Israel Medical Association Journal

Background: Transcatheter tricuspid valve-in-valve implantation (TVIV) is an attractive yet under-explored alternative to redo valve surgery. 

Objectives: To report the multicenter TVIV experience in Israel.

Methods: We approached multiple centers and collected data regarding seven TVIV cases. 

Results: The study group comprised seven participants: five females and two males, with a mean age of 63 ± 12 years and EuroSCORE-II 13.6 ± 3.3%. Follow-up ranged from 3 to 21 months (mean 8 ± 6 months). All presented with advanced heart failure. The indication for valve intervention was a predominant tricuspid stenosis in three patients, significant tricuspid regurgitation in one and a mixture in three. Six procedures were conducted via a transfemoral approach and one by transatrial access. The Edwards SAPIENTM XT valve was used in four cases and the SAPIENTM 3 in three. Without pre-stenting/rapid pacing, all participants underwent successful valve implantation. Mean transvalvular gradient decreased from 11 ± 3 mmHg to 6 ± 3 mmHg (P = 0.003) and regurgitation decreased from moderate/severe (in four cases) to none/trace (in six of the seven cases). One patient remained severely symptomatic and died 3.5 months after the implantation. All others achieved a functional capacity improvement and amelioration of symptoms soon after the implantation, which persisted during follow-up. 

Conclusions: TVIV may be a safe and effective strategy to treat carefully selected patients with degenerated bioprosthetic tricuspid valve at high operative risk. 

 

Background: Deliberate self-harm (DSH) increases the danger of future suicide death and the risk increases with age. Self-harm in older adults is often associated with greater suicidal intent and lethality. 

Objectives: To investigate clinical and psychosocial variables of older patients (age ≥ 65 years) assessed due to DSH, compared with younger adults.

Methods: Patients admitted to the Emergency Department following DSH during an 8 year period were included.

Results: Of 1149 participants, 187 (16.6%) were older adults (age ≥ 65) and 962 (83.4%) were younger adults (< 65). The older adults reported DSH closer to mid-day (P < 0.01) and suffered more frequently from adjustment disorder and depression. Personality disorders and schizophrenia were less commonly diagnosed (P < 0.001). Prescription medication (sedatives and hypnotics) were a more frequent means (88% vs. 71%) of DSH among older patients. Younger patients with DSH used over-the-counter medications (21.9% vs. 6.4%) three times more than did the older patients (P < 0.01). Past DSH was significantly more frequent in younger adults. Following DSH the older patients were frequently admitted for further general hospitalization (P < 0.001). 

Conclusions: Older adults with DSH are a unique group with different clinical characteristics. There is a need for targeted prevention strategies and education of caregivers regarding DSH in older adults.

 

Background: More than 90% of all thyroid cancers are differentiated thyroid carcinomas (DTC) with a 10 year survival rate greater than 90%. The commonly used risk stratification systems for DTC include: European Organization for Research and Treatment of Cancer (EORTC), AGES (Age, histologic Grade, Extent of tumor, Size), AMES (Metastasis) and MACIS (Completeness of resection, local Invasion). Other systems are also utilized. Several new factors that may be involved in DTC risk stratification have emerged in recent studies, with other "traditional" factors being challenged. 

Objectives: To present recent updates in the literature on new potential prognostic factors for DTC.

Methods: We conducted a literature review and analysis of publications regarding DTC prognostic factors or risk stratification published in the last 10 years. 

Results: Several new factors with potential prognostic implications for DTC were noted, including family history, lymph node involvement parameters, positive PET-CT findings, multifocal disease, thyroglobulin level and several molecular markers including BRAF. Increasing age is associated with poorer outcome in DTC; however, recent studies suggest that the cutoff point of 45 years may be contested. Furthermore, several studies have shown contradictory results regarding male gender as a negative prognostic factor, thus questioning its prognostic significance. 

Conclusions: A number of new factors with potential prognostic implications for DTC have emerged and should be addressed. However, their role and possible inclusion in new staging systems has yet to be determined.

 

Antiphospholipid syndrome (APS) is an autoimmune systemic disease characterized by vascular thrombosis (arterial or venous) and/or pregnancy complications associated with the occurrence of autoantibodies, specifically lupus anticoagulant, anticardiolipin antibodies, and/or anti-β2 glycoprotein-I antibodies confirmed at least twice over a 12 week period according to the 2006 Sydney criteria. Antiphospholipid antibodies are encountered  in the general population with a reported prevalence of 1% to 5%  However, APS is far more infrequent with a prevalence of 40–50/100,000 persons and an incidence of about 5 new patients/100,000 persons. APS can be diagnosed in patients with no apparent clinical or laboratory pathology (primary APS) or it may be related to numerous other conditions, autoimmune diseases (usually systemic lupus erythematosus), malignancies, infections and drugs (secondary APS). Women are at risk for APS since the disease is encountered in both the primary and the secondary state in females more often than in men. In addition, women in their reproductive years can develop APS (either classical or obstetric), and special attention is warranted in pregnant women with a diagnosis of APS. The benefits of hormonal therapy in the form of contraception or hormone replacement treatment should be carefully weighed against the increased risk for vascular complications in women with APS.

