Aligning digital CD8+ scoring and targeted next-generation sequencing with programmed death ligand 1 expression: a pragmatic approach in early-stage squamous cell lung carcinoma.

AIMS: To study programmed death ligand 1 (PD-L1) expression, tumour-infiltrating T lymphocytes (TILs) and the molecular context in patients with early-stage squamous cell lung carcinomas (SCCs). METHODS AND RESULTS: The study included samples from 40 patients (discovery cohort) and 29 patients (validation cohort) diagnosed with early-stage SCC. PD-L1 immunohistochemistry (IHC) was performed with three commercially available clones (E1L3N, SP263 and SP142). CD8+ TILs were scored with a digital algorithm. All tumours were analysed with targeted next-generation sequencing (NGS). Additionally, TP53 mutations were investigated with direct sequencing. In both cohorts, we observed a significant association between CD8+ TILs density and high PD-L1 IHC expression in tumour cells (TCs). Furthermore, high SP142 PD-L1 expression in immune cells (ICs) was also associated significantly with CD8+ TILs density. Therefore, CD8+ TILs density discriminated between patients with high versus low PD-L1 IHC expression with excellent sensitivity and specificity. Interestingly, the highest percentages of PD-L1-positive TCs with the three antibodies were found in samples with cyclin-dependent kinase 6 (CDK6) amplification, with high amplification of proto-oncogene C-Myc (CMYC) or with cyclin D1-PI3 kinase subunit alpha (CCND1-PIK3CA) co-amplification. High SP142 PD-L1 IHC expression in ICs showed a non-significant correlation with TP53 mutations. Conversely, most cases with fibroblast growth factor receptor 1 (FGFR1) amplification were negative for all PD-L1 clones. CONCLUSIONS: Our preliminary results support the use of digital CD8+ TILs scoring and targeted NGS alongside PD-L1 expression. The approach presented herein could help define patients with SCCs candidates to immune checkpoints inhibitors.

Relationship of immunohistochemical biomarker expression and lymph node involvement in patients undergoing surgical treatment of NSCLC with long-term follow-up.

We try to identify the relationship between immunohistochemical marker expression and lymph node involvement in a cohort of 282 patients followed for 5 years after curative resection for NSCLC. In 189 patients (67%), lymph nodes were unaffected while 93 patients (33%) showed nodal involvement. The expression of 15 molecular markers was determined from each patient by tissue-array immunohistochemistry. Univariate analysis indicated significantly higher expression of E-cadherin, γ-catenin, p27, and p53 in patients with lymph node involvement. In those with unaffected nodes, p16 and Rb were expressed. E-cadherin expression was related to a 50% mortality reduction in patients with node involvement (hazard ratio (HR) 0.5; p = 0.017). c-erbB-2 expression was correlated with a 3.4-fold increase in mortality compared to patients without expression of this marker in subjects without node involvement (HR 3.41; p = 0.017). Multivariate analysis identified c-erbB-2 (HR 2.22; p = 0.089) and p27 (HR 1.44; p = 0.019) as prognostics of mortality while Rb (HR 0.74) indicated a good prognosis. The expression of proteins encoded by oncogenes and tumor suppressor genes was different according to lymph node involvement. The increased mortality related to c-erbB-2 expression in patients with unaffected lymph nodes would suggests a need for adjuvant treatment.

[Resected non-small cell bronchogenic carcinoma stage pIIIA-N2. Which patients will benefit most from adjuvant therapy?]. / Carcinoma broncogénico no microcítico resecado, estadio pIIIA-N2. ¿En qué pacientes la adyuvancia ofrece mayor beneficio?

