Post-COVID-19 Pain Is Not Associated with DNA Methylation Levels of the ACE2 Promoter in COVID-19 Survivors Hospitalized Due to SARS-CoV-2 Infection.

One of theories explaining the development of long-lasting symptoms after an acute severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection include changes in the methylation pattern of the host. The current study aimed to investigate whether DNA methylation levels associated with the angiotensin-converting enzyme 2 (ACE2) promoter are different when comparing individuals previously hospitalized due to COVID-19 who then developed long-lasting post-COVID pain with those previously hospitalized due to COVID-19 who did not develop post-COVID-19 pain symptoms. Non-stimulated saliva samples were obtained from a cohort of 279 (mean age: 56.5, SD: 13.0 years old, 51.5% male) COVID-19 survivors who needed hospitalization. Clinical data were collected from hospital medical records. Participants were asked to disclose pain symptoms developed during the first three months after hospital admission due to COVID-19 and persisting at the time of the interview. Methylations of five CpG dinucleotides in the ACE2 promoter were quantified (as percentages). Participants were evaluated up to 17.8 (SD: 5.3) months after hospitalization. Thus, 39.1% of patients exhibited post-COVID-19 pain. Most patients (77.05%) in the cohort developed localized post-COVID-19 pain. Headache and pain in the lower extremity were experienced by 29.4% of the patients. Seven patients received a post-infection diagnosis of fibromyalgia based on the presence of widespread pain characteristics (11.6%) and other associated symptoms. No significant differences in methylation percentages at any CpG location of the ACE2 promoter were identified when comparing individuals with and without post-COVID-19 pain. The current study did not observe differences in methylation levels of the ACE2 promoter depending on the presence or absence of long-lasting post-COVID-19 pain symptoms in individuals who needed hospitalization due to COVID-19 during the first wave of the pandemic.

Immune response against the SARS-CoV-2 spike protein in cancer patients after COVID-19 vaccination during the Omicron wave: a prospective study.

BACKGROUND: Cancer patients often have weakened immune systems, resulting in a lower response to vaccines, especially those receiving immunosuppressive oncological treatment (OT). We aimed to assess the impact of OT on the humoral and T-cell response to the B.1 lineage and Omicron variant following COVID-19 vaccination in patients with solid and hematological neoplasms. METHODS: We conducted a prospective study on cancer patients, stratified into OT and non-OT groups, who received a two-dose series of the COVID-19 mRNA vaccine and a booster six months later. The outcomes measured were the humoral (anti-SARS-CoV-2 S IgG titers and ACE2-S interaction inhibition capacity) and cellular (SARS-CoV-2 S-specific T-cell spots per million PBMCs) responses against the B.1 lineage and Omicron variant. These responses were evaluated four weeks after the second dose (n = 98) and eight weeks after the booster dose (n = 71). RESULTS: The humoral response after the second vaccine dose against the B.1 lineage and Omicron variant was significantly weaker in the OT group compared to the non-OT group (q-value<0.05). A booster dose of the mRNA-1273 vaccine significantly improved the humoral response in the OT group, making it comparable to the non-OT group. The mRNA-1273 vaccine, designed for the original Wuhan strain, elicited a weaker humoral response against the Omicron variant compared to the B.1 lineage, regardless of oncological treatment or vaccine dose. In contrast, T-cell responses against SARS-CoV-2, including the Omicron variant, were already present after the second vaccine dose and were not significantly affected by oncological treatments. CONCLUSIONS: Cancer patients, particularly those receiving immunosuppressive oncological treatments, should require booster doses and adapted COVID-19 vaccines for new SARS-CoV-2 variants like Omicron. Future studies should evaluate the durability of the immune response and the efficacy of individualized regimens.

Is Antiviral Treatment with Remdesivir at the Acute Phase of SARS-CoV-2 Infection Effective for Decreasing the Risk of Long-Lasting Post-COVID Symptoms?

