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The Application of Clinical Genetics 2021H syndrome is an extremely rare autosomal recessive affection caused by biallelic mutations in the SLC29A3 gene encoding the human equilibrative nucleoside transporter...
H syndrome is an extremely rare autosomal recessive affection caused by biallelic mutations in the SLC29A3 gene encoding the human equilibrative nucleoside transporter hENT3. The hallmark signs are cutaneous consisting of hyperpigmentation and hypertrichosis patches. Besides, associated systemic manifestations are highly various reflecting phenotypic pleiotropism. Herein, we report a first case of pseudo-Meigs' syndrome occurring in a young Tunisian H syndrome diagnosed patient with a novel homozygous frameshift mutation in exon 2 of the SLC29A3 gene: p.S15Pfs*86 inducing a premature stop codon. The patient developed ascites associated with left ovarian mass and she underwent surgery. After tumor resection, ascites disappeared rapidly. Histological examination showed serous cystadenoma of the ovary orienting the diagnosis towards pseudo-Meigs' syndrome.
PubMed: 33883924
DOI: 10.2147/TACG.S306298 -
Respiratory Medicine Case Reports 2021A 63-year-old female was admitted to our hospital with history of persistent dyspnea. Right pleural effusion and ovarian tumor were discovered, but here were no...
A 63-year-old female was admitted to our hospital with history of persistent dyspnea. Right pleural effusion and ovarian tumor were discovered, but here were no significant findings on thoracoscopy under local anesthesia. The pleural effusion was suspected to be secondary to Meigs' syndrome, and a diagnosis of endometriotic ovarian cyst was made. Since the pleural effusion resolved after surgery, the patient was diagnosed with incomplete pseudo-Meigs' syndrome. We consider this to be a valuable case, as there are no previously reported cases of pseudo-Meigs' syndrome derived from an endometriotic ovarian cyst, to the best of our knowledge.
PubMed: 33854937
DOI: 10.1016/j.rmcr.2021.101387 -
Science Advances Apr 2021The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) macrodomain within the nonstructural protein 3 counteracts host-mediated antiviral adenosine...
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) macrodomain within the nonstructural protein 3 counteracts host-mediated antiviral adenosine diphosphate-ribosylation signaling. This enzyme is a promising antiviral target because catalytic mutations render viruses nonpathogenic. Here, we report a massive crystallographic screening and computational docking effort, identifying new chemical matter primarily targeting the active site of the macrodomain. Crystallographic screening of 2533 diverse fragments resulted in 214 unique macrodomain-binders. An additional 60 molecules were selected from docking more than 20 million fragments, of which 20 were crystallographically confirmed. X-ray data collection to ultra-high resolution and at physiological temperature enabled assessment of the conformational heterogeneity around the active site. Several fragment hits were confirmed by solution binding using three biophysical techniques (differential scanning fluorimetry, homogeneous time-resolved fluorescence, and isothermal titration calorimetry). The 234 fragment structures explore a wide range of chemotypes and provide starting points for development of potent SARS-CoV-2 macrodomain inhibitors.
Topics: Catalytic Domain; Crystallography, X-Ray; Humans; Models, Molecular; Molecular Docking Simulation; Protein Binding; Protein Conformation; SARS-CoV-2; Viral Nonstructural Proteins; COVID-19 Drug Treatment
PubMed: 33853786
DOI: 10.1126/sciadv.abf8711 -
BMJ Case Reports Mar 2021A 64-year-old woman referred to Gynaecological Oncology secondary to the finding of pelvic mass and ascites. Imaging showed multiple pelvic masses, with the largest mass...
A 64-year-old woman referred to Gynaecological Oncology secondary to the finding of pelvic mass and ascites. Imaging showed multiple pelvic masses, with the largest mass measuring 20 cm in diameter, as well as bilateral pleural effusions and abdominal ascites, suspicious for ovarian carcinoma. Laboratory findings included elevated cancer antigen 125 (CA-125) of 2124 units/mL. The patient underwent an exploratory laparotomy, total abdominal hysterectomy and bilateral salpingo-oophorectomy for pathological evaluation. Postoperatively, the patient had resolution of ascites and pleural effusion. Surgical pathology revealed a 26 cm right ovarian fibroma, confirming the diagnosis of Meigs syndrome. Despite the high suspicion for ovarian carcinoma in patients presenting with elevated CA-125 level, pelvic mass, ascites and pleural effusion, the diagnosis of Meigs syndrome cannot be excluded without pathological evaluation of mass.
