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This article discusses the importance of balancing haemodynamic priorities in obstetrics, using a case study of a patient with severe preeclampsia and an uncorrected cardiac lesion. It emphasizes the need for a multidisciplinary team and specialized care in managing complex cases. The article also highlights the high rate of preventable maternal deaths in South Africa and the increased risk when conditions like preeclampsia and cardiac pathology coexist. It provides information on expected haemodynamic changes during pregnancy and various conditions, and discusses the importance of balancing preload, afterload, and heart rate in managing these conditions. The article also mentions the use of positive pressure ventilation and cardiac ultrasound in assessing cardiovascular function, and the limitations of available resources in managing certain complications. It concludes by emphasizing the importance of clinical judgment in determining priorities for cardiovascular intervention. [Extracted from the article]

Background: Complications during airway management can be life-threatening. This study aimed to identify anatomical and physiological risk factors for hypoxaemia during tracheal intubation in obstetric general anaesthesia (GA). Methods: A retrospective analysis was performed of data from an obstetric airway management registry (ObAMR) on tracheal intubation during GA in patients with a gestational age from 20 weeks, and until 7 days post-delivery. The primary outcome was arterial desaturation to < 90% during airway management. Logistic regression was performed to identify associations with hypoxaemia. Results: Data were collected for 1 095 general anaesthetics in the ObAMR. Overall, 143/1 091 of patients (13.1%, 95% CI 11.1-15.4%) experienced arterial oxygen desaturation. Univariate analysis showed that 91/142 (64.1%) of patients who desaturated were obese (body mass index [BMI] > 30 kg/m²), compared with 347/915 (37.9%) who were obese and did not experience desaturation (p < 0.001). A receiver operating characteristic curve was constructed post hoc, which showed a cut-off point for BMI of 29.76 kg/m², with a sensitivity of 0.66 and specificity of 0.62 for predicting hypoxaemia. Desaturation occurred in 17.0% of patients with hypertensive disorders of pregnancy, versus 11.0% without the condition (p = 0.005). Increasing Mallampati class was associated with an increased incidence of hypoxaemia. The incidence of hypoxaemia was 25.8% when intubation was performed by interns, compared with 8.0% for specialist anaesthetists (p = 0.005). In the multivariate analysis of factors associated with hypoxaemia, BMI (p < 0.001), room air saturation prior to preoxygenation (p = 0.008), and airway oedema (p = 0.027) were independently associated with hypoxaemia. Conclusion: In this study, hypoxaemia was used as a composite indicator of anatomical and physiological difficulty. Using this concept, a predictive tool could be developed to identify a difficult airway in obstetrics. Further research is required to show whether simple interventions such as face mask ventilation and the use of high-flow nasal oxygenation during intubation reduce the incidence of life-threatening hypoxaemia. [ABSTRACT FROM AUTHOR]

Background: The ease of administration and relative safety of spinal anaesthesia have made this the preferred technique for both elective and many emergency caesarean sections. Complications include incomplete sensory block, resulting in intraoperative breakthrough pain, which is commonly associated with a successful medicolegal claim. If documentation of the spinal anaesthesia technique was found to be inadequate during the course of the medicolegal proceedings, it is likely that the decision would be against the anaesthetist. The purpose of this study was to evaluate documentation by anaesthetists relating to the establishment of surgical anaesthesia utilising subarachnoid block. Methods: A retrospective folder analysis was conducted at Mowbray Maternity Hospital in Cape Town, South Africa. One hundred consecutive spinal anaesthesia charts, each completed by a different anaesthetist, either a registrar or specialist, were analysed. Starting from 31 December 2018 and proceeding retrospectively in time, charts were included until the desired sample size was achieved. Results: Of the 100 cases of spinal anaesthesia for caesarean section analysed, 68 were emergency and 32 were elective operations. Following a literature review, 12 variables were identified that required documentation so that adequate information would be available in the event of medicolegal action. Of these variables, 7 and 8 were recorded in 23% and 32% of the charts, respectively. Ninety per cent of the anaesthesia charts had inadequate documentation, defined as information on fewer than 10 of the specified variables. Conclusion: The quality of documentation of both the procedure and block level during spinal anaesthesia for caesarean section was inadequate. National guidelines should be drafted and standardised to improve the quality of these records, both for quality of care and medicolegal purposes. [ABSTRACT FROM AUTHOR]

Background: Bipolar disorder (BD) is associated with inhibitory control impairments, but traditional inhibitory control tasks may be confounded by reading ability, which is impaired in some BD patients. Eye-movement tasks assessing antisaccade performance avoid these limitations, but few studies have examined inhibitory control in BD using such tasks, particularly those modulating valence and attention., Method: We used eye-tracking in a sample of 44 euthymic BD patients and 30 controls to measure antisaccade performance on tasks employing emotional "hot" and nonemotional "cold" stimuli. Attentional modulation was examined by comparing performance across step and gap trials., Results: No significant between-group differences were found in antisaccade error rates or latencies for neutral or emotional stimuli. Both groups performed worse during neutral compared to emotional stimuli. BD patients showed a slight negativity bias, trending toward slower responses to negative compared to positive stimuli. Both groups performed more quickly and accurately during gap compared to step condition., Conclusions: These findings suggest that inhibitory control in BD, as measured by antisaccade performance, is influenced by valence and attentional modulation in a similar way to controls. The lack of significant group differences contrasts with previous research, necessitating further investigation into the mechanisms of antisaccade performance in BD., Competing Interests: Declaration of competing interest None, (Copyright © 2025 The Author(s). Published by Elsevier B.V. All rights reserved.)

