Israel Medical Association Journal

Background: Immunoglobulin 4 (IgG4) is the least abundant immunoglobulin in the sera of healthy individuals; however, its levels can vary in different diseases such as IgG4-related disease (high) or Sjögren's syndrome (low). While previous studies have suggested the importance of IgG4 in autoimmune diseases, the clinical and biological significance of high or low levels remains unclear.

Objectives: To investigate the association between IgG4 antibody levels and systemic sclerosis (SSc), as well as the clinical features of the disease.

Methods: We measured IgG4 levels in the sera of 74 SSc patients from the years 2000 to 2019 and compared them to IgG4 levels in 80 healthy donors from the Israeli national blood bank. We performed correlation analyses between IgG4 levels and various factors, including age, sex, disease subtype, disease duration, organs involved, and medications taken by the patients.

Results: Our findings revealed significantly lower IgG4 levels in SSc patients compared to healthy participants. SSc patients receiving steroid treatment exhibited prominently lower IgG4 levels. In addition, SSc patients with Raynaud's phenomenon tended to have lower IgG4 levels compared to those without Raynaud's phenomenon.

Conclusions: Our study demonstrates that IgG4 levels are lower in SSc patients. Further research is needed to elucidate whether this observation contributes to the etiology of the disease or if it represents a common manifestation among other autoimmune diseases.

Background: Cloacal malformation represents the rarest and most complex congenital anorectal malformation in females and is characterized by the convergence of urinary, gynecological, and intestinal systems within a single common channel. Three-dimensional computed tomography reconstruction (3D CT cloacagram) has emerged as a valuable method for anatomical assessment and preoperative planning.

Objectives: To evaluate our experience with 3D CT cloacagram and assess its results.

Methods: This retrospective case series included all patients with cloacal malformation who underwent preoperative 3D CT cloacagram at a single institution during 2019–2023. Collected data included patient characteristics, timing of the 3D CT cloacagram, results of the 3D CT cloacagram, comparison with endoscopic results, surgical procedures, and postoperative outcome.

Results: Six patients with cloacal malformation were included in this study, including two with posterior cloaca. The median common channel length on 3D CT cloacagram was 24.5 mm (range 9–48 mm) and the median urethral length was 15.5 mm (range 13-24 mm). The surgical approach involved a combined abdominoperineal approach in three patients and posterior sagittal anorectal vaginal urethral plasty in one patient. Two patients were awaiting surgical reconstruction at the time of publication.

Conclusions: Our implementation of 3D cloacagram has facilitated precise measurements of both the urethra and common channel lengths, two key factors in formulating surgical strategies for cloacal reconstruction. Moreover, this technique has markedly improved our capacity for surgical planning contributing to colorectal, gynecological, and urological perspectives.

Background: The management of complicated appendicitis is inconclusive. Guidelines have not been established for the use of personalized antibiotic treatment.

Objectives: To investigate specific risk factors to consider during the initial first-choice antibiotic therapy in children with complicated appendicitis.

Methods: This study included all pediatric patients younger than 18 years of age who underwent a laparoscopic appendectomy during 2012–2022 at a single tertiary medical center.

Results: In total, 300 pediatric patients underwent laparoscopic appendectomy due to complicated appendicitis. The patients were treated with ceftriaxone + metronidazole (CM). For 57 (19%) patients, the empirical treatment was changed to tazobactam/piperacillin (TP) due to resistant bacteria or clinical deterioration. The presence of generalized peritonitis during surgery and C-reactive protein (CRP) levels above 20 mg/L at admission were identified as risk factors for changing the antibiotic regimen from CM to TP.

Conclusions: Generalized peritonitis and CRP > 20 gr/L were highly correlated with changing the antibiotic regimen to TP. For such patients, initial treatment with TP may result in clinical improvement and shorter hospitalization. 

Background: Chronic fatigue is common among patients with rheumatoid arthritis (RA), affecting quality of life. Osteoporosis is a prevalent co-morbidity in RA patients.

Objectives: To assess the effect of long-term treatment with tocilizumab on fatigue and bone mineral density (BMD) in RA patients with inadequate response to synthetic or biologic disease-modifying anti-rheumatic drugs. 

Methods: In this multicenter, open-label, non-controlled, single-arm study, patients ≥ 18 years of age received intravenous tocilizumab 8 mg/kg every 4 weeks for 96 weeks. The primary outcome was the change in Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue score from baseline to weeks 24, 48, 72, and 96. BMD was assessed before and 96 weeks after treatment. 

