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BACKGROUND: Penetrating thoracic injuries have a significant risk of morbi-mortality. Despite the advancements in damage control methods, a subset of patients with severe pulmonary vascular lesions and bronchial injuries persists. In some of these cases, post-traumatic pneumonectomy is required, and perioperative extracorporeal membrane oxygenation (ECMO) support may be required due to right ventricular failure and respiratory failure. CASE DESCRIPTION: A male was brought to the emergency department (ED) with a penetrating thoracic injury, presenting with massive right hemothorax and active bleeding that required ligation of the right pulmonary hilum to control the bleeding. Subsequently, he developed right ventricular dysfunction and ARDS, necessitating a dynamic hybrid ECMO configuration to support his condition and facilitate recovery. CONCLUSIONS: Penetrating thoracic injuries with severe pulmonary vascular lesions may need pneumonectomy to control bleeding. ECMO support reduces the associated mortality by decreasing the complications rate. A multidisciplinary team is essential to achieve good outcomes in severe compromised patients.
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Oxigenación por Membrana Extracorpórea , Neumonectomía , Humanos , Oxigenación por Membrana Extracorpórea/métodos , Masculino , Lesión Pulmonar/cirugía , Lesión Pulmonar/etiología , Adulto , Traumatismos Torácicos/cirugía , Traumatismos Torácicos/complicaciones , Heridas Penetrantes/cirugía , Hemotórax/etiología , Hemotórax/cirugía , Cuidados Posoperatorios/métodosRESUMEN
Background: Demographic analyses may reveal current patterns of change in the outcomes of rapidly developing medical procedures because they incorporate the period perspective. Methods: We analyzed the changes in size, age structure, and hospitalizations in the population of liver transplantation (LT) survivors in our center during the last 30 y (nâ =â 1114 patients) and generated projections, including life expectancy (LE), considering cohort and period effects. Life tables were used to project the complete LE (overall 1990-2020 experience), the cohort LE (according to the decade of surgery: 1990-2000, 2000-2010, and 2010-2020), and the period LE (current 2015-2020 experience). Results: The population of LT recipients in follow-up continued to experience progressive growth and aging since 1990 (492 patients [41.9% >65 y] in 2020), and the magnitude of these phenomena may double in the next 30 y. However, the number of admissions and days of admission has been decreasing. The complete LE at LT was 12.4 y, whereas the period LE was 15.8 y. The cohort LE (limited to 10 y) was 5.3, 6.3, and 7.3 y for the 1990-2000, 2000-2010, and 2010-2020 cohorts, respectively. Conclusions: The target population of our medical care after LT is growing and aging. The prevalence of both of these phenomena is expected to increase in the coming years and is associated with a current improvement in LE. However, the hospitalization burden associated with LT survivors is declining. The period effect should be considered for generating up-to-date information on these current trends, which are crucial when designing health policies for LT survivors.
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Background: The COVID-19 pandemic in Latin America generated the need to develop low-cost, fast-manufacturing mechanical ventilators. The Universidad de La Sabana and the Fundacion Neumologica Colombiana designed and manufactured the Unisabana-HERONS (USH) ventilator. Here, we present the preclinical and clinical study results to evaluate its effectiveness and safety characteristics in an animal model (Yorkshire Sow) and five patients with acute respiratory failure receiving mechanical ventilatory support for 24 h. Methods: The effectiveness and safety outcomes included maintaining arterial blood gases and pulse oximetry saturation (SpO2), respiratory pressures and volumes (during continuous monitoring) in the range of ARDS and lung-protective strategy goals, and the occurrence of barotrauma. A significance level of 0.05 was used for statistical tests. This clinical trial was registered on Clinicaltrials.gov (NCT04497623) and approved by the ethics committee. Results: Among patients treated with the Unisabana-HERONS, the most frequent causes of acute respiratory failure were pneumonia in 3/5 (60 %) and ARDS in 2/5 (40 %). During the treatment, the ventilatory parameters related to lung protection protocols were kept within the safety range, and vital signs and blood gas were stable. The percentage of time that the respiratory pressures or volumes were out of safety range were plateau pressure >30 cm H2O: 0.00 %; driving pressure >15 cm H2O: 0.06 %; mechanical power >15 J/min: 0.00 %; and Tidal volume >8 mL/kg: 0.00 %. There were no adverse events related to the ventilator. The usability questionnaire retrieved a median score for all items between 9 and 10 (best score: 10), indicating great ease of use. Conclusion: The Unisabana-HERONS ventilator effectively provided adequate gas exchange and maintained the ventilatory parameters in the range of lung protection strategies in humans and an animal model. Furthermore, it is straightforward to use and is a low-cost medical device.
