Organizations in science and medicine must hold each other accountable for discriminatory practices.

Many organizations persist in working with others that engage in known, remediable structural discrimination. We name this practice interorganizational structural discrimination (ISD) and argue it is a pivotal contributor to inequities in science and medicine. We urge organizations to leverage their relationships and demand progress from collaborators.

On the development and validation of large language model-based classifiers for identifying social determinants of health.

The assessment of social determinants of health (SDoH) within healthcare systems is crucial for comprehensive patient care and addressing health disparities. Current challenges arise from the limited inclusion of structured SDoH information within electronic health record (EHR) systems, often due to the lack of standardized diagnosis codes. This study delves into the transformative potential of large language models (LLM) to overcome these challenges. LLM-based classifiers-using Bidirectional Encoder Representations from Transformers (BERT) and A Robustly Optimized BERT Pretraining Approach (RoBERTa)-were developed for SDoH concepts, including homelessness, food insecurity, and domestic violence, using synthetic training datasets generated by generative pre-trained transformers combined with authentic clinical notes. Models were then validated on separate datasets: Medical Information Mart for Intensive Care-III and our institutional EHR data. When training the model with a combination of synthetic and authentic notes, validation on our institutional dataset yielded an area under the receiver operating characteristics curve of 0.78 for detecting homelessness, 0.72 for detecting food insecurity, and 0.83 for detecting domestic violence. This study underscores the potential of LLMs in extracting SDoH information from clinical text. Automated detection of SDoH may be instrumental for healthcare providers in identifying at-risk patients, guiding targeted interventions, and contributing to population health initiatives aimed at mitigating disparities.

PHF6-mediated transcriptional control of NSC via Ephrin receptors is impaired in the intellectual disability syndrome BFLS.

The plant homeodomain zinc-finger protein, PHF6, is a transcriptional regulator, and PHF6 germline mutations cause the X-linked intellectual disability (XLID) Börjeson-Forssman-Lehmann syndrome (BFLS). The mechanisms by which PHF6 regulates transcription and how its mutations cause BFLS remain poorly characterized. Here, we show genome-wide binding of PHF6 in the developing cortex in the vicinity of genes involved in central nervous system development and neurogenesis. Characterization of BFLS mice harbouring PHF6 patient mutations reveals an increase in embryonic neural stem cell (eNSC) self-renewal and a reduction of neural progenitors. We identify a panel of Ephrin receptors (EphRs) as direct transcriptional targets of PHF6. Mechanistically, we show that PHF6 regulation of EphR is impaired in BFLS mice and in conditional Phf6 knock-out mice. Knockdown of EphR-A phenocopies the PHF6 loss-of-function defects in altering eNSCs, and its forced expression rescues defects of BFLS mice-derived eNSCs. Our data indicate that PHF6 directly promotes Ephrin receptor expression to control eNSC behaviour in the developing brain, and that this pathway is impaired in BFLS.

Once-weekly insulin efsitora alfa versus once-daily insulin degludec in adults with type 1 diabetes (QWINT-5): a phase 3 randomised non-inferiority trial.

