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Sat, 20.07.24

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November 2006
Y. Schwammenthal, R. Tsabari, M. Bakon, D. Orion, O. Merzeliak and D. Tanne
 Background: Rapid restoration of cerebral blood flow is the principle goal of acute ischemic stroke therapy. Intravenous recombinant tissue plasminogen activator is an effective therapy for acute ischemic stroke, has been available in the United States for over a decade and was approved for use in Israel at the end of 2004.

Objectives: To assess the implementation of intravenous rt-PA[1] in routine clinical care at our center after its formal approval in Israel, and the therapeutic and logistic implications for reperfusion therapy for acute ischemic stroke in Israel.

Methods: Patients with acute ischemic stroke, admitted between January 2005 and June 2006, who were treated with intravenous rt-PA or endovascular-based reperfusion were reviewed. Implementation, timing, safety and clinical outcomes were assessed.

Results: Forty-six patients received reperfusion therapy (37 with intravenous rt-PA and 9 with endovascular-based therapy), corresponding to 4.0% of ischemic stroke patients in 2005 and a projection of 6.2% in 2006. Mean age of intravenously treated patients was 67 years (range 22–85 years), median baseline NIHSS score was 14 (range 10–18, 25–75%) and the median ‘onset to drug time’ was 150 minutes (range 120–178, 25–75%). Symptomatic intracerebral hemorrhage and orolingual angioedema each occurred in one patient (2.7%). Significant clinical improvement occurred in 54% of treated patients and 38% of patients were independent at hospital discharge.

Conclusions: Use of reperfusion therapy for acute ischemic stroke has increased in our center after the formal approval of rt-PA therapy to over 5%, with ‘onset to drug time’, safety and outcome after intravenous rt-PA treatment comparing favorably with worldwide experience. A prerequisite for the implementation of effective reperfusion therapy and expansion of the proportion of patients treated nationwide is the establishment of a comprehensive infrastructure.


 





[1] rt-PA = recombinant tissue plasminogen activator


R.R. Leker, R. Eichel, G. Rafaeli and T. Ben-Hur
 Acute ischemic stroke is one of the leading causes of mortality and chronic disability in the western world. Yet, despite the enormous socioeconomic burden that it imposes, therapies to combat AIS are not widely available. Moreover, revascularization of the ischemic tissue with tissue plasminogen activator, the only FDA-approved therapy for AIS[1], is hampered by a very narrow therapeutic time window and is only used in a minority of patients. Cerebral ischemia leads to brain damage caused by several pathologic mechanisms that can potentially be blocked by neuroprotective drugs that aim to salvage the ischemic penumbra. However, despite numerous clinical trials no single drug candidate has proved efficacious in AIS. The current situation clearly calls for novel therapeutic strategies to be used in acute ischemic stroke. This review surveys some of these novel and promising cutting edge therapies.







[1] AIS = acute ischemic stroke


R. Hirsch and J.Y. Streifler
 Congenital heart disease is usually regarded as an esoteric field of medicine, dealt with primarily by dedicated specialists. However, over the last two decades a much broader attention has been given by the medical profession, the media and the general public, to the possible association between a minor and common congenital heart defect, namely a patent foramen ovale, and stroke. In recent months, unusual and unfortunate circumstances have made this topic one of the most fiercely debated medical issues in Israel. It is the belief of the authors of this paper that the association of PFO[1] and stroke can be better understood if the PFO is viewed as part of a broader aspect of congenital heart disease, and as such it will be presented. Paradoxical embolism is a mechanism of stroke unique to congenital heart disease. The direction and volume of shunted blood in various conditions have a central role in determining the risk of stroke, as will be explained. With this basic knowledge in mind, we shall critically assess the potential role of PFO in stroke patients, suggesting that each case be evaluated individually using the above-mentioned principles. Conditions that enhance the formation of clot or other embolic material will be discussed briefly. The review will conclude with the various treatment options and our center's own experience with this challenging topic.







