Israel Medical Association Journal

Mesenchymal stem cells, or mesenchymal stromal cells, have emerged as a major new cell technology with a diverse spectrum of potential clinical applications. MSCs[1] were originally conceived as stem/progenitor cells to rebuild diseased or damaged tissues. Over the last 14 years, since the first report of MSC infusions in patients, the cells have been shown to suppress graft vs. host disease, stimulate linear growth in a genetic disorder of bone, and foster engraftment of haplo-identical hematopoietic stem cells. In all cases, few, if any, MSCs were identified at the site of clinical activity. This experience suggests a remarkable clinical potential, but a different general mechanism of action. Systemically infused MSCs seem to exert a therapeutic effect effect through the release of cytokines that act on local, or perhaps distant, target tissues. Rather than serving as stem cells to repair tissues, they serve as cellular factories that secrete mediators to stimulate the repair of tissues or other beneficial effects. Since both the tissue source of MSCs and the ex vivo expansion system may significantly impact the cytokine expression profile, these parameters may be critically important determinants of clinical activity. Furthermore, cell processing protocols may be developed to optimize the cell product for a specific clinical indication. For example, MSC-like cells isolated from placenta and expanded in a three-dimensional bioreactor have recently been shown to increase blood flow in critical limb ischemia. Future efforts to understand the cytokine expression profile will undoubtedly expand the range of MSC clinical applications.

The incidence of aortic valve stenosis is growing rapidly in the elderly. Nonetheless, many symptomatic patients are not referred for surgery usually because of high surgical risk. Unfortunately, percutaneous balloon valvuloplasty is unsatisfactory due to high recurrence rates. In 2002, Cribier and colleagues were the first to describe percutaneous aortic valve implantation, opening a new era of aortic stenosis management. In the present review we report a patient treated by this novel method, discuss and assess how it is implanated, report the findings of studies conducted to date, and suggest future directions for percutaneous treatment of aortic valve disease.
 

Background: Although unprotected left main coronary artery disease is considered by contemporary guidelines to be an indication for surgery, percutaneous coronary intervention may be necessary in patients at high surgical risk.

Objectives: To assess the outcome of angioplasty in the treatment of unprotected LMCA[1] disease.

Methods: Angiographic and clinical data were collected prospectively for all patients who underwent emergent or non-emergent (planned) therapeutic PCI[2] for unprotected LMCA disease at our center from 2003 to 2007. Baseline values were compared with findings at 1, 6 and 12 months after the procedure.

Results: The study group comprised 71 consecutive patients with a mean age of 74 ± 12 years; 63% were men, and 31% had diabetes. Forty-three patients had a planned procedure and 28 an emergent procedure. Mean EuroScore was 7.3 ± 3.6 (range 5–12). Forty-nine percent of the procedures were performed with bare metal stents and 51% with drug-eluting stents. Procedural success was achieved in 100% of cases. The overall mortality rate was 11.3% at 1 month, 18.3% at 6 months and 19.7% at 12 months. Elective PCI was associated with significantly lower mortality (2.3% vs. 25% at 1 month, 4.6% vs. 39% at 6 months and 6.9% vs. 39% at 12 months), and the use of drug-eluting stents was associated with lower rates of target vessel revascularization and major adverse cardiac events than use of bare metal stents (2.8% vs. 14% at 1 month, 8.3% vs. 43% at 6 and 12 months). Variables that correlated with increased mortality or MACE[3] at 6 and 12 months were cardiogenic shock, emergent PCI, ejection fraction < 35%, renal failure, distal left main stenosis location, and reference diameter < 3 mm.

Conclusions: PCI is a feasible and relatively safe therapeutic option for unprotected LMCA. The less favorable outcome of emergent compared to planned PCI is probably attributable to the overwhelming acute myocardial ischemic injury in emergent cases. The use of drug-eluting stents may improve the intermediate-term restenosis rate.

[1] LMCA = left main coronary artery

[2] PCI = percutaneous coronary intervention

Organophosphate and carbamate are mainly used to kill insects, thereby protecting livestock, crops, homes and communities. Yet, these compounds also convey great danger. OP[1] and CRB[2] poisoning is an important clinical problem, often life-threatening, especially in the pediatric population in rural areas where reaching a physician or hospital on time is difficult. We present a summary of accumulated toxicological knowledge as well as clinical and laboratory experience from a medical center serving a relatively vast rural area and pediatric population. We stress the importance of knowing how to recognize the classic signs of OP and CRB poisoning and when it is appropriate to investigate for such poisoning even in the absence of those signs. Like any medical emergency, OP and CRB poisoning requires prompt resuscitation and use of antidotes. Atropine, oxygen and fluids are the mainstay of therapy. Oximes, which were found useful in some cases of OP poisoning and useless in some cases of CRB poisoning, are absolutely safe as empiric treatment, which is often needed since the major differential diagnosis of OP poisoning is CRB poisoning that is clinically indistinguishable. We hope that continuing research will offer further insights into the management of such events, and we are confident that improved medical management of OP and CRB poisoning will result in a reduction of morbidity and other complications associated with intensive care procedures and hospitalization. 

