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Female Urogenital Diseases and Pregnancy Complications - Top 30 Publications

Sleep duration and quality in relation to chronic kidney disease and glomerular hyperfiltration in healthy men and women.

It is unclear whether sleep duration and quality are associated with chronic kidney disease (CKD) and glomerular hyperfiltration. The aim of this study was to examine the association of sleep duration and quality with CKD and glomerular hyperfiltration in young and middle-aged adults.

Inflammation-induced fetal growth restriction in rats is associated with increased placental HIF-1α accumulation.

Hypoxia-inducible factor 1-alpha (HIF-1α) is the oxygen-sensitive subunit of the transcription factor HIF-1, and its expression is increased in placentas from pregnancies complicated by pre-eclampsia (PE). Fetal growth restriction (FGR) and PE often share a common pathophysiology; however, it is unknown whether increased placental HIF-1α occurs in FGR. We previously demonstrated that aberrant maternal inflammation in rats resulted in altered utero-placental perfusion and FGR, both of which were prevented by administration of the nitric oxide mimetic glyceryl trinitrate (GTN). Our aim here was to determine whether abnormal maternal inflammation causing FGR is linked to placental HIF-1α accumulation and whether GTN administration could prevent increases in placental HIF-1α.

Metabolic syndrome, serum uric acid and renal risk in patients with T2D.

Metabolic Syndrome (Mets) and increased serum uric acid (SUA), are well known renal risk predictors and often coexist in patients with type 2 diabetes (T2D). Whether they independently contribute to the onset of CKD is at present unclear.

Microwave ablation of malignant renal tumours: intermediate-term results and usefulness of RENAL and mRENAL scores for predicting outcomes and complications.

The aim of this study was to evaluate intermediate-term results after microwave ablation (MWA) of renal tumours and determine the association of RENAL and modified RENAL (mRENAL) scores with oncological outcomes and complications. In May 2008-September 2014, 58 patients affected by early-stage RCC (renal cell carcinoma; T1a or T1b) were judged unsuitable for surgery and treated with percutaneous MWA. Follow-up was performed with contrast-enhanced computed tomography at 1, 3, 6, 12 and 24 months after the procedure. Technical success (TS), primary technical effectiveness (PTE), secondary technical effectiveness (STE), the local tumour progression rate (LTPR), the cancer-specific survival rate (CSSR), disease-free survival (DFS), overall survival (OS) and safety were recorded. All lesions were evaluated using RENAL and mRENAL scores, and complications were assessed with RENAL scores. The TS rate was 100%, PTE was 93%, STE was 100%, LTPR was 15.7% at 1 year, CSSR was 96.5%, DFS was 87.9% at 5 years, and OS was 80.6%. Mean follow-up was 25.7 months (range 3-72). The mean ± standard deviation (SD) RENAL and mRENAL scores of all treated tumours were 6.7 ± 2.05 (range 4-11) and 7 ± 2.3 (range 4-12), respectively. Major complications occurred in two (2/58) and minor complications in three patients (3/58). Overall complications correlated significantly with RENAL scores; in particular, E and L represent negative predictors for safety and effectiveness. MWA is a valuable alternative for treating RCCs. The correlation with outcomes and complications of RENAL and mRENAL scores could help to customise MWA indications in RCC patients.

Insufficient activation of Akt upon reperfusion because of its novel modification by reduced PP2A-B55α contributes to enlargement of infarct size by chronic kidney disease.

