Prospective Study Assessing Impact of Ethylene Oxide Sterilization on Endoscopic Ultrasound Image Quality.

BACKGROUND & AIMS: Duodenoscope-associated transmission of infections has raised questions about efficacy of endoscope reprocessing using high-level disinfection (HLD). Although ethylene oxide (ETO) gas sterilization is effective in eradicating microbes, the impact of ETO on endoscopic ultrasound (EUS) imaging equipment remains unknown. In this study, we aimed to compare the changes in EUS image quality associated with HLD vs HLD followed by ETO sterilization. METHODS: Four new EUS instruments were assigned to 2 groups: Group 1 (HLD) and Group 2 (HLD + ETO). The echoendoscopes were assessed at baseline, monthly for 6 months, and once every 3 to 4 months thereafter, for a total of 12 time points. At each time point, review of EUS video and still image quality was performed by an expert panel of reviewers along with phantom-based objective testing. Linear mixed effects models were used to assess whether the modality of reprocessing impacted image and video quality. RESULTS: For clinical testing, mixed linear models showed minimal quantitative differences in linear analog score (P = .04; estimated change, 3.12; scale, 0-100) and overall image quality value (P = .007; estimated change, -0.12; scale, 1-5) favoring ETO but not for rank value (P = .06). On phantom testing, maximum depth of penetration was lower for ETO endoscopes (P < .001; change in depth, 0.49 cm). CONCLUSIONS: In this prospective study, expert review and phantom-based testing demonstrated minimal differences in image quality between echoendoscopes reprocessed using HLD vs ETO + HLD over 2 years of clinical use. Further studies are warranted to assess the long-term clinical impact of these findings. In the interim, these results support use of ETO sterilization of EUS instruments if deemed clinically necessary.

Evaluating the Link Between Self-Reported Endometriosis and Female Sexual Dysfunction.

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. Kling JM, Ghaith S, Smith T, et al. Evaluating the Link Between Self-Reported Endometriosis and Female Sexual Dysfunction. J Sex Med 2022;19:1533-1561.

Chemical Characterization and Quantification of Circulating Intact PTH and PTH Fragments by High-Resolution Mass Spectrometry in Chronic Renal Failure.

BACKGROUND: The precise concentrations of full-length parathyroid hormone (PTH1-84) and the identity and concentrations of PTH fragments in patients with various stages of chronic renal failure are unknown. METHODS: We developed a liquid chromatography-high resolution mass spectrometry (LC-HRMS) method to characterize and quantify PTH1-84 and PTH fragments in serum of 221 patients with progressive renal dysfunction. Following capture by matrix-bound amino-terminal or carboxyl-terminal region-specific antibodies and elution from matrix, PTH1-84 and PTH fragments were identified and quantitated using LC-HRMS. PTH was simultaneously measured using an intact PTH (iPTH) immunoassay. RESULTS: Full-length PTH1-84 and 8 PTH fragments (PTH28-84, 34-77, 34-84, 37-77, 37-84, 38-77, 38-84, and 45-84) were unequivocally identified and were shown to increase significantly when an eGFR declined to ≤17-23 mL/min/1.73m2. Serum concentrations of PTH1-84 were similar when measured by LC-HRMS following capture by amino-terminal or carboxyl-terminal immunocapture methods. In patients with an eGFR of <30 mL/min/1.73 m2, serum PTH concentrations measured using LC-HRMS were significantly lower than PTH measured using an iPTH immunoassay. PTH7-84 and oxidized forms of PTH1-84 were below the limit of detection (30 and 50 pg/mL, respectively). CONCLUSIONS: LC-HRMS identifies circulating PTH1-84, carboxyl-terminal PTH fragments, and mid-region PTH fragments, in patients with progressive renal failure. Serum PTH1-84 and its fragments markedly rise when an eGFR decreases to ≤17-23 mL/min/1.73 m2. PTH concentrations measured using LC-HRMS tend to be lower than those measured using an iPTH immunoassay, particularly in severe chronic renal failure. Our data do not support the existence of circulating PTH7-84 and oxidized PTH1-84.

