Thapa, Prabin

416 Background: Urethral recurrence (UR) has been reported to occur in up to 5% of patients following radical cystectomy (RC). Debate continues regarding the utility of screening for UR after RC. Moreover, oncologic outcomes of patients with UR remain incompletely described, and reports have been limited by small cohort sizes. Herein, we evaluated risk factors for UR as well as cancer-specific survival (CSS) and overall survival (OS) among patients with UR. Methods: We reviewed our institutional RC registry to identify patients with UR following RC. Logistic regression was used to assess risk factors for UR. Kaplan-Meier and Cox proportional hazard regression were used to compare outcomes in those with UR diagnosis prompted by symptoms versus those with asymptomatic UR diagnosed on surveillance cytology. Results: Overall, 2930 patients underwent RC from 1980-2018, with a median post-operative follow-up of 4.9 years (IQR 1.6-11.0), of whom 144 (4.9%) were subsequently diagnosed with UR. Prostatic urethral involvement at RC (odds ratio [OR] 5.75 [3.67-9.01], p < 0.0001) and higher pT-stage (OR 3.57 [2.07-6.14], p < 0.0001) were associated with an increased risk of UR, whereas receipt of continent urinary diversion (OR 0.34 [0.20-0.58], p < 0.0001) was associated with a decreased risk of UR. A total of 72/144 (50%) patients were diagnosed with UR based on symptoms, and 104/144 (72.2%) patients with UR underwent subsequent urethrectomy. Patients with symptomatic recurrence had higher tumor stage on urethrectomy than those with asymptomatic recurrence (≥pT2 in 13.1% vs 3.1%, p = 0.007). At a median follow-up of 2.6 years (IQR 1.0-7.1) after UR, 68 of the patients with UR died of urothelial carcinoma. Kaplan-Meier analyses suggest longer median overall and cancer-specific survival for patients with UR detected by cytology than those presenting with symptoms (p = 0.05 for both). On multivariable analyses, patients who experienced UR had significantly increased risk of cancer-specific (hazard ratio [HR] 1.93 [95% confidence interval 1.50-2.50), p < 0.0001) and all-cause mortality (HR 1.34 [1.13-1.65], p = 0.001). Conclusions: Approximately 5% of patient undergoing RC experience UR, with higher pT-stage and prostatic urethral involvement increasing the risk of UR. Asymptomatic detection of UR was associated with lower pathologic stage at urethrectomy as well as longer cancer-specific and overall survival, supporting urethral surveillance after RC.

Abstract Introduction: Patients and their families and medical providers have assumed that psychologic stress impacts glucose control in T1D (Type 1 Diabetes) though studies providing confirmatory evidence in real world settings are, to our knowledge, lacking. We hypothesized that self-reported psychologic stress worsens glucose control in T1D. Method: We studied 20 adults with T1D on continuous glucose monitor (CGM), sensor augmented insulin pump (SAP) prospectively at 2 clinical research centers. Patients reported psychological stress through stress diaries for 5 weeks on a severity scale of 1-7 using hard copy logs including time of onset and offset of stress and severity. For analytic purpose, grades 1-4 are classified as mild and grades 5-7 as severe. Results: Baseline characteristics were age 44.9±15.0 years, F/M 12/8, HbA1c 6.8 ± 0.7%, and diabetes duration of 22.9±15.9 years. We analyzed glucose variability during days of stress versus days without stress. During a 24 hour period, patients experienced less hypoglycemia during days with stress versus days without stress (p value 0.03). During the 5 week period, patients reported 23 ± 19.5 events. We analyzed the impact of self-reported stress on CGM data streams after excluding stress events associated with missing CGM data, nocturnal events (from 12 MN to 6 AM, too few events) and events for which subjects did not provide duration of stress. Thus, we analyzed 19.5 ± 17 events per patient from 6AM to 12MN. From 6 AM to 12 MN, the episodes lasted 179 ± 255 minutes with 83 % episodes being mild/moderate and 17% moderate/ severe. Number of CGM readings during daytime stress episodes were 717± 1120 compared to 8768± 1238 during non-stress periods. Impact of stress from 6 AM to 12 MN (Mid-Night) on CGM glucose was analyzed using matched paired t test. Mean glucose (160.6±41.9 vs 148.3± 28.6) and SD (53.2 ±17.7 vs 56.1±14.6) did not show a difference; however % of time spent below 70 mg/dl was less (4 ± 5) in patients during stressful periods compared to times without stress (6.3± 5.5, P value 0.02). Conclusions: To our knowledge, this is the first study attempting to analyze the impact of self-reported stress using daily stress diaries on CGM data streams in T1D patients on SAP. The study revealed significant challenges experienced by patients in reporting adequate data. Self-reported stress was not associated with hyperglycemia. However, days of self-reported stress and periods during patients reported stress were characterized by less hypoglycemia on CGM data streams.

