Citations

Background There are no risk scores designed specifically for mortality risk prediction in unselected cardiac intensive care unit ( CICU ) patients. We sought to develop a novel CICU ‐specific risk score for prediction of hospital mortality using variables available at the time of CICU admission. Methods and Results A database of CICU patients admitted from January 1, 2007 to April 30, 2018 was divided into derivation and validation cohorts. The top 7 predictors of hospital mortality were identified using stepwise backward regression, then used to develop the Mayo CICU Admission Risk Score (M‐ CARS ), with integer scores ranging from 0 to 10. Discrimination was assessed using area under the receiver‐operator curve analysis. Calibration was assessed using the Hosmer–Lemeshow statistic. The derivation cohort included 10 004 patients and the validation cohort included 2634 patients (mean age 67.6 years, 37.7% females). Hospital mortality was 9.2%. Predictor variables included in the M‐ CARS were cardiac arrest, shock, respiratory failure, Braden skin score, blood urea nitrogen, anion gap and red blood cell distribution width at the time of CICU admission. The M‐ CARS showed a graded relationship with hospital mortality (odds ratio 1.84 for each 1‐point increase in M‐ CARS , 95% CI 1.78–1.89). In the validation cohort, the M‐ CARS had an area under the receiver‐operator curve of 0.86 for hospital mortality, with good calibration ( P =0.21). The 47.1% of patients with M‐ CARS <2 had hospital mortality of 0.8%, and the 5.2% of patients with M‐ CARS >6 had hospital mortality of 51.6%. Conclusions Using 7 variables available at the time of CICU admission, the M‐ CARS can predict hospital mortality in unselected CICU patients with excellent discrimination.

Abstract Background Fungal infections of inflatable penile prostheses (IPPs) are inadequately understood in the literature. Aim To review a multi-institution database of IPP infections to examine for common patient and surgical factors related to IPP fungal infections. Methods This is a retrospective Institutional Review Board–approved analysis of 217 patients at 26 institutions who underwent salvage or device explant between 2001 and 2018. Patient data were compiled after an extensive record review. Outcomes 26 patients (12%) with fungal infections were identified. Results 23 of 26 patients (83%) with a fungal IPP infection were either diabetic or overweight. 15 patients had undergone primary IPP implantation, and the other 11 had previously undergone an average of 1.7 IPP-related surgeries (range 1–3; median 2). The average age at implantation was 63 years (range 31–92; median 63). 18 of the 26 patients with fungal infection had diabetes (69%), with a mean hemoglobin A1c (HbA1c) value of 8.4 (range 5.8–13.3; median 7.5). Twenty-two patients (85%) were overweight or obese. The mean body mass index for all patients was 30.1 kg/m2 (range 23.7–45 kg/m2; median 28.4 kg/m2), and that for diabetic patients was 30.8 kg/m2 (range 24.1–45 kg/m2, median 29.7 kg/m2). Ninety-one percent of implants were placed with intravenous antibiotics, consistent with current American Urological Association guidelines: an aminoglycoside plus first- or second-generation cephalosporin or vancomycin or ampicillin/sulbactam or piperacillin/tazobactam. 65% (17 of 26) of infected IPPs had only fungal growth in culture. No patient had concomitant immunosuppressive disease or recent antibiotic exposure before IPP implantation. Clinical Implications More than two-thirds of the fungal infections occurred in diabetic patients and 85% occurred in overweight or obese patients, suggesting that antifungal prophylaxis may be appropriate in these patients. Strengths & Limitations This is the largest series of fungal infections reported to date in the penile prosthesis literature. The overall number of such cases, however, remains small. Conclusion Fungal infections represent 12% of all penile prosthesis infections in our series and were seen mostly in diabetic or overweight patients, who may benefit from antifungal prophylaxis.

