Mayanei Hayeshua Medical Center

This review provides timely information concerning clinical, surgical, and pathologic findings of adnexal torsion (AT). AT mostly occurs in the child-bearing age group, but is not uncommon in premenarchal girls or postmenopausal women. When AT is suspected, urgent surgical intervention is indicated, and is usually performed by laparoscopy. Incidence of AT is 3.5% of all benign cystic teratomas. Despite the "necrotic" appearance of the twisted ischemic ovary, detorsion is the only procedure which should be performed at surgery. Adnexectomy should be avoided as ovarian function is preserved in 88% to 100% of cases. Awareness and suspicion of the diagnosis of AT is needed in patients who present with lower abdominal pain.

Background: Most pregnancy-related medical complications appear to resolve at delivery or shortly thereafter. Common examples are preterm labor, placental abruption, preeclampsia, and gestational diabetes. Women who developed such complications are known to be at increased risk of developing similar complications in future pregnancies. It has recently become evident that these women are at an increased risk of long term medical complications. Methods: A search through scientific publications in English regarding the association of obstetric complications and long-term maternal illness. Results: There is a clear association between various obstetric complications and long-term effects on maternal health. Conclusions: Women with a history of adverse pregnancy outcomes are at increased risk of cardiovascular and metabolic diseases later in life. Data increasingly links maternal vascular, metabolic, and inflammatory complications of pregnancy with an increased risk of vascular disease in later life.

BACKGROUND: KPC-type carbapenemases are increasingly prevalent in parts of the USA and Israel and are an emerging concern in South America, Europe and China. We investigated the UK's first two KPC-producing Klebsiella pneumoniae isolates. METHODS: The isolates were referred to the UK's national reference laboratory for confirmation of carbapenem resistance. Susceptibilities were determined by agar dilution, and bla(KPC) and Tn4401-like elements were sought by PCR and sequencing. Isolates were compared by PFGE of XbaI- and SpeI-digested genomic DNA. RESULTS: The isolates were from patients in different UK hospitals, with no epidemiological connection. Both were resistant to carbapenems (MICs > 16 mg/L), with imipenem MICs unchanged by EDTA, and also to all other beta-lactams (including inhibitor combinations), tobramycin, amikacin and ciprofloxacin. They were susceptible to gentamicin (MICs </= 1 mg/L) and colistin (MICs </= 0.5 mg/L), with intermediate susceptibility to tigecycline (MICs 1-2 mg/L). The isolates belonged to the same PFGE-defined strain, highly related to a disseminated KPC-producing strain characterized previously in Tel Aviv, Israel. Like this Israeli strain, the UK isolates produced KPC-3 carbapenemase, with the bla(KPC-3) gene located within a Tn4401-like element. CONCLUSIONS: The first KPC-3-producing K. pneumoniae isolates detected in the UK were highly genetically related to a KPC-3-producing Israeli K. pneumoniae strain. This relatedness was consistent with the history of one UK patient, who had been hospitalized previously in Israel. However, this strain may be circulating more widely since the second UK patient had no identifiable links with Israel or other overseas countries.

Asymmetry of spatial attention has long been described in both disease (hemispatial neglect) and healthy (pseudoneglect) states. Although right-hemisphere specialization for spatial attention has been suggested, the exact neural mechanisms of asymmetry have not been deciphered yet. A recent functional magnetic resonance imaging study from our laboratory serendipitously revealed bihemispheric left-hemifield superiority in activation of a visuospatial attention-related network. Nineteen right-handed healthy adult females participated in two experiments of visual half-field presentation. Either facial expressions (experiment 1) or house images (experiment 2) were presented unilaterally and parafoveally for 150 ms while subjects were engaging a central fixation task. Brain regions previously associated with a visuospatial attention network, in both hemispheres, were found to be more robustly activated by left visual field stimuli. The consistency of this finding with manifestations of attention lateralization is discussed, and a revised model based on neural connectivity asymmetry is proposed. Support for the revised model is given by a dynamic causal modeling analysis. Unraveling the basis for attention asymmetry may lead to better understanding of the pathogenesis of attention disorders, followed by improved diagnosis and treatment. Additionally, the proposed model for asymmetry of visuospatial attention might provide important insights into the mechanisms underlying functional brain lateralization in general.

