Monoclonal Gammopathy and Its Association with Progression to Kidney Failure and Mortality in Patients with CKD.

BACKGROUND: Little is known about the prognostic significance of monoclonal gammopathy of undetermined and renal significance (MGUS and MGRS) in patients with CKD. The objective of this study was to determine the clinical and kidney outcomes of patients with CKD with either MGUS or MGRS compared with those with CKD without MGUS or MGRS. METHODS: We conducted a retrospective cohort study from 2013 to 2018. Patients who had both CKD diagnosis and monoclonal testing were identified. Patients were divided into MGRS, MGUS, and no monoclonal gammopathy groups. Cumulative incidence functions and Cox proportional hazards regression were used to model time to event data and to evaluate the association between monoclonal gammopathy status and risk of kidney failure, with death treated as a competing risk. RESULTS: Among 1535 patients, 59 (4%) had MGRS, 648 (42%) had MGUS, and 828 (54%) had no monoclonal gammopathy. Unadjusted analysis showed that compared with no monoclonal gammopathy patients, patients with MGRS were at higher risk of kidney failure (hazard ratio [HR] [95% confidence interval]: 2.5 [1.5 to 4.2] but not patients with MGUS (HR [95% confidence interval]: 1.3 [0.97 to 1.6]), after taking death into account as a competing risk. However, in the multivariable analysis, after adjusting for age, sex, eGFR, proteinuria, and Charlson Comorbidity Index, the risk of progression to kidney failure (with death as competing risk) in the MGRS group was no longer statistically significant (HR: 0.9 [0.5 to 1.8]). The same was also true for the MGUS group compared with the group with no monoclonal gammopathy (HR: 1.3 [0.95 to 1.6]). When evaluating the association between MGUS/MGRS status and overall survival, MGRS was significantly associated with mortality in fully adjusted models compared with the group with no monoclonal gammopathy, while MGUS was not. CONCLUSIONS: After adjusting for traditional risk factors, MGUS/MGRS status was not associated with a greater risk of kidney failure, but MGRS was associated with a higher risk of mortality compared with patients with no monoclonal gammopathy.

Extracorporeal membrane oxygenation and acute kidney injury: a single-center retrospective cohort.

To assess the relationship between acute kidney injury (AKI) with outcomes among patients requiring extracorporeal membrane oxygenation (ECMO). This is a single-center, retrospective cohort study of adult patients admitted to intensive care units (ICU) at a tertiary referral hospital requiring ECMO from July 1, 2015, to August 30, 2019. We assessed the temporal relationship of AKI and renal replacement therapy with ECMO type (VV vs. VA). The primary outcome was in-hospital mortality rates. We used Kruskal-Wallis or chi-square tests for pairwise comparisons, cause-specific Cox proportional hazards models were utilized for the association between AKI prevalence and in-hospital mortality, and a time-dependent Cox model was used to describe the association between AKI incidence and mortality. After the screening, 190 patients met eligibility criteria [133 (70%) AKI, 81 (43%) required RRT]. The median age was 61 years, and 61% were males. Among AKI patients, 48 (36%) and 85 (64%) patients developed AKI before and after ECMO, respectively. The SOFA Day 1, baseline creatinine, respiratory rate (RR), use of vasopressin, vancomycin, proton pump inhibitor, antibiotics, duration of mechanical ventilation and ECMO, and ICU length of stay were higher in AKI patients compared with those without AKI (P < 0.01). While ICU and in-hospital mortality rates were 46% and 50%, respectively, there were no differences based on the AKI status. The type and characteristics of ECMO support were not associated with AKI risk. Among AKI patients, 77 (58%) were oliguric, and 46 (60%) of them received diuretics. Urine output in the diuretic group was only higher on the first day than in those who did not receive diuretics (P = 0.03). Among ECMO patients, AKI was not associated with increased mortality but was associated with prolonged duration of mechanical ventilation and ICU length of stay.

Changes in Doppler-Derived Kidney Venous Flow and Adverse Cardiorenal Outcomes in Patients With Heart Failure.

