Mara, Kristin C.

The use of the kidney function biomarker cystatin C (cysC) can improve the accuracy of vancomycin dosing for target trough attainment in nonobese patients. It is unknown whether cysC can also improve vancomycin target trough attainment in overweight and obese patients. We conducted a retrospective observational study of overweight or obese hospitalized adults with stable renal function administered intravenous vancomycin between January 2011 and July 2019. Linear regression models were used to predict initial steady-state vancomycin troughs using several factors, including various cysC- and serum creatinine (SCr)-based estimates of kidney function.

Abstract Data directly demonstrating the relationship between urinary oxalate (UOx) excretion and stone events in those with enteric hyperoxaluria (EH) are limited. Therefore, we assessed the relationship between UOx excretion and risk of kidney stone events in a retrospective population-based EH cohort. In all, 297 patients from Olmsted County, Minnesota were identified with EH based upon having a 24-h UOx ≥40 mg/24 h preceded by a diagnosis or procedure associated with malabsorption. Diagnostic codes and urologic procedures consistent with kidney stones during follow-up after baseline UOx were considered a new stone event. Logistic regression and accelerated failure time modeling were performed as a function of UOx excretion to predict the probability of new stone event and the annual rate of stone events, respectively, with adjustment for urine calcium and citrate. Mean ± standard deviation age was 51.4 ± 11.4 years and 68% were female. Median (interquartile range) UOx was 55.4 (46.6–73.0) mg/24 h and 81 patients had one or more stone event during a median follow-up time of 4.9 (2.8–7.8) years. Higher UOx was associated with a higher probability of developing a stone event (P < 0.01) and predicted an increased annual risk of kidney stones (P = 0.001). Estimates derived from these analyses suggest that a 20% decrease in UOx is associated with 25% reduction in the annual odds of a future stone event. Thus, these data demonstrate an association between baseline UOx and stone events in EH patients and highlight the potential benefit of strategies to reduce UOx in this patient group. Background Data directly demonstrating the relationship between urinary oxalate (UOx) excretion and stone events in those with enteric hyperoxaluria (EH) are limited. Methods We assessed the relationship between UOx excretion and risk of kidney stone events in a retrospective population-based EH cohort. In all, 297 patients from Olmsted County, Minnesota were identified with EH based upon having a 24-h UOx ≥40 mg/24 h preceded by a diagnosis or procedure associated with malabsorption. Diagnostic codes and urologic procedures consistent with kidney stones during follow-up after baseline UOx were considered a new stone event. Logistic regression and accelerated failure time modeling were performed as a function of UOx excretion to predict the probability of new stone event and the annual rate of stone events, respectively, with adjustment for urine calcium and citrate. Results Mean ± SD age was 51.4 ± 11.4 years and 68% were female. Median (interquartile range) UOx was 55.4 (46.6–73.0) mg/24 h and 81 patients had ≥1 stone event during a median follow-up time of 4.9 (2.8–7.8) years. Higher UOx was associated with a higher probability of developing a stone event (P < 0.01) and predicted an increased annual risk of kidney stones (P = 0.001). Estimates derived from these analyses suggest that a 20% decrease in UOx is associated with 25% reduction in the annual odds of a future stone event. Conclusions These data demonstrate an association between baseline UOx and stone events in EH patients and highlight the potential benefit of strategies to reduce UOx in this patient group.

Objective The diagnosis of autoimmune pancreatitis (AIP) is challenging. Sonographic and cross-sectional imaging findings of AIP closely mimic pancreatic ductal adenocarcinoma (PDAC) and techniques for tissue sampling of AIP are suboptimal. These limitations often result in delayed or failed diagnosis, which negatively impact patient management and outcomes. This study aimed to create an endoscopic ultrasound (EUS)-based convolutional neural network (CNN) model trained to differentiate AIP from PDAC, chronic pancreatitis (CP) and normal pancreas (NP), with sufficient performance to analyse EUS video in real time. Design A database of still image and video data obtained from EUS examinations of cases of AIP, PDAC, CP and NP was used to develop a CNN. Occlusion heatmap analysis was used to identify sonographic features the CNN valued when differentiating AIP from PDAC. Results From 583 patients (146 AIP, 292 PDAC, 72 CP and 73 NP), a total of 1 174 461 unique EUS images were extracted. For video data, the CNN processed 955 EUS frames per second and was: 99% sensitive, 98% specific for distinguishing AIP from NP; 94% sensitive, 71% specific for distinguishing AIP from CP; 90% sensitive, 93% specific for distinguishing AIP from PDAC; and 90% sensitive, 85% specific for distinguishing AIP from all studied conditions (ie, PDAC, CP and NP). Conclusion The developed EUS-CNN model accurately differentiated AIP from PDAC and benign pancreatic conditions, thereby offering the capability of earlier and more accurate diagnosis. Use of this model offers the potential for more timely and appropriate patient care and improved outcome.

