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Female Urogenital Diseases and Pregnancy Complications - 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 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.

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.

Malignant pheochromocytoma with multiple vertebral metastases causing acute incomplete paralysis during pregnancy: Literature review with one case report.

We present a rare case of malignant pheochromocytoma with thoracic metastases during pregnancy that presented with symptoms of myelopathy and was treated with circumferential decompression, stabilization, and radiation. The management of this unique case is not well documented. The clinical manifestations, imaging results, pathological characteristics, treatment and prognosis of the case were analyzed.

Umbilical cord mesenchyme stem cell local intramuscular injection for treatment of uterine niche: Protocol for a prospective, randomized, double-blinded, placebo-controlled clinical trial.

Uterine niche is defined as a triangular anechoic structure at the site of the scar or a gap in the myometrium at the site of a previous caesarean section. The main clinical manifestations are postmenstrual spotting and intrauterine infection, which may seriously affect the daily life of nonpregnant women. Trials have shown an excellent safety and efficacy for the potential of mesenchymal stem cells (MSCs) as a therapeutic option for scar reconstruction. Therefore, this study is designed to investigate the safety and efficacy of using MSCs in the treatment for the uterine niche.

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.

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.

Intergenerational diabetes and obesity-A cycle to break?

Ronald Ma and Barry Popkin discuss the urgent need and challenges to reduce intergenerational transmission of obesity and diabetes.

Estimating the fitness cost and benefit of cefixime resistance in Neisseria gonorrhoeae to inform prescription policy: A modelling study.

Gonorrhoea is one of the most common bacterial sexually transmitted infections in England. Over 41,000 cases were recorded in 2015, more than half of which occurred in men who have sex with men (MSM). As the bacterium has developed resistance to each first-line antibiotic in turn, we need an improved understanding of fitness benefits and costs of antibiotic resistance to inform control policy and planning. Cefixime was recommended as a single-dose treatment for gonorrhoea from 2005 to 2010, during which time resistance increased, and subsequently declined.

Prenatal Exposure to Acetaminophen and Risk of ADHD.

To estimate the association between maternal use of acetaminophen during pregnancy and of paternal use before pregnancy with attention-deficit/hyperactivity disorder (ADHD) in offspring while adjusting for familial risk for ADHD and indications of acetaminophen use.

Erythematous plaques and papules on a premature infant.

A 2240 gram boy was born at 33.2 weeks gestation with nonblanching, deeply erythematous plaques and papules on the back, flanks, and scalp (Figure 1). His mother was GBS positive and on antibiotic suppression for prior cutaneous MRSA and urinary tract infections. Intrapartum intravenous Penicillin G was administered, and the amniotic sac was artificially ruptured 4 hours prior to delivery to facilitate labor. The delivery was uncomplicated without concern for chorioamnionitis, but the patient initially required CPAP for respiratory distress with 1-minute and 5-minute Apgar scores of 7 and 8, respectively. A skin punch biopsy is shown (Figure 2).

Management Strategies for Patients with Diabetic Kidney Disease and Chronic Kidney Disease in Diabetes.

Diabetes mellitus is a leading cause of chronic kidney disease, prompting the need for monitoring and management of this complex condition in those diagnosed with diabetes. Management is often multifaceted and includes lifestyle modification, management of hyperglycemia, and management of hypertension and hyperlipidemia to slow progression of kidney disease and to mitigate cardiovascular risks associated with diabetes and kidney disease. This article reviews the current literature regarding monitoring and management of diabetic kidney disease and chronic kidney disease in diabetes.

Immune checkpoint inhibitors in renal cell carcinoma.

The immune system has long been known to play a critical role in the body's defence against cancer, and there have been multiple attempts to harness it for therapeutic gain. Renal cancer was, historically, one of a small number of tumour types where immune manipulation had been shown to be effective. The current generation of immune checkpoint inhibitors are rapidly entering into routine clinical practice in the management of a number of tumour types, including renal cancer, where one drug, nivolumab, an anti-programmed death-1 (PD-1) monoclonal antibody (mAb), is licensed for patients who have progressed on prior systemic treatment. Ongoing trials aim to maximize the benefits that can be gained from this new class of drug by exploring optimal timing in the natural course of the disease as well as combinations with other checkpoint inhibitors and drugs from different classes.

