Contribution of plasma MicroRNA-21, MicroRNA-155 and circulating monocytes plasticity to childhood neuroblastoma development and induction treatment outcome.

Neuroblastoma (NB) accounts for 15% of all pediatric cancer fatalities (NB). Biomarkers that facilitate early NB detection are needed because by the time of diagnosis, over half of NBs had spread. MicroRNA-21(miR-21) and miR-155 are involved in cancer biology due to their immune modulation functions. Altered monocyte subset distribution is thought to be involved in a number of solid tumors due to its immunological role. We aimed to investigate the expression levels of miR-21 and miR-155 and their association with circulating monocytes subsets in NB and to evaluate if they correlate to the disease pathogenesis and outcome. PATIENTS AND METHODS: This case control study involved 79 children classified into 39 newly diagnosed NB children and 40 age and sex matched healthy children. Real-time PCR was used to assess the expression of plasma miR-21 and miR-155. The frequency of circulating monocytes subsets was assessed by flow cytometry. RESULTS: NB group showed significant up-regulation in expression of miR-21(20.9 folds) and miR-155 (1.8 folds) when compared to the control group (p < 0.001) and (p = 0.02) respectively. Also, frequency of circulating intermediate monocytes revealed significant up regulation in children with NB. In NB patients, there was a positive correlation between miR-21 and frequency of total and intermediate monocytes (r = 0.5 p < 0.001 and r = 0.7, p < 0.001, respectively). We found no discernible differences when we compared study markers between the high risk and intermediate risk groups. In addition, no significant difference was seen in study markers when patients were sub-grouped according to their induction treatment response. ROC curve analysis revealed that miR-21 up-regulation distinguished NB in childhood at an AUC of 0.94 (82% sensitivity and 100% specificity) while miR-155 up-regulation had less capacity to distinguish NB in childhood at an AUC of 0.65 (38% sensitivity and 93% specificity). CONCLUSION: miR-21 can be utilized as a sensitive biomarker for childhood NB development. In pediatric NB, miR-21 was linked to intermediate monocyte plasticity. Both, miR-21 and miR-155 had no impact on NB outcome.

From diagnosis to resistance: a symphony of miRNAs in pheochromocytoma progression and treatment response.

Pheochromocytoma (PCC) is a neuroendocrine tumor that produces and secretes catecholamine from either the adrenal medulla or extra-adrenal locations. MicroRNAs (miRNAs, miR) can be used as biomarkers to detect cancer or the return of a previously treated disease. Blood-borne miRNAs might be envisioned as noninvasive markers of malignancy or prognosis, and new studies demonstrate that microRNAs are released in body fluids as well as tissues. MiRNAs have the potential to be therapeutic targets, which would greatly increase the restricted therapy options for adrenal tumors. This article aims to consolidate and synthesize the most recent studies on miRNAs in PCC, discussing their potential clinical utility as diagnostic and prognostic biomarkers while also addressing their limitations.

Possible role of miRNAs in pheochromocytoma pathology - Signaling pathways interaction.

Pheochromocytoma (PCC) is a type of neuroendocrine tumor that originates from adrenal medulla or extra-adrenal chromaffin cells and results in the production of catecholamine. Paroxysmal hypertension and cardiovascular crises were among the clinical signs experienced by people with PCC. Five-year survival of advanced-stage PCC is just around 40% despite the identification of various molecular-level fundamentals implicated in these pathogenic pathways. MicroRNAs (miRNAs, miRs) are a type of short, non-coding RNA (ncRNA) that attach to the 3'-UTR of a target mRNA, causing translational inhibition or mRNA degradation. Evidence is mounting that miRNA dysregulation plays a role in the development, progression, and treatment of cancers like PCC. Hence, this study employs a comprehensive and expedited survey to elucidate the potential role of miRNAs in the development of PCC, surpassing their association with survival rates and treatment options in this particular malignancy.

Metastatic prostate cancer is associated with distinct higher frequency of genetic mutations at diagnosis.