BACKGROUND: Controversy persists as regards the indications and results of surgery in the treatment of patients with stage pIIIA-N2 non-small cell lung cancer (NSCLC). The objective of this study was to analyze the overall survival of a multicentre series of these patients and the role of adjuvant treatment, looking for factors that may define subgroups of patients with an increased benefit from this treatment. METHODS: A retrospective study was conducted on 287 patients, with stage pIIIA-N2 NSCLC subjected to complete resection, taken from a multi-institutional database of 2.994 prospectively collected consecutive patients who underwent surgery for lung cancer. Adjuvant treatment was administered in 238 cases (82.9%). Analyses were made of the age, gender, histological type, administration of induction and adjuvant chemotherapy and/or radiation therapy treatments. RESULTS: The 5-year survival was 24%, with a median survival of 22 months. Survival was 26.5% among patients receiving with adjuvant treatment, versus 10.7% for those without it (P=.069). Age modified the effect of adjuvant treatment on survival (interaction P=.049). In patients under 70 years of age with squamous cell carcinoma, adjuvant treatment reduced the mortality rate by 37% (hazard ratio: 0,63; 95% CI; 0,42-0,95; P=.036). CONCLUSIONS: Completely resected patients with stage pIIIA-N2 NSCLC receiving adjuvant treatment reached higher survival rates than those who did not. Maximum benefit was achieved by the subgroup of patients under 70 years of age with squamous cell carcinoma.

Gut Microbiota Signatures with Potential Clinical Usefulness in Colorectal and Non-Small Cell Lung Cancers.

The application of bacterial metagenomic analysis as a biomarker for cancer detection is emerging. Our aim was to discover gut microbiota signatures with potential utility in the diagnosis of colorectal cancer (CRC) and non-small cell lung cancer (NSCLC). A prospective study was performed on a total of 77 fecal samples from CRC and NSCLC patients and controls. DNA from stool was analyzed for bacterial genomic sequencing using the Ion Torrent™ technology. Bioinformatic analysis was performed using the QIIME2 pipeline. We applied logistic regression to adjust for differences attributable to sex, age, and body mass index, and the diagnostic accuracy of our gut signatures was compared with other previously published results. The feces of patients affected by different tumor types, such as CRC and NSCLC, showed a differential intestinal microbiota profile. After adjusting for confounders, Parvimonas (OR = 53.3), Gemella (OR = 6.01), Eisenbergiella (OR = 5.35), Peptostreptococcus (OR = 9.42), Lactobacillus (OR = 6.72), Salmonella (OR = 5.44), and Fusobacterium (OR = 78.9) remained significantly associated with the risk of CRC. Two genera from the Ruminococcaceae family, DTU089 (OR = 20.1) and an uncharacterized genus (OR = 160.1), were associated with the risk of NSCLC. Our two panels had better diagnostic capacity for CRC (AUC = 0.840) and NSLC (AUC = 0.747) compared to the application of two other published panels to our population. Thus, we propose a gut bacteria panel for each cancer type and show its potential application in cancer diagnosis.

Role of Telomere Length in Survival of Patients with Idiopathic Pulmonary Fibrosis and Other Interstitial Lung Diseases.

Interstitial lung diseases (ILDs) constitute a group of more than 200 disorders, with idiopathic pulmonary fibrosis (IPF) being one of the most frequent. Telomere length (TL) shortening causes loss of function of the lung parenchyma. However, little is known about its role as a prognostic factor in ILD patients. With the aim of investigating the role of TL and telomerase activity in the prognosis of patients affected by ILDs, we analysed lung tissue samples from 61 patients. We measured relative TL and telomerase activity by conventional procedures. Both clinical and molecular parameters were associated with overall survival by the Kaplan-Meier method. Patients with IPF had poorer prognosis than patients with other ILDs (p = 0.034). When patients were classified according to TL, those with shortened telomeres reported lower overall survival (p = 0.085); differences reached statistical significance after excluding ILD patients who developed cancer (p = 0.021). In a Cox regression analysis, TL behaved as a risk-modifying variable for death associated with rheumatic disease (RD) co-occurrence (p = 0.029). Also, in patients without cancer, ferritin was significantly increased in cases with RD and IPF co-occurrence (p = 0.032). In relation to telomerase activity, no significant differences were detected. In conclusion, TL in lung tissue emerges as a prognostic factor in ILD patients. Specifically, in cases with RD and IPF co-occurrence, TL can be considered as a risk-modifying variable for death.

