Hydrometrocolpos: a Contemporary Review of the Last 5 Years.

PURPOSE OF REVIEW: The goal of this review is to provide a comprehensive overview of hydrometrocolpos, covering disease etiology, pathophysiology, clinical presentation, and diagnostic and management techniques, and known outcomes. RECENT FINDINGS: This narrative review presents the literature on hydrometrocolpos in the pediatric population from the past 5 years. We highlight the 69 reported cases of hydrometrocolpos and classify them based on type of obstruction or associated anomaly, discuss new diagnostic algorithms based on imaging, and present novel and underutilized surgical techniques for definitive management. Hydrometrocolpos, a condition characterized by retained fluid causing a distended vagina and uterus in the setting of a distal vaginal outflow obstruction, has a wide range of presentation severity based on the type of obstruction. Whether hydrometrocolpos is due to an isolated condition like imperforate hymen, a complex abnormality like cloacal malformation, or a part of a large congenital syndrome, the mainstay of treatment is decompression of the dilated vagina and surgical correction of the outflow obstruction. Imaging-based diagnostic algorithms and new treatment techniques reported in the literature, as well as longitudinal and patient-reported outcome research, can improve the lives of children affected by this condition.

Understanding factors influencing primary treatment with intradetrusor onabotulinumtoxinA versus augmentation cystoplasty in patients with spina bifida.

PURPOSE: Surgical interventions in the urologic management of children with neurogenic bladder secondary to spina bifida aim to preserve upper tract function, prevent urinary tract infections, and optimize quality of life. However, since the introduction of intravesical onabotulinumtoxinA (Botox) in the management of these patients, the indications for choosing Botox over augmentation cystoplasty (AC) remain undefined. The objective of this study was to determine which factors lead patients to undergo Botox versus AC as a primary surgical treatment after failing medical management. METHODS: We retrospectively reviewed the records of pediatric patients with myelomeningocele undergoing either primary Botox or primary AC at our institution between 2013 and 2018. We recorded demographic and clinical information. We identified 10 important clinical decision-making factors: bladder trabeculation, vesicoureteral reflux, or hydronephrosis on imaging; end-filling pressure (EFP) ≥40 cm H2O, detrusor overactivity, detrusor-sphincter dyssynergia, or reduced capacity on urodynamic studies; physician-perceived bladder hostility; and patient/family desire for continence and independence. The presence of these factors was compared between patients undergoing either primary Botox or primary AC. RESULTS: We identified 14 and 50 myelomeningocele patients who underwent primary AC and primary Botox, respectively. We found no significant differences in age, sex, race, or history of reconstructive surgery (antegrade continence enema or catheterizable channel). For the 10 decision-making factors, desire for independence/continence (p = <0.001) and reduced capacity (p = 0.002) were significantly associated with AC, while trabeculation (p = 0.006), EFP ≥40 cm H2O (p = 0.029), rising slope (p = 0.019), and physician-perceived hostility (p = 0.012) were significantly more common with Botox. CONCLUSIONS: At our institution, quality of life measures prompted AC over objective urodynamic or imaging findings before attempting Botox. These findings support a shared decision-making approach when considering surgical intervention for neurogenic bladder secondary to myelomeningocele.

Virilization of a 46,XX Fetus Following Aromatase Inhibitor Treatment of Breast Cancer.

Virilization of the 46,XX infant may be attributed to maternal or fetoplacental origin. Maternal sources may be endogenous, as with an androgen-producing tumor, or drug-related. Iatrogenic virilization by maternal drug exposure is rarely reported, with individual case reports and case series demonstrating the effects of progesterone and other medications affecting the pituitary-ovarian axis.1-3 The class of medications known as aromatase inhibitors are recognized as effective in treating hormone receptor-positive breast cancer by preventing the conversion of androgens into estrogens by aromatase. In fetal development, placental aromatase plays a critical role in preventing virilization of the XX fetus by maternal and fetal androgens during development. In the setting of placental aromatase deficiency, the XX fetus may be virilized. It is conceivable, therefore, that maternal exposure to aromatase inhibitors early in gestation may lead to in utero virilization, though there have been no known reports of this phenomenon to date. We present a case of virilization of a 46,XX infant attributed to pharmacologic aromatase inhibition. The infant's parents provided informed consent for the reporting of this case.

