Israel Medical Association Journal

Background: The incidence of Clostridium difficile-associated diarrhea (CDAD) is increasing and is associated with significant morbidity and mortality. Therefore, there is a need to find new tools to determine the severity of the disease.

Objectives: To investigate the prognostic values of inflammatory markers such as mean platelet volume (MPV), neutrophil-lymphocyte ratio (NLR), and C-reactive protein (CRP) in patients with CDAD.

Methods: The study comprised of 100 patients diagnosed with CDAD. The study included an additional control group of 69 patients with diarrhea who were negative for C. difficile toxin. The control group was age- and sex-matched and hospitalized at the same time period. NLR and MPV were obtained from complete blood count results. Serum CRP levels were measured by the latex particle enhanced immunoturbidimetric assay. Blood samples for all inflammatory markers were collected at time of diagnosis and prior to initiating the antibiotic therapy. Demographic, clinical, laboratory, and prognostic data were collected from medical records for a period of 90 days from the initial diagnosis of CDAD.

Results: The mean age of the CDAD group was 68.6 ± 21.5 years compared to 65.6 ± 24.5 in the control group (P = 0.29). Our findings show that patients with CDAD had significantly higher NLR, MPV and serum CRP levels compared to the control group (P < 0.001)). Moreover, significantly higher levels were observed when CDAD was fatal (P < 0.001).

Conclusions: Elevated NLR, MPV, and serum CRP levels may serve as biomarkers for prediction of recurrence and mortality in patients with CDAD.

Background: Crohn’s disease and ulcerative colitis are the two major classic presentations of inflammatory bowel diseases (IBD). Studies have shown a wide variation in the incidence and prevalence attributed to different geographic and ethnic populations.

Objectives: To assess the clinical characteristics of IBD among Arabs in Israel and to compare them to characteristics of IBD among Ashkenazi Jews.

Methods: This retrospective, comparative study compared the clinical characteristics of IBD among 150 Arabs from the Holy Family Hospital and the Nazareth Hospital EMMS, both located in Nazareth, Israel, to those of 97 age- and sex-matched Ashkenazi Jewish patients from Shaare Zedek Medical Center, Jerusalem, Israel.

Results: The Arab cohort, which included 106 patients (70%) with Crohn's disease and 44 (29%) with ulcerative colitis, was compared to 97 Ashkenazi patients (81% with Crohn's disease and 17% with ulcerative colitis) (P < 0.05). Alcohol consumption was found in both groups, but Arabs smoked more (46% vs. 12%, respectively, P < 0.05). Obstructive phenotype was lower in Arabs (10% vs. 32%, P < 0.05). 5-aminosalicylic acid and anti-tumor necrosis factor alpha were prescribed for the Arab and Ashkenazi groups (89% and 21%, respectively). The need for surgical intervention due to disease severity and/or complications was not significant (22% vs. 24%).

Conclusions: Despite similar reports of NOD2/CARD15 mutations, Crohn's disease is more common than ulcerative colitis within the Arab-Israeli population. Increased smoking rates may explain milder disease severities in Arabs, as reflected by lower obstructive pattern and frequent use of milder therapeutic modalities.

Background: Male breast cancer (MBC) is a rare disease representing less than 1% of breast cancers. In the absence of a screening program, such as for females, the diagnostic workup is critical for early detection of MBC.

Objectives: To summarize our institutional experience in the workup of male patients referred for breast imaging, emphasizing the clinical, imaging, and histopathological characteristics of the MBC cohort.

Methods: All male patients who underwent breast imaging between 2011 and 2016 in our institution were retrospectively reviewed. Clinical, radiological, and histopathological data were collected and statistically evaluated. All images were reviewed using the American College of Radiology Breast Imaging Reporting and Data System.

Results: 178 male patients (average age 61 years, median age 64), underwent breast imaging in our institution. The most common indication for referral was palpable mass (49%) followed by gynecomastia (16%). Imaging included mostly mammography or ultrasound. Biopsies were performed on 56 patients, 38 (68%) were benign and 18 (32%) were malignant. In all, 13 patients had primary breast cancer and 5 had metastatic disease to the breast. Palpable mass at presentation was strongly associated with malignancy (P = 0.007).

Conclusion: Mammography and ultrasound remain the leading modalities in breast imaging among males for diagnostic workup of palpable mass, with gynecomastia being the predominant diagnosis. However, presentation with palpable mass was also associated with malignancy. Despite a notable MBC rate in our cohort, the likelihood of cancer is low in young patients and in cases of gynecomastia.

