The role of weather conditions and normal level of air pollution in appearance of stroke in the region of Southeast Europe

We investigated correlation between the normal level of air pollution, weather conditions and stroke occurrence in the region of Southeast Europe with a humid continental climate. This retrospective study included 1963 patients, 1712 (87.2%) with ischemic (IS) and 251 (12.8%) with hemorrhagic stroke (HS) admitted to emergency department. The number of patients, values of weather condition (meteorological parameters) [air temperature (°C), atmospheric pressure (kPa), relative humidity (%)] and concentrations of air pollutants [particulate matter (PM₁₀), nitrogen dioxide (NO₂), ozone (O₃)], were recorded and evaluated for each season (spring, summer, autumn, winter) during 2 years (July 2008–June 2010). The highest rate of IS was observed during spring (28.9%) (p = 0.0002) and HS in winter (33.9%) (p = 0.0006). We have found negative Spearman’s correlations (after Bonferroni adjustment for the multiple correlations) of the number of males with values of relative humidity (%) (day 0, rho = ? 0.15), the total number of strokes (day 2, rho = ? 0.12), females (day 2, rho = ? 0.12) and IS (day 2, rho = ? 0.13) with concentrations of PM₁₀ (µg/m³), as well as negative correlations of the number of females (day 2, rho = ? 0.12) and IS (day 2, rho = ? 0.12) with concentrations of NO₂ (µg/m³) (for all p < 0.002). In winter, the number of HS (day 0, rho = 0.25, p = 0.001) positively correlated with concentrations of O₃ (µg/m³). The appearance of stroke has seasonal variations, with the highest rates during spring and winter. Positive correlation between the number of HS and values of O₃ requires an additional reduction of the legally permitted pollutants concentrations.     

Enzymatic depletion of tumor hyaluronan induces antitumor responses in preclinical animal models

Hyaluronan (HA) is a glycosaminoglycan polymer that often accumulates in malignancy. Megadalton complexes of HA with proteoglycans create a hydrated connective tissue matrix, which may play an important role in tumor stroma formation. Through its colloid osmotic effects, HA complexes contribute to tumor interstitial fluid pressure, limiting the effect of therapeutic molecules on malignant cells. The therapeutic potential of enzymatic remodeling of the tumor microenvironment through HA depletion was initially investigated using a recombinant human HA-degrading enzyme, rHuPH20, which removed HA-dependent tumor cell extracellular matrices in vitro. However, rHuPH20 showed a short serum half-life (t(1/2) < 3 minutes), making depletion of tumor HA in vivo impractical. A pegylated variant of rHuPH20, PEGPH20, was therefore evaluated. Pegylation improved serum half-life (t(1/2) = 10.3 hours), making it feasible to probe the effects of sustained HA depletion on tumor physiology. In high-HA prostate PC3 tumors, i.v. administration of PEGPH20 depleted tumor HA, decreased tumor interstitial fluid pressure by 84%, decreased water content by 7%, decompressed tumor vessels, and increased tumor vascular area >3-fold. Following repeat PEGPH20 administration, tumor growth was significantly inhibited (tumor growth inhibition, 70%). Furthermore, PEGPH20 enhanced both docetaxel and liposomal doxorubicin activity in PC3 tumors (P < 0.05) but did not significantly improve the activity of docetaxel in low-HA prostate DU145 tumors. The ability of PEGPH20 to enhance chemotherapy efficacy is likely due to increased drug perfusion combined with other tumor structural changes. These results support enzymatic remodeling of the tumor stroma with PEGPH20 to treat tumors characterized by the accumulation of HA.     

