Timing of surgery following SARS‐CoV‐2 infection: an international prospective cohort study

Peri-operative SARS-CoV-2 infection increases postoperative mortality. The aim of this study was to determine the optimal duration of planned delay before surgery in patients who have had SARS-CoV-2 infection. This international, multicentre, prospective cohort study included patients undergoing elective or emergency surgery during October 2020. Surgical patients with pre-operative SARS-CoV-2 infection were compared with those without previous SARS-CoV-2 infection. The primary outcome measure was 30-day postoperative mortality. Logistic regression models were used to calculate adjusted 30-day mortality rates stratified by time from diagnosis of SARS-CoV-2 infection to surgery. Among 140,231 patients (116 countries), 3127 patients (2.2%) had a pre-operative SARS-CoV-2 diagnosis. Adjusted 30-day mortality in patients without SARS-CoV-2 infection was 1.5% (95%CI 1.4–1.5). In patients with a pre-operative SARS-CoV-2 diagnosis, mortality was increased in patients having surgery within 0–2 weeks, 3–4 weeks and 5–6 weeks of the diagnosis (odds ratio (95%CI) 4.1% (3.3–4.8), 3.9% (2.6–5.1) and 3.6% (2.0–5.2), respectively). Surgery performed ≥ 7 weeks after SARS-CoV-2 diagnosis was associated with a similar mortality risk to baseline (odds ratio (95%CI) 1.5% (0.9– 2.1%)). After a ≥ 7 week delay in undertaking surgery following SARS-CoV-2 infection, patients with ongoing symptoms had a higher mortality than patients whose symptoms had resolved or who had been asymptomatic (6.0% (95%CI 3.2–8.7) vs. 2.4% (95%CI 1.4–3.4) vs. 1.3% (95%CI 0.6–2.0%), respectively). Where possible, surgery should be delayed for at least 7 weeks following SARS-CoV-2 infection. Patients with ongoing symptoms ≥ 7 weeks from diagnosis may benefit from further delay

Off-label long acting injectable antipsychotics in real-world clinical practice: a cross-sectional analysis of prescriptive patterns from the STAR Network DEPOT study

Introduction Information on the off-label use of Long-Acting Injectable (LAI) antipsychotics in the real world is lacking. In this study, we aimed to identify the sociodemographic and clinical features of patients treated with on- vs off-label LAIs and predictors of off-label First- or Second-Generation Antipsychotic (FGA vs. SGA) LAI choice in everyday clinical practice. Method In a naturalistic national cohort of 449 patients who initiated LAI treatment in the STAR Network Depot Study, two groups were identified based on off- or on-label prescriptions. A multivariate logistic regression analysis was used to test several clinically relevant variables and identify those associated with the choice of FGA vs SGA prescription in the off-label group. Results SGA LAIs were more commonly prescribed in everyday practice, without significant differences in their on- and off-label use. Approximately 1 in 4 patients received an off-label prescription. In the off-label group, the most frequent diagnoses were bipolar disorder (67.5%) or any personality disorder (23.7%). FGA vs SGA LAI choice was significantly associated with BPRS thought disorder (OR = 1.22, CI95% 1.04 to 1.43, p = 0.015) and hostility/suspiciousness (OR = 0.83, CI95% 0.71 to 0.97, p = 0.017) dimensions. The likelihood of receiving an SGA LAI grew steadily with the increase of the BPRS thought disturbance score. Conversely, a preference towards prescribing an FGA was observed with higher scores at the BPRS hostility/suspiciousness subscale. Conclusion Our study is the first to identify predictors of FGA vs SGA choice in patients treated with off-label LAI antipsychotics. Demographic characteristics, i.e. age, sex, and substance/alcohol use co-morbidities did not appear to influence the choice towards FGAs or SGAs. Despite a lack of evidence, clinicians tend to favour FGA over SGA LAIs in bipolar or personality disorder patients with relevant hostility. Further research is needed to evaluate treatment adherence and clinical effectiveness of these prescriptive patterns

Genetic determinants in a critical domain of ns5a correlate with hepatocellular carcinoma in cirrhotic patients infected with hcv genotype 1b