To introduce the UChicago PBI Imaging score, a novel characterization of imaging features using head computed tomography (HCT) in patients with gunshot wounds to the head (GSWH) resulting in penetrating brain injury (PBI) and to quantify the association with mortality. We retrospectively collected and analyzed data from 230 patients with GSWH admitted to our Level 1 trauma center between May 1, 2018, and October 31, 2023. HCT images obtained on hospital arrival were evaluated for predefined imaging features by two blinded readers and arbitrated, when needed, by a third. The average contribution of each radiological feature to mortality at hospital discharge was assessed using a SuperLearner ensemble model trained on ∼77% of the cohort. Each feature's contribution was scaled to ensure the additive final score per patient ranged between 0 and 100. The HCT features predicting in-hospital mortality, ranked from highest to lowest importance, were transhemispheric projectile below the level of the third ventricle (18 [16.8, 19.9]), presence of blood in the lateral ventricles (ventricles casted) (18[16.8, 19.6]), brainstem involvement (14 [12.7, 15.1]), transhemispheric projectile above the level of the third ventricle (11 [9.7, 11.6]), presence of any amount of blood in the ambient cistern (9[8.2, 10]), presence of any amount of blood in the lateral ventricles (9 [7.9, 9.8]), cerebellar involvement (9 [7.9, 9.5]), any evidence of ventricular effacement (4 [3.4, 4.6]), midline shift (MLS) >0 mm (4 [3.4, 4.4]), perforating injury (3 [2.4, 3.2]), and presence of an intracerebral hematoma (ICH) >20 mm in the largest diameter (2 [1.4, 1.9]). The UChicago PBI Imaging score showed a strong performance, achieving an area under the curve (AUC) of 0.86 (95% CI: [0.77, 0.96]) on a test set of 56 patients who were not included in model training. This indicates better prediction accuracy compared to both the Rotterdam score (AUC 0.8, 95% CI: [0.68, 0.96]) and the Marshall score (AUC 0.66, 95% CI: [0.52, 0.81]). Our model performed particularly well for patients with a Glasgow Coma Scale (GCS) score between 5 and 9. In this range, our model's performance (AUC 0.86) remained stable, while the Rotterdam and Marshall Scores showed notably lower predictive accuracy, with AUCs of 0.61 and 0.52, respectively. A dedicated evaluation of GSWH HCT reveals an association between disease burden, as quantified by unique features not native to blunt TBI imaging models, and mortality. Specifically, transhemispheric injury below the level of the third ventricle along with blood-casting bilateral ventricles and brainstem involvement was highly associated with mortality. The model is optimized for intermediate GCS scores where greater prognostic uncertainty exists. This study parallels efforts to refine TBI classification, underscoring the necessity for precise imaging-based classification in PBI to identify imaging biomarkers and ultimately enhance prognostication and targeted treatment.

Introduction: Human papillomavirus (HPV) infection is a common sexually transmitted infection often associated with cancer development. This study aimed to estimate the prevalence of HPV in women receiving care at the AUNA healthcare network in Peru., Methods: We conducted an observational, descriptive, cross-sectional, retrospective study. A de-identified database of HPV-positive women who underwent the BD Onclarity™ HPV Assay between December 2018 and December 2021 at Auna clinics was analyzed. The database contained information regarding age, city, and HPV type. High-risk HPV types were analyzed individually (16, 18, 31, 45, 51, 52) and pooled [P1 (33, 58), P2 (56,59,66), and P3 (35,39,68)]. The study was approved by an independent research ethics committee in Peru., Results: Of 68,714 women included in the study, the HPV prevalence was 14.21% (N = 9765, 95%CI:13.95%-14.47%). The highest prevalence was detected in Piura (16.85%, 95%CI:15.40%-18.38%), where HPV-51, HPV-52, HPV-P1, HPV-P2, and HPV-P3 were most common compared to other Peruvian cities included in the study. In Arequipa, the prevalence was the lowest (13.58%, 95%CI:12.38%-14.85%), but the percentage prevalence of HPV-16 was the highest compared to other cities. The prevalence of multiple HPV infections was 2.88% (N = 1981, 95%CI:2.76%-3.01%), with most of them co-presenting two types of HPV (N = 1522). The most frequent co-occurrences were P2 and P3, P2 and 52, and P2 and 16. Among HPV-positive women, the mean age was 41.31 years (±9.48) and 25.29% were in the 31-35 years group. HPV-P2 was the most frequent in all age groups except in the 65-72 years group, where HPV-P3 was the most common., Conclusion: HPV prevalence was shown to be highest in Piura, with the most prevalent types being HPV-16, HPV-52, and HPV-P2 (HPV-56, -59, -66). HPV infection was found to be more frequent among women in the 31-35 years age group., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Objective: Preterm infants need enrichment of human milk (HM) for optimal growth. This study evaluated a novel, point-of-care human milk concentration (HMC) process for water removal from fresh HM samples by passive osmotic concentration., Study Design: Nineteen fresh HM samples were concentrated by incubation with the HMC devices for 3 h at 4 °C. Pre- and post-concentration HM samples were compared by HM properties for: pH, osmolality, macronutrients, enzyme activity, bioactive, and total cell viability., Results: Passive osmotic concentration reduced HM volume by an average of 16.3% ± 3.8% without a significant effect on pH or cell viability. Ten of the 41 HM components did not differ significantly (p > 0.05) between pre- and post-concentration samples. Twenty-three increased within the expected range by volume reduction. Six increased more than expected, two less than expected, and none decreased significantly., Conclusion: Passive osmotic concentration of fresh HM can concentrate HM components by selective removal of water. HM osmolality and pH remained within neonatal feeding parameters., (© 2024. The Author(s).)

The aim of this study was to evaluate transcriptional changes in the sole epidermis and dermis of bovine claws with septic sole ulceration of the lateral claw. Assessment included changes in transcripts orchestrating epidermal homeostatic processes, including epidermal proliferation, differentiation, inflammation, and cell signaling. Sole epidermis and dermis samples were removed from region 4 of lesion-bearing lateral and lesion-free medial claws of pelvic limbs in multiparous, lactating Holstein cows. Control sole epidermis and dermis samples were obtained from region 4 of lateral claws of normal pelvic limbs. Transcript abundances were evaluated by real-time PCR, and relative expression analyzed by ANOVA. Relative to normal lateral claws, sole epidermis and dermis in ulcer-bearing claws exhibited downregulation of genes associated with growth factors, growth factor receptors, activator protein 1 (AP-1) and proto-oncogene (CMYC) transcription components, cell cycle elements, lateral cell-to-cell signaling elements, and structures of early and late keratinocyte differentiation. These changes were accompanied by upregulation of proinflammatory transcripts interleukin 1 α (IL1A), interleukin1 β (IL1B), interleukin 1 receptor 1 (IL1R1), inducible nitric oxide synthase (NOS2), the inflammasome components NOD-like receptor protein 3 (NLRP3), pyrin and caspase recruitment domain (PYCARD), caspase-1 interleukin converting enzyme (CASPASE), the matrix metalloproteinases (MMP2 and MMP9), and the anti-inflammatory genes interleukin 1 receptor antagonist (IL1RN) and interleukin1 receptor 2 (IL1R2). Transcript abundance varied across epidermis and dermis from the ulcer center, margin, and epidermis and dermis adjacent to the lesion. Sole epidermis and dermis of lesion-free medial claws exhibited changes paralleling those in the adjacent lateral claws in an environment lacking inflammatory transcripts and downregulated IL1A, interleukin 18 (IL18), tumor necrosis factor α (TNFA), and NOS2. These data imply perturbations in signal pathways driving epidermal proliferation and differentiation are associated with, but not inevitably linked to epidermis and dermis inflammation. Further work is warranted to better define the role of crushing tissue injury, sepsis, metalloproteinase activity, and inflammation in sole ulceration., (The Authors. Published by Elsevier Inc. on behalf of the American Dairy Science Association®. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).)

