Circadian tumor infiltration and function of CD8+ T cells dictate immunotherapy efficacy.

The quality and quantity of tumor-infiltrating lymphocytes, particularly CD8+ T cells, are important parameters for the control of tumor growth and response to immunotherapy. Here, we show in murine and human cancers that these parameters exhibit circadian oscillations, driven by both the endogenous circadian clock of leukocytes and rhythmic leukocyte infiltration, which depends on the circadian clock of endothelial cells in the tumor microenvironment. To harness these rhythms therapeutically, we demonstrate that efficacy of chimeric antigen receptor T cell therapy and immune checkpoint blockade can be improved by adjusting the time of treatment during the day. Furthermore, time-of-day-dependent T cell signatures in murine tumor models predict overall survival in patients with melanoma and correlate with response to anti-PD-1 therapy. Our data demonstrate the functional significance of circadian dynamics in the tumor microenvironment and suggest the importance of leveraging these features for improving future clinical trial design and patient care.

"A Life Slips Through Our Fingers" Experiences of Nurses Working in Pediatric Intensive Care Units About Children's Death: A Qualitative Study.

Caring for a dying child can be an experience full of all kinds of negative emotions, pain and stress for the pediatric nurse. In this study, which was carried out in Turkey, we aimed to determine how nurses working in a pediatric intensive care unit remembered and made sense of their experiences regarding children's deaths. In-depth interviews were held with 13 nurses. The data were analyzed using the content analysis method. Three themes were identified. These were (1) Personal effects of death, (2) Difficulties in care, and (3) Coping with death. It was clear that the nurses were traumatised by their exposure to infant deaths. The findings showed that nurses experienced regret, fatigue and posttraumatic stress disorder. In addition, it was determined that nurses should be supported to cope with child deaths, which is a complicated process involving the child and the family, especially emotionally. Moreover, providing institutional support to nurses and referring them to cognitive-behavioral therapies may make it easier for them to cope with the emotional burden they carry, as well as the burnout they experience.

Telemedicine in urologic oncology care: Will telemedicine exacerbate disparities?

INTRODUCTION: Disparities in prostate, bladder, and kidney cancer outcomes are associated with access to care. Telemedicine can improve access but may be underutilized by certain patient populations. Our objective was to determine if the patient populations who suffer worse oncologic outcomes are the same as those who are less likely to use telemedicine. METHODS: Using an institutional database, we identified all prostate, bladder and kidney cancer encounters from March 14, 2020 to October 31, 2021 (n = 15,623; n = 4, 14; n = 3,830). Telemedicine was used in 13%, 8%, and 12% of these encounters, respectively. We performed random effects modeling analysis to examine patient and provider characteristics associated with telemedicine use. Adjusted odds ratios (OR) and 95% confidence intervals (CI) were reported as measures of association. RESULTS: Among prostate, bladder, and kidney cancer patients, Black patients had lower odds of a telemedicine encounter (OR 0.51, 95% CI 0.37-0.69; OR 0.22, 95% CI 0.07-0.70; OR 0.46, 95% CI 0.24-0.86), and patients residing in small and isolated small rural towns areas had higher odds of a telemedicine encounter (OR 1.44, 95% CI 1.09-1.91; OR 2.12, 95% CI 1.14-3.94; OR 1.89, 95% CI 1.12-3.19). Compared to providers in practice ≤5 years, providers in practice for 6 to 15 years had significantly higher odds of a telemedicine encounter for prostate and bladder cancer patients (OR 4.10, 95% CI 1.4511.58; OR 3.42, 95% CI 1.09-10.77). CONCLUSION: The lower rates of telemedicine use among Black patients could exacerbate pre-existing disparities in prostate, bladder, and kidney cancer outcomes.

Exhaled Breath Analysis Using Selected Ion Flow Tube Mass Spectrometry and Disease Severity in Heart Failure.

