Israel Medical Association Journal

Mesenchymal stromal cells are multipotent cells capable of tissue repair and immune modulation. They are primarily found in bone marrow, but are also present in other tissues of mesenchymal origin, such as fatty tissue, muscle, tendons, etc. MSC[1] can easily be obtained by bone marrow aspiration, showing a rapid expansion in vitro. New protocols enable cell culture without the use of animal-derived sera and artificial growth factors. Avascular necroses of the bone may have different causes. AVN[2] in autoimmune and hematological diseases show a strong association with corticosteroid treatment, which is often unavoidable in severe cases. Until recently, core decompression of the affected osseous area was the standard approach. Because of their differentiation properties, easy accessibility and proliferative capacity, autologous MSCs could potentially complement AVN treatment by adding fresh “osteogenic cells” to the healing process.

Treatment of vasculitides has progressed markedly over the past few decades. Recent therapeutic strategies in severe and refractory anti-neutrophil cytoplasmic antibodies-associated vasculitides include immunomodulating methods (e.g., plasma exchanges), products (such as intravenous immunoglobulins) and, more recently, new agents called biotherapies. Some of them (e.g., anti-tumor necrosis factor-alpha and anti-CD20 monoclonal antibodies) have achieved promising results and are now often used to treat severe cases.

Surgical resection offers the best opportunity for cure in patients with colorectal cancer metastasis to the liver, with 5 year survival rates of up to 58% following resection. However, only a small percentage of patients are eligible for resection at the time of diagnosis and the average recurrence rate is still high. Consequently, research endeavors have focused on methods aimed to increase the number of patients eligible for surgical resection, refine the selection criteria for surgery, and improve the disease-free and overall survival time in these patients. Improvements in imaging techniques and the increasing use of FDG-PET allow more accurate preoperative staging and superior identification of patients likely to benefit from surgical resection. Advances in the use of neoadjuvant chemotherapy allows up to 38% of patients previously considered unresectable to be significantly downstaged and eligible for hepatic resection. Many reports have critically evaluated the surgical techniques applied to liver resection, the concurrent or alternative use of local ablative therapies, such as radiofrequency ablation, and the subsequent utilization of adjuvant chemotherapy in patients undergoing surgical resection for hepatic metastases.

Background: Depression is a leading cause of morbidity, disability and health care utilization. It is commonly encountered in primary care settings yet is often missed or suboptimally managed.

Objective: To summarize studies conducted in Israel on the prevalence of depression in primary care settings, its correlates, and predictors of treatment and outcome, and to discuss their implications for clinical practice and public health policy.

Methods: An electronic search was conducted using the MEDLINE and PsychINFO databases. The inclusion criteria were original studies that assessed aspects of depression in a population aged 18 or older, were conducted in primary care settings in Israel, and with sufficient detailed description of depression-related measures, study sample and outcome measures. Twelve articles reporting results from 7 studies met these criteria.

Results: The prevalence of current depression in primary care varied considerably across studies: 1.6–5.9% for major depression, 1.1–5.4% for minor depression, 14.3–24% for depressive symptoms. Depression was consistently related to female gender and few years of education, and was associated with disability, decreased quality of life, and increased health-related expenditure. Many cases of depression were undiagnosed and most patients had persistent depression or achieved only partial remission.

Conclusions: Depression represents a serious challenge for the primary health care system in Israel. Greater efforts should be focused on screening and treating depression in primary care. However, the studies reviewed here used different methodologies and assessed different aspects of depression, and, therefore, should be generalized cautiously. Systematic research on the prevalence, correlates and management of depression in primary care, with emphasis on collaborative care models, is strongly needed to inform research, clinicians and health care policy makers.

Background: It is not entirely clear when and how steroids should be used to treat trichinellosis.

Objectives: To describe the course of consecutive patients with trichinellosis treated with antihelminthic drugs with and without the addition of prednisone.

Methods: We extracted data from the hospital records of 30 patients hospitalized for trichinellosis contracted after eating poorly cooked pork that came from two pigs killed in the Golan Heights, and contacted them for follow-up 5–6 weeks and 6 months after hospital discharge.

Results: All the patients who attended a party and ingested the infected pork (100% attack rate) were hospitalized after 2–16 days (median 9 days); 29 were symptomatic and 1 patient without symptoms had creatine phosphokinase levels 17.9 times above the upper limit of normal. Twelve of 23 patients (52%) treated with antihelminthic drugs without prednisone were rehospitalized with worsening fever, increased peripheral blood eosinophil counts, but decreasing CPK[1] values. These patients and another seven at the time of admission were treated with prednisone 40 mg/day for 5 days in addition to antihelminthic drugs for at least 14 days. All became asymptomatic within 24 hours and were asymptomatic 6 weeks and 6 months later.