Risk of Symptomatic Kidney Stones During and After Pregnancy.

RATIONALE & OBJECTIVE: There are several well-known anatomical and physiological changes during pregnancy that could contribute to kidney stone formation, but evidence that they increase the risk of kidney stones during pregnancy is lacking. We determined whether there was an increased risk of a first-time symptomatic kidney stone during and after pregnancy. STUDY DESIGN: A population-based matched case-control study. SETTING & PARTICIPANTS: 945 female first-time symptomatic kidney stone formers aged 15-45 years and 1,890 age-matched female controls in Olmsted County, MN, from 1984-2012. The index date was the date of onset of a symptomatic kidney stone for both the case and her matched controls. EXPOSURE: The primary exposure was pregnancy with assessment for variation in risk across different time intervals before, during, and after pregnancy. Medical records were manually reviewed to determine the conception and delivery dates for pregnancies. OUTCOME: Medical record-validated first-time symptomatic kidney stone. ANALYTICAL APPROACH: Conditional and unconditional multivariable logistic regression analysis. RESULTS: Compared with nonpregnant women, the odds of a symptomatic kidney stone forming in women was similar in the first trimester (OR, 0.92; P=0.8), began to increase during the second trimester (OR, 2.00; P=0.007), further increased during the third trimester (OR, 2.69; P=0.001), peaked at 0 to 3 months after delivery (OR, 3.53; P<0.001), and returned to baseline by 1year after delivery. These associations persisted after adjustment for age and race or for diabetes mellitus, hypertension, and obesity. These results did not significantly differ by age, race, time period, or number of prior pregnancies. Having a prior pregnancy (delivery date>1year ago) was also associated with a first-time symptomatic kidney stone (OR, 1.27; P=0.01). LIMITATIONS: Observational study design in a predominantly White population. The exact timing of stone formation cannot be determined. CONCLUSIONS: Pregnancy increases the risk of a first-time symptomatic kidney stone. This risk peaks close to delivery and then improves by 1 year after delivery, though a modest risk of a kidney stone still exists beyond 1 year after delivery.

Subsequent urinary stone events are predicted by the magnitude of urinary oxalate excretion in enteric hyperoxaluria.

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.

Automated radiomic analysis of CT images to predict likelihood of spontaneous passage of symptomatic renal stones.

PURPOSE: To evaluate the ability of a semi-automated radiomic analysis software in predicting the likelihood of spontaneous passage of urinary stones compared with manual measurements. METHODS: Symptomatic patients visiting the emergency department with suspected stones in either kidney or ureters who underwent a CT scan were included. Patients were followed for up to 6 months for the outcome of a trial of passage. Maximum stone diameters in axial and coronal images were measured manually. Stone length, width, height, max diameter, volume, the mean and standard deviation of the Hounsfield units, and morphologic features were also measured using automated radiomic analysis software. Multivariate models were developed using these data to predict subsequent spontaneous stone passage, with results expressed as the area under a receiver operating curve (AUC). RESULTS: One hundred eighty-four patients (69 females) with a median age of 56 years were included. Spontaneous stone passage occurred in 114 patients (62%). Univariate analysis demonstrated an AUC of 0.83 and 0.82 for the maximum stone diameter determined manually in the axial and coronal planes, respectively. Multivariate models demonstrated an AUC of 0.82 for a model including manual measurement of maximum stone diameter in axial and coronal planes. The same AUC was found for a model including automatic measurement of maximum height and diameter of the stone. Further addition of morphological parameters measured automatically did not increase AUC beyond 0.83. CONCLUSION: The semi-automated radiomic analysis of urinary stones shows similar accuracy compared with manual measurements for predicting urinary stone passage. Further studies are needed to predict clinical impacts of reporting the likelihood of urinary stone passage and improving inter-observer variation using automatic radiomic analysis software.

Clinical features of genetically confirmed patients with primary hyperoxaluria identified by clinical indication versus familial screening.

