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Κυριακή 24 Ιουλίου 2022

Concordance of B and T cell responses to SARS‐CoV‐2 infection, irrespective of symptoms suggestive of COVID‐19

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Abstract

Objectives

To assess T cell responses in individuals with and without a positive antibody response to SARS-CoV-2, in symptomatic and asymptomatic individuals during the COVID-19 pandemic.

Methods

Participants were drawn from the TwinsUK cohort, grouped by a) presence or absence of COVID-associated symptoms (S+, S-), logged prospectively through the COVID Symptom Study app, and b) Anti-IgG Spike and anti-IgG Nucleocapsid antibodies measured by ELISA (Ab+, Ab-), during the first wave of the UK pandemic. T cell helper and regulatory responses after stimulation with SARS-CoV-2 peptides were assessed.

Results

32 participants were included in final analysis. 14 of 15 with IgG Spike antibodies had a T cell response to SARS-CoV-2-specific peptides; none of 17 participants without IgG Spike antibodies had a T cell response (Chi-squared 28.2, p<0.001). Quantitative T cell responses correlated strongly with fold-change in IgG Spike antibody titre (rho=0 .79, p<0.0001) but not to symptom score (rho=0.17, p=0.35).

Conclusions

Humoral and cellular immune responses to SARS-CoV-2 are highly correlated. We found no evidence of cellular immunity suggestive of SARS-CoV2 infection in individuals with a COVID-19-like illness but negative antibodies.

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Sustained within-season vaccine effectiveness against influenza-associated hospitalization in children: Evidence from the New Vaccine Surveillance Network, 2015-2016 through 2019-2020

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Abstract
Background
Adult studies have demonstrated within-season declines in influenza vaccine effectiveness (VE); data in children are limited.
Methods
We conducted a prospective, test-negative study of children 6 months–17 years hospitalized with acute respiratory illness at 7 pediatric medical centers during the 2015-2016 through 2019-2020 influenza seasons. Case-patients were children with an influenza-positive molecular test matched by illness onset to influenza-negative control-patients. We estimated VE [100% x (1 – odds ratio)] by comparing the odds of receipt of ≥1 dose of influenza vaccine ≥14 days before illness onset among influenza-positive children to influenza-negative children. Changes in VE over time between vaccination date and illness onset date were estimated using multivariable logistic regression.
Results
Of 8,430 children, 4,653 (55%) received ≥1 dose of influenza vaccine. On average, 48% were v accinated through October and 85% through December each season. Influenza vaccine receipt was lower in case-patients than control-patients (39% vs. 57%, p < 0.001); overall VE against hospitalization was 53% (95% CI: 46%-60%). Pooling data across 5 seasons, the odds of influenza-associated hospitalization increased 4.2% (-3.2%-12.2%) per month since vaccination, with an average VE decrease of 1.9% per month (n = 4,000, p = 0.275). Odds of hospitalization increased 2.9% (95% CI: -5.4%-11.8%) and 9.6% (95% CI: -7.0%-29.1%) per month in children ≤8 years (n = 3,084) and 9-17 years (n = 916), respectively. These findings were not statistically significant.
Conclusions
We observed minimal, not statistically significant within-season declines in VE. Vaccination following current ACIP guidelines for timing of vaccine receipt remains the best strategy for preventing influenza-associated hospitalizations in children.
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A soluble DR5‐Fc chimeric protein (sDR5‐Fc) attenuates inflammatory responses induced by coronavirus MHV‐A59 and SARS‐CoV‐2

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Abstract

Mortality in COVID-19 patients has been linked to the presence of "cytokine storm" induced by SARS-CoV-2 infection, which involves elevated levels of circulating cytokines and immune-cell hyperactivation. Targeting cytokines during the management of COVID-19 patients has the potential to improve survival rates and reduce mortality. Although cytokine blockers and immune-host modulators are currently being tested in severely ill COVID-19 patients to cope with the overwhelming systemic inflammation, no significant efficacy has been observed yet, thus finding new cytokine blockers to attenuate the cytokine storm syndrome is meaningful. In this paper, we significantly attenuated the inflammatory responses induced by mouse hepatitis viruses A59 (MHV-A59) and SARS-CoV-2 through a soluble DR5-Fc (sDR5-Fc) chimeric protein that blocking the TRAIL-DR5 interaction. Our finding indicates that blocking TRAIL-DR5 pathway through sDR5-Fc chimeric protein is a promising strategy to treat with COVID-19 severe patients requiring ICU admission or with chronic metabolic diseases.

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Factors associated with high alanine aminotransferase (ALT) and cirrhosis in people living with HIV on combination antiretroviral treatment (cART) in the Asia‐Pacific

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Abstract

Introduction:

Liver disease is a growing burden among PLHIV in resource-limited settings. As an indicator of liver disease, risk factors of high alanine aminotransferase (ALT) and cirrhosis were assessed among PLHIV in the TREAT Asia HIV Observational Database (TAHOD).

