Role of IP-10 to Predict Clinical Progression and Response to IL-6 Blockade With Sarilumab in Early COVID-19 Pneumonia. A Subanalysis of the SARICOR Clinical Trial.

Background: The Clinical Trial of Sarilumab in Adults With COVID-19 (SARICOR) showed that patients with coronavirus disease 2019 (COVID-19) pneumonia and increased levels of interleukin (IL)-6 might benefit from blockade of the IL-6 pathway. However, the benefit from this intervention might not be uniform. In this subanalysis, we sought to determine if other immunoactivation markers, besides IL-6, could identify which subgroup of patients benefit most from this intervention. Methods: The SARICOR trial was a phase II, open-label, multicenter, controlled trial (July 2020-March 2021) in which patients were randomized to receive usual care (UC; control group), UC plus a single dose of sarilumab 200 mg (sarilumab-200 group), or UC plus a single dose of sarilumab 400 mg (sarilumab-400 group). Patients who had baseline serum samples for cytokine determination (IL-8, IL-10, monocyte chemoattractant protein-1, interferon-inducible protein [IP]-10) were included in this secondary analysis. Progression to acute respiratory distress syndrome (ARDS) according to cytokine levels and treatment received was evaluated. Results: One hundred one (88%) of 115 patients enrolled in the SARICOR trial had serum samples (control group: n = 33; sarilumab-200: n = 33; sarilumab-400: n = 35). Among all evaluated biomarkers, IP-10 showed the strongest association with treatment outcome. Patients with IP-10 ≥2500 pg/mL treated with sarilumab-400 had a lower probability of progression (13%) compared with the control group (58%; hazard ratio, 0.19; 95% CI, 0.04-0.90; P = .04). Conversely, patients with IP-10 <2500 pg/mL did not show these differences. Conclusions: IP-10 may predict progression to ARDS in patients with COVID-19 pneumonia and IL-6 levels >40 pg/mL. Importantly, IP-10 value <2500 pg/mL might discriminate those individuals who might not benefit from sarilumab therapy among those with high IL-6 levels.

Early Use of Sarilumab in Patients Hospitalized with COVID-19 Pneumonia and Features of Systemic Inflammation: the SARICOR Randomized Clinical Trial.

The objective of this study was to investigate the efficacy and safety of early treatment with sarilumab, added to standard of care (SOC), in hospitalized adults with COVID-19. Methods included phase II, open-label, randomized, controlled clinical trial of hospitalized patients with COVID-19 pneumonia and interleukin (IL)-6 levels ≥ 40 pg/mL and/or d-dimer > 1,500 ng/mL. Participants were randomized (1:1:1) to receive SOC (control group), SOC plus a single subcutaneous dose of sarilumab 200 mg (sarilumab-200 group), or SOC plus a single subcutaneous dose of sarilumab 400 mg (sarilumab-400 group). The primary outcome variable was the development of acute respiratory distress syndrome (ARDS) requiring high-flow nasal oxygenation (HFNO), non-invasive mechanical ventilation (NIMV) or invasive mechanical ventilation (IMV) at day 28. One-hundred and 15 participants (control group, n = 39; sarilumab-200, n = 37; sarilumab-400, n = 39) were included. At randomization, 104 (90%) patients had supplemental oxygen and 103 (90%) received corticosteroids. Eleven (28%) patients in the control group, 10 (27%) in sarilumab-200, and five (13%) in sarilumab-400 developed the primary outcome (hazard ratio [95% CI] of sarilumab-400 vs control group: 0.41 [0.14, 1.18]; P = 0.09). Seven (6%) patients died: three in the control group and four in sarilumab-200. There were no deaths in sarilumab-400 (P = 0.079, log-rank test for comparisons with the control group). In patients recently hospitalized with COVID-19 pneumonia and features of systemic inflammation, early IL-6 blockade with a single dose of sarilumab 400 mg was safe and associated with a trend for better outcomes. (This study has been registered at ClinicalTrials.gov under identifier NCT04357860.).

[Anaphylaxis sugammadex-induced in a pediatric patient]. / Anafilaxia por sugammadex en paciente pediátrico.

INTRODUCTION: Sugammadex is a cyclodextrin that reverses neuromuscular blockade, especially of rocuronium. The occurrence of anaphylaxis produced by its use is of 1:1000 and 1:20000; it is observed mainly in subjects of Asian origin. CASE REPORT: A 9-year-old boy of Asian origin who, after the administration of sugammadex, immediately manifested an episode of anaphylaxis, which was reverted by using adrenaline and antihistamines. The serum tryptase at two hours was 27.7 µg/L; at 6 weeks, it was 3 µ/L. The sugammadex 100 mg/mL skin test was positive. The basophil activation test was positive with sugammadex 20 mg/mL. CONCLUSION: The temporal relationship between the administration of the drug, the clinical manifestations, the elevation of tryptase, and the diagnostic tests performed, disclosed the episode of anaphylaxis associated with hypersensitivity to sugammadex.

