Human papillomavirus infection and lung adenocarcinoma: special benefit is observed in patients treated with immune checkpoint inhibitors.

BACKGROUND: Human papilloma virus (HPV) has been associated with the development and modulation of response in a series of neoplasms. In the case of lung adenocarcinoma, its role in etiology and pathogenesis is still controversial. Considering that this infection brings foreign epitopes, it could be of prognostic significance in patients with lung adenocarcinoma treated with immunotherapy. METHODS: In a retrospective cohort study we evaluated the presence of HPV genomic material in lung adenocarcinoma primary lesions with the INNO-LiPA platform. Viral replication was also evaluated by detecting the presence of oncoprotein E6/E7 messenger RNA (mRNA) by quantitative RT-PCR. To confirm possible hypotheses regarding viral oncogenesis, vascular endothelial growth factor (VEGF) and hypoxia-inducible factor 1 (HIF1) were evaluated with stromal fibrosis and immunoscore. RESULTS: A total of 133 patients were included in the analysis, of whom 34 tested positive for HPV, reaching an estimated prevalence of 25.6% [95% confidence interval (CI) 18.2% to 32.9%]. E6/7 mRNA was identified in 28 out of the 34 previously positive cases (82.3%). In immune checkpoint inhibitor (ICI)-treated patients, the median overall survival reached 22.3 months [95% CI 19.4 months- not reached (NR)] for HPV-negative and was not reached in HPV-positive (HPV+) ones (95% CI 27.7-NR; P = 0.008). With regard to progression-free survival, HPV- patients reached a median of 9.2 months (95% CI 7.9-11.2 months) compared to 14.3 months (95% CI 13.8-16.4 months) when HPV was positive (P = 0.001). The overall response rate for HPV+ patients yielded 82.4% compared to 47.1% in negative ones. No differences regarding programmed death-ligand 1, VEGF, HIF1, stromal fibrosis, or immunoscore were identified. CONCLUSIONS: In patients with HPV+ lung adenocarcinoma, a significant benefit in overall response and survival outcomes is observed.

Electronic nicotine delivery systems (ECs) and COVID-19: the perfect storm for young consumers.

The COVID-19 pandemic caused a change in our society and put health systems in crisis worldwide. Different risk factors and comorbidities have been found that increase the risk of mortality when acquiring this infection. The use of alternative devices to the cigarette like the electronic cigarettes, the vapers have been studied widely and generators of great controversy since it has been discovered that they also produce different pulmonary affections. When developing the SARS-CoV2 infection, different theories have been generated about the greater predisposition to a worse prognosis of people who use electronic cigarettes; however, the information on this continues in discovery. A group of experts made up of oncologists, infectologists, pulmonologists, and epidemiologists met to review the literature and then generate theories about the impact of electronic cigarettes on SARS-CoV2 infection.

A comprehensive analysis of factors related to carmustine/bevacizumab response in recurrent glioblastoma.

PURPOSE: Patients with recurrent glioblastoma (rGBM) have a poor prognosis, with survival ranging from 25 to 40 weeks. Antiangiogenic agents are widely used, showing a variable response. In this study, we explored the efficacy of carmustine plus bevacizumab (BCNU/Bev) for treating rGBM. METHODS/PATIENTS: In this study, we assessed 59 adult patients with histologically confirmed rGBM who were treated with BCNU/Bev as second-line regimen. The response rate (RR), progression-free survival (PFS) and overall survival (OS) were evaluated according to their molecular expression profile, including CD133 mRNA expression, MGMT methylation (pMGMT), PDGFR amplification, YKL40 mRNA expression, IDH1/2 condition, p53 and EGFRvIII mutation status. RESULTS: Median follow-up was 18.6 months, overall RR to the combination was 56.3%, and median PFS was 9.0 months (95% CI 8.0-9.9). OS from time of diagnosis was 21.0 months (95% CI 13.2-28.7) and from starting BCNU/Bev it was 10.7 months (95% CI 9.5-11.8). IDH1/2 mutations were found in 30.5% of the patients, pMGMT in 55.9% and high CD133 mRNA expression in 57.6%. Factors which positively affected PFS included performance status (p = 0.015), IDH+ (p = 0.05), CD133 mRNA expression (p = 0.009) and pMGMT+ (p = 0.007). OS was positively affected by pMGMT+ (p = 0.05). Meanwhile, YKL40 negatively affected PFS (p = 0.01) and OS (p = 0.0001). Grade ≥ 3 toxicities included hypertension (22%) and fatigue (12%). CONCLUSIONS: BCNU/Bev is a safe and tolerable treatment for rGBM. Patients with MGMT+/IDH+ derive the greatest benefit from the treatment combination in the second-line setting. Nonetheless, high YKL40 expression discourages the use of antiangiogenic therapy.