The aim of this study was to investigate the effects of administrating Remdesivir at the acute COVID-19 phase on developing post-COVID symptoms in previously hospitalized COVID-19 survivors by controlling factors such as age, sex, body mass index, and vaccination status. A case-control study was performed. Hospitalized COVID-19 survivors who had received intravenous Remdesivir during the acute phase (n = 216) were matched by age, sex, body mass index, and vaccination status with survivors who did not receive antiviral treatment (n = 216). Participants were asked to self-report the presence of any post-COVID symptom (defined as a symptom that started no later than three months after infection) and whether the symptom persisted at the time of study (mean: 18.4, SD: 0.8 months). Anxiety levels (HADS-A), depressive symptoms (HADS-D), sleep quality (PSQI), and severity/disability (FIC) were also compared. The multivariate analysis revealed that administration of Remdesivir at the acute COVID-19 phase was a protective factor for long-term COVID development (OR0.401, 95%CI 0.256-0.628) and specifically for the following post-COVID symptoms: fatigue (OR0.399, 95%CI 0.270-0.590), pain (OR0.368, 95% CI 0.248-0.548), dyspnea at rest (OR0.580, 95%CI 0.361-0.933), concentration loss (OR0.368, 95%CI 0.151-0.901), memory loss (OR0.399, 95%CI 0.270-0.590), hair loss (OR0.103, 95%CI 0.052-0.207), and skin rashes (OR0.037, 95%CI 0.005-0.278). This study supports the potential protective role of intravenous administration of Remdesivir during the COVID-19 acute phase for long-lasting post-COVID symptoms in previously hospitalized COVID-19 survivors.

External validation of the RIETE and SOME scores for occult cancer in patients with venous thromboembolism: a multicentre cohort study.

INTRODUCTION: Venous thromboembolism (VTE) may be the first sign of an undiagnosed cancer. The RIETE and SOME scores aim to identify patients with acute VTE at high risk of occult cancer. In the present study, we evaluated the performance of both scores. METHODS: The scores were evaluated in a retrospective cohort from two centers. The area under the receiver-operating characteristics curve (AUC) evaluated the discriminatory performance. RESULTS: The RIETE score was applied to 815 patients with provoked and unprovoked VTE, of whom 56 (6.9%) were diagnosed with cancer. Of the 203 patients classified as high-risk, 18 were diagnosed with cancer, representing 32.1% (18/56) of the total cancer diagnoses. In the group of 612 low-risk patients, 67.9% of the cancer cases were diagnosed (38/56). Sensitivity, specificity, negative and positive predictive values, and AUC were 32%, 76%, 94%, 9%, and 0.430 (95% confidence interval [CI], 0.38‒0.47), respectively. The SOME score could be calculated in 418 patients with unprovoked VTE, of whom 33 (7.9%) were diagnosed with cancer. Of the 45 patients classified as high-risk, three were diagnosed with cancer, representing 9.1% (3/33) of the total cancer diagnoses. In the group of 373 low-risk patients, 90.9% of the cancer cases were diagnosed (30/33). Sensitivity, specificity, negative and positive predictive values, and AUC were 33%, 88%, 94%, 20%, and 0.351 (95% CI, 0.27‒0.43), respectively. CONCLUSIONS: The performance of both scores was poor. Our results highlight the need to develop new models to identify high-risk patients who may benefit from an extensive cancer screening strategy.

Inflammatory Polymorphisms (IL-6 rs1800796, IL-10 rs1800896, TNF-α rs1800629, and IFITM3 rs12252) Are Not Associated with Post-COVID Symptoms in Previously Hospitalized COVID-19 Survivors.

