adjustment for baseline and time-dependent confounders (CD4 cell count and viral load), to assess the 10-year risk for non-AIDS-defining and AIDS-defining cancer of immediate versus deferred (at CD4 counts RESULTS: During 64 021 person-years of follow-up, 231 cases of non-AIDS-defining cancer and 272 of AIDS-defining cancer occurred among HIV-positive persons with a median age of 36 years (interquartile range, 29 to 43 years). With immediate ART, the 10-year risk for non-AIDS-defining cancer was 2.97% (95% CI, 2.37% to 3.50%) and that for AIDS-defining cancer was 2.50% (CI, 2.37% to 3.38%). Compared with immediate ART initiation, the 10-year absolute risk differences when deferring ART to CD4 counts less than 500 × 10 9 cells/L and less than 350 × 10 9 cells/L were 0.12 percentage point (CI, -0.01 to 0.26 percentage point) and 0.29 percentage point (CI, -0.03 to 0.73 percentage point), respectively, for non-AIDS-defining cancer and 0.32 percentage point (CI, 0.21 to 0.44 percentage point) and 1.00 percentage point (CI, 0.67 to 1.44 percentage points), respectively, for AIDS-defining cancer. LIMITATION: Potential residual confounding due to observational study design.CONCLUSION: In this young cohort, effects of immediate ART on 10-year risk for cancer were small, and further supportive data are needed for non-AIDS-defining cancer.PRIMARY FUNDING SOURCE: Highly Active Antiretroviral Therapy Oversight Committee.

INTRODUCTION: Despite the significant clinical importance of sex among factors affecting cancer progression and survival, it remains one of the least studied factors. Therefore, we sought to examine these differences in relation to primary malignant cardiac tumors (PMCTs) using a national data set.METHODS: The 2004-2017 National Cancer Database was queried for patients with PMCTs. Annual trend of females' percent was assessed. Overall survival predictors were evaluated with Kaplan-Meier and Cox-regression. Subgroup analysis was done based on histology, comorbidity index, race, insurance, and surgical treatment.RESULTS: PMCTs were identified in 736 patients (median age 52, female [47.8%]). Most of them were high-grade (49.2%). About 60% underwent surgery. Angiosarcoma (43%), fibrosarcoma (5.2%), and leiomyosarcoma (5.2%) were the most common pathologies. Based on multivariate Cox-regression, higher income, higher comorbidity index, angiosarcoma, and Stage III/IV were associated with higher late mortality, while year of diagnosis and use of surgery or chemotherapy were associated with lower mortality. Among the surgical group, age, higher income, higher comorbidity index, angiosarcoma, and Stage III/IV were independent predictors of higher late mortality, while private insurance and year of diagnosis were associated with lower late mortality. No difference was seen between males and females in 30-day and late mortality (p = .71). Subgroup analysis based on Cox-regression showed no differences in late mortality between males and females.CONCLUSION: PMCTs have poor overall survival. Surgery and chemotherapy were associated with longer survival benefits. On the contrary, the associated risk factors for mortality were advanced age, higher comorbidity index, angiosarcoma histology, and Stage III/IV.

Introduction: Due to established teratogenicity of valproates, the EU risk minimisation measures (RMMs) with a pregnancy prevention programme (PPP) for valproate were updated in March 2018. Objectives: To investigate the effectiveness of the 2018 EU RMMs on valproate utilisation in five European countries/regions. Methods: A multi-database, times series study of females of childbearing potential (12–55 years) was conducted using electronic medical records from five countries/regions (01.01.2010–31.12.2020): Denmark, Tuscany (Italy), Spain, the Netherlands, and the UK. Clinical and demographic information from each database was transformed to the ConcePTION Common Data Model, quality checks were conducted and a distributed analysis was performed using common scripts. Incident and prevalent use of valproate, proportion of discontinuers and switchers to alternative medicine, frequency of contraception coverage during valproate use, and occurrence of pregnancies during valproate exposure were estimated per month. Interrupted time series analyses were conducted to estimate the level or trend change in the outcome measures. Results: We included 69,533 valproate users from 9,699,371 females of childbearing potential from the five participating centres. A significant decline in prevalent use of valproates was observed in Tuscany, Italy (mean difference post-intervention −7.7%), Spain (−11.3%), and UK (−5.9%) and a non-significant decline in the Netherlands (−3.3%), but no decline in incident use after the 2018 RMMs compared to the period before. The monthly proportion of compliant valproate prescriptions/dispensings with a contraceptive coverage was low (

An inclusive contemporary analysis of spinal cord injury (SCI) rates in patients undergoing aneurysm repair and the factors associated with complications has not been performed.Following a systematic literature search, studies from 2008 to 2018 on repair of descending thoracic aneurysm (DTA) and thoracoabdominal aortic aneurysm (TAAA) were pooled in a meta-analysis performed using the generic inverse variance method. The primary outcome was permanent SCI. Secondary outcomes were temporary SCI, operative mortality, long-term mortality, postoperative stroke, and cerebrospinal fluid (CSF) drain-related complications.One-hundred sixty-nine studies (22,634 patients) were included. The pooled rate of permanent SCI was 4.5% (95% confidence interval [CI], 3.8-5.4); 3.5% (95% CI, 1.8-6.7) for DTA and 7.6% (96% CI, 6.2-9.3) for TAAA repair (P for subgroups = .02), 5.7% (95% CI, 4.3-7.5) for open repair and 3.9% (95% CI, 3.1-4.8) for endovascular repair (P for subgroups = .03). Rates for Crawford extents I, II, III, IV, and V aneurysms were 4.0% (95% CI, 3.0-5.0), 15.0% (95% CI, 10.0-22.0), 7.0% (95% CI, 6.0-9.0), 2.0% (95% CI, 2.0-4.0), and 7.0% (95% CI, 2.0-23.0) respectively (P for subgroups.001). The pooled rates for operative mortality, late mortality at a mean follow-up of 5.0 years, stroke, and temporary SCI were 7.4% (95% CI, 6.1-9.4), 1.0% (95% CI, 0.0-1.0), 4.2% (95% CI, 3.6-4.8), and 3.7% (95% CI, 3.0-4.6), respectively. The pooled rates for severe, moderate, and minor CSF-drain related complications were 5.1% (95% CI, 2.23-11.1), 4.1% (95% CI, 0.6-22.0), and 3.6% (95% CI, 1.2-8.0) respectively.Despite improvement, both open and endovascular aneurysm repair remain associated with a substantial risk of permanent SCI. The risk is greater for TAAA repair, especially extent II, III, and V.

Summary Chromosome imbalance (aneuploidy) is the major cause of pregnancy loss and congenital disorders in humans. Analyses of small biopsies from human embryos suggest that aneuploidy commonly originates during early divisions, resulting in mosaicism. However, the developmental potential of mosaic embryos remains unclear. We followed the distribution of aneuploid chromosomes across 73 unselected preimplantation embryos and 365 biopsies, sampled from four multifocal trophectoderm (TE) samples and the inner cell mass (ICM). When mosaicism impacted fewer than 50% of cells in one TE biopsy (low-medium mosaicism), only 1% of aneuploidies affected other portions of the embryo. A double-blinded prospective non-selection trial (NCT03673592) showed equivalent live-birth rates and miscarriage rates across 484 euploid, 282 low-grade mosaic, and 131 medium-grade mosaic embryos. No instances of mosaicism or uniparental disomy were detected in the ensuing pregnancies or newborns, and obstetrical and neonatal outcomes were similar between the study groups. Thus, low-medium mosaicism in the trophectoderm mostly arises after TE and ICM differentiation, and such embryos have equivalent developmental potential as fully euploid ones.

