Emerging pharmacological strategies for treating and preventing mpox.

INTRODUCTION: Since May 2022, there have been nearly 87,000 documented cases of mpox worldwide, with 119 deaths. Pharmacological interventions for mpox include the MVA-BN smallpox vaccine, tecovirimat, cidofovir, its pro-drug brincidofovir, and vaccinia immune globulin intravenous (VIGIV). AREAS COVERED: The literature search and information gathering for this review included the PubMed database focusing on mpox and monkeypox, in combination with tecovirimat, brincidofovir, cidofovir, VIGIV, and smallpox vaccine. WHO.int, CDC.gov, FDA.gov, and ClinicalTrials.gov websites were accessed for the most recent information on the mpox outbreak. Mechanisms for deployment and access to treatment including expanded access, emergency use, and clinical trials will be discussed. Treatment outcomes with safety data will be presented. EXPERT OPINION: The vaccine as a preventive measure, along with numerous treatment options, largely controlled the outbreak, although deployment of each could be improved upon to hasten and broaden access. More widespread coverage by the vaccine is necessary to prevent future resurgence of mpox. Tecovirimat has emerged as a safe frontline treatment for mpox, while brincidofovir use has been limited by safety concerns. VIGIV and cidofovir should be reserved for the most severe cases in which other options are not fully effective.

Posterior urethral morphology on initial voiding cystourethrogram correlates to early renal outcomes in infants with posterior urethral valves.

INTRODUCTION: Posterior urethral valves (PUV) is a leading cause of chronic renal failure in childhood. Bladder and posterior urethral deformity in infants with PUV are highly variable on initial voiding cystourethrogram (VCUG). Some types of deformity may be more important than others in determining the severity of the condition. Identification of specific VCUG features may allow for a simple, early screening assessment for patients. OBJECTIVE: Determine whether morphologic features on the initial VCUG correlate to renal outcomes as measured by the creatinine nadir in the first year after ablation. METHODS: Children with PUV treated by primary valve ablation before 12 months old and followed >1 year were identified. Initial diagnostic VCUG was evaluated for the bladder height to width ratio (HW-B), posterior urethral height to width ratio (HW-PU), and posterior-anterior urethral ratio (PA-UR). A trabeculation grade was assigned by three pediatric urologists, and reflux was noted. Univariable analyses with chi-square and t-test were used to compare bladder and posterior urethral morphology factors among those who obtained a creatinine nadir <0.8 or ≥0.8 mg/dL in the first year after ablation. Linear regression was performed to correlate morphology values with true creatinine nadir. RESULTS: A total of 120 boys were ablated at mean age of 40.5 days (range 0-342) and followed for 5.9 years (± 3.85). Among these, 21 (17.5%) had a creatinine nadir ≥0.8 mg/dL. Mean overall HW-B and mean PA-UR were not significantly different between those with creatinine nadir <0.8 versus ≥0.8 mg/dL. Bladder trabeculation grade was not associated with creatinine nadir. For the entire cohort, only the difference in HW-PU was statistically significant between creatinine nadir groups with a much higher ratio among those with a nadir ≥0.8 (p < 0.001). Linear regression demonstrated a significant positive correlation between the HW-PU and creatinine nadir (R 2 = 0.097, p = 0.002). The presence of bilateral reflux is significantly associated with creatinine nadir ≥0.8 mg/dL (p = 0.001). DISCUSSION: We investigate for the first time the association of morphology features on the initial VCUG with renal outcome in PUV patients. Posterior urethral deformity as quantified by a higher HW-PU ratio is significantly correlated with a higher creatinine nadir, whereas measured bladder morphology metrics are not. HW-PU may be an indirect measure of the severity of obstruction in posterior urethral valves. CONCLUSION: The HW-PU appears to be a meaningful early morphologic metric for renal outcome.

Predicting childhood chronic kidney disease severity in infants with posterior urethral valve: a critical analysis of creatinine values in the first year of life.