Introducción: Sugammadex es una ciclodextrina que revierte el bloqueo neuromuscular, especialmente de rocuronio. La incidencia de anafilaxia producida por su uso es de 1:1.000 y 1:20.000, se observa principalmente en sujetos de origen asiático. Reporte de caso: Niño de 9 años, de raza asiática que tras la administración de sugammadex, inmediatamente manifestó un episodio de anafilaxia, la cual revirtió con el uso de adrenalina y antihistamínicos. La triptasa sérica a las 2 h fue de 27.7 µg/L; a las 6 semanas fue 3 µg/L. La prueba cutánea a sugammadex 100 mg/mL fue positiva. La prueba de activación de basófilos fue positiva con 20 mg/mL sugammadex. Conclusión: La relación temporal de la administración del medicamento, las manifestaciones clínicas, la elevación de la triptasa y las pruebas diagnósticas realizadas, identificaron el episodio de anafilaxia asociado con hipersensibilidad por sugammadex.

Efficacy and safety of early treatment with sarilumab in hospitalised adults with COVID-19 presenting cytokine release syndrome (SARICOR STUDY): protocol of a phase II, open-label, randomised, multicentre, controlled clinical trial.

INTRODUCTION: About 25% of patients with COVID-19 develop acute respiratory distress syndrome (ARDS) associated with a high release of pro-inflammatory cytokines such as interleukin-6 (IL-6). The aim of the SARICOR study is to demonstrate that early administration of sarilumab (an IL-6 receptor inhibitor) in hospitalised patients with COVID-19, pulmonary infiltrates and a high IL-6 or D-dimer serum level could reduce the progression of ARDS requiring high-flow nasal oxygen or mechanical ventilation (non-invasive or invasive). METHODS AND ANALYSIS: Phase II, open-label, randomised, multicentre, controlled clinical trial to study the efficacy and safety of the administration of two doses of sarilumab (200 and 400 mg) plus best available therapy (BAT) in hospitalised adults with COVID-19 presenting cytokine release syndrome. This strategy will be compared with a BAT control group. The efficacy and safety will be monitored up to 28 days postadministration. A total of 120 patients will be recruited (40 patients in each arm). ETHICS AND DISSEMINATION: The clinical trial has been approved by the Research Ethics Committee of the coordinating centre and authorised by the Spanish Agency of Medicines and Medical Products. If the hypothesis is verified, the dissemination of the results could change clinical practice by increasing early administration of sarilumab in adult patients with COVID-19 presenting cytokine release syndrome, thus reducing intensive care unit admissions. TRIAL REGISTRATION NUMBER: NCT04357860.

Screening for and decolonization of Staphylococcus aureus carriers before total joint replacement is associated with lower S aureus prosthetic joint infection rates.

BACKGROUND: Prosthetic joint infections (PJI) can be devastating postoperative complications after total joint replacement (TJR). The role of decolonization of Staphylococcus aureus carriers prior to surgery still remains unclear, and the most recent guidelines do not state a formal recommendation for such strategy. Our purpose was to seek further evidence supporting preoperative screening and S aureus decolonization in patients undergoing TJR. METHODS: This was a quasiexperimental quality improvement study comparing a 5-year baseline of deep and organ-space PJIs (2005- 2010) to a 1-year intervention period (May 2015 to July 2016). The intervention consisted of nasal and throat screening for S aureus preoperatively and decolonization of carriers over 5 days prior to surgery. RESULTS: Prior to the intervention, we identified 42 deep and/or organ-space PJIs in 8,505 patients undergoing TJR (0.5%). S aureus was the causal microorganism in 28 of 42 (66.6%) cases. During the intervention, 22.5% (424 of 1,883) of patients were S aureus carriers. The PJI rate was similar overall (0.4%, 7 of 1,883; odds ratio, 0.75; 95% confidence interval, 0.34-1.67; P = .58), but there was a significant reduction in S aureus PJI to only 1 case during the intervention (odds ratio, 0.15; 95% confidence interval, 0.004-0.94; P = .039). CONCLUSIONS: Active screening for S aureus and decolonization of carriers prior to TJR was associated with a reduction in PJI due to S aureus, but no changes in overall PJI rates were observed.

Correction to: Prevention of Infections in Cardiac Surgery study (PICS): study protocol for a pragmatic cluster-randomized factorial crossover pilot trial.

Following publication of the original article [1], we have been notified of a few mistakes in the "Sample size calculations" section, second paragraph.