Chronic kidney disease (CKD) increases myocardial infarct size by an unknown mechanism. Here we examined the hypothesis that impairment of protective PI3K-PDK1-Akt and/or mTORC-Akt signaling upon reperfusion contributes to CKD-induced enlargement of infarct size. CKD was induced in rats by 5/6 nephrectomy (SNx group) 4 weeks before myocardial infarction experiments, and sham-operated rats served as controls (Sham group). Infarct size as a percentage of area at risk after ischemia/reperfusion was significantly larger in the SNx group than in the Sham group (56.3 ± 4.6 vs. 41.4 ± 2.0%). In SNx group, myocardial p-Akt-Thr308 level at baseline was elevated, and reperfusion-induced phosphorylation of p-Akt-Ser473, p-p70s6K and p-GSK-3β was significantly suppressed. Inhibition of Akt-Ser473 phosphorylation upon reperfusion by Ku-0063794 significantly increased infarct size in the Sham group but not in the SNx group. There was no difference between the two groups in activities of mTORC2 and PDK1 and protein level of PTEN. However, the PP2A regulatory subunit B55α, which specifically targets Akt-Thr308, was reduced by 24% in the SNx group. Knockdown of B55α by siRNA increased baseline p-Akt-Thr308 and blunted Akt-Ser473 phosphorylation in response to insulin-like growth factor-1 (IGF-1) in H9c2 cells. A blunted response of Akt-Ser473 to IGF-1 was also observed in HEK293 cells transfected with a p-Thr308-mimetic Akt mutant (T308D). These results indicate that increased Akt-Thr308 phosphorylation by down-regulation of B55α inhibits Akt-Ser473 phosphorylation upon reperfusion in CKD and that the impaired Akt activation by insufficient Ser473 phosphorylation upon reperfusion contributes to infarct size enlargement by CKD.

Arsenic treatment increase Aurora-A overexpression through E2F1 activation in bladder cells.

Arsenic is a widely distributed metalloid compound that has biphasic effects on cultured cells. In large doses, arsenic can be toxic enough to trigger cell death. In smaller amounts, non-toxic doses may promote cell proliferation and induces carcinogenesis. Aberration of chromosome is frequently detected in epithelial cells and lymphocytes of individuals from arsenic contaminated areas. Overexpression of Aurora-A, a mitotic kinase, results in chromosomal instability and cell transformation. We have reported that low concentration (≦1 μM) of arsenic treatment increases Aurora-A expression in immortalized bladder urothelial E7 cells. However, how arsenic induces carcinogenesis through Aurora-A activation remaining unclear.

Pregnancy and Labor Complications in Female Survivors of Childhood Cancer: The British Childhood Cancer Survivor Study.

Female survivors of childhood cancer treated with abdominal radiotherapy who manage to conceive are at risk of delivering premature and low-birthweight offspring, but little is known about whether abdominal radiotherapy may also be associated with additional complications during pregnancy and labor. We investigated the risk of developing pregnancy and labor complications among female survivors of childhood cancer in the British Childhood Cancer Survivor Study (BCCSS).

Reversion of BRCA1/2 Germline Mutations Detected in Circulating Tumor DNA From Patients With High-Grade Serous Ovarian Cancer.

Purpose Germline BRCA1 or BRCA2 mutations in patients with high-grade serous ovarian cancer (HGSC) are associated with favorable responses to chemotherapy. However, secondary intragenic (reversion) mutations that restore protein function lead to clinically significant rates of acquired resistance. The goal of this study was to determine whether reversion mutations could be found in an unbiased manner in circulating cell-free DNA (cfDNA) to predict treatment response in HGSC. Patients and Methods Plasma and tumor samples were obtained from 30 patients with HGSC with either BRCA1 or BRCA2 germline mutation. Two cohorts were ascertained: patients with a malignancy before undergoing primary HGSC debulking surgery (n = 14) or patients at disease recurrence (n = 16). Paired tumor and plasma samples were available for most patients (24 of 30). Targeted amplicon, next-generation sequencing was performed using primers that flanked germline mutations, whose design did not rely on prior knowledge of reversion sequences. Results Five patients were identified with intragenic mutations predicted to restore BRCA1/2 open reading frames, including two patients with multiple independent reversion alleles. Reversion mutations were only detected in tumor samples from patients with recurrent disease (five of 16) and only in cfDNA from patients with a tumor-detected reversion (three of five). Findings from a rapid autopsy of a patient with multiple independent reversions indicated that reversion-allele frequency in metastatic sites is an important determinant of assay sensitivity. Abundance of tumor-derived DNA in total cell-free DNA, as measured by TP53 mutant allele frequency, also affected assay sensitivity. All patients with reversions detected in tumor-derived DNA were resistant to platin- or poly ADP ribose polymerase inhibitor-based chemotherapy. Conclusion Reversion mutations can be detected in an unbiased analysis of cfDNA, suggesting clinical utility for predicting chemotherapy response in recurrent HGSC.