[Morbidity and mortality in a series of patients suffering from intraperitoneal neoplasia treated with peritoneal cytoreduction and hyperthermic intraperitoneal chemotherapy at the Fundación Santa Fe de Bogotá Teaching Hospital (ONCOLGroup--ATIA study)]. / Morbilidad y mortalidad en una serie de pacientes con neoplasias del peritoneo, tratados con citorreducción peritoneal más quimioterapia hipertérmica intraperitoneal en el Hospital Universitario de la Fundación Santa Fe de Bogotá (ONCOLGroup--estudio ATIA).

BACKGROUND: The procedure of radical peritonectomy followed by hyperthermic intraperitoneal chemotherapy (HIPEC) is considered the standard treatment for peritoneal cancers. AIMS: To evaluate various outcomes in a cohort of patients with peritoneal tumors treated with HIPEC. METHODS: Twenty-four patients consecutively treated with radical peritonectomy plus HIPEC within the time frame of November 2007 to July 2010 were enrolled; 15 (62%) had tumors of appendicular origin, 4 (16.7%) had primary peritoneal tumors, 2 had ovarian carcinomas and there was one case of colon cancer, one carcinosarcoma and one hemangioendothelioma. Mean age was 53 years (range: 26-68) and median follow-up was 14.2 months (range: 1-32). Demographic data, histology, peritoneal cancer index (PCI), surgical procedure characteristics, recurrence-free survival (RFS), and overall survival (OS) were all evaluated. Short-term morbidity and mortality were also determined. RESULTS: Complete cytoreduction was achieved in 18 patients (75%). Mean PCI was 15 (<10: 41% and >10: 58%), and the median (range) for surgery duration, length of stay in the Intensive Care Unit, parenteral nutritional support, and hospital stay were 12,5 (7-20) hours, 11,4 (2-74) days, 13,8 (12-65) days, and 29,1 (10-90) days, respectively. One patient (4%) died 6 months after the procedure, due to multiple associated complications. Considerable morbidity was seen in 52% of cases, including thromboembolic events (41%), catheter-related bacteremia (29%), fistulas (29%), and nephrotoxicity (25%). Six patients (25%) recurred after a median of 21 months of RFS. CONCLUSIONS: Cytoreductive surgery plus HIPEC in well-selected patients presenting with tumors that affect the peritoneum is a procedure that can be carried out in Colombia with an adequate safety and effectiveness profile. Mortality was similar to that reported in the international literature.

Palliative endobronchial brachytherapy for non-small cell lung cancer.