The impact of early versus late tocilizumab administration in patients with cytokine release syndrome secondary to immune effector cell therapy.

INTRODUCTION: Cytokine release syndrome is a life-threatening hyper-inflammatory state induced by immune effector cell therapy. Anti-interleukin 6-(IL-6) therapy, such as tocilizumab, is the standard treatment for cytokine release syndrome since it reverses symptoms without compromising immune effector cell therapy efficacy. Glucocorticoids are reserved for refractory or severe cytokine release syndrome due to concern for attenuating antitumor activity. Optimizing the timing of tocilizumab could avoid glucocorticoid use and improve outcomes. This study assesses tocilizumab timing on patient outcomes and healthcare resource utilization. METHODS: This is a retrospective single-institution analysis of 28 patients who received tocilizumab for cytokine release syndrome secondary to immune effector cell therapy. Patients were categorized into two groups: Early Tocilizumab (within 24 h) or Late Tocilizumab groups (more than 24 h) from fever onset. The composite primary endpoint was glucocorticoid use, intensive care unit admission, or inpatient mortality. Secondary outcomes include comparing the various presentations of cytokine release syndrome, need for vasopressors, length of stay, rates of neurotoxicity, and C-reactive protein and ferritin trends. RESULTS: The Early Tocilizumab group presented with more rapid fever onset (35 vs.113 h, P = 0.017) and higher maximum cytokine release syndrome grade (Median, Grade 2 vs. Grade 1, P = 0.025). Additionally, the Early Tocilizumab group required more doses of tocilizumab (Median, 2 vs. 1, P = 0.037). Despite the difference in cytokine release syndrome presentation, the primary composite endpoint was not statistically different between groups. CONCLUSION: Earlier onset of fever appears to be associated with more severe, progressive cytokine release syndrome requiring multiple doses of anti-interleukin-6 therapy. Prompt and aggressive tocilizumab treatment could be protective against the negative consequences of cytokine release syndrome.

Robotic-assisted laparoscopic repair of a congenital rectourethral fistula with duplicated urethra.

OBJECTIVE: To describe our experience with robot-assisted laparoscopic transperitoneal repair of a congenital rectourethral fistula in a pediatric patient with a urethral duplication. METHODS: The patient is a 2-year-old male with a past medical history of Tetralogy of Fallot presenting with a febrile urinary tract infection (UTI). He was diagnosed with urethral duplication and a rectourethral fistula by voiding cystourethrogram (VCUG). The parents were counseled on various options and agreed to proceed with a robotic repair. RESULTS: Robotic-assisted transperitoneal rectourethral fistula repair was performed. The procedure time was 229 min with an estimated blood loss (EBL) of 15 mL. His postoperative course was unremarkable. At his 2-week follow-up, the urethral catheter was removed and the patient was voiding normally and having normal bowel movements. CONCLUSION: Congenital rectourethral fistula with urethral duplication is a rare anomaly with only a few reports in the literature. Pediatric robotic-assisted transperitoneal rectourethral fistula repair is a technically feasible approach in infants with minimal morbidity that allows for excellent visualization and avoids open repair.

Inhibition of hypoxia-inducible factor-prolyl hydroxylation protects from cyclophosphamide-induced bladder injury and urinary dysfunction.

