Israel Medical Association Journal

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: Fertility treatments are responsible for the rise in high order pregnancies in recent decades and their associated complications. Reducing the number of embryos returned to the uterus will reduce the rate of high order pregnancies.     

Objectives: To explore whether obstetric history and parity have a role in the clinician’s decision making regarding the number of embryos transferred to the uterus during in vitro fertilization (IVF).

Methods: In a retrospective study for the period August 2005 to March 2012, data were collected from twin deliveries > 24 weeks, including parity, mode of conception (IVF vs. spontaneous), gestational age at delivery, preeclampsia, birth weight, admission to the neonatal intensive care unit (NICU), and Apgar scores. 

Results: A total of 1651 twin deliveries > 24 weeks were recorded, of which 959 (58%) were at term (> 37 weeks). The early preterm delivery (PTD) rate (< 32 weeks) was significantly lower with increased parity (12.6%, 8.5%, and 5.6%, in women with 0, 1, and ≥ 2 previous term deliveries, respectively). Risks for PTD (< 37 weeks), preeclampsia and NICU admission were significantly higher in primiparous women compared to those who had one or more previous term deliveries. Primiparity and preeclampsia, but not IVF, were significant risk factors for PTD. 

Conclusions: The risk for PTD in twin pregnancies is significantly lower in women who had a previous term delivery and decreases further after two or more previous term deliveries. This finding should be considered when deciding on the number of embryos to be transferred in IVF.  

 

Background: Catastrophic life events are associated with the occurrence of cardiovascular incidents and worsening of the clinical course following such events.

Objectives: To evaluate the characteristics and long-term prognosis of Holocaust survivors presenting with acute myocardial infarction (AMI) compared to non-Holocaust survivors.

Methods: Israeli Jews who were born before 1941 and had been admitted to a tertiary medical center due to AMI during the period 2002–2012 were studied. Holocaust survivors were compared with non-Holocaust survivor controls using individual age matching.

Results: Overall 305 age-matched pairs were followed for up to 10 years after AMI. We found a higher prevalence of depression (5.9% vs. 3.3%, P = 0.045) yet a similar rate of cardiovascular risk factors, non-cardiovascular co-morbidity, severity of coronary artery disease, and in-hospital complications in survivors compared to controls. Throughout the follow-up period, similar mortality rates (62.95% vs. 63.9%, P = 0.801) and reduced cumulative mortality (0.9 vs. 0.96, HR = 0.780, 95%CI 0.636–0.956, P = 0.016) were found among survivors compared to age-matched controls, respectively. However, in a multivariate analysis survival was not found to be an independent predictor of mortality, although some tendency towards reduced mortality was seen (AdjHR = 0.84, 95%CI 0.68–1.03, P = 0.094). Depression disorder was associated with a 77.9% increase in the risk for mortality. 

Conclusions: Holocaust survivors presenting with AMI were older and had a higher prevalence of depression than controls. No excessive, and possibly even mildly improved, risk of mortality was observed in survivors compared with controls presenting with AMI. Possibly, specific traits that are associated with surviving catastrophic events counter the excess risk of such events following AMI.

 

Background: Recently we observed patients with chronic liver disease (CLD) or chronic reflux symptoms (CRS) who developed gastric polyps (GPs) while undergoing surveillance gastroscopies for the detection of either esophageal varices or Barrett's esophagus, respectively.

Objectives: To identify risk factors for GP growth and estimate the gastric polyp growth rate (GPGR).

Methods: GPGR was defined as the number of days since the first gastroscopy (without polyps) in the surveillance program, until the gastroscopy when a GP was discovered.

Results: Gastric polyp growth rates in CLD and CRS patients were similar. However, hyperplastic gastric polyps (HGPs) were detected more often (87.5% vs. 60.5%, P = 0.051) and at a higher number (2.57 ± 1.33 vs. 1.65 ± 0.93, P = 0.021) in the CLD patients. Subgroup analysis revealed the following findings only in CLD patients with HGPs: (i) a positive correlation between the GPGR and the patient's age; the older the patient, the longer the GPGR (r = 0.7, P = 0.004). (ii) A negative correlation between the patient's age and the Ki-67 proliferation index value; the older the patient, the lower the Ki-67 value (r = -0.64, P = 0.02). No correlation was detected between Ki-67 values of HGPs in CLD patients and the presence of portal hypertension, infection with Helicobacter pylori, or proton pump inhibitor use.

Conclusions: In comparison with CRS patients, CLD patients developed HGPs more often and at a greater number. Young CLD patients may have a tendency to develop HGPs at a faster rate than elderly CLD patients.

Long-term extension studies and observational drug registers have revealed an increased risk of serious infections in patients treated with anti-tumor necrosis factor agents, particularly infliximab, etanercept and adalimumab. The same may be true for the newer biological drugs rituximab, tocilizumab and abatacept, although this has yet to be confirmed by long-term observational studies. We review the risk of tuberculosis, herpes zoster and other opportunistic infections, and the recommendations for screening for tuberculosis and hepatitis B and C infections in patients affected by rheumatoid arthritis, with the aim of informing patients and encouraging greater awareness among physicians.