[1] PFO = patent foramen ovale


D. Soffer
 Cerebral amyloid angiopathy is characterized by deposition of amyloid in the walls of leptomeninged and cerebral blood vessels. Its most common form, sporadic CAA[1] that results from deposition of β-amyloid peptide, which is the subject of this short review, is present in virtually all cases of Alzheimer diseases and is also common among non-demented subjects where its prevalence increases with age. Stroke due to massive cerebral lobar hemorrhage is the main clinical presentation of CAA, but transient neurologic symptoms due to microhemorrhages may also occur. CAA is also a risk factor for cerebral infarction and there is increasing evidence that CAA contributes to cognitive impairment in the elderly, usually in association with white matter abnormalities on imaging. Although the definitive diagnosis of CAA is neuropathologic, reliable diagnosis can be reached clinically, based on the occurrence of strictly lobar hemorrhages, particularly in the cortico-subcortical area when using gradient-echo or T2*-weighted magnetic resonance imaging. Experimental studies have shown that the origin of the vascular amyloid is neuronal, and age-related degenerative changes in the vessel walls prevent its clearance from the brain along perivascular spaces and promote Aβ[2] aggregation and CAA formation. The entrapped Aβ aggregetes are toxic to various vascular wall components, including smooth muscle cells, pericytes and endothelial cells, leading to their eventual destruction and predisposition of the vessel wall to rupture and hemorrhage. However, more research is necessary to decipher the mechanism of CAA formation and its relation to cognitive decline in the elderly.







[1] CAA = cerebral amyloid angiopathy

[2] Aβ = β-amyloid peptide


R. Segal, A. Furmanov and F. Umansky
 Background: The recent occurrence of a spontaneous intracerebral hemorrhage in Israel’s Prime Minister placed the scrutiny of local and international media on neurosurgeons as they made therapeutic decisions. In the ensuing public debate, it was suggested that extraordinary measures (surgical treatment) were undertaken only because of the celebrity of the patient.

Objectives: To evaluate the criteria used to select surgical versus medical management for SICH.

Methods: We retrospectively reviewed the files of 149 consecutive patients admitted with SICH[1] from January 2004 through January 2006 to our medical center. Their mean age was 66 (range 3–92 years), and 62% were male. SICH localization was lobar in 50% of patients, thalamus in 23%, basal ganglia in 15%, cerebellum in 13%, intraventricular in 6%, and pontine in 1%. Mean admission Glasgow Coma Score was 9 (range 3–15). Risk factors included hypertension in (74%), diabetes mellitus (34%), smoking (14%) and amyloid angiopathy (4%). Fifty percent of patients were on anticoagulant/antiplatelet therapy, including enoxaparin (3%), warfarin (7%), warfarin and aspirin (9%), or aspirin alone (34%).      

Results: Craniotomy was performed in 30% of patients, and ventriculostomy alone in 3%. Rebleed occurred in 9% of patients. Six months after the treatment 36% of operated patients were independent, 42% dependent, and 13% had died. At 6 months, 37% of non-operated patients were independent, 15% dependent, and 47% had died.

Conclusions: One-third of the SICH patients, notably those who were experiencing ongoing neurologic deterioration and had accessible hemorrhage, underwent craniotomy. The results are good, considering the inherent mortality and morbidity of SICH.


 





[1] SICH = spontaneous intracerebral hemorrhage


October 2006
S. Linden
 Approximately 60% of all worldwide deaths are caused by chronic disease resulting from modifiable health behaviors. In the United States, structured programs tailored to identify and modify health behaviors of patients with chronic illness have grown into a robust industry called disease management. DM[1] is premised upon the basic assumption that health services utilization and morbidity can be reduced for those with chronic illness by augmenting traditional episodic medical care services and support between physician visits. Given that Israel and the U.S. have similar demographics in their chronically ill populations, it would make intuitive sense for Israel to replicate efforts made in the U.S. to incorporate DM strategies. This paper provides a conceptual framework of how DM could be integrated within the current organizational structure of the Israeli healthcare system, which is uniquely conducive to the implementation of DM on a population-wide basis. While ultimately the decision to invest in DM lies with stakeholders at various institutional levels in Israel, this paper is intended to provide direction and support for that decision-making process.







[1] DM = disease management


M. Shtalrid, L. Shvidel, E. Vorst, E.E. Weinmann, A. Berrebi and E. Sigler
 Background: Post-transfusion purpura is a rare syndrome characterized by severe thrombocytopenia and bleeding caused by alloimunization to human platelet specific antigens following a blood component transfusion. The suggested incidence is 1:50,000–100,000 transfusions, most often occurring in multiparous women. The diagnosis is not easy because these patients, who are often critically ill or post-surgery, have alternative explanations for thrombocytopenia such as infection, drugs, etc.

