Publications by authors named "Hila Elinav"

31 Publications

Influence of Hepatitis C Coinfection and Treatment on Risk of Diabetes Mellitus in HIV-Positive Persons.

Open Forum Infect Dis 2020 Dec 7;7(12):ofaa470. Epub 2020 Oct 7.

Centre for Clinical Research, Epidemiology, Modelling and Evaluation (CREME), Institute for Global Health, University College London, London, UK.

Background: The role of hepatitis C virus (HCV) coinfection and HCV-RNA in the development of diabetes mellitus (DM) in HIV-positive persons remains unclear.

Methods: Poisson regression was used to compare incidence rates of DM (blood glucose >11.1 mmol/L, HbA1C >6.5% or >48 mmol/mol, starting antidiabetic medicine or physician reported date of DM onset) between current HIV/HCV groups (anti-HCV-negative, spontaneously cleared HCV, chronic untreated HCV, successfully treated HCV, HCV-RNA-positive after HCV treatment).

Results: A total of 16 099 persons were included; at baseline 10 091 (62.7%) were HCV-Ab-negative, 722 (4.5%) were spontaneous clearers, 3614 (22.4%) were chronically infected, 912 (5.7%) had been successfully treated, and 760 (4.7%) were HCV-RNA-positive after treatment. During 136 084 person-years of follow-up (PYFU; median [interquartile range], 6.9 [3.6-13.2]), 1108 (6.9%) developed DM (crude incidence rate, 8.1/1000 PYFU; 95% CI, 7.7-8.6). After adjustment, there was no difference between the 5 HCV strata in incidence of DM (global  = .33). Hypertension (22.2%; 95% CI, 17.5%-26.2%) and body mass index >25 (22.0%; 95% CI, 10.4%-29.7%) had the largest population-attributable fractions for DM.

Conclusions: HCV coinfection and HCV cure were not associated with DM in this large study. The biggest modifiable risk factors were hypertension and obesity, and continued efforts to manage such comorbidities should be prioritized.
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http://dx.doi.org/10.1093/ofid/ofaa470DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7772946PMC
December 2020

Increase in bone turnover markers in HIV patients treated with tenofovir disoproxil fumarate combined with raltegravir or efavirenz.

Bone Rep 2020 Dec 16;13:100727. Epub 2020 Oct 16.

Hadassah AIDS Center, Department of Clinical Microbiology and Infectious Diseases, Hadassah Hebrew University Medical Center, Jerusalem, Israel.

Introduction: Accelerated bone loss and osteoporosis are multifactorial comorbidities related to HIV and its treatments; however, their mechanisms remain elusive. Identifying HIV treatments that are differentially linked to osteoporosis risk, and clinical factors associated with HIV-related osteoporosis may enable optimizing anti-retroviral treatment (ART) and anti-osteoporosis therapy in preventing or treating this debilitating complication. This study aims to evaluate the dynamics of bone turnover markers after initiation of two commonly used antiretroviral regimens.

Methods: A prospective matched cohort study. Thirty treatment-naïve male patients (mean age 40 ± 10y) who initiated treatment with truvada (tenofovir disoproxil fumarate (TDF)/emtricitabine (FTC)) + raltegravir or TDF/FTC + efavirenz were included in the study. Control group included 15 treatment-naive HIV patients. Serum morning fasting level of P1NP and CTX were measured 0, 1, 6, and 12 months after treatment initiation in the two study groups, and at 0, 6 and 12 months in the control group.

Results: In both treatment groups, but not in the control group, both markers increased significantly over time with no difference in BTM between patients treated with raltegravir or efavirenz. Levels of P1NP were statistically higher at 6 and 12 months after treatment initiation in both treatment groups compared to the controls, while CTX during treatment increased in both treatment groups but was significantly higher only in the raltegravir treatment group after 12 months. The ratio of area under the curve of P1NP/CTX correlated with CD4 increment.

Conclusions: Treatment initiation with raltegravir or efavirenz combined with TDF/FTC is associated with increased bone turnover. Thus, therapy that optimize bone turnover is needed to reduce bone loss at this vulnerable period and improve long-term bone health.
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http://dx.doi.org/10.1016/j.bonr.2020.100727DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7607241PMC
December 2020

False-positive galactomannan antigen testing in pulmonary nocardiosis.

Med Mycol 2021 Feb;59(2):206-209

Department of Clinical Microbiology and Infectious Diseases, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.

Early diagnosis of invasive aspergillosis (IA) is facilitated by detection of galactomannan (GM) in serum and bronchoalveolar lavage fluid (BALF) using an enzyme-linked immunosorbent assay (ELISA). Although accurate, false positive results have been reported with these tests in numerous contexts. We report for the first time the occurrence of false positive GM ELISA due to nocardiosis, initially in a clinical sample of BALF from a patient with pulmonary nocardiosis, and subsequently corroborated by in vitro reactivity of 26% of tested isolates. Since patients at risk for IA are also at risk for nocardiosis, this finding has important clinical implications.

