Solitary Fibrous Tumor of the Masticator Space with Unusual Extension: a Case Report.

Background: We present the case of a patient with solitary fibrous tumor of the masticator space with unusual extension. Case presentation: A 43-year-old woman presented with a painless mass with intraoral extension on the right cheek. The B-scan sonograph and magnetic resonance imaging revealed the extension of the tumor. The biopsy performed under local anesthesia raised the suspicion of a solitary fibrous tumor. Tumor excision included a preoperative tumor embolization. The surgical removal of the tumor included a partial parotidectomy on the right side, insertion of masseteric and temporalis muscle, resection of the middle part of the zygomatic bone and stabilization of the bone with a plate, mobilization of the tumor from the maxillary sinus and the pterygopalatine fossa through an endoscopic approach and an approach via partial resection of the anterior wall of the maxillary sinus after identifying and sparing the infraorbital nerve. Ôhe histological findings confirmed the diagnosis of solitary fibrous tumor. The patient's treatment completed with radiation therapy, and 2.5 years later, there was recurrence in the right temporal area. Conclusion:To our knowledge, this is the second reported case of solitary fibrous tumor arising in the masticator space and the only case with extension intraorally and in the paranasal sinuses. Tumor embolization and complete surgical excision are the most frequently recommended treatments.

Antimicrobial Use during the SARS-CoV-2 Pandemic in a Greek Tertiary University Hospital.

In cases of SARS-CoV-2 hospitalization, despite low bacterial co-infection rates, antimicrobial use may be disproportionately high. Our aim was to quantify such usage in COVID-19 patients and identify factors linked to increased antibiotic use. We retrospectively studied patients with SARS-CoV-2 infection who were hospitalized at our institution during the pandemic. In the initial two waves of the pandemic, antimicrobial use was notably high (89% in the first wave and 92% in the second), but it decreased in subsequent waves. Elevated procalcitonin (>0.5 µg/mL) and C-reactive protein (>100 mg/L) levels were linked to antibiotic usage, while prior vaccination reduced antibiotic incidence. Antimicrobial use decreased in the pandemic, suggesting enhanced comprehension of SARS-CoV-2's natural course. Additionally, it was correlated with heightened SARS-CoV-2 severity, elevated procalcitonin, and C-reactive protein levels.

The Utility of Stroboscopy in Evaluating Patients with Benign Vocal Fold Lesions.

Purpose: The present study aims to provide a comprehensive analysis of the use of stroboscopy as an assessment tool for patients with benign lesions of the vocal folds. Methods: The current study was based on an extensive review of the international bibliography regarding the evaluation of voice in patients with benign lesions of the vocal cords using videostroboscopy. Results: Stroboscopy is a convenient technique used by otolaryngologists that has been established as a valuable diagnostic tool for assessing patients with dysphonia and benign vocal cords lesions. Conclusions: Stroboscopy is recommended in the literature as the preferred method for assessing vocal cord vibratory function. The future poses challenges in standardizing guidelines and quantifying measurements of stroboscopic findings.

Inflammation and Venous Thromboembolism in Hospitalized Patients with COVID-19.

BACKGROUND: A link between inflammation and venous thromboembolism (VTE) in COVID-19 disease has been suggested pathophysiologically and clinically. The aim of this study was to investigate the association between inflammation and disease outcomes in adult hospitalized COVID-19 patients with VTE. METHODS: This was a retrospective observational study, including quantitative and qualitative data collected from COVID-19 patients hospitalized at the Infectious Diseases Unit (IDU) of the University Hospital of Ioannina, from 1 March 2020 to 31 May 2022. Venous thromboembolism was defined as a diagnosis of pulmonary embolism (PE) and/or vascular tree-in-bud in the lungs. The burden of disease, assessed by computed tomography of the lungs (CTBoD), was quantified as the percentage (%) of the affected lung parenchyma. The study outcomes were defined as death, intubation, and length of hospital stay (LoS). A chi-squared test and univariate logistic regression analyses were performed in IBM SPSS 28.0. RESULTS: After propensity score matching, the final study cohort included 532 patients. VTE was found in 11.2% of the total population. In patients with VTE, we found that lymphocytopenia and a high neutrophil/lymphocyte ratio were associated with an increased risk of intubation and death, respectively. Similarly, CTBoD > 50% was associated with a higher risk of intubation and death in this group of patients. The triglyceride-glucose (TyG) index was also linked to worse outcomes. CONCLUSIONS: Inflammatory indices were associated with VTE. Lymphocytopenia and an increased neutrophil-to-lymphocyte ratio negatively impacted the disease's prognosis and outcomes. Whether these indices unfavorably affect outcomes in COVID-19-associated VTE must be further evaluated.

