Effects of Transendocardial Delivery of Bone Marrow-Derived CD133+ Cells on Left Ventricle Perfusion and Function in Patients With Refractory Angina: Final Results of Randomized, Double-Blinded, Placebo-Controlled REGENT-VSEL Trial.

RATIONALE: New therapies for refractory angina are needed. OBJECTIVE: Assessment of transendocardial delivery of bone marrow CD133+ cells in patients with refractory angina. METHODS AND RESULTS: Randomized, double-blinded, placebo-controlled trial enrolled 31 patients with recurrent Canadian Cardiovascular Society II-IV angina, despite optimal medical therapy, ≥1 myocardial segment with inducible ischemia in Tc-99m SPECT who underwent bone marrow biopsy and were allocated to cells (n=16) or placebo (n=15). Primary end point was absolute change in myocardial ischemia by SPECT. Secondary end points were left ventricular function and volumes by magnetic resonance imaging and angina severity. After 4 months, there were no significant differences in extent of inducible ischemia between groups (summed difference score mean [±SD]: 2.60 [2.6] versus 3.63 [3.6], P=0.52; total perfusion deficit: 3.60 [3.6] versus 5.01 [4.3], P=0.32; absolute changes of summed difference score: -1.38 [5.2] versus -0.73 [1.9], P=0.65; and total perfusion deficit: -1.33 [3.3] versus -2.19 [6.6], P=0.65). There was a significant reduction of left ventricular volumes (end-systolic volume: -4.3 [11.3] versus 7.4 [11.8], P=0.02; end-diastolic volume: -9.1 [14.9] versus 7.4 [15.8], P=0.02) and no significant change of left ventricular ejection fraction in the cell group. There was no difference in number of patients showing improvement of ≥1 Canadian Cardiovascular Society class after 1 (41.7% versus 58.3%; P=0.68), 4 (50% versus 33.3%; P=0.63), 6 (70% versus 50.0%; P=0.42), and 12 months (55.6% versus 81.8%; P=0.33) and use of nitrates after 12 months. CONCLUSION: Transendocardial CD133+ cell therapy was safe. Study was underpowered to conclusively validate the efficacy, but it did not show a significant reduction of myocardial ischemia and angina versus placebo. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01660581.

[Drugs acting on the heart-conductive system in suicide attempts]. / Leki dzialajace na uklad bodzcotwórczo-przewodzacy serca spozywane w celach samobójczych.

UNLABELLED: The prevalence of diseases of the cardiovascular system is the cause of their frequent use, and thus, easy availability of drugs acting on the cardiovascular system, including people they do not require. In Poland, annually are taken from 4.5 to 5.5 thousand suicide attempts, about 3.7% of them due to excessive consumption of pharmaceuticals. The aim of this study was to analyze patients who for suicidal attempts ingested drugs acting on the cardiac conduction system, and to study performed diagnostic and therapeutic procedures and obtained results. MATERIAL AND METHODS: The study included all hospitalized in the years 1995-2010 in the Department of Anesthesiology and Intensive Care patients after excessive suicidal ingestion of drugs acting on the heart conductive system. The study group comprised a total of 40 patients aged from 15 to 70 years. RESULTS: Suicide attempts in the study group were mostly taken by the lonely people and by the subjects with disturbed adaptation. The patients were unconscious mainly after ingestion of psychotropic drugs. From the 40-person group of patients after suicidal ingestion of drugs affecting the conduction system of heart eight patients (20%) required respirator. It has not been shown that any group of drugs significantly more frequent induced respiratory distress requiring mechanical assistance. Rhythm and conduction disturbances during hospitalization occurred in 15 patients (38%), of which 12 (30%) required temporary endocardial stimulation. The study revealed the longest ventricular stimulation need in patients after consumption of calcium channel blockers. Blood pressure in half of the patients was depressed, and 15 of them (38%) required the use of pressor amines. From the 40-person group 2 people died (one patient after ingestion of 4000 mg of propranolol and the other after eating 6000 mg of verapamil). Patients who died differed from the other patients with in younger age, longer time elapsed since the consumption of drugs to their hospitalization, during admission they had undetectable blood pressure, bradycardia, and decreased serum potassium levels. The remaining 38 patients (95%) were discharged from the Department of Anesthesiology and Intensive Care. CONCLUSIONS: Attempts to take his own life with the use of drugs in the cardiac conduction system in the study group were taken by a lonely and adaptive disturbances. The most commonly used preparations for suicide were beta-adrenergic receptors blockers, whereas hemodynamic abnormalities, arrhythmias and conduction disturbances were observed more frequently after the drugs that block calcium channels. In patients with life-saving use in suicide attempts important role in addition to medication dosage plays an elapsed time of their consumption and speed of action taken to remove and prevent absorbtion the poison", as well as close supervision in the intensive care unit.

