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In the pursuit of efficient electrocatalysts for the hydrogen evolution reaction (HER), a series of manganese and cobalt heterodinuclear complexes have been synthesized and characterized that have a stark resemblance with the [NiFe]-hydrogenase active site structure. Irradiation of [Mn 2 (CO) 10 ] in the presence of 1.5 eq of [NaEPh] [E = S, Se, Te] followed by reaction with [Cp*CoCl] 2 led to the formation of half-sandwiched trichalcogenate-bridged heterodinuclear complexes [{Mn(CO) 3 }(μ-EPh) 3 (CoCp*)] [E = S ( C1 ); Se ( C2 ) and Te ( C3 )]. The reaction of these heterodinuclear trichalcogenate-bridged complexes with [LiBH 4 ·THF] yielded the corresponding dichalcogenate hydride-bridged heterobimetallic complexes [(CO) 3 Mn(μ-EPh) 2 (μ-H)(CoCp*)] [E = S ( C5 ); Se ( C6 ) and Te ( C7 )], which closely imitate the Ni-R intermediate of [NiFe]-hydrogenase. The resultant complexes ( C5-C7 ) displayed impressive H 2 production in DMF in the presence of HBF 4 , whereas the Te-based complex ( C7 ) showcased the highest TON (184 h -1 ) with an impressive Faradaic efficiency of >98%. The DFT investigations revealed a unique role of bridging chalcogens in catalysis, wherein, depending on the identity of the chalcogen (S, Se, or Te), protonation could occur via two distinct routes. This study represents a rare example of the full trio of S/Se/Te-based heterodinuclear complexes whose electrocatalytic HER activity has been probed under analogous conditions.

This article describes a case of a man in his early 40s who was diagnosed with pulmonary pleomorphic carcinoma (PPC). PPCs are rare and aggressive forms of lung cancer. Chemotherapy is of limited efficacy. We present a case that has seemingly recurred shortly after adjuvant chemotherapy and immunotherapy following an R0 resection for localised disease. Biopsy however was negative for recurrence. PPCs may bear actionable mutations and tyrosine kinase inhibitors may be used when appropriate. Immunotherapy with or without chemotherapy is emerging as the mainstay for metastatic disease despite a lack of evidence from randomised clinical trials., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

We aim to compare the outcomes in patients with atrial fibrillation detected after stroke (AFDAS) and their counterparts with known AF (KAF) presenting with large vessel occlusion (LVO) treated with mechanical thrombectomy (MT). This observational, prospective study included consecutive patients with acute LVO ischemic stroke of the anterior circulation with AFDAS, KAF and without AF. The primary study outcome was functional independence at 90 days after stroke. The secondary study outcomes were variation of the NIHSS score at 24 h, rate of successful reperfusion, death at 90 days and rate of immediate complications post-procedure. Overall, our cohort included 518 patients with acute ischemic stroke and LVO treated with MT, with 289 (56.8%) without a diagnosis of AF; 107 (21%) with AFDAS; 122 (22.2%) with KAF. There was no significant difference in terms of functional independence at 90 days after stroke between the three groups. Regarding the secondary study outcome, the rate of symptomatic intracranial haemorrhage (sICH) and/or parenchymal hematoma (PH) were significantly higher in the group of patients without AF (respectively, P = 0.030 and  < 0.010). Logistic regression analysis showed that the subtypes of AF were not statistically significantly associated with functional independence at 90 days after stroke and with the likelihood of any ICH. Our results suggest that the subtypes of AF are not associated with clinical and safety outcomes of MT in patients with acute stroke and LVO. Further studies are needed to confirm our findings., (© 2023. The Author(s).)

Background: Although previous studies investigated the main predictors of outcomes after endovascular thrombectomy (EVT) in patients aged 80 years and older, less is known about the impact of the procedural features on outcomes in elderly patients. The aim of this study was to investigate the influence of EVT technical procedures on the main 3-month outcomes in a population of patients aged 80 years and older., Methods: This observational, prospective, single-centre study included consecutive patients with acute LVO ischaemic stroke of the anterior circulation. The study outcomes were functional independence at 3 months after EVT (defined as a mRS score of 0-2), successful reperfusion (mTICI ≥ 2b), incidence of haeamorrhagic transformation, and 90-day all cause of mortality., Results: Our cohort included 497 patients with acute ischaemic stroke due to LVO treated with EVT. Among them, 105 (21.1%) patients were aged ≥ 80 years. In the elderly group, multivariable regression analysis showed that thromboaspiration technique vs stent-retriever was the single independent predictor of favourable post-procedural TICI score (OR = 7.65, 95%CI = 2.22-26.32, p = 0.001)., Conclusions: Our study suggests that EVT for LVO stroke in the elderly could be safe. The use of thromboaspiration was associated with positive reperfusion outcome in this population. Further studies in larger series are warranted to confirm the present results and to evaluate the safety and efficacy of EVT in the elderly and oldest adults., (© 2023. The Author(s).)