Traqueobronquitis obstructiva por Aspergillus fumigatus en un paciente inmunocompetente / Obstructive tracheobronchitis due to Aspergillus fumigatus in an immunocompetent patient

Antecedentes: La traqueobronquitis aspergilar (TBA) es una forma clínica infrecuente de aspergilosis pulmonar invasiva donde la afectación fúngica se limita al árbol traqueobronquial. Aunque las formas más graves, como la TBA pseudomembranosa y ulcerativa, son casi exclusivas de pacientes inmunocomprometidos, la forma obstructiva, más leve, puede cursar en pacientes sin déficit inmunitario. Caso clínico: Se presenta el caso de un varón de 32 años sin antecedentes de interés que es evaluado por presentar neumonía recidivante del lóbulo inferior derecho. En los estudios microbiológicos del esputo destacaba el crecimiento de Serratia marcescens y escaso crecimiento de Aspergillus fumigatus, que se interpretó como una contaminación de la muestra. La fibrobroncoscopia reveló al nivel B10 del lóbulo inferior derecho un tapón mucoso muy denso que no se pudo extraer; no hubo otros hallazgos macroscópicos de interés. Durante la hospitalización el paciente logró expectorar el tapón mucoso y presentó una importante broncorrea posterior; en los cultivos microbiológicos se observaron numerosas colonias de A. fumigatus. Se indicó tratamiento con voriconazol, lo que llevó a la resolución del cuadro, sin nuevas recidivas. Conclusiones: La TBA obstructiva se caracteriza por la producción excesiva de moco denso cargado de hifas que puede llegar a obstruir la luz de la vía aérea y generar neumonías postobstructivas recidivantes. Es importante considerar este diagnóstico en pacientes inmunocompetentes con infecciones respiratorias recurrentes que presentan aislamiento repetido de colonias de Aspergillus en el esputo, aunque sean en escasa cuantía

Background: Aspergillus tracheobronchitis (ATB) is an uncommon type of invasive pulmonary aspergillosis in which fungal involvement is limited to the tracheobronchial tree. While the more severe forms, such as pseudomembranous and ulcerative ATB, occur almost exclusively in immunocompromised patients, the milder obstructive form may occur in patients without immune deficiency. Case report: The case of a 32 year-old man with no previous history of illness, who was evaluated for recurrent right lower lobe pneumonia, is presented. Microbiological sputum studies revealed growth of Serratia marcescens, and a limited growth of Aspergillus fumigatus, the latter interpreted as a contaminant in the specimen. Bronchoscopy revealed a dense mucous plug at level B10 of the right lower lobe, which could not be removed; no other macroscopic findings of interest were observed. During his hospital admission, the patient expectorated the mucous plug and had a significant subsequent bronchorrhoea. A substantial number of colonies of A. fumigatus grown in the sputum cultures. The patient was given voriconazole, leading to a clinical resolution, with no recurrences. Conclusions: Obstructive ATB is characterised by the excessive production of thick, hyphae-laden mucus, which can obstruct the airway lumen and generate relapsing post-obstructive pneumonias. It is important to consider this diagnosis in immunocompetent patients with recurrent respiratory infections and who show repeated isolation of Aspergillus colonies in the sputum, even in small quantities

[Obstructive tracheobronchitis due to Aspergillus fumigatus in an immunocompetent patient]. / Traqueobronquitis obstructiva por Aspergillus fumigatus en un paciente inmunocompetente.

BACKGROUND: Aspergillus tracheobronchitis (ATB) is an uncommon type of invasive pulmonary aspergillosis in which fungal involvement is limited to the tracheobronchial tree. While the more severe forms, such as pseudomembranous and ulcerative ATB, occur almost exclusively in immunocompromised patients, the milder obstructive form may occur in patients without immune deficiency. CASE REPORT: The case of a 32 year-old man with no previous history of illness, who was evaluated for recurrent right lower lobe pneumonia, is presented. Microbiological sputum studies revealed growth of Serratia marcescens, and a limited growth of Aspergillus fumigatus, the latter interpreted as a contaminant in the specimen. Bronchoscopy revealed a dense mucous plug at level B10 of the right lower lobe, which could not be removed; no other macroscopic findings of interest were observed. During his hospital admission, the patient expectorated the mucous plug and had a significant subsequent bronchorrhoea. A substantial number of colonies of A. fumigatus grown in the sputum cultures. The patient was given voriconazole, leading to a clinical resolution, with no recurrences. CONCLUSIONS: Obstructive ATB is characterised by the excessive production of thick, hyphae-laden mucus, which can obstruct the airway lumen and generate relapsing post-obstructive pneumonias. It is important to consider this diagnosis in immunocompetent patients with recurrent respiratory infections and who show repeated isolation of Aspergillus colonies in the sputum, even in small quantities.