Results in mediastinal lymph node staging of surgical lung cancer: Data from the prospective cohort of the Spanish Video-Assisted Thoracic Surgery Group.

OBJECTIVES: The objective of this study was to assess the diagnostic performance of combined computerised tomography (CT) and positron emission tomography (PET) in mediastinal staging of surgical lung cancer based on data obtained from the prospective cohort of the Spanish Group for Video-Assisted Thoracic Surgery (GEVATS). METHODS: A total of 2782 patients underwent surgery for primary lung carcinoma. We analysed diagnostic success in mediastinal lymph node staging (cN2) using CT and PET. Bivariate and multivariate analyses were performed of the factors involved in this success. The risk of unexpected pN2 disease was analysed for cases in which an invasive testing is recommended: cN1, the tumour centrally located or the tumour diameter >3 cm. RESULTS: The overall success of CT together with PET was 82.9% with a positive predictive value of 0.21 and negative predictive value of 0.93. If the tumour was larger than 3 cm and for each unit increase in mediastinal SUVmax, the probability of success was lower with OR 0.59 (0.44-0.79) and 0.71 (0.66-0.75), respectively. In the video-assisted thoracic surgery (VATS) approach, the probability of success was higher with OR 2.04 (1.52-2.73). The risk of unexpected pN2 increased with the risk factors cN1, the tumour centrally located or the tumour diameter >3 cm: from 4.5% (0 factors) to 18.8% (3 factors) but did not differ significantly as a function of whether invasive testing was performed. CONCLUSIONS: CT and PET together have a high negative predictive value. The overall success of the staging is lower in the case of tumours >3 cm and high mediastinal SUVmax, and it is higher when VATS is performed. The risk of unexpected pN2 is higher if the disease is cN1, the tumour centrally located or the tumour diameter >3 cm but does not vary significantly as a function of whether patients have undergone invasive testing.

Differential expression of senescence and cell death factors in non-small cell lung and colorectal tumors showing telomere attrition.

OBJECTIVE: The main aim of this work is to investigate the expression of factors related to senescence and cell death pathways in non-small cell lung cancers (NSCLCs) and colorectal cancers (CRCs) in relation to telomere status. METHODS: We analyzed 158 tissue samples, 36 NSCLCs, 43 CRCs, and their corresponding control tissues obtained from patients submitted to surgery. Telomere function was evaluated by determining telomerase activity and telomere length. Expression of factors related to senescence, cell death pathways, transformation and tumorigenesis was investigated using arrays. Results were validated by real-time quantitative PCR. RESULTS: Considering tumors with telomere shortening, expression for BNIP3, DAPK1, NDRG1, EGFR, and CDKN2A was significantly higher in NSCLC than in CRC, whereas TP53 was overexpressed in CRC with respect to NSCLC. Moreover, compared to nontumor samples, DAPK1, GADD45A, SHC1, and TP53 were downregulated in the group of NSCLCs with telomere shortening, and no significant differences were found in CRC. CONCLUSIONS: In NSCLC, the failure of pathways which involve factors such as DAPK1, GADD45A, SHC1, and TP53, in response to short telomeres, could promote tumor progression. In CRC, the viability of these pathways in response to short telomeres could contribute to limiting tumorigenesis.

More than one pulmonary resections or combined lung-liver resection in 79 patients with metastatic colorectal carcinoma.