Background: In developed countries, hepatitis A virus (HAV) infection occurs mainly in adults. It is usually symptomatic and may cause acute liver failure (ALF). In patients with chronic liver disease, serum ferritin levels (SFL) can predict short-term prognosis.

Objectives: To determine whether admission SFL can serve as a prognostic marker in patients with HAV infection.

Methods: A retrospective analysis of 33 adults with HAV infection was conducted. Because none of our patients presented with ALF, the parameter "length of hospital stay," was used as a surrogate marker of disease severity.

Results: The mean (± SD) at admission SFL was 2529 ± 4336 ng/ml. SFL correlated with the levels of international normalized ratio (INR), liver enzymes, and degree of hemolysis that occurred during the disease course. SFL did not correlate with the levels of either albumin or bilirubin or with the length of the hospital stay. The mean length of hospital stay was 5.1 ± 2.0 days, which correlated with the levels of INR, albumin, and bilirubin as well as the degree of hemolysis. However, in multivariate analysis only albumin and bilirubin predicted the length of the hospital stay. Follow-up SFL, which were available only in eight patients, decreased during the hospital stay.

Conclusions: In adults with acute HAV infection, SFL may be increased. SFL correlated with the degree of liver injury and hemolysis that occur during the disease. However, in our cohort of HAV patients, who had a relatively benign disease course, SFL were of no prognostic value.

Background: Recurrent miscarriages are associated with a high prevalence of thrombophilia. Use of a calibrated automated thrombogram (CAT) can serve as a universal test for thrombophilia.

Objectives: To examine whether thrombin generation measured by CAT is elevated during the first trimester in women with unexplained recurrent miscarriages.

Methods: This study comprised 25 pregnant women with recurrent pregnancy loss referred for thrombophilia screening and treated with low-molecular-weight heparin (LMWH). Thrombin generation parameters were measured in women who had miscarriages or live births and who were diagnosed as positive or negative for thrombophilia.

Results: Of the pregnancies, 76% resulted in live birth and 24% ended in miscarriages. Among the women, 76% were positive for thrombophilia. Thrombin generation parameters between pregnancies that ended in miscarriage compared to live births were not significantly different, and CAT parameters failed to predict pregnancy outcome. Although the CAT parameters demonstrated a trend toward a hypercoagulable state in women with thrombophilia, there was no statistical significance (P > 0.05).

Conclusions: Women with unexplained pregnancy loss demonstrated similar thrombin generation in the first trimester, regardless of the pregnancy outcome. CAT parameters failed to predict pregnancy outcome in women with recurrent unexplained pregnancy loss. Our results should be interpreted with caution due to the small number of participants.

Background: C-reactive protein (CRP) blood level is associated with clinical outcomes of several diseases. However, the independent predictive role of CRP in the heterogeneous population of patients admitted to internal medicine wards is not known. 

Objectives: To determine whether single CRP levels at admission independently predicts clinical outcome and flow of patients in general medicine wards.

Methods: This study comprised 275 patients (50.5% female) with a mean age of 68.25 ± 17.0 years, hospitalized with acute disease in a general internal medicine ward. The association between admission CRP levels and clinical outcomes including mortality, the need for mechanical ventilation, duration of hospitalization, and re-admission within 6 months was determined.

Results: A significant association was found between CRP increments of 80 mg/L and risk for the major clinical outcomes measured. The mortality odds ratio (OR) was 1.89 (95% confidence interval (95%CI, 1.37–2.61, P < 0.001), mechanical ventilation OR 1.67 (95%CI, 1.10–2.34, P = 0.006), re-admission within 6 months OR 2.29 (95%CI, 1.66–3.15 P < 0.001), and prolonged hospitalization >7 days OR 2.09 (95%CI, 1.59–2.74, P < 0.001). Lower increments of10 mg/L in CRP levels were associated with these outcomes although with lower ORs. Using a stepwise regression model for admission CRP levels resulted in area under the receiver operating characteristics curves between 0.70 and 0.76 for these outcomes.

Conclusions: A single admission CRP blood level is independently associated with major parameters of clinical outcomes in acute care patients hospitalized in internal medicine wards.

