Recruiting transgender men in the Southeastern United States for genital microbiome research: Lessons learned.

BACKGROUND: Transgender men (TGM) are underrepresented in genital microbiome research. Our prospective study in Birmingham, AL investigated genital microbiota changes over time in TGM initiating testosterone, including the development of incident bacterial vaginosis (iBV). Here, we present lessons learned from recruitment challenges encountered during the conduct of this study. METHODS: Inclusion criteria were assigned female sex at birth, TGM or non-binary identity, age ≥18 years, interested in injectable testosterone but willing to wait 7 days after enrollment before starting, and engaged with a testosterone-prescribing provider. Exclusion criteria were recent antibiotic use, HIV/STI infection, current vaginal infection, pregnancy, or past 6 months testosterone use. Recruitment initiatives included community advertisements via flyers, social media posts, and referrals from local gender health clinics. RESULTS: Between February 2022 and October 2023, 61 individuals contacted the study, 17 (27.9%) completed an in-person screening visit, and 10 (58.8%) of those screened were enrolled. The primary reasons for individuals failing study screening were having limited access to testosterone-prescribing providers, already being on testosterone, being unwilling to wait 7 days to initiate testosterone therapy, or desiring the use of topical testosterone. Engagement of non-White TGM was also minimal. CONCLUSION: Despite robust study inquiry by TGM, screening and enrollment challenges were faced including engagement by TGM not yet in care and specific study eligibility criteria. Excitement among TGM for research representation should be leveraged in future work by engaging transgender community stakeholders at the inception of study development, particularly regarding feasibility of study inclusion and exclusion criteria, as well as recruitment of TGM of color. These results also highlight the need for more clinical resources for prescribing gender-affirming hormone therapy, especially in the Southeastern US.

"Society Isn't Designed for Us to Win": Trauma and Sexual Healthcare Experiences Among Transgender Women in the Southeastern United States.

Transgender women (TGW) are disproportionately affected by sexually transmitted infections (STIs). Experienced trauma threatens TGW's commitment to sexual healthcare. Trauma-informed approaches to sexual healthcare can improve engagement. This study aimed to characterize the trauma experienced by TGW in the Southeastern US, especially related to sexual health. TGW completed in-depth individual interviews guided by the Modified Social Ecological Model (MSEM) and Minority Stress framework. Interviews explored the nature of trauma, sexual health, and their intersection in TGW's lives, and a thematic analysis was performed. Between August 2022 and January 2023, 13 TGW enrolled (69% Black, 31% White). Mental illness was common (77%). Five participants (38%) were HIV+, and seven (54%) reported lifetime STI history. Themes reflected societal (barriers to healthcare, anti-transgender legislation), community (misgendering/deadnaming), network (limited support), and individual (dysphoria, sex work, fear for physical safety, stigma, mental health conditions, race) stressors. The physical/sexual violence and resilience themes pervaded all stressor levels. Medical mistrust was exacerbated by past traumatic experiences within sexual healthcare settings. Resilience and transgender representation in healthcare settings were protective. Various experienced traumas and their cumulative effects were pervasive in the daily lives of TGW. Development of targeted interventions to improve sexual health engagement of TGW must optimize personal strengths and provide holistic support.

Association between frailty and overall survival among older adults with hepatocellular carcinoma.

INTRODUCTION: Older adults undergoing cancer treatment often experience more treatment-related toxicities and increased risk of mortality compared to younger patients. The role of frailty among older individuals as a predictor of outcomes has gained growing significance. We evaluated the association between frailty and overall survival (OS) in patients with hepatocellular carcinoma (HCC) ≥60 years. MATERIALS AND METHODS: Older adults ≥60 years with HCC enrolled in a prospective single-institution registry underwent a patient-reported geriatric assessment (GA) covering multiple health domains related to prior to their initial medical oncology appointment. Frailty was measured using a 44-item deficit accumulation frailty index. We categorized patients as robust, pre-frail, and frail using standard cutpoints. The primary outcome was overall survival (OS). Univariable and multivariable models were built to evaluate the association between frailty and OS after adjusting for potential confounders. RESULTS: Total of 116 older adults with HCC with a median age of 67 years were enrolled; 82% male, 27% Black, and 78% with stage III/IV disease. Overall, 19 (16.3%) were robust, 39 (33.6%) pre-frail, and 58 (50.1%) frail. There were 76 patients receiving liver directed therapy. Of these, 13 (17%) were robust, 26 (34%) were pre-frail, and 37 (49%) were frail. Over a median follow up of 0.9 years, 53 patients died. After adjusting for age, stage, etiology, and Child-Pugh class, being frail (vs. robust) was associated with worse OS (hazard ratio (HR) 2.6 [95% CI 1.03-6.56]; p = 0.04). DISCUSSION: Half of the participants in this study were frail, which was independently associated with worse survival in adults ≥60 years of age with HCC. Identification of pre-treatment frailty may allow opportunities to guide treatment decisions and prognostication.

Impact of testosterone use on the vaginal microbiota of transgender men, including susceptibility to bacterial vaginosis: study protocol for a prospective, observational study.

