Israel Medical Association Journal

Background: Behçet's disease is a multi-systemic chronic relapsing inflammatory disease, classified among the vasculitides. The heterogeneity of clinical manifestations challenges the disease management.

Objectives: To assess efficacy and safety of adalimumab in patients with active persistent Behçet's arthritis who did not respond to disease-modifying anti-rheumatic drugs and to assess the impact of treatment on the cytokine milieu.

Methods: Our cohort comprised 10 patients with active arthritis who received adalimumab in a 24-week investigator-initiated prospective open-label study. Patients who relapsed within 12 weeks following adalimumab discontinuation could enter a 3-year extension study. The patients underwent a comprehensive assessment including questionnaires and measurement of inflammatory cytokines, adalimumab serum levels, and anti-drug antibodies.

Results: A significant improvement was observed in arthritis, disease activity visual analogue scales, Behçet's disease current activity form, and interleukin-6 (IL-6) levels, but not in health assessment questionnaire and functional assessment of chronic illness therapy fatigue scale questionnaire. Resolution of oral and urogenital ulcers was achieved in all patients. Significant reduction of pain was reported by 40% of patients. The disease relapsed in 9 of 10 patients, within 2–6 weeks following adalimumab discontinuation. Of the 7 patients who continued the study, arthritis was resolved in 5. Two patients with high neutralizing antidrug antibodies titer relapsed.

Conclusions: Adalimumab treatment achieved a significant improvement in arthritis, mucocutaneous manifestations, and IL-6 levels in all study patients but only 40% reported significant pain reduction. The arthritis relapsed in 90% of patients following adalimumab discontinuation and long-term treatment was required.

Background: Although indwelling catheters are increasingly used in modern medicine, they can be a source of microbial contamination and hard-to-treat biofilms, which jeopardize patient lives. At times 70% ethanol is used as a catheter-lock solution due to its bactericidal properties. However, high concentrations of ethanol can result in adverse effects and in malfunction of the catheters.

Objective: To determine whether low concentrations of ethanol can prevent and treat biofilms of Pseudomonas aeruginosa.

Methods: Ethanol was tested at a concentration range of 0.625–80% against laboratory and clinical isolates of P. aeruginosa for various time periods (2–48 hours). The following parameters were evaluated following ethanol exposure: prevention of biofilm formation, reduction of biofilm metabolic activity, and inhibition of biofilm regrowth.

Results: Exposing P. aeruginosa to twofold ethanol gradients demonstrated a significant biofilm inhibition at concentrations as low as 2.5%. Treating pre-formed biofilms of P. aeruginosa with 20% ethanol for 4 hours caused a sharp decay in the metabolic activity of both the laboratory and clinical P. aeruginosa isolates. In addition, treating mature biofilms with 20% ethanol prevented the regrowth of bacteria encased within it.

Conclusions: Low ethanol concentrations (2.5%) can prevent in vitro biofilm formation of P. aeruginosa. Treatment of previously formed biofilms can be achieved using 20% ethanol, thereby keeping the catheters intact and avoiding complications that can result from high ethanol concentrations.

Background: Survivors of acute myocardial infarction (AMI) are at increased risk for recurrent cardiac events and tend to use excessive healthcare services, thus resulting in increased costs.

Objectives: To evaluate the disparities in healthcare resource utilization and costs throughout a decade following a non-fatal AMI according to sex and ethnicity groups in Israel.

Methods: A retrospective study included AMI patients hospitalized at Soroka University Medical Center during 2002–2012. Data were obtained from electronic medical records. Post-AMI annual length of hospital stay (LOS); number of visits to the emergency department (ED), primary care facilities, and outpatient consulting clinics; and costs were evaluated and compared according sex and ethnicity groups.

Results: A total of 7685 patients (mean age 65.3 ± 13.6 years) were analyzed: 56.8% Jewish males (JM), 26.6% Jewish females (JF), 12.4% Bedouin males (BM), and 4.2% Bedouin females (BF). During the up-to 10-years follow-up (median 5.8 years), adjusted odds ratios [AdjOR] for utilizations of hospital-associated services were highest among BF (1.628 for LOS; 1.629 for ED visits), whereas AdjOR for utilization of community services was lowest in BF (0.722 for primary clinic, 0.782 for ambulatory, and 0.827 for consultant visits), compared with JM. The total cost of BF was highest among the study groups (AdjOR = 1.589, P < 0.01).

Conclusions: Long-term use of hospital-associated healthcare services and total costs were higher among Bedouins (especially BF), whereas utilization of ambulatory services was lower in these groups. Culturally and economically sensitive programs optimizing healthcare resources utilization and costs is warranted.

