Outcomes of surgical repair of Retinoschisis-associated retinal detachment compared to Rhegmatogenous retinal detachment

Abstract Background The aim of this study is to compare outcomes of primary retinal detachment (RD) repair in retinoschisis-associated RD (RSRD) and rhegmatogenous RD (RRD). Methods This is a retrospective observational cohort study. Charts of 2247 consecutive patients operated for RD repair at the Centre hospitalier universitaire de Québec – Université Laval between 2014 and 2018 were reviewed. Patients with RSRD and RRD were included to compare the visual and anatomical outcomes of both groups. Results There were 41 patients (1.8%) with RSRD and 1661 patients (74%) with RRD. RSRD patients had more primary repair failures (n = 9, 22%, vs. n = 166, 10%; p = 0.013). The primary anatomical success rates for pars plana vitrectomy with and without scleral buckle (PPV-SB vs. PPV) as primary repair method were similar in both RSRD patients (n = 11/14, 79% vs. n = 20/25, 80%; p = 0.92) and RRD patients (n = 751/827, 91% vs. n = 641/721, 89%; p = 0.21). At final follow-up, best corrected visual acuity (VA) in logarithm of the minimum angle of resolution (logMAR) was 0.30 [0.10, 0.88] and 0.18 [0.10, 0.40] (p = 0.03) in RSRD patients and RRD patients, respectively. Presence of retinoschisis was associated with worse final VA (β 0.082, p < 0.001). Other predictive variables included female sex, macula-off presentation, number of RD quadrants involved, longer symptoms duration, worse baseline VA, and primary repair failure. The greatest predictors were worse baseline VA, primary repair failure, and macula-off status at presentation. Presence of retinoschisis did not significantly increase risk of primary repair failure in multivariable analysis (OR 1.45, 95% CI: 0.50–4.17; p = 0.49). Symptoms duration was the greatest effect factor associated with for primary repair failure (OR 1.37, 95% CI: 1.12–1.69; p = 0.003). Conclusions RSRD is associated with more primary repair failure in univariate analysis, but not in multivariate analysis after adjusting for symptoms duration. It is however associated with worse final VA even after adjusting for primary repair failure. Both PPV and PPV-SB are valid repair methods for RSRD. However, RSRD remains a challenge to treat.

Download Full-text

Obesity and smoking as risk factors for invasive mechanical ventilation in COVID-19: A retrospective, observational cohort study

PLoS ONE ◽

10.1371/journal.pone.0238552 ◽

2020 ◽

Vol 15 (12) ◽

pp. e0238552

Author(s):

Ana C. Monteiro ◽

Rajat Suri ◽

Iheanacho O. Emeruwa ◽

Robert J. Stretch ◽

Roxana Y. Cortes-Lopez ◽

...

Keyword(s):

Mechanical Ventilation ◽

Cohort Study ◽

Smoking Status ◽

Univariate Analysis ◽

Invasive Mechanical Ventilation ◽

Multivariable Analysis ◽

Observational Cohort Study ◽

Smoking History ◽

Observational Cohort ◽

Retrospective Observational Cohort Study

Purpose To describe the trajectory of respiratory failure in COVID-19 and explore factors associated with risk of invasive mechanical ventilation (IMV). Materials and methods A retrospective, observational cohort study of 112 inpatient adults diagnosed with COVID-19 between March 12 and April 16, 2020. Data were manually extracted from electronic medical records. Multivariable and Univariable regression were used to evaluate association between baseline characteristics, initial serum markers and the outcome of IMV. Results Our cohort had median age of 61 (IQR 45–74) and was 66% male. In-hospital mortality was 6% (7/112). ICU mortality was 12.8% (6/47), and 18% (5/28) for those requiring IMV. Obesity (OR 5.82, CI 1.74–19.48), former (OR 8.06, CI 1.51–43.06) and current smoking status (OR 10.33, CI 1.43–74.67) were associated with IMV after adjusting for age, sex, and high prevalence comorbidities by multivariable analysis. Initial absolute lymphocyte count (OR 0.33, CI 0.11–0.96), procalcitonin (OR 1.27, CI 1.02–1.57), IL-6 (OR 1.17, CI 1.03–1.33), ferritin (OR 1.05, CI 1.005–1.11), LDH (OR 1.57, 95% CI 1.13–2.17) and CRP (OR 1.13, CI 1.06–1.21), were associated with IMV by univariate analysis. Conclusions Obesity, smoking history, and elevated inflammatory markers were associated with increased need for IMV in patients with COVID-19.