Remdesivir: Effectiveness and Safety in Hospitalized Patients with COVID-19 (ReEs-COVID-19)-Analysis of Data from Daily Practice.

Remdesivir was the first antiviral approved for treating COVID-19. We investigated its patterns of use, effectiveness and safety in clinical practice in Greece. This is a retrospective observational study of hospitalized adults who received remdesivir for COVID-19 in September 2020-February 2021. The main endpoints were the time to recovery (hospital discharge within 30 days from admission) and safety. The "early" (remdesivir initiation within 24 h since hospitalization) and "deferred" (remdesivir initiation later on) groups were compared. One thousand and four patients (60.6% male, mean age 61 years, 74.3% with severe disease, 70.9% with ≥1 comorbidities) were included, and 75.9% of them were on a 5-day regimen, and 86.8% were in the early group. Among those with a baseline mild/moderate disease, the median (95% CI) time to recovery was 8 (7-9) and 12 (11-14) days for the early and deferred groups, respectively (p < 0.001). The corresponding estimates for those with a severe disease were 10 (9-10) and 13 (11-15) days, respectively (p = 0.028). After remdesivir initiation, increased serum transaminases and an acute kidney injury were observed in 6.9% and 2.1%, respectively. Nine (0.9%) patients discontinued the treatment due to adverse events. The effectiveness of remdesivir was increased when it was taken within 24 h since admission regardless of the disease severity. Remdesivir's safety profile is similar to that described in clinical trials and other real-world cohorts.

Mycobacterium marinum: A Case-Based Narrative Review of Diagnosis and Management.

Skin and soft tissue infections caused by non-tuberculous mycobacteria are occurring more frequently in recent years. However, chronic skin and soft tissue lesions present a challenge for clinicians, as the diagnostic work-up and definitive diagnosis require knowledge and available laboratory resources. We present here the case of a 66-year-old male patient who presented with painful abscess-like nodules on his right hand and forearm, which worsened after treatment with an anti-TNF-a agent. The fluid specimen taken from the lesion was positive for mycobacteria according to the acid-fast stain. Mycobacterium marinum was identified, first by next-generation sequencing and finally grown on culture, after eight weeks. Acknowledging the complexity of diagnosing and managing infections by non-tuberculous mycobacteria, and especially Mycobacterium marinum, we provide a review of the current epidemiology, clinical characteristics, diagnosis and management of Mycobacterium marinum infection.

Glycemic Dysregulation, Inflammation and Disease Outcomes in Patients Hospitalized with COVID-19: Beyond Diabetes and Obesity.

