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HBOT increases the proportion of dissolved oxygen in the blood, generating hyperoxia. This increased oxygen diffuses into the mitochondria, which consume the majority of inhaled oxygen and constitute the epicenter of HBOT effects. In this way, the oxygen entering the mitochondria can reverse tissue hypoxia, activating the electron transport chain to generate energy. Furthermore, intermittent HBOT is sensed by the cell as relative hypoxia, inducing cellular responses such as the activation of the HIF-1α pathway, which in turn, activates numerous cellular processes, including angiogenesis and inflammation, among others. These effects are harnessed for the treatment of various pathologies. This review summarizes the evidence indicating that the use of medium-pressure HBOT generates hyperoxia and activates cellular pathways capable of producing the mentioned effects. The possibility of using medium-pressure HBOT as a direct or adjunctive treatment in different pathologies may yield benefits, potentially leading to transformative therapeutic advancements in the future.

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OBJECTIVE: To determine the association between race/ethnicity and COVID-19 outcomes in individuals with systemic lupus erythematosus (SLE). METHODS: Individuals with SLE from the US with data entered into the COVID-19 Global Rheumatology Alliance registry between March 24, 2020 and August 27, 2021 were included. Variables included age, sex, race, and ethnicity (White, Black, Hispanic, other), comorbidities, disease activity, pandemic time period, glucocorticoid dose, antimalarials, and immunosuppressive drug use. The ordinal outcome categories were: not hospitalized, hospitalized with no oxygenation, hospitalized with any ventilation or oxygenation, and death. We constructed ordinal logistic regression models evaluating the relationship between race/ethnicity and COVID-19 severity, adjusting for possible confounders. RESULTS: We included 523 patients; 473 (90.4%) were female and the mean ± SD age was 46.6 ± 14.0 years. A total of 358 patients (74.6%) were not hospitalized; 40 patients (8.3%) were hospitalized without oxygen, 64 patients (13.3%) were hospitalized with any oxygenation, and 18 (3.8%) died. In a multivariable model, Black (odds ratio [OR] 2.73 [95% confidence interval (95% CI) 1.36-5.53]) and Hispanic (OR 2.76 [95% CI 1.34-5.69]) individuals had higher odds of more severe outcomes than White individuals. CONCLUSION: Black and Hispanic individuals with SLE experienced more severe COVID-19 outcomes, which is consistent with findings in the US general population. These results likely reflect socioeconomic and health disparities and suggest that more aggressive efforts are needed to prevent and treat infection in this population.

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AIM: To determine characteristics associated with more severe outcomes in a global registry of people with systemic lupus erythematosus (SLE) and COVID-19. METHODS: People with SLE and COVID-19 reported in the COVID-19 Global Rheumatology Alliance registry from March 2020 to June 2021 were included. The ordinal outcome was defined as: (1) not hospitalised, (2) hospitalised with no oxygenation, (3) hospitalised with any ventilation or oxygenation and (4) death. A multivariable ordinal logistic regression model was constructed to assess the relationship between COVID-19 severity and demographic characteristics, comorbidities, medications and disease activity. RESULTS: A total of 1606 people with SLE were included. In the multivariable model, older age (OR 1.03, 95% CI 1.02 to 1.04), male sex (1.50, 1.01 to 2.23), prednisone dose (1-5 mg/day 1.86, 1.20 to 2.66, 6-9 mg/day 2.47, 1.24 to 4.86 and ≥10 mg/day 1.95, 1.27 to 2.99), no current treatment (1.80, 1.17 to 2.75), comorbidities (eg, kidney disease 3.51, 2.42 to 5.09, cardiovascular disease/hypertension 1.69, 1.25 to 2.29) and moderate or high SLE disease activity (vs remission; 1.61, 1.02 to 2.54 and 3.94, 2.11 to 7.34, respectively) were associated with more severe outcomes. In age-adjusted and sex-adjusted models, mycophenolate, rituximab and cyclophosphamide were associated with worse outcomes compared with hydroxychloroquine; outcomes were more favourable with methotrexate and belimumab. CONCLUSIONS: More severe COVID-19 outcomes in individuals with SLE are largely driven by demographic factors, comorbidities and untreated or active SLE. Patients using glucocorticoids also experienced more severe outcomes.