Varicocele is a bilateral vascular disease which occurs when the one-way valves in the internal spermatic veins, the testicular venous drainage system, malfunction. Based on new findings and fluid-mechanics analysis we showed that this process results in vertical blood columns, which cause pathological hydrostatic pressure in the testicular venous microcirculatory system. Ultimately, these pressures exceed the pressure in the arteriolar system. This unique phenomenon of reversal of pressures gradient between the arteriolar and venular systems leads to persistent hypoxia in the testosterone production site, namely, the Leydig cells. The result of bilateral varicocele is decreased testosterone production. Adequate treatment of bilateral varicocele significantly elevates the testosterone production. We found that the prevalence of varicocele increases with age with a rise of about 10% for each decade of life with the incidence reaching 75% in the eight decade of life. Based on our findings the following statements can be made: (1) varicocele prevalence is increased over time. (2) The rise of the incidence is about 10% for each decade of life. (3) 75% of men in the eight decade of their life have varicocele. As varicocele decreases testosterone production and it is reversible by appropriate treatment, it raises two interesting and important issues to be studied: (i) it is possible that varicocele accelerates the process of the ageing male. (ii) It is possible to retard, at least partially, the process of ageing in men by adequate treatment of bilateral varicocele.

BACKGROUND: A truly noninvasive glucose-sensing device could revolutionalize diabetes treatment by leading to improved compliance with recommended glucose levels, thus reducing the long-term complications and cost of diabetes. Herein, we present the technology and evaluate the efficacy of a truly noninvasive device for continuous blood glucose monitoring, the NBM (OrSense Ltd.). METHODS: In vitro analysis was used to validate the technology and algorithms. A clinical study was performed to quantify the in vivo performance of the NBM device. A total of 23 patients with type 1 (n = 12) and type 2 (n = 11) diabetes were enrolled in the clinical study and participated in 111 sessions. Accuracy was assessed by comparing NBM data with paired self-monitoring of blood glucose meter readings. RESULTS: In vitro experiments showed a strong correlation between calculated and actual glucose concentrations. The clinical trial produced a total of 1690 paired glucose values (NBM vs reference). In the paired data set, the reference glucose range was 40-496 mg/dl. No systematic bias was found at any of the glucose levels examined (70, 100, 150, and 200 mg/dl). The mean relative absolute difference was 17.2%, and a Clarke error grid analysis showed that 95.5% of the measurements fall within the clinically acceptable A&B regions (zone A, 69.7%; and zone B, 25.7%). CONCLUSIONS: This study indicates the potential use of OrSense's NBM device as a noninvasive sensor for continuous blood glucose evaluation. The device was safe and well tolerated.

The contribution of African ancestry to the risk of focal segmental glomerulosclerosis and chronic kidney disease has been partially explained by the recently described chromosome 22q variants in the gene apolipoprotein L1 (APOL1). The APOL1 variants appear at a high allele frequency in populations of West African ancestry as a result of apparent adaptive selection of the heterozygous state. Heterozygosity protects from infection with Trypanosoma brucei rhodesiense. This review will describe the role of the approaches in population genetics for the description of APOL1-associated nephropathies and draw inferences as to the biologic mechanisms from genetic epidemiology findings to date. Modifier loci can influence APOL1 risk for the development of kidney disease. 'Second hits', both viral and non-viral, may explain the discrepancy between the remarkably high odds ratios and the low lifetime risks of kidney disease in two allele carriers of APOL1 risk variants. Therapeutic strategies for APOL1-associated nephropathies will require the prevention and treatment of these 'second hits' and the development of drugs to protect the APOL1 downstream renal injury pathways.