INTRODUCTION: During the COVID-19 pandemic, diabetes mellitus (DM) and obesity were associated with high rates of morbidity and mortality. The aim of this study was to investigate the relationship between markers of inflammation, disease severity, insulin resistance, hyperglycemia, and outcomes in COVID-19 patients with and without diabetes and obesity. MATERIALS AND METHODS: Epidemiological, clinical, and laboratory data were collected from the University Hospital of Ioannina COVID-19 Registry and included hospitalized patients from March 2020 to December 2022. The study cohort was divided into three subgroups based on the presence of DM, obesity, or the absence of both. RESULTS: In diabetic patients, elevated CRP, IL-6, TRG/HDL-C ratio, and TyG index, severe pneumonia, and hyperglycemia were associated with extended hospitalization. Increased IL-6, NLR, and decreased PFR were associated with a higher risk of death. In the obese subgroup, lower levels of PFR were associated with longer hospitalization and a higher risk of death, while severe lung disease and hyperglycemia were associated with extended hospitalization. In patients without DM or obesity severe pneumonia, NLR, CRP, IL-6, insulin resistance indices, and hyperglycemia during hospitalization were associated with longer hospitalization. CONCLUSION: Inflammatory markers and disease severity indices were strongly associated with disease outcomes and hyperglycemia across all subgroups.

Acute Ethanol Intoxication: Αn Overlooked Cause of High Anion Gap Metabolic Acidosis With a Marked Increase in Serum Osmolal Gap.

Measurement of serum osmolal gap is a useful tool in suspected toxic alcohol ingestion. Normal levels of osmolal gap are typically <10 mOsm/kg). Osmolal gap >20 mOsm/kg is usually caused by ingestion of methanol, ethylene glycol, isopropanol, propylene glycol, diethylene glycol, or organic solvents such as acetone but rarely of ethanol alone. Herein, we describe the case of a severe ethanol intoxication presenting with a marked increase in the osmolal gap. An 18-year-old male was referred to the emergency department of our hospital, in a comatose state, following binge drinking. blood gas analysis revealed a high anion gap metabolic acidosis. In addition, it was found an extremely elevated osmolal gap of 91 mOsm/kg. The increment of the osmolal gap and the high anion gap acidosis could not be attributed to methanol/ethylene glycol intoxication, alcoholic ketoacidosis, or other cause of acidosis. The calculated osmolal concentration of ethanol was 91 mOsm/kg (osmolal concentration of ethanol is equal to the serum ethanol levels (mg/dL) divided by 3.7). Thus, the increase in the osmolal gap was a result of ethanol intoxication solely. Acute, isolated, ethanol intoxication may be a rare cause of a marked increase of osmolal gap with high anion gap metabolic acidosis. Clinicians should be alerted to the possibility of acute ethanol intoxication in a patient presenting with high anion gap metabolic acidosis and an extremely elevated osmolal gap. Toxicologic screen tests should be performed to identify the aetiology of the gap rise and proper therapy should be administered.

Visual Analogue Scale for the Evaluation of Olfactory and Gustatory Dysfunction of COVID-19 Patients in Northwestern Greece.

Background The visual analogue scale (VAS) has been used as a diagnostic tool for the evaluation of the severity of olfactory and gustatory dysfunction (OGD) caused by SARS-CoV2 infection. The main objective of the present study was the evaluation of OGD with VAS in COVID-19-positive patients in Northwestern Greece and its possible association with the patients' self-reported symptoms of olfactory and gustatory dysfunction. Methods The presence of olfactory and gustatory symptoms and their severity were assessed by questionnaire along with the use of specific odorants and tastant ingredients, in three time periods: prior to COVID-19, during COVID-19 (initial diagnosis) and post-COVID-19 disease (at four weeks from disease onset). Three hundred COVID-19-positive patients (home-quarantined and hospitalized) tested with RT-PCR test in the University Hospital of Ioannina Greece were included in this study. Statistical analysis was performed on SPSS Statistics 26.0 (IBM Corp., Armonk, NY) Results Out of a total of 300 patients, 146 and 190 patients had mild hyposmia and hypogeusia respectively, followed by patients with severe hyposmia or hypogeusia (118 and 88 respectively), at the time of COVID-19 onset (initial diagnosis). An increase in the number of patients with recovery of symptoms was observed during the follow-up period, during which only eight patients had non-resolving severe symptoms (six patients with hyposmia and two with hypogeusia). On further analysis, a statistically significant association was found between the severity of symptoms (assessed by VAS score) and the self-reported symptoms of sensory dysfunction by the patients. There was a significant association between the groups of patients with mild hyposmia and patients that reported no loss of smell; between the patients with moderate hyposmia and the patients who reported "loss of smell"; and between the patients with severe hyposmia and the group of patients who reported a loss of smell, at the COVID-19 onset period. Similarly, patients with mild hyposmia were associated with those that reported a loss of smell at the same time. The severity of hyposmia was also associated with the reported symptom of "loss of taste" at the time of COVID-19 diagnosis. Similar findings were observed regarding the severity of hypogeusia and the reported symptom of "loss of taste" among the groups of patients. Finally, the severity of hypogeusia was associated with smell loss at the time of initial diagnosis of the infection. Conclusion Similar to the literature data, our findings indicate that hyposmia and hypogeusia are common symptoms of COVID-19 disease with varying severity. In our study, most of the patients exerted a complete recovery of these OGD symptoms. In addition, we found an association between olfactory dysfunction and self-reported sensory of taste as well as gustatory dysfunction and sensory of smell. Finally, we found that the VAS score was a reliable diagnostic tool in the estimation of OGD in this cohort of patients. However, our results need to be confirmed by larger-scale trials.

