Estimating the prevalence of potential and actionable drug-gene interactions in Irish primary care: A cross-sectional study.

AIMS: Pharmacogenetics (PGx) is increasingly recognized as a strategy for medicines optimisation and prevention of adverse drug reactions. According to guidelines produced by the Clinical Pharmacogenetics Implementation Consortium (CPIC) and the Dutch Pharmacogenetic Working Group (DPWG), most medicines with drug-gene interactions (DGIs) are prescribed in primary care. This study aimed to estimate the prevalence of potential and actionable DGIs involving all medicines dispensed in Irish primary care. METHODS: Dispensings of 46 drugs to General Medical Services (GMS) patients in the Health Service Executive Primary Care Reimbursement Service Irish pharmacy claims database from 01 January 2021 to 31 December 2021 were analysed to estimate the national prevalence of total dispensings and incidence of first-time dispensings of drugs with potential DGIs according to the CPIC and/or DPWG guidelines. Phenotype frequency data from the UK Biobank and the CPIC were used to estimate the incidence of actionable DGIs. RESULTS: One in five dispensings (12 443 637 of 62 754 498, 19.8%) were medicines with potential DGIs, 1 878 255 of these dispensed for the first time. On application of phenotype frequencies and linked guideline based therapeutic recommendations, 2 349 055 potential DGIs (18.9%) required action, such as monitoring and guarding against maximum dose, drug or dose change. One in five (369 700, 19.7%) first-time dispensings required action, with 139 169 (7.4%) requiring a change in prescribing. Antidepressants, weak opioids and statins were most commonly identified as having actionable DGIs. CONCLUSIONS: This study estimated a high prevalence of DGIs in primary care in Ireland, identifying the need and opportunity to optimize drug therapy through PGx testing.

Advances in Intraoperative Glioma Tissue Sampling and Infiltration Assessment.

Gliomas are infiltrative brain tumors that often involve functional tissue. While maximal safe resection is critical for maximizing survival, this is challenged by the difficult intraoperative discrimination between tumor-infiltrated and normal structures. Surgical expertise is essential for identifying safe margins, and while the intraoperative pathological review of frozen tissue is possible, this is a time-consuming task. Advances in intraoperative stimulation mapping have aided surgeons in identifying functional structures and, as such, has become the gold standard for this purpose. However, intraoperative margin assessment lacks a similar consensus. Nonetheless, recent advances in intraoperative imaging techniques and tissue examination methods have demonstrated promise for the accurate and efficient assessment of tumor infiltration and margin delineation within the operating room, respectively. In this review, we describe these innovative technologies that neurosurgeons should be aware of.

Evidencing general acceptability of open-label placebo use for tackling overtreatment in primary care: a mixed methods study.

BACKGROUND: Overtreatment poses a challenge to healthcare systems due to harmful consequences of avoidable side-effects and costs. This study presents the first account for examining the feasibility of placebo use for reducing overtreatment in primary care, including whether public attitudes support the use of different placebo types in place of inappropriate prescriptions of antibiotics, antidepressants, or analgesics. METHODS: We used a multi-study, mixed-methods design, including patient and public (PPI) consultations, focus groups (Study 1) and two pre-registered online experiments (Studies 2 and 3). RESULTS: Study 1 (N = 16) explored everyday conceptions and practicalities of potential placebo use in the context of respiratory infections. Findings highlighted the importance of trusting doctor-patient relationships and safety-netting. Study 2 employed a randomised experiment with a representative UK sample (N = 980), investigating attitudes towards 5 different treatment options for respiratory infections: (1) blinded + pure placebo, (2) open-label + pure placebo, (3) open-label + impure placebo, (4) antibiotic treatment, and (5) no treatment. Study 2 also examined how attitudes varied based on wording and individual differences. Findings indicated general support (ηp2 = .149, large effect size) for replacing inappropriate antibiotics with open-label + impure placebos, although personal placebo acceptability was lower. Also, older people, individuals suffering from chronic illness or those showing higher levels of health anxiety appeared less amenable to placebo use. Study 3 (N = 1177) compared attitudes towards treatment options across three clinical scenarios: respiratory infection, depression and pain. Findings suggested significant differences in the acceptability of placebo options based on the clinical context. In the infection scenario, options for open-label + pure placebos, open-label + impure placebos and no treatment were rated significantly more acceptable (ηp2 = .116, medium effect size) compared to the depression and pain scenarios. Again, general support for placebos was higher than placebo acceptability for personal use. CONCLUSIONS: Findings from PPI and three studies indicate general support for combatting overprescribing in primary care through clinical placebo use. This is an indicator for wider UK public support for a novel, behavioural strategy to target a long-standing healthcare challenge. General acceptability appears to be highest for the use of open-label + impure placebos in the context of antibiotic overprescribing.