Background: Prophylaxis for hospitalized venous-thromboembolic events (VTEs) is frequently underutilized, in part due to lack of a simple risk assessment model (RAM). 

Objectives: To compare patient selection and administration of VTE prophylaxis according to the American College of Chest Physicians (ACCP) 2008 guidelines versus the newer 2012 guidelines, and assess the feasibility of developing simpler local RAMs.

Methods: We conducted a prospective assessment of VTE risk among 300 unselected consecutive patients admitted to a medical hospital ward, using the 2008 and 2012 ACCP guidelines. The frequency and relative weight of each risk factor in the 2012 ACCP guidelines were used to develop a local VTE RAM.

Results: VTE prophylaxis was indicated by the 2008 and 2012 ACCP guidelines in 40% and 42% of the cohort respectively, and was administered in 28% and 26% of eligible patients, respectively. Contraindication to VTE prophylaxis was found in 29% of patients according to both guidelines. In comparison to the 2008 guidelines, sensitivity and specificity of the 2012 guidelines were 96% and 88%, respectively. A local RAM based on the following concise score, comprising age, malignancy and immobility, correctly identified 99% of at-risk patients based on the 2012 guidelines, with a sensitivity and specificity of 98% and 95%, respectively.

Conclusions: Both guidelines performed to a similar degree and were poorly implemented in daily practice. A simplified RAM accurately identified the vast majority of these eligible patients. The development of local RAMs is feasible and may result in higher utilization rates.

 

Background: Clinicopathological risk factors for cutaneous squamous cell carcinoma of the head and neck (CSCCHN) are associated with local recurrence and metastasis. 

Objectives: To compare the incidence and risk factors of CSCCHN by age and gender in order to help refine the clinical evaluation and treatment process.

Methods: Clinical and pathological data of all patients diagnosed with CSCCHN during 2009–2011 were obtained from a central pathology laboratory in Israel. Estimated incidence rate calculation was standardized to the 2010 Israeli population. Independent risk factors for poorly differentiated CSCCHN were analyzed using logistic regression.

Results: CSCCHN was diagnosed in 621 patients. Mean age was 75.2 years; mean tumor horizontal diameter was 11.1 ± 6.8 mm. The overall estimated incidence rate in males was higher than in females (106.2 vs. 54.3 per 1,000,000, P < 0.001). Twenty cases (3.2%) had poorly differentiated CSCCHN. Scalp and ear anatomic locations were observed more often in males than in females (22.1% vs. 6.1% and 20.3% vs. 3.3%, respectively, P < 0.001). Per 1 mm increment, tumor horizontal diameter increased the risk for poorly differentiated CSCCHN by 6.7% (95%CI 1.3–12.4%, P = 0.014). 

Conclusions: CSCCHN clinicopathological risk factors are not distributed evenly among different age and gender groups. 

 

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.

Background: Prolonged life expectancy has increased the number of elderly high risk patients referred for surgical aortic valve replacement (AVR). These referred high risk patients may benefit from sutureless bioprosthesis procedures which reduce mortality and morbidity.

Objectives: To present our initial experience with sutureless aortic bioprotheses, including clinical and echocardiographic results, in elderly high risk patients referred for AVR. 

Methods: Forty patients (15 males, mean age 78 ± 7 years) with symptomatic severe aortic stenosis underwent AVR with the 3F Enable™ or Perceval™ sutureless bioprosthesis during the period December 2012 to May 2014. Mean logistic EuroScore was 10 ± 3%. Echocardiography was performed preoperatively, intraoperatively, at discharge and at follow-up.

Results: There was no in-hospital mortality. Nine patients (22%) underwent minimally invasive AVR via a right anterior mini-thoracotomy and one patient via a J-incision. Four patients underwent concomitant coronary aortic bypass graft, two needed intraoperative repositioning of the valve, one underwent valve exchange due to inappropriate sizing, three (7.5%) had a perioperative stroke with complete resolution of neurologic symptoms, and one patient (2.5%) required permanent pacemaker implantation due to complete atrioventricular block. Mean preoperative and postoperative gradients were 44 ± 14 and 13 ± 5 mmHg, respectively. At follow-up, 82% of patients were in New York Heart Association functional class I and II.

Conclusions: Sutureless AVR can be used safely in elderly high risk patients with relatively low morbidity and mortality. The device can be safely implanted via a minimally invasive incision. Mid-term hemodynamic results are satisfactory, demonstrating significant clinical improvement.

 

Background: Transvenous lead extraction can lead to tricuspid valve damage. 

