Hagit Daum

Tissue microarray-based study of patients with lymph node-positive breast cancer shows tyrosine phosphorylation of signal transducer and activator of transcription 3 (tyrosine705-STAT3) is a marker of good prognosis.

BackgroundAlthough lymph node-positive breast cancers are associated with poorer prognosis, individual patients may have different clinical outcomes. Signal transducer and activator of transcription 3 (STAT3) is a point of convergence for numerous oncogenic signalling pathways. The goal of this study was to determine the prognostic value of phosphorylated (tyrosine705)-STAT3 in node-positive breast cancer patients.MethodsImmunohistochemical analysis of Phospho-STAT3 was performed on a tissue microarray of breast cancer specimens. The expression pattern of Phospho-STAT3 was correlated with survival outcome, and clinical and pathological parameters.ResultsOut of 125 interpretable tumours, positive Phospho-STAT3 nuclear expression was seen in 35 (28%) of tumours. There was no significant relationship between Phospho-STAT3 expression and clinical-pathological parameters including age, hormonal receptor status, grade and tumour size. Interestingly positive tumours had a significantly improved disease-free survival at 5 years (p=0.035). Additionally, positive Phospho-STAT3 nuclear expression was correlated with significantly improved survival at both 5 years (p=0.023) and 10 years (p=0.026). Finally, in multivariate analyses Phospho-STAT3 was found to be an independent prognostic marker of overall survival in node-positive breast cancer patients.ConclusionThese findings support the role of Phospho-STAT3 as an important independent prognostic marker in node-positive breast cancer patients.

Monozygotic multiple gestation after intracytoplasmic sperm injection and preimplantation genetic diagnosis.

OBJECTIVE To report a possible association between intracytoplasmic sperm injection (ICSI)-preimplantation genetic diagnosis (PGD) and monozygotic multiple gestation. DESIGN Small case series. SETTING In vitro fertilization unit in an academic medical center. PATIENT(S) Three patients were treated with ICSI-PGD for sexing as well as selection against a known translocation. INTERVENTION(S) Transfer of day 4 embryos to the uterus. MAIN OUTCOME MEASURE(S) Clinical pregnancy. RESULT(S) Two pairs of monozygotic twins and a triplet pregnancy. CONCLUSION(S) Repeated manipulation of the zona pellucida as well as extended embryo culture during ICSI-PGD treatments may result in monozygotic twin and triplet pregnancies.

Detailed Transabdominal Fetal Anatomic Scanning in the Late First Trimester Versus the Early Second Trimester of Pregnancy

To compare visualization rates for early targeted organ scanning at gestational ages ranging from 11 weeks 3 days to 13 weeks 2 days versus 14 weeks 3 days to 16 weeks 2 days.

Autosomal dominant gain of function STAT1 mutation and severe bronchiectasis

BACKGROUND In a substantial number of patients with non-cystic fibrosis (CF) bronchiectasis an etiology cannot be found. Various complex immunodeficiency syndromes account for a significant portion of these patients but the mechanism elucidating the predisposition for suppurative lung disease often remains unknown. OBJECTIVE To investigate the cause and mechanism predisposing a patient to severe bronchiectasis. METHODS A patient presenting with severe non-CF bronchiectasis was investigated. Whole exome analysis (WES) was performed and complemented by extensive immunophenotyping. RESULTS The genetic analysis revealed an autosomal dominant gain-of-function mutation (AD- GOF) in the signal transducer and activator of transcription 1 (STAT1) in the patient. STAT1 phosphorylation studies showed increased phosphorylation of STAT1 after stimulation with interferon γ (IFN-γ). Immunophenotyping showed normal counts of CD4 and CD8 T cells, B and NK cells, but a reduction of all memory B cells especially class switched memory B cells. Minor changes in the CD8 T cell subpopulations were seen. CONCLUSIONS Early use of WES in the investigation of non-CF bronchiectasis was highly advantageous. The degree of impairment in class-switched memory B cells may predispose patients with AD- GOF mutations in STAT1 to suppurative sinopulmonary disease.