Background The impact of changes in Doppler-derived kidney venous flow in heart failure (HF) is not well studied. We aimed to investigate the association of Doppler-derived kidney venous stasis index (KVSI) and intrakidney venous-flow (IKVF) patterns with adverse cardiorenal outcomes in patients with HF. Methods and Results In this observational cohort study, consecutive inpatients with HF referred to a nephrologist because of a history of diuretic resistance and abnormal kidney function (n=216) underwent spectral kidney assessments after admission (Doppler 1) and 25 to 35 days later (Doppler 2) to identify IKVF patterns (continuous/pulsatile/biphasic/monophasic) and KVSI levels. Cox proportional hazard regression models were used to evaluate the associations between KVSI/IKVF patterns at Doppler 1 as well as changes from Doppler 1 to Doppler 2 and risk of cardiorenal events up to 18 months after admission. Worsening HF or death occurred in 126 patients. Both baseline KVSI (hazard ratio [HR], 1.49 [95% CI, 1.37-1.61] per 0.1-unit increase) and baseline IKVF pattern (HR, 2.47 [95% CI, 2.01-3.04] per 1 pattern severity increase) were significantly associated with worsening HF/death. Increases in both KVSI and IKVF pattern severity from Doppler 1 to 2 were also associated with an increased risk of worsening HF/death (HR, 3.00 [95% CI, 2.08-4.32] per 0.1-unit increase change; and HR, 6.73 [95% CI, 3.27-13.86] per 1 pattern increase in severity change, respectively). Similar results were observed for kidney outcomes. Conclusions Baseline kidney venous flow predicted adverse cardiorenal events, and inclusion of serial kidney venous flow in cardiorenal risk stratification could facilitate clinical decision-making for patients with HF. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT03039959.

Whole Body Retrograde Perfusion Combined With Central Aortic Perfusion Strategy in the Repair of Distal Arch Pathology Through a Lateral Thoracotomy.

OBJECTIVE: To compare the results of the hypothermic circulatory arrest (HCA) + retrograde whole-body perfusion (RBP) technique with those of deep hypothermic circulatory arrest (DHCA-only) approach. METHODS: Limited data are available on cerebral protection techniques when distal arch repairs are performed through a lateral thoracotomy. In 2012, the RBP technique was introduced as adjunct to HCA during open distal arch repair via thoracotomy. We reviewed the results of the HCA + RBP technique compared with those of the DHCA-only approach. From February 2000 to November 2019, 189 patients (median age, 59 [IQR, 46 to 71] years; 30.7% female) underwent open distal arch repair via lateral thoracotomy to treat aortic aneurysms. The DHCA technique was used in 117 patients (62%, median age 53 [IQR, 41 to 60] years), whereas HCA + RBP was used in 72 patients (38%, median age 65 [IQR, 51 to 74] years). In HCA + RBP patients, cardiopulmonary bypass was interrupted when systemic cooling achieved isoelectric electroencephalogram; once the distal arch had been opened, RBP was then initiated via the venous cannula (flow of 700 to 1000 mL/min, central venous pressure <15 to 20 mm Hg). RESULTS: The stroke rate was significantly lower in the HCA + RBP group (3%, n=2) compared with the DHCA-only (12%, n=14) (P=.031), despite longer circulatory arrest times in HCA + RBP compared with the DHCA-only (31 [IQR, 25 to 40] minutes vs 22 [IQR, 17 to 30] minutes, respectively; P<.001). Operative mortality for patients undergoing HCA + RBP was 6.7% (n=4), whereas for those undergoing DHCA-only it was 10.4% (n=12) (P=.410). The 1-, 3-, and 5-year age-adjusted survival rates for the DHCA group are 86%, 81%, and 75%, respectively. The 1-, 3-, and 5-year age-adjusted survival rates for the HCA + RBP group are 88%, 88%, and 76%, respectively. CONCLUSION: The addition of RBP to HCA in the treatment of distal open arch repair via a lateral thoracotomy is safe and provides excellent neurological protection.

Apixaban for Anticoagulation After Robotic Mitral Valve Repair.

BACKGROUND: There is no consensus regarding postoperative anticoagulation after mitral valve repair (MVRep). We compared the outcomes of post-MVRep anticoagulation with apixaban compared to warfarin. METHODS: We reviewed data of 666 patients who underwent isolated robotic MVRep between January 2008 and October 2019. We excluded patients who had conversion to sternotomy and those discharged without anticoagulation or on clopidogrel (n = 40). Baseline and intraoperative characteristics and antiplatelet/anticoagulation records were collected. In-hospital and post-discharge complications and overall survival were compared. RESULTS: Among the 626 studied patients the median age was 58 years (interquartile range, 51-66), 71% were male, and 1% (n = 9) had atrial fibrillation. Eighty percent (n = 499) were discharged on warfarin and 20% on apixaban (n = 127). Almost all patients (126 of 127, 99%) in the apixaban group were also on aspirin at discharge, whereas in the warfarin group only 79% (n = 395) were also on aspirin at discharge. Baseline characteristics were similar, except that the apixaban group had more female patients (46 of 127, 36% vs 136 of 499, 27%, P = .047). There were no differences in in-hospital complications, including stroke. Readmission rate was higher in the apixaban group (15 of 127, 12% vs 30 of 499, 6%, P = .02), driven mostly by postoperative atrial fibrillation (6 of 127 [5%] vs 5 of 499 [1%], respectively; P = .01). There was no difference in other complications (including bleeding and thromboembolic events), or overall mortality within 3 years. Exclusion of patients who did not receive aspirin at discharge did not affect the results. CONCLUSIONS: Anticoagulation with apixaban after minimally invasive robotic MVRep is safe and has similar rates of bleeding and thromboembolism compared to patients treated with warfarin.