BACKGROUND: Non-small cell lung cancers (NSCLC) constitutes about 80% of all lung cancer cases. Although surgery is the only curative treatment of NSCLC, fewer than 20% of tumors can be radically resected. Radiotherapy is one of the main treatment modalities in lung cancer, contributing to both its cure and palliation. Endobronchial brachytherapy (EBB) has been used as one approach to improve local control either alone or in combination with other treatments. OBJECTIVES: To assess the effectiveness of palliative EBB in increasing survival and to control thoracic symptoms in patients with advanced NSCLC compared with external beam radiation therapy (EBRT) or other alternative endoluminal treatments. SEARCH STRATEGY: The Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE and other databases were searched, as were reference lists and handsearching of selected journals and conference proceedings. SELECTION CRITERIA: Randomized controlled trials (RCTs) comparing different regimens of palliative EBB with EBRT or other endobronchial interventions in patients with advanced NSCLC. DATA COLLECTION AND ANALYSIS: Thirteen RCTs were included. There were important differences in the doses of radiotherapy investigated, patient characteristics and the outcomes measured. Because of this heterogeneity no meta-analysis was attempted. MAIN RESULTS: We found trials comparing EBB to EBRT alone, EBB plus EBRT to EBRT alone, EBB plus chemotherapy to EBB alone, EBB to Nd-YAG laser and comparisons between diverse fractionation schedules of high dose rate EBB. From the heterogeneous information obtained from several small RCTs, we concluded that EBRT alone is more effective for palliation of NSCLC symptoms than EBB alone. Our findings did not provide conclusive evidence to recommend EBB plus EBRT to relieve symptoms compared to EBRT alone. Overall, for the primary endpoint of survival there was no evidence of benefit for EBB compared to EBRT and Nd-YAG laser or for the combination of EBB with chemotherapy. Additionally, findings from one trial suggested that twice 7.4 Gy was superior to the four times per week 3.8 Gy schedule for mean time of local control and fatal haemoptysis. No significant differences were found for fatal haemoptysis as an adverse event of EBB. AUTHORS' CONCLUSIONS: The evidence did not provide conclusive results that EBB plus EBRT improved symptom relief over EBRT alone. We were not able to provide conclusive evidence to recommend EBB with EBRT, chemotherapy or Nd-YAG laser. For patients previously treated by EBRT who are symptomatic from recurrent endobronchial central obstruction, EBB may be considered in selected cases.

Human recombinant activated protein C for severe sepsis.

BACKGROUND: Sepsis is a common, expensive and frequently fatal condition. There is an urgent need for developing new therapies to further reduce severe sepsis-induced mortality. One of those approaches is the use of human recombinant activated protein C (APC). OBJECTIVES: We assessed the clinical effectiveness of APC for the treatment of patients with severe sepsis or septic shock. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2005, Issue 2); MEDLINE (1966 to 2005); EMBASE (1980 to 2005) and LILACS (1982 to 2005). We contacted researchers and organizations working in the field. We did not have any language restriction. SELECTION CRITERIA: We included randomized controlled trials (RCTs) assessing the effects of APC for severe sepsis in adults and children. We excluded studies on neonates. DATA COLLECTION AND ANALYSIS: We independently performed study selection, quality assessment and data extraction. We estimated relative risks (RR) for dichotomous outcomes. We measured statistical heterogeneity using I-squared (I(2)). We used a random-effects model. MAIN RESULTS: We included four studies involving 4911 participants (4434 adults and 477 paediatric patients). For 28-day mortality, APC did not reduce the risk of death in adult participants with severe sepsis (pooled RR 0.92, 95% confidence interval (CI) 0.72 to 1.18; P = 0.50, I(2) = 72%). The effectiveness of APC did not seem to be associated with the degree of severity of sepsis (two studies): for an APACHE II score less than 25 the RR was 1.04 (95% CI 0.89 to 1.21; P = 0.70), and in participants with an APACHE II score of 25 or more the RR was 0.90 (95% CI 0.54 to 1.49; P = 0.68). APC use was, however, associated with a higher risk of bleeding (RR 1.48 (95% CI 1.07 to 2.06; P = 0.02, I(2) = 8%). Two studies were stopped early because there was little chance of reaching the efficacy endpoint by completion of the trial. AUTHORS' CONCLUSIONS: This updated review found no evidence suggesting that APC should be used for treating patients with severe sepsis or septic shock. Additionally, APC seems to be associated with a higher risk of bleeding. Unless additional RCTs provide evidence of a treatment effect, policy-makers, clinicians and academics should not promote the use of APC.

Human recombinant activated protein C for severe sepsis.

