Short-term outcome of pregnant women vaccinated with BNT162b2 mRNA COVID-19 vaccine.

OBJECTIVES: To determine the immunogenicity and reactogenicity of the Pfizer/BioNTech BNT162b2 mRNA coronavirus disease 2019 (COVID-19) vaccine among pregnant women compared with non-pregnant women, and to evaluate obstetric outcome following vaccination. METHODS: This was an observational case-control study of pregnant women who were vaccinated with a two-dose regimen of the BNT162b2 vaccine during gestation between January and February 2021 (study group) and age-matched non-pregnant women who received the vaccine during the same time period (control group). Participants received a digital questionnaire 1-4 weeks after the second dose and were asked to provide information regarding demographics, medication, medical history, history of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, timing of COVID-19 vaccine doses and side effects after each vaccine dose. A second digital questionnaire, regarding current pregnancy and delivery outcomes, was sent to patients in the study group after the calculated due date. All recruited women were offered a serology blood test for SARS-CoV-2 immunoglobulin G (IgG) following the second vaccination dose and SARS-CoV-2 IgG levels were compared between the two groups. RESULTS: Of 539 pregnant women who were recruited after completion of the two-dose regimen of the vaccine, 390 returned the digital questionnaire and were included in the study group and compared to 260 age-matched non-pregnant vaccinated women. The rates of rash, fever and severe fatigue following vaccination among pregnant women were comparable to those in non-pregnant women. Myalgia, arthralgia and headache were significantly less common among pregnant women after each dose, local pain or swelling and axillary lymphadenopathy were significantly less common among pregnant women after the first and second doses, respectively, while paresthesia was significantly more common among the pregnant population after the second dose. Among pregnant women, there were no significant differences in the rates of side effects according to whether the vaccine was administered during the first, second or third trimester of pregnancy, except for local pain/swelling, which was significantly less common after the first dose when administered during the third trimester, and uterine contractions, which were significantly more common after the second dose when administered during the third trimester. The rates of obstetric complications, including uterine contractions (1.3% after the first dose and 6.4% after the second dose), vaginal bleeding (0.3% after the first dose and 1.5% after the second dose) and prelabor rupture of membranes (0% after the first dose and 0.8% after the second dose), were very low following vaccination. All serum samples in both groups were positive for SARS-CoV-2 IgG. However, pregnant women had significantly lower serum SARS-CoV-2 IgG levels compared to non-pregnant women (signal-to-cut-off ratio, 27.03 vs 34.35, respectively; P < 0.001). Among the 57 pregnant women who delivered during the study period and who completed the second questionnaire, median gestational age at delivery was 39.5 (interquartile range, 38.7-40.0) weeks, with no cases of preterm birth < 37 weeks, no cases of fetal or neonatal death and two (3.5%) cases of admission to the neonatal intensive care unit for respiratory support. CONCLUSIONS: The adverse-effect profile and short-term obstetric and neonatal outcomes among pregnant women who were vaccinated with the BNT162b2 vaccine at any stage of pregnancy do not indicate any safety concerns. The vaccine is effective in generating a humoral immune response in pregnant women, although SARS-CoV-2 IgG levels were lower than those observed in non-pregnant vaccinated women. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.

Prophylactic irradiation to the contralateral breast for BRCA mutation carriers with early-stage breast cancer.

