Risk of major adverse cardiovascular events in rural vs urban settings among patients with erectile dysfunction: a propensity-weighted retrospective cohort study of 430 621 men.

BACKGROUND: The relationship between erectile dysfunction (ED) and cardiovascular (CV) events has been postulated, with ED being characterized as a potential harbinger of CV disease. Location of residence is another important consideration, as the impact of rural residence has been associated with worse health outcomes. AIM: To investigate whether men from rural settings with ED are associated with a higher risk of major adverse CV events (MACEs). METHODS: A propensity-weighted retrospective cohort study was conducted with provincial health administrative databases. ED was defined as having at least 2 ED prescriptions filled within 1 year. MACE was defined as the first hospitalization for an episode of acute myocardial infarction, heart failure, or stroke that resulted in a hospital visit >24 hours. We classified study groups into ED urban, ED rural, no ED urban, and no ED rural. A multiple logistic regression model was used to determine the propensity score. Stabilized inverse propensity treatment weighting was then applied to the propensity score. OUTCOMES: A Cox proportional hazard model was used to examine our primary outcome of time to a MACE. RESULTS: The median time to a MACE was 2731, 2635, 2441, and 2508 days for ED urban (n = 32 341), ED rural (n = 18 025), no ED rural (n = 146 358), and no ED urban (n = 233 897), respectively. The cohort with ED had a higher proportion of a MACE at 8.94% (n = 4503), as opposed to 4.58% (n = 17 416) for the group without ED. As compared with no ED urban, no ED rural was associated with higher risks of a MACE in stabilized time-varying comodels based on inverse probability treatment weighting (hazard ratio, 1.06-1.08). ED rural was associated with significantly higher risks of a MACE vs no ED rural, with the strength of the effect estimates increasing over time (hazard ratio, 1.10-1.74). CLINICAL IMPLICATIONS: Findings highlight the need for physicians treating patients with ED to address CV risk factors for primary and secondary prevention of CV diseases. STRENGTHS AND LIMITATIONS: This is the most extensive retrospective study demonstrating that ED is an independent risk factor for MACE. Due to limitations in data, we were unable to assess certain comorbidities, including obesity and smoking. CONCLUSIONS: Our study confirms that ED is an independent risk factor for MACE. Rural men had a higher risk of MACE, with an even higher risk among those who reside rurally and are diagnosed with ED.

Cardiovascular outcomes improve in children with renovascular hypertension following endovascular and surgical interventions.

BACKGROUND: Renovascular hypertension (RenoVH) is a cause of hypertension in children. A common cause of RenoVH is renal artery stenosis which acts by reducing blood supply to renal parenchyma and activating the renin-angiotensin-aldosterone axis, often leading to cardiac remodelling. This longitudinal observational study aims to describe occurrence of cardiovascular changes secondary to RenoVH and also any improvement in cardiac remodelling after successful endovascular and/or surgical intervention. METHODS: All patients with RenoVH referred to our centre, who received ≥ 1 endovascular intervention (some had also undergone surgical interventions) were included. Data were collected by retrospective database review over a 22-year period. We assessed oscillometric blood pressure and eight echocardiographic parameters pre- and post-intervention. RESULTS: One hundred fifty-two patients met inclusion criteria and had on average two endovascular interventions; of these children, six presented in heart failure. Blood pressure (BP) control was achieved by 54.4% of patients post-intervention. Average z-scores improved in interventricular septal thickness in diastole (IVSD), posterior Wall thickness in diastole (PWD) and fractional shortening (FS); left ventricular mass index (LVMI) and relative wall thickness (RWT) also improved. PWD saw the greatest reduction in mean difference in children with abnormal (z-score reduction 0.25, p < 0.001) and severely abnormal (z-score reduction 0.23, p < 0.001) z-scores between pre- and post-intervention echocardiograms. Almost half (45.9%) had reduction in prescribed antihypertensive medications, and 21.3% could discontinue all antihypertensive therapy. CONCLUSIONS: Our study reports improvement in cardiac outcomes after endovascular + / - surgical interventions. This is evidenced by BP control, and echocardiogram changes in which almost half achieved normalisation in systolic BP readings and reduction in the number of children with abnormal echocardiographic parameters. A higher resolution version of the Graphical abstract is available as Supplementary information.