Background: General hospital staff are often required to care for physically ill patients who arouse concern regarding risk of harm to themselves or others. Some of these patients will receive one-to-one "constant observation." This is the first Israeli study of general hospital patients with high risk behavior.

Objectives: To examine a population of general hospital patients whose behavioral management required the use of constant observation. Demographic and clinical parameters including physical diagnoses were examined, and risk factors for constant observation were identified. The findings of this study were compared to findings in previous studies.

Methods: This prospective observational study examined 714 inpatients referred for psychiatric consultation; 150 were found to require constant observation, and 156 who did not served as a control group.

Results: In this study younger age, suicidal concerns and alcohol/substance abuse were identified as risk factors for ordering constant observation. Ischemic heart disease and chronic obstructive pulmonary disease were the only physical diagnoses found to be significantly correlated with a longer duration of observation, regardless of admission duration. Constant observation was less frequently used in the management of organic brain syndrome patients in this study compared to other studies.  

Conclusions: Some of our results (predictive factors for constant observation) confirmed the findings of overseas studies. Our finding that a diagnosis of organic brain syndrome was not a predictive factor for constant observation was unexpected and requires further investigation. The correlation between a diagnosis of ischemic heart disease or COPD[1] and duration of observation has not been reported previously and warrants further studies.  

Background: Multi-detector computed tomography has advanced enormously and now enables non-invasive evaluation of coronary arteries as well as cardiac anatomy, function and perfusion. However, the role of cardiac MDCT[1] is not yet determined in the medical community and, consequently, many clinically unnecessary scans are performed solely on a self-referral basis.

Objectives: To prospectively evaluate the role of a cardiologist consultation and recommendation prior to the scan, and the influence on the diagnostic yield of cardiac MDCT.

Methods: In our center, a CT service was initiated, but with the prerequisite approval of a cardiologist before performance of the CT. Each individual who wanted and was willing to pay for a cardiac CT was interviewed by an experienced cardiologist who determined whether cardiac MDCT was the most appropriate next test in the cardiovascular evaluation. Subjects were classified into three groups: a) those with a normal or no prior stress test, no typical symptoms and no significant risk factors of coronary artery disease were recommended to perform a stress test or to remain under close clinical follow-up without MDCT; b) those with an equivocal stress test, atypical symptoms and/or significant risk factors were allowed to have cardiac MDCT; and c) those with positive stress test or clinically highly suspected CAD[2] were advised to go directly to invasive coronary angiography. CT findings were categorized as normal CAD (normal calcium score and no narrowings), < 50% and > 50% CAD.

Results: A total of 254 people were interviewed, and in only 39 cases did the cardiologist approve the CT. However, 61 of the 215, despite our recommendation not to undergo CT, decided to have the scan. Assessment of the 100 cases that underwent MDCT showed a statistically significant better discrimination of significant CAD, according to the cardiologist’s recommendation: MDCT not recommended in 3/54 (6%) vs. MDCT recommended in 12/39 (31%) vs. recommended invasive coronary angiography in 4/7 (57%) (P < 0.001).

Conclusions: Detection of coronary calcification, as well as MDCT angiography can provide clinically useful information if applied to suitable patient groups. It is foreseeable that MDCT angiography will become part of the routine workup in some subsets of patients with suspected CAD. Selection of patients undergoing MDCT scans by a cardiologist improves the ability of the test to stratify patients, preventing unnecessary scans in both high and low risk patients

Background: Cardiac computed tomography angiography is a relatively new imaging modality to detect coronary atherosclerosis.

Objectives: To explore the diagnostic value of CTA[1] in assessing coronary artery disease among asymptomatic patients.

Methods: In this retrospective single-centered analysis, 622 consecutive patients underwent CTA of coronary arteries between November 2004 and May 2006 at the Mor Institute for Cardiovascular Imaging in Bnei Brak, Israel. All patients were asymptomatic but had at least one risk factor for atherosclerotic CAD[2]. The initial 244 patients were examined with the 16-slice Brilliance CT scanner (Philips, Cleveland, OH, USA), and in the remaining 378 patients the 64-slice scanner (GE Healthcare, The Netherlands) with dedicated cardiac reconstruction software and electrocardiography triggering was used. Scanning was performed in the cranio-caudal direction. Images reconstructed in different phases of the cardiac cycle using a retrospective ECG-gated reconstruction algorithm were transferred to a dedicated workstation for review by experienced CT radiologists and cardiologists.

Results: Of 622 patients, 52 (8.4%) had severe obstructive atherosclerosis (suspected ≥ 75% stenosis) according to CTA interpretation. Invasive coronary angiography was performed in 48 patients while 4 patients had no further procedure. A non-significant CAD (e.g., diameter stenosis < 70%) was identified in 6 of 48 patients (12%) by selective coronary angiography. Forty-two patients showed severe CAD with at least one lesion of ≥ 70% stenosis. Percutaneous coronary intervention was performed in 35 patients and coronary artery bypass grafting surgery in the other 4 patients. Angioplasty procedures were successful in all 35 patients and stents were utilized in all cases without complications. No further complications occurred among the study cohort undergoing either PCI[3] or surgery. The 6 month survival rate in these patients was 100%.

