PubTransformer

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Male Urogenital Diseases - Top 30 Publications

Acute Kidney Injury.

Acute kidney injury is a heterogeneous group of conditions characterized by a sudden decrease in glomerular filtration rate, manifested by an increase in serum creatinine concentration or oliguria, and classified by stage and cause. This type of injury occurs in approximately 20% of hospitalized patients, with major complications including volume overload, electrolyte disorders, uremic complications, and drug toxicity. Management includes specific treatments according to the underlying cause and supportive treatment to prevent and manage complications. Kidney replacement therapy is used when complications cannot be managed with medical therapy alone. Despite advances in care, the mortality rate in patients requiring kidney replacement therapy remains approximately 50%.

Symptomatic treatment of uncomplicated lower urinary tract infections in the ambulatory setting: randomised, double blind trial.

Objective To investigate whether symptomatic treatment with non-steroidal anti-inflammatory drugs (NSAIDs) is non-inferior to antibiotics in the treatment of uncomplicated lower urinary tract infection (UTI) in women, thus offering an opportunity to reduce antibiotic use in ambulatory care.Design Randomised, double blind, non-inferiority trial.Setting 17 general practices in Switzerland.Participants 253 women with uncomplicated lower UTI were randomly assigned 1:1 to symptomatic treatment with the NSAID diclofenac (n=133) or antibiotic treatment with norfloxacin (n=120). The randomisation sequence was computer generated, stratified by practice, blocked, and concealed using sealed, sequentially numbered drug containers.Main outcome measures The primary outcome was resolution of symptoms at day 3 (72 hours after randomisation and 12 hours after intake of the last study drug). The prespecified principal secondary outcome was the use of any antibiotic (including norfloxacin and fosfomycin as trial drugs) up to day 30. Analysis was by intention to treat.Results 72/133 (54%) women assigned to diclofenac and 96/120 (80%) assigned to norfloxacin experienced symptom resolution at day 3 (risk difference 27%, 95% confidence interval 15% to 38%, P=0.98 for non-inferiority, P<0.001 for superiority). The median time until resolution of symptoms was four days in the diclofenac group and two days in the norfloxacin group. A total of 82 (62%) women in the diclofenac group and 118 (98%) in the norfloxacin group used antibiotics up to day 30 (risk difference 37%, 28% to 46%, P<0.001 for superiority). Six women in the diclofenac group (5%) but none in the norfloxacin group received a clinical diagnosis of pyelonephritis (P=0.03).Conclusion Diclofenac is inferior to norfloxacin for symptom relief of UTI and is likely to be associated with an increased risk of pyelonephritis, even though it reduces antibiotic use in women with uncomplicated lower UTI.Trial registration ClinicalTrials.gov NCT01039545.

Cardiovascular disease (CVD) and chronic kidney disease (CKD) event rates in HIV-positive persons at high predicted CVD and CKD risk: A prospective analysis of the D:A:D observational study.

The Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) study has developed predictive risk scores for cardiovascular disease (CVD) and chronic kidney disease (CKD, defined as confirmed estimated glomerular filtration rate [eGFR] ≤ 60 ml/min/1.73 m2) events in HIV-positive people. We hypothesized that participants in D:A:D at high (>5%) predicted risk for both CVD and CKD would be at even greater risk for CVD and CKD events.

Judging causal associations in observational research on caudal anesthesia and hypospadias repair.

Castration-Resistant Prostate Cancer: An Algorithmic Approach.

Since 2010, 5 new agents have been approved for advanced prostate cancer treatment. The American Urologic Association (AUA) published guidelines for the management of castration-resistant prostate cancer in 2013. These guidelines identify 6 index patients to consider when selecting the most appropriate treatment. No comparative trials have provided an approach to optimize the sequencing of these drugs. For the urologist, incorporating the guidelines into clinical practice typically requires a multidisciplinary team. This article provides an algorithmic approach based on indication and mechanism of action that complements the AUA guidelines to ensure patients receive the most optimal care.

Approach to the Patient with High-Risk Prostate Cancer.

