Israel Medical Association Journal

Systemic sclerosis (SSc) is characterized by extensive collagen deposition, microvasculopathy and autoantibodies. All three features can be promoted by activation of T cells and B cells. T cells are of Th2 type producing profibrotic cytokines IL-4 and IL-13 and inducing dendritic cell maturation that promotes Th2 response. B cells are overactivated and promote fibrosis by autoantibodies that activate fibroblasts or inhibit the degradation of extracellular matrix. They also promote fibrosis by cell-cell contact with fibroblasts or dendritic cells. B cells, through autoantibodies, may promote vasoconstriction and obliterative vasculopathy. They may also sustain activation of T cells by functioning as antigen-presenting cells. An immunoregulatory subset of B cells, namely IL-10-producing Bregs, is decreased in SSc. Finally, B cells have a critical role in animal models of SSc. All this evidence suggests an important role for B cells in the pathogenesis of SSc and makes B cells a potential target for therapeutic intervention in this disease. 

 

Autoimmune diseases constitute a diverse group of disorders characterized by cellular and humoral responses against self. The humoral autoimmune responses are directed against various cellular and extracellular components. These responses are highly specific for each autoimmune disease and result in the production of autoantibodies that characterize certain disease entities, representing a valuable tool for the diagnosis of autoimmune diseases. Furthermore, certain autoantibodies are helpful in the prognosis of disease development, progression and severity, as well as in the classification of patients with distinct disease subtypes. Today, the value of autoantibodies in the follow-up of patients is limited, but preliminary data suggest that they may be useful in predicting response to treatment. 

Background: Systemic lupus erythematosus (SLE) is an autoimmune disease with multiorgan involvement and wide variability in presentation and course. Although it can appear at any age, women of childbearing age are primarily affected. This has led to the proposal of a hormonal role in the development of SLE. Among the main hormones shown to have immunomodulatory effects are estradiol, progesterone and prolactin.

Objectives: To report the levels of estradiol and prolactin in SLE patients and establish the relationship between these levels and disease activity, and to determine whether the phases of the menstrual cycle influence the activity of SLE and its relationship to hormone levels.

Methods: In this cross-sectional study, we examined 60 women with SLE. We measured disease activity using SLEDAI and BILAG. We obtained peripheral blood samples to determine the levels of estradiol, progesterone, and prolactin. 

Results: Patients’ age ranged between 16 and 65 years and the mean disease duration was 5.5 years (0–20). SLE was active (SLEDAI > 6) in 13 patients and inactive in 47. Thirty patients were in a pre-ovulatory menstrual cycle phase, 13 in a post-ovulatory cycle, and 17 were menopausal. We found a significant association between C4 levels and disease activity (P = 0.01) and between estradiol levels and disease activity in the kidney (P = 0.04). We did not find hyperprolactinemia in any patient. 

Conclusions: In this population, we found an association between estradiol levels and organ-specific activity in the kidney. One may speculate as to whether our population might benefit from the implementation of anti-estrogen therapy for control of disease activity, particularly in the kidney.

 

Women who carry the BRCA gene mutation have an up to 80% chance of developing cancer, primarily of breast and ovarian origin. Confirmation of carrier status is described by many women as an overwhelming, life-changing event. Healthy individuals harboring a BRCA mutation constitute a high risk population with unique needs, often overlooked by health authorities. As such, we felt the need to create a specialized service dedicated specifically to this high risk population. The clinic staff comprises an experienced multidisciplinary team of health professionals who can support the medical and emotional needs of this population. Since its inception in 2001 the clinic has served 318 women. The mean age of patients is 46 years. With a median follow-up of 46 months, 21 women have developed malignancies, including 17 breast cancers, 1 ovarian cancer and 3 additional cancers. All but one of the patients above the age of 40 underwent bilateral salpingo-oophorectomy (BSO). The median and mean ages at BSO were 46.5 and 48 years, respectively (range 33–68). However, only 28.3% underwent bilateral preventive mastectomy. A multidisciplinary clinic for BRCA mutation carriers provides a “home” for this unique population with unmet needs. The high rate of BSO in women before natural menopause indicates that both the medical community and this population are aware of international guidelines supporting this procedure. We believe that a dedicated clinic, with a multidisciplinary team, is likely to contribute to the health, quality of life and survival of BRCA carriers.