Abstract Aims To assess functional tricuspid regurgitation (FTR) determinants, consequences, and independent impact on outcome in degenerative mitral regurgitation (DMR). Methods and results All patients diagnosed with isolated DMR 2003–2011, with structurally normal tricuspid leaflets, prospective FTR grading and systolic pulmonary artery pressure (sPAP) estimation by Doppler echocardiography at diagnosis were identified and long-term outcome analysed. The 5083 DMR eligible patients [63 ± 16 years, 47% female, ejection fraction (EF) 63 ± 7%, and sPAP 35 ± 13 mmHg] presented with FTR graded trivial in 45%, mild in 37%, moderate in 15%, and severe in 3%. While pulmonary hypertension (PHTN-sPAP ≥ 50 mmHg) was the most powerful FTR severity determinant, other strong FTR determinants were older age, female sex, lower left ventricle EF, DMR, and particularly atrial fibrillation (AFib) (all P ≤ 0.002). Functional tricuspid regurgitation moderate/severe was independently linked to more severe clinical presentation, more oedema, lower stroke volume, and impaired renal function (P ≤ 0.01). Survival (95% confidence interval) throughout follow-up [70% (69–72%) at 10 years] was strongly associated with FTR severity [82% (80–84%) for trivial, 69% (66–71%) for mild, 51% (47–57%) for moderate, and 26% (19–35%) for severe, P &lt; 0.0001]. Excess mortality persisted after comprehensive adjustment [adjusted hazard ratio 1.40 (1.18–1.67) for moderate FTR and 2.10 (1.63–2.70) for severe FTR, P ≤ 0.01]. Excess mortality persisted adjusting for sPAP/right ventricular function (P &lt; 0.0001), by matching [adjusted hazard ratios 2.08 (1.50–2.89), P &lt; 0.0001] and vs. expected survival [risk ratio 1.79 (1.48–2.16), P &lt; 0.0001]. Within 5-year of diagnosis valve surgery was performed in 73% (70–75%) and 15% (13–17%) of severe and moderate DMR and in only 26% (19–34%) and 6% (4–8%) of severe and moderate FTR. Valvular surgery improved outcome without alleviating completely higher mortality associated with FTR (P &lt; 0.0001). Conclusion In this large DMR cohort, FTR was frequent and causally, not only linked to PHTN but also to other factors, particularly AFib. Higher FTR severity is associated at diagnosis with more severe clinical presentation. Long term, FTR is independently of all confounders, associated with considerably worse mortality. Functional tricuspid regurgitation moderate and even severe is profoundly undertreated. Thus careful assessment, consideration for tricuspid surgery, and testing of new transcatheter therapy is warranted.

AbstractBackgroundCurrent therapy for Type 1 diabetes (T1D) is characterized by significant glucose variability (GV). Pancreas transplantation (PT) is performed in certain T1D patients with and without end‐stage renal disease. To date, GV has been examined to a limited extent after PT.MethodsWe investigated GV using continuous glucose monitoring (CGM) 3‐6 weeks after PT.ResultsEleven patients had simultaneous kidney pancreas transplantation (SPK), nine pancreas after kidney (PAK), and six pancreas transplantation alone (PTA). Mean CGM showed no difference between SPK, 126.5 ± 13.9, PAK 119.9 ± 12.8, and PTA 131.1 ± 29 mg/dL (P value .6). Percentage of time in range (TIR, 70‐180 mg/dL) was 92% for SPK, 93.4% in PAK, and 88.5% in PTA with only 0.3%, 1.5%, and 0.3% of time <70 mg/dL. Percentage >180 mg/dL was 7.9% for SPK, 4.9% PAK, and 11% in PTA. Other measures of GV were similar in the three cohorts. In six patients, CGM was performed before and after PT and improved significantly. GV was also better compared with a matched cohort of T1D patients.ConclusionsAll 3 types of PT resulted in excellent glucose control 3‐6 weeks post‐procedure. CGM outcomes represent an important objective outcome after PT.

Abstract Objective Several studies indicate that patients with primary hyperparathyroidism (PHPT) undergoing parathyroid surgery have improvement in mood and neuropsychological functioning. The current analysis aims to examine the relationship between biochemical and clinical variables and the improvement in depression scores and in specific symptoms, after parathyroidectomy. Design A prospective observational case‐control study at a referral centre. Patients Patients with PHPT undergoing parathyroidectomy (n = 88) or thyroid surgery (n = 85). Measurements The Patient Health Questionnaire‐9 (PHQ‐9) was utilized to obtain depression scores at enrolment and 12 months after surgery. The changes in PHQ‐9 were analysed and correlated with baseline clinical and biochemical parameters. Results At enrolment, there was no difference between the groups in the number with a depression diagnosis (PHPT 34.1%, thyroid surgery, 35.5%, P = 0.86). However, baseline PHQ‐9 scores were significantly higher in PHPT (median 7.5, range 0‐27) than thyroid surgery patients (median 3.0, range 0‐18, P < 0.0001). Following surgery, all PHQ‐9 scores, total and symptom group (cognitive, somatic) improved and were no longer different between PHPT (total PHQ‐9 median 2, range 0‐16) and thyroid (median 1, range 0‐14, P = 0.31) groups. Baseline parathyroid hormone level, but not calcium, had a weak relationship with change in PHQ‐9 score after parathyroid surgery ( P = 0.003). Baseline PHQ‐9 score was correlated with change in PHQ‐9 score at 12 months after parathyroid surgery ( P < 0.001). Conclusions Depression scores improve in both somatic and cognitive domains after parathyroidectomy for PHPT and baseline severity of depression predicts the response.