Robotic vs. minimally invasive mitral valve repair: A 5-year comparison of surgical outcomes.

BACKGROUND: Minimally invasive mitral valve repair (MVr) is commonly performed. Data on the outcomes of robotic MVr versus nonrobotic minimally invasive MVr are lacking. We sought to compare the short-term and mid-term outcomes of robotic and nonrobotic MVr. METHODS: We reviewed all patients who underwent robotic MVr (n = 424) or nonrobotic MVr via right mini-thoracotomy (n = 86) at Mayo Clinic, Rochester, MN, from January 2015 to February 2020. Data on baseline and operative characteristics, operative and long-term outcomes were analyzed. Patients were matched 1:1 using propensity scores. RESULTS: Sixty-nine matched pairs were included in the study. The median age was 59 years (interquartile range [IQR]: 54-69) and 75% (n = 103) were male. Baseline characteristics were similar after matching. Robotic and nonrobotic MVr had similar operative characteristics, except that robotic had longer cross-clamp times (57 [48-67] vs. 47 [37-58] min, p < .001) and more P2 resections (83% vs. 68%, p = .05) compared to nonrobotic MVr. There was no difference in operative outcomes between groups. Hospital stay was shorter after robotic MVr (4 [3-4] vs. 4 [4-6] days, p = .003). After a median follow-up of 3.3 years (IQR, 2.1-4.5), there was no mortality in either group, and there was no difference in freedom from mitral valve reoperations between robotic and nonrobotic MVr (5 years: 97.1% vs. 95.7%, p = .63). Follow-up echocardiogram analysis predicted excellent freedom from recurrent moderate-or-severe mitral regurgitation at 3 years after robotic and nonrobotic MVr (90% vs. 92%, p = .18, respectively). CONCLUSIONS: Both short-term and mid-term outcomes of robotic and nonrobotic minimally invasive mitral repair surgery are comparable.

Clinical outcomes of mitral valve repair for degenerative mitral regurgitation in elderly patients.

OBJECTIVES: This study analyzes the safety and outcomes of mitral valve repair for degenerative mitral valve regurgitation in patients 75 years of age or older. METHODS: We retrospectively reviewed the clinical results of 343 patients aged ≥75 years who underwent mitral valve repair for degenerative mitral valve regurgitation as a primary indication between January 1998 and June 2017. RESULTS: The median (interquartile range) age of the patients was 79.4 (76.9, 82.9) years, and 132 (38.5%) patients were women. Concomitant procedures were performed in 123 patients: tricuspid surgery in 68 (19.8%) and a maze procedure or pulmonary vein isolation in 55 (16.0%). Operative mortality was 1.2%. Operative complications included atrial fibrillation in 37.9%, prolonged ventilation in 7.0%, pacemaker implantation in 3.8, renal failure requiring dialysis in 1.5 and stroke in 3 (0.9%). The median follow-up was 7.4 years (interquartile range, 3.5-14.1 years). The cumulative incidence rates of mitral valve reoperation were 2.2%, 3.2% and 3.2% at 1, 5 and 10 years, respectively. Overall survival at 1, 5 and 10 years were 95%, 83% and 51%, respectively. Older age, smoking and over and underweight were associated with increased risk of mortality, while higher left ventricular ejection fraction and hypertension were associated with reduced risk. CONCLUSIONS: Mitral valve repair in elderly patients can be accomplished with low operative mortality and complications. Mitral valve repair in the elderly remains the preferred treatment for degenerative mitral regurgitation.

Telehealth versus face-to-face visits: A comprehensive outpatient perspective-based cohort study of patients with kidney disease.