Pododermatitis aseptica hemorrhagica circumscripta is associated with metalloproteinase 2 weakening of distal phalangeal suspensory structures and sinkage of the distal phalanx in the claw capsule. Pressure from the tuberculum flexorium on the sole epidermis and dermis produces hemorrhagic tissue injury and defective horn production appearing as yellow-red, softened claw horn in region 4 of the sole. A model of the MAPK/ERK signal cascade orchestrating epidermal-dermal homeostasis was employed to determine if sterile inflammatory responses are linked to disturbed signal transduction for epidermal homeostasis in sole epidermis and dermis. The objective was to assess shifts in target genes of inflammation, up- and downstream MAPK/ERK signal elements, and targeted genes supporting epidermal proliferation and differentiation. Sole epidermis and dermis were removed from lateral claws bearing lesions of PAHC, medial claws from the same limb and lateral claws from completely normal limbs of multiparous, lactating Holstein cows. The abundance levels of targeted transcripts were evaluated by real-time PCR. Lesion effects were assessed by ANOVA, and mean comparisons were performed with t-tests to assess variations between mean expression in ulcer-bearing or medial claw dermis and epidermis and completely normal lateral claw dermis and epidermis or between ulcer-bearing dermis and epidermis and medial claw dermis and epidermis. The lesions were sterile and showed losses across multiple growth factors, their receptors, several downstream AP1 transcription components, CMYC, multiple cell-cycle and terminal differentiation elements conducted by MAPK/ERK signals and β 4, α 6, and collagen 17A hemidesmosome components. These losses coincided with increased cytokeratin 6, β 1 integrin, proinflammatory metalloproteinases 2 and 9, IL1B and physiologic inhibitors of IL1B, the decoy receptor, and receptor antagonist. Medial claw epidermis and dermis from limbs with lateral claws bearing PAHC showed reductions in upstream MAPK/ERK signal elements and downstream targets that paralleled those in hemorrhagic lesions. Inhibitors of IL1B increased in the absence of real increases in inflammatory targets in the medial claw dermis and epidermis. Losses across multiple signal path elements and downstream targets were associated with negative effects on targeted transcripts supporting claw horn production and wound repair across lesion-bearing lateral claws and lesion-free medial claw dermis and epidermis. It was unclear if the sterile inflammation was causative or a consequence of these perturbations., (The Authors. Published by Elsevier Inc. on behalf of the American Dairy Science Association®. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).)

Hypothermia during obstetric spinal anaesthesia is a common and important problem, yet temperature monitoring is often not performed due to the lack of a suitable, cost-effective monitor. This study aimed to compare a noninvasive core temperature monitor with two readily available peripheral temperature monitors during obstetric spinal anaesthesia. We undertook a prospective observational study including elective and emergency caesarean deliveries, to determine the agreement between affordable reusable surface temperature monitors (Welch Allyn SureTemp® Plus oral thermometer and the Braun 3-in-1 No Touch infrared thermometer) and the Dräger T-core© (using dual-sensor heat flux technology), in detecting thermoregulatory changes during obstetric spinal anaesthesia. Predetermined clinically relevant limits of agreement (LOA) were set at ± 0.5 °C. We included 166 patients in our analysis. Hypothermia (heat flux temperature < 36 °C) occurred in 67% (95% CI 49 to 78%). There was poor agreement between devices. In the Bland-Altman analysis, LOA for the heat flux monitor vs. oral thermometer were 1.8 °C (CI 1.7 to 2.0 °C; bias 0.5 °C), for heat flux monitor vs. infrared thermometer LOA were 2.3 °C (CI 2.1 to 2.4 °C; bias 0.4 °C) and for infrared vs. oral thermometer, LOA were 2.0 °C (CI 1.9 to 2.2 °C; bias 0.1 °C). Error grid analysis highlighted a large amount of clinical disagreement between methods. While monitoring of core temperature during obstetric spinal anaesthesia is clinically important, agreement between monitors was below clinically acceptable limits. Future research with gold-standard temperature monitors and exploration of causes of sensor divergence is needed., (© 2024. The Author(s).)

Introduction: A significant proportion of individuals suffering from post COVID-19 condition (PCC, also known as long COVID) can present with persistent, disabling fatigue similar to myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and post-viral fatigue syndromes. There remains no clear pharmacological therapy for patients with this subtype of PCC, which can be referred to as post-COVID fatigue syndrome (PCFS). A low dose of the opioid antagonist naltrexone (ie, low-dose naltrexone (LDN)) has emerged as an off-label treatment for treating fatigue and other symptoms in PCC. However, only small, non-controlled studies have assessed LDN in PCC, so randomised trials are urgently required., Methods and Analysis: A prospective, randomised, double-blind, parallel arm, placebo-controlled phase II trial will be performed to assess the efficacy of LDN for improving fatigue in PCFS. The trial will be decentralised and open to eligible individuals throughout the Canadian province of British Columbia (BC). Participants will be recruited through the province-wide Post-COVID-19 Interdisciplinary Clinical Care Network (PC-ICCN) and research volunteer platform (REACH BC). Eligible participants will be 19-69 years old, have had a confirmed or physician-suspected SARS-CoV-2 infection at least 3 months prior and meet clinical criteria for PCFS adapted from the Institute of Medicine ME/CFS criteria. Individuals who are taking opioid medications, have a history of ME/CFS prior to COVID-19 or history of significant liver disease will be excluded. Participants will be randomised to an LDN intervention arm (n=80) or placebo arm (n=80). Participants in each arm will be prescribed identical capsules starting at 1 mg daily and follow a prespecified schedule for up-titration to 4.5 mg daily or the maximum tolerated dose. The trial will be conducted over 16 weeks, with assessments at baseline, 6, 12 and 16 weeks. The primary outcome will be fatigue severity at 16 weeks evaluated by the Fatigue Severity Scale. Secondary outcomes will include pain Visual Analogue Scale score, overall symptom severity as measured by the Patient Phenotyping Questionnaire Short Form, 7-day step count and health-related quality of life measured by the EuroQol 5-Dimension questionnaire., Ethics and Dissemination: The trial has been authorised by Health Canada and approved by The University of British Columbia/Children's and Women's Health Centre of British Columbia Research Ethics Board. On completion, findings will be disseminated to patients, caregivers and clinicians through engagement activities within existing PCC and ME/CFS networks. Results will be published in academic journals and presented at conferences., Trial Registration Number: NCT05430152., Competing Interests: Competing interests: HN is a member of the Canadian Guidelines for Post-COVID-19 Condition Guideline Team for Pharmacologic and Nonpharmacologic Clinical Interventions. The other authors have no competing interests to declare., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