Primary hyperoxaluria is a rare monogenic disorder characterized by excessive hepatic production of oxalate leading to recurrent nephrolithiasis, nephrocalcinosis, and progressive kidney damage. Most patients with primary hyperoxaluria are diagnosed after clinical suspicion based on symptoms. Since some patients are detected by family screening following detection of an affected family member, we compared the clinical phenotype of these two groups. Patients with primary hyperoxaluria types 1, 2, and 3 enrolled in the Rare Kidney Stone Consortium Primary Hyperoxaluria Registry were retrospectively analyzed following capture of clinical and laboratory results in the Registry. Among 495 patients with primary hyperoxaluria, 47 were detected by family screening. After excluding 150 patients with end stage kidney disease at diagnosis, 300 clinical suspicion and 45 family screening individuals remained. Compared to patients with clinical suspicion, those identified by family screening had significantly fewer stones at diagnosis (mean 1.2 vs. 3.6), although initial symptoms occurred at a similar age (median age 6.1 vs. 7.6 years). Urinary oxalate did not differ between these groups. The estimated glomerular filtration rate at diagnosis and its decline over time were similar for the two groups. Altogether, five of 45 in family screening and 67 of 300 of clinical suspicion individuals developed end stage kidney disease at last follow-up. Thus, patients with primary hyperoxaluria identified through family screening have significant disease despite no outward clinical suspicion at diagnosis. Since promising novel treatments are emerging, genetic screening of family members is warranted because they are at significant risk for disease progression.

A single center randomized double blind controlled trial of pentoxifylline in acute pancreatitis: Challenges and opportunities.

OBJECTIVES: Despite substantial morbidity and mortality associated with acute pancreatitis (AP), only one small randomized controlled drug trial (RCT) is available in the past few decades from the United States. Hence, we conducted a single-center, double-blind, placebo-controlled RCT of pentoxifylline in AP. METHODS: A total of 9 doses of oral pentoxifylline 400 mg or placebo tablet, three times daily, was administered within 72 h of diagnosis, using randomization blocks by pharmacy. Primary outcome was a composite outcome including any of the following: death, peripancreatic and/or pancreatic necrosis, infected pancreatic necrosis, persistent organ failure, persistent systemic inflammatory response syndrome, hospital stay longer than 4 days, need for intensive care, and need for intervention for necrosis. RESULTS: Between July 7, 2015, and April 4, 2017, we identified 685 patients with AP, 233 met eligibility criteria and 176 were approached for the study. Of these, 91 (51.7%) declined and finally 45 in pentoxifylline group and 38 in placebo group (83 total) were compared. There were no significant differences in primary outcome (27 [60.0%] vs 15 [39.5%]; P = .06). Pentoxifylline group was not associated with any benefit, but withlonger stay (42% vs. 21%; P = .04) and higher readmission rates (16 %vs 3%; P = .047). CONCLUSIONS: We could not demonstrate superiority of pentoxifylline over placebo. Smaller sample size and inclusion of all types of severity might be the reasons for lack of efficacy. The challenges observed in the present study indicate that, in order to conduct a successful drug trial in AP, a multi center collaboration is essential.

Urinary monocyte chemoattractant protein 1 associated with calcium oxalate crystallization in patients with primary hyperoxaluria.

BACKGROUND: Patients with primary hyperoxaluria (PH) often develop kidney stones and chronic kidney disease. Noninvasive urine markers reflective of active kidney injury could be useful to gauge the effectiveness of ongoing treatments. METHODS: A panel of biomarkers that reflect different nephron sites and potential mechanisms of injury (clusterin, neutrophil gelatinase-associated lipocalin (NGAL), 8-isoprostane (8IP), monocyte-chemoattractant protein 1(MCP-1), liver-type fatty acid binding protein (L-FABP), heart-type fatty acid binding protein (H-FABP), and osteopontin (OPN)) were measured in 114 urine specimens from 30 PH patients over multiple visits. Generalized estimating equations were used to assess associations between biomarkers and 24 h urine excretions, calculated proximal tubular oxalate concentration (PTOx), and eGFR. RESULTS: Mean (±SD) age at first visit was 19.5 ± 16.6 years with an estimated glomerular filtration rate (eGFR) of 68.4 ± 21.0 ml/min/1.73m2. After adjustment for age, sex, and eGFR, a higher urine MCP-1 concentration and MCP-1/creatinine ratio was positively associated with CaOx supersaturation (SS). Higher urine NGAL and NGAL/creatinine as well as OPN and OPN/creatinine were associated with higher eGFR. 8IP was negatively associated with PTOx and urinary Ox, but positively associated with CaOx SS. CONCLUSION: In PH patients greater urine MCP-1 and 8IP excretion might reflect ongoing collecting tubule crystallization, while greater NGAL and OPN excretion may reflect preservation of kidney mass and function. CaOx crystals, rather than oxalate ion may mediate oxidative stress in hyperoxaluric conditions. Further studies are warranted to determine whether urine MCP-1 excretion predicts long term outcome or is altered in response to treatment.