Disruption of the blood-urine barrier can result in acute or chronic inflammatory bladder injury. Activation of the oxygen-regulated hypoxia-inducible factor (HIF) pathway has been shown to protect mucosal membranes by increasing the expression of cytoprotective genes and by suppressing inflammation. The activity of HIF is controlled by prolyl hydroxylase domain (PHD) dioxygenases, which have been exploited as therapeutic targets for the treatment of anemia of chronic kidney disease. Here, we established a mouse model of acute cyclophosphamide (CYP)-induced blood-urine barrier disruption associated with inflammation and severe urinary dysfunction to investigate the HIF-PHD axis in inflammatory bladder injury. We found that systemic administration of dimethyloxalylglycine or molidustat, two small-molecule inhibitors of HIF-prolyl hydroxylases, profoundly mitigated CYP-induced bladder injury and inflammation as assessed by morphological analysis of transmural edema and urothelial integrity and by measuring tissue cytokine expression. Void spot analysis to examine bladder function quantitatively demonstrated that HIF-prolyl hydroxylase inhibitor administration normalized micturition patterns and protected against CYP-induced alteration of urinary frequency and micturition patterns. Our study highlights the therapeutic potential of HIF-activating small-molecule compounds for the prevention or therapy of bladder injury and urinary dysfunction due to blood-urine barrier disruption.NEW & NOTEWORTHY Disruption of the blood-urine barrier can result in acute or chronic inflammatory bladder injury. Here, we demonstrate that pharmacological inhibition of hypoxia-inducible factor (HIF)-prolyl hydroxylation prevented bladder injury and protected from urinary dysfunction in a mouse model of cyclophosphamide-induced disruption of the blood-urine barrier. Our study highlights a potential role for HIF-activating small-molecule compounds in the prevention or therapy of bladder injury and urinary dysfunction and provides a rationale for future clinical studies.

Exploring the Feasibility of a Mindfulness-Music Therapy Intervention to Improve Anxiety and Stress in Adolescents and Young Adults with Cancer.

CONTEXT: Adolescent and young adults (AYAs) with cancer experience significant psychological distress due to cancer treatment that can persist long after treatment. However, little is known regarding optimal interventions to support the psychosocial needs of AYAs with cancer. OBJECTIVE: The overall objective of this single arm, longitudinal, pilot study was to determine the feasibility of implementing a mindfulness-based music therapy intervention to improve anxiety and stress in AYAs receiving cancer treatment. METHODS: AYAs (15 - 39 years old) who were to receive cancer treatment for ≥ eight weeks were recruited from the pediatric, melanoma, sarcoma, breast, lymphoma, and leukemia oncology outpatient centers at Dana-Farber Cancer Institute. The music therapy intervention included four sessions of individual mindfulness-based music therapy in-person or using Zoom over twelve weeks. Prior to-and after the intervention period, participants completed the Patient-Reported Outcomes Measurement Information Anxiety 4a and Perceived Stress Scale. Changes in patient-reported outcomes are compared using Wilcoxon signed-rank tests. RESULTS: Over ∼14 months, 37 of 93 eligible AYAs were enrolled to the study (39.8% consent rate). Overall, 27 of 37 (73%) participants (Median age=32; 56.8% Female) completed at least two music therapy sessions and the baseline measures and end of study measures. Participation in the mindfulness-based music therapy sessions resulted in significant pre-to-posttest improvements in perceived stress (median change: -4.0, P = 0.013) and non-significant changes in anxiety (median change: -1.9, P = 0.20). Satisfaction and acceptability were highly rated. CONCLUSIONS: The delivery of a four-session mindfulness-based music therapy intervention to AYAs receiving chemotherapy was feasible and significantly improved perceived stress. These preliminary findings should be confirmed in a randomized controlled trial. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03709225.

Hidden consequences of patient satisfaction: A survey of pediatric surgeons.