Evidence of Chemoresponsiveness in Unresectable Metastatic Angiomatoid Fibrous Histiocytoma.

Angiomatoid fibrous histiocytoma (AFH) is a soft tissue neoplasm of intermediate biological potential. Typically a slow-growing tumor, it can recur locally. Rarely, it manifests as a soft tissue sarcoma capable of metastasis. When metastases are nonamenable to local therapy, it is believed uniformly fatal. We present 3 patients with metastatic AFH who demonstrated a sustained response to chemotherapy; including one who achieved complete remission with cryoablation. These cases reinforce the potential value of chemotherapy in some patients with unresectable metastatic AFH and provide the first case in the literature of cryoablation in AFH.

Diagnostic yield and safety of ultrasound-guided percutaneous testicular biopsies in children.

BACKGROUND: Traditionally, testicular biopsy is performed using an open surgical approach. Ultrasound-guided percutaneous biopsy is a less invasive alternative and can be performed in children. OBJECTIVE: The aim of this study is to report our technique and to assess the diagnostic accuracy and safety of ultrasound-guided percutaneous biopsy of testicular masses in children. MATERIALS AND METHODS: This is a 16-year retrospective review of ultrasound-guided percutaneous testicular biopsies at a single pediatric hospital. RESULTS: We performed nine ultrasound-guided testicular biopsies in 9 patients (median age: 3 years, range: 4 months-11 years; median weight: 20.9 kg, range: 8.4-35 kg; median volume of testicular lesion biopsied: 4.4 mL, range: 1.2-17 mL). A percutaneous co-axial technique was used for 5/9 biopsies with absorbable gelatin sponge tract embolization performed in 4 of those biopsies. A non-co-axial technique was used in 4/9 biopsies. A median of three cores, range 2-6, were obtained. The diagnostic yield was 89% with one biopsy yielding material suggestive of, but insufficient for, a definitive diagnosis. The most common histological diagnosis was leukemic infiltration, occurring in 6/9 biopsies. Of the remaining three biopsies, one biopsy was suggestive of, but not confirmatory for, juvenile granulosa cell tumor and two biopsies confirmed normal testicular tissue; the long-term follow-up of which demonstrated normal growth and no lasting damage. There was one (clinically insignificant) complication out of nine biopsies (11%, 95% confidence interval 0-44%): a mild, self-resolving scrotal hematoma. CONCLUSION: Ultrasound-guided testicular biopsy can be performed safely in children as an alternative to open surgical biopsy, with a high diagnostic yield and low complication rate.

Fostering research in pediatric interventional radiology: needs assessment and suggestions for support.

BACKGROUND: Due to the rarity of pediatric diseases, collaborative research is the key to maximizing the impact of research studies. A research needs assessment survey was created to support initiatives to foster pediatric interventional radiology research. OBJECTIVE: To assess the status of pediatric interventional radiology research, identify perceived barriers, obtain community input on areas of research/education/support, and create metrics for evaluating changes/responses to programmatic initiatives. MATERIALS AND METHODS: A survey link was sent to approximately 275 members of the Society for Pediatric Interventional Radiology (SPIR) between May and October 2020. Data was collected using a web-based interface. Data collected included practice setting, clinical role, research experience, research barriers, and suggestions for future initiatives. RESULTS: Fifty-nine surveys were analyzed with a staff physician survey response rate of 28% (56/198). A wide range of practice sizes from 15 countries were represented. Respondents were predominantly staff physicians (95%; 56/59) with an average of 11 years (range: 1-25 years) of clinical experience working at academic or freestanding children's hospitals. A total of 100% (59/59) had research experience, and 70% (41/58) had published research with a mean of 30 peer-reviewed publications (range: 1-200). For job security, 56% (33/59) of respondents were expected or required to publish, but only 19% (11/58) had research support staff, and 42% (25/59) had protected research time, but of those, 36% (9/25) got the time "sometimes or never." Lack of support staff, established collaborative processes, and education were identified as top barriers to performing research. CONCLUSIONS: The needs assessment survey demonstrated active research output despite several identified barriers. There is a widespread interest within the pediatric interventional radiology community for collaborative research.