The aim of this study was to identify the association between four selected inflammatory polymorphisms with the development of long-term post-COVID symptoms in subjects who had been hospitalized due to SARS-CoV-2 infection during the first wave of the pandemic. These polymorphisms were selected as they are associated with severe COVID-19 disease and cytokine storm, so they could be important to prognoses post-COVID. A total of 408 (48.5% female, age: 58.5 ± 14.0 years) previously hospitalized COVID-19 survivors participated. The three potential genotypes of the following four single-nucleotide polymorphisms, IL-6 rs1800796, IL-10 rs1800896, TNF-α rs1800629, and IFITM3 rs12252, were obtained from non-stimulated saliva samples of the participants. The participants were asked to self-report the presence of any post-COVID symptoms (defined as symptoms that had started no later than one month after SARS-CoV-2 acute infection) and whether the symptoms persisted at the time of the study. At the time of the study (mean: 15.6, SD: 5.6 months after discharge), 89.4% of patients reported at least one post-COVID symptom (mean number of symptoms: 3.0; SD: 1.7). Fatigue (69.3%), pain (40.9%), and memory loss (27.2%) were the most prevalent post-COVID symptoms in the total sample. Overall, no differences in the post-COVID symptoms depending on the IL-6 rs1800796, IL-10 rs1800896, TNF-α rs1800629, and IFITM3 rs12252 genotypes were seen. The four SNPs assessed, albeit having been previously associated with inflammation and COVID-19 severity, did not cause a predisposition to the development of post-COVID symptoms in the previously hospitalized COVID-19 survivors.

Prediction of Venous Thromboembolism in Patients With Cancer Using Machine Learning Approaches: A Systematic Review and Meta-Analysis.

PURPOSE: Recent studies have suggested that machine learning (ML) could be used to predict venous thromboembolism (VTE) in cancer patients with high accuracy. METHODS: We aimed to evaluate the performance of ML in predicting VTE events in patients with cancer. PubMed, Web of Science, and EMBASE to identify studies were searched. RESULTS: Seven studies involving 12,249 patients with cancer were included. The combined results of the different ML models demonstrated good accuracy in the prediction of VTE. In the training set, the global pooled sensitivity was 0.87, the global pooled specificity was 0.87, and the AUC was 0.91, and in the test set 0.65, 0.84, and 0.80, respectively. CONCLUSION: The prediction ML models showed good performance to predict VTE. External validation to determine the result's reproducibility is necessary.

Main applications of point-of-care ultrasound in palliative care.

Combined with a physical examination, clinical ultrasound offers a valuable complement that can help guide clinical decision-making. In various medical and surgical specialties, it is increasingly used for diagnostic and therapeutic purposes. Due to recent technological advances, smaller and more affordable ultrasound machines are now being developed for use in home hospice care. The purpose of this paper is to describe how clinical ultrasound may be applied in Palliative Care, where it can be a valuable tool to assist the clinician in making better clinical decisions and to assist in accurately guiding palliative procedures. Furthermore, it can be used to identify unnecessary hospitalizations and prevent them from occurring. Training programs with specific objectives are necessary to implement clinical ultrasound in Palliative Care, as well as defining learning curves and promoting alliances with scientific societies that recognize the teaching, care and research trajectory for accreditation of competencies.

Age-Adjusted Endothelial Activation and Stress Index for Coronavirus Disease 2019 at Admission Is a Reliable Predictor for 28-Day Mortality in Hospitalized Patients With Coronavirus Disease 2019.