Methods:

Patients on cART with a pre-cART ALT measurement and at least one follow-up ALT measurement were included. Factors associated with high ALT (ALT levels >5 times its upper limit of normal) were analysed using repeated measure logistic regression over a ten-year follow-up period. Liver cirrhosis was defined as having an APRI score >1.5, FIB-4 score >3.25, or a clinical diagnosis of cirrhosis. Cox regression analysis stratified by site was used to analyse factors associated with cirrhosis among those in follow-up after 2015.

Results:

Of 5182 patients, 101 patients (1.9%) had high ALT levels with HCV-antibody positive (OR 4.98, 95%CI 2.82-8.77, p <0.001) an d ever high alcohol consumption (OR 2.33, 95% CI 1.00-5.46, p=0.050) as likely factors. Among 6318 PLHIV in the liver cirrhosis analysis, 151 (2%) developed cirrhosis (incidence rate= 0.82 per 100 person-years). Those HCV-antibody positive (HR 5.54, 95% CI 3.75-8.18, p<0.001) and had high alcohol consumption (HR 2.06, 95%CI 1.23-3.45, p=0.006) were associated with liver cirrhosis.

Conclusion:

HCV-antibody positive and high alcohol consumption are factors associated with high ALT. With raised ALT levels as a known factor associated with liver cirrhosis, greater efforts are required in managing ALT levels and reduce the risk of developing liver cirrhosis among those positive for HCV-antibody and those who consume alcohol.

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Protective Effects of Cannabis sativa on chemotherapy‐induced nausea

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Abstract

Cyclophosphamide is an anticancer and immunosuppressive agent used in the treatment of various malignancies but causing gastrointestinal distress. Cannabis sativa (C. sativa) and its derivatives have been used for the treatment of human gastrointestinal disorders. A purpose of this study was to investigate the effect of C. sativa on nausea induced by cyclophosphamide in rats. The rats were divided into four groups (8 animals per group): Group 1: Normal control (saline i.p). Group 2: rats received cyclophosphamide (200 mg/kg i.p) 3 consecutive days. Group 3 and 4: Rats received cyclophosphamide (200 mg/kg ip) across days 1 – 7 and C. sativa (20 and 40 mg/kg sc) was administered on cyclophosphamide days 4 – 7. We examined intake of kaolin, normal food and changes in body weight, as an indicator of the emetic stimulus. Oxidative stress markers, antioxidant enzymes status, serotonin (5HT), dopamine, noradrenaline and CB1R levels were evaluated in the intestina l homogenate. Moreover, histopathological study was performed. Results showed that C. sativa ameliorates cyclophosphamide-induced emesis by increasing in body weight and normal diet intake with a decrease in kaolin diet intake after 7 days. Moreover, C. sativa significantly decreases (serotonin) 5HT, dopamine and noradrenaline, as well as, decreasing oxidative stress and inflammation. Administration of C. sativa significantly increased the expression of CB1R in intestinal homogenate. Treatment with C. sativa, also, improved the histological feature of an intestinal tissue. These results suggested that C. sativa possess antiemetic, antioxidant and anti-inflammatory effects in chemotherapy-induced nausea in rats by activating CB1R.
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Risk factor analysis for cytomegalovirus reactivation under prophylaxis with letermovir after allogeneic hematopoietic stem cell transplantation

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Abstract

Background

Letermovir has been approved as a novel cytomegalovirus (CMV) prophylactic agent after allogeneic hematopoietic stem cell transplantation (HSCT). However, there are still insufficient data to properly evaluate the real-world role of letermovir, and the risk factors for CMV reactivation under letermovir prophylaxis have not been clarified.

Methods

We performed a single-institution retrospective analysis of patients under prophylaxis with or without letermovir who underwent allogeneic HSCT between March 2012 and December 2019. In August 2018, letermovir was added to the clinical practice at our institution for the prophylaxis of CMV reactivation in allogeneic SCT recipients. Patients who underwent SCT without prophylactic letermovir from March 2012 until September 2018 served as a historical control.

Results

The cumulative incidence of clinically significant CMV infection (CS-CMVi) was significantly lower in the letermovir group than in the historical control group not receiving letermovir (30.2% vs 71.6%, P < 0.05, at 100 days). In addition, the cumulative incidence of non-relapse mortality (NRM) at day 500 was significantly lower in the letermovir group (4.7% vs 19.8%, P < 0.05). We then performed a risk factor analysis for developing CS-CMVi in the letermovir group. The only significant factor identified by this multivariable analysis was transplantation from a CMV seronegative donor to a seropositive recipient (HR = 2.76, 95% confidence interval 1.14 – 6.68, P < 0.05).

Conclusion

Our study showed that letermovir prophylaxis significantly reduced the incidence of CS-CMVi and NRM in a real-world setting and that the CMV serostatus of the donor remained as a risk factor for CS-CMVi even under letermovir prophylaxis.