Summary Background Atrial fibrillation is the most common complication after cardiac surgery and is associated with extended in-hospital stay and increased adverse outcomes, including death and stroke. Pericardial effusion is common after cardiac surgery and can trigger atrial fibrillation. We tested the hypothesis that posterior left pericardiotomy, a surgical manoeuvre that drains the pericardial space into the left pleural cavity, might reduce the incidence of atrial fibrillation after cardiac surgery. Methods In this adaptive, randomised, controlled trial, we recruited adult patients (aged ≥18 years) undergoing elective interventions on the coronary arteries, aortic valve, or ascending aorta, or a combination of these, performed by members of the Department of Cardiothoracic Surgery from Weill Cornell Medicine at the New York Presbyterian Hospital in New York, NY, USA. Patients were eligible if they had no history of atrial fibrillation or other arrhythmias or contraindications to the experimental intervention. Eligible patients were randomly assigned (1:1), stratified by CHA2DS2-VASc score and using a mixed-block randomisation approach (block sizes of 4, 6, and 8), to posterior left pericardiotomy or no intervention. Patients and assessors were blinded to treatment assignment. Patients were followed up until 30 days after hospital discharge. The primary outcome was the incidence of atrial fibrillation during postoperative in-hospital stay, which was assessed in the intention-to-treat (ITT) population. Safety was assessed in the as-treated population. This study is registered with ClinicalTrials.gov, NCT02875405, and is now complete. Findings Between Sept 18, 2017, and Aug 2, 2021, 3601 patients were screened and 420 were included and randomly assigned to the posterior left pericardiotomy group (n=212) or the no intervention group (n=208; ITT population). The median age was 61·0 years (IQR 53·0–70·0), 102 (24%) patients were female, and 318 (76%) were male, with a median CHA2DS2-VASc score of 2·0 (IQR 1·0–3·0). The two groups were balanced with respect to clinical and surgical characteristics. No patients were lost to follow-up and data completeness was 100%. Three patients in the posterior left pericardiotomy group did not receive the intervention. In the ITT population, the incidence of postoperative atrial fibrillation was significantly lower in the posterior left pericardiotomy group than in the no intervention group (37 [17%] of 212 vs 66 [32%] of 208 [p=0·0007]; odds ratio adjusted for the stratification variable 0·44 [95% CI 0·27–0·70; p=0·0005]). Two (1%) of 209 patients in the posterior left pericardiotomy group and one ( Interpretation Posterior left pericardiotomy is highly effective in reducing the incidence of atrial fibrillation after surgery on the coronary arteries, aortic valve, or ascending aorta, or a combination of these without additional risk of postoperative complications. Funding None

Objectives The COMMENCE trial was conducted to evaluate the safety and effectiveness of an aortic bioprosthesis with novel RESILIA tissue (Edwards Lifesciences, Irvine, Calif). Reports of early noncalcific valve failure resulting from thrombosis or leaflet tears in other valves warrant careful evaluation of early valve performance. Methods Patients underwent clinically indicated surgical aortic valve replacement with the Edwards Pericardial Aortic Bioprosthesis, Model 11000A (Edwards Lifesciences) in a prospective, multinational, multicenter (n = 27), single-arm, Food and Drug Administration Investigational Device Exemption trial. Events were adjudicated by an independent clinical events committee; echocardiograms were analyzed by an independent core laboratory. Results Between January 2013 and March 2016, 689 patients received the study valve. Mean age was 67.0 ± 11.6 years. Mean Society of Thoracic Surgeons predicted risk of mortality was 2.0% ± 1.8%. Follow-up duration was 3.7 ± 1.2 years, with a total of 2533 patient years of follow-up and a median follow-up of 4 years. Early all-cause mortality was 1.2%, thromboembolism 2.3%, all bleeding 1.0%, and major paravalvular leak 0.1%. One- and 4-year actuarial freedom from all-cause mortality was 97.7% (95% confidence interval, 96.5%-98.8%) and 91.9% (95% confidence interval, 89.7%-94.1%), respectively. At 4 years, New York Heart Association functional class improved compared with baseline in 63.0%, effective orifice area was 1.5 ± 0.5 cm2, and mean gradient was 11.0 ± 5.6 mm Hg. Freedom from moderate or greater transvalvular insufficiency was 99.7%. There were no events of structural valve deterioration. Conclusions Safety and hemodynamic performance of this aortic bioprosthesis with RESILIA tissue at 4 years are favorable. This novel tissue does not appear to result in unexpected early thrombosis events or noncalcific structural valve deterioration.

Osteoarthritis (OA) is one of the most prevalent musculoskeletal ailments worldwide. Numerous conservative therapies exist, but evidence for such treatments remains conflicting. Recently, there has been growing interest surrounding bioactive sleeves for managing knee arthritis; however, the literature on their efficacy for relieving pain and improving function in the setting of knee OA is limited. As such, we sought to investigate the effect of a bioactive sleeve on patient-reported outcome measures in a small cohort of patients with OA.Patients with knee OA were given a bioactive sleeve (Reparel, Chico, CA) and asked to refrain from lifestyle modifications and intraarticular corticosteroid injections. Lysholm Knee Score, Oxford Knee Score, Knee Injury and OA Outcome Score (KOOS), Single Assessment Numeric Evaluation, and Visual Analog Scale score were obtained at baseline, 2 weeks, 6 weeks, and 3 months. OA severity was evaluated using the Kellgren and Lawrence (KL) classification system. The Wilcoxon signed rank test was used to compare baseline patient-reported outcomes with 2-week, 6-week, and 3-month time points. Bivariate correlation was used to evaluate the relation between patient-reported outcome measures and KL classification.The cohort was composed of 14 participants-4 males and 10 females-with a mean age of 62.2 ± 13.2 years and a body mass index of 33.7 ± 5.8. The average KL grade was 2.9 (range 2-4). KOOS pain, symptoms, activities of daily living, and quality of life increased significantly at 2 weeks, 6 weeks, and 3 months. KOOS sport and recreation significantly increased at 3 months. The Oxford Knee Score was significantly greater at 2 weeks, 6 weeks, and 3 months. The Lysholm Knee Score was significantly greater at 6 weeks and 3 months. The Single Assessment Numeric Evaluation attained significant improvement at 3 months, and the Visual Analog Scale improvement was significant at 2 weeks. No statistically significant difference was attained with University of California at Los Angeles activity score. Outcome scores did not correlate with KL classification.These data suggest that a bioactive sleeve may improve patient-reported pain, symptoms, and function in the setting of knee OA. Further research is needed to better understand the role of bioactive sleeves for patients with knee arthritis.