ABSTRACT Background: The use of norepinephrine may be associated with better outcomes in some patients with shock. We sought to determine whether norepinephrine was associated with lower mortality in unselected cardiac intensive care unit (CICU) patients compared with other vasopressors, and whether patterns of vasopressor and inotrope usage in the CICU have changed over time. Methods: We retrospectively evaluated consecutive adult patients admitted to a tertiary care hospital CICU from January 1, 2007 to December 31, 2015. Vasoactive drug doses were quantified using the peak Vasoactive-Inotropic Score (VIS). Temporal trends were assessed using the Cochran–Armitage trends test and multivariable logistic regression was used to determine predictors of hospital mortality. Results: We included 10,004 patients with a mean age of 67 ± 15 years; vasoactive drugs were used in 2,468 (24.7%) patients. Use of norepinephrine increased over time, whereas dopamine utilization decreased ( P < 0.001 for trends). After adjustment for illness severity and other variables, the peak VIS was a predictor of hospital mortality across the entire population (unit odds ratio [OR] 1.013, 95% confidence interval [CI], 1.009–1.017, P < 0.001) and among patients receiving vasoactive drugs (OR 1.018, 95% CI, 1.013–1.022, P < 0.001). Among patients receiving vasoactive drugs, norepinephrine was associated with a lower risk of hospital mortality (OR 0.66, 95% CI, 0.49–0.90, P = 0.008) after adjustment for illness severity and peak VIS. Conclusions: Vasoactive drug use in CICU patients has a dose-dependent association with short-term mortality. Use of norepinephrine in CICU patients is associated with decreased odds of death when compared with other vasoactive drugs.

Abstract The Society of Nuclear Medicine and Molecular Imaging convened a task group to examine the evidence for the risk of carcinogenesis from low-dose radiation exposure and to assess evidence in the scientific literature related to the overall validity of the linear no-threshold (LNT) hypothesis and its applicability for use in risk assessment and radiation protection. In the low-dose and dose-rate region, the group concluded that the LNT hypothesis is invalid as it is not supported by the available scientific evidence and, instead, is actually refuted by published epidemiology and radiation biology. The task group concluded that the evidence does not support the use of LNT either for risk assessment or radiation protection in the low-dose and dose-rate region.

Background and objectives To evaluate the growth pattern of kidney cyst number and cyst volume in association with kidney size, demographics, and genotypes in autosomal dominant polycystic kidney disease. Design, setting, participants, & measurements Kidney cyst number and cyst volume were measured from serial magnetic resonance images, giving a maximum follow-up of 14.23 years, from 241 patients with autosomal dominant polycystic kidney disease (15–46 years old at baseline). The growth pattern was analyzed, in association with sex, age, height-adjusted total kidney volume, and genotype, using linear mixed models of repeated measurements and tests of interactions with age (as a time-dependent covariate) to assess rates of change over time. Models were also fit using Irazabal class. Genotypic groups were characterized as either ( 1 ) PKD1 truncating, PKD1 nontruncating, and PKD2 plus patients with no mutation detected; or ( 2 ) in combination with PKD1 mutation strength groups. Results Imaging and genetic data were collected (at least one visit) for 236 participants. The mean height-adjusted total cyst number increased exponentially over time from a baseline value of 762 to 1715 at the last clinic visit, while the mean height-adjusted total cyst volume increased exponentially from 305 to 770 ml. Height-adjusted total kidney volume, height-adjusted total cyst number, and height-adjusted total cyst volume were all highly correlated over time. Female participants and participants with larger height-adjusted total kidney volume at baseline showed smaller rates of change in the log of height-adjusted total cyst number and cyst volume. PKD1 was associated with significant increases in both cyst number and volume at a given age, but genotype did not significantly affect the rate of growth. Conclusions Both height-adjusted total cyst number and height-adjusted total cyst volume increased exponentially and more than doubled over 14.23 years of follow-up. Compared with PKD2 plus no mutation detected, PKD1 was associated with a greater cyst number and volume at a given age, but no significant difference in the rate of growth.