Technical Aspects of Motor and Language Mapping in Glioma Patients.

Gliomas are infiltrative primary brain tumors that often invade functional cortical and subcortical regions, and they mandate individualized brain mapping strategies to avoid postoperative neurological deficits. It is well known that maximal safe resection significantly improves survival, while postoperative deficits minimize the benefits associated with aggressive resections and diminish patients' quality of life. Although non-invasive imaging tools serve as useful adjuncts, intraoperative stimulation mapping (ISM) is the gold standard for identifying functional cortical and subcortical regions and minimizing morbidity during these challenging resections. Current mapping methods rely on the use of low-frequency and high-frequency stimulation, delivered with monopolar or bipolar probes either directly to the cortical surface or to the subcortical white matter structures. Stimulation effects can be monitored through patient responses during awake mapping procedures and/or with motor-evoked and somatosensory-evoked potentials in patients who are asleep. Depending on the patient's preoperative status and tumor location and size, neurosurgeons may choose to employ these mapping methods during awake or asleep craniotomies, both of which have their own benefits and challenges. Regardless of which method is used, the goal of intraoperative stimulation is to identify areas of non-functional tissue that can be safely removed to facilitate an approach trajectory to the equator, or center, of the tumor. Recent technological advances have improved ISM's utility in identifying subcortical structures and minimized the seizure risk associated with cortical stimulation. In this review, we summarize the salient technical aspects of which neurosurgeons should be aware in order to implement intraoperative stimulation mapping effectively and safely during glioma surgery.

Recognizing the psychological impact of a glioma diagnosis on mental and behavioral health: a systematic review of what neurosurgeons need to know.

A cancer diagnosis is life altering and frequently associated with both acute and long-lasting psychosocial and behavioral distress for patients. The impact of a diffuse glioma diagnosis on mental health is an important aspect of the patient experience with their disease. This needs to be understood by neurosurgeons so these concerns can be appropriately addressed in a timely fashion and integrated into the multidisciplinary care of neuro-oncology patients. The relatively grave prognosis associated with diffuse gliomas, the morbidity associated with treatment, and the constant threat of developing a new neurological deficit all can negatively affect a patient's mental ability to cope and ultimately manifest in mental health disorders such as anxiety and depression. The objective of this systematic review was to describe the variety of behavioral health disorders patients may experience following a glioma diagnosis and discuss possible treatment options. The PubMed, Web of Science, Embase, and PsycINFO databases were searched through July 1, 2022, using broad search terms, which resulted in 5028 studies that were uploaded to Covidence systematic review software. Duplicates, non-English-language studies, and studies with irrelevant outcomes or incorrect design were removed (n = 3167). A total of 92 articles reporting behavioral health outcomes in brain tumor patients were categorized and extracted for associations with overall mental health, anxiety, depression, distress, stress, pharmacology, interventions, and mental health in caregivers. The authors identified numerous studies reporting the prevalence of mental health disorders and their negative influence in this population. However, there is a paucity of literature on therapeutic options for patients. Given the strong correlation between patient quality of life and mental well-being, there is a considerable need for early recognition and treatment of these behavioral health disorders to optimize everyday functioning for patients.

Methylprednisolone, dexamethasone or hydrocortisone for acute severe pediatric asthma: does it matter?

