The histopathology of severe persistent asthma and chronic obstructive pulmonary disease is predominantly characterized by neutrophilic inflammation. It is posited that chronic hypoxia from hypoventilation in combination with hypoperfusion and hypercapnia are associated with induction of pulmonary tissue acidosis in SPA[1] and COPD[2], which in turn provide ideal conditions to induce danger-associated molecular patterns, i.e., crystallized and calcium pyrophosphate. These stimuli in combination with other danger-related biochemical signals are capable of stimulating an innate immune receptor (cryopyrin inflammasome, NALP3) and cause interleukin-1β secretion with subsequent neutrophilic inflammation. There is evidence to suggest that the mechanisms and pathobiology associated with chronic hypoxia, reduced perfusion and reoxygenation in SPA/COPD may exhibit similarities to the biphasic pathobiology involved in ischemia-reperfusion injury. A rationale is suggested for trials of IL-1β[3] targeted therapies as an adjunct strategy to control neutrophilic inflammation in these conditions.

Background: Peritoneal carcinomatosis is an advanced form of cancer with poor prognosis that in the past was treated mainly palliatively. Today, the definitive approach to peritoneal surface malignancy involves peritonectomy, visceral resection and perioperative intra-abdominal hyperthermic chemotherapy. The anticipated results range from at least palliative to as far as intent to cure. Proper patient selection is mandatory.

Objectives: To determine whether cytoreductive surgery and intraperitoneal hyperthermic chemotherapy can extend survival, and with minor complications only, in patients with peritoneal carcinomatosis.

Methods: Twenty-two IPHP[1] procedures were performed in 17 patients with peritoneal carcinomatosis in our institution between 1998 and 2007: 6 had pseudomyxoma peritonei, 5 had colorectal carcinoma, 3 had ovarian cancer and 3 had mesotheliomas. All patients underwent cytoreductive surgery, leaving only residual metastasis < 1 cm in size. Intraperitoneal chemotherapy was administered through four large catheters (2F) using a closed system of two pumps, a heat exchanger and two filters. After the patient’s abdominal temperature reached 41°C, 30–60 mg mitomycin C was circulated intraperitoneally for 1 hour.

Results: The patients had a variety of anastomoses. None demonstrated anastomotic leak and none experienced major complications. Six patients had minor complications (pleural effusion, leukopenia, fever, prolonged paralytic ileus, sepsis), two of which may be attributed to chemotherapy toxicity (leukopenia). There was no perioperative mortality. Some patients have survived more than 5 years.

Conclusions: IPHP is a safe treatment modality for patients with peritoneal carcinomatosis. It has an acceptable complications rate and ensures a marked improvement in survival and in the quality of life in selected patients.

Background: Spontaneous coronary reperfusion occurs in 7–27% of patients with ST elevation myocardial infarction, and is an independent predictor of myocardial salvage, percutaneous coronary intervention success, and improved outcome.

Objectives: To determine the optimal PCI[1] time for patients admitted to the hospital due to STEMI[2] with SCR[3].

Methods: We performed a retrospective analysis of all patients admitted to the coronary care unit between July 2002 and November 2004 with a diagnosis of STEMI with SCR.

Results: The study group comprised 86 patients. There was not a single reinfarction episode during an observation period of 6579 patient hours. Cardiac catheterization was executed early (< 24 hours from pain onset) in 26 patients and late (> 24 hours) in 55. Pre-PCI angiographic TIMI flow 2–3 was seen in > 95% in both groups. PCI was performed more frequently in the “early” group (P = 0.024), while multi-vessel coronary artery disease (P = 0.094) requiring coronary bypass surgery (P = 0.056) was observed more frequently in the “late catheterization” group. Myocardial infarction and angina pectoris at 30 days occurred more frequently in the early catheterization group (P = 0.039), however no difference in any major adverse cardiac events was detected during long-term follow-up (491 ± 245 days).

Conclusions: Reinfarction after STEMI with SCR is a rare event. Early PCI in patients with STEMI and SCR, even when executed with aggressive anti-platelet therapy, seems to result in an excess of early MACE, without any long-term advantage. Prospective randomized trials should determine the optimal PCI timing for these patients.

Background: The significance of arrhythmia occurring after successful recanalization of an occluded artery during treatment following primary percutaneous coronary intervention for ST-segment elevation myocardial infarction is controversial.

Objectives: To study the association of reperfusion arrhythmia with short and long-term survival.

Methods: We used a prospective registry of consecutive STEMI[1] patients undergoing PPCI[2]. Patients with an impaired epicardial flow (TIMI flow grade < 3) at the end of the procedure were excluded.

Results: Of the 688 patients in the study group, 22% were women. Mean (± SD) age of the cohort was 61 (± 14) years and frequent co-morbidities included diabetes mellitus (25%), dyslipidemia (55%), hypertension (43%) and smoking (41%). RA[3] was recorded in 200 patients (29%). Patients with RA had lower rates of diabetes (16% vs. 30%, P < 0.01) and hypertension (48% vs. 62%, P < 0.01), and a shorter median pain-to-balloon time (201 vs. 234 minutes, P < 0.01) than patients without RA. Thirty day mortality was 3.7% and 8.3% for patients with and without RA, respectively (P = 0.04). After controlling for age, gender and pain-to-balloon time the hazard ratio for mortality for patients with RA during a median follow-up period of 466 days was 0.46 (95% confidence interval 0.23–0.92).