Topics: Ascites; CA-125 Antigen; Female; Humans; Meigs Syndrome; Middle Aged; Ovarian Neoplasms; Pleural Effusion; Salpingo-oophorectomy
PubMed: 33653838
DOI: 10.1136/bcr-2020-238931 -
World Journal of Clinical Cases Feb 2021Leiomyoma of the uterus is relatively common, but uterine leiomyoma of the greater omentum is rare.
BACKGROUND
Leiomyoma of the uterus is relatively common, but uterine leiomyoma of the greater omentum is rare.
CASE SUMMARY
Here, we report the case of a 22-year-old woman who presented with a 3 mo history of progressive abdominal distension and a hypervascular abdominopelvic mass. Due to a high serum concentration of CA125, the preoperative diagnosis was unclear. During surgery, 5 L of ascites was removed. An 18.8 cm solid mass, which was pedunculated from the uterine fundus and exhibited complex adhesion to the greater omentum, was removed. The CA125 level was reduced postoperatively, and a pathologic study confirmed that the mass was a leiomyoma that originated in the uterus.
CONCLUSION
Uterine leiomyoma can share vessels with the greater omentum. This case highlights the difficulty of diagnosing pseudo-Meigs syndrome and the importance of imaging and laboratory examinations.
PubMed: 33644211
DOI: 10.12998/wjcc.v9.i6.1424 -
BMJ Case Reports Feb 2021
Topics: Female; Humans; Meigs Syndrome
PubMed: 33541974
DOI: 10.1136/bcr-2020-241337 -
Scientific Reports Jan 2021Because single genetic variants may have pleiotropic effects, one trait can be a confounder in a genome-wide association study (GWAS) that aims to identify loci... (Meta-Analysis)
Meta-Analysis
Because single genetic variants may have pleiotropic effects, one trait can be a confounder in a genome-wide association study (GWAS) that aims to identify loci associated with another trait. A typical approach to address this issue is to perform an additional analysis adjusting for the confounder. However, obtaining conditional results can be time-consuming. We propose an approximate conditional phenotype analysis based on GWAS summary statistics, the covariance between outcome and confounder, and the variant minor allele frequency (MAF). GWAS summary statistics and MAF are taken from GWAS meta-analysis results while the traits covariance may be estimated by two strategies: (i) estimates from a subset of the phenotypic data; or (ii) estimates from published studies. We compare our two strategies with estimates using individual level data from the full GWAS sample (gold standard). A simulation study for both binary and continuous traits demonstrates that our approximate approach is accurate. We apply our method to the Framingham Heart Study (FHS) GWAS and to large-scale cardiometabolic GWAS results. We observed a high consistency of genetic effect size estimates between our method and individual level data analysis. Our approach leads to an efficient way to perform approximate conditional analysis using large-scale GWAS summary statistics.
Topics: Algorithms; Databases, Factual; Genetic Predisposition to Disease; Genome-Wide Association Study; Humans; Metabolic Syndrome; Models, Statistical; Phenotype
PubMed: 33510268
DOI: 10.1038/s41598-021-82000-1 -
IJU Case Reports Jan 2021I-metaiodobenzylguanidine scanning has high sensitivity and specificity for the diagnosis of tumors derived from sympathetic nerves or the adrenal medulla. We report the...
False-positive I-metaiodobenzylguanidine scan in a patient with renal cell carcinoma: A case of chromophobe renal cell carcinoma oncocytic variant with a complicated clinical course.
INTRODUCTION
I-metaiodobenzylguanidine scanning has high sensitivity and specificity for the diagnosis of tumors derived from sympathetic nerves or the adrenal medulla. We report the rare case of a I-metaiodobenzylguanidine false-positive renal cell carcinoma.
CASE PRESENTATION
The patient was referred to our hospital with an incidental left renal mass during evaluation for hypertension. An ovarian tumor and prominent ascites were also observed. Serum and urine catecholamine levels were high to suspect a catecholamine-producing tumor of the kidney. I-metaiodobenzylguanidine scintigraphy showed increased I-metaiodobenzylguanidine intake in the tumor. Laparoscopic radical left nephrectomy was performed. The pathologic diagnosis was an oncocytic variant of chromophobe renal cell carcinoma. No pheochromocytoma features were found.
