Israel Medical Association Journal

Abstract

Background: Diabetes mellitus-related lower extremity amputation is a major complication severely affecting patient survival and quality of life.

Objectives: To analyze epidemiological and clinical trends in the incidence and survival of lower extremity amputations among diabetes patients.

Methods: We conducted a retrospective observational cohort study of 565 consecutive diabetes patients who underwent their first non-traumatic lower extremity amputation between January 2002 and December 2009.

Results: Major amputations were performed in 316 (55.9%) patients: 142 above the knee (25.1%) and 174 below (30.8%); 249 (44.1%) had a minor amputation. The incidence rates of amputations decreased from 2.9 to 2.1 per 1000 diabetes patients. Kaplan-Meier survival analysis showed that first year mortality rates were lower among patients with minor amputations (31.7% vs. 39.6%, P = 0.569). First year mortality rates following below-knee amputation were somewhat lower than above-knee amputation (33.1 vs.45.1%, respectively). Cox regression model of survival at 1 year after the procedure found that age (HR 1.06 per year, 95% CI 1.04–1.07, P < 0.001), above-knee amputation (HR 1.36, 95% CI 1.01–1.83, P = 0.045) and ischemic heart disease (HR 1.68, 95% CI 1.26–2.24, P < 0.001) significantly increased one year mortality risk.

Conclusions: In this population-based study the incidence rate of non-traumatic amputations in diabetes patients between January 2002 and December 2009 decreased slightly. However, one year mortality rates after the surgery did not decline and remained high, stressing the need for a multidisciplinary effort to prevent amputations in diabetes patients.

Abstract

Background: Scleroderma lung disease (ILD-SSc) is treated mainly with cyclophosphamide (CYC). The effectiveness of CYC was judged after 12–24 months in most reports.

Objectives: To analyze the effect of monthly intravenous CYC on pulmonary function tests including forced vital capacity (FVC) and diffusing lung capacity (DLCO), as well as Rodnan skin score (mRSS), during long-term follow-up.

Methods: We retrospectively collected the data on 26 ILD-SSc patients who began CYC treatments before 2007. Changes in FVC, DLCO and mRSS before treatment, and at 1, 4 and 7 years after completion of at least six monthly intravenous CYC treatments for ILD-SSc were analyzed.

Results: Mean cumulative CYC dose was 8.91 ± 3.25 G. More than 30% reduction in FVC (0%, 8%, and 31% of patients), DLCO (15%, 23%, 31%), and mRSS (31%, 54%, 62%) at years 1, 4 and 7 was registered. During the years 0–4 and 4–7, annual changes in FVC, DLCO and mRSS were 3.2 vs. 0.42% (P < 0.040), 4.6 vs. 0.89% (P < 0.001), and 1.8 vs. 0.2 (P = 0.002). The greatest annual FVC and DLCO reduction over the first 4 years correlated with mortality (P = 0.022). There were no differences in the main variables regarding doses of CYC (< 6 G and > 6 G).

Conclusions: In patients with ILD-SSc, CYC stabilized the reduction of FVC during treatment, but this effect was not persistent. The vascular characteristic of ILD-SSc (DLCO) was not affected by CYC treatment. CYC rapidly improved the mRSS. This effect could be achieved with at least 6 G of CYC. Higher rates of annual reduction in FVC and DLCO in the first 4 years indicate the narrow window of opportunity and raise the question regarding ongoing immunosuppression following CYC infusions.

 

Abstract

Background: Renal hemangiomas are rare benign tumors seldom distinguished from malignant tumors preoperatively.

Objectives: To describe the Memorial Sloan-Kettering Cancer Center (MSKCC) experience with diagnosing and treating renal hemangiomas, and to explore possible clinical and radiologic features that can aid in diagnosing renal hemangiomas preoperatively.

Methods: Patients with renal hemangiomas treated at MSKCC were identified in our prospectively collected renal tumor database. Descriptive statistics were used to describe the patient characteristics and the tumor characteristics. All available preoperative imaging studies were reviewed to assess common findings and explore possible characteristics distinguishing benign hemangiomas from malignant renal tumors preoperatively.

Results: Of 6341 patients in our database 15 were identified. Eleven (73%) were males, median age at diagnosis was 53.3 years, and the affected side was evenly distributed. All but two patients were treated surgically. The mean decrease in estimated glomerular filtration rate (eGFR) after surgery was 36.3%; one patient had an abnormal presurgical eGFR and only two patients had a normal eGFR after surgery. We could not identify radiographic features that would make preoperative diagnosis certain, but we did identify features characteristic of hepatic hemangiomas that were also present in some of the renal hemangiomas.

Conclusions: Most renal hemangiomas cannot be distinguished from other common renal cortical tumors preoperatively. In select cases a renal biopsy can identify this benign lesion and the deleterious effects of extirpative surgery can be avoided.

Background: Gaucher disease is the most prevalent inherited disorder among Ashkenazi Jews (carrier frequency of about 6%) and six mutations account for about 96% of their mutant alleles. Two mutations, N370S and R496H, have been reported only in mildly affected or asymptomatic patients, Due to the rarity of R496H, it was recommended that it be excluded from screening programs. 

Objectives: To verify the frequency and trace the origin of Gaucher mutations in screened individuals whose Ashkenazi ethnicity was confirmed by the birthplace of their grandparents.