Lay Summary: Early diagnosis of aspergillosis has been facilitated by the routine use of antibody-based detection of galactomannan in various bodily fluids. We report for the first time the occurrence of false positive results of this assay in the context of nocardiosis.
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http://dx.doi.org/10.1093/mmy/myaa084DOI Listing
February 2021

Influence of hepatitis C virus co-infection and hepatitis C virus treatment on risk of chronic kidney disease in HIV-positive persons.

AIDS 2020 08;34(10):1485-1495

Department of Infectious Diseases, Rigshospitalet, University of Copenhagen, Centre of Excellence for Health, Immunity and Infections (CHIP), Copenhagen, Denmark.

Background: Hepatitis C virus (HCV) infection has been associated with increased risk of chronic kidney disease (CKD). We investigated the impact of HCV cure on CKD in HIV-positive persons in the EuroSIDA study.

Methods: HIV-positive persons with known HCV status and at least three serum creatinine measurements after 1/1/2004 were compared based on time-updated HCV-RNA and HCV treatment: anti-HCV-negative, spontaneously cleared HCV, chronic untreated HCV, successfully treated HCV, and HCV-RNA positive after HCV treatment. Poisson regression compared incidence rates of CKD [confirmed (>3 months apart) eGFR <60 ml/min per 1.73 m] between HCV strata.

Results: Fourteen thousand, seven hundred and fifty-four persons were included; at baseline 9273 (62.9%) were HCV-Ab negative, 696 (4.7%) spontaneous clearers, 3021 (20.5%) chronically infected, 922 (6.2%) successfully treated and 842 (5.7%) HCV-RNA positive after treatment. During 115 335 person-years of follow-up (PYFU), 1128 (7.6%) developed CKD; crude incidence 9.8/1000 PYFU (95% CI 9.2-10.4). After adjustment, persons anti-HCV negative [adjusted incidence rate ratio (aIRR) 0.59; 95% CI 0.46-0.75] and spontaneous clearers (aIRR 0.67; 95% CI 0.47-0.97) had significantly lower rates of CKD compared with those cured whereas persons chronically infected (aIRR 0.85; 95% CI 0.65-1.12) and HCV-RNA positive after treatment (aIRR 0.71; 95% CI 0.49-1.04) had similar rates. Analysis in those without F3/F4 liver fibrosis using a more rigorous definition of CKD showed similar results.

Conclusion: This large study found no evidence that successful HCV treatment reduced CKD incidence. Confounding by indication, where those with highest risk of CKD were prioritized for HCV treatment in the DAA era, may contribute to these findings.
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http://dx.doi.org/10.1097/QAD.0000000000002570DOI Listing
August 2020

Community Vs. hospital HIV testing sites in Jerusalem, Israel - who's tested and who's at risk?

Isr J Health Policy Res 2020 05 18;9(1):10. Epub 2020 May 18.

Tel Aviv Department of Health, Tel Aviv, Israel.

Background: After decades of constant increase in HIV diagnoses among men who have sex with men (MSM), a gradual decrease has been reported in recent years. Timely detection of HIV leads to early treatment and behavioral changes which decrease further transmissions. This cross-sectional study aimed to assess demographic and behavioral characteristics of individuals who were tested for HIV in Jerusalem, Israel.

Methods: This study compared individuals who were tested at Hadassah AIDS Center (HAC) with those tested at the Jerusalem Open House (JOH) - an LGBTQ community center. Participants completed anonymous questionnaires regarding their demographic, HIV-testing history, and sexual behaviors. High-risk sexual behavior (HRSB) was defined as a diagnosis of sexually transmitted disease or condomless anal/vaginal sex during the last year.

Results: Among 863 participants, 104 (12.1%) were tested in HAC and 759 (87.9%) in JOH. Of those, 19 (18.3%) and 227 (29.9%) were HRSB, respectively. Two MSM were tested positive in JOH. JOH received more MSM, HRSB and individuals who were previously tested for HIV, while HAC received more migrants and health-care workers. HRSB-participants were more commonly younger, males, non-Jewish, with lower income, previously tested for HIV, reported more sexual partners, payed for sex or used drugs.

Conclusions: MSM and HRSB-individuals were more likely to be tested in JOH, while migrants and health-care workers in HAC, possibly due to the geographic location, reputation and specific atmosphere. In order to encourage HIV-tests among HRSB and non-Jews, additional interventions should be employed, including outreach activities, extending opening hours and reducing testing costs should be employed.
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http://dx.doi.org/10.1186/s13584-020-00368-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7232836PMC
May 2020

Massive osteopetrosis caused by non-functional osteoclasts in R51Q SNX10 mutant mice.

Bone 2020 07 8;136:115360. Epub 2020 Apr 8.

Department of Molecular Genetics, The Weizmann Institute of Science, Rehovot 76100, Israel. Electronic address:

The R51Q mutation in sorting nexin 10 (SNX10) was shown to cause a lethal genetic disease in humans, namely autosomal recessive osteopetrosis (ARO). We describe here the first R51Q SNX10 knock-in mouse model and show that mice homozygous for this mutation exhibit massive, early-onset, and widespread osteopetrosis. The mutant mice exhibit multiple additional characteristics of the corresponding human disease, including stunted growth, failure to thrive, missing or impacted teeth, occasional osteomyelitis, and a significantly-reduced lifespan. Osteopetrosis in this model is the result of osteoclast inactivity that, in turn, is caused by absence of ruffled borders in the mutant osteoclasts and by their inability to secrete protons. These results confirm that the R51Q mutation in SNX10 is a causative factor in ARO and provide a model system for studying this rare disease.
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http://dx.doi.org/10.1016/j.bone.2020.115360DOI Listing
July 2020

Case Report of Increased Exposure to Antiretrovirals following Sleeve Gastrectomy.