BACKGROUND: Insulin efsitora alfa (efsitora) is a once-weekly basal insulin. This phase 3 study aimed to assess the efficacy and safety of efsitora compared with insulin degludec (degludec) in adults with type 1 diabetes. METHODS: This randomised, 52-week, parallel-design, open-label, treat-to-target non-inferiority study conducted at 82 global health-care centres, randomly assigned (1:1) adults (ie, those aged ≥18 years) with type 1 diabetes glycated haemoglobin A1c (HbA1c) 7·0-10·0% (53·0-85·8 mmol/mol) to efsitora (n=343) or, degludec (n=349), both in combination with insulin lispro. The primary endpoint was the change in HbA1c from baseline to week-26 (non-inferiority margin=0·4%). The trial was registered at ClinicalTrials.gov (NCT05463744) and is completed. FINDINGS: Between Aug 12, 2022, and May 7, 2024, of 893 participants enrolled, 692 (77%) participants were randomly assigned to once-weekly efsitora or once-daily degludec, and 623 (90%) participants completed the study. Mean HbA1c decreased from 7·88% (62·66 mmol/mol) at baseline to 7·41% (57·5 mmol/mol) at week 26 with efsitora and from 7·94% (63·3 mmol/mol) at baseline to 7·36% (56·9 mmol/mol) at week 26 with degludec. Mean HbA1c change from baseline to week 26 was -0·51% with efsitora and -0·56% with degludec (estimated treatment difference 0·052%, 95% CI -0·077 to 0·181; p=0·43), confirming a non-inferiority margin of 0·4% for efsitora compared with degludec. Rates of combined level 2 (<54 mg/dL [3·0 mmol/L]) or level 3 severe hypoglycaemia were higher with efsitora compared with degludec (14·03 vs 11·59 events per patient year of exposure; estimated rate ratio 1·21, 95% CI 1·04 to 1·41; p=0·016) during weeks 0-52, with the highest rates during weeks 0-12. Severe hypoglycaemia incidence was higher with efsitora (35 [10%] of 343) versus degludec (11 [3%] of 349) during weeks 0-52. Overall incidence of treatment-emergent adverse events was similar across treatment groups. One death not related to the study treatment occurred in the degludec group. INTERPRETATION: In adults with type 1 diabetes, once-weekly efsitora showed non-inferior HbA1c reduction compared with daily insulin degludec. Higher rates of combined level 2 or level 3 hypoglycaemia and greater incidence of severe hypoglycaemia in participants treated with efsitora compared with participants treated with degludec might suggest the need for additional evaluation of efsitora dose initiation and optimisation in people with type 1 diabetes. FUNDING: Eli Lilly and Company.

Nodal positivity in patients with clinically and radiologically node-negative breast cancer treated with neoadjuvant chemotherapy: multicentre collaborative study.

BACKGROUND: The necessity of performing a sentinel lymph node biopsy in patients with clinically and radiologically node-negative breast cancer after neoadjuvant chemotherapy has been questioned. The aim of this study was to determine the rate of nodal positivity in these patients and to identify clinicopathological features associated with lymph node metastasis after neoadjuvant chemotherapy (ypN+). METHODS: A retrospective multicentre study was performed. Patients with cT1-3 cN0 breast cancer who underwent sentinel lymph node biopsy after neoadjuvant chemotherapy between 2016 and 2021 were included. Negative nodal status was defined as the absence of palpable lymph nodes, and the absence of suspicious nodes on axillary ultrasonography, or the absence of tumour cells on axillary nodal fine needle aspiration or core biopsy. RESULTS: A total of 371 patients were analysed. Overall, 47 patients (12.7%) had a positive sentinel lymph node biopsy. Nodal positivity was identified in 22 patients (29.0%) with hormone receptor+/human epidermal growth factor receptor 2- tumours, 12 patients (13.8%) with hormone receptor+/human epidermal growth factor receptor 2+ tumours, 3 patients (5.6%) with hormone receptor-/human epidermal growth factor receptor 2+ tumours, and 10 patients (6.5%) with triple-negative breast cancer. Multivariable logistic regression analysis showed that multicentric disease was associated with a higher likelihood of ypN+ (OR 2.66, 95% c.i. 1.18 to 6.01; P = 0.018), whilst a radiological complete response in the breast was associated with a reduced likelihood of ypN+ (OR 0.10, 95% c.i. 0.02 to 0.42; P = 0.002), regardless of molecular subtype. Only 3% of patients who had a radiological complete response in the breast were ypN+. The majority of patients (85%) with a positive sentinel node proceeded to axillary lymph node dissection and 93% had N1 disease. CONCLUSION: The rate of sentinel lymph node positivity in patients who achieve a radiological complete response in the breast is exceptionally low for all molecular subtypes.