Prevention of Infections in Cardiac Surgery study (PICS): study protocol for a pragmatic cluster-randomized factorial crossover pilot trial.

BACKGROUND: A wide range of prophylactic antibiotic regimens are used for patients undergoing open-heart cardiac surgery. This reflects clinical equipoise in choice and duration of antibiotic agents. Although individual-level randomized control trials (RCT) are considered the gold standard when evaluating the efficacy of an intervention, this approach is highly resource intensive and a cluster RCT can be more appropriate for testing clinical effectiveness in a real-world setting. METHODS/DESIGN: We are conducting a factorial cluster-randomized crossover pilot trial in cardiac surgery patients to evaluate the feasibility of this design for a definite trial to evaluate the optimal duration and choice of perioperative antibiotic prophylaxis. Specifically, we will evaluate: (a) the non-inferiority of a single preoperative dose compared to prolonged prophylaxis and (b) the potential superiority of adding vancomycin to routine cefazolin in terms of preventing deep and organ/space sternal surgical site infections (s-SSIs). There are four strategies: (i) short-term cefazolin, (ii) long-term cefazolin, (iii) short-term cefazolin + vancomycin, and (iv) long-term cefazolin + vancomycin. These strategies are delivered in a different order in each health-care center participating in the trial. The centers are randomized to an order, and the current strategy becomes the standard operating procedure in that center during the study. The three feasibility outcomes include: (1) the proportion of patients receiving preoperative, intra-operative, and postoperative antibiotics according to the study protocol, (2) the proportion of completed follow-up assessments, and (3) a full and final assessment of the incidence of s-SSIs by the outcome adjudication committee. DISCUSSION: We believe that a cluster-randomized factorial crossover trial is an effective and feasible design for these research questions, allowing an evaluation of the clinical effectiveness in a real-world setting. A waiver of individual informed consent was considered appropriate by the research ethics boards in each participating site in Canada as long as an information letter with an opt-out option was provided. However, a waiver of consent was not approved at two sites in Germany and Switzerland, respectively. TRIAL REGISTRATION: Clinicaltrials.gov, NCT02285140 . Registered on 15 October 2015.

Unsolicited consultation by infectious diseases specialist improves outcomes in patients with bloodstream infection: A prospective cohort study.

INTRODUCTION: The objective of this study was to evaluate the impact of an intervention based on unsolicited consultations by an infectious diseases specialist (IDS) on the adequacy of antimicrobial treatment and mortality in patients with BSI. METHODS: A prospective cohort study was performed in a 410-bed hospital. An intervention based on unsolicited consultation by an IDS for patients with BSI was performed only on days when an IDS was available. Outcomes were the percentage of days on optimal antimicrobial treatment (PDOAT) and mortality. Analyses were performed by linear regression and multivariate logistic regression. RESULTS: Of 400 episodes of BSI included, 292 received the intervention. The median (interquartile range) PDOAT among those with and without the intervention was 93 (6-100) and 0 (0-53), respectively. The intervention was independently associated with a higher PDOAT (r = 0.5; p < 0.001) but not with mortality. The IDS recommendations were followed in full in 183 episodes, and not in 109. Mortality was 10.4% and 27.6%, respectively. Adherence to recommendations was associated with lower mortality (adjusted OR = 0.3; 95% CI: 0.1-0.5). CONCLUSIONS: An intervention based on unsolicited IDS consultation for BSI episodes was associated with improved use of antibiotics and, when the recommendations were fully followed, with lower mortality.

High quality of life, treatment tolerability, safety and efficacy in HIV patients switching from triple therapy to lopinavir/ritonavir monotherapy: A randomized clinical trial.