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BACKGROUND AND AIMS: Alcohol-associated hepatitis (AH) poses significant short-term mortality. Existing prognostic models lack precision for 90-day mortality. Utilizing artificial intelligence in a global cohort, we sought to derive and validate an enhanced prognostic model. APPROACH AND RESULTS: The Global AlcHep initiative, a retrospective study across 23 centers in 12 countries, enrolled patients with AH per National Institute for Alcohol Abuse and Alcoholism criteria. Centers were partitioned into derivation (11 centers, 860 patients) and validation cohorts (12 centers, 859 patients). Focusing on 30 and 90-day postadmission mortality, 3 artificial intelligence algorithms (Random Forest, Gradient Boosting Machines, and eXtreme Gradient Boosting) informed an ensemble model, subsequently refined through Bayesian updating, integrating the derivation cohort's average 90-day mortality with each center's approximate mortality rate to produce posttest probabilities. The ALCoholic Hepatitis Artificial INtelligence Ensemble score integrated age, gender, cirrhosis, and 9 laboratory values, with center-specific mortality rates. Mortality was 18.7% (30 d) and 27.9% (90 d) in the derivation cohort versus 21.7% and 32.5% in the validation cohort. Validation cohort 30 and 90-day AUCs were 0.811 (0.779-0.844) and 0.799 (0.769-0.830), significantly surpassing legacy models like Maddrey's Discriminant Function, Model for End-Stage Liver Disease variations, age-serum bilirubin-international normalized ratio-serum Creatinine score, Glasgow, and modified Glasgow Scores ( p < 0.001). ALCoholic Hepatitis Artificial INtelligence Ensemble score also showcased superior calibration against MELD and its variants. Steroid use improved 30-day survival for those with an ALCoholic Hepatitis Artificial INtelligence Ensemble score > 0.20 in both derivation and validation cohorts. CONCLUSIONS: Harnessing artificial intelligence within a global consortium, we pioneered a scoring system excelling over traditional models for 30 and 90-day AH mortality predictions. Beneficial for clinical trials, steroid therapy, and transplant indications, it's accessible at: https://aihepatology.shinyapps.io/ALCHAIN/ .
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A 47-year-old male patient was referred to a level 1 trauma center with refractory acute respiratory distress syndrome, bilateral lung contusions, and flail chest after initial management for injuries sustained 5 days prior from an 8-m fall from a tower crane. Surgical stabilization of the rib fractures was achieved under extracorporeal membrane oxygenation support, with successful decannulation 4 days after surgery. The patient was discharged after 42 days and following multidisciplinary interventions. Use of extracorporeal membrane oxygenation support in blunt chest trauma patients presents a valuable opportunity as it may enable earlier surgical intervention and reduce in-hospital complications.
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Technological advances in radiation oncology are oriented towards improving treatment precision and tumor control. Among these advances, magnetic-resonance-image-guided radiation therapy (MRgRT) stands out, with technological advances to deliver targeted treatments adapted to a tumor's anatomy on the day while minimizing incidental exposure to organs at risk, offering an unprecedented therapeutic advantage compared to X-ray-based IGRT delivery systems. This new technology changes the traditional workflow in radiation oncology and requires an evolution in team coordination to administer more precise treatments. Once implemented, it paves the way for newer indication for radiation therapy to safely deliver higher doses than ever before, with better preservation of healthy tissues to optimize patient outcomes. In this narrative review, we assess the technical aspects of the novel linear accelerators that can deliver MRgRT and summarize the available published experience to date, focusing on oncological results and future challenges.
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Evaluation and staging of liver disease is essential in the clinical decision-making process of liver tumors. The severity of portal hypertension (PH) is the main prognostic factor in advanced liver disease. Performing an accurate hepatic venous pressure gradient (HVPG) measurement is not always possible, especially when veno-venous communications are present. In those complex cases, a refinement in HVPG measurement with a thorough evaluation of each of the components of PH is mandatory. We aimed at describing how some technical modifications and complementary procedures may contribute to an accurate and complete clinical evaluation to improve therapeutic decisions.