Correlation of Lymphocyte Subpopulations, Clinical Features and Inflammatory Markers during Severe COVID-19 Onset.

BACKGROUND: Dysregulation of the immune response in the course of COVID-19 has been implicated in critical outcomes. Lymphopenia is evident in severe cases and has been associated with worse outcomes since the early phases of the pandemic. In addition, cytokine storm has been associated with excessive lung injury and concomitant respiratory failure. However, it has also been hypothesized that specific lymphocyte subpopulations (CD4 and CD8 T cells, B cells, and NK cells) may serve as prognostic markers for disease severity. The aim of this study was to investigate possible associations of lymphocyte subpopulations alterations with markers of disease severity and outcomes in patients hospitalized with COVID-19. MATERIALS/METHODS: A total of 42 adult hospitalized patients were included in this study, from June to July 2021. Flow-cytometry was used to calculate specific lymphocyte subpopulations on day 1 (admission) and on day 5 of hospitalization (CD45, CD3, CD3CD8, CD3CD4, CD3CD4CD8, CD19, CD16CD56, CD34RA, CD45RO). Markers of disease severity and outcomes included: burden of disease on CT (% of affected lung parenchyma injury), C-reactive protein and interleukin-6 levels. PO2/FiO2 ratio and differences in lymphocytes subsets between two timepoints were also calculated. Logistic and linear regressions were used for the analyses. All analyses were performed using Stata (version 13.1; Stata Corp, College Station, TX, USA). RESULTS: Higher levels of CD16CD56 cells (Natural Killer cells) were associated with higher risk of lung injury (>50% of lung parenchyma). An increase in CD3CD4 and CD4RO cell count difference between day 5 and day 1 resulted in a decrease of CRP difference between these timepoints. On the other hand, CD45RARO difference was associated with an increase in the difference of CRP levels between the two timepoints. No other significant differences were found in the rest of the lymphocyte subpopulations. CONCLUSIONS: Despite a low patient number, this study showed that alterations in lymphocyte subpopulations are associated with COVID-19 severity markers. It was observed that an increase in lymphocytes (CD4 and transiently CD45RARO) resulted in lower CRP levels, perhaps leading to COVID-19 recovery and immune response homeostasis. However, these findings need further evaluation in larger scale trials.

The Effect of Commonly Used Fixed-Dose Single Pill Combinations of Renin-Angiotensin-System Blockers and Calcium Channel Blockers on HOMA-IR Index in Hypertensive Patients with Impaired Fasting Glucose: a 12-Week Randomized Open-Label Prospective Study.