INTRODUCTION AND OBJECTIVES: We explored characteristic genetic mutations associated with metastatic prostate cancer (PCa) by comparing next generation sequencing (NGS) data between men with or without metastatic disease at diagnosis. METHODS: We queried the American Association for Cancer Research Project Genomics Evidence Neoplasia Information Exchange (GENIE) registry for men diagnosed with PCa. Patients were categorized into with (M1) or without metastatic disease (M0) groups. The difference in the frequency of genetic mutations between the two groups and the prognostic significance of the mutations were analyzed using SPSS V28. We included frequency rate of > 5% and P values < 0.05 were considered statistically significant to maintain over 95% true positive detection rate. RESULTS: Of a total of 10,580 patients with diagnosis of PCa in the dataset, we selected a study cohort of 1268 patients without missing data; 700 (55.2%) had nonmetastatic PCa, 421 (33.2%) and 147 (11.6%) patients had metastatic castration sensitive and resistant PCa respectively. The median age at diagnosis and serum prostate specific antigen (PSA) level for the entire cohort was 62.8 years (IQR 56.3-68.4) and 8.0 ng/ml (IQR 4.9-20.9) respectively. A vast majority of the cohort were of Caucasian ancestry (89.1%). Of a total of 561 genes sequenced, there were mutations in 79 genes (14.1%). The mutation frequency was significantly higher in M1PCa compared to M0PCa, 35.7% and 23.3%, respectively (P = <0.001). The median tumor mutational burden was also significantly higher in the samples from M1PCa (2.59 mut/MB) compared to M0PCa (1.96 mut/MB) (P < 0.001). Compared to M0PCa patients, M1PCa patients demonstrated significantly higher rate of genetic mutations; TP53 (38.73% vs. 17.71% P < 0.001), PTEN (25.70% vs. 11.71% P < 0.001), AR (17.25% vs. 1.43% P < 0.001), APC (11.8% vs. 4.43% P < 0.001), TMPRSS2 (31.5% vs. 11.14% P < 0.001), ERG (23.59% vs. 13.13% P < 0.001), FOXA1 (17.43% vs. 6.33% P < 0.001), MYC (8.45% vs. 2.29% P < 0.001), RB1 (10.39% vs. 2.43% P < 0.001) and CDK12 (8.45% vs. 1.31% P < 0.001).  Of the various cellular signaling pathways, the androgen receptor signaling pathway was most often impacted. In the cohort with M1 disease, compared to men without genetic mutations the men with genetic mutations demonstrated worse survival (P = <0.001, log rank test). Compared to castration sensitive M1 patients, AR (57% vs. 4% P < 0.001), TP53 (50.7% vs. 34% P < 0.001), PTEN (35.2% vs. 22.1% P < 0.001), RB1(23.9% vs. 4.75% P < 0.001) were significantly more frequently mutated in castration resistant M1 patients. In contrast, mutations of SPOP (13.3% vs. 7.9% P < 0.001), FOXA1 (17.6% vs. 5.3% P < 0.001) and CDK12 (12% vs. 6.45% P < 0.001) were significantly more frequently found in castration sensitive M1 patients compared to castration resistant patients. CONCLUSION: Patients with M1PCa demonstrated characteristic genetic mutations compared to M0PCa, which most often influenced androgen receptor signaling and is associated with worse survival. In addition, we identified distinct genetic mutations between castration sensitive and resistant M1PCa. These findings may be used to further our understanding and management of men with PCa.

Salvage Cryoablation for Recurrent Prostate Cancer Following Primary External Beam Radiotherapy or Primary Cryotherapy: A Propensity Score Matched Analysis of Mid-term Oncologic and Functional Outcomes.

INTRODUCTION: Local prostate cancer recurrence following radiotherapy (XRT) or cryoablation (CRYO) may be addressed with salvage cryotherapy (SCT), although little is known about how the primary treatment modality affects SCT results. Oncologic and functional outcomes of patients who underwent SCT after primary XRT (XRT-SCT) or cryoablation (CRYO-SCT) were studied. METHODS: Data was collected using the Duke Prostate Cancer database and the Cryo On-Line Data (COLD) registry. The primary outcome was biochemical progression-free survival (BPFS).  Urinary incontinence, rectourethral fistula, and erectile dysfunction were secondary outcomes. The Kaplan-Meier log-rank test and univariable/multivariable Cox proportional hazards (CPH) models were utilized to evaluate BPFS between groups. RESULTS: 419 XRT-SCT and 63 CRYO-SCT patients met inclusion criteria, that was reduced to 63 patients in each cohort after propensity matching. There was no difference in BPFS at 2 and 5 years both before (P = .5 and P = .7) and after matching (P = .6 and P = .3). On multivariable CPH, BPFS was comparable between treatment groups (CRYO-SCT, HR=1.1, [0.2-2.2]).  On the same analysis, BPFS was lower in D'Amico high-risk (HR 3.2, P < .01) and intermediate-risk (HR 1.95, P < .05) categories compared to low-risk. There was no significant difference in functional outcomes between cohorts. CONCLUSION: Following primary cryotherapy, salvage cryoablation provides comparable intermediate oncological outcomes and functional outcomes compared to primary radiotherapy.