BACKGROUND: Sepsis is a common, expensive and frequently fatal condition. There is an urgent need for developing new therapies to further reduce severe sepsis-induced mortality. One of those approaches is the use of human recombinant activated protein C (APC). OBJECTIVES: We assessed the clinical effectiveness of APC for the treatment of patients with severe sepsis or septic shock. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2005, Issue 2); MEDLINE (1966 to 2005); EMBASE (1980 to 2005) and LILACS (1982 to 2005). We contacted researchers and organizations working in the field. We did not have any language restriction. SELECTION CRITERIA: We included randomized controlled trials (RCTs) assessing the effects of APC for severe sepsis in adults and children. We excluded neonates. DATA COLLECTION AND ANALYSIS: We independently performed study selection, quality assessment and data extraction. We estimated relative risks (RR) for dichotomous outcomes. We measured statistical heterogeneity using I-squared (I(2)). We used a random-effects model. MAIN RESULTS: We included four studies involving 4911 participants (4434 adults and 477 paediatric patients). For 28-day mortality, APC did not reduce the risk of death in adult participants with severe sepsis (pooled RR 0.92, 95% confidence interval (CI) 0.72 to 1.18; P = 0.50, I(2) = 72%). The effectiveness of APC did not seem to be associated with the degree of severity of sepsis (two studies): for an APACHE II score less than 25 the RR was 1.04 (95% CI 0.89 to 1.21; P = 0.70), and in participants with an APACHE II score of 25 or more the RR was 0.90 (95% CI 0.54 to 1.49; P = 0.68). APC use was, however, associated with a higher risk of bleeding (RR 1.48 (95% CI 1.07 to 2.06; P = 0.02, I(2) = 8%). Two studies were stopped early because there was little chance of reaching the efficacy endpoint by completion of the trial. AUTHORS' CONCLUSIONS: This review suggests that APC should not be used in sepsis with an APACHE II score of less than 25 or, in paediatric patients. There is very weak evidence supporting APC use in patients with severe sepsis and at high-risk of death. As a result, policy-makers, clinicians and academics should be cautious when promoting the use of APC to patients with severe sepsis and an APACHE II score of 25 or greater. There is a need for further RCTs to answer with certainty what the role of APC is for patients with severe sepsis and an APACHE II score of at least 25. Those RCTs should be designed and conducted by non-profit organizations.

Antibiotics for acute laryngitis in adults.

BACKGROUND: Acute laryngitis is a common illness worldwide. Diagnosis is often made by case history alone and treatment is often directed towards controlling symptoms. OBJECTIVES: The aim of this review was to assess the effectiveness of different antibiotic therapies in adults suffering acute laryngitis. A secondary objective was to report the rates of adverse events associated with these treatments. SEARCH STRATEGY: We systematically screened the following electronic databases: the Cochrane Central Register of Controlled Trials (The Cochrane Library Issue 4, 2006); MEDLINE (January 1966 to December Week 2 2006); and EMBASE (1974 to June 2006), LILACS (from 1982 to December 2006 ) and BIOSIS (1980 to June 2002). Other strategies included hand searching relevant journals, searching ongoing trial databases and general databases such as Google scholar. SELECTION CRITERIA: Randomized controlled trials comparing any antibiotic therapy with placebo in acute laryngitis. The main outcome measurement was objective voice scores. DATA COLLECTION AND ANALYSIS: Data were independently extracted by two review authors and then descriptively synthesized. MAIN RESULTS: Only two trials met study inclusion criteria after extensive literature searches. One hundred participants were randomly selected to receive either penicillin V (800 mg twice a day for five days), or an identical placebo, in a study of penicillin V in acute laryngitis in adults. A tape recording of each patient reading a standardized text was obtained during the first visit, subsequently during re-examination after one and two weeks, and at follow up after two to six months. No significant differences were found between the groups. The trial also measured symptoms reported by participants and found no significant differences. The second trial investigated erythromycin for treating acute laryngitis in 106 adults. The mean objective voice scores measured at the first visit, at re-examination after one and two weeks, and at follow up after two to six months did not significantly differ between control and intervention groups. At one week there were significant beneficial differences in the severity of reported vocal symptoms as judged by the participants (P = 0.042). Comparing the erythromycin and placebo groups on subjective voice scores the a priori relative risk (RR) was 0.7 (95% confidence interval (CI) 0.51 to 0.96, P = 0.034) and the number needed to treat (NNT) was 4.5. AUTHORS' CONCLUSIONS: Antibiotics appear to have no benefit in treating acute laryngitis. Erythromycin could reduce voice disturbance at one week and cough at two weeks when measured subjectively. We consider that these outcomes are not relevant in clinical practice. The implications for practice are that prescribing antibiotics should not be done in the first instance as they will not objectively improve symptoms.