Background: Endothelial Activation and Stress Index (EASIX) predict death in patients undergoing allogeneic hematopoietic stem cell transplantation who develop endothelial complications. Because coronavirus disease 2019 (COVID-19) patients also have coagulopathy and endotheliitis, we aimed to assess whether EASIX predicts death within 28 days in hospitalized COVID-19 patients. Methods: We performed a retrospective study on COVID-19 patients from two different cohorts [derivation (n = 1,200 patients) and validation (n = 1,830 patients)]. The endpoint was death within 28 days. The main factors were EASIX [(lactate dehydrogenase * creatinine)/thrombocytes] and aEASIX-COVID (EASIX * age), which were log2-transformed for analysis. Results: Log2-EASIX and log2-aEASIX-COVID were independently associated with an increased risk of death in both cohorts (p < 0.001). Log2-aEASIX-COVID showed a good predictive performance for 28-day mortality both in the derivation cohort (area under the receiver-operating characteristic = 0.827) and in the validation cohort (area under the receiver-operating characteristic = 0.820), with better predictive performance than log2-EASIX (p < 0.001). For log2 aEASIX-COVID, patients with low/moderate risk (<6) had a 28-day mortality probability of 5.3% [95% confidence interval (95% CI) = 4-6.5%], high (6-7) of 17.2% (95% CI = 14.7-19.6%), and very high (>7) of 47.6% (95% CI = 44.2-50.9%). The cutoff of log2 aEASIX-COVID = 6 showed a positive predictive value of 31.7% and negative predictive value of 94.7%, and log2 aEASIX-COVID = 7 showed a positive predictive value of 47.6% and negative predictive value of 89.8%. Conclusion: Both EASIX and aEASIX-COVID were associated with death within 28 days in hospitalized COVID-19 patients. However, aEASIX-COVID had significantly better predictive performance than EASIX, particularly for discarding death. Thus, aEASIX-COVID could be a reliable predictor of death that could help to manage COVID-19 patients.

The PANDEMYC Score. An Easily Applicable and Interpretable Model for Predicting Mortality Associated With COVID-19.

This study aimed to build an easily applicable prognostic model based on routine clinical, radiological, and laboratory data available at admission, to predict mortality in coronavirus 19 disease (COVID-19) hospitalized patients. METHODS: We retrospectively collected clinical information from 1968 patients admitted to a hospital. We built a predictive score based on a logistic regression model in which explicative variables were discretized using classification trees that facilitated the identification of the optimal sections in order to predict inpatient mortality in patients admitted with COVID-19. These sections were translated into a score indicating the probability of a patient's death, thus making the results easy to interpret. RESULTS: Median age was 67 years, 1104 patients (56.4%) were male, and 325 (16.5%) died during hospitalization. Our final model identified nine key features: age, oxygen saturation, smoking, serum creatinine, lymphocytes, hemoglobin, platelets, C-reactive protein, and sodium at admission. The discrimination of the model was excellent in the training, validation, and test samples (AUC: 0.865, 0.808, and 0.883, respectively). We constructed a prognostic scale to determine the probability of death associated with each score. CONCLUSIONS: We designed an easily applicable predictive model for early identification of patients at high risk of death due to COVID-19 during hospitalization.

Diagnostic Capacity of Pocket-Sized Ultrasound Devices at Point of Care by a Non-radiologist Resident in Patients with Suspected Abdominal Pathology.

Studies have reported the usefulness and tolerability in practice of abdominal ultrasound performed by non-radiologists in various clinical situations. This prospective observational single-center study included 184 patients hospitalized in an internal medicine department who underwent conventional abdominal ultrasound. A medical resident with basic training performed point-of-care clinical ultrasound using a pocket-sized device. The concordance obtained between the researcher and the radiologist was good (k >0.6) for the gallbladder, splenomegaly, longitudinal diameter of the kidney, presence of renal cysts and hydronephrosis. The specificity was >90% for all parameters assessed except normal renal size. A negative predictive value >90% was obtained for all variables studied except the presence of hepatic space-occupying lesions and gallbladder pathology, the negative predictive values for which were >80%. A positive predictive value >80% was obtained for all of these variables, except the presence of adenopathies, hepatomegaly, space-occupying lesions, echogenicity and/or enlargement of the biliary tract, left renal atrophy and right renal masses. We conclude there was a high concordance between a conventional abdominal study and that performed with a pocket-sized ultrasound device after a brief learning curve.

First plasma glucose value after urgent admission and in-hospital mortality in acutely decompensated heart failure.