Mitochondria as central regulators of neural stem cell fate and cognitive function.

Emerging evidence now indicates that mitochondria are central regulators of neural stem cell (NSC) fate decisions and are crucial for both neurodevelopment and adult neurogenesis, which in turn contribute to cognitive processes in the mature brain. Inherited mutations and accumulated damage to mitochondria over the course of ageing serve as key factors underlying cognitive defects in neurodevelopmental disorders and neurodegenerative diseases, respectively. In this Review, we explore the recent findings that implicate mitochondria as crucial regulators of NSC function and cognition. In this respect, mitochondria may serve as targets for stem-cell-based therapies and interventions for cognitive defects.

Overcoming the Impact of Students for Fair Admission v Harvard to Build a More Representative Health Care Workforce: Perspectives from Ending Unequal Treatment.

Policy Points In a recently commissioned report on solutions for eliminating racial and ethnic health care inequities entitled Ending Unequal Treatment, the National Academies of Sciences, Engineering, and Medicine found a health workforce that is representative of the communities it serves is essential for health care equity. The Supreme Court decision to ban race-conscious admission constraints pathways toward health workforce representativeness and equity. This paper draws on the National Academies report's findings that health care workforce representativeness improves care quality, population health, and equity to discuss policy and programmatic options for various participants to promote health workforce representativeness in the context of race-conscious admissions bans.

Supporting the 'lived expertise' of older adults with type 1 diabetes: An applied focus group analysis to characterize barriers, facilitators, and strategies for self-management in a growing and understudied population.

INTRODUCTION: There is a growing number of older adults (≥65 years) who live with type 1 diabetes. We qualitatively explored experiences and perspectives regarding type 1 diabetes self-management and treatment decisions among older adults, focusing on adopting care advances such as continuous glucose monitoring (CGM). METHODS: Among a clinic-based sample of older adults ≥65 years with type 1 diabetes, we conducted a series of literature and expert informed focus groups with structured discussion activities. Groups were transcribed followed by inductive coding, theme identification, and inference verification. Medical records and surveys added clinical information. RESULTS: Twenty nine older adults (age 73.4 ± 4.5 years; 86% CGM users) and four caregivers (age 73.3 ± 2.9 years) participated. Participants were 58% female and 82% non-Hispanic White. Analysis revealed themes related to attitudes, behaviours, and experiences, as well as interpersonal and contextual factors that shape self-management and outcomes. These factors and their interactions drive variability in diabetes outcomes and optimal treatment strategies between individuals as well as within individuals over time (i.e. with ageing). Participants proposed strategies to address these factors: regular, holistic needs assessments to match people with effective self-care approaches and adapt them over the lifespan; longitudinal support (e.g., education, tactical help, sharing and validating experiences); tailored education and skills training; and leveraging of caregivers, family, and peers as resources. CONCLUSIONS: Our study of what influences self-management decisions and technology adoption among older adults with type 1 diabetes underscores the importance of ongoing assessments to address dynamic age-specific needs, as well as individualized multi-faceted support that integrates peers and caregivers.

An examination of episodic future thinking in the emergency department among youth experiencing suicidal thoughts and behaviors.

Youth experiencing suicidal thoughts and/or behaviors (STBs) frequently present to emergency departments for acute psychiatric care. These settings offer a transitory yet pivotal opportunity to assess, intervene on, and plan continued care for STBs. This study examined a clinically relevant, understudied aspect of psychological functioning among youth experiencing STBs in the emergency department: episodic future thinking, or the ability to imagine discrete autobiographical future events. A sample of 167 youths (10-17 years) presenting to a pediatric psychiatric emergency department for STBs completed a performance-based measure of episodic future thinking assessing richness in detail and subjective characteristics of imagined future events. STB recurrence was assessed 6 months later. Immediately following a suicide-related crisis, youth demonstrated mixed abilities to imagine their future: they generated some concrete future event details but did not subjectively perceive these events as being very detailed or likely to occur. Older adolescents (i.e., 15-17) generated more episodic details than pre-/younger adolescents (i.e., 10-14), particularly those pertaining to actions or sensory perceptions. There was no evidence linking less detailed episodic future thinking and greater likelihood of STBs following the emergency department visit; instead, hopelessness was a more robust risk factor. Findings underscore the importance and clinical utility of better understanding the psychological state of youth during or immediately following a suicide-related crisis. In particular, assessing youths' future thinking abilities in the emergency department may directly inform approaches to acute care delivery.