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Hipertensión Portal , Cirrosis Hepática , Humanos , Hipertensión Portal/diagnóstico , Presión Portal , HemodinámicaRESUMEN
Background: Transarterial radioembolization (TARE) is increasingly used in patients with hepatocellular carcinoma (HCC). This treatment can induce or impair portal hypertension, leading to hepatic decompensation. TARE also promotes changes in liver and spleen volumes that may modify therapeutic decisions and outcomes after therapy. Objectives: We aimed to investigate the impact of TARE on the incidence of decompensation events and its predictive factors. Design: In all, 63 consecutive patients treated with TARE between February 2012 and December 2018 were retrospectively included. Methods: We assessed clinical (including Barcelona Clinic Liver Cancer stage, portal hypertension assessment, and liver decompensation), laboratory parameters, and liver and spleen volumes before and 6 and 12 weeks after treatment. A multivariate analysis was performed. Results: In total, 18 out of 63 (28.6%) patients had liver decompensation (ascites, variceal bleeding, jaundice, or encephalopathy) within the first 3 months after therapy, not associated with tumor progression. Clinically significant portal hypertension (CSPH) and bilobar treatment independently predicted the development of liver decompensation after TARE. A significant volume increase in the non-treated hemi-liver was observed only in patients with unilobar treatment (median volume increase of 20.2% in patients with right lobe TARE; p = 0.007), especially in those without CSPH. Spleen volume also increased after TARE (median volume increase of 16.1%; p = 0.0001) and was associated with worsening liver function scores and decreased platelet count. Conclusion: Bilobar TARE and CSPH may be associated with an increased risk of liver decompensation in patients with intermediate or advanced HCC. A careful assessment considering these variables before therapy may optimize candidate selection and improve treatment planning.
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BACKGROUND: for the management of locally advanced rectal cancer (LARC), initial treatment with neoadjuvant chemoradiotherapy followed by surgery and chemotherapy in selected patients is considered one of the recommended options by the main international clinical guidelines. Nonetheless, the administration of all chemotherapy before definitive treatment (total neoadjuvant therapy or TNT) is an optimal alternative with a growing level of evidence that must be evaluated in multidisciplinary boards. This review summarizes the available data and controversies in this scenario. SUMMARY: we have analyzed the characteristics of the main published studies that assess the use of TNT in patients with LARC, evaluating their inclusion criteria and distinguishing between the employed radiotherapy fractionations, systemic agents, timing, and the implications of these treatments in regard to surgery and long-term oncological results. Our aim is to describe the evidence that supports the use of a specific regime in everyday clinical practice. KEY POINTS: there is solid evidence for the use of TNT in patients with LARC. There is no data indicating the superiority of one specific TNT scheme among all the existing options. International clinical guidelines leave the door open to choose the most adequate treatment based on the clinical and pathological characteristics of each patient. This review shows the different approaches to TNT and assesses the best options based on clinical evidence.
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Background & Aims: Clinically significant portal hypertension (CSPH) is a landmark in the natural history of cirrhosis, influencing clinical decisions in patients with hepatocellular carcinoma (HCC). Previous small series suggested that splanchnic volume measurements may predict portal hypertension. We aimed to evaluate whether volumetry obtained by standard multidetector computerised tomography (MDCT) can predict CSPH in patients with HCC. Methods: We included 175 patients with HCC, referred for hepatic venous pressure gradient (HVPG) evaluation, in whom contemporary MDCT was available. Liver volume, spleen volume (SV) and liver segmental volume ratio (LSVR: volume of the segments I-III/volume of the segments IV-VIII) were calculated semi-automatically from MDCT. Other non-invasive tests (NITs) were also employed. Results: Volume parameters could be measured in almost 100% of cases with an excellent inter-observer agreement (intraclass correlation coefficient >0.950). SV and LSVR were independently associated with CSPH (HVPG ≥10 mmHg) and did not interact with aetiology. The volume Index (VI), calculated as the product of SV and LSVR, predicted CSPH (AUC 0.83; 95% CI 0.77-0.89). Similar results were observed in an external cohort (n = 23) (AUC 0.87; 95% CI 0.69-1.00). Setting a sensitivity and specificity of 98%, VI could have avoided 35.9% of HVPG measurements. The accuracy of VI was similar to that of other NITs. VI also accurately predicted HVPG greater than 12, 14, 16 and 18 mmHg (AUC 0.81 [95% CI 0.74-0.88], 0.84 [95% CI 0.77-0.91], 0.85 [95% CI 0.77-0.92] and 0.87 [95% CI 0.79-0.94], respectively). Conclusions: Quantification of liver and spleen volumes by MDCT is a simple, accurate and reliable method of CSPH estimation in patients with compensated cirrhosis and HCC. Impact and implications: An increase in portal pressure strongly impacts outcomes after surgery in patients with early hepatocellular carcinoma (HCC). Direct measurement through hepatic vein catheterization remains the reference standard for portal pressure assessment, but its invasiveness limits its application. Therefore, we evaluated the ability of CT scan-based liver and spleen volume measurements to predict portal hypertension in patients with HCC. Our results indicate that the newly described index, based on quantification of liver and spleen volume, accurately predicts portal hypertension. These results suggest that a single imaging test may be used to diagnose and stage HCC, while providing an accurate estimation of portal hypertension, thus helping to stratify surgical risks.