Background Radiology is an essential tool in the management of a patient. The aim of this manuscript was to build structured report (SR) Mammography based in Breast Cancer. Methods A working team of 16 experts (group A) was composed to create a SR for Mammography Breast Cancer. A further working group of 4 experts (group B), blinded to the activities of the group A, was composed to assess the quality and clinical usefulness of the SR final draft. Modified Delphi process was used to assess level of agreement for all report sections. Cronbach’s alpha (Cα) correlation coefficient was used to assess internal consistency and to measure quality analysis according to the average inter-item correlation. Results The final SR version was built by including n = 2 items in Personal Data, n = 4 items in Setting, n = 2 items in Comparison with previous breast examination, n = 19 items in Anamnesis and clinical context; n = 10 items in Technique; n = 1 item in Radiation dose; n = 5 items Parenchymal pattern; n = 28 items in Description of the finding; n = 12 items in Diagnostic categories and Report and n = 1 item in Conclusions. The overall mean score of the experts and the sum of score for structured report were 4.9 and 807 in the second round. The Cronbach’s alpha (Cα) correlation coefficient was 0.82 in the second round. About the quality evaluation, the overall mean score of the experts was 3.3. The Cronbach’s alpha (Cα) correlation coefficient was 0.90. Conclusions Structured reporting improves the quality, clarity and reproducibility of reports across departments, cities, countries and internationally and will assist patient management and improve breast health care and facilitate research.

Introduction Delirium and sarcopenia are common, although underdiagnosed, geriatric syndromes. Several pathological mechanisms can link delirium and low skeletal muscle mass, but few studies have investigated their association. We aimed to investigate (1) the association between delirium and low skeletal muscle mass and (2) the possible role of calf circumference mass in finding cases with delirium. Methods The analyses were conducted employing the cross-sectional “Delirium Day” initiative, on patient 65 years and older admitted to acute hospital medical wards, emergency departments, rehabilitation wards, nursing homes and hospices in Italy in 2017. Delirium was diagnosed as a 4 + score at the 4-AT scale. Low skeletal muscle mass was operationally defined as calf circumference ≤ 34 cm in males and ≤ 33 cm in females. Logistic regression models were used to investigate the association between low skeletal muscle mass and delirium. The discriminative ability of calf circumference was evaluated using non-parametric ROC analyses. Results A sample of 1675 patients was analyzed. In total, 73.6% of participants had low skeletal muscle mass and 24.1% exhibited delirium. Low skeletal muscle mass and delirium showed an independent association (OR: 1.50; 95% CI 1.09–2.08). In the subsample of patients without a diagnosis of dementia, the inclusion of calf circumference in a model based on age and sex significantly improved its discriminative accuracy [area under the curve (AUC) 0.69 vs 0.57, p Discussion and conclusion Low muscle mass is independently associated with delirium. In patients without a previous diagnosis of dementia, calf circumference may help to better identify those who develop delirium.

Impulsivity has been proposed as an endophenotype for bipolar disorder (BD); moreover, impulsivity levels have been shown to carry prognostic significance and to be quality-of-life predictors. To date, reports about the genetic determinants of impulsivity in mood disorders are limited, with no studies on BD individuals. Individuals with BD and healthy controls (HC) were recruited in the context of an observational, multisite study (GECOBIP). Subjects were genotyped for three candidate single-nucleotide polymorphisms (SNPs) (5-HTTLPR, COMT rs4680, BDNF rs6265); impulsivity was measured through the Italian version of the Barratt Impulsiveness Scale (BIS-11). A mixed-effects regression model was built, with BIS scores as dependent variables, genotypes of the three polymorphisms as fixed effects, and centers of enrollment as random effect. Compared to HC, scores for all BIS factors were higher among subjects with euthymic BD (adjusted β for Total BIS score: 5.35, p < 0.001). No significant interaction effect was evident between disease status (HC vs. BD) and SNP status for any polymorphism. Considering the whole sample, BDNF Met/Met homozygosis was associated with lower BIS scores across all three factors (adjusted β for Total BIS score: −10.2, p < 0.001). A significant 5-HTTLPR x gender interaction was found for the SS genotype, associated with higher BIS scores in females only (adjusted β for Total BIS score: 12.0, p = 0.001). Finally, COMT polymorphism status was not significantly associated with BIS scores. In conclusion, BD diagnosis did not influence the effect on impulsivity scores for any of the three SNPs considered. Only one SNP—the BDNF rs6265 Met/Met homozygosis—was independently associated with lower impulsivity scores. The 5-HTTLPR SS genotype was associated with higher impulsivity scores in females only. Further studies adopting genome-wide screening in larger samples are needed to define the genetic basis of impulsivity in BD.

Aims: The clinical significance of nonvisualized sentinel lymph nodes (non-vSLNs) is unknown. The authors sought to determine the incidence of non-vSLNs on lymphoscintigraphy, the identification rate during surgery, factors associated with non-vSLNs and related axillary management. Patients & methods: A total of 30,508 consecutive SLN procedures performed at a single institution from 2000 to 2017 were retrospectively studied. Associations between clinicopathological factors and the identification of SLNs during surgery were assessed. Results: Non-vSLN occurred in 525 of the procedures (1.7%). In 73.3%, at least one SLN was identified intraoperatively. Nodal involvement was only significantly associated with SLN nonidentification (p

OBJECTIVES Previous reports have found females are a higher risk of morbidity and mortality following isolated coronary artery bypass grafting (CABG). Here, we describe the differences in outcomes following isolated CABG between males and females. METHODS Following a systematic literature search, studies reporting sex-related outcomes following isolated CABG were pooled in a meta-analysis performed using the generic inverse variance method. The primary outcome was operative mortality. Secondary outcomes included rates of stroke, repeat revascularization, myocardial infarction, major adverse cardiac events, and late mortality. Subgroup analyses were performed for studies published before and after the year 2000 and for the type of risk adjustment. RESULTS Eighty-four studies were included with a total of 903 346 patients. Females were at higher risk for operative mortality (odds ratio: 1.77, 95% confidence interval [CI]: 1.64–1.92, P 0.001) but not repeat revascularization (IRR: 0.99, 95% CI: 0.76–1.29, P = 0.95). The use of the off-pump technique or multiple arterial grafts was not associated with the primary outcome. CONCLUSIONS Females undergoing CABG are at higher risk for operative and late mortality as well as postoperative events including major adverse cardiac events, myocardial infarction and stroke. PROSPERO registration CRD42020187556

Research for innovative drugs is crucial to contribute to parasitic infections control and eradication. Inspired by natural antiprotozoal triterpenes, a library of 12 hemisynthetic 3‐O‐arylalkyl esters was derived from ursolic and oleanolic acids through one‐step synthesis. Compounds were tested on Trypanosoma, Leishmania and the WI38 cell line alongside with a set of triterpenic acids. Results showed that the triterpenic C3 esterification keeps the antitrypanosomal activity (IC50≈1.6–5.5 μm) while reducing the cytotoxicity compared to parent acids. Unsaturation of the ester alkyl chain leads to an activity loss interestingly kept when a sterically hindered group replaces the double bond or shields the ester group. An ursane/oleanane C3 hydroxylation was the only important feature for antileishmanial activity. Two candidates, dihydrocinnamoyl and 2‐fluorophenylpropionyl ursolic acids, were tested on an acute mouse model of African trypanosomiasis with significant parasitemia reduction at day 5 post‐infection for the dihydrocinnamoyl derivative. Further evaluation on other alkyl/protective groups should be investigated both in vitro and in vivo., A library of 12 C3 triterpenic esters was readily synthesized and tested for antiparasitic activity and cytotoxicity evaluation. C3 esterification kept the activity while lowering the cytotoxicity. The most potent antitrypanosomal activity, coupled with great selectivity, was shown by 2‐fluoro phenylpropionate, phenylpropionate and α‐methyl phenylpropionate esters of ursolic acids. The phenylpropionate derivative showed significant in vivo parasitemia reduction at day 5 post‐infection.

