Mara, Kristin

ABSTRACTBackgroundIntraductal papillary mucinous neoplasms (IPMNs) are the most commonly identified pancreatic cystic neoplasms. Incidentally detected IPMNs are common among liver transplant recipients. The risk of IPMN progression to pancreatic cancer in transplant recipients and the impact of immunosuppression on the risk of malignant transformation of IPMN are unclear.MethodsIn this retrospective study of consecutive liver transplant recipients across Mayo Clinic over a 13‐year period, patients were assessed for possible IPMN by automated chart review. Pancreatic cystic lesions were characterized as suspected IPMNs based on imaging criteria. Cox proportional hazards models were used to determine the association between IPMN progression (the development of cancer or worrisome features) and clinical and immunosuppression regimen characteristics.ResultsOf 146 patients with suspected IPMNs, progression occurred in 7 patients (2 cases of IPMN‐associated cancer and 5 cases of worrisome features) over an average follow‐up of 66.6 months. Immunosuppression type, medication number, and tacrolimus trough levels were not associated with IPMN progression (p > 0.05). Combined kidney and liver transplantation (p = 0.005) and pretransplant cholangiocarcinoma (p = 0.012) were associated with IPMN progression.ConclusionIPMN progression is rare after liver transplantation even over an extended follow‐up period. The findings were notable for the absence of an association between IPMN progression and immunosuppression regimen. Larger studies are needed given the low incidence.

AbstractLiver transplantation (LT) with hepatitis B core antibody (anti‐HBc) positive grafts to hepatitis B surface‐antigen (HBsAg) negative recipients is safe and has likely contributed to improvements in organ access over the years. The incidence of de novo hepatitis B infection (HBV) in these instances is low with appropriate prophylaxis and is affected by recipient immunologic status. There is debate as to whether hepatitis B surface antibody (anti‐HBs) positivity may safely inform prophylaxis discontinuation post‐LT. In this retrospective study of all hepatitis B surface antigen (HBsAg) negative recipients of anti‐HBc positive organs at three large academic centers between January 2014 and December 2019, nine LT recipients discontinued prophylaxis after developing anti‐HBs antibodies 1 year or later post‐LT. Three of the nine patients (33%) developed de novo HBV, defined by positive HBsAg or hepatitis B virus (HBV) DNA, during the study period. The remaining six patients had no evidence of HBV infection after a mean follow‐up of 37 months. The patients without de novo HBV had higher anti‐HBs titers at the time of prophylaxis discontinuation and were less likely to have negative anti‐HBs at the time of transplant or negative anti‐HBc at any time point. These results suggest that quantitative anti‐HBs titer thresholds rather than qualitative anti‐HBs positivity at 1 year or later after LT should be used to identify patients at decreased risk of de novo infection and help guide prophylaxis duration.

Background: Dofetilide and sotalol are potassium channel antagonists that require inpatient QTc monitoring during initiation, due to increased risk of fatal arrhythmias. Elderly patients are especially subject to an increased risk of fatal arrhythmias due to polypharmacy, comorbidities, and physiologic cardiac changes with aging. This study will describe the tolerability and risk factors associated with the initiation of sotalol or dofetilide in patients ≥80 years of age. Methodology: This is a multicenter, retrospective, descriptive study of patients ≥80 years old who were initiated on either dofetilide or sotalol between May 8, 2018 and July 31, 2021 at institutions within the Mayo Clinic Health System. The percentage of patients who received nonpackage insert recommended doses was identified. Incidence of and reasons for dose reductions or discontinuations due to safety-related events or clinical concerns during the initial loading period were collected. Results: The final analysis included 104 patients. The majority of patients (75%) received nonstandard initial doses of dofetilide or sotalol based on baseline estimated creatinine clearance or QTc. Overall, 39% ( N = 41) of patients experienced a dose reduction or discontinuation due to a safety-related event or concern. Patients who received nonstandard initial doses of dofetilide or sotalol had 4.7 times greater odds of experiencing a safety-related event requiring dose reduction or discontinuation. Conclusion: Following package insert dosing in elderly patients increases safety and tolerability relative to more aggressive dosing of dofetilide or sotalol.