HCV is an important cause of hepatocellular carcinoma (HCC). HCV NS5A domain‐1 interacts with cellular proteins inducing pro‐oncogenic pathways. Thus, we explore genetic variations in NS5A domain‐1 and their association with HCC, by analyzing 188 NS5A sequences from HCV genotype‐1b infected DAA‐naïve cirrhotic patients: 34 with HCC and 154 without HCC. Specific NS5A mutations significantly correlate with HCC: S3T (8.8% vs. 1.3%, p = 0.01), T122M (8.8% vs. 0.0%, p < 0.001), M133I (20.6% vs. 3.9%, p < 0.001), and Q181E (11.8% vs. 0.6%, p < 0.001). By multivariable analysis, the presence of >1 of them independently correlates with HCC (OR (95%CI): 21.8 (5.7–82.3); p < 0.001). Focusing on HCC‐group, the presence of these mutations correlates with higher viremia (median (IQR): 5.7 (5.4–6.2) log IU/mL vs. 5.3 (4.4–5.6) log IU/mL, p = 0.02) and lower ALT (35 (30–71) vs. 83 (48–108) U/L, p = 0.004), suggesting a role in enhancing viral fitness without affecting necroinflammation. Notably, these mutations reside in NS5A regions known to interact with cellular proteins crucial for cell‐cycle regulation (p53, p85‐PIK3, and β‐ catenin), and introduce additional phosphorylation sites, a phenomenon known to ameliorate NS5A interaction with cellular proteins. Overall, these results provide a focus for further investigations on molecular bases of HCV‐mediated oncogenesis. The role of these NS5A domain‐1 mutations in triggering pro‐oncogenic stimuli that can persist also despite achievement of sustained virological response deserves further investigation

The Role of Attitudes Toward Medication and Treatment Adherence in the Clinical Response to LAIs: Findings From the STAR Network Depot Study

Background: Long-acting injectable (LAI) antipsychotics are efficacious in managing psychotic symptoms in people affected by severe mental disorders, such as schizophrenia and bipolar disorder. The present study aimed to investigate whether attitude toward treatment and treatment adherence represent predictors of symptoms changes over time. Methods: The STAR Network \u201cDepot Study\u201d was a naturalistic, multicenter, observational, prospective study that enrolled people initiating a LAI without restrictions on diagnosis, clinical severity or setting. Participants from 32 Italian centers were assessed at three time points: baseline, 6-month, and 12-month follow-up. Psychopathological symptoms, attitude toward medication and treatment adherence were measured using the Brief Psychiatric Rating Scale (BPRS), the Drug Attitude Inventory (DAI-10) and the Kemp's 7-point scale, respectively. Linear mixed-effects models were used to evaluate whether attitude toward medication and treatment adherence independently predicted symptoms changes over time. Analyses were conducted on the overall sample and then stratified according to the baseline severity (BPRS < 41 or BPRS 65 41). Results: We included 461 participants of which 276 were males. The majority of participants had received a primary diagnosis of a schizophrenia spectrum disorder (71.80%) and initiated a treatment with a second-generation LAI (69.63%). BPRS, DAI-10, and Kemp's scale scores improved over time. Six linear regressions\u2014conducted considering the outcome and predictors at baseline, 6-month, and 12-month follow-up independently\u2014showed that both DAI-10 and Kemp's scale negatively associated with BPRS scores at the three considered time points. Linear mixed-effects models conducted on the overall sample did not show any significant association between attitude toward medication or treatment adherence and changes in psychiatric symptoms over time. However, after stratification according to baseline severity, we found that both DAI-10 and Kemp's scale negatively predicted changes in BPRS scores at 12-month follow-up regardless of baseline severity. The association at 6-month follow-up was confirmed only in the group with moderate or severe symptoms at baseline. Conclusion: Our findings corroborate the importance of improving the quality of relationship between clinicians and patients. Shared decision making and thorough discussions about benefits and side effects may improve the outcome in patients with severe mental disorders

Global disparities in surgeons’ workloads, academic engagement and rest periods: the on-calL shIft fOr geNEral SurgeonS (LIONESS) study