Abstract Aims Calmodulinopathies are rare life-threatening arrhythmia syndromes which affect mostly young individuals and are, caused by mutations in any of the three genes (CALM 1–3) that encode identical calmodulin proteins. We established the International Calmodulinopathy Registry (ICalmR) to understand the natural history, clinical features, and response to therapy of patients with a CALM-mediated arrhythmia syndrome. Methods and results A dedicated Case Report File was created to collect demographic, clinical, and genetic information. ICalmR has enrolled 74 subjects, with a variant in the CALM1 (n = 36), CALM2 (n = 23), or CALM3 (n = 15) genes. Sixty-four (86.5%) were symptomatic and the 10-year cumulative mortality was 27%. The two prevalent phenotypes are long QT syndrome (LQTS; CALM-LQTS, n = 36, 49%) and catecholaminergic polymorphic ventricular tachycardia (CPVT; CALM-CPVT, n = 21, 28%). CALM-LQTS patients have extremely prolonged QTc intervals (594 ± 73 ms), high prevalence (78%) of life-threatening arrhythmias with median age at onset of 1.5 years [interquartile range (IQR) 0.1–5.5 years] and poor response to therapies. Most electrocardiograms (ECGs) show late onset peaked T waves. All CALM-CPVT patients were symptomatic with median age of onset of 6.0 years (IQR 3.0–8.5 years). Basal ECG frequently shows prominent U waves. Other CALM-related phenotypes are idiopathic ventricular fibrillation (IVF, n = 7), sudden unexplained death (SUD, n = 4), overlapping features of CPVT/LQTS (n = 3), and predominant neurological phenotype (n = 1). Cardiac structural abnormalities and neurological features were present in 18 and 13 patients, respectively. Conclusion Calmodulinopathies are largely characterized by adrenergically-induced life-threatening arrhythmias. Available therapies are disquietingly insufficient, especially in CALM-LQTS. Combination therapy with drugs, sympathectomy, and devices should be considered.

Background: Patients (pts) with classical Hodgkin lymphoma (cHL) frequently experience reduced health-related quality of life (HRQoL) (Oerlemans et al, Ann Hematol 2011). Nivolumab, a fully human IgG4 anti-programmed death-1 (PD-1) immune checkpoint inhibitor monoclonal antibody, demonstrated efficacy and clinically meaningful improvement in pt-reported outcomes (PROs) in pts with relapsed/refractory cHL in cohorts A, B, and C of CheckMate 205 (NCT02181738) (Armand et al, J Clin Oncol 2018; Engert et al, ASH 2017). Nivolumab monotherapy followed by nivolumab + doxorubicin, vinblastine and dacarbazine (N-AVD) demonstrated an objective response rate of 84% in newly diagnosed cHL (cohort D of CheckMate 205; Ramchandren et al, EHA 2018). We present PROs in CheckMate 205 cohort D. Methods: Pts ≥18 years of age with untreated, advanced-stage cHL, with ECOG performance status (PS) of 0–1 received 4 doses of nivolumab monotherapy (240 mg IV Q2W) followed by N-AVD for 6 cycles (12 doses). Pts then entered the follow-up (FU) period. PROs were an exploratory endpoint, assessed using the EuroQol 5 Dimensions-3 level (EQ-5D-3L) and associated visual analog scale (EQ-VAS) in all treated pts who had both a baseline (monotherapy cycle 1) and post-baseline assessment. EQ-VAS ranges from 0–100, with higher scores indicating better HRQoL. In EQ-5D-3L, pts can report no, some, or extreme problems in each of 5 dimensions (mobility, self-care, activity, pain, and anxiety). Results: 51 pts were treated. At baseline, median age was 37 years, 63% were male, 59% had ECOG PS of 0. 49 pts (96%) completed baseline EQ-VAS. Mean EQ-VAS scores exceeded the mean baseline score at the end of monotherapy, after 2 combination cycles, at the end of therapy, and during follow-up (Table 1). The proportion of pts reporting some or extreme problems in EQ-5D-3L was numerically lower than or similar to baseline after monotherapy for all dimensions, but was numerically higher than baseline (dimensions of mobility and activity) after 2 combination cycles, and remained close to or numerically below baseline during follow-up (dimensions of self-care, activity, pain, and anxiety). Conclusions: Pt-reported HRQoL, as assessed by observed mean EQ-VAS scores, did not deteriorate from baseline during treatment with nivolumab followed by N-AVD. Proportions of pts reporting problems in individual EQ-5D-3L dimensions were generally similar to baseline during treatment and follow-up.