Antimicrob Agents Chemother 2020 03 24;64(4). Epub 2020 Mar 24.

Hadassah AIDS Center, Department of Clinical Microbiology and Infectious Diseases, Hebrew University Hadassah Medical Center, Jerusalem, Israel.

Bariatric surgery is increasingly performed in morbidly obese HIV patients. Limited data exist regarding antiretroviral drug exposure after bariatric surgery. We report a case of a morbidly obese HIV patient who underwent sleeve gastrectomy. Abacavir, lamivudine, and dolutegravir therapeutic drug monitoring was performed at several time points pre- and postsurgery. Significantly increased levels were measured, particularly for abacavir, whose levels increased ∼12-fold. Several mechanistic explanations for these findings are discussed.
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http://dx.doi.org/10.1128/AAC.02453-19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7179309PMC
March 2020

Malignant deep brain stimulator withdrawal syndrome.

BMJ Case Rep 2019 May 15;12(5). Epub 2019 May 15.

Internal Medicine, St. Vincent Charity Medical Center, Cleveland, Ohio, USA.

Parkinsonism-hyperpyrexia syndrome (PHS) is a neurologic potentially fatal emergency that mimics neuroleptic malignant syndrome. It commonly presents as systemic inflammatory response syndrome, acute onset worsening of muscular rigidity, autonomic instability, hyperpyrexia, confusion, diaphoresis and high creatine phosphokinase. The most common trigger for PHS is reduction or withdrawal of anti-Parkinson's medications, especially levodopa. It was also reported in a few cases following deep brain stimulation of the subthalamic nucleus surgery shortly after anti-Parkinson's medications were discontinued. Rare causes of PHS include deep brain stimulator (DBS) malfunction due to battery depletion. To the best of our knowledge, PHS following DBS battery depletion was reported only in three occasions. Here, we report a case of PHS due to DBS battery depletion presented as sepsis and was successfully treated with the administration of dopamine agonists, intravenous fluids and changing the DBS battery.
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http://dx.doi.org/10.1136/bcr-2018-229122DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6536166PMC
May 2019

Limited awareness of the effective timing of HIV post-exposure prophylaxis among people with high-risk exposure to HIV.

Eur J Clin Microbiol Infect Dis 2019 Apr 24;38(4):779-784. Epub 2019 Jan 24.

Hadassah AIDS Center, Clinical Microbiology and Infectious Diseases Department, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.

The effectiveness of post-exposure prophylaxis (PEP), a major strategy in the battle against HIV, depends on awareness of this modality and its proper timing among high-risk groups. While general awareness of PEP is improving, recently estimated to be 36-47% among men who have sex with men (MSM), PEP implementation remains disappointingly low and may be driven by limited awareness of effective PEP timing window. The level of detailed understanding of PEP timing and effectiveness among populations at risk has not been prospectively assessed to date. We prospectively evaluated, for the first time, actionable awareness regarding effective timing of PEP among a large cohort of individuals tested for HIV following unprotected sexual intercourse. Four hundred participants were assessed between December 2014 and February 2016. Overall awareness of the option of PEP was 60% and was significantly higher among male members of the LGBTQ community (75·5% as compared to 52·6% among heterosexual males) and those undergoing past HIV testing (67·1%). However, only 24% of individuals at risk were aware as to the proper timing of effective PEP treatment, thereby leading, in the majority of cases, to missing the window of opportunity for PEP treatment. This study highlights the lack of knowledge as to the specific requirements needed for effective PEP timing. Expanded advertising, better targeting of the heterosexual population, training of family physicians in the field of gender, sexuality, and LGBTQ medicine, may improve effective PEP availability, thereby reducing HIV transmission.
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http://dx.doi.org/10.1007/s10096-019-03476-4DOI Listing
April 2019

Persistent disparities in antiretroviral treatment (ART) coverage and virological suppression across Europe, 2004 to 2015.

Euro Surveill 2018 05;23(21)

The members of the EuroSIDA Study Group are acknowledged at the end of the article.

Background: Direct comparisons between countries in core HIV care parameters are often hampered by differences in data collection.

Aim: Within the EuroSIDA study, we compared levels of antiretroviral treatment (ART) coverage and virological suppression (HIV RNA < 500 copies/mL) across Europe and explored temporal trends.

Methods: In three cross-sectional analyses in 2004-05, 2009-10 and 2014-15, we assessed country-specific percentages of ART coverage and virological suppression among those on ART. Temporal changes were analysed using logistic regression.