: The workload of general surgeons is multifaceted, encompassing not only surgical procedures but also a myriad of other responsibilities. From April to May 2023, we conducted a CHERRIES-compliant internet-based survey analyzing clinical practice, academic engagement, and post-on-call rest. The questionnaire featured six sections with 35 questions. Statistical analysis used Chi-square tests, ANOVA, and logistic regression (SPSS® v. 28). The survey received a total of 1.046 responses (65.4%). Over 78.0% of responders came from Europe, 65.1% came from a general surgery unit; 92.8% of European and 87.5% of North American respondents were involved in research, compared to 71.7% in Africa. Europe led in publishing research studies (6.6 ± 8.6 yearly). Teaching involvement was high in North America (100%) and Africa (91.7%). Surgeons reported an average of 6.7 ± 4.9 on-call shifts per month, with European and North American surgeons experiencing 6.5 ± 4.9 and 7.8 ± 4.1 on-calls monthly, respectively. African surgeons had the highest on-call frequency (8.7 ± 6.1). Post-on-call, only 35.1% of respondents received a day off. Europeans were most likely (40%) to have a day off, while African surgeons were least likely (6.7%). On the adjusted multivariable analysis HDI (Human Development Index) (aOR 1.993) hospital capacity > 400 beds (aOR 2.423), working in a specialty surgery unit (aOR 2.087), and making the on-call in-house (aOR 5.446), significantly predicted the likelihood of having a day off after an on-call shift. Our study revealed critical insights into the disparities in workload, access to research, and professional opportunities for surgeons across different continents, underscored by the HDI

Clinical features and outcomes of elderly hospitalised patients with chronic obstructive pulmonary disease, heart failure or both

Background and objective: Chronic obstructive pulmonary disease (COPD) and heart failure (HF) mutually increase the risk of being present in the same patient, especially if older. Whether or not this coexistence may be associated with a worse prognosis is debated. Therefore, employing data derived from the REPOSI register, we evaluated the clinical features and outcomes in a population of elderly patients admitted to internal medicine wards and having COPD, HF or COPD + HF. Methods: We measured socio-demographic and anthropometric characteristics, severity and prevalence of comorbidities, clinical and laboratory features during hospitalization, mood disorders, functional independence, drug prescriptions and discharge destination. The primary study outcome was the risk of death. Results: We considered 2,343 elderly hospitalized patients (median age 81 years), of whom 1,154 (49%) had COPD, 813 (35%) HF, and 376 (16%) COPD + HF. Patients with COPD + HF had different characteristics than those with COPD or HF, such as a higher prevalence of previous hospitalizations, comorbidities (especially chronic kidney disease), higher respiratory rate at admission and number of prescribed drugs. Patients with COPD + HF (hazard ratio HR 1.74, 95% confidence intervals CI 1.16-2.61) and patients with dementia (HR 1.75, 95% CI 1.06-2.90) had a higher risk of death at one year. The Kaplan-Meier curves showed a higher mortality risk in the group of patients with COPD + HF for all causes (p = 0.010), respiratory causes (p = 0.006), cardiovascular causes (p = 0.046) and respiratory plus cardiovascular causes (p = 0.009). Conclusion: In this real-life cohort of hospitalized elderly patients, the coexistence of COPD and HF significantly worsened prognosis at one year. This finding may help to better define the care needs of this population

Histone H3.3 beyond cancer: Germline mutations in Histone 3 Family 3A and 3B cause a previously unidentified neurodegenerative disorder in 46 patients

Although somatic mutations in Histone 3.3 (H3.3) are well-studied drivers of oncogenesis, the role of germline mutations remains unreported. We analyze 46 patients bearing de novo germline mutations in histone 3 family 3A (H3F3A) or H3F3B with progressive neurologic dysfunction and congenital anomalies without malignancies. Molecular modeling of all 37 variants demonstrated clear disruptions in interactions with DNA, other histones, and histone chaperone proteins. Patient histone posttranslational modifications (PTMs) analysis revealed notably aberrant local PTM patterns distinct from the somatic lysine mutations that cause global PTM dysregulation. RNA sequencing on patient cells demonstrated up-regulated gene expression related to mitosis and cell division, and cellular assays confirmed an increased proliferative capacity. A zebrafish model showed craniofacial anomalies and a defect in Foxd3-derived glia. These data suggest that the mechanism of germline mutations are distinct from cancer-associated somatic histone mutations but may converge on control of cell proliferation

Observation of the B0 → ρ0ρ0 decay from an amplitude analysis of B0 → (π+π−)(π+π−) decays