OBJECTIVE: Various intravenous (IV) corticosteroids are available for acute severe asthma (ASA) treatment. The choice of IV corticosteroids varies broadly and depends on institution, country, or physician preferences. In this study, we compared the efficacy of IV methylprednisolone, hydrocortisone and dexamethasone in ASA treatment during pediatric intensive care unit (PICU) admission. METHODS: The study was a prospective randomized clinical trial. We enrolled patients of 1-21 years after they were admitted to the PICU requiring continuous beta-2 agonist treatment. Patients were randomized into three groups: Group A: IV Methylprednisolone, Group B: IV Hydrocortisone and Group C: IV Dexamethasone. The primary outcomes measured were durations of beta-2 agonist continuous nebulization treatment. Secondary outcomes, included PICU and hospital length of stay (LOS), pediatric asthma severity score (PASS), need for mechanical ventilation and maximum dose of beta-2 agonist treatment. RESULTS: 61 patients were included in the analysis. 22 patients recruited in Group A, 20 in group B and 19 group C. Median durations of beta-2-agonist treatment were 23 h (QR 16-38) for methylprednisolone, 27 h (QR 16-40) for hydrocortisone, and 32 h (QR 16-48) for dexamethasone (p = 0.90). There was no difference in PICU LOS, hospital LOS, PASS score, B2 agonist maximum dose, or need for ventilation support. CONCLUSIONS: The use of IV methylprednisolone, hydrocortisone, and dexamethasone have equivalent efficacy when used at the appropriate doses. Studies with larger cohorts are needed to compare the effectiveness of IV corticosteroids in the management of ASA in the PICU setting.

Repurposing a PICU for Adult Care in a State Mandated COVID-19 Only Hospital: Outcome Comparison to the MICU Cohort to Determine Safety and Effectiveness.

Objective: The ongoing coronavirus 2019 (COVID-19) pandemic is disproportionally impacting the adult population. This study describes the experiences after repurposing a PICU and its staff for adult critical care within a state mandated COVID-19 hospital and compares the outcomes to adult patients admitted to the institution's MICU during the same period. Design: A retrospective chart review was performed to analyze outcomes for the adults admitted to the PICU and MICU during the 27-day period the PICU was incorporated into the institution's adult critical care surge plan. Setting: Tertiary care state University hospital. Patients: Critically ill adult patients with proven or suspected COVID-19. Interventions: To select the most ideal adult patients for PICU admission a tiered approach that incorporated older patients with more comorbidities at each stage was implemented. Measurements and Main Results: There were 140 patients admitted to the MICU and 9 patients admitted to the PICU during this period. The mean age of the adult patients admitted to the PICU was lower (49.1 vs. 63.2 p = 0.017). There was no statistically significant difference in the number of comorbidities, intubation rates, days of ventilation, dialysis or LOS. Patients selected for PICU care did not have coronary artery disease, CHF, cerebrovascular disease or COPD. Mean admission Sequential Organ Failure Assessment (SOFA) score was lower in patients admitted to the PICU (4 vs. 6.4, p = 0.017) with similar rates of survival to discharge (66.7 vs. 44.4%, p = 0.64). Conclusion: Outcomes for the adult patients who received care in the PICU did not appear to be worse than those who were admitted to the MICU during this time. While limited by a small sample size, this single center cohort study revealed that careful assessment of critical illness considering age and type of co-morbidities may be a safe and effective approach in determining which critically ill adult patients with known or suspected COVID-19 are the most appropriate for PICU admission in general hospitals with primary management by its physicians and nurses.

Use of Hydroxychloroquine and Risk of Heart Failure in Patients With Rheumatoid Arthritis.

OBJECTIVE: To examine the relationship between the use of hydroxychloroquine (HCQ) and risk of developing heart failure (HF) in rheumatoid arthritis (RA). METHODS: In this nested case-control study, cases were Olmsted County, Minnesota residents with incident RA (based on 1987 American College of Rheumatology criteria) from 1980 to 2013 who developed HF after RA incidence. Each case was matched on year of birth, sex, and year of RA incidence with an RA control who did not develop HF. Data on HCQ use including start and stop dates, as well as dose changes, were reviewed and used to calculate HCQ duration and cumulative dose. Age-adjusted logistic regression models were used to examine the association between HCQ and HF. RESULTS: The study identified 143 RA cases diagnosed with HF (mean age 65.8 yrs, 62% females) and 143 non-HF RA controls (mean age 64.5, 62% female). HCQ cumulative dose was not associated with HF (OR 0.96 per 100-g increase in cumulative dose, 95% CI 0.90-1.03). Likewise, no association was found for patients with a cumulative dose ≥ 300 g (OR 0.92, 95% CI 0.41-2.08). The HCQ duration of intake in years prior to index was not associated with HF (OR 0.98, 95% CI 0.91-1.05). CONCLUSION: Use of HCQ was not associated with development of HF in patients with RA in this study. Further studies are needed to understand the effect of higher doses of HCQ on the development of HF in RA.