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Πέμπτη 21 Ιουλίου 2022

Evaluate the safety and efficacy of dura sealant patch in reducing cerebrospinal fluid leakage following elective cranial surgery (ENCASE II): study protocol for a randomized, two-arm, multicenter trial

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Cerebrospinal fluid (CSF) leakage is a frequent and challenging complication in neurosurgery, especially in the posterior fossa, with a prevalence of 8%. It is associated with substantial morbidity and increas...
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Three-dimensional evaluation of postoperative stability: a comparative study between surgery-first and surgery-late protocols

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The main objective of this study was to compare the stability of the surgery-first and surgery-late approaches according to the standardized centre protocols, by three-dimensional evaluation after 1 year of follow-up. A retrospective study was designed that included a test group (surgery-first protocol) and a control group (surgery-late protocol), with a follow-up period of at least 1 year (average 14 months; range 12 –24 months). Stability was evaluated using linear and angular measurements by superimposing cone beam computed tomography images obtained at specific points in time: preoperatively, 1 month after surgery, and at the end of the orthodontic treatment. (Source: International Journal of Oral and Maxillofacial Surgery)
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Τετάρτη 20 Ιουλίου 2022

Diagnostic Delay in Human Papillomavirus Negative Oropharyngeal Squamous Cell Carcinoma

alexandrossfakianakis shared this article with you from Inoreader
Diagnostic Delay in Human Papillomavirus Negative Oropharyngeal Squamous Cell Carcinoma

Delays in care related to evaluations by multiple providers and misdiagnosis prolonged time to diagnosis in HPV(−)OPSCC. Improved patient and provider education is necessary to expedite the diagnosis of HPV(−)OPSCC.


Objective

Failure to recognize symptoms of non-human papillomavirus-associated oropharyngeal squamous cell carcinoma (HPV(−)OPSCC) at presentation can delay diagnosis and treatment. We aim to identify patient factors and provider practice patterns that delay presentation and care in HPV(−)OPSCC.

Methods

Retrospective review at a tertiary care center. Patients with HPV(−)OPSCC receiving treatment from 2006 to 2016. Patients were excluded if their date of symptom onset or diagnosis was unknown after thorough review of the electronic medical record or their tissue was not tested for HPV or p16. Clinical data, workup, and care timelines were abstracted. Univariate and multivariable linear regressions were performed to determine associations between patient and provider factors and delays in care.

Results

Of 70 included patients, 52 (74%) were male and mean age was 60.5 (SD = 9.0). Median time to diagnosis was 69 days (IQR = 32–127 days), with a median latency of 30 days (IQR = 12–61 days) from symptom onset to first presentation and 19.5 days (IQR = 4–46 days) from the first presentation to diagnosis. Most patients visited at least 2 providers (n = 52, 74%) before diagnosis. Evaluation by 3 or more providers prior to diagnosis was associated with significant delays in diagnosis of nearly a year (357.7 days, p < 0.001) and being treated or prescribed analgesia prior to diagnosis was significantly associated with delays in diagnosis (p = 0.004) on univariate regression analysis.

Conclusions

Delays in care related to evaluations by multiple providers and misdiagnosis prolonged time to diagnosis in HPV(−)OPSCC. Improved patient and provider education is necessary to expedite the diagnosis of HPV(−)OPSCC.

Level of Evidence

Level 4 Laryngoscope, 2022
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Safety and efficacy of molnupiravir in SARS‐CoV‐2 infected patients: a real‐life experience

alexandrossfakianakis shared this article with you from Inoreader

Abstract

Introduction

Since the start of the SARS-CoV-2 pandemic, several treatments have been proposed to cure Coronavirus Disease 2019 (COVID-19) and prevent it. Molnupiravir is a ribonucleoside prodrug of N-hydroxycytidine with an in vitro e in vivo activity against SARS-CoV-2.

Methods

We conducted a retrospective cohort study including all people treated with Molnupiravir between the 10th of January and the 31th of March 2022 at the University Hospital of Sassari. Molnupiravir was prescribed, according to the Italian Agency of Drug indications, in patients with recent symptoms onset (≤5five days), no need of oxygen supplementation, and with a high risk of disease progression for the presence chronic diseases.

Results

We included 192 people with a mean age of 70.4±15.4 years; 144 (75%) patients were over 60 years. During the follow-up, 20 (10.4%) patients showed a disease progression. At the multivariate analysis, older age, having neurological dis ease, and having dyspnea at the onset of the symptoms, and acquiring SARS-CoV-2 infeciton during an hospital admission were associated with an increased risk of progression. On the contrary, early start of treatment was associated with a reduced risk of disease progression. Molnupiravir was also extremely safe since 13 (6.8%) adverse events were reported, with only one interruption.

Conclusion

Our study shows that Monlupiravir confirmed its efficacy and safety in a real-life cohort that included a high percentage of elderly people with a high comorbidity burden.

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