White, Launia

ABSTRACTObjectivesPrior studies have raised concerns about postpartum hemorrhage (PPH) risk associated with selective serotonin and serotonin‐norepinephrine reuptake inhibitors (SSRIs and SNRIs), although limitations include possible confounding by maternal indications. The current study examined the risk of PPH associated with prenatal S/NRIs accounting for diagnosed maternal depression during pregnancy.MethodsThe current study is a secondary analysis of data from a cohort of 2213 pregnancies (1997–2010) identified from a large electronic medical record‐linkage system. Exposures were identified from electronic prescriptions records and resulted in three main groups: S/NRI‐exposed pregnancies (S/NRI users), antidepressant‐unexposed pregnancies (non‐users), and S/NRI exposure in the year prior to (but not during) pregnancy (former users). Data used to identify PPH occurrences included obstetrician chart diagnoses, diagnosis codes, and recorded estimated blood loss (EBL). The risk of PPH by exposure group was estimated using unadjusted, minimally adjusted (maternal age at delivery, delivery year, parity, and maternal smoking), and depression‐adjusted models (previous covariates and maternal depression). Supplemental analyses included an examination of PPH risk with prenatal bupropion monotherapy.ResultsThe study cohort consisted of 837 S/NRI users, 401 former users, and 786 non‐users, as well as 114 bupropion users identified for additional analyses. The frequency of PPH was 11.6% in the overall cohort, and was 14.7% for S/NRI users, 10.2% for former users, and 8.7% for non‐users. The risk of PPH was significantly higher for S/NRI users than non‐users in unadjusted (OR 1.82 [95% CI 1.33, 2.49]), minimally adjusted (aOR 1.66 [1.19, 2.31]), and depression‐adjusted models (aOR 1.46 [1.02, 2.10]). The risk of PPH was also higher for S/NRI former users than non‐users in unadjusted models (OR 1.54 [1.05, 2.26]) but not minimally adjusted (aOR 1.42 [0.95, 2.11]) or depression‐adjusted models (aOR 1.41 [0.95, 2.10]). No significant differences in PPH risk were observed between S/NRI users and former users, between bupropion users and non‐users, or between S/NRI users and bupropion users.ConclusionsPrenatal S/NRI exposure was associated with an increased risk of PPH after adjusting for maternal depression, although residual confounding and confounding by other factors (including unmeasured factors) may be possible, as the risk of PPH appeared to be similar between S/NRI users and former users. Best‐practice PPH risk management strategies should be adhered to for depressed patients, especially those who require treatment with antidepressants during pregnancy.

AbstractBackgroundSimultaneous liver kidney (SLK) transplant protects against acute cellular rejection. In 2017, UNOS implemented a “safety net” policy to allow patients with renal recovery to avoid renal transplantation. Whether kidney after liver transplantation (KALT) increases the risk of rejection is unknown.MethodsWe performed a retrospective analysis of the Organ Procurement and Transplantation Network (OPTN) database of adult patients who received liver transplant, SLK or KALT between 2010 and 2020. We examined rejection of the liver within 6 months and 1 year of the liver transplant, as well as rejection of the kidney within 6 months and 1 year of receiving the kidney, as well as patient and graft loss.ResultsSixty‐six thousand seventy‐nine patients were transplanted; 60 168 with liver transplant alone, 5627 with SLK, and 284 with KALT. Acute or chronic liver rejection rates within 6 or 12 months were statistically higher in the KALT group (10.0% and 10.9%) compared to the SLK group (6.1% and 7.5%), but comparable to the LTA group (9.3% and 11.1%). Kidney rejection and graft survival rates were not different. Liver graft survival was worse in KALT than SLK or LTA (Kaplan‐Meier estimates .61 vs. .89 and .90), but these patients were more ill at the time of transplantation. KDPI and LDRI scores were notably lower in the SLK than KALT group. Patient survival was not clinically different between the groups.ConclusionKALT does not increase the risk of acute or chronic kidney rejection. SLK has a lower risk of early liver rejection, but this effect diminishes by one year to being not clinically different compared to KALT. Given that KALT is immunologically safe, and potentially avoids unnecessary renal graft use, it should be preferred over SLK.Brief summaryPatients undergoing sequential kidney after liver transplant do not have an increased risk of liver or kidney rejection when compared to liver transplant alone or simultaneous liver and kidney transplant.