Men classified as having high-risk prostate cancer warrant treatment because durable outcomes can be achieved. Judicious use of imaging and considerations of risk factors are essential when caring for men with high-risk disease. Radical prostatectomy, radiation therapy, and androgen deprivation therapy all play pivotal roles in the management of men with high-risk disease, and potentially in men with metastatic disease. The optimal combinations of therapeutic regimens are an evolving area of study and future work looking into therapies for men with high-risk disease will remain critical.

The Role of Local Therapy for Oligometastatic Prostate Cancer: Should We Expect a Cure?

The role of local treatment in oligometastatic prostate cancer remains contentious. Treatment of the prostate in metastatic disease may confer benefit, but prospective data are lacking. With improvements in treatments, aggressive strategies directed at metastases have increasingly become of clinical interest. Current evidence suggests good local control can be achieved; however, further data are required to determine overall cancer outcomes. This article evaluates the evidence available and consider whether local treatment of oligometastatic disease is a feasible, safe, and a positive strategy in this disease cohort. Cure should not be expected, although prolonged disease and treatment-free survival may be observed.

Newly Diagnosed Metastatic Prostate Cancer: Has the Paradigm Changed?

Androgen deprivation therapy (ADT) has been conventional treatment of newly diagnosed metastatic prostate cancer for more than 70 years. However, all patients eventually become castration-resistant and a significant proportion of life span is spent in the castration-resistant state. Prospective randomized control trials have incorporated early chemotherapy along with ADT based on the hypothesis that a significant level of resistance to ADT already exists in newly diagnosed metastatic prostate cancer and ADT exhibits synergistic antitumor activity with taxanes. We discuss the changing landscape of management of patients with newly diagnosed metastatic prostate cancer based on recently published landmark randomized trials.

Managing Cancer Relapse After Radical Prostatectomy: Adjuvant Versus Salvage Radiation Therapy.

An increasing proportion of men are undergoing radical prostatectomy for locally advanced prostate cancer. More than half of men with adverse pathologic features are expected to experience disease recurrence within 10 years. This article discusses the use of postoperative radiation therapy to decrease this risk. Evidence from 3 randomized trials and multiple retrospective studies indicates that either adjuvant or salvage radiation improve biochemical progression-free survival and may improve overall survival. Novel imaging and genomic analysis can improve patient selection for either modality, however current tests are unable to identify all patients who may benefit from additional local therapy.

Extent of Lymphadenectomy at Time of Prostatectomy: An Evidence-Based Approach.

Pelvic lymph node dissection (PLND) at the time of radical prostatectomy is the most accurate method of lymph node staging in prostate cancer. Although there are varied practices in anatomic extent of PLND, evidence favors an extended PLND (ePLND) including external iliac, obdurator, and internal iliac nodes. Removing presacral and/or common iliac nodes to the ureteric crossing can improve staging. The oncologic benefits of extended dissection are unclear based on methodologic limitations and bias in the available evidence. Diverse nomograms may clarify which patients warrant ePLND. Higher level evidence is needed to clarify the therapeutic effects of ePLND and who benefits most.

Focal Ablation of Early-Stage Prostate Cancer: Candidate Selection, Treatment Guidance, and Assessment of Outcome.

Prostate cancer lesions smaller than 0.5 m(3), or Gleason pattern 3, are likely clinically insignificant. Clinically significant disease is often limited to a single index lesion. Focal ablation targets this index lesion, maintains oncological control, and minimizes complications by preserving healthy prostate tissue. Template mapping biopsy or multiparametric MRI-targeted biopsies are used to identify appropriate index lesions. Multiple energy modalities have been tested, including high-intensity frequency ultrasound, cryoablation, laser ablation, photodynamic therapy, focal brachytherapy, radiofrequency ablation, irreversible electroporation. Outcome is assessed by biopsy of the target area, triggered by prostate-specific antigen measurements or MRI imaging, or performed per protocol at 12 months.

Contemporary Active Surveillance: Candidate Selection, Follow-up Tools, and Expected Outcomes.