BACKGROUND: Posterior urethral valve (PUV) is a leading cause of chronic kidney failure in children. Studies have shown that a creatinine nadir above historical cutoff values of 0.8 or 1.0 mg/dL correlates with worse kidney outcomes. The ability to use nadir creatinine more discriminately as a test of kidney outcomes is otherwise limited. METHODS: We performed a retrospective review of 102 infants treated with primary valve ablation prior to 1 year of age. Patient factors including creatinine at presentation (Cr-P), nadir within 6 weeks after ablation (Cr-6 W), and nadir within 1 year after ablation (Cr-1Y) were assessed as predictors of final chronic kidney disease (CKD) severity. An optimal threshold for four CKD levels was defined in incremental fashion using binary outcome with receiver operating characteristic (ROC). Multivariable logistic regression models compared Cr-P, Cr-6 W, and Cr-1Y while adjusting for patient factors. RESULTS: Boys were ablated at mean age of 36.3 days and followed for 6.6 years (± 3.7). When compared to other demographics, only creatinine remained independently predictive of CKD outcomes on multivariable analysis. ROC analysis demonstrated excellent diagnostic accuracy for Cr-6 W and Cr-1Y (p < 0.001) and acceptable accuracy for Cr-P (p < 0.005). Using the Cr-6 W and Cr-1Y models, high sensitivity and specificity creatinine nadir cutoffs were determined to predict each CKD outcome. CONCLUSIONS: The severity of childhood CKD can be predicted with high accuracy using the creatinine nadir within 6 weeks of ablation. The cutoff values described can be incorporated into a clinical setting for patient counseling and individual risk stratification.

Role of a Preoperative Catheter Regimen in Achieving Early Primary Endoscopic Valve Ablation in Neonates with Posterior Urethral Valves.

PURPOSE: Primary valve ablation is preferred to vesicostomy in the initial management of posterior urethral valves. However, some neonates have a prohibitively small urethra. We describe our experience with a preoperative urethral catheter regimen to enhance the likelihood of neonatal valve ablation. MATERIALS AND METHODS: We performed a retrospective review of 126 neonates with posterior urethral valves treated between 2003 and 2019 with valve ablation prior to 10 weeks of age. The preoperative indwelling catheter either was gradually upsized to an 8Fr (progressive urethral dilation), was not upsized (nondilated) or was initially larger bore (8Fr only). The primary outcome was the ability to perform primary ablation by neonatal resectoscope. The secondary objective was to establish the parameters for considering progressive urethral dilation as well as its associated risks. RESULTS: Overall 97% could be ablated. The progressive urethral dilation group had the lowest mean weight (p <0.001). Only a larger catheter at the time of ablation was significantly associated with feasible ablation (p <0.001) and not urethral dilation, the infant's weight or his gestational age. Progressive urethral dilation was associated with a longer duration of catheterization as well as double the rate of febrile urinary tract infections (8.5%) over the nondilated group (3.6%). CONCLUSIONS: A much higher rate of primary ablation is feasible (97%) than previously reported (82%). More important than the infant's weight is whether a 6Fr to 8Fr catheter is in place at ablation. If an initial 6Fr to 8Fr catheter cannot be placed, urethral dilation to 8Fr should be performed before attempting ablation. This is both a technique and preoperative assessment that is useful for operative planning.

Did COVID-19 Affect Time to Presentation in the Setting of Pediatric Testicular Torsion?

OBJECTIVES: To determine if boys with acute testicular torsion, a surgical emergency requiring prompt diagnosis and treatment to optimize salvage of the testicle, delayed presentation to a medical facility and experienced an extended duration of symptoms (DoS), and secondarily, a higher rate of orchiectomy, during the coronavirus disease 2019 (COVID-19) pandemic. METHODS: Single-center, descriptive retrospective chart review of boys presenting with acute testicular torsion from March 15, to May 4, 2020 ("during COVID-19" or group 2), as well as for the same time window in the 5-year period from 2015 to 2019 ("pre-COVID-19" or group 1). RESULTS: A total of 78 boys met inclusion criteria, group 1 (n = 57) and group 2 (n = 21). The mean age was 12.86 ± 2.63 (group 1) and 12.86 ± 2.13 (group 2). Mean DoS before presentation at a medical facility was 23.2 ± 35.0 hours in group 1 compared with 21.3 ± 29.7 hours in group 2 (P < 0.37). When DoS was broken down into acute (<24 hours) versus delayed (≥24 hours), 41 (71.9%) of 57 boys in group 1 and 16 (76.2%) of 21 boys in group 2 presented within less than 24 hours of symptom onset (P < 0.78). There was no difference in rate of orchiectomy between group 1 and group 2 (44.7% vs 25%, P < 0.17), respectively. CONCLUSIONS: Boys with acute testicular torsion in our catchment area did not delay presentation to a medical facility from March 15, to May 4, 2020, and did not subsequently undergo a higher rate of orchiectomy.

