Risk factors for reperfusion injury after lung transplantation

Objective To assess the influence of recipient's and donor's factors as well as surgical events on the occurrence of reperfusion injury after lung transplantation. Design and setting Retrospective study in the surgical intensive care unit (ICU) of a university hospital. Methods We collected data on 60 lung transplantation donor/recipient pairs from June 1993 to May 2001, and compared the demographic, peri- and postoperative variables of patients who experienced reperfusion injury (35%) and those who did not. Results The occurrence of high systolic pulmonary pressure immediately after transplantation and/or its persistence during the first 48 h after surgery was associated with reperfusion injury, independently of preoperative values. Reperfusion injury was associated with difficult hemostasis during transplantation (p = 0.03). Patients with reperfusion injury were more likely to require the administration of catecholamine during the first 48 h after surgery (p = 0.014). The extubation was delayed (p = 0.03) and the relative odds of ICU mortality were significantly greater (OR 4.8, 95% CI: 1.06, 21.8) in patients with reperfusion injury. Our analysis confirmed that preexisting pulmonary hypertension increased the incidence of reperfusion injury (p < 0.01). Conclusions Difficulties in perioperative hemostasis were associated with reperfusion injury. Occurrence of reperfusion injury was associated with postoperative systolic pulmonary hypertension, longer mechanical ventilation and higher mortality. Whether early recognition and treatment of pulmonary hypertension during transplantation can prevent the occurrence of reperfusion injury needs to be investigated. The preliminary results of the present study were presented at the 14th Annual Meeting of the European Society of Intensive Care Medicine, September 2001, Geneva, Switzerland     

Point of care management of heparin administration after heart surgery

Objectives Determination of activated partial thromboplastin time (aPTT) is used in coagulation management after heart surgery. Results from the central laboratory take long to be obtained. We sought to shorten the time to obtain coagulation results and the desired coagulation state and to reduce blood loss and transfusions using point of care (POC) aPTT determination.Design Randomized, controlled trial.Setting University-affiliated 20-bed surgical ICU.Patients and participants Forty-two patients planned for valve surgery (Valves) and 84 for coronary artery bypass grafting (CABG) with cardiopulmonary bypass.Interventions Valves and CABG were randomized to postoperative coagulation management monitored either by central laboratory aPTT (Lab group) or by POC aPTT (POC group). Heparin was administered according to guidelines.Measurements and results POC aPTT results were available earlier than Lab aPTT after venipuncture in Valves (3 ± 2 vs. 125 ± 68 min) and in CABG (3 ± 4 vs. 114 ± 62 min). Heparin was introduced earlier in the POC group in Valves (7 ± 23 vs. 13 ± 78 h, p = 0.01). Valves of the POC group bled significantly less than Valves in the Lab group (647 ± 362 ml vs. 992 ± 647ml, p < 0.04), especially during the first 8 h after ICU admission. There was no difference in bleeding in CABG (1074 ± 869 ml vs. 1102 ± 620, p = NS). In Valves, fewer patients in the POC group than in the Lab group needed blood transfusions (1/21 vs. 8/21; p = 0.03). No difference was detected in CABG.Conclusions In Valves in the POC group the time to the desired coagulation state was reduced, as was the thoracic blood loss, reducing the number of patients transfused. This improvement was not observed in CABG. Side effects were similar in the two groups.Electronic supplementary material The electronic reference of this article is . The online full-text version of this article includes electronic supplementary material. This material is available to authorised users and can be accessed by means of the ESM button beneath the abstract or in the structured full-text article. To cite or link to this article you can use the above reference.Presented in part at the annual congress of the European Society of Intensive Care Medicine (ESICM) in Amsterdam, 6–8 October 2003.     