BACKGROUND: Women who carry germ-line mutations in BRCA1/2 are at very high risk of developing breast and ovarian cancer. Breast conserving therapy is associated with a similar risk of ipsilateral cancer recurrence in BRCA carriers compared with non-carriers. However, the risk of subsequent contralateral breast cancer in carriers is markedly increased. Therefore, mastectomy of the diseased breast along with risk reducing mastectomy of the contralateral breast is often advocated for BRCA carriers who are treated for early breast cancer. Yet, many BRCA carriers forgo this option for fear of harmful effects and choose breast conserving treatment and observation instead. In Israel, BRCA-associated breast cancer is relatively common. Accordingly, a national protocol was devised for this enriched population. PATIENTS AND METHODS: In this Institutional Review Board-approved phase II trial, the option of prophylactic irradiation to the contralateral breast, in addition to standard loco-regional treatment, was offered to BRCA carrier patients treated for early breast cancer who declined contralateral mastectomy. The primary end point was contralateral breast cancer. RESULTS: Between May 2007 and October 2017, 162 patients were enrolled. Eighty-one patients opted for standard loco-regional treatment including surgery and radiation to the involved side (control arm) and 81 patients chose additional contralateral breast irradiation (intervention arm). At a median follow-up of 58 months, 10 patients developed contralateral breast cancer in the control arm at a median of 32 months, as compared with 2 patients in the intervention arm who developed contralateral breast cancer 80 and 105 months after bilateral breast irradiation (log-rank P = 0.011). CONCLUSIONS: Among BRCA carrier patients treated for early breast cancer, the addition of contralateral breast irradiation was associated with a significant reduction of subsequent contralateral breast cancers and a delay in their onset. CLINICAL TRIAL: Phase II, comparative two-arm trial (NCT00496288).

Role of late amniocentesis in the era of modern genomic technologies.

OBJECTIVE: Traditionally, amniocentesis is performed between 17 and 23 weeks of gestation. This enables decisions regarding the course of pregnancy to be made before viability. Less frequently, amniocentesis is performed in the third trimester. Advanced genomic technologies such as chromosomal microarray analysis (CMA) provide more detailed information about the fetus compared with traditional G-banded chromosomal analysis. The aim of this study was to assess the indications for and safety of late amniocentesis, genetic-test results (especially in the context of CMA technology) and outcome of pregnancies that underwent the procedure after 24 weeks. METHODS: Medical records were analyzed retrospectively of all women in whom amniocentesis was performed at a gestational age of 24 + 0 to 38 + 6 weeks, at Hadassah Medical Center, between June 2013 and March 2017. Parameters investigated included indications for late amniocentesis, complications, CMA results and pregnancy outcome. RESULTS: During the study period, 291 women (303 fetuses, 277 singleton and 14 twin pregnancies; in two twin pairs, one fetus was terminated before amniocentesis) underwent late amniocentesis. CMA was performed in all instances of amniocentesis. The most frequent indication was abnormal sonographic finding(s) (204/303 fetuses, 67%). Preterm delivery occurred in 1.7% and 5.1% of pregnancies within the first week and within 1 month following the procedure, respectively. Aneuploidy was detected in nine (3%) fetuses and nine (3%) others had a pathogenic/likely pathogenic copy number variant, suggesting that CMA doubled the diagnostic yield of traditional karyotyping. Maximal diagnostic yield (17.5%) was achieved for the subgroup of fetuses referred with abnormal sonographic findings in two or more fetal anatomical systems. Variants of uncertain significance or susceptibility loci were found in another nine (3%) fetuses. CONCLUSIONS: In pregnancies undergoing late amniocentesis, CMA increased detection rates of fetal abnormalities and had a shorter turnaround time compared with traditional chromosomal analysis; therefore, late amniocentesis may serve as a helpful tool for detecting fetal abnormalities or reassuring parents following late-appearing abnormal sonographic findings. However, CMA may expose findings of uncertain significance, about which the couple should be precounseled. The procedure appears to be safe. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd.

Short communication: Detection of lameness in dairy cows using a grooming device.

Lameness in dairy cattle is a common welfare problem with significant economic implications. All too often, appropriate treatment is delayed or neglected due to insufficient detection of lame cows. Brush usage is considered a low-resilience activity; that is, one that typically decreases when energy resources are limited or when the cost involved in the activity increases, such as during sickness and stress. The aim of this study was to determine the association between brush usage and different degrees of lameness. Locomotion scores of 209 lactating Holstein dairy cows were collected individually once a week for 14 consecutive weeks, using a 5-point visual assessment scoring system (1 = nonlame, 2 = uneven gait, 3 = mild lameness, 4 = lameness, 5 = severe lameness). Daily brush usage was collected automatically from 3 cowsheds of similar size and structure located on a commercial dairy farm. In each of the 3 cowsheds, 2 brushes were installed, one next to the feed bunk, and the other away from the feed bunk (on the opposite side of the cowshed). Linear and generalized linear mixed-effects models were used to evaluate the association between locomotion scores and daily measures of brush usage. We found a significant interaction between locomotion score and brush location (near to/distant from feed bunk) on the daily proportion of cows using the brush at least once and on daily duration of brush usage. Specifically, we showed that lame and severely lame cows did not use brushes that were installed away from the feed bunk but continued to use brushes that were installed next to the feed bunk. Brush usage by cows with uneven gait (locomotion score 2) or with mild lameness (locomotion score 3) did not differ from that of nonlame cows (locomotion score 1). The results of this study suggest that monitoring of daily usage of brushes located away from the feed bunk could be a useful method for detecting lameness and severe lameness in dairy cows. However, the use of this method to detect mild lameness or cases of abnormal gait is, at this stage, less promising.