BACKGROUND: We used data from three <250-bed hospitals to test how plasma glucose (PG) values influenced in-hospital mortality (IHM) in acute heart failure in people without diabetes. METHODS AND RESULTS: We identified 788 HF admissions (62% female; median age 83.3 years). 20.9% had chronic kidney disease, 7.7% cancer history, 24.7% acute renal failure and 29.7% concomitant infection. Mean first PG was 124.3 ± 32.4 mg/dl; 22.7% had stress hyperglycemia. Fifty-six people died (IHM = 7.1%). Women, older patients and people with infections showed higher PG values. People who died had higher PG values (136.3 ± 43.9 vs. 123.4 ± 31.2 mg/dl; p = 0.029). In a multivariate regression model with IHM as main outcome, the first PG (per mg/dl, odds ratio (OR): 1.01 [1.00-1.02]; p = 0.045), age (per year, OR: 1.06 [1.02-1.10]; p = 0.003) and acute renal failure (OR: 0.42 [0.24-0.74]; p = 0.003) remained significantly associated with IHM. CONCLUSIONS: The first PG value predicted IHM in participants without diabetes after admission for heart failure.

Clinical features of patients inappropriately undiagnosed of pulmonary embolism.

PURPOSES: The objective of this study was to identify clinical factors associated with delayed diagnosis of acute pulmonary embolism (PE) in the emergency department (ED). BASIC PROCEDURES: A retrospective observational study was performed at three University affiliated Hospitals; 436 consecutive patients who presented to the ED with an acute PE confirmed by chest computed tomography from 2008 to 2011 were included. Patients were divided into 3 groups: group 1, PE was diagnosed while the patient was still in the ED; group 2, PE was diagnosed during hospitalization; group 3, patients who were sent home with a wrong alternative diagnosis and returned to the ED and were diagnosed of PE. MAIN FINDINGS: One hundred forty-six patients (33.5%) had a delayed diagnosis of PE--21.5% belong to group 2 and 11.9% to Group 3. Chronic coexisting medical conditions like asthma or chronic obstructive pulmonary disease were independent predictors of a delayed diagnosis in patients who were admitted to hospital whereas non-specific and less severe symptoms like the presence of pleuro-mechanic thoracic pain, fever, hemoptysis, or the presence of a pulmonary infiltrate in chest x-ray were independent predictors of a delayed diagnosis in patients who were sent home. PRINCIPAL CONCLUSIONS: Delay in diagnosis of acute PE is frequent despite current diagnostic strategies. Patients are sent home or admitted to hospital with a wrong diagnosis depending on clinical presentation or coexisting medical conditions.

Effect of platelet-rich plasma on sinus lifting: a randomized-controlled clinical trial.

OBJECTIVE: The combination of anorganic bovine bone (ABB) with platelet-rich plasma (PRP) has been widely used in bone regeneration procedures although its benefits are still unclear. The purpose of this study was to evaluate whether or not PRP improves the efficacy of ABB in sinus floor augmentation. In addition, we have investigated the effect of residual bone height and tobacco on implant survival in sinus augmentation procedures. PATIENT AND METHODS: Eighty-seven patients recruited for this study underwent 144 sinus floor augmentation procedures using ABB alone or ABB plus PRP (ABB+PRP) in a randomized clinical trial. A total of 286 implants were placed in the augmented bone, and their evolution was followed up for a period of 24 months. In order to investigate on a histological level and any adjunctive effects, we performed an ancillary study in five edentulous patients with a symmetrical severely resorbed maxilla. In these patients, a bilateral sinus augmentation was randomly performed using ABB or ABB+PRP in a split-mouth design, and after 6 months, bone biopsies were taken from the implant sites for histological and histomorphometric analysis. RESULTS: Overall, 96.2% of ABB and 98.6% of ABB+PRP implant success were obtained during the monitoring period and differences were not found between sites grafted with and without PRP in the 87 patients studied. Densitometry assessments and graft resorption were similar in both experimental groups. However, the histological and histomorphometrical analysis in the five edentulous patients revealed that bone augmentation was significantly higher in sites treated with ABB+PRP (p