Are there predictors of flexible ureteroscopic aptitude among novice trainees? objective assessment using simulation-based trainer.

PURPOSE: Non-surgical skills involving hand-eye coordination and bimanual dexterity may have a transferable impact on the acquisition of ureteroscopy skills. In this study, we aim to investigate the predictors of initial flexible ureteroscopy skills among novice trainees. METHODS: This was a prospective study involving students with no prior ureteroscopy exposure. Non-surgical parameters were assessed with a detailed survey, including demographics, video game, and musical history. Musical ability was objectively evaluated with the mini-Profile of Music Perception Skills test. Ureteroscopic performance was evaluated using a Boston Scientific© flexible ureteroscope on a bench model. Each participant completed diagnostic ureteroscopy and stone extraction. Outcomes included both speed and quality of performance, based on an Objective Structured Assessment of Technical Skills rubric. RESULTS: A total of 28 pre-clerkship medical students and 10 urology residents were included. Age and musical background were not associated with ureteroscopic aptitude. Those with video game history tended to perform ureteroscopy tasks faster with a higher OSATS score, although no statistical significance was reached. Male gender was associated with faster task completion with statistically higher OSATS score independent of video game activities (p = 0.011), however, the absolute score difference was small. CONCLUSIONS: Among novice trainees, musical and video game experience was not predictive of ureteroscopy skills. Male gender was associated with slightly faster and higher ureteroscopy technique scores, however, the differences are small and unlikely to represent clinical significance. Nevertheless, the use of ureteroscopy trainer provides useful insights and should be adopted in training programs as a marker of skills progression.

Presentation, treatment, and outcome of renovascular hypertension below 2 years of age.

Renovascular hypertension in most cases requires endovascular treatment and/or surgery. This is technically much more difficult in small children and there is very limited published knowledge in this age group. We here present treatment and outcome of young children with renovascular hypertension at our institution. Children below 2 years of age, with renovascular hypertension between January 1998 and March 2020 were retrospectively reviewed. Demographics and treatment modalities were noted. Primary outcome was blood pressure within a week after the procedures and at last available visit. Sixty-six angiographies were performed in 34 patients. Median age at time of first angiography was 1.03 (interquartile range (IQR) 0.4-1.4) years and systolic blood pressure at presentation 130 (IQR 130-150) mm Hg. Thirty-eight percent (13/34) of children were incidentally diagnosed and 18% (6/34) presented with heart failure. Twenty-six (76%) children had main renal artery stenosis and 17 (50%) mid-aortic syndrome. Seventeen (50%) children showed intrarenal, six (18%) mesenteric, and three (9%) cerebrovascular involvement. Twenty patients underwent 45 percutaneous transluminal angioplasty procedures and seven children surgeries. In 44% of the 16 patients who underwent only percutaneous transluminal angioplasty blood pressure was normalized, 38% had improvement on same or decreased treatment and 19% showed no improvement. Complications were seen in 7.5% (5/66) of angiographies. In four of the seven (57%) children who underwent surgery blood pressure was normalized, two had improved (29%) and one unchanged (14%) blood pressure. CONCLUSION: In small children with renovascular hypertension below the age of 2 years, percutaneous transluminal angioplasty caused significant improvement in blood pressure with low complication profile. Surgery can be recommended where percutaneous transluminal angioplasty and medical treatments failed. WHAT IS KNOWN: • Renovascular hypertension is diagnosed in all age groups from a few weeks of life until adulthood. • Both angioplasty and surgery are significantly more difficult to perform in small children and the published information on short and long-term outcome in these children is very scarce. WHAT IS NEW: • Children below the age of two years can safely and successfully undergo selective renal angiography and also safely be treated with angioplasty. • We here present a large group of babies and infants where angioplasty and in some cases surgery effectively and safely improved their blood pressure.

Long-term outcomes following failure of Nissen fundoplication.

