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Female Urogenital Diseases and Pregnancy Complications - Top 30 Publications

The clinical utility and cost impact of cystatin C measurement in the diagnosis and management of chronic kidney disease: A primary care cohort study.

To reduce over-diagnosis of chronic kidney disease (CKD) resulting from the inaccuracy of creatinine-based estimates of glomerular filtration rate (GFR), UK and international guidelines recommend that cystatin-C-based estimates of GFR be used to confirm or exclude the diagnosis in people with GFR 45-59 ml/min/1.73 m2 and no albuminuria (CKD G3aA1). Whilst there is good evidence for cystatin C being a marker of GFR and risk in people with CKD, its use to define CKD in this manner has not been evaluated in primary care, the setting in which most people with GFR in this range are managed.

Points to consider in renal involvement in systemic sclerosis.

This article discusses points to consider when undertaking a clinical trial to test therapy for renal involvement in SSc, not including scleroderma renal crisis. Double-blind, randomized controlled trials vs placebo or standard background therapy should be strongly considered. Inclusion criteria should consider a pre-specified range of renal functions or stratification of renal function. Gender and age limitations are probably not necessary. Concomitant medications including vasodilators, immunosuppressants and endothelin receptor antagonists and confounding illnesses such as diabetes, kidney stones, hypertension and heart failure need to be considered. A measure of renal function should be strongly considered, while time to dialysis, mortality, prevention of scleroderma renal crisis and progression of renal disease can also be considered, although they remain to be validated. Detailed, pre-planned analysis should be strongly considered and should include accounting for missing data.

Clinicopathological features of progressive renal involvement in TAFRO syndrome: A case report and literature review.

TAFRO syndrome is a systemic inflammatory disease characterized by a constellation of symptoms: Thrombocytopenia, Anasarca, MyeloFibrosis, Renal dysfunction, and Organomegaly. Progressive renal insufficiency is a predominant symptom; however, the mechanism of acute kidney injury (AKI) remains unclear, probably because severe thrombocytopenia prevents kidney biopsy. We report a rare case of TAFRO syndrome with histologically confirmed renal involvement.

Ovarian torsion of mixed epithelial tumor misdiagnosed as a malignancy in postmenopausal woman: A case report.

Adnexal torsion is 1 of the most common emergency gynecological disease. It is more often diagnosed in reproductive age, but rarely in postmenopausal women. The clinical symptoms of adnexal torsion are nonspecific in postmenopausal women. Epithelial ovarian tumors are common in adults, and the risk of malignancy increases with age, especially after menopause. So, it is difficult to diagnose adnexal torsion precisely compared with reproductive women, and most cases of adnexal torsion with postmenopausal women are diagnosed as a malignancy preoperatively. We report a case of ovarian torsion with mixed epithelial tumor misdiagnosed as a malignancy in postmenopausal woman.

Management of iatrogenic renal arteriovenous fistula and renal arterial pseudoaneurysm by transarterial embolization: A single center analysis and outcomes.

The purpose of this study was to evaluate the efficacy and safety of transarterial embolization (TAE) for iatrogenic renal arterial pseudoaneurysm and arteriovenous fistula at our center.Our retrospective analysis included 27 patients who received TAE for iatrogenic renal arterial pseudoaneurysm and arteriovenous fistula between January 2006 and January 2016. Data on demographics, type of minimally invasive renal procedures, clinical manifestation, imaging features, embolization procedure, and perioperative details were collected. The technical and clinical success rates were analyzed. Furthermore, the changes in serum creatinine and eGFR before and after embolization were recorded and compared by t test.The median time between iatrogenic renal injury and TAE was 3 days (range, 0-110 days), with most patients (24/27, 88.9%) receiving TAE within 14 days. Only 1 patient was diagnosed with renal artery pseudoaneurysm 110 days after laproscopic partial nephrectomy. The technical and clinical success rates were 100% and 96.3%, respectively, with 1 patient requiring a second embolotherapy at the third postoperative day. No other patient required additional endovascular or surgical intervention due to recurrent hemorrhage. The mean serum creatinine before TAE was 92.8 ± 25.3 μmol/L and after TAE, 96.1 ± 27.7 μmol/L (P = .095). The eGFR of pre- and postembolization was 75.2 ± 26.5 mL/min/1.73 m and 72.5 ± 26.2 mL/min/1.73 m (P = .16). No severe complications were observed during follow-up.This retrospective review demonstrated that TAE for the treatment of iatrogenic renal artery pseudoaneurysm and/or arteriovenous fistula was safe and associated with high technical and clinical success rate.

