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There has been increasing debate around how or if race and ethnicity should be used in medical research-including the conceptualization of race as a biological entity, a social construct, or a proxy for racism. The objectives of this narrative review are to identify and synthesize reported racial and ethnic inequalities in obstetrics and gynecology (ob/gyn) and develop informed recommendations for racial and ethnic inequity research in ob/gyn. A reproducible search of the eight highest impact ob/gyn journals was conducted. Articles published between January 1, 2010, and June 30, 2023 containing keywords related to racial and ethnic disparities, bias, prejudice, inequalities, and inequities were included (n=318). Data were abstracted and summarized into four themes: 1) access to care, 2) adherence to national guidelines, 3) clinical outcomes, and 4) clinical trial diversity. Research related to each theme was organized topically under the headings i) obstetrics, ii) reproductive medicine, iii) gynecologic cancer, and iv) other. Additionally, interactive tables were developed. These include data on study timeline, population, location, and results for every article. The tables enable readers to filter by journal, publication year, race and ethnicity, and topic. Numerous studies identified adverse reproductive outcomes among racial and ethnic minorities as compared to white patients, that persist despite adjusting for differential access to care, socioeconomic or lifestyle factors, and clinical characteristics. These include higher maternal morbidity and mortality among Black and Hispanic/Latinx patients; reduced success during fertility treatments for Black, Hispanic/Latinx, and Asian patients; and lower survival rates and lower likelihood of receiving guideline concordant care for gynecological cancers for non-white patients. We conclude that many racial and ethnic inequities in ob/gyn cannot be fully attributed to patient characteristics or access to care. Research focused on explaining these disparities based on biological differences incorrectly reinforces the notion of race as a biological trait. More research that deconstructs race and assesses efficacy of interventions to reduce these disparities is needed.
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OBJECTIVE: To assess whether the provision of fertility treatment for patients with polycystic ovary syndrome (PCOS) varies by patient and physician-level demographic characteristics. DESIGN: Retrospective cohort study. SETTING: University health system. PATIENT(S): Patients seeking care for PCOS and infertility from 2007-2021. INTERVENTION(S): Patient age, body mass index, race, ethnicity, estimated household income, primary insurance payor, provider sex, and provider medical specialty. MAIN OUTCOME MEASURE(S): Prescriptions for fertility treatment, including clomiphene citrate (CC), letrozole, and injectable gonadotropins. Differences in patient and physician demographics between patients who did as well as did not receive a prescription were identified with univariable analysis. Multilevel mixed-effects logistic regression was performed to determine associations between patient and physician demographics and prescription receipt. RESULT(S): A total of 3,435 patients with PCOS and infertility were identified, with a mean age of 31.1 ± 5.7 years. Of the 68.8% of patients who received a prescription, 47.8% of prescriptions were CC, 38.6% were letrozole, and 13.7% were injectable gonadotropins. There were lower odds of prescription receipt for Black patients compared with White patients (adjusted odds ratio [aOR], 0.75; 95% confidence interval [CI], 0.61-0.93), those with estimated household income below the federal poverty level compared with those above the national median (aOR, 0.71; 95% CI, 0.46-0.97), and those with public compared with commercial insurance (aOR, 0.53; 95% CI, 0.40-0.71). These disparities persisted in a subanalysis of patients prescribed oral medications only with lower odds of prescription receipt for Black compared with White patients (aOR, 0.74; 95% CI, 0.57-0.95), those with estimated household income below the federal poverty level compared with above the national median (aOR, 0.93; 95% CI, 0.87-0.98), and those with public compared with commercial insurance (aOR, 0.57; 95% CI, 0.42-0.76). Black patients waited, on average, 153.3 days longer than White patients, from the initial visit to the prescription receipt. Patients had lower odds of receiving any prescription from family medicine physicians (aOR, 0.36; 95% CI, 0.24-0.52) and general internal medicine physicians (aOR, 0.55; 95% CI, 0.42-0.73) compared with reproductive endocrinologists. CONCLUSION(S): Racial and socioeconomic disparities exist in the provision of infertility treatments for patients with PCOS. Fewer primary care physicians engaged in first-line fertility treatment, indicating an opportunity for physician education to improve access to fertility care.