Airway Sensory Nerve Density Is Increased in Chronic Cough.

Rationale: Chronic cough is characterized by frequent urges to cough and a heightened sensitivity to inhaled irritants. Airway sensory nerves trigger cough. We hypothesized that sensory nerve density is increased in chronic cough, which may contribute to excessive and persistent coughing.Objectives: To measure airway nerve density (axonal length) and complexity (nerve branching, neuropeptide expression) in humans with and without chronic cough.Methods: Bronchoscopic human airway biopsies were immunolabeled for nerves and the sensory neuropeptide substance P. Eosinophil peroxidase was also quantified given previous reports showing associations between eosinophils and nerve density. Three-dimensional image z-stacks of epithelium and subepithelium were generated using confocal microscopy, and from these z-stacks, total nerve length, the number of nerve branch points, substance P expression, and eosinophil peroxidase were quantified within each airway compartment.Measurements and Main Results: Nerve length and the number of branch points were significantly increased in epithelium, but not subepithelium, in chronic cough compared with healthy airways. Substance P expression was scarce and was similar in chronic cough and healthy airways. Nerve length and branching were not associated with eosinophil peroxidase nor with demographics such as age and sex in either group.Conclusions: Airway epithelial sensory nerve density is increased in chronic cough, suggesting sensory neuroplasticity contributes to cough hypersensitivity.

High incidence of abnormal imaging findings in circumcised boys diagnosed with urinary tract infections.

BACKGROUND: The American Academy of Pediatrics guidelines recommend delaying voiding cystourethrogram (VCUG) until the second febrile urinary tract infection (UTI). Similarly, the NICE Guidelines do not recommend VCUG after the first febrile UTI in infants and children under three years of age. Currently, there is no good clinical indicator to determine which patients would benefit from an earlier cystogram. Here, we sought to identify clinical and bacteriologic findings that are associated with an increased risk of urinary tract anatomic anomalies in pediatric males presenting to the Emergency Department with a UTI. METHODS: A retrospective review was performed of all urine cultures from the Emergency Department at our institution between 2006 and 2015. Males under 18 years of age with ≥50,000 CFU/mL of Proteus, Klebsiella, Escherichia coli, Staphylococcus, Streptococcus and Enterococcus were included. Clean catch, catheterized and suprapubic aspiration specimens were included. Bagged specimens and specimens from patients on intermittent catheterization were excluded. Ultrasound and cystogram images were reviewed when available. Univariate and multivariable Poisson regression with robust variance was used to calculate and compare prevalence ratios. Statistical analysis was performed with Stata software, version 15.1 MP (Stata Corporation, College Station, Texas, USA). RESULTS: We reviewed 1585 urine cultures, of which 812 met eligibility criteria including 619 (76.2%) E. coli, 84 (10.3%) Proteus, 55 (6.8%) Klebsiella, 29 (3.6%) Staphylococcus, 13 (1.6%) Enterococcus and 12 (1.5%) Streptococcus. Median age was six months (2.4-36 months IQR). After adjusting for age, ethnicity and bacterial species, the prevalence of dilating vesicoureteral reflux (VUR, defined as grades III-V) was 5.3 times higher in circumcised males compared to uncircumcised males (95% CI: 2.4-11.4, p = 0.001). Circumcised males had a 3.1 times increased prevalence of high-grade hydronephrosis (defined as SFU grades 3 and 4) compared to uncircumcised males (prevalence ratio: 3.1, 95% CI: 1.0-10.0, p = 0.05). Among bacterial pathogens, no patients with Proteus UTI had high-grade hydronephrosis or dilating VUR. In contrast, Staphylococcal infections were associated significantly with dilating VUR (prevalence ratio 10.1, 95% CI: 2.3, 44.8; p = 0.002) and high-grade hydronephrosis (prevalence ratio 8.1, 95% CI: 1.7, 39.7; p = 0.010). CONCLUSIONS: Circumcision status is an independent predictor of structural urinary anomalies of the bladder and upper tracts in pediatric males with UTI, therefore circumcised males should be considered for early imaging, including VCUG, after their first UTI. Furthermore, Staphylococcal infections were associated with an even higher prevalence of high-grade hydronephrosis and dilating VUR and therefore warrant early investigation with VCUG. In contrast, none of the Proteus infections, which were seen almost exclusively in uncircumcised males, were associated with dilating VUR or hydronephrosis, making initial observation more appropriate in these patients.