This article is a summary of the rationale for conservative management, the molecular biology of low-grade cancer, the principles of management, the expected outcome of surveillance, unanswered questions, and research opportunities.

(68)Gallium-Prostate-Specific Membrane Antigen PET/Computed Tomography for Primary and Secondary Staging in Prostate Cancer.

Prostate-specific membrane antigen (PSMA) PET has been recently introduced for the diagnosis of patients with metastatic prostate cancer (PCa). Until today, staging of patients with PCa relied mostly on morphologic features, such as size or shape, resulting in low detection rates in disease recurrence. PSMA PET imaging provides molecular information and, in combination with conventional imaging, offers improved sensitivity and specificity. This review discusses the benefits and limitations of PSMA imaging in the setting of primary staging and detection of recurrent disease in comparison with standard-of-care imaging techniques.

Whom to Treat: Postdiagnostic Risk Assessment with Gleason Score, Risk Models, and Genomic Classifier.

Management of prostate cancer presents unique challenges because of the disease's variable natural history. Accurate risk stratification at the time of diagnosis in clinically localized disease is crucial in providing optimal counseling about management options. To accurately distinguish pathologically indolent tumors from aggressive disease, risk groups are no longer sufficient. Rather, multivariable prognostic models reflecting the complete information known at time of diagnosis offer improved accuracy and interpretability. After diagnosis, further testing with genomic assays or other biomarkers improves risk classification. These postdiagnostic risk assessment tools should not supplant shared decision making, but rather facilitate risk classification and enable more individualized care.

Prediagnostic Risk Assessment with Prostate MRI and MRI-Targeted Biopsy.

Prostate MRI is commonly used in the detection of prostate cancer to reduce the detection of clinically insignificant disease; maximize the detection of clinically significant cancer; and better assess disease size, grade, and location. The clinical utility of MRI seems to apply to men with no prior biopsy, who have had a previous negative biopsy, and men who are candidate for active surveillance. In conjunction with traditional clinical parameters and secondary biomarkers, MRI may allow more accurate risk stratification and assessment of need for prostate biopsy.

How to Biopsy: Transperineal Versus Transrectal, Saturation Versus Targeted, What's the Evidence?

Until recently, prostate biopsy for the detection of prostate cancer has been performed transrectally and in an untargeted sampling fashion. Consequently, the procedure has suffered a small but significant risk of severe morbidity through infection, and low diagnostic accuracy, with undergrading and missed diagnosis being common. MRI is revolutionizing prostate cancer diagnosis by improving detection accuracy via targeted biopsy. Transperineal biopsy is eradicating sepsis as a risk of prostate biopsy, while avoiding the need for broad-spectrum or combination prophylactic antibiotics. This article analyzes the data on the various current methods of performing prostate biopsy and recommends an optimal technique.

Whom to Biopsy: Prediagnostic Risk Stratification with Biomarkers, Nomograms, and Risk Calculators.

This article describes markers used for prostate biopsy decisions, including prostrate-specific antigen (PSA), free PSA, the prostate health index, 4Kscore, PCA3, and ConfirmMDx. It also summarizes the use of nomograms combining multiple variables for prostate cancer detection.

Mitochondrial DNA quantity as a biomarker for blastocyst implantation potential.

Of all the factors currently available for the evaluation of embryonic potential, chromosomal status appears to be the most definitive. The debate around this hotly contested issue does not focus on the question of whether aneuploidy is detrimental to development, but on whether current preimplantation genetic testing for aneuploidy methods are capable of accurately determining whether an embryo is chromosomally normal, aneuploid or a mixture of normal and abnormal cells (i.e., mosaic). Despite the importance of aneuploidy, it is clear that this is only one factor amongst many of relevance to embryo viability, as evidenced by the fact that even the transfer of a chromosomally normal embryo cannot guarantee a pregnancy. Mounting evidence supports the hypothesis that blastocysts having unusually high levels of mitochondrial DNA detected in the trophectoderm have greatly reduced implantation potential, but there remain significant areas where further validation is necessary and where our understanding is currently inadequate. This should provide fertile ground for future research and is likely to yield some fascinating insights in the coming years.