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INTRODUCTION: LV intrinsic systolic cardiac function in cirrhotic patients is conditioned by the degree of sympathetic activation and the use of non-selective beta-blockers (NSBBs). Systolic function can be non-invasively measured by ultrasound using Ejection Intraventricular Pressure Differences in the LV (EIVPD). We aimed to address the relationship between systolic function and long-term clinical outcomes using EIVPD. METHODS: We studied 45 Child-Pugh B or C patients (13 female, 24 on NSBBs) using echocardiography. The primary endpoint was the combination of any-cause mortality or liver transplantation. After a follow-up of 7 years (796 person-months) and a median period of 17 (10-42) months, 41 patients (91%) reached the primary endpoint: 13 (29%) died and 28 (62%) underwent transplantation. RESULTS: By univariable analysis the primary endpoint was related exclusively to MELD score. However, in a multivariable proportional-hazards analysis, adjusted for age, sex and MELD score, EIVPD was inversely related to the primary endpoint, showing interaction with NSBBs. In patients without NSBBs, EIVPD inversely predicted the primary endpoint, whereas in patients with NSBBs, EIVPD was unrelated to outcomes. These relationships were undetected by myocardial strain or conventional cardiac indices. CONCLUSIONS: LV intrinsic systolic function, as noninvasively measured by EIVPD is a predictor of long-term outcomes in patients with cirrhosis. The prognostic value of EIVPD is present along any degree of liver dysfunction but blunted by NSBBs. Because NSBBs have a deep effect on myocardial contractility, these drugs need to be considered when assessing the prognostic implications of cardiac function in these patients.
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Cirrosis Hepática , Trasplante de Hígado , Humanos , Femenino , Pronóstico , Cirrosis Hepática/complicaciones , EcocardiografíaRESUMEN
BACKGROUND: Up to 30% of hospitalised patients with COVID-19 require advanced respiratory support, including high-flow nasal cannulas (HFNC), non-invasive mechanical ventilation (NIV), or invasive mechanical ventilation (IMV). We aimed to describe the clinical characteristics, outcomes and risk factors for failing non-invasive respiratory support in patients treated with severe COVID-19 during the first two years of the pandemic in high-income countries (HICs) and low middle-income countries (LMICs). METHODS: This is a multinational, multicentre, prospective cohort study embedded in the ISARIC-WHO COVID-19 Clinical Characterisation Protocol. Patients with laboratory-confirmed SARS-CoV-2 infection who required hospital admission were recruited prospectively. Patients treated with HFNC, NIV, or IMV within the first 24 h of hospital admission were included in this study. Descriptive statistics, random forest, and logistic regression analyses were used to describe clinical characteristics and compare clinical outcomes among patients treated with the different types of advanced respiratory support. RESULTS: A total of 66,565 patients were included in this study. Overall, 82.6% of patients were treated in HIC, and 40.6% were admitted to the hospital during the first pandemic wave. During the first 24 h after hospital admission, patients in HICs were more frequently treated with HFNC (48.0%), followed by NIV (38.6%) and IMV (13.4%). In contrast, patients admitted in lower- and middle-income countries (LMICs) were less frequently treated with HFNC (16.1%) and the majority received IMV (59.1%). The failure rate of non-invasive respiratory support (i.e. HFNC or NIV) was 15.5%, of which 71.2% were from HIC and 28.8% from LMIC. The variables most strongly associated with non-invasive ventilation failure, defined as progression to IMV, were high leukocyte counts at hospital admission (OR [95%CI]; 5.86 [4.83-7.10]), treatment in an LMIC (OR [95%CI]; 2.04 [1.97-2.11]), and tachypnoea at hospital admission (OR [95%CI]; 1.16 [1.14-1.18]). Patients who failed HFNC/NIV had a higher 28-day fatality ratio (OR [95%CI]; 1.27 [1.25-1.30]). CONCLUSIONS: In the present international cohort, the most frequently used advanced respiratory support was the HFNC. However, IMV was used more often in LMIC. Higher leucocyte count, tachypnoea, and treatment in LMIC were risk factors for HFNC/NIV failure. HFNC/NIV failure was related to worse clinical outcomes, such as 28-day mortality. Trial registration This is a prospective observational study; therefore, no health care interventions were applied to participants, and trial registration is not applicable.