Mutations in the familial Mediterranean fever gene of patients with IgA nephropathy and other forms of glomerulonephritis.

Glomerulonephritis, particularly IgA nephropathy (IgAN), seems to be more common in familial Mediterranean fever (FMF), an inherited disease caused by mutations in the MEditerranean FeVer gene (MEFV). The present study is aimed to determine, in populations not suffering from FMF, whether carriage of MEFV mutations may modify or precipitate IgAN and other forms of primary glomerulonephritis (PGN). Forty patients with biopsy proven IgAN and 40 with PGN were surveyed for the presence of the three most common MEFV mutations (M694V, V726A and E148Q), using polymerase chain reaction amplification and restriction enzyme analysis. The rate of MEFV mutations in the patients was related to the expected carrier rate in the general population of the same ethnic extraction. The effect of mutation carriage on the disease course was determined in the IgAN patient group. The frequency of MEFV mutations in IgAN or PGN was comparable to that found in ethnically adjusted general population (p = 0.1 and 0.5, respectively). Carriage of mutated MEFV was not associated with the course and severity of the disease or findings in kidney biopsy and urine analysis. In a population, mostly of Jewish extraction, MEFV mutations do not seem to predispose to the development of IgAN and other forms of PGN or affect the phenotype.

Development of ascites-resistant and ascites-susceptible broiler lines.

The rapid growth of modern broilers is associated with enhanced appetite and high metabolic rate and, consequently, high O(2) demand. Ascites syndrome (AS) develops in individuals that fail to fully supply the increasing demand for O(2) in their bodies under ascites-inducing conditions (AIC) such as high altitude or low temperatures. The tendency of broilers to develop AS is heritable, but efficacious selection against AS susceptibility (without affecting the normal expression of other important traits) requires identification of indirect selection criteria. In the present study, divergent AS-susceptible (AS-S) and AS-resistant (AS-R) lines were developed to confirm the heritability of AS and to facilitate future detection of criteria for indirect selection against AS susceptibility. The base population consisted of 85 sire families with a mean of 73 progeny per sire, reared in a commercial broiler house under low-challenge AIC (cold environment and pelleted feed). Chicks dying with AS manifestations were designated AS-susceptible, whereas the surviving birds were designated AS-resistant. By the end of the trial (d 48), AS mortality had accumulated to 17.2%, but AS incidence per family (%ASF) ranged from 0 to 49%, with a high heritability (0.57). Parents of 7 families with very high %ASF produced the first generation (S(1)) of the AS-S line, and parents of 7 families with very low %ASF produced the S(1) of the AS-R line. The S(1) males and females reproduced generation S(2) of the selected lines, whereas additional S(1) males were tested under high-challenge AIC (individual cages, cool wind, and pelleted feed). Progeny testing under this high-challenge AIC, followed by sib selection, was repeated in generations S(2) and S(3), resulting in a divergence of 86.6% in the incidence of AS between the AS-S (91.3%) and AS-R (4.7%) lines. The rapid genetic divergence, and family analysis of %ASF suggested that a single or few major genes are responsible for the difference between the 2 selected lines. These lines may facilitate more sensitive and effective genomic research aimed at detecting these genes or identifying the primary physiological cause of AS.

Content words in Hebrew child-directed speech.