Results: The study comprised 145 patients (mean age 53.4 ± 13.4 years, 83.4% women). Of these, 88 (60.7%) completed the 2 year treatment period. The mean FACIT-Fatigue score improved consistently starting from week 4 and showed a statistically significant increase of 5.0 ± 9.7, 6.8 ± 10.5, 7.3 ± 10.9, and 7.3 ± 10.4 from baseline to weeks 24, 48, 72, and 96, respectively (P < 0.0001). Mean BMD of femoral neck and total spine remained stable. Disease activity, acute phase reactants, and composite efficacy measures decreased during the study, while hemoglobin levels increased. Adverse events and serious adverse events were as expected for the known and previously described data.

Conclusions: Tocilizumab therapy for 2 years significantly and clinically decreased fatigue. BMD remained stable and no new safety issue was reported. 

 

Background: Mycetoma is a chronic and destructive infection caused by either fungus or bacteria. Mycetoma has a characteristic clinical presentation of a triad of tumor-like swelling, draining sinuses, and macroscopic grains. Mycetoma infection is extremely rare in Israel; however, in view of the recent immigration from mycetoma-hyperendemic regions of Africa to Israel, physicians in Israel may encounter this infection.

Objectives: To present two cases of mycetoma caused by Madurella mycatomatis in immigrants from endemic regions in Sudan treated at our hospital, and review the current literature. 

Conclusions: Health care professionals in Israel should suspect mycetoma in patients from endemic countries who present with tumor-like swelling especially in the lower extremity. Health care workers should be able to recognize mycetoma and provide the optimal treatment before the lesion progresses to an advanced and disabling disease. 

 

Background: Discharge summaries after hospitalization provide the most reliable description and implications of the hospitalization. A concise discharge summary is crucial for maintaining continuity of care through the transition from inpatient to ambulatory care. Discharge summaries often lack information and are imprecise. Errors and insufficient recommendations regarding changes in the medical regimen may harm the patient’s health and may result in readmission.

Objectives: To evaluate a quality improvement model and training program for writing postoperative discharge summaries for three surgical procedures.

Methods: Medical records and surgical discharge summaries were reviewed and scored. Essential points for communication between surgeons and family physicians were included in automated forms. Staff was briefed twice regarding required summary contents with an interim evaluation. Changes in quality were evaluated.

Results: Summaries from 61 cholecystectomies, 42 hernioplasties and 45 colectomies were reviewed. The average quality score of all discharge summaries increased from 72.1 to 78.3 after the first intervention (P < 0.0005) to 81.0 following the second intervention. As the discharge summary’s quality improved, its length decreased significantly.

Conclusions: Discharge summaries lack important information and are too long. Developing a model for discharge summaries and instructing surgical staff regarding their contents resulted in measurable improvement. Frequent interventions and supervision are needed to maintain the quality of the surgical discharge summary.  

Objectives: To review our experience with laparoscopic repair of GDH, emphasizing preoperative investigation, technical aspects, and outcome.

Methods: We conducted a retrospective review of patients operated on for GDH who were diagnosed when at least half the stomach was found in the mediastinum at surgery. Technical aspects and surgical outcomes were evaluated.

Results: Fifty patients underwent laparoscopic GDH repair during an 8 year period. Four patients admitted with acute symptomatic volvulus of the stomach were initially treated by endoscopic decompression followed by surgery during the same admission. Two cases were converted to open surgery. Initial surgery was successful in 45 patients; 3 had an immediate recurrence, 1 was reoperated for dysphagia during the same admission, and 1 had a mediastinal abscess. During long-term follow-up, six patients required reoperation for recurrent hernias. Another four patients had asymptomatic partial herniation of the stomach. The main reason for failure was incomplete reduction of the hernia sac, especially the posterior component. No correlation was found between the type of repair and surgical failure. Most patients who did not undergo an anti-reflux procedure had postoperative reflux unrelated to their preoperative workup.

Conclusions: Laparoscopic repair of GDH is challenging, but practical and safe. It should be the treatment of choice for this potentially life-threatening condition. Careful attention to pitfalls, such as the posterior element of the sac, and routine performance of an anti-reflux procedure are crucial.

Background: Percutaneous angioplasty (PTA) and stenting is an established procedure for the treatment of hypertension caused by atherosclerotic renal artery stenosis. However recently, the decision whether or not to perform this procedure has raised considerable debate.

Objectives: To examine the association between the basic clinical and radiological characteristics of candidates for renal artery PTA and the clinical outcome of the procedure in terms of improvement of blood pressure control and renal function.