Opioid utilization is minimal after outpatient pediatric urologic surgery.

INTRODUCTION: There are no guidelines for opioid use after pediatric urologic surgery, and it is unknown to what extent prescriptions written for these patients may be contributing to the opioid epidemic in the United States. We sought to characterize opioid utilization in a prospective fashion following outpatient pediatric urologic surgery at our institution. MATERIALS AND METHODS: After obtainingapproval from the Institutional Review Board, we prospectively recruited pediatric patients undergoing outpatient urologic surgery. All patients and families were counseled regarding appropriate use of over-the-counter pain medications as first-line agents, with opioids for breakthrough pain only. All patients received an opioid prescription (ORx), which we attempted to standardize to 10 doses. Parents were provided with a log for keeping track of pain medication administration. Postoperative surveys were sent at various time points after surgery to assess utilization of pain medications at home. We quantified unused opioids prescribed and evaluated factors potentially associated with opioid use. RESULTS: Two hundred and two patients were recruited. All patients were male, with a median age of 2.7 years (interquartile range (IQR) 5.5, range 0.5-17.9 years). One hundred and fifty-four children underwent penile surgery, 22 underwent scrotal surgery, and 27 underwent inguinal surgery. Nearly half of our study patients were black, 33.2% were white, 12.9% were Latino, and 4.0% were Asian. The median number of doses prescribed was 10 (IQR 0, range 4.0-20.8). Postoperative surveys were completed by 80.7% of study patients. The median number of opioid doses used was 0 (IQR 2), whereas the mean was 1.28 (standard deviation (SD) 1.98). None of the factors evaluated (including patient age, surgery type, perioperative pain management techniques, length of surgery, and insurance type) were associated with the amount of opioid used at home after surgery, as utilization was equally low across all groups. DISCUSSION AND CONCLUSIONS: Ensuring adequate postoperative pain control for children is critical, yet it is also important to minimize excess ORx. We found that the majority of pediatric patients used 0-2 doses of prescription pain medication after discharge following outpatient urologic surgery, representing a small percentage of the total prescribed amount. Low utilization was seen irrespective of patient age, procedure, and perioperative factors. These data can be used to guide perioperative patient and family counseling and to guide future efforts to standardize ORx following outpatient pediatric urologic surgery.

Optimization of patient-specific inhaler regimens with the use of the aerosol inhalation monitor.

OBJECTIVES: To describe the addition of a Vitalograph Aerosol Inhalation Monitor (AIM) assessment to a pharmacy bundle to optimize inhaler devices in patients with asthma and chronic obstructive pulmonary disease (COPD). SETTING: Hospital-based outpatient pulmonary clinic. PRACTICE DESCRIPTION: Ambulatory pharmacy service for underserved pulmonary patients in Detroit, MI. PRACTICE INNOVATION: Patients with asthma and COPD received a pharmacy bundle service that included inhaler technique assessment with the use of the AIM. Based on the patient's performance, an optimized pulmonary regimen was developed for the patient in collaboration with the pulmonologists. Follow-up telephone calls were made 1 and 4 weeks after the visit. EVALUATION: A 1-group pretest-posttest quasiexperimental study was conducted over a 6-month period. The primary objective of the study was to describe the impact that a pharmacist had on optimizing individuals' inhaled regimens. In addition, clinical outcomes including changes in asthma control test (ACT) and COPD assessment test (CAT) scores, rescue inhaler use, and patient adherence were assessed. RESULTS: A total of 44 patients were included in the study, of which 27 (61%) were determined to be on an inappropriate inhaler regimen according to their AIM assessment. The pharmacist subsequently made recommendations to change the device(s) for those patients, with the most common recommendation being a change to a nebulized regimen. There was a significant improvement in ACT/CAT scores, patient-reported inhaler use, and patient adherence at week 4 compared with baseline. CONCLUSION: Assessing inhaler technique with the use of the AIM allows pharmacists to identify an optimized inhaled regimen for patients with asthma and COPD and may be a potential solution to the problem of poor inhaler technique.