Objectives: To assess the incidence, risk factors and clinical outcome of tricuspid regurgitation (TR) following lead extraction.

Methods: We prospectively collected data on patients who underwent lead extraction at the Sheba Medical Center prior to laser use (i.e., before 2012). Echocardiography results before and following the procedure were used to confirm TR worsening, defined as an echocardiographic increase of at least one TR grade. Various clinical and echocardiographic parameters were analyzed as risk factors for TR. Clinical and echocardiographic follow-up was conducted to assess the clinical significance outcome of extraction-induced TR.

Results: Of 152 patients who underwent lead extraction without laser before 2012, 86 (56%) (192 electrodes) had echocardiography results before and within one week following the procedure. New or worsening TR was discovered in 13 patients (15%). Use of mechanical tools and younger age at extraction were found on multivariate analysis to be factors for TR development (P = 0.04 and P = 0.03 respectively). Average follow-up was 22.25 ± 21.34 months (range 8–93). There were no significant differences in the incidence of right-sided heart failure (50% vs. 23%, P = 0.192) or hospitalizations due to heart failure exacerbations (37.5% vs. 11%, P = 0.110). No patient required tricuspid valve repair or replacement. Death rates were similar in the TR and non-TR groups (20% vs. 33%).

Conclusions: TR following lead extraction is not uncommon but does not seem to affect survival or outcomes such as need for valve surgery. Its long-term effects remain to be determined. 

 

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: Stroke is a leading cause of death and disability worldwide. The risk factors for stroke overlap those for cardiovascular disease. Atrial fibrillation (AF) is a particularly strong risk factor and is common, particularly in the elderly. Maccabi Healthcare Services (MHS) has maintained a vascular registry of clinical information for over 100,000 members, among them patients with heart disease and stroke. 

Objectives: To determine the prevalence of stroke in MHS, and whether the association of AF and stroke, along with other risk factors, in the Maccabi population is similar to that in published studies.

Methods: Data on stroke and AF patients aged 45 and older were collected from the database for the year 2010, including age, previous transient ischemic attack (TIA), body mass index (BMI), prior myocardial infarction (MI), diabetes, hypertension, anticoagulation and dyslipidemia. A cross-sectional analysis was used to estimate stroke prevalence by AF status. A case-control analysis was also performed comparing a sample of stroke and non-stroke patients. This permitted estimation of the strength of associations for atrial fibrillation and various other combinations of risk factors with stroke. 

Results: Stroke prevalence ranged from 3.5 (females, age 45–54 years) to 74.1 (males, age 85+) per thousand in non-AF members, and from 29 (males, age 45–54) to 165 (males, age 85+) per thousand for patients with AF. AF patients had significantly more strokes than non-AF patients in all age groups. Stroke prevalence increased with age and was significantly higher in males. Multivariable analysis revealed that male gender, increasing age, AF, hypertension, diabetes, and history of TIA were highly significant risk factors for stroke. In addition, for males, dyslipidemia and prior MI were moderately strong risk factors. 

Conclusions: Analysis of the MHS vascular database yielded useful information on stroke prevalence and association of known risk factors with stroke, which is consistent with the epidemiological literature elsewhere. Further analysis of health fund data could potentially provide useful information in the future. 

 

Background: Obstructive sleep apnea (OSA) is a common health problem with an estimated prevalence of 4% among men, many of whom are undiagnosed and untreated. 

Objectives: To compare demographic characteristics, health profiles, risk factors, and disease severity in Arab and Jewish men with OSA syndrome.

Methods: In this cross-sectional study we retrospectively analyzed clinical data from the medical files of men ≥ 22 years old who were referred to the Rambam Medical Center sleep clinic during the period 2001–2009 with a suspected diagnosis of OSA. OSA severity was measured using the apnea-hypopnea index (AHI). Categorical variables were compared using the chi-square test. Relations between OSA severity and a set of independent risk factors were assessed by linear regression analysis.

Results: A total of 207 men were included (39 Arabs, 19%; 168 Jews, 81%). Arab participants were younger than their Jewish counterparts (45.5 ± 8.9 years vs. 49.8 ± 11.8, P = 0.04) and their body mass index (BMI) was higher (33.1 ± 5.1 vs. 30.0 ± 4.4, P = 0.001). OSA severity (AHI score) was higher among Arab men, with low, medium and high severity scores seen in 10%, 33% and 56% of Arab men vs 35%, 29% and 37% of Jewish men, respectively [T(198)=2.39, P = 0.02]. Mean blood oxygen saturation was comparable.

Conclusions: Arab men presenting for evaluation of sleep apnea harbored more severe OSA symptoms, were younger, and had higher BMI compared to Jewish men. Since OSA syndrome evolves for several years until it becomes severe, these findings suggest that Arab men seek medical assistance later than Jewish men with OSA.

 

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.