BACKGROUND: Telenephrology has become an important health care delivery modality during the COVID-19 pandemic. However, little is known about patient perspectives on the quality of care provided via telenephrology compared to face-to-face visits. We aimed to use objective data to study patients' perspectives on outpatient nephrology care received via telenephrology (phone and video) versus face-to-face visits. METHODS: We retrospectively studied adults who received care in the outpatient Nephrology & Hypertension division at Mayo Clinic, Rochester, from March to July 2020. We used a standardized survey methodology to evaluate patient satisfaction. The primary outcome was the percent of patients who responded with a score of good (4) or very good (5) on a 5-point Likert scale on survey questions that asked their perspectives on access to their nephrologist, relationship with care provider, their opinions on the telenephrology technology, and their overall assessment of the care received. Wilcoxon rank sum tests and chi-square tests were used as appropriate to compare telenephrology versus face-to-face visits. RESULTS: 3,486 of the patient encounters were face-to-face, 808 phone and 317 video visits. 443 patients responded to satisfaction surveys, and 21% of these had telenephrology encounters. Established patients made up 79.6% of telenephrology visits and 60.9% of face-to-face visits. There was no significant difference in patient perceived access to health care, satisfaction with their care provider, or overall quality of care between patients cared for via telenephrology versus face-to-face. Patient satisfaction was also equally high. CONCLUSIONS: Patient satisfaction was equally high amongst those patients seen face-to-face or via telenephrology.

Hypertrophic Obstructive Cardiomyopathy: Discrepancy Between Hemodynamic Measurements in the Cardiac Laboratory and Operating Room Is to Be Expected.

OBJECTIVES: It is not uncommon to observe some discrepancy in hemodynamic values characterizing left ventricular outflow tract (LVOT) obstruction preoperatively and in the operating room in patients with hypertrophic obstructive cardiomyopathy. Interpretation of this discrepancy can be challenging. To clarify the extent of the discrepancy, the authors compared hemodynamic variables in patients undergoing septal myectomy at the time of preoperative and intraoperative evaluation. DESIGN: Retrospective study. SETTING: Single academic medical center. INTERVENTIONS: Medical records review, study group-173 patients. MEASUREMENTS AND MAIN RESULTS: While there was no statistically significant difference in resting peak LVOT gradients by preoperative transthoracic echocardiography (TTE) compared to intraoperative transesophageal echocardiography (46 mmHg [19-87 mmHg] v 36 mmHg [16-71 mmHg], p = 0.231), the former were higher compared to direct needle-resting LVOT gradient measurements before myectomy (49 mmHg [19-88 mmHg] v 32 mmHg [14-67 mmHg], p = 0.0022). The prevalence of systolic anterior motion was high (94.6% v 91.6%, P = 1.000) both on pre- and intraoperative evaluation. The incidence of moderate/severe mitral was higher intraoperatively (p < 0.0001). Pulmonary artery systolic pressures measured by pulmonary artery catheter provided higher values compared to preoperative TTE estimate (39 mmHg [34-45 mmHg] v 34 mmHg [28-41 mmHg], p < 0.0001). CONCLUSIONS: Discrepancy between hemodynamic measurements in the cardiac laboratory and operating room is common and generally should not affect planned patients' care. These changes in hemodynamics might be explained by preoperative fasting, anesthetic agents, volume shifts while supine, and positive-pressure ventilation, as well as the difference in measurement techniques.

Posttransplant recurrence of calcium oxalate crystals in patients with primary hyperoxaluria: Incidence, risk factors, and effect on renal allograft function.

Primary hyperoxaluria (PH) is a metabolic defect that results in oxalate overproduction by the liver and leads to kidney failure due to oxalate nephropathy. As oxalate tissue stores are mobilized after transplantation, the transplanted kidney is at risk of recurrent disease. We evaluated surveillance kidney transplant biopsies for recurrent calcium oxalate (CaOx) deposits in 37 kidney transplants (29 simultaneous kidney and liver [K/L] transplants and eight kidney alone [K]) in 36 PH patients and 62 comparison transplants. Median follow-up posttransplant was 9.2 years (IQR: [5.3, 15.1]). The recurrence of CaOx crystals in surveillance biopsies in PH at any time posttransplant was 46% overall (41% in K/L, 62% in K). Higher CaOx crystal index (which accounted for biopsy sample size) was associated with higher plasma and urine oxalate following transplant (p < .01 and p < .02, respectively). There was a trend toward higher graft failure among PH patients with CaOx crystals on surveillance biopsies compared with those without (HR 4.43 [0.88, 22.35], p = .07). CaOx crystal deposition is frequent in kidney transplants in PH patients. The avoidance of high plasma oxalate and reduction of CaOx crystallization may decrease the risk of recurrent oxalate nephropathy following kidney transplantation in patients with PH. This study was approved by the IRB at Mayo Clinic.

Clinical characterization of primary hyperoxaluria type 3 in comparison with types 1 and 2.