Results: Overall, the percentage of people on ART increased from 2004-05 (67.8%) to 2014-15 (78.2%), as did the percentage among those on ART who were virologically suppressed (75.2% in 2004-05, 87.7% in 2014-15). However, the rate of improvement over time varied significantly between regions (p < 0.01). In 2014-15, six of 34 countries had both ART coverage and virological suppression of above 90% among those on ART. The pattern varied substantially across clinics within countries, with ART coverage ranging from 61.9% to 97.0% and virological suppression from 32.2% to 100%. Compared with Western Europe (as defined in this study), patients in other regions were less likely to be virologically suppressed in 2014-15, with the lowest odds of suppression (adjusted odds ratio = 0.16; 95% confidence interval (CI): 0.13-0.21) in Eastern Europe.

Conclusions: Despite overall improvements over a decade, we found persistent disparities in country-specific estimates of ART coverage and virological suppression. Underlying reasons for this variation warrant further analysis to identify a best practice and benchmark HIV care across EuroSIDA.
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http://dx.doi.org/10.2807/1560-7917.ES.2018.23.21.1700382DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6152212PMC
May 2018

Breast Implant Q Fever as a Source of In-Hospital Transmission.

Clin Infect Dis 2018 02;66(5):793-795

Department of Plastic and Reconstructive Surgery, Jerusalem, Israel.

Herein, we describe the first case of mammary implant infection caused by Coxiella burnetii, resulting in delayed diagnosis and treatment and an in-hospital cross-transmission of Q fever to medical personnel.
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http://dx.doi.org/10.1093/cid/cix912DOI Listing
February 2018

The gut microbiome in human immunodeficiency virus infection.

BMC Med 2016 06 3;14(1):83. Epub 2016 Jun 3.

Department of Immunology, Weizmann Institute of Science, 234 Herzl Street, Rehovot, 76100, Israel.

HIV/AIDS causes severe dysfunction of the immune system through CD4+ T cell depletion, leading to dysregulation of both the adaptive and innate immune arms. A primary target for viral infection is the gastrointestinal tract, which is a reservoir of CD4+ T cells. In addition to being a major immune hub, the human gastrointestinal tract harbors trillions of commensal microorganisms, the microbiota, which have recently been shown to play critical roles in health. Alterations in the composition and function of microbiota have been implicated in a variety of 'multi-factorial' disorders, including infectious, autoimmune, metabolic, and neoplastic disorders. It is widely accepted that, in addition to its direct role in altering the gastrointestinal CD4+ T cell compartment, HIV infection is characterized by gut microbiota compositional and functional changes. Herein, we review such alterations and discuss their potential local and systemic effects on the HIV-positive host, as well as potential roles of novel microbiota-targeting treatments in modulating HIV progression and associated adverse systemic manifestations.
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http://dx.doi.org/10.1186/s12916-016-0625-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4891875PMC
June 2016

Pregnancy-associated listeriosis: many beliefs, few facts.

Lancet Infect Dis 2015 Oct 20;15(10):1128-1130. Epub 2015 Sep 20.

Department of Clinical Microbiology and Infectious Diseases, Hadassah-Hebrew University Medical Center, Jerusalem 91120, Israel. Electronic address:

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http://dx.doi.org/10.1016/S1473-3099(15)00302-3DOI Listing
October 2015

A Population-Structured HIV Epidemic in Israel: Roles of Risk and Ethnicity.

PLoS One 2015 24;10(8):e0135061. Epub 2015 Aug 24.

National Cancer Institute, Frederick, MD, United States of America.

Background: HIV in Israel started with a subtype-B epidemic among men who have sex with men, followed in the 1980s and 1990s by introductions of subtype C from Ethiopia (predominantly acquired by heterosexual transmission) and subtype A from the former Soviet Union (FSU, most often acquired by intravenous drug use). The epidemic matured over the last 15 years without additional large influx of exogenous infections. Between 2005 and 2013 the number of infected men who have sex with men (MSM) increased 2.9-fold, compared to 1.6-fold and 1.3-fold for intravenous drug users (IVDU) and Ethiopian-origin residents. Understanding contemporary spread is essential for effective public health planning.

Methods: We analyzed demographic and virologic data from 1,427 HIV-infected individuals diagnosed with HIV-I during 1998-2012. HIV phylogenies were reconstructed with maximum-likelihood and Bayesian methods.

Results: Subtype-B viruses, but not A or C, demonstrated a striking number of large clusters with common ancestors having posterior probability ≥0.95, including some suggesting presence of transmission networks. Transmitted drug resistance was highest in subtype B (13%). MSM represented a frequent risk factor in cross-ethnic transmission, demonstrated by the presence of Israeli-born with non-B virus infections and FSU immigrants with non-A subtypes.

Conclusions: Reconstructed phylogenetic trees demonstrated substantial grouping in subtype B, but not in non-MSM subtype-A or in subtype-C, reflecting differences in transmission dynamics linked to HIV transmission categories. Cross-ethnic spread occurred through multiple independent introductions, with MSM playing a prevalent role in the transmission of the virus. Such data provide a baseline to track epidemic trends and will be useful in informing and quantifying efforts to reduce HIV transmission.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0135061PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4547742PMC
May 2016

Pregnancy-associated listeriosis: clinical characteristics and geospatial analysis of a 10-year period in Israel.

Clin Infect Dis 2014 Oct 27;59(7):953-61. Epub 2014 Jun 27.