BACKGROUND: The way to select patients who will benefit from surgical resection of pulmonary metastases of colorectal carcinoma (CRC) remains unclear. METHODS: We analyze overall survival and potential prognostic factors in 101 pulmonary resections of CRC metastases in 79 patients, focusing on cases with repeated pulmonary resection or with hepatic metastasectomy. RESULTS: Number of pathological pulmonary metastases was higher than that of preoperatively suspected pulmonary nodules in 18% of the resections. Morbidity rate was 16.5%. There was no mortality. Five-year survival rates from the resection of the CRC and from the first pulmonary metastasectomy were 74.6% and 53.3%, respectively. Prognosis did not decrease in patients with history of hepatic metastasectomy or in those in which repeated pulmonary resection was performed. Age ≥70, preoperative carcinoembrionary antigen (CEA) ≥5 ng/dl and mediastinal lymph node involvement entailed worse prognosis. Pathological lymph node involvement and age were shown as independent prognostic factors in the multivariate analysis. CONCLUSIONS: Resection of pulmonary metastases of CRC is a safe procedure, with 5-year survival rates over 50%. History of resected hepatic metastases or needs for more than one pulmonary resection do not seem to decrease survival rates. Only lymph node involvement and age seem to be clearly associated to worse prognosis.

Complete Spontaneous Regression of Lung Metastases after Resection of CIC-Rearranged Sarcoma: A Case Report.

The vast majority of patients with soft tissue sarcomas (STS) of the trunk and bilateral lung metastases at diagnosis are considered incurable. These tumors have poor prognosis as only a palliative therapeutic approach can be offered to patients. We report on an extremely rare case in which bilateral lung metastases disappeared spontaneously following surgical resection of the primary CIC-rearranged sarcoma with no addition of chemotherapy or any other systemic therapy. A 53-year-old female presented with a rapidly swelling mass on her back. A magnetic resonance imaging scan of the chest revealed a large soft tissue mass on the posterior chest wall and bilateral lung metastases. Soon after stereotactic core-needle biopsy confirmation of round-cell sarcoma, the patient underwent surgery of the primary tumor as it started to be increasingly symptomatic. The resected specimen was pathologically diagnosed a poorly differentiated grade 3 sarcoma. Approximately 1 month later, a new CT scan revealed that the lung metastases were smaller and some of them had completely disappeared. Shortly afterward, the patient started adjuvant external beam radiotherapy of the tumor bed for 14 months. During the last follow-up visit, the patient confirmed no evidence of disease for 35 months postoperatively. In parallel, a histological study of pulmonary nodules, molecular analyses of the tumor, and a comprehensive study of the patient's immunophenotype were performed to gain some additional insights in the potential causes of this rare phenomenon.

Recommendations for acting in elective and urgent thoracic surgery during SARS-CoV-2 pandemic. Spanish Society of Thoracic Surgery. / Recomendaciones de actuación en cirugía torácica electiva y urgente en contexto de pandemia por SARS-CoV-2 de la Sociedad Española de Cirugía Torácica (SECT).

Expansion of the pandemic produced by new coronavirus SATS-CoV-2 has made healthcare focused on patients with COVID-19 disease, leading to discontinue most of elective surgical procedures. Being thoracic surgery eminently oncological, an optimal triage of patients amenable to be safely operated on is mandatory. Moreover, severe pulmonary involvement by COVID-19 causes complications frequently needing urgent thoracic surgical procedures under a new context. The Spanish Society of Thoracic Surgery (SECT) has developed this document to establish basic recommendations to keep up essential elective surgical activity and to guide surgeons facing thoracic urgencies in this new and unknown environment.

Telomere shortening is associated with poor prognosis and telomerase activity correlates with DNA repair impairment in non-small cell lung cancer.