Backround: The effect of antihypertensive drugs on glucose homeostasis and insulin resistance remains an issue under investigation. There is evidence that renin-angiotensin system (RAS) blockers may favorably affect glucose metabolism, while treatment with calcium channel blockers (CCBs) is considered to have an overall neutral metabolic effect. However, the effects on glycemic indices may differ among agents within the same class of antihypertensive drugs. Objective: To evaluate the effects of different fixed-dose single pill combinations of RAS blockers with CCBs on homeostatic model assessment for insulin resistance (HOMA-IR). Methods:Drug-naive patients with arterial hypertension (AH) and impaired fasting glucose (IFG) were randomly allocated to open-label fixed, single pill combinations of valsartan 160 mg/day plus amlodipine 5 mg/day (VAL/AMLO group, n = 54), delapril 30 mg/day and manidipine 10 mg/day (DEL/MANI group, n = 53) or telmisartan 80 mg/day and amlodipine 5 mg/day (TEL/AMLO group, n = 51) for 12 weeks. Glycemic indices and HOMA-IR were determined at baseline and post-treatment. Results:A total of 158 patients were included. All treatment combinations effectively reduced blood pressure (systolic and diastolic) to similar levels (all p < 0.001). A decrease in the HOMA-IR index by 22.55% (p <0.01) was noted following treatment with TEL/AMLO, while an increase by 1.4% (p = 0.57) and 12.65% (p = 0.072) was observed in the VAL/AMLO group and the DEL/MANI group, respectively. These changes were significantly different between TEL/AMLO and DEL/MANI (p < 0.05) as well as between TEL/AMLO and VAL/AMLO (p < 0.001). Conclusion:Despite similar antihypertensive action, the effect of fixed, single pill combinations with TEL/AMLO, VAL/AMLO and DEL/MANI on insulin resistance is in favor of TEL/AMLO. Trial registration: The study protocol was published online in https://diavgeia.gov.gr/ (No: ÂÈ6Ó46906Ç-ÁÅÓ) via the Ministry of Digital Governance, after receiving approval from the Scientific Council and Administrative Council of University Hospital of Ioannina (No. of approval: 1/12-06-2014 (issue 150). https://diavgeia.gov.gr/decision/view/%CE%92%CE%986%CE%A346906%CE%97- %CE%91%CE%95%CE%A3 h t t p s : / / d i a v g e i a . g o v . g r / d o c / % C E % 9 2 % C E % 9 8 6 % C E % A 3 4 6 9 0 6 % C E % 9 7 - %CE%91%CE%95%CE%A3?inline=true.

Treatment of Merkel Cell Carcinoma Using Intraoperative Flow Cytometry (iFC) Protocol, Optimized for Head and Neck Lesions, as a Means for Tumor Margin Evaluation - a Case Presentation.

Background: We present the case of a patient with a Merkel cell carcinoma (MCC) of the left preauricular area. Case presentation:A 84-year-old Greek man was examined at the outpatient ENT Department of our clinic with a lesion in the preauricular area that had appeared four months ago. The patient history included antihypertensive and antihyperlipidemic therapy as well as treatment for dementia. The excision of the skin lesion was performed under local anesthesia. The histological examination revealed a Merkel cell carcinoma. The patient underwent a computed tomography (CT) scan that showed a lesion with clear limits in the left parotid gland and lymph nodes. Under general anesthesia, he underwent a left superficial parotidectomy, left submandibular gland excision and radical neck dissection. Histological preparations were analyzed using an intraoperative flow cytometry (iFC) protocol. A radiation therapy concluded the patient's treatment. Conclusion:Even if MCC appears as a less common and more aggressive skin cancer type, a clinician always has to include it in the differential diagnosis of a skin lesion. We found the use of iFC very useful for the diagnosis of this skin cancer.

Predicting the need for mechanical ventilation and mortality in hospitalized COVID-19 patients who received heparin.

