Dines, Virginia

Abstract Preeclampsia and other hypertensive disorders of pregnancy are major contributors to maternal morbidity and mortality worldwide. This group of disorders includes chronic hypertension, gestational hypertension, preeclampsia, preeclampsia superimposed on chronic hypertension, and eclampsia. The body undergoes important physiological changes during pregnancy to allow for normal placental and fetal development. Several mechanisms have been proposed that may lead to preeclampsia, including abnormal placentation and placental hypoxia, impaired angiogenesis, excessive pro‐inflammatory response, immune system imbalance, abnormalities of cellular senescence, alterations in regulation and activity of angiotensin II, and oxidative stress, ultimately resulting in upregulation of multiple mediators of endothelial cell dysfunction leading to maternal disease. The clinical implications of preeclampsia are significant as there are important short‐term and long‐term health consequences for those affected. Preeclampsia leads to increased risk of preterm delivery and increased morbidity and mortality of both the developing fetus and mother. Preeclampsia also commonly leads to acute kidney injury, and women who experience preeclampsia or another hypertensive disorder of pregnancy are at increased lifetime risk of chronic kidney disease and cardiovascular disease. An understanding of normal pregnancy physiology and the pathophysiology of preeclampsia is essential to develop novel treatment approaches and manage patients with preeclampsia and hypertensive disorders of pregnancy. © 2023 American Physiological Society. Compr Physiol 13:4231‐4267, 2023.

BACKGROUND: Hypertensive disorders of pregnancy (HDP) have been associated with an increased risk of chronic hypertension for both mothers and offspring. We sought to quantify the incidence of chronic hypertension in offspring from HDP-affected pregnancies in a large, population-based cohort study. Furthermore, we evaluate the association of HDP exposure in utero and maternal chronic hypertension in offspring. METHODS: We performed a population-based cohort study of 8755 individuals born during 1976 to 1982 to 7544 women who all resided in the same community at the time of delivery. HDP were identified using a previously validated algorithm. Diagnosis of chronic hypertension in mothers and their offspring was determined using diagnostic codes. Cox proportional hazards regression was used to assess the association between HDP and chronic hypertension. RESULTS: HDP exposure (hazard ratio, 1.50 [95% CI, 1.18–1.90]) and maternal chronic hypertension (hazard ratio, 1.73 [95% CI, 1.48–2.02]) were both associated with a significant increased risk for chronic hypertension in offspring. Both risk factors remained significantly associated with increased risk of hypertension in offspring when included together in a multivariate model. Having both exposures was associated with a 2.4-fold increase in the risk of hypertension in offspring, suggesting a synergistic additive interaction. CONCLUSIONS: HDP exposure in gestation and maternal hypertension are both independently associated with an increased risk of chronic hypertension in offspring. Our results suggest that HDP exposure in utero, in addition to maternal chronic hypertension, may lead to a greater risk for the development of hypertension in offspring.