PURPOSE: To determine the management and outcomes of patients with gastro-oesophageal reflux (GOR) that requires further intervention following failure of Nissen fundoplication (NF). METHODS: After institutional audit department approval, a retrospective review of paediatric patients who had further intervention following failure of primary NF between January 2006 and December 2015 for GOR at our centre was performed. Data are presented as median (range). RESULTS: Of 820 patients who underwent NF, 190 (23%) received further procedures for GOR management at a median of 21 months of age (6-186); 90/190 (47%) had gastro-jejunal feeding (GJ). Of these, 67 (74%) remained on GJ feeds up to a median of 48 months and 23/90 (26%) had a second NF after GJ feeding. 97/190 (51%) had a redo fundoplication without having had a GJ; thus, 120/190 (63%) of patients having a further procedure went on to have a second NF after a median period of 15 months (1-70 months). Three patients (2%) had early emergency wrap revision 4 days after first fundoplication (we classed this as an 'early complication'). Of the seven patients who failed a 3rd NF, 4 continued GJ feeding, 2 of had oesophagogastric dissociation; 2 had 4th NF of which 1 was successful and 1 patient had gastric pacemaker and is successfully feeding orally. Patients who were finally successfully managed with GJ underwent 2 (2-5) tube changes/year. We found patients who had a previous GJ were more likely to have failure of the redo fundoplication than those who had not to have the GJ (16/24 vs. 30/90, p = 0.005). CONCLUSION: The chance of success decreases with every further attempt at fundoplication. The only factor significantly associated with failure of redo fundoplication was whether the patient previously had a GJ tube. In patients with failed fundoplications, when symptom free on jejunal feedings, further anti-reflux surgical intervention should be avoided. A randomized prospective study is needed for patient selection.

Impact of Time to Surgery and Surgical Delay on Oncologic Outcomes for Renal Cell Carcinoma.

PURPOSE: The time between radiographic identification of a renal tumor and surgery can be concerning for patients and clinicians due to fears of tumor progression while awaiting treatment. This study aimed to evaluate the association between surgical wait time and oncologic outcomes for patients with renal cell carcinoma. MATERIALS AND METHODS: The Canadian Kidney Cancer Information System is a multi-institutional prospective cohort initiated in January 2011. Patients with clinical stage T1b or greater renal cell carcinoma diagnosed between January 2011 and December 2019 were included in this analysis. Outcomes of interest were pathological up staging, cancer recurrence, cancer specific survival and overall survival. Time to recurrence and death were estimated using Kaplan-Meier estimates and associations were determined using Cox proportional hazards models. RESULTS: A total of 1,769 patients satisfied the study criteria. Median wait times were 54 days (IQR 29-86) for the overall cohort and 81 days (IQR 49-127) for cT1b tumors (1,166 patients), 45 days (IQR 27-71) for cT2 tumors (672 cases) and 35 days (IQR 18-61) for cT3/4 tumors (563). Adjusting for comorbidity, tumor size, grade, histological subtype, margin status and pathological stage, there was no association between prolonged wait time and cancer recurrence or death. CONCLUSIONS: In the context of current surgeon triaging practices surgical wait times up to 24 weeks were not associated with adverse oncologic outcomes after 2 years of followup.

A phase Ib open-label dose escalation study of the safety, pharmacokinetics, and pharmacodynamics of cobimetinib (GDC-0973) and ipatasertib (GDC-0068) in patients with locally advanced or metastatic solid tumors.