Identification of miR-106b-5p, miR-601, and miR-760 Expression and Their Clinical Values in Non-Small Cell Lung Cancer (NSCLC) Patients' Serum.

AIM: to explore the relative quantitative determination of the serum level of three miRNAs (miR-601, 760, and 106b-5p) and determine their expression pattern in non-small cell lung cancer (NSCLC) patients in comparison to controls. Also, to reveal each miRNA's diagnostic and prognostic impact on NSCLC patients. MATERIALS AND METHODS: Serum miR-106b-5p, 601, and 760 expression profiles were estimated by real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) for 70 NSCLC patients, age-matched with 30 control subjects. The receiver operating characteristic (ROC) curve analysis estimated their diagnostic and prognostic potentials. RESULTS: In comparison to the control, the miR-106b-5p expression pattern was upregulated (1.836 ± 0.254, p = 0.0012) while both miR-601 and miR-760 expression patterns were considerably downregulated (-0.586 ± 0.1906, p < 0.0001) and (-1.633 ± 0.152, p < 0.0001), respectively with predominant down-expression for miR-760 among cases. MiR-760 showed the highest diagnostic potential (AUC = 0.943 and 0.864 respectively), whereas miR-601 has a higher prognostic power (AUC = 0.771 and 0.682, respectively) for differentiating early stages (I/II) NSCLC patients from control subjects. Moreover, miR-760 presented the highest prognostic potential for differentiating NSCLC stages. CONCLUSION: Both serum miR-760 and miR-601 may be used as potential biomarkers of NSCLC in Egyptian patients with a stronger staging and diagnostic potential for miR-760.

Genetic mutations in smoking-associated prostate cancer.

OBJECTIVES: Tobacco smoking is known to cause cancers potentially predisposed by genetic risks. We compared the frequency of gene mutations using a next generation sequencing database of smokers and nonsmokers with prostate cancer (PCa) to identify subsets of patients with potential genetic risks. MATERIALS AND METHODS: Data from the American Association for Cancer Research Project Genomics Evidence Neoplasia Information Exchange (GENIE) registry was analyzed. The GENIE registry contains clinically annotated sequenced tumor samples. We included 1832 men with PCa in our cohort, categorized as smokers and nonsmokers, and compared the frequency of mutations (point mutations, copy number variations, and structural variants) of 47 genes with more than 5% mutation rate between the two categories and correlated with overall survival using logistic regression analysis. RESULTS: Overall, 1007 (55%) patients were nonsmokers, and 825 (45%) were smokers. The mutation frequency was significantly higher in smokers compared to nonsmokers, 47.6% and 41.3%, respectively (p = 0.02). The median tumor mutational burden was also significantly higher in the samples from smokers (3.59 mut/MB) compared to nonsmokers (1.87 mut/MB) (p < 0.001). Patients with a smoking history had a significantly higher frequency of PREX2, PTEN, AGO2, KMT2C, and a lower frequency of adenomatous polyposis coli (APC) and KMT2A mutations than compared to nonsmokers. The overall mortality rate (28.5% vs. 22.8%) was significantly higher among smokers (p = 0.006). On a multivariate logistic regression analysis, the presence of metastatic disease at the time of diagnosis (OR: 2.26, 95% CI: 1.78-2.89, p < 0.001), smoking history (OR: 1.32, 95% CI: 1.05-1.65, p = 0.02), and higher frequency of PTEN somatic gene mutation (OR: 1.89, 95% CI: 1.46-2.45, p < 0.001) were independent predictors of increased overall mortality among patients with PCa. Patients with PTEN mutation had poorer overall survival compared to men without PTEN mutations: 96.00 (95% CI: 65.36-113.98) and 120.00 (95% CI: 115.05-160.00) months, respectively (p < 0.001) irrespective of smoking history although the G129R PTEN mutation was characteristically detected in smokers. CONCLUSIONS: PCa patients with a tobacco smoking history demonstrated a significantly higher frequency of somatic genetic mutations. Whereas mutations of PREX2, KMT2C, AGO2, and PTEN genes were higher in smokers, the APC and KMT2A mutations were higher in nonsmokers. The PTEN somatic gene mutation was associated with increased overall mortality among patients with PCa irrespective of smoking history. We found that G129R PTEN mutation known to reduce the PTEN phosphatase activity and K267Rfs*9 a frameshift deletion mutation in the C2 domain of PTEN associated with membrane binding exclusively detected in smokers and nonsmokers, respectively. These findings may be used to further our understanding of PCa associated with smoking.

