Estimation of diagnosis and prognosis in ET by assessment of CALR and JAK2<Superscript>V617F</Superscript> mutations and laboratory findings: a meta-analysis

Background

Essential thrombocythemia (ET) is a benign disease with slow progress in which thrombosis is a cause of mortality. JAK2^V617F and calreticulin (CALR) are the most frequent mutations in this disease. In this systematic review and meta-analysis, we compared the prevalence of JAK2^V617F and CALR mutations in ET and examined the incidence of thrombosis and other hematologic indices.

Methods

After choosing MeSH keywords, including essential thrombocythemia, JAK2^V617F, calreticulin, prognosis, and diagnosis, as well as searching Medline/PubMed and Scopus, 12 papers were selected. Data were pooled, and summary prevalence and OR were estimated using either a random-effects model or a fixed-effects model.

Results

The frequency of JAK2^V617F and CALR shows heterogeneity in Caucasian population [JAK2^V617 I ²% = 84.3, P < 0.001, 95% CI 0.56 (0.51–0.61)], [CALR I ²% = 96.1, P < 0.001, 95% CI 0.23 (0.15–0.31)]. The prevalence of JAK2^V617F and CALR was 0.57 (95% CI 0.53–0.61), I ²% = 79.3 and 0.22 (95% CI 0.16–0.27), I ²% = 94, respectively. JAK2^V617F positive ET was associated with increasing odds of thrombosis [OR 2.35 (95% CI 1.83–3.02), P < 0.001]. The incidence of splenomegaly was not statistically different between these two mutations. Hemoglobin, platelet, and WBC count did not affect the risk of thrombosis.

Conclusions

Detection of CALR mutation is helpful for molecular diagnosis of ET patients as well as JAK2^V617F. Due to reduction of thrombosis in CALR-positive patients, it can be stated that such patients have less thrombotic disorders and better prognosis relative to patients bearing JAK2^V617F mutation. Therefore, detection of mutation in CALR and JAK2^V617F may contribute to diagnosis and prognosis of ET patients.

     

Ductus venosus Doppler and the postnatal outcomes of growth restricted fetuses with absent end-diastolic blood flow in the umbilical arteries

Objective

We aimed to evaluate the outcomes of growth-restricted fetuses with absent end-diastolic velocity in the umbilical arteries (UA-AEDV), and investigate the relationship between Doppler flow velocity waveforms in the ductus venosus (DV) and the clinical features.

Clinical and Genetic Features in Patients with Cystic Fibrosis in Southwestern Iran

Objective

Cystic fibrosis (CF) is a common autosomal recessive genetic disease caused by a mutation in the CF transmembrane conductance regulatory (CFTR) gene. This study attempted to identify the most common CFTR mutations and any correlations between certain mutations and the clinical presentation of the disease in CF patients in southwestern Iran.

Methods

Twenty nine common CFTR gene mutations were examined in 45 CF patients.

Findings

Chronic cough, intestinal obstruction, dehydration, heat exhaustion and steatorrhea were the most common early clinical symptoms among our patients. The most common mutation was ΔF508, with an allele frequency of 21%. The homozygous ΔF508 mutation was observed in eight patients (18%), and three patients (7%) were ΔF508 carriers. The 2183AA > G mutation was observed in four patients, one of whom was also a ΔF508 carrier. The R1162X mutation was detected in two patients. The G542X, R334W and N1303K mutations were detected each in one patient, the first of whom was also a ΔF508 carrier.

Conclusion

Out of 45 patients, 27 (60%) had none of the CFTR gene mutations we tested for. The most frequent mutations in southwestern Iranian patients with CF should be identified by sequencing the entire CFTR gene in order to optimize the design of a diagnostic kit for common regional mutations.     

Assessment of in vitro antiovulatory activities of nonsteroidal anti‐inflammatory drugs and comparison with in vivo reproductive toxicities of medaka (Oryzias latipes)

Nonsteroidal anti‐inflammatory drugs (NSAIDs) are widely used therapeutic agents; however, their pharmacological actions raise concerns about potential risks to the reproductive health of aquatic vertebrates. In the present study, a medaka ovulation assay was applied as an in vitro model to evaluate NSAID‐induced antiovulatory activity. We first tested five NSAIDs, including diclofenac sodium (DCF), ketoprofen (KP), salicylic acid (SA), mefenamic acid (MA), and acetylsalicylic acid (ASA) for their antiovulatory activities toward the follicles isolated from the ovaries of spawning females. Of all the chemicals tested, DCF had the highest antiovulatory activity, with the concentration that caused 50% inhibition (IC50) (101 µM). MA was the second most potent inhibitor following DCF, but KP, SA, or ASA had little inhibitory effect on the ovulation of the follicles. The in vitro antiovulatory activity of five NSAIDs showed good correlation with data published on the inhibitory activity on human COX‐2. Second, we selected DCF and SA as the most and least potent NSAIDs, respectively, and examined the effects on reproduction of intact fish in order to evaluate whether the ovulation assay was a reasonable predictor of potential reproductive effects in fish. Females exposed to DCF showed a concentration‐dependent decrease in the number of spawned eggs and an increment in the gonadosomatic index (GSI), possibly due to an anovulation in the females. In contrast, neither fecundity nor the GSI of females decreased at up to 20 mg/L of SA, at which acute lethality to medaka was induced. In conclusion, the medaka ovulation assay reflected the potency of NSAID‐induced antiovulatory activity and may thus serve as an in vitro model for the prediction of NSAID‐induced reproductive toxicity. © 2015 Wiley Periodicals, Inc. Environ Toxicol 31: 1710–1719, 2016.     

Genetically Diverse Highly Pathogenic Avian Influenza A(H5N1/H5N8) Viruses among Wild Waterfowl and Domestic Poultry,Japan, 2021

Genetic analyses of highly pathogenic avian influenza H5 subtype viruses isolated from the Izumi Plain, Japan, revealed cocirculation of 2 genetic groups of clade 2.3.4.4b viruses among migratory waterfowl. Our findings demonstrate that both continuous surveillance and timely information sharing of avian influenza viruses are valuable for rapid risk assessment.     

A case of non-palpating breast cancer with huge lymph node metastasis

We report a case of non-palpating breast cancer with huge lymph node metastasis. The patient was a 58-year-old woman who had a huge tumor at her right armpit. The tumor was 4 cm in diameter. Aspiration biopsy cytology for the tumor was performed. The diagnosis is Class V. Mammography showed an ill-defined mass at her right breast. Ultrasonography revealed a low echoic mass at the C area of her right breast. A core needle biopsy for the breast tumor led to a diagnosis of an invasive ductal carcinoma positive for estrogen receptor and progesterone receptor, and negative for HER2/neu protein expression. She received 4 cycles of CEF (E: 60 mg/tri-weekly) plus 12 cycles of paclitaxe (l80 mg/weekly). After chemotherapy, she received muscle preserving mastectomy plus axillary lymph nodes dissection. In histopathology, there were no carcinoma cells in resected breast tissue and resected lymph nodes. Therefore, the effect of chemotherapy was diagnosed as a pathological complete response. After operation, she was administered aromatase inhibitor. The patient has been well and remained disease-free during a follow-up period of 6 years.