BACKGROUND: Patient satisfaction surveys are increasingly utilized to assess patients' perceptions of their health care. Recently, these scores have been linked to payment, potentially incentivizing practices to meet certain metrics. We hypothesize that increasing pressures to receive positive reviews have led physicians to alter the delivery of their care to accommodate patient expectations over standards of care. METHODS: An 11-question REDCap™ survey was developed and emailed anonymously to all sixty-two surgeons across all surgical subspecialties at our children's hospital. Multiple-choice and open-ended questions were included. A modified Delphi method was used to acquire general consensus. RESULTS: Survey response rate for analysis was 41/62 (66%). 23 (56%) stated that they have changed their clinical practice patterns due to concerns regarding patient dissatisfaction. Examples of such changes included: requesting imaging tests or laboratory studies, performing invasive procedures, referring for second opinions, and prescribing medications. Only 2% felt that these interventions led to any significant change in outcome of a patient's condition. Several respondents expressed concerns that factors outside their control (scheduling, parking, wait times) contributed to patient dissatisfaction and affected providers' ratings, while others expressed concerns about inherent biases driving survey participants. CONCLUSIONS: As a result of patient satisfaction surveys, a significant number of surgeons reported altering their clinical practice beyond standard care to meet patient expectations. Some of these modifications included performing unnecessary interventions. Reliance on these surveys may be at odds with reducing health care costs and avoiding physician burnout. These and other unintended consequences of patient satisfaction surveys warrant further study before they are widely accepted as appropriate quality metrics. LEVEL OF EVIDENCE: Level IV, questionnaire.

Stem cell antigen/Ly6a protects against bladder fibrosis in mice.

We have defined a population of stem cell antigen (Sca)-1+/CD34+/lin- mesenchymal stem cells in the mouse urinary bladder. These cells are reduced after partial bladder outlet obstruction (PO). To test the role of Sca-1 expressed by these cells, we analyzed bladders from Sca-1 knockout (KO) mice in both uninjured male mice and male mice subjected to PO. We found that loss of Sca-1 alone had little effect on bladder development or function but reduced the total number of mesenchymal stem cells by 30%. After PO, bladders from Sca-1-null KO male mice were larger, with more collagen and less muscle, than obstructed wild-type mice. Steady-state levels of caldesmon were significantly reduced and levels of fibroblast-specific protein 1 were significantly increased in Sca-1 KO mice compared with wild-type mice after PO. In investigating the effects of PO on cell proliferation, we found that loss of Sca-1 changed the timing of cell division in CD34+/lin-, collagen-producing, and smooth muscle cells. PO in combination with loss of Sca-1 drastically reduced the ability of CD34+/lin- cells to form colonies in vitro. Our findings therefore support the hypothesis that Sca-1 protects the bladder from fibrotic remodeling after obstruction, in part by influencing the proliferation of cells responding to the injury.

Thirty-day hospital revisits after prostate brachytherapy: who is at risk?

BACKGROUND: Transperineal prostate brachytherapy is a common outpatient procedure for the treatment of prostate cancer. Whereas long-term morbidity and toxicities are widely published, rates of short-term complications leading to hospital revisits have not been well described. MATERIALS AND METHODS: Patients who underwent brachytherapy for prostate cancer in an ambulatory setting were identified in the Healthcare Cost and Utilization Project State Ambulatory Surgery Database for California between 2007 and 2011. Emergency department (ED) visits and inpatient admissions within 30 days of treatment were determined from the California Healthcare Cost and Utilization Project State Emergency Department Database and State Inpatient Database, respectively. RESULTS: Between 2007 and 2011, 9,042 patients underwent brachytherapy for prostate cancer. Within 30 days postoperatively, 543 (6.0%) patients experienced 674 hospital encounters. ED visits comprised most encounters (68.7%) at a median of 7 days (interquartile range 2-16) after surgery. Inpatient hospitalizations occurred on 155 of 674 visits (23.0%) at a median of 12 days (interquartile range 5-20). Common presenting diagnoses included urinary retention, malfunctioning catheter, hematuria, and urinary tract infection. Logistic regression demonstrated advanced age {65-75 years: odds ratio [OR], 1.3 [95% confidence interval (CI) 1.06-1.60, P = 0.01]; >75 years: OR 1.5 [95% CI 1.18-1.97, P = 0.001]}, inpatient admission within 90 days before surgery [OR 2.68 (95% CI 1.8-4.0, P < 0.001)], and ED visit within 180 days before surgery [OR 1.63 (95% CI 1.4-1.89, P < 0.001)] as factors that increased the risk of hospital-based evaluation after outpatient brachytherapy. Charlson comorbidity score did not influence risk. CONCLUSIONS: ED visits and inpatient admissions are not uncommon after prostate brachytherapy. Risk of revisit is higher in elderly patients and those who have had recent inpatient or ED encounters.