Symptomatic and Radiographic Manifestations of Kidney Stone Recurrence and Their Prediction by Risk Factors: A Prospective Cohort Study.

BACKGROUND: Meaningful interpretation of changes in radiographic kidney stone burden requires understanding how radiographic recurrence relates to symptomatic recurrence and how established risk factors predict these different manifestations of recurrence. METHODS: We recruited first-time symptomatic stone formers from the general community in Minnesota and Florida. Baseline and 5-year follow-up study visits included computed tomography scans, surveys, and medical record review. We noted symptomatic recurrence detected by clinical care (through chart review) or self-report, and radiographic recurrence of any new stone, stone growth, or stone passage (comparing baseline and follow-up scans). To assess the prediction of different manifestations of recurrence, we used the Recurrence of Kidney Stone (ROKS) score, which sums multiple baseline risk factors. RESULTS: Among 175 stone formers, 19% had symptomatic recurrence detected by clinical care and 25% detected by self-report; radiographic recurrence manifested as a new stone in 35%, stone growth in 24%, and stone passage in 27%. Among those with a baseline asymptomatic stone (54%), at 5 years, 51% had radiographic evidence of stone passage (accompanied by symptoms in only 52%). Imaging evidence of a new stone or stone passage more strongly associated with symptomatic recurrence detected by clinical care than by self-report. The ROKS score weakly predicted one manifestation-symptomatic recurrence resulting in clinical care (c-statistic, 0.63; 95% confidence interval, 0.52 to 0.73)-but strongly predicted any manifestation of symptomatic or radiographic recurrence (5-year rate, 67%; c-statistic, 0.79; 95% confidence interval, 0.72 to 0.86). CONCLUSIONS: Recurrence after the first stone episode is both more common and more predictable when all manifestations of recurrence (symptomatic and radiographic) are considered.

Plasma Oxalate as a Predictor of Kidney Function Decline in a Primary Hyperoxaluria Cohort.

This retrospective analysis investigated plasma oxalate (POx) as a potential predictor of end-stage kidney disease (ESKD) among primary hyperoxaluria (PH) patients. PH patients with type 1, 2, and 3, age 2 or older, were identified in the Rare Kidney Stone Consortium (RKSC) PH Registry. Since POx increased with falling estimated glomerular filtration rate (eGFR), patients were stratified by chronic kidney disease (CKD) subgroups (stages 1, 2, 3a, and 3b). POx values were categorized into quartiles for analysis. Hazard ratios (HRs) and 95% confidence intervals (95% CIs) for risk of ESKD were estimated using the Cox proportional hazards model with a time-dependent covariate. There were 118 patients in the CKD1 group (nine ESKD events during follow-up), 135 in the CKD 2 (29 events), 72 in CKD3a (34 events), and 45 patients in CKD 3b (31 events). During follow-up, POx Q4 was a significant predictor of ESKD compared to Q1 across CKD2 (HR 14.2, 95% CI 1.8-115), 3a (HR 13.7, 95% CI 3.0-62), and 3b stages (HR 5.2, 95% CI 1.1-25), p < 0.05 for all. Within each POx quartile, the ESKD rate was higher in Q4 compared to Q1-Q3. In conclusion, among patients with PH, higher POx concentration was a risk factor for ESKD, particularly in advanced CKD stages.

