Israel Medical Association Journal

Background: Dialysate purity contributes to the inflammatory response that afflicts hemodialysis patients.

Objectives: To compare the clinical and laboratory effects of using ultrapure water produced by a water treatment system including two reverse osmosis (RO) units in series, with a system that also includes an ultrapure filter (UPF).

Methods: We performed a retrospective study in 193 hemodialysis patients during two periods: period A (no UPF, 6 months) and period B (same patients, with addition of UPF, 18 months), and a historical cohort of patients treated in the same dialysis unit 2 years earlier, which served as a control group.

Results: Mean C-reactive protein, serum albumin and systolic blood pressure worsened in period B compared to period A and in the controls.

Conclusions: A double RO system to produce ultrapure water is not inferior to the use of ultrapure filters.

Background: Frequent chronic obstructive pulmonary disease (COPD) exacerbators are at a higher risk of adverse health outcomes when compared to infrequent exacerbators. A COPD frequent exacerbator phenotype and its definition has been reported. Haptoglobin (Hp) polymorphism has been associated with differing clinical outcomes in cardiovascular and renal disease. The Hp 2-2 phenotype has been found to have bacteriostatic properties, while the Hp 1-1 phenotype was found to be associated with infections.

Objectives: To determine the correlation in haptoglobin phenotypes and the frequent exacerbator status compared to COPD non-exacerbators.

Methods: Inclusion criteria included previous diagnosis of COPD and presence of at least two documented exacerbations of COPD in the previous 12 months (frequent exacerbator group) or absence of such exacerbations in the previous 24 months (non-exacerbator group). Descriptive data was analyzed using Fisher's exact test and the nonparametric Kruskal–Wallis test. Multivariate logistic regression analysis was performed.

Results: The multivariate logistic regression yielded a model in which haptoglobin phenotype did not have a statistically significant association with frequent exacerbator status. Smoking status was found to be negatively related with the frequent exacerbator status (odds ratio [OR] 0.240, 95% confidence interval (95%CI) 0.068–0.843, P = 0.03). Number of pack-years was negatively related to being a frequent exacerbator (OR 0.979, 95%CI 0.962–0.996, P = 0.02).

Conclusions: We found no relationship between haptoglobin polymorphism and frequent exacerbator status. However, frequent exacerbator status had a statistically significant association with COPD Assessment Test scores and pack-years and a negative correlation with current smoking status.

Because fragility fractures have an enormous impact on the practice of medicine and global health systems, effective screening is imperative. Currently, dual-energy X-ray absorptiometry (DXA), which has limited ability to predict fractures, is being used. We evaluated the current literature for a method that may constitute a better screening method to predict fragility fractures. A systematic review of the literature was conducted on computed tomography (CT), magnetic resonance imaging (MRI), and ultrasound to evaluate screening methods to predict fragility fractures. We found that ultrasound had sufficient data on fracture prediction to perform meta-analysis; therefore, we analyzed prospective ultrasound cohort studies. Six study populations, consisting of 29,299 individuals (87,296 person-years of observation) and including 992 fractures, were analyzed. MRI was found to be sensitive and specific for osteoporosis, but its use for screening has not been sufficiently evaluated and more research is needed on cost, accessibility, technical challenges, and sensitivity and specificity. CT could predict fracture occurrence; however, it may be problematic for screening due to cost, exposure to radiation, and availability. Ultrasound was found to predict fracture occurrence with an increased risk of 1.45 (95% confidence interval 1.21–1.73) to fracture. Ultrasound has not replaced DXA as a screening tool for osteoporosis, perhaps due to operator-dependency and difficulty in standardization of testing.

Background: When a breast lesion is suspected based on a physical exam, mammography, or ultrasound, a stereotactic core needle biopsy (CNB) is usually performed to help establish a definitive diagnosis. CNBs are far less invasive than excisional biopsies, with no need for general anesthetics or hospitalization, and no recovery period. However, since only samples of the mass are removed in a CNB and not the whole mass, sampling errors can occur.

Objectives: To compare the degree of agreement between the pathological data from CNBs and excisional biopsies from a single tertiary referral hospital.

Methods: The concordance of pathological data was compared in patients who underwent CNBs and had their surgical procedures at the same medical center.

Results: From the 894 patients who underwent CNBs, 254 (28.4%) underwent subsequent excisional biopsies at our medical center. From the total of 894 patients, 227 (25.3%) who underwent a CNB were diagnosed with a malignancy, with the rest of the CNBs being diagnosed as benign pathologies. The pathological findings in the CNBs and in the excisional biopsies concurred in 232/254 (91.3%) of the cases.