Eosinophils increase airway sensory nerve density in mice and in human asthma.

In asthma, airway nerve dysfunction leads to excessive bronchoconstriction and cough. It is well established that eosinophils alter nerve function and that airway eosinophilia is present in 50 to 60% of asthmatics. However, the effects of eosinophils on airway nerve structure have not been established. We tested whether eosinophils alter airway nerve structure and measured the physiological consequences of those changes. Our results in humans with and without eosinophilic asthma showed that airway innervation and substance P expression were increased in moderate persistent asthmatics compared to mild intermittent asthmatics and healthy subjects. Increased innervation was associated with a lack of bronchodilator responsiveness and increased irritant sensitivity. In a mouse model of eosinophilic airway inflammation, the increase in nerve density and airway hyperresponsiveness were mediated by eosinophils. Our results implicate airway nerve remodeling as a key mechanism for increased irritant sensitivity and exaggerated airway responsiveness in eosinophilic asthma.

Eosinophil and airway nerve interactions in asthma.

Airway eosinophils are increased in asthma and are especially abundant around airway nerves. Nerves control bronchoconstiction and in asthma, airway hyperreactivity (where airways contract excessively to inhaled stimuli) develops when eosinophils alter both parasympathetic and sensory nerve function. Eosinophils release major basic protein, which is an antagonist of inhibitory M2 muscarinic receptors on parasympathetic nerves. Loss of M2 receptor inhibition potentiates parasympathetic nerve-mediated bronchoconstriction. Eosinophils also increase sensory nerve responsiveness by lowering neurons' activation threshold, stimulating nerve growth, and altering neuropeptide expression. Since sensory nerves activate parasympathetic nerves via a central neuronal reflex, eosinophils' effects on both sensory and parasympathetic nerves potentiate bronchoconstriction. This review explores recent insights into mechanisms and effects of eosinophil and airway nerve interactions in asthma.

Anticoagulation of Percutaneous Ventricular Assist Device Using Argatroban-Based Purge Solution: A Case Series.

Impella devices are percutaneously inserted ventricular assist devices which require a continuous purge solution that contains heparin to prevent pump thrombosis and device failure. We describe 2 patients with heparin-induced thrombocytopenia (HIT) supported with an Impella device utilizing an argatroban-based purge solution. Case 1 involved an 83-year-old female with biventricular failure which resulted in right ventricle Impella support. The purge solution was changed to include argatroban due to concern of device clotting in the setting of HIT. Case 2 involved a 55-year-old male with worsening cardiogenic shock which resulted in left ventricle Impella support. Due to decreased purge flow rates and concerns for clotting, argatroban was added to the purge solution. Both patients' total argatroban regimens were monitored and adjusted by pharmacy, resulting in therapeutic anticoagulation without any major bleeding or thrombotic events. Subsequently, a protocol was designed and implemented. These case reports appear to demonstrate the safe and effective use of argatroban purge solutions for the necessary anticoagulation with an Impella device. Further studies are needed to confirm these results and determine the optimal dosing regimen.

Early Detection of Ureteropelvic Junction Obstruction Using Signal Analysis and Machine Learning: A Dynamic Solution to a Dynamic Problem.