Background Most studies of patients with isolated proximal left anterior descending (PLAD) coronary artery disease do not include all 3 procedural options: percutaneous coronary intervention (PCI), conventional coronary artery bypass graft (CABG) surgery, or minimally invasive CABG. Methods New York’s cardiac registries were used to identify patients who underwent revascularization for isolated PLAD disease between January 1, 2010, and November 30, 2016, in New York State. After exclusions, 14,327 patients, of whom 13,115 received PCI, 1001 of whom underwent CABG surgery, and 211 of whom underwent minimally invasive CABG were monitored through the end of 2017 to compare outcomes. Registry data were matched to vital statistics data to obtain deaths occurring after discharge and matched to claims data to obtain subsequent admissions for myocardial infarction and stroke. Results There were no significant differences in mortality or in mortality/myocardial infarction/stroke after 7 years (with median follow-up times in excess of 4 years) among the 3 procedures after adjusting for differences in patient risk factors. However, conventional CABG surgery was associated with a lower subsequent revascularization rate than PCI (adjusted hazard ratio, 0.45; 95% confidence interval, 0.35-0.58) and minimally invasive CABG surgery (adjusted hazard ratio, 0.46; 95% confidence interval, 0.32-0.66). Conclusions Among patients with isolated PLAD disease undergoing any of 3 revascularization options (PCI, conventional CABG surgery, or minimally invasive CABG surgery), conventional CABG surgery was associated with lower subsequent revascularization rates, but there were no differences in mortality or mortality/myocardial infarction/stroke rates.

Epilepsy affects around 50 million people worldwide, and an important number of patients (30%) fail to respond to any available antiepileptic drug. Previous studies have shown that luteolin presents a promising potential as an anticonvulsant. On the other hand, different studies showed that luteolin does not promote anticonvulsant effects. Therefore, there is a lack of consensus about the use of luteolin for seizure control. Luteolin low bioavailability could be a limiting factor to obtain better results. Attractively, micronization technology has been applied to improve flavonoids bioavailability. Thus, the present study aimed to investigate the effects of luteolin on its raw form and micronized luteolin in a PTZ-induced seizure model in adult zebrafish (Danio rerio). Our results demonstrate that luteolin and micronized luteolin did not block PTZ-induced seizures in adult zebrafish. Also, luteolin and micronized luteolin did not provoke behavioral changes. Finally, our results show that 24 h after seizure occurrence, no changes were detected for p70S6Kb, interleukin 1β, and caspase-3 transcript levels. Altogether, we failed to observe an anticonvulsant potential of luteolin in adult zebrafish, even in its micronized form. However, we recommend new studies to investigate luteolin benefits in epilepsy.

STUDY DESIGN Retrospective descriptive study. OBJECTIVE To create topographical maps of occipital bone thickness and venous sinus (VS) presence to assess the risks of screw insertion in four commercially available occipital plates. SUMMARY OF BACKGROUND DATA Craniocervical junction instability and deformity are serious pathological conditions that require posterior fixation of the occipital bone to the cervical vertebrae. Insertion of occipital bone screws requires evaluation of both occipital bone thickness for effective internal fixation and intracranial venous sinus presence for vascular injury prevention. Despite the surgical risks, there is a paucity of research on safe screw placement. METHODS We created a matrix of 231 standardized measurement points to analyze the occipital bone thickness and venous sinus presence in cervical spine CT angiograms. These measurements were used to create topographical maps of occipital bone thickness and likelihood of venous sinus presence, which we then compared to the screw hole configurations of four occipital plates. RESULTS 100 patients were assessed. Maximum occipital bone thickness of 13.9 ± 3.3 mm was midline in the occipital bone, 45 mm from the foramen magnum, around the external occipital protuberance (EOP). Regions with thicknesses >8 mm were 2 cm lateral to the EOP at the level of the superior nuchal line and 2.5 cm inferior to the EOP. The area with the highest VS presence rate was around the EOP and the superior nuchal line. The right transverse VS was more prominent in both sexes. CONCLUSION There is a limited area of the occipital bone with thicknesses for enough screw purchase. Previous studies have shown 8 mm as the minimum screw length to reduce the risk of implant failure. In our analysis, only "T"-shaped plates had configurations with thicknesses >8 mm for each screw hole. For every screw hole in the analyzed occipital plates, there was a possibility of venous sinus presence ranging from 8-33%.Level of Evidence: 5.

Background and objectives The oncological benefit of axillary surgery (AS), with sentinel lymph node biopsy (SLNB) or axillary dissection (ALND), in elderly women affected by breast cancer (BC) is controversial. We evaluated AS trends over a 10-year follow-up period as well as locoregional and survival outcomes in this subset of patients. Methods Patients aged 70 years or older, treated between 1994 and 2008, were selected and divided in two groups, depending on whether or not AS was performed. A (1:1) matched analysis for all relevant clinicopathological features was performed. Outcomes were analyzed using the Kaplan–Meier method and univariate Cox-proportional hazard ratio analysis. Results A total of 1.748 patients were identified and stratified by age (70–74, 75–79, 80–84). A matched analysis was performed for 252 patients: 122 who underwent AS and 122 who did not. At 10-year follow-up, ipsilateral breast tumor recurrence, distant metastasis and contralateral BC were similar, p = 0.83, p = 0.42 and p = 0.28, respectively. In the no-AS group, a significant increased risk of axillary lymph-node recurrence was identified at 5- and confirmed at 10-years (p = 0.038), without impact on overall survival at 5- and 10-years (p = 0.52). In the non-AS group, higher rate of axillary recurrence at 10-years was observed in patients with poorly differentiated (24.1%, 95% CI 7.2–46.2), highly proliferative (Ki67 ≥ 20%: 17.1%, 95% CI 0.6–33.3) and luminal B tumors (16.8%, 95% CI 5.9–35.5). Conclusions Axillary staging in elderly women does not impact long-term survival. Tailoring surgery according to tumor biology and age may improve locoregional outcome.

