Efficacy and safety of treatments for hospitalized COVID-19 are uncertain. We systematically reviewed efficacy and safety of remdesivir for the treatment of COVID-19.
Studies evaluating remdesivir in ...adults with hospitalized COVID-19 were searched in several engines until August 21, 2020. Primary outcomes included all-cause mortality, clinical improvement or recovery, need for invasive ventilation, and serious adverse events (SAEs). Inverse variance random effects meta-analyses were performed.
We included four randomized controlled trials (RCTs) (n = 2296) two vs. placebo (n = 1299) and two comparing 5-day vs. 10-day regimens (n = 997), and two case series (n = 88). Studies used intravenous remdesivir 200mg the first day and 100mg for four or nine more days. One RCT (n = 236) was stopped early due to AEs; the other three RCTs reported outcomes between 11 and 15 days. Time to recovery was decreased by 4 days with remdesivir vs. placebo in one RCT (n = 1063), and by 0.8 days with 5-days vs. 10-days of therapy in another RCT (n = 397). Clinical improvement was better for 5-days regimen vs. standard of care in one RCT (n = 600). Remdesivir did not decrease all-cause mortality (RR 0.71, 95%CI 0.39 to 1.28, I2 = 43%) and need for invasive ventilation (RR 0.57, 95%CI 0.23 to 1.42, I2 = 60%) vs. placebo at 14 days but had fewer SAEs; 5-day decreased need for invasive ventilation and SAEs vs. 10-day in one RCT (n = 397). No differences in all-cause mortality or SAEs were seen among 5-day, 10-day and standard of care. There were some concerns of bias to high risk of bias in RCTs. Heterogeneity between studies could be due to different severities of disease, days of therapy before outcome determination, and how ordinal data was analyzed.
There is paucity of adequately powered and fully reported RCTs evaluating effects of remdesivir in hospitalized COVID-19 patients. Until stronger evidence emerges, we cannot conclude that remdesivir is efficacious for treating COVID-19.
We systematically reviewed benefits and harms of convalescent plasma (CP) in hospitalized COVID-19 patients.
Randomized controlled trials (RCTs) and observational studies assessing CP effects on ...hospitalized, adult COVID-19 patients were searched until November 24, 2020. We assessed risk of bias (RoB) using Cochrane RoB 2.0 and ROBINS-I tools. Inverse variance random effect meta-analyses were performed. Quality of evidence was evaluated using GRADE methodology. Primary outcomes were all-cause mortality, clinical improvement, and adverse events.
Five RCTs (
= 1067) and 6 cohorts (
= 881) were included. Three and 1 RCTs had some concerns and high RoB, respectively; and there was serious RoB in all cohorts. Convalescent plasma did not reduce all-cause mortality in RCTs of severe (RR = 0.60, 95% CI: 0.33-1.10) or moderate (RR = 0.60, 95% CI: 0.09-3.86) COVID-19 vs. standard of care (SOC); CP reduced all-cause mortality vs. SOC in cohorts (RR = 0.66, 95% CI: 0.49-0.91). Convalescent plasma did not reduce invasive ventilation vs. SOC in moderate disease (RR = 0.85, 95% CI: 0.47-1.55). In comparison to placebo + SOC, CP did not affect all-cause mortality (RR = 0.75, 95% CI: 0.48-1.16) or clinical improvement (HR = 1.07, 95% CI: 0.82-1.40) in severe patients. Adverse and serious adverse events were scarce, similar between CP and controls. Quality of evidence was low or very low for most outcomes.
In comparison to SOC or placebo + SOC, CP did not reduce all-cause mortality in RCTs of hospitalized COVID-19 patients. Convalescent plasma did not have an effect on other clinical or safety outcomes. Until now there is no good quality evidence to recommend CP for hospitalized COVID-19 patients.
We systematically assessed benefits and harms of tocilizumab (TCZ), which is an antibody blocking IL-6 receptors, in hospitalized COVID-19 patients.
Five electronic databases and two preprint ...webpages were searched until March 4, 2021. Randomized controlled trials (RCTs) and inverse probability treatment weighting (IPTW) cohorts assessing TCZ effects in hospitalized, COVID-19 adult patients were included. Primary outcomes were all-cause mortality, clinical worsening, clinical improvement, need for mechanical ventilation, and adverse events (AE). Inverse variance random-effects meta-analyses were performed with quality of evidence (QoE) evaluated using GRADE methodology.