Interventions for treating AIDS-associated Hodgkin s lymphoma in treatment-naive adults.

BACKGROUND: Hodgkin's disease (HD) is the most common non-AIDS-defining malignancy in HIV-infected patients. Its unusually aggressive tumour behaviour includes a higher frequency of unfavourable histologic subtypes, high-stage and extranodal involvement by the time of presentation (anal canal, stomach), and poor therapeutic outcome, in comparison with HD outside the HIV setting. The optimal therapeutic strategy is still controversial, and median overall survival is short, ranging from 12 to 18 months. Thus, there is a need to identify the efficacy and safety of different interventions for AIDS-associated HD on overall survival and disease-free survival in treatment-naive adults with AIDS. OBJECTIVES: To assess the effects of different interventions for treating AIDS-associated Hodgkin's disease including chemotherapy, bone marrow transplantation (BMT), and gene therapy on overall survival and disease-free survival in treatment-naive adults with AIDS. SEARCH STRATEGY: We searched The Cochrane HIV/AIDS Group Trials Register (September 2006), which comprises references identified from comprehensive electronic database searches and handsearching of relevant journals and abstract books of conference proceedings. We also searched the Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library (Issue 3, 2006), MEDLINE (1966 to September 2006), EMBASE (1974 to September 2006) LILACS (1982 to September 2006), ISI Web of Knowledge (1993 to September 2006), and AIDSearch (1980 to December 2006). Date of most recent search: December 2006. SELECTION CRITERIA: We searched for published or unpublished randomised controlled trials. DATA COLLECTION AND ANALYSIS: We intended to summarise data by standard Cochrane Collaboration methodologies, but no eligible randomised controlled trials were identified. MAIN RESULTS: We were unable to find any randomised controlled trials of interventions for treating AIDS-associated HD in treatment-naive adults with AIDS. AUTHORS' CONCLUSIONS: Randomised controlled trials are needed to establish the efficacy and safety of interventions for treating AIDS-associated HD in treatment-naive adults with AIDS.

Antibiotics for acute laryngitis in adults.

BACKGROUND: Acute laryngitis is a common illness worldwide. Diagnosis is often made by case history alone and treatment is often directed towards controlling symptoms. OBJECTIVES: The aim of this review was to assess the effectiveness of different antibiotic therapies in adults suffering acute laryngitis. A secondary objective was to report the rates of adverse events associated with these treatments. SEARCH STRATEGY: We systematically screened the following electronic databases: the Cochrane Central Register of Controlled Trials (The Cochrane Library Issue 3, 2004); MEDLINE (January 1966 to June Week 3 2004); and EMBASE (1974 to June 2004), LILACS (from 1982 to the 40th edition) and BIOSIS (1980 to June 2002). Other strategies included hand searching relevant journals, searching ongoing trial databases and general databases such as Alta Vista. SELECTION CRITERIA: Randomized controlled trials comparing any antibiotic therapy with placebo in acute laryngitis. The main outcome measurement was objective voice scores. DATA COLLECTION AND ANALYSIS: Data were independently extracted by two people and then descriptively synthesised. MAIN RESULTS: Only two trials met study inclusion criteria after extensive literature searches. One hundred patients were randomly selected to receive either penicillin V (800 mg twice a day for five days), or an identical placebo, in a study of penicillin V in acute laryngitis in adults. A tape recording of each patient reading a standardised text was obtained during the first visit, subsequently during re-examination after one and two weeks, and at follow up after two to six months. No significant differences were found between the groups. The trial also measured symptoms reported by patients and found no significant differences. The second trial investigated erythromycin for treating acute laryngitis in 106 adults. The mean objective voice scores measured at the first visit, at re-examination after one and two weeks, and at follow up after two to six months did not significantly differ between control and intervention groups. At one week there were significant beneficial differences in the severity of reported vocal symptoms as judged by the patients (p = 0.042). Comparing the erythromycin and placebo groups on subjective voice scores the a priori relative risk (RR) was 0.7 (95% confidence interval (CI) 0.51 to 0.96, p = 0.034) and the number needed to treat (NNT) was 4.5. AUTHORS' CONCLUSIONS: Antibiotics appear to have no benefit in treating acute laryngitis. Erythromycin could reduce voice disturbance at one week and cough at two weeks when measured subjectively. We consider that these outcomes are not relevant in clinical practice. The implications for practice are that prescribing antibiotics should not be done in the first instance as they will not objectively improve symptoms.