Download Full-text

Lipid levels do not influence the risk of venous thromboembolism

Thrombosis and Haemostasis ◽

10.1160/th12-06-0426 ◽

2012 ◽

Vol 108 (11) ◽

pp. 923-929 ◽

Cited By ~ 19

Author(s):

Bakhtawar Mahmoodi ◽

Ron Gansevoort ◽

Friso Muntinghe ◽

Robin Dullaart ◽

Hanneke Kluin-Nelemans ◽

...

Keyword(s):

Cohort Study ◽

Venous Thromboembolism ◽

Low Density Lipoprotein ◽

Univariate Analysis ◽

Multivariable Analysis ◽

Density Lipoprotein ◽

Population Based ◽

Apolipoprotein A1 ◽

Observational Cohort ◽

Multivariable Analyses

SummaryStudies on the association between lipid profile and venous thromboembolism (VTE) are inconsistent. This could be caused by classical lipoproteins being inferior to apolipoproteins as markers for VTE risk. Therefore, we examined whether apolipoproteins are more strongly related to VTE than lipoproteins. For this analysis we used the PREVEND prospective community based observational cohort study. Levels of apolipoprotein A1 (ApoA1), apolipoprotein B (ApoB), total cholesterol (TC), high-density lipoprotein (HDL), non-HDL, low-density lipoprotein (LDL), triglycerides (TG), lipoprotein(a), ApoB/ApoA1 and TC/HDL ratio were assessed. Subjects with VTE were identified using databases of the national registries of hospital discharge diagnoses, death certificates, and the regional anticoagulation clinic. Out of 7,627 subjects, 110 developed VTE during a median follow-up of 10.5 years. In both univariate and multivariable analyses no significant associations between apolipoproteins and overall VTE were observed. Of the classical lipoproteins, TC, non-HDL, LDL, TG, and TC/HDL ratio were significantly associated with overall VTE in univariate analysis. Significant associations were no longer present in multivariable analysis. TGL and LDL were significantly associated with unprovoked VTE in univariate analysis. After adjustment for age and sex this significance was lost. No significant associations between (apo-) lipoproteins and provoked VTE were found. We conclude that apolipoproteins are not better in predicting VTE risk than the classical lipoproteins. Our population-based cohort study does not show an association between both apolipoproteins and the classical lipoproteins and VTE risk.

Download Full-text

Obesity and Smoking as Risk Factors for Invasive Mechanical Ventilation in COVID-19: a Retrospective, Observational Cohort Study

10.1101/2020.08.12.20173849 ◽

2020 ◽

Author(s):

Ana Carolina Costa Monteiro ◽

Rajat Suri ◽

Ileanacho Obi Emeruwa ◽

Robert J Stretch ◽

Roxana Y Cortes Lopez ◽

...