Combined Celiac Ganglia and Plexus Neurolysis Shortens Survival, Without Benefit, vs Plexus Neurolysis Alone.

BACKGROUND & AIMS: Pancreatic cancer produces debilitating pain that opioids often ineffectively manage. The suboptimal efficacy of celiac plexus neurolysis (CPN) might result from brief contact of the injectate with celiac ganglia. We compared the effects of endoscopic ultrasound-guided celiac ganglia neurolysis (CGN) vs the effects of CPN on pain, quality of life (QOL), and survival. METHODS: We performed a randomized, double-blind trial of patients with unresectable pancreatic ductal adenocarcinoma and abdominal pain; 60 patients (age 66.4±11.6 years; male 66%) received CPN and 50 patients (age 66.8±10.0 years; male 56%) received CGN. Primary outcomes included pain control and QOL at week 12 and survival (overall median and 12 months). Secondary outcomes included morphine response, performance status, secondary neurolytic effects, and adverse events. RESULTS: Rates of pain response at 12 weeks were 46.2% for CGN and 40.4% for CPN (P = .84). There was no significant difference in improvement of QOL between the techniques. The median survival time was significantly shorter for patients receiving CGN (5.59 months) compared to (10.46 months) (hazard ratio for CGN, 1.49; 95% CI, 1.02-2.19; P = .042), particularly for patients with non-metastatic disease (hazard ratio for CGN, 2.95; 95% CI, 1.61-5.45; P < .001). Rates of survival at 12 months were 42% for patients who underwent CPN vs 26% for patients who underwent CGN. The number of adverse events did not differ between techniques. CONCLUSION: In a prospective study of patients with unresectable pancreatic ductal adenocarcinoma and abdominal pain, we found CGN to reduce median survival time without improving pain, QOL, or adverse events, compared to CPN. The role of CGN must be therefore be reassessed. Clinicaltrials.gov no: NCT01615653.

Risk of Pancreatic Cancer in Patients With Pancreatic Cysts and Family History of Pancreatic Cancer.

BACKGROUND & AIMS: A diagnosis of pancreatic cancer in a first-degree relative increases an individuals' risk of this cancer. However, it is not clear whether this cancer risk increases in individuals with pancreatic cystic lesions who have a first-degree relative with pancreatic cancer. The Fukuoka criteria are used to estimate risk of pancreatic cancer for patients with pancreatic cystic lesions: individuals with cysts with high risk or worrisome features (Fukuoka positive) have a higher risk of pancreatic cancer than individuals without these features (Fukuoka negative). We aimed to compare the risk of pancreatic cancer and surgery based on presence or absence of pancreatic cystic lesions and a first-degree relative with pancreatic cancer. METHODS: We performed a retrospective study of patients seen at the Mayo Clinic in Rochester, Minnesota, from January 1, 2000, through December 31, 2012. We identified individuals with: pancreatic cystic lesions and first-degree relative with pancreatic cancer (group 1, n = 269), individuals with pancreatic cystic lesions but no first-degree relative with pancreatic cancer (group 2, n = 1195), and individuals without pancreatic cystic lesions but with a first-degree relative with pancreatic cancer (group 3, n = 720). We compared, among groups, as well among patients with cysts classified according to Fukuoka criteria, proportions of individuals who developed pancreatic cancer or underwent pancreatic surgery within a 5-year period. RESULTS: A significantly higher proportion of individuals in group 1 developed pancreatic cancer during the 5-year period than in group 3 (6.64% vs 1.69%; P = .03); there was no significant difference between the percentage of individuals in group 1 vs group 2 who developed pancreatic cancer (6.64% vs 4.05%; P = .41). There was no significant difference in pancreatic cancer development among individuals with Fukuoka-positive cysts with vs without a family history of pancreatic cancer (P = .39). There was no significant difference in the proportion of patients in group 1 vs group 2 who underwent pancreatic surgery for their pancreatic cyst over the 5-year period (14.37% vs 11.80%; P = .59). Among patients with Fukuoka-negative cysts, a significantly higher proportion underwent surgery in group 1 than in group 2 (10.90% vs 5.90%; P = .03). However, among patients with Fukuoka-positive cysts, there was no difference in proportions of patients who underwent surgery between groups 1 and 2 (P = .66). CONCLUSIONS: In a retrospective study of patients with pancreatic cysts and/or cancer, we found that a family history of pancreatic cancer does not affect 5-year risk of pancreatic cancer in patients with pancreatic cystic lesions. Despite this, among patients with Fukuoka-negative cysts, a higher proportion of those with a family history of pancreatic cancer undergo surgery than patients without family history of pancreatic cancer.