PURPOSE: We sought to define features that describe the dynamic information in diuresis renograms for the early detection of clinically significant hydronephrosis caused by ureteropelvic junction obstruction. MATERIALS AND METHODS: We studied the diuresis renogram of 55 patients with a mean ± SD age of 75 ± 66 days who had congenital hydronephrosis at initial presentation. Five patients had bilaterally affected kidneys for a total of 60 diuresis renograms. Surgery was performed on 35 kidneys. We extracted 45 features based on curve shape and wavelet analysis from the drainage curves recorded after furosemide administration. The optimal features were selected as the combination that maximized the ROC AUC obtained from a linear support vector machine classifier trained to classify patients as with or without obstruction. Using these optimal features we performed leave 1 out cross validation to estimate the accuracy, sensitivity and specificity of our framework. Results were compared to those obtained using post-diuresis drainage half-time and the percent of clearance after 30 minutes. RESULTS: Our framework had 93% accuracy, including 91% sensitivity and 96% specificity, to predict surgical cases. This was a significant improvement over the same accuracy of 82%, including 71% sensitivity and 96% specificity obtained from half-time and 30-minute clearance using the optimal thresholds of 24.57 minutes and 55.77%, respectively. CONCLUSIONS: Our machine learning framework significantly improved the diagnostic accuracy of clinically significant hydronephrosis compared to half-time and 30-minute clearance. This aids in the clinical decision making process by offering a tool for earlier detection of severe cases and it has the potential to reduce the number of diuresis renograms required for diagnosis.

Prediction of Clinical Outcomes in Prenatal Hydronephrosis: Importance of Gravity Assisted Drainage.

PURPOSE: In infants with SFU (Society for Fetal Urology) grade 3-4 congenital hydronephrosis, 99mTc-mercaptoacetyltriglycine diuretic renography assesses differential function and drainage half-time. We routinely also include the percent of radiotracer drained after 30 minutes of diuresis as well as after 15 minutes with the patient in the upright position. We investigated whether any 1 or more of these parameters on initial diuretic renography predicts persistent or worsening drainage parameters. MATERIALS AND METHODS: Infants 6 months or younger with grade 3-4 congenital hydronephrosis who presented between January 2009 and December 2014 were identified from billing data and included in analysis if they underwent at least 1 baseline diuretic renography. Those with structural anomalies were excluded from study. Baseline and followup differential function, diuresis half-time, clearance at 30 minutes and clearance with the patient upright were abstracted and comparisons were made between those with initially indeterminate diuresis half-time who underwent pyeloplasty vs those showing spontaneous improvement. RESULTS: A total of 74 patients (82 renal units) with presumed ureteropelvic junction obstruction met inclusion/exclusion criteria. All 10 renal units with initial diuresis half-time less than 5 minutes resolved spontaneously and all 25 renal units with initial diuresis half-time greater than 75 minutes underwent pyeloplasty. Therefore, we defined the indeterminate group as the 47 renal units with initial half-time between 5 and 75 minutes. Of those 47 renal units with indeterminate initial diuresis half-time 23 (47%) underwent pyeloplasty and 25 (53%) resolved spontaneously. Indications for pyeloplasty included worsening in 17 cases, persistent obstruction in 4 and urinary tract infection in 1. Among renal units with indeterminate drainage clearance while upright and clearance at 30 minutes were the only variables that differed significantly between surgical cases and those that resolved spontaneously. CONCLUSIONS: Radiotracer clearance with the patient upright and clearance at 30 minutes are more predictive of surgical management than diuresis half-time or differential function for renal units with indeterminate drainage. They should be included in the standard assessment of ureteropelvic junction obstruction.

Robotically assisted ureteroscopy for kidney exploration.

Ureteroscopy is a minimally invasive procedure for diagnosis and treatment of a wide range of urinary tract pathologies. It is most commonly performed in the diagnostic work-up of hematuria and the diagnosis and treatment of upper urinary tract malignancies and calculi. Ergonomic and visualization challenges as well as radiation exposure are limitations to conventional ureteroscopy. For example, for diagnostic tumor inspection, the urologist has to maneuver the ureteroscope through each of the 6 to 12 calyces in the kidney under fluoroscopy to ensure complete surveillance. Therefore, we have been developing a robotic system to "power drive" a flexible fiber-optic ureteroscope with 3D tip tracking and pre-operative image overlay. Our goal is to provide the urologist precise control of the ureteroscope tip with less radiation exposure. Our prototype system allows control of the three degrees of freedom of the ureteroscope via brushless motors and a joystick interface. The robot provides a steady platform for controlling the ureteroscope. Furthermore, the robot design facilitates a quick "snap-in" of the ureteroscope, thus allowing the ureteroscope to be mounted midway through the procedure. We have completed the mechanical system and the controlling software and begun evaluation using a kidney phantom. We put MRI-compatible fiducials on the phantom and obtained MR images. We registered these images with the robot using an electromagnetic tracking system and paired-point registration. The system is described and initial evaluation results are given in this paper.