Will noninvasive methods surpass invasive for assessing gametes and embryos?

The need to identify the most viable embryo following in vitro fertilization (IVF) was established early in the history of human IVF. The stalwart of identifying the best embryos has been morphology. Other techniques have however seen wide acceptance, including the use of preimplantation genetic screening, even though concerns exist over the invasive nature of the technique. Alternatively, noninvasive assessment technologies have tried to determine an embryo's viability through measurements of factors in the media or by imaging of the embryo. We present data showing that the metabolic blueprint of an embryo is linked to viability, and argue that analysis of metabolic function, using either spent medium or by novel microscopies, could provide the basis for selecting the embryo with the highest viability. This review therefore asks, "Will noninvasive methods surpass invasive for assessing gametes and embryos?" We examine the current state of research on noninvasive technologies, including novel optical methods, and conclude noninvasive embryo viability assessment will assist in embryo selection for transfer.

Assessment of embryo morphology and developmental dynamics by time-lapse microscopy: is there a relation to implantation and ploidy?

Time-lapse microscopy (TLM) is an exciting novel technology with great potential for enhancing embryo selection in the embryology laboratory. This non-invasive objective assessment of embryos has provided a new tool for predicting embryo development and implantation potential. TLM detects several morphological phenomena that are often missed with static observations using conventional incubators, such as irregular divisions, blastocyst collapse and re-expansion, timing of blastocoel appearance, and timing of formation and internalization of fragments. Nevertheless, it should be recognized that conventional morphological assessment has been widely accepted as the gold standard by most embryologists. TLM can enhance conventional morphological assessments to improve embryo selection and subsequent reproductive outcomes. Furthermore, morphokinetic parameters can aid in differentiating between euploid and aneuploid embryos, although they are not sufficiently accurate to replace preimplantation genetic testing for aneuploidy. Morphokinetic assessment together with chromosomal screening may ultimately help identify euploid embryos with the highest developmental potential.

Introduction: Biomarkers of embryo viability: the search for the "holy grail" of embryo selection.

Over the past four decades we have witnessed great progress and increasing pregnancy success rates with in vitro fertilization. However, this apparent success has been accompanied by the burden of multiple pregnancies. While efforts to reduce the number of embryos transferred have had a salutary impact on the incidence of high order multiple pregnancies, twin gestations have not diminished significantly. Thus, the search for a marker of embryo quality with the goal of selecting the single best embryo for transfer continues to be the major challenge facing our field. The four contributions in this Views and Reviews present several contemporary approaches, both invasive and non-invasive, for evaluating embryo viability. Each group makes the case that recent techniques, including time-lapse microscopy, biomechanical markers for oocytes and embryos, novel non-invasive methods of evaluating embryo metabolism and function as well as measurement of mitochondrial DNA, will allow the identification of the single best embryo for transfer. They describe several promising markers of embryo viability, although the goal of finding the "holy grail" of embryo selection has not yet been realized.

Mutations in GREB1L Cause Bilateral Kidney Agenesis in Humans and Mice.

Congenital anomalies of the kidney and urinary tract (CAKUT) constitute a major cause of chronic kidney disease in children and 20% of prenatally detected anomalies. CAKUT encompass a spectrum of developmental kidney defects, including renal agenesis, hypoplasia, and cystic and non-cystic dysplasia. More than 50 genes have been reported as mutated in CAKUT-affected case subjects. However, the pathophysiological mechanisms leading to bilateral kidney agenesis (BKA) remain largely elusive. Whole-exome or targeted exome sequencing of 183 unrelated familial and/or severe CAKUT-affected case subjects, including 54 fetuses with BKA, led to the identification of 16 heterozygous variants in GREB1L (growth regulation by estrogen in breast cancer 1-like), a gene reported as a target of retinoic acid signaling. Four loss-of-function and 12 damaging missense variants, 14 being absent from GnomAD, were identified. Twelve of them were present in familial or simplex BKA-affected case subjects. Female BKA-affected fetuses also displayed uterus agenesis. We demonstrated a significant association between GREB1L variants and BKA. By in situ hybridization, we showed expression of Greb1l in the nephrogenic zone in developing mouse kidney. We generated a Greb1l knock-out mouse model by CRISPR-Cas9. Analysis at E13.5 revealed lack of kidneys and genital tract anomalies in male and female Greb1l(-/-) embryos and a slight decrease in ureteric bud branching in Greb1l(+/-) embryos. We showed that Greb1l invalidation in mIMCD3 cells affected tubulomorphogenesis in 3D-collagen culture, a phenotype rescued by expression of the wild-type human protein. This demonstrates that GREB1L plays a major role in early metanephros and genital development in mice and humans.