Detection and Characterization of Renal Stones by Using Photon-Counting-based CT.

Purpose To compare a research photon-counting-detector (PCD) CT scanner to a dual-source, dual-energy CT scanner for the detection and characterization of renal stones in human participants with known stones. Materials and Methods Thirty study participants (median age, 61 years; 10 women) underwent a clinical renal stone characterization scan by using dual-energy CT and a subsequent research PCD CT scan by using the same radiation dose (as represented by volumetric CT dose index). Two radiologists were tasked with detection of stones, which were later characterized as uric acid or non-uric acid by using a commercial dual-energy CT analysis package. Stone size and contrast-to-noise ratio were additionally calculated. McNemar odds ratios and Cohen k were calculated separately for all stones and small stones (≤3 mm). Results One-hundred sixty renal stones (91 stones that were ≤ 3 mm in axial length) were visually detected. Compared with 1-mm-thick routine images from dual-energy CT, the odds of detecting a stone at PCD CT were 1.29 (95% confidence interval: 0.48, 3.45) for all stones. Stone segmentation and characterization were successful at PCD CT in 70.0% (112 of 160) of stones versus 54.4% (87 of 160) at dual-energy CT, and was superior for stones 3 mm or smaller at PCD CT (45 vs 25 stones, respectively; P = .002). Stone characterization agreement between scanners for stones of all sizes was substantial (k = 0.65). Conclusion Photon-counting-detector CT is similar to dual-energy CT for helping to detect renal stones and is better able to help characterize small renal stones. © RSNA, 2018.

Risk of ESRD and Mortality in Kidney and Bladder Stone Formers.

RATIONALE & OBJECTIVES: Kidney stones have been associated with increased risk for end-stage renal disease (ESRD). However, it is unclear whether there is also an increased risk for mortality and if these risks are uniform across clinically distinct categories of stone formers. STUDY DESIGN: Historical matched-cohort study. SETTING & PARTICIPANTS: Stone formers in Olmsted County, MN, between 1984 and 2012 identified using International Classification of Diseases, Ninth Revision codes. Age- and sex-matched individuals who had no codes for stones were the comparison group. PREDICTOR: Stone formers were placed into 5 mutually exclusive categories after review of medical charts: incident symptomatic kidney, recurrent symptomatic kidney, asymptomatic kidney, bladder only, and miscoded (no stone). OUTCOMES: ESRD, mortality, cardiovascular mortality, and cancer mortality. ANALYTICAL APPROACH: Cox proportional hazards models with adjustment for baseline comorbid conditions. RESULTS: Overall, 65 of 6,984 (0.93%) stone formers and 102 of 28,044 (0.36%) non-stone formers developed ESRD over a mean follow-up of 12.0 years. After adjusting for baseline hypertension, diabetes mellitus, dyslipidemia, gout, obesity, and chronic kidney disease, risk for ESRD was higher in recurrent symptomatic kidney (HR, 2.34; 95% CI, 1.08-5.07), asymptomatic kidney (HR, 3.94; 95% CI, 1.65-9.43), and miscoded (HR, 6.18; 95% CI, 2.25-16.93) stone formers, but not in incident symptomatic kidney or bladder stone formers. The adjusted risk for all-cause mortality was higher in asymptomatic kidney (HR, 1.40; 95% CI, 1.18-1.67) and bladder (HR, 1.37; 95% CI, 1.12-1.69) stone formers. Chart review of asymptomatic and miscoded stone formers suggested increased risk for adverse outcomes related to diagnoses including urinary tract infection, cancer, and musculoskeletal or gastrointestinal pain. CONCLUSIONS: The higher risk for ESRD in recurrent symptomatic compared with incident symptomatic kidney stone formers suggests that stone events are associated with kidney injury. The clinical indication for imaging in asymptomatic stone formers, the correct diagnosis in miscoded stone formers, and the cause of a bladder outlet obstruction in bladder stone formers may explain the higher risk for ESRD or death in these groups.