Background: In an effort to alter eye color during World War II, devout Nazi researcher Karin Magnussen had adrenaline eye drops administered to inmates at the concentration camp Auschwitz-Birkenau. A Sinti family, with a high prevalence of heterochromia iridis, was forced to participate in this study. Members of this family, as well as other victims, were later killed and had their eyes enucleated and sent to Magnussen for examination. Magnussen articulated the findings of these events in a manuscript that has never been published. The author is the first ophthalmologist to review this manuscript. The generation who experienced the atrocities of World War II will soon be gone and awareness of what happened during this tragic chapter of world history is fading.

Objectives: To describe these events to raise awareness among future generations.

Methods: A literature review and archival search was conducted.

Results: Magnussen’s research was based on an animal study published in 1937. For Magnussen’s study, adrenaline drops were administered to inmates, including a 12-year-old girl from the Sinti family. As there was a reported case of deaf-mutism within the family, Waardenburg syndrome seems to be the most plausible explanation for this family’s heritable heterochromia.

Conclusions: The effort to change eye color was doomed to fail from the beginning because there was a probable diagnosis of Waardenburg syndrome. Extinction of humans for ophthalmological research is an insane act beyond imagination. For the sake of these victims, and for the generations who still feel their pain, it is imperative to tell their stories.

Background: Immune thrombocytopenia (ITP) is an autoimmune disorder of variable origin that results in bleeding and decreased platelet count. Autoimmune abnormalities have been described in patients with malignancies including non-Hodgkin's lymphoma but are rarely described in patients with Hodgkin's lymphoma.

Objectives: To describe an unusual presentation of Hodgkin's lymphoma in an unusual age and alarm pediatricians of the challenging diagnosis.  

Methods: We present two cases that highlight an unusual clinical presentation of childhood Hodgkin's lymphoma occurring at an atypical age.

Results: Over a 4-year period, two children aged 5 and 6 years were admitted for suspected ITP, both had cervical lymphadenopathy. Bone marrow examination showed no evidence of tumor or fibrosis. Biopsy of the lymph node was possible only after administration of intravenous immunoglobulins and normalization of the platelet count. Platelet counts increased after initiation of chemotherapy.

Conclusions: The identification of the clinical presentation of ITP as a possible presentation of Hodgkin's lymphoma is important to facilitate timely diagnosis and management.

Background: Solar urticaria (SU) is a rare and disabling photodermatosis. SU typically manifests as urticarial wheals and erythema appearing shortly after sun exposure. SU is often initially diagnosed clinically with subsequent confirmation through photoprovocation tests. Early diagnosis is important for correct management of patients.

Objective: To present the clinical features of three cases of atypical presentation of SU and to discuss possible underlying mechanisms.

Methods: We report a series of three patients who presented with transient pruritic erythema without wheals after sun exposure. All patients had photoprovocation tests conducted to confirm SU diagnosis and to determine their action spectra. Treatment outcomes were recorded.

Results: All three patients developed classical manifestations of SU during photoprovocation tests within the UVA1 spectrum. Two patients required high-dose irradiation to provoke urticaria.

Conclusions: Erythema without urticaria can be the primary manifestation of SU, especially in countries with sunny climates where natural skin hardening is common. Such cases require a high index of suspicion for SU and highlight the importance of photoprovocation testing to confirm the diagnosis.

Background: Urinary tract infection (UTI) is a common bacterial infection in children.

Early treatment may prevent renal damage in pyelonephritis. The choice of empiric antibiotic treatment is based on knowledge of the local susceptibility of urinary bacteria to antibiotics. In Israel the recommended empiric oral antibiotic treatment are First or second generation cephalosporin, trimethoprim-sulfamethoxazole or amoxicillin-clavulanic acid.

Objectives: To describe resistance rates of urine bacteria isolated from children with UTI in the community settings. Identify risk factors for resistance.

Methods: A retrospective cross-sectional study of UTI in children aged 3 months to 18 years diagnosed with UTI and treated as outpatients in a large community clinic between 7/2015 and 7/2017 with a diagnosis of UTI.

Results: A total of 989 urinary samples were isolated, 232 were included in the study. Resistance rates to cephalexin, cefuroxime, ampicillin/clavulanate and Trimethoprim-Sulfamethoxazole were 9.9%, 9.1%, 20.7%, and 16.5%, respectively. Urinary tract abnormalities and recurrent UTI were associated with an increase in antibiotic resistance rates. Other factors such as age, fever, and previous antibiotic treatment were not associated with resistance differences.

Conclusions: Resistance rates to common oral antibiotics were low compared to previous studies performed in Israel in hospital settings. First generation cephalosporins are the preferred empiric antibiotics for febrile UTI for outpatient children. Amoxicillin/clavulanate is not favorable due to resistance of over 20% and the broad spectrum of this antibiotic. Care should be taken in children with renal abnormalities as there is a worrying degree of resistance rates to the oral first line antibiotic therapy.