Background: To assess the clinical usefulness of serum tumor markers for early detection of distant breast cancer recurrence using FDG-PET/CT. Methods: We retrospectively analyzed 561 consecutive patients who underwent surgery for invasive primary breast cancer and had increased tumor markers (CA 15-3 and CEA) after completion of locoregional therapy. FDG-PET/CT data were reviewed for all cases. CA 15-3 and CEA were evaluated both in a continuous and in a quartile (Q) distribution. The Wilcoxon rank-sum test and logistic regression models were used to evaluate the association between increased tumor marker values and the presence (and type) of distant metastases. Results: The median value of CA 15-3 was 35.0 U/mL (IQR, 29.5–43.0) in cases where no distant metastases were detected, and it was 58.9 U/mL (IQR, 40.0–108.0) in cases where metastases were detected (p < 0.001). The median value of CEA was 6.6 U/mL (IQR, 4.4–10.0) in cases of no metastases and 12.4 U/mL (IQR, 6.9–30.0) in cases of metastases (p < 0.001). Increased levels of both tumor markers (Q3 and Q4) were strongly associated with the presence of distant metastases. The association between CA 15-3 and bone/liver metastases was stronger compared with other types of metastases (p heterogeneity between odds ratios [ORs] = 0.03 for Q3 and Conclusion: Increased tumor marker levels detected in asymptomatic breast cancer patients during adjuvant therapies and follow-up are significantly predictive of distant metastases identified on FDG-PET/CT.

OBJECTIVES Both the open and endovascular techniques are commonly used for harvesting the radial artery (ORAH and ERAH, respectively), and yet, very little is known about the effects of these 2 techniques on endothelial integrity and function of the radial artery (RA). The aim of this study was to assess the endothelial integrity and function of RA harvested using the 2 approaches. METHODS Two independent surgical teams working in the same institution routinely use the RA for coronary artery bypass grafting exclusively employing either ORAH or ERAH. Thirty-nine consecutive patients were enrolled in this comparative study. Endothelial function after ORAH or ERAH was assessed by using the wire myograph system. The integrity of the RA endothelium was evaluated by immunohistochemical staining for erythroblast transformation specific-related gene. RESULTS The vasodilation in response to acetylcholine was significantly higher in RA harvested with ORAH (P ≤ 0.001 versus ERAH). Endothelial integrity was not different between the 2 groups. CONCLUSIONS ORAH is associated with a significantly higher endothelium-dependent vasodilation. Further investigation on the potential implications of these findings in terms of graft spasm and patency as well as clinical outcomes are needed.

Study design Retrospective observational study. Objectives To investigate the spinal cord safety margins for C2 instrumentation. Summary of background data Intraoperative spinal cord injury during C2 spine surgery is a rare, but potentially life-threatening complication. Pre-operative planning for C2 instrumentation mainly focuses on C2 pedicle bony dimensions on CT and the vertebral artery location and few studies have evaluated C2 spinal cord safety margins. Methods We measured two distances in C2 bilaterally: 1) C2 pedicle to dura distance (P-D), defined as a transverse line that measured the shortest distance between the medial wall of the C2 pedicle and the dural sac, 2) C2 pedicle to spinal cord (P-SC), defined as a transverse line that measured the shortest distance between the medial wall of the C2 pedicle and spinal cord. We defined the distances above 4 mm as safe for instrumentation. Result A total of 146 patients (mean age 71.2, 50.7% female) were included. The average distances were 5.5 mm for C2 left P-D, 5.9 mm for C2 right P-D, 10.1 mm for C2 left P-SC and 10.6 mm for C2 right P-SC. Twenty eight (21.4%) patients had C2 P-D distances under 4 mm and out of those 2 (7%) patients had distances under 2 mm. There were more female patients with C2 P-D distances under 4 mm compared to males. No patient had C2 P-SC distances under 4 mm. Conclusion We demonstrated that around 20% of patients had C2 P-D distance below 4 mm, but no patient had C2 P-SC distance less than 4 mm. Since a lateral misplacement can lead to a potentially fatal vertebral artery injury, medial screw trajectory is recommended for C2 pedicle instrumentation with consideration of these safety margins.Level of Evidence: 3.

Pathogenic CDH1 germline mutations are associated with lobular breast cancer in the so-called hereditary lobular breast cancer (HLBC) syndrome, without apparent correlation with the classic hereditary diffuse gastric cancer (HDGC). Recent international guidelines recommend CDH1 screening also in absence of diffuse gastric cancer (DGC) history. Genomic characteristics underlying gastric and breast tumorigenesis in this varied population of patients is still unclear. In this review we revised all CDH1 germline mutations described in literature associated with lobular breast cancer (LBC). We distinguish two subgroups of CDH1 mutant carriers: (a) 'mixed' HDGC syndrome, showing both DGC plus LBC and (b) HLBC, in which DGC is absent and the LBC phenotype is predominant. A higher frequency of CDH1 mutations was identified in the HLBC syndrome with an early age at LBC diagnosis; it is possible that LBCs with CDH1 germline mutations are an independent inherited syndrome. This evidence allows us to gain biological insight into the pathophysiological mechanisms responsible for the different phenotypes of the disease and potentially tailor the prophylactic and screening procedures.

BACKGROUND: Treatment outcomes in multidrug‐resistant TB (MDR‐TB) patients are suboptimal in several low‐incidence countries.METHODS: The primary outcome measure was the proportion of successfully treated patients in Italy during an 18‐year period. Secondary outcomes were treatment outcomes in certain drug‐containing regimens and the possibility for the WHO shorter MDR‐TB regimen.RESULTS: In the 191 patients included (median age at admission: 33 years; 67.5% male, following drug‐resistance patterns were found: MDR‐TB in 68.6%, pre‐extensively drug‐resistant TB (pre‐XDR‐TB) in 30.4% and XDR‐TB in 1.1% patients. The most frequently prescribed drugs were fluoroquinolones in 84.6% cases, amikacin in 48.7%, linezolid in 34.6% and meropenem/clavulanic acid in 29.5%. The median duration of treatment was 18 months. Treatment success was achieved in 71.2% patients, of whom, 44% were cured and 27.2% completed treatment. Treatment success rates did not statistically differ between the MDR‐ (68.8%) and pre‐XDR‐TB (77.6%) groups (P = 0.26). Treatment success rates had large variability between North and South of Italy (81.3% vs. 53.3%). Only 22.5% of the cases would have been eligible for shorter MDR‐TB regimensCONCLUSION: Our study highlights variability in treatment outcomes in MDR‐ and pre‐XDR‐TB patients. Study findings confirmed the potential utility of linezolid and, for patients with limited oral options, meropenem/clavulanic acid and amikacin.

Background The preoperative assessment of C2 morphology is important for safe instrumentation. Sclerotic changes are often seen in C2 pedicles. Evaluating the diameter measurements solely might not accurately assess the safety of screw insertion. We have proposed a novel grading system of the C2 pedicle that includes sclerosis and evaluated the predictive value of this grading system with the surgeon's safety evaluation. Methods We reviewed and measured the dimensional values in 220 cervical computed tomography angiograms. Additionally, we used a grading system that divides the findings into 5 grades according to the width measurement and degree of sclerosis in the C2 pedicle. Two spine surgeons independently classified the pedicles as follows: safe (minimal risk of pedicle violation), caution needed (caution to minimize pedicle violation), or dangerous (a high risk of pedicle violation). Finally, we compared the measurements and the surgeons' safety assessments. Results A total of 411 pedicles of 203 patients (mean age, 69.5 years; 49.5% women) were included. Of the 411 C2 pedicles, 170 were classified as high risk by ≥1 surgeon. Between the dimensional measurements and grading system, the sclerotic grade showed the best predictive value. Conclusions We have introduced a novel tool to evaluate the safety of C2 pedicle screw placement. Our results suggest that our pedicle width–sclerosis grading system is reproducible and predicts the surgeon's assessment of safe screw placement better than C2 pedicle diametrical measurements alone.