Third- or Fourth-Degree Intrapartum Anal Sphincter Tears Are Associated With Levator Ani Avulsion in Primiparas

We evaluated primiparous women with clinically diagnosed third‐ and fourth‐degree and anal sphincter tears, to evaluate the rate of levator ani muscle injury compared to primiparous women without sphincter tears.

Sonographic finding of postpartum levator ani muscle injury correlates with pelvic floor clinical examination

Correlation of the sonographic finding of levator ani muscle (LAM) injuries with clinical examination in primiparous women following vaginal delivery has not been fully described. We aimed to examine the correlation of three‐dimensional transperineal ultrasound (3D‐TPS) finding of LAM defects with results of clinical examination of the pelvic floor, at intermediate follow‐up.

Rectus Sheath Hematoma as a Rare Complication of Genetic Amniocentesis

Arectus sheath hematoma (RSH) is a rare and dramatic complication involving bleeding from the inferior epigastric artery into the rectus abdominis sheath. This complication has been reported after abdominal wall trauma, subcutaneous drug injection, 1,2 paracentesis, 3 and acupuncture 4 and spontaneously, especially during pregnancy.5 The clinical hallmark of RSH is severe, worsening abdominal pain exacerbated by movement. For this reason, RSH often presents a clinical dilemma of differentiating this condition from an acute abdomen or placental abruption in pregnant women. Genetic amniocentesis is a frequently performed procedure. Although the list of common and rare complications caused by this procedure is not short, to the best of our knowledge, RSH has never been mentioned as a complication of amniocentesis. A few cases of extraperitoneal hemorrhage were reported after amniocentesis almost.

An Ashkenazi founder mutation in the PKHD1 gene.

Autosomal recessive polycystic kidney disease (ARPKD) is usually detected late in pregnancies in embryos with large echogenic kidneys accompanied by oligohydramnios. Hundreds of private pathogenic variants have been identified in the large PKHD1 gene in various populations. Yet, because of the large size of the gene, segregation analysis of microsatellite polymorphic markers residing in the PKDH1 locus has commonly been utilized for prenatal diagnosis. Keeping in mind the limitations of this strategy, we utilized it for testing 7 families with affected fetuses or newborns, of which in 5 at least one parent was Ashkenazi, and identified that the same haplotype was shared by the majority of the Ashkenazi parents (7/9). This led us to suspect that they carry the same founder mutation. Whole Exome analysis of DNA from a fetus of one of the families detected an already known pathogenic variant c.3761_3762delCCinsG, an indel variant resulting in frameshift (p.Ala1254GlyfsX49). This variant was detected in 9 parents (5 families), of them 7 individuals were Ashkenazi and one Moroccan Jew who shared the same haplotype, and one Ashkenazi, who carried the same variant on a recombinant haplotype. Screening for this variant in 364 Ashkenazi individuals detected 2 carriers. These findings suggest that although c.3761_3762delCCinsG is considered one of the frequent variants detected in unrelated individuals, and was thought to have occurred independently on various haplotypes, it is in fact a founder mutation in the Ashkenazi population.

Persistence of Levator Ani Sonographic Defect Detected by 3DTUS in Primiparous Women

Correlation of the sonographic appearance of levator ani muscle (LAM) injury soon after delivery with that at long‐term follow‐up has not been described fully. We aimed to compare results of three‐dimensional (3D) transperineal sonographic (TPS) evaluation of the LAM from the period immediately postpartum with long‐term follow‐up, to determine whether sonographic findings persist over time.

Persistence of levator ani sonographic defect detected by three-dimensional transperineal sonography in primiparous women.

Correlation of the sonographic appearance of levator ani muscle (LAM) injury soon after delivery with that at long‐term follow‐up has not been described fully. We aimed to compare results of three‐dimensional (3D) transperineal sonographic (TPS) evaluation of the LAM from the period immediately postpartum with long‐term follow‐up, to determine whether sonographic findings persist over time.