Background: Mechanical thrombectomy (MT) remains an effective treatment for patients with acute ischemic stroke receiving oral anticoagulation (OAC) and large vessel occlusion (LVO). However, to date, it remains unclear whether MT is safe in patients on treatment with OAC., Aims: In our study, we performed a propensity-matched analysis to investigate the safety and efficacy of MT in patients with acute ischemic stroke receiving anticoagulants. A propensity score method was used to target the causal inference of the observational study design., Methods: This observational, prospective, single-centre study included consecutive patients with acute LVO ischemic stroke of the anterior circulation. Demographic, neuro-imaging and clinical data were collected and compared according to the anticoagulation status at baseline, patients on OAC vs those not on OAC. The primary study outcomes were the occurrence of any intracerebral haemorrhage (ICH) and symptomatic ICH. The secondary study outcomes were functional independence at 90 days after stroke (defined as modified Rankin Scale (mRS) scores of 0 through 2), mortality at 3 months and successful reperfusion rate according to the modified treatment in cerebral infarction (mTICI) score., Results: Overall, our cohort included 573 patients with acute ischemic stroke and LVO treated with MT. After propensity score matching, 495 patients were matched (99 OAC group vs 396 no OAC group). There were no differences in terms of clinical characteristics between the two groups, except for the rate of intravenous thrombolysis less frequently given in the OAC group. There was no significant difference in terms of the rate of any ICH and symptomatic ICH between the two groups. With regards to the secondary study outcome, there was no significant difference in terms of the rate of successful recanalization post-procedure and functional independence at 3 months between the two groups. Patients in the OAC group showed a reduced mortality rate at 90 days compared to the patients with no previous use of anticoagulation (20.2% vs 21.2%, p = 0.031). Logistic regression analysis did not reveal a statistically significant influence of the anticoagulation status on the likelihood of any ICH (OR = 0.95, 95% CI = 0.46-1.97, p = 0.900) and symptomatic ICH (OR = 4.87, 95% CI = 0.64-37.1, p = 0.127). Our analysis showed also that pre-admission anticoagulant use was not associated with functional independence at 90 days after stroke (OR = 0.76, 95% CI = 0.39-1.48, p = 0.422) and rate of successful reperfusion (OR = 0.81, 95% CI = 0.38-1.72, p = 0.582)., Conclusion: According to our findings anticoagulation status at baseline did not raise any suggestion of safety and efficacy concerns when MT treatment is provided according to the standard guidelines. Confirmation of these results in larger controlled prospective cohorts is necessary., (© 2023. The Author(s).)

Background The 2022 Ukraine-Russian War has led to significant anxiety, anguish, and trauma among the people in Ukraine. The objective of this study was to analyze the Google Trend results of common cardiac symptoms in Ukraine, Russia, and worldwide in 2022 and compare that to 2021 with the hypothesis that common cardiac symptoms in the war-affected regions would be higher compared to the rest of the world. We hypothesize that the search trends of cardiac symptoms would increase in Ukraine given the turmoil caused by the Russian invasion. Methods We queried Google Trends for common cardiac symptoms such as chest pain, dizziness, palpitations, syncope, etc. Google Trends provides results as relative search volume (RSV) displayed in a geographical format. The RSV ranges from 0 to 100, with 0 indicating that the search term is not popular, and 100 indicating the search term's popularity is at its peak. Google Trends of cardiac symptoms in Russia, Ukraine, and worldwide was taken two weeks before and after February 24, 2022, compared with the same period in 2021. To assess the difference in Google Trends between the study periods in 2022 and 2021, the paired t-test was used. Results Overall, Google Trends for cardiac symptoms was lower in Ukraine and Russia than worldwide, in both 2021 and 2022 during the study period. There was a significant reduction in search for chest pain (14 vs. 30.5; p<0.049), pedal edema (40.0 vs 66.6; p approaching 0), and syncope (37.8 vs. 58.4; p<0.002) in Ukraine during the study periods in 2022 compared to 2021. There was a decrease in the searches for dyspnea (44.6 vs. 55.4; p<0.029) in Russia and for dizziness (87.6 vs. 92.8; p<0.005) worldwide. There was an increase in the searches for edema (93.6 vs. 91; p <0.002) and for fatigue (88.6 vs 79.5; p approaching 0) worldwide in study periods in 2022 as compared to 2021. There was no other significant difference between cardiac symptom search trends during the periods evaluated in Ukraine, Russia, and worldwide. Conclusion There appears to be a significant reduction in searching for a few cardiovascular symptoms, namely, chest pain, pedal edema, and syncope in Ukraine, which may be due to a focus on other immediate problems related to war and the availability of the Internet., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Dolkar et al.)