Behçet’s disease (BD) is a systemic inflammatory disorder characterized by a protean clinical spectrum and an enigmatic pathogenesis. After being classified as an autoimmune disorder, spondyloarthritis and vasculitis, today BD is considered at the crossroad between autoimmune and auto-inflammatory syndromes. Many pathogenetic, clinical and therapeutic clues support this recent interpretation, enabling novel treatment choices such as interleukin (IL)-1 inhibition. Thus, in the last decade the IL-1 receptor antagonist anakinra and the anti-IL-1β monoclonal antibody canakinumab were increasingly administered in BD patients resistant to standard therapies, leading to interesting results and new intriguing pathogenetic implications. However, further studies are essential to both establish how the innate and acquired immune systems interact in BD patients and identify the best way of administering anti-IL-1 agents with regard to dosage, interval of administration and organ response.

Background: Balneotherapy is one of the most commonly used non-pharmacological approaches for osteoarthritis (OA). Recent data indicate that some biomarkers could be useful to predict OA progression and to assess therapeutic response.

Objectives: To evaluate the effects of mud-bath therapy on serum biomarkers in patients with knee OA. 

Methods: The study group comprised 103 patients with primary symptomatic bilateral knee OA who were randomly assigned to receive a cycle of mud-bath therapy over a period of 2 weeks or to continue their standard therapy alone. Clinical and biochemical parameters were assessed at baseline and after 2 weeks. Clinical assessments included global pain score on a Visual Analogue Scale (VAS) and the Western Ontario and McMaster Universities Index (WOMAC) subscores for knee OA. Cartilage oligomeric matrix protein (COMP), C-terminal cross-linked telopeptide type II collagen (CTX-II), myeloperoxidase (MPO) and high sensitivity C-reactive protein (hsCRP) serum levels were assessed by ELISA.

Results: At the end of mud-bath therapy we observed a statistically significant improvement in VAS and WOMAC subscores. Serum levels of COMP, MPO and hsCRP did not show any significant modification in both groups, while a significant increase (P < 0.001) in CTX-II serum levels was observed in the mud-bath group after the treatment.

Conclusions: A cycle of mud-bath therapy added to usual treatment had a beneficial effect on pain and function in patients with knee OA. The evaluation of serum biomarkers showed only a significant increase of CTX-II, perhaps due to an increase of cartilage turnover induced by thermal stress.

Behçet's disease (BD) is a multi-systemic disorder of unknown etiology characterized by relapsing oral-genital ulcers, uveitis, and involvement of the articular, gastrointestinal, neurologic, and vascular systems. The choice of treatment is based on the severity of systemic involvement, clinical presentation and the site affected, and includes corticosteroids, azathioprine, interferon, cyclophosphamide, methotrexate or tumor necrosis factor-alpha and interleukin-1 blockers. We present a case series of four refractory BD patients successfully treated with intravenous immunoglobulins (IVIG). All patients fulfilled International Study Group criteria. The patients’ mean age was 38.75 ± 12.09 years and mean disease duration 10.25 ± 8.5 years. Human leukocyte antigen B51 was positive in two of four patients. In addition to oral aphthosis, all patients suffered from genital ulcers and cutaneous BD-related manifestations; central nervous system involvement and arthralgia were found in two patients. Peripheral nervous system, gastrointestinal and eye involvement occurred in 25% of cases. In all patients, previously treated according to EULAR recommendations without reaching satisfactory results, IVIG induced immediate and sustained response over time without incurring any side effects. We propose IVIG administration as an additional effective and safe treatment option in patients with severe and resistant BD.

Background: Radiation exposure is a well-known risk factor for well-differentiated thyroid cancer (WDTC). However, disease characteristics, optimal treatment, time from exposure to disease appearance, and the effect on outcome of age at initial exposure have yet to be determined. 

Objectives: To identify the characteristics of radiation-induced thyroid carcinoma.

Methods: We retrieved the charts of all patients previously exposed to radiation who were diagnosed with WDTC between the years 1985 and 2013 in a tertiary referral center. 

Results: Forty-four patients were reviewed. Median time from radiation exposure to diagnosis was 23 years. These patients had higher rates of aerodigestive symptoms and distant metastases on presentation than seen in non-radiated patients. Patients who were exposed to radiation before age 15 years tended to develop the disease at a younger age but had a longer latency period (34.7 ± 15.3 vs. 16.3 ± 10 years, P < 0.001) and none had significantly higher rates of vocal cord palsy, hoarseness on presentation, or aggressive variants on histology compared to patients exposed to radiation at an older age. Disease-specific survival (DSS) was the same for both groups and were similar to that seen in the general population (95% 20 year DSS).

Conclusions: Radiation-induced thyroid cancer has a more aggressive presentation and the age at exposure affects the presentation of disease. Nonetheless, appropriate treatment leads to a favorable prognosis.

 

Background: Enoxaparin is frequently used as prophylaxis for deep venous thrombosis in critically ill patients. 

Objectives: To evaluate three enoxaparin prophylactic regimens in critical care patients with and without administration of a vasopressor.

Methods: Patients admitted to intensive care units (general and post-cardiothoracic surgery) without renal failure received, once daily, a subcutaneous fixed dose of 40 mg enoxaparin, a subcutaneous dose of 0.5 mg/kg enoxaparin, or an intravenous dose of 0.5 mg/kg enoxaparin. Over 5 days anti-activated factor X levels were collected before the daily administration and 4 hours after the injection.

Results: Overall, 16 patients received the subcutaneous fixed dose, 15 received the subcutaneous weight-based dosage, and 8 received the dose intravenously. Around two-fifths (38%) of the patients received vasopressors. There was no difference between anti-activated factor X levels regarding vasopressor administration. However, in all three groups the levels were outside the recommended range of 0.1 IU/ml and 0.3 IU/ml.

Conclusions: Although not influenced by vasopressor administration, the enoxaparin regimens resulted in blood activity levels outside the recommended range.