Outcome of liver cancer patients with SARS-CoV-2 infection: An International, Multicentre, Cohort Study.

BACKGROUND & AIMS: Information about the impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in patients with liver cancer is lacking. This study characterizes the outcomes and mortality risk in this population. METHODS: Multicentre retrospective, cross-sectional, international study of liver cancer patients with SARS-CoV-2 infection registered between February and December 2020. Clinical data at SARS-CoV-2 diagnosis and outcomes were registered. RESULTS: Two hundred fifty patients from 38 centres were included, 218 with hepatocellular carcinoma (HCC) and 32 with intrahepatic cholangiocarcinoma (iCCA). The median age was 66.5 and 64.5 years, and 84.9% and 21.9% had cirrhosis in the HCC and iCCA cohorts respectively. Patients had advanced cancer stage at SARS-CoV-2 diagnosis in 39.0% of the HCC and 71.9% of the iCCA patients. After a median follow-up of 7.20 (IQR: 1.84-11.24) months, 100 (40%) patients have died, 48% of the deaths were SARS-CoV-2-related. Forty (18.4%) HCC patients died within 30-days. The death rate increase was significantly different according to the BCLC stage (6.10% [95% CI 2.24-12.74], 11.76% [95% CI 4.73-22.30], 20.69% [95% CI 11.35-31.96] and 34.52% [95% CI 17.03-52.78] for BCLC 0/A, B, C and D, respectively; p = .0017). The hazard ratio was 1.45 (95% CI 0.49-4.31; p = .5032) in BCLC-B versus 0/A, and 3.13 (95% CI 1.29-7.62; p = .0118) in BCLC-C versus 0/A in the competing risk Cox regression model. Nineteen out of 32 iCCA (59.4%) died, and 12 deaths were related to SARS-CoV-2 infection. CONCLUSIONS: This is the largest cohort of liver cancer patients infected with SARS-CoV-2. It characterizes the 30-day mortality risk of SARS-CoV-2 infected patients with HCC during this period.

Ruxolitinib as a treatment strategy for SARS-CoV-2 pneumonia: clinical experience in a real-world setting.

INTRODUCTION: Severe acute respiratory syndrome-related coronavirus (SARS-CoV-2) infection is characterised by a viral phase and a severe pro-inflammatory phase. The inhibition of the JAK/STAT pathway limits the pro-inflammatory state in moderate to severe COVID-19. METHODOLOGY: We analysed the data obtained by an observational cohort of patients with SARS-CoV-2 pneumonia treated with ruxolitinib in 22 hospitals of Mexico. The applied dose was determined based on physician's criteria. The benefit of ruxolitinib was evaluated using the 8-points ordinal scale developed by the NIH in the ACTT1 trial. Duration of hospital stay, changes in pro-inflammatory laboratory values, mortality, and toxicity were also measured. RESULTS: A total of 287 patients were reported at 22 sites in Mexico from March to June 2020; 80.8% received ruxolitinib 5 mg BID and 19.16% received ruxolitinib 10 mg BID plus standard of care. At beginning of treatment, 223 patients were on oxygen support and 59 on invasive ventilation. The percentage of patients on invasive ventilation was 53% in the 10 mg and 13% in the 5 mg cohort. A statistically significant improvement measured as a reduction by 2 points on the 8-point ordinal scale was described (baseline 5.39 ± 0.93, final 3.67± 2.98, p = 0.0001). There were 74 deaths. Serious adverse events were presented in 6.9% of the patients. CONCLUSIONS: Ruxolitinib appears to be safe in COVID-19 patients, with clinical benefits observed in terms of decrease in the 8-point ordinal scale and pro-inflammatory state. Further studies must be done to ensure efficacy against mortality.

Impact of COVID-19 on the burden of care of families of people with intellectual and developmental disabilities.

AIM: This study analysed the impact that COVID-19 and the response measures implemented by the Spanish Government have had on families of individuals with intellectual and developmental disabilities. METHOD: Data on 323 family members (M = 52.3 years old; SD = 10.5) were collected through an online survey, which was focused on analysing difficulties experienced and service provision during lockdown. RESULTS: Many families (66.3%) have seen their level of stress increased during lockdown because of, among other reasons, a greater burden of care. Difficulties were associated with the closure and changes in disability-related services. Families of people with extensive support needs have generally experienced greater difficulties. CONCLUSION: Support services should have been considered essential services during lockdown. The failure to receive support has resulted in excessive burden on families, who had to assume a multitude of roles to support their family member with intellectual and developmental disability.

Characteristics of patients coinfected with Severe Acute Respiratory Syndrome Coronavirus 2 and dengue virus, Lambayeque, Peru, May-August 2020: A retrospective analysis.