INTRODUCTION: The effect of testosterone (T) therapy on the vaginal microbiota of transgender men (TGM) is not well characterised, although one cross-sectional study comparing the vaginal microbiota of cisgender women to TGM on T≥1 year found that, in 71% of the TGM, the vaginal microbiota was less likely to be Lactobacillus-dominated and more likely to be enriched with >30 other bacterial species, many associated with bacterial vaginosis (BV). This prospective study aims to investigate changes in the composition of the vaginal microbiota over time in TGM who retain their natal genitalia (ie, vagina) and initiate T. In addition, we will identify changes in the vaginal microbiota preceding incident BV (iBV) in this cohort while investigating behavioural factors, along with hormonal shifts, which may be associated with iBV. METHODS AND ANALYSIS: T-naïve TGM who have not undergone gender-affirming genital surgery with normal baseline vaginal microbiota (ie, no Amsel criteria, normal Nugent Score with no Gardnerella vaginalis morphotypes) will self-collect daily vaginal specimens for 7 days prior to initiating T and for 90 days thereafter. These specimens will be used for vaginal Gram stain, 16S rRNA gene sequencing and shotgun metagenomic sequencing to characterise shifts in the vaginal microbiota over time, including development of iBV. Participants will complete daily diaries on douching, menses and behavioural factors including sexual activity during the study. ETHICS AND DISSEMINATION: This protocol is approved through the single Institutional Review Board mechanism by the University of Alabama at Birmingham. External relying sites are the Louisiana State University Health Sciences Center, New Orleans Human Research Protection Program and the Indiana University Human Research Protection Program. Study findings will be presented at scientific conferences and peer-reviewed journals as well as shared with community advisory boards at participating gender health clinics and community-based organisations servicing transgender people. REGISTRATION DETAILS: Protocol # IRB-300008073.

SPONTANEOUS RESOLUTION OF PRIMARY HYPERCORTISOLISM OF CUSHING DISEASE AFTER PITUITARY HEMORRHAGE.

OBJECTIVE: To describe a case of spontaneous resolution of primary hypercortisolism from Cushing disease (CD) due to pituitary apoplexy (PA). METHODS: Clinical, laboratory, and pathologic information are described. RESULTS: A 59-year-old female presented with a headache, a 2.3 cm sellar mass with a questionable hemorrhagic component, and clinical signs of hypercortisolism. On further evaluation, she had an increased 24-hour urine free cortisol, abnormal serum cortisol during a low dose dexamethasone suppression test, and an elevated plasma adrenocorticotropic hormone (ACTH), consistent with pituitary CD. As she was being prepared for surgical resection, she was noted to have spontaneous biochemical remission associated with resolution of her symptoms of hypercortisolism, and a repeat magnetic resonance imaging scan showed shrinkage of the sellar mass. She has been managed conservatively since and remains in clinical/biochemical remission until present time, 18 months following her initial presentation. CONCLUSION: We report a case of spontaneous resolution of CD from symptomatic hemorrhage within an ACTH-secreting pituitary adenoma, or PA. This has been rarely reported in the medical literature. The fact that she did not pass through a phase of adrenal withdrawal, makes us suspect a residual functional adenoma within or around the sella which may eventually grow, causing her disease to recur, as has been reported. Hence, continued monitoring will be required.

Empagliflozin in Heart Failure: Diuretic and Cardiorenal Effects.

BACKGROUND: Sodium-glucose cotransporter-2 inhibitors improve heart failure-related outcomes. The mechanisms underlying these benefits are not well understood, but diuretic properties may contribute. Traditional diuretics such as furosemide induce substantial neurohormonal activation, contributing to the limited improvement in intravascular volume often seen with these agents. However, the proximal tubular site of action of the sodium-glucose cotransporter-2 inhibitors may help circumvent these limitations. METHODS: Twenty patients with type 2 diabetes mellitus and chronic, stable heart failure completed a randomized, placebo-controlled crossover study of empagliflozin 10 mg daily versus placebo. Patients underwent an intensive 6-hour biospecimen collection and cardiorenal phenotyping at baseline and again after 14 days of study drug. After a 2-week washout, patients crossed over to the alternate therapy with the above protocol repeated. RESULTS: Oral empagliflozin was rapidly absorbed as evidenced by a 27-fold increase in urinary glucose excretion by 3 hours (P<0.0001). Fractional excretion of sodium increased significantly with empagliflozin monotherapy versus placebo (fractional excretion of sodium, 1.2±0.7% versus 0.7±0.4%; P=0.001), and there was a synergistic effect in combination with bumetanide (fractional excretion of sodium, 5.8±2.5% versus 3.9±1.9%; P=0.001). At 14 days, the natriuretic effect of empagliflozin persisted, resulting in a reduction in blood volume (-208 mL [interquartile range, -536 to 153 mL] versus -14 mL [interquartile range, -282 to 335 mL]; P=0.035) and plasma volume (-138 mL, interquartile range, -379 to 154±453 mL; P=0.04). This natriuresis was not, however, associated with evidence of neurohormonal activation because the change in norepinephrine was superior (P=0.02) and all other neurohormones were similar (P<0.34) during the empagliflozin versus placebo period. Furthermore, there was no evidence of potassium wasting (P=0.20) or renal dysfunction (P>0.11 for all biomarkers), whereas both serum magnesium (P<0.001) and uric acid levels (P=0.008) improved. CONCLUSIONS: Empagliflozin causes significant natriuresis, particularly when combined with loop diuretics, resulting in an improvement in blood volume. However, off-target electrolyte wasting, renal dysfunction, and neurohormonal activation were not observed. This favorable diuretic profile may offer significant advantage in the management of volume status in patients with heart failure and may represent a mechanism contributing to the superior long-term heart failure outcomes observed with these agents. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03027960.