PFTK1 kinase regulates axogenesis during development via RhoA activation.

BACKGROUND: PFTK1/Eip63E is a member of the cyclin-dependent kinases (CDKs) family and plays an important role in normal cell cycle progression. Eip63E expresses primarily in postnatal and adult nervous system in Drosophila melanogaster but its role in CNS development remains unknown. We sought to understand the function of Eip63E in the CNS by studying the fly ventral nerve cord during development. RESULTS: Our results demonstrate that Eip63E regulates axogenesis in neurons and its deficiency leads to neuronal defects. Functional interaction studies performed using the same system identify an interaction between Eip63E and the small GTPase Rho1. Furthermore, deficiency of Eip63E homolog in mice, PFTK1, in a newly generated PFTK1 knockout mice results in increased axonal outgrowth confirming that the developmental defects observed in the fly model are due to defects in axogenesis. Importantly, RhoA phosphorylation and activity are affected by PFTK1 in primary neuronal cultures. We report that GDP-bound inactive RhoA is a substrate of PFTK1 and PFTK1 phosphorylation is required for RhoA activity. CONCLUSIONS: In conclusion, our work establishes an unreported neuronal role of PFTK1 in axon development mediated by phosphorylation and activation of GDP-bound RhoA. The results presented add to our understanding of the role of Cdks in the maintenance of RhoA-mediated axon growth and its impact on CNS development and axonal regeneration.

Understanding Providers' Readiness and Attitudes Toward Autoantibody Screening: A Mixed-Methods Study.

Screening for autoantibodies associated with type 1 diabetes can identify people most at risk for progressing to clinical type 1 diabetes and provide an opportunity for early intervention. Drawbacks and barriers to screening exist, and concerns arise, as methods for disease prevention are limited and no cure exists today. The availability of novel treatment options such as teplizumab to delay progression to clinical type 1 diabetes in high-risk individuals has led to the reassessment of screening programs. This study explored awareness, readiness, and attitudes of endocrinology providers toward type 1 diabetes autoantibody screening.

Patient-Reported Outcomes Improve with a Virtual Diabetes Care Model that Includes Continuous Glucose Monitoring.

Background: The objective was to examine patient-reported outcomes (PROs) associated with access to a virtual clinic model for diabetes care. Methods: Adults with diabetes (N = 234) received virtual care, including support for continuous glucose monitoring (CGM) over a 6-month study period. Care was led by a Certified Diabetes Care and Education Specialist and focused on optimizing self-management skills and response to glucose values observed on CGM. After 6 months of CGM use and access to diabetes education, participants could opt in to another 6 months of follow-up with access to the virtual care team. Participants completed PRO surveys and had health and glycemic measures collected at baseline, 3, 6, and 12 months. Results: Participants with type 1 diabetes (N = 160) were 44 ± 14 years and had mean baseline HbA1c of 61 mmol/mol (7.7%). Participants with type 2 diabetes (N = 74) were 52 ± 12 years and had mean baseline HbA1c of 66 mmol/mol (8.2%). Compared with baseline levels, at 6 months participants experienced less depression, diabetes distress, and hypoglycemic fears while also experiencing greater satisfaction with glucose monitoring, diabetes technology and specifically with CGM, and confidence for managing hypoglycemic (p < 0.05). For participants with type 1 diabetes, more time in the target range for glucose levels (70-180 mg/dL) was associated with less depression, diabetes distress, and hypoglycemic fears. Conclusions: PROs improved for adults with diabetes utilizing virtual diabetes care, including support for CGM use. Paired with the glycemic improvements observed in this virtual clinic study, there were robust benefits on the quality of life of adults with diabetes. ClinicalTrials.gov Identifier: NCT04765358.