Exhaled breath volatile organic compounds (VOCs) are elevated in heart failure (HF). The ability of VOCs to predict long term cardiovascular mortality and morbidity has not been independently verified. In 55 patients admitted with acute decompensated heart failure (ADHF), we measured exhaled breath acetone and pentane levels upon admission and after 48 h of diuresis. In a separate cohort of 51 cardiac patients undergoing cardiopulmonary exercise testing (CPET), we measured exhaled breath acetone and pentane levels before and at peak exercise. In the ADHF cohort, admission acetone levels correlated with lower left ventricular ejection fraction (LVEF, r = -0.297, p = 0.035). Greater weight loss with diuretic therapy correlated with a greater reduction in both acetone levels (r = -0.398, p = 0.003) and pentane levels (r = -0.309, p = 0.021). In patients with above-median weight loss (≥4.5 kg), patients demonstrated significantly greater percentage reduction in acetone (59% reduction vs. 7% increase, p < 0.001) and pentane (23% reduction vs. 2% reduction, p = 0.008). In the CPET cohort, admission acetone and pentane levels correlated with higher VE/VCO2 (r = 0.39, p = 0.005), (r = 0.035, p = 0.014). However, there were no significant correlations between baseline or peak exercise acetone and pentane levels and peak VO2. In longitudinal follow-up with a median duration of 33 months, patients with elevated exhaled acetone and pentane levels experienced higher composite adverse events of death, ventricular assist device implantation, or orthotopic heart transplantation. In patients admitted with ADHF, higher exhaled breath acetone levels are associated with lower LVEF and poorer outcomes, and greater reductions in exhaled breath acetone and pentane tracked with greater weight loss. Exhaled acetone and pentane may be novel biomarkers in heart failure worthy of future investigation.

TW68, cryptochromes stabilizer, regulates fasting blood glucose levels in diabetic ob/ob and high fat-diet-induced obese mice.

Cryptochromes (CRYs), transcriptional repressors of the circadian clock in mammals, inhibit cAMP production when glucagon activates G-protein coupled receptors. Therefore, molecules that modulate CRYs have the potential to regulate gluconeogenesis. In this study, we discovered a new molecule called TW68 that interacts with the primary pockets of mammalian CRY1/2, leading to reduced ubiquitination levels and increased stability. In cell-based circadian rhythm assays using U2OS Bmal1-dLuc cells, TW68 extended the period length of the circadian rhythm. Additionally, TW68 decreased the transcriptional levels of two genes, Phosphoenolpyruvate carboxykinase 1 (PCK1) and Glucose-6-phosphatase (G6PC), which play crucial roles in glucose biosynthesis during glucagon-induced gluconeogenesis in HepG2 cells. Oral administration of TW68 in mice showed good tolerance, a good pharmacokinetic profile, and remarkable bioavailability. Finally, when administered to fasting diabetic animals from ob/ob and HFD-fed obese mice, TW68 reduced blood glucose levels by enhancing CRY stabilization and subsequently decreasing the transcriptional levels of Pck1 and G6pc. These findings collectively demonstrate the antidiabetic efficacy of TW68 in vivo, suggesting its therapeutic potential for controlling fasting glucose levels in the treatment of type 2 diabetes mellitus.

A Multipronged Intervention to Reduce Readmissions and Readmission Intensity After Radical Cystectomy.

OBJECTIVE: To develop a multipronged, evidence-based protocol to reduce readmission risk and readmission intensity, as represented by the duration of the index readmission, after radical cystectomy. MATERIALS AND METHODS: A per-protocol study was performed. The protocol included preoperative nutritional supplementation, early stent removal, and a follow-up phone call within 4-5days of discharge. The preprotocol period was from February 1, 2020 to July 31, 2021 and the postprotocol period was from December 1, 2020 to November 31, 2021. Using multivariate regression models, we compared outcomes among patients treated with radical cystectomy before and after protocol initiation. RESULTS: We identified 70 preprotocol patients and 126 postprotocol patients. After adjusting for age, sex, BMI, and frailty score, there was a significant reduction in 90-day readmission intensity (7 vs 5days; P = .048) among postprotocol patients. CONCLUSION: After implementation of an evidence-based protocol for patients undergoing radical 90-day readmission intensity decreased significantly. This protocol may move the needle forward on reducing readmissions, but a larger randomized trial is needed.

