NGS-defined measurable residual disease (MRD) after initial chemotherapy as a prognostic biomarker for acute myeloid leukemia.

Treated AML patients often have measurable residual disease (MRD) due to persisting low-level clones. This study assessed whether residual post-treatment somatic mutations, detected by NGS, were significantly prognostic for subsequent clinical outcomes. AML patients (n = 128) underwent both pre-and post-treatment testing with the same 42-gene MRD-validated NGS assay. After induction, 59 (46%) patients were mutation-negative (0.0024 VAF detection limit) and 69 (54%) had ≥1 persisting NGS-detectable mutation. Compared with NGS-negative patients, NGS-positive patients had shorter overall survival (17 months versus median not reached; P = 0.004; hazard ratio = 2.2 [95% CI: 1.3-3.7]) and a shorter time to relapse (14 months versus median not reached; P = 0.014; HR = 1.9 [95% CI: 1.1-3.1]). Among 95 patients with a complete morphologic remission (CR), 43 (45%) were MRD-positive by NGS and 52 (55%) were MRD-negative. These MRD-positive CR patients had a shorter overall survival (16.8 months versus median not reached; P = 0.013; HR = 2.1 [95% CI: 1.2-3.9]) than did the MRD-negative CR patients. Post-treatment persisting MRD positivity, defined by the same NGS-based test used at diagnosis, is thus a more sensitive biomarker for low-level leukemic clones compared to traditional non-molecular methods and is prognostic of subsequent relapse and death.

Facilitating Mental Health Treatment Through Proactive Screening and Concierge Services in the Workplace.

OBJECTIVE: The aim of this study is to determine if a proactive employer-sponsored mental health program closed gaps in detection and treatment of mental health conditions. METHODS: Of n = 56,442 eligible, n = 8170 (14.5%) participated in the optional screening. Participants with mental health risk were offered care concierge services including support, care planning, and connection to care. Difference in behavioral health care utilization, diagnoses, and prescriptions were evaluated postintervention through claims analysis. RESULTS: Compared with controls (n = 2433), those receiving concierge services (n = 369) were more likely to fill mental health prescriptions (adjusted hazards ratio [HR], 1.2; 1.0-1.5; P = 0.042), use professional mental health services (adjusted HR, 1.4; 1.1-1.8; P = 0.02), and use new mental health services (adjusted HR, 1.9; 1.2-2.8; P = 0.004) in the following 6 months. CONCLUSIONS: This proactive mental health program with care concierge services identified risk, connected individuals to mental health care, and facilitated mental health treatment, among program participants.

A Blunt Scrotal Trauma With More Than Meets the Eye.

Extrarenal Wilms' tumors (ERWT) are exceedingly rare with an estimated occurrence of 0.5%-1% of all Wilms' tumors.1 ERWT was first described by Moyson et al in 1961 with the most commonly reported extrarenal sites in the retroperitoneum, inguinal region, uterus and ovaries.2 Here we detail a patient who presented to our institution with a blunt scrotal trauma that was later diagnosed with primary paratesticular ERWT.

Urine leaks in children sustaining blunt renal trauma.

BACKGROUND: Few consensus statements exist to guide the timely diagnosis and management of urine leaks in children sustaining blunt renal trauma (BRT). The aims of this study were to characterize kidney injuries among children who sustain BRT, evaluate risk factors for urine leaks, and describe the negative impact of urinoma on patient outcomes and resource consumption. METHODS: A retrospective review was performed of 347 patients, younger than 19 years, who presented with BRT to a single American College of Surgeons-verified Level I Pediatric Trauma Center between 2005 and 2020. Frequency of and risk factors for urine leak after BRT were evaluated, and impact on patient outcomes and resource utilization were analyzed. RESULTS: In total, 44 (12.7%) patients developed urine leaks, which exclusively presented among injury Grade 3 (n = 5; 11.4%), Grade 4 (n = 27; 61.4%), and Grade 5 (n = 12; 27.3%). A minority of urine leaks (n = 20; 45.5%) were discovered on presenting CT scan but all within 3 days. Kidney-specific operative procedures (nephrectomy, cystoscopy with J/ureteral stent, percutaneous nephrostomy) were more common among urine leak patients (n = 17; 38.6%) compared with patients without urine leaks (n = 3; 1.0%; p = 0.001). Patients with urine leak had more frequent febrile episodes during hospital stay (n = 24; 54.5%; p = 0.001) and showed increased overall 90-day readmission rates (n = 14; 33.3%; p < 0.001). Independent risk factors that associated with urine leak were higher grade (odds ratio [OR], 7.9; 95% confidence interval [CI], 2.6-24.3; p < 0.001), upper-lateral quadrant injuries (OR, 2.9; 95% CI, 1.2-7.1; p = 0.02), and isolated BRT (OR, 2.6; 95% CI, 1.0-6.5; p = 0.04). CONCLUSION: In a large cohort of children sustaining BRT, urine leaks result in considerable morbidity, including more febrile episodes, greater 90-day readmission rates, and increased operative or image-guided procedures. This study is the first to examine the relationship between kidney quadrant injury and urine leaks. Higher grade (Grade 4-5) injury, upper lateral quadrant location, and isolated BRT were independently predictive of urine leaks. LEVEL OF EVIDENCE: Therapeutic/Care Management; Level III.