Although several studies have utilized AI (artificial intelligence)-based solutions to enhance the decision making for mechanical ventilation, as well as, for mortality in COVID-19, the extraction of explainable predictors regarding heparin's effect in intensive care and mortality has been left unresolved. In the present study, we developed an explainable AI (XAI) workflow to shed light into predictors for admission in the intensive care unit (ICU), as well as, for mortality across those hospitalized COVID-19 patients who received heparin. AI empowered classifiers, such as, the hybrid Extreme gradient boosting (HXGBoost) with customized loss functions were trained on time-series curated clinical data to develop robust AI models. Shapley additive explanation analysis (SHAP) was conducted to determine the positive or negative impact of the predictors in the model's output. The HXGBoost predicted the risk for intensive care and mortality with 0.84 and 0.85 accuracy, respectively. SHAP analysis indicated that the low percentage of lymphocytes at day 7 along with increased FiO2 at days 1 and 5, low SatO2 at days 3 and 7 increase the probability for mortality and highlight the positive effect of heparin administration at the early days of hospitalization for reducing mortality.

Complement C3 inhibition in severe COVID-19 using compstatin AMY-101.

Complement C3 activation contributes to COVID-19 pathology, and C3 targeting has emerged as a promising therapeutic strategy. We provide interim data from ITHACA, the first randomized trial evaluating a C3 inhibitor, AMY-101, in severe COVID-19 (PaO2/FiO2 ≤ 300 mmHg). Patients received AMY-101 (n = 16) or placebo (n = 15) in addition to standard of care. AMY-101 was safe and well tolerated. Compared to placebo (8 of 15, 53.3%), a higher, albeit nonsignificant, proportion of AMY-101-treated patients (13 of 16, 81.3%) were free of supplemental oxygen at day 14. Three nonresponders and two placebo-treated patients succumbed to disease-related complications. AMY-101 significantly reduced CRP and ferritin and restrained thrombin and NET generation. Complete and sustained C3 inhibition was observed in all responders. Residual C3 activity in the three nonresponders suggested the presence of a convertase-independent C3 activation pathway overriding the drug's inhibitory activity. These findings support the design of larger trials exploring the potential of C3-based inhibition in COVID-19 or other complement-mediated diseases.

Clinical Symptoms in Hospitalized and Self-Quarantined Patients with SARS-CoV-2 Infection in Northwestern Greece - Association with Olfactory and Gustatory Dysfunction.

Backround: We aimed to assess the relation of chemosensory dysfunction with the reported symptoms in two subgroups of patients in Northwestern Greece: the first one included patients with moderate to severe symptomatology who needed hospitalization and the second one, patients with mild symptoms who recovered at home. Methods:We used a questionnaire to select information about patient demographics, medical history and reported symptoms during infection. Three hundred COVID-19 positive patients who were identified via RT-PCR test in the University Hospital of Ioannina, Greece, were included in the present study, of which 150 recovered at home and the remaining 150 needed hospitalization. Statistical analysis was based on IBM-SPSS Statistics 26.0. Results:The majority of patients had fever during infection, while o minor percentage of those who needed hospitalization (12.67%) suffered from sore throat. There was a statistically significant difference between the loss of smell and clinical symptoms including fatigue, nose congestion, body aches and headache, and loss of taste and reported symptoms including fatigue, body aches, runny nose, headache and sore throat. Conclusion: Fever was the symptom with the highest percentage rate, while sore throat was the symptom with the lowest percentage rate. There are reported clinical symptoms related with olfactory and gustatory dysfunction during COVID-19 infection.

Dizziness in the Emergency Department: Insights and Epidemiological Data - a Population Based Study.

Background:Dizziness is a commonly referred symptom in emergency departments (EDs). The aim of this study is to describe the epidemiology of dizziness included acute vestibular syndrome (AVS) in the ED of the University Hospital of Ioannina, Grecce, during a six-month period. Methods:A total of 60 patients presenting with dizziness to the ED of our hospital during a short period of six months in 2021 were identified. Data were obtained through retrospective and prospective review of medical records. Statistical analysis was based on ÉBM-SPSS Statistics 26.0. Results:Among the 60 patients, 16.67% received the diagnosis of cerebellar stroke, 3.33% Meniere disease, 16.67% vestibular neuritis, 20% benign paroxysmal positional vertigo, 3.33% cardiovascular disease, and 1.67% had a neurological disease. Finally, 35% of patients left the ED undiagnosed. Conclusion:Benign paroxysmal positional vertigo was found to be the most common cause of dizziness in the ED, followed by cerebellar stroke and vestibular neuritis. A detailed neurological examination is recommended for the diagnosis of dizziness in the ED. Our data confirm the findings of previous studies in the GreeK population of patients presenting with dizziness to the ED of our hospital.