[The clinical implications in patients after calcium channel blockers overdose--own observations]. / Implikacje kliniczne u chorych po spozyciu nadmiernej dawki leków blokujacych kanaly wapniowe--obserwacje wlasne.

UNLABELLED: Calcium channel blockers are drugs often used in circulatory system diseases. Their overdose can cause asystoly, III grade of atrioventricular dissociation, heart insufficiency and cardiogenic shock. Due to wide availability of these drugs access to them for subjects who want commit suicide is easy. In a specialist literature predominantly you can find case reports about calcium channel blockers suicidal overdose. Our experience includes 12 such cases. The aim of the study was to analyze patients after suicidal calcium channel blockers overdose. MATERIAL AND METHODS: In all cases medical interview, physical examination, neurological consultation, ecg, echocardiography, laboratory tests and in most cases--gasometry and toxicology test were performed. RESULTS: In analyzed 12 subjects group during admission, 7 patients were conscious, 2 had consciousness disturbances and 3 subjects were unconscious. Due to significant hypotonia 10 patients were treated with pressive amines. Arrhythmia and conduction disturbances were treated with endocavitary heart stimulation. There were 2 patients who needed mechanical respiratory support and one person, who due to refractory on farmacologic treatment, cardiogenic shock - needed intra aortal balloon pumping assistance. One person died during the first day of hospitalization. All other patients were discharged from the ward with improvement. CONCLUSIONS: Calcium channel blockers intoxications are rare, but usually are characterized by serious course and uncertain prognosis. Temporary endocavitary heart stimulation during calcium channel blockers intoxication usually needs electrode repositions due to ineffective stimulation depending on stimulation threshold increase. Our results show, that extremely fundamental for intoxicated patient are, easy to perform, activities which limit gastro-intestinal drug absorbtion.

Risk factors of complications during noninvasive mechanical ventilation -assisted flexible bronchoscopy.

PURPOSE: Flexible bronchoscopy (FB) causes airway narrowing and may cause respiratory failure (RF). Noninvasive mechanical ventilation (NIV) is used to treat RF. Until recently, little was known about noninvasive mechanical ventilation assisted flexible bronchoscopy (NIV-FB) risk and complications. MATERIALS AND METHODS: A retrospective analysis of NIV-FB performed in 20 consecutive months (July 1, 2018-February 29, 2020) was performed. Indications for: FB and NIV, as well as impact of comorbidities, blood gas results, pulmonary function test results and sedation depth, were analyzed to reveal NIV-FB risk. Out of a total of 713 FBs, NIV-FB was performed in 50 patients with multiple comorbidities, acute or chronic RF, substantial tracheal narrowing, or after previously unsuccessful FB attempt. RESULTS: In three cases, reversible complications were observed. Additionally, due to the severity of underlining disease, two patients were transferred to the ICU where they passed away after >48h. In a single variable analysis, PaO2 69 â€‹± â€‹18.5 and 49 â€‹± â€‹9.0 [mmHg] (p â€‹< â€‹0.05) and white blood count (WBC) 10.0 â€‹± â€‹4.81 and 14.4 â€‹± â€‹3.10 (p â€‹< â€‹0.05) were found predictive for complications. Left heart disease indicated unfavorable NIV-FB outcome (p â€‹= â€‹0.046). CONCLUSIONS: NIV-FB is safe in severely ill patients, however procedure-related risk should be further defined and verified in prospective studies.