miRNAs driving diagnosis, progression, and drug resistance in multiple myeloma.

Multiple myeloma (MM) is a tumor of transformed plasma cells. It's the second most common hematologic cancer after non-Hodgkin lymphoma. MM is a complex disease with many different risk factors, including ethnicity, race, and epigenetics. The microRNAs (miRNAs) are a critical epigenetic factor in multiple myeloma, influencing key aspects such as pathogenesis, prognosis, and resistance to treatment. They have the potential to assist in disease diagnosis and modulate the resistance behavior of MM towards therapeutic regimens. These characteristics could be attributed to the modulatory effects of miRNAs on some vital pathways such as NF-KB, PI3k/AKT, and P53. This review discusses the role of miRNAs in MM with a focus on their role in disease progression, diagnosis, and therapeutic resistance.

Urinary stone disease burden is increased in patients with cognitive impairment.

Mental illness and brain disorders such as dementia are commonly encountered in patients with cognitive impairment in urology. In this cohort study, we assessed the prevalence and outcomes of inpatient admissions for stone disease in patients with cognitive impairment. Using the National Inpatient Sample database, we identified adults (>18 years) with stone disease between 2015 and 2019. The patients were dichotomized based on the presence or absence of cognitive impairment. The groups were compared for baseline differences in inpatient admissions and hospital complications. We evaluated the independent factors associated with urinary complications in the population using multivariate logistic regression. We identified 223,072 patients with stone disease. Patients with cognitive impairment were significantly (P<0.001) older (68 vs. 62 years), female (55.7% vs. 47.4%), had government-issued insurance (77.5% vs. 64.4%), and were discharged to a nursing facility (31.7% vs. 14.2%). Patients with cognitive impairment had significantly higher rates of urinary tract infection (29.7% vs. 21.5%, P<0.001), pneumonia (5.6% vs. 4.6%, P<0.001), systemic sepsis (4.3% vs. 3.8%, P<0.001), and acute renal failure (0.9% vs. 0.7%, P = 0.008). Female sex, low income, and cognitive impairment were all independently more likely to experience a urinary complication, with significant differences (P<0.001). Patients with cognitive impairment have a higher prevalence of stone disease and urinary complications associated with inpatient admissions than the rest of the population. Health care inequities among cognitively impaired patients should be a topic of further study.

Decoding the role of miRNAs in multiple myeloma pathogenesis: A focus on signaling pathways.

Multiple myeloma (MM) is a cancer of plasma cells that has been extensively studied in recent years, with researchers increasingly focusing on the role of microRNAs (miRNAs) in regulating gene expression in MM. Several non-coding RNAs have been demonstrated to regulate MM pathogenesis signaling pathways. These pathways might regulate MM development, apoptosis, progression, and therapeutic outcomes. They are Wnt/ß-catenin, PI3K/Akt/mTOR, P53 and KRAS. This review highlights the impending role of miRNAs in MM signaling and their relationship with MM therapeutic interventions.

The role of miRNAs in laryngeal cancer pathogenesis and therapeutic resistance - A focus on signaling pathways interplay.

Laryngeal cancer (LC)is the malignancy of the larynx (voice box). The majority of LC are squamous cell carcinomas. Many risk factors were reported to be associated with LC as tobacco use, obesity, alcohol intake, human papillomavirus (HPV) infection, and asbestos exposure. Besides, epigenetics as non-coding nucleic acids also have a great role in LC. miRNAs are short nucleic acid molecules that can modulate multiple cellular processes by regulating the expression of their genes. Therefore, LC progression, apoptosis evasions, initiation, EMT, and angiogenesis are associated with dysregulated miRNA expressions. miRNAs also could have some vital signaling pathways such as mTOR/P-gp, Wnt/-catenin signaling, JAK/STAT, KRAS, and EGF. Besides, miRNAs also have a role in the modulation of LC response to different therapeutic modalities. In this review, we have provided a comprehensive and updated overview highlighting the microRNAs biogenesis, general biological functions, regulatory mechanisms, and signaling dysfunction in LC carcinogenesis, in addition to their clinical potential for LC diagnosis, prognosis, and chemotherapeutics response implications.