Background: Underweight patients may be at an increased risk of bleeding while receiving venous thromboembolism (VTE) prophylaxis. Additional evidence is needed to identify patient-specific factors associated with bleeding. The objective of the study was to describe the incidence and identify risk factors associated with bleeding in low-weight (⩽ 60 kg) adult patients receiving subcutaneous unfractionated heparin (SQH) for VTE prophylaxis. Methods: This was a single-center, retrospective, nested case–control study of low-weight patients receiving SQH for VTE prophylaxis for ⩾ 48 hours. Cases, patients with clinically relevant bleeding while receiving SQH, and controls, patients without a bleeding event, were matched in a 1:3 ratio for age, sex, primary service (surgical or medical), and time at risk of bleeding on SQH to determine factors associated with bleeding. Results: A total of 3761 patients met the inclusion criteria, of which 38 cases of clinically relevant bleeding were identified. The bleeding incidence was 1% at hospital day 6 and 2.8% at hospital day 14. Most patients in this study (69%) received SQH 5000 units three times daily. ICU admission at SQH start was associated with bleeding, OR 2.97 (95% CI 1.21–7.29). Conclusion: Bleeding in low-weight patients on prophylactic SQH was uncommon. Patients admitted to the ICU at time of SQH start may be at a higher risk of bleeding. Further studies are needed to detect additional risk factors associated with bleeding and investigate the effects of reduced dosing in this population.

AbstractBackgroundInfertility has been linked with an increased risk of sexual dysfunction in reproductive-aged women, with longer periods of infertility associated with a greater risk.AimThe study’s aim was to examine whether a history of infertility treatment in women is linked to sexual dysfunction during midlife.MethodsThe cross-sectional study was conducted among sexually active women, between the ages of 45 and 65 years, who sought consultation at the women’s health clinics at a US tertiary care center. History of infertility treatment was assessed with a single question that asked participants if they were treated for infertility in the past. The association between a history of infertility treatment and sexual dysfunction—which was diagnosed by a combination of Female Sexual Function Index score ≤26.55 and Female Sexual Distress Scale–Revised score ≥11—was assessed in a multivariable logistic regression model that adjusted for multiple confounders.OutcomesThe primary outcome was sexual dysfunction in midlife women.ResultsThe analysis included 5912 women, with a mean age of 54.1 years. Nearly 16% of women reported receiving treatment for infertility. More than half the women (55%) had sexual dysfunction: 56.3% of those with previous fertility treatments and 54.4% of those without any fertility treatment (P = .3). Receiving treatment for infertility in the younger years did not significantly increase the odds of sexual dysfunction in midlife in univariate (odds ratio, 1.08; 95% CI, 0.94-1.24; P = .3) and multivariable analyses (odds ratio, 1.11; 95% CI, 0.96-1.29; P = .17).Clinical ImplicationsWhile infertility is known to be predictive of sexual dysfunction in women during their reproductive years, there was no association between a history of infertility treatment and sexual dysfunction in midlife women in the current study.Strengths and LimitationsThe study used validated questionnaires accounting for sexual complaints and distress and adjusted for multiple confounding factors. Limitations include the selection bias introduced by the study of women presenting for evaluation of sexual dysfunction, which may have been a result of factors stronger than the influence of infertility. Other limitations include the study’s cross-sectional nature with suboptimal racial and ethnic representation.ConclusionAlthough infertility is commonly associated with female sexual dysfunction in women of reproductive age, the association was not present in midlife women in the current study.