Birth outcomes in pregnant women with epilepsy: A Nationwide multicenter study from Türkiye.

OBJECTIVE: The present study was aimed at investigating the effects of anti-seizure medications (ASMs), patient demographic characteristics, and the seizure type and frequency on the development of congenital malformations (CMs) in the infants of pregnant women with epilepsy (PWWE). METHODS: PWWE followed up at the neurology outpatient clinic of 21 centers between 2014 and 2019 were included in this prospective study. The follow-up of PWWE was conducted using structured, general pregnant follow-up forms prepared by the Pregnancy and Epilepsy Study Committee. The newborns were examined by a neonatologist after delivery and at 1 and 3 months postpartum. RESULTS: Of the infants of 759 PWWE, 7.2% had CMs, with 5.6% having major CMs. Polytherapy, monotherapy, and no medications were received by 168 (22.1%), 548 (72.2 %), and 43 (5.7 %) patients, respectively. CMs were detected at an incidence of 2.3% in infants of PWWE who did not receive medication, 5.7% in infants of PWWE who received monotherapy, and 13.7% in infants of PWWE who received polytherapy. The risk of malformation was 2.31-fold (95% confidence interval (CI): 1.48-4.61, p < .001) higher in infants of PWWE who received polytherapy. Levetiracetam was the most frequently used seizure medication as monotherapy, with the highest incidence of CMs occurring with valproic acid (VPA) use (8.5%) and the lowest with lamotrigine use (2.1%). The incidence of CMs was 5% at a carbamazepine dose <700 mg, 10% at a carbamazepine dose ≥700 mg, 5.5% at a VPA dose <750 mg, and 14.8% at a VPA dose ≥750 mg. Thus the risk of malformation increased 2.33 times (p = .041) in infants of PWWE receiving high-dose ASMs. SIGNIFICANCE: Birth outcomes of PWWE receiving and not receiving ASMs were evaluated. The risk of CMs occurrence was higher, particularly in infants of PWWE using VPA and receiving polytherapy. The incidence of CMs was found to be lower in infants of PWWE receiving lamotrigine.

Utilizing a Questionnaire to Implement a Risk-based Antibiotic Prophylaxis Protocol for Transrectal Prostate Biopsy.

OBJECTIVE: To develop and evaluate a risk-based antibiotic prophylaxis protocol for patients undergoing transrectal prostate biopsy. METHODS: We created a risk-based protocol for antibiotic prophylaxis before transrectal prostate biopsy. Patients were screened for infection risk-factors with a self-administered questionnaire. The protocol was implemented from January 1, 2020 to March 31, 2020. We compared patient risk-factors, antibiotic regimens, and 30-day infection rates for patients undergoing transrectal prostate biopsies during the intervention and for a 3-month period before the intervention. RESULTS: There were 116 prostate biopsies in the preintervention group and 104 in the intervention group. Although there was no significant difference in the number of high-risk patients between the 2 groups (48% vs 55%; P = .33), the percentage of patients treated with augmented prophylaxis decreased from 74% to 45% (P = 0.03). The duration of antibiotic administration and the median number of doses prescribed also decreased significantly. Despite significant decreases in antibiotic use, there were no differences in infection rates (5% vs 5%; P = .90) or sepsis rates (1% vs 2%; P = .60). CONCLUSION: We developed a risk-based protocol for prophylactic antibiotics before prostate biopsy. The protocol was associated with less antibiotic use but did not lead to an increase in infectious complications.

Large Variations in the Prices of Urologic Procedures at Academic Medical Centers 1 Year After Implementation of the Price Transparency Final Rule.