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Infections caused by mumps virus (MuV) have been successfully prevented through vaccination; however, in recent years, an increasing number of mumps outbreaks have been reported within vaccinated populations. In this study, MuV was genotyped for the first time in Mexico. Saliva samples were obtained from two previously vaccinated patients in Mexico City who had developed parotitis. Viral isolation was carried out in Vero cells, and the SH and HN genes were amplified by RT-PCR. Amplicons were sequenced and compared to a set of reference sequences to identify the MuV genotype.

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UNLABELLED: Liver biopsy is the gold standard method to assess nonalcoholic steatohepatitis (NASH) resolution after therapeutic interventions. We developed and validated a simple and noninvasive scoring system to predict NASH resolution without fibrosis worsening after 1 year of lifestyle intervention. This was a prospective cohort study conducted in 261 patients with histologically proven NASH who were treated with lifestyle changes for 52 weeks and underwent a second liver biopsy to confirm NASH resolution. We divided the data into development (140 subjects) and validation (121 individuals) sets. NASH resolution occurred in 28% (derivation group) and 27% (validation group). At the multivariable analysis, weight loss (odds ratio [OR] = 2.75, 95% confidence interval [CI] 1.65-4.58; P < 0.01), type 2 diabetes (OR = 0.04, 95% CI 0.005-0.49; P = 0.01), normal levels of alanine aminotransferase at the end of intervention (OR = 9.84, 95% CI 2.21-44.1; P < 0.01), age (OR = 0.89, 95% CI 0.83-0.97; P = 0.01), and a nonalcoholic fatty liver activity score ≥5 (OR = 0.08, 95% CI 0.01-0.43; P < 0.01) were independent predictors of NASH resolution. The area under the receiver operating characteristic curve of the selected model was 0.956 and 0.945 in the derivation and validation cohorts, respectively. Using a score threshold of ≤46.15, negative predictive values were 92% in the derivation and validation groups, respectively. By applying a cutoff ≥69.72, positive predictive values were 92% and 89% in the derivation and validation groups, respectively. Using both cutoffs, a liver biopsy would have been avoided in 229 (88%) of 261 patients, with a correct prediction in 209 (91%) CONCLUSIONS: A noninvasive prediction model including weight loss, type 2 diabetes, alanine aminotransferase normalization, age, and a nonalcoholic fatty liver activity score ≥5 may be useful to identify NASH resolution in patients under lifestyle intervention. (Hepatology 2016;63:1875-1887).

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BACKGROUND: Arterial blood pressure (BP) is a reliable marker of circulatory dysfunction in cirrhotic patients. There are no prospective studies evaluating the association between different levels of arterial BP and ascites development in compensated cirrhotic patients. Therefore, we evaluated the relationship between arterial BP and ascites development in compensated cirrhotic patients. MATERIALS AND METHODS: A total of 402 patients with compensated HCV-related cirrhosis were prospectively followed during 6 years to identify ascites development. At baseline, patients underwent systolic, diastolic and mean arterial pressure (MAP) measurements. Any history of arterial hypertension was also recorded. The occurrence of events such as bleeding, hepatocellular carcinoma, death and liver transplantation prior to ascites development were considered as competing risk events. RESULTS: Over a median of 156 weeks, ascites occurred in 54 patients (13%). At baseline, MAP was significantly lower in patients with ascites development (75.9 mm/Hg [95%CI, 70.3-84.3]) than those without ascites (93.6 mm/Hg [95% CI: 86.6-102.3]). After adjusting for covariates, the 6-year cumulative incidence of ascites was 40% (95%CI, 34%-48%) for patients with MAP<83.32 mm/Hg. In contrast, cumulative incidences of ascites were almost similar among patients with MAP values between 83.32 mm/Hg and 93.32 mm/Hg (7% [95% CI: 4%-12%]), between 93.32 mm/Hg and 100.31 mm/Hg (5% [95% CI: 4%-11%]) or higher than 100.31 mm/Hg (3% [95% CI: 1%-6%]). The MAP was an independent predictor of ascites development. CONCLUSIONS: The MAP is closely related to the development of ascites in compensated HCV-related cirrhosis. The risk of ascites development increases in 4.4 fold for subjects with MAP values <83.32 mm/Hg.

