The benefit to waitlist patients in a national paired kidney exchange program: Exploring characteristics of chain end living donor transplants.

Nondirected kidney donors can initiate living donor chains that end to patients on the waitlist. We compared 749 National Kidney Registry (NKR) waitlist chain end transplants to other transplants from the NKR and the Scientific Registry of Transplant Recipients between February 2008 and September 2020. Compared to other NKR recipients, chain end recipients were more often older (53 vs. 52 years), black (32% vs. 15%), publicly insured (71% vs. 46%), and spent longer on dialysis (3.0 vs. 1.0 years). Similar differences were noted between chain end recipients and non-NKR living donor recipients. Black patients received chain end kidneys at a rate approaching that of deceased donor kidneys (32% vs. 34%). Chain end donors were older (52 vs. 44 years) with slightly lower glomerular filtration rates (93 vs. 98 ml/min/1.73 m2 ) than other NKR donors. Chain end recipients had elevated risk of graft failure and mortality compared to control living donor recipients (both p < .01) but lower graft failure (p = .03) and mortality (p < .001) compared to deceased donor recipients. Sharing nondirected donors among a multicenter network may improve the diversity of waitlist patients who benefit from living donation.

Randomized controlled trial of a quadratus lumborum block with liposomal bupivacaine for postoperative analgesia in laparoscopic donor nephrectomy.

Perioperative pain management is an important consideration in early recovery and patient satisfaction following laparoscopic donor nephrectomy. Transmuscular quadratus lumborum block has been described to reduce pain and opioid usage following several abdominal surgeries. In this prospective single-blind randomized controlled trial, we compared 52 patients who adhered to our institutional donor nephrectomy Early Recovery After Surgery pathway, which includes a laparoscopic-guided transversus abdominus plane block, to 40 patients who additionally received a transmuscular quadratus lumborum block with liposomal bupivacaine. Compared to control patients, those who received the block spent longer in the operating room prior to the surgical start (65.4 vs. 51.6 min, P < .001). Both groups had similar total hospital length of stay (33.3 h vs. 34.4 h, P = .61). Pain scores from postoperative days 0-30, number of patients requiring opioids, postoperative nausea, and pain management satisfaction were similar between both groups. Patients who received the block consumed less opioid on postoperative day 1 compared to controls (P = .006). No complications were attributable to the block. The quadratus lumborum block provides a safe pain management adjunct for some patients, and may reduce opioid use in the early postoperative period when combined with our standard institutional protocol for kidney donors.

Ancillary benefits of bladder chemodenervation for SCI neurogenic bladder.

STUDY DESIGN: Case series. OBJECTIVE: Bladder chemodenervation is effective in treating neurogenic detrusor overactivity (NDO) in patients with neurogenic bladder due to spinal cord injury. Anecdotal reports also describe the improvement of non-bladder symptoms, specifically those related to autonomic dysreflexia (AD) and muscle spasticity. We conducted a study to further investigate this phenomenon. SETTING: USA, Urban Tertiary Care Center. METHODS: Twenty-one persons with SCI completed the study between March and December 2015. Mean age was 45 years (range 21-69). All were scheduled to undergo bladder chemodenervation with onabotulinumtoxinA 200 units to treat bothersome NDO refractory to oral medications. Each completed a questionnaire detailing symptoms unrelated to NDO immediately prior to the procedure, and again between 6 and 12 weeks after. RESULTS: All patients reported improvement in NDO symptoms following chemodenervation. Ten patients with prior symptoms of AD reported improvement in AD symptoms after injection. Seventeen patients reported skeletal muscle spasticity in the 3-month period before chemodenervation. In the follow up period, only 14 patients reported having muscle spasticity. In aggregate, 12 of 21 patients reported improvement of non-bladder symptomatology following chemodenervation. CONCLUSIONS: Chemodenervation of the bladder in patients with SCI can provide ancillary benefits in addition to mitigation of lower urinary symptoms. The mechanism may be related to dampening the bladder's ability to initiate noxious reflex responses.

Low-Volume vs High-Volume Centers and Management of Fournier's Gangrene in Washington State.