Importance: Patients with urologic diseases often experience financial toxicity, defined as high levels of financial burden and concern, after receiving care. The Price Transparency Final Rule, which requires hospitals to disclose both the commercial and cash prices for at least 300 services, was implemented to facilitate price shopping, decrease price dispersion, and lower health care costs. Objective: To evaluate compliance with the Price Transparency Final Rule and to quantify variations in the price of urologic procedures among academic hospitals and by insurance class. Design, Setting, and Participants: This was a cross-sectional study that determined the prices of 5 common urologic procedures among academic medical centers and by insurance class. Prices were obtained from the Turquoise Health Database on March 24, 2022. Academic hospitals were identified from the Association of American Medical Colleges website. The 5 most common urologic procedures were cystourethroscopy, prostate biopsy, laparoscopic radical prostatectomy, transurethral resection of the prostate, and ureteroscopy with laser lithotripsy. Using the corresponding Current Procedural Terminology codes, the Turquoise Health Database was queried to identify the cash price, Medicare price, Medicaid price, and commercial insurance price for these procedures. Exposures: The Price Transparency Final Rule, which went into effect January 1, 2021. Main Outcomes and Measures: Variability in procedure price among academic medical centers and by insurance class (Medicare, Medicaid, commercial, and cash price). Results: Of 153 hospitals, only 20 (13%) listed a commercial price for all 5 procedures. The commercial price was reported most often for cystourethroscopy (86 hospitals [56%]) and least often for laparoscopic radical prostatectomy (45 hospitals [29%]). The cash price was lower than the Medicare, Medicaid, and commercial price at 24 hospitals (16%). Prices varied substantially across hospitals for all 5 procedures. There were significant variations in the prices of cystoscopy (χ23 = 85.9; P = .001), prostate biopsy (χ23 = 64.6; P = .001), prostatectomy (χ23 = 24.4; P = .001), transurethral resection of the prostate (χ23 = 51.3; P = .001), and ureteroscopy with laser lithotripsy (χ23 = 63.0; P = .001) by insurance type. Conclusions and Relevance: These findings suggest that, more than 1 year after the implementation of the Price Transparency Final Rule, there are still large variations in the prices of urologic procedures among academic hospitals and by insurance class. Currently, in certain situations, health care costs could be reduced if patients paid out of pocket. The Centers for Medicare & Medicaid Services may improve price transparency by better enforcing penalties for noncompliance, increasing penalties, and ensuring that hospitals report prices in a way that is easy for patients to access and understand.

Discovery of a small molecule that selectively destabilizes Cryptochrome 1 and enhances life span in p53 knockout mice.

Cryptochromes are negative transcriptional regulators of the circadian clock in mammals. It is not clear how reducing the level of endogenous CRY1 in mammals will affect circadian rhythm and the relation of such a decrease with apoptosis. Here, we discovered a molecule (M47) that destabilizes Cryptochrome 1 (CRY1) both in vitro and in vivo. The M47 selectively enhanced the degradation rate of CRY1 by increasing its ubiquitination and resulted in increasing the circadian period length of U2OS Bmal1-dLuc cells. In addition, subcellular fractionation studies from mice liver indicated that M47 increased degradation of the CRY1 in the nucleus. Furthermore, M47-mediated CRY1 reduction enhanced oxaliplatin-induced apoptosis in Ras-transformed p53 null fibroblast cells. Systemic repetitive administration of M47 increased the median lifespan of p53-/- mice by ~25%. Collectively our data suggest that M47 is a promising molecule to treat forms of cancer depending on the p53 mutation.

Comparison of AUA and phoenix definitions of biochemical failure following permanent brachytherapy for prostate cancer.

PURPOSE: To compare biochemical recurrence free survival (BCRFS) and cancer-specific survival (CSS) after brachytherapy using the AUA and the Phoenix definitions. METHODS AND MATERIALS: 2634 men with T1-T4N0M0 prostate cancer were treated with brachytherapy with or without neoadjuvant hormonal therapy or external beam radiation therapy. Five, 10, and 15- year BCRFS and CSS were estimated with Kaplan-Meier estimates with log rank. Multivariate analysis of survival was performed with Cox regression analysis. RESULTS: Median age was 66, follow-up was 8.6 years, and prostate specific antigen was 6.9. Overall, 11.1% (n = 293) of patients experienced Phoenix BCR and 17.48% (n = 457) experienced AUA BCR. The rates of AUA BCR and Phoenix BCR were significantly different at 5 and 10-years but not at 15 years. Patients treated with BED ≤ 200 Gy were more likely to experience AUA BCR (22.5% vs. 12.4%, OR 1.44, p < 0.001) and Phoenix BCR (14.3% and 8.3%, OR 1.37, p < 0.001) than patients treated with a BED > 200 Gy. CONCLUSIONS: Compared to the Phoenix definition, the AUA definition of BCR after brachytherapy is associated with significantly worse BCRFS for the first 15 years after treatment. Receiving a BED > 200, which cannot be achieved without the addition of brachytherapy, is associated with better BCRFS and CSS. Our findings reaffirm the importance of dose in the management of prostate cancer.