BACKGROUNDBroadly neutralizing monoclonal antibodies (bNAbs) represent a promising strategy for HIV-1 immunoprophylaxis and treatment. 10E8VLS and VRC07-523LS are bNAbs that target the highly conserved membrane-proximal external region (MPER) and the CD4-binding site of the HIV-1 viral envelope glycoprotein, respectively.METHODSIn this phase 1, open-label trial, we evaluated the safety and pharmacokinetics of 5 mg/kg 10E8VLS administered alone, or concurrently with 5 mg/kg VRC07-523LS, via s.c. injection to healthy non-HIV-infected individuals.RESULTSEight participants received either 10E8VLS alone (n = 6) or 10E8VLS and VRC07-523LS in combination (n = 2). Five (n = 5 of 8, 62.5%) participants who received 10E8VLS experienced moderate local reactogenicity, and 1 participant (n = 1/8, 12.5%) experienced severe local reactogenicity. Further trial enrollment was stopped, and no participant received repeat dosing. All local reactogenicity resolved without sequelae. 10E8VLS retained its neutralizing capacity, and no functional anti-drug antibodies were detected; however, a serum t1/2 of 8.1 days was shorter than expected. Therefore, the trial was voluntarily stopped per sponsor decision (Vaccine Research Center, National Institute of Allergy and Infectious Diseases [NIAID], NIH). Mechanistic studies performed to investigate the underlying reason for the reactogenicity suggest that multiple mechanisms may have contributed, including antibody aggregation and upregulation of local inflammatory markers.CONCLUSION10E8VLS resulted in unexpected reactogenicity and a shorter t1/2 in comparison with previously tested bNAbs. These studies may facilitate identification of nonreactogenic second-generation MPER-targeting bNAbs, which could be an effective strategy for HIV-1 immunoprophylaxis and treatment.TRIAL REGISTRATIONClinicaltrials.gov, accession no. NCT03565315.FUNDINGDivision of Intramural Research, National Institute of Allergy and Infectious Diseases, NIH.

Traumatic brain injury (TBI) is a global health challenge; however, penetrating brain injury (PBI) remains under-represented in evidence-based knowledge and research efforts. This study utilized data from the Trauma Quality Improvement Program (TQIP) of the National Trauma Data Bank (NTDB) to investigate outcomes of PBI as compared with clinical-severity-matched non-penetrating or blunt TBI. A total of 1765 patients with PBI were 1:1 propensity score-matched for clinical severity with blunt TBI patients. The intent of PBI was self-inflicted in 34.1% of the cases, and the mechanism was firearm-inflicted in 89.1%. Mortality was found to be significantly more common in PBI than in the severity- matched TBI cohort (33.9% vs. 14.3 %, p  < 0.001) as was unfavorable outcome. Mortality was mediated by withdrawal of life-sustaining therapies (WOLST) 30% of the time, and WOLST occurred earlier (median 3 days vs. 6 days, p  < 0.001) in PBI. Increased rate of mortality was observed with a Glasgow Coma Scale (GCS) of <11 in PBI as compared with <7 in blunt TBI. In conclusion, PBI patients exhibited higher mortality rates and unfavorable outcomes; one third of excess mortality was mediated by WOLST. The study also brings into question the applicability of the conventional TBI classification, based on GCS, in PBI. We emphasize the need to address the observed disparities and better understand the distinctive characteristics and mechanisms underlying PBI outcomes to improve patient care and reduce mortality., Competing Interests: No competing financial interests exist., (© Ali Mansour et al., 2024; Published by Mary Ann Liebert, Inc.)

Like many polar animals, emperor penguin populations are challenging to monitor because of the species' life history and remoteness. Consequently, it has been difficult to establish its global status, a subject important to resolve as polar environments change. To advance our understanding of emperor penguins, we combined remote sensing, validation surveys and using Bayesian modelling, we estimated a comprehensive population trajectory over a recent 10-year period, encompassing the entirety of the species' range. Reported as indices of abundance, our study indicates with 81% probability that there were fewer adult emperor penguins in 2018 than in 2009, with a posterior median decrease of 9.6% (95% credible interval (CI) -26.4% to +9.4%). The global population trend was -1.3% per year over this period (95% CI = -3.3% to +1.0%) and declines probably occurred in four of eight fast ice regions, irrespective of habitat conditions. Thus far, explanations have yet to be identified regarding trends, especially as we observed an apparent population uptick toward the end of time series. Our work potentially establishes a framework for monitoring other Antarctic coastal species detectable by satellite, while promoting a need for research to better understand factors driving biotic changes in the Southern Ocean ecosystem.

Given that ketogenic diets (KDs) are extremely high in dietary fat, we compared different fats in KDs to determine which was the best for cancer prevention. Specifically, we compared a Western and a 15% carbohydrate diet to seven different KDs, containing either Western fats or fats enriched in medium chain fatty acids (MCTs), milk fat (MF), palm oil (PO), olive oil (OO), corn oil (CO) or fish oil (FO) for their ability to reduce nicotine-derived nitrosamine ketone (NNK)-induced lung cancer in mice. While all the KDs tested were more effective at reducing lung nodules than the Western or 15% carbohydrate diet, the FO-KD was most effective at reducing lung nodules. Correlating with this, mice on the FO-KD had low blood glucose and the highest β-hydroxybutyrate level, lowest liver fatty acid synthase/carnitine palmitoyl-1a ratio and a dramatic increase in fecal Akkermansia. We found no liver damage induced by the FO-KD, while the ratio of total cholesterol/HDL was unchanged on the different diets. We conclude that a FO-KD is superior to KDs enriched in other fats in reducing NNK-induced lung cancer, perhaps by being the most effective at skewing whole-body metabolism from a dependence on glucose to fats as an energy source., (© 2024. The Author(s).)