Early dialysis initiation does not improve clinical outcomes in elderly end-stage renal disease patients: A multicenter prospective cohort study.

The optimal timing for initiating dialysis in end-stage renal disease (ESRD) is controversial, especially in the elderly.

Reduction in the copy number and expression level of the recurrent human papillomavirus integration gene fragile histidine triad (FHIT) predicts the transition of cervical lesions.

Cervical cancer is the second most common cancer and the third leading cause of cancer death in females worldwide, especially in developing countries. High risk human papillomavirus (HR-HPV) infection causes cervical cancer and precancerous cervical intraepithelial neoplasia (CIN). Integration of the HR-HPV genome into the host chromatin is an important step in cervical carcinogenesis. The detection of integrated papillomavirus sequences-PCR (DIPS-PCR) allowed us to explore HPV integration in the human genome and to determine the pattern of this integration. We performed DIPS-PCR for 4 cell lines including 3 cervical cancer cell lines and 40 tissue samples. Overall, 32 HR-HPV integration loci were detected in the clinical samples and the HeLa and SiHa cell lines. Among all the integration loci, we identified three recurrent integration loci: 3p14.2 (3 samples), 13q22.1 (2 samples and a SiHa cell line) and 8q24 (1 sample and a HeLa cell line). To further explore the effect of HR-HPV integration in the 3p14.2 locus, we used fluorescence in situ hybridization (FISH) to determine the copy number of the 3p14.2 locus and immunohistochemistry (IHC) to determine the protein expression levels of the related FHIT gene in the clinical samples. Both the 3p14.2 locus copy number and FHIT protein expression levels showed significant decreases when CIN transitioned to cervical cancer. HPV copy number was also evaluated in these clinical samples, and the copy number of HPV increased significantly between CIN and cervical cancer samples. Finally, we employed receiver operating characteristic curve (ROC curve) analysis to evaluate the potential of all these indexes in distinguishing CIN and cervical cancer, and the HPV copy number, FHIT copy number and FHIT protein expression levels have good diagnostic efficiencies.

Dividing CKD stage 3 into G3a and G3b could better predict the prognosis of IgA nephropathy.

Chronic kidney disease (CKD) stage 3 was divided into stage G3a and stage G3b in the 2013 Kidney Disease Improving Global Outcomes guidelines. Whether it is appropriate to regard 45 mL/min/per 1.73 m2 as the threshold value of G3a/G3b staging and whether dividing CKD stage 3 into G3a/G3b plays a useful role in assessing the prognosis of patients with IgA nephropathy (IgAN) remain unknown. Three hundred and ninety patients from the First Affiliated Hospital of Zhengzhou University and Peking University First Hospital diagnosed with IgAN in CKD stage 3 were enrolled and successfully followed up. Cox proportional hazards model was used to analyze hazard ratios of reaching the composite endpoints (doubling of serum creatinine, end-stage renal disease: estimated glomerular filtration rate (eGFR) <15 ml/min/per 1.73 m2 or renal replacement therapy, or death) for patients with different eGFR and risk factors affecting composite endpoints. The Kaplan-Meier method was used to calculate the cumulative renal survival rate of patients. When eGFR was lower than 45 ml/min/per 1.73 m2, the hazard ratio increased sharply for patients in CKD stage 3 who reached the composite endpoints. Renal injury and prognosis were significantly different between patients in the G3a and G3b groups. Stage G3b was a major risk factor affecting prognosis. A threshold value of 45 ml/min/per 1.73 m2 appears appropriate to assess the prognosis of IgAN patients with CKD stage 3. Dividing IgAN patients with CKD stage 3 into G3a and G3b is very useful to help understand disease conditions and for predicting the risk for disease progression.

Long Noncoding RNA MNX1-AS1 Knockdown Inhibits Cell Proliferation and Migration in Ovarian Cancer.