Background and purpose. Mechanical thrombectomy (MT) is the standard of care for eligible patients with a large vessel occlusion (LVO) acute ischemic stroke. Among patients undergoing MT there has been uncertainty regarding the role of intravenous thrombolysis (IVT) and previous trials have yielded conflicting results regarding clinical outcomes. We aim to investigate clinical, reperfusion outcomes and safety of MT with or without IVT for ischemic stroke due to anterior circulation LVO. Materials and Methods. This observational, prospective, single-centre study included consecutive patients with acute LVO ischemic stroke of the anterior circulation. The primary outcomes were the rate of in-hospital mortality, symptomatic intracranial haemorrhage and functional independence (mRS 0-2 at 90 days). Results. We enrolled a total of 577 consecutive patients: 161 (27.9%) were treated with MT alone while 416 (72.1%) underwent IVT and MT. Patients with MT who were treated with IVT had lower rates of in-hospital mortality ( p = 0.037), higher TICI reperfusion grades ( p = 0.007), similar rates of symptomatic intracranial haemorrhage ( p = 0.317) and a higher percentage of functional independence mRS (0-2) at 90 days ( p = 0.022). Bridging IVT with MT compared to MT alone was independently associated with a favorable post-intervention TICI score (>2b) (OR, 1.716; 95% CI, 1.076-2.735, p = 0.023). Conclusions. Our findings suggest that combined treatment with MT and IVT is safe and results in increased reperfusion rates as compared to MT alone.

Rationale: Ketamine has been used as a sedative analgesic in trauma setting, but data regarding its efficacy and safety is lacking in severe ARDS. This retrospective study aims to determine if Ketamine is safer as a sedative agent in mechanically ventilated patients. During the COVID pandemic, as there was a shortage of sedative agents, Ketamine was used., Objectives: The primary objective was to compare the safety of ketamine to other sedatives. The secondary objective was to compare the effect of ketamine to other sedatives regarding the need for vasopressor, incidence of delirium, infectious complications, acute kidney injury, hospital length of stay, and length of ventilator days., Methods: A retrospective, observational cohort study was conducted., Measurements and Main Results: One hundred and twenty-four patients (63 men and 61 women) were included. Thirty-four patients received ketamine, while 90 patients received other traditionally used sedatives such as propofol and midazolam. The patients' median age was 64 years in the ketamine group and 68 years in the non-ketamine group. Seventeen patients in the ketamine group (50%) and 65 patients (72%) in the non-ketamine group had mortality (p < 0.02). The hospital length of stay was 22.85 days (± 16.36) in the ketamine group and 15.62 days (± 14.63) in the non-ketamine group (p < 0.02). There was no statistically significant difference among the outcomes of the need for vasopressor, the incidence of delirium, infectious complications, and acute kidney injury., Conclusions: Ketamine as a sedative-analgesic agent in COVID-19 patients with severe acute respiratory distress syndrome demonstrated safety with reduced mortality. The ketamine group had a higher hospital length of stay, but a similar complication profile compared to the non-ketamine group. Further prospective randomized controlled trials are warranted to confirm these findings., Competing Interests: No potential conflict of interest was reported by the author(s)., (© 2021 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group on behalf of Greater Baltimore Medical Center.)