INTRODUCTION: Before the Coronavirus Disease 2019 (COVID-19) arrival and its pandemic, dengue was already a significant cause of epidemics in South East Asia and Latin America. In 2020 with their cocirculation, coinfections began to be observed and reported in different countries. As expected, this syndemic is evident in different areas and deserves proper characterisation and studies in Peru. METHODS: We retrospectively assessed the clinical, epidemiological, diagnostic characteristics and outcomes in a Social Security Hospital of Chiclayo, Lambayeque, Peru, of patients that were diagnosed simultaneously with COVID-19 and dengue during May-August 2020. RESULTS: A total of 50 patients with COVID-19/dengue coinfection were identified. Of them, 60% presented thrombocytopenia, and 52% fever, among other findings. The case fatality rate in this group was 28%, being higher in those patients initially classified as severe dengue (100%), as well as in females (55%) than males (21%) (OR = 4.65; 95%CI 1.18-18.45). DISCUSSION: Co-occurrence of COVID-19/Dengue is growing as a consequence of the syndemic of these viral diseases in endemic areas, such as Latin America, and as both conditions may evolve to severe disease, their epidemiological but clinical interaction in terms of outcomes need further assessment in future studies in the region.

Assessing the impact of COVID-19 on liver cancer management (CERO-19).

BACKGROUND & AIMS: The coronavirus disease 2019 (COVID-19) pandemic has posed unprecedented challenges to healthcare systems and it may have heavily impacted patients with liver cancer (LC). Herein, we evaluated whether the schedule of LC screening or procedures has been interrupted or delayed because of the COVID-19 pandemic. METHODS: An international survey evaluated the impact of the COVID-19 pandemic on clinical practice and clinical trials from March 2020 to June 2020, as the first phase of a multicentre, international, and observational project. The focus was on patients with hepatocellular carcinoma or intrahepatic cholangiocarcinoma, cared for around the world during the first COVID-19 pandemic wave. RESULTS: Ninety-one centres expressed interest to participate and 76 were included in the analysis, from Europe, South America, North America, Asia, and Africa (73.7%, 17.1%, 5.3%, 2.6%, and 1.3% per continent, respectively). Eighty-seven percent of the centres modified their clinical practice: 40.8% the diagnostic procedures, 80.9% the screening programme, 50% cancelled curative and/or palliative treatments for LC, and 41.7% modified the liver transplantation programme. Forty-five out of 69 (65.2%) centres in which clinical trials were running modified their treatments in that setting, but 58.1% were able to recruit new patients. The phone call service was modified in 51.4% of centres which had this service before the COVID-19 pandemic (n = 19/37). CONCLUSIONS: The first wave of the COVID-19 pandemic had a tremendous impact on the routine care of patients with liver cancer. Modifications in screening, diagnostic, and treatment algorithms may have significantly impaired the outcome of patients. Ongoing data collection and future analyses will report the benefits and disadvantages of the strategies implemented, aiding future decision-making. LAY SUMMARY: The coronavirus disease 2019 (COVID-19) pandemic has posed unprecedented challenges to healthcare systems globally. Herein, we assessed the impact of the first wave pandemic on patients with liver cancer and found that routine care for these patients has been majorly disrupted, which could have a significant impact on outcomes.

Generation and validation of in-hospital mortality prediction score in COVID-19 patients: Alba-score.

BACKGROUND: COVID-19 has a wide range of symptoms reported, which may vary from very mild cases (even asymptomatic) to deadly infections. Identifying high mortality risk individuals infected with the SARS-CoV-2 virus through a prediction instrument that uses simple clinical and analytical parameters at admission can help clinicians to focus on treatment efforts in this group of patients. METHODS: Data was obtained retrospectively from the electronic medical record of all COVID-19 patients hospitalized in the Albacete University Hospital Complex until July 2020. Patients were split into two: a generating and a validating cohort. Clinical, demographical and laboratory variables were included. A multivariate logistic regression model was used to select variables associated with in-hospital mortality in the generating cohort. A numerical and subsequently a categorical score according to mortality were constructed (A: mortality from 0% to 5%; B: from 5% to 15%; C: from 15% to 30%; D: from 30% to 50%; E: greater than 50%). These scores were validated with the validation cohort. RESULTS: Variables independently related to mortality during hospitalization were age, diabetes mellitus, confusion, SaFiO2, heart rate and lactate dehydrogenase (LDH) at admission. The numerical score defined ranges from 0 to 13 points. Scores included are: age ≥71 years (3 points), diabetes mellitus (1 point), confusion (2 points), onco-hematologic disease (1 point), SaFiO2 ≤ 419 (3 points), heart rate ≥ 100 bpm (1 point) and LDH ≥ 390 IU/L (2 points). The area under the curve (AUC) for the numerical and categorical scores from the generating cohort were 0.8625 and 0.848, respectively. In the validating cohort, AUCs were 0.8505 for the numerical score and 0.8313 for the categorical score. CONCLUSIONS: Data analysis found a correlation between clinical admission parameters and in-hospital mortality for COVID-19 patients. This correlation is used to develop a model to assist physicians in the emergency department in the COVID-19 treatment decision-making process.

Tenofovir-Amino Acid Conjugates Act as Polymerase Substrates-Implications for Avoiding Cellular Phosphorylation in the Discovery of Nucleotide Analogues.