Autoimmune encephalitis and paraneoplastic syndromes in Turkey: a multi-centre study.

BACKGROUND: Autoimmune encephalitis (AIE) and paraneoplastic syndromes (PNS) are both rare groups of neurological diseases that are difficult to diagnose. AIM: We aimed to determine the common and distinct aspects of these two aetiologies of encephalitis as well as the characteristics of our patient group. METHODS: We respectively analysed the records of the patients including symptoms, demographic features, neurological examination, cranial-magnetic-resonance-imaging (MRI), electroencephalography (EEG) findings, cerebrospinal fluid results (CSF) findings. Autoimmune/paraneoplastic autoantibodies in blood and/or CSF were all documented. RESULTS: Forty-six patients fulfilled the diagnostic criteria. Thirty-eight of them were diagnosed with AIE, and 8 of them were diagnosed with PNS. The PNS group had higher nonconvulsive status epilepticus than the AIE (2/8 vs 0/38; p=0.027). PNS patients were diagnosed with a malignancy in their follow-ups more than those in the AIE group [4/38 vs 8/8] (p<0.001). When the symptoms of antibody-positive and negative patients were compared in the AIE group, the rates of consciousness/memory problems (13/15 vs 11/23; p=0.020) and speech impairment (8/15 vs 2/23; p=0.004) were significantly higher in patients without antibodies (n: 15) than in antibody-positive patients (n: 23). In antibody-negative groups, the rates of memory problems in neurological examination (13/15 vs 12/23 p=0.028) and temporal findings on electroencephalography were more prominent than antibody-positive groups (1/23 vs 5/15; p=0.027). The number of patients with cerebellar signs was higher in antibody-positive patients (6/23 vs 0/15; p=0.038). CONCLUSION: Although the positivity of autoantibodies is critical in the diagnosis of AIE and PNS, even minor differences in clinical and laboratory findings of patients are helpful in the diagnosis, especially in the autoantibody-negative patients. Comparing the data with other population studies has shown that several inherited and environmental factors may contribute to the pathophysiology of AIE and PNS, as well as clinical and laboratory differences.

Depression and sexual functions in epilepsy patients: Comparison before and during the COVID-19 pandemic.

OBJECTIVE: The new coronavirus disease 2019 (COVID-19) is a major health problem with a high rate of spread. We aimed to investigate herein the effects of the COVID-19 outbreak on depression and sexual dysfunction in patients with epilepsy. MATERIAL AND METHODS: One hundred and sixteen epilepsy patients admitted to our hospital from October-November 2019 were evaluated for sexual functions and depression using the Arizona Sexual Experiences Scale (ASEX) and Beck Depression Scale, respectively. These scales were re-applied in June 2020 and July 2020 to assess the impact of the outbreak on sexual function and depression in the same group of patients. The demographic and clinical characteristics of the patients were recorded and analyzed in SPSS. RESULTS: During the pandemic period, the total Beck Depression Scale values increased significantly in the patients with epilepsy compared to the pre-pandemic period (P = 0.048), and depressive symptoms showed an increasing trend (P = 0.032). Although an increase in sexual dysfunction was also recorded, it was not statistically significant compared to the pre-pandemic period. In eight patients (6.9%), seizure frequency increased during the pandemic period. In the multivariate analysis, the only parameter that predicted the increase in seizure frequency was the number of drugs used. The Beck Depression Scale values were positively correlated with total male/female ASEX values, age, marital status, duration of illness, and seizure frequency. CONCLUSION: The COVID-19 outbreak caused an increase in the tendency to depression in epilepsy patients and has also had a negative effect on sexual function. During public health outbreaks, clinicians should focus not only on seizure control in patients with epilepsy but also on their mental health.