Abstract Background Fecal microbiota transplantation (FMT) is highly effective for preventing recurrent Clostridioides difficile infection (CDI). Durability (no recurrence despite additional risk factor exposure) of FMT protection is largely unknown. We studied the durability of FMT in patients with recurrent CDI. Methods We conducted a retrospective study of adults undergoing FMT for recurrent CDI. Data collected included demographics, CDI risk factors (comorbidities, healthcare exposure, non-CDI antibiotic use, acid suppressant medications), and future CDI episodes. Durable response to FMT was defined as lack of CDI episodes within 1 year post-FMT despite risk factor exposure. Results Overall, 460 patients were included (median age, 57 years [18–94]; 65.2% female). Comorbidities included chronic liver disease, 12.8% (n = 59); cancer, 11.7% (n = 54); chronic kidney disease, 3.9% (n = 18); and inflammatory bowel disease, 21.9% (n = 101). Overall, 31.3% (n = 144) received antibiotics, 21.7% (n = 100) received acid suppressants, and 76.8% (n = 350) had healthcare exposure after FMT. Of 374 patients with risk factor exposure, 78.1% (95% confidence interval [CI], 72.7%–84.0%) had durable response to FMT at 1 year. On multivariable analysis, antibiotic use was independently associated with decreased durability of FMT (hazard ratio, 0.27; 95% CI, .15–.49; P < .001). Conclusions The majority of patients had a durable response to FMT despite exposure to CDI risk factors. Antibiotic exposure after FMT independently predicted loss of durability of FMT. Larger studies are needed to define predictors of durable response in patients with and without exposure to antibiotics.

Background: Periacetabular osteotomy (PAO) remains the gold-standard treatment for acetabular dysplasia in skeletally mature patients with preserved cartilage. The purpose of this multicenter cohort study was to delineate the long-term radiographic natural history of the dysplastic hip following PAO based on the final position of the acetabular fragment. Methods: We evaluated patients who underwent PAO performed by 4 hip preservation surgeons to treat acetabular dysplasia with or without concomitant retroversion from 1996 to 2012 at 3 academic institutions. There were 288 patients with a mean clinical and radiographic follow-up of 9 years (range, 5 to 21 years). Postoperative radiographs made at the first clinical visit were used to determine if the acetabular fragment fell into a safe zone according to the absence of retroversion, a lateral center-edge angle (LCEA) of 25° to 40°, an anterior center-edge angle (ACEA) of 25° to 40°, and a Tönnis angle of 0° to 10°. Every available subsequent radiograph was assessed for degenerative changes by the Tönnis classification (grades 0 to 3). The time to progression was analyzed using Cox proportional hazards regression and multistate modeling. Results: Only the absence of retroversion was independently associated with a decreased risk of progressing at least 1 Tönnis grade during follow-up: hazard ratio (HR), 0.60 (95% confidence interval [CI], 0.38 to 0.94; p = 0.025). Achieving the ACEA safe zone yielded the greatest time increase for remaining in Tönnis grade 0 or 1 (43 years for having an ACEA in the safe zone compared with 28 years for not having an ACEA in the safe zone), followed by the absence of retroversion (34 years for the absence of retroversion compared with 24 years for the presence of retroversion). However, attaining the Tönnis angle or LCEA safe zones did not delay progression. The achievement of additional safe zones generally increased the length of time that patients spent in Tönnis grade 0 or 1: 25 years for 0 safe zones, 36 years for 1 safe zone, 29 years for 2 safe zones, 37 years for 3 safe zones, and 44 years for 4 safe zones. Conclusions: This study demonstrates the importance of achieving appropriate acetabular reorientation to enhance the longevity of the native hip following PAO. Although the LCEA and the Tönnis angle are the most common metrics used to assess appropriate acetabular correction, this study shows that adequately addressing retroversion and the ACEA has a greater impact on improving the natural history. Level of Evidence: Therapeutic Level IV . See Instructions for Authors for a complete description of levels of evidence.