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STUDY OBJECTIVE: To compare the prevalence and accrual of 30-day postoperative complications by operative time for open myomectomy (OM) and minimally invasive myomectomy (MIM). DESIGN: Retrospective cohort study SETTING: Hospitals participating in the National Surgical Quality Improvement Program database from January 2015 to December 2021. PATIENTS: Female patients aged ≥18 years undergoing OM or MIM. INTERVENTIONS: Patients were categorized into OM and MIM cohorts. Covariates associated with operative time and composite complications were identified using general linear model and chi-square or Fisher's exact test as appropriate. Adjusted spline regression was performed as a test of linearity between operative time and composite complications. Adjusted risk ratios of 30-day postoperative individual, minor, major, and composite complications by 60-minute operative time increments were estimated using Poisson regression with robust error variance. MEASUREMENTS AND MAIN RESULTS: Of 27 728 patients, 11 071 underwent MIM and 16 657 underwent OM. Mean operative times (SD) were 164.6 (82.0) for MIM and 129.2 (67.0) for OM. Raw composite complication rates were 5.5% for MIM and 15.8% for OM. Adjusted spline regression demonstrated linearity between operative time and relative risk of composite postoperative complications for both MIM and OM. MIM had higher adjusted relative risk (aRR, 95% CI) compared to OM of blood transfusion (1.55, 1.45-1.64 versus 1.29, 1.25-1.34), overall minor complications (1.13, 1.03-1.23 versus 1.01, 0.92-1.10), and overall major complications (1.43, 1.35-1.51 versus 1.27, 1.12-1.32). Operative time had greater impact on risk of composite complications for MIM than OM, reaching aRR 2.0 at 296 minutes versus 461 minutes for OM. CONCLUSION: OM has a higher overall rate of composite, minor, and major complications compared to MIM. While operative time is independently and linearly associated with postoperative complications with myomectomy regardless of approach, optimizing surgical efficiency for MIM may be more critical than for OM.
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Sistemas de Notificação de Reações Adversas a Medicamentos , Anafilaxia , Cefalosporinas , Hipersensibilidade a Drogas , United States Food and Drug Administration , Humanos , Anafilaxia/epidemiologia , Estados Unidos/epidemiologia , Sistemas de Notificação de Reações Adversas a Medicamentos/estatística & dados numéricos , Masculino , Adulto , Hipersensibilidade a Drogas/diagnóstico , Hipersensibilidade a Drogas/epidemiologia , Feminino , Cefalosporinas/efeitos adversos , Pessoa de Meia-Idade , Adolescente , Idoso , Criança , Adulto Jovem , Antibacterianos/efeitos adversos , Pré-Escolar , LactenteRESUMO
Excess body fat is a risk factor for metabolic diseases and is a leading preventable cause of morbidity and mortality worldwide. There is a strong need to find new treatments that decrease the burden of obesity and lower the risk of obesity-related comorbidities, including cardiovascular disease and type 2 diabetes. Pharmacologic mitochondrial uncouplers represent a potential treatment for obesity through their ability to increase nutrient oxidation. Herein, we report the in vitro and in vivo characterization of compound SHD865, the first compound to be studied in vivo in a newly discovered class of imidazolopyrazine mitochondrial uncouplers. SHD865 is a derivative of the furazanopyrazine uncoupler BAM15. SHD865 is a milder mitochondrial uncoupler than BAM15 that results in a lower maximal respiration rate. In a mouse model of diet-induced adiposity, 6-week treatment with SHD865 completely restored normal body composition and glucose tolerance to levels like those of chow-fed controls, without altering food intake. SHD865 treatment also corrected liver steatosis and plasma hyperlipidemia to normal levels comparable with chow-fed controls. SHD865 has maximal oral bioavailability in rats and slow clearance in human microsomes and hepatocytes. Collectively, these data identify the potential of imidazolopyrazine mitochondrial uncouplers as drug candidates for the treatment of obesity-related disorders.
