Israel Medical Association Journal

Background: Tumor necrosis factor-alpha (TNFα) inhibitors are indicated for patients with psoriatic arthritis (PsA) in whom conventional disease-modifying anti-rheumatic drugs (DMARDs) are insufficient to achieve disease remission. 

Objectives: To determine the value of acute-phase reactant levels at diagnosis of psoriatic arthritis in predicting the need for biologic treatment with TNFα inhibitors.

Methods: We conducted a longitudinal observational study of an inception cohort of 71 consecutive patients diagnosed with psoriatic arthritis. C-reactive protein (CRP) was assayed for all patients at their first visit.

Results: All patients were treated with one or more DMARDs, mainly methotrexate (81.6%). Thirty-seven patients (52.11%) had an inadequate response and received at least one TNF inhibitor. CRP level at diagnosis was positively correlated with need for a TNF inhibitor (P = 0.009, HR 1.8, 95%CI 1.27–1.85). Patients with CRP > 0.9 mg/dl at diagnosis started biologic treatment significantly earlier than patients with a lower level (P = 0.003, HR 2.62, 95%CI 0.393–2.5).

Conclusions: In patients with psoriatic arthritis, CRP ≥ 0.9 mg/dl at diagnosis significantly predicts an earlier need for a TNF inhibitor to achieve disease control.

 

Lung involvement is a well-recognized extra-articular manifestation of ankylosing spondylitis (AS). Anecdotal reports suggest that the use of anti-TNF drugs may be related to lung disease and pulmonary fibrosis. To examine the association between anti-TNF drugs and the development of lung disease in patients with AS or  psoriatic arthritis (PsA) we conducted a systematic review. Of the 670 papers identified by means of key word and hand search, only one full-text paper was considered potentially relevant but had to be discarded as it did not meet the eligibility criteria. Although no conclusion was reached, this is the first systematic review to examine this problem which is becoming increasingly important as these drugs are widely prescribed in patients with spondyloarthritis.

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.

There is growing interest in the contribution of vitamin D deficiency to autoimmunity. Several studies have shown an association between low levels of vitamin D and autoimmune disorders, including multiple sclerosis, rheumatoid arthritis, type 1 diabetes, autoimmune thyroid diseases, celiac disease, and systemic lupus erythematosus (SLE). Vitamin D receptor ligands can mediate immunosuppressive effects. It has been suggested that low levels of this hormone contribute to the immune activation in lupus and other autoimmune diseases. This review updates and summarizes the literature on the association between vitamin D and SLE, and discusses the various correlations between vitamin D and SLE activity, clinical expressions, serology, and gene polymorphisms of vitamin D receptors.

Background: High density breast mammography has been associated with a greater risk for breast cancer and an increased likelihood of false negative results. 

Objectives: To assess whether the degree of mammographic breast density correlates with an increased risk for the presence of radiographic findings requiring further histological investigation. 

Methods: Included in the study were 2760 consecutive screening mammograms performed in a large volume, early detection mammography unit. All mammograms were complemented by high resolution ultrasound and interpreted by a single expert radiologist. Breast density (BD) was evaluated using a semi-quantitative 5 grade scale and grouped into low breast density (LBD) and high breast density (HBD) mammograms. Demographic and all relevant obstetric, personal and family history of breast cancer data were recorded. 

Results: Of the 2760 mammograms 2096 (76%) were LBD and 664 (24%) were HBD. Mean age of the LBD and HBD groups was 59 ± 10.5 and 50.9 ± 9.3 years respectively (P = 0.001). Breast density significantly correlated with presence of mammographic findings requiring further histological assessment (8.7% and 12.3% for LBD and HBD respectively, P < 0.01). In women younger than 60 years in whom histological assessment was required due to these findings, malignant pathology was significantly more prevalent in the HBD group (2.3% and 4.1% respectively, P = 0.03). Age, parity, patient history and HBD were identified as independent risk factors for any pathological mammographic finding. 

Conclusions: Highly dense mammography, aside from being an indicator of higher risk for breast cancer, appears to be associated with a significantly higher incidence of findings that will prompt further investigation to achieve a definite diagnosis. 

 

Background: Despite awareness regarding tubal pregnancy, ovarian pregnancy still remains a diagnostic challenge. The correct diagnosis is most frequently made intraoperatively and requires histopathologic confirmation. Therefore, additional diagnostic measurements are needed for earlier and more accurate detection of ovarian pregnancies which will allow more rapid and efficient treatment. 

Objectives: To assess the time trends, clinical manifestations, surgical management and post-procedure outcome of 46 primary ovarian pregnancies in a single institution during three time periods.