Day and time of admissions to intensive care units - does it matter?

BACKGROUND: The literature data pertaining to the significance of day and time of ICU admission for outcomes of patients are inconsistent. The issue has not been analysed in Poland to date. The aim of the study was to gather information about differences between patients admitted to ICU outside regular working hours (off-hours) and those admitted during working hours (on-hours). METHODS: Analysis involved 20,651 patients from the Silesian Registry of Intensive Care Units carried out since 2010. The findings demonstrated that 34.8% of patients were admitted to ICUs during on-hours (between 8.00 a.m. and 3 p.m. on weekdays) and 65.2% were admitted during off-hours (outside regular working hours). The incidence of admissions and data of patients in both groups were compared in terms of the population characteristics and treatment outcomes. RESULTS: The incidence of admissions (calculated per each 24 hours of treatment) was found to be almost twice as high during on-hours, as compared to off-hours (14.5 vs. 6.9 patients/day). Patients admitted to the ICU during on-hours were less likely to be admitted from the surgical department (19.1% vs. 31.0%, P < 0.001), and more likely to be admitted from the emergency department (25.3% vs. 14.2%, P < 0.001). The incidence of off-hours admissions of cancer patients was lower (5.3% vs. 10.8%, P < 0.001), as compared with patients with alcohol dependence syndrome (10.3% vs. 6.9%, P < 0.001). Patients admitted during off-hours were in more severe conditions and had higher APACHE II scores (on average, 23.8 ± 8.8 vs. 21.8 ± 8.8, P < 0.001); their mortality rates were higher compared to the remaining population (46.8% vs. 39.4%, P < 0.001). CONCLUSIONS: Patients admitted to ICUs during off-hours are in more severe general condition and their treatment outcomes are worse, as compared to patients admitted to ICU during on-hours.

Effects of trans-endocardial delivery of bone marrow-derived CD133+ cells on angina and quality of life in patients with refractory angina: A sub-analysis of the REGENT-VSEL trial.

BACKGROUND: The REGENT-VSEL trial demonstrated a neutral effect of transendocardial injection of autologous bone marrow (BM)-derived CD133+ in regard to myocardial ischemia. The current sub-analysis of the REGENT VSEL trial aims to assess the effect stem cell therapy has on quality of life (QoL) in patients with refractory angina. METHODS: Thirty-one patients (63.0 ± 6.4 years, 70% male) with recurrent CCS II-IV angina, despite optimal medical therapy, enrolled in the REGENT-VSEL single center, randomized, double-blinded, and placebo-controlled trial. Of the 31 patients, 16 individuals were randomly assigned to the active stem cell group and 15 individuals were randomly assigned to the placebo group on a 1:1 basis. The inducibility of ischemia, (≥ one myocardial segment) was confirmed for each patient using Tc-99m SPECT. QoL was measured using the Seattle Angina Questionnaire. Each patient completed the questionnaire prior to treatment and at the time of their outpatient follow-up visits at 1, 4, 6, and 12 months after cell/placebo treatment. RESULTS: The main finding of the REGENT-VSEL trial sub-analysis was that transendocardial injection of autologous BM-derived CD133+ stem cells in patients with chronic refractory angina did not show significant improvement in QoL in comparison to the control group. Moreover, there was no significant difference between cell therapy and placebo in a number of patients showing improvement of at least 1 Canadian Cardiovascular Society class during the follow-up period. CONCLUSIONS: Intra-myocardial delivery of autologous CD133+ stem cells is safe and feasible but does not show a significant improvement in the QoL or angina pectoris symptoms in patients with chronic myocardial ischemia.

OLIGO 7 primer analysis software.