BACKGROUND: Primary hyperoxaluria (PH) type 3 (PH3) is caused by mutations in the hydroxy-oxo-glutarate aldolase 1 gene. PH3 patients often present with recurrent urinary stone disease in the first decade of life, but prior reports suggested PH3 may have a milder phenotype in adults. This study characterized clinical manifestations of PH3 across the decades of life in comparison with PH1 and PH2. METHODS: Clinical information was obtained from the Rare Kidney Stone Consortium PH Registry (PH1, n = 384; PH2, n = 51; PH3, n = 62). RESULTS: PH3 patients presented with symptoms at a median of 2.7 years old compared with PH1 (4.9 years) and PH2 (5.7 years) (P = 0.14). Nephrocalcinosis was present at diagnosis in 4 (7%) PH3 patients, while 55 (89%) had stones. Median urine oxalate excretion was lowest in PH3 patients compared with PH1 and PH2 (1.1 versus 1.6 and 1.5 mmol/day/1.73 m2, respectively, P < 0.001) while urine calcium was highest in PH3 (112 versus 51 and 98 mg/day/1.73 m2 in PH1 and PH2, respectively, P < 0.001). Stone events per decade of life were similar across the age span and the three PH types. At 40 years of age, 97% of PH3 patients had not progressed to end-stage kidney disease compared with 36% PH1 and 66% PH2 patients. CONCLUSIONS: Patients with all forms of PH experience lifelong stone events, often beginning in childhood. Kidney failure is common in PH1 but rare in PH3. Longer-term follow-up of larger cohorts will be important for a more complete understanding of the PH3 phenotype.

A Population-Based Study of the Incidence and Natural History of Degenerative Thoracic Aortic Aneurysms.

OBJECTIVE: To investigate the incidence and natural history of degenerative thoracic aortic aneurysms (TAAs) and compare results between ascending (aTAAs) and descending TAAs (dTAAs). PATIENTS AND METHODS: This population-based cohort study used the Rochester Epidemiology Project database from January 1, 1995, through December 31, 2015. Patients were classified as the aTAA or dTAA group. RESULTS: Of 238 Olmsted County residents studied, 131 (55.0%) were women; 154 (64.7%) were in the aTAA group, and 84 (35.3%) were in the dTAA group. Median age was 77.0 years (interquartile range, 69.1-83.8 years). The overall age- and sex-adjusted incidence rate was 13.8 per 100,000 person-years (95% CI, 12.1 to 15.6) and varied from 9.9 in 1995 to 1999 to 19.0 in 2005 to 2009. It was 9.0 (95% CI, 7.5 to 10.4) for the aTAA and 4.9 (95% CI, 3.8 to 5.9) for the dTAA group. Overall 5-year survival was 62.5%, lower than the expected survival of 73.7% for the US 2010 census population (P<.001). The 5-year survival was 42.9% for the aTAA and 73.4% for the dTAA group (P<.001). On multivariable analysis, advanced age and smoking status were associated with all-cause mortality. The 5-year estimate of freedom from an aortic-related event was 80.0%, lower for dTAAs (67.8%) than for aTAAs (85.2%; P<.001). Maximal aortic diameter and dTAAs were associated with aortic-related events. CONCLUSION: The incidence of TAAs was stable from 1995 to 2015 and mortality for those with TAAs remains higher than for the general population. Older age and smoking status were associated with overall mortality, whereas larger aneurysms and dTAAs were associated with aortic-related events.

Oncologic Outcomes for Head and Neck Skin Malignancies Treated with Protons.

PURPOSE: Radiation therapy (RT) is the standard treatment for patients with inoperable skin malignancies of the head and neck region (H&N), and as adjuvant treatment post surgery in patients at high risk for local or regional recurrence. This study reports clinical outcomes of intensity-modulated proton therapy (IMPT) for these malignancies. MATERIALS AND METHODS: We retrospectively reviewed cases involving 47 patients with H&N malignancies of the skin (squamous cell, basal cell, melanoma, Merkel cell, angiosarcoma, other) who underwent IMPT for curative intent between July 2016 and July 2019. Overall survival was estimated via Kaplan-Meier analysis, and oncologic outcomes were reported as cumulative incidence with death as a competing risk. RESULTS: The 2-year estimated local recurrence rate, regional recurrence rate, local regional recurrence rate, distant metastasis rate, and overall survival were 11.1% (95% confidence interval [CI], 4.1%-30.3%), 4.4% (95% CI, 1.1%-17.4%), 15.5% (95% CI, 7%-34.3%), 23.4% (95% CI, 5.8%-95.5%), and 87.2% (95% CI, 75.7%-100%), respectively. No patient was reported to have a grade 3 or higher adverse event during the last week of treatment or at the 3-month follow-up visit. CONCLUSION: IMPT is safe and effective in the treatment of skin malignancies of the H&N.

