Philip J. Hashkes MD MSc and Bin Huang PhD
Background: The familial Mediterranean fever 50 score (FMF50) score was recently devised to define response to treatment and as an outcome measure for clinical trials of FMF.
Objectives: To examine the performance of the FMF50 score in a previously published trial of rilonacept for patients whose FMF was resistant or intolerant to colchicine.
Methods: We reanalyzed the data from our controlled trial of rilonacept vs. placebo in 14 patients with colchicine-resistant or intolerant FMF using the FMF50 score as the primary outcome. The FMF50 score required improvement by ≥ 50 in five of six criteria (attack frequency, attack duration, global patient assessment, global physician assessment, frequency of attacks with arthritis, and levels of acute-phase reactants without worsening of the sixth criterion).
Results: In the original trial rilonacept was considered effective according to the primary outcome measure (differences in the attack frequency) with eight analyzable patients considered responders and four as non-responders. According to the FMF50 score, only two participants would have been considered responders to rilonacept, and one to placebo. Only two participants had ≥ 50% differences between rilonacept and placebo in five criteria. The major explanation for non-response to treatment was that with rilonacept the duration of attack decreased by ≥ 50% in only 2 participants and 5 participants had no attacks of arthritis either during screening (before randomization) or during treatment with rilonacept.
Conclusions: The proposed FMF50 score did not differentiate well between responders and non-responders compared to the a priori defined primary outcome measure in this successful controlled study.
Sigal Tal MD, Nadav Berkovitz MD, Paul Gottlieb MD and Konstantin Zaitsev MD
Background: Forensic imaging was officially introduced in Israel in 2011. Religious and cultural opposition to autopsies prevails in most of the population in Israel.
Objectives: To examine the extent to which forensic imaging has been accepted as an adjuvant or partial replacement of forensic autopsy, particularly among those opposed to forensic autopsy.
Methods: The study was conducted in a pediatric population. Data were collected from the National Center of Forensic Medicine and Assaf Harofeh Medical Center during the 18 month period following the introduction of forensic imaging (group A). The data were compared to those of the previous 18 months (group B). The examined parameters were cases submitted, examined, autopsied or imaged depending on family consent.
Results: Consent to autopsy was similar in both groups (A = 56% vs. B = 54%). In group A, consent for imaging was 24% of all cases, and of those imaged 77% underwent autopsy. Of those examined externally only, 16% consented to imaging. For 7% of the total cases in group A, estimation of cause of death was based on virtopsy alone.
Conclusions: In a country with a high level of religious opposition to autopsy, it is a challenge to add forensic to the pediatric forensic investigation. Those consenting to forensic imaging are more likely to be those consenting to autopsy. Consent for forensic imaging only was given in 7% of cases. Greater efforts should be invested to educate and inform the public regarding the benefits of virtual autopsy and the importance of data acquired from forensic images.
Maya Paryente Wiessman MD, Idit F. Liberty MD, Renana Wilkof Segev BSc, Tiberiu Katz MD, Muhammad Abu Tailakh RN MPH and Victor Novack MD PhD
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.
Alexandra Balbir-Gurman MD, Mordechai Yigla MD, Ludmila Guralnik MD, Emilia Hardak MD, Anna Solomonov MD, Alexander P. Rozin MD, Kohava Toledano MD, Amir Dagan MD, Rema Bishara MD, Doron Markovits MD PhD, Menahem A. Nahir MD and Yolanda Braun-Moscovici MD
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.
Itay A. Sternberg MD, Benjamin F. Katz MD, Lauren Baldinger DO, Roy Mano MD, Gal E. Keren Paz MD, Melanie Bernstein BA, Oguz Akin MD, Paul Russo MD and Christoph Karlo MD
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.
Dan Oieru MD, Nir Shlomo, Israel Moalem, Eli Rozen MD, Alexey Naimushin MD, Robert Klempfner MD, Ilan Goldenberg MD and Ronen Goldkorn MD
Background: Heart rate variability (HRV) analysis has been shown to be a predictor of sudden cardiac death and all-cause mortality in patients with cardiac disease.
Objectives: To examine whether newer HRV analysis algorithms, as used by the HeartTrends device, are superior to exercise stress testing (EST) for the detection of myocardial ischemia in patients without known coronary artery disease (CAD).
Methods: We present pilot data of the first 100 subjects enrolled in a clinical trial designed to evaluate the yield of short-term (1 hour) HRV testing for the detection of myocardial ischemia. The study population comprised subjects without known CAD referred to a tertiary medical center for EST with single-photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI). All patients underwent a 1 hour electrocardiographic acquisition for HRV analysis with a HeartTrends device prior to EST with MPI. Sensitivity, specificity, and positive and negative predictive values (PPV and NPV, respectively) were calculated for EST and HRV analysis, using MPI as the gold standard for the non-invasive detection of myocardial ischemia.
Results: In this cohort 15% had a pathologic MPI result. HRV analysis showed superior sensitivity (85%), PPV (50%) and NPV (97%) as compared to standard EST (53%, 42%, 90%, respectively), while the specificity of the two tests was similar (86% and 85%, respectively). The close agreement between HRV and MPI was even more pronounced among patients > 65 years of age.
Conclusions: Our pilot data suggest that the diagnostic yield of the novel HeartTrends HRV algorithm is superior to conventional EST for the non-invasive detection of myocardial ischemia.
Slavomíra Mattošová MSc, Ján Chandoga MD PhD, Anna Hlavatá MD PhD MPH, Jana Šaligová MD and Danka Maceková PhD
Background: Gaucher disease is the most common lysosomal storage disorder and is caused by a deficiency of the enzyme glucocerebrosidase. Enzyme deficiency leads to the accumulation of undegraded substrates, mainly in cells of the monocyte/macrophage lineage, which is responsible for the clinical manifestations of the disease. To date, no study has attempted to identify the mutation spectrum of the glucocerebrosidase gene (GBA) in Slovak patients
Objectives: To identify mutations in 14 Slovak patients with confirmed glucocerebrosidase deficiency.
Methods: Using molecular genetics methods PCR-RFLP (polymerase chain reaction-restriction fragment length polymorphism) and direct sequencing of coding region GBA we identified the spectrum of mutations in our patients.
Results: Five mutations (N370S, L444P, G377S, D409H and RecNciI) accounted for 75% of the mutant alleles. The remaining 25% were rare and probably individual mutations.
Conclusions: The mutational spectrum in our patients is similar to that observed in other European countries and corresponds to a Caucasian population, with N370S, L444P, RecNciI being the most common mutation. Interestingly, mutation G377S was more frequent in our patients as compared to other published data. The C4W, L96P, H311N, 745delG and 1127_1128delTT mutations are described here for the first time in Gaucher disease, contributing to the panel of published GBA mutations.