Keyword(s):

Mechanical Ventilation ◽

Cohort Study ◽

Smoking Status ◽

Univariate Analysis ◽

Invasive Mechanical Ventilation ◽

Multivariable Analysis ◽

Observational Cohort Study ◽

Smoking History ◽

Observational Cohort ◽

Retrospective Observational Cohort Study

Purpose: To describe the trajectory of respiratory failure in COVID-19 and explore factors associated with risk of invasive mechanical ventilation (IMV). Materials and Methods: A retrospective, observational cohort study of 112 inpatient adults diagnosed with COVID-19 between March 12 and April 16, 2020. Data were manually extracted from electronic medical records. Multivariable and Univariable regression were used to evaluate association between baseline characteristics, initial serum markers and the outcome of IMV. Results: Our cohort had median age of 61 (IQR 45-74) and was 66% male. In-hospital mortality was 6% (7/112). ICU mortality was 12.8% (6/47), and 18% (5/28) for those requiring IMV. Obesity (OR 5.82, CI 1.74-19.48), former (OR 8.06, CI 1.51-43.06) and current smoking status (OR 10.33, CI 1.43-74.67) were associated with IMV after adjusting for age, sex, and high prevalence comorbidities by multivariable analysis. Initial absolute lymphocyte count (OR 0.33, CI 0.11-0.96), procalcitonin (OR 1.27, CI 1.02-1.57), IL-6 (OR 1.17, CI 1.03-1.33), ferritin (OR 1.05, CI 1.005-1.11), LDH (OR 1.57, 95% CI 1.13-2.17) and CRP (OR 1.13, CI 1.06-1.21), were associated with IMV by univariate analysis. Conclusions: Obesity, smoking history, and elevated inflammatory markers were associated with increased need for IMV in patients with COVID-19.

Download Full-text

Neurophysiological seizure-onset predictors of epilepsy surgery outcome: a multivariable analysis

Journal of Neurosurgery ◽

10.3171/2019.9.jns19527 ◽

2020 ◽

Vol 133 (6) ◽

pp. 1863-1872 ◽

Cited By ~ 1

Author(s):

Hideaki Tanaka ◽

Jean Gotman ◽

Hui Ming Khoo ◽

André Olivier ◽

Jeffery Hall ◽

...

Keyword(s):

Surgical Outcome ◽

Focal Epilepsy ◽

Univariate Analysis ◽

Multivariable Analysis ◽

Postoperative Outcome ◽

Seizure Onset ◽

Resective Surgery ◽

Scalp Eeg ◽

Surgery Outcome ◽

Intracerebral Eeg

OBJECTIVEThe authors sought to determine which neurophysiological seizure-onset features seen during scalp electroencephalography (EEG) and intracerebral EEG (iEEG) monitoring are predictors of postoperative outcome in a large series of patients with drug-resistant focal epilepsy who underwent resective surgery.METHODSThe authors retrospectively analyzed the records of 75 consecutive patients with focal epilepsy, who first underwent scalp EEG and then iEEG (stereo-EEG) for presurgical assessment and who went on to undergo resective surgery between 2004 and 2015. To determine the independent prognostic factors from the neurophysiological scalp EEG and iEEG seizure-onset information, univariate and standard multivariable logistic regression analyses were used. Since scalp EEG and iEEG data were recorded at different times, the authors matched scalp seizures with intracerebral seizures for each patient using strict criteria.RESULTSA total of 3057 seizures were assessed. Forty-eight percent (36/75) of patients had a favorable outcome (Engel class I–II) after a minimum follow-up of at least 1 year. According to univariate analysis, a localized scalp EEG seizure onset (p < 0.001), a multilobar intracerebral seizure-onset zone (SOZ) (p < 0.001), and an extended SOZ (p = 0.001) were significantly associated with surgical outcome. According to multivariable analysis, the following two independent factors were found: 1) the ability of scalp EEG to localize the seizure onset was a predictor of a favorable postoperative outcome (OR 6.073, 95% CI 2.011–18.339, p = 0.001), and 2) a multilobar SOZ was a predictor of an unfavorable outcome (OR 0.076, 95% CI 0.009–0.663, p = 0.020).CONCLUSIONSThe study findings show that localization at scalp seizure onset and a multilobar SOZ were strong predictors of surgical outcome. These predictors can help to select the better candidates for resective surgery.