Methods: We conducted a retrospective cohort study of all patients who underwent percutaneous transluminal renal artery angioplasty (PTRA) and stent implantation in a tertiary medical center during the period 2000–2007. The clinical and radiological data were extracted from the medical file of each patient. Blood pressure measurements and creatinine level were recorded before the procedure and 1 month, 6 months, 12 months and 18 months after PTRA.

Results: Thirty-two patients were included in the final statistical analysis. The mean age of the study population was 66.6 ± 8.8 years old and 75% were men. There was a significant reduction in both systolic and diastolic blood pressure 1 month after the procedure: 160.5 ± 24.7 vs. 141.8 ± 23.6 mmHg and 83.8 ± 12.9 vs. 68.8 ± 11.8 mmHg respectively (P < 0.001). The reduction in blood pressure was constant throughout the follow-up period and was evident 18 months after the procedure: 160.5 ± 24.7 vs. 135.0 ± 35.1 mmHg and 83.8 ± 12.9 vs. 71.3 ± 16.5 mmHg respectively (P < 0.001). However, no improvement in renal function was observed at any time during the follow-up period. We could not demonstrate an association between clinical or radiological features and the clinical outcome after PTRA.

Conclusions: Our findings show that PTRA[1] can be considered an effective procedure for improving blood pressure control in patients with atherosclerotic renal artery stenosis (ARAS) and resistant hypertension. This research, together with previous studies, strengthens the knowledge that the decline in glomerular filtration rate seen in many patients with ARAS is non-reversible and is not improved by PTRA.

Background: The prognostic significance of biologic markers in women with ductal carcinoma in situ is not fully understood. HER2/neu is a marker of prognostic significance that is routinely assessed in invasive cancer but its correlation with clinical outcome in DCIS[1] is still obscure.

Objectives: To evaluate the significance of HER-2/neu expression as a prognostic marker in DCIS.

Methods: Clinical and pathologic data from 84 patients treated for DCIS were analyzed. HER-2/neu expression was determined by immunohistochemical staining. Histopathologic parameters (nuclear grade, histologic subtype, necrosis, calcifications, margins) were reviewed by an experienced pathologist. Local recurrence and/or metastatic spread were used as endpoints to determine the prognostic significance of HER-2/neu expression.

Results: With a median follow-up of 94.8 months, nine recurrences were reported. Neither univariate nor multivariate analysis showed a significant correlation between HER-2/neu expression and disease recurrence or the time to disease recurrence. Although HER-2/neu expression demonstrated a significant association with high nuclear grade (P < 0.0001) and comedo subtype (P < 0.0001), there was no correlation between these histologic features and recurrence rate. The correlation between high nuclear grade and disease recurrence approached statistical significance (P = 0.07).

Conclusions: No significant association was found between HER-2/neu expression in DCIS and disease recurrence. However, HER-2/neu correlated with negative markers such as nuclear grading and comedo necrosis, and its role should therefore be investigated in larger studies.
 

[1] DCIS = ductal carcinoma in situ

Background: Anti-ribosomal-P antibodies have been associated with central nervous manifestations of systemic lupus erythematosus. However, inconsistencies in their prevalence and clinical correlations have become an obstacle to their use as a diagnostic marker of the disease. This lack of consistency might stem from several factors, such as the lag period between clinical manifestations and the time blood was drawn, or the different methods used for antibodies detection.

Objectives: To evaluate three different enzyme-linked immunosorbent assay tests for the detection of anti-Rib-P Abs[1] in patients with SLE[2] and normal controls.

Methods: Sera from 50 SLE outpatients and 50 healthy subjects were tested with three ELISA[3] kits: Kit-1, which uses synthetic peptide comprising the 22 C-terminal amino-acids; Kit-2, which uses native human ribosomal proteins (P0, P1, P2); and Kit-3, which is coated with affinity-purified human ribosomal proteins. ELISA studies were performed according to the manufacturers' instructions.

Results: The prevalence of anti-Rib-P Abs in SLE patients and controls was 30% vs. 0%, 17% vs. 21%, and 30% vs. 14% in kits 1-3 respectively. Anti-Rib-P Abs detected by Kit-1 correlated with the SLEDAI score (SLE Disease Activity Index). No correlation between prior CNS[4] manifestations and anti-Rib-P Abs was observed.

Conclusions: A significant difference was documented between the ELISA kits used for the detection of anti-Rib-P Abs. A correlation was found between these antibodies (evaluated by Kit-1) and concurrent SLEDAI scores, in contrast to the lack of correlation with previous CNS manifestations. This supports the notion of "active serology" that is evaluated at the same time manifestations are present, as well as the need for standardization of laboratory assays in the future that enable a better assessment of anti-Rib-P Abs presence and clinical correlation.