Background and Objectives: To compare the outcomes of early vs no-neurosurgical intervention in civilians with penetrating brain injury (PBI)., Methods: We collected data from the National Trauma Data Bank for PBI between 2017 and 2019. A total of 10 607 cases were identified; 1276 cases met the following criteria: age 16-60 years, an intensive care unit (ICU) length of stay (LOS) of >2 days, a Glasgow Coma Scale of 3-12, and at least one reactive pupil on presentation. Patients with withdrawal of life-sustaining treatments within 72 hours were excluded, leaving 1231 patients for analysis. Neurosurgical intervention was defined as an open-approach cranial procedure involving release, drainage, or extirpation of brain matter performed within 24 hours. Outcomes of interest were mortality, withdrawal of life-sustaining treatments, ICU LOS, and dispositional outcome., Results: The target population was 1231 patients (84.4% male; median [IQR] age, 29 [18] years); 267 (21.7%) died, and 364 (29.6%) had a neurosurgical intervention within the first 24 hours. 1:1 matching yielded 704 patients (352 in each arm). In the matched cohort (mortality 22.6%), 64 patients who received surgery (18.2%) died compared with 95 (27%) in the nonsurgical group. Survival was more likely in the surgical group (odds ratio [OR] 1.66, CI 1.16-2.38, P < .01; number needed to treat 11). Dispositional outcome was not different. Overlap propensity score-weighted analysis (1231 patients) resulted in higher odds of survival in the surgical group (OR 1.8, CI 1.16-2.80, P < .01). The E-value for the OR calculated from the matched data set was 2.83. Early neurosurgical intervention was associated with longer ICU LOS (median 12 days [7.0, 19.0 IQR] vs 8 days [4.0, 15.0 IQR], P < .05)., Conclusion: Management including early neurosurgical intervention is associated with decreased mortality and increased ICU LOS in matched cohorts of PBI., (Copyright © Congress of Neurological Surgeons 2023. All rights reserved.)

Background: The heart relies heavily on external fatty acid (FA) for energy production. VEGFB (vascular endothelial growth factor B) has been shown to promote endothelial FA uptake by upregulating FA transporters. However, its impact on LPL (lipoprotein lipase)-mediated lipolysis of lipoproteins, a major source of FA for cardiac use, is unknown., Methods: VEGFB transgenic (Tg) rats were generated by using the α-myosin heavy chain promoter to drive cardiomyocyte-specific overexpression. To measure coronary LPL activity, Langendorff hearts were perfused with heparin. In vivo positron emission tomography imaging with [ 18 F]-triglyceride-fluoro-6-thia-heptadecanoic acid and [ 11 C]-palmitate was used to determine cardiac FA uptake. Mitochondrial FA oxidation was evaluated by high-resolution respirometry. Streptozotocin was used to induce diabetes, and cardiac function was monitored using echocardiography., Results: In Tg hearts, the vectorial transfer of LPL to the vascular lumen is obstructed, resulting in LPL buildup within cardiomyocytes, an effect likely due to coronary vascular development with its associated augmentation of insulin action. With insulin insufficiency following fasting, VEGFB acted unimpeded to facilitate LPL movement and increase its activity at the coronary lumen. In vivo PET imaging following fasting confirmed that VEGFB induced a greater FA uptake to the heart from circulating lipoproteins as compared with plasma-free FAs. As this was associated with augmented mitochondrial oxidation, lipid accumulation in the heart was prevented. We further examined whether this property of VEGFB on cardiac metabolism could be useful following diabetes and its associated cardiac dysfunction, with attendant loss of metabolic flexibility. In Tg hearts, diabetes inhibited myocyte VEGFB gene expression and protein secretion together with its downstream receptor signaling, effects that could explain its lack of cardioprotection., Conclusions: Our study highlights the novel role of VEGFB in LPL-derived FA supply and utilization. In diabetes, loss of VEGFB action may contribute toward metabolic inflexibility, lipotoxicity, and development of diabetic cardiomyopathy., Competing Interests: Disclosures None.

Competing Interests: The authors declare that they have no conflicts of interest.

Background: Current guidelines recommend prophylactic vasopressor administration during spinal anesthesia for cesarean delivery to maintain intraoperative blood pressure above 90% of the baseline value. We sought to determine the optimum baseline mean arterial pressure (MAP) reading to guide the management of spinal hypotension., Methods: We performed a secondary analysis of data collected from normotensive patients presenting for elective cesarean delivery in a tertiary care institution from October 2018 to August 2020. We compared the magnitude of hypotension in patients who reported nausea versus those who did not, using a case-control design. Baseline MAPs at last office visit, morning of surgery, or operating room (pre-spinal) were determined. We calculated the duration and degree of hypotension using the area under the curve (AUC) when the MAP of the respective patient was below 90% of each baseline., Results: The patients who experienced nausea (n=45) had longer and more profound periods of hypotension than those who did not develop nausea (n=240). A comparison of AUC using MAP baseline at the last office visit or on the morning of surgery showed a statistically significant between-group difference, P=0.02, and P=0.005, respectively, and no significant between-group difference when 90% of the MAP baseline in the operating room was used., Conclusions: Patients had the highest preoperative MAP in the operating room and the AUC was similar for those with and without nausea when the pre-spinal MAP baseline was used. Therefore, maintaining higher intraoperative blood pressure using individual pre-spinal MAP as baseline should reduce intraoperative maternal nausea., Competing Interests: Vesela P. Kovacheva reports patent #WO2021119593A1 for control of a therapeutic delivery system, which is assigned to the Mass General Brigham., (Copyright © 2023, Kovacheva et al.)

Introduction and Problem Statement: The Neurocritical Care (NCC) Society Resident and Fellow Task Force's NEURON study concluded that learners had significant concerns regarding the need for educational improvement in NCC. To address these shortcomings, we identified the lack of an educational curriculum for trainees in NCC and developed a Twitter-based educational curriculum for trainees to improve knowledge in NCC., Objectives: The objectives of this study were to describe the pathophysiology, delineate a systematic diagnostic approach, and apply evidence-based strategies in the management of diseases in NCC., Methods and Curriculum Description: Ten trainees developed a Tweetorial (educational content available on Twitter)-based curriculum, with individual review by at least 2 NCC faculty. Learners were recruited through Twitter and randomized to 1 of 2 groups in a wait-list control prospective study. Group 1 completed the curriculum in the first 6 months of the 2021-2022 academic year, and group 2 completed the curriculum in the second half. Tweetorials were posted weekly on a private Twitter account only available to the active learner group. Learners were assessed by a multiple-choice format test (written by the trainees and reviewed by faculty) at 3 time points: before the first Tweetorial was released (preeducational curriculum assessment), after group 1 completed all tutorials and before group 2 started the curriculum (assessment 1), and after both groups finished (assessment 2). The primary outcome was the mean score on the second and third assessments., Results and Assessment Data: One hundred forty-six learners were assigned to group 1 or 2 using stratified block randomization including 99 (68%) Neurology residents, 81 (55%) US-based. Each group was composed of 73 participants. A total of 20 Tweetorials were published on a private Twitter account (@NeurocriticalE). Completed assessments were obtained from 100, 32, and 18 learners for the pre-educational curriculum assessment, assessment 1, and assessment 2, respectively. Group 1 and group 2 performed similarly in the pre-educational curriculum assessment. A potential for knowledge improvement was observed in group 1 at assessments 1 and 2 when compared with the learner group 2. Group 1 had more impressions, engagements, likes, URL clicks, and media views., Discussion and Lessons Learned: Although there was some learner attrition, our study demonstrates that social media can effectively deliver educational content and engage a diverse group of trainees around the globe., Competing Interests: The authors report no disclosures relevant to the manuscript. Go to Neurology.org/NE for full disclosures., (© 2023 American Academy of Neurology.)