Alteration of glyoxalase genes expression in response to testosterone in LNCaP and PC3 human prostate cancer cells

Glyoxalase system, a ubiquitous detoxification pathway protecting against cellular damage caused by potent cytotoxic metabolites, is involved in the regulation of cellular growth. Aberrations in the expression of glyoxalase genes in several human cancers have been reported. Recently, we described a possible regulatory effect by estrogens on glyoxalase genes in human breast cancer cell lines. This result, along with those ones regarding changes in glyoxalases activity and expression in other human hormone-regulated cancers, such as prostate cancer, has prompted us to investigate whether also androgens, whose functional role in prostate cancer pathogenesis is well known, could modulate glyoxalases gene expression. Therefore, we treated LNCaP androgen-responsive and PC3 androgen-independent human prostate cancer cell lines with testosterone at the concentrations of 1 nM and 100 nM. After a two days treatment, glyoxalases mRNA levels as well as cell proliferation were evaluated by real-time RT-PCR analysis and [3H]thymidine incorporation, respectively. Results pointed out that testosterone affects the expression of glyoxalase system genes and cell proliferation in a different manner in the two cell lines. The possibility that modulation of glyoxalase genes expression by testosterone is due to glyoxalases-mediated intracellular response mechanisms to the androgen-induced oxidative stress or to the presence of androgen response elements (ARE) in glyoxalase promoters are discussed. Knowledge regarding the regulation of glyoxalases by testosterone may provide insights into the importance of these enzymes in human prostate carcinomas in vivo.     

Obesity is a Major Risk Factor for Hospitalization in Community-Managed COVID-19 Pneumonia

ObjectiveWe aimed to investigate whether the stratification of outpatients with coronavirus disease 2019 (COVID-19) pneumonia by body mass index (BMI) can help predict hospitalization and other severe outcomes.Patients and MethodsWe prospectively collected consecutive cases of community-managed COVID-19 pneumonia from March 1 to April 20, 2020, in the province of Bergamo and evaluated the association of overweight (25 kg/m² ≤ BMI <30 kg/m²) and obesity (≥30 kg/m²) with time to hospitalization (primary end point), low-flow domiciliary oxygen need, noninvasive mechanical ventilation, intubation, and death due to COVID-19 (secondary end points) in this cohort. We analyzed the primary end point using multivariable Cox models.ResultsOf 338 patients included, 133 (39.4%) were overweight and 77 (22.8%) were obese. Age at diagnosis was younger in obese patients compared with those overweight or with normal weight (P<.001), whereas diabetes, dyslipidemia, and heart diseases were differently distributed among BMI categories. Azithromycin, hydroxychloroquine, and prednisolone use were similar between BMI categories (P>.05). Overall, 105 (31.1%) patients were hospitalized, and time to hospitalization was significantly shorter for obese vs over- or normal-weight patients (P<.001). In the final multivariable analysis, obese patients were more likely to require hospitalization than nonobese patients (hazard ratio, 5.83; 95% CI, 3.91 to 8.71). Results were similar in multiple sensitivity analyses. Low-flow domiciliary oxygen need, hospitalization with noninvasive mechanical ventilation, intubation, and death were significantly associated with obesity (P<.001).ConclusionIn patients with community-managed COVID-19 pneumonia, obesity is associated with a higher hospitalization risk and overall worse outcomes than for nonobese patients.     

N-Acetyl-aspartyl-glutamic acid inhibits cellular recruitment and mediator release during the late allergen-induced nasal reaction

Objective: N-acetyl-aspartyl-glutamic acid (NAAGA) was effective in the treatment of allergic rhinitis, with an action on early allergen-induced nasal symptoms and mediator release. The aim of this study was to evaluate the clinical activity of NAAGA and its effects on the late antigen-induced reaction in the nose. Methods: Ten patients with allergic seasonal rhinitis were included in this randomized double-blind crossover trial of a 6% wt/vol solution of NAAGA (daily dosage 84 mg) versus placebo (lactose). The drug and placebo were administered intranasally five times daily for 1 week, with a 2-week interval between treatments. Results: Treatment with NAAGA, but not with placebo, significantly reduced the late antigen-induced nasal symptoms, mainly nasal obstruction. Eosinophil numbers in the nasal lavages collected 6 h and 24 h after challenge were significantly lower after NAAGA than after placebo. Active treatment also significantly reduced the neutrophil count 6 h after antigen challenge, and significantly lowered eosinophil cationic protein and myeloperoxidase levels in nasal lavages 6 h and 24 h after antigen challenge. Conclusion: These results indicate that treatment for 1 week with NAAGA can reduce the late antigen-induced reaction in the nose. This is accompanied by a reduction in eosinophil and neutrophil recruitment and release of eosinophil cationic protein and myeloperoxidase. Received: 30 December 1997 / Accepted in revised form: 19 May 1998     

An integrated system for the automation of the clinical chemistry laboratory

Summary A user programmable microcomputer based integrated system for automatic analysis in the clinical chemistry laboratory is presented. Friendly user-instrument interaction helps the operator when defining tests and analytical conditions or entering sample data and test requests. Quality control data are retained for the automatic production of various statistical lists and graphs. Routine operator intervention is limited to reagent preparation, sample loading onto the autosampler plate, definition of the tests to be performed on each of the samples and data validation before the generation of reports. Finally, connection with an existing laboratory management system is provided by means of a standard serial interface. Deceased on September 15, 1983.     