Department of Clinical Microbiology and Infectious Diseases, Hadassah Hebrew University Medical Center, Ein Kerem.

Background: Listeria monocytogenes is a foodborne pathogen that causes life-threatening infections in elderly, immunocompromised, and pregnant women. In pregnancy it may cause fetal loss or a preterm delivery, and the neonate is prone to neonatal sepsis and death.

Methods: We created a cohort of all L. monocytogenes cases during 10 years (1998-2007) in Israel, by a comprehensive review of cases in hospitals throughout the country and cases reported to the Ministry of Health.

Results: One hundred sixty-six pregnancy-related listeriosis cases were identified, resulting in a yearly incidence of 5-25 cases per 100 000 births. Presentation associated with fetal demise was more common in the second trimester (55.3%), and preterm labor (52.3%) and abnormal fetal heart rate monitoring (22.2%) were more common in the third trimester (P = .001). Fetal viability was low in the second trimester (29.2%) and much higher (95.3%) in the third trimester. Each additional week of pregnancy increased the survival chance by 33% (odds ratio, 1.331 [95% confidence interval, 1.189-1.489]). A single case of maternal mortality was identified. Listeria monocytogenes serotype 4b was more common in pregnancy-related than in non-pregnancy-related cases (79.5% vs 61.3%, P = .011). Pulsed-field gel electrophoresis analysis suggested that 1 pulsotype is responsible for 35.7% of the pregnancy cases between 2001 and 2007. This clone is closely related to the Italian gastroenteritis-associated HPB2262 and the invasive US Scott A L. monocytogenes strains.

Conclusions: Our survey emphasizes the high rate of pregnancy-related listeriosis in Israel and shows that specific clones might account for this.
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http://dx.doi.org/10.1093/cid/ciu504DOI Listing
October 2014

Comparable long-term efficacy of Lopinavir/Ritonavir and similar drug-resistance profiles in different HIV-1 subtypes.

PLoS One 2014 27;9(1):e86239. Epub 2014 Jan 27.

Kaplan Medical Center, Rehovot, Israel.

Background: Analysis of potentially different impact of Lopinavir/Ritonavir (LPV/r) on non-B subtypes is confounded by dissimilarities in the conditions existing in different countries. We retrospectively compared its impact on populations infected with subtypes B and C in Israel, where patients infected with different subtypes receive the same treatment.

Methods: Clinical and demographic data were reported by physicians. Resistance was tested after treatment failure. Statistical analyses were conducted using SPSS.

Results: 607 LPV/r treated patients (365 male) were included. 139 had HIV subtype B, 391 C, and 77 other subtypes. At study end 429 (71%) were receiving LPV/r. No significant differences in PI treatment history and in median viral-load (VL) at treatment initiation and termination existed between subtypes. MSM discontinued LPV/r more often than others even when the virologic outcome was good (p = 0.001). VL was below detection level in 81% of patients for whom LPV/r was first PI and in 67% when it was second (P = 0.001). Median VL decrease from baseline was 1.9±0.1 logs and was not significantly associated with subtype. Median CD4 increase was: 162 and 92cells/µl, respectively, for patients receiving LPV/r as first and second PI (P = 0.001), and 175 and 98, respectively, for subtypes B and C (P<0.001). Only 52 (22%) of 237 patients genotyped while under LPV/r were fully resistant to the drug; 12(5%) were partially resistant. In48%, population sequencing did not reveal resistance to any drug notwithstanding the virologic failure. No difference was found in the rates of resistance development between B and C (p = 0.16).

Conclusions: Treatment with LPV/r appeared efficient and tolerable in both subtypes, B and C, but CD4 recovery was significantly better in virologically suppressed subtype-B patients. In both subtypes, LPV/r was more beneficial when given as first PI. Mostly, reasons other than resistance development caused discontinuation of treatment.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0086239PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3903498PMC
November 2014

Coxsackievirus A6-related hand foot and mouth disease: skin manifestations in a cluster of adult patients.

J Clin Virol 2014 Mar 7;59(3):201-3. Epub 2014 Jan 7.

Hadassah-Hebrew University Medical Center, Jerusalem, Israel.

Background: Hand foot and mouth disease (HFMD) is a common childhood manifestation of enterovirus (EV) infection. It predominantly affects young children, and has been mainly associated with coxsackievirus (CV) A16 and EV 71.

Objectives: We report an unusual cluster of adult patients with HFMD.

Study Design: Throat swabs and vesicular fluid samples obtained from patients admitted to the emergency room (ER) with HFMD were tested for EV by reverse transcription (RT)-real time PCR, and further subjected to sequencing and phylogenetic analysis.

Results: CVA6 was identified as the causative agent of HFMD in five epidemiologically-unrelated adult patients (28-37 years old) admitted to the ER between December 2012 and February 2013. Phylogenetic analysis mapped the CVA6 strains into one cluster. All patients manifested with fever and a severe vasculitis-like rash, followed by spontaneous recovery.

Conclusions: This cluster identifies CVA6 as an emerging cause of HFMD of unusual age distribution, seasonality, and clinical severity, underscoring the need for continued alertness and clinical-genotypic surveillance of EV HFMD.
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http://dx.doi.org/10.1016/j.jcv.2013.12.012DOI Listing
March 2014

Human CRM1 augments production of infectious human and feline immunodeficiency viruses from murine cells.

