Israel Medical Association Journal

Background: Systemic sclerosis (SSc) is a chronic disease with prominent vasculopathy, inflammation, production of autoantibodies, and tissue fibrosis. Periodontitis is a chronic inflammatory oral condition manifesting as microbial infection, inflammation and destruction of the alveolar bone. In both conditions tumor necrosis factor-alpha (TNFα) and other pro-inflammatory cytokines play an important role in pathogenesis. 

Objectives: To assess the periodontal status in SSc patients and compare these parameters to TNFα level in gingival crevicular fluid (GCF) of SSc patients and healthy controls.

Methods: Twenty SSc patients and 20 controls underwent periodontal examination, including probing depth (PD), plaque index (PI), gingival index (GI), bleeding on probing (BOP), and measurement of TNFα levels in collected GCF. 

Results: SSc patients had a greater PD (3.74 ± 0.32 mm vs. 3.35 ± 0.31 mm, P > 0.003), GI (1.53 ± 0.34 vs. 1.12 ± 0.54, P > 0.049), and non-significantly higher BOP than controls. TNFα levels in GCF were higher in SSc patients (1.63 ± 0.36 vs. 1.15 ± 0.34 pg/ml, P = 0.001). Periodontitis parameters correlated with several SSc variables; PI in particular was higher in patients with longer disease duration, sclerodactyly, more severe skin involvement, and SSc activity score.

Conclusions: Patients with SSc have higher indices of periodontal inflammation and higher TNFα level in GCF than did healthy individuals. These changes probably reflect the complexity of factors that influence oral health in SSc. Common pathologic pathways may be responsible for the association between SSc and periodontitis, which requires further study.

 

Background: Evidence suggests that prolonged bisphosphonate (BP) treatment predisposes to atypical fractures (AF), but the etiology has yet to be determined. Addressing causality begins with case identification, which requires radiological adjudication. However, many trials based their case findings on coded diagnoses. 

Objectives: To investigate the feasibility of case findings by the coding system and the reproducibility of radiological evaluations in two hospitals in Israel, and to compare BP exposure of AF patients to a control group with typical (intertrochanteric of femoral neck) fractures. 

Methods: Diagnostic databases from 2007–2010 were reviewed and admission X-rays of patients were examined in two steps by two radiologists. Fractures were classified as atypical or not atypical according to published criteria. A 2:1 control group was created. Ambulatory drug acquisition was reviewed. 

Results: Of the 198 patients who fulfilled the search criteria, 38 were classified by initial radiological opinion as AF. Subsequent radiological opinion judged 16 as not atypical. Of the AF patients, 80% were exposed to BP. Of those, 81% continued to receive BP treatment for 2.4 years after AF. Only one AF patient was discharged with suspected AF diagnosis. In the control group, 27% were exposed to BP prior to fracture (P < 0.001). 

Conclusions: Thorough radiological revision is mandatory for proper classification of AF, and even when performed there is significant inconsistency in interpretation. Conclusions drawn from trials based solely on coded diagnoses lead to significant bias. BP exposure was significantly higher in the AF group. Caregiver unawareness of AF leads to improper management. 

 

Background: Cardiac resynchronization therapy (CRT) is a non-pharmacological option for patients with heart failure and interventricular dyssynchrony. Elevated red cell distribution width (RDW) reflects higher size and heterogeneity of erythrocytes and is associated with poor outcome in patients with chronic heart failure. 

Objectives: To examine the association between RDW levels and outcomes after CRT implantation.

Methods: We conducted a cohort analysis of 156 patients (126 men, median age 69.0 years) who underwent CRT implantation in our institution during 2004–2008. RDW was measured at three time points before and after implantation. Primary outcome was defined as all-cause mortality, and secondary outcome as hospital re-admissions. We investigated the association between RDW levels and primary outcome during a median follow-up of 61 months.

