Antifungal pipeline: Is there light at the end of the tunnel?

The misuse and overuse of classic antifungals have accelerated the development of resistance mechanisms, diminishing the efficacy of established therapeutic pathways and necessitating a shift towards alternative targets. Despite this pressing need for new treatments, the antifungal drug pipeline has been largely stagnant for the past three decades, primarily due to the high risks and costs associated with antifungal drug development, compounded by uncertain market returns. Extensive research durations, special patient populations and rigorous regulatory demands pose significant barriers to bringing novel antifungal agents to market. In response, the "push-pull" incentive model has emerged as a vital strategy to invigorate the pipeline and encourage innovation. This editorial critically examines the current clinical landscape and spotlights emerging antifungal agents, such as Fosmanogepix, Ibrexafungerp, and Olorofim, while also unraveling the multifaceted challenges faced in new antifungal drug development. The generation of novel antifungals offers a beacon of hope in the battle against antimicrobial resistance, but it is premature to declare them as definitive solutions. Their future role hinges on thorough clinical validation, cost-effectiveness assessments, and continuous post-marketing surveillance. Only through strategic implementation and integration with market strategies we can transform the landscape of antifungal development, addressing both the resistance crisis and the treatment challenges.

Bone Disease in HIV: Need for Early Diagnosis and Prevention.

The transformation of HIV into a manageable chronic condition has unveiled new clinical challenges associated with aging-related pathologies, including bone disease. This review explores the intricate relationship between HIV, antiretroviral therapy (ART), and bone disease, highlighting the necessity of early diagnosis and preventative strategies to mitigate the increased risk of osteopenia, osteoporosis, and fractures in people living with HIV (PLWHIV). It synthesizes the current literature to elucidate the multifactorial etiology of bone pathology in this population, that includes direct viral effects, chronic immune activation, ART-associated risks, and the impact of traditional risk factors for bone loss. Through a critical examination of modern diagnostic methods, lifestyle modifications, evidence-based preventive actions, and pharmacological treatments, the necessity for comprehensive management is highlighted, along with recommendations for integrated healthcare approaches vital for achieving optimal patient outcomes. By advocating for a proactive, patient-centered, and multidisciplinary strategy, this review proposes a plan to integrate bone health into standard HIV care through active risk identification, vigilant screening, effective preventive measures, tailored treatments, and informed decision-making, in an effort to ultimately enhance the quality of life for PLWHIV.

Amphotericin B in the Era of New Antifungals: Where Will It Stand?

Amphotericin B (AmB) has long stood as a cornerstone in the treatment of invasive fungal infections (IFIs), especially among immunocompromised patients. However, the landscape of antifungal therapy is evolving. New antifungal agents, boasting novel mechanisms of action and better safety profiles, are entering the scene, presenting alternatives to AmB's traditional dominance. This shift, prompted by an increase in the incidence of IFIs, the growing demographic of immunocompromised individuals, and changing patterns of fungal resistance, underscores the continuous need for effective treatments. Despite these challenges, AmB's broad efficacy and low resistance rates maintain its essential status in antifungal therapy. Innovations in AmB formulations, such as lipid complexes and liposomal delivery systems, have significantly mitigated its notorious nephrotoxicity and infusion-related reactions, thereby enhancing its clinical utility. Moreover, AmB's efficacy in treating severe and rare fungal infections and its pivotal role as prophylaxis in high-risk settings highlight its value and ongoing relevance. This review examines AmB's standing amidst the ever-changing antifungal landscape, focusing on its enduring significance in current clinical practice and exploring its potential future therapeutic adaptations.

Acalculous Cholecystitis as a Complication of Primary Epstein-Barr Virus Infection: A Case-Based Scoping Review of the Literature.

Primary Epstein-Barr virus (EBV) infection manifests with diverse clinical symptoms, occasionally resulting in severe complications. This scoping review investigates the rare occurrence of acute acalculous cholecystitis (AAC) in the context of primary EBV infection, with a focus on understanding its prevalence, clinical features, and underlying mechanisms. The study also explores EBV infection association with Gilbert syndrome, a condition that potentially exacerbates the clinical picture. Additionally, a case report of an 18-year-old female presenting with AAC and ascites secondary to EBV infection enhances the review. A comprehensive literature review was conducted, analyzing reported cases of AAC secondary to EBV infection. This involved examining patient demographics, clinical presentations, laboratory findings, and outcomes. The search yielded 44 cases, predominantly affecting young females. Common clinical features included fever, cervical lymphadenopathy, tonsillitis/pharyngitis, and splenomegaly. Laboratory findings highlighted significant hepatic involvement. The review also noted a potential link between AAC in EBV infection and Gilbert syndrome, particularly in cases with abnormal bilirubin levels. AAC is a rare but significant complication of primary EBV infection, primarily observed in young females, and may be associated with Gilbert syndrome. This comprehensive review underscores the need for heightened clinical awareness and timely diagnosis to manage this complication effectively.