TRIAL DESIGN: The QoLKAMON study evaluated quality of life, efficacy and treatment safety in HIV patients receiving lopinavir/ritonavir in monotherapy (MT) versus continuing combined antiretroviral triple treatment with a boosted protease inhibitor (TT). METHODS: This was a 24-week, open-label, multicentre study in virologically-suppressed HIV-infected participants (N = 225) with a 2:1 randomization: 146 patients who switched to MT were compared with 79 patients who remained on a TT regimen. The primary endpoint was change in patient-reported outcomes in quality of life as measured by the MOS-HIV and EQ-5D questionnaires. Secondary endpoints included treatment adherence, patient satisfaction, incidence of adverse events and differences in plasma HIV-1 RNA viral load (VL) and CD4 cell counts. RESULTS: Baseline quality of life, measured with the MOS-HIV score, was very good (overall score of 83 ± 10.5 in the MT arm and 82.3 ± 11.3 in the TT arm) and suffered no change during the study in any of the arms (at week 24, 83.5 ± 12.2 in MT arm and 81.9 ± 12.7 in TT arm), without statistically significant differences when compared. In regards to adherence to therapy and patient satisfaction, some aspects (number of doses forgotten in the last week and satisfaction of treatment measured with the CESTA score, dimension 1) improved significantly with MT. There were also no differences in the incidence and severity of adverse events, even though 22.8% of those in the MT arm switched their treatment when they were included in the study. Moreover, there was also no significant difference between the immunological and virological evolution of MT and TT. In the MT arm, the VL was always undetectable in 83% of patients (vs 90.7% in the TT arm) and there were only 6.7% of virological failures with VL > 50 copies/mL (vs 2.3% in the TT arm), without resistance mutations and with resuppression of VL after switching back to TT. CONCLUSIONS: In a new clinical trial, monotherapy as a treatment simplification strategy in HIV-1 infected patients with sustained viral suppression has demonstrated quality of life, safety and efficacy profiles comparable to those of conventional triple therapy regimens.

Apneic Oxygenation During Prolonged Laryngoscopy in Obese Patients: A Randomized, Controlled Trial of Buccal RAE Tube Oxygen Administration.

BACKGROUND: Despite optimal preoxygenation, obese patients undergoing induction of general anesthesia exhibit significant hypoxemia after 2 to 4 minutes of apnea. Apneic oxygenation techniques can assist airway management by extending the safe apnea time. We hypothesized that a novel method of apneic oxygenation via the oral route would effectively prolong safe apnea in an obese surgical population. METHODS: In this open-label, parallel-arm, randomized-controlled efficacy trial, 40 ASA physical status I-II obese patients with body mass index (BMI) 30-40 were randomly assigned to standard care (n = 20) or buccal oxygenation (n = 20) during induction of total IV anesthesia. Buccal oxygen was administered via a modified 3.5-mm Ring-Adair-Elwyn (RAE) tube apposed to the left internal cheek. Prolonged laryngoscopy maintained apnea with a patent airway until SpO2 dropped below 95% or 750 seconds elapsed. The primary outcome was time to reach SpO2 < 95%. RESULTS: Patient characteristics were similar in both study arms. Recipients of buccal oxygenation were less likely to exhibit SpO2 < 95% during 750 seconds of apnea; hazard ratio 0.159 (95% confidence interval 0.044-0.226, P < .0001). Median (interquartile range [IQR]) apnea times with SpO2 ≥ 95% were prolonged in this group; 750 (389-750) versus 296 (244-314) seconds, P < .0001. CONCLUSIONS: Clinically important prolongation of safe apnea times can be achieved delivering buccal oxygen to obese patients on induction of anesthesia. This novel use of apneic oxygenation via the oral route may improve management of the difficult airway and overcome some of the limitations of alternative techniques.

Real-life experience with sorafenib for the treatment of hepatocellular carcinoma in HIV-infected patients.

OBJECTIVE: To report the real-life results of sorafenib use in a cohort of HIV-infected patients with hepatocellular carcinoma (HCC). METHODS: The GEHEP-002 cohort (ClinicalTrials.gov ID: NCT02785835) has recruited 302 HCC cases diagnosed in HIV-infected patients from 32 centers from Spain. RIS-HEP12 study included 44 (14%) cases that have received at least one dose of sorafenib. The overall survival after the start of treatment was the main efficacy outcome. Permanent discontinuation due to adverse events was the primary safety end point. RESULTS: Reasons for sorafenib use are HCC recurrence after previous curative therapy (n = 7), progression following transarterial chemoembolization (n = 6) and first treatment against HCC (n = 31). Nineteen (43%) patients harbored Child-Pugh B cirrhosis. Barcelona-Clinic Liver Cancer stage was A 3 (7%), B 6 (14%), C 30 (68%) and D 5 (11%). All patients were on antiretroviral therapy (ART). The median (Q1-Q3) duration of sorafenib treatment was 70 (31-158) days. Median survival was 7.2 months, whereas the median (Q1-Q3) duration of overall survival after the start of treatment was 4 (2-9.7) months. Twenty-six (59%) patients had any grade adverse events and 19 (43%) suffered a decompensation. Discontinuation due to adverse events occurred in 17 (38.6%) patients. There were no modifications or discontinuations of ART. CD4 cell counts and HIV viral load remained stable. CONCLUSION: The efficacy of sorafenib under real-life conditions in HIV-infected patients seems lower than that reported in the registration clinical trial. On the contrary, the tolerability of sorafenib appears to be similar to what is seen in patients without HIV infection. Sorafenib does not seem to modify the efficacy of ART.