Results: Ninety-five patients (60.9%) died during follow-up. Higher baseline RDW levels were associated with all-cause mortality (unadjusted HR 1.35, 95%CI 1.20–1.52, P < 0.001). On multivariate analysis adjusted for clinical, electrocardiographic and laboratory variables, baseline RDW levels were associated with mortality (HR 1.33, 95%CI 1.16–1.53). RDW levels 6 months and 12 months post-implantation were also associated with mortality (HR 1.22, 95%CI 1.08–1.38, P = 0.001; and HR 1.15, 95%CI 1.01–1.32, P = 0.02, respectively). Patients who were re-admitted to hospital during follow-up (n=78) had higher baseline RDW levels as compared to those who were not (14.9%, IQR 14.0, 16.0% vs. 14.3%, IQR 13.7, 15.0%, respectively, P = 0.03). 

Conclusion: An elevated RDW level before and after CRT implantation is independently associated with all-cause mortality. 

 

Background: Admission glucose levels correlate with clinical outcome in patients with type 2 diabetes mellitus (T2DM) hospitalized in general medicine wards. 

Objective: To investigate whether in-hospital hyperglycemia alone and after adjustment for age, gender and lipidemia correlates with in- and out-of-hospital mortality.

Methods: Capillary glucose, serum lipids and diagnoses at discharge among patients with T2DM hospitalized in the general medical wards of our hospital were documented. Correlation with in- and out-of-hospital mortality was determined through uni- and multivariate analyses. 

Results: Of the 4607 patients included in the study 22% died while hospitalized. From a median of five capillary glucose tests obtained per patient, average capillary glucose level was significantly lower in those who survived than in those who died (174 ± 64 vs. 180 ± 65 mg/dl, P = 0.005). Overall, blood cholesterol was higher in those who survived than in those who died (P < 0.001). Multivariate analysis, however, including age, gender, lipidemia and glycemia, showed that only age and male gender correlated with mortality.

Conclusions: Hyperglycemia was associated with increased in- and out-of-hospital mortality on univariate analysis. However, it was not an independent risk factor when corrected for age, gender and hyperlipidemia. 

 

Studies of the respiratory effects of air pollution in Israel published in peer-reviewed journals have been infrequent. Most empiric evidence relates to the association between air pollution and childhood asthma; other air pollution effects on other illnesses are less thoroughly studied. Our evaluation provides a possible explanation for the quite contradictory results demonstrated in the various studies. Actual effect estimates appear to differ considerably, ranging from no air pollution effect to a reasonably strong association detected between PM10 and asthma. We attribute these discrepancies to different research methodologies and different types of data used in various studies.

Abstract

Background: The impact of admission glycated hemoglobin (HbA1c) on hospital outcome is controversial.

Objectives: To evaluate the association between admission glucose and HbA1c levels and mortality 1 year after hospitalization in the internal medicine ward.

Methods: HbA1c level of consecutive patients was measured during the first 24 hours of admission to the internal medicine ward and divided at the cutoff point of 6.5%. Three groups of patients were prospectively identified: patients with preexisting diabetes mellitus (DM), patients with glucose > 140 mg/dl (hyperglycemia) on admission and no known diabetes (H), and patients without diabetes or hyperglycemia (NDM). The primary end-point was 1 year all-cause mortality.

Results: A total of 1024 patients were enrolled, 592 (57.8%) belonged to the DM group, 119 (11.6%) to the H group and 313 (30.6%) to the NDM group. At 1 year, death occurred in 70 (11.9%) in the DM group, 12 (10.0%) in the H group and 15 (4.8%) in the NDM group (P = 0.002). Elevated admission glucose levels did not influence outcome in any of the groups. HbA1c levels were similar for survivors and non-survivors (P = 0.60). Within-group multivariate analysis adjusted for comorbidities and age showed that in the H group HbA1C levels of 6.5% or above were associated with increased mortality risk [hazard ratio (HR) 8.25, 95% confidence interval (CI) 1.93–35.21). In the DM group, HbA1c levels below 6.5% were associated with increased mortality risk (HR = 2.05, 95%CI 1.25–3.36).

Conclusions: Glucose levels upon admission did not affect mortality. However, HbA1c levels below 6.5% had opposite effects on 1 year mortality in diabetes patients and patients with hyperglycemia.

Abstract

Background: Hyperhomocysteinemia is associated with increased cardiovascular risk, but treatment with folic acid has no effect on outcome in unselected patient populations.