The World Health Organization considers excess morbidity and mortality among people with mental disorders as a high public health priority. This study aims to estimate the mortality risk and causes of death among a large population-based cohort of psychiatric patients. All residents in Veneto (Northeastern Italy) aged between 18 and 84 years with a contact with Community Mental Health Centers in 2008 and a psychiatric diagnosis (n = 54,350) were followed-up for 10 years. Standardized Mortality Ratios (SMR) and excess mortality were computed, with the general regional population as a reference. Mortality was more than doubled (males SMR = 2.4; females SMR = 2.2) and the relative increase in mortality was much larger in young and middle-aged adults (18–44 and 45–64 years) across all diagnostic groups. The most frequent causes were circulatory diseases (27%) and neoplasms (26%). Although the risk was increased by about tenfold, deaths from suicide were limited to 6% and 4% of all decedents in males and females, respectively. Patients with schizophrenia showed a very high risk for mortality for diabetes and cardiovascular disorders. A large excess was found also for respiratory diseases and a two-fold increase for lung cancer in males and breast cancer in females. Although chronic physical disorders are known to be the main causes of mortality in such patients, they receive far less attention than suicide or accidents. Our results suggest that there is still a need to plan actions to prevent excess mortality and to improve the quality of life of patients with mental disorders.

HCV infection has been hypothesized as a contributor of poor CD4+ recovery in patients living with HIV (PLWHIV). Aim of this study was to evaluate CD4+, CD8+ cells and CD4/CD8 ratio trends before and after HCV treatment with direct acting agents (DAA) in PLWHIV. HIV/HCV patients enrolled in ICONA and HepaICONA cohorts with HIV-RNA≤50copies/ml who achieved a sustained viral response after DAA treatment were studied. A linear regression model was used to investigate CD4+, CD8+ and CD4/CD8 changes 12months before and after DAA treatment. A total of 939 HIV/HCV patients were included, 225 (24.0%) female, median age: 53years (IQR 50–56). At DAA initiation, CD4+ T cell count was 12.5kPa. Trends of CD4+ and CD4/CD8 ratio were similar before and after DAA in all study populations (CD4+ change +17.6 cells/mm3 (95%CI −33.5; 69.4, p=0.494); CD4/CD8 change 0.013 (95%CI −0.061; 0.036, p=0.611). However, patients treated with ribavirin (RBV)-free DAA showed a significant decrease in CD8+ cells (−204.3 cells/mm3, 95%CI −375.0;-33.4, p=0.019), while patients treated with RBV experienced CD8+ cell increase (+141.2 cells/mm3, 95%CI 40.3; 242.1, p=0.006). In conclusion, HCV eradication following DAA treatment does not seem to have an impact on CD4+ T cell recovery in PLWHIV. However, a fast decline of CD8+T cells has been observed in patients treated without RBV, suggesting a favourable effect of HCV clearance on the general state of immune activation.

Objetivo: O presente estudo busca identificar os fatores associados que aumentamas taxas de partos cesáreos primários. Métodos: Estudo transversal, avaliando o número de cesáreas primárias realizadas nos anos de 2006 e 2018 no Hospital de Clínicas de Porto Alegre (HCPA), pormeio da coleta de dados nos prontuários das pacientes. Resultados: Idade materna avançada, gravidez gemelar e índice de massa corporal (IMC) mais elevado tornaram-se mais frequentes em 2018. Para mitigar o impacto dos fatores de confusão nas comparações entre os grupos, fizemos um ajuste por escores de propensão e detectamos diferenças significativas nas taxas de gravidez gemelar, diabetes mellitus gestacional e doença da tireoide. Conclusão: Os dados do presente estudo podem ser utilizados para prevenir e melhorar o manejo de morbidades, impactando em melhores resultados na prática obstétrica. Objective: The present study seeks to identify the associated factors that increased primary cesarean delivery rates. Methods: This was a cross-sectional study that evaluated the number of primary cesarean sections performed in the years 2006 and 2018 at the Hospital de Clínicas de Porto Alegre (HCPA, in the Portuguese acronym), through the collection of data from the medical records of the patients. Results: Advanced maternal age, twin pregnancy, and higher body mass index (BMI) became more frequent in 2018 in comparison with 2006. To mitigate the impact of confounding in comparisons among groups, we made an adjustment by propensity scores and detected significant differences when comparing both age groups on twin pregnancy rates, gestational diabetes mellitus, and thyroid disease. Conclusion: Data from the present study can be used to prevent and improve the management of morbidities, impacting on better outcomes in obstetrical practice.

Background In prior work we observed differences in morphology features in placentas from an autism-enriched cohort as compared to those from a general population sample. Here we sought to examine whether these differences associate with ASD-related outcomes in the child. Methods Participants (n = 101) were drawn from the Early Autism Risk Longitudinal Investigation (EARLI), a cohort following younger siblings of children with autism spectrum disorder (ASD). ASD-related outcomes, including the Social Responsiveness Scale (SRS), Mullen Scales of Early Learning (MSEL) Early Learning Composite, and ASD diagnosis, were assessed at age 3. Crude and adjusted linear regression was used to examine associations between placental morphological features (parametrized continuously and in quartiles) and SRS and MSEL scores; comparisons by ASD case status were explored as secondary analyses due to the small number of cases (n = 20). Results In adjusted analyses, we observed a modest positive association between umbilical cord eccentricity, defined as the ratio of the maximum:minimum radius from the cord insertion point, and SRS scores (Beta = 1.68, 95%CI = 0.45, 2.9). Positive associations were also suggested between placental maximum thickness and cord centrality and SRS scores, though these were estimated with little precision. Associations between other placental morphological features and outcomes were not observed. Conclusions Our analyses suggested a potential association between umbilical cord features and ASD-related traits, of interest as non-central cord insertion may reflect reduced placenta efficiency. Future studies with larger sample sizes are needed to further examine these and other placental features in association with ASD-related outcomes.

Cannabis is the most commonly used federally illegal drug in the United States and the world, especially among people of reproductive age. In addition, the potency of cannabis products has increased significantly in the past decade. This is concerning because the available evidence suggests an adverse effect of cannabis exposure on male and female reproductive health. Exposure to cannabinoids may have differential impacts on female reproductive health across a woman's lifespan, from preconception to pregnancy, throughout lactation, and during menopause. Moreover, cannabis use has been associated with adverse effects on fetal outcomes and longer-term offspring health and developmental trajectories. Despite the prevalence of cannabis use, there is limited available evidence regarding its safety, especially in regard to reproductive health, pregnancy, and lactation. The biological effects of cannabis are mediated by the endocannabinoid system, and studies have reported the presence of cannabinoid receptors in the male and female reproductive tract, on sperm and the placenta, suggesting that the endocannabinoid system plays a role in regulating reproduction. Cannabis use can affect male and female fertility and has been associated with altered reproductive hormones, menstrual cyclicity, and semen parameters. Use of cannabis in male patients has also been associated with erectile dysfunction, abnormal spermatogenesis, and testicular atrophy. In female patients, cannabis use has been associated with infertility and abnormal embryo implantation and development. The main psychoactive component of cannabis, the delta-9-tetrahydrocannabinol, can also cross the placenta and has been detected in breast milk. Maternal cannabis use during pregnancy and lactation has been associated with adverse effects, including small-for-gestational-age infants, preterm birth, fetal neurodevelopmental consequences, and impaired offspring sociobehavioral and cognitive development. The prevalence of cannabis use for alleviating menopausal symptoms has also increased despite the limited information on its benefits and safety. Given that cannabis use is on the rise, it is critical to understand its impact on reproductive health and offspring developmental outcomes. This is an understudied but timely subject requiring much further information to guide healthcare providers and those interested in conceiving or who are pregnant and lactating, and those at the end of their reproductive time span.