Relationships between blood pressure and blood glucose among offspring of parents with type 2 diabetes: Prediction of incident dysglycemia in a biracial cohort.

AIMS: We assessed blood pressure (BP) and blood glucose (BG) values in healthy subjects, and examined baseline BP as a predictor of incident prediabetes during follow-up. METHODS: Participants in the Pathobiology of Prediabetes in a Biracial Cohort (POP-ABC) study underwent screening assessments (anthropometry, BP, OGTT) and were stratified into normal BP (NBP), prehypertension, or hypertension, and normal glucose regulation (NGR), prediabetes (IFG/IGT), or type 2 diabetes (T2D) status. NGR subjects who met all inclusion criteria were enrolled in a 5-yr prospective study, with the primary outcome of incident prediabetes. RESULTS: We screened 602 adults (341 black, 261 white) and enrolled 343 (193 black, 150 white) for prospective follow-up. Systolic and diastolic BP correlated significantly with fasting and nonfasting BG (P=0.003-<0.0001). Compared to NGR group, more prediabetic subjects had prehypertension (42.5% vs. 36.2%) and fewer had NBP (35.9% vs. 48.6%) (P=0.009). During ~5years of follow-up, 26.3% of NBP and 35.7% of prehypertensive subjects developed prediabetes (P=0.02). Kaplan-Meier analysis showed higher probability of incident prediabetes among participants with prehypertension compared to NBP during ~5years of follow-up (P=0.0012). CONCLUSIONS: In our biracial cohort, BP and BG values were significantly correlated, and BP status predicted incident prediabetes among initially normoglycemic individuals. These findings suggest co-evolution of factors involved in the dysregulation of BP and BG.

Penetrating aortic ulcer leading to aortic dissection.

Rarely, penetrating atherosclerotic ulcers can rupture into the wall of the aorta, resulting in acute aortic dissection. This article describes a woman with an incidental diagnosis of type A aortic dissection secondary to a penetrating atherosclerotic ulcer of the ascending aorta. Although surgical repair of the aortic root was recommended, the patient refused treatment and left against medical advice.

Renal Cancer in Recipients of Kidney Transplant.

The aim of our study is to determine characteristics and outcomes of kidney cancer in renal transplant recipients. MEDLINE® database was searched in June 2015 to identify cases of kidney cancer in renal transplant recipients. We include also a new case. Descriptive statistics were used for analysis. Forty-eight (48) recipients reported in 25 papers met the eligibility criteria. The median age was 47 years (range 9-66); 27% were females. Chronic glomerulonephritis, cystic kidney disease and hypertension were common indications for renal transplant. Among donors 24% were females and the median age was 52.5 years (17-73); 62% of kidney cancers were donor-derived. The median interval between transplant and cancer diagnosis was shorter for cancer of recipient versus donor origin (150 vs. 210 days). Clear cell carcinoma was diagnosed in 17%. 25% had metastasis at diagnosis. Kidney explantation or excision was done in 90% and 84% of cases with and without metastasis respectively. The median survival was 72 months. Actuarial 1-year and 5-year survival rates were 73.4% and 55.1% respectively. Among the recipients from 7 donors who subsequently developed malignancy, 57% were dead within a year. Kidney transplant recipients have a small risk of kidney cancer, which affects younger patients and occurs within a year of transplant, likely due to immunosuppression. Whether the use of older donors may increase the likelihood needs further investigation. The presence of metastasis, explantation or excision of affected kidney and development of cancer in donors predict outcomes. The results may guide patient education and informed decision-making.

Cerebral edema among adults with diabetic ketoacidosis and hyperglycemic hyperosmolar syndrome: Incidence, characteristics, and outcomes.

Ischemic stroke is an uncommon complication among adults with DKA, that confers a worse prognosis. Traditional risk factors for stroke including older age, stroke history, hypertension and hyperlipidemia appear to predict the risk of IS in these patients. Demographic and clinical characteristics of patients with diabetic ketoacidosis and hyperosmolar hyperglycemic syndrome patients, with and without cerebral edema.

An uncommon cause of acute pulmonary edema.

Acute cardiogenic pulmonary edema secondary to catecholamine-induced cardiomyopathy is a very uncommon and fatal initial presentation of pheochromocytoma. However, with early clinical suspicion and aggressive management, the condition is reversible. This case report describes a patient who presented with hypertension, dyspnea, and cough with bloody streaks, and who recovered within 48 hours after appropriate treatment.