Liver Stiffness Measured by Either Magnetic Resonance or Transient Elastography Is Associated With Liver Fibrosis and Is an Independent Predictor of Outcomes Among Patients With Primary Biliary Cholangitis.

GOALS: We aimed to describe the diagnostic and prognostic performance of transient elastography (TE) and magnetic resonance elastography (MRE) in patients with primary biliary cholangitis (PBC). BACKGROUND: The diagnostic performance of TE and MRE in detecting advanced fibrosis in PBC and in predicting outcomes independent of existing serologic prognostic markers is incompletely understood. MATERIALS AND METHODS: Five hundred thirty-eight consecutive patients with PBC at 3 centers with liver stiffness (LS) measurements by TE (n=286) or MRE (n=332) were reviewed. LS cutoffs for predicting fibrosis stages were determined by receiver operating characteristic curves among those with a liver biopsy (TE, n=63; MRE, n=98). Cox proportional hazard regression modeling was used to identify associations between covariates and hepatic decompensation. RESULTS: The optimal LS thresholds for predicting histologic stage F4 were 14.40 kPa (area under the curve=0.94) for TE and 4.60 kPa (area under the curve=0.82) for MRE. Both TE and MRE outperformed biochemical markers for the prediction of histologic advanced fibrosis. Optimal LS thresholds to predict hepatic decompensation were 10.20 kPa on TE and 4.30 kPa on MRE. LS by TE and MRE (respectively) remained predictors of hepatic decompensation after adjusting for ursodeoxycholic acid responsiveness [hazard ratio (HR), 1.14; 95% confidence interval (CI), 1.05-1.24 and HR, 1.68; 95% CI, 1.28-2.19] and the GLOBE score (HR, 1.13; 95% CI, 1.07-1.19 and HR, 2.09; 95% CI, 1.57-2.78). CONCLUSION: LS measurement with either TE or MRE can accurately detect advanced fibrosis and offers additional prognostic value beyond existing serologic predictive tools.

Does ablation of atrial fibrillation at the time of septal myectomy improve survival of patients with obstructive hypertrophic cardiomyopathy?

OBJECTIVE: To evaluate the outcomes after septal myectomy in patients with obstructive hypertrophic cardiomyopathy according to atrial fibrillation and surgical ablation of atrial fibrillation. METHODS: We reviewed patients with obstructive hypertrophic cardiomyopathy who underwent septal myectomy at the Mayo Clinic from 2001 to 2016. History of atrial fibrillation was obtained from patient histories and electrocardiograms. All-cause mortality was the primary end point. RESULTS: A total of 2023 patients underwent septal myectomy, of whom 394 (19.5%) had at least 1 episode of atrial fibrillation preoperatively. Among patients with atrial fibrillation, 76 (19.3%) had only 1 known episode, 278 (70.6%) had recurrent paroxysmal atrial fibrillation, and 40 (10.2%) had persistent atrial fibrillation. Surgical ablation was performed in 190 patients at the time of septal myectomy, including 148 with pulmonary vein isolation and 42 with the classic maze procedure. Among all patients, operative mortality was 0.4%, and there were no early deaths in patients undergoing surgical ablation. Over a median follow-up of 5.6 years, patients with preoperative atrial fibrillation had increased mortality (hazard ratio, 1.36; 95% confidence interval, 0.97-1.91; P = .070) after multivariable adjustment for comorbidities. When considering the impact of atrial fibrillation with or without surgical treatment, the adjusted hazard ratio for mortality in patients undergoing ablation compared with no ablation was 0.93 (95% confidence interval, 0.52-1.69; P = .824). CONCLUSIONS: Atrial fibrillation is present preoperatively in one-fifth of patients with obstructive hypertrophic cardiomyopathy undergoing myectomy and showed a trend toward higher all-cause mortality. Survival of patients undergoing septal myectomy with preoperative atrial fibrillation was similar between those who did and did not receive concomitant surgical ablation.

Septal Myectomy and Concomitant Coronary Artery Bypass Grafting for Patients With Hypertrophic Cardiomyopathy and Coronary Artery Disease.