CONCLUSION
We report the first case of a I-metaiodobenzylguanidine false-positive renal cell carcinoma. This case was diagnosed with primary aldosteronism and Meigs' syndrome, which made the clinical course more complicated.
PubMed: 33426495
DOI: 10.1002/iju5.12233 -
Nihon Hinyokika Gakkai Zasshi. the... 2021We present a case of pelvic organ prolapse and inguinal hernia worsened by a benign ovarian tumor with ascites. A 61-year-old woman was referred to us complaining of...
We present a case of pelvic organ prolapse and inguinal hernia worsened by a benign ovarian tumor with ascites. A 61-year-old woman was referred to us complaining of feeling of something protruding from her vagina. She was diagnosed with Stage III cystocele. Behavioral therapy was administered as she had only slight subjective symptoms. She visited us eight months later due to a rapid aggravation of cystocele and voiding difficulty. She subsequently developed acute abdominal pain caused by incarcerated inguinal hernia. Abdominal ultrasound, MRI and CT showed a 10.6×9.0 cm pelvic mass with ascites. As an ovarian cancer with peritoneal dissemination was suspected, she immediately underwent total abdominal hysterectomy, bilateral salpingo-oophorectomy and colposuspension. Pathological diagnosis was fibrothecoma, a benign ovarian tumor. Postoperative course was uneventful, and ascites quickly disappeared in a manner similar to Meigs syndrome. Although no procedure was done to manage inguinal hernia, it was unproblematic for 18 months, after that it worsened, necessitating hernial repair. She had no recurrence of prolapse or ascites.Increased intra-abdominal pressure due to abdominal mass or ascites can worsen prolapse and hernial diseases such as inguinal, umbilical, and abdominal hernia. In this case, ovarian fibrothecoma with ascites seemed to be responsible for worsening of the prolapse and inguinal hernia. To conclude, it is important to consider background diseases when examining patients with prolapse and coexisting hernial diseases.
PubMed: 35858808
DOI: 10.5980/jpnjurol.112.137 -
Diabetes Care Feb 2021We investigated sex and racial differences in insulin sensitivity, β-cell function, and glycated hemoglobin (HbA) and the associations with selected phenotypic...
Association of Baseline Characteristics With Insulin Sensitivity and β-Cell Function in the Glycemia Reduction Approaches in Diabetes: A Comparative Effectiveness (GRADE) Study Cohort.
OBJECTIVE
We investigated sex and racial differences in insulin sensitivity, β-cell function, and glycated hemoglobin (HbA) and the associations with selected phenotypic characteristics.
RESEARCH DESIGN AND METHODS
This is a cross-sectional analysis of baseline data from 3,108 GRADE (Glycemia Reduction Approaches in Diabetes: A Comparative Effectiveness Study) participants. All had type 2 diabetes diagnosed <10 years earlier and were on metformin monotherapy. Insulin sensitivity and β-cell function were evaluated using the HOMA of insulin sensitivity and estimates from oral glucose tolerance tests, including the Matsuda Index, insulinogenic index, C-peptide index, and oral disposition index (DI).
RESULTS
The cohort was 56.6 ± 10 years of age (mean ± SD), 63.8% male, with BMI 34.2 ± 6.7 kg/m, HbA 7.5 ± 0.5%, and type 2 diabetes duration 4.0 ± 2.8 years. Women had higher DI than men but similar insulin sensitivity. DI was the highest in Black/African Americans, followed by American Indians/Alaska Natives, Asians, and Whites in descending order. Compared with Whites, American Indians/Alaska Natives had significantly higher HbA, but Black/African Americans and Asians had lower HbA. However, when adjusted for glucose levels, Black/African Americans had higher HbA than Whites. Insulin sensitivity correlated inversely with BMI, waist-to-hip ratio, triglyceride-to-HDL-cholesterol ratio (TG/HDL-C), and the presence of metabolic syndrome, whereas DI was associated directly with age and inversely with BMI, HbA, and TG/HDL-C.
CONCLUSIONS
In the GRADE cohort, β-cell function differed by sex and race and was associated with the concurrent level of HbA. HbA also differed among the races, but not by sex. Age, BMI, and TG/HDL-C were associated with multiple measures of β-cell function and insulin sensitivity.
Topics: Blood Glucose; C-Peptide; Child; Child, Preschool; Cross-Sectional Studies; Diabetes Mellitus, Type 2; Female; Humans; Infant; Insulin; Insulin Resistance; Male
PubMed: 33334808
DOI: 10.2337/dc20-1787