J Virol 2012 Nov 29;86(22):12053-68. Epub 2012 Aug 29.

Section of Infectious Diseases, Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut, USA.

Productive replication of human immunodeficiency virus type 1 (HIV-1) occurs efficiently only in humans. The posttranscriptional stages of the HIV-1 life cycle proceed poorly in mouse cells, with a resulting defect in viral assembly and release. Previous work has shown that the presence of human chromosome 2 increases HIV-1 production in mouse cells. Recent studies have shown that human chromosome region maintenance 1 (hCRM1) stimulates Gag release from rodent cells. Here we report that expressions of hCRM1 in murine cells resulted in marked increases in the production of infectious HIV-1 and feline immunodeficiency virus (FIV). HIV-1 production was also increased by hSRp40, and a combination of hCRM1 and hSRp40 resulted in a more-than-additive effect on HIV-1 release. In contrast, the overexpression of mouse CRM1 (mCRM1) minimally affected HIV-1 and FIV production and did not antagonize hCRM1. In the presence of hCRM1 there were large increases in the amounts of released capsid, which paralleled the increases in the infectious titers. Consistent with this finding, the ratios of unspliced to spliced HIV-1 mRNAs in mouse cells expressing hCRM1 and SRp40 became similar to those of human cells. Furthermore, imaging of intron-containing FIV RNA showed that hCRM1 increased RNA export to the cytoplasm.By testing chimeras between mCRM1 and hCRM1 and comparing those sequences to feline CRM1, we mapped the functional domain to HEAT (Huntingtin, elongation factor 3, protein phosphatase 2A, and the yeast kinase TOR1) repeats 4A to 9A and a triple point mutant in repeat 9A, which showed a loss of function. Structural analysis suggested that this region of hCRM1 may serve as a binding site for viral or cellular factors to facilitate lentiviral RNA nuclear export.
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http://dx.doi.org/10.1128/JVI.01970-12DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3486471PMC
November 2012

Training laboratory technicians from the Ethiopian periphery in the MODS technique enables rapid and low-cost diagnosis of Mycobacterium tuberculosis infection.

Am J Trop Med Hyg 2012 Apr;86(4):683-9

Department of Clinical Microbiology and Infectious Diseases, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.

Tuberculosis (TB) is a leading cause of morbidity and mortality and is frequently complicated by emergence of drug-resistant strains. Diagnosis of TB in developing countries is often based on the relatively insensitive acid-fast staining that does not enable susceptibility profiling. Microscopic observation drug susceptibility assay (MODS) is an inexpensive, simple method that enables rapid TB culture coupled with susceptibility testing. A 3-week MODS training of three Ethiopian laboratory technicians was conducted at Hadassah-Hebrew University Medical Center, Israel. Results of the trainee readings were blindly assessed by an experienced instructor. Two hundred fifty-five (255) trainee culture readings were evaluated throughout the course. The sensitivity and specificity were 75-100% and 31.5-100%, respectively. Multivariate analysis revealed that sensitivity and duration of incubation were positively correlated, although specificity was positively correlated with the length of training. MODS can be reliably performed by laboratory technicians inexperienced in culture techniques in developing countries, with high sensitivity and specificity reached after a brief learning period.
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http://dx.doi.org/10.4269/ajtmh.2012.11-0516DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3403761PMC
April 2012

HIV/AIDS profile and realities at a regional antiretroviral therapy clinic in Jerusalem: 12 years analysis.

Scand J Infect Dis 2012 Jan 19;44(1):65-9. Epub 2011 Sep 19.

AIDS Center, Department of Clinical Microbiology and Infectious Diseases, Hadassah University Medical Center, Ein-Kerem, Jerusalem, Israel.

The diagnosis of HIV, quality of follow-up, and treatment among immigrants are greatly influenced by cultural factors and access to the healthcare system. Israel, an immigrant-based society, features 3 cardinal HIV-positive patient groups, namely non-immigrant Israelis, legal immigrants (mainly from Ethiopia), and illegal African work-immigrants. While the first 2 groups are covered by a national health insurance, the latter group depends on an unstructured system of antiretroviral therapy (ART) supply. In the early 1990s, a national mentoring programme was implemented for legal immigrants. The programme involves community-based Ethiopian mentors who follow HIV-positive Ethiopians. In this retrospective cohort study we reviewed the files of HIV-positive patients diagnosed between 1995 and 2007, focusing on comparison between HIV-positive non-immigrant populations with both legal Ethiopian immigrants and the often overlooked illegal immigrants. Our results point to a substantial rate of loss to follow-up among the illegal immigrants. When comparing non-immigrants to legal immigrants, both feature similar adherence to follow-up, exposure and response to ART, despite profound cultural differences. Our results suggest that ethnic-related obstacles in HIV diagnosis and treatment may be overcome by 'cultural mediators', yet, addressing the silent mass of HIV-positive illegal work-immigrants, who are deprived of such programme benefits, poses a major challenge to Western health authorities.
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http://dx.doi.org/10.3109/00365548.2011.608713DOI Listing
January 2012

HIV/AIDS among Palestinians: detection, clinical presentation, prognosis and HIV testing patterns, 1994-2010.