Background: Studies in lung transplantation demonstrate that the ancestry and gender dissimilarities of donor–recipients lead to a decrease in survival of the recipient. 

Objectives: To evaluate the survival of lung transplant recipients in Israel based on whether the donors and recipients are of Jewish or Arab ancestry as well as survival based on gender match or mismatch.

Methods: We performed a retrospective observational cohort study of 345 lung transplant recipients at the Rabin Medical Center, Petah Tikva, Israel between January 1997 and January 2013. We compared the survival of lung transplant recipients in two ancestry categories: ancestry matched (Jewish donors to Jewish recipients or Arab donors to Arab recipients) and ancestry mismatched (Jewish donors to Arab recipients and vice versa). We also compared the survival among the four gender donor and recipient combinations (male to male, female to female, male to female, and female to male). 

Results: Survival analysis revealed no significant differences between the two ancestry groups (P = 0.51) and among the four gender combinations (P = 0.58). On Cox multivariate analysis, younger donor age was the only significant parameter for longer survival (hazards ratio 1.025, 95% confidence interval 1.012–1.037).

Conclusions: Gender and ancestry mismatches in these two Israeli populations do not appear to alter the clinical outcomes following lung transplantation.

 

Background: Only a minority of patients with essential tremor (ET) and Parkinson’s disease (PD) undergo deep brain stimulation (DBS) surgery. Data on patient selection factors are useful.

Objectives: To compare the clinical characteristics of ET and PD patients who underwent DBS surgery with those of patients who had not undergone surgery.

Methods: We abstracted data from the electronic medical records of 121 PD and 34 ET patients who underwent DBS surgery at Columbia University Medical Center during the period 2009–2014. We compared this group with 100 randomly selected PD and 100 randomly selected ET patients at the Center who had not undergone DBS surgery. 

Results: Among other differences, age of onset in PD patients who had undergone surgery was younger than in those who did not: 14.9% vs. 3.0% with onset before age 40 (P = 0.003). They had also tried nearly double the number of medications (3.9 ± 1.7 vs. 2.3 ± 1.5, P < 0.001). Interestingly, there was no difference in the proportion of patients with tremor (81.0% vs. 88.0%, P = 0.16). Medical co-morbidities (heart and lungs) were less common in the PD patients who underwent DBS surgery. In the ET group, tremor causing impairment in activities of daily living occurred in all surgical patients compared to 73.0% of non-surgical patients (P < 0.001). The former had tried nearly double the number of medications compared to the latter (3.2 ± 1.7 vs. 1.3 ± 1.3, P < 0.001).

Conclusions: These data add to our understanding of the numerous clinical factors associated with patient referral to DBS surgery. 

 

Background: Temporomandibular joint (TMJ) disorders affect roughly 5% of the population. Chronic closed lock is one of the more common temporomandibular disorders and is characterized by limited mouth opening and various degrees of joint pain and dysfunction. 

Objectives: To evaluate the efficacy and safety of arthroscopic lysis and lavage of the TMJ to treat limited mouth opening in patients suffering from chronic closed lock. 

Methods: This is a retrospective analysis of the medical records of 47 patients with chronic closed lock treated with arthroscopic lysis and lavage. Patients were diagnosed preoperatively with closed lock of the TMJ and were unresponsive to previous conservative therapy. Three outcome variables were used to assess the efficacy of treatment: maximal mouth opening, subjective evaluation of overall improvement by the patient (on a 3 grade scale: “excellent,” “fair,” and “poor”), and length of hospital stay. In addition, complications were reported. 