The number of kidney after liver transplants (KALT) increased after the implementation of the United Network of Organ Sharing (UNOS) safety net policy, but the effects of the policy on KALT outcomes remain unknown. Using the UNOS database, we identified KALT between 60 and 365 days from liver transplant from January 1, 2010, to December 31, 2020. The main outcome was 1- and 3-year patient, liver, and kidney graft survival. Secondary outcomes included 6-month and 1-year acute rejection (AR) of liver and kidney, and 1-year kidney allograft function. Of the 256 KALT, 90 were pre-policy and 166 post-policy. Compared to pre-policy, post-policy 1- and 3-year liver graft survival was higher (54% and 54% vs. 86% and 81%, respectively, p <0.001), while 1- and 3-year kidney graft survival (99% and 75% vs. 92% and 79%, respectively, p =0.19), and 1- and 3-year patient survival (99% and 99% vs. 95% and 89%, respectively, p =0.11) were not significantly different. Subgroup analysis revealed similar trends in patients with and without renal failure at liver transplant. Liver AR at 6 months was lower post-policy (6.3% vs. 18.3%, p =0.006) but was similar (10.5% vs. 13%, p =0.63) at 1 year. Kidney AR was unchanged post-policy at 6 months and 1 year. Creatinine at 1 year did not differ post-policy versus pre-policy (1.4 vs. 1.3 mg/dL, p =0.07) despite a higher proportion of deceased donors, higher Kidney Donor Profile Index, and longer kidney cold ischemia time post-policy ( p <0.05 for all). This 3-year follow-up after the 2017 UNOS policy revision demonstrated that the safety net implementation has resulted in improved liver outcomes for patients who underwent KALT with no increased AR of the liver or the kidney allografts.

Abstract Animal studies implicate one-carbon metabolism and DNA methylation genes in hepatocellular carcinoma (HCC) development in the setting of metabolic perturbations. Using human samples, we investigated the associations between common and rare variants in these closely related biochemical pathways and risk for metabolic HCC development in a multicenter international study. We performed targeted exome sequencing of 64 genes among 556 metabolic HCC cases and 643 cancer-free controls with metabolic conditions. Multivariable logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs), adjusting for multiple comparisons. Gene-burden tests were used for rare variant associations. Analyses were performed in the overall sample and among non-Hispanic whites. The results show that among non-Hispanic whites, presence of rare functional variants in ABCC2 was associated with 7-fold higher risk of metabolic HCC (OR = 6.92, 95% CI: 2.38–20.15, P = 0.0004), and this association remained significant when analyses were restricted to functional rare variants observed in ≥2 participants (cases 3.2% versus controls 0.0%, P = 1.02 × 10−5). In the overall multiethnic sample, presence of rare functional variants in ABCC2 was nominally associated with metabolic HCC (OR = 3.60, 95% CI: 1.52–8.58, P = 0.004), with similar nominal association when analyses were restricted to functional rare variants observed in ≥2 participants (cases 2.9% versus controls 0.2%, P = 0.006). A common variant in PNPLA3 (rs738409[G]) was associated with higher HCC risk in the overall sample (P = 6.36 × 10−6) and in non-Hispanic whites (P = 0.0002). Our findings indicate that rare functional variants in ABCC2 are associated with susceptibility to metabolic HCC in non-Hispanic whites. PNPLA3-rs738409 is also associated with metabolic HCC risk.