Abstract Background: Accurate interpretation of laboratory values with sex-specific reference ranges presents a challenge in transgender individuals on gender affirming hormone therapy (GAHT). Creatinine (Cr), the most common marker used for kidney function, varies significantly with body mass and composition. Both Modification of Diet in Renal Disease (MDRD) and Chronic Kidney Disease Epidemiology Collaboration (CKD-Epi) equations account for sex in estimating glomerular filtration rate. GAHT can effect Cr values in 2 potential ways: 1) by causing changes in muscle mass and body fat redistribution as early as 3 months after GAHT initiation and 2) by direct effects of sex hormones on kidney function. Previous studies have shown Cr values approaching affirmed gender identity as early as 6 months when on GAHT without mention of sex steroid levels. In this study we sought to describe the changes in serum Cr after initiation of GAHT in an effort to better understand expected changes and interpretation of lab data in TG individuals. Methods: A retrospective chart analysis on all adult TG patients initiated on GAHT at our institution from January 2011 to 2020 was completed. We reviewed demographics, baseline health information, body mass index, and lab values including Cr, sex hormone levels, A1C, and fasting blood glucose. Lab values were obtained prior to GAHT, at the start of GAHT, at 3, 6, and 12 months after GAHT. Matched pair testing was conducted with sex steroid levels and Cr values in transgender men (TM) on testosterone and transgender women (TW) on estradiol in order to compare the median pre GAHT Cr to median Cr levels at 3, 6, and 12 months. Results: 84 TW with a median age of 30 and 24 TM with a median age of 23 were included for analysis. TW and TM had a low rate of existing kidney disease (4.9%, 0%), diabetes mellitus (4.8%, 0%), and hypertension (10.8%, 4.5%) respectively. TW on GAHT achieved a goal estradiol level (≥100 pg/ml) at a rate of 37.3%, 51.7%, and 71.1% and suppressed testosterone to a goal level (<60ng/ml) at a rate of 44.4%, 54.7%, and 76.5% at 3, 6, and 12 months respectively. There was no significant change in Cr values at 3 months, but significantly decreased on average by -0.07 (p<0.001) at 6 months, and by -0.09 (p<0.001) at 12 months. TM on GAHT achieved a goal testosterone level (≥240 ng/dl) at a rate of 64.3%, 80.0%, and 72.3% at 3, 6, and 12 months respectively. Cr values increased significantly on average by 0.14 (p=0.036) at 3 months, by 0.21 (p=0.004) at 6 months, and by 0.15 (p=0.003) at 12 months. Conclusions: In TW on GAHT, clinicians can consider using affirmed gender Cr reference ranges as early as 6 months. Similarly in TM on GAHT, affirmed gender Cr reference ranges can be used as early at 3 months. It remains to be seen whether changes in Cr levels reflect changes in sex steroid levels or sex steroid direct effects. Additionally, research is needed to determine if change in Cr levels reflect true changes in GFR.

Background: Parenthood during medical training is common and impacts trainee well-being. However, current graduate medical education parental health policies are often limited in scope. We explored current fellowship trainees’ knowledge of/satisfaction with current policies as well as interest in potential changes/additions to existing policies. Methods: Fellowship program directors/coordinators at a three-site academic institution were surveyed and information was collected from 2015 to 2019 regarding fellow demographics and parental health policies. We distributed an electronic survey to fellows containing Likert-type-scale questions rating knowledge/level of satisfaction with current parental health policies and interest in potential additions/modifications to current policies. Results: Thirty-five of 47 (74%) fellowship programs responded. An average of 11% of female fellows and 15% of male fellows took parental leave during the study period. Three (9%) of the programs had at least one additional parental health policy beyond institutional graduate medical education policies. In the fellow survey, 175 of 609 fellows responded (28.7%), of which 84 (48.6%) were female. Although 89.1% agreed/strongly agreed that parental health is an important part of health and well-being for fellows, only 32% were satisfied/very satisfied with current policies (no significant sex-related differences). Fellows reported the following potential interventions as important/very important: 79.2% increased (paid) maternity leave (72.7% male, 86.7% female, p = 0.02), 78% increased (paid) paternity leave (76.4% male, 81.9% female, p = 0.37), 72.3% part-time return to work (60.2% male, 84.3% female, p = 0.0005), 63% coverage for workup/management of infertility (52.3% male, 74.7% female, p = 0.002), and 79.9% on-site day care (70.7% male, 89.2% female, p = 0.003). Conclusions: Parental health includes multiple domains, not all of which are covered by current policies. Fellows feel that parental health is an important part of overall health and well-being, but most are not satisfied with current policies. Expanded access to parental leave and new policies (part-time return to work, infertility management, and on-site day care) are opportunities for innovation.