Conclusions: Non-invasive coronary CTA appears to be a reliable technique, with reasonably high accuracy, to detect obstructive atherosclerosis in asymptomatic high risk patients for atherosclerotic CAD.

Background: Angiotensin-converting enzyme inhibitors and angiotensin receptor blockers improve prognosis in congestive heart failure and are the treatment of choice in these patients; despite this, the rates of ACE-I[1] usage in heart failure patients remain low in clinical practice.

Objectives: To evaluate the rate of ACE-I/ARB[2] treatment in hospitalized patients with CHF[3], and analyze the reasons for non-treatment.

Methods: We prospectively evaluated 362 consecutive patients hospitalized with CHF. Patients were evaluated for ACE-I/ARB usage at discharge and were followed for 1 year.

Results: At hospital discharge 70% of the patients were prescribed ACE-I/ARB treatment. Only 69% received recommended target or sub-target dosages, proven to improve prognosis. This decreased to 63% and 59% at 6 months and 12 months of follow-up respectively, due to a shift from sub-target levels to low dosages. Justified reasons for under-treatment were apparent in only 25% not optimally treated discharged patients and this decreased to 12% and 4% at 6 and 12 months follow-up, respectively. Common reasons for non-treatment at discharge were hyperkalemia and elevation in serum creatinine, while hypotension and cough were more prominent at follow-up. Clinical parameters associated with increased treatment rates were ischemic heart disease and the absence of chronic renal failure. Patients receiving treatment had lower hospitalization and mortality rates.

Conclusions: ACE-I/ARB treatment is still underutilized in patients discharged from hospital with a diagnosis of CHF. Increasing the awareness of the importance of these drugs may increase the number of patients treated.

Background: Diseases causing increased pulmonary pressure will subsequently cause a dilation of the pulmonary arteries and right heart chambers.

Objectives: To assess the capability of computed tomography angiography and high resolution CT to diagnose and estimate the severity of pulmonary arterial hypertension as compared with standard means of right heart catheterization, echocardiography and pulmonary function tests.

Methods: The study included 38 patients with PHT[1] who underwent CT angiography and HRCT[2] as part of their routine evaluation. Diagnose included: primary PHT (n=20), Eisenmenger syndrome (n=6), scleroderma (n=3), thromboembolic disease (n=3), and others (n=6). Mean pulmonary artery pressure was 58 mmHg (range 39–92 mmHg) by catheterization and peak systolic pressure 79 mmHg (range 40–135) by echocardiography. Findings for the diameters of the main pulmonary artery and its main branches, the ascending aorta, the right atria and ventricle as well as the position of the interventricular septum were compared with 22 chest CT scans as compared to patients with no known clinical history of pulmonary hypertension, performed for other reasons (trauma, oncology follow-up) during the study period. Correlations were also calculated with recent right heart catheterization, echocardiography and pulmonary function tests of the study group.

Results: Mean main pulmonary artery diameter in the study group was 3.55 ± 0.66 cm, pulmonary artery/ascending aorta ratio 1.2 ± 0.29, right pulmonary artery 2.63 ± 0.49 cm, left pulmonary artery 2.57 ± 0.5 cm. All diameters were significantly different from the control group (P < 0.0001). Main and right pulmonary artery diameters correlated to the pressure measurement by echocardiography (P = 0.001). Bronchial collaterals were found in 11 patients (30%). The position of the interventricular septum correlated well with the echocardiography study.

Conclusions: The size of the main pulmonary artery on CT angiography has a good predictive value regarding the severity of PHT.

Background: Carotid artery stenting is used as an alternative to surgical endarterectomy.

Objectives: To determine the outcome of CAS[1] in a retrospective cohort of patients.

Methods: Between July 1999 and March 2003, 56 consecutive patients with carotid artery stenosis who were considered ineligible for surgery were treated (45 male, 11 female, mean age 69). All cases were performed prior to the introduction of distal protective devices in Israel.

Results: Intraprocedural complications included transient neurological findings in 5 patients (8%), cerebrovascular accident in 2 (3%), hemodynamic changes in 11 (18%), and 4 procedural failures. Post-procedural complications included transient ischemic attack in 3 patients and cardiovascular accident in 6 (10%). At 30 days follow-up, three patients (5%) remained with signs of CVA[2]. Two patients (3%) died during the post-procedural period and 16 (28%) during the 5 year follow-up, one due to recurrent CVA and the remainder to non-neurological causes. Five-year carotid Doppler follow-up was performed in 25 patients (45%), which revealed normal stent flow in 21 (84%), 50–60% restenosis in 3 patients (12%) and > 70% restenosis in one patient (4%).

Conclusions: This study confirms that stent procedures are beneficial for symptomatic carotid stenosis in patients not eligible for surgery.