BACKGROUND: This Phase Ib study explored combination dosing of the allosteric MEK1/2 inhibitor cobimetinib and the ATP-competitive pan-AKT inhibitor ipatasertib. METHODS: Patients with advanced solid tumors were enrolled to two dose escalation arms, each using a 3 + 3 design in 28-day cycles. In Arm A, patients received concurrent cobimetinib and ipatasertib on days 1-21. In Arm B, cobimetinib was administered intermittently with ipatasertib for 21 days. Primary objectives evaluated dose-limiting toxicities (DLTs), maximum tolerated doses (MTD), and the recommended Phase II dose (RP2D). Secondary objectives included analysis of pharmacokinetic parameters, MAPK and PI3K pathway alterations, changes in tissue biomarkers, and preliminary anti-tumor efficacy. Expansion cohorts included patients with PTEN-deficient triple-negative breast cancer and endometrial cancer. RESULTS: Among 66 patients who received ≥1 dose of study drug, all experienced an adverse event (AE). Although no DLTs were reported, 6 patients experienced Cycle 1 DLT-equivalent AEs. The most common treatment-related AEs were diarrhea, nausea, vomiting, dermatitis acneiform, and fatigue. Thirty-five (53%) patients experienced drug-related AEs of ≥ grade 3 severity. Cobimetinb/ipatasertib MTDs were 60/200 mg on Arm A and 150/300 mg on Arm B; the latter was chosen as the RP2D. No pharmacokinetic interactions were identified. Biomarker analyses indicated pathway blockade and increases in IFNγ and PD-L1 gene expression following the combination. Three patients with endometrial or ovarian cancer achieved partial response, all with PTEN-low disease and two with tumor also harboring KRAS mutation. CONCLUSION: There was limited tolerability and efficacy for this MEK and AKT inhibitor combination. Nonetheless, pharmacodynamic analyses indicated target engagement and suggest rationale for further exploration of cobimetinib or ipatasertib in combination with other anticancer agents. ClinicalTrials.gov identifier: NCT01562275.

Cortical spectral matching and shape and volume analysis of the fetal brain pre- and post-fetal surgery for spina bifida: a retrospective study.

PURPOSE: A retrospective study was performed to study the effect of fetal surgery on brain development measured by MRI in fetuses with myelomeningocele (MMC). METHODS: MRI scans of 12 MMC fetuses before and after surgery were compared to 24 age-matched controls without central nervous system abnormalities. An automated super-resolution reconstruction technique generated isotropic brain volumes to mitigate 2D MRI fetal motion artefact. Unmyelinated white matter, cerebellum and ventricles were automatically segmented, and cerebral volume, shape and cortical folding were thereafter quantified. Biometric measures were calculated for cerebellar herniation level (CHL), clivus-supraocciput angle (CSO), transverse cerebellar diameter (TCD) and ventricular width (VW). Shape index (SI), a mathematical marker of gyrification, was derived. We compared cerebral volume, surface area and SI before and after MMC fetal surgery versus controls. We additionally identified any relationship between these outcomes and biometric measurements. RESULTS: MMC ventricular volume/week (mm3/week) increased after fetal surgery (median: 3699, interquartile range (IQR): 1651-5395) compared to controls (median: 648, IQR: 371-896); P = 0.015. The MMC SI is higher pre-operatively in all cerebral lobes in comparison to that in controls. Change in SI/week in MMC fetuses was higher in the left temporal lobe (median: 0.039, IQR: 0.021-0.054), left parietal lobe (median: 0.032, IQR: 0.023-0.039) and right occipital lobe (median: 0.027, IQR: 0.019-0.040) versus controls (P = 0.002 to 0.005). Ventricular volume (mm3) and VW (mm) (r = 0.64), cerebellar volume and TCD (r = 0.56) were moderately correlated. CONCLUSIONS: Following fetal myelomeningocele repair, brain volume, shape and SI were significantly different from normal in most cerebral layers. Morphological brain changes after fetal surgery are not limited to hindbrain herniation reversal. These findings may have neurocognitive outcome implications and require further evaluation.

Importance of Magnetic Resonance Imaging With Diffusion-weighted Imaging in Guiding Biopsy of Nodular Ganglioneuroblastoma: A Case Report.

BACKGROUND: Nodular ganglioneuroblastoma is a rare peripheral neuroblastic tumor of variable prognosis. Accurate diagnosis, staging, and risk categorization can be particularly challenging in patients with nodular ganglioneuroblastoma due to the inherent heterogeneity of these lesions. CASE PRESENTATION: We illustrate the use of diffusion-weighted magnetic resonance imaging to identify tumor nodules and guide tumor biopsy in an almost 5-year-old boy with a large abdominal tumor. CONCLUSIONS: Diffusion-weighted magnetic resonance imaging was successful in detecting and guiding biopsy of a poorly differentiated neuroblastoma nodule within the context of a well-differentiated ganglioneuroma, allowing the diagnosis and characterization of a ganglioneuroblastoma nodular, thus influencing the child's prognosis and treatment.