Exome-wide Association Study Identifies GREB1L Mutations in Congenital Kidney Malformations.

Renal agenesis and hypodysplasia (RHD) are major causes of pediatric chronic kidney disease and are highly genetically heterogeneous. We conducted whole-exome sequencing in 202 case subjects with RHD and identified diagnostic mutations in genes known to be associated with RHD in 7/202 case subjects. In an additional affected individual with RHD and a congenital heart defect, we found a homozygous loss-of-function (LOF) variant in SLIT3, recapitulating phenotypes reported with Slit3 inactivation in the mouse. To identify genes associated with RHD, we performed an exome-wide association study with 195 unresolved case subjects and 6,905 control subjects. The top signal resided in GREB1L, a gene implicated previously in Hoxb1 and Shha signaling in zebrafish. The significance of the association, which was p = 2.0 × 10(-5) for novel LOF, increased to p = 4.1 × 10(-6) for LOF and deleterious missense variants combined, and augmented further after accounting for segregation and de novo inheritance of rare variants (joint p = 2.3 × 10(-7)). Finally, CRISPR/Cas9 disruption or knockdown of greb1l in zebrafish caused specific pronephric defects, which were rescued by wild-type human GREB1L mRNA, but not mRNA containing alleles identified in case subjects. Together, our study provides insight into the genetic landscape of kidney malformations in humans, presents multiple candidates, and identifies SLIT3 and GREB1L as genes implicated in the pathogenesis of RHD.

Incidence of End-Stage Renal Disease Attributed to Diabetes Among Persons with Diagnosed Diabetes - United States and Puerto Rico, 2000-2014.

During 2014, 120,000 persons in the United States and Puerto Rico began treatment for end-stage renal disease (ESRD) (i.e., kidney failure requiring dialysis or transplantation) (1). Among these persons, 44% (approximately 53,000 persons) had diabetes listed as the primary cause of ESRD (ESRD-D) (1). Although the number of persons initiating ESRD-D treatment each year has increased since 1980 (1,2), the ESRD-D incidence rate among persons with diagnosed diabetes has declined since the mid-1990s (2,3). To determine whether ESRD-D incidence has continued to decline in the United States overall and in each state, the District of Columbia (DC), and Puerto Rico, CDC analyzed 2000-2014 data from the U.S. Renal Data System and the Behavioral Risk Factor Surveillance System. During that period, the age-standardized ESRD-D incidence among persons with diagnosed diabetes declined from 260.2 to 173.9 per 100,000 diabetic population (33%), and declined significantly in most states, DC, and Puerto Rico. No state experienced an increase in ESRD-D incidence rates. Continued awareness of risk factors for kidney failure and interventions to improve diabetes care might sustain and improve these trends.

Prevalence of depression and suicidal ideation increases proportionally with renal function decline, beginning from early stages of chronic kidney disease.

