Adults with cystic fibrosis: spiritual coping with lifelong disease.

Cystic fibrosis (CF) is a chronic life-shortening disease requiring significant coping. Spiritual belief relates to treatment behaviors. Little is known about spirituality's role in adults diagnosed as children, nor how it compares with adults diagnosed as adults. Adults over 18 years, diagnosed as children completed a questionnaire; some were randomized to also participate in an interview or daily phone diary to measure adherence. Qualitative analyses of 25 adults are presented. Participants reframed their disease as part of a Divine Plan, in which Divine assistance was conditional upon adherence. Linear regression models of spiritual constructs on airway clearance, nebulized medication, and exercise are presented. Adults diagnosed as children related spirituality to CF in ways both consistent and different from adults diagnosed as adults. Spiritual beliefs were related to adherence determinants and intentions. Increased understanding of the relationship between spirituality and health behaviors is important to providing person-centered care.

Accuracy of American College of Surgeons National Surgical Quality Improvement Program Universal Surgical Risk Calculator in Predicting Complications Following Robot-Assisted Radical Cystectomy at a National Comprehensive Cancer Center.

Introduction: There is paucity of literature about the validation of the American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP®) surgical risk calculator for prediction of outcomes after robot-assisted radical cystectomy (RARC). We sought to evaluate the accuracy of the ACS NSQIP surgical risk calculator in the patients who underwent RARC at our institute. Methods: We retrospectively reviewed our prospectively maintained database for patients who underwent RARC between 2005 and 2017. Accuracy of the ACS NSQIP surgical risk calculator was assessed, by comparing the rate of actual complication events after surgery with the receiver operating characteristics curve analysis by calculating the fractional area under the curve (AUC) and the Brier score (BS). We utilized the code number 51595 and 51596 in the ACS NSQIP calculator for the patients undergoing radical cystectomy and reconstructed with the ileal conduit and neobladder, respectively. Results: A total of 462 patients were included in this study: 99 (22%) had diabetes, 302 (66%) had hypertension requiring medication, and 241 (52%) were classified as high American Society of Anesthesiologists (≥3) class. The actual observed rates of any complication and serious complications were 48% and 11%, vs 29% and 25% predicted by the ACS NSQIP, respectively. The actual mean length of hospital stay (10.6 ± 7.8 days) was longer compared with the predicted length (8.5 ± 1.6 days). AUC values were low and the BSs were high for any complication (AUC: 0.50 and BS: 0.29), serious complication (AUC: 0.53 and BS: 0.12), urinary tract infection (AUC: 0.61 and BS: 0.14), renal insufficiency (AUC: 0.64 and BS: 0.08), return to operation room (AUC: 0.58 and BS: 0.07), and early readmission (AUC: 0.55 and BS: 0.11, respectively). Conclusions: The ACS NSQIP calculator demonstrated low accuracy in predicting postoperative outcomes after RARC. These findings highlight the need for development of procedure- and technique-specific RARC calculators.

Development and Validation of a Novel Integrated Clinical-Genomic Risk Group Classification for Localized Prostate Cancer.

Purpose It is clinically challenging to integrate genomic-classifier results that report a numeric risk of recurrence into treatment recommendations for localized prostate cancer, which are founded in the framework of risk groups. We aimed to develop a novel clinical-genomic risk grouping system that can readily be incorporated into treatment guidelines for localized prostate cancer. Materials and Methods Two multicenter cohorts (n = 991) were used for training and validation of the clinical-genomic risk groups, and two additional cohorts (n = 5,937) were used for reclassification analyses. Competing risks analysis was used to estimate the risk of distant metastasis. Time-dependent c-indices were constructed to compare clinicopathologic risk models with the clinical-genomic risk groups. Results With a median follow-up of 8 years for patients in the training cohort, 10-year distant metastasis rates for National Comprehensive Cancer Network (NCCN) low, favorable-intermediate, unfavorable-intermediate, and high-risk were 7.3%, 9.2%, 38.0%, and 39.5%, respectively. In contrast, the three-tier clinical-genomic risk groups had 10-year distant metastasis rates of 3.5%, 29.4%, and 54.6%, for low-, intermediate-, and high-risk, respectively, which were consistent in the validation cohort (0%, 25.9%, and 55.2%, respectively). C-indices for the clinical-genomic risk grouping system (0.84; 95% CI, 0.61 to 0.93) were improved over NCCN (0.73; 95% CI, 0.60 to 0.86) and Cancer of the Prostate Risk Assessment (0.74; 95% CI, 0.65 to 0.84), and 30% of patients using NCCN low/intermediate/high would be reclassified by the new three-tier system and 67% of patients would be reclassified from NCCN six-tier (very-low- to very-high-risk) by the new six-tier system. Conclusion A commercially available genomic classifier in combination with standard clinicopathologic variables can generate a simple-to-use clinical-genomic risk grouping that more accurately identifies patients at low, intermediate, and high risk for metastasis and can be easily incorporated into current guidelines to better risk-stratify patients.

Sucralose Promotes Food Intake through NPY and a Neuronal Fasting Response.