Cost evaluation of two types of gastrojejunal feeding tubes used in pediatric patients.

BACKGROUND: Gastrojejunal tubes are important feeding devices for children with gastro-esophageal reflux, allowing medication and feeding into the small bowel, and allowing gastric venting to prevent reflux. As with many medical devices, there are multiple manufacturers and designs, including balloon-retained tubes and disc-retained tubes. OBJECTIVE: This study evaluated the cost difference between these two types of gastrojejunal tube. MATERIALS AND METHODS: We conducted a 3.5-year retrospective cost evaluation for all pediatric patients undergoing an insertion or change of gastrojejunal tube using a bottom-up micro-costing analysis. We calculated days between encounters and a subsequent cost per day for each patient. RESULTS: A total of 187 children and adolescents were included, with an average age of 9.2 years. They underwent a total of 1,240 encounters, an average of 6.6 encounters per patient during the study period. A total of 82% of these encounters were related to balloon-retained tubes and 18% to disc-retained tubes. The most common reason for an encounter was a routine change (57%), with mechanical complications accounting for 31%. Disc-retained tubes had a longer period between encounters (117.5 days) than balloon-retained tubes (95 days; P=0.038). However, disc-retained tubes cost 6.9 British pound sterling (GBP) per day, which was significantly higher than balloon-retained tubes at 5.2 GBP per day (P<0.0001). CONCLUSION: Despite being more expensive to purchase, balloon-retained tubes were noted to be the least costly device in a cost-per-day analysis.

Elevated sperm DNA fragmentation does not predict recurrent implantation failure.

In this study, we sought to determine whether sperm DNA fragmentation (DFI%) and high DNA stainability (HDS%) evaluated by sperm chromatin structure assay (SCSA) predict recurrent implantation failure (RIF) or pregnancy rate. A retrospective study was performed of consecutive cycles of ICSI treatment from 2009 to 2018. A total of 386 couples that underwent 1,216 frozen embryo transfer (FET) cycles were analysed. Mean female and male age was 34 ± 3.6 years and 37.3 ± 6.6 years, respectively, and a median total motile sperm count (TMSC) was 43.5 [9.9-105.5] million. Overall median DFI% and HDS% was 12 [7.1-18.9] and 9.6 [6.5-14.4] respectively. On multivariable analysis, DFI% and HDS% were not associated with RIF (DFI%: OR = 1.01, 95% CI: 0.98-1.04, p = .414; HDS%: OR = 0.97, 95% CI: 0.94-1.01, p = .107) or IVF success, defined as clinical pregnancy (DFI%: OR = 1.00, 95% CI: 0.99-1.01, p = .641; HDS%: OR = 1.01, 95% CI: 0.99-1.02, p = .565). We found that neither DFI% or HDS%, as assessed by SCSA, were predictive of RIF or pregnancy rate. This finding suggests that sperm DNA fragmentation does not predict RIF or pregnancy rate.

An automated framework for localization, segmentation and super-resolution reconstruction of fetal brain MRI.

High-resolution volume reconstruction from multiple motion-corrupted stacks of 2D slices plays an increasing role for fetal brain Magnetic Resonance Imaging (MRI) studies. Currently existing reconstruction methods are time-consuming and often require user interactions to localize and extract the brain from several stacks of 2D slices. We propose a fully automatic framework for fetal brain reconstruction that consists of four stages: 1) fetal brain localization based on a coarse segmentation by a Convolutional Neural Network (CNN), 2) fine segmentation by another CNN trained with a multi-scale loss function, 3) novel, single-parameter outlier-robust super-resolution reconstruction, and 4) fast and automatic high-resolution visualization in standard anatomical space suitable for pathological brains. We validated our framework with images from fetuses with normal brains and with variable degrees of ventriculomegaly associated with open spina bifida, a congenital malformation affecting also the brain. Experiments show that each step of our proposed pipeline outperforms state-of-the-art methods in both segmentation and reconstruction comparisons including expert-reader quality assessments. The reconstruction results of our proposed method compare favorably with those obtained by manual, labor-intensive brain segmentation, which unlocks the potential use of automatic fetal brain reconstruction studies in clinical practice.