Estimated kidney function in children and young adults with spina bifida: A retrospective cohort study.

AIMS: Current estimated glomerular filtration rate (eGFR) equations may be inaccurate in patients with spina bifida (SB) because of reduced muscle mass and stature. Cross-sectional and longitudinal variability of eGFR were analyzed in these patients across multiple equations, hypothesizing greater variability in creatinine-based than cystatin-C (Cys-C)-based equations. METHODS: This retrospective cohort study included children (age, 1-17.9 years) and adults (≥18 years) with SB from 2002-2017 at a large SB clinic. Those without all data needed to calculate eGFR were excluded. Four pediatric and three adult eGFR equations were compared for cross-sectional outcomes of eGFR and elevated office blood pressures using chronic kidney disease (CKD) stage classification, and for longitudinal outcome of eGFR slope over time using covariance pattern models accounting for repeated measures. RESULTS: One hundred and eighty two children and 75 adults had greater than or equal to 1 set of data measurements; 118 and 52, respectively, had greater than or equal to 2 sets. The pediatric bedside Schwartz equation had the highest median eGFR and coefficient of variation. CKD stage classification by eGFR showed large differences across equations in children, with rates of eGFR < 60 and <90 ml/min/1.73 m2 ranging from 2%-9% and 5%-69%, respectively. Only one equation showed a significant inverse association between eGFR and blood pressure. Longitudinally, eGFR slopes over time were different across pediatric equations (P < .001) but not adult equations. The bedside Schwartz equation had a positive eGFR slope; the other Cys-C-containing equations had negative slopes. CONCLUSIONS: Creatinine-based equations in children with SB vary considerably from cystatin-C-containing equations in calculating both single point-in-time eGFR values and eGFR trends over time.

The July Effect in Urological Surgery-Myth or Reality?

INTRODUCTION: The July effect is the widely held belief that medical care is compromised at the beginning of the academic year due to transitioning medical trainees. We determined its impact on surgical outcomes in urological surgery. METHODS: The Healthcare Cost and Utilization Project State Inpatient Database, State Ambulatory Surgery and Services Database and State Emergency Department Database for California were used for the years 2007 to 2011. Patients were identified who underwent surgery in July, August, April and May, and separated into early (July and August) and late (April and May) cohorts. Surgical outcomes for early vs late surgery were compared for academic centers. Adjusted multivariate models were fit to determine the effect of early surgery as a predictor of adverse outcomes. RESULTS: For major urological surgery July/August timing had no impact on length of stay, 30-day readmission, 30-day emergency room visits, never events, perioperative complications or mortality (all values p >0.05). Similarly, for stone, groin, bladder outlet and cystoscopic bladder procedures, July/August surgery had no impact on rates of urinary retention, emergency room visits within 30 days, clot evacuations within 30 days, perioperative complications or 30-day readmissions (all values p >0.05). At the end of the year cystectomies had increased odds of intraoperative complications (OR 0.63, 95% CI 0.4-0.97) while nephrectomies had higher odds of major complications (OR 0.69, 95% CI 0.53-0.89). CONCLUSIONS: Surgical outcomes are not compromised by having surgery at the beginning of the academic year, despite resident turnover, representing appropriate oversight during this potentially vulnerable time.