Download Full-text

Acute kidney injury and its outcomes in melioidosis

Journal of Nephrology ◽

10.1007/s40620-021-00970-x ◽

2021 ◽

Author(s):

Ravindra Attur Prabhu ◽

Tushar Shaw ◽

Indu Ramachandra Rao ◽

Vandana Kalwaje Eshwara ◽

Shankar Prasad Nagaraju ◽

...

Keyword(s):

Acute Kidney Injury ◽

Kidney Function ◽

Univariate Analysis ◽

Kidney Injury ◽

Function Recovery ◽

Kidney Involvement ◽

Duration Of Hospitalization ◽

Observational Cohort ◽

Stage 1 ◽

Urinary Abnormalities

Abstract Background Melioidosis is a potentially fatal tropical infection caused by Burkholderia pseudomallei. Kidney involvement is possible, but has not been well described. Aim This study aimed to assess the risk of acute kidney injury (AKI) and its outcomes in melioidosis. Methods A retrospective observational cohort study was performed. Case records of consecutive patients with culture-confirmed melioidosis, observed from January 1st, 2012 through December 31st, 2019 were analysed for demographics, presence of comorbidities, including chronic kidney disease (CKD), diabetes mellitus (DM), and presence of bacteraemia, sepsis, shock, AKI, and urinary abnormalities. The outcomes we studied were: mortality, need for hospitalisation in an intensive care unit (ICU), duration of hospitalization. We then compared the outcomes between patients with and without AKI. Results Of 164 patients, AKI was observed in 59 (35.98%), and haemodialysis was required in eight (13.56%). In the univariate analysis, AKI was associated with CKD (OR 5.83; CI 1.140–29.90, P = 0.03), bacteraemia (OR 8.82; CI 3.67–21.22, P < 0.001) and shock (OR 3.75; CI 1.63–8.65, P = 0.04). In the multivariate analysis, CKD (adjusted OR 10.68; 95% CI 1.66–68.77; P = 0.013) and bacteraemia (adjusted OR 8.22; 95% CI 3.15–21.47, P < 0.001) predicted AKI. AKI was associated with a greater need for ICU care (37.3% vs. 13.3%, P = 0.001), and mortality (32.2% vs. 5.7%, P < 0.001). Mortality increased with increasing AKI stage, i.e. stage 1 (OR 3.52, CI 0.9–13.7, P = 0.07), stage 2 (OR 6.79, CI 1.92–24, P = 0.002) and stage 3 (OR 17.8, CI 5.05–62.8, P < 0.001), however kidney function recovered in survivors. Hyponatremia was observed in 138 patients (84.15%) and isolated urinary abnormalities were seen in 31(18.9%). Conclusions AKI is frequent in melioidosis and occurred in 35.9% of our cases. Hyponatremia is likewise common. AKI was predicted by bacteraemia and CKD, and was associated with higher mortality and need for ICU care; however kidney function recovery was observed in survivors. Graphic abstract

Download Full-text

Predictors of brain infarction in adult patients on extracorporeal membrane oxygenation: an observational cohort study

Scientific Reports ◽

10.1038/s41598-021-83157-5 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Riccardo Iacobelli ◽

Alexander Fletcher-Sandersjöö ◽

Caroline Lindblad ◽

Boris Keselman ◽

Eric Peter Thelin ◽

...

Keyword(s):