Abstract Objective: Hypertensive disorders of pregnancy and menopausal symptoms, specifically vasomotor symptoms, have both been associated with cardiovascular disease risk in women. However, data are sparse on the association between these two female-specific cardiovascular risk factors. This study was conducted to investigate the association between a history of a hypertensive disorder of pregnancy and menopausal symptoms. Methods: This was a cross-sectional study of women aged 40 to 65 years seen for specialty consultation in women's health clinics at Mayo Clinic Rochester, MN and Scottsdale, AZ, between May, 2015 and September, 2019. A self-reported history of hypertensive disorders of pregnancy served as the independent variable, and menopause symptoms as assessed by the Menopause Rating Scale were the primary outcome measure. Results: Of 2,684 women included in the analysis, 180 had a self-reported history of a hypertensive disorder of pregnancy. The total menopausal symptom scores as well as somatic and psychological domain scores were higher in women with a history of a hypertensive disorder of pregnancy compared to women without a history of a hypertensive disorder of pregnancy or to women without a pregnancy. On multivariable analysis, women with a hypertensive disorder of pregnancy using hormone therapy had significantly higher total menopause symptom scores than women with no such history. Conclusions: In this large cross-sectional study, a history of hypertensive disorders of pregnancy was associated with more bothersome menopausal symptoms. Additional study is needed to determine the strength of this association, underlying mechanisms of the association, and clinical implications for cardiovascular risk prediction in women.

Abstract Background Obesity and female sexual dysfunction (FSD) are prevalent conditions, and both are associated with significant adverse effects on health and well-being. Aim To investigate the association between body mass index and FSD, as well as potential moderators. Methods This cross-sectional study was performed by analyzing medical records of 6,688 women seeking consultation for menopause-related or sexual health–related concerns at women’s health clinics at Mayo Clinic Rochester, MN, and Scottsdale, AZ, between May 1, 2015, and September 15, 2019. Outcomes Female sexual function was assessed by the Female Sexual Function Index, and sexual distress was assessed by the Female Sexual Distress Scale-Revised. Results Being overweight or obese was associated with a lack of sexual activity. Among sexually active women, those who were overweight or obese had lower Female Sexual Function Index total scores and sexual function domain scores (indicating worse sexual function), including sexual arousal, lubrication, satisfaction, orgasm, and pain, and higher levels of sexual distress than those with normal weight. However, on multivariable analysis, these associations were found to be mediated by other factors, including age, level of education, reproductive stage, medication use, and mood disturbances, which are known to impact body weight and sexual function in women. Clinical Implications Overweight and obesity were associated with sexual inactivity and greater odds of having FSD, which should prompt proactive assessment of sexual function. Strengths and Limitations The strengths of this study include the large cohort size and assessment of sexual problems in addition to sexual distress, a key component of the definition of sexual dysfunction. This study also took into account multiple potential moderating factors. Limitations include the cross-sectional design, which precludes determination of causality as well as lack of diversity in the cohort, potentially limiting generalizability of results. In addition, sexual function was not assessed in women reporting no recent sexual activity, which may confound results. Conclusion Overweight/obesity and FSD are highly prevalent conditions, which appear to be indirectly associated. These results highlight the need to identify and address FSD in all overweight and obese women, with particular attention to potential contributing factors.

AbstractObjectiveOrthostatic intolerance (OI) and autonomic dysfunction (AD) are common in adolescents and young adults. Patients experience multisystem symptoms including gastrointestinal (GI), postural orthostatic tachycardia syndrome (POTS), orthostatic hypotension (OH), or only symptoms of OI (SOI) without significant findings on 70‐degree head‐up tilt testing (HUT). We hypothesize that patients with POTS, OH, and SOI show differences in GI symptoms and motility test and that heart rate (HR) changes on HUT predict severity of GI dysmotility.Study designFrom medical records of patients (<18 years) with OI, we collected demographics, presenting symptoms, GI manifestations, and GI motility testing. Data were compared between the 3 groups (POTS, OH, and SOI). We assessed changes in HR on HUT with changes on GI motility evaluation.ResultsTwo hundred twenty‐nine patients were included (73% females). Abdominal pain (65%), nausea (49%), vomiting (18%), and constipation (24%) were the most common GI symptoms. In patients who had motility evaluation, there were 27% (53/193) with delayed gastric emptying (GE) at 4 hours, 35% (32/92) with delayed colonic transit (CT), 55% (17/31) with reduced gastric accommodation (GA), and 75% (21/28) with dyssynergic defecation (DD). Among 100 POTS, 34 OH, and 95 SOI patients, no significant differences in GI symptoms or motility tests were identified and HR changes on HUT were not associated with changes on motility tests.ConclusionGI symptoms are frequent in adolescents with OI and are associated with delayed GE, reduced GA, delayed CT, and presence of DD.