Int J Infect Dis 2011 Jun 3;15(6):e377-81. Epub 2011 Apr 3.

Faculty of Medicine, The Hebrew University of Jerusalem, POB 12272, 91120 Jerusalem, Israel.

Objectives: To describe the detection, clinical presentation, and prognosis of West Bank and East Jerusalem Palestinians infected with HIV/AIDS, and HIV testing patterns of Palestinians in the Jerusalem area.

Design And Methods: This was a case-control analysis comparing all 33 Palestinian HIV/AIDS patients who were referred to the Hadassah AIDS Center (HAC) over 17 years (1994-2010) with 77 non-Palestinian patients seen over the same period. The systematic sampling method was used to select the control group. Patterns of HIV testing were observed for the years 2002 and 2007.

Results: Many Palestinian patients (36%) were diagnosed during their initial hospitalization, while 47.1% of non-Palestinians were diagnosed as outpatients. Significantly more opportunistic infections were detected during diagnosis among Palestinians (48.5%) than among non-Palestinians (9.1%, p<0.001). Overall mortality among Palestinian patients was 36.4% (12/33) vs. 6.5% (5/77) among non-Palestinians (p<0.001). No significant differences in the initial CD4 counts and viral load levels were noted between Palestinians and non-Palestinians (256/mm(3) and log 4.58 copies/ml vs. 271/mm(3) and log 4.49 copies/ml, respectively). Follow-up visits were more infrequent among Palestinians than among non-Palestinians: 9.8 (± 1.0) compared with 23.4 (± 12.9), respectively (p<0.001), over a median follow-up of 2.7 years for Palestinians and 8.1 years for non-Palestinians (p<0.001). With regard to HIV testing, 7.3% (72/989) of individuals tested in 2002 and 10.9% (202/1851) in 2007 were Palestinians. The most frequent reason for being tested among Palestinians was 'medical' (e.g., before in vitro fertilization, 69.4% in 2007); among non-Palestinians it was 'intimate relationships' (31% in 2007).

Conclusion: These results show that despite an overall small number of Palestinian HIV/AIDS patients, late diagnosis and high mortality are very much in evidence.
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http://dx.doi.org/10.1016/j.ijid.2010.12.012DOI Listing
June 2011

Invasive Scytalidium dimidiatum infection in an immunocompetent adult.

J Clin Microbiol 2009 Apr 4;47(4):1259-63. Epub 2009 Feb 4.

Department of Clinical Microbiology and Infectious Diseases, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.

Scytalidium dimidiatum, a dematiaceous fungus, has been well established as an agent of dermatomycosis. There are few reports of invasive infection caused by S. dimidiatum; most infections occurred in immunocompromised hosts. We present an immunocompetent patient with pleural S. dimidiatum infection and review nine other published cases of invasive S. dimidiatum infections.
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http://dx.doi.org/10.1128/JCM.01874-08DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2668342PMC
April 2009

In-hospital treatment of hyperglycemia: effects of intensified subcutaneous insulin treatment.

Curr Med Res Opin 2007 Apr;23(4):757-65

Endocrinology and Metabolism Service and the Hadassah Diabetes Center, Department of Medicine, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.

Background: Hyperglycemia is common in hospitalized patients; however, glycemic control obtained during hospitalization is often suboptimal. No methods for achievement of proper glycemic control in this population have been validated in the in-hospital setting.

Aims: To study the effect of a novel intensive subcutaneous insulin protocol on the quality of in-hospital glycemic control.

Methods: Included in this prospective controlled study were all diabetic patients admitted to the internal medicine departments in a tertiary medical center during a 1-year period. The study was divided into pre-intervention (n = 94), intervention (n = 102) and post-intervention (n = 79) periods. During the intervention period all hospitalized diabetic patients with blood glucose > 200 mg/dL were treated with an intensive multi-injection protocol consisting of two or four times daily regular/NPH insulin injections.

Results: Mean glucose level throughout hospitalization was 178.7 +/- 47 mg/dL in the intervention period versus 198.8 +/- 60 mg/dL in the pre-intervention period (p < 0.05). During the intervention period, the difference between mean admission and discharge day glucose levels was 43 mg/dL in patients treated with four times daily insulin injections, in contrast to no change noted in the other treatment groups. During the post-intervention period the rate of implementation of the intensive protocol by the internal medicine teams declined to 47.5%, in contrast to a 78.4% implementation rate during the intervention period. This decline was associated with deterioration of glycemic control.

Conclusions: The use of intensified insulin regimen improved the glycemic control of hospitalized diabetic patients. Successful incorporation of such intensive protocols into daily medical routines requires close involvement and continuous physician guidance by the hospital diabetes team.
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http://dx.doi.org/10.1185/030079907x178748DOI Listing
April 2007

Plantar ulcers and eyebrow-hair paucity.

Clin Infect Dis 2006 Mar;42(5):684-5, 722-4

Department of Intenal Medicine, Hadassah University Medical Centre, Ein Kerem, Jerusalem, Israel.