Epidemic hemorrhagic fever complicated with late pregnancy: A case report.

Hantaviruses cause two forms of diseases in humans, namely hemorrhagic fever with renal syndrome (HFRS) and hantavirus pulmonary syndrome. Hantavirus infections can occur in pregnant women, and could influence the maternal and fetal outcomes, although this is a rare finding, even in endemic areas.

The association between diabetes/hyperglycemia and the prognosis of cervical cancer patients: A systematic review and meta-analysis.

The predictive roles of diabetes in the prognosis of many types of cancer have been well studied, but its role in predicting the prognosis of cervical cancer is still controversial. The aim of the study is to evaluate the association between diabetes/hyperglycemia and the prognosis of cervical cancer.

MECHANISMS IN ENDOCRINOLOGY: Maternal thyroid dysfunction during pregnancy and behavioural and psychiatric disorders of children: a systematic review.

Maternal thyroid dysfunction during pregnancy may lead to persistent neurodevelopmental disorders in the offspring appearing in later life. This study aimed to review the available evidence concerning the relationship between maternal thyroid status during pregnancy and offspring behavioural and psychiatric disorders.

Transanal Assisted Resection with Closure of Anal Canal for Lower Rectal Diseases.

Abdominoperineal resection (APR) has been performed for lower rectal cancer, anal cancer and inflammatory diseases, but is associated with postoperative complications such as inflammation of pelvic dead space or perineal wound infection. We are performing a novel procedure (transanal assisted resection with closure of anal canal, TARC) that resects the intestine by using transanal assist and close the anal canal for patients who do not require resection of the anus and anal canal.

The Use of External-beam Radiotherapy for Muscle-invasive Bladder Cancer in Elderly or Medically-fragile Patients.

To evaluate the clinical results of external-beam radiotherapy (EBRT) for muscle-invasive bladder cancer (MIBC) in elderly or medically-fragile patients.

ABO Blood Group and Rhesus Factor Are Not Associated with Outcomes After Radical Cystectomy for Non-metastatic Urothelial Carcinoma of the Bladder.

To investigate the role of ABO blood group and Rhesus factor as a predictor of outcome in patients undergoing radical cystectomy (RC) for non-metastatic urothelial carcinoma of the bladder.

Debulking Surgery for Clear Cell Carcinoma of the Ovary - A Case Report and Literature Review.

Ovarian clear cell carcinoma represents a distinct histopathological subtype of epithelial ovarian cancer, with poor outcomes, especially in cases diagnosed in advanced stages of disease. However, even in these cases, it seems that the most effective treatment remains debulking surgery to no residual disease. We present the case of a 56-year-old patient diagnosed with a large pelvic mass invading the rectosigmoidal colon, and ileal loop who was successfully submitted to cytoreductive surgery to no residual disease. The histopathological studies demonstrated the presence of a well-differentiated clear cell ovarian carcinoma of the ovary. At 1-year follow-up there is no evidence of residual disease.

The Impact of Surgical Staging on the Prognosis of Mucinous Borderline Tumors of the Ovaries: A Multicenter Study.

The purpose of this study was to prove the effect of complete surgical staging of patients with mucinous borderline ovarian tumors (mBOTs) especially appendectomy on progression-free survival (PFS) and overall survival (OS).

Radical Cystectomy Versus Chemoradiation for Muscle-invasive Bladder Cancer: Impact of Treatment Facility and Sociodemographics.

The present study sought to compare the differences in practice patterns, as well as clinical outcomes for patients with muscle-invasive bladder cancer undergoing treatment with either radical cystectomy (RC) or concurrent chemoradiaiton (CRT).

Clinical Impact of Re-irradiation with Carbon-ion Radiotherapy for Lymph Node Recurrence of Gynecological Cancers.

To evaluate the safety and efficacy of re-irradiation with carbon-ion radiotherapy (C-ion RT) for lymph node recurrence of gynecological cancers after definitive radiotherapy.

Clinicopathological Characteristics of Ovarian Sclerosing Stromal Tumor with an Emphasis on TFE3 Overexpression.