BACKGROUND: Fournier's gangrene (FG) is a life-threatening infection affecting the perineum and genitals. Complex patient management often necessitates transfer to tertiary centers. We aimed to characterize hospital transfer patterns and assess morbidity among patients with FG in Washington State. STUDY DESIGN: The Washington State Comprehensive Hospital Abstract Reporting System includes claims from all hospital discharges in Washington. We identified patients with FG between 2007 and 2013, based on diagnosis and treatment codes. Analyses were stratified by center volume (low-volume centers [LVCs] or high-volume centers [HVCs]), and transfer status. Variables of interest included number of debridements, septic shock, acute renal failure, acute respiratory failure, length of hospitalization, and death. RESULTS: We identified 165 FG patients. Only 1 HVC treated more than 2 FG patients per year. Overall mortality was 6.7%. Most patients (57%) were treated entirely at LVCs; 87% of patients treated at the HVC were transferred from an LVC. High-volume center-treated patients had similar baseline comorbidities (p = 0.77) and similar mortality (p = 0.87), despite higher rates of septic shock (p < 0.01) and respiratory failure (p = 0.01) compared with LVC patients. Among HVC-transferred patients, immediate compared with delayed transfer was associated with fewer debridements (p < 0.01), lower rates of septic shock (p = 0.05), and acute renal failure (p = 0.04). CONCLUSIONS: Patients treated at the HVC were more acutely ill, yet mortality was similar compared with patients treated solely at LVCs, suggesting a benefit to transfer of high acuity patients. Immediate vs delayed transfer may benefit FG health outcomes; however, this may also reflect greater disease acuity of patients with delayed transfer status.

Characteristics of Patients With Sertoli and Leydig Cell Testis Neoplasms From a National Population-Based Registry.

INTRODUCTION: Sertoli and Leydig cell tumors (SCT and LCT) are uncommon testis neoplasms. Data regarding patient demographics and outcomes are limited to small series. We further characterized these tumors using a large cancer database. METHODS: The Surveillance, Epidemiology, and End Results (SEER) database was queried from 2004 to 2012. International Classification of Diseases for Oncology (ICD-O) codes identified SCT and LCT. Common germ cell tumors (GCT) provided a reference group. Age, race, histology, tumor size, stage, and cancer-specific mortality (CSM) were compared. RESULTS: Thirty-one men had SCT, 76 had LCT, and 17,998 had GCTs. Median follow-up for SCT, LCT, and GCTs was 46, 38, and 50 months, respectively. Median ages for SCT and LCT were 39 and 47, respectively, which was older than those with GCT (34 years; P < .001). African American race was more common in SCT (23%) and LCT (24%) patients compared to GCT (3%, P < .001). LCT most commonly presented with stage I disease (98.5%), while patients with SCT presented at higher stages (35% with stage II/III). CSM was highest in patients with SCT (32% vs. 2% LCT and 7% GCT, P < .001). Median survival of those with CSM was similar between SCT, LCT, and GCTs (15, 12, and 14 months, respectively). CONCLUSION: Compared to GCT, SCT and LCT present at older ages and are more common in African Americans. Metastasic disease at presentation and CSM rates are higher in SCT compared to LCT and GCT, suggesting a clinically relevant distinction between these histologies. Better characterization of these rare neoplasms will continue to inform patient counseling and management.

Exposure to and Attitudes Regarding Transgender Education Among Urology Residents.

INTRODUCTION: Transgender individuals are underserved within the health care system but might increasingly seek urologic care as insurers expand coverage for medical and surgical gender transition. AIM: To evaluate urology residents' exposure to transgender patient care and their perceived importance of transgender surgical education. METHODS: Urology residents from a representative sample of U.S. training programs were asked to complete a cross-sectional survey from January through March 2016. MAIN OUTCOME MEASURES: Respondents were queried regarding demographics, transgender curricular exposure (didactic vs clinical), and perceived importance of training opportunities in transgender patient care. RESULTS: In total, 289 urology residents completed the survey (72% response rate). Fifty-four percent of residents reported exposure to transgender patient care, with more residents from Western (74%) and North Central (72%) sections reporting exposure (P ≤ .01). Exposure occurred more frequently through direct patient interaction rather than through didactic education (psychiatric, 23% vs 7%, P < .001; medical, 17% vs 6%, P < .001; surgical, 33% vs 11%, P < .001). Female residents placed greater importance on gender-confirming surgical training than did their male colleagues (91% vs 70%, P < .001). Compared with Western section residents (88%), those from South Central (60%, P = .002), Southeastern (63%, P = .002), and Mid-Atlantic (63%, P = .003) sections less frequently viewed transgender-related surgical training as important. Most residents (77%) stated transgender-related surgical training should be offered in fellowships. CONCLUSION: Urology resident exposure to transgender patient care is regionally dependent. Perceived importance of gender-confirming surgical training varies by sex and geography. A gap exists between the direct transgender patient care urology residencies provide and the didactic transgender education they receive.

Robot-Assisted Laparoscopic Excision of Ureteral and Ureteropelvic Junction Fibroepithelial Polyps in Children.