Nucleotide analogues are used for treating viral infections such as HIV, hepatitis B, hepatitis C, influenza, and SARS-CoV-2. To become polymerase substrates, a nucleotide analogue must be phosphorylated by cellular kinases which is rate-limiting. The goal of this study is to develop dNTP/NTP analogues directly from nucleotides. Tenofovir (TFV) analogues were synthesized by conjugating with amino acids. We demonstrate that some conjugates act as dNTP analogues and HIV-1 reverse transcriptase (RT) catalytically incorporates the TFV part as the chain terminator. X-ray structures in complex with HIV-1 RT/dsDNA showed binding of the conjugates at the polymerase active site, however, in different modes in the presence of Mg2+ versus Mn2+ ions. The adaptability of the compounds is seemingly essential for catalytic incorporation of TFV by RT. 4d with a carboxyl sidechain demonstrated the highest incorporation. 4e showed weak incorporation and rather behaved as a dNTP-competitive inhibitor. This result advocates the feasibility of designing NTP/dNTP analogues by chemical substitutions to nucleotide analogues.

Incidence of surgical abdominal emergencies during SARS-CoV-2 pandemic

Introduction Since the appearance of SARS-CoV-2 in December 2019 in the Chinese city of Wuhan, we have experienced a reduction in admissions in our Service and a decrease in urgent surgical activity. Therefore, this study aimed to assess the incidence of potentially surgical abdominal emergency in our center during the epidemic of COVID-19. Methods A retrospective study was designed. It included all patients admitted for urgent abdominal pathology with potential surgical treatment in our General and Digestive Surgery Department from February 24, 2020 to April 19, 2020. Results Eighty-nine patients with a mean age of 58.85±22.2 were included. The median time from symptom onset to the Emergency Department (ED) visit was 48 (P25-P75 = 24-96) hours. On arrival at the ED, 18 (20%) patients presented with systemic inflammatory response syndrome criteria. Fifty-one (57%) surgical procedures were performed. The rate of post-surgical complications at 30 days was 31% and the mortality rate was 2%. Concerning the same period from 2017 to 2019, the mean number of admissions from the ED to our Department decreased by 14% during the epidemic period. Conclusion There has been a decrease in the number of patients admitted for urgent, potentially surgical, abdominal pathology during the period of the COVID-19 epidemic in our center. Resumen Introducción Desde la aparición en diciembre de 2019 del SARS-CoV-2 en la ciudad de Wuhan, China, hemos experimentado un descenso en los ingresos en nuestro Servicio y disminución de la actividad quirúrgica urgente. Por ello, el objetivo de este estudio fue analizar la incidencia de la patología abdominal urgente potencialmente quirúrgica en nuestro centro durante la epidemia por COVID-19. Métodos Se diseñó un estudio retrospectivo que incluyó a todos los pacientes ingresados por patología abdominal urgente potencialmente quirúrgica en nuestro Servicio de Cirugía General y del Aparato Digestivo desde el 24 de febrero de 2020 hasta el 19 de abril de 2020. Resultados Se incluyeron 89 pacientes con una edad media de 58,85 ± 22,2. La mediana de tiempo transcurrido desde el inicio de los síntomas hasta la consulta en el Servicio de Urgencias fue de 48 (P25-P75 = 24-96) horas. A su llegada a Urgencias 18 (20%) pacientes presentaban criterios de síndrome de respuesta inflamatoria sistémica (SRIS). Se realizaron 51 (57%) intervenciones quirúrgicas. La tasa de complicaciones postquirúrgicas a los 30 días fue del 31% y la tasa de mortalidad de 2%. Con respecto al mismo período de los años 2017 a 2019, la media de ingresos desde Urgencias en nuestro Servicio descendió un 14% durante el período de epidemia. Conclusiones Se ha producido un descenso en el número de pacientes que son ingresados por patología abdominal urgente potencialmente quirúrgica durante la epidemia por COVID-19 en nuestro centro.

Incidence of surgical abdominal emergencies during SARS-CoV-2 pandemic. / Incidencia de la patología abdominal quirúrgica urgente durante la pandemia por SARS-CoV-2.

INTRODUCTION: Since the appearance of SARS-CoV-2 in December 2019 in the Chinese city of Wuhan, we have experienced a reduction in admissions in our Service and a decrease in urgent surgical activity. Therefore, this study aimed to assess the incidence of potentially surgical abdominal emergency in our center during the epidemic of COVID-19. METHODS: A retrospective study was designed. It included all patients admitted for urgent abdominal pathology with potential surgical treatment in our General and Digestive Surgery Department from February 24, 2020 to April 19, 2020. RESULTS: Eighty-nine patients with a mean age of 58.85±22.2 were included. The median time from symptom onset to the Emergency Department (ED) visit was 48 (P25-P75 = 24-96) hours. On arrival at the ED, 18 (20%) patients presented with systemic inflammatory response syndrome criteria. Fifty-one (57%) surgical procedures were performed. The rate of post-surgical complications at 30 days was 31% and the mortality rate was 2%. Concerning the same period from 2017 to 2019, the mean number of admissions from the ED to our Department decreased by 14% during the epidemic period. CONCLUSION: There has been a decrease in the number of patients admitted for urgent, potentially surgical, abdominal pathology during the period of the COVID-19 epidemic in our center.