A sclerosing stromal tumor is a very rare benign sex cord-stromal tumor of the ovary. Because its clinical presentation and imaging findings are similar to those of borderline or malignant epithelial tumors and other sex cord-stromal tumors, accurate preoperative clinical diagnosis can be difficult. The aim of this study was to analyze the clinicopathological characteristics of SSTs and examine the immunohistochemical expression TFE3, which has not been studied in SSTs. Our study cohort consisted of 9 patients diagnosed as having SST; the median age was 36 years. Radiologically, SSTs presented as multiseptated cystic masses, mixed echoic masses, pseudolobular masses, solid pelvic masses, or uterine subserosal nodules. In 4 of the 9 cases, the preoperative clinical impression was a borderline or malignant ovarian tumor. SSTs displayed the following histopathological features: 1) relatively well-circumscribed cellular nodules that were randomly distributed in the fibrous or edematous stroma; 2) a characteristic alternating pattern of hypercellular and hypocellular areas; 3) a hemangiopericytoma-like vascular growth pattern in the cellular nodules; 4) bland-looking spindle-shaped cells and round or polygonal cells densely clustered around blood vessels; and 5) red blood cell-containing intracytoplasmic vacuole-like spaces in the tumor cell cytoplasm, possibly indicating epithelioid hemangioendothelioma. Immunohistochemically, the tumor cells exhibited diffuse and moderate-to-strong TFE3 expression in 7 of the 9 SSTs. TFE3 was strongly expressed in the nuclei of round or polygonal cells and lutein cells. In contrast, neither luteinized thecomas nor fibromas appreciably expressed TFE3. In summary, our study describes characteristic histopathological features that may be useful for differentiating SSTs from other sex-cord stromal tumors and demonstrates for the first time that SSTs show strong TFE3 expression. Further investigations are necessary to clarify the role of TFE3 in the development of SSTs.

Multi-micronutrient supplementation during pregnancy for prevention of maternal anaemia and adverse birth outcomes in a high-altitude area: a prospective cohort study in rural Tibet of China.

Anaemia during pregnancy, characterised by Hb <110 g/l, is a specific risk factor for adverse maternal and perinatal outcomes in developing countries. The objective of this study was to determine the effectiveness of daily antenatal supplementation with multiple micronutrients (MMN) compared with folic acid (FA) on the occurrence of anaemia among pregnant women and their infants' health in a high-altitude area. A prospective cohort study was carried out in two rural counties in Tibet from 2007 to 2012. A total of 1149 eligible pregnant women were allocated daily supplementation with FA in one county and MMN containing a recommended allowance of twenty-three vitamins and minerals in another county starting ≤24 weeks of gestation and continuing until delivery. Compared with the FA group, prenatal supplementation with MMN was significantly associated with reduced odds of anaemia in the third trimester. This was demonstrated in the primary outcome, with an adjusted OR (AOR) of 0·63; 95 % CI 0·45, 0·88 and P=0·007 and also reduced odds of preterm delivery (AOR: 0·31; 95 % CI 0·15, 0·61; P=0·001). There was no difference between MMN and FA groups in mean birth weight (adjusted mean difference: 36·78; 95 % CI -19·42, 92·98 g; P=0·200), whereas MMN supplementation significantly reduced the odds of low-birth weight (LBW) babies (AOR: 0·58; 95 % CI 0·36, 0·91; P=0·019). In conclusion, the antenatal MMN supplementation in rural Tibet is associated with a reduction of maternal anaemia in the third trimester, and may potentially decrease the risk of preterm delivery and LBW babies.

Assessing the neuroprotective benefits for babies of antenatal magnesium sulphate: An individual participant data meta-analysis.

Babies born preterm are at an increased risk of dying in the first weeks of life, and those who survive have a higher rate of cerebral palsy (CP) compared with babies born at term. The aim of this individual participant data (IPD) meta-analysis (MA) was to assess the effects of antenatal magnesium sulphate, compared with no magnesium treatment, given to women at risk of preterm birth on important maternal and fetal outcomes, including survival free of CP, and whether effects differed by participant or treatment characteristics such as the reason the woman was at risk of preterm birth, why treatment was given, the gestational age at which magnesium sulphate treatment was received, or the dose and timing of the administration of magnesium sulphate.

Brain MRI in Infants after Maternal Zika Virus Infection during Pregnancy.

Breast Cancer Survivorship: Patient Characteristics and Plans for High-Quality Care.