The impact of socioeconomic status on the survival of men with early-onset prostate cancer.

Prostate cancer (PCa) is generally considered a disease of older men; however, about 10% of new diagnoses in the US occur in men ≤ 55 years old. Socioeconomic status (SES) has been shown to influence survival in patients with PCa; however, the impact of SES on men with early-onset PCa remains undescribed. Using the National Cancer Database, we identified adult men ≤ 55 years of age with a diagnosis of prostatic adenocarcinoma between 2004-2018. Descriptive statistics were used to characterize differences among different SES groups. Kaplan-Meier (KM) and Cox regression analyses were used to assess the effect of SES on overall survival (OS). A total of 112,563 young patients with PCa with a median follow-up of 79.0 months were identified. Compared to high SES patients, low SES patients were more likely to be African American (42.4% vs. 8.6%; P<0.001), Hispanic (9.5% vs. 2.7%; P<0.001), and uninsured (5.2% vs. 1.1%; P<0.001); they were also more likely to live in a rural area (3.2% vs. 0.1%; P<0.001) and have stage IV disease (5.5% vs. 3.1%; P<0.001). KM analysis showed that a decreasing SES was directly associated with lower rates of OS (log-rank test P<0.001). On multivariable analysis, SES was found to have a negative effect on OS (low SES vs. high SES; hazard ratio [HR] 1.54; 95% confidence interval [CI] 1.41-1.68; P<0.001). In patients with early-onset PCa, SES was associated with lower OS. SES may be considered when implementing programs to improve the management of patients with early-onset PCa.

Extramural venous invasion: a novel magnetic resonance imaging biomarker for adverse pathology in bladder cancer.

Extramural venous invasion (EMVI) recognized on magnetic resonance imaging (MRI) is an unequivocal biomarker for detecting adverse outcomes in rectal cancer: however it has not yet been explored in the area of bladder cancer. In this study, we assessed the feasibility of identifying EMVI findings on MRI in patients with bladder cancer and its avail in identifying adverse pathology. In this single-institution retrospective study, the MRI findings inclusive of EMVI was described in patients with bladder cancer that had available imaging between January 2018 and June 2020. Patient demographic and clinical information were retrieved from our electronic medical records system. Histopathologic features frequently associated with poor outcomes including lymphovascular invasion (LVI), variant histology, muscle invasive bladder cancer (MIBC), and extravesical disease (EV) were compared to MRI-EMVI. A total of 38 patients were enrolled in the study, with a median age of 73 years (range 50-101), 76% were male and 23% were females. EMVI was identified in 23 (62%) patients. There was a significant association between EMVI and MIBC (OR = 5.30, CI = 1.11-25.36; P = 0.036), and extravesical disease (OR = 17.77, CI = 2.37-133; P = 0.005). We found a higher probability of presence of LVI and histologic variant in patients with EMVI. EMVI had a sensitivity, specificity, negative predictive value (NPV) and positive predictive value (PPV) of 90%, 73%, 94% and 63% respectively in detecting extravesical disease. Our study suggests, EMVI may be a useful biomarker in bladder cancer imaging, is associated with adverse pathology, and could be potentially integrated in the standard of care with regards to MRI reporting systems. A larger study sample size is further warranted to assess feasibility and applicability.

An emphasis on the interaction of signaling pathways highlights the role of miRNAs in the etiology and treatment resistance of gastric cancer.

Gastric cancer (GC) is 4th in incidence and mortality rates globally. Several genetic and epigenetic factors, including microRNAs (miRNAs), affect its initiation and progression. miRNAs are short chains of nucleic acids that can regulate several cellular processes by controlling their gene expression. So, dysregulation of miRNAs expressions is associated with GC initiation, progression, invasion capacity, apoptosis evasions, angiogenesis, promotion and EMT enhancement. Of important pathways in GC and controlled by miRNAs are Wnt/ß-catenin signaling, HMGA2/mTOR/P-gp, PI3K/AKT/c-Myc, VEGFR and TGFb signaling. Hence, this review was conducted to review an updated view of the role of miRNAs in GC pathogenesis and their modulatory effects on responses to different GC treatment modalities.