The Impact of Age and Gender and Their Association with Chemosensory Dysfunction, in Hospitalized and Self-Quarantine Patients with Covid-19 Infection, in Epirus, Greece.

Objective:Olfactory and gustatory dysfunction that relates with the infection from severe acute respiratory syndrome-related coronavirus (SARS-CoV-2) has already improved. The relation between chemosensory dysfunction and age and gender in covid-19 positive patients is the main objective of the present study. Methods:We used a questionnaire to select information about medical history, patient demographics and reported symptoms during infection. Three hundred covid-19 positive patients, who underwent a RT-PCR test in the University Hospital of Ioannina, Grecce, were included in this study; 150 of them recovered at home and the remaining 150 were admitted to hospital. Statistical analysis based on ÉBM-SPSS Statistics 26.0 was done. Results:The total sample included 300 patients, of which 106 females and 194 males. There was a statistically significant difference between the subgroup of patients aged 21-25, 61-65 and 71-75 with loss of smell, that of hospitalized patients aged 41-45 with loss of smell and the subgroup of those aged 31-35 and 71-75 with loss of taste. Conclusion:There is a significant association between chemosensory dysfunction and younger age groups. Olfactory and gustatory dysfunction appears more frequently in women than men. Male gender relates with disease severity.

Intensive-Dose Tinzaparin in Hospitalized COVID-19 Patients: The INTERACT Study.

(1) Background: It is well-established that coronavirus disease-2019 (COVID-19) is highly pro-inflammatory, leading to activation of the coagulation cascade. COVID-19-induced hypercoagulability is associated with adverse outcomes and mortality. Current guidelines recommend that hospitalized COVID-19 patients should receive pharmacological prophylaxis against venous thromboembolism (VTE). (2) INTERACT is a retrospective, phase IV, observational cohort study aiming to evaluate the overall clinical effectiveness and safety of a higher than conventionally used prophylactic dose of anticoagulation with tinzaparin administered for VTE prevention in non-critically ill COVID-19 patients with moderate disease severity. (3) Results: A total of 705 patients from 13 hospitals in Greece participated in the study (55% men, median age 62 years). Anticoagulation with tinzaparin was initiated immediately after admission. A full therapeutic dose was received by 36.3% of the participants (mean ± SD 166 ± 33 IU/Kgr/day) and the remaining patients (63.9%) received an intermediate dose (mean ± SD 114 ± 22 IU/Kgr/day). The median treatment duration was 13 days (Q1−Q3: 8−20 days). During the study (April 2020 to November 2021), 14 thrombotic events (2.0%) were diagnosed (i.e., three cases of pulmonary embolism (PE) and 11 cases of deep venous thrombosis, DVT). Four bleeding events were recorded (0.6%). In-hospital death occurred in 12 patients (1.7%). Thrombosis was associated with increasing age (median: 74.5 years, Q1−Q3: 62−79, for patients with thrombosis vs. 61.9 years, Q1−Q3: 49−72, p = 0.0149), increased D-dimer levels for all three evaluation time points (at admission: 2490, Q1−Q3: 1580−6480 vs. 700, Q1−Q3: 400−1475, p < 0.0001), one week ± two days after admission (3510, Q1−Q3: 1458−9500 vs. 619, Q1−Q3: 352−1054.5, p < 0.0001), as well as upon discharge (1618.5, Q1−Q3: 1010−2255 vs. 500, Q1−Q3: 294−918, p < 0.0001). Clinical and laboratory improvement was affirmed by decreasing D-dimer and CRP levels, increasing platelet numbers and oxygen saturation measurements, and a drop in the World Health Organization (WHO) progression scale. (4) Conclusions: The findings of our study are in favor of prophylactic anticoagulation with an intermediate to full therapeutic dose of tinzaparin among non-critically ill patients hospitalized with COVID-19.