Objective We sought to determine the prevalence and possible features associated with symptoms in adult patients diagnosed with an aberrant right subclavian artery (ARSA). Methods In this single-center retrospective study, 386 adult patients were diagnosed with ARSA on chest CT scans performed between June 2016 and April 2021. Patients were grouped by the presence of symptoms, which included dysphagia, shortness of breath, cough, and upper airway wheezing. Four cardiothoracic radiologists reviewed the chest CT scans to assess features of ARSA. Agreement and multivariable logistic regression analyses were performed to determine interobserver variability and features associated with the presence of symptoms, respectively. Results The prevalence of ARSA was 1.02% and 81.3% of patients were asymptomatic. Shortness of breath (74.6%) was the most common symptom. Interobserver agreement was acceptable with most variables having an interclass correlation coefficient or κ >0.80. A patient's height > 158 cm (OR: 2.50, P = 0.03), cross-sectional area > 60 mm2 of ARSA at the level of the esophagus (OR: 2.39, P = 0.046), and angle >108 degrees formed with the aortic arch (OR: 1.99, P = 0.03) were associated with the presence of symptoms on multivariable logistic regression. A distance increase per 1 mm between ARSA and trachea (OR: 0.85, P = 0.02) was associated with decreased odds of symptoms. Conclusions Aberrant right subclavian artery is an incidental finding in most adult patients. The cross-sectional area at the level of the esophagus, angle formed with the medial wall of the aortic arch, distance between the ARSA and the trachea, and a patient's height were features associated with the presence of symptoms.

ObjectiveRecent evidence supports a link between increased TDP‐43 burden and the presence of an APOE4 gene allele in Alzheimer's disease (AD); however, it is difficult to conclude the direct effect of APOE on TDP‐43 pathology due to the presence of mixed AD pathologies. The goal of this study is to address how APOE isoforms impact TDP‐43 pathology and related neurodegeneration in the absence of typical AD pathologies.MethodsWe overexpressed human TDP‐43 via viral transduction in humanized APOE2, APOE3, APOE4 mice, and murine Apoe‐knockout (Apoe‐KO) mice. Behavior tests were performed across ages. Animals were harvested at 11 months of age and TDP‐43 overexpression‐related neurodegeneration and gliosis were assessed. To further address the human relevance, we analyzed the association of APOE with TDP‐43 pathology in 160 postmortem brains from autopsy‐confirmed amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration with motor neuron disease (FTLD‐MND) in the Mayo Clinic Brain Bank.ResultsWe found that TDP‐43 overexpression induced motor function deficits, neuronal loss, and gliosis in the motor cortex, especially in APOE2 mice, with much milder or absent effects in APOE3, APOE4, or Apoe‐KO mice. In the motor cortex of the ALS and FTLD‐MND postmortem human brains, we found that the APOE2 allele was associated with more severe TDP‐43‐positive dystrophic neurites.InterpretationOur data suggest a genotype‐specific effect of APOE on TDP‐43 proteinopathy and neurodegeneration in the absence of AD pathology, with the strongest association seen with APOE2. ANN NEUROL 2023;93:830–843

AbstractBackgroundAbdominal arterial calcification (AAC) is common among candidates for kidney transplant. The aim of this study is to correlate AAC score value with post‐kidney transplant outcomes.MethodsWe modified the coronary calcium score by changing the intake data points and used it to quantitate the AAC. We conducted a retrospective clinical study of all adult patients who were transplanted at our center, between 2010 and 2013, and had abdominal computed tomography scan done before transplantation. Outcomes included mortality, pulse pressure (PP) measured by 24 h ambulatory blood pressure monitoring system, and kidney allograft function measured by iothalamate clearance.ResultsFor each 1000 increase of AAC score value, there is an associated 1.05 increase in the risk of death (95% CI 1.02, 1.08) (p < 0.001). Overall median AAC value for all patients was 1784; Kaplan–Meier curve showed reduced survival of all‐cause mortality for patients with AAC score value above median and reduced survival among patients with cardiac related mortality. The iothalamate clearance was lower among patients with total AAC score value above the median. Patients with abnormal PP (< 40 or > 60 mmHg) had an elevated median AAC score value at 4319.3 (IQR 1210.4, 11097.1) compared to patients with normal PP with AAC score value at 595.9 (IQR 9.9, 2959.9) (p < 0.001).ConclusionWe showed an association of AAC with patients’ survival and kidney allograft function after kidney transplant. The AAC score value could be used as a risk stratification when patients are considered for kidney transplant.