Workplace Outreach Program Improves Management of Chronic Kidney Disease.

OBJECTIVE: Assess whether an employee outreach program improved management of chronic kidney disease (CKD). METHODS: Participants with suspected CKD (eGFR <60 mL/min/1.73m 2 ) identified in employee health assessments in 2017 and 2018 were contacted by phone and offered physician consultation. Subsequent nephrologist visits at 11 months of follow up were compared between those who were (outreach group) and were not (control group) successfully contacted. RESULTS: Most CKD risk factors at baseline were similar in outreach and control groups. At the end of the follow-up, outreach participants had more than 2-fold greater incidence of visiting a nephrologist compared with controls (HR = 2.3; 95% CI 1.2-4.2, P = 0.01), after adjusting for potential confounders. Conclusions: Employee outreach program increased utilization of nephrologist care.

Association of changes in lipid levels with changes in vitamin D levels in a real-world setting.

In clinical trials, vitamin D supplementation has been reported to reduce serum levels of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and triglycerides (TG) but not high-density lipoprotein cholesterol (HDL-C). In this cohort study we evaluated the association between changes in vitamin D (25-hydroxyvitamin D) and changes in lipid levels in a real-world setting. Changes in lipid levels over a 1-year period were evaluated among individuals whose vitamin D levels increased (group 1) or decreased (group 2) by ≥ 10 ng/mL in year 2018 versus 2017 (cohort 1; n = 5580), in 2019 versus 2018 (cohort 2, n = 6057), or in 2020 versus 2019 (cohort 3, n = 7249). In each cohort, levels of TC, LDL-C, and TG decreased in group 1 and increased in group 2. Between-group differences in average changes in the 3 cohorts ranged from 10.71 to 12.02 mg/dL for TC, from 7.42 to 8.95 mg/dL for LDL-C, and from 21.59 to 28.09 mg/dL for TG. These differences were significant after adjusting for age, sex, race, education, body mass index, blood pressure, smoking status, geographical location, and baseline levels of vitamin D and lipids (P < 0.001). Changes in vitamin D levels were not significantly associated with changes in HDL-C levels.

Assessment of the Association of Vitamin D Level With SARS-CoV-2 Seropositivity Among Working-Age Adults.

Importance: Low vitamin D levels have been reported to be associated with increased risk of SARS-CoV-2 infection. Independent, well-powered studies could further our understanding of this association. Objective: To examine whether low levels of vitamin D are associated with SARS-CoV-2 seropositivity, an indicator of previous infection. Design, Setting, and Participants: This is a cohort study of employees and spouses who elected to be tested for SARS-CoV-2 IgG as part of an annual employer-sponsored health screening program conducted in August to November 2020. This program includes commonly assessed demographic, biometric, and laboratory variables, including total vitamin D measurement. Baseline (prepandemic) levels of vitamin D and potential confounders were obtained from screening results from the previous year (September 2019 to January 2020). Data analysis was performed from December 2020 to March 2021. Exposures: Low total serum 25-hydroxyvitamin D, defined as either less than 20 ng/mL or less than 30 ng/mL. Main Outcomes and Measures: The main outcome was SARS-CoV-2 seropositivity, as determined with US Food and Drug Administration emergency use-authorized assays. The association of SARS-CoV-2 seropositivity with vitamin D levels was assessed by multivariable logistic regression analyses and propensity score analyses. Results: The 18 148 individuals included in this study had test results for SARS-CoV-2 IgG in 2020 and vitamin D levels from the prepandemic and pandemic periods. Their median (interquartile range) age was 47 (37-56) years, 12 170 (67.1%) were women, 900 (5.0%) were seropositive, 4498 (24.8%) had a vitamin D level less than 20 ng/mL, and 10 876 (59.9%) had a vitamin D level less than 30 ng/mL before the pandemic. In multivariable models adjusting for age, sex, race/ethnicity, education, body mass index, blood pressure, smoking status, and geographical location, SARS-CoV-2 seropositivity was not associated with having a vitamin D level less than 20 ng/mL before (odds ratio [OR], 1.04; 95% CI, 0.88-1.22) or during (OR, 0.93; 95% CI, 0.79-1.09) the pandemic; it was also not associated with having a vitamin D level less than 30 ng/mL before (OR, 1.09; 95% CI, 0.93-1.27) or during (OR, 1.05; 95% CI, 0.91-1.23) the pandemic. Similar results were observed in propensity score analyses. SARS-CoV-2 seropositivity was associated with obesity (OR, 1.26; 95% CI, 1.08-1.46), not having a college degree (OR, 1.40; 95% CI, 1.21-1.62), and Asian (OR, 1.46; 95% CI, 1.13-1.87), Black (OR, 2.74; 95% CI, 2.25-3.34), Hispanic (OR, 2.65; 95% CI, 2.15-3.27), American Indian or Alaska Native, and Native Hawaiian or other Pacific Islander (OR, 2.01; OR, 1.54-2.62) race/ethnicity, and was inversely associated with high blood pressure (OR, 0.82; 95% CI, 0.70-0.96), smoking (OR, 0.60; 95% CI, 0.47-0.78), and residing in the US Northeast (OR, 0.75; 95% CI, 0.62-0.92) and West (OR, 0.54; 95% CI, 0.44-0.67). Conclusions and Relevance: In this cohort study, SARS-CoV-2 seropositivity was not associated with low levels of vitamin D independently of other risk factors.