Methods: We conducted a retrospective analysis of the screened results for the period 2006–2011. Mutations were identified by restriction analysis, Tag-It^TM detection system, Pronto® diagnostic kit and Nanogen technology (NanoChip® 400).

Results: The heterozygote frequency of eight mutations was estimated in a cohort of 16,910 alleles. Two mutations, N370S and R496H, were the most frequent in our population. However, while the occurrence of N370S carriers was similar to other reports (1:19.4), that of R496H carriers was considerably elevated (1:207). Examination of the screened individuals' ethnicity showed a significant difference in the distribution pattern of the country of origin between the carriers of these two mutations.

Conclusions: The origin pattern differences between the two groups of heterozygotes might reflect a separate geographic region of introduction for various mutations. As a result, secondary subgroups could be formed within the Ashkenazi population. This might clarify the dissimilarities in the occurrence of R496H mutation reported by various centers. 

Background: C-reactive protein (CRP) is often used to distinguish bacterial from viral infections. However, the CRP level does have implications, which depend on the clinical scenario and are still under research.

Objectives: To evaluate the distribution of CRP levels in children with primary herpetic gingivostomatitis.

Methods: The electronic database of a tertiary pediatric medical center was searched for all inpatients with a diagnosis of primary herpetic gingivostomatitis without bacterial co-infection. Background and clinical information was collected and CRP levels were analyzed.

Results: The study group consisted of 66 patients aged 8 months to 7.1 years who met the study criteria. The average CRP was 7.4 mg/dl (normal < 0.5 mg/dl). More than a third of the patients had a level higher than 7 mg/dl.

Conclusions: High values of CRP are prevalent in patients with primary herpetic gingivostomatitis, similar to adenoviral infections and some bacterial infections. 

Background: The efficacy of subcutaneous immunotherapy for the treatment of allergic rhinitis, allergic conjunctivitis, allergic asthma and stinging insect hypersensitivity has been demonstrated in several studies.

Objectives: To investigate the effectiveness and side effects of immunotherapy in Israel and the relationship between local and systemic side effects.

Methods: This retrospective study was based on patient records and a computerized database for drug dispensing over a 5 year period. Success was rated as partial or complete. Side effects were classified as local or systemic. Systemic side effects were further classified according to severity, as mild (cutaneous), moderate (respiratory symptoms), or severe (cardiovascular).

Results: Of the 135 patients on aero-allergen immunotherapy who reached maintenance, 120 (88.9%) exhibited complete or partial improvement and 15 (11.1%) did not improve. All of the 44 patients on hymenoptera immunotherapy reached effective maintenance doses. The mean percent side effects calculated per treatment (injection) were 2.49 for local and 1.58 for a systemic reaction during the build-up phase, and 1.13 and 1.12 during the maintenance phase, respectively. Rates of systemic reactions were 1.3% for cutaneous, 1.14% for respiratory and 0.97% for cardiovascular reactions during the build-up phase, and 1.11%, 0.53%, and 0.51% during the maintenance phase, respectively. The odds of systemic reactions were significantly higher in patients with local reactions both in the build-up phase (P = 0.03) and in the maintenance phase (P = 0.0003). The number of annual medications dispensed per patient decreased from 31.5 to 26.0 during the first year after reaching maintenance, and to 22.5 in the second year. Pharmaceutical costs were 67% lower 1 year after the start of the maintenance phase, compared to the year before the start of immunotherapy, and 63% lower in the second year (P = NS).

Conclusions: Immunotherapy was effective and safe. Recognizing the benefits and safety of immunotherapy is necessary for physicians and health authorities in order to provide better care for allergic patients.

Background: Chronic spontaneous urticaria (CSU) is a common, debilitating disease that is frequently resistant to standard therapy. Omalizumab, anti-immunoglobulin-E humanized monoclonal antibody, was recently shown to be effective in treating resistant CSU.

Objectives: To investigated the treatment of CSU with omalizumab in Israel.

Methods: We conducted a multicenter retrospective analysis of patients with refractory CSU treated with omalizuamb in Israel during 2012–2013. Complete improvement was defined as resolution of symptoms with no need for other medications, or satisfactory when patients’ condition improved but required regular or intermittent doses of antihistamines.

Results: Forty-three patients received omalizumab off-label for refractory CSU. Their mean age was 45 ± 12 years and CSU duration was 4.3 ± 4 years. In this cohort, 98% were unsuccessfully treated with high dose H(1)-antihistamines, 88% with systemic glucocorticoids and 30% with cyclosporine and/or other immune-modulators. Fourteen patients received only one injection of omalizumab, while the other 29 received on average of 4.3 ± 3.2 injections; 30 patients received 150 mg/month and 13 received 300 mg/month. Following omalizumab therapy, disease remitted within weeks in 86% of patients, of whom half achieved complete remission. The latter was associated with usage of high dose omalizumab, 300 mg/month vs. 150 mg/month (P = 0.02) and repeated therapy (i.e., multiple injections vs. a single injection) (P = 0.0005).

Conclusions: Omalizumab is an effective and safe treatment for refractory CSU with rapid onset of action for inducing and maintaining remission. Treating CSU patients mandates an individual approach, because while low dose omalizumab will suffice for some patients others might need higher doses and prolonged therapy.