Nine RCTs (n = 7,021) and nine IPTW cohorts (n = 7,796) were included. TCZ significantly reduced all-cause mortality in RCTs (RR 0.89, 95%CI 0.81-0.98, p = 0.03; moderate QoE) and non-significantly in cohorts (RR 0.67, 95%CI 0.44-1.02, p = 0.08; very low QoE) vs. control (standard of care SOC or placebo). TCZ significantly reduced the need for mechanical ventilation (RR 0.80, 95%CI 0.71-0.90, p = 0.001; moderate QoE) and length of stay (MD -1.92 days, 95%CI -3.46 to -0.38, p = 0.01; low QoE) vs. control in RCTs. There was no significant difference in clinical improvement or worsening between treatments. AEs, severe AEs, bleeding and thrombotic events were similar between arms in RCTs, but there was higher neutropenia risk with TCZ (very low QoE). Subgroup analyses by disease severity or risk of bias (RoB) were consistent with main analyses. Quality of evidence was moderate to very low in both RCTs and cohorts.
In comparison to SOC or placebo, TCZ reduced all-cause mortality in all studies and reduced mechanical ventilation and length of stay in RCTs in hospitalized COVID-19 patients. Other clinical outcomes were not significantly impacted. TCZ did not have effect on AEs, except a significant increased neutropenia risk in RCTs. TCZ has a potential role in the treatment of hospitalized COVID-19 patients.
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Background: Pediatric sarcomas make up 10% of pediatric tumors and involve a varied range of histological patterns with different prognosis which creates therapeutic challenges. Neonatal ...presentation is rare among sarcomas and poses further challenges in therapy. Methods: We present 5 cases of congenital sarcomas reporting pathology, genetics, treatment, and outcomes. We retrospectively identified 5 patients with sarcomas diagnosed in the neonatal period from a single institution in Miami from 2017 – 2022 in order to identify similarities between neonatal sarcomas. Our sarcomas included an embryonal rhabdomyosarcoma (RMS), infantile fibrosarcoma (IFS), rhabdoid tumor, and two undifferentiated sarcomas. Results: The presentation occurred between birth and four days old. Location at presentation was varied. Four of our patients were Nonrhabdomyosarcoma Soft Tissue Sarcomas (NRSTS). Only one patient was diagnosed prenatally, while three were diagnosed at birth, and one at 4 days of life. Three patients presented spindle cell pathology. One of our undifferentiated sarcomas was classified as IFS-like, Archer FusionPlex was negative for mutation. Our other undifferentiated sarcoma showed a COL1A1 gene rearrangement on chromosome 17q.21 with immunostains positive for BCOR, SMARCB1, SMARCA4. Congenital fibrosarcoma showed ETV6 fusion with NTRK and immunostains positive for FLI-1, SMA, CD34, INI-1. The RMS showed focal loss of PTCH1 and FANCC and had immunostains positive for desmin and myogenin. The metastatic rhabdoid tumor showed SMARCB1 whole gene deletion as well as a 570kB deletion in chromosome 22q11.23. Three patients were treated on ARST 0331 with vincristine, doxorubicin, and cyclophosphamide (VAC), with the undifferentiated sarcoma requiring advancement to ARST 0332. The patient with metastatic rhabdoid tumor was treated with AREN 0321. Four patients required surgery. We had 1-year-survival in three patients, all treated on ARST 0331 or ARST 0332. The patient with metastatic rhabdoid tumor died at 4 months of age while on AREN 0321, and our patient with IFS-like sarcoma decompensate and died at ten days old, prior to starting therapy. Conclusions: We show multiple genetic mutations with SMARCB1 alteration in both an undifferentiated sarcoma and a malignant rhabdoid tumor but otherwise found no significant pattern among individual sarcomas. Our cases show good outcomes for patients qualifying for ARST 0331. We highlight the need for improved methods of detection of pediatric tumors in utero.
Abstract
Primary central nervous system malignancy treatment remains a difficult problem despite advancement in techniques. Personalized medicine is evolving in making treatment decisions and ...particular molecular characteristics allow new targeted therapies to be specific and effective. We retrospectively present patients with primary CNS tumors receiving targeted therapy from 2016 to the present date. Outcomes included length of therapy, time until progression of disease, and overall response. Our study includes 32 patients with malignancies such as Astrocytoma, Ganglioglioma, Glioblastoma, and Diffuse Intrinsic Pontine Glioma (DIPG), among others. Analysis was based on patients’ underlying malignancy and included variables such as identified mutations, targeted therapy, progression vs resolution of disease, and time to progression of disease after initiation of targeted therapy. Overall results show 23 patients with at least 1-year-survival. The most common targeted therapy was Trametinib, treating tumors of glial origin. 14 patients showed no progression after starting targeted therapy, the majority low grade Gliomas and Medulloblastomas. Multiple mutations were found with the most frequent being BRAF. Of our 11 patients with BRAF mutations, 8 had no progression of disease after starting Trametinib or Dabrafenib. Patients with Atypical Teratoid Rhabdoid Tumors (ATRT) were treated with either Alisertib or Alisertib/Tazemetostat and 2 out of 4, both treated with Alisertib maintenance therapy, had no disease progression after targeted therapy. Best outcomes with no disease progression were primarily Gliomas, treated with Trametinib, and Medulloblastomas, treated with Vismodegib. Of our patients with DIPG, treated with Ribociclib, average time to disease progression on targeted therapy was 4.7 months and survival rate was 33%. We have shown excellent use of targeted therapy and our analysis highlights the need for continued exploration of targeted therapy among patients with CNS tumors.