Background: Whole-body integrated positron emission tomography / contrast-enhanced computed tomography (PET/CT) scan is increasingly used in cutaneous lymphomas. However, the value of PET/CT in the detection of cutaneous lesions in primary cutaneous B-cell lymphoma (PCBCL) has barely been investigated.

Objectives: To investigate the diagnostic accuracy of PET/CT in tracking cutaneous involvement in PCBCL.

Methods: A retrospective study was conducted on 35 consecutive patients diagnosed with cutaneous B-cell lymphoma according to the World Health Organization classification who were evaluated with PET/CT as the initial staging procedure before treatment.

Results: Thirty-five patients met the study criteria. In two patients extracutaneous disease was detected by PET/CT and CT and confirmed by biopsy. Of the 33 patients with PCBCL, 26 (79%) had small cell PCBCL (18 marginal-zone, 8 follicle-center lymphoma) and 7 (21%) had large cell PCBCL (3 follicle-center, 3 leg-type, 1 indeterminate). PET/CT detected skin lesions in 3 of 26 patients (12%) with small-cell PCBCL as compared to 6 of 7 patients with large-cell PCBLC (86%), a 7.4-fold detection risk (95% confidence interval, 2.4–22, P = 0.004). The PET-positive subgroup was characterized by larger lesion size (P < 0.001) and a higher Ki-67 proliferation index (P < 0.001).

Conclusions: The sensitivity of PET/CT for detecting cutaneous involvement of lymphomas is low for small-cell PCBCL but high for large-cell types, and thus may facilitate therapeutic strategies.

Background: Cryptosporidium is a major threat to water supplies worldwide. Various biases and obstacles in case identification are recognized. In Israel, Cryptosporidiosis was included among notifiable diseases in 2001 in order to determine the burden of parasite-inflicted morbidity and to justify budgeting a central drinking water filtration plant.

Objective: To summarize the epidemiologic features of 14 years of Cryptosporidium surveillance and to assess the effects of advanced water purification treatment on the burden of disease.

Methods: From 2001 to 2014, a passive surveillance system was used. Cases were identified based on microscopic detection in stool samples. Confirmed cases were reported electronically to the Israeli Ministry of Health. Overall rates as well as age, gender, ethnicity and specific annual incidence were calculated per 100,000 population in five age groups: 0–4, 5–14, 15–44, 45–64, > 65 years.

Results: A total of 522 Cryptosporidium cases were reported in all six public health districts. More cases were detected among Jews and among males, and mainly in young children, with a seasonal peak during summer. The Haifa sub-district reported 69% of the cases. Most were linked to an outbreak from the summer of 2008, which was attributed to recreational swimming pool activity. Cases decreased after installation of a central filtration plant in 2007.

Conclusions: As drinking water in Israel is treated to maximal international standards, the rationale for further inclusion of Cryptosporidium among mandatory notifiable diseases should be reconsidered. Future surveillance efforts should focus on timely detection of outbreaks using molecular high-throughput testing.

Background: Adenovirus is responsible for 2–7% of childhood viral respiratory infections, 5–11% of viral pneumonia and bronchiolitis. Most are self-limited but may cause severe respiratory infection.

Objectives: To describe adenovirus respiratory infection in immunocompetent children in a pediatric intensive care unit (PICU).

Methods: Children with adenovirus respiratory infection in our PICU from 2007 to 2016 were included. Data were retrospectively retrieved, including background, clinical manifestation, and treatment. Adenovirus was diagnosed by polymerase chain reaction, immune fluorescence, or both.

Results: Of 9397 samples, 956 were positive for adenovirus in children hospitalized during the study period. In total, 49 patients (aged 2 months–11.5 years) were admitted to our PICU, five were immunocompromised and excluded from the study, 19/44 (43%) were referred from other hospitals. Twenty-eight (64%) had underlying conditions, 66% had fever and cough, 11% had conjunctivitis, and 34% received antibiotics before admission. White blood cell counts ranged from 790 to 34,300 (mean 14,600) and 36% had counts above 15,000. Chest X-ray was consistent with viral infection in 77% of patients and normal in three (13.6%). Viral co-infection was found in 9 patients, 7 had presumed bacterial super-infection, and 27 (61.4%) needed mechanical ventilation. Two patients received cidofovir, 33 (75%) steroids, and 37 (84 %) antibiotics. Four patients died.

Conclusions: Adenovirus respiratory infection may cause severe disease necessitating PICU admission and mechanical ventilation, mostly in patients with underlying conditions. Many patients received steroids and antibiotics, which may be unnecessary. Mortality was 9%, mainly among young infants and those with underlying conditions.