Registro latinoamericano de experimentos clínicos en curso (latin-rec) / Latin-American registration of clinical experiments under way (latin-rec)

Es bien conocido que tanto los experimentos clínicos aleatorizados así como las revisiones sistemáticas de la literatura y los meta análisis bien conducidos, ofrecen la evidencia más confiable y de mejor calidad, sobre el efecto de las intervenciones en salud. Los autores de revisiones sistemáticas, así como de otros estudios integrativos entre los que se encuentran guías de práctica clínica basadas en evidencia, y análisis económicos, deben tratar de encontrar toda la evidencia relevante en un intento para minimizar el riesgo del sesgo de publicación, que corresponde al hecho que los resultados negativos, es decir aquellos que no encuentran diferencias entre los grupos de intervención, es menos probable que lleguen a la publicación, tardan más tiempo en ser publicados cuando lo hacen y tienden a publicarse más frecuentemente en el idioma nativo del autor cuando no es el inglés; todo esto podría conducir a una distorsión de la evidencia disponible para la toma de decisiones en la práctica clínica. Adicionalmente, algunos resultados de experimentos no son fácilmente recuperados en búsquedas de la literatura porque nunca han sido publicados o lo han hecho en revistas biomédicas no indexadas en las grandes bases de datos1 y 3. Desde mucho tiempo atrás se ha reconocido la importancia de registrar de manera sistemática y prospectiva los experimentos clínicos aleatorizados. Sin embargo, existen varias barreras que han impedido el desarrollo de un registro comprehensivo para los experimentos clínicos a saber: resistencia de la industria farmacéutica y tecnológica, recursos insuficientes para hacer sostenible la empresa del registro a largo plazo, dificultades para forzar a los investigadores a registrar su ensayo y carencia de conocimiento acerca de los problemas de no registrar los experimentos4...

[Effectiveness of flunarizine in the prophylaxis of migraine: a meta-analytical review of the literature]. / Eficacia de flunaricina en la profilaxis de migraña: revisión metaanalítica de la bibliografía.

BACKGROUND: Migraine is a common and disabling health problem among young and middle aged adults. Flunarizine have been used as a prophylactic medication in its management for more than two decades. OBJECTIVE: The aim of the study is to systematically review the evidence obtained from randomized controlled trials about the efficacy and security of flunarizine versus placebo for the prevention of migraine in adults. MATERIALS AND METHODS: Electronic search were performed using the databases MEDLINE, EMBASE, Biosis, the Cochrane Library, Lilacs and others. Reference lists of retrieved studies, reviews and conference abstracts were used to found another articles. Additionally, the authors performed a handsearched in recognized journals related to migraine and neurological topics. Randomized, placebo controlled, double blind trials assessing the efficacy of flunarizine for preventing migraine were included. We evaluated the frequency of the attacks by comparing the mean frequency before and after the intervention for each group of treatment and then the two groups were compared. To evaluate the security of flunarizine we used included and excluded studies and open trials. RESULTS: Nine studies were obtained but only four met the inclusion criteria. The fixed effects model reported a reduction in the frequency of attacks by using flunarizine. The monthly difference was 0.55 attacks (CI 95%= 0.215 0.895; p= 0.002). Somnolence was the most frequent adverse effect in 20.5% of the subjects (n= 1,987). CONCLUSIONS: Based on a small number of trials, flunarizine, at a daily dose of 10 mg lightly reduces the frequency of migraine attacks.