Proton–proton collision data recorded in 2011 and 2012 by the LHCb experiment, corresponding to an integrated luminosity of 3.0 fb−1 , are analysed to search for the charmless B0→ρ0ρ0 decay. More than 600 B0→(π+π−)(π+π−) signal decays are selected and used to perform an amplitude analysis, under the assumption of no CP violation in the decay, from which the B0→ρ0ρ0 decay is observed for the first time with 7.1 standard deviations significance. The fraction of B0→ρ0ρ0 decays yielding a longitudinally polarised final state is measured to be fL=0.745−0.058+0.048(stat)±0.034(syst) . The B0→ρ0ρ0 branching fraction, using the B0→ϕK⁎(892)0 decay as reference, is also reported as B(B0→ρ0ρ0)=(0.94±0.17(stat)±0.09(syst)±0.06(BF))×10−6

Measurement of the (eta c)(1S) production cross-section in proton-proton collisions via the decay (eta c)(1S) -> p(p)over-bar

The production of the $\eta_c (1S)$ state in proton-proton collisions is probed via its decay to the $p \bar{p}$ final state with the LHCb detector, in the rapidity range $2.0 6.5$ GeV/c. The cross-section for prompt production of $\eta_c (1S)$ mesons relative to the prompt $J/\psi$ cross-section is measured, for the first time, to be $\sigma_{\eta_c (1S)}/\sigma_{J/\psi} = 1.74 \pm 0.29 \pm 0.28 \pm 0.18 _{B}$ at a centre-of-mass energy $\sqrt{s} = 7$ TeV using data corresponding to an integrated luminosity of 0.7 fb$^{-1}$, and $\sigma_{\eta_c (1S)}/\sigma_{J/\psi} = 1.60 \pm 0.29 \pm 0.25 \pm 0.17 _{B}$ at $\sqrt{s} = 8$ TeV using 2.0 fb$^{-1}$. The uncertainties quoted are, in order, statistical, systematic, and that on the ratio of branching fractions of the $\eta_c (1S)$ and $J/\psi$ decays to the $p \bar{p}$ final state. In addition, the inclusive branching fraction of $b$-hadron decays into $\eta_c (1S)$ mesons is measured, for the first time, to be $B ( b \rightarrow \eta_c X ) = (4.88 \pm 0.64 \pm 0.25 \pm 0.67 _{B}) \times 10^{-3}$, where the third uncertainty includes also the uncertainty on the $J/\psi$ inclusive branching fraction from $b$-hadron decays. The difference between the $J/\psi$ and $\eta_c (1S)$ meson masses is determined to be $114.7 \pm 1.5 \pm 0.1$ MeV/c$^2$.The production of the $\eta _c (1S)$ state in proton-proton collisions is probed via its decay to the $p\overline{p}$ final state with the LHCb detector, in the rapidity range $2.0 6.5 \mathrm{{\,GeV/}{ c}}$ . The cross-section for prompt production of $\eta _c (1S)$ mesons relative to the prompt ${{ J}}/{\psi }$ cross-section is measured, for the first time, to be $\sigma _{\eta _c (1S)}/\sigma _{{{{ J}}/{\psi }}} = 1.74\, \pm \,0.29\, \pm \, 0.28\, \pm \,0.18 _{{\mathcal{B}}}$ at a centre-of-mass energy ${\sqrt{s}} = 7 {~\mathrm{TeV}}$ using data corresponding to an integrated luminosity of 0.7 fb$^{-1}$ , and $\sigma _{\eta _c (1S)}/\sigma _{{{{ J}}/{\psi }}} = 1.60 \pm 0.29 \pm 0.25 \pm 0.17 _{{\mathcal{B}}}$ at ${\sqrt{s}} = 8 {~\mathrm{TeV}}$ using 2.0 fb$^{-1}$ . The uncertainties quoted are, in order, statistical, systematic, and that on the ratio of branching fractions of the $\eta _c (1S)$ and ${{ J}}/{\psi }$ decays to the $p\overline{p}$ final state. In addition, the inclusive branching fraction of ${b}$ -hadron decays into $\eta _c (1S)$ mesons is measured, for the first time, to be ${\mathcal{B}}( b {\rightarrow } \eta _c X ) = (4.88\, \pm \,0.64\, \pm \,0.29\, \pm \, 0.67 _{{\mathcal{B}}}) \times 10^{-3}$ , where the third uncertainty includes also the uncertainty on the ${{ J}}/{\psi }$ inclusive branching fraction from ${b}$ -hadron decays. The difference between the ${{ J}}/{\psi }$ and $\eta _c (1S)$ meson masses is determined to be $114.7 \pm 1.5 \pm 0.1 {\mathrm {\,MeV\!/}c^2}$ .The production of the $\eta_c (1S)$ state in proton-proton collisions is probed via its decay to the $p \bar{p}$ final state with the LHCb detector, in the rapidity range $2.0 6.5$ GeV/c. The cross-section for prompt production of $\eta_c (1S)$ mesons relative to the prompt $J/\psi$ cross-section is measured, for the first time, to be $\sigma_{\eta_c (1S)}/\sigma_{J/\psi} = 1.74 \pm 0.29 \pm 0.28 \pm 0.18 _{B}$ at a centre-of-mass energy $\sqrt{s} = 7$ TeV using data corresponding to an integrated luminosity of 0.7 fb$^{-1}$, and $\sigma_{\eta_c (1S)}/\sigma_{J/\psi} = 1.60 \pm 0.29 \pm 0.25 \pm 0.17 _{B}$ at $\sqrt{s} = 8$ TeV using 2.0 fb$^{-1}$. The uncertainties quoted are, in order, statistical, systematic, and that on the ratio of branching fractions of the $\eta_c (1S)$ and $J/\psi$ decays to the $p \bar{p}$ final state. In addition, the inclusive branching fraction of $b$-hadron decays into $\eta_c (1S)$ mesons is measured, for the first time, to be $B ( b \rightarrow \eta_c X ) = (4.88 \pm 0.64 \pm 0.29 \pm 0.67 _{B}) \times 10^{-3}$, where the third uncertainty includes also the uncertainty on the $J/\psi$ inclusive branching fraction from $b$-hadron decays. The difference between the $J/\psi$ and $\eta_c (1S)$ meson masses is determined to be $114.7 \pm 1.5 \pm 0.1$ MeV/c$^2$