Serum Urate Lowering with Allopurinol and Kidney Function in Type 1 Diabetes.

BACKGROUND: Higher serum urate levels are associated with an increased risk of diabetic kidney disease. Lowering of the serum urate level with allopurinol may slow the decrease in the glomerular filtration rate (GFR) in persons with type 1 diabetes and early-to-moderate diabetic kidney disease. METHODS: In a double-blind trial, we randomly assigned participants with type 1 diabetes, a serum urate level of at least 4.5 mg per deciliter, an estimated GFR of 40.0 to 99.9 ml per minute per 1.73 m2 of body-surface area, and evidence of diabetic kidney disease to receive allopurinol or placebo. The primary outcome was the baseline-adjusted GFR, as measured with iohexol, after 3 years plus a 2-month washout period. Secondary outcomes included the decrease in the iohexol-based GFR per year and the urinary albumin excretion rate after washout. Safety was also assessed. RESULTS: A total of 267 patients were assigned to receive allopurinol and 263 to receive placebo. The mean age was 51.1 years, the mean duration of diabetes 34.6 years, and the mean glycated hemoglobin level 8.2%. The mean baseline iohexol-based GFR was 68.7 ml per minute per 1.73 m2 in the allopurinol group and 67.3 ml per minute per 1.73 m2 in the placebo group. During the intervention period, the mean serum urate level decreased from 6.1 to 3.9 mg per deciliter with allopurinol and remained at 6.1 mg per deciliter with placebo. After washout, the between-group difference in the mean iohexol-based GFR was 0.001 ml per minute per 1.73 m2 (95% confidence interval [CI], -1.9 to 1.9; P = 0.99). The mean decrease in the iohexol-based GFR was -3.0 ml per minute per 1.73 m2 per year with allopurinol and -2.5 ml per minute per 1.73 m2 per year with placebo (between-group difference, -0.6 ml per minute per 1.73 m2 per year; 95% CI, -1.5 to 0.4). The mean urinary albumin excretion rate after washout was 40% (95% CI, 0 to 80) higher with allopurinol than with placebo. The frequency of serious adverse events was similar in the two groups. CONCLUSIONS: We found no evidence of clinically meaningful benefits of serum urate reduction with allopurinol on kidney outcomes among patients with type 1 diabetes and early-to-moderate diabetic kidney disease. (Funded by the National Institute of Diabetes and Digestive and Kidney Diseases and others; PERL ClinicalTrials.gov number, NCT02017171.).

NPC1 deficiency impairs cerebellar postnatal development of microglia and climbing fiber refinement in a mouse model of Niemann-Pick disease type C.

Little is known about the effects of NPC1 deficiency in brain development and whether these effects contribute to neurodegeneration in Niemann-Pick disease type C (NPC). Degeneration of cerebellar Purkinje cells occurs at an earlier stage and to a greater extent in NPC; therefore, we analyzed the effect of NPC1 deficiency on microglia and on climbing fiber synaptic refinement during cerebellar postnatal development using the Npc1nmf164 mouse. Our analysis revealed that NPC1 deficiency leads to early phenotypic changes in microglia that are not associated with an innate immune response. However, the lack of NPC1 in Npc1nmf164 mice significantly affected the early development of microglia by delaying the radial migration, increasing the proliferation and impairing the differentiation of microglia precursor cells during postnatal development. Additionally, increased phagocytic activity of differentiating microglia was observed at the end of the second postnatal week in Npc1nmf164 mice. Moreover, significant climbing fiber synaptic refinement deficits along with an increased engulfment of climbing fiber synaptic elements by microglia were found in Npc1nmf164 mice, suggesting that profound developmental defects in microglia and synaptic connectivity might precede and predispose Purkinje cells to early neurodegeneration in NPC.