INTRODUCTION: Fibroepithelial polyps of the ureter are a rare cause of asymptomatic and symptomatic upper urinary tract obstruction in children. While these lesions can often be managed endoscopically, large or multifocal polyps may preclude such an approach. OBJECTIVE: We aim to describe our institutional experience with robot-assisted laparoscopic treatment of ureteral polyps and show that a robotic approach is an effective alternative for large or multifocal polyps. MATERIALS AND METHODS: Four children were identified with ureteral polyps over a 5-year period and underwent transperitoneal robot-assisted laparoscopic excision. Patients presented with flank pain and/or worsening hydronephrosis. All patients were evaluated preoperatively with ultrasound and Tc99m-mercaptoacetyltriglycine (MAG3) diuretic renogram or MR urogram. Retrograde pyelography corroborated the diagnosis of ureteral polyps. We reviewed the charts of these patients and compared the specific robotic approach for each patient, length of hospitalization, surgical complications, need for additional procedures, and resolution of symptoms and hydronephrosis. RESULTS: In one patient, more than 20 polyps were identified over a long ureteral segment and all were excised; for the remaining three patients, 1 to 2 polyps were found. Mean postoperative length of stay was 1.5 days. One patient developed a ureteral stricture requiring repeat ureteroureterostomy, and another patient required repeat retrograde pyelography for gross hematuria that occurred several months after surgery. No polyps or obstruction was observed on retrograde pyelography in these patients. Mean duration of follow-up was 29 months (9-62 months). Symptoms and degree of hydronephrosis have improved in the three patients who have been followed for at least 12 months. CONCLUSIONS: Robot-assisted laparoscopy is a safe and feasible alternative to endoscopic treatment of fibroepithelial ureteral polyps. The robotic platform may be preferred in cases of multifocal or large ureteral polyps, or in cases in which a concomitant ureteropelvic junction narrowing may be present.

Quantitative trait loci for interhemispheric commissure development and social behaviors in the BTBR T⁺ tf/J mouse model of autism.

BACKGROUND: Autism and Agenesis of the Corpus Callosum (AgCC) are interrelated behavioral and anatomic phenotypes whose genetic etiologies are incompletely understood. We used the BTBR T⁺ tf/J (BTBR) strain, exhibiting fully penetrant AgCC, a diminished hippocampal commissure, and abnormal behaviors that may have face validity to autism, to study the genetic basis of these disorders. METHODS: We generated 410 progeny from an F2 intercross between the BTBR and C57BL/6J strains. The progeny were phenotyped for social behaviors (as juveniles and adults) and commisural morphology, and genotyped using 458 markers. Quantitative trait loci (QTL) were identified using genome scans; significant loci were fine-mapped, and the BTBR genome was sequenced and analyzed to identify candidate genes. RESULTS: Six QTL meeting genome-wide significance for three autism-relevant behaviors in BTBR were identified on chromosomes 1, 3, 9, 10, 12, and X. Four novel QTL for commissural morphology on chromosomes 4, 6, and 12 were also identified. We identified a highly significant QTL (LOD score = 20.2) for callosal morphology on the distal end of chromosome 4. CONCLUSIONS: We identified several QTL and candidate genes for both autism-relevant traits and commissural morphology in the BTBR mouse. Twenty-nine candidate genes were associated with synaptic activity, axon guidance, and neural development. This is consistent with a role for these processes in modulating white matter tract development and aspects of autism-relevant behaviors in the BTBR mouse. Our findings reveal candidate genes in a mouse model that will inform future human and preclinical studies of autism and AgCC.

Genetic and functional analyses identify DISC1 as a novel callosal agenesis candidate gene.

Agenesis of the corpus callosum (AgCC) is a congenital brain malformation that occurs in approximately 1:1,000-1:6,000 births. Several syndromes associated with AgCC have been traced to single gene mutations; however, the majority of AgCC causes remain unidentified. We investigated a mother and two children who all shared complete AgCC and a chromosomal deletion at 1q42. We fine mapped this deletion and show that it includes Disrupted-in-Schizophrenia 1 (DISC1), a gene implicated in schizophrenia and other psychiatric disorders. Furthermore, we report a de novo chromosomal deletion at 1q42.13 to q44, which includes DISC1, in another individual with AgCC. We resequenced DISC1 in a cohort of 144 well-characterized AgCC individuals and identified 20 sequence changes, of which 4 are rare potentially pathogenic variants. Two of these variants were undetected in 768 control chromosomes. One of these is a splice site mutation at the 5' boundary of exon 11 that dramatically reduces full-length mRNA expression of DISC1, but not of shorter forms. We investigated the developmental expression of mouse DISC1 and find that it is highly expressed in the embryonic corpus callosum at a critical time for callosal formation. Taken together our results suggest a significant role for DISC1 in corpus callosum development.