Background: Functional tricuspid regurgitation (FTR) is common in heart failure with reduced ejection fraction and mostly consequent to pulmonary hypertension. However, the intrinsic clinical implications of FTR are not fully understood. Methods: The cohort of all Mayo Clinic patients from 2003 to 2011 diagnosed with heart failure stage B-C and ejection fraction<50%, with FTR grading and systolic pulmonary artery pressure estimation by Doppler echocardiography was identified and outcomes were analyzed. Patients with pacemakers/defibrillators, organic valve disease, or previous valve surgery were excluded. The primary outcome measure was overall mortality (censored at implantation of a defibrillator, ventricular assist device, or cardiac transplantation), adjusting for clinical and echocardiographic associates with mortality and major comorbidities. Results: Among 13 026 patients meeting inclusion criteria, FTR was detected in 88% (N=11 507: 33% trivial, 32% mild, 17% moderate, and 6% severe), aged 68±14 years, 35% women, ejection fraction 36±10%, systolic pulmonary artery pressure 41±14 mm Hg with 20% atrial fibrillation. Covariates independently associated with FTR included elevated systolic pulmonary artery pressure, older age, female sex, lower ejection fraction, mitral regurgitation, and atrial fibrillation (all P <0.0001). FTR was independently associated with more dyspnea, impaired kidney function, and lower cardiac output ( P <0.003 for all). For long-term outcome, higher FTR degree compared with trivial tricuspid regurgitation was independently associated with higher mortality (adjusted hazard ratios 1.09 [1.01-1.17] for mild FTR, 1.21 [1.11-1.33] for moderate FTR and 1.57 [1.39-1.78] for severe FTR); hence, 5-year survival was substantially lower with increasing severity of functional FTR, 68±1% for trivial FTR, 58±2% for mild FTR, 45±2% for moderate FTR, and 34±4% for severe FTR. Conclusions: In this large cohort of patients with heart failure with reduced ejection fraction, FTR was common and independently associated with pulmonary hypertension, atrial fibrillation, and more severe heart failure presentation. Long-term, higher FTR severity is associated with considerably worse survival, independently of baseline characteristics. Given these untoward outcomes associated with FTR in patients with heart failure with reduced ejection fraction, clinical trials should be directed at testing FTR treatment.

Abstract Aims To define the hitherto unknown aetiology/mechanism distributions of mitral regurgitation (MR) in the community and the linked clinical characteristics/outcomes. Methods and results We identified all isolated, moderate/severe MR diagnosed in our community (Olmsted County, MN, USA) between 2000 and 2010 and classified MR aetiology/mechanisms. Eligible patients (n = 727) were 73 ± 18 years, 51% females, with ejection fraction (EF) 49 ± 17%. MR was functional (FMR) in 65%, organic (OMR) in 32% and 2% mixed. Functional MR was linked to left ventricular remodelling (FMR-v) 38% and isolated atrial dilatation (FMR-a) 27%. At diagnosis FMR-v vs. FMR-a, vs. OMR displayed profound differences (all P &lt; 0.0001) in age (73 ± 14, 80 ± 10, 68 ± 21years), male-sex (59, 33, 51%), atrial-fibrillation (28, 54, 13%), EF (33 ± 14, 57 ± 11, 61 ± 10%), and regurgitant-volume (38 ± 13, 37 ± 11, 51 ± 24 mL/beat). Dominant MR mechanism was Type I (normal valve-movement) 38%, Type II (excessive valve-movement) 25%, Type IIIa (diastolic movement-restriction) 3%, and Type IIIb (systolic movement-restriction) 34%. Outcomes were mediocre with excess-mortality vs. general-population in FMR-v [risk ratio 3.45 (2.98–3.99), P &lt; 0.0001] but also FMR-a [risk ratio 1.88 (1.52–2.25), P &lt; 0.0001] and OMR [risk ratio 1.83 (1.50–2.22), P &lt; 0.0001]. Heart failure was frequent, particularly in FMR-v (5-year 83 ± 3% vs. 59 ± 4% FMR-a, 40 ± 3% OMR, P &lt; 0.0001). Mitral surgery during patients’ lifetime was performed in 4% of FMR-v, 3% of FMR-a, and 37% of OMR. Conclusion Moderate/severe isolated MR in the community displays considerable aetiology/mechanism heterogeneity. Functional MR dominates, mostly FMR-v but FMR-a is frequent and degenerative MR dominates OMR. Outcomes are mediocre with excess-mortality particularly with FMR-v but FMR-a, despite normal EF incurs notable excess-mortality and frequent heart failure. Pervasive undertreatment warrants clinical trials of therapies tailored to specific MR cause/mechanisms.