Cohort Study ◽

Extracorporeal Membrane Oxygenation ◽

Brain Infarction ◽

Multivariable Analysis ◽

Group Analysis ◽

Observational Cohort Study ◽

Adult Patients ◽

Membrane Oxygenation ◽

Observational Cohort ◽

Va Ecmo

AbstractNon-hemorrhagic brain infarction (BI) is a recognized complication in adults treated with extracorporeal membrane oxygenation (ECMO) and associated with increased mortality. However, predictors of BI in these patients are poorly understood. The aim of this study was to identify predictors of BI in ECMO-treated adult patients. We conducted an observational cohort study of all adult patients treated with venovenous or venoarterial (VA) ECMO at our center between 2010 and 2018. The primary endpoint was a computed tomography (CT) verified BI. Logistic regression models were employed to identify BI predictors. In total, 275 patients were included, of whom 41 (15%) developed a BI. Pre-ECMO Simplified Acute Physiology Score III, pre-ECMO cardiac arrest, VA ECMO and conversion between ECMO modes were identified as predictors of BI. In the multivariable analysis, VA ECMO demonstrated independent risk association. VA ECMO also remained the independent BI predictor in a sub-group analysis excluding patients who did not undergo a head CT scan during ECMO treatment. The incidence of BI in adult ECMO patients may be higher than previously believed and is independently associated with VA ECMO mode. Larger prospective trials are warranted to validate these findings and ascertain their clinical significance.

Download Full-text

ATRT-26. META-ANALYSIS OF TREATMENT MODALITIES IN METASTATIC ATYPICAL TERATOID/RHABDOID TUMORS IN CHILDREN

Neuro-Oncology ◽

10.1093/neuonc/noaa222.025 ◽

2020 ◽

Vol 22 (Supplement_3) ◽

pp. iii281-iii281

Author(s):

Reena M Underiner ◽

Mostafa Eltobgy ◽

Joseph R Stanek ◽

Jonathan L Finlay ◽

Mohamed S AbdelBaki

Keyword(s):

Surgical Resection ◽

Meta Analysis ◽

Univariate Analysis ◽

Multivariable Analysis ◽

Substantial Effect ◽

Treatment Modalities ◽

Risk Of Death ◽

Atypical Teratoid ◽

Atypical Teratoid Rhabdoid Tumors ◽

Rhabdoid Tumors

Abstract BACKGROUND Metastatic atypical teratoid/rhabdoid tumors (AT/RT) are aggressive central nervous system tumors that present during infancy and are associated with dismal outcomes. Patients receive multimodal treatment including surgical resection, systemic chemotherapy and one or more of intrathecal chemotherapy (IT), marrow-ablative chemotherapy with autologous hematopoietic cell rescue (AuHCR) and radiation therapy (XRT). While data regarding treatment modalities for AT/RT patients exist, no comprehensive data have been published regarding the metastatic patient population. METHODS We performed a meta-analysis of 1,578 articles published through September 2018, including 44 studies with a total of 123 subjects. Additionally, seven patients were incorporated through chart review of patients treated at Nationwide Children’s Hospital. RESULTS Analysis of 130 patients revealed a 3-year overall survival (OS) of 25%. Age at diagnosis had a significant impact on survival (p=0.0355); 3-year OS for infants < 18 months was 21%; 18–36 months was 26%; and > 36 months was 36%. Location of the primary tumor, metastatic stage and extent of surgical resection did not have significant impact on OS. On univariate analysis, XRT (p<0.0001), IT (p=0.01) and AuHCR (p<0.0001) were found to significantly improve survival. The most substantial effect was noted in patients who received AuHCR (3-year OS of 60% versus 9% in those who did not). On multivariable analysis XRT (p=0.0006), IT (p=0.0124) and AuHCR (p<0.0001) were independently associated with reduced risk of death.

Download Full-text

Impact of Physician Training Level on Neonatal Tracheal Intubation Success Rates and Adverse Events: A Report from National Emergency Airway Registry for Neonates (NEAR4NEOS)

Neonatology ◽

10.1159/000516372 ◽

2021 ◽

pp. 1-9

Author(s):

Lindsay Johnston ◽

Taylor Sawyer ◽

Anne Ades ◽

Ahmed Moussa ◽

Jeanne Zenge ◽

...