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http://dx.doi.org/10.1086/502983DOI Listing
March 2006

Liver abscess in inflammatory bowel disease: report of two cases and review of the literature.

J Gastroenterol Hepatol 2004 Dec;19(12):1338-42

Department of Internal Medicine A, Hadassah University Hospital, Jerusalem, Israel.

Hepatic abscesses are a rare complication of inflammatory bowel disease (IBD). Despite the fact that certain hepatobiliary complications of IBD, including cholelithiasis, primary sclerosing cholangitis (PSC) and cholangiocarcinoma predispose patients with IBD to ascending cholangitis, previously published data does not demonstrate that biliary infection is an important mechanism underlying liver abscess development in these patients. We describe two patients with inflammatory bowel disease, both with PSC, who developed multiple liver abscesses, and review the literature on liver abscesses in association with inflammatory bowel disease.
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http://dx.doi.org/10.1111/j.1440-1746.2004.03368.xDOI Listing
December 2004

Differential role of platelet granular mediators in angiogenesis.

Cardiovasc Res 2004 Aug;63(2):226-35

Blood Coagulation Unit, Hematology Department, Hadassah Medical Center, Jerusalem, Israel.

Objectives: Platelets contain numerous substances regulating angiogenic response. However, the regulatory role of platelets in blood vessel development remains to be elucidated. We investigated the comprehensive effect of platelets as a cellular system on angiogenesis.

Methods: The following approaches were applied: (a) in vitro-aortic ring assay and chemotaxis assay; (b) in vivo-injection of platelet-containing matrigel plug subcutaneously into a mouse followed by immunohistochemical analysis of angiogenic response.

Results: Platelets stimulated formation of blood vessels in vitro in the rat aortic ring model via VEGF and bFGF, while blocking of platelet factor-4 promoted this effect. Addition of platelets to the matrigel followed by its subcutaneous injection into a mouse resulted in an intensive migration of fibroblasts into the matrigel as well as formation of blood capillaries de novo. This platelet effect was mediated through bFGF, VEGF, and heparanase. Furthermore, platelet releasate was found to induce endothelial cell chemotaxis. This effect was mediated by a concerted action of intraplatelet bFGF, PDGF, VEGF, and heparanase.

Conclusion: Platelets affect different stages of the angiogenic response with a trend to a pro-angiogenic net effect despite the presence of angiogenesis inhibitors such as platelet factor 4. While a concomitant effect of bFGF and VEGF seemed to be essential for the entire process of vessel formation (aortic ring and matrigel models), PDGF and heparanase were effective only at the migration stage.
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http://dx.doi.org/10.1016/j.cardiores.2004.04.012DOI Listing
August 2004

The coexistence of Sweet's syndrome and Still's disease--is it merely a coincidence?

J Am Acad Dermatol 2004 May;50(5 Suppl):S90-2

Department of Medicine "A," Institute of Pathology, Hadassah-Hebrew University School of Medicine, Ein-Karem, Jerusalem 91120, Israel.

Sweet's syndrome has a wide range of clinical manifestations. It may appear as a solitary cutaneous disorder but often it is associated with systemic signs and symptoms. This disorder might be idiopathic but it often is paraneoplastic or associated with medications or autoimmune diseases. In its systemic manifestation Sweet's disease resembles adult-onset Still's disease in many aspects. We present a case of a young man in whom Sweet's syndrome and Still's disease developed. Although the diagnosis of adult-onset Still's disease is made by exclusion, he fulfilled all the criteria of both conditions. Considering the clinical similarities of these diseases, it may be presumed that similar patients may have been overlooked in the past.
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http://dx.doi.org/10.1016/s0190-9622(03)02796-8DOI Listing
May 2004

Deep infection by Trichophyton rubrum in an immunocompromised patient.

J Clin Microbiol 2003 Nov;41(11):5298-301

Department of Clinical Microbiology, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.

Dermatophytes are common pathogens of skin but rarely cause invasive disease. We present a case of deep infection by Trichophyton rubrum in an immunocompromised patient. T. rubrum was identified by morphological characteristics and confirmed by PCR. Invasiveness was apparent by histopathology and immunohistochemistry. The patient was treated successfully with itraconazole.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC262492PMC
http://dx.doi.org/10.1128/JCM.41.11.5298-5301.2003DOI Listing
November 2003

[Retroperitoneal fibrosis--clinical response to steroid treatment].

Harefuah 2003 Mar;142(3):166-9, 240

Hadassah University Hospital, Jerusalem, Israel.

Retroperitoneal fibrosis is an inflammatory disease, which is either idiopathic or secondary to infection, neoplasm, hemorrhage, aortic aneurysm or drugs. This is a rare disease usually presenting constitutional symptoms, abdominal, back or flank pain and urinary frequency. Treatment includes surgical relief of urethral obstruction and corticosteroids. There is no clear evidence of the beneficial effect of corticosteroids treatment on the course of retroperitoneal fibrosis. We report a patient diagnosed with retroperitoneal fibrosis with an unusual presentation--uncontrolled HTN and renal failure due to renal arteries obstruction, without any abdominal symptoms. This patient responded to steroids and tamoxifen. A review of the literature is also presented.
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March 2003
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