Robot-assisted laparoscopic transplant-to-native ureteroureterostomy of an intraperitoneal renal allograft.

OBJECTIVE: The objective is to describe our experience with robot-assisted laparoscopic transplant-to-native ureteroureterostomy (UU) in a pediatric patient with an intraperitoneal renal allograft. We have previously demonstrated this technique for an extraperitoneal allograft. METHODS: The patient is a 17-year-old female who had undergone a deceased donor renal transplant at 5 years of age. She developed acute kidney injury and hydronephrosis because of a ureteral stricture that developed after a right ovarian cyst excision. A retrograde pyelogram of her native ureter showed normal morphology. Her options were discussed and she proceeded with a robotic transplant-to-native UU. RESULTS: Robot-assisted laparoscopic transplant-to-native UU was performed via an intraperitoneal approach. The procedure time was 217 min with an estimated blood loss of 10 mL. Her postoperative course was unremarkable. After ureteral stent removal, her serum creatinine remained stable and follow-up imaging showed an improvement in hydronephrosis. CONCLUSIONS: Pediatric robot-assisted laparoscopic transplant-to-native UU for an intraperitoneal allograft is a technically feasible approach for the treatment of transplant ureteral strictures that combines the durability of open revision with the minimal invasiveness of endourologic management.

Pushing Boundaries: Robotic Nephrectomy of an Auto-transplanted Kidney for Recurrent Renal Cell Carcinoma.

Advances in robotic technology continue to expand the boundaries of minimally invasive approaches in transplant surgery. A single report has previously described the use of the robotic approach in transplant nephrectomy for a failed allograft. Our objective is to describe our technique and experience for the first reported robotic nephrectomy of an auto-transplanted solitary kidney for a recurrence of renal cell carcinoma (RCC). We highlight technical considerations during allograft mobilization and hilum dissection with the additional demands of a previously operated auto-transplant kidney.

Implications of postoperative pulmonary aspiration following major urologic surgery.

INTRODUCTION: The purpose of this article is to assess the incidence of pulmonary aspiration following major urologic surgery, predictors of an aspiration event, and subsequent clinical outcomes. MATERIALS AND METHODS: The Healthcare Cost and Utilization Project State Inpatient Database for California between 2007-2011 was used to identify cystectomy, prostatectomy, partial and radical nephrectomy patients. Aspiration events were identified within 30 days of surgery. The primary outcome was 30 day mortality and secondary outcomes included total length of stay, discharge location, and diagnoses of acute renal failure, pneumonia or sepsis. Descriptive statistics were performed. A multivariable logistic regression was performed to determine independent predictors of an aspiration event. A separate nonparsimonious logistic regression was fit to determine the independent effect of an aspiration event on 30 day mortality. RESULTS: Of 84,837 major urologic surgery patients 319 (0.4%) had an aspiration event. Risk factors for aspiration included ileus, congestive heart failure, paraplegia, chronic lung disease, and age = 80 years (all p < 0.01). Aspiration patients had higher rates of renal failure (36.1% versus 2.5%), pneumonia (36.1% versus 2.5%), sepsis (35.7% versus 0.7%), a prolonged length of stay (17 days versus 3 days), and discharge to nursing facility(26.3% vs 2.3%) (all p<0.001). The 30 day mortality rate following aspiration was 20.7% compared to 0.8% (p < 0.001). Aspiration independently increases the risk of 30 day mortality (OR 3.1 (95%CI 2.2-4.5). CONCLUSIONS: Postoperative aspiration following major urologic surgery is a devastating complication and precautions must be undertaken in high risk patient populations to avoid such an event.

Robot-assisted laparoscopic megaureter tapering with ureteral reimplantation: Tips and tricks.