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Diabetes Mellitus Tipo 2 , Intolerância à Glucose , Camundongos , Ratos , Humanos , Animais , Adiposidade , Intolerância à Glucose/tratamento farmacológico , Intolerância à Glucose/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Obesidade/etiologia , Fígado/metabolismo , Dieta Hiperlipídica/efeitos adversos , Camundongos Endogâmicos C57BLRESUMO
Metabolic disorders such as type 2 diabetes, fatty liver disease, hyperlipidemia, and obesity commonly co-occur but clinical treatment options do not effectively target all disorders. Calorie restriction, semaglutide, rosiglitazone, and mitochondrial uncouplers have all demonstrated efficacy against one or more obesity-related metabolic disorders, but it currently remains unclear which therapeutic strategy best targets the combination of hyperglycaemia, liver fat, hypertriglyceridemia, and adiposity. Herein we performed a head-to-head comparison of 5 treatment interventions in the female db/db mouse model of severe metabolic disease. Treatments included â¼60 % calorie restriction (CR), semaglutide, rosiglitazone, BAM15, and niclosamide ethanolamine (NEN). Results showed that BAM15 and CR improved body weight and liver steatosis to levels superior to semaglutide, NEN, and rosiglitazone, while BAM15, semaglutide, and rosiglitazone improved glucose tolerance better than CR and NEN. BAM15, CR, semaglutide, and rosiglitazone all had efficacy against hypertriglyceridaemia. These data provide a comprehensive head-to-head comparison of several key treatment strategies for metabolic disease and highlight the efficacy of mitochondrial uncoupling to correct multiple facets of the metabolic disease milieu in female db/db mice.
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Diabetes Mellitus Tipo 2 , Hepatopatia Gordurosa não Alcoólica , Camundongos , Animais , Feminino , Niclosamida/uso terapêutico , Rosiglitazona/farmacologia , Rosiglitazona/uso terapêutico , Etanolamina/uso terapêutico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/metabolismo , Restrição Calórica , Etanolaminas/uso terapêutico , Hepatopatia Gordurosa não Alcoólica/metabolismo , Obesidade/tratamento farmacológico , Obesidade/metabolismoRESUMO
Metagenomic next-generation sequencing (mNGS) is an untargeted technique capable of detecting all microbial nucleic acid within a sample. This protocol outlines our wet laboratory method for mNGS of cerebrospinal fluid (CSF) specimens and tissues from sterile sites. We use this method routinely in our clinical service, processing 178 specimens over the past 2.5 years in a laboratory that adheres to ISO:15189 standards. We have successfully used this protocol to diagnose multiple cases of encephalitis and hepatitis.
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A phytobezoar is the result of poorly digestible vegetable matter that accumulates in the gastrointestinal tract often forming a hard mass in the stomach. We present a case of a phytobezoar in a patient without predisposing risk factors, resulting in significant stomach distension initially believed to require high-risk surgical intervention but which ultimately resolved after 3 days of conservative treatment with prokinetic agents. The patient was discharged uneventfully and was recommended a low-fiber diet indefinitely while undergoing further workup for motility disorders.
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Dupilumab is a monoclonal antibody that targets interleukin (IL)-4 and IL-13 for use in moderate to severe eczema, asthma, and nasal polyposis. Our case report presents a 47-year-old woman with a history of nasal polyposis who developed angioedema after being treated with dupilumab for recurrent polyposis. She tolerated her first dose of dupilumab without reaction, but 10 days after her second injection, she developed swelling of the lips and forehead. She was treated with steroids with partial resolution. She received two further doses, which followed similar courses before dupilumab was discontinued. To the best of the authors' knowledge, this is the first report of dupilumab-associated angioedema in an adult. This report may be instructional for prescribers providing patients with anticipatory guidance or evaluating otherwise unexplained angioedema.