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COVID-19 , Insuficiencia Respiratoria , COVID-19/terapia , Humanos , Estudios Prospectivos , Insuficiencia Respiratoria/terapia , SARS-CoV-2 , TaquipneaRESUMEN
OBJECTIVE: Cirrhosis is characterized by the complex interplay among biological, histological and haemodynamic events. Liver and spleen remodelling occur throughout its natural history, but the prognostic role of these volumetric changes is unclear. We evaluated the relationship between volumetric changes assessed by multidetector computerised tomography (MDCT) and landmark features of cirrhosis. METHODS: We included consecutive cirrhotic patients who underwent liver transplantation (LT) or hepatocellular carcinoma (HCC) resection in whom dynamic MDCT was available. Different volumetric indices were calculated. Fibrosis was evaluated by the collagen proportional area and Laennec sub-stages. Correlation and logistic regression analysis were performed to explore associations of volumetric indexes and fibrosis with key prognostic features across the clinical stages of cirrhosis. RESULTS: 185 patients were included (146 LT; 39 HCC); the predominant aetiology was viral hepatitis (51.35%); 65.9% had decompensated disease and 85.08% clinically significant portal hypertension (CSPH). The standardised liver volume and liver-spleen volume ratio negatively correlated with Model for End-stage Liver Disease (MELD), albumin and hepatic venous pressure gradient (HVPG) and were significantly lower in decompensated patients. The liver segmental volume ratio (segments I-III/segments IV-VIII) best captured the characteristic features of the compensated phase, showing a positive correlation with HVPG and a good discrimination between patients with and without CSPH and varices. Volumetric changes and fibrosis severity were independently associated with key prognostic events, with no association between these two parameters. CONCLUSIONS: Liver and spleen volumetric indices evolve differently along the natural history of cirrhosis and are associated with key prognostic factors in each phase, regardless of fibrosis severity and portal hypertension.
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Carcinoma Hepatocelular , Enfermedad Hepática en Estado Terminal , Hipertensión Portal , Neoplasias Hepáticas , Albúminas , Carcinoma Hepatocelular/patología , Colágeno , Enfermedad Hepática en Estado Terminal/complicaciones , Fibrosis , Humanos , Hipertensión Portal/diagnóstico por imagen , Hipertensión Portal/etiología , Cirrosis Hepática/diagnóstico , Cirrosis Hepática/diagnóstico por imagen , Neoplasias Hepáticas/patología , Pronóstico , Índice de Severidad de la Enfermedad , Bazo/diagnóstico por imagen , Bazo/patologíaRESUMEN
Background and objective: The emergence of highly tolerable, effective, and shorter duration direct-acting antivirals (DAAs) regimens offers the opportunity to simplify hepatitis C virus management but medical costs are unknown. Thus, we aimed to determine the direct medical costs associated with a combo-simplified strategy (one-step diagnosis and low monitoring) to manage HCV infection within an 8-week glecaprevir/pibrentasvir (GLE/PIB) regimen in clinical practice in Spain. Patients and methods: Healthcare resources and clinical data were collected retrospectively from medical charts of 101 eligible patients at 11 hospitals. Participants were adult, treatment naïve subjects with HCV infection without cirrhosis in whom a combo-simplified strategy with GLE/PIB for 8 weeks were programmed between Apr-2018 and Nov-2018. Results: The GLE/PIB effectiveness was 100% (CI95%: 96.2100%) in the mITT population and 94.1% (CI95%: 87.597.8%) in the ITT population. Three subjects discontinued the combo-simplified strategy prematurely, none of them due to safety reasons. Five subjects reported 8 adverse events, all of mild-moderate intensity. Combo-simplified strategy mean direct costs were 754.35±103.60 compared to 1689.42 and 2007.89 of a theoretical 12-week treatment with 4 or 5 monitoring visits, respectively; and 1370.95 and 1689.42 of a theoretical 8-week with 3 or 4 monitoring visits, respectively. Only 4.9% of the subjects used unexpected health care resources. Conclusions: 8-week treatment with GLE/PIB combined with a combo simplified strategy in real-life offers substantial cost savings without affecting the effectiveness and safety compared to traditional approaches.(AU)