LRP1 is a master regulator of tau uptake and spread.

The spread of protein aggregates during disease progression is a common theme underlying many neurodegenerative diseases. The microtubule-associated protein tau has a central role in the pathogenesis of several forms of dementia known as tauopathies-including Alzheimer's disease, frontotemporal dementia and chronic traumatic encephalopathy1. Progression of these diseases is characterized by the sequential spread and deposition of protein aggregates in a predictable pattern that correlates with clinical severity2. This observation and complementary experimental studies3,4 have suggested that tau can spread in a prion-like manner, by passing to naive cells in which it templates misfolding and aggregation. However, although the propagation of tau has been extensively studied, the underlying cellular mechanisms remain poorly understood. Here we show that the low-density lipoprotein receptor-related protein 1 (LRP1) controls the endocytosis of tau and its subsequent spread. Knockdown of LRP1 significantly reduced tau uptake in H4 neuroglioma cells and in induced pluripotent stem cell-derived neurons. The interaction between tau and LRP1 is mediated by lysine residues in the microtubule-binding repeat region of tau. Furthermore, downregulation of LRP1 in an in vivo mouse model of tau spread was found to effectively reduce the propagation of tau between neurons. Our results identify LRP1 as a key regulator of tau spread in the brain, and therefore a potential target for the treatment of diseases that involve tau spread and aggregation.

A farnesyltransferase inhibitor activates lysosomes and reduces tau pathology in mice with tauopathy.

Tau inclusions are a shared feature of many neurodegenerative diseases, among them frontotemporal dementia caused by tau mutations. Treatment approaches for these conditions include targeting posttranslational modifications of tau proteins, maintaining a steady-state amount of tau, and preventing its tendency to aggregate. We discovered a new regulatory pathway for tau degradation that operates through the farnesylated protein, Rhes, a GTPase in the Ras family. Here, we show that treatment with the farnesyltransferase inhibitor lonafarnib reduced Rhes and decreased brain atrophy, tau inclusions, tau sumoylation, and tau ubiquitination in the rTg4510 mouse model of tauopathy. In addition, lonafarnib treatment attenuated behavioral abnormalities in rTg4510 mice and reduced microgliosis in mouse brain. Direct reduction of Rhes in the rTg4510 mouse by siRNA reproduced the results observed with lonafarnib treatment. The mechanism of lonafarnib action mediated by Rhes to reduce tau pathology was shown to operate through activation of lysosomes. We finally showed in mouse brain and in human induced pluripotent stem cell-derived neurons a normal developmental increase in Rhes that was initially suppressed by tau mutations. The known safety of lonafarnib revealed in human clinical trials for cancer suggests that this drug could be repurposed for treating tauopathies.

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.

Robot-Assisted Radical Cystectomy in Men: Technique of Spaces.

The past decade has witnessed a dramatic increase in utilization of robot-assisted radical cystectomy (RARC). RARC has been shown to offer some perioperative benefits in terms of blood loss, transfusion rates, hospital stay, and recovery when compared with its open counterpart without jeopardizing oncologic outcomes. In this article, we review the indications, perioperative care, and describe the "Technique of Spaces" of RARC employed at our institution, and highlight the key steps for male RARC.

Gynecological organ involvement at robot-assisted radical cystectomy in females: Is anterior exenteration necessary?