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OBJECTIVE: Calorie restriction is a first-line treatment for overweight individuals with metabolic impairments. However, few patients can adhere to long-term calorie restriction. An alternative approach to calorie restriction that also causes negative energy balance is mitochondrial uncoupling, which decreases the amount of energy that can be extracted from food. Herein we compare the metabolic effects of calorie restriction with the mitochondrial uncoupler BAM15 in the db/db mouse model of severe hyperglycemia, obesity, hypertriglyceridemia, and fatty liver. METHODS: Male db/db mice were treated with â¼50% calorie restriction, BAM15 at two doses of 0.1% and 0.2% (w/w) admixed in diet, or 0.2% BAM15 with time-restricted feeding from 5 weeks of age. Mice were metabolically phenotyped over 4 weeks with assessment of key readouts including body weight, glucose tolerance, and liver steatosis. At termination, liver tissues were analysed by metabolomics and qPCR. RESULTS: Calorie restriction and high-dose 0.2% BAM15 decreased body weight to a similar extent, but mice treated with BAM15 had far better improvement in glucose control. High-dose BAM15 treatment completely normalized fasting glucose and glucose tolerance to levels similar to lean db/+ control mice. Low-dose 0.1% BAM15 did not affect body mass but partially improved glucose tolerance to a similar degree as 50% calorie restriction. Both calorie restriction and high-dose BAM15 significantly improved hyperglucagonemia and liver and serum triglyceride levels. Combining high-dose BAM15 with time-restricted feeding to match the time that calorie restricted mice were fed resulted in the best metabolic phenotype most similar to lean db/+ controls. BAM15-mediated improvements in glucose control were associated with decreased glucagon levels and decreased expression of enzymes involved in hepatic gluconeogenesis. CONCLUSIONS: BAM15 and calorie restriction treatments improved most metabolic disease phenotypes in db/db mice. However, mice fed BAM15 had superior effects on glucose control compared to the calorie restricted group that consumed half as much food. Submaximal dosing with BAM15 demonstrated that its beneficial effects on glucose control are independent of weight loss. These data highlight the potential for mitochondrial uncoupler pharmacotherapies in the treatment of metabolic disease.
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Fígado Gorduroso , Doenças Metabólicas , Masculino , Camundongos , Animais , Restrição Calórica , Glicemia/análise , Peso Corporal , Glucose , Camundongos EndogâmicosRESUMO
STUDY OBJECTIVE: To compare postoperative complication rates between same-day discharge patients and patients admitted to hospital after minimally invasive myomectomy, stratified by patient demographics and perioperative variables including myoma burden. DESIGN: Retrospective cohort study. Setting Hospitals participating in the National Surgical Quality Improvement Program database from January 2015 to December 2019. PATIENTS: Female patients aged ≥18 years undergoing minimally invasive myomectomy. INTERVENTIONS: Patients were categorized into either the same-day discharge or admitted patient cohort. Univariate comparisons of demographics, perioperative variables, and 30-day postoperative complications were performed. Multivariate logistic regression was used to 1) identify demographic and perioperative factors associated with admission, and 2) compare postoperative complication rates of same-day discharge patients with those of admitted patients while adjusting for demographic and perioperative factors. MEASUREMENTS AND MAIN RESULTS: Eight thousand one hundred patients were recruited during the study period. The overall rate of same-day discharge was 57.2% in 2015 and 65.0% in 2019. The same-day discharge rate was 64.6% for patients with a smaller myoma burden (1-4 fibroids and ≤250 grams, Current Procedural Terminology 58545) and 56.8% for larger myoma burden (≥5 fibroids or >250 grams, Current Procedural Terminology 58546). Age, race, American Society of Anesthesiologists classification III or IV, preoperative hematocrit <36%, hypertension, diabetes, bleeding disorder, and increasing operative time were associated with admission to hospital. After adjusting for these variables, composite postoperative complication rates were similar between admitted patients and patients who were discharged the same day regardless of myoma burden (adjusted OR [aOR], 0.66; 95% confidence interval [CI] 0.18-2.47 for low myoma burden and aOR, 0.91; 95% CI 0.18-4.63 for high myoma burden). Admitted patients with both low (aOR, 9.1; 95% CI 2.27-37.04) and high (aOR, 8.24; 95% CI 1.59-42.49) myoma burdens were significantly more likely to receive a blood transfusion compared to same-day discharge patients. CONCLUSION: Same-day discharge after minimally invasive myomectomy, regardless of myoma burden, is associated with low complication rates. Our findings may aid in shared decision making on discharge planning.