Results: The maximal mouth opening values increased from a mean of 27 ± 4.7 mm preoperatively to a mean of 38 mm ± 5.4 mm postoperatively. The subjective evaluation of overall improvement was “excellent” in 15 patients (32%), “fair” in 21 (45%), and “poor” in 11 (23%). Success was defined as a maximal mouth opening of 35 mm or more after arthroscopy, and not reporting a “poor” result in the subjective evaluation. This was achieved in 36 patients, yielding a success rate of 77%. The mean length of hospital stay was less than one day (0.78 days). The complication rate was low (8%) and all complications resolved within 2 weeks. 

Conclusion: Arthroscopic lysis and lavage is a simple, safe, and efficient minimally invasive intervention for the treatment of chronic closed lock of the TMJ. 

 

Background: Despite the lack of clinical studies supporting the use of routine surveillance FDG-positron emission tomography (PET) in patients with diffuse large B cell lymphoma (DLBCL) who achieved remission, many centers still use this strategy, especially in high risk patients. Surveillance FDG-PET computed tomography (CT) is associated with a high false positive (FP) rate in DLBCL patients. 

Objectives: To investigate whether use of specific CT measurements could improve the positive predictive value (PPV) of surveillance FDG-PET/CT. 

Methods: This retrospective study included DLBCL patients treated with CHOP or R-CHOP who achieved complete remission and had at least one positive surveillance PET. CT-derived features of PET-positive sites, including long and short diameters and presence of calcification and fatty hilum within lymph nodes, were assessed. Relapse was confirmed by biopsy or consecutive imaging. The FP rate and PPV of surveillance PET evaluated with/without CT-derived measurements were compared. 

Results: Seventy surveillance FDG-PET/CT scans performed in 53 patients were interpreted as positive for relapse. Of these studies 25 (36%) were defined as true-positive (TP) and 45 (64%) as FP. Multivariate analysis found long or short axis measuring ≥ 1.5 and ≥ 1.0 cm, respectively, in PET-positive sites, International Prognostic Index (IPI) ≥ 2, lack of prior rituximab therapy and FDG uptake in a previously involved site, to be independent predictors of true positive surveillance PET (odds ratio 5.4, 6.89, 6.6, 4.9, P < 0.05 for all). 

Conclusion: PPV of surveillance PET/CT may be improved by its use in selected high risk DLBCL patients and combined assessment of PET and CT findings.

 

Background: Proteinuria and albuminuria are markers of kidney injury and function, serving as a screening test as well as a means of assessing the degree of kidney injury and risk for cardiovascular disease and death in both the diabetic and the non-diabetic general population.

Objectives: To evaluate the association between proteinuria below 300 mg/24 hours and albuminuria, as well as a possible association with kidney function in patients with diabetes mellitus (DM).

Methods: The medical files of patients with type 1 and type 2 DM with proteinuria below 300 mg/24 hours at three different visits to the Diabetic Nephropathy Clinic were screened. This involved 245 patient files and 723 visits. The data collected included demographics; protein, albumin and creatinine levels in urine collections; blood biochemistry; and clinical and treatment data. 

Results: The association between proteinuria and albuminuria is non-linear. However, proteinuria in the range of 162–300 mg/24 hours was found to be linearly and significantly correlated to albuminuria (P < 0.001, r = 0.58). Proteinuria cutoff, based on albuminuria cutoff of 30 mg/24 hours, was found to be 160.5 mg/24 hr. Body mass index (BMI) was the sole independent predictor of proteinuria above 160.5 mg/24 hr. Changes in albuminuria, but not proteinuria, were associated with changes in creatinine clearance. 

Conclusions: A new cutoff value of 160.5 mg/hr was set empirically, for the first time, for abnormal proteinuria in diabetic patients. It appears that proteinuria below 300 mg/24 hr is not sufficient as a sole prognostic factor for kidney failure.