Non-nutritive sweeteners like sucralose are consumed by billions of people. While animal and human studies have demonstrated a link between synthetic sweetener consumption and metabolic dysregulation, the mechanisms responsible remain unknown. Here we use a diet supplemented with sucralose to investigate the long-term effects of sweet/energy imbalance. In flies, chronic sweet/energy imbalance promoted hyperactivity, insomnia, glucose intolerance, enhanced sweet taste perception, and a sustained increase in food and calories consumed, effects that are reversed upon sucralose removal. Mechanistically, this response was mapped to the ancient insulin, catecholamine, and NPF/NPY systems and the energy sensor AMPK, which together comprise a novel neuronal starvation response pathway. Interestingly, chronic sweet/energy imbalance promoted increased food intake in mammals as well, and this also occurs through an NPY-dependent mechanism. Together, our data show that chronic consumption of a sweet/energy imbalanced diet triggers a conserved neuronal fasting response and increases the motivation to eat.

Standardizing the definition of adverse pathology for lower risk men undergoing radical prostatectomy.

PURPOSE: Numerous definitions of adverse pathology at radical prostatectomy (RP) have been proposed and implemented for both research and clinical care, and there is tremendous variation in the specific criteria used to define adverse pathology in these settings. Given the current landscape in which magnetic resonance imaging criteria and biomarker cutoffs are validated for disparate adverse pathology definitions, we sought to identify which of these is most closely tied to biochemical recurrence (BCR) after RP. MATERIALS AND METHODS: A total of 2,837 patients who underwent RP at a single institution for localized prostate cancer (PCa) were included. We evaluated the following existing definitions of adverse pathology at RP: (1) Gleason score ≥7, (2) primary Gleason pattern ≥4, (3) Gleason score ≥7 or pathologic stage T3-4, (4) pathologic stage T3-4, (5) primary Gleason pattern ≥4 or pathologic stage T3-4. The primary outcome measure was BCR. Multiple statistical techniques were used to assess BCR prediction. RESULTS: Of the 5 definitions assessed, 1 (primary Gleason pattern ≥4 or pathologic stage T3-4, 540 patients [19% of cohort]) consistently outperformed the other definitions across all statistical measures. Additionally, a total of only 13 (6.6%) and 34 (10.3%) men with very-low-risk and low-risk cancer per National Comprehensive Cancer Network guideline, respectively, met this definition of adverse pathology at the time of RP. CONCLUSIONS: Varying definitions of adverse pathology differ in their prognostic performance. The criteria defined by either primary Gleason pattern ≥4 or pT3-4 disease appears to most accurately predict BCR in this subset of patients with lower risk PCa at the time of diagnosis. Additionally, men with very-low-risk or low-risk PCa per National Comprehensive Cancer Network guidelines are relatively unlikely to have adverse pathology at the time of surgical resection. These data may help inform the use of imaging and molecular markers as well as the intensity of surveillance in men with newly diagnosed PCa.

Fine needle aspiration of a metastatic germ cell tumor to supraclavicular lymph node.

OBJECTIVE: Germ cell tumors are the most common tumors in men in their second decade. According to the National Comprehensive Cancer Network, the management of germ cell tumors depends on whether the tumor is diagnosed as a seminoma or a nonseminoma. Fine needle aspiration biopsy, compared to incisional biopsy, is relatively safe and facilitates rapid assessment of these tumors. METHODS: An ultrasound guided FNA biopsy was performed, and air-dried slides and alcohol-fixed slides were made for Diff-Quik staining and Papanicolaou staining, respectively. The syringes were rinsed and cell block was prepared. The resected specimen was fixed in 10% formalin and processed by routine histology techniques. RESULTS: We report a case of a 22-year-old male with an enlarged scrotal mass and a supraclavicular nodule. A superficial fine needle aspiration biopsy was performed on the nodule and the correct diagnosis was made via cytomorphology and immunohistochemistry. The cytologic diagnosis was correlated with the incisional biopsy results. CONCLUSION: Fine needle aspiration biopsy is very helpful in the initial triage of germ cell tumors. When the aspirate contains sufficient diagnostic material, a specific diagnosis may be reached. Likewise, as different germ cell tumors have characteristic immunohistochemical profiles, a cell block from an aspirate may be critical for correct diagnosis. However, because germ cell tumors often contain mixed elements, cytologic diagnosis may not be entirely representative due to incomplete sampling. Thus, it is important to correlate cytologic diagnosis with the excisional tissue biopsy results.

Co-encapsulation and sustained-release of four components in ginkgo terpenes from injectable PELGE nanoparticles.

It is difficult to develop injectable sustained delivery systems for herbal medicines because of their composition complexity. Encapsulating various compounds with different physiochemical properties and achieving their synchronized and sustained release seem too hard to realize. In this paper, an injectable nanoparticulate system based on an mPEG-PLGA-mPEG (PELGE) platform was prepared for co-encapsulation and sustained release of four active components (ginkgolides A, B, C and bilobalide) in Ginkgo biloba extract. Different carriers were screened by macrophage uptake experiment for their ability to be long-circulation. Drug loaded nanoparticles were prepared with 10% PEG(2000) modified PLGA by a co-precipitation method. The encapsulation efficiency of the total ginkgo terpenes (GT) in the optimal formulation was 78.84±2.06% with a loading dose of 11.90±0.31mg/150mg PELGE. The particles exhibited a spherical shape with a mean diameter of 123.3±44.0nm and zeta potential of -30.86±2.49mV. Sustained and synchronized release of the four components from PELGE nanoparticles was observed both in vitro and in vivo, which was mainly contributed to the long circulation of PEGylated nanoparticles and the slow degradation of PLGA. The half-life time of the four terpenoid compounds were also significantly improved by incorporation into PELGE nanoparticles. The results indicate that a PELGE nanoparticle is a promising carrier system for sustained and synchronized release of herbal medicines containing multiple components.