In December 2019, the first cases of a new contagious disease were diagnosed in the city of Wuhan, the capital of Hubei province in China. Within a short period of time the outbreak developed exponentially into a pandemic that infected millions of people, with a global death toll of more than 500,000 during its first 6 months. Eventually, the novel disease was named coronavirus disease 2019 (COVID-19), and the new virus was identified as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Similar to all known pandemics throughout history, COVID-19 has been accompanied by a large degree of fear, anxiety, uncertainty, and economic disaster worldwide. Despite multiple publications and increasing knowledge regarding the biological secrets of SARS-CoV-2, as of the writing of this paper, there is neither an approved vaccine nor medication to prevent infection or cure for this highly infectious disease. Past pandemics were caused by a wide range of microbes, primarily viruses, but also bacteria. Characteristically, a significant proportion of them originated in different animal species (zoonoses). Since an understanding of the microbial cause of these diseases was unveiled relatively late in human history, past pandemics were often attributed to strange causes including punishment from God, demonic activity, or volatile unspecified substances. Although a high case fatality ratio was common to all pandemic diseases, some striking clinical characteristics of each disease allowed contemporaneous people to clinically diagnose the infection despite null microbiological information. In comparison to past pandemics, SARS-CoV-2 has tricky and complex mechanisms that have facilitated its rapid and catastrophic spread worldwide.

APOL1 harbors C–terminal sequence variants (G1 and G2), which account for much of the increased risk for kidney disease in sub–Saharan African ancestry populations. Expression of the risk variants has also been shown to cause injury to podocytes and other cell types, but the underlying mechanisms are not understood. We used Drosophila melanogaster and Saccharomyces cerevisiae to help clarify these mechanisms. Ubiquitous expression of the human APOL1 G1 and G2 disease risk alleles caused near-complete lethality in D. melanogaster , with no effect of the G0 nonrisk APOL1 allele, corresponding to the pattern of human disease risk. We also observed a congruent pattern of cellular damage with tissue-specific expression of APOL1. In particular, expression of APOL1 risk variants in D. melanogaster nephrocytes caused cell-autonomous accumulation of the endocytic tracer atrial natriuretic factor-red fluorescent protein at early stages and nephrocyte loss at later stages. We also observed differential toxicity of the APOL1 risk variants compared with the APOL1 nonrisk variants in S. cerevisiae , including impairment of vacuole acidification. Yeast strains defective in endosomal trafficking or organelle acidification but not those defective in autophagy displayed augmented APOL1 toxicity with all isoforms. This pattern of differential injury by the APOL1 risk alleles compared with the nonrisk alleles across evolutionarily divergent species is consistent with an impairment of conserved core intracellular endosomal trafficking processes. This finding should facilitate the identification of cell injury pathways and corresponding therapeutic targets of interest in these amenable experimental platforms.

Recently, there has been an increasing demand for SoCs in the biomedical field. In implantable applications, SoCs are designed under very stringent power and area constraints. The analog and mixed-signal circuits as well as digital circuits in those SoCs require a clock source, because clock-based signal-processing techniques, such as sampling and chopper stabilization, are often used. The primary clock source for such SoCs needs to provide good accuracy and long-term stability of the oscillation frequency foscto minimize variations and drifts of the system characteristics. A fairly pure clock signal is required to avoid signal distortion when sampling or chopping techniques are applied. Considering such a source is typically a free-running oscillator, and biomedical signals of typical interest reside at low frequencies, the close-in phase noise is important. For implantable biomedical sensor SoCs, due to high power consumption of quartz crystal oscillators and their bulky size, monolithic oscillators are preferred as a primary clock source. Relaxation oscillators can operate with low power and set their oscillation period Tosc in well-defined manner while consuming small silicon area. However, their performance is limited by process variations, noisy current sources, and noise and offset voltages of the comparators. Geraedts et al. presented an idea of subtracting a fixed charge packet and filtering out the comparator noise to improve the phase noise particularly at large offset frequencies. In this work, a self-clocked offset-cancellation scheme is presented for comparators in the relaxation oscillator, resulting in smaller frequency drifts and lower close-in phase fluctuations, which are more relevant parameters for primary clock sources in implantable biomedical SoCs.