Objectives: To describe patients with initially misdiagnosed PTP[1] and to emphasize the diagnostic pitfalls of this disorder.

Patients and Results: During a period of 11 years we have diagnosed six patients with PTP, four women and two men. The incidence of PTP was approximately 1:24,000 blood components transfused. We present the detailed clinical course of three of the six patients in whom the diagnosis was particularly challenging. The patients were initially misdiagnosed as having heparin-induced thrombocytopenia, systemic lupus erythematosus complicated by autoimmune thrombocytopenia, and disseminated intravascular coagulation. A history of recent blood transfusion raised the suspicion of PTP and the diagnosis was confirmed by appropriate laboratory workup.

Conclusions: PTP seems to be more frequent than previously described. The diagnosis should be considered in the evaluation of life threatening thrombocytopenia in both men and women with a recent history of blood transfusion.


 





[1] PTP = post-transfusion purpura


J-N. Zhou, D-Z. Wang, X-E. Huang, F-P Xu, J-Q. Shang and R-M. Gu
 Background: The combination of high dose preoperative radiotherapy and transanal abdominal transanal with radical proctosigmoidectomy and colo-anal anastomosis as a sphincter-preserving method has never been performed in mainland China.

Objectives: To assess the feasibility and efficacy of high dose preoperative radiotherapy and TATA[1] as a sphincter-preserving method in Jiangsu, an economically well-developed region of China with a population of 70 million people.

Methods: From September 1994 to September 2000, 25 consecutive patients with pathologically confirmed distal rectal adenocarcinoma were treated preoperatively with a total dose of 45–46 Gy at 1.8–2.0 Gy per fraction during 5 weeks. Sphincter-preserving surgery by TATA was performed 4–6 weeks after radiotherapy. 

Results: Acute toxicity of preoperative radiotherapy was tolerable. Eight percent of the patients presented pathologic complete tumor response after preoperative radiotherapy. All patients underwent TATA as scheduled. During a median follow-up of 70 months, the 5 year survival rate was 88%. The 5 year survival rate for those tumors down-staged to pathological T0 or to pT1 was 100%.

Conclusions: High dose preoperative radiotherapy and TATA as a sphincter-preserving method was feasible and efficient in Chinese patients with distal rectal cancer. In this study, the subset of patients with a good response to radiotherapy had a better clinical outcome.


 





[1] TATA = transanal abdominal transanal


E. Kaluski, Z. Gabara, N. Uriel, O. Milo, M. Leitman, J. Weisfogel, V. Danicek, Z. Vered and G. Cotter
 Background: External counter-pulsation is a safe and effective method of alleviating angina pectoris, but the mechanism of benefit is not understood.

Objectives: To evaluate the safety and efficacy of external counter-pulsation therapy in heart failure patients.

Methods: Fifteen symptomatic heart failure patients (subsequent to optimal medical and device therapy) underwent 35 hourly sessions of ECPT[1] over a 7 week period. Before and after each ECPT session we performed pro-B-type natriuretic peptide and brachial artery function studies, administered a quality of life questionnaire, and assessed exercise tolerance and functional class.

Results: Baseline left ventricular ejection fraction was 28.1 ± 5.8%. ECPT was safe and well tolerated and resulted in a reduction in pro-BNP[2] levels (from 2245 ± 2149 pcg/ml to 1558 ± 1206 pcg/ml, P = 0.022). Exercise duration (Naughton protocol) improved (from 720 ± 389 to 893 ± 436 seconds, P = 0.0001), along with functional class (2.63 ± 0.6 vs. 1.93 ± 0.7, P = 0.023) and quality of life scores (54 ± 22 vs. 67 ± 23, P = 0.001). Nitroglycerine-mediated brachial vasodilatation increased (11.5 ± 7.3% vs. 15.6 ± 5.2%, P =0.049), as did brachial flow-mediated dilation (8.35 ± 6.0% vs. 11.37 ± 4.9%, P = 0.09).

Conclusions: ECPT is safe for symptomatic heart failure patients and is associated with functional and neurohormonal improvement. Larger long-term randomized studies with a control arm are needed to confirm these initial encouraging observations.