ICU admission and mortality classifiers for COVID-19 patients based on subgroups of dynamically associated profiles across multiple timepoints.

The coronavirus disease 2019 (COVID-19) which is caused by severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) is consistently causing profound wounds in the global healthcare system due to its increased transmissibility. Currently, there is an urgent unmet need to identify the underlying dynamic associations among COVID-19 patients and distinguish patient subgroups with common clinical profiles towards the development of robust classifiers for ICU admission and mortality. To address this need, we propose a four step pipeline which: (i) enhances the quality of multiple timeseries clinical data through an automated data curation workflow, (ii) deploys Dynamic Bayesian Networks (DBNs) for the detection of features with increased connectivity based on dynamic association analysis across multiple points, (iii) utilizes Self Organizing Maps (SOMs) and trajectory analysis for the early identification of COVID-19 patients with common clinical profiles, and (iv) trains robust multiple additive regression trees (MART) for ICU admission and mortality classification based on the extracted homogeneous clusters, to identify risk factors and biomarkers for disease progression. The contribution of the extracted clusters and the dynamically associated clinical data improved the classification performance for ICU admission to sensitivity 0.83 and specificity 0.83, and for mortality to sensitivity 0.74 and specificity 0.76. Additional information was included to enhance the performance of the classifiers yielding an increase by 4% in sensitivity and specificity for mortality. According to the risk factor analysis, the number of lymphocytes, SatO2, PO2/FiO2, and O2 supply type were highlighted as risk factors for ICU admission and the percentage of neutrophils and lymphocytes, PO2/FiO2, LDH, and ALP for mortality, among others. To our knowledge, this is the first study that combines dynamic modeling with clustering analysis to identify homogeneous groups of COVID-19 patients towards the development of robust classifiers for ICU admission and mortality.

Anakinra in hospitalized non-intubated patients with coronavirus disease 2019: a Systematic review and meta-analysis.

OBJECTIVES: Acute respiratory distress syndrome and cytokine release syndrome are the major complications of coronavirus disease 2019 (COVID-19) associated with increased mortality risk. We performed a meta-analysis to assess the efficacy and safety of anakinra in adult hospitalized non-intubated patients with COVID-19. METHODS: Relevant trials were identified by searching literature until 24 April 2021 using the following terms: anakinra, IL-1, coronavirus, COVID-19, SARS-CoV-2. Trials evaluating the effect of anakinra on the need for invasive mechanical ventilation and mortality in hospitalized non-intubated patients with COVID-19 were included. RESULTS: Nine studies (n = 1119) were eligible for inclusion in the present meta-analysis. Their bias risk with reference to the assessed parameters was high. In pooled analyses, anakinra reduced the need for invasive mechanical ventilation (odds ratio (OR): 0.38, 95% CI: 0.17-0.85, P = 0.02, I2 = 67%; six studies, n = 587) and mortality risk (OR: 0.32, 95% CI: 0.23-0.45, P < 0.00001, I2 = 0%; nine studies, n = 1119) compared with standard of care therapy. There were no differences regarding the risk of adverse events, including liver dysfunction (OR: 0.75, 95% CI: 0.48-1.16, P > 0.05, I2 = 28%; five studies, n = 591) and bacteraemia (OR: 1.07, 95% CI: 0.42-2.73, P > 0.05, I2 = 71%; six studies, n = 727). CONCLUSIONS: Available evidence shows that treatment with anakinra reduces both the need for invasive mechanical ventilation and mortality risk of hospitalized non-intubated patients with COVID-19 without increasing the risk of adverse events. Confirmation of efficacy and safety requires randomized placebo-controlled trials.