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Laparoscopia , Leiomioma , Mioma , Miomectomia Uterina , Neoplasias Uterinas , Humanos , Feminino , Adolescente , Adulto , Miomectomia Uterina/efeitos adversos , Alta do Paciente , Estudos Retrospectivos , Leiomioma/cirurgia , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/cirurgia , Mioma/cirurgia , Hospitais , Neoplasias Uterinas/cirurgiaRESUMO
Acquired angioedema (AAE) due to deficiency of a C1 esterase inhibitor (C1-INH; AAE-C1-INH) is a rare and potentially fatal syndrome characterized by recurrent episodes of angioedema without urticaria. Often underdiagnosed due to its rarity and mimicry of common allergic reactions, AAE-C1-INH is associated with lymphoproliferative disorders, necessitating early recognition for improved outcomes. We present a case of a 63-year-old male diagnosed with AAE-C1-INH and concurrent stage 0 chronic lymphocytic leukemia (CLL), a rarely documented association. Despite chemotherapy, the patient experienced persistent angioedema until C1 esterase inhibitor therapy was initiated. This case underscores the importance of screening for lymphoproliferative disorders in AAE-C1-INH patients and explores refractory cases, urging further research into mechanisms and treatment strategies.
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Hydralazine, a commonly prescribed medication for hypertension, has been associated, albeit rarely, with the development of vasculitis. The case presentation involves a 51-year-old female with diabetes and hypertension who presented with a distinctive rash, pancytopenia, and positive findings for various antibodies. A collaborative approach involving rheumatology, hematology, and dermatology was crucial in diagnosing leukocytoclastic vasculitis attributed to hydralazine. Prompt discontinuation of hydralazine and the initiation of a tailored treatment plan led to favorable outcomes. The study sheds light on the clinical manifestations, diagnostic challenges, and management strategies associated with this rare side effect, providing valuable insights for healthcare providers. Increased awareness of hydralazine-induced vasculitis is crucial for early recognition and proper management, ultimately contributing to improved patient outcomes in hypertension management.
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Eosinophilic cellulitis (EC) or Wells' syndrome, characterized by its rarity and diverse clinical presentations, presents substantial challenges in diagnosis and treatment. This case study details the challenging journey of a 48-year-old woman with non-specific skin lesions, showcasing the persistence of dermatitis despite exhaustive attempts at various interventions outlined in the literature. In the absence of a consensus on optimal management for EC, this study introduces a transformative solution through the utilization of dupilumab, a monoclonal antibody targeting interleukin-4/interleukin-13. The patient experienced marked improvement and resolution of dermatitis following dupilumab treatment alone, highlighting the efficacy of this targeted immunomodulatory approach in cases refractory to traditional therapies. This pioneering case underscores the significance of exploring innovative treatments and suggests dupilumab as a potential breakthrough therapeutic option in addressing EC refractory to standard medical management.