OBJECTIVE: The aim was to demonstrate surgical techniques used in pediatric robot-assisted laparoscopic megaureter tapering (RALMT) with ureteral reimplantation. We report on our preliminary experience. METHODS: We reviewed video of patients who underwent RALMT with ureteral reimplantation between August 2012 and November 2015. MT was performed extravesically and ureteral reimplantation was performed by extravesical detrusorrhaphy with ureteral anchoring. All patients had an intraoperatively placed ureteral stent. RESULTS: Between August 2012 and November 2015, 14 patients underwent RALMT with ureteral reimplantation. Highlighted techniques include variations in ureteral stent insertion, method of excisional tapering, and approach to reimplantation. All (10/10) patients with postoperative ultrasounds following ureteral stent removal demonstrated radiographic improvement at a mean follow-up of 9 months. No patients had postoperative febrile urinary tract infections. The only complication was one patient with postoperative ileus. CONCLUSIONS: We demonstrate variations in surgical techniques which may facilitate the surgical steps of RALMT with ureteral reimplantation. Our preliminary experience suggests the procedure is safe and feasible for pediatric patients with symptomatic megaureter.

Functional Implications of Renal Tumor Enucleation Relative to Standard Partial Nephrectomy.

OBJECTIVE: To compare the surgical precision for optimizing nephron-mass preservation of tumor enucleation (TE) vs standard partial nephrectomy (SPN), with primary focus on functional outcomes. TE is presumed to optimize preservation of parenchymal mass and function but this has not yet been rigorously studied and quantified. MATERIALS AND METHODS: Robotic partial nephrectomy patients who had appropriate pre- and postoperative studies for analysis of parenchymal mass preservation specific to the operated kidney were included. Computed tomography or magnetic resonance imaging and estimated glomerular filtration rate were required to be <2 months prior and 4-12 months after surgery. Parenchymal mass preservation and surgical precision were estimated for each technique, with precision defined as actual postoperative parenchymal volume or predicted postoperative parenchymal volume, presuming loss of a 5 mm rim of parenchyma associated with tumor excision and reconstruction. RESULTS: Analysis included 57 TE and 53 SPN. Median age, body mass index, and tumor size were comparable. Percent parenchymal mass preserved in the operated kidney with TE was 96% (interquartile range [IQR] = 90-100) vs 89% (IQR = 83-96) for SPN (P = .003). Precision of excision or reconstruction was 101% (IQR = 96-105) for TE vs 94% (IQR = 88-100) for SPN (P < .001). On multivariable analysis, only TE correlated with improved surgical precision (coefficient = 6.7, 95% confidence interval = 1.6-11.8, P = .01). Although preservation of global renal function also favored TE, the differences were marginal (96% vs 93%), and statistical significance was not observed (P = .2). CONCLUSION: Our analysis, which specifically focuses on the functional implications of TE, demonstrates that TE maximally spares normal parenchyma compared to SPN. Thus far, functional differences remain marginal and not statistically significant. Clinical significance of these findings in various clinical settings will require further investigation.

Targeting CBLB as a potential therapeutic approach for disseminated candidiasis.

Disseminated candidiasis has become one of the leading causes of hospital-acquired blood stream infections with high mobility and mortality. However, the molecular basis of host defense against disseminated candidiasis remains elusive, and treatment options are limited. Here we report that the E3 ubiquitin ligase CBLB directs polyubiquitination of dectin-1 and dectin-2, two key pattern-recognition receptors for sensing Candida albicans, and their downstream kinase SYK, thus inhibiting dectin-1- and dectin-2-mediated innate immune responses. CBLB deficiency or inactivation protects mice from systemic infection with a lethal dose of C. albicans, and deficiency of dectin-1, dectin-2, or both in Cblb(-/-) mice abrogates this protection. Notably, silencing the Cblb gene in vivo protects mice from lethal systemic C. albicans infection. Our data reveal that CBLB is crucial for homeostatic control of innate immune responses mediated by dectin-1 and dectin-2. Our data also indicate that CBLB represents a potential therapeutic target for protection from disseminated candidiasis.