Prenatal Care Coordination (PNCC) is a Medicaid fee-for-service that provides reimbursement for supportive services to mothers and infants at high risk of adverse outcomes. Services include health education, care coordination, referral to needed services, and social support. Currently, the implementation of PNCC programs is highly variable. We aimed to identify and describe the contextual factors that influence implementation of PNCC. Using a qualitative descriptive approach and theoretical reflexive thematic analysis techniques, we conducted observation and semistructured interviews with all PNCC staff at two PNCC sites in Wisconsin, representing diversity in region and patient population. We thematically analyzed interview data to examine how contextual factors influenced program implementation with the Consolidated Framework for Implementation Research as a sensitizing model. Observational field notes were used to triangulate interview data. Overall, participants endorsed the goals of PNCC and believed in its potential. However, participants asserted that the external policy context limited their impact. In response, they developed local strategies to combat barriers and work toward better outcomes. Our findings support the need to study the implementation of perinatal public and community health interventions and consider "health in all policies." Several changes would maximize PNCC's impact on maternal health: increased collaboration among policy stakeholders would reduce barriers; increased reimbursement would enable PNCC providers to better meet the complex needs of clients; and expansions in postpartum Medicaid coverage would extend the PNCC eligibility period. Nurses who provide PNCC have unique insights that should be leveraged to inform maternal-child health policy.

Objectives: The COVID-19 pandemic has heightened awareness of health disparities associated with socioeconomic status (SES) across the United States. We examined whether household income is associated with functional outcomes after stroke and COVID-19., Materials and Methods: This was a multi-institutional, retrospective cohort study of consecutively hospitalized patients with SARS-CoV-2 and radiographically confirmed stroke presenting from March through November 2020 to any of five comprehensive stroke centers in metropolitan Chicago, Illinois, USA. Zip-code-derived household income was dichotomized at the Chicago median. Logistic regression was used to examine the relationship between household income and good functional outcome (modified Rankin Scale 0-3 at discharge, after ischemic stroke)., Results: Across five hospitals, 159 patients were included. Black patients comprised 48.1%, White patients 38.6%, and Hispanic patients 27.7%. Median household income was $46,938 [IQR: $32,460-63,219]. Ischemic stroke occurred in 115 (72.3%) patients (median NIHSS 7, IQR: 0.5-18.5) and hemorrhagic stroke in 37 (23.7%). When controlling for age, sex, severe COVID-19, and NIHSS, patients with ischemic stroke and household income above the Chicago median were more likely to have a good functional outcome at discharge (OR 7.53, 95% CI 1.61 - 45.73; P=0.016). Race/ethnicity were not included in final adjusted models given collinearity with income., Conclusions: In this multi-institutional study of hospitalized patients with stroke, those residing in higher SES zip codes were more likely to have better functional outcomes, despite controlling for stroke severity and COVID-19 severity. This suggests that area-based SES factors may play a role in outcomes from stroke and COVID-19., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

South Africa is classified as a low- and middle-income country, with a complex mixture of resource-rich and resource-limited settings. In the major referral hospitals, the necessary skill level exists for the management of complex challenges. However, this contrasts with the frequently-inadequate skill levels of anaesthesia practitioners in resource-limited environments. In Japan, obstetricians administer anaesthesia for 40% of caesarean deliveries and 80% of labour analgesia. Centralisation of delivery facilities is now occurring and it is expected that obstetric anaesthesiologists will be available 24 h a day in centralised facilities in the future. In China, improvements in women's reproductive, maternal, neonatal, child, and adolescent health are critical government policies. Obstetric anaesthesia, especially labour analgesia, has received unprecedented attention. Chinese obstetric anaesthesiologists are passionate about clinical research, focusing on efficacy, safety, and topical issues. The Latin-American region has different landscapes, people, languages, and cultures, and is one of the world's regions with the most inequality. There are large gaps in research, knowledge, and health services, and the World Federation of Societies of Anaesthesiologists is committed to working with governmental and non-governmental organisations to improve patient care and access to safe anaesthesia. Anaesthesia workforce challenges, exacerbated by coronavirus disease 2019, beset North American healthcare. Pre-existing struggles by governments and decision-makers to improve health care access remain, partly due to unfamiliarity with the role of the anaesthesiologist. In addition to weaknesses in work environments and dated standards of work culture, the work-life balance demanded by new generations of anaesthesiologists must be acknowledged., Competing Interests: Declaration of interests The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Severe traumatic brain injury (sTBI) is a condition of increasing epidemiologic concern worldwide. Outcomes are worse as observed in low- and middle-income countries (LMICs) versus high-income countries. Global targets are in place to address the surgical burden of disease. At the same time, most of the published literature and evidence on the clinical approach to sTBI comes from wealthy areas with an abundance of resources. The available paradigms, including the Brain Trauma Foundation guidelines, the Seattle International Severe Traumatic Brain Injury Consensus Conference, Consensus Revised Imaging and Clinical Examination, and multimodality approaches, may fit differently depending on local resources, expertise, and sociocultural factors. A first step toward addressing heterogeneity in practice is to consider comparative effectiveness approaches that can capture actual practice patterns and record short-term and long-term outcomes of interest. Decompressive craniectomy (DC) decreases intracranial pressure burden and can be lifesaving. Nevertheless, completed randomized controlled trials took place within high-income settings, leaving important questions unanswered and making extrapolations to LMICs questionable. The concept of preemptive DC specifically to address limited neuromonitoring resources may warrant further study to establish a benefit/risk profile for the procedure and its role within local protocols of care., (© 2023. The Author(s).)