Antecedentes y objetivo: La aparición de regímenes antivirales de acción directa altamente tolerables, eficaces y de corta duración permite simplificar el manejo de la hepatitis C, pero los costes médicos se desconocen. Así, se pretende determinar los costes médicos directos asociados a una estrategia simplificada (diagnóstico en un solo paso y monitorización reducida) para controlar la infección por VHC con un régimen de 8 semanas de glecaprevir/pibrentasvir (GLE/PIB) en la práctica clínica en España. Pacientes y métodos: Los recursos sanitarios y los datos clínicos se recopilaron retrospectivamente de las historias médicas de 101 pacientes elegibles en 11 hospitales. Los participantes fueron sujetos adultos, sin tratamiento previo de la infección por VHC y sin cirrosis, en los que se programó una estrategia combinada simplificada con GLE/PIB durante 8 semanas entre abril y noviembre de 2018. Resultados: La eficacia de GLE/PIB fue del 100% (IC 95% 96,2-100) en la población mITT y del 94,1% (IC 95% 87,5-97,8) en la población ITT. Tres sujetos suspendieron prematuramente la estrategia combinada simplificada, ninguno de ellos por razones de seguridad. Cinco sujetos reportaron 8 acontecimientos adversos de intensidad leve-moderada. Los costes directos fueron de 754,35±103,60 frente a 1.689,42 y 2.007,89 de un tratamiento teórico de 12 semanas con 4 o 5 visitas de monitorización, respectivamente; y 1.370,95 y 1.689,42 de un tratamiento teórico de 8 semanas con 3 o 4 visitas de monitorización, respectivamente. El 4,9% de los sujetos utilizaron recursos de atención médica inesperados. Conclusiones: En la vida real, el tratamiento de 8 semanas con GLE/PIB junto con una estrategia simplificada ofrece ahorros sustanciales de costos, sin afectar la eficacia y seguridad, en comparación con abordajes tradicionales.(AU)
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Humanos , Adulto , Hepatitis C/tratamiento farmacológico , Hepatitis C Crónica/tratamiento farmacológico , Hepacivirus , Lactamas Macrocíclicas , Leucina/análogos & derivados , Gastroenterología , Estudios RetrospectivosRESUMEN
BACKGROUND AND PURPOSE: Hepatitis C virus (HCV) infection is associated with neuropsychiatric disturbances that impact on functioning and health-related quality of life (HRQoL). Reversibility at different liver disease stages is unknown, particularly in cirrhosis. We aimed to evaluate cognition, functioning, and HRQoL following HCV eradication at different liver disease stages. METHODS: A random sample (n = 152) of consecutive patients treated with direct-acting antiviral agents (DAAs) between April 2015 and March 2017 were included. A comprehensive neuropsychological assessment, functioning and HRQoL questionnaires were applied at baseline, and 12 and 48 weeks after the end of antivirals. RESULTS: One-hundred thirty-five patients who achieved virological response completed the follow-up, of whom 44 had cirrhosis (27% decompensated). Twenty-one percent had cognitive impairment before starting DAAs (34.1% cirrhotic vs. 14.4% noncirrhotic, p < 0.011). Viral eradication was associated with a decrease in cognitive impairment to 23% of cirrhotic and 6% of noncirrhotic patients (p < 0.05). Interestingly, older patients (B = 0.11, 95% confidence interval [CI] = 0.03-0.19) with baseline cognitive impairment (B = 3.58, 95% CI = 1.54-5.62) were those with higher cognitive benefit, regardless of liver disease. Persistent cognitive impairment was associated with having higher cardiovascular risk, cirrhosis, lower education, and higher anxiety and depression scores. Functioning and HRQoL also improved after eradication but remained worse in the cirrhotic group. CONCLUSIONS: Viral eradication decreases the prevalence of cognitive impairment and improves functioning and HRQoL. Patients with lower brain reserve (older patients) and baseline cognitive impairment may benefit the most. Identification and treatment of HCV patients through screening programs may reduce the burden of cognitive disturbances beyond the prevention of liver disease progression.