AbstractBackground: Liver transplant (LT) recipients with untreated hepatitis C (HCV) are at risk for cirrhosis graft failure. The advent of direct acting antiviral agents (DAA) has improved outcomes in HCV.Aims: We aim to examine liver transplant outcomes and allograft fibrosis development/progression after sustained virologic response (SVR).Methods: We performed a retrospective cohort study of 226 consecutive liver transplant recipients with HCV from 2007 to 2018. The cohort was split into transplants pre (Group A) and post (Group B) 2014 to reflect the introduction of DAAs. Fibrosis was monitored with liver biopsy and non‐invasive imaging.Results: Group B had significantly improved HCV treatment rates and earlier SVR compared to Group A, with a cumulative incidence rate of SVR at 2 years of 86.7% versus 15.4% (HR = .11, p < .001). Prior to achieving SVR, Group A demonstrated worsening of fibrosis stage per year (+.21, p < .001) whereas Group B showed minimal change on protocol annual biopsy (−.02, p = .80). After SVR, most patients were followed non‐invasively and demonstrated stable or improved fibrosis stage over time. Patients undergoing transient elastography showed regression in fibrosis stage per year (−.19, p < .001).Conclusion: HCV patients undergoing LT after 2014 had higher rates of SVR and improved clinically relevant transplant outcomes, namely less graft loss and death relating to HCV. Fibrosis progression halted or improved after SVR in both cohorts, suggesting that LT recipients with SVR do not require fibrosis monitoring even with established fibrosis prior to SVR.

Abstract Background One in 3 children has had at least 1 adverse childhood experience (ACE), and ACEs have been associated with multiple medical and psychiatric morbidities in women later in life, including greater menopause symptom burden. Aim To evaluate the association between ACEs and female sexual dysfunction (FSD) in midlife women. Methods A cross-sectional analysis from DREAMS—the Data Registry on Experiences of Aging, Menopause, and Sexuality—was conducted with questionnaires completed by women aged 40 to 65 years who presented to a women’s health clinic at Mayo Clinic in Rochester, Minnesota, from May 2015 to December 2016. History of ACEs was obtained with the validated ACE questionnaire. FSD was assessed by the Female Sexual Function Index and the Female Sexual Distress Scale–Revised. Outcomes The association between ACEs and FSD (defined as Female Sexual Function Index score ≤26.55 and Female Sexual Distress Scale–Revised score ≥11) was evaluated via a multivariable logistic regression model, adjusting for age, menopause status, hormone therapy use, anxiety, depression, relationship satisfaction, hot flash severity, and history of abuse in the past year. Results Women (N = 1572) had a mean age of 53.2 years. Overall 59% reported having at least 1 ACE. When compared with no ACEs, a history of ≥4 ACEs significantly increased the odds of not being sexually active (odds ratio, 1.83; 95% CI, 1.30-2.57; P &lt; .001). Among sexually active women, the proportion of women with FSD increased sequentially as the number of ACEs increased. In the univariate analysis, a history of ≥4 ACEs significantly increased the odds of FSD as compared with no ACEs (odds ratio, 2.12; 95% CI, 1.50-2.99; P &lt; .001). The association remained statistically significant in the multivariable analysis after adjusting for confounders (odds ratio, 1.75; 95% CI, 1.15-2.68; P = .009). Clinical Implications The findings highlight an opportunity for clinicians to screen for ACEs in women with sexual dysfunction and offer appropriate treatment and counseling as indicated. Strengths and Limitations Strengths of the study include the large cohort, the use of validated tools for assessment of ACEs and FSD, and the adjustment for multiple potential confounding factors. Limitations include the cross-sectional study design, recall bias in reporting ACEs and recent abuse, and the low representation of racially and ethnically diverse women in the cohort. Conclusion The study demonstrates an increased risk of sexual inactivity and sexual dysfunction in midlife women who experienced childhood adversity. The sexual dysfunction in women with ACEs seems to be independent of other factors that potentially affect female sexual function in midlife.

Antistaphylococcal penicillins (ASP) and cefazolin are first-line treatment of methicillin-susceptible Staphylococcus aureus (MSSA) bacteremia. Borderline oxacillin resistance (i.e., oxacillin MICs 1-8 μg/mL) is observed in strains hyperproducing beta-lactamases.