Leisure-Time Sedentary Behavior,Alcohol Consumption,and Sexual Intercourse Among Adolescents Aged 12-15 Years in 19 Countries From Africa,the Americas,and Asia

BackgroundThe association between sedentary behavior and sexual behavior has not been investigated among adolescents.AimThe aim of this study was to: (i) investigate the association between leisure-time sedentary behavior and sexual intercourse, and (ii) test for mediation by alcohol consumption, drug use, physical activity, bullying victimization, parental support/monitoring, loneliness, and depressive symptoms in a large global sample of young adolescents.MethodsData were analyzed from 34,674 adolescents aged 12?15 years participating in the Global School-based Student Health Survey. Participants reported the number of hours spent in leisure-time sedentary behavior on a typical day (<1, 1?2, 3?4, 5?8, and >8 hours). Data on alcohol consumption, drug use, physical activity, bullying victimization, parental support/monitoring, loneliness, and depressive symptoms were considered as potential mediators.OutcomeParticipants reported whether or not they had sexual intercourse in the past 12 months (yes/no).ResultsThe prevalence of past 12-month sexual intercourse was 11.9%, whereas the prevalence of <1, 1?2, 3?4, 5?8, and >8 hours per day of leisure-time sedentary behavior were 26.7%, 35.6%, 21.4%, 11.5%, and 4.9%, respectively. There was a dose-dependent relationship between sedentary behavior and odds of reporting sexual intercourse: compared with <1 hour/day of sedentary behavior, the odds ratio (95% CI) of sexual intercourse associated with 1?2, 3?4, 5?8, and >8 hours/day of sedentary behavior were 1.12 (0.94?1.33), 1.22 (1.01?1.48), 1.34 (1.08?1.66), and 1.76 (1.37?2.27), respectively. There was no significant interaction by sex. The largest proportion of the association between sedentary behavior and sexual intercourse was explained by alcohol use (% mediated 21.2%), with other factors explaining an additional 11.2%.Clinical TranslationInterventions to reduce leisure-time sedentary and/or alcohol consumption may contribute to a reduction in the proportion of adolescents engaging in sexual intercourse at a young age. The strengths and limitations of this study are the large, representative sample of adolescents from 19 countries. However, the cross-sectional design means causality or temporal associations could not be established.ConclusionsIn young adolescents, leisure-time sedentary behavior is positively associated with odds of having sexual intercourse in both boys and girls, in a dose-dependent manner. Alcohol consumption seems to be a key mediator of this relationship.Smith L, Jackson SE, Jacob L, et al. Leisure-Time Sedentary Behavior, Alcohol Consumption, and Sexual Intercourse Among Adolescents Aged 12-15 Years in 19 Countries From Africa, the Americas, and Asia. J Sex Med 2019;16:1355–1363.     

Myocardial damage size assessment in the zone of infarction for indicating rescue percutaneous coronary intervention

BACKGROUND: The most important predictors of subsequent patients outcome after acute myocardial infarction (AIM) are infarct size, left ventricular ejection fraction, left ventricular volumes and presence and extent of residual myocardial ischemia. All of these variables can be directly determined through scintigraphic approaches. The presence and extent of myocardial ischemia are strong pre dictors for fatal and nonfatal cardiac events and improve risk statification beyound the information gleaned from clinical variables. CASE REPORT: We presented a case of 66-years-old male with myocardial infarction of anteroseptal localization. Myocardial perfusion imaging (MPI) detected a large zone of residual ischemia (culprit lesion) within infarction zone. It has an important role in risk stratification after myocardial infarction, and indicates subsequent therapeutic decision making, in this case rescue percutaneous coronary intervention (PCI). After PCI we followed the therapy effect by MPI, and we found practically normal perfusion with minimal zone of defect perfusion in the apex. CONCLUSION: Myocardial perfusion imaging has an important role in the initial evaluation and risk stratification of patients surviving myocardial infarction. It also plays a major role in guiding subsequent therapeutic decision making, and in monitoring the benefits of these therapeutic measures.     