Background: Ocular trauma in the pediatric population may lead to cataract formation. Managing traumatic cataracts in a visually immature child is a major challenge and can result in poor visual outcome.

Objectives: To review our long-term surgical experience with childhood unilateral traumatic cataracts.

Methods: A retrospective observational study of children with unilateral traumatic cataracts with minimal follow-up of 5 years was conducted. Main outcomes included final visual acuity (VA) and occurrence of complications.

Results: Of the 18 children included in the study, 83% were male. Mean follow-up time was 12.5 years. Median age at injury was 7.5 years. Eleven patients (61%) presented with penetrating trauma injuries and 7 (39%) with blunt trauma. Sixteen patients (89%) had cataracts at presentation, while in two the cataracts developed during follow-up. Of the 18 total, cataract removal surgery was conducted in 16 (89%) with intraocular lens (IOL) implantation in 14 (87.5%), while 2 remained aphakic (12.5%). Two (11%) were treated conservatively. Long-term complications included IOL dislocation in 5 (36%), glaucoma in 8 (44%), and posterior capsular opacity in 10 (71%). No correlation was found between final visual acuity and the time interval between injury and IOL implantation nor between final VA and age at trauma. However, the final VA did correlate with time of follow-up.

Conclusions: Severe complications occurred in over 30% of the patients during a long follow-up (mean 12.5 years). This finding shows the importance of discussions between the operating physician and the parents regarding the prognosis and necessity of scheduled follow-up.

Background: With the recent introduction of high-sensitivity troponin (hsTn), the incremental benefit of stress myocardial perfusion imaging (MPI) in the evaluation of patients who present to the emergency department (ED) with acute coronary syndrome (ACS) is unclear.

Objectives: To assess the added value of stress MPI in low-risk ACS patients with normal range hsTnI.

Methods: We analyzed all patients who were hospitalized at our medical center from February 2016 to November 2017, who presented with low-risk ACS and underwent stress MPI, and in whom hsTnI was in the normal range after the introduction of hsTnI.

Results: During the study period, 161 patients were admitted with a diagnosis of unstable angina (i.e., ACS with normal range hsTnI) and underwent stress MPI during index admission. The study population included 52/161 patients (31.7%) with low-risk ACS who had no indication for initial invasive strategy. No patients had positive MPI. One patient underwent coronary angiography due to suggestive history; however, he did not have a significant coronary artery disease and had no indication for percutaneous coronary intervention.

Conclusions: In patients with low-risk ACS and normal range hsTnI without additional high-risk features, stress MPI has little additional value for the correct diagnosis and management. Prospective studies are warranted to confirm whether resting hsTnI could serve as a powerful triage tool in chest pain patients in the ED before diagnostic testing and thus, improve patient management.

Background: Ophthalmic pathologies may further complicate the sensory input of patients with congenital hearing loss; however, data on children with coexisting impairment of vision and hearing is outdated, from before universal implementation of hearing screening programs.

Objectives: To examine the different ophthalmic pathologies among children with congenital sensorineural hearing loss (SNHL) before or after the introduction of a universal newborn hearing screening program (UNHSP).

Methods: Retrospective cohort study was conducted of 91 children diagnosed with congenital SNHL between 2005 and 2016 in a tertiary pediatric hospital. All patients completed an ophthalmologic examination, including assessment of visual acuity, refraction, ocular motility, slit lamp examination, and indirect funduscopy. Radiological assessment and genetic analysis were offered to all caregivers.

Results: Average age at diagnosis was 4.1 years. Nineteen children (21%) were diagnosed with an ophthalmic condition, of which the most common were refractive pathologies. Diagnosis of an ophthalmic pathology was twice as likely in the pre-UNHSP era (14 children, 27%) compared to the post-UNHSP era (5 children, 13%). Out of 91 children, 57 (63%) underwent a computed tomography scan and/or magnetic resonance imaging. Imaging was positive for structural abnormalities in 23 children (40%). There was no correlation between imaging and ophthalmic conditions. Genetic analysis was performed in 67 patients (74%).

Conclusions: The ophthalmic assessment of babies and children with congenital SNHL may yield in significant numbers of children with concomitant ophthalmic pathologies. Implementation of a UNHSP allows early diagnosis and treatment of coexisting ophthalmic and hearing conditions.