Severe coronary artery disease is associated with disproportionately increased risks of death in patients with hypertrophic cardiomyopathy. There is a paucity of data on the long-term effect of coronary revascularization at the time of myectomy. Between January 1, 1961, and October 31, 2017, 2913 adult patients underwent transaortic septal myectomy at Mayo Clinic. Concomitant coronary artery bypass grafting (CABG) was performed in 246 (8.4%). We compared baseline characteristics of patients who underwent septal myectomy with and without CABG and assessed the effect of surgical revascularization on the risk of all-cause mortality. Patients who underwent concomitant CABG were older (median [interquartile range], 66.3 [59.8-72.1] years vs 54.4 [43.5-64.8] years; P<.0001) and more likely to be male (63.0% vs 54.2%; P=.008) than those who did not undergo coronary revascularization at operation. There was no significant difference in preoperative left ventricular outflow tract gradients (55 [25-81] mm Hg vs 58 [25-88] mm Hg; P=.116). Overall operative mortality (≤30 days after surgery) was 1.0% and higher in patients who underwent concomitant CABG (2.2% vs 0.8%; P=.048). In multivariable analysis (n=2641), factors independently associated with mortality included concomitant CABG (hazard ratio [95% CI], 1.89 [1.39-2.58]; P<.0001), older age at operation (per interquartile range increase, 2.79 [1.95-3.98]; P<.0001), atrial fibrillation (1.46 [1.11-1.92]; P=.006), diabetes (1.45 [1.04-2.04]; P=.031), higher body mass index (change from 0.95 to 0.5 quantile, 1.95 [1.46-2.59]; P<.0001), and surgery performed earlier in the study period (2.02 [1.31-3.11]; P=.001). In conclusion, obstructive coronary artery disease severe enough to prompt concomitant CABG at the time of septal myectomy is an important risk factor for late mortality.

An update on primary sclerosing cholangitis epidemiology, outcomes and quantification of alkaline phosphatase variability in a population-based cohort.

BACKGROUND: Contemporary primary sclerosing cholangitis (PSC) population-based cohorts describing the epidemiology, natural history, and long-term fluctuations in serum alkaline phosphatase (SAP) and their prognostic relevance are lacking. Therefore, we investigated the incidence and natural history of PSC and quantified SAP fluctuations among those with PSC in Olmsted County, Minnesota over the last 41 years. METHODS: The Rochester Epidemiology Project was used to identify 56 subjects diagnosed with PSC between 1976 and 2017 in Olmsted County. The primary endpoint (n = 19) included liver transplantation, hepatic decompensation, and cholangiocarcinoma. RESULTS: The age- and sex-adjusted incidence of PSC (per 100,000 person years) nearly doubled from 2001 to 2017 compared to 1976-2000 (1.47; 95% CI 0.99-1.96 versus 0.79; 95% CI 0.42-1.16, p = 0.02). This increase paralleled a rise in patients with markers of a milder phenotype at the time of diagnosis: normal SAP (26.32% versus 0%, p < 0.01) and lower Mayo PSC risk score [0.36 (- 0.57 to 1.55) versus - 0.50 (- 1.25 to 0.35), p = 0.03]. Intra-individual SAP fluctuates with a median coefficient of variation of 36.20%. SAP normalization and dropping below 1.5 × upper limit of normal (ULN) occurs at a rate of 5% and 10% per year, respectively. SAP less than 1.5 × ULN was associated with a lower risk of PSC-related complications (hazard ratio 0.11; 95% CI 0.03-0.42). CONCLUSIONS: The patients with PSC are increasingly being diagnosed with a milder phenotype. While a lower SAP is associated with improved outcomes, the high intra-individual variation of SAP levels calls into question the practice of using a single SAP value as a surrogate endpoint in clinical trials.

Incorporation of Biologic Response Variance Modeling Into the Clinic: Limiting Risk of Brachial Plexopathy and Other Late Effects of Breast Cancer Proton Beam Therapy.

PURPOSE: The relative biologic effectiveness (RBE) rises with increasing linear energy transfer toward the end of proton tracks. Presently, there is no consensus on how RBE heterogeneity should be accounted for in breast cancer proton therapy treatment planning. Our purpose was to determine the dosimetric consequences of incorporating a brachial plexus (BP) biologic dose constraint and to describe other clinical implications of biologic planning. METHODS AND MATERIALS: We instituted a biologic dose constraint for the BP in the context of MC1631, a randomized trial of conventional versus hypofractionated postmastectomy intensity modulated proton therapy (IMPT). IMPT plans of 13 patients treated before the implementation of the biologic dose constraint (cohort A) were compared with IMPT plans of 38 patients treated on MC1631 after its implementation (cohort B) using (1) a commercially available Eclipse treatment planning system (RBE = 1.1); (2) an in-house graphic processor unit-based Monte Carlo physical dose simulation (RBE = 1.1); and (3) an in-house Monte Carlo biologic dose (MCBD) simulation that assumes a linear relationship between RBE and dose-averaged linear energy transfer (product of RBE and physical dose = biologic dose). RESULTS: Before implementation of a BP biologic dose constraint, the Eclipse mean BP D0.01 cm3 was 107%, and the MCBD estimate was 128% (ie, 64 Gy [RBE = biologic dose] in 25 fractions for a 50-Gy [RBE = 1.1] prescription), compared with 100.0% and 116.0%, respectively, after the implementation of the constraint. Implementation of the BP biologic dose constraint did not significantly affect clinical target volume coverage. MCBD plans predicted greater internal mammary node coverage and higher heart dose than Eclipse plans. CONCLUSIONS: Institution of a BP biologic dose constraint may reduce brachial plexopathy risk without compromising target coverage. MCBD plan evaluation provides valuable information to physicians that may assist in making clinical judgments regarding relative priority of target coverage versus normal tissue sparing.