Keyword(s):

Tracheal Intubation ◽

Adverse Events ◽

Multivariable Analysis ◽

Estimating Equation ◽

Oxygen Desaturation ◽

Physician Training ◽

Training Level ◽

Success Rates ◽

Emergency Airway ◽

Significant Difference

Introduction: Neonatal tracheal intubation (TI) outcomes have been assessed by role, but training level may impact TI success and safety. Effect of physician training level (PTL) on the first-attempt success, adverse TI-associated events (TIAEs), and oxygen desaturation was assessed. Methods: Prospective cohort study in 11 international NEAR4NEOS sites between October 2014 and December 2017. Primary TIs performed by pediatric/neonatal physicians were included. Univariable analysis evaluated association between PTL, patient/practice characteristics, and outcomes. Multivariable analysis with generalized estimating equation assessed for independent association between PTL and outcomes (first-attempt success, TIAEs, and oxygen desaturation ≥20%; attending as reference). Results: Of 2,608 primary TIs, 1,298 were first attempted by pediatric/neonatal physicians. PTL was associated with patient age, weight, comorbidities, TI indication, difficult airway history, premedication, and device. First-attempt success rate differed across PTL (resident 23%, fellow 53%, and attending 60%; p < 0.001). There was no statistically significant difference in TIAEs (resident 22%, fellow 20%, and attending 25%; p = 0.34). Desaturation occurred more frequently with residents (60%), compared to fellows and attendings (46 and 53%; p < 0.001). In multivariable analysis, adjusted odds ratio of the first-attempt success was 0.18 (95% CI: 0.11–0.30) for residents and 0.80 (95% CI: 0.51–1.24) for fellows. PTL was not independently associated with adjusted odds of TIAEs or severe oxygen desaturation. Conclusion: Higher PTL was associated with increased first-attempt success but not TIAE/oxygen desaturation. Identifying strategies to decrease adverse events during neonatal TI remains critical.

Download Full-text

Abstract WP7: Leukoaraiosis And Outcomes After Intra-arterial Therapy In Acute Ischemic Stroke

Stroke ◽

10.1161/str.44.suppl_1.awp7 ◽

2013 ◽

Vol 44 (suppl_1) ◽

Author(s):

Dan-Victor V Giurgiutiu ◽

Albert J Yoo ◽

Kaitlin Fitzpatrick ◽

Zeshan Chaudhry ◽

Lee H Schwamm ◽

...

Keyword(s):

Ischemic Stroke ◽

Acute Ischemic Stroke ◽

Functional Outcome ◽

Univariate Analysis ◽

Multivariable Analysis ◽

Artery Occlusion ◽

Post Stroke ◽

Good Functional Outcome ◽

Grade 3 ◽

Risk Of Hemorrhage

Background: Selecting patients most likely to benefit (MLTB) from intra-arterial therapy (IAT) is essential to assure favorable outcomes after intervention for acute ischemic stroke (AIS). Leukoaraiosis (LA) has been linked to infarct growth, risk of hemorrhage after IV rt-PA, and poor post-stroke outcomes. We investigated whether LA severity is associated with AIS outcomes after IAT. Methods: We analyzed consecutive AIS subjects from our institutional GWTG-Stroke database enrolled between 01/01/2007-06/30/2009, who met our pre-specified criteria for MLTB: CTA and MRI within 6 hours from last known well, NIHSS score ≥8, baseline DWI volume (DWIv) ≤ 100 cc, and proximal artery occlusion and were treated with IAT. LA volume (LAv) was assessed on FLAIR using validated, semi-automated protocols. We analyzed CTA to assess collateral grade; post-IAT angiogram for recanalization status (TICI score ≥2B); and the 24-hour CT for symptomatic ICH (sICH). Logistic regression was used to determine independent predictors of good functional outcome (mRS≤ 2) and mortality at 90 days post-stroke. Results: There were 48 AIS subjects in this analysis (mean age 69.2, SD±13.8; 55% male; median LAv 4cc, IQR 2.2-8.8cc; median NIHSS 15, IQR 13-19; median DWIv 15.4cc, IQR 9.2-20.3cc). Of these, 34 (72%) received IV rt-PA; 3 (6%) had sICH; 21 (44.7%) recanalized; and 23 (50%) had collateral grade ≥3. At 90 days, 15/48 (36.6%) were deceased and 15/48 had mRS≤ 2. In univariate analysis, recanalization (OR 6.2, 95%CI 1.5-25.5), NIHSS (OR 0.8 per point, 95%CI 0.64-0.95), age (OR 0.95 per yr, 95%CI 0.89-0.99) were associated with good outcome, whereas age (OR 1.1, 95%CI 1.01-1.14) and HTN (OR 5.6, 95%CI 1.04-29.8) were associated with mortality. In multivariable analysis including age, NIHSS, recanalization, collateral grade, and LAv, only recanalization independently predicted good functional outcome (OR 21.3, 95%CI 2.3-199.9) and reduced mortality (OR 0.15, 95%CI 0.02-1.12) after IAT. Conclusions: LA severity is not associated with poor outcome in patients selected MLTB for IAT. Among AIS patients considered likely to benefit from IAT, only recanalization independently predicted good functional outcome and decreased mortality.