Outcomes of ophtalmologic surgical procedures of esotropia in children and adolescents

BACKGROUND/AIM: Esotropia is the most common manifestation form of strabism accompanied by refraction deviations and amblyopia. The aim of this prospective study was to present the outcomes of surgical treatment of esotropia in children and adolescents. METHODS: Within the period from January 1st 2006 to February 1st 2007 at the Clinic for Ophtalmology, Military Medical Academy, Belgrade a total of 25 patients with esotropia (34 eyes) and previously corrected refraction anomaly and treated amblyopia were operated on. The patients were 4-19-year of age. All of the patients were submitted to a complete ophtalmologic and orthoptic examination prior to the surgery, and a month, three months and six months after the surgery. The surgery was performed under general anesthesia. Out of the total number of the patients nine were operated on both eyes, while 16 patients on one eye with amblyopia or frequent esodeviation. Nine patients were submitted to retroposition of the inner straight muscle, two to myectomy of the outer straight muscle, while in 14 of the patients a combination of retroposition and myectomy was performed. The patients were divided into three groups according to the preoperative angle at the distance and followed-up accordingly after the surgery. Deviation angle at the distance in the group I was 18-25 DP, in the group II 26-35 PD, while in the group III it was 36-60 PD. RESULTS: The most numerous, group I (12 patients; 48%), a month following the surgery showed angle reduction by 55.58%, after three months 63.25%, and after six months 63.92%. The group II consisted of 8 patients (32%) showed angle reduction by 70.75% a month following the surgery, by 76% after three months, and by 79.12% after six months. The group III (5 patients; 20%) showed angle reduction by 72.20% a month following the surgery, 79.20 after three months, and 80.12% after six months following the surgery. CONCLUSION: The best postoperative outcomes after a month, three and six months were obtained in the group of patients with the highest esodeviation angle at the distance solved by the surgery on both eyes. Timely surgical treatment befell into major precondition for developing and maintaining the elements of binocular vision in the operated on patients.     

Resolution of ST-segment elevation in acute myocardial infarction — Early prognostic significance after thrombolytic therapy

In acute myocardial infarction, early identification of patients at a high mortality risk is important for planning further therapeutic strategies. Previous studies have demonstrated that the extent of early resolution of ST-segment elevation may represent a simple, quick and noninvasive assessment to identify high risk groups of patients. In a subgroup of the COBALT Study population (Continuous Infusion vs Double Bolus Administration of Alteplase), ST-segment elevation was measured before and 90 to 120 minutes after treatment with alteplase. The subgroup of n = 1,760 patients was not different from the total COBALT population of n = 7169 patients regarding most clinical parameters except Killip Class before treatment. However, the overall 30-day mortality differed significantly between the main study and the substudy (7.76% vs 3.52%; p < 0.001). Three groups of ST-segment resolution were defined: 1. complete resolution (resolution > or = 70%; 762 patients), 2. partial resolution (< 70% and > 30%; 491 patients), 3. no resolution (< 30%; 507 patients). Mortality rate at 30 days for complete, partial and no resolution of ST-segment elevation was 1.31%, 4.28% and 6.11%, respectively (p < 0.001). While this significant correlation between the extent of ST-segment resolution and mortality could be observed for inferior acute myocardial infarction, it could not be found in patients with anterior acute myocardial infarction. This in part may be due to a selection bias that leads to an extremely divergent mortality rate of anterior acute myocardial infarction in the main study and the substudy (10.1% vs 3.94%; p < 0.0001). Despite this limitation, resolution of ST-segment elevation in acute myocardial infarction after thrombolytic therapy allows to identify patients at a high mortality risk and may help to select patients for early invasive procedures such as PTCA. Patients with complete ST-segment resolution showed a particularly low mortality rate, irrespective of the alteplase regimen used (front-loaded alteplase vs double bolus alteplase).     

Effects of partial left ventriculectomy on left ventricular performance in patients with nonischemic dilated cardiomyopathy

Objectives. This study sought to assess the effects of partial left ventriculectomy (PLV) on left ventricular (LV) performance in a series of consecutive patients with nonischemic dilated cardiomyopathy.