Abstract Objective The aim of this study was to compare the association between migraine and sleep quality in premenopausal versus perimenopausal women. Methods A cross-sectional analysis from the Data Registry on the Experiences of Aging, Menopause and Sexuality was conducted using questionnaire data from premenopausal and perimenopausal women seen at women's health clinics at 3 geographic locations from 2015 to 2021. Sleep quality and duration were assessed with the Pittsburgh Sleep Quality Index. Associations between poor sleep quality (Pittsburgh Sleep Quality Index >5) and self-reported migraine history (Y/N) were evaluated using a multivariable logistic regression model, adjusting for body mass index, anxiety, depression, and vasomotor symptoms. Results Of 2,067 women (mean age 43.2 years) included in the analysis, 594 (28.7%) reported a migraine history. Women were mostly white (92.2%), partnered (75.1%), and educated (86% with at least some college); 46.5% (n = 962) were premenopausal, 53.5% (n = 1,105) were perimenopausal, and 71.2% met the criteria for poor sleep. In univariate analysis, migraine history predicted poor sleep in both premenopausal and perimenopausal women (P = 0.005 and P = 0.004, respectively). However, in multivariable analysis, migraine history remained associated with poor sleep in premenopausal women (P = 0.044), but not in perimenopausal women (P = 0.46). Conclusions A migraine history was associated with poor sleep in premenopausal women. The relationship in perimenopausal women seemed to be influenced by confounding factors that are more prevalent during the menopause transition and are known to affect the frequency of migraine and sleep disturbances, such as anxiety, depression, and vasomotor symptoms. These conditions may need to be the focus of management in migraineurs with sleep disturbances during the menopause transition.

ABSTRACT Background Studies have found that women with endometriosis have a higher risk of female sexual dysfunction (FSD). Aim To evaluate the relationship between self-reported endometriosis and FSD utilizing validated surveys. Methods A cross-sectional analysis was conducted among sexually active women aged 18–90 who presented to 3 Mayo Clinic sites from 2015 to 2021. FSD was determined utilizing a combined endpoint of Female Sexual Function Index score ≤ 26.55 and Female Sexual Distress Scale-Revised score ≥ 11. Associations between history of endometriosis and FSD were evaluated by fitting 3 multivariable logistic models and were stratified by menopause status. In the first model, the association was adjusted for age, BMI, race/ethnicity, marital status, and education. The second model adjusted for the variables in Model 1 and hormone therapy, hormonal contraceptive use, self-reported history of abuse within the last year, and co-morbidities including the history of diabetes, heart disease, hypertension, osteoporosis, and stroke. The third model adjusted for the variables in Model 1, Model 2, and anxiety, depression, relationship satisfaction, and SSRI/SNRI use. Outcomes The outcomes included self-reported endometriosis and female sexual dysfunction determined utilizing a combined endpoint of Female Sexual Function Index score ≤ 26.55 and Female Sexual Distress Scale-Revised score ≥ 11. Results Of 7118 patients (mean age 51.3), 92.2% were white, 78.4% were peri- or postmenopausal, 8.7% reported endometriosis history, and 57.2% met the criteria for FSD. Women with endometriosis were more likely to be overweight or obese, be smokers, have had a history of heart disease and osteoporosis, have had anxiety and depressed mood, have had a hysterectomy and bilateral salpingo-oophorectomy, and have used hormone therapy. Compared to those without endometriosis, women with endometriosis were significantly more likely to have FSD only among premenopausal women (74.2% vs 57.4%). Similarly, in multivariable analysis the relationship was only seen for premenopausal women in all 3 models (Model 1: OR 2.74 (95% CI 1.43–5.27); Model 2: OR 2.55 (95% CI 1.30–5.04); Model 3: OR 2.30 (95% CI 1.13–4.68)). Clinical Implications These findings highlight the opportunity for healthcare practitioners to evaluate sexual function in premenopausal women with endometriosis. For peri and postmenopausal women with endometriosis, the risk of FSD was lower than for premenopausal women with endometriosis. Strengths and Limitations This study analyzed the association between endometriosis and FSD in women by menopause status using validated tools that included a measure of distress associated with sexual dysfunction. Limitations include its cross-sectional design which does not allow for determination of the direction of this association. Conclusion The risk for FSD associated with endometriosis depends on menopause status. Endometriosis increased the odds of FSD only in premenopausal women.