BACKGROUND AND PURPOSE: Telomere function and DNA damage response pathways are frequently inactivated in cancer. Moreover, some telomere-binding proteins have been implicated in DNA repair. The purpose of this work consists of evaluating the prognostic impact of telomere dysfunction and its relationship with DNA repair systems in non-small cell lung cancer (NSCLC). PATIENTS AND METHODS: We analysed 83 NSCLCs and their corresponding control samples obtained from patients submitted to surgery. Telomere function was evaluated by determining telomerase activity and telomere length. DNA repair expression assays were established by using cDNA arrays containing 96 DNA-repair genes and by Real Time Quantitative PCR. RESULTS: Our data indicated that telomere attrition was significantly associated with poor clinical outcome of patients (P=0.02), being this parameter a significant prognostic factor independent of tumour stage (P=0.012; relative risk=1.887; 95% CI: 1.147-3.102). DNA-repair gene expression studies showed down regulation of DCLRE1C and GTF2H1 and a clear FLJ10858 up regulation in tumour tissues, as compared to controls. In addition, a number of genes related to DNA-repair were significantly down regulated in tumours that reactivated telomerase (DCLRE1C, GTF2H1, PARP-3, MLH1, and TRF2). CONCLUSIONS: Telomere shortening emerged as a poor clinical evolution parameter in NSCLC. Moreover, results from this work suggest a relationship between the loss of several DNA repair genes and telomerase activity, which may be of relevance in the pathogenesis of non-small lung cancer.

Combined Hepatic and Pulmonary Metastasectomies From Colorectal Carcinoma. Data From the Prospective Spanish Registry 2008-2010.

INTRODUCTION: Resection of both liver and lung metastases from colorectal carcinoma (CRC) is a standard of care in selected patients with oligometastatic disease. We present here the analysis of the subgroup of patients undergoing combined surgery from the Spanish Group of Surgery of Pulmonary Metastases (PM) from Colorectal Carcinoma (GECMP-CCR-SEPAR). METHODS: We analyze characteristics, survival and prognostic factors of patients undergoing combined resection from March-2008 to February-2010 and followed-up during at least 3 years, from the prospective multicenter Spanish Registry. RESULTS: A total of 138 patients from a whole series of 543 cases from 32 thoracic surgery units underwent both procedures. Seventy-seven (43.8%) resected liver metastases were synchronic with colorectal tumor. Median disease specific survival (DSS) from first pulmonary metastasectomy was 48.9 months, being three and 5-year DSS 65.1% and 41.7%, respectively. From CRC-surgery median DSS was 97.2 months, with 3 and 5-year DSS rates of 96.7% and 77%, respectively. Five-year DSS from pulmonary metastasectomy was 41.7% for patients with combined resection and 52.4% for those without hepatic involvement (P=.04). Differences disappeared when considering DSS from colorectal surgery. Carcinoembrionary antigen (CEA) before lung surgery over 10mg/dl and bilateral PM were independent prognostic factors for survival (hazard ratio 2.4 and 2.5, respectively). CONCLUSIONS: Patients with resection of PM of CRC with history of resected hepatic metastases presented significantly lower disease specific survival rates than those undergoing pulmonary metastasectomy alone. CEA before lung surgery and bilateral PM associated worse prognosis.

Biological and clinical significance of MMP-2, MMP-9, TIMP-1 and TIMP-2 in non-small cell lung cancer.

Our main aim consists of investigating the clinical usefulness of gelatinases and their tissue inhibitors in non-small cell lung cancer (NSCLC). Thus, we have analysed in 111 NSCLCs, levels and activity of MMP-2, MMP-9, TIMP-1 and TIMP-2, by Enzymoimmunoassay and Gelatine zymography, respectively. Our data revealed higher MMP-2 net activity in the NSCLC population analyzed in this study, this parameter showing a significant association with the TNM stage of tumours (P=0.002). Moreover, MMP-9 levels were significantly associated with poor clinical evolution of patients (P=0.02). Also, disease-free survival time was higher for patients whose tumours showed TIMP-1 increased levels (P=0.04). Of interest, Cox multivariate analysis revealed that TIMP-1 levels can be considered as an independent prognostic factor in NSCLC. Relative Risk (RR) to tumour relapse was more than two times lower for patients showing high TIMP-1 levels (RR=0.420, P=0.041). Therefore, according to our results, we conclude that MMP-9 and TIMP-1 levels of synthesis could be useful for the selection of patients with potentially unfavourable clinical evolution in order to establish adjuvant therapy protocols. Among these parameters, TIMP-1 level evaluation emerges as the main factor to predict the clinical outcome of patients.