BACKGROUND: Although studied in a few randomized controlled trials, the efficacy of medical cannabis (MC) for chronic pain remains controversial. Using an alternative approach, this multicentre, questionnaire-based prospective cohort was aimed to assess the long-term effects of MC on chronic pain of various aetiologies and to identify predictors for MC treatment success. METHODS: Patients with chronic pain, licensed to use MC in Israel, reported weekly average pain intensity (primary outcome) and related symptoms before and at 1, 3, 6, 9 and 12 months following MC treatment initiation. A general linear model was used to assess outcomes and identify predictors for treatment success (≥30% reduction in pain intensity). RESULTS: A total of 1,045 patients completed the baseline questionnaires and initiated MC treatment, and 551 completed the 12-month follow-up. At 1 year, average pain intensity declined from baseline by 20% [-1.97 points (95%CI = -2.13 to -1.81; p < 0.001)]. All other parameters improved by 10%-30% (p < 0.001). A significant decrease of 42% [reduction of 27 mg; (95%CI = -34.89 to 18.56, p < 0.001)] from baseline in morphine equivalent daily dosage of opioids was also observed. Reported adverse effects were common but mostly non-serious. Presence of normal to long sleep duration, lower body mass index and lower depression score predicted relatively higher treatment success, whereas presence of neuropathic pain predicted the opposite. CONCLUSIONS: This prospective study provides further evidence for the effects of MC on chronic pain and related symptoms, demonstrating an overall mild-to-modest long-term improvement of the tested measures and identifying possible predictors for treatment success.

The prostate is an androgen-regulated exocrine gland producing over 30% of the noncellular components of the semen and promoting optimal conditions for survival and motility of sperm in the vagina. Benign prostate hyperplasia (BPH) is the most common benign neoplasm in men. Its aetiology is not clear, and therefore, current medical treatments are directed towards the symptoms. Though testosterone is known to be the promoter of prostate cell proliferation, no causal relation between serum testosterone levels and BPH has been found. In this study, we propose a novel and tested pathophysiological mechanism for the evolution of BPH and suggest a tested and effective treatment. We found that in all BPH patients, the one-way valves in the vertically oriented internal spermatic veins are destroyed (clinically manifested as varicocele), causing elevated hydrostatic pressure, some 6-fold greater than normal, in the venous drainage of the male reproductive system. The elevated pressure propagates to all interconnected vessels leading to a unique biological phenomenon: venous blood flows retrograde from the higher pressure in the testicular venous drainage system to the low pressure in the prostatic drainage system directly to the prostate (law of communicating vessels). We have found that free testosterone levels in this blood are markedly elevated, with a concentration of some 130-fold above serum level. Consequently, the prostate is exposed to: (i) increased venous pressure that causes hypertrophy; (ii) elevated concentration of free testosterone causing hyperplasia. We have treated 28 BPH patients using a technique that restores normal pressure in the venous drainage in the male reproductive system. The back-pressure and the back-flow of blood from the testicular to the prostate drainage system were eliminated and, consequently, a rapid reduction in prostate volume and a regression of prostate symptoms took place.

A catalase-positive, rod-shaped, non-proteolytic, non-motile, anaerobic bacterial strain, designated B086562(T), was isolated from a blood culture of an 84-year-old male patient in Israel. According to 16S rRNA gene sequence phylogeny, this strain has no known close relatives among recognized bacteria but should be placed within the family Lachnospiraceae. The most closely related recognized bacteria were from the 'Clostridium clostridioforme group': C. clostridioforme (92.4%) and Clostridium bolteae (92.3%). The isolate produced butyrate, lactate, acetate and succinate as major metabolic end products. The major fatty acids were C16:0 and C18:1 cis 9 DMA and the DNA G+C content was 46.0 mol%. On the basis of the phenotypic properties and phylogenetic distinctiveness, the blood isolate represents a novel species of a new genus in the family Lachnospiraceae, for which the name Eisenbergiella tayi gen. nov., sp. nov. is proposed. The type strain of Eisenbergiella tayi is B086562(T) ( = LMG 27400(T) = DSM 26961(T) = ATCC BAA-2558(T)).

: The COVID-19 pandemic is challenging our cardiovascular care of patients with heart diseases. In the setting of pericardial diseases, there are two possible different scenarios to consider: the patient being treated for pericarditis who subsequently becomes infected with SARS-CoV-2, and the patient with COVID-19 who develops pericarditis or pericardial effusion. In both conditions, clinicians may be doubtful regarding the safety of nonsteroidal anti-inflammatory drugs (NSAIDs), corticosteroids, colchicine, and biological agents, such as anti-IL1 agents (e.g. anakinra), that are the mainstay of therapy for pericarditis.For NSAIDs, there is no clear scientific evidence linking ibuprofen and other NSAIDs to worsening of COVID-19; however, it seems prudent to continue them, if necessary to control pericarditis, and on the other hand, to prefer paracetamol for fever and systemic symptoms related to COVID-19. Treatments with corticosteroids, colchicine, and anakinra appear well tolerated in the context of COVID-19 infection and are currently actively evaluated as potential therapeutic options for COVID infection at different stages of the disease. On this basis, currently most treatments for pericarditis do not appear contraindicated also in the presence of possible COVID-19 infection and should not be discontinued, and some (corticosteroids, colchicine, and anakinra) can be considered to treat both conditions.