Serum 17-Hydroxyprogesterone is a Potential Biomarker for Evaluating Intratesticular Testosterone.

PURPOSE: Intratesticular testosterone is essential for spermatogenesis and can only be reliably measured with invasive testicular sampling. Previous studies have demonstrated good correlation between intratesticular testosterone and serum 17-hydroxyprogesterone (17-OHP) in men treated with human chorionic gonadotropin. Based on this observation we hypothesized that we can use serum 17-OHP as a serum biomarker for evaluating intratesticular testosterone in men receiving medications that alter serum testosterone. MATERIALS AND METHODS: Initially, we conducted a cross-sectional analysis of men with a single serum 17-OHP evaluation from July 2018 to March 2019. We followed this with a prospective analysis from July 2018 to October 2019 with evaluation of 140 men including fertile controls, and those receiving treatments that alter serum testosterone at baseline and after 3 months of therapy. According to the data distribution, we reported the median and interquartile ranges, and used the Mann Whitney U or Wilcoxon tests. RESULTS: In the initial cross-sectional analysis of 93 men, a total of 30 men received treatments that increase or maintain intratesticular testosterone concentrations, such as clomiphene citrate and/or human chorionic gonadotropin; 21 men received treatments that suppress intratesticular testosterone concentrations (various exogenous testosterone replacement therapy formulations) and 42 fertile men with normal serum testosterone (greater than 300 ng/dl) were used as control. We demonstrated that serum testosterone levels were within normal range among men receiving the various therapies. In contrast, we found that serum 17-OHP was undetectable in men who received exogenous testosterone replacement therapy, as opposed to men receiving human chorionic gonadotropin and/or clomiphene citrate or fertile controls (p <0.05). In the prospective evaluation that ensued, 17-OHP values decreased in the 21 men who received testosterone replacement therapy (47.5 [21-70] to 13.5 [10-23] ng/dl, p <0.05). Conversely, 17-OHP increased in the 55 men who received human chorionic gonadotropin and/or clomiphene citrate when compared to their baseline levels (42 [24-72] to 88 [61-135] ng/dl, p <0.05). CONCLUSIONS: Serum 17-OHP appears to be a reliable serum marker for intratesticular testosterone levels and could potentially be used to titrate or change medications that alter intratesticular testosterone.

Reasons for worldwide decline in male fertility.

PURPOSE OF REVIEW: To review the evidence regarding a decrease in worldwide sperm parameters and discuss potential causative factors. RECENT FINDINGS: The topic of worldwide decline in sperm parameters is contentious; however, recent high-quality studies have demonstrated that there is indeed a decline in sperm parameters. Several retrospective and basic science studies have shown possible links for this decline in sperm parameters such as obesity, diet, and environmental toxins. SUMMARY: There exist substantial data to suggest a decline in sperm counts over time. Although causative factors have yet to be fully elucidated, potential causes include, increased rates of obesity, poor diet, and exposure to environmental toxins. How this decline in sperm counts reflects fertility has yet to be determined. As such, further studies are necessary to evaluate whether this decline in sperm count correlates with decreased fecundity and how to identify and mitigate potential causative factors.

Super-resolution for upper abdominal MRI: Acquisition and post-processing protocol optimization using brain MRI control data and expert reader validation.