Diagnostic Significance of hsa-miR-21-5p, hsa-miR-192-5p, hsa-miR-155-5p, hsa-miR-199a-5p Panel and Ratios in Hepatocellular Carcinoma on Top of Liver Cirrhosis in HCV-Infected Patients.

Early hepatocellular carcinoma (HCC) diagnosis is challenging. Moreover, for patients with alpha-fetoprotein (AFP)-negative HCC, this challenge is augmented. MicroRNAs (miRs) profiles may serve as potential HCC molecular markers. We aimed to assess plasma homo sapiens-(hsa)-miR-21-5p, hsa-miR-155-5p, hsa-miR-192-5p, and hsa-miR-199a-5p-expression levels as a panel of biomarkers for HCC in chronic hepatitis C virus (CHCV) patients with liver cirrhosis (LC), especially AFP-negative HCC cases, as a step toward non-protein coding (nc) RNA precision medicine. SUBJECTS AND METHODS: 79 patients enrolled with CHCV infection with LC, subclassified into an LC group without HCC (n = 40) and LC with HCC (n = 39). Real-time quantitative PCR was used to measure plasma hsa-miR-21-5p, hsa-miR-155-5p, hsa-miR-192-5p, and hsa-miR-199a-5p. RESULTS: Plasma hsa-miR-21-5p and hsa-miR-155-5p demonstrated significant upregulation, while hsa-miR-199a-5p demonstrated significant downregulation in the HCC group (n = 39) when compared to the LC group (n = 40). hsa-miR-21-5p expression was positively correlated with serum AFP, insulin, and insulin resistance (r = 0.5, p < 0.001, r = 0.334, p = 0.01, and r = 0.303, p = 0.02, respectively). According to the ROC curves, for differentiating HCC from LC, combining AFP with each of hsa-miR-21-5p, hsa-miR-155-5p, and miR199a-5p improved the diagnostic sensitivity to 87%, 82%, and 84%, respectively, vs. 69% for AFP alone, with acceptable specificities of 77.5%, 77.5%, and 80%, respectively, and AUC = 0.89, 0.85, and 0.90, respectively vs. 0.85 for AFP alone. hsa-miR-21-5p/hsa-miR-199a-5p and hsa-miR-155-5p/hsa-miR-199a-5p ratios discriminated HCC from LC at AUC = 0.76 and 0.71, respectively, with sensitivities = 94% and 92% and specificities = 48% and 53%, respectively. Upregulation of plasma hsa-miR-21-5p was considered as an independent risk factor for HCC development [OR = 1.198(1.063-1.329), p = 0.002]. CONCLUSIONS: Combining each of hsa-miR-21-5p, hsa-miR-155-5p, and hsa-miR-199a-5p with AFP made it possible to identify HCC development in the LC patients' cohort with higher sensitivity than using AFP alone. hsa-miR-21-5p/hsa-miR-199a-5p and hsa-miR-155-5p/hsa-miR-199a-5p ratios are potential HCC molecular markers for AFP-negative HCC patients. hsa-miR-21-5p was linked, clinically and via in silico proof, to insulin metabolism, inflammation, dyslipidemia, and tumorigenesis in the HCC patients' group as well as for an upregulated independent risk factor for the emergence of HCC from LC in the CHCV patients.

Does care fragmentation in patients with bladder cancer lead to worse outcomes?