The number of breast cancer survivors has increased and this increase is expected to continue, likely as a result of population and age growth, the implementation of earlier detection strategies, and the development of more effective therapies. Breast cancer treatment requires a multidisciplinary approach with surgery, radiation, chemotherapy, targeted therapy, and hormonal therapy. Breast cancer survivors may develop various long-term adverse effects from these therapies. Care of the survivor may transition eventually to the primary care physician. Survivorship care plans have been developed to facilitate care transition, guide the content and coordination of posttreatment care, and engender greater self-management of health by cancer survivors. Guidelines for posttreatment follow-up care are discussed in this article, and interventions that patients may practice to promote a healthy lifestyle also are presented.

Treatment of the Pregnant Patient with Breast Cancer.

Pregnancy-associated breast cancer is defined as invasive breast cancer diagnosed during gestation, within 1 year postpartum, or during lactation. Of particular interest is the treatment of invasive breast cancer during gestation; standard treatment protocols must take into account the health of the fetus. This article reviews the literature and emerging data regarding the treatment of pregnancy-associated breast cancer. Existing staging and treatment practices need slight modification in the setting of pregnancy. The timing of surgery and the administration of cytotoxic chemotherapy must take into account age of gestation, but these modalities are safe in pregnancy.

Fertility Preservation in Breast Cancer.

As more young women survive breast cancer, fertility preservation (FP) is an important component of care. This review highlights the importance of early pretreatment referral, reviews the risks of infertility associated with breast cancer treatment, and defines existing and emerging techniques for FP. The techniques reviewed include ovarian suppression, embryo cryopreservation, oocyte cryopreservation, and ovarian tissue cryopreservation and transplantation. The barriers women face, such as not being appropriately referred and the costs of treatment, also are addressed. Multidisciplinary, patient-centered care is essential to discussing FP with patients with breast cancer and ensuring appropriate care that includes quality of life in survivorship.

Association Between Use of Antithrombotic Medication and Hematuria-Related Complications.

Antithrombotic medications are among the most commonly prescribed medications.

Urinary Tract Infection.

Urinary tract infections (UTIs) are common in both inpatient and outpatient settings. This article provides an evidence-based, clinically relevant overview of management of UTIs, including screening, diagnosis, treatment, and prevention. Conditions covered include acute cystitis (both uncomplicated and complicated), catheter-associated UTI, and asymptomatic bacteriuria in both women and men.

Biallelic Mutations in PATL2 Cause Female Infertility Characterized by Oocyte Maturation Arrest.

Oocyte maturation arrest results in female infertility, but the genetic determinants of human oocyte maturation arrest remain largely unknown. Previously, we identified TUBB8 mutations responsible for human oocyte maturation arrest, indicating the important role of genetic factors in the disorder. However, TUBB8 mutations account for only around 30% of individuals with oocyte maturation arrest; thus, the disorder is likely to involve other genetic factors that are as yet unknown. Here, we initially identified a homozygous nonsense mutation of PATL2 (c.784C>T [p.Arg262(∗)]) in a consanguineous family with a phenotype characterized by human oocyte germinal vesicle (GV) arrest. Subsequent mutation screening of PATL2 in a cohort of 179 individuals identified four additional independent individuals with compound-heterozygous PATL2 mutations with slight phenotypic variability. A genetic burden test further confirmed the genetic contribution of PATL2 to human oocyte maturation arrest. By western blot in HeLa cells, identification of splicing events in affected individuals' granulosa cells, and immunostaining in affected individuals' oocytes, we provide evidence that mutations in PATL2 lead to decreased amounts of protein. These findings suggest an important role for PATL2 mutations in oocyte maturation arrest and expand our understanding of the genetic basis of female infertility.

Hypomorphic Recessive Variants in SUFU Impair the Sonic Hedgehog Pathway and Cause Joubert Syndrome with Cranio-facial and Skeletal Defects.

The Sonic Hedgehog (SHH) pathway is a key signaling pathway orchestrating embryonic development, mainly of the CNS and limbs. In vertebrates, SHH signaling is mediated by the primary cilium, and genetic defects affecting either SHH pathway members or ciliary proteins cause a spectrum of developmental disorders. SUFU is the main negative regulator of the SHH pathway and is essential during development. Indeed, Sufu knock-out is lethal in mice, and recessive pathogenic variants of this gene have never been reported in humans. Through whole-exome sequencing in subjects with Joubert syndrome, we identified four children from two unrelated families carrying homozygous missense variants in SUFU. The children presented congenital ataxia and cerebellar vermis hypoplasia with elongated superior cerebellar peduncles (mild "molar tooth sign"), typical cranio-facial dysmorphisms (hypertelorism, depressed nasal bridge, frontal bossing), and postaxial polydactyly. Two siblings also showed polymicrogyria. Molecular dynamics simulation predicted random movements of the mutated residues, with loss of the native enveloping movement of the binding site around its ligand GLI3. Functional studies on cellular models and fibroblasts showed that both variants significantly reduced SUFU stability and its capacity to bind GLI3 and promote its cleavage into the repressor form GLI3R. In turn, this impaired SUFU-mediated repression of the SHH pathway, as shown by altered expression levels of several target genes. We demonstrate that germline hypomorphic variants of SUFU cause deregulation of SHH signaling, resulting in recessive developmental defects of the CNS and limbs which share features with both SHH-related disorders and ciliopathies.