PURPOSE: Magnetic resonance (MR) cholangiopancreatography (MRCP) is an established specialist method for imaging the upper abdomen and biliary/pancreatic ducts. Due to limitations of either MR image contrast or low through-plane resolution, patients may require further evaluation with contrast-enhanced computed tomography (CT) images. However, CT fails to offer the high tissue-ductal-vessel contrast-to-noise ratio available on T2-weighted MR imaging. METHODS: MR super-resolution reconstruction (SRR) frameworks have the potential to provide high-resolution visualizations from multiple low through-plane resolution single-shot T2-weighted (SST2W) images as currently used during MRCP studies. Here, we (i) optimize the source image acquisition protocols by establishing the ideal number and orientation of SST2W series for MRCP SRR generation, (ii) optimize post-processing protocols for two motion correction candidate frameworks for MRCP SRR, and (iii) perform an extensive validation of the overall potential of upper abdominal SRR, using four expert readers with subspeciality interest in hepato-pancreatico-biliary imaging. RESULTS: Obtained SRRs show demonstrable advantages over traditional SST2W MRCP data in terms of anatomical clarity and subjective radiologists' preference scores for a range of anatomical regions that are especially critical for the management of cancer patients. CONCLUSIONS: Our results underline the potential of using SRR alongside traditional MRCP data for improved clinical diagnosis.

Impact of Abnormal Sperm Morphology on Live Birth Rates Following Intrauterine Insemination.

PURPOSE: We evaluated the live birth rate and the prevalence of congenital anomalies in couples undergoing intrauterine insemination with abnormal sperm morphology (less than 4% normal forms). MATERIALS AND METHODS: We retrospectively reviewed intrauterine insemination outcomes from January 2012 to March 2015. Patients who were found to have an ultrasound confirmed clinical pregnancy were contacted to determine the live birth rate and the prevalence of congenital abnormalities. We used chi-square analysis to assess categorical variables and the Student t-test to assess continuous variables. Logistic regression was done to assess the odds of achieving pregnancy and the risk of spontaneous abortion while assessing female age, the total motile count and sperm morphology. RESULTS: In 984 intrauterine insemination procedures performed in a total of 501 couples we found no difference in the ultrasound clinical pregnancy rate in couples with sperm morphology less than 4% vs 4% or greater (12.3% vs 13.6%, p=0.59). We collected live birth and birth abnormality data on 95 of the 130 couples with ultrasound confirmed clinical pregnancy for a 73% response rate. We found no difference in the live birth rate or the spontaneous abortion rate after an ultrasound confirmed clinical pregnancy in couples with abnormal sperm morphology (less than 4% normal forms). There was also no increased risk of birth abnormalities for patients with abnormal sperm morphology. CONCLUSIONS: Abnormal sperm morphology impacted neither the pregnancy rate nor the live birth rate in couples undergoing intrauterine insemination. These results can be used to reassure couples who undergo intrauterine insemination that there is a minimal impact of abnormal sperm morphology on the live birth rate and the prevalence of birth abnormalities.

Impaired sleep is associated with low testosterone in US adult males: results from the National Health and Nutrition Examination Survey.

PURPOSE: Testosterone deficiency has been linked to several adverse health outcomes and recent data have suggested that abnormal sleep quality may result in lower testosterone levels. We assessed the effect of self-reported sleep patterns on serum testosterone while controlling for co-morbidities, and baseline demographics. MATERIALS AND METHODS: Using data collected from the 2011-2012 National Health and Nutrition Examination Survey (NHANES), we extracted serum total testosterone level, sleep duration, demographic, and co-morbidities for men aged 16 years and older. Univariate and multivariate linear regression was used to estimate the association of number of hours slept, co-morbidities, and demographics with serum testosterone. RESULTS: Among the 9756 individuals in the NHANES dataset, 2295 (23.5%) were males 16 years and older with a median (interquartile range) age of 46 years (29-62) who also had serum testosterone levels drawn. Median serum testosterone level was 377 ng/dL (IQR: 279-492 ng/dL). Median number of hours slept was 7 h (IQR: 6-8 h). On multivariate linear regression, we found serum testosterone decreased by 0.49 ng/dL per year of age (p = 0.04), 5.85 ng/dL per hour loss of sleep (p < 0.01) and 6.18 ng/dL per unit of body mass index (BMI) increase (p < 0.01). CONCLUSIONS: Among men aged 16-80 in the United States, we found increasing age, impaired sleep and elevated BMI is associated with low testosterone. It is important, therefore, that evaluation and treatment of reduced serum testosterone should also include improving sleep duration in combination with weight management.