Tissue optical clearing, three-dimensional imaging, and computer morphometry in whole mouse lungs and human airways.

In whole adult mouse lung, full identification of airway nerves (or other cellular/subcellular objects) has not been possible due to patchy distribution and micron-scale size. Here we describe a method using tissue clearing to acquire the first complete image of three-dimensional (3D) innervation in the lung. We then created a method to pair analysis of nerve (or any other colabeled epitope) images with identification of 3D tissue compartments and airway morphometry by using fluorescent casting and morphometry software (which we designed and are making available as open-source). We then tested our method to quantify a sparse heterogeneous nerve population by examining visceral pleural nerves. Finally, we demonstrate the utility of our method in human tissue to image full thickness innervation in irregular 3D tissue compartments and to quantify sparse objects (intrinsic airway ganglia). Overall, this method can uniquely pair the advantages of whole tissue imaging and cellular/subcellular fluorescence microscopy.

Understanding clinic options for overactive bladder.

Overactive bladder (OAB) is a symptom complex of urinary frequency, nocturia and urgency with or without urgency incontinence that adversely impacts patient's quality of life. Conservative management begins in the outpatient clinic, often with significant improvement and patient satisfaction. In this review we will discuss the evaluation of OAB and review treatment options focusing on behavioral modification, medical therapy, and neuromodulation. These treatment options are offered in a stepwise fashion, remembering that more than one may be needed and can be used concomitantly.

Hypomethylation of the IL17RC promoter associates with age-related macular degeneration.

Age-related macular degeneration (AMD) is the leading cause of irreversible blindness in the elderly population worldwide. Although recent studies have demonstrated strong genetic associations between AMD and SNPs in a number of genes, other modes of regulation are also likely to play a role in the etiology of this disease. We identified a significantly decreased level of methylation on the IL17RC promoter in AMD patients. Furthermore, we showed that hypomethylation of the IL17RC promoter in AMD patients led to an elevated expression of its protein and messenger RNA in peripheral blood as well as in the affected retina and choroid, suggesting that the DNA methylation pattern and expression of IL17RC may potentially serve as a biomarker for the diagnosis of AMD and likely plays a role in disease pathogenesis.

Cardiovascular risk factors in hematopoietic cell transplantation survivors: role in development of subsequent cardiovascular disease.

Hematopoietic cell transplantation (HCT) recipients may be at an increased risk of developing hypertension, diabetes, and dyslipidemia (referred to as cardiovascular risk factors [CVRFs]); and these factors can potentially increase the risk of cardiovascular disease (CVD). We examined the incidence and predictors of CVRFs and subsequent CVD in 1885 consecutive 1+year survivors of HCT performed at City of Hope between 1995 and 2004. Ten-year cumulative incidence of hypertension, diabetes, dyslipidemia, and multiple (≥ 2) CVRFs was 37.7%, 18.1%, 46.7%, and 31.4%, respectively. The prevalence of CVRFs was significantly higher among HCT recipients compared with the general population; contributed to largely by allogeneic HCT recipients. Older age and obesity at HCT were associated with increased risk of CVRFs. History of grade II-IV acute graft versus host disease was associated with an increased risk for hypertension (relative risk [RR] = 9.1, P < .01), diabetes (RR = 5.8, P < .01), and dyslipidemia (RR = 3.2, P < .01); conditioning with total body irradiation was associated with an increased risk of diabetes (RR = 1.5, P = .01) and dyslipidemia (RR = 1.4, P < .01). There was an incremental increase in 10-year incidence of CVD by number of CVRFs (4.7% [none], 7.0% [1 CVRF], 11.2% [≥ 2 CVRFs], P < .01); the risk was especially high (15.0%) in patients with multiple CVRFs and pre-HCT exposure to anthracyclines or chest radiation.