Effectiveness of Ritonavir-Boosted Protease Inhibitor Monotherapy in Clinical Practice Even with Previous Virological Failures to Protease Inhibitor-Based Regimens.

BACKGROUND AND OBJECTIVE: Significant controversy still exists about ritonavir-boosted protease inhibitor monotherapy (mtPI/rtv) as a simplification strategy that is used up to now to treat patients that have not experienced previous virological failure (VF) while on protease inhibitor (PI) -based regimens. We have evaluated the effectiveness of two mtPI/rtv regimens in an actual clinical practice setting, including patients that had experienced previous VF with PI-based regimens. METHODS: This retrospective study analyzed 1060 HIV-infected patients with undetectable viremia that were switched to lopinavir/ritonavir or darunavir/ritonavir monotherapy. In cases in which the patient had previously experienced VF while on a PI-based regimen, the lack of major HIV protease resistance mutations to lopinavir or darunavir, respectively, was mandatory. The primary endpoint of this study was the percentage of participants with virological suppression after 96 weeks according to intention-to-treat analysis (non-complete/missing = failure). RESULTS: A total of 1060 patients were analyzed, including 205 with previous VF while on PI-based regimens, 90 of whom were on complex therapies due to extensive resistance. The rates of treatment effectiveness (intention-to-treat analysis) and virological efficacy (on-treatment analysis) at week 96 were 79.3% (CI95, 76.8-81.8) and 91.5% (CI95, 89.6-93.4), respectively. No relationships were found between VF and earlier VF while on PI-based regimens, the presence of major or minor protease resistance mutations, the previous time on viral suppression, CD4+ T-cell nadir, and HCV-coinfection. Genotypic resistance tests were available in 49 out of the 74 patients with VFs and only four patients presented new major protease resistance mutations. CONCLUSION: Switching to mtPI/rtv achieves sustained virological control in most patients, even in those with previous VF on PI-based regimens as long as no major resistance mutations are present for the administered drug.

Renal safety of coformulated tenofovir/emtricitabine vs other nucleoside analogues in combination therapy in antiretroviral-naive patients aged 50 years or older in Spain: The TRIP study.

OBJECTIVES: Our aim is to describe the impact of emtricitabine (FTC)/tenofovir (TDF) versus other nucleoside reverse transcriptase inhibitor (NRTIs)-based regimens on renal function of human immunodeficiency virus (HIV) naïve patients >50 years old who started combination antiretroviral therapy (cART). DESIGN: National, retrospective cohort analysis of patients >50 years old when they started cART (January 1, 2006-December 31, 2009). METHODS: We compared renal safety (changes in estimated glomerular filtration rate [eGFR] during the first year, and time to renal events during 4 years of follow-up) in FTC/TDF versus non-FTC/TDF users. Among FTC/TDF users, we compared protease inhibitors vs non-nucleoside reverse transcriptase inhibitors and Lopinavir/ritonavir vs Efavirenz. RESULTS: We included 103 patients: median age: 54.9 years, 84% males, median CD4 count 247 cells/µl, median viral load 4.7 log; median follow up 18 months (max: 48 months); 73 started with FTC/TDF and 30 with other NRTIs. Change in eGFR was significantly worse for ritonavir-boosted lopinavir (LPV/r) vs efavirenz (EFV) users in the FTC/TDF group (71.2 vs 98.9 ml/min/1.73 m(2) at month 12, P < 0.05). The risk of renal events (progression to an Chronic Kidney Disease Epidemiology Collaboration value < 60 ml/min/1.73 m(2) in subjects with baseline values >60) was comparable for FTC/TDF users and non users, but was higher and almost significant for LPV/r as compared to EFV users in the FTC/TDF group (adjusted hazard ratio 6.1, 95% CI 0.8-45.5). CONCLUSIONS: In our study with a population of HIV infected subjects ≥ 50 years old, renal safety was similar for FTC/TDF and other NRTI-based regimens, but worse for LPV/r as compared to other regimens.

The 'Can't intubate can't oxygenate' scenario in pediatric anesthesia: a comparison of the Melker cricothyroidotomy kit with a scalpel bougie technique.