INTRODUCTION: We aimed to investigate patient and disease variables associated with gynecological organ invasion in females with bladder cancer at the time of robot-assisted radical cystectomy (RARC). METHODS: We conducted a retrospective review of female patients who underwent robot-assisted anterior pelvic exenteration (RAAE) between 2005 and 2016. Patients were divided into two groups: those with gynecological organ involvement at RAAE and those without. Data were reviewed for perioperative and pathological outcomes. Kaplan-Meier method was used to depict survival outcomes. Multivariable stepwise regression analysis was performed to identify predictors of gynecological organ involvement. RESULTS: A total of 118 female patients were identified; 17 (14%) showed evidence of gynecological organ invasion at RAAE. Patients with gynecological organ invasion had more lymphovascular invasion at transurethral resection of bladder tumour (TURBT) (82% vs. 46%; p=0.006), trigonal tumours at TURBT (59% vs. 18%; p=0.001), multifocal disease (65% vs. 33%; p=0.01), pN+ (71% vs. 22%; p<0.001), positive surgical margins (24% vs. 4%; p=0.02), and they less commonly demonstrated pure urothelial carcinoma at TURBT (18% vs. 66%; p<0.001). On multivariate analysis, significant predictors of gynecological organ invasion were pN positive disease (odds ratio [OR] 6.48; 95% confidence interval [CI] 1.64-25.51; p=0.008), trigonal tumour location (OR 5.72; 95% CI 1.39-23.61; p=0.02), and presence of variant histology (OR18.52; 95% CI 3.32-103.4; p=0.001). CONCLUSIONS: Patients with trigonal tumours, variant histology, and nodal involvement are more likely to have gynecological organs invasion at RAAE. This information may help improve counselling of patients and better identify candidates for gynecological organ-sparing cystectomy.

Development of a Patient-Based Model for Estimating Operative Times for Robot-Assisted Radical Prostatectomy.

OBJECTIVES: To develop a methodology for predicting operative times for robot-assisted radical prostatectomy (RARP) using preoperative patient, disease, procedural, and surgeon variables to facilitate operating room (OR) scheduling. METHODS: The model included preoperative metrics: body mass index (BMI), American Society of Anesthesiologists score, clinical stage, National Comprehensive Cancer Network risk, prostate weight, nerve-sparing status, extent and laterality of lymph node dissection, and operating surgeon (six surgeons were included in the study). A binary decision tree was fit using a conditional inference tree method to predict operative times. The variables most associated with operative time were determined using permutation tests. Data were split at the value of the variable that results in the largest difference in mean for surgical time across the split. This process was repeated recursively on the resultant data. RESULTS: A total of 1709 RARPs were included. The variable most strongly associated with operative time was the surgeon (surgeons 2 and 4-102 minutes shorter than surgeons 1, 3, 5, and 6, p < 0.001). Among surgeons 2 and 4, BMI had the strongest association with surgical time (p < 0.001). Among patients operated by surgeons 1, 3, 5, and 6, RARP time was again most strongly associated with the surgeon performing RARP. Surgeons 1, 3, and 6 were on average 76 minutes faster than surgeon 5 (p < 0.001). The regression tree output in the form of box plots showed operative time median and ranges according to patient, disease, procedural, and surgeon metrics. CONCLUSION: We developed a methodology that can predict operative times for RARP based on patient, disease and surgeon variables. This methodology can be utilized for quality control, facilitate OR scheduling, and maximize OR efficiency.

Variability and interpretation of communication taxonomy during robot-assisted surgery: do we all speak the same language?

OBJECTIVE: To investigate and analyse the different ways surgeons communicate with bedside assistants during robot-assisted surgery (RAS). METHODS: We retrospectively reviewed video and audio recordings of 26 RAS procedures (23 prostatectomies and three cystectomies). Three cameras and eight lapel microphones were used to record the operating theatre environment. We identified five common tasks and categorized them into 'specific', 'non-specific' and 'unclear' categories. We also determined the frequency, time to execute the task, inconveniences and acknowledgements associated with each category. The most efficient category was the one that took the shortest duration to accomplish and was associated with the fewest inconveniences. RESULTS: A total of 1 000 requests were made by three surgeons for six bedside assistants by three surgeons. The five identified tasks were: instrument change; clipping; suction; irrigation; and retraction. For instrument change, non-specific requests were the most frequent compared with the other categories (77% vs 18% vs 5%; P < 0.001). For suction, specific requests were the most frequently used of the three categories (73% vs 27% vs 0%; P < 0.001) and this task was associated with the fewest inconveniences (38% vs 62%; P = 0.01). For clipping, irrigation and retraction, both specific and non-specific requests were similar in terms of their frequency, action time and inconveniences. Comparing complete vs incomplete requests, incomplete requests had significantly shorter median action time (5 vs 8 s; P < 0.001) but did not significantly differ in terms of inconveniences and acknowledgement. CONCLUSION: To our knowledge, this is the first study to provide a detailed analysis of communication during RAS. It lays a foundation for standardized taxonomy to improve communication, surgical efficiency and patient safety.