Pulmonary hypertension is not a risk factor for grade 3 primary graft dysfunction after lung transplantation

Grade 3 primary graft dysfunction (PGD3) represents the most important risk factor for patient mortality during the first year after lung transplantation (LTX). We investigated whether pretransplant pulmonary hypertension (PH) is a risk factor for the development of PGD3. This retrospective, single‐center cohort study included 96 candidates undergoing right heart catheterization (RHC) prior to being listed for LTX between March 2000 and October 2015. Based on their mean pulmonary artery pressure (mPAP) levels, the patients were classified into 3 groups: (1) <25 mm Hg, (2) 25‐34 mm Hg and (3) ≥35 mm Hg. Forty‐seven patients were classified in group 1, 31 in group 2, and 18 in group 3. Fifteen recipients (16%, 95%‐CI 8‐23) developed PGD3. In the univariate analysis, the diagnosis of interstitial lung disease (ILD) compared to COPD (OR: 7.06, P = .005), blood transfusion >1000 mL during surgery (OR: 5.25, P = .005), the need for intra‐operative cardio‐pulmonary bypass (CPB) or extra‐corporeal membrane oxygenation (ECMO) (OR: 4, P = .027), mPAP (OR 1.06, P = .007) and serum high density lipoprotein‐cholesterol (HDL‐C) (OR 0.09, P = .005) were associated with PGD3. In the multivariable logistic regression analysis, only HDL‐C (OR 0.10, P = .016) was associated with PGD3 based on our single‐center cohort data analysis.     

On the association between date of birth and pollen sensitization: is age an effect modifier?

An association between date of birth and development of allergy has been proposed by prior research. Yet, the presence of a dose-response relationship or any potential effect modification for this association has not been widely studied. The aims of our study were to investigate whether an association between birth during pollen season and symptomatic sensitization to pollens exists, whether this association is stronger for patients with high rather than low allergic reactivity to pollens, and whether this association is modified by the age of the patients. Among 3318 asthmatic and/or rhinitic outpatients, we selected 805 patients sensitized exclusively to pollens (78 with low reactivity [LR] and 727 with high reactivity [HR]) and 629 patients with negative skin-prick tests (SPT) (control group). The association between being born during pollen season (February-July) and each of the pollen reactivity levels was assessed by estimating the odds ratios (OR). HR pollinosis patients were more likely than SPT negative patients of being born in February-July (OR 1.38, 95% Confidence Intervals (CI) 1.11-1.71). The likelihood of having been born in pollen season significantly increased across the levels of reactivity to pollens (HR > LR > SPT negative). These findings were valid only among patients with an early onset of symptoms. Although the OR for being born in pollen season was 1.91 (95% CI 1.32-2.77) for HR pollinosis patients with onset of symptoms < or = 15 years, it was 1.13 (95% CI 0.87-1.48) for those with later onset of symptoms (test of homogeneity: p = 0.026). Our results suggest that the exposure to allergenic pollens in the first months of life increases the risk of developing clinically relevant sensitization to them, particularly in the first 15 years of life.     

Increasing hematocrit above 28% during early resuscitative phase is not associated with decreased mortality following severe traumatic brain injury

Background  

To prevent iatrogenic damage, transfusions of red blood cells should be avoided. For this, specific and reliable transfusion triggers must be defined. To date, the optimal hematocrit during the initial operating room (OR) phase is still unclear in patients with severe traumatic brain injury (TBI). We hypothesized that hematocrit values exceeding 28%, the local hematocrit target reached by the end of the initial OR phase, resulted in more complications, increased mortality, and impaired recovery compared to patients in whom hematocrit levels did not exceed 28%.