BACKGROUND: While the majority of pediatric intubations are uncomplicated, the 'Can't intubate, Can't Oxygenate' scenario (CICO) does occur. With limited management guidelines available, CICO is still a challenge even to experienced pediatric anesthetists. OBJECTIVES: To compare the COOK Melker cricothyroidotomy kit (CM) with a scalpel bougie (SB) technique for success rate and complication rate in a tracheotomy on a cadaveric 'infant airway' animal model. METHODS: Two experienced proceduralists repeatedly attempted tracheotomy in eight rabbits, alternately using CM and SB (4 fr) technique. The first attempt was performed at the level of the first tracheal cartilage with subsequent experimental trials of insertion progressively more caudad. Success was defined as intratracheal placement of cannula as seen on bronchoscope. Complications were assessed both by bronchoscopic and macropathological appearance. RESULTS: 32 attempts were made at tracheotomy. CM had an overall success rate of 100% compared to a 75% success rate for SB. Success rate for the first attempt was dependent on the level of the tracheotomy (Level 1 100%, level 2 62.5% and level 3 & 4 25%). While CM was associated with lateral and/or posterior wall damage on bronchoscopy/macropathology in 6% of 19% and 25% of 50% respectively, the damage observed was greater and more frequent with SB (19%/44% and 31%/50%, respectively). CONCLUSIONS: At level 1, the first attempt success rate was 100% for both devices. Overall CM showed a better success rate than SB; however, both techniques were associated with significant complication rates, which were more pronounced following the scalpel bougie technique.

Nivel de conocimiento sobre VIH/sida en estudiantes de Medicina Integral Comunitaria / Level of knowledge about HIV/ AIDS in students of Communitary Integral Medicine

La pandemia VIH/sida se convirtió en la enfermedad transmisible más temible del pasado siglo y aún en este no hay respuesta científica adecuada de un tratamiento eficaz, se hace necesario el estudio de este fenómeno social ya que el desconocimiento por parte de la población en general sobre su prevención y tratamiento, sumado a la insuficiente percepción del riesgo, son las razones principales de su creciente diseminación y difícil control. El objetivo de esta investigación es determinar el nivel de conocimiento sobre el VIH/sida en estudiantes de Medicina Integral Comunitaria del ÁSIC: La Chamarreta, para ello se realizó un estudio observacional, descriptivo, transversal con el propósito de determinar el nivel de conocimiento sobre VIH/sida en estudiantes de Medicina Integral Comunitaria, del Área de Salud Integral Comunitaria: La Chamarreta, Maracaibo, Estado Zulia, Venezuela. El universo fue de 47 estudiantes y la muestra de 43, que cursan sus estudios en dicha área de salud, aplicándoles una encuesta, la cual permitió dar salida a los objetivos planteados. Se utilizaron los métodos teóricos, empíricos y estadísticos. El 67,4 por ciento perteneció al sexo femenino y el 39,5 por ciento al grupo de edad de 18 a 23 años. Los conceptos de VIH y sida no los tienen bien identificado, (65,1 por ciento). El único medio de protección que identificaron fue el preservativo (60,5 por ciento). El 51,2 por ciento fue evaluado de mal y el 37,2 por ciento de regular, predominando el sexo femenino y el grupo de edad de 18 a 23 años. La mayoría de los estudiantes fueron evaluados globalmente entre mal y regular siendo el sexo femenino el de menos conocimiento(AU)

The HIV/ AIDS pandemia became the most fearful transmitted disease of the last century and even in this century it has no suitable scientific answers for the effective treatment. It is necessary then to make a study of this social phenomenon because the ignorance of the population in regards to the prevention and treatment and the insufficient risk perception are the main causes of its growing dissemination and difficult control. The objective of this research is to determine the level of knowledge about HIV/ AIDS in students of Communitary Integral Medicine, belonging to the Communitary Integral Health Area La Chamarreta, Maracaibo, in Zulia State, Venezuela. The universe was about 47 students and 43 were the sample. They studied in the afore mentioned health area and it was applied a survey to them, which allowed to fulfilled the stated objectives. There were used the theoretical, empirical and statistical methods. The 67.4 percent belonged to females and the 39.5 percent belonged to the age group of 18 to 23 years old. The HIV AIDS concepts were not clearly identified (65.1 percent). The only means of protection that they identified was the preservative (60.5 percent). The 51.2 percent was evaluated as wrong and 37.2 percent was regular, the female sex and the age group of 18 to 23 years old prevailed. Most of the students were generally evaluated as wrong and regular and the feminine sex had less knowledge about the topic(EU)

Clinical and virological efficacy of etravirine plus two active Nucleos(t)ide analogs in an heterogeneous HIV-infected population.