The goal of the study was to examine whether the 'noun-bias' phenomenon, which exists in the lexicon of Hebrew-speaking children, also exists in Hebrew child-directed speech (CDS) as well as in Hebrew adult-directed speech (ADS). In addition, we aimed to describe the use of the different classes of content words in the speech of Hebrew-speaking parents to their children at different ages compared to the speech of parents to adults (ADS). Thirty infants (age range 8:5-33 months) were divided into three stages according to age: pre-lexical, single-word, and early grammar. The ADS corpus included 18 Hebrew-speaking parents of children at the same three stages of language development as in the CDS corpus. The CDS corpus was collected from parent-child dyads during naturalistic activities at home: mealtime, bathing, and play. The ADS corpus was collected from parent-experimenter interactions including the parent watching a video and then being interviewed by the experimenter. 200 utterances of each sample were transcribed, coded for types and tokens and analyzed quantitatively and qualitatively. Results show that in CDS, when speaking to infants of all ages, parents' use of types and tokens of verbs and nouns was similar and significantly higher than their use of adjectives or adverbs. In ADS, however, verbs were the main lexical category used by Hebrew-speaking parents in both types and tokens. It seems that both the properties of the input language (e.g. the pro-drop parameter) and the interactional styles of the caregivers are important factors that may influence the high presence of verbs in Hebrew-speaking parents' ADS and CDS. The negative correlation between the widespread use of verbs in the speech of parents to their infants and the 'noun-bias' phenomenon in the Hebrew-child lexicon will be discussed in detail.

Hantavirus seropositivity in Israeli patients with renal failure.

The hantavirus is known to cause hemorraghic fever with renal syndrome (HFRS), which is widely spread in Europe and Asia. Several reports have shown an association of hantavirus antibody titers and the occurrence of renal dysfunction. From these observations, it appears that the virus is widely distributed, and different strains prevail in various areas. In the present work we studied 81 patients with end-stage renal-failure under hemodialysis (HD) treatment, 55 with mild to moderate renal failure, and 50 healthy subjects for the presence of antibodies to Hantaan and Puumala viruses. We found that 12.3% of the hemodialysis patients and 9% of the mild to moderate renal failure patients had elevated IgG anti-body titers to Puumala virus compared with 2% of the controls. IgM antibodies to Puumala virus was principally elevated in patient with chronic renal failure (CRF) not on hemodialysis (14.5%) compared with the hemodialyzed (1.2%) and controls (0%) subjects. Hantaan virus IgG antibodies were detected in 3.7% of the HD patients, 5.5% of the CRF not on HD, and in none of the controls. IgM Hantaan antibodies were found only in the non-HD renal failure patients. None of the sera were found to contain antibodies to phospholipids or single-stranded DNA. These results emphasize the widespread nature of infection with hantaviruses and imply that elaborate testing for these serologies should be performed, especially in patients with unexplained renal failure.

Using hospital site visits for teaching occupational health.

In medical schools, the factory visit is an important ingredient of occupational health instruction at all levels. Usually the time allotted for teaching this subject in the undergraduate curriculum is limited; as a response to this constraint, the Tel Aviv University Sackler Faculty of Medicine has used its associated teaching hospitals as the "factory" since 1982. Following an introductory discussion, the students are divided into small groups and sent to various departments of the hospital--wards, kitchen, laundry, maintenance workshop, X-ray department, and surgery--to observe and evaluate the work environment. Following this activity, the students reconvene and discuss the health implications of what they have seen. This way of providing the factory visit is well accepted by the students, saves time, and contributes directly to the students' awareness of their own working environment.

CT findings in ten patients with failed renal allografts: comparison with findings in functional grafts.

Our aim is to report the computed tomography (CT) features of the long-term failed renal allograft. Ten patients with failed renal transplants in whom the graft was left in situ underwent CT for various unrelated indications. The majority of the failed grafts showed marked shrinkage and coarse punctate diffuse parenchymal calcifications. Small cysts were seen in four grafts. A long-term failed renal transplant appeared on CT as a small rounded soft tissue mass. The graft was almost always heavily calcified. Lack of awareness of the nature of such a mass may mislead the radiologist in interpreting it as a space-occupying lesion.