Esophagorespiratory Fistulas: Survival and Outcomes of Treatment.

GOAL: The purpose of this study was to characterize outcomes of esophagorespiratory fistulas (ERF) by etiology and initial treatment strategy. BACKGROUND: ERF is a morbid condition for which optimal treatment strategies and outcomes are still in evolution. STUDY: Medical records and images were reviewed for all patients diagnosed with ERF at Mayo Clinic in Rochester, MN, between September 1, 2001 and January 1, 2012. Fistulas were classified as malignant or benign. Treatment strategies were classified as surgical or nonsurgical (typically esophageal stent placement). Technical and clinical success, survival, and survival free of second intervention were assessed. RESULTS: A total of 123 patients with acquired ERF were identified, of whom 65 (53%) were malignant and 58 (47%) benign. Initial treatment strategy was nonsurgical in 88 (72%) patients and surgical in 35 (28%); lower Charlson comorbidity scores were associated with increased likelihood of surgery. Technical and clinical success was seen in a majority of patients treated both surgically and nonsurgically. Patients with malignant ERF treated surgically survived longer than patients undergoing nonsurgical treatment (hazard ratio=5.6, P=0.005). In contrast, those with benign ERF had similar overall survival regardless of whether they received initial surgical or nonsurgical treatment; reintervention was more common in those who underwent nonsurgical treatment (hazard ratio=2.3, P=0.03). CONCLUSIONS: We conclude that survival in malignant ERF is better with surgical intervention in selected patients. Surgical and nonsurgical techniques achieve similar survival in benign ERF, but reintervention is more common in those treated endoscopically.

A Randomized, Controlled Trial of Rituximab in IgA Nephropathy with Proteinuria and Renal Dysfunction.

IgA nephropathy frequently leads to progressive CKD. Although interest surrounds use of immunosuppressive agents added to standard therapy, several recent studies have questioned efficacy of these agents. Depleting antibody-producing B cells potentially offers a new therapy. In this open label, multicenter study conducted over 1-year follow-up, we randomized 34 adult patients with biopsy-proven IgA nephropathy and proteinuria >1 g/d, maintained on angiotensin-converting enzyme inhibitors or angiotensin receptor blockers with well controlled BP and eGFR<90 ml/min per 1.73 m2, to receive standard therapy or rituximab with standard therapy. Primary outcome measures included change in proteinuria and change in eGFR. Median baseline serum creatinine level (range) was 1.4 (0.8-2.4) mg/dl, and proteinuria was 2.1 (0.6-5.3) g/d. Treatment with rituximab depleted B cells and was well tolerated. eGFR did not change in either group. Rituximab did not alter the level of proteinuria compared with that at baseline or in the control group; three patients in each group had ≥50% reduction in level of proteinuria. Serum levels of galactose-deficient IgA1 or antibodies against galactose-deficient IgA1 did not change. In this trial, rituximab therapy did not significantly improve renal function or proteinuria assessed over 1 year. Although rituximab effectively depleted B cells, it failed to reduce serum levels of galactose-deficient IgA1 and antigalactose-deficient IgA1 antibodies. Lack of efficacy of rituximab, at least at this stage and severity of IgA nephropathy, may reflect a failure of rituximab to reduce levels of specific antibodies assigned salient pathogenetic roles in IgA nephropathy.

The Importance of Statistical Competencies for Medical Research Learners.

It is very important for medical professionals and medical researchers to be literate in statistics. However, we have found that the degree of literacy that is required should not be identical for every statistical competency or even for every learner. We first begin by describing why the development, teaching, and assessment of statistical competencies for medical professionals and medical researchers are critical tasks. We next review our three substantial efforts at developing a comprehensive list of statistical competencies that can be used as a guide for what medical research learners should know about statistics, for curricular development, and for assessment of statistical education. We then summarize the origin and the inclusion of the statistical competency items. We follow this with a description of potential uses and applications of the statistical competencies to improve targeted learning for medical research learners. Finally, we discuss implications of the statistical competencies for undergraduate statistics education.