Conclusions: Worsening symptoms in patients treated with antihelminthic drugs alone is common. A short course of prednisone is safe and alleviates symptoms due to tissue larvae in patients with trichinellosis.

Background: Patients with severe persistent asthma despite GINA 2002 step 4 treatment are at risk for asthma-related morbidity and mortality. This study constitutes the Israeli arm of the international INNOVATE study.

Objectives: To determine the efficacy and safety of Xolair® as an add-on treatment in patients with severe persistent asthma.

Methods: Asthma patients (age 12–75 years) not controlled with high dose inhaled corticosteroids and long-active beta-2 agonists were randomized to receive either Xolair® or placebo for 28 weeks in a double-blind study in two Israeli centers.

Results: Thirty-three patients, 20 females and 13 males, mean age 54 ± 11.7 years, were included in the Israeli arm of the INNOVATE study. There were neither major adverse events nor withdrawals from the study. Xolair® (omalizumab) significantly reduced the rate of clinically significant asthma exacerbations (55% reduction) and all asthma-related emergency visits (53% reduction).
Conclusions: In patients with severe persistent difficult-to-treat asthma, despite regular treatment with LABA[1] and inhaled corticosteroids (GINA 2002 step 4), Xolair® is a safe and effective treatment

Background: Invasive fungal infections by Mucorales or Aspergillus spp. are lethal infections in immune compromised patients. For these infections a multimodal approach is required. One potential tool for treating these infections is hyperbaric oxygen.

Objectives: To evaluate the clinical course and utility of hyperbaric oxygen in patients with invasive fungal infections by Mucorales or Aspergillus spp.

Methods: We conducted a retrospective chart review of 14 patients treated with HBO[1] as part of their multimodal therapy over a 12 year period.

Results: Most patients had significant immune suppression due to either drug treatment or their underlying disorder. Thirteen of the 14 underwent surgery as part of the treatment and all were receiving antifungal therapy while treated with the hyperbaric oxygen. The number of HBO sessions ranged between 1 and 44. Seven of the patients survived the infection. No patient developed complications due to HBO therapy.

Conclusions: HBO is a potentially significant adjunct in the treatment of invasive fungal infections. Evidence on its usefulness as a standard of care in these infections is still lacking. Since it will be difficult to generate conclusive data regarding the importance of HBO in these infections, the value of HBO in these patients should be considered on an individual basis.

Renal vein occlusion in adults is usually a result of vein thrombosis, which is frequently associated with the nephrotic syndrome. The anatomy of renal vascularization is of primary importance for understanding its pathophysiological responses and the clinical and diagnostic presentation of patients with this condition. The reaction of the kidney to its vein occlusion is determined by the balance between the acuteness of the disease, extent of the development of collateral circulation, involvement of one or both kidneys and the origin of the underlying disease. Renal vein occlusion is generally a complication of some other condition, but may also occur as a primary event. The main goals of therapy should be to conserve renal parenchyma in order to maintain renal function and prevent thromboembolic phenomena.

Background: Hyperglycemia is common among patients admitted to intensive care units, and carries the risk for complications and prolonged ICU[1] stay. With intensive insulin control of blood glucose, morbidity and mortality can be reduced.

Objectives: To determine whether intensive or conventional insulin control of blood glucose in hyperglycemic ICU patients correlated with the prognosis.

Methods: Following admission to the ICU, hyperglycemic patients were randomly assigned to a group treated intensively with insulin targeting glucose at 110–140 mg/dl, or to a conventional insulin therapy group, where glucose, upon exceeding 200 mg/dl, was controlled at 140–200 mg/dl. Rates of morbidity and mortality, hypoglycemic episodes, and insulin dosage were compared.

Results: In the 41 patients treated intensively with insulin the glucose level was 142 ± 14 mg/dl, as compared to 174 ± 20 mg/dl in the 48 patients on conventional insulin treatment. Both groups were similar in age, acute physiology and chronic health evaluation score. Morbidity was also similar, except for increased vascular damage in the conventional treatment group and slightly shorter ICU stay in the intensive therapy group. Both groups had similar in-ICU, in-hospital, and 28 day mortalities, and similar rates of hypoglycemic episodes. The daily dosage of insulin was significantly higher with the conventional treatment (P = 0.004).

Conclusions: Intensive insulin treatment did not affect the mortality or morbidity rates in ICU patients. The increased insulin dosage of conventional insulin treatment was attributable to the group's higher prevalence of diabetes. Future studies should address this bias and determine the optimal glucose target.