Precise measurements of the properties of the B-1(5721)(0,+) and B-2*(5747)(0,+) states and observation of B-+,B-0 pi(-,+) mass structures

Invariant mass distributions of $B^+\pi^-$ and $B^0\pi^+$ combinations are investigated in order to study excited B mesons. The analysis is based on a data sample corresponding to $3.0 fb^{-1}$ of $pp$ collision data, recorded by the LHCb detector at centre-of-mass energies of 7 and 8 TeV. Precise measurements of the masses and widths of the $B_1(5721)^{0,+}$ and $B_2^*(5747)^{0,+}$ states are reported. Clear enhancements, particularly prominent at high pion transverse momentum, are seen over background in the mass range $5850$-$6000$ MeV in both $B^+\pi^-$ and $B^0\pi^+$ combinations. The structures are consistent with the presence of four excited B mesons, labelled $B_J(5840)^{0,+}$ and $B_J(5960)^{0,+}$, whose masses and widths are obtained under different hypotheses for their quantum numbers.Invariant mass distributions of B$^{+}$ π$^{−}$ and B$^{0}$ π$^{+}$ combinations are investigated in order to study excited B mesons. The analysis is based on a data sample corresponding to 3.0 fb$^{−1}$ of pp collision data, recorded by the LHCb detector at centre-of-mass energies of 7 and 8 TeV. Precise measurements of the masses and widths of the B$_{1}$(5721)$^{0,+}$ and B$^{2}$(5747)$^{0,+}$ states are reported. Clear enhancements, particularly prominent at high pion transverse momentum, are seen over background in the mass range 5850-6000 MeV in both B$^{+}$ π$^{−}$ and B$^{0}$ π$^{+}$ combinations. The structures are consistent with the presence of four excited B mesons, labelled B$_{J}$ (5840)$^{0,+}$ and B$_{J}$ (5960)$^{0,+}$, whose masses and widths are obtained under different hypotheses for their quantum numbers.Invariant mass distributions of B+pi- and B0pi+ combinations are investigated in order to study excited B mesons. The analysis is based on a data sample corresponding to 3.0 fb-1 of pp collision data, recorded by the LHCb detector at centre-of-mass energies of 7 and 8 TeV. Precise measurements of the masses and widths of the B_1(5721)^(0,+) and B_2*(5747)^(0,+) states are reported. Clear enhancements, particularly prominent at high pion transverse momentum, are seen over background in the mass range 5850--6000 MeV in both B+pi- and B0pi+ combinations. The structures are consistent with the presence of four excited B mesons, labelled B_J(5840)^(0,+) and B_J(5960)^(0,+), whose masses and widths are obtained under different hypotheses for their quantum numbers