Nonrelaxing Pelvic Floor Dysfunction Is an Underestimated Complication of Ileal Pouch-Anal Anastomosis.

BACKGROUND & AIMS: Nonrelaxing pelvic floor dysfunction (N-RPFD), or dyssynergic defecation, is the paradoxical contraction and/or impaired relaxation of pelvic floor and anal muscles during defecation. Few studies have evaluated this disorder in patients with an ileal pouch-anal anastomosis (IPAA). We investigated the frequency of N-RPFD in patients with and without chronic pouchitis following IPAA and the effectiveness of biofeedback therapy within this population. METHODS: We conducted a retrospective study of all patients with an IPAA who underwent anorectal manometry between January 2000 and March 2015 (n = 111). N-RPFD was diagnosed in patients with symptoms consistent with a pouch evacuation disorder and 1 or more of the following abnormal tests: anorectal manometry, balloon expulsion test, barium or magnetic resonance defecography, or external anal sphincter electromyography. Patients who completed biofeedback therapy were identified and assessed to determine symptomatic response. RESULTS: Of the 111 patients evaluated, 83 (74.8%) met criteria for N-RPFD. A significantly higher proportion of patients with chronic pouchitis were diagnosed with N-RPFD than patients without chronic pouchitis (83.3% vs 62.2%, respectively; P = .012). Most patients diagnosed with N-RPFD had abnormal results from the balloon expulsion test (78.3%); 53.0% of patients diagnosed with N-RPFD had abnormal findings from external anal sphincter electromyography, 25.3% had abnormal defecography findings, and 20.5% had abnormal findings from anorectal manometry. Twenty-two patients completed biofeedback therapy: 15 patients (68.2%) had mild-moderate improvement and 5 patients (22.7%) had significant improvement of symptoms. CONCLUSIONS: N-RPFD occurs in almost 75% of patients with an IPAA, especially in patients with chronic pouchitis. Biofeedback seems to be an effective therapy for patients with an IPAA and N-RPFD, but further studies are needed for validation.

Montelukast Does not Maintain Symptom Remission After Topical Steroid Therapy for Eosinophilic Esophagitis.

BACKGROUND & AIMS: Montelukast, a cysteinyl leukotriene type-1 receptor blocker, has been shown in small retrospective studies to reduce symptoms in patients with eosinophilic esophagitis (EoE). We performed a randomized, placebo-controlled, double-blind trial to determine whether montelukast maintains symptomatic remission induced by topical steroid therapy in patients with EoE. METHODS: We performed a prospective study of adult patients with EoE (solid-food dysphagia and a peak esophageal eosinophil count of >20 cells/high-powered field) enrolled at the Mayo Clinic in Rochester, Minnesota, from April 2008 through February 2015. All patients had been treated previously for at least 6 weeks with a topical steroid until their symptoms were in remission. Steroids were discontinued and patients then were assigned randomly to groups given montelukast (20 mg/day, n = 20) or placebo (n = 21) for 26 weeks (groups were matched for age, sex, history of allergic disease, reflux symptoms, and endoscopic findings of EoE). Study participants were assessed via a structured telephone interview at weeks 2, 4, 8, 12, 16, 20, and 24. Remission was defined as the absence of solid-food dysphagia. RESULTS: Based on an intention-to-treat analysis, after 26 weeks, 40.0% of subjects in the montelukast group and 23.8% in the placebo group were in remission. The odds ratio for remission in the montelukast group was 0.48 (95% confidence interval, 0.10-2.16) (P = .33). No side effects were reported from either group. CONCLUSIONS: In a randomized controlled trial of the ability of montelukast to maintain remission in patients in remission from EoE after steroid therapy, we found montelukast to be well tolerated; 40% of patients remained in remission, but this proportion did not differ significantly from that of the placebo group. ClinicalTrials.gov no: NCT00511316.