Methods: In this retrospective study we compared 20 patients with primary ovarian pregnancy during the years 1971–1989 (first period), 19 patients in 1990–2001 (second period) and 7 patients in 2002–2013 (third period). In all cases the pathology examination confirmed primary ovarian pregnancy.

Results: The number of tubal ectopic pregnancies almost doubled, from 637 in the first period to 1279 in the third period (P < 0.001). However, there was a significant fall in the number of ovarian ectopic pregnancies, from 20 cases in the first period to 7 cases in the third (P = 0.009). A significant difference was noted when we compared the postoperative hospitalization time (4.06 ± 1.4 vs. 2.0 ± 0.6 days respectively, P = 0.001) in the second versus the third time period.

Conclusions: Ovarian pregnancy continues to be a diagnostic challenge, associated with a high rate of circulatory collapse, hemoperitoneum and requirements for blood transfusions, all leading to longer hospitalization.

 

Background: Gallbladder (GB) cancer is rare. Most cases are incidentally found in specimens after a cholecystectomy. Cholelithiasis is almost always present when this diagnosis is made. Obesity is a known risk factor for gallstone formation and thus may be related to GB cancer. 

Objectives: To highlight the importance of evaluation of the gallbladder before surgery, resection of the gallbladder whenever required, and screening the resected tissue for malignancy.

Methods: We retrospectively queried a prospectively maintained database of all bariatric procedures during the last 8 years for cases of concomitant laparoscopic sleeve gastrectomy (LSG) and laparoscopic cholecystectomy (LC). Pathologic reports of the gallbladders were reviewed. Demographic data and perioperative parameters were documented. 

Results: Of 2708 patients reviewed, 1721 (63.55%) were females and 987 (36.45%) males. Excluded were 145 (5.35%) who had a previous cholecystectomy. Of the remaining 2563, 180 (7.02%) had symptomatic gallbladder disease and underwent LSG with LC. Of these, two females (BMI 53 kg/m² and BMI 47 kg/m², both age 60) were found by histological examination to have adenocarcinoma in their GB specimens (1.11%). Both were reoperated, which included partial hepatectomy of the GB bed, resection of the cystic stump, lymph node dissection, and resection of the port sites. One patient is doing well, with no evidence of disease at a postoperative follow-up of 4 years. The second patient had recurrent disease with peritoneal spread and ascites 20 months post-surgery and died 18 months later. 

Conclusions: GB cancer is a rare finding in cholecystectomy specimens. The incidence of this entity might be higher in obese older females owing to the higher incidence of cholelithiasis in these patients. 

 

Background: Left cardiac sympathetic denervation (LCSD) was reported to be effective in patients with intractable ryanodine receptor mutation-associated catecholaminergic polymorphic ventricular tachycardia (CPVT). 

Objectives: To report our experience with LCSD in calsequestrin (CASQ2) mutation-associated CPVT. 

Methods: LCSD was performed in three patients with CASQ2 mutation-associated CPVT with symptoms and exercise-induced ventricular arrhythmia despite high dose beta-blocker. 

Results: None of them experienced symptoms or exercise-induced ventricular arrhythmia after LCSD. However, all had recurrence of symptoms and/or exercise-induced ventricular arrhythmia after 6 months (6–18 months).

Conclusions: LCSD conferred short-term suppression but less than optimal long-term suppression of exercise-induced ventricular arrhythmia among CASQ2-associated CPVT patients.

 

Background: Gastric bezoars in children are infrequent. Most are trichobezoars. Surgical intervention is sometimes necessary.

Objectives: To describe the clinical findings and radiological workup, as well as treatment and outcome of patients with complicated gastric bezoars who underwent surgery in our institution.

Methods: We conducted a retrospective review of all cases of surgery for gastric bezoars performed in our institution between 2000 and 2010. Data collected included gender and age of the patients, composition and extent of the bezoar, presenting signs and symptoms, imaging studies used, performance of endoscopy, and surgical approach. Outcome was measured by the presence of postoperative complications.

Results: We identified seven patients with gastric bezoars who underwent surgery. All were females aged 4–19 years. Six had trichobezoars and one had a mass composed of latex gloves. Presenting symptoms included abdominal pain, vomiting, weight loss, and halitosis. All patients had a palpable epigastric mass. A large variety of imaging modalities was used. Endoscopic removal was attempted in three patients but failed, and the laparoscopic approach was attempted in one patient and failed. All patients eventually underwent laparotomy with gastrotomy and recovered without complications. 

Conclusions: The presence of gastric bezoars should be suspected in any child with unexplained abdominal pain, vomiting, weight loss, or halitosis, or with a palpable abdominal mass, especially in girls. A variety of imaging modalities can aid in diagnosis. Endoscopic removal might be attempted, although failure of this approach is frequent and must prompt surgical intervention, preferably laparotomy and gastrotomy, which has an excellent outcome.