UNLABELLED: Etravirine (ETV) is recommended in combination with a boosted protease inhibitor plus an optimized background regimen for salvage therapy, but there is limited experience with its use in combination with two nucleos(t)ide reverse-transcriptase inhibitors (NRTIs). This multicenter study aimed to assess the efficacy of this combination in two scenarios: group A) subjects without virologic failure on or no experience with non-nucleoside reverse-transcriptase inhibitors (NNRTIs) switched due to adverse events and group B) subjects switched after a virologic failure on an efavirenz- or nevirapine-based regimen. The primary endpoint was efficacy at 52 weeks analysed by intention-to-treat. Virologic failure was defined as the inability to suppress plasma HIV-RNA to <50 copies/mL after 24 weeks on treatment, or a confirmed viral load >200 copies/mL in patients who had previously achieved a viral suppression or had an undetectable viral load at inclusion. Two hundred eighty seven patients were included. Treatment efficacy rates in group A and B were 88.0% (CI95, 83.9-92.1%) and 77.4% (CI95, 65.0-89.7%), respectively; the rates reached 97.2% (CI95, 95.1-99.3%) and 90.5% (CI95, 81.7-99.3), by on-treatment analysis. The once-a-day ETV treatment was as effective as the twice daily dosing regimen. Grade 1-2 adverse events were observed motivating a treatment switch in 4.2% of the subjects. In conclusion, ETV (once- or twice daily) plus two analogs is a suitable, well-tolerated combination both as a switching strategy and after failure with first generation NNRTIs, ensuring full drug activity. TRIAL REGISTRATION: ClinicalTrials.gov NCT01437241.

HIV/hepatitis C virus-coinfected patients who achieved sustained virological response are still at risk of developing hepatocellular carcinoma.

OBJECTIVE: To describe the frequency and the characteristics of hepatocellular carcinoma (HCC) cases that appeared in HIV/hepatitis C virus (HCV)-coinfected patients with previous sustained virological response (SVR) and to compare these cases to those diagnosed in patients without SVR. METHODS: All HIV/HCV-coinfected patients diagnosed with HCC in 26 hospitals in Spain before 31 December 2012 were analyzed. Comparisons between cases diagnosed in patients with and without previous SVR were made. RESULTS: One hundred and sixty-seven HIV/HCV-coinfected patients were diagnosed with HCC in the participant hospitals. Sixty-five (39%) of them had been previously treated against HCV. In 13 cases, HCC was diagnosed after achieving consecution of SVR, accounting for 7.8% of the overall cases. The median (Q1-Q3) elapsed time from SVR to diagnosis of HCC was 28 (20-39) months. HCC was multicentric and was complicated with portal thrombosis in nine and six patients, respectively. Comparisons with HCC cases diagnosed in patients without previous SVR only yielded a significantly higher proportion of genotype 3 infection [10 (83%) out of 13 cases versus 34 (32%) out of 107; P = 0.001)]. The median (Q1-Q3) survival of HCC was 3 (1-39) months among cases developed in patients with previous SVR, whereas it was 6 (2-20) months in the remaining individuals (P = 0.7). CONCLUSION: HIV/HCV-coinfected patients with previous SVR may develop HCC in the mid term and long term. These cases account for a significant proportion of the total cases of HCC in this setting. Our findings reinforce the need to continue surveillance of HCC with ultrasound examinations in patients with cirrhosis who respond to anti-HCV therapy.

Safety, efficacy, and persistence of emtricitabine/tenofovir versus other nucleoside analogues in naive subjects aged 50 years or older in Spain: the TRIP study.

OBJECTIVES: Current antiretroviral guidelines state that being older than 50 to 55 years of age is an indication to start antiretroviral therapy (ART), regardless of CD4 status. However, no references to the preferred combination ART (cART) for these patients have been described. Our study compares emtricitabine and tenofovir disoproxil fumarate (FTC/TDF) versus other nucleoside reverse transcriptase inhibitor (NNRTI) regimens in HIV ART-naïve patients who are ≥50 years. DESIGN: National, retrospective cohort analysis of patients who were ≥50 years old when they began the first cART (January 1, 2006 to December 31, 2009). METHODS: We compared safety, effectiveness, and persistence of treatment in FTC/TDF versus non-FTC/TDF users. Among FTC/TDF users, we compared protease inhibitor (PI) versus NNRTI users and lopinavir/r versus efavirenz users. RESULTS: We included 161 patients: median age was 54.6 years, 83% were men, median CD4 count was 191 cells/µL, median viral load was 4.7 log, and median follow-up was 19 months (maximum, 48 months). Of these participants, 112 started with FTC/TDF and 49 with other nucleotide reverse transcriptase inhibitors (NRTIs). During follow-up, 21.9% of subjects developed at least one laboratory event ≥grade 3, 5.6% interrupted cART due to adverse events,19.3% had virologic failure, and 49.1% modified cART. There were no statistically significant differences between FTC/TDF and non-FTC/TDF users for any output except for persistence: The proportion of subjects who changed cART was 71.4% for non-FTC/TDF users and 38.6% for FTC/TDF users (log rank 0.001; adjusted hazard ratio, 2.10; 95% CI, 1.34-3.29). CONCLUSIONS: In a population of HIV-infected subjects who were ≥50 years old, our study suggests that the use of FTC/TDF is generally safe and effective, with a longer persistence as compared to other regimens.