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Hepatitis C Crónica , Hepatitis C , Antivirales/uso terapéutico , Cognición , Hepacivirus , Hepatitis C/complicaciones , Hepatitis C/tratamiento farmacológico , Hepatitis C Crónica/complicaciones , Hepatitis C Crónica/tratamiento farmacológico , Humanos , Cirrosis Hepática/complicaciones , Estudios Prospectivos , Calidad de VidaRESUMEN
BACKGROUND AND OBJECTIVE: The emergence of highly tolerable, effective, and shorter duration direct-acting antivirals (DAAs) regimens offers the opportunity to simplify hepatitis C virus management but medical costs are unknown. Thus, we aimed to determine the direct medical costs associated with a combo-simplified strategy (one-step diagnosis and low monitoring) to manage HCV infection within an 8-week glecaprevir/pibrentasvir (GLE/PIB) regimen in clinical practice in Spain. PATIENTS AND METHODS: Healthcare resources and clinical data were collected retrospectively from medical charts of 101 eligible patients at 11 hospitals. Participants were adult, treatment naïve subjects with HCV infection without cirrhosis in whom a combo-simplified strategy with GLE/PIB for 8 weeks were programmed between Apr-2018 and Nov-2018. RESULTS: The GLE/PIB effectiveness was 100% (CI95%: 96.2-100%) in the mITT population and 94.1% (CI95%: 87.5-97.8%) in the ITT population. Three subjects discontinued the combo-simplified strategy prematurely, none of them due to safety reasons. Five subjects reported 8 adverse events, all of mild-moderate intensity. Combo-simplified strategy mean direct costs were 754.35±103.60 compared to 1689.42 and 2007.89 of a theoretical 12-week treatment with 4 or 5 monitoring visits, respectively; and 1370.95 and 1689.42 of a theoretical 8-week with 3 or 4 monitoring visits, respectively. Only 4.9% of the subjects used unexpected health care resources. CONCLUSIONS: 8-week treatment with GLE/PIB combined with a combo simplified strategy in real-life offers substantial cost savings without affecting the effectiveness and safety compared to traditional approaches.
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Hepatitis C Crónica , Hepatitis C , Adulto , Ácidos Aminoisobutíricos , Antivirales/efectos adversos , Bencimidazoles , Ciclopropanos , Genotipo , Hepacivirus , Hepatitis C/tratamiento farmacológico , Hepatitis C Crónica/tratamiento farmacológico , Humanos , Lactamas Macrocíclicas , Leucina/análogos & derivados , Prolina/análogos & derivados , Prolina/uso terapéutico , Pirrolidinas , Quinoxalinas , Estudios Retrospectivos , SulfonamidasRESUMEN
IMPORTANCE: The effect of high-flow oxygen therapy vs conventional oxygen therapy has not been established in the setting of severe COVID-19. OBJECTIVE: To determine the effect of high-flow oxygen therapy through a nasal cannula compared with conventional oxygen therapy on need for endotracheal intubation and clinical recovery in severe COVID-19. DESIGN, SETTING, AND PARTICIPANTS: Randomized, open-label clinical trial conducted in emergency and intensive care units in 3 hospitals in Colombia. A total of 220 adults with respiratory distress and a ratio of partial pressure of arterial oxygen to fraction of inspired oxygen of less than 200 due to COVID-19 were randomized from August 2020 to January 2021, with last follow-up on February 10, 2021. INTERVENTIONS: Patients were randomly assigned to receive high-flow oxygen through a nasal cannula (n = 109) or conventional oxygen therapy (n = 111). MAIN OUTCOMES AND MEASURES: The co-primary outcomes were need for intubation and time to clinical recovery until day 28 as assessed by a 7-category ordinal scale (range, 1-7, with higher scores indicating a worse condition). Effects of treatments were calculated with a Cox proportional hazards model adjusted for hypoxemia severity, age, and comorbidities. RESULTS: Among 220 randomized patients, 199 were included in the analysis (median age, 60 years; n = 65 women [32.7%]). Intubation occurred in 34 (34.3%) randomized to high-flow oxygen therapy and in 51 (51.0%) randomized to conventional oxygen therapy (hazard ratio, 0.62; 95% CI, 0.39-0.96; P = .03). The median time to clinical recovery within 28 days was 11 (IQR, 9-14) days in patients randomized to high-flow oxygen therapy vs 14 (IQR, 11-19) days in those randomized to conventional oxygen therapy (hazard ratio, 1.39; 95% CI, 1.00-1.92; P = .047). Suspected bacterial pneumonia occurred in 13 patients (13.1%) randomized to high-flow oxygen and in 17 (17.0%) of those randomized to conventional oxygen therapy, while bacteremia was detected in 7 (7.1%) vs 11 (11.0%), respectively. CONCLUSIONS AND RELEVANCE: Among patients with severe COVID-19, use of high-flow oxygen through a nasal cannula significantly decreased need for mechanical ventilation support and time to clinical recovery compared with conventional low-flow oxygen therapy. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04609462.