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PURPOSE: The clinical course of hepatitis C virus-related cirrhosis and its temporal progression across the different clinical stages has not been completely investigated. Our study evaluated the cumulative incidences (CIs) of clinical outcomes marking disease progression across the different clinical stages. METHODS: At baseline, 660 patients were classified as compensated [absence (294), or presence (108) of gastroesophageal varices] or decompensated [ascites (144), variceal bleeding alone (45) or in combination with ascites (17) and encephalopathy alone or together with bleeding and/or ascites (52)]. Subjects were followed for 312 weeks to identify time to a first event marking disease progression. RESULTS: Among compensated patients without varices, the 312-week CIs for developing varices, ascites, and encephalopathy were 37.4, 13.6 and 3.5 %, respectively. The 312-week CIs of development of ascites, bleeding and encephalopathy were 24, 12.5 and 9.9 % for compensated subjects with varices, respectively. Among patients with ascites, the 312-week CIs of bleeding, liver-related deaths/transplant and encephalopathy were 23.5, 27.8, and 47.3 %, respectively. The 312-week CIs of ascites, liver-related deaths/transplant and encephalopathy were 22.5, 14.7 and 5.7 % among patients with bleeding; however, CIs of liver-related deaths were significantly higher in those with ascites plus bleeding (77.6 %). Patients with encephalopathy alone or in combination with ascites and/or bleeding displayed the highest rates of deaths (312 weeks, 90 %). CONCLUSIONS: Among compensated patients, the presence of varices suggests a more accelerated course of the disease. Decompensated patients show the most severe clinical course, particularly in those with a combination of two or more clinical events.

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BACKGROUND & AIMS: The natural history of HCV-related compensated cirrhosis has been poorly investigated in Latin-American countries. Our study evaluated mortality and clinical outcomes in compensated cirrhotic patients followed for 6 years. METHODS: Four hundred and two patients with compensated HCV-related cirrhosis were prospectively recruited in a tertiary care academic center. At the time of admission, patients were stratified as compensated (absence [stage 1] or presence [stage 2] of esophageal varices) as defined by D'Amico et al. Subjects were followed to identify overall mortality or liver transplantation and clinical complication rates. RESULTS: Among 402 subjects, 294 were categorized as stage 1 and 108 as stage 2. Over a median of 176 weeks, 42 deaths occurred (10%), of which 30 were considered liver-related (7%) and 12 non-liver-related (3%); eight individuals (2%) underwent liver transplantation; 30 patients (7%) developed HCC, 67 individuals in stage 1 (22%) developed varices and any event of clinical decompensation occurred in 80 patients (20%). The 6-year cumulative overall mortality or liver transplantation was 15% and 45%, for stages 1 and 2, respectively (p<0.001). The cumulative 6-year HCC incidence was significantly higher among patients with varices (29%) than those without varices (9%), p<0.001. Similarly, the cumulative 6-year incidence of any clinical liver-related complication was higher in patients with stage 2 (66%) as compared to 26% in those with stage 1, respectively (p<0.001). CONCLUSIONS: Our results indicate significant morbidity and mortality and clinical outcome rates in compensated cirrhotic patients with varices (stage 2).

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OBJECTIVES: Viusid is a nutritional supplement with recognised antioxidant and immunomodulatory properties which could have beneficial effects on cirrhosis-related clinical outcomes such as survival, disease progression and development of hepatocellular carcinoma (HCC). This study evaluated the efficacy and safety of viusid in patients with HCV-related decompensated cirrhosis. DESIGN: A randomised double-blind and placebo-controlled study was conducted in a tertiary care academic centre (National Institute of Gastroenterology, Havana, Cuba). The authors randomly assigned 100 patients with HCV-related decompensated cirrhosis to receive viusid (three oral sachets daily, n=50) or placebo (n=50) during 96 weeks. The primary outcome of the study was overall survival at 96 weeks, and the secondary outcomes included time to disease progression, time to HCC diagnosis, time to worsening of the prognostic scoring systems Child-Pugh and Model for End-Stage Liver Disease, and time to a new occurrence or relapse for each one of the main clinical complications secondary to portal hypertension at 96 weeks. RESULTS: Viusid led to a significant improvement in overall survival (90%) versus placebo (74%) (HR 0.27, 95% CI 0.08 to 0.92; p=0.036). A similar improvement in disease progression was seen in viusid-treated patients (28%), compared with placebo-treated patients (48%) (HR 0.47, 95% CI 0.22 to 0.89; p=0.044). However, the beneficial effects of viusid were wholly observed among patients with Child-Pugh classes B or C, but not among patients with Child-Pugh class A. The cumulative incidence of HCC was significantly reduced in patients treated with viusid (2%) as compared with placebo (12%) (HR 0.15, 95% CI 0.019 to 0.90; p=0.046). Viusid was well tolerated. CONCLUSIONS: The results indicate that treatment with viusid leads to a notable improvement in overall clinical outcomes such as survival, disease progression and development of HCC in patients with HCV-related decompensated cirrhosis. Trial registration number http://ClinicalTrials.gov (NCT00502086).