Telomere length and telomerase activity in non-small cell lung cancer prognosis: clinical usefulness of a specific telomere status.

BACKGROUND: Considering previous data and the need to incorporate new biomarkers for the prognosis of solid tumours into the clinic, our aim in this work consists of evaluating the potential clinical use of telomeres and telomerase in non-small cell lung cancer (NSCLC). METHODS: Telomere status was established by determination of telomere length using the Terminal Restriction Fragment length method, and telomerase activity by the Telomeric Repeat Amplification Protocol in 142 NSCLCs and their corresponding control samples, obtained from patients submitted to surgery. Group-oriented curves for disease-free survival were calculated according to the Kaplan-Meier method considering telomere length, T/N ratio (telomere length in tumour to control tissue) and telomerase activity. RESULTS: Overall, tumours had significantly shorter telomeres compared with telomeres in control tissues (P = 0.027). More than 80 % of NSCLCs displayed telomerase activity. Regarding prognosis studies, patients whose tumours showed a mean telomere length (MTL) <7.29 Kb or T/N ratio <0.97 showed a significantly poor clinical evolution (P = 0.034 and P = 0.040, respectively). As result of a Cox multivariate analysis including pathologic state and lymph node dissemination, the MTL and T/N ratio emerged as independent significant prognostic factors. CONCLUSIONS: Telomerase activity was identified as a marker of poor prognosis. The novel finding of this study is the independent prognosis role of a specific telomere status in NSCLC patients. According to our results, telomere function may emerge as a useful molecular tool that allow to select groups of NSCLC patients with different clinical evolution, in order to establish personalized therapy protocols.

Poly (ADP-ribose) polymerase 3 (PARP3), a potential repressor of telomerase activity.

BACKGROUND: Considering previous result in Non-Small Cell Lung Cancer (NSCLC), we investigated in human cancer cells the role of PARP3 in the regulation of telomerase activity. METHODS: We selected A549 (lung adenocarcinoma cell line) and Saos-2 (osteosarcoma cell line), with high and low telomerase activity levels, respectively. The first one was transfected using a plasmid construction containing a PARP3 sequence, whereas the Saos-2 cells were submitted to shRNA transfection to get PARP3 depletion. PARP3 expression on both cell systems was evaluated by real-time quantitative PCR and PARP3 protein levels, by Western-blot. Telomerase activity was determined by TRAP assay. RESULTS: In A549 cells, after PARP3 transient transfection, data obtained indicated that twenty-four hours after transfection, up to 100-fold increased gene expression levels were found in the transfected cells with pcDNA/GW-53/PARP3 in comparison to transfected cells with the empty vector. Moreover, 48 hours post-transfection, telomerase activity decreased around 33%, and around 27%, 96 hours post-transfection. Telomerase activity average ratio was 0.67 ± 0.05, and 0.73 ± 0.06, respectively, with significant differences. In Saos-2 cells, after shRNA-mediated PARP3 silencing, a 2.3-fold increase in telomerase activity was detected in relation to the control. CONCLUSION: Our data indicated that, at least in some cancer cells, repression of PARP3 could be responsible for an increased telomerase activity, this fact contributing to telomere maintenance and, therefore, avoiding genome instability.

Methylation profiling in non-small cell lung cancer: clinical implications.