Conclusions: The occurrence of RA immediately following PPCI for acute STEMI is associated with better clinical characteristics and identifies a subgroup with a particularly favorable prognosis.

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.

Background: The degree of left ventricular dysfunction determines the prognostic outcome of patients with acute myocardial infarction.

Objectives: To define the clinical, angiographic and procedural variables related to LV[1][1] dysfunction in patients with  with anterior wall AMI[1][2] referred for primary percutaneous coronary intervention.

Methods: The sample included 168 patients treated by primary PCI[1][3] for first anterior wall AMI. Clinical, demographic and medical data were collected prospectively into a computerized registry, and clinical outcome (death, reinfarction, major cardiovascular event) were evaluated during hospitalization and 30 days after discharge. Patients were divided into three groups by degree of LV dysfunction (mild, moderate, severe) and compared for clinical, angiographic and procedural variables.

Results: LV dysfunction was associated with pre-PCI renal failure (serum creatinine > 1.4 mg/dl), peripheral vascular disease, high peak creatine kinase level, longer door to balloon time, low TIMI flow grade before and after PCI, and use of an intraaortic balloon pump. On multivariate analysis adjusted for baseline differences, peak creatine kinase level (r = 0.3, P = 0.0001) and door to needle time (r = 0.2, P = 0.008) were the most significant independent predictors of moderate or severe LV dysfunction after anterior AMI.

Conclusion: Abnormal LV function after first anterior AMI can be predicted by door to balloon time and the size of the infarction as assessed by creatine kinase levels. Major efforts should be made to decrease the time to myocardial reperfusion.

[1][1] LV = left ventricular

[1][2] AMI = acute myocardial infarction

[1][3] PCI = percutaneous coronary intervention 

Background: Intravenous recombinant tissue plasminogen activator therapy within 3 hours of stroke onset is a proven effective treatment for acute ischemic stroke.

Objectives: To assess the feasibility and safety of rt-PA[1] therapy for reperfusion in routine clinical practice in Israel, in a setting of a dedicated stroke unit.

Methods: Consecutive patients presenting within less than 3 hours of stroke onset were evaluated by an emergency physician and the neurology stroke team. After brain computerized tomography eligible patients were treated with intravenous rt-PA (0.9 mg/kg; maximum dose 90 mg) according to an in-hospital protocol corresponding to recommended criteria. Patients were admitted to the acute stroke unit. Safety and clinical outcome were routinely assessed. Re-canalization was assessed by serial transcranial Doppler.

Results: The study group comprised 16 patients, mean age 61 years (range 47–80 years), male to female ratio 10:6, whose median baseline National Institutes of Health stroke scale was 13 (range 6–24). They were treated within a mean door-to-CT time of 39 minutes (range 17–62 min), door-to-drug time 101 minutes (range 72–150), and stroke onset-to-drug time 151 minutes (range 90–180). There was an early improvement within 24 hours (of ≥ 4 points in the NIHSS[2] score) in 7 patients (44%) and no early deteriorations. There were no protocol deviations, no symptomatic intracranial hemorrhages, and no major systemic hemorrhage within 36 hours of rt-PA treatment. Three asymptomatic hemorrhagic transformations of the infarct were noted on routine follow-up brain CT associated with neurologic improvement. Outcome data were comparable to the National Institute of Neurological Disorders and Stroke rt-PA Stroke Study.

Conclusion: Intravenous rt-PA treatment within 3 hours of stroke onset in routine clinical practice in Israel is feasible and appears safe in the setting of a neurology stroke unit and team. Careful implementation of rt-PA therapy for selected patients in Israel is encouraged.

Background: Reperfusion practices have changed markedly over the last few years with the introduction of primary percutaneous coronary intervention. This technique has gained growing popularity in Israel, but little published data are available regarding the delays to primary PCI[1] in real life in this country.

Objectives: To examine temporal trends in time to reperfusion achieved in a large tertiary center over 6 years.

Results: Between 1997 and 2002, 1,031 patients were admitted to our hospital with ST elevation myocardial infarction. Of these, 62% underwent thrombolysis and 38% primary PCI. The proportion of patients referred for primary PCI increased steadily, from 14% in 1997 to 68% in 2002. Door to treatment time among patients referred for thrombolysis or primary PCI was 54 ± 42 and 117 ± 77 minutes, respectively (P < 0.00001). The door to needle time in patients given thrombolysis remained virtually unchanged during the study period at around 54 minutes. In contrast, the door to balloon time has progressively and substantially decreased, from 175 ± 164 minutes in 1997 to 96 ± 52 minutes in 2002.

Conclusions: There is a steady increase in the proportion of patients referred for primary PCI than for thrombolysis. The door to needle delay in patients given thrombolysis substantially exceeds the recommended time. The door to balloon time has declined considerably but still slightly exceeds the recommended time. Given the inherent delay between initiation of lysis and arterial recanalization, it appears from our experience that PCI does not substantially delay arterial reperfusion as compared to thrombolysis. Efforts should continue to minimize delays to reperfusion therapy.