Efficacy of predictive models for polycystic ovary syndrome using serum levels of two antimüllerian hormone isoforms (proAMH and AMHN,C).

To compare total antimüllerian hormone (AMH), proAMH, AMHN,C, and the ratio of the two forms in predictive models for polycystic ovary syndrome (PCOS) diagnosis. Total AMH consists of proAMH (inactive precursor) and AMHN,C (receptor-competent), but neither isoform has been tested individually for their ability to predict PCOS diagnosis.

Endometriosis, especially mild disease: a risk factor for miscarriages.

To investigate the prevalence of miscarriage in women with endometriosis (WwE) compared with disease-free control women (CW).

Secondary Hyperparathyroidism in Heart Failure.

Secondary hyperparathyroidism (SHPT) is a well-known pathophysiologic feature of chronic renal failure. In recent years, SHPT has become recognized as a complication of the aldosteronism associated with congestive heart failure and where excretory Ca(2+) and Mg(2+) wasting results in plasma-ionized hypocalcemia and hypomagnesemia. Elevations in plasma parathyroid hormone have adverse systemic consequences, including intracellular Ca(2+) overloading of myocytes and vascular smooth muscle with the induction of oxidative stress. Herein, we briefly review the presence and adverse outcomes of SHPT in persons with heart failure.

The Pelvic Girdle Questionnaire: Responsiveness and Minimal Important Change in Women With Pregnancy-Related Pelvic Girdle Pain, Low Back Pain, or Both.

The Pelvic Girdle Questionnaire (PGQ) is a condition-specific measure for women with pelvic girdle pain (PGP). The PGQ includes items relating to activity/participation and bodily symptoms and has reliability, validity, and feasibility for use in research and clinical practice.

Prompted Voiding Offers Long-Term Benefits to Nursing Home Residents.

According to this study.

Obesity and gynaecological and obstetric conditions: umbrella review of the literature.

Objective To study the strength and validity of associations between adiposity and risk of any type of obstetric or gynaecological conditions.Design An umbrella review of meta-analyses.Data sources PubMed, Cochrane database of systematic reviews, manual screening of references for systematic reviews or meta-analyses of observational and interventional studies evaluating the association between adiposity and risk of any obstetrical or gynaecological outcome.Main outcomes Meta-analyses of cohort studies on associations between indices of adiposity and obstetric and gynaecological outcomes.Data synthesis Evidence from observational studies was graded into strong, highly suggestive, suggestive, or weak based on the significance of the random effects summary estimate and the largest study in the included meta-analysis, the number of cases, heterogeneity between studies, 95% prediction intervals, small study effects, excess significance bias, and sensitivity analysis with credibility ceilings. Interventional meta-analyses were assessed separately.Results 156 meta-analyses of observational studies were included, investigating associations between adiposity and risk of 84 obstetric or gynaecological outcomes. Of the 144 meta-analyses that included cohort studies, only 11 (8%) had strong evidence for eight outcomes: adiposity was associated with a higher risk of endometrial cancer, ovarian cancer, antenatal depression, total and emergency caesarean section, pre-eclampsia, fetal macrosomia, and low Apgar score. The summary effect estimates ranged from 1.21 (95% confidence interval 1.13 to 1.29) for an association between a 0.1 unit increase in waist to hip ratio and risk endometrial cancer up to 4.14 (3.61 to 4.75) for risk of pre-eclampsia for BMI >35 compared with <25. Only three out of these eight outcomes were also assessed in meta-analyses of trials evaluating weight loss interventions. These interventions significantly reduced the risk of caesarean section and pre-eclampsia, whereas there was no evidence of association with fetal macrosomia.Conclusions Although the associations between adiposity and obstetric and gynaecological outcomes have been extensively studied, only a minority were considered strong and without hints of bias.