The aim of this study was to identify a panel of methylation markers that distinguish non-small cell lung cancers (NSCLCs) from normal lung tissues. We also studied the relation of the methylation profile to clinicopathological factors in NSCLC. We collected a series of 46 NSCLC samples and their corresponding control tissues and analyzed them to determine gene methylation status using the Illumina GoldenGate Methylation bead array, which screens up to 1505 CpG sites from 803 different genes. We found that 120 CpG sites, corresponding to 88 genes were hypermethylated in tumor samples and only 17 CpG sites (16 genes) were hypomethylated when compared with controls. Clustering analysis of these 104 genes discriminates almost perfectly between tumors and normal samples. Global hypermethylation was significantly associated with a worse prognosis in stage IIIA NSCLC patients (P=0.012). Moreover, hypermethylation of the CALCA and MMP-2 genes were statistically associated to a poor clinical evolution of patients, independently of TNM tumor stage (P=0.06, RR=2.64; P=0.04, RR=2.96, respectively). However, hypermethylation of RASSF1 turned out to be a protective variable (P=0.02; RR=0.53). In conclusion, our results could be useful for establishing a gene methylation pattern for the detection and prognosis of NSCLC.

Profitability of our lung retrieval program from non heart beating donors.

OBJECTIVE: In 2002 the first lung transplant from non heart beating (NHB) donors took place in Madrid. The objective of this study was to analyse our Maastricht type I NHB lung donors retrieval program and to check out its profitability. MATERIALS AND METHODS: Based on the NHB lung donors retrieval program carried out at Hospital Clínico San Carlos (Madrid) in association with Hospital Puerta de Hierro (Madrid), all lung donors from the beginning of the program from June 2002 to December 2006 have been analysed. When faced with a case of sudden death, advanced life support manoeuvres are initiated before 15 min. If the patient meets a given set of criteria, code 0/9 is activated. Arrival time to the hospital cannot exceed 90 min. Femoral artery and vein are cannulated, extracorporeal circulation is started and lungs are preserved. After the relatives' and judicial authorisation lungs are retrieved. RESULTS: Out of a total of 322 occurrences of code 0/9, 43 lung retrievals and 25 implants were reported. A total of 95% of donors were male, with an average age of 41 years and 91% with blood group A or O. 2004 saw the highest number of retrievals (14). January, May and December showed the highest number of retrievals. Incidence of sudden deaths was higher from 7 to 10 a.m. and from 7 to 10 p.m. Twenty-three implants at Hospital Puerta de Hierro and three more at Hospital Marqués de Valdecilla (Santander) were reported. A considerable amount of preserved lungs, valid for transplant, were not retrieved because of a lack of an appropriate recipient at the time. CONCLUSIONS: A total of 58.1% of preserved lungs were implanted. The ratio of obtained lungs was 11.4% of actual donors and 7.7% of total occurrences. However, this percentage could have been higher if we take into account the number of valid lungs that were not transplanted because of the lack of recipients.

Effect of adverse drug reactions on length of stay in surgical intensive care units.

OBJECTIVE: To determine the frequency of adverse drug reactions in surgical intensive care units and evaluate their effect on the length of stay. DESIGN: Prospective cohort study. Between May 1997 and December 1999, while the patients were staying in the surgical intensive care unit, data were gathered regarding suspected adverse drug reactions and on different variables related to the length of stay. SETTING: Surgical intensive care units of our hospital. PATIENTS: A total of 401 patients hospitalized in the surgical intensive care unit. MAIN RESULTS: In 37 of the 401 patients seen (9.2%; 95% confidence interval, 6.6-12.5), 39 different adverse drug reactions were detected. The adverse drug reactions were most frequently caused by the following drugs: morphine hydrochloride (n = 13), meperidine hydrochloride (n = 9), and metamizole (n = 7). Five adverse drug reactions were severe, the suspected medication had to be discontinued in 14 cases, and new drugs were necessary to manage the adverse drug reaction in 28 cases. The crude estimation of the effect of adverse drug reactions performed on the length of stay with a bivariant regression model indicated that each adverse drug reaction was related to an increase of 3.39 days (95% confidence interval, 1.47-5.31) in the length of stay. This estimation was reduced to 2.31 days (95% confidence interval, 0.64-3.99) when considering other variables that might cause confusion for analysis, although it is still important. CONCLUSIONS: Adverse drug reactions are a significant clinical and economic problem in surgical intensive care units.