Psychosocial Factors Predicting Healthcare Usage in Young Adults with Youth-Onset Type 2 Diabetes: The TODAY2 iCount Observational Study.

BACKGROUND: Established diabetes care ("diabetes home") and regular healthcare visits are important to achieve optimal health. Nothing is known about psychosocial factors that predict healthcare usage (HCU) in young adults with youth-onset type 2 diabetes, at risk for early complications. OBJECTIVE: To identify psychosocial predictors of HCU in the Treatment Options for type 2 Diabetes in Adolescents and Youth (TODAY2) cohort. DESIGN: Longitudinal, measured at T1 (baseline) and T2 (1 year later). Logistic and linear regressions, adjusted for potential confounders, identified predictors of sub-optimal HCU (defined as no diabetes home, 0 visits for routine care, or ≥ 1 urgent care visit in prior 6 months). PARTICIPANTS: N = 366 TODAY2 participants with T1 and T2 data (381 consented). Mean age = 26.0 years, 67.8% female, 37.7% non-Hispanic Black, 35.8% Hispanic, 20.2% non-Hispanic white, 6.3% "other," mean HbA1c = 9.4%. MAIN MEASURES: HCU survey; reliable and valid measures of diabetes self-efficacy, depressive symptoms, anxiety symptoms, diabetes distress, beliefs about medicines, diabetes attitudes, material need insecurities, self-management support. KEY RESULTS: 25.4% had no diabetes home, 23.7% had 0 routine care visits, 46% had ≥ 1 urgent care visit (prior 6 months). Beliefs in the necessity of (adjusted odds ratio [OR] = 1.28; 95% confidence interval [CI] = 1.12, 1.46, p < 0.001), and concerns about (OR = 1.29;CI = 1.08,1.54, p = 0.004), diabetes medicines, and its negative psychosocial impacts (OR = 1.57;CI = 1.04, 2.38, p = 0.03), predicted higher odds of having a diabetes home at T2. Beliefs that medicines are harmful predicted lower odds of a diabetes home (OR = 0.56;CI = 0.37,0.85, p = 0.006). Necessity beliefs (OR = 1.2;CI = 1.06,1.36, p = 0.004), and self-management support (OR = 1.5;CI = 1.08,2.07, p = 0.01) predicted higher odds of having ≥ 1 diabetes care visit, harm beliefs predicted lower odds (OR = 0.6;CI = 0.41,0.88, p = 0.01). CONCLUSIONS: Sub-optimal healthcare usage, common in young adults with youth-onset type 2 diabetes, is predicted by beliefs about medicines, diabetes impact, and self-management support. We must address these factors to help this vulnerable group establish stable diabetes care.

Psychosocial factors predict medication adherence in young adults with youth-onset type 2 diabetes: Longitudinal results from the TODAY2 iCount study.

AIM: To identify psychosocial predictors of medication adherence in young adults with youth-onset type 2 diabetes in the Treatment Options for type 2 Diabetes in Adolescents and Youth (TODAY2) cohort. METHODS: Participants (mean age: 26 years) completed validated psychosocial measures. Unannounced telephone pill counts were completed at T1 (baseline) and T2 (follow-up, approximately 1 year later) to assess adherence to oral hypoglycaemia agents (OHAs). Adherence to insulin was assessed by self-report. Logistic and linear regressions identified factors that predicted 'low adherence' (<80% of pills/insulin) and per cent adherence, adjusted for potential confounders. RESULTS: Of 171 participants with OHA adherence scores at T1 and T2 (65% women, 43% Hispanic and 35% non-Hispanic Black), 65.4% were low adherent. After adjustment (including T1 adherence), concerns about diabetes medicines (adverse effects, dependence) at T1 predicted higher odds of being low adherent (categorical) at T2 (p = 0.019). Housing insecurity (p = 0.045) and reporting ≥2 need insecurities (p = 0.027) at T1 predicted lower per cent adherence (continuous) at T2. Of 157 participants with insulin adherence scores at T1 and T2 (69% women, 38% Hispanic and 38% non-Hispanic Black), 36.3% were low adherent. After adjustment (including T1 adherence), beliefs that medicines are overused predicted higher odds of insulin low adherence at T2 (p = 0.013), and beliefs that medicines are harmful (p = 0.004) and overused (p = 0.010) predicted lower per cent insulin adherence at T2. CONCLUSIONS: Suboptimal medication adherence, common in young adults with youth-onset type 2 diabetes, is predicted by interfering beliefs about medicines and social factors. We must address these beliefs and unmet needs to develop tailored interventions for this vulnerable group.