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AIM: To investigate the efficacy of Viusid, a nutritional supplement, as an antioxidant and an immunomodulator in patients with chronic hepatitis C. METHODS: Sixty patients with chronic hepatitis C who were non-responders to standard antiviral treatment were randomly assigned to receive Viusid (3 sachets daily, n = 30) or placebo (n = 30) for 24 wk. The primary outcome was the change in serum malondialdehyde and 4-hydroxyalkenals (lipid peroxidation products). Secondary outcomes were changes in serum tumor necrosis factor-alpha (TNF-alpha), interferon-gamma (IFN-gamma) and interleukin-10 (IL-10). RESULTS: Statistically significant reductions in serum 4-hydroxyalkenals and malondialdehyde levels were observed in both groups in comparison with pretreatment values, but the patients who received Viusid showed a more marked reduction as compared with the control group (P = 0.001). TNF-alpha levels significantly increased from 6.9 to 16.2 pg/mL (P < 0.01) in the patients who received placebo in comparison with almost unchanged levels, from 6.6 to 7.1 pg/mL (P = 0.26), in the patients treated with Viusid (P = 0.001). In addition, IL-10 levels were markedly increased in the patients treated with Viusid (from 2.6 to 8.3 pg/mL, P = 0.04) in contrast to the patients assigned to placebo (from 2.8 to 4.1 pg/mL, P = 0.09) (P = 0.01). Likewise, the administration of Viusid markedly increased mean IFN-gamma levels from 1.92 to 2.89 pg/mL (P < 0.001) in comparison with a reduction in mean levels from 1.80 to 1.68 pg/mL (P = 0.70) in the placebo group (P < 0.0001). Viusid administration was well tolerated. CONCLUSION: Our results indicate that treatment with Viusid leads to a notable improvement of oxidative stress and immunological parameters in patients with chronic hepatitis C.

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Los medios diagnósticos para explorar el intestino delgado no son los ideales. La enteroscopia con doble balón es una alternativa nueva con potencial diagnóstico y terapéutico. Se realizaron 14 enteroscopias: 4 anterógradas, 9 retrógradas y 1 por ambas vías, en el período comprendido entre julio y diciembre de 2007, a 8 mujeres y 6 hombres entre 18 y más de 80 años de edad para evaluar la utilidad, eficacia y seguridad de la enteroscopia de doble balón, realizada en el Instituto de Gastroenterología de Cuba. Se incluyeron 14 pacientes adultos de ambos sexos a los que se les estaba estudiando por: diarrea crónica, hemorragia de origen desconocido, melena de causa no precisada, sospecha o seguimiento de enfermedad intestinal y anemia crónica. Se realizaron abordajes anterógrado (oral) y retrógrado (anal) y se evaluó tiempo de realización del proceder, hallazgos y complicaciones. Los 14 pacientes recibieron sedación profunda. Los tiempos promedio de realización del proceder por las vías anterógrada y retrógada fueron 65 y 90 min, respectivamente. Se estudiaron 6 pacientes con diagnóstico clínico y radiológico de enfermedad de Crohn, 4 con el de diarreas crónicas, 3 con el de anemia crónica, y el resto por otros motivos. En 10 pacientes (71,4 por ciento) se confirmaron hallazgos endoscópicos de enfermedad del intestino delgado y en 4 (28,6 por ciento), la exploración fue normal. Los efectos adversos fueron leves y transitorios. Se concluyó que la enteroscopia de doble balón es un método diagnóstico y terapéutico, útil en pacientes con afecciones del intestino delgado, que permite explorar todo el órgano, así como la toma de biopsia de cada lesión observada y el uso de métodos tintoriales, si se requiere, posee escasas contraindicaciones, con un tiempo de realización aceptable, prácticamente sin complicaciones (AU)