Natural History and Predictors of Parastomal Hernia after Robot-Assisted Radical Cystectomy and Ileal Conduit Urinary Diversion.

PURPOSE: We investigated the prevalence of and variables associated with parastomal hernia and its outcomes after robot-assisted radical cystectomy and ileal conduit creation for bladder cancer. MATERIALS AND METHODS: We retrospectively reviewed the records of patients who underwent robot-assisted radical cystectomy at our institution. Parastomal hernia was defined as the protrusion of abdominal contents through the stomal defect in the abdominal wall on cross-sectional imaging. Parastomal hernia was further described in terms of patient and hernia characteristics, symptoms, management and outcomes. The Kaplan-Meier method was used to determine time to parastomal hernia and time to surgery. Multivariate stepwise logistic regression was done to evaluate variables associated with parastomal hernia. RESULTS: A total of 383 patients underwent robot-assisted radical cystectomy and ileal conduit creation. Of the patients 75 (20%) had parastomal hernia, which was symptomatic in 23 (31%), and 11 (15%) underwent treatment. Median time to parastomal hernia was 13 months (IQR 9-22). Parastomal hernia developed in 9%, 23% and 32% of cases at 1, 2 and 3 years, respectively. Patients with parastomal hernia had a significantly higher body mass index (30 vs 28 kg/m2, p = 0.02), longer overall operative time (357 vs 340 minutes, p = 0.01) and greater blood loss (325 vs 250 ml, p = 0.04). On multivariate analysis operative time (OR 1.25, 95% CI 1.21-3.90, p <0.001), a fascial defect 30 mm or greater (OR 5.23, 95% CI 2.32-11.8, p <0.001) and a lower postoperative estimated glomerular filtration rate (OR 2.17, 95% CI 1.21-3.90, p = 0.01) were significantly associated with parastomal hernia. CONCLUSIONS: Symptoms develop in approximately a third of patients with parastomal hernia and 15% will require surgery. The risk of parastomal hernia plateaued after postoperative year 3. Longer operative time, a larger fascial defect and lower postoperative kidney function were associated with parastomal hernia.

Outcomes of Intracorporeal Urinary Diversion after Robot-Assisted Radical Cystectomy: Results from the International Robotic Cystectomy Consortium.

PURPOSE: This study aimed to provide an update and compare perioperative outcomes and complications of intracorporeal and extracorporeal urinary diversion following robot-assisted radical cystectomy using data from the multi-institutional, prospectively maintained International Robotic Cystectomy Consortium database. MATERIALS AND METHODS: We retrospectively reviewed the records of 2,125 patients from a total of 26 institutions. Intracorporeal urinary diversion was compared with extracorporeal urinary diversion. Multivariate logistic regression models using stepwise variable selection were fit to evaluate preoperative, operative and postoperative predictors of intracorporeal urinary diversion, operative time, high grade complications and 90-day hospital readmissions after robot-assisted radical cystectomy. RESULTS: In our cohort 1,094 patients (51%) underwent intracorporeal urinary diversion. These patients demonstrated shorter operative time (357 vs 400 minutes), less blood loss (300 vs 350 ml) and fewer blood transfusions (4% vs 19%, all p <0.001). They experienced more high grade complications (13% vs 10%, p = 0.02). Intracorporeal urinary diversion use increased from 9% of all urinary diversions in 2005 to 97% in 2015. Complications after this procedure decreased significantly with time (p <0.001). On multivariable analysis higher annual cystectomy volume (OR 1.02, 95% CI 1.01-1.03, p <0.002), year of robot-assisted radical cystectomy (2013-2016 OR 68, 95% CI 44-105, p <0.001) and American Society of Anesthesiologists® score less than 3 (OR 1.75, 95% CI 1.38-2.22, p <0.001) were associated with undergoing intracorporeal urinary diversion. The procedure was associated with a shorter operative time of 27 minutes (p = 0.001). CONCLUSIONS: The use of intracorporeal urinary diversion has increased in the last decade. A higher annual institutional volume of robot-assisted radical cystectomy was associated with intracorporeal urinary diversion as well as with shorter operative time. Although intracorporeal urinary diversion was associated with higher grade complications than extracorporeal urinary diversion, they decreased with time.