A systematic review of oncological outcomes after nipple-sparing mastectomy for breast cancer.

Nipple-sparing mastectomy is an alternative to skin-sparing mastectomy in select patients. Increasing evidence supports its use in the setting of breast cancer, however concerns still exist regarding oncological safety. The aim of this systematic review was to evaluate long-term oncological outcomes of patients who underwent nipple-sparing mastectomy for breast cancer. A systematic review of the literature was performed to evaluate oncological outcomes in patients with breast cancer who underwent nipple-sparing mastectomy. Five major databases (PubMed, Embase, Scopus, Web of Science and Cochrane) were searched. The review included all original articles published in English reporting long-term oncological outcomes. 2334 studies were identified. After applying inclusion and exclusion criteria, 17 retrospective studies involving 7107 patients were included. The indication for nipple-sparing mastectomy was invasive carcinoma in 6069 patients (85.4%) and in situ disease in 1038 (14.6%). Median follow up was 48 months (range 25-94). The weighted mean rates of local recurrence and recurrence involving the nipple-areola complex were 5.4% (0.9-11.9) and 1.3% (0-4.9), respectively. The weighted mean distant failure rate was 4.8% (1.5-23.0). Therapeutic nipple-sparing mastectomy is oncologically safe in select patients with breast cancer.

Epidemiology and susceptibility of Nakaseomyces (formerly Candida) glabrata bloodstream isolates from hospitalised adults in South Africa.

During 2016-2017, Nakaseomyces glabrata (formerly Candida glabrata) caused 14% of cases of candidaemia in South Africa. We aimed to describe the clinical characteristics of adults with N. glabrata candidaemia at 20 sentinel hospitals (accounting for 20% (172/917) of cases) and the antifungal susceptibility of the corresponding isolates. A higher proportion of patients with N. glabrata candidaemia were older (median age: 55 years [interquartile range (IQR): 41-65 years] vs. 49 years [IQR: 35-63 years]; p = 0.04), female (87/164, 53% vs. 283/671, 42%; p = 0.01), admitted to a public-sector hospital (152/172, 88% vs. 470/745, 63%; p < 0.001), treated with fluconazole only (most with suboptimal doses) (51/95, 54% vs. 139/361, 39%; p < 0.001), and had surgery (47/172, 27% vs. 123/745, 17%; p = 0.001) and a shorter hospital stay (median 7 days [IQR: 2-20 days] vs. 13 days [IQR: 4-27 days]; p < 0.001) compared to patients with other causes of candidaemia. Eight N. glabrata isolates (6%, 8/131) had minimum inhibitory concentrations in the intermediate or resistant range for ≥ 1 echinocandin and a R1377K amino acid substitution encoded by the hotspot 2 region of the FKS2 gene. Only 11 isolates (8%, 11/131) were resistant to fluconazole. Patients with confirmed N. glabrata candidaemia are recommended to be treated with an echinocandin (or polyene), thus further guideline training is required.