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COVID-19/complicaciones , Intubación Intratraqueal/estadística & datos numéricos , Terapia por Inhalación de Oxígeno/métodos , Oxígeno/uso terapéutico , Insuficiencia Respiratoria/terapia , Anciano , Anciano de 80 o más Años , COVID-19/terapia , Enfermedad Crítica/mortalidad , Enfermedad Crítica/terapia , Femenino , Humanos , Unidades de Cuidados Intensivos , Intubación Intratraqueal/efectos adversos , Masculino , Persona de Mediana Edad , Terapia por Inhalación de Oxígeno/instrumentación , Respiración Artificial , Insuficiencia Respiratoria/etiología , Insuficiencia Respiratoria/mortalidad , SARS-CoV-2 , Factores de Tiempo , Resultado del TratamientoRESUMEN
The increased risk of cardiovascular disease (CVD) conferred by hepatitis C virus (HCV) is especially relevant after liver transplantation (LT), but its mechanism is still not well defined. This study aimed to evaluate the influence of HCV eradication in inflammatory and endothelial activation markers after LT. We evaluated inflammatory (TNF-alfa, IL-6, IL-8, and MCP-1) and endothelial activation (E-selectin, ICAM-1, VCAM-1, and MMP-9) markers before and after eradication in 45 LT recipients with HCV infection (LT+/HCV+) and 44 non-transplanted HCV-infected patients (LT-/HCV+). We also considered an additional group of 40 LT recipients without HCV infection (LT+/HCV-). LT+/HCV+ patients presented a higher endothelial activation status before eradication compared with LT+/HCV- patients. However, levels of E-selectin, ICAM-1, VCAM-1, and MMP-9 were comparable between LT+/HCV+ and LT-/HCV+ patients before eradication. HCV eradication decreased ICAM-1 (5466.55 pg/ml vs. 3354.88 pg/ml, P < 0.001) and VCAM-1 (10456.52 pg/ml vs. 6658.85 pg/ml, P < 0.001) levels in LT+/HCV+ and LT-/HCV+ patients. Remarkably, HCV eradication restored levels of endothelial activation markers of LT+/HCV+ patients compared with that of LT+/HCV- patients. HCV plays a major role in endothelial dysfunction after LT. Furthermore, HCV eradication restores endothelial activation despite the exposure to immunosuppressive therapy.
Asunto(s)
Hepatitis C Crónica , Hepatitis C , Trasplante de Hígado , Antivirales/uso terapéutico , Hepacivirus , Hepatitis C/complicaciones , Hepatitis C/tratamiento farmacológico , Hepatitis C Crónica/tratamiento farmacológico , HumanosRESUMEN
BACKGROUND: Diseases transmitted by invasive Aedes aegypti and Aedes albopictus mosquitoes are public health issues in the tropics and subtropics. Understanding the ecology of mosquito vectors is essential for the development of effective disease mitigation programs and will allow for accurate predictions of vector occurrence and abundance. Studies that examine mosquito population dynamics are typically focused on female presence or total adult captures without discriminating the temporal and spatial distribution of both sexes. METHODS: We collected immature and adult mosquitoes bimonthly for 2 years (2018-2019) in the Medellín Botanical Garden. Collection sites differed in proximity to buildings and nearby vegetation, and were classified by their overhead vegetation cover. We used linear mixed models (LMMs) and Spatial Analysis by Distance Indices (SADIE) to assess the spatial distribution of Ae. aegypti and Ae. albopictus. Using our Ae. albopictus captures exclusively, we assessed (1) the spatial and temporal distribution of males and females using SADIE and a generalized linear mixed model (GLMM), (2) the relationship between climatic variables/vegetation coverage and adult captures using GLMMs and LMMs, and (3) the correlation of male and female size in relation to climatic variables and vegetation coverage using LMMs. RESULTS: Spatial analysis showed that Ae. aegypti and Ae. albopictus were distributed at different locations within the surveilled area. However, Ae. albopictus was the predominant species in the park during the study period. Adult Ae. albopictus captures were positively correlated with precipitation and relative humidity, and inversely correlated with temperature and wind speed. Moreover, we observed a spatial misalignment of Ae. albopictus males and females-the majority of males were located in the high vegetation coverage sites, while females were more evenly distributed. We observed significant associations of the size of our adult Ae. albopictus captures with precipitation, temperature, and wind speed for both sexes and found that overhead vegetation cover influenced male size, but observed no effect on female size. CONCLUSIONS: Our work elucidates the differential dynamics of Ae. albopictus males and females, which is pivotal to develop accurate surveillance and the successful establishment of vector control programs based on the disruption of insect reproduction.