Background. Hepatocellular carcinoma results in most cases from underlying chronic liver disease. The most common causes are the Hepatitis B virus and the Hepatitis C virus infections, the alcoholism ...and the aflatoxin. Mortality statistics of liver cell carcinoma in Peru is limited. Objectives. Update statistics on hepatocellular carcinoma mortality in Peru between the years 2005 and 2016. Methods. Observational, descriptive studyand secondary analysis of the Ministry of Health database. Records with the basic cause of death ICD 10: C22, the liver cell carcinoma were reviewed. Mortality was calculated according to the age, the sex and the department in which death was recorded; Also, standardized mortality by age was calculated. Results. 2,170 people were registered as deceased due to hepatocellular carcinoma. The 50.1% were male and the 67.5% older than 60 years. The standardized mortality rate in Peru decreased from 1.1 to 0.7 per 100,000 population from 2005 to 2016. The raw cup of mortality per 100,000 population shows that when comparing the first period (2005-2010) with the second (2011-2016), the tendency in Peru has decreased. The only region that presented a decrease in mortality was the Mountains (% change = -40.1). Conclusions. Standardized mortality by age had a slight decrease from 2005 to 2016; however, this difference does not show considerable variations. Mortality from this neoplasm seems to remain high and stable since the period from 1995 to 2000.
El pseudotumor hemofílico es una complicación muy rara vista en pacientes con hemofilia severa, y que cuyo manejo aún no se encuentra estandarizado. Se presenta el caso de un paciente varón de 33 ...años de edad admitido en el servicio de cirugía del Hospital Nacional Dos de Mayo por presentar una tumoración localizada en fosa iliaca izquierda, dolorosa a la palpación, asociada a alteración de la marcha. Realizada la exéresis, se identificó un pseudotumor hemofílico gigante ubicado en retroperitoneo. Este caso expone el primer reporte de manejo de pseudotumor hemofílico en nuestro país, con resultados satisfactorios a los 12 meses del posoperatorio.
El pseudotumor hemofílico es una complicación muy rara vista en pacientes con hemofilia severa, y que cuyo manejo aún no se encuentra estandarizado. Se presenta el caso de un paciente varón de 33 ...años de edad admitido en el servicio de cirugía del Hospital Nacional Dos de Mayo por presentar una tumoración localizada en fosa iliaca izquierda, dolorosa a la palpación, asociada a alteración de la marcha. Realizada la exéresis, se identificó un pseudotumor hemofílico gigante ubicado en retroperitoneo. Este caso expone el primer reporte de manejo de pseudotumor hemofílico en nuestro país, con resultados satisfactorios a los 12 meses del posoperatorio.
Introduction We systematically assessed benefits and harms of tocilizumab (TCZ), which is an antibody blocking IL-6 receptors, in hospitalized COVID-19 patients. Methods Five electronic databases and ...two preprint webpages were searched until March 4, 2021. Randomized controlled trials (RCTs) and inverse probability treatment weighting (IPTW) cohorts assessing TCZ effects in hospitalized, COVID-19 adult patients were included. Primary outcomes were all-cause mortality, clinical worsening, clinical improvement, need for mechanical ventilation, and adverse events (AE). Inverse variance random-effects meta-analyses were performed with quality of evidence (QoE) evaluated using GRADE methodology. Results Nine RCTs (n = 7,021) and nine IPTW cohorts (n = 7,796) were included. TCZ significantly reduced all-cause mortality in RCTs (RR 0.89, 95%CI 0.81–0.98, p = 0.03; moderate QoE) and non-significantly in cohorts (RR 0.67, 95%CI 0.44–1.02, p = 0.08; very low QoE) vs. control (standard of care SOC or placebo). TCZ significantly reduced the need for mechanical ventilation (RR 0.80, 95%CI 0.71–0.90, p = 0.001; moderate QoE) and length of stay (MD -1.92 days, 95%CI -3.46 to -0.38, p = 0.01; low QoE) vs. control in RCTs. There was no significant difference in clinical improvement or worsening between treatments. AEs, severe AEs, bleeding and thrombotic events were similar between arms in RCTs, but there was higher neutropenia risk with TCZ (very low QoE). Subgroup analyses by disease severity or risk of bias (RoB) were consistent with main analyses. Quality of evidence was moderate to very low in both RCTs and cohorts. Conclusions In comparison to SOC or placebo, TCZ reduced all-cause mortality in all studies and reduced mechanical ventilation and length of stay in RCTs in hospitalized COVID-19 patients. Other clinical outcomes were not significantly impacted. TCZ did not have effect on AEs, except a significant increased neutropenia risk in RCTs. TCZ has a potential role in the treatment of hospitalized COVID-19 patients.
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