Post-mastectomy intensity modulated proton therapy after immediate breast reconstruction: Initial report of reconstruction outcomes and predictors of complications.

PURPOSE: To report reconstructive outcomes of patients treated with post-mastectomy intensity modulated proton therapy (IMPT) following immediate breast reconstruction (IBR). MATERIALS AND METHODS: Consecutive women with breast cancer who underwent implant-based IBR and post-mastectomy IMPT were included. Clinical characteristics, dosimetry, and acute toxicity were collected prospectively and reconstruction complications retrospectively. RESULTS: Fifty-one women were treated between 2015 and 2017. Forty-two had bilateral reconstruction with unilateral IMPT. The non-irradiated contralateral breasts served as controls. Conventional fractionation (median 50 Gy/25 fractions) was administered in 37 (73%) and hypofractionation (median 40.5 Gy/15 fractions) in 14 (27%) patients. Median mean heart, ipsilateral lung V20Gy, and CTV-IMN V95% were 0.6 Gy, 13.9%, and 97.4%. Maximal acute dermatitis grade was 1 in 32 (63%), 2 in 17 (33%), and 3 in 2 (4%) patients. Surgical site infection (hazard ratio [HR] 13.19, 95% confidence interval [CI] 1.67-104.03, p = 0.0012), and unplanned surgical intervention (HR 9.86, 95% CI 1.24-78.67, p = 0.0068) were more common in irradiated breasts. Eight of 51 irradiated breasts and 2 of 42 non-irradiated breasts had reconstruction failure (HR 3.59, 95% CI 0.78-16.41, p = 0.084). Among irradiated breasts, hypofractionation was significantly associated with reconstruction failure (HR 4.99, 95% CI 1.24-20.05, p = 0.024), as was older patient age (HR 1.14, 95% CI 1.05-1.24, p = 0.002). CONCLUSIONS: IMPT following IBR spared underlying organs and had low rates of acute toxicity. Reconstruction complications are more common in irradiated breasts, and reconstructive outcomes appear comparable with photon literature. Hypofractionation was associated with higher reconstruction failure rates. Further investigation of optimal dose-fractionation after IBR is needed.

Preliminary Normative Standards of the Mayo Clinic Esophagectomy CONDUIT Tool.

OBJECTIVE: To collect patient-reported outcomes after esophagectomy to establish a set of preliminary normative standards to aid in symptom-score interpretation. PATIENTS AND METHODS: Patients undergoing esophagectomy often have little understanding about postoperative symptom management. The Mayo Clinic esophageal CONDUIT tool is a validated questionnaire comprising 5 multi-item symptom-assessment domains and 2 health-assessment domains. A prospective nonrandomized cohort study was conducted on adult patients who have had esophagectomies using the CONDUIT tool from August 17, 2015, to July 30, 2018 (NCT02530983). The Statistical Analysis System v9.4 (SAS Institute Inc., Cary, NC) was used to calculate and analyze the scores. RESULTS: Over the study period, 569 patients were assessed for eligibility, and 241 patients consented and were offered the tool. Of these, 188 patients (median age: 65 years; range: 24 to 87 years; 80% male patients) had calculable scores. Of the 188 patients, 50 (26.6%) patients were identified as potential beneficiaries for educational intervention to improve symptoms (received moderate scores for a domain), and 131 (69.7%) patients were identified as needing further testing or provider intervention (received poor scores for a domain) based on the tool. CONCLUSION: The CONDUIT tool scores, when compared with standardized scales with established preliminary normative scores, could be used to identify and triage patients who need targeted education, further testing, or provider interventions. These score ranges will serve as the first set of normative standards to aid in the interpretation of conduit performance among providers and patients.