The diagnostic aids to explore the small intestine are not the ideal ones. The double balloon enteroscopy is a new alternative with diagnostic and therapeutic potential. 14 enteroscopies were performed: 4 anterogrades, 9 retrogrades, and 1 by both routes, from July to December, 2007. 14 adult patients of both sexes, 8 females and 6 males, aged 18-over 80 took part in the study to evaluate the usefulness, efficacy and safety of double balloon enteroscopy performed in the Institute of Gastroenterology of Cuba. These patients were under study due to chronic diarrhea, hemorrhage of unknown origin, melena of undetermined cause, suspicion or follow-up of intestinal disease and chronic anemia. Anterograde (oral) and retrograde (anal) approaches were carried out and the time devoted to the procedure, the findings and the complications were evaluated. The 14 patients received deep sedation. The average time for the procedures by the anterograde and retrograde routes was 65 and 90 minutes, respectively. 6 patients with clinical and radiological diagnosis of Crohn disease were studied: 4 with chronic diarrheas, 3 with chronic anemia and the rest for other reasons. Endoscopic findings of the small intestine disease were confirmed in 10 patients (71.4 percent), whereas in 4 (28.6 percent) the exploration was normal. The adverse effects were mild and transient. It was concluded that double balloon enteroscopy is a diagnostic and therapeutic method useful in patients with affections of the small intestine that allows to explore the whole organ, as well as to perform a biopsy of each lesion observed and the use of staining methods, if necessary. It also has a few contraindications, and the procedure takes an acceptable time with practically no complications(AU)

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Los medios diagnósticos para explorar el intestino delgado no son los ideales. La enteroscopia con doble balón es una alternativa nueva con potencial diagnóstico y terapéutico. Se realizaron 14 enteroscopias: 4 anterógradas, 9 retrógradas y 1 por ambas vías, en el período comprendido entre julio y diciembre de 2007, a 8 mujeres y 6 hombres entre 18 y más de 80 años de edad para evaluar la utilidad, eficacia y seguridad de la enteroscopia de doble balón, realizada en el Instituto de Gastroenterología de Cuba. Se incluyeron 14 pacientes adultos de ambos sexos a los que se les estaba estudiando por: diarrea crónica, hemorragia de origen desconocido, melena de causa no precisada, sospecha o seguimiento de enfermedad intestinal y anemia crónica. Se realizaron abordajes anterógrado (oral) y retrógrado (anal) y se evaluó tiempo de realización del proceder, hallazgos y complicaciones. Los 14 pacientes recibieron sedación profunda. Los tiempos promedio de realización del proceder por las vías anterógrada y retrógada fueron 65 y 90 min, respectivamente. Se estudiaron 6 pacientes con diagnóstico clínico y radiológico de enfermedad de Crohn, 4 con el de diarreas crónicas, 3 con el de anemia crónica, y el resto por otros motivos. En 10 pacientes (71,4 por ciento) se confirmaron hallazgos endoscópicos de enfermedad del intestino delgado y en 4 (28,6 por ciento), la exploración fue normal. Los efectos adversos fueron leves y transitorios. Se concluyó que la enteroscopia de doble balón es un método diagnóstico y terapéutico, útil en pacientes con afecciones del intestino delgado, que permite explorar todo el órgano, así como la toma de biopsia de cada lesión observada y el uso de métodos tintoriales, si se requiere, posee escasas contraindicaciones, con un tiempo de realización aceptable, prácticamente sin complicaciones.

The diagnostic aids to explore the small intestine are not the ideal ones. The double balloon enteroscopy is a new alternative with diagnostic and therapeutic potential. 14 enteroscopies were performed: 4 anterogrades, 9 retrogrades, and 1 by both routes, from July to December, 2007. 14 adult patients of both sexes, 8 females and 6 males, aged 18-over 80 took part in the study to evaluate the usefulness, efficacy and safety of double balloon enteroscopy performed in the Institute of Gastroenterology of Cuba. These patients were under study due to chronic diarrhea, hemorrhage of unknown origin, melena of undetermined cause, suspicion or follow-up of intestinal disease and chronic anemia. Anterograde (oral) and retrograde (anal) approaches were carried out and the time devoted to the procedure, the findings and the complications were evaluated. The 14 patients received deep sedation. The average time for the procedures by the anterograde and retrograde routes was 65 and 90 minutes, respectively. 6 patients with clinical and radiological diagnosis of Crohn disease were studied: 4 with chronic diarrheas, 3 with chronic anemia and the rest for other reasons. Endoscopic findings of the small intestine disease were confirmed in 10 patients (71.4 percent), whereas in 4 (28.6 percent) the exploration was normal. The adverse effects were mild and transient. It was concluded that double balloon enteroscopy is a diagnostic and therapeutic method useful in patients with affections of the small intestine that allows to explore the whole organ, as well as to perform a biopsy of each lesion observed and the use of staining methods, if necessary. It also has a few contraindications, and the procedure takes an acceptable time with practically no complications.

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