Conclusions: A CNB to confirm mammographic or clinical findings of breast lesions is an accurate method to establish a pathological diagnosis of breast lesions. The accuracy is higher for invasive carcinomas than for non-invasive cancers. Excisional biopsies are necessary for lesions with anticipated sampling errors or when the core needle biopsy findings are discordant with clinical or mammographic findings.

Background: Uterine carcinosarcoma (UCS) is a rare tumor with a poor prognosis. An elevated thrombocyte count and thrombocytosis were found to be associated with poor prognosis in several gynecological tumors. Data regarding an elevated thrombocyte count and thrombocytosis, particularly in UCS, are scarce.

Objectives: To assess the frequency of a preoperative elevated thrombocyte count and of thrombocytosis in UCS patients and their association with clinicopathological prognostic factors and survival.

Methods: The preoperative thrombocyte count of 29 consecutive verified USC patients diagnosed in our medical center from January 2000 to July 2015 was recorded, and clinicopathological data of these patients were abstracted from hospital files. 

Results: Thrombocytosis was found in two patients (6.8 %) and both died of the disease. An elevated thrombocyte count was found in nine patients (31.0%). The percentage of patients with the poor prognostic factors who had a preoperative elevated thrombocyte count was not statistically different from those without these risk factors. The cumulative survival of patients with an elevated count was 22.1 months and that of those without an elevated count was 31.1 months. This difference was statistically not significant (P = 0.85). There was also no difference between the groups regarding the progression free survival.

Conclusions: No association between an elevated thrombocyte count and prognosis was found. Larger studies are needed to clarify this issue.

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: Enthesopathy may lead to calcification of the stylohyoid ligament and can cause elongation of the styloid process (SP).

Objectives: To evaluate whether SP elongation is associated with two common enthesitis-related diseases: ankylosing spondylitis (AS) and diffuse idiopathic skeletal hyperostosis (DISH).

Methods: Cervical spine computed tomography (CT) examinations of patients with DISH (n=64, Resnick criteria), AS (n=24, New York criteria) and a controls (no radiological signs of DISH or AS, n=54) were retrospectively evaluated. The DISH group was further divided into patients with and without cervical DISH. The length of right and left SP was measured independently by two readers on coronal and sagittal curved reformats. The average right and left styloid length and average length per person were compared among the groups.

Results: Demographic characteristics were similar between the DISH and control groups (average age 68.2 ± 15.7, 69.2 ± 12.7 years, male:female ratio 48:16 and 35:19, respectively, P > 0.05), whereas age was significantly lower (average age: 53 ± 15 years, P < 0.0001) in the AS group, which was also composed mainly of men. The AS and DISH groups had significantly longer SP compared to controls (AS 37.9 ± 9.6 mm, DISH 34.4 ± 9 mm, control 30.3 ± 10.1 mm, P < 0.05). There was no correlation between age and SP length. Inter-reader reliability of SP measurements was excellent in all groups (ICC = 0.998, P < 0.0001).

Conclusions: SP elongation is associated with both AS and DISH substantiating the enthesopathy-related pathophysiology of this finding.

Background: In colon cancer, data regarding proximal and distal metastasis to lymph nodes remains scarce.

Objectives: To evaluate lymph node distribution along the longitudinal axis of the colon as related to a tumor to re-examine the common practice of 5 cm proximal and 2 cm distal resection margins.

Methods: We studied 106 patients (53 males and 53 females, mean age 67.9 ± 10 years) who had undergone left hemicolectomy or sigmoidectomy. Colonic cancer specimens were divided into five zones proximally and distally to the tumor. For each zone, overall lymph node evaluation and ratio was performed.

Results: The mean number of retrieved lymph nodes per patient was 24.3 ± 12, with 54.9% of the nodes concentrated in zone I, 22.1% in zone II, 9.5% in zone III, 10.3% in zone IV, and 3% in zone V. While most positive nodes were found in zone I, significant numbers were also detected in both directions proximally and distally to the tumor.

Conclusions: It seems that longer colonic segments proximally, and especially distally, should be considered for resection to significantly reduce the chances of finding involved lymph node.

Background: Several studies have addressed the issue of undetected uterine pathology in women undergoing hysterectomy for pelvic organ prolapse (POP). However, these studies differ largely with respect to the incidence of malignancy found, study population, and preoperative evaluation.

Objectives: To assess the risk of unexpected pre-malignant and malignant uterine pathological findings after vaginal hysterectomy for POP repair, in a single medical center in Israel.

Methods: A retrospective study was performed of all patients who underwent vaginal hysterectomy due to symptomatic POP between January 1990 and April 2015 in a single tertiary medical center. Selected clinical and pathological data were retrieved from the computerized medical records. All specimens were routinely sent for histopathological assessment. All women were managed according to a uniform protocol that required the presence of a preoperative normal Pap smear, and included preoperative transvaginal sonography and endometrial biopsy when indicated. Patients in whom premalignant or malignant lesions were found preoperatively were not included in the study.