Serum IL-17 in patients with erythema multiforme or Stevens-Johnson syndrome/toxic epidermal necrolysis drug reaction, and correlation with disease severity.

BACKGROUND: There is strong evidence that drug-induced cutaneous eruptions have an immunological component. Interleukin (IL)-17, a proinflammatory cytokine that is predominantly produced by T helper 17 cells, has been linked to various autoimmune and inflammatory diseases. AIM: To measure serum IL-17 levels in patients with cutaneous drug reactions [erythema multiforme (EM) and Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN)] in order to study the associations between IL-17 and disease severity. METHODS: In total, 32 patients (13 with EM and 19 with SJS/TEN) and 15 age- and sex-matched healthy controls (HCs) were enrolled. Patients with SJS/TEN were assessed clinically using the SCORe of Toxic Epidermal Necrosis (SCORTEN) scale. Serum IL-17 levels were determined by ELISA. RESULTS: Serum IL-17 levels were significantly higher compared with HCs (16.46 ± 5.21 pg/mL) in the EM (35.1 ± 23.89 pg/mL, P < 0.02) and SJS/TEN (68.19 ± 35.42 pg/mL, P = 0.001) groups. IL-17 levels were also significantly higher in the SJS/TEN group than in the EM group (P = 0.004). Mean affected body surface area percentage was 0.9 ± 0.21 in the EM group and 22.8 ± 10.67 in the SJS/TEN group. The SJS/TEN SCORTEN ranged from 1 to 5, with a mean of 2.5 ± 1. Serum IL-17 level correlated positively with both percentage surface area of detached skin and SCORTEN. CONCLUSIONS: Serum IL-17 levels may have prognostic and diagnostic value in patients with EM or SJS/TEN reactions, and can provide a valuable approach in managment.

Development of a patient and institutional-based model for estimation of operative times for robot-assisted radical cystectomy: results from the International Robotic Cystectomy Consortium.

OBJECTIVES: To design a methodology to predict operative times for robot-assisted radical cystectomy (RARC) based on variation in institutional, patient, and disease characteristics to help in operating room scheduling and quality control. PATIENTS AND METHODS: The model included preoperative variables and therefore can be used for prediction of surgical times: institutional volume, age, gender, body mass index, American Society of Anesthesiologists score, history of prior surgery and radiation, clinical stage, neoadjuvant chemotherapy, type, technique of diversion, and the extent of lymph node dissection. A conditional inference tree method was used to fit a binary decision tree predicting operative time. Permutation tests were performed to determine the variables having the strongest association with surgical time. The data were split at the value of this variable resulting in the largest difference in means for the surgical time across the split. This process was repeated recursively on the resultant data sets until the permutation tests showed no significant association with operative time. RESULTS: In all, 2 134 procedures were included. The variable most strongly associated with surgical time was type of diversion, with ileal conduits being 70 min shorter (P < 0.001). Amongst patients who received neobladders, the type of lymph node dissection was also strongly associated with surgical time. Amongst ileal conduit patients, institutional surgeon volume (>66 RARCs) was important, with those with a higher volume being 55 min shorter (P < 0.001). The regression tree output was in the form of box plots that show the median and ranges of surgical times according to the patient, disease, and institutional characteristics. CONCLUSION: We developed a method to estimate operative times for RARC based on patient, disease, and institutional metrics that can help operating room scheduling for RARC.