INTRODUCTION: Varicella Zoster Virus (VZV) is a DNA virus that leads to two clinical syndromes: varicella (primary) and herpes zoster or shingles (secondary). Disseminated infection is most common in immunocompromised hosts and can lead to multi-organ involvement including hepatitis, pneumonitis, encephalitis and others. Here, we describe a case of a young woman with human immunodeficiency virus (HIV) and primary varicella infection leading to VZV hepatitis. CASE DESCRIPTION/METHODS: A 35-year-old woman presented with a 1-week history of fevers, right upper quadrant and epigastric pain, and a non-pruritic, non-painful rash. Her past medical history was significant for a diagnosis of HIV 5 years prior, not currently on treatment. Upon presentation, vital signs were within normal limits except for a fever of 38.8°C. Physical examination was notable for multiple crusted erosions and papules present on her face, trunk and extremities (Figures 1 and 2). Laboratory evaluation was notable for alanine aminotransferase level 291 U/L, aspartate aminotransferase level 260 U/L, alkaline phosphatase level 135 U/L, total bilirubin 0.4 mg/dL, leukocytes 8 × 10 9 /L, and platelet count 132 × 10 9 /L. CD4 count was 118 cells/mcL and HIV-1 RNA 4,120,000 copies/mL. Computed tomography abdomen/pelvis demonstrated diffuse heterogeneity of the hepatic parenchyma (Figure 3). She underwent liver biopsy and pathology demonstrated hepatic parenchyma with portal and lobular inflammation but no necrosis. VZV polymerase chain reaction (PCR) from the liver and facial lesion swab returned positive. She was treated with 4 days of IV acyclovir with improvement in her fevers and transaminitis and then transitioned to oral valacyclovir. HAART was also initiated two days after the start of IV acyclovir. DISCUSSION: The differential for fever and widespread rash in an immunocompromised individual is broad, and includes disseminated herpes simplex virus, VZV, secondary syphilis, disseminated gonococcal infection, parvovirus, cryptococcosis and others. While uncomplicated VZV can be treated with supportive care or oral antivirals, such as acyclovir, valacyclovir, or famciclovir, an immunocompromised host with disseminated VZV should typically be admitted to the hospital for intravenous acyclovir. Biopsy proven VZV hepatitis is rare and is associated with a high mortality. Notably, our patient's VZV IgM and IgG were negative, indicating the need for a high degree of suspicion if the clinical scenario is consistent with VZV.

INTRODUCTION: Recurrent pancreatitis with pseudocyst can present with gastric outlet obstruction. Endoscopic evaluation should be utilized in certain contexts, especially to exclude more sinister causes of this presentation. CASE DESCRIPTION/METHODS: A 43-year-old woman with a history of alcohol use disorder presented with a gastric outlet obstruction. This was felt secondary to a pancreatic pseudocyst given multiple episodes of recurrent pancreatitis, the last being 1 week prior to her current admission. On presentation, physical exam was significant for ascites and epigastric tenderness. Labs were notable for AST 214 U/L, ALT 99 U/L, alkaline phosphatase 147 U/L, lipase of 203 U/L, and negatives serum alcohol. Notably, Ca 19-9 was elevated to 154 IU/mL during admission 2 weeks prior. Computed tomography chest and abdomen revealed bilateral pleural effusions, pseudocyst, and abdominal ascites. A thoracentesis and paracentesis were performed with cytology for both peritoneal fluid and pleural fluid confirming metastatic adenocarcinoma. Given her refractory symptoms, an esophagogastroduodenoscopy (EGD) was performed which showed an obstructing tumor at the gastric outlet with biopsies revealing poorly differentiated gastric adenocarcinoma. A gastric stent was placed; however, she had continued nausea and vomiting. Repeat EGD showed gastric stent failure and subsequent endoscopic gastrojejunostomy with Axios stent was placed. The patient's functional status declined rapidly as a result of her advanced malignancy and on hospital day 8 she suffered a cardiac arrest, passing shortly after being transitioned to comfort cares. DISCUSSION: The patient's prior history of alcohol use disorder, recurrent pancreatitis, and imaging consistent with pancreatic pseudocyst made this case prone to numerous cognitive errors initially obscuring the etiology of her gastric outlet obstruction and pancreatitis. By reframing the presentation, we were able to question pancreatic pseudocyst as the sole source of the gastric outlet obstruction. Traditionally, Ca 19-9 is associated with pancreatic adenocarcinoma. It also can be elevated in the setting of other gastric malignancies and acute pancreatitis. In pancreatitis, absolute value and trends of Ca 19-9 can help differentiate between pancreatitis and malignancy. The diagnostic uncertainty around this patient's presentation with recurrent pancreatitis, pseudocyst, and gastric outlet obstruction required endoscopic evaluation to ultimately diagnose metastatic gastric adenocarcinoma.