We present criteria for establishing a triangulation of a manifold. Given a manifold M , a simplicial complex  A , and a map H from the underlying space of A to  M , our criteria are presented in local coordinate charts for  M , and ensure that H is a homeomorphism. These criteria do not require a differentiable structure, or even an explicit metric on  M . No Delaunay property of A is assumed. The result provides a triangulation guarantee for algorithms that construct a simplicial complex by working in local coordinate patches. Because the criteria are easily verified in such a setting, they are expected to be of general use., (© The Author(s) 2022.)

Background and Objective: Cerebral venous thrombosis (CVT) is a rare cause of stroke carrying a nearly 4% risk of recurrence after 1 year. There are limited data on predictors of recurrent venous thrombosis in patients with CVT. In this study, we aim to identify those predictors., Methods: This is a secondary analysis of the ACTION-CVT study which is a multicenter international study of consecutive patients hospitalized with a diagnosis of CVT over a 6-year period. Patients with cancer-associated CVT, CVT during pregnancy, or CVT in the setting of known antiphospholipid antibody syndrome were excluded per the ACTION-CVT protocol. The study outcome was recurrent venous thrombosis defined as recurrent venous thromboembolism (VTE) or de novo CVT. We compared characteristics between patients with vs without recurrent venous thrombosis during follow-up and performed adjusted Cox regression analyses to determine important predictors of recurrent venous thrombosis., Results: Nine hundred forty-seven patients were included with a mean age of 45.2 years, 63.9% were women, and 83.6% had at least 3 months of follow-up. During a median follow-up of 308 (interquartile range 120-700) days, there were 5.05 recurrent venous thromboses (37 VTE and 24 de novo CVT) per 100 patient-years. Predictors of recurrent venous thrombosis were Black race (adjusted hazard ratio [aHR] 2.13, 95% CI 1.14-3.98, p = 0.018), history of VTE (aHR 3.40, 95% CI 1.80-6.42, p < 0.001), and the presence of one or more positive antiphospholipid antibodies (aHR 3.85, 95% CI 1.97-7.50, p < 0.001). Sensitivity analyses including events only occurring on oral anticoagulation yielded similar findings., Discussion: Black race, history of VTE, and the presence of one or more antiphospholipid antibodies are associated with recurrent venous thrombosis among patients with CVT. Future studies are needed to validate our findings to better understand mechanisms and treatment strategies in patients with CVT., (© 2022 American Academy of Neurology.)

Background: Significant challenges exist in downstream purification of bispecific antibodies (BsAbs) due to the complexity of BsAb architecture. A unique panel of mispaired species can result in a higher level of product-related impurities. In addition to process-related impurities such as host cell proteins (HCPs) and residual DNA (resDNA), these product-related impurities must be separated from the targeted BsAb product to achieve high purity. Therefore, development of an efficient and robust chromatography purification process is essential to ensure the safety, quality, purity and efficacy of BsAb products that consequently meet regulatory requirements for clinical trials and commercialization., Methods: We have developed a robust downstream BsAb process consisting of a mixed-mode ceramic hydroxyapatite (CHT) chromatography step, which offers unique separation capabilities tailored to BsAbs, and assessed impurity clearance., Results: We demonstrate that the CHT chromatography column provides additional clearance of low molecular weight (LMW) and high molecular weight (HMW) species that cannot be separated by other chromatography columns such as ion exchange for a particular BsAb, resulting in ≥98% CE-SDS (non-reduced) purity. Moreover, through Polysorbate-80 (PS-80) spiking and LC-MS HCP assessments, we reveal complete clearance of potential PS-80-degrading HCP populations in the CHT eluate product pool., Conclusions: In summary, these results demonstrate that CHT mixed-mode chromatography plays an important role in separation of product- and process-related impurities in the BsAb downstream process., (© The Author(s) 2022. Published by Oxford University Press on behalf of Antibody Therapeutics. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Background: Unplanned readmission to the neurological intensive care unit (ICU) is an underinvestigated topic in patients admitted after spontaneous intracerebral hemorrhage (ICH). The purpose of this study is to investigate the frequency, clinical risk factors, and outcome of bounce back to the neurological ICU in a cohort of patients admitted after ICH., Methods: This is a retrospective observational study inspecting bounce back to the neurological ICU in patients admitted with spontaneous ICH over an 8-year period. For each patient, demographics, medical history, clinical presentation, length of ICU stay, unplanned readmission to neurological ICU, cause of readmission, and mortality were reviewed. Bounce back to the neurological ICU was defined as an unplanned readmission to the neurological ICU from a general floor service during the same hospitalization. A multivariable analysis was used to define independent variables associated with bounce back to the neurological ICU as well as association between bounce back to the neurological ICU and mortality. The significance level was set at p < 0.05., Results: A total of 221 patients were included. Among those, 20 (9%) had a bounce back to the neurological ICU. Respiratory complications (n = 11) was the most common reason for bounce back to the neurological ICU, followed by neurological (n = 5) and cardiological (n = 4) complications. In a multivariable logistic regression, location of hemorrhage in the basal ganglia (odds ratio [OR]: 3.0, 95% confidence interval [CI]: 1.0-8.9, p = 0.03) and dysphagia at the time of transfer (OR: 3.9, 95% CI: 1.0-15.4, p = 0.04) were significantly associated with bounce back to the neurological ICU. After we controlled for ICH score, readmission to the ICU was also independently associated with higher mortality (OR: 14.1, 95% CI: 2.8-71.7, p < 0.01)., Conclusions: Bounce back to the neurological ICU is not an infrequent complication in patients with spontaneous ICH and is associated with higher hospital length of stay and mortality. We identified relevant and potentially modifiable risk factors associated with bounce back to the neurological ICU. Future prospective studies are necessary to develop patient-centered strategies that may improve transition from the neurological ICU to the general floor., (© 2022. Springer Science+Business Media, LLC, part of Springer Nature and Neurocritical Care Society.)

Background: Triple-negative breast cancer (TNBC) is a complex and molecularly heterogeneous entity, with the poorest outcome compared with other breast cancer subtypes. Previously, we developed a TNBC 3-gene score with a significant prognostic capability. This study aims to test the 3-gene score in the different TNBC subtypes. Methods: Data from 204 TNBC patients treated with neoadjuvant chemotherapy were retrieved from public datasets and pooled (GSE25066, GSE58812, and GSE16446). After removing batch effects, cases were classified into Lehman’s TNBC subtypes and then the TNBC 3-gene score was used to evaluate the risk of distant recurrence in each subgroup. In addition, the association with tumor-infiltrating lymphocyte (TILs) levels was evaluated in a retrospective group of 72 TNBC cases. Results: The TNBC 3-gene score was able to discriminate patients with different risks within the pooled cohort (HR = 2.41 for high vs. low risk; 95%CI: 1.50−3.86). The score showed predictive capability in the immunomodulatory subtype (HR = 4.16; 95%CI: 1.63−10.60) and in the mesenchymal stem-like subtype (HR = 18.76; 95%CI: 1.68−208.97). In the basal-like 1, basal-like-2, and mesenchymal subtypes, the observed differential risk patterns showed no statistical significance. The score had poor predictive capability in the luminal androgen receptor subtype (p = 0.765). In addition, a low TNBC 3-gene score was related to a high level of TIL infiltration (p < 0.001). Conclusions: The TNBC 3-gene score is able to predict the risk of distant recurrence in TNBC patients, specifically in the immunomodulatory and mesenchymal stem-like subtype. Despite a small sample size in each subgroup, an improved prognostic capability was seen in TNBC subtypes with tumor-infiltrating components.