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Pembrolizumab, a humanized monoclonal anti-programmed cell death protein 1 (PD1) antibody, has shown efficacy in various malignancies. This article presents a case of stage III squamous cell carcinoma of the bladder treated with pembrolizumab, resulting in the development of a rare overlap syndrome known as myocarditis, myositis, and myasthenia gravis (IM3OS). While immune checkpoint inhibitors like pembrolizumab demonstrate notable antitumor activity, they also pose the risk of severe immune-related adverse events. The case underscores the importance of the early detection of IM3OS and the potential dangers associated with delayed diagnosis, offering valuable insights for healthcare providers managing patients on pembrolizumab therapy.
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Objective: To evaluate racial and ethnic disparities in the surgical management of ectopic pregnancy over time. Design: Retrospective cohort study. Setting: None. Patients: Surgically-managed cases of patients with tubal ectopic pregnancy within the American College of Surgeons National Surgical Quality Improvement Program database between 2010 and 2019. Interventions: None. Main outcome measures: Surgical approach (laparoscopic compared with open) and procedure (salpingectomy compared with salpingostomy/other). Results: Of 7791 patients undergoing surgical management of tubal ectopic pregnancy, 21.8% identified as Hispanic, 24.5% as Black, 9.4% as Asian/other, and 44.3% as White. Use of laparoscopy increased 1.3% per year from 81.4% in 2010 to 91.0% in 2019 (95% confidence interval [CI], 0.010-0.016). Odds of undergoing laparoscopic surgery were lower in Black (adjusted odds ratio [aOR] 0.52; 95% CI, 0.45-0.61) and Hispanic patients (aOR 0.52; 95% CI, 0.44-0.61) compared with White patients and remained similar over time. The use of salpingectomy increased by 1.1% per year from 80.6% in 2010 to 94.7% in 2019 (95% CI, 0.009-0.014). Odds of undergoing salpingectomy were higher among Black (aOR 1.78, 95% CI 1.43-2.23) and Hispanic patients (aOR 1.54; 95% CI, 1.24-1.93) and lower among Asian patients (aOR 0.73, 95% CI, 0.56-0.95) compared with White patients. These ratios remained similar for Black and Asian patients over time. Conclusions: Despite the increased use of laparoscopy and salpingectomy in the surgical management of ectopic pregnancy over time, Black and Hispanic patients remain less likely to undergo minimally invasive surgery and more likely to undergo salpingectomy compared with White patients.
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OBJECTIVE: To investigate whether herpes simplex virus type 1 (HSV-1) infection was associated with rates of cognitive decline or whole brain atrophy among individuals from the Dominantly Inherited Alzheimer Network (DIAN). METHODS: Among two subsets of the DIAN cohort (age range 19.6-66.6 years; median follow-up 3.0 years) we examined (i) rate of cognitive decline (N = 164) using change in mini-mental state examination (MMSE) score, (ii) rate of whole brain atrophy (N = 149), derived from serial MR imaging, calculated using the boundary shift integral (BSI) method. HSV-1 antibodies were assayed in baseline sera collected from 2009-2015. Linear mixed-effects models were used to compare outcomes by HSV-1 seropositivity and high HSV-1 IgG titres/IgM status. RESULTS: There was no association between baseline HSV-1 seropositivity and rates of cognitive decline or whole brain atrophy. Having high HSV-1 IgG titres/IgM was associated with a slightly greater decline in MMSE points per year (difference in slope - 0.365, 95% CI: -0.958 to -0.072), but not with rate of whole brain atrophy. Symptomatic mutation carriers declined fastest on both MMSE and BSI measures, however, this was not influenced by HSV-1. Among asymptomatic mutation carriers, rates of decline on MMSE and BSI were slightly greater among those who were HSV-1 seronegative. Among mutation-negative individuals, no differences were seen by HSV-1. Stratifying by APOE4 status yielded inconsistent results. INTERPRETATION: We found no evidence for a major role of HSV-1, measured by serum antibodies, in cognitive decline or whole brain atrophy among individuals at high risk of early-onset AD.