BACKGROUND: We assessed outcome of patients with moderate and severe COVID-19 following treatment with convalescent plasma (CP) and the association with IgG levels in transfused CP. METHODS: A prospective cohort study. Primary outcome was improvement at day 14 defined as alive, not on mechanical ventilation, and moderate, mild, or recovered from COVID-19. Antibody levels in CP units were unknown at the time of treatment. IgG against the spike protein S1 was subsequently measured by ELISA. Neutralizing antibodies titers were determined in a subset. Outcome was assessed in relation to the mean antibody level transfused to the patients (≤4.0 versus >4.0). FINDINGS: = 0.007. No serious adverse events were reported. INTERPRETATION: Treatment with CP with higher levels of IgG against S1 may benefit patients with moderate and severe COVID-19. IgG against S1 level in CP predicts neutralization antibodies titers.

We examined the dynamics of coronavirus 2019 (COVID-19) transmission within families. Our investigation demonstrated significantly lower rates of COVID-19 positivity in children compared with adults residing in the same household. Children of 5-17 years of age were 61% and children of 0-4 years of age were 47% less likely to have positive polymerase chain reaction results compared with adults residing in the same household.

The study was conducted to assess the prevalence of stress urinary incontinence in premenopausal nulliparae, primiparae, and grand multiparae, and to examine possible obstetric risk factors. Three hundred consecutive nulliparae, primiparae, and grand multiparae, 20 to 43 years of age, were interviewed during the third postpartum day of their consequent delivery about the symptom of stress urinary incontinence. Women were asked whether they had experienced stress urinary incontinence before, during, or after previous pregnancies and how troubled they were by their incontinence. Details of general and gynecologic history, parity, mode of previous deliveries, and birth weights were sought. Main outcome measures included prevalence of pregnancy-related and (persistent) nonpregnancy-related stress urinary incontinence. Prevalence of persistent stress urinary incontinence was significantly higher in grand multiparae compared with nulliparae (21% vs. 5%, respectively; P = 0.0008). Prevalence of persistent stress urinary incontinence among grand multiparae who had been delivered of at least one baby weighing more than 4,000 g was significantly higher than in those who did not (29.4% vs. 16.7%, respectively). The birth weight of the first newborn and operative vaginal delivery were not found to be associated with increased risk of stress urinary incontinence. Grand multiparity was found to be associated with an increased risk of developing persistent stress urinary incontinence during reproductive ages. The delivery of at least one baby weighing more than 4,000 g seems to be a predominant factor. Neurourol. Urodynam. 18:419-425, 1999.

The aim of this study was to examine whether motivating patients to gain expertise and closely follow their risk parameters will attenuate the course of microvascular and cardiovascular sequelae of diabetes. A randomized, prospective study was conducted of 165 patients who had type 2 diabetes, hypertension, and hyperlipidemia and were referred for consultation to a diabetes clinic in an academic hospital. Patients were randomly allocated to standard consultation (SC) or to a patient participation (PP) program. Both groups were followed by their primary care physicians. The mean follow-up was 7.7 yr. The SC group attended eight annual consultations. The PP patients initiated on average one additional consultation per year. There were 80 cardiovascular events (eight deaths) in the SC group versus 47 events (five deaths) in the PP group (P = 0.001). The relative risk (RR) over 8 yr for a cardiovascular event in the intervention (PP) versus the control (SC) group was 0.65 (95% confidence interval, 0.89 to 0.41). There were 17 and eight cases of stroke in the SC and PP groups, respectively (P = 0.05). RR for stroke was 0.47 (95% confidence interval, 0.85 to 0.32). In the SC group, 14 patients developed overt nephropathy (four ESRD) versus seven (one ESRD) in the PP group (P = 0.05). Throughout the study period, BP, LDL cholesterol, and hemoglobin A1c were significantly lower in the PP than in the SC patients. Well informed and motivated patients were more successful in obtaining and maintaining good control of their risk factors, resulting in reduced cardiovascular risk and slower progression of microvascular disease.