Depression and suicidal ideation are prevalent mental health problems in patients with chronic kidney disease (CKD. However, the association between mental health problems and kidney disease has been investigated in severe cases only. Thus, this study evaluated the relationship between mental health problems and renal function in a community-based prospective cohort study comprising patients with mild to moderate kidney disease. A total of 44,938 participants who were participated in Korean National Health and Nutrition Examination Survey IV, V, and VI from 2007 to 2014 were enrolled. Estimated glomerular filtration rate (eGFR) was calculated using the CKD Epidemiology Collaboration equation. The study outcome was the prevalence of depression and suicidal ideations assessed by self-reporting surveys. Logistic regression analysis was performed to evaluate the relationship between renal function and outcomes. The mean age of the study subjects was 49.2 ± 16.6 years, and the mean eGFR was 94.0 mL/min/1.73 m. The prevalence of depression and suicidal ideation increased with decreasing eGFR. Multivariate logistic regression analysis showed that the risk of depression increased in subjects with eGFR <45 mL/min/1.73 m [odds ratio (OR) 1.47; 95% confidence interval (CI) 1.09-1.98]. The risk of suicidal ideation gradually increased in groups with eGFR <90 mL/min/1.73 m (OR, 1.11; 95% CI, 1.03-1.20), even after adjustments for confounding variables. In conclusion, depression and suicidal ideation are related closely with renal dysfunction. The risk of having depression and suicidal ideation increased even in patient with mild renal dysfunction. Therefore, evaluation and management strategies regarding mental health problems should be taken into account throughout all stages of CKD.

Primary hypothyroidism and isolated ACTH deficiency induced by nivolumab therapy: Case report and review.

Nivolumab is a monoclonal IgG antibody blocking programmed death receptor-1 (PD1), leading to restoration of the natural T-cell-mediated immune response against the cancer cells. However, it also causes plenty of autoimmune-related adverse events, which often involves endocrine system.

The additional benefit of weighted subjective global assessment (SGA) for the predictability of mortality in incident peritoneal dialysis patients: A prospective study.

Although subjective global assessment (SGA) is a widely used tool for nutritional investigation, the scores are dependent on the inspectors' subjective opinions, and there are only few studies that directly assessed the usefulness of SGA and modified SGA in incident peritoneal dialysis (PD) patients. A total of 365 incident PD patients between 2009 and 2015 were enrolled and measured with SGA and calculated using serum albumin and total iron binding capacity (TIBC) levels for weighted SGA. Cox analyses were performed to delineate the association between SGA or weighted SGA and all-cause mortality, and a receiver-operating characteristic was conducted to reveal the additional benefit of weighted SGA on predicting adverse clinical outcomes. The Kaplan-Meier curve showed that the cumulative survival rate in patients with "Good nutrition" (G1) was significantly higher compared to those with "Mild to severe malnutrition" (G2). G2 was significantly associated with an increase in the mortality even after adjusting for several covariates compared with G1. Moreover, a 1-unit increase in weighted SGA was also significantly correlated with mortality after adjustment of the same covariates, while G2 was not significantly associated with an increase in the mortality among young-aged (under 65 years) groups. Meanwhile, a 1-unit increase in weighted SGA was significantly related to an increase in mortality in all the subgroup analyses. Furthermore, the AUCs of weighted SGAs in all groups were significantly increased compared with those of SGA alone. In conclusions, the evaluation of nutritional status based on SGA in incident PD patients might be useful for predicting mortality. However, weighted SGA with serum albumin and TIBC can provide additional predictive power for mortality compared with SGA alone in incident PD patients.

Comparison of the effects of extracorporeal shock wave therapy and a vacuum erectile device on penile erectile dysfunction: a randomized clinical trial.

This randomized clinical trial (October 2012-December 2013) compared extracorporeal shock wave therapy (ESWT) and a vacuum erectile device (VED) for management of erectile dysfunction (ED).

ACE Inhibitors and Statins in Adolescents with Type 1 Diabetes.

Among adolescents with type 1 diabetes, rapid increases in albumin excretion during puberty precede the development of microalbuminuria and macroalbuminuria, long-term risk factors for renal and cardiovascular disease. We hypothesized that adolescents with high levels of albumin excretion might benefit from angiotensin-converting-enzyme (ACE) inhibitors and statins, drugs that have not been fully evaluated in adolescents.

Nutritional Management of Chronic Kidney Disease.