Female Infertility Caused by Mutations in the Oocyte-Specific Translational Repressor PATL2.

Infertility is a relatively common disorder of the reproductive system and remains unexplained in many cases. In vitro fertilization techniques have uncovered previously unrecognized infertility phenotypes, including oocyte maturation arrest, the molecular etiology of which remains largely unknown. We report two families affected by female-limited infertility caused by oocyte maturation failure. Positional mapping and whole-exome sequencing revealed two homozygous, likely deleterious variants in PATL2, each of which fully segregates with the phenotype within the respective family. PATL2 encodes a highly conserved oocyte-specific mRNP repressor of translation. Previous data have shown the strict requirement for PATL2 in oocyte-maturation in model organisms. Data gathered from the families in this study suggest that the role of PATL2 is conserved in humans and expand our knowledge of the factors that are necessary for female meiosis.

Development of in vitro maturation techniques for clinical applications.

In vitro maturation (IVM) refers to maturation in culture of immature oocytes at different stages that may or may not have been exposed to short courses of gonadotropins. The source of immature oocytes is an important feature for subsequent embryonic development, pregnancy, and healthy live births. IVM is an effective treatment that has already achieved significant outcomes of acceptable pregnancy and implantation rates and has led to the births of several thousand healthy babies. As the development of IVM treatment continues, an attractive possibility for improving the already successful outcome is to combine a natural-cycle in vitro fertilization (IVF) treatment with immature-oocyte retrieval followed by IVM of those immature oocytes. If the treatment processes can be simplified for immature-oocyte retrieval, different types of infertile women may be able to take advantage of these treatments. Mild-stimulation IVF combined with IVM treatment may represent a viable alternative to the standard treatment. Although IVM treatment is still considered to be experimental, it is now time to reconsider the IVM technology and its development. Mild-stimulation IVF combined with IVM may prove to be not just alternatives to standard treatments, but potentially first-line treatment choices.

In vitro fertilization treatments with the use of clomiphene citrate or letrozole.

There has been increasing interest in combining the oral agents clomiphene citrate (CC) and letrozole with gonadotropins in IVF: for poor responders to reduce the amount of gonadotropins used, and in normal responders to reduce the incidence of ovarian hyperstimulation (OHSS). In normal responders, mild stimulation with the use of CC and gonadotropins was found to decrease the number of oocytes retrieved and result in good pregnancy rates, but in most studies the cumulative pregnancy rate was lower compared with conventional ovarian stimulation when frozen embryo transfers were considered. Coadministration of letrozole and gonadotropins has mainly been used in patients with breast cancer to prevent the massive elevation of serum E2 concentrations with the use of standard controlled ovarian hyperstimulation. CC and letrozole have both been used with gonadotropins in poor responders and have been shown to reduce the amount of gonadotropin used without reducing the pregnancy rate. Letrozole use with gonadotropins in IVF cycles may increase endometrial receptivity by increasing integrin expression in the endometrium and by lowering estrogen concentrations to more physiologic levels.

Mild stimulation for in vitro fertilization.

It has been proven that the use of high gonadotropin dose does not necessarily improve the final outcome of IVF. Mild ovarian stimulation is based on the principle of optimal utilization of competent oocytes/embryos and endometrial receptivity. There is growing evidence that the pregnancy or live birth rates with mild-stimulation protocols are comparable to those with conventional IVF; the cumulative pregnancy outcome has been shown to be no different, despite having fewer numbers of oocytes or embryos available with milder ovarian stimulation. Although equally effective, mild-stimulation IVF is associated with a greater safety profile, in terms of the incidence of ovarian hyperstimulation syndrome and venous thromboembolism. It is also found to be better tolerated by patients and less expensive. Emerging research evidence may lead to widespread acceptance of mild IVF, by both patients and IVF providers, and make IVF more accessible to women and couples worldwide.