INTRODUCTION: Care fragmentation may influence oncologic outcomes. The impact of care fragmentation on the outcomes of patients receiving neoadjuvant chemotherapy (NAC) and radical cystectomy (RC) for muscle-invasive bladder cancer (MIBC) is not well defined. We aimed to compare outcomes between patients who received fragmented care (FC) versus non-fragmented care (NFC). METHODS: The National Cancer Database was queried for adult (≥18 years old) patients with cT2-T4aN0M0 urothelial carcinoma of the bladder receiving NAC followed by RC between 2004 and 2017. Patients were dichotomized based on whether they received FC (defined as receiving NAC at a different facility from where RC was performed) or NFC (defined as receiving NAC and RC at a single facility). The main outcome of interest was overall survival (OS). Secondary outcomes included time from diagnosis to treatment (NAC and RC) and perioperative outcomes. Kaplan-Meier survival estimates were calculated after stratifying by type of care received. Multivariable Cox regression analysis was performed to evaluate the association between FC and OS in the context of other clinically relevant covariates. RESULTS: A total of 2223 patients were included: 1035 (46.6%) received FC whereas 1188 (53.4%) received NFC. Factors associated with FC included greater travel distance, higher comorbidity burden, and surgical treatment at a high-volume facility. Patients who received FC had a slightly longer median time to RC (160 vs. 154 days, P = 0.001). However, on Kaplan-Meier analysis no differences in median OS were found between the two groups. On multivariable Cox regression analysis, factors associated with worse OS included age, advanced TNM stage, lymphovascular invasion, and positive surgical margins; yet FC was not associated with worse OS (hazard ratio [HR] 1.02; 95% confidence interval [CI] 0.88-1.17). On subgroup analysis, we found that FC received at academic facilities (HR 0.76; 95% CI 0.58-0.99), as well as NFC received at high-volume centers (HR 0.65; 95% CI 0.43-0.98), were associated with a decrease in overall mortality. CONCLUSIONS: Fragmented care is not associated with worse survival outcomes in patients with MIBC receiving NAC followed by RC.

Emergency holmium laser enucleation of the prostate (HoLEP): a novel approach in the management of refractory hematuria for patients with benign prostatic hyperplasia (BPH): a single-institution experience.

INTRODUCTION: Refractory hematuria secondary to prostatic disease typically resolves with conservative management; however, this condition may require hospitalization with extensive measures to control life-threatening bleeding. The aim of this study was to report our experience using holmium laser enucleation of the prostate (HoLEP) as an emergency treatment in this clinical setting. METHODS: We conducted a retrospective review of all patients that presented to the emergency department with refractory hematuria of prostatic origin from October 2017 to September 2021, for whom hospitalization and conservative management failed to control bleeding. All emergency HoLEP procedures were performed by a single surgeon. Preoperative and intraoperative parameters, as well as perioperative outcomes, were collected and analyzed. Postoperative outcomes included duration of foley catheterization, length of postoperative hospital stay, and hospital readmissions. RESULTS: A total of 40 emergency HoLEP procedures were performed. Our cohort had a median prostate volume of 110.5 cc and a median resected weight of 81 g. Twenty-seven patients (67.5%) were on anticoagulant or antiplatelet medications on admission. The urethral catheter was removed within 1 day in 95% of patients with a successful trial of void (TOV). Moreover, 92.5% of patients were discharged home within 24 h of their procedure. Two patients (5%) experienced clot retention within one-week post-discharge with a 2.5% overall readmission rate. All postoperative parameters, including International Prostate Symptom Score (IPSS), quality of life (QoL), maximum flow rate (Qmax), and post-void residual volume (PVR), showed significant improvement at 1 year follow up. CONCLUSION: Our experience demonstrates that emergency HoLEP is an effective treatment option for patients with refractory hematuria of prostatic origin. Further studies are warranted to consolidate our results.

Depressive symptoms among mothers with hospitalized children in South Asia and sub-Saharan Africa.

BACKGROUND: Poor maternal mental health during childhood hospitalization is associated with post-discharge child mortality. We aimed to establish if maternal PHQ-9 scores during hospitalization are associated with acute stressors or longer trends in mental health status. METHOD: Mothers of children admitted to nine hospitals in six countries completed a PHQ-9 assessment during hospitalization and 45-days post-discharge. Community participants were recruited from homes near the hospitalized children. The prevalence and correlates of high PHQ-9 scores among hospitalized and community mothers were compared. OUTCOMES: Among 2762 mothers of hospitalized children, 514 (19 %) had PHQ-9 scores ≥10, significantly more than the 116 (10 %, p < 0·001) of 1159 community participants. Recruitment site and food insecurity were PHQ-9 correlates in both groups. Correlates of higher mean PHQ-9 scores among the hospitalized cohort included maternal illness (mean difference [MD]: 1·27, 95%CI: 0·77, 1·77), pregnancy (MD: 0·77, 95%CI: 0·27, 1·28), child HIV-infection (MD: 2·51. 95%CI: 1·55, 3·52), and lower child weight-for-height (MD: 0·21, 95%CI: 0·32, 0·11). Marriage (MD -0·92, 95%CI: -1·36, -0·48) and a positive malaria test (MD: -0·63, 95%CI: -1·15, -0·10) were associated with lower PHQ-9 scores among mothers of hospitalized children. Among mothers with PHQ-9 ≥10 during admission, 410 had repeat assessments 45-days after their child's discharge, and 108 (26 %) continued to meet the high PHQ-9 criterion. INTERPRETATION: Among mothers of hospitalized children, there are subgroups with transient and persistent depressive symptoms. Interventions tailored to address acute stressors may improve post-discharge pediatric and maternal health outcomes. FUNDING: Bill & Melinda Gates Foundation OPP1131320.