Background: Tuberculosis (TB) rates among Tibetan refugee children and adolescents attending boarding schools in India are extremely high. We undertook a comprehensive case finding and TB preventive treatment (TPT) program in 7 schools in the Zero TB Kids project. We aimed to measure the TB infection and disease burden and investigate the risk of TB disease in children and adults who did and did not receive TPT in the schools., Methods and Findings: A mobile team annually screened children and staff for TB at the 7 boarding schools in Himachal Pradesh, India, using symptom criteria, radiography, molecular diagnostics, and tuberculin skin tests. TB infection (TBI) was treated with short-course regimens of isoniazid and rifampin or rifampin. TB disease was treated according to Tibetan and Indian guidelines. Between April 2017 and December 2019, 6,582 schoolchildren (median age 14 [IQR 11-16] years) and 807 staff (median age 40 [IQR 33-48] years) were enrolled. Fifty-one percent of the students and 58% of the staff were females. Over 13,161 person-years of follow-up in schoolchildren (median follow-up 2.3 years) and 1,800 person-years of follow-up in staff (median follow-up 2.5 years), 69 TB episodes occurred in schoolchildren and 4 TB episodes occurred in staff, yielding annual incidence rates of 524/100,000 (95% CI 414-663/100,000) person-years and 256/100,000 (95% CI 96-683/100,000) person-years, respectively. Of 1,412 schoolchildren diagnosed with TBI, 1,192 received TPT. Schoolchildren who received TPT had 79% lower risk of TB disease (adjusted hazard ratio [aHR] 0.21; 95% CI 0.07-0.69; p = 0.010) compared to non-recipients, the primary study outcome. Protection was greater in recent contacts (aHR 0.07; 95% CI 0.01-0.42; p = 0.004), the secondary study outcome. The prevalence of recent contacts was 28% (1,843/6,582). Two different TPT regimens were used (3HR and 4R), and both were apparently effective. No staff receiving TPT developed TB. Overall, between 2017 and 2019, TB disease incidence decreased by 87%, from 837/100,000 (95% CI 604-1,129/100,000) person-years to 110/100,000 (95% CI 36-255/100,000) person-years (p < 0.001), and TBI prevalence decreased by 42% from 19% (95% CI 18%-20%) to 11% (95% CI 10%-12%) (p < 0.001). A limitation of our study is that TB incidence could be influenced by secular trends during the study period., Conclusions: In this study, following implementation of a school-wide TB screening and preventive treatment program, we observed a significant reduction in the burden of TB disease and TBI in children and adolescents. The benefit of TPT was particularly marked for recent TB contacts. This initiative may serve as a model for TB detection and prevention in children and adolescents in other communities affected by TB., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: Spouse of RC owns stock in Merck. RC has received consulting fees from Sanofi. Other authors have declared that no competing interests exist.

LL-37 is a naturally occurring 37-amino-acid peptide that is part of the innate immune system in human skin. Preclinical studies have showed that intra-tumoral injections of LL-37 stimulate the innate immune system by activation of plasmacytoid dendritic cells, which mediate tumor destruction. LL-37 intra-tumoral injections have been utilized in a phase 1 clinical trial for melanoma patients with cutaneous metastases. We report dermatologic toxicity in a 63-year-old woman with stage IIIC melanoma of the right calf and inguinal lymph nodes. She was previously treated with nivolumab and combination chemotherapy (cisplatin, vinblastine and dacarbazine) and subsequently treated with LL-37 injections upon progression of both prior regimens. She received a total of 8 weekly LL-37 injections, with interval clinical shrinkage of injected lesions. However, approximately 45 days after initiation of this therapy, she presented with multiple verrucous papules and a vesiculo-bullous lesion on the trunk and extremities. Clinically, most of these lesions were thought to be either squamous cell carcinoma or inflamed seborrheic keratosis. Histologically, 11 of the total 12 skin biopsies showed similar histopathologic features, with a prominent lichenoid inflammatory infiltrate admixed with eosinophils and an overlying atypical squamous epithelial proliferation with verrucous and keratoacanthoma-like features and varying degrees of keratinocytic atypia. Interestingly, a majority of the lesions did not show spongiosis (11/12). All lesions resolved within 2 months of cessation of LL-37 injection therapy. This case highlights adverse dermatological manifestations of LL-37 therapy, similar to the consequences of other novel therapies., (© 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Introduction: Image-guided core needle biopsy (CNB) is the standard for diagnostic breast biopsy. However, the upgrade rate to a higher order lesion defined as identification of malignancy on final pathology from surgical excision remains problematic., Materials and Methods: A retrospective chart review of all core needle biopsies from 2008 to 2012 was performed. We identified lesions demonstrating atypia without associated malignancy on core needle biopsy and recorded multiple factors to evaluate predictors of upgrade., Results: Of 151 independent core needle biopsies recorded, 26.5% were upgraded to a higher order lesion. Concurrent mammogram and ultrasound (US) were associated with higher sampling error than any individual imaging modality (P = .021). MRI had a trend toward lower rate of upgrade rate but did not reach statistical significance., Discussion: Although MRI had a lower rate of upgrade rate due to sampling error, this did not reach significance possibly because of our small sample size.

Context: A significant portion of colorectal biopsies are performed for evaluation of polyps or polypoid lesions. Accurately identifying these lesions will promote better patient care., Objective: Review of the pathology of major colon polyps and polypoid lesions and highlight the most diagnostically useful features and their molecular biology., Data Source: Review of recent literature., Conclusions: Polypoid lesions of the colon can be thought of to be under 3 broad categories: syndromic, mesenchymal, and epithelial.