Long noncoding RNAs (lncRNAs) have recently emerged as pivotal regulators that govern fundamental biological processes and disease pathogenesis. LncRNA MNX1-AS1 has been reported to promote cell proliferation and invasion in gallbladder cancer, but its biological role and regulatory mechanism in ovarian cancer are poorly defined. In this study, it was found that higher expression of lncRNA MNX1-AS1 is closely associated with International Federation of Gynecology and Obstetrics stage and lymphatic metastasis in ovarian cancer patients. RNA interference (RNAi) to downregulate the expression of lncRNA MNX1-AS1 was used in the ovarian cancer cell lines, OVCA433 and SKOV-3. CCK-8, EdU staining, and colony formation assays was used to test the viability and proliferation ability of these cells. Wound healing and transwell migration assays were performed to determine the migration ability of the cells. Cell cycle progression and apoptotic assays were carried out using flow cytometry. These in vitro loss-of-function experiments revealed that downregulation of lncRNA MNX1-AS1 suppressed cell proliferation, colony formation, cell migration ability, induced cell cycle arrest at the G0/G1 phase, and promoted apoptosis. Furthermore, MNX1-AS1 knockdown altered the protein expressions of CDK4, cyclin D, Bax, and Bcl-2. These findings demonstrated for the first time that lncRNA MNX1-AS1 functions as an oncogene in ovarian cancer and could be a potential target for this disease.

Expression of Long Noncoding RNA Urothelial Cancer Associated 1 Promotes Cisplatin Resistance in Cervical Cancer.

Cisplatin resistance is still one of the main reasons for failure of clinical therapy for cervical cancer. But the underlying molecular mechanisms involved in cisplatin resistance of cervical cancer have still remained unclear. Recent studies reported that long noncoding RNAs (lncRNAs) are novel nonprotein-coding transcripts, which might play a key role in cancer biogenesis and prognosis. One of the lncRNAs, urothelial cancer associated 1 (UCA1), has been shown to promote different types of cancer cell proliferation, migration, and invasion. This study showed that overexpression of UCA1 confers cisplatin resistance by promoting cancer cell proliferation and inhibiting apoptosis. In addition, knockdown of UCA1 remarkably decreased cisplatin resistance in cervical cancer cells. Moreover, results also indicated that UCA1 was involved in signaling pathways modulating cell apoptosis and proliferation. UCA1 suppressed apoptosis by downregulating caspase 3 and upregulating CDK2, whereas enhanced cell proliferation by increased level of survivin and decreased level of p21. This study reports for the first time that UCA1 might play an important role in the cisplatin resistance in cervical cancer, and also explain partially how UCA1 promotes cisplatin resistance in cancer cells. These results provide evidence to support that UCA1 can be used as a potential target for a novel therapeutic strategy for cervical cancer.

Acute ethanol exposure during late mouse neurodevelopment results in long-term deficits in memory retrieval, but not in social responsiveness.

Prenatal alcohol exposure can result in neurological changes in affected individuals and may result in the emergence of a broad spectrum of neurobehavioral abnormalities termed fetal alcohol spectrum disorders (FASD). The effects of ethanol exposure during development are both time and dose dependent. Although many animal models of FASD use more chronic ethanol exposure, acute developmental alcohol exposure may also cause long-lasting neuronal changes. Our research employed behavioral measures to assess the effects of a single early postnatal ethanol intoxication event in mice.

Postoperative Surveillance for Renal Cell Carcinoma.

Postoperative surveillance is an integral part of renal cell carcinoma (RCC) care. However, evidence supporting the practice is lacking. RCC guidelines offer disparate recommendations leading to variation in care. Recently, the effectiveness of guidelines has been questioned and a debate has ignited over whether current protocols merit optimization. Guidelines show limitations in RCC risk assessment, protocol stratification, and definition of duration of follow-up. Alternative strategies have addressed some of these limitations, but further analysis is warranted. Until challenges with assessing a survival benefit are negotiated, efforts should be made to optimize and standardize guidelines and learn of more tangible benefits to surveillance.

Salvage Surgery After Renal Mass Ablation.

Thermal ablative techniques represent treatment options for patients with small renal masses who are not candidates for surgery. The oncologic efficacy of ablation has not been compared in a randomized fashion with nephron-sparing surgery, and the urologist must be knowledgeable regarding the workup and treatment of patients with suspected residual or recurrent tumor following these therapies. Surveillance of patients with tumor recurrence after ablation may be indicated in select circumstances. When patients are deemed appropriate for salvage therapy, most undergo a repeat course of the same ablative modality. Salvage surgery is possible but often complicated by the prior ablative techniques.