Horse transport is a common practice and is usually associated as a cause of stress in animals, with consequences for their well-being. There are several of evidence that stress can increase an acute phase response. The aim of this study was to verify whether the road transport of horses over distances of 50 and 300 kilometers induces changes in the values of acute phase proteins. To do this, the serum SDS-PAGE was performed and the bands obtained were identified by mass spectrometry (MALDI-TOF). The blood samples were collected in tubes without anticoagulant to obtain the serum, and the evaluations occurred before the road transportation (T0), immediately after the journey (T1), six hours later (T2), and 24 hours (T3), 48 hours (T4), 72 hours (T5), 96 hours (T6), 120 hours (T7) and 144 hours (T8) after the end of the trip. All analyzes were performed using the Minitab 17 statistical package, and significance was considered when P0.05. The APPs found through SDS-PAGE and properly identified were α2-macroglobulin, ceruloplasmin, transferrin, albumin, α1-antitrypsin, haptoglobin, apolipoprotein alpha 1, and α1-acid glycoprotein. No differences were observed in the concentration values between 50 and 300 km or between the moments after each route. The distances covered with the horses were not challenging enough to provoke an acute phase response reflected in changes in APPs.

The concept of sagittal spinal malalignment is well established in spinal surgery. However, the effect of musculature on its development has not been fully considered and the position of the pelvis is mostly seen as compensatory and not necessarily a possible cause of sagittal imbalance.This study aimed to investigate the influence of the posterior paraspinal muscles (PPM, erector spinae, and multifidus) and the psoas muscle on spinopelvic and spinal alignment.Retrospective cross-sectional study.Patients undergoing posterior lumbar fusion between 2014 and 2021 for degenerative conditions at a tertiary care center, with preoperative lumbar magnetic resonance imaging (MRI) within 12 months prior the surgery and a preoperative whole spine radiograph were included.PPM and psoas muscle measurements including the cross-sectional area (CSA), the functional cross-sectional area (fCSA), the amount of intramuscular fat (FAT), and the percentage of fat infiltration (FI). Spinopelvic measurements including lumbar lordosis (LL), pelvic tilt (PT), sacral slope (SS), pelvic incidence (PI), and sagittal vertical axis (SVA).A T2-weighted MRI-based quantitative assessment of the CSA, the fCSA and the amount FAT was conducted, and FI was further calculated. The regions of interest included the psoas muscle and the PPM on both sides at the L4 level that were summarized and normalized by the patient's height (cmA total of 150 patients (53.3% female) were included in the final analysis with a median age of 65.6 years and a median BMI of 28.2 kg/mThis study demonstrated the potential role of posterior paraspinal muscles and psoas muscle on pelvic retroversion and elucidated the relation to sagittal spinal malalignment. Although we cannot establish causality, we propose that increasing FI

The aim of this study was to determine the effect of age on the psoas and posterior paraspinal muscles (PPM; multifidus muscle and erector spinae) and to evaluate potential sex-related differences.MRI-based quantitative assessments of the cross-sectional area (CSA), the functional cross-sectional area (fCSA), the fat area (FAT) and the proportion of intramuscular fat (FI) were conducted on patients undergoing lumbar fusion surgery between 2014 and 2021. The regions of interest were the psoas muscle and the PPM at the superior endplate of L4. The left and right sides of the muscle groups were summarized and normalized by the patient's height (cmA total of 195 patients (57.9%female) with a median age of 64.2 years and a body mass index of 28.3 kg/mThis study demonstrated sex-specific differences in spinal muscle morphology in relation to patient age. With increasing age there was a decrease in FI

Highlights • EBV reactivation was observed in patients with COVID-19. • NK + and CD8 + T cell reduction was related to the severity of COVID-19 infection. • An increase of B cells in patients with severe symptoms was documented., Objectives The immunologic profile and opportunistic viral DNA increase were monitored in Italian patients with COVID-19 in order to identify markers of disease severity. Methods A total of 104 patients infected with SARS-CoV-2 were evaluated in the study. Of them, 42/104 (40.4%) were hospitalized in an intensive care unit (ICU) and 62/104(59.6%) in a sub-intensive care unit (SICU). Human cytomegalovirus (HCMV) and Epstein-Barr virus (EBV), Parvovirus B19 and Human Herpesvirus 6 virus reactivations were determined by real-time PCR, and lymphocyte subpopulation counts were determined by flow cytometry. Results Among opportunistic viruses, only EBV was consistently detected. EBV DNA was observed in 40/42 (95.2%) of the ICU patients and in 51/61 (83.6%) of the SICU patients. Comparing the two groups of patients, the EBV DNA median level among ICU patients was significantly higher than that observed in SICU patients. In parallel, a significant reduction of CD8 T cell and NK count in ICU patients as compared with SICU patients was observed (p

Objective Zero risk of linked HIV transmission in serodiscordant couples when the HIV-infected partner had viral load less than 200 copies/ml ('U status') was found in observational studies. We aimed at estimating the proportion of time in which 'U status' was maintained and identifying factors associated with the risk of losing it. Design Observational cohort study. Methods We included participants in the ICONA cohort who had reached an established 'U status' (viral load ≤200 copies/ml for >6 months) as of December 2010. The outcome was the number of person-days of follow-up (PDFU) above a viral load greater than 200 copies/ml, relative to the total number of PDFU observed. A logistic regression model was used to identify factors independently associated with the risk of losing 'U status'. Results Eight thousand, two hundred and forty-one persons living with HIV were included in the analysis who contributed 2 670 888 PDFU. Of these, 1648 (20%) were women, 768 (9%) were people who inject drugs (PWID), and 2066 (25%) were foreign-born. The median of viral load measurements was 9 (IQR: 4-15). Overall, only 3.1% of PDFU were observed when viral load was above 200 copies/ml. The proportion of PDFU with viral load more than 200 copies/ml was higher than average in women (5.3%), unemployed (5.4%), PWID (4.7%), and in people with more than three previous virologic failures (6.3%). These variables were significant predictors of losing 'U status' in the multivariable logistic regression. Conclusion Our results reinforce the validity of the U=U message in real-world setting. However, we identified subsets of our study population at higher risk of losing the 'U status' for whom additional efforts are needed.