Nakaseomyces (formerly Candida) glabrata is a yeast-like fungus that forms part of the commensal gut flora and among people with certain risk factors, can invade into the bloodstream. Nakaseomyces glabrata is a relatively more common cause of candidaemia in high-income vs. low- and middle-income countries. There are no N. glabrata clinical isolates that are considered susceptible to fluconazole, and thus echinocandins are recommended for treatment. However, echinocandin resistance is emerging. We described the characteristics of South African patients with N. glabrata bloodstream infections and the antifungal susceptibility of corresponding isolates. We found that patients infected with N. glabrata were more likely to be older, female, admitted to public hospitals and to be post-surgery and these patients were also more likely to be treated with fluconazole monotherapy and to have stayed a shorter time in hospital compared to patients infected with other Candida species. Only 6% of N. glabrata isolates were echinocandin-resistant with mutations in specific resistance genes that we have found in South African N. glabrata isolates previously. Eight percent of N. glabrata isolates were resistant to fluconazole and the remainder were in the susceptible dose dependent category, requiring higher fluconazole treatment doses. Patients with confirmed N. glabrata bloodstream infection should ideally be treated with an echinocandin or polyene rather than fluconazole and training is required for doctors treating these patients.

Identification and management of tomato brown rugose fruit virus in greenhouses in Mexico.

Tomato brown rugose fruit virus (ToBRFV) has become a cause of great concern in the global tomato agro-industry since its first report in Israel in 2014. Global tomato production is affected by ToBRFV, and management practices are being evaluated. We tested seed lots from international producers as well as greenhouse substrates and water wells as possible sources of virus contamination. We identified a second introduction of ToBRFV in Mexico by a strain closely resembling isolates from the Netherlands and the Middle East. ToBRFV was detected by RT-PCR in seed coats and epicotyls (from commercial seeds and seedlings obtained from infected tomato plants), indicating a transmission rate of 9%. Virus-like particles (VLPs) were found in wells used for irrigation in greenhouses, but these exhibited low infectivity. These findings suggest that water sources could serve as ToBRFV reservoirs. We evaluated four chemical and six thermal methods for sanitizing substrates, plasticware, and other greenhouse utensils, using detached leaf bioassays in Nicotiana rugosa. The most effective chemical sanitization method was treatment with glutaraldehyde plus quaternary ammonium salts and pentapotassium salts. The most effective heat treatment was at 92°C for 30 minutes, which inactivated the virus. Tomato producers could implement these sanitization methods to control ToBRFV.

Use of sentinel lymph node biopsy in elderly patients with breast cancer - 10-year experience from a Swiss university hospital.

BACKGROUND: The Choosing Wisely initiative recommended the omission of routine sentinel lymph node biopsy (SLNB) in patients ≥ 70 years of age, with clinically node-negative, early stage, hormone receptor (HR) positive and human epidermal growth factor receptor 2 (Her2) negative breast cancer in August 2016. Here, we assess the adherence to this recommendation in a Swiss university hospital. METHODS: We conducted a retrospective single center cohort study from a prospectively maintained database. Patients ≥ 18 years of age with node-negative breast cancer were treated between 05/2011 and 03/2022. The primary outcome was the percentage of patients in the Choosing Wisely target group who underwent SLNB before and after the initiative went live. Statistical significance was tested using chi-squared test for categorical and Wilcoxon rank-sum tests for continuous variables. RESULTS: In total, 586 patients met the inclusion criteria with a median follow-up of 2.7 years. Of these, 163 were ≥ 70 years of age and 79 were eligible for treatment according to the Choosing Wisely recommendations. There was a trend toward a higher rate of SLNB (92.7% vs. 75.0%, p = 0.07) after the Choosing Wisely recommendations were published. In patients ≥ 70 years with invasive disease, fewer received adjuvant radiotherapy after omission of SLNB (6.2% vs. 64.0%, p < 0.001), without differences concerning adjuvant systemic therapy. Both short-term and long-term complication rates after SLNB were low, without differences between elderly patients and those < 70 years. CONCLUSIONS: Choosing Wisely recommendations did not result in a decreased use of SLNB in the elderly at a Swiss university hospital.