Abstract Background The objective of this study was to characterize clinical features and outcomes among patients with calf deep vein thrombosis (DVT) limited to the muscular veins compared with axial veins. Methods Consecutive patients with ultrasound confirmed acute DVT involving the calf veins (January 1, 2016–August 1, 2018) were identified from the Gonda Vascular Center ultrasound database. Patients were divided into axial or muscular groups based on thrombus location. Demographics, management, and outcomes were compared. Results Over the study period, there were 647 patients with calf DVT equally distributed between axial (n = 321) and muscular (n = 326) locations. Within these groups, peroneal and soleal veins were most commonly involved. Nearly all cases were provoked (97%). Synchronous pulmonary embolism (PE) were more common for axial (30.8%) compared to muscular groups (20.2%; p = 0.001); nearly one-third had no pulmonary symptoms. Anticoagulation for a median of 3 months was initiated for 85.5% of both groups. Venous thromboembolism (VTE) recurrence was more common in the axial group (15.9% vs. 7.1%, p = 0.0015) including more frequent DVT propagation (9.4% vs. 3.1%; p = 0.0017) and PE (3.4% vs. 0.6%; p = 0.0168). Major bleeding, clinically relevant nonmajor bleeding, and mortality rates did not differ between groups. Withholding anticoagulation led to more frequent thrombus propagation in the axial group (3.4% vs. 0.9%; p = 0.029). Conclusion Several important features distinguish muscular from axial DVT. Axial DVT are more likely to have an associated PE and are more likely to experience recurrent VTE, particularly if anticoagulation is withheld.

Background: Managing the safety climate in health care is a promising tool for improving employee and patient safety in the health care work environment. Gaps in the theoretical and conceptual underpinnings of safety climate, as well as the evidence base for its practical application in health care remain. The purpose of this study was to evaluate the number of work injuries occurring in health care work units and associated safety climate beliefs. Methods: A retrospective analysis was conducted utilizing organizational staff survey data collected by a large medical hospital in the Midwest in 2015. Employees ( n = 32,327) were invited to identify safety climate perceptions via survey. Injuries, days restricted, and days absent were identified through the Hospital’s Occupational Safety and Health Administration (OSHA) log. Zero inflated negative binomial regressions used injuries as dependent variables and safety climate perceptions as independent variables. Findings: In all, 23,599 employees completed the survey (73% response rate) across 1,805 employee work units which were defined as groupings of employees reporting to a single supervisor. We found that there was an association between fewer injuries and health care workers indicating that they share responsibility for compliance with safety rules and procedures (relative risk [RR] = 0.98, 95% confidence interval [CI] = [0.98, 0.99]). Conclusion/Application to Practice: This study supports the use of a safety climate measure to assess working units’ perceptions of employee safety. A continued focus on the health and safety of employees who interact directly with patients is warranted, as well as employees who do not provide direct patient care.

PURPOSE: Quality payment programs aim to adjust payments on the basis of quality and cost; however, few quality metrics exist in radiation oncology. This study evaluates and predicts the top spenders (TS) after radiation therapy (RT). MATERIALS AND METHODS: Patient characteristics, cancer details, treatments, toxicity, and survival data were collected for patients treated with RT at Mayo Clinic from 2007 to 2016. Standardized costs were obtained and adjusted for inflation. TSs were identified as those with greater than 93rd percentile costs (≥ $120,812). Prediction models were developed to predict TSs using training and validation sets using information available at consultation, after RT, and at last follow-up. RESULTS: A total of 15,131 patients were included and 1,065 TSs identified. Mean cost overall was $55,290 (median, $39,996) for all patients. Prediction models 1, 2, and 3 had concordance statistics of 0.83 to 0.83, 0.85 to 0.85, and 0.87 to 0.88, respectively in training and validation, indicating excellent prediction of TSs. Factors that were most predictive of TSs included stage N/A and stage 4 ( v stage 0; odds ratio [OR], 18.23 and 8.44, respectively; P < .001); hematologic, upper GI, skin and lung cancers ( v breast; OR, 11.45, 7.69, 3.81, and 2.43, respectively; P < .01); immunotherapy, surgery, and chemotherapy use (OR, 4.36, 2.51, and 1.61, respectively; P < .01); hospitalizations within 90 days of RT (OR, 2.26; P < .01); or death during the episode (OR, 1.56; P < .01). CONCLUSION: This is the first study of its kind to predict with high accuracy the highest spenders in radiation oncology. These patients may benefit from pre-emptive management to mitigate costs, or may require exclusion or adjustment from quality payment programs.