OBJECTIF: La nouvelle maladie à coronavirus 2019 (COVID-19) est un problème de santé majeur avec un taux de propagation élevé. Nous visons à étudier ici les effets de l'épidémie de COVID-19 sur la dépression et la dysfonction sexuelle chez les patients atteints d'épilepsie. MATÉRIEL ET MÉTHODES: Cent seize patients atteints d'épilepsie admis dans notre hôpital d'octobre à novembre 2019 ont été évalués pour les fonctions sexuelles et la dépression en utilisant respectivement l'échelle des expériences sexuelles de l'Arizona (ASEX) et l'échelle de dépression de Beck. Ces échelles ont été réappliquées en juin 2020 et juillet 2020 pour évaluer l'impact de l'épidémie sur la fonction sexuelle et la dépression dans le même groupe de patients. Les caractéristiques démographiques et cliniques des patients ont été enregistrées et analysées dans SPSS. RÉSULTATS: Pendant la période pandémique, les valeurs totales de l'échelle de dépression de Beck ont augmenté de manière significative chez les patients atteints d'épilepsie par rapport à la période pré-pandémique (p = 0,048), et les symptômes dépressifs ont montré une tendance à la hausse (p = 0,032). Bien qu'une augmentation de la dysfonction sexuelle ait également été enregistrée, elle n'était pas statistiquement significative par rapport à la période pré-pandémique. Chez huit patients (6,9 %), la fréquence des crises a augmenté pendant la période pandémique. Dans l'analyse multivariée, le seul paramètre qui prédisait l'augmentation de la fréquence des crises était le nombre de médicaments utilisés. Les valeurs de l'échelle de dépression de Beck étaient positivement corrélées avec les valeurs ASEX totales des hommes/femmes, l'âge, l'état matrimonial, la durée de la maladie et la fréquence des crises. CONCLUSION: L'épidémie de COVID-19 a provoqué une augmentation de la tendance à la dépression chez les patients épileptiques et a également eu un effet négatif sur la fonction sexuelle. Pendant les flambées de santé publique, les cliniciens devraient se concentrer non seulement sur le contrôle des crises chez les patients atteints d'épilepsie, mais aussi sur leur santé mentale.

Large Variation in International Prescribing Rates of Opioids After Robotic Prostatectomy.

OBJECTIVE: To compare international opioid prescribing patterns for patients undergoing robotic assisted laparoscopic prostatectomy. To our knowledge, this is the first study to assess international opioid prescribing trends among urologists. METHODS: An anonymous Web-based survey assessing the frequency and quantity of opioid prescriptions for robotic assisted laparoscopic prostatectomy was designed using Qualtrics software. The survey was distributed to urologists internationally via Twitter and email in early 2021. Prescribing patterns were analyzed based on country of practice in three groups: United States, Canada, and all other countries. RESULTS: 160 participants from 26 countries completed the survey including the United States (51%), Greece (19%), Canada (9%), Israel (3.1%). The percentage of providers prescribing post-discharge opioids significantly differed between Canada, the United States, and other countries (86%, 63%, and 11%, respectively, P <.0001). There was a significant difference between years of experience in those who provide opioids compared to those who do not (8 years vs 5 years, P = .0004). The average morphine milligram equivalents (MME) provided in those who did prescribe opioids was greatest in the United States but was not significantly different between groups (mean MME: United States 58 mg, Canada 46 mg, all others 54 mg; P = .63). Attending physicians prescribed more MME than trainees (residents, fellows) on average (attending mean MME = 75 mg, trainee mean MME = 40 mg, P = .017). CONCLUSION: Opioid prescriptions after robotic assisted prostatectomy are common in North America and used sparingly in the rest of the world.