 





[1] ECPT = external counter-pulsation therapy

[2] BNP = B-type natriuretic peptide


M. Klein, N. Weksler, A. Borer, L. Koyfman, J. Kesslin and G.M. Gurman
 Background: Transport of hemodynamic unstable septic patients for diagnostic or therapeutic interventions outside the intensive care unit is complex but sometimes contributes to increasing the chance of survival.

Objective: To report our experience with terlipressin treatment for facilitation of transport to distant facilities for diagnostic or therapeutic procedures in septic patients treated with norepinephrine.

Methods:  We conducted a retrospective analysis of the records of our ICU[1], identifying the patients with septic shock who required norepinephrine for hemodynamic support.

Results: Terlipressin was given to 30 septic shock patients (15 females and 15 males) who were on high dose norepinephrine (10 μg/min or more) in order to facilitate their transport outside the ICU. The dose of terlipressin ranged from 1 to 4 mg, with a mean of 2.13 ± 0.68 mg. The dose of norepinephrine needed to maintain systolic blood pressure above 100 mmHg decreased following terlipressin administration, from 21.9 ± 10.4 μg/min (range 5–52 μg/min) to 1.0 ± 1.95 (range 0–10) (P < 0.001). No patients required norepinephrine dose adjustment during transport. No serious complications or overshoot in blood pressure values were observed following terlipressin administration. Acrocyanosis occurred only in eight patients receiving more than 1 mg of the drug. The overall mortality rate was 50%.

Conclusions: Our data suggest that terlipressin is effective in septic shock. Because it is long-acting and necessitates less titration it might be indicated for patient transportation.


 





[1] ICU = intensive care unit



 
V.H. Eisenberg, D. Raveh, Y. Meislish, B. Rudensky, Y. Ezra, A. Samueloff, A.I. Eidelman and M.S. Schimmel
 Background: Previous assessments of maternal group B Streptococcus carrier rates in women delivering at Shaare Zedek Medical Center ranged between 3.5 and 11% with neonatal sepsis rates of 0.2–0.9/1000 live births. Because of low colonization and disease rates, routine prenatal cultures of GBS[1] were not recommended, and intrapartum prophylaxis was mainly based on maternal risk factors.

Objectives: To determine whether this policy is still applicable. 

Methods: We performed prospective sampling and follow-up of women admitted for labor and delivery between February 2002 and July 2002. Vaginal and rectal cultures were obtained before the first pelvic examination. GBS isolation was performed using selective broth medium, and identified by latex agglutination and serotyping. Demographic data were collected by means of a standardized questionnaire. Data on the newborns were collected throughout 2002.

Results: Of the 629 sampled women, 86 had a positive culture and a carrier rate of 13.7%. A borderline significantly higher carriage rate was observed among mothers of North American origin (21% vs. 13.1%, P = 0.048), and a higher attack rate in their infants (3.8/1000 compared with 0.5/1000 live births in our general maternal population, P = 0.002). Eight newborns had early-onset neonatal GBS sepsis (a rate of 0.8/1000 live births), but none of them benefited from intrapartum antibiotic prophylaxis.

Conclusions: An increased neonatal disease rate was observed in a population with a higher colonization rate than previously seen. In lieu of the higher carrier rates, we now recommend routine prenatal screening for GBS in our perinatal population.


 





[1] GBS = group B Streptococcus


H.S. Oster, M. Hoffman, S. Prutchi-Sagiv, O. Katz, D. Neumann and M. Mittelman
 Recombinant human erythropoietin has become an essential part of the management of anemic patients with end-stage renal disease. It is also used to treat the anemia associated with cancer and other diseases, and it improves quality of life. In recent years, studies in animals and humans have focused on the use of rHuEPO[1] for other indications. It has been found to play a role in both cardioprotection and neuroprotection. It has effects on the immune system, and can cause regression in hematologic diseases such as multiple myeloma. It may also improve the response of solid tumors to chemotherapy and radiation therapy. On the other hand, concerns have been raised following two studies of patients with solid tumors in whom those treated with rHuEPO had diminished survival. Criticism of the design of these studies makes it clear that large, well-designed, randomized trials must be performed to determine the role of rHuEPO in the treatment of cancer, and more generally to clarify the full clinical benefits of the drug, while minimizing the harm.







[1] rHuEPO = recombinant human erythropoietin


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