OLIGO performs a range of functions for researches in PCR and related technologies such as PCR and sequencing primer selection, hybridization probe design, inverse and real-time PCR, analysis of false priming using a unique priming efficiency (PE) algorithm, design of consensus and multiplex, nested primers and degenerate primers, reverse translation, and restriction enzyme analysis and prediction; based on a protein sequence, oligonucleotide database allows fully automatic multiplexing, primer secondary structure analysis, and more. OLIGO allows for sequence file batch processing that is essential for automation. This chapter describes the major functions of OLIGO version 7 software.

Relationship between blood, nasopharyngeal and urinary bladder temperature during intravascular cooling for therapeutic hypothermia after cardiac arrest.

OBJECTIVES: Therapeutic hypothermia improves survival and neurological outcome in patients successfully resuscitated after cardiac arrest. Accurate temperature control during cooling is essential to prevent cooling-related side effects. METHODS: Prospective observational study of 12 patients assessed during therapeutic hypothermia (32-34°C) achieved by intravascular cooling following cardiac arrest. Simultaneous temperature measurements were taken using a Swan-Ganz catheter (blood temperature BLT), nasopharyngeal probe (nasopharyngeal temperature NPT) and the urinary bladder catheter (urinary bladder temperature UBT). A total of 1728 measurements (144 measurements per patient) were recorded over a 48-h period and analyzed. Blood temperature was considered as the reference measurement. RESULTS: Temperature profiles obtained from BLT, NPT and UBT compared with the use of analysis of variance did not differ significantly. Pearson correlation revealed that the correlation between BLT and NPT as well as BLT and UBT was statistically significant (r=0.96, p<0.001 and r=0.95, p<0.001, respectively). Bland-Altman analysis proved that the agreement between all measurements was satisfactory and the differences were not clinically important. CONCLUSIONS: In 12 post-cardiac arrest patients undergoing intravascular cooling, both nasopharyngeal and urinary bladder temperature measurements were similar to blood temperatures measured using a pulmonary artery catheter.

Comparison of intravascular and conventional hypothermia after cardiac arrest.

BACKGROUND: Therapeutic hypothermia is currently the best-documented method of improving neurological outcomes in patients after cardiac arrest and successful resuscitation. There is a variety of methods for lowering body temperature. However, there are no data showing that any specific method of cooling improves the results or increases survival. A simple method involving surface cooling and ice-cold intravenous fluids, as well as more technologically advanced methods, are used in clinical practice. One of the more advanced methods is intravascular hypothermia, during which cooling is carried out with the use of a special catheter located in the central vein. AIM: To compare cooling with the use of intravascular hypothermia and cooling using the traditional method. METHODS: A prospective study was performed in 41 patients with acute coronary syndromes who did not regain consciousness after out-of-hospital or in-hospital cardiac arrest and restoration of spontaneous circulation. Therapeutic hypothermia (32-34°C) was obtained with the use of an intravascular method (group A, n = 20) or a traditional method (group B, n = 21) for a period of 24 hours. Intravascular cooling involved the use of a catheter inserted in the femoral vein connected to a heat exchanger (Alsius Coolgard, Zoll, Chelmsford, MA, USA). Traditional cooling was carried out using uncontrolled surface cooling, ice-cold intravenous fluids and ice-cold gastric lavage. Nasopharyngeal and urinary bladder temperatures were recorded hourly. The main analysed temperature was the urinary bladder temperature, as the heat exchanger in the intravascular hypothermia group was controlled by the readings taken from this site. Temperature profiles were compared. RESULTS: Temperature < 34°C was reached in 19 (95.0%) patients in group A and in 11 (52.4%) patients in group B (p = 0.004). Stable temperature profile (temperature in the range 32-34°C during the final 12 h of cooling) was reached in 16 (80%) patients in group A and in three (14.3%) patients in group B (p < 0.001). Periods of inadequate cooling (temperature > 34°C) and temperature overshoots (temperature < 32°C) were significantly more frequent in group B. Temperature profiles were significantly different in both groups in the readings taken from both sites. CONCLUSIONS: The presented technique of intravascular hypothermia provides more precise temperature control in comparison with the traditional method.