Kidney epithelial targeted mitochondrial transcription factor A deficiency results in progressive mitochondrial depletion associated with severe cystic disease.

Abnormal mitochondrial function is a well-recognized feature of acute and chronic kidney diseases. To gain insight into the role of mitochondria in kidney homeostasis and pathogenesis, we targeted mitochondrial transcription factor A (TFAM), a protein required for mitochondrial DNA replication and transcription that plays a critical part in the maintenance of mitochondrial mass and function. To examine the consequences of disrupted mitochondrial function in kidney epithelial cells, we inactivated TFAM in sine oculis-related homeobox 2-expressing kidney progenitor cells. TFAM deficiency resulted in significantly decreased mitochondrial gene expression, mitochondrial depletion, inhibition of nephron maturation and the development of severe postnatal cystic disease, which resulted in premature death. This was associated with abnormal mitochondrial morphology, a reduction in oxygen consumption and increased glycolytic flux. Furthermore, we found that TFAM expression was reduced in murine and human polycystic kidneys, which was accompanied by mitochondrial depletion. Thus, our data suggest that dysregulation of TFAM expression and mitochondrial depletion are molecular features of kidney cystic disease that may contribute to its pathogenesis.

Gaussia Luciferase as a Reporter for Quorum Sensing in Staphylococcus aureus.

Gaussia luciferase (GLuc) is a secreted protein with significant potential for use as a reporter of gene expression in bacterial pathogenicity studies. To date there are relatively few examples of its use in bacteriology. In this study we show that GLuc can be functionally expressed in the human pathogen Staphylococcus aureus and furthermore show that it can be used as a biosensor for the agr quorum sensing (QS) system which employs autoinducing peptides to control virulence. GLuc was linked to the P3 promoter of the S. aureusagr operon. Biosensor strains were validated by evaluation of chemical agent-mediated activation and inhibition of agr. Use of GLuc enabled quantitative assessment of agr activity. This demonstrates the utility of Gaussia luciferase for in vitro monitoring of agr activation and inhibition.

Insulin Resistance Probability Scores for Apparently Healthy Individuals.

CONTEXT: Insulin resistance (IR) can progress to type 2 diabetes. Therefore, timely identification of IR could facilitate disease prevention efforts. However, direct measurement of IR is not feasible in a clinical setting. OBJECTIVE: Develop a clinically practical probability score to assess IR in apparently healthy individuals based on levels of insulin, C-peptide, and other risk factors. DESIGN: Cross-sectional study. PARTICIPANTS: Apparently healthy individuals who volunteered to participate in studies of IR. MAIN OUTCOME MEASURE: IR, defined as the top tertile of steady-state plasma glucose during an insulin-suppression test. RESULTS: In a study of 535 participants, insulin, C-peptide, creatinine, body mass index (BMI), and triglycerides to high-density lipoprotein cholesterol ratio (TG/HDL-C) were independently associated with IR (all P < 0.05) in a model that included age, sex, ethnicity, BMI, blood pressure, insulin, C-peptide, fasting glucose, low-density lipoprotein cholesterol, TG/HDL-C, alanine aminotransferase, and creatinine. For an IR probability score based on a model that included insulin, C-peptide, creatinine, TG/HDL-C, and BMI, the odds ratio was 26.7 (95% CI 14.0 to 50.8) for those with scores >66% compared with those with scores <33%. When only insulin and C-peptide were included in the model, the odds ratio was 15.6 (95% CI 7.5 to 32.4) for those with scores >66% compared with those with scores <33%. CONCLUSIONS: An IR probability score based on insulin, C-peptide, creatinine, TG/HDL-C, and BMI or a score based on only insulin and C-peptide may help assess IR in apparently healthy individuals.