The solar conversion of CO 2 to low carbon fuels has been heralded as a potential solution to combat the rise in greenhouse gas emissions. Here we report the first light-driven activation of [NiFe] CODH II from Carboxydothermus hydrogenoformans for the reduction of CO 2 to CO. To accomplish this, a hybrid photosystem composed of CODH II and CdSe/CdS dot-in-rod nanocrystals was developed. By incorporating a low-potential redox mediator to assist electron transfer, quantum yields up to 19% and turnover frequencies of 9 s -1 were achieved. These results represent a new standard in efficient CO 2 reduction by an enzyme-based photocatalytic systems. Furthermore, successful photoactivation of CODH II allows for future exploration into the enzyme's not fully understood mechanism.

Background: Von Hippel-Lindau (VHL) disease is an inherited tumour predisposition syndrome and a paradigm for the importance of early diagnosis and surveillance. However, there is limited information on the "real world" management of VHL disease., Methods: A national audit of VHL disease in the United Kingdom., Results: VHL disease was managed mostly via specialist clinics coordinated through regional clinical genetics services (but frequently involving additional specialties). Over the study period, 19 genetic centres saw 842 individuals (393 males, 449 females) with a clinical and/or molecular diagnosis of VHL disease and 74 individuals (35 male, 39 female) with a prior risk of 50% (affected parent). All centres offered retinal, central nervous system and abdominal surveillance to affected individuals and at-risk relatives though surveillance details differed between centres (but complied with international recommendations). Renal lesions detected on the first surveillance scan were, on average, larger than those detected during subsequent scans and the larger the diameter at detection the greater the likelihood of early intervention., Conclusions: In a state-funded health care system individuals with a rare inherited cancer predisposition syndrome are generally able to access appropriate surveillance and patient management is improved compared to historical data. The "real world" data from this study will inform the future development of VHL management protocols., (© 2022. The Author(s).)

Objective: Phaeochromocytomas and paragangliomas (PPGL) are rare, but strongly heritable tumours. Variants in succinate dehydrogenase (SDH) subunits are identified in approximately 25% of cases. However, clinical and genetic information of patients with SDHC variants are underreported., Design: This retrospective case series collated data from 18 UK Genetics and Endocrinology departments., Patients: Both asymptomatic and disease-affected patients with confirmed SDHC germline variants are included., Measurements: Clinical data including tumour type and location, surveillance outcomes and interventions, SDHC genetic variant assessment, interpretation, and tumour risk calculation., Results: We report 91 SDHC cases, 46 probands and 45 non-probands. Fifty-one cases were disease-affected. Median age at genetic diagnosis was 43 years (range: 11-79). Twenty-four SDHC germline variants were identified including six novel variants. Head and neck paraganglioma (HNPGL, n = 30, 65.2%), extra-adrenal paraganglioma (EAPGL, n = 13, 28.2%) and phaeochromocytomas (PCC) (n = 3, 6.5%) were present. One case had multiple PPGLs. Malignant disease was reported in 19.6% (9/46). Eight cases had non-PPGL SDHC-associated tumours, six gastrointestinal stromal tumours (GIST) and two renal cell cancers (RCC). Cumulative tumour risk (95% CI) at age 60 years was 0.94 (CI: 0.79-0.99) in probands, and 0.16 (CI: 0-0.31) in non-probands, respectively., Conclusions: This study describes the largest cohort of 91 SDHC patients worldwide. We confirm disease-affected SDHC variant cases develop isolated HNPGL disease in nearly 2/3 of patients, EAPGL and PCC in 1/3, with an increased risk of GIST and RCC. One fifth developed malignant disease, requiring comprehensive lifelong tumour screening and surveillance., (© 2021 John Wiley & Sons Ltd.)

Background: A small randomized controlled trial suggested that dabigatran may be as effective as warfarin in the treatment of cerebral venous thrombosis (CVT). We aimed to compare direct oral anticoagulants (DOACs) to warfarin in a real-world CVT cohort., Methods: This multicenter international retrospective study (United States, Europe, New Zealand) included consecutive patients with CVT treated with oral anticoagulation from January 2015 to December 2020. We abstracted demographics and CVT risk factors, hypercoagulable labs, baseline imaging data, and clinical and radiological outcomes from medical records. We used adjusted inverse probability of treatment weighted Cox-regression models to compare recurrent cerebral or systemic venous thrombosis, death, and major hemorrhage in patients treated with warfarin versus DOACs. We performed adjusted inverse probability of treatment weighted logistic regression to compare recanalization rates on follow-up imaging across the 2 treatments groups., Results: Among 1025 CVT patients across 27 centers, 845 patients met our inclusion criteria. Mean age was 44.8 years, 64.7% were women; 33.0% received DOAC only, 51.8% received warfarin only, and 15.1% received both treatments at different times. During a median follow-up of 345 (interquartile range, 140-720) days, there were 5.68 recurrent venous thrombosis, 3.77 major hemorrhages, and 1.84 deaths per 100 patient-years. Among 525 patients who met recanalization analysis inclusion criteria, 36.6% had complete, 48.2% had partial, and 15.2% had no recanalization. When compared with warfarin, DOAC treatment was associated with similar risk of recurrent venous thrombosis (aHR, 0.94 [95% CI, 0.51-1.73]; P =0.84), death (aHR, 0.78 [95% CI, 0.22-2.76]; P =0.70), and rate of partial/complete recanalization (aOR, 0.92 [95% CI, 0.48-1.73]; P =0.79), but a lower risk of major hemorrhage (aHR, 0.35 [95% CI, 0.15-0.82]; P =0.02)., Conclusions: In patients with CVT, treatment with DOACs was associated with similar clinical and radiographic outcomes and favorable safety profile when compared with warfarin treatment. Our findings need confirmation by large prospective or randomized studies.