Background. Reduction of LV systolic function in patients with heart failure is associated with an increase of LV volume and alteration of its shape. Recently, PLV, a novel surgical procedure, was proposed as a treatment option to alter this process in patients with dilated cardiomyopathy.

Methods. We studied 19 patients with severely symptomatic nonischemic dilated cardiomyopathy, before and 13 ± 3 days after surgery, and 12 controls. Single-plane left ventriculography with simultaneous measurements of femoral artery pressure was performed during right heart pacing.

Results. The LV end-diastolic and end-systolic volume indexes decreased after PLV (from 169 to 102 ml/m², and from 127 to 60 ml/m², respectively, p < 0.0001 for both). Despite a decrease in LV mass index (from 162 to 137 g/m², p < 0.0001), there was a significant decrease in LV circumferential end-systolic and end-diastolic stresses (from 277 to 159 g/cm², p < 0.0001 and from 79 to 39 g/cm², p = 0.0014, respectively). Ejection fraction improved (from 24% to 41%, p < 0.0001); the stroke work index remained unchanged.

Conclusions. The PLV improves LV performance by a dramatic reduction of ventricular end-systolic and end-diastolic stresses. Further studies are needed to assess whether this effect is sustained during long-term follow-up and to define the role of PLV in the treatment of patients with dilated cardiomyopathy.     

Improved cardiac function with glucose-insulin-potassium after aortocoronary bypass grafting

To assess the effectiveness of metabolic support for the heart in patients with refractory heart failure after hypothermic ischemic arrest for aortocoronary bypass grafting we assigned 22 patients to receive either intravenous glucose (50%), insulin (80 IU/L), and potassium (100 mEq/L) at a rate of 1 mL/kg/h for up to 48 hours (GIK) or glucose (5%) and NaCl (0.225%) at the same rate (control). All patients started out with a mean cardiac index of less than 3.0 L/min/m2, were on intraaortic balloon pump assistance, and required inotropic drugs. At 12 and 24 hours cardiac index had increased significantly in the GIK group when compared with the control group (3.6 and 3.4 versus 2.5 and 2.7 L/min/m2, respectively). Time on the intraaortic balloon pump (39 versus 61 hours) and requirements for inotropic drug support were significantly less in GIK group than in the control group. All 11 GIK patients could be weaned from intraaortic balloon pump assistance. At 30 days after operation survival was 10/11 in the GIK group, compared with 7/11 in the control group. We conclude that GIK is both safe and effective in the treatment of refractory left ventricular failure after aortocoronary bypass grafting. The exact mechanism for the beneficial effect of GIK on myocardial contractility remains to be elucidated.     

TSLP or IL‐7 provide an IL‐7Rα signal that is critical for human B lymphopoiesis

Thymic stromal lymphopoietin (TSLP) and IL‐7 are cytokines that signal via the IL‐7 receptor alpha (IL‐7Rα) to exert both overlapping and unique functions during early stages of mouse B‐cell development. In human B lymphopoiesis, the requirement for IL‐7Rα signaling is controversial and the roles of IL‐7 and TSLP are less clear. Here, we evaluated human B‐cell production using novel in vitro and xenograft models of human B‐cell development that provide selective IL‐7 and human TSLP (hTSLP) stimulation. We show that in vitro human B‐cell production is almost completely blocked in the absence of IL‐7Rα stimulation, and that either TSLP or IL‐7 can provide a signal critical for the production and proliferation of human CD19⁺ PAX5⁺ pro‐B cells. Analysis of primary human bone marrow stromal cells shows that they express both IL‐7 and TSLP, providing an in vivo source of these cytokines. We further show that the in vivo production of human pro‐B cells under the influence of mouse IL‐7 in a xenograft scenario is reduced by anti‐IL‐7 neutralizing antibodies, and that this loss can be restored by hTSLP at physiological levels. These data establish the importance of IL‐7Rα mediated signals for normal human B‐cell production.