Valve-sparing root replacement using reimplantation techniques is increasingly applied to bicuspid aortopathy. Long-term durability of cusp repair is unclear. We analyze midterm results using a conservative approach to cusp repair.From 2006 to 2018, 327 patients underwent valve-sparing reimplantation, 66 with bicuspid valves. Leaflets were analyzed after reimplantation. A majority (51/66) required no cusp repair. Fifteen patients had cusp repair limited to closure of unfused raphe or central plication. Patients were followed by echocardiography.Mean age of patients was 44.7 ± 12.3 years. The cusp repair group had a higher incidence of preoperative moderate (10% vs 40%) or severe (4% vs 33.3%) aortic insufficiency (P .001). There was no operative mortality or major complication. Mean follow-up was 51.6 ± 40.8 months. On postoperative echocardiography, incidence of none, trace, or mild aortic insufficiency was 41.3% (19/46), 43.5% (20/46), and 15.2% (7/46) in the no cusp repair group and 40% (6/15), 40% (6/15), and 20% (3/15) in the cusp repair group, respectively (P = .907). Few patients progressed in degree of aortic insufficiency. No patients required reoperation. At 5 years, freedom from any aortic insufficiency was 46.9% versus 15.8% (P = .013), and freedom from greater than trace aortic insufficiency was 59.1% versus 36.9% (P = .002) due to the higher rate of postoperative trace and mild aortic insufficiency with cusp repair. There was no difference in freedom from greater than mild aortic insufficiency (92.1% vs 100%; P = .33).Valve-sparing root replacement is reliably performed with bicuspid aortic valves whether or not cusp reconstruction is necessary. Few patients progress to greater than mild aortic insufficiency. Need for reoperation is rare in midterm follow-up.

BackgroundThe aim of this secondary analysis of the TESEO cohort is to identify, early in the course of treatment with tocilizumab, factors associated with the risk of progressing to mechanical ventilation and death and develop a risk score to estimate the risk of this outcome according to patients' profile.MethodsPatients with COVID-19 severe pneumonia receiving standard of care + tocilizumab who were alive and free from mechanical ventilation at day 6 after treatment initiation were included in this retrospective, multicenter cohort study. Multivariable logistic regression models were built to identify predictors of mechanical ventilation or death by day-28 from treatment initiation and β-coefficients were used to develop a risk score. Secondary outcome was mortality. Patients with the same inclusion criteria as the derivation cohort from 3 independent hospitals were used as validation cohort.Results266 patients treated with tocilizumab were included. By day 28 of hospital follow-up post treatment initiation, 40 (15%) underwent mechanical ventilation or died [26 (10%)]. At multivariable analysis, sex, day-4 PaO2/FiO2 ratio, platelets and CRP were independently associated with the risk of developing the study outcomes and were used to generate the proposed risk score. The accuracy of the score in AUC was 0.80 and 0.70 in internal validation and test for the composite endpoint and 0.92 and 0.69 for death, respectively.ConclusionsOur score could assist clinicians in identifying, early after tocilizumab administration, patients who are likely to progress to mechanical ventilation or death, so that they could be selected for eventual rescue therapies.

Objectives: HCV shows complex interactions with lipid metabolism. Our aim was to examine total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) changes in HIV/HCV coinfected patients, after achieving sustained virological response (SVR), according to different HCV genotypes and specific antiretroviral use. Methods: HIV/HCV coinfected patients, enrolled in the ICONA and HepaICONA cohorts, who achieved DAA-driven SVR were included. Paired t-tests were used to examine whether the pre- and post-SVR laboratory value variations were significantly different from zero. ANCOVA regression models were employed to estimate the causal effect of SVR and of PI/r use on lipid changes. The interaction between the effect of eradication and HCV genotype was formally tested. Results: six hundred and ninety-nine HIV/HCV coinfected patients were enrolled. After HCV eradication, a significant improvement in liver function occurred, with a significant decrease in AST, ALT, GGT, and total plasmatic bilirubin. TC and LDL-C significantly increased by 21.4 mg/dL and 22.4 mg/dL, respectively (p &lt, 0.001), after SVR, whereas there was no evidence for a change in HDL-C (p = 0.45) and triglycerides (p = 0.49). Notably, the TC and LDL-C increase was higher for participants who were receiving darunavir/ritonavir, and the TC showed a more pronounced increase among HCV genotype 3 patients (interaction-p value = 0.002). Conclusions: complex and rapid changes in TC and LDL-C levels, modulated by HCV genotype and PI/r-based ART combinations, occurred in HIV/HCV coinfected patients after SVR. Further studies are needed to evaluate the clinical impact of these changes on the long-term risk of cardiovascular disease.

Despite the actual availability of COVID-19 vaccines to combat the pandemic, many people are still vacillating in their decision to vaccinate. In this study, we considered the effect of two relevant contextual issues on vaccination intention: the number of people infected with COVID-19 is increasing, and the pace of vaccination is gaining speed. Specifically, we hypothesized that having already contracted SARS-CoV-2 (post-positive reluctance) could lead people to underestimate the importance of vaccination. Moreover, as the number of vaccinated people increases, more hesitant people could fall into the free-riding intention category, benefitting from the immunity provided by others' vaccinations. Vaccine hesitancy becomes more critical as the vaccination campaign proceeds: at one point, it will be inevitable to deal with hesitant people. This study is part of a WHO Regional Office for Europe project and involved a representative sample of 5006 Italians interviewed in January-February 2021. In case of post-positive reluctance, both young age and female gender increase vaccine hesitancy, while a high level of education reduces free-riding intention. Considering post-positive reluctance and free riding, a protective effect on hesitancy is associated with negative affective states, adherence to protective behaviors, trust in health information sources, and resilience. In contrast, increased vaccine hesitancy is associated with a high level of conspiracy-mindedness and trust in media information sources. Recognizing and studying the post-positive reluctance and the phenomenon of free-riding people can help us to become more efficient in combatting the virus.

Giant malignant phyllodes tumor of the breast: Insights into optimal management and reconstructive options for a rare and challenging entity

Background Ascending aorta replacement can be performed safely in high-volume centers. What remains unknown is whether concomitant coronary revascularization with bypass grafting affects postoperative outcomes. Methods This study retrospectively reviewed a prospectively maintained institutional database for patients who underwent ascending aorta replacement (AAR) during the period from 1997 to 2018. Patients were stratified into AAR alone (AAR) vs AAR and coronary artery bypass graft (AAR with CABG), further categorized as 1 or more than 1 CABG. Aortic dissection and root replacement cases were excluded. The primary end point consisted of major adverse events (MAE), including operative mortality, perioperative myocardial infarction, stroke, need for tracheostomy, and need for dialysis. Secondary end points were operative mortality, each MAE component, and late survival. Results A total of 951 patients were included in the analysis; 725 (76.2%) underwent isolated AAR, and 226 (23.8%) underwent AAR with CABG. Operative mortality was similar across the 2 groups (1.8% for AAR with CABG and 0.8% for AAR; P = .40). The unadjusted incidence of MAE was higher in the AAR with CABG group (5.8% vs 1.9%; P = .005).). On multivariable analysis, the performance of 1 CABG (odds ratio [OR], 1.90; 95% confidence interval [CI], 0.67 to 5.33; P = .23) and more than 1 CABG (OR, 2.65; 95% CI, 0.93 to 7.53; P = .07) was not associated with higher rates of MAE. Preoperative pulmonary dysfunction (OR, 2.51; 95% CI, 1.07 to 5.85; P = .03) was the only independent predictor of MAE. Conclusions In patients undergoing concomitant CABG with AAR, the performance of concomitant CABG is not associated with an increased risk of MAE.