Pineal region tumors: an optimal approach for simultaneous endoscopic third ventriculostomy and biopsy.

OBJECT: Simultaneous endoscopic third ventriculostomy (ETV) and tumor biopsy is a widely accepted therapeutic and diagnostic procedure for patients with noncommunicating hydrocephalus secondary to a pineal region tumor. Multiple approaches have been advocated, including the use of a steerable fiberoptic or rigid lens endoscope via 1 or 2 trajectories. However, the optimal approach has not been established based on the individual anatomical characteristics of the patient. METHODS: A retrospective review of patients undergoing simultaneous ETV and tumor biopsy was undertaken. Preoperative MR images were examined to measure the width of the anterior third ventricle and maximal diameters of the tumor, Monro foramen (right), and massa intermedia. The distances between the tumor and massa intermedia, tumor and anterior commissure, midbrain and massa intermedia, and the dorsum sella and anterior commissure were also recorded. Single and dual trajectory approaches were compared using paired t-tests for each parameter. RESULTS: Over an 8-year interval, 15 patients underwent simultaneous ETV and tumor management. These patients ranged from 6 to 71 years of age (mean 36.7 years); 5 were younger than 18 years of age. Seven were treated using a dual trajectory approach, and 8 were treated using a single trajectory approach. All cases were completed without complications or the need for an additional CSF diversionary procedure within 6 months. The diagnostic yield at biopsy was 86.7%. There were no statistically significant differences between the single and dual trajectory groups for the measured parameters. However, the dual trajectory group demonstrated a larger anterior third ventricular diameter (1.43 vs 1.21 cm, p = 0.29). The single trajectory group trended toward a smaller tumor-anterior commissure interval (2.23 vs 2.51 cm, p = 0.24) and a larger dorsum sella-anterior commissure distance (1.67 vs 1.49 cm, p = 0.28). CONCLUSIONS: These data confirm the safety and diagnostic efficacy of simultaneous ETV and biopsy for tumors of the pineal region. Although no statistically significant differences were seen in the authors' recorded measurements, several trends suggest a role for a tailored approach to selecting a single or dual trajectory approach when using a rigid endoscope.

Arabidopsis POT1 associates with the telomerase RNP and is required for telomere maintenance.

POT1 is a single-copy gene in yeast and humans that encodes a single-strand telomere binding protein required for chromosome end protection and telomere length regulation. In contrast, Arabidopsis harbors multiple, divergent POT-like genes that bear signature N-terminal OB-fold motifs, but otherwise share limited sequence similarity. Here, we report that plants null for AtPOT1 show no telomere deprotection phenotype, but rather exhibit progressive loss of telomeric DNA. Genetic analysis indicates that AtPOT1 acts in the same pathway as telomerase. In vitro levels of telomerase activity in pot1 mutants are significantly reduced and are more variable than wild-type. Consistent with this observation, AtPOT1 physically associates with active telomerase particles. Although low levels of AtPOT1 can be detected at telomeres in unsynchronized cells and in cells arrested in G2, AtPOT1 binding is significantly enhanced during S-phase, when telomerase is thought to act at telomeres. Our findings indicate that AtPOT1 is a novel accessory factor for telomerase required for positive telomere length regulation, and they underscore the coordinate and extraordinarily rapid evolution of telomere proteins and the telomerase enzyme.

The Arabidopsis Pot1 and Pot2 proteins function in telomere length homeostasis and chromosome end protection.

Pot1 (protection of telomeres 1) is a single-stranded telomere binding protein that is essential for chromosome end protection and telomere length homeostasis. Arabidopsis encodes two Pot1-like proteins, dubbed AtPot1 and AtPot2. Here we show that telomeres in transgenic plants expressing a truncated AtPot1 allele lacking the N-terminal oligonucleotide/oligosaccharide binding fold (P1DeltaN) are 1 to 1.5 kb shorter than in the wild type, suggesting that AtPot1 contributes to the positive regulation of telomere length control. In contrast, telomere length is unperturbed in plants expressing the analogous region of AtPot2. A strikingly different phenotype is observed in plants overexpressing the AtPot2 N terminus (P2DeltaC) but not the corresponding region in AtPot1. Although bulk telomeres in P2DeltaC mutants are 1 to 2 kb shorter than in the wild type, these plants resemble late-generation telomerase-deficient mutants with severe growth defects, sterility, and massive genome instability, including bridged chromosomes and aneuploidy. The genome instability associated with P2DeltaC mutants implies that AtPot2 contributes to chromosome end protection. Thus, Arabidopsis has evolved two Pot genes that function differently in telomere biology. These findings provide unanticipated information about the evolution of single-stranded telomere binding proteins.