Neoadjuvant Targeted Molecular Therapy Before Renal Surgery.

Neoadjuvant targeted molecular therapy may benefit select patients with metastatic renal cell carcinoma. The primary use of this therapy in patients with metastatic disease is to reduce tumor burden, prevent distant metastasis, and increase overall survival. Neoadjuvant therapy may reduce tumor size and tumor complexity, facilitate partial nephrectomy rather than radical nephrectomy, downstage tumor thrombus facilitating thrombectomy, and make unresectable tumors resectable when applied to selected patients. These potential benefits of neoadjuvant therapy require further clinical trials to better define the renal function and oncological and survival outcomes in patients receiving each active agent.

Complications of Renal Surgery.

The incidence of the small renal mass continues to increase owing to the aging population and the ubiquity imaging. Most of these tumors are stage I tumors. Management strategies include surveillance, ablation, and extirpation. There is a wide body of literature favoring nephron-sparing approaches. Although nephron-sparing surgery may yield decreased long-term morbidity, it is not without its drawbacks, including a higher rate of complications. Urologists must be attuned to the complications of surgery and develop strategies to minimize risk. This article reviews expected complications of surgery on renal masses and risk stratification schema.

Lymph Node Dissection for Small Renal Masses.

Because the majority of small renal masses (SRMs; <4 cm) demonstrate low metastatic potential and can be effectively treated with radical or partial nephrectomy, the role of lymph node dissection (LND) at the time of surgery is unclear. A randomized trial demonstrated no survival benefit of LND in clinically localized renal cell carcinoma. Thus, LND is not recommended routinely for SRMs. For patients with high-risk features or radiographic evidence of lymphadenopathy, however, LND may improve local staging and potentially provide a survival benefit. If performed, a LND template should be based on the known lymphatic drainage of the kidneys.

Comparative Effectiveness of Surgical Treatments for Small Renal Masses.

In the management of small renal masses (SRMs), treatment options include partial nephrectomy (PN), radical nephrectomy (RN), ablation, renal biopsy, and active surveillance. Large series retrospective and meta-analyses demonstrate PN may confer greater preservation of renal function, overall survival, and equivalent cancer control when compared with RN. As newer therapies emerge, we should critically evaluate the risks and benefits associated with the surgical management of SRMs among patients with competing comorbidities, complex tumors, and high-risk disease. Among younger patients with SRMs amenable to resection, optimization of postoperative patient health should be prioritized.

Renal Ischemia and Functional Outcomes Following Partial Nephrectomy.

Renal function after renal cancer surgery is a critical component of survivorship. Quantity and quality of preserved parenchyma are the most important determinants of functional recovery; type and duration of ischemia play secondary roles. Several studies evaluated surgical techniques to minimize ischemia; however, long-term outcomes and potential benefits over clamped partial nephrectomy (PN) have not been consistently demonstrated. Analysis of acute kidney injury (AKI) after PN suggest that most kidneys recover strongly even if AKI is experienced after surgery. Ongoing study is required to evaluate long-term implications of AKI after PN and further assess impact of ischemia on functional outcomes.

Surgical Techniques in the Management of Small Renal Masses.

This article provides a review and outline of the various surgical techniques for small renal masses. It covers surgical approaches and compares outcomes of open versus minimally invasive surgery. The article discusses renal nephrometry scoring and renal ischemia at time of resection. Techniques for controlling the renal hilum and controlling blood flow to the kidney are described. Extirpative techniques for small renal masses are reviewed along with a comparison of outcomes. With careful adherence to key oncologic and surgical principles, negative margins, no complications, and no or minimal decline in renal functional outcomes can be achieved.

Ablative Therapy for Small Renal Masses.

The management of small renal masses has become an important public health topic. The increased use of cross-sectional imaging and ultrasound has led to a downward stage migration for the detection of small renal masses. Cancer-specific survival, however, has not reflected this trend accordingly. Although partial nephrectomy has been the mainstay of treatment of small renal masses less than 4 cm, there is growing interest in ablative therapies, such as cryoablation and radiofrequency ablation, due to decreased morbidity. Oncologic outcomes are limited by methodology and length of follow-up, but short-term recurrence rates are low.