Background: Admission to an intensive care unit (ICU) is an objective marker of severe maternal morbidity (SMM).

Objectives: To determine the prevalence of obstetric ICU admissions in one medical center in Israel and to characterize this population.

Methods: In this retrospective study the files of women coded for pregnancy, birth, or the perinatal period and admission to the ICU were pulled for data extraction (2005–2013).

Results: During the study period, 111 women were admitted to the ICU among 120,279 women who delivered babies (0.09%). Their average age was 30 ± 6 years, most were multigravida, a few had undergone fertility treatments, and only 27% had complicated previous pregnancies. Most pregnancies (71.2%) were uneventful prior to admission. ICU admissions were divided equally between direct (usually hemorrhage) and indirect (usually cardiac disease) obstetric causes.

Conclusions: The indications for obstetrics ICU admission correlated with the proximate causes of maternal arrest observed worldwide. While obstetric hemorrhage is often unpredictable, deterioration of heart disease is foreseeable. Attention should be directed specifically toward improving the diagnosis and treatment of maternal heart disease during pregnancy in Israel.

Background: Opposition to neonatal Hepatitis B vaccination is a growing trend in Israel.

Objectives: To assess the sociodemographic factors and attitudes associated with non-vaccination of term singleton newborns.

Methods: This prospective, pair-matched, controlled trial was conducted in a tertiary university-affiliated hospital. Data on maternal sociodemographic parameters, delivery, and infant care practices were gathered. Knowledge and references of Hepatitis B virus (HBV) vaccination, vaccination schedule, and health government policies were assessed. A follow-up telephone survey was completed at the age of 7 weeks postpartum regarding vaccine catch-up rate.

Results: Mothers in the study group were mostly Jewish white middle class married multiparous women with some higher education. Hepatitis B serology was not tested in most. Higher rates of rooming-in and exclusive breastfeeding were observed. Knowledge about HBV was stated, multiple sources of information were significantly associated with newborn non-vaccination. Many objected to the timing of the vaccine and its necessity. Multiple medical encounters are viewed as missed opportunities.

Conclusions: Multiple sources of vaccine information are associated with non-vaccination. Medical encounters prior and post-delivery should be used for vaccination education and may improve vaccination coverage.

Background: The use of a high flow nasal cannula (HFNC) was examined for different clinical indications in the critically ill.

Objectives: To describe a single center experience with HFNC in post-extubation critical care patients by using clinical indices.

Methods: In this single center study, the authors retrospectively evaluated the outcome of patients who were connected to the HFNC after their extubation in the intensive care unit (ICU). At 48 hours after the extubation, the patients were divided into three groups: the group weaned from HFNC, the ongoing HFNC group, and the already intubated group.

Results: Of the 80 patients who were included, 42 patients were without HFNC support at 48 hours after extubation, 22 and 16 patients were with ongoing HFNC support and already intubated by this time frame, respectively. The mean ROX index (the ratio of SpO₂ divided by fraction of inspired oxygen to respiratory rate) at 6 hours of the weaned group was 12.3 versus 9.3 in the ongoing HFNC group, and 8.5 in the reintubated group (P = 0.02). The groups were significantly different by the ICU length of stay, tracheostomy rate, and mortality.

Conclusions: Among patients treated with HFNC post-extubation of those who had a higher ROX index were less likely to undergo reintubation.

The authors reviewed the two most common current uses of brain ¹⁸F-labeled fluoro-2-deoxyglucose positron emission tomography (FDG-PET) at a large academic medical center. For epilepsy patients considering surgical management, FDG-PET can help localize epileptogenic lesions, discriminate between multiple or discordant EEG or MRI findings, and predict prognosis for post-surgical seizure control. In elderly patients with cognitive impairment, FDG-PET often demonstrates lobar-specific patterns of hypometabolism that suggest particular underlying neurodegenerative pathologies, such as Alzheimer’s disease. FDG-PET of the brain can be a key diagnostic modality and contribute to improved patient care.

We describe the features of nocebo, and its impact in studies of transition from the originator to the respective biosimilar in inflammatory rheumatic diseases. Investigations in healthy volunteers as well as in the neurology and anesthesiology fields demonstrated the involved cerebral areas and the neurotransmitter pathways responsible for the nocebo response. Whether these findings are applicable to patients with inflammatory rheumatic diseases remains to be demonstrated. Nocebo may account for part of the after-switching biosimilar failures. However, in the absence of validated classification or diagnostic criteria, specific neurochemical and neuroimaging studies, the lack of data on serum tumor necrosis factor and drug levels, and the disease improvement after the switching back to the originator biologic observed in some patients, the nocebo diagnosis remains the role of the individual clinician. Investigations on nocebo pathophysiology and diagnosis are required to address its impact in after-transition biosimilar studies in rheumatology.