COMPARISON OF REAL WORLD LIPID PROFILE OF PATIENTS WITH TYPE 2 DIABETES AND GUIDELINE RECOMMENDATIONS.

Diabetes is a major risk factor for cardiovascular disease. Despite recommendations and available therapeutic options, patients with diabetes do not always reach the recommended lipid levels. In this study, our aim was to compare the real world lipid profile of type 2 diabetes patients with guideline recommendations for dyslipidemia. Four hundred and sixty eight consecutive patients referred to Outpatient Diabetes Clinic of Istanbul Medeniyet University were recruited. Patient anthropometric measurements (height, weight, waist circumference), biochemical test results (LDL cholesterol (LDL-c), triglycerides, HDL cholesterol, HbA1c) and treatment modalities were recorded. Patients were stratified into cardiovascular risk categories according to the risk factors and their treatment dose was compared to the recommendations. Among 468 patients, 56 (12%) patients had coronary heart disease (CHD). Thirty-four percent of these patients were not on statin treatment (n=19) and their mean LDL-c level was 114±29 mg/dL (2.9±0.75 mmol/L). Nineteen percent of these patients were on high intensity statin treatment (atorvastatin 40-80 mg, rosuvastatin 20 mg). Only four patients with CHD had LDL-c levels <70 mg/dL (1.8 mmol/L). Four hundred and twelve patients had no CHD. In these patients, the mean LDL-c level was 132±38 mg/dL (3.4±0.9 mmol/L). Eighty (19%) patients had LDL-c level lower than 100 mg/dL (2.5 mmol/L). Overall 82% (n=384) of the cohort had not achieved treatment goal. In conclusion, a more pronounced approach for statin treatment is needed in diabetes patients for both primary and secondary prevention of cardiovascular diseases.

Robotic assisted radical cystectomy versus open radical cystectomy: a review of what we do and don't know.

Radical cystectomy (RC) is the gold standard treatment for muscle-invasive and high-risk, noninvasive bladder cancer. Since 2003, robot-assisted radical cystectomy (RARC) has been gaining popularity. Metanalyses show that the primary advantage of RARC is less blood loss and the primary advantage of open radical cystectomy (ORC) is shorter operative times. There do not appear to be significant differences in complications, cancer-related outcomes or survival between the two approaches. Cost analyses comparing RARC and ORC are complicated by the often-ill-defined distinction between the cost to the hospital versus the cost to payors. However, it is likely that for both hospitals and payors, RARC is cost effective at high-volume centers. It is feasible that in the future, increased experience with RARC will lead to improved outcomes and justify the use of RARC over ORC.

Genetic Differences Between Bladder and Upper Urinary Tract Carcinoma: Implications for Therapy.

CONTEXT: Bladder urothelial carcinoma (BUC) and upper tract urothelial carcinoma (UTUC) have genetic differences, which may influence therapy. OBJECTIVE: The aim of the current review was to summarize the current genetic understanding of upper tract and BUC. EVIDENCE ACQUISITION: PubMed, Cochrane, and Web of Science online databases were searched systematically up to February 2020, using the following keywords: urothelial carcinomas, upper urinary tract, renal pelvis, ureter, bladder cancer, and genetics. EVIDENCE SYNTHESIS: UTUC and BUC share mutations in similar genes, such as FGFR3, TP53, and HRAS, and epigenetic genes, such as KDM6A and KMT2A-C, but at varying frequencies. Furthermore, subtyping of UTUC and BUC has identified similar expression subtypes, but UTUC is more often luminal with more T-cell depletion. Clonal studies indicate that BUC after UTUC is also likely luminal, while UTUC after BUC is often basal. CONCLUSIONS: UTUC and BUC share many genomic alterations, but at different frequencies, which recapitulate with their metachronous recurrences. These differences likely contribute to the behavior of these two cancers and imply that they and their metachronous recurrences should be treated as two related yet distinct entities. PATIENT SUMMARY: Urothelial carcinoma of the bladder has distinct genomic features, which are different from distinct genomic features of urothelial carcinoma of the renal pelvis and/or ureter. These features can be used for tailored treatment options specific to tumors of different locations.