Active Surveillance for the Small Renal Mass: Growth Kinetics and Oncologic Outcomes.

Active surveillance for small renal masses (SRMs) is an accepted management strategy for patients with prohibitive surgical risk. Emerging prospectively collected data support the concept that a period of initial active surveillance in an adherent patient population with well-defined criteria for delayed intervention is safe. This article summarizes the literature describing growth kinetics of SRMs managed initially with observation and oncologic outcomes for patients managed with active surveillance. Existing clinical tools to determine and contextualize competing risks to mortality are explored. Finally, current prospective clinical trials with defined eligibility criteria, surveillance schema, and triggers for delayed intervention are highlighted.

Current Role of Renal Biopsy in Urologic Practice.

Most small renal masses (SRMs) are indolent. In fact, only approximately 80% of SRMs are malignant. Furthermore, SRMs are commonly detected in elderly and comorbid patients. Therefore, opportunities for better care intensity calibration exist. Renal mass biopsy (RMB), when appropriately used, is a valuable clinical tool to help with critical clinical decision-making in patients with SRM. This article summarizes the role of modern RMB in helping gauge care for patients with SRM.

Risk Assessment in Small Renal Masses: A Review Article.

The incidence of localized renal cell carcinoma (RCC) has been steadily increasing, in large part because of the increased use of imaging. Optimizing the management of localized RCC has become one of the leading priorities and foremost challenges within the urologic-oncologic community. Adequate risk stratification of patients following the diagnosis of localized RCC has become meaningful in deciding whether to treat, how to treat, and how intensively to treat. This article characterizes the existing risk assessment models that can be useful as treatment decision aids for patients with localized RCC.

Renal Tumor Anatomic Complexity: Clinical Implications for Urologists.

Anatomic tumor complexity can be objectively measured and reported using nephrometry. Various scoring systems have been developed in an attempt to correlate tumor complexity with intraoperative and postoperative outcomes. Nephrometry may also predict tumor biology in a noninvasive, reproducible manner. Other scoring systems can help predict surgical complexity and the likelihood of complications, independent of tumor characteristics. The accumulated data in this new field provide provocative evidence that objectifying anatomic complexity can consolidate reporting mechanisms and improve metrics of comparisons. Further prospective validation is needed to understand the full descriptive and predictive ability of the various nephrometry scores.

Current Trends in Renal Surgery and Observation for Small Renal Masses.

There has been a rising incidence of small renal masses and concomitant downward stage migration. This has led to an evolution in the management of kidney cancer from radical nephrectomy to nephron-sparing treatment options including observation. The adoption of partial nephrectomy continues to increase but is still incomplete leading to significant disparities in the delivery of care throughout the country. Surgical excision remains the treatment of choice for small kidney cancers; however, ablative therapies and active surveillance are emerging as reasonable options for select patients. With continued refinements in treatment options and improvements in ability to risk stratify SRMs, the current treatment trends will likely continue to evolve.

Hereditary Kidney Cancer Syndromes and Surgical Management of the Small Renal Mass.

The management of patients with hereditary kidney cancers presents unique challenges to clinicians. In addition to an earlier age of onset compared with patients with sporadic kidney cancer, those with hereditary kidney cancer syndromes often present with bilateral and/or multifocal renal tumors and are at risk for multiple de novo lesions. This population of patients may also present with extrarenal manifestations, which adds an additional layer of complexity. Physicians who manage these patients should be familiar with the underlying clinical characteristics of each hereditary kidney cancer syndrome and the suggested surgical approaches and recommendations of genetic testing for at-risk individuals.

Epidemiology of the Small Renal Mass and the Treatment Disconnect Phenomenon.

The incidence of kidney cancer has steadily increased over recent decades, with most new cases now found when lesions are asymptomatic and small. This downward stage migration relates to the increasing use of abdominal imaging. Three public health epidemics-smoking, hypertension, and obesity-also play roles in the increase. Treatment mirrors the rise in incidence, with increasing interest in nephron-sparing therapies. Despite earlier detection and increasing treatment, the mortality rate has not decreased. This treatment disconnect phenomenon highlights the need to decrease unnecessary treatment of indolent tumors and address modifiable risk factors to reduce incidence and mortality.