Download Full-text

TERT promoter mutation as a prognostic marker in patients with advanced urothelial carcinoma treated with immune checkpoint inhibitors.

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.6_suppl.476 ◽

2021 ◽

Vol 39 (6_suppl) ◽

pp. 476-476

Author(s):

Ivan de Kouchkovsky ◽

Li Zhang ◽

Errol Philip ◽

Francis Wright ◽

Daniel Myung Kim ◽

...

Keyword(s):

Urothelial Carcinoma ◽

Immune Checkpoint ◽

Immune Checkpoint Inhibitors ◽

Checkpoint Inhibitors ◽

Univariate Analysis ◽

Multivariable Analysis ◽

Genomic Profiling ◽

Clinical Variables ◽

Tert Promoter ◽

Visceral Metastases

476 Background: Reliable predictive markers are lacking in patients (pts) with locally advanced or metastatic urothelial carcinoma (aUC) treated with immune checkpoint inhibitors (ICI). We sought to determine whether specific genomic alterations could be used to predict overall survival (OS) in this patient population. Methods: We undertook a retrospective cohort study of pts with aUC who received ICI and underwent genomic profiling by next-generation sequencing (NGS). All patients underwent NGS using commercially available platforms (e.g. Foundation Medicine, Strata, Invitae), or testing on the CLIA-certified institutional panel UCSF500. Associations between the 20 most frequently altered genes and OS were first examined by Cox regression. Genes with a p <0.1 on univariate analysis and relevant clinical variables were then included in a multivariable analysis. Results: We identified 78 pts treated with ICI for aUC with available genomic profiling results. Median age at ICI initiation was 71; the majority of patients had visceral metastases (70.5%), ECOG performance status ≤1 (62.8%) and received ICI in the post-platinum setting (52.6%). Objective response rate in this cohort was 35.9%, median progression free survival was 4.0 months (95% CI 2.6-10.5) and median OS was 17.5 months (95% CI 14.1-NR) from ICI start. The most commonly altered genes were the TERT promoter (TERTp) (61%), TP53 (52%), RB1 (31%), CDKN2A(29%) and CDKN2B (27%). On univariable analysis there was a trend towards longer OS in pts with TERTp mutations (HR 0.53, 95% CI 0.27-1.06, p = 0.07), and shorter OS in pts with CDKN2B mutations (HR 1.91, 95% CI 0.98-3.73, p = 0.06). Both mutations were included in a multivariable analysis. After adjusting for known prognostic variables (ECOG PS, visceral metastases, albumin, hemoglobin, body mass index [BMI], neutrophil to lymphocyte ratio [NLR], and histology), the presence of a TERTp mutation was significantly associated with improved OS (HR 0.30, 95% CI 0.10-0.93, p = 0.04; Table). Conclusions: The presence of a TERTp mutation was an independent predictor of improved OS in a cohort of aUC pts treated with ICI. Other common mutations and clinical variables were not associated with OS on a multivariable analysis. These findings are hypothesis-generating and prospective validation is needed. [Table: see text]

Download Full-text