Objectives: To confirm previous observations on the association of homozygosity for the TT MTHFR genotype with B12 deficiency and endothelial dysfunction, and to investigate whether patients with B12 deficiency should be tested for 677MTHFR genotype.

Methods: We enrolled 100 individuals with B12 deficiency, tested them for the MTHFR C677T polymorphism and measured their homocysteine levels. Forearm endothelial function was checked in 23 B12-deficient individuals (13 with TT MTHFR genotype and 10 with CT or CC genotypes). Flow-mediated dilatation (FMD) was tested after short-term treatment with B12 and folic acid in 12 TT MTHFR homozygotes.

Results: Frequency of the TT MTHFR genotype was 28/100 (28%), compared with 47/313 (15%) in a previously published cohort of individuals with normal B12 levels (P = 0.005). Mean homocysteine level was 21.2 ± 16 mM among TT homozygotes as compared to 12.3 ± 5.6 mM in individuals with the CC or CT genotype (P = 0.008). FMD was abnormal (£ 6%) in 9/13 TT individuals with B12 deficiency (69%), and was still abnormal in 7/12 of those tested 6 weeks after B12 and folic treatment (58%).

Conclusions: Among individuals with B12 deficiency, the frequency of the TT MTHFR genotype was particularly high. The TT polymorphism was associated with endothelial dysfunction even after 6 weeks of treatment with B12 and folic acid. Based on our findings we suggest that B12 deficiency should be tested for MTHFR polymorphism to identify potential vascular abnormalities and increased cardiovascular risk. 

Abstract

Background: Human herpes virus-6 (HHV-6) reactivation after hematopoietic stem cell transplantation (HSCT) is well known and has been linked with several clinical manifestations. The significance of HHV-6 viremia and related complications in this setting is still unclear.

Objective: To estimate the incidence of HHV-6 reactivation and associated morbidity in children undergoing allogeneic HSCT.

Methods: Blood samples obtained weekly (for cytomegalovirus surveillance) from children who underwent allogeneic HCST during the period January 2006–June 2010 were retrospectively tested for the presence of HHV-6 DNA using standard real-time polymerase chain reaction (PCR) assay. Clinical records were reviewed for correlation between viremia and clinical manifestations.

Results: Samples from 39 children were tested. Twenty patients had viral loads above 1000 copies/ml (51%) in at least one sample. Higher viral loads were seen in patients with primary immunodeficiency and in those with cord blood transplant. Attributable symptoms were present in 12 patients (60%) concurrently with positive PCR. Clinical manifestations spontaneously resolved without treatment in most cases, concomitantly with a decrease in viral load.

Conclusions: HHV6 reactivation during allogeneic HSCT is common. HHV-6 reactivation should be considered in patients with graft-vs-host disease-like rash, onset of CNS symptoms, delay in engraftment, and in patients after cord blood transplantation.

Background: The surgical treatment of hip fractures remains controversial especially when considering age. 

Objectives: To investigate the long-term functional outcomes of displaced subcapital hip fractures that were reduced and surgically fixed using parallel cannulated screws in patients aged 60 years and younger. 

Methods: During the period 1996–2005, 27 patients under age 60 with displaced subcapital hip fractures classified as Garden III or IV were treated with fracture reduction and surgical internal fixation using cannulated screws. Patient outcomes were assessed using the Harris Hip Score (HHS) and physical examination.

Results: During a follow-up period of 8–17 years 4 of the 27 patients (14.8%) developed non-union/femoral head avascular necrosis and had undergone hip arthroplasty. All reoperations were performed within the first year after fracture fixation, all in the 50–60 year old age group. The revision rate among patients 50–60 years old was significantly higher than that of patients 50 years and younger (40% vs. 0%, P = 0.037). Mean HHS was higher for patients not requiring revision surgery (85.4) than for patients with revision surgery (75.5), but this difference was not significant.

Conclusions: Internal fixation using fracture reduction and cannulated screw fixation is a successful treatment modality for displaced subcapital hip fractures in patients younger than 50 years old. Patients aged 50–60 years may have a higher risk of avascular necrosis or non-union and require arthroplasty, often within the first year after fracture fixation. The long-term outcome following these fractures is good when excluding patients who had early complications.