Use of Google Trends to Track Online Behavior and Interest in Kidney Stone Surgery.

OBJECTIVE: To explore internet search trends data as a unique resource for monitoring online health information-seeking behavior. We utilized Google trends to sample population interest and search inquiries into surgical treatment options of kidney stones, and we examined the relative frequency of searches across the United States. METHODS: Google trends was queried via the Google Insights for Search (http://google.com/trends) using terms related to kidney stone surgeries from 2011 to 2017. "Kidney stone surgery" was identified to be the most common term. The search volume index graph for the U.S. was recorded as well as regional distribution and related queries. For specific surgical treatment modalities, the following medical terminology was used: percutaneous nephrolithotomy, extracorporeal shockwave lithotripsy, ureteroscopy, and laser lithotripsy. Each query was then compared and analyzed to assess changes in the interest in these search terms over time. RESULTS: The research trends for the search "kidney stone surgery" as well as specific surgical modalities remained constant over time. extracorporeal shockwave lithotripsy had the highest search volume index and laser lithotripsy had the lowest. The top 5 US states with greatest search volume was Tennessee, Indiana, Ohio, Michigan, and North Carolina, whereas the top 5 metropolitan regions were Atlanta, Tampa, Detroit, Philadelphia, and Boston. CONCLUSION: Google trends data is a useful tool to analyze online health information-seeking behavior. Despite an increase in stone prevalence over the past decade, search rates have remained relatively constant. High relative search volume was seen from states within and outside the traditional stone belt, suggesting a possible changing trend.

Laparoscopic inguinal hernia repair by modified peritoneal leaflet closure: Description and initial results in children.

INTRODUCTION: Inguinal hernias are common in infants and children. While the gold standard for hernia repair in the pediatric period has been via an open inguinal incision with dissection and high ligation of the hernia sac, over the past two decades laparoscopic herniorrhaphy has increased in popularity. The advantages of laparoscopy include decreased post-operative pain, improved cosmetic results, ability to easily assess the contralateral side for an open internal inguinal ring, and decreased risk of metachronous hernias. Herein, we describe a modified laparoscopic herniorrhaphy using a peritoneal leaflet closure and report our operative experience with intermediate-term results. METHODS: We retrospectively reviewed our IRB-approved registry for all children who underwent initial laparoscopic herniorrhaphy at our tertiary care center over a 2.5-year period. All surgeries were performed by a single surgeon using a technique we have termed the peritoneal leaflet closure. This technique involves incising the peritoneum circumferentially around the open internal ring and developing peritoneal leaflets which are then closed together over the ring with a running non-absorbable barbed stitch (Figure). Intraoperative findings and complications, operative times, and post-operative complications were reviewed for all children. RESULTS: A total of 50 initial laparoscopic hernia repairs (4 bilateral, 42 unilateral) were performed in 46 children (43 boys, 3 girls) at a median age of 5.9 years (range 0.5-16.7). Median operative time was 73 min (range 48-138) for unilateral and 106 min (range 104-135) for bilateral herniorrhaphy. No patient had an intraoperative complication. Two children (4%) had contralateral open rings discovered at time of surgery and underwent unplanned bilateral laparoscopic hernia repair. All patients went home on the same day as the procedure and three children (6%) had minor post-operative complaints (umbilical bulge, thigh pain, and urine holding) that all self-resolved. Thirty-nine children had follow-up data available. Intermediate-term complications occurred in two children (5%): one boy developed a contralateral hydrocele (despite a closed ring at surgery) and one boy had a hernia recurrence that required open repair. Overall, operative success with the modified peritoneal leaflet closure technique was therefore 97% (38 of 39 children with follow-up). All 37 boys who followed up had bilateral descended testes of normal size and consistency. CONCLUSIONS: Laparoscopic herniorrhaphy using a peritoneal leaflet closure technique is safe and effective when used in infants and children to close an indirect hernia (i.e. patent processus vaginalis). No intraoperative complications occurred in this cohort and success rate was 97%.

A Review of Translocation T(6;11) Renal Cell Carcinoma Tumors in the Adult Patient.