Results: The study comprised 667 patients. The overall rate of malignant or significant premalignant pathologies (6 cases) was 0.89%, including one (0.14%) case of endometrial carcinoma. All premalignant and malignant pathologies were found only in post-menopausal patients. The rate of significant endometrial pathological lesions found in asymptomatic post-menopausal women was only 0.35%.

Conclusions: The rate of preoperatively undetected abnormal histopathological findings in patients who undergo vaginal hysterectomy due to POP is very low, and therefore more extensive preoperative evaluation is not warranted in them.

Background: Systemic CD11b+ cells have been associated with several cardiac diseases, such as chronic heart failure.

Objectives: To assess the levels of circulating CD11b+ cells and pro-inflammatory cytokines in cardiomyopathy induced by chronic adrenergic stimulation.

Methods: Male Lewis rats were injected with low doses of isoproterenol (isoprel) for 3 months. Cardiac parameters were tested by echocardiography. The percentage of CD11b+ cells was tested by flow cytometry. The levels of inflammatory cytokines in the sera were determined by an inflammation array, and the expression levels of cardiac interleukin-1 (IL-1) receptors were analyzed by real-time polymerase chain reactions. Cardiac fibrosis and inflammation were determined by histological analysis.

Results: Chronic isoprel administration resulted in increased heart rate, cardiac hypertrophy, elevated cardiac peri-vascular fibrosis, reduced fractional shortening, and increased heart weight per body weight ratio compared to control animals. This clinical presentation was associated with accumulation of CD11b+ cells in the spleen with no concomitant cardiac inflammation. Cardiac dysfunction was also associated with elevated sera levels of IL-1 alpha and over expression of cardiac IL-1 receptor type 2.

Conclusions: CD11b+ systemic levels and IL-1 signaling are associated with cardiomyopathy induced by chronic adrenergic stimulation. Further studies are needed to define the role of systemic immunomodulation in this cardiomyopathy.

 

The identification and prompt diagnosis of Horner syndrome (HS) is essential for preventing permanent damage. HS may arise when a lesion presents anywhere along the three-neuron oculosympathetic pathway that begins at the posterior-lateral nuclei of the hypothalamus all the way through to the orbit. We present four cases and review the literature to familiarize the reader with the identification, diagnosis and treatment of Horner syndrome. The four patients, three adults and one child, were followed for at least 6 months following the initial diagnosis (range 6–18 months). There was partial resolution in three of the four cases, while the fourth resolved completely. There are numerous causes of HS, some of them iatrogenic. While iatrogenic cases of HR are rare in both adults and children, HS is seen more often following surgical procedures. Prompt recognition of the syndrome and correction of the offending agent may prevent permanent damage to the neuronal pathway. It is therefore recommended that practitioners be aware of the risks for development of iatrogenic HS and the signs for early detection.

Background: Silicone breast augmentation is a common cosmetic surgery. Previous case reports demonstrated lymphadenopathy in the presence of implant ruptures.

Objectives: To investigate the association between enlarged axillary lymph nodes and silicone implant ruptures as seen on breast magnetic resonance imaging (MRI).

Methods: Two groups were derived retrospectively from breast MRI reports in our institution for the period December 2011–May 2014. A search of our hospital records for "silicone" and "lymph node" was performed (group A), and the relationship between the presence of enlarged nodes and ruptures was evaluated. The prevalence of ruptures in the presence of nodes was calculated and the association between MRI imaging features and ruptures evaluated. A search for "silicone" and "implant rupture" was performed (group B) and, as for group A, the relationship between the presence of ruptures and nodes was evaluated and the prevalence of enlarged nodes in the presence of ruptures calculated.

Results: Group A comprised 45 women with enlarged nodes. Intracapsular ruptures were associated with nodes (P = 0.005), while extracapsular ruptures showed a trend of association with nodes (P = 0.08). The prevalence of ruptures in the presence of nodes was 31.4%. Nodes associated with ruptures showed a strong silicone signal (P = 0.008) and absent enhancement (P = 0.005). Group B comprised 73 women with ruptures. Enlarged nodes were associated with both intra- and extracapsular ruptures (P < 0.001 and P = 0.002 respectively). The prevalence of nodes in the presence of ruptures was 22.2%.

Conclusions: Enlarged axillary nodes were associated with ruptures in two groups of patients. This finding can guide clinical decisions when either enlarged nodes or ruptures are encountered in patients with silicone implants. The association between silicone lymphadenopathy and implant rupture raises concerns regarding the role of rupture in silicone-induced systemic disease.