OBJECTIVES: Fetal tricuspid annular plane systolic excursion (f-TAPSE) is a modified method to measure the vertical movement of the tricuspid valve annulus by M-mode ultrasound, in order to assess the fetal right heart. Evaluation of right heart function is well-recognized in pediatric and adult cardiology, but has not been studied widely in the fetus. We aimed to study f-TAPSE in the second half of gestation in normal fetuses, to establish reference ranges for this measure, to evaluate the usefulness of spatiotemporal image correlation (STIC) M-mode in obtaining it, and to compare conventional M-mode and STIC M-mode-based measures of f-TAPSE. METHODS: We recruited gravidae presenting to our centers from 20 to 38 weeks for targeted organ scans, fetal echocardiography or third-trimester fetal surveillance, with structurally normal singleton fetuses and verified gestational age (GA). Because of the small number of subjects at the lower limit, fetuses at 20 and those at 21 weeks were combined into a single group ('21 weeks'). During the booked scan, in addition to standard biometry, M-mode was applied to the tricuspid annulus, parallel to the ventricular septum, and the amplitude of the resulting wave was measured. To allow comparison with STIC M-mode, a STIC volume was acquired and saved. In post-processing, the volume was rotated to show an apical four-chamber view, and f-TAPSE was investigated in a similar fashion to that used for conventional M-mode. Two to three measures of TAPSE were taken and the results averaged. In thirty women, measurements were performed by two observers and inter- and intraobserver variation were calculated. RESULTS: We examined 341 fetuses at GA 20-39 weeks. Conventional M-mode f-TAPSE values ranged from a mean of 3.6 (± 1.1) mm at 21 weeks to a mean of 8.6 (± 1.5) mm at 39 weeks. In 45 cases we were unable to perform conventional M-mode ultrasound because of fetal lie; in eight cases STIC volumes were found in post-processing to be unsuitable for analysis. STIC f-TAPSE values ranged from a mean of 4.2 (± 1.4) mm at 21 weeks to a mean of 8.3 (± 1.5) mm at 39 weeks. Scatterplots of f-TAPSE measures obtained with conventional M-mode and with STIC M-mode were created vs GA and estimated fetal weight (EFW). For both modalities, f-TAPSE increased linearly with GA and with EFW. Good correlation was found between the two methods (Pearson's R(2) = 0.904). No significant difference was found in mean or variance of the distributions or slopes of the regression equations. Inter- and intraobserver variation (intraclass correlation coefficient) in conventional M-mode and STIC M-mode f-TAPSE measures were 0.94 and 0.97, respectively. CONCLUSION: F-TAPSE in normal fetuses increases over the course of gestation and correlates to EFW. F-TAPSE measurement is easy to perform and available on all ultrasound machines; STIC f-TAPSE is possible on machines with STIC capability and produces similar measures with a greater success rate. We suggest the addition of f-TAPSE measurement to fetal right cardiac function evaluation.

Toxic peripheral neuropathy is still a significant limiting factor for chemotherapy with paclitaxel (PAC), although glutamate and its closely related amino acid glutamine were claimed to ameliorate PAC neurotoxicity. This pilot trial aimed to evaluate the role of glutamate supplementation for preventing PAC-induced peripheral neuropathy in a randomized, placebo-controlled, double-blinded clinical and electro-diagnostic study. Forty-three ovarian cancer patients were available for analysis following six cycles of the same PAC-containing regimen: 23 had been supplemented by glutamate all along the treatment period, at a daily dose of three times 500 mg (group G), and 20 had received a placebo (group P). Patients were evaluated by neurological examinations, questionnaires and sensory-motor nerve conduction studies. There was no significant difference in the frequency of signs or symptoms between the two groups although neurotoxicity symptoms presented mostly with lower scores of severity in group G. However, this difference reached statistical significance only with regard to reported pain sensation (P = 0.011). Also the frequency of abnormal electro-diagnostic findings showed similarity between the two groups (G: 7/23 = 30.4%; P: 6/20 = 30%). This pilot study leads to the conclusion that glutamate supplementation at the chosen regimen fails to protect against peripheral neurotoxicity of PAC.