Historically, T(6;11) renal cell carcinoma (RCC) has been associated with the pediatric and adolescent populations and documentation of this tumor in adults has been rare. However, the frequency of translocation renal cell carcinoma (TRCC) may be widely underestimated in the adult population due to an inadequate immunohistochemical workup or misdiagnosis from similar gross and histological findings to other RCC. A subset of MiT family translocation carcinomas, t(6:11) (p21;q12) translocation tumors cause an alpha-TFEB gene fusion. Morphologically, this neoplasm tends to mimic the various types of RCC's, including clear cell, papillary, and even epitheloid angiomyolipomas. Adult cases of TRCC have shown to behave more aggressively than their indolent pediatric counterpart, but due to the limited number of reported cases the true nature of these tumors has yet to be determined. The aim of this review is to bring an awareness of translocation RCC to better understand its diagnoses, treatment and prognosis, and, in turn, to allow for new cases to further highlight the behavior of this rare variant.

Reconstructive Management Options of Delayed Complications Following Bladder Outlet Surgery.

PURPOSE OF REVIEW: Technological advancements in urologic endoscopy within the last decades have improved outcomes following bladder outlet reduction surgery while minimizing risks of short- and intermediate-term complications. This review aims to examine late complications of endoscopic reduction of the prostate and the various treatment options available. RECENT FINDINGS: Urinary incontinence, ejaculatory dysfunction, urethral strictures, bladder neck contractures, and fistula formations are the most common delayed complications following bladder outlet reduction surgery. Evaluation of these complications typically involves a combination of endoscopic examination, urodynamic findings, pelvic imaging, and review of pre-existing symptoms. Treatment options range from conservative measures such as pelvic floor muscle therapy to complex reconstructive procedures including anti-incontinence surgery, urethral reconstruction, and permanent urinary diversion. Although rare, late complications of bladder outlet reduction surgery are important to recognize in order to manage appropriately. Careful evaluation involving multiple diagnostic modalities with consideration for referral to a dedicated reconstructive urologist may be warranted in complex cases.

Extracorporeal Shock Wave Therapy: Current Perspectives and Future Directions.

PURPOSE OF REVIEW: Since its introduction, extracorporeal shock wave lithotripsy (ESWL) has undergone a variety of changes; however, it remains one of the most utilized treatment modalities for urolithiasis. The goal of this review is to provide the practicing urologist an update on contemporary trends, new technologies, and related controversies in utilizing ESWL for stone treatment. RECENT FINDINGS: ESWL use has come under scrutiny with a shift in focus to cost-effectiveness and healthcare outcomes. Fortunately, advances in lithotripter technology have spawned several generations of devices that strive to improve stone-free rates and decrease complications. Most of all, a focus on patient selection criteria has helped improve procedural success. Years of experience utilizing ESWL for stone treatment have helped urologists better optimize its use and minimize complications. Improvements in technique along with more stringent patient and stone selection have helped ESWL remain a mainstay in the treatment of stone disease.

Urological Findings in Beckwith-Wiedemann Syndrome With Chromosomal Duplications of 11p15.5: Evaluation and Management.

Beckwith-Wiedemann Syndrome (BWS) is an overgrowth disorder with various congenital anomalies. Although the most classic constellation includes macrosomia, macroglossia, and omphalocele, nephrourological findings are commonly associated with BWS. Clinical presentation is highly variable because of its complex molecular heterogeneity, which involves changes in DNA methylation and disruption of growth regulatory genes. We report 3 pediatric patients, ages 13 months to 3 years old, who presented with clinical features consistent with BWS. A variety of nephrourological abnormalities were also noted, including posterior urethral valves, hydroureteronephrosis, and undescended testes. Genetic testing for all 3 patients revealed duplication of the region chromosome 11p15.5.

Metastatic Prostate Cancer Presenting as Lower Extremity Soft Tissue Mass: A Rare Case Presentation.

A 69-year-old homeless African American male with prostate cancer diagnosed 2 years prior presents a large mass in the right thigh. An evaluation of the patient revealed a prostate-specific antigen of 9362 ng/mL. Biopsy of the leg mass was performed and final pathology indicated metastatic adenocarcinoma of the prostate. Although metastatic prostate cancer presents most commonly in bone, lymph nodes, lungs, and liver, metastatic disease presenting as a soft tissue mass is extremely rare (Bubendorf et al, 2000; Molenaar et al, 1996; Ward and Bourken, 1984). The advent of screening with prostate-specific antigen has led to earlier diagnosis of lower-grade disease, yet underserved populations continue to present with aggressive and morbid disease (Winer et al, 2014).