Magnetic resonance imaging radiomic features for recurrent prostate cancer following proton radiation therapy-A pilot study.

OBJECTIVE: The role of multiparametric MRI (mp-MRI) for postproton radiation evaluation is unclear. In this pilot study, we characterize the mp-MRI features using the Prostate Imaging-Reporting and Data System (PI-RADS) for recurrent prostate cancer (PCa) following proton radiation therapy. METHODS: After obtaining IRB approval, we identified 163 consecutive cases who underwent MRI-fusion prostate biopsy at our institution from November 2017 to May 2020. This study evaluated patients with prostate cancer (PCa) with biochemical recurrence following proton radiation. Patients were excluded if they had grossly metastatic disease, metal fragments, implanted devices, or with surgically removed prostates. The mpMRI studies were reviewed in depth and scored by 2 fellowship-trained radiologists. Following MRI-fusion biopsy of lesions of interest (LOI), slides were read by fellowship-trained pathologists. RESULTS: We found 14 patients with 16 lesions who met the study inclusion criteria. The median age was 69 years (range 57-79) and median time to biochemical recurrence was 7.3 years (range 3-13). On post-treatment imaging, decreases in prostate size and diffusely decreased T2 signal intensity were observed, making the use of apparent diffusion coefficient (ADC) and early enhancement at dynamic contrast enhanced (DCE) imaging often necessary for diagnosis of disease recurrence. We identified a total of 16 lesions with PIRADS scores of 3 or higher. Of these lesions, there were 5 PIRADS 3 lesions (4/5 (80%) without prostate cancer), 7 PIRADS 4-5 lesions (6 (86%) had high risk Pca), and 4 lesions with unassigned PIRADS scores (100% had high risk cancers). Among the MRI variables, diffusion weighted imaging (DWI) heterogeneity had the strongest association with recurrence of PCa (P < 0.001). CONCLUSIONS: Results of our pilot study showed that the PIRADS scoring system in the postproton radiation therapy setting has some correlations with prostate cancer recurrence; However, the clinical value of these findings are unclear. While definitive PIRADS categorization of lesions demonstrated expected frequency of cancer consistent with the scoring system, all unassigned lesions also harbored malignancy suggesting a cautious approach to PIRADS scoring system in postproton radiation setting. The findings from this study may be validated using a larger cohort.

Complications after neoadjuvant chemotherapy and radical cystectomy for patients with bladder cancer: A propensity score matched analysis.

INTRODUCTION: Neoadjuvant chemotherapy (NAC) in combination with radical cystectomy (RC) is the standard of care for muscle-invasive bladder cancer (MIBC). We investigated the impact of NAC on postoperative complications after RC in patients with bladder cancer (BCa). METHODS: Using the recently available American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) Targeted Cystectomy database, we identified adult (>18 years old) patients who underwent RC for the treatment of BCa. Patients were then dichotomized based on whether they received NAC. We performed a 1:1 propensity score matched (PSM) analysis based on demographic and perioperative covariates. Postoperative outcomes were then compared between the two matched groups. A multivariable analysis was also performed to identify if NAC was associated with any complication. RESULTS: We identified 1582 eligible patients: 913 (57.7%) in the group that did not receive NAC and 669 (42.3%) in the group that did receive NAC. Before PSM, patients in the NAC group were younger, had lower American Society of Anesthesiology (ASA) scores, had higher rates of preoperative anemia, and were more likely to undergo continent urinary diversion. Similarly, before PSM patients in the NAC group had significantly higher rates of major complications, sepsis, urinary leak/fistula, and intraoperative/postoperative blood transfusion compared to the group that did not receive NAC; however, after 1:1 PSM, we did not find any significant difference postoperative complication rates. Multivariable analysis confirmed that NAC was not associated with any complications. CONCLUSIONS: We demonstrated that NAC does not impact 30-day postoperative complications in patients undergoing RC for BCa.