Clarithromycin for early anti-inflammatory responses in community-acquired pneumonia in Greece (ACCESS): a randomised, double-blind, placebo-controlled trial.

BACKGROUND: Addition of macrolide antibiotics to ß-lactam antibiotics for the treatment of patients in hospital with community-acquired pneumonia is based on results from observational studies and meta-analyses rather than randomised clinical trials. We investigated if addition of the macrolide clarithromycin to treatment with a ß-lactam antibiotic in this population could improve early clinical response-the new regulatory endpoint for community-acquired pneumonia-and explored the possible contribution of modulation of the inflammatory host response to that outcome. METHODS: The ACCESS trial was a phase 3 prospective, double-blind, randomised controlled trial, in which adults in hospital with community-acquired pneumonia who had systemic inflammatory response syndrome, Sequential Organ Failure Assessment (SOFA) score of 2 or more, and procalcitonin 0·25 ng/mL or more were enrolled in 18 internal medicine departments of public Greek hospitals. Patients were randomly assigned (1:1) by computer-generated block randomisation to standard of care medication (including intravenous administration of a third-generation cephalosporin or intravenous administration of ß-lactam plus ß-lactamase inhibitor combination) plus either oral placebo or oral clarithromycin 500 mg twice daily for 7 days. Investigators, staff, and patients were masked to group allocation. The primary composite endpoint required that patients fulfilled both of the following conditions after 72 hours (ie, day 4 of treatment): (1) decrease in respiratory symptom severity score of 50% or more as an indicator of early clinical response and (2) decrease in SOFA score of at least 30% or favourable procalcitonin kinetics (defined as ≥80% decrease from baseline or procalcitonin <0·25 ng/mL), or both, as an indicator of early inflammatory response. Participants who were randomly assigned and received allocated treatment were included in the primary analysis population. This trial is complete and is registered with the EU Clinical Trials Register (2020-004452-15) and ClinicalTrials.gov (NCT04724044). FINDINGS: Patients were enrolled between Jan 25, 2021, and April 11, 2023, and 278 individuals were randomly allocated to receive standard of care in combination with either clarithromycin (n=139) or placebo (n=139). 134 patients in the clarithromycin group (five withdrew consent) and 133 patients in the placebo group (six withdrew consent) were included in the analysis of the primary endpoint. The primary endpoint was met in 91 (68%) patients in the clarithromycin group and 51 (38%) patients in the placebo group (difference 29·6% [95% CI 17·7-40·3]; odds ratio [OR] 3·40 [95% CI 2·06-5·63]; p<0·0001). Serious treatment-emergent adverse events (TEAEs) occurred in 58 (43%) patients in the clarithromycin group and 70 (53%) patients in the placebo group (difference 9·4% [95% CI -2·6 to 20·9]; OR 0·67 [95% CI 0·42 to 1·11]; p=0·14). None of the serious TEAEs was judged to be related to treatment assignment. INTERPRETATION: Addition of clarithromycin to standard of care enhances early clinical response and attenuates the inflammatory burden of community-acquired pneumonia. The mechanism of benefit is associated with changes in the immune response. These findings suggest the importance of adding clarithromycin to ß-lactams for treatment of patients in hospital with community-acquired pneumonia to achieve early clinical response and early decrease of the inflammatory burden. FUNDING: Hellenic Institute for the Study of Sepsis and Abbott Products Operations.

Antimicrobial resistance rates of urogenital Mycoplasma hominis and Ureaplasma species before and during the COVID-19 pandemic: results from a Greek survey, 2014 to 2022.

The prevalence of antibiotic-resistant urogenital mycoplasmas and ureaplasmas has been gradually increasing over the years, leading to greater concern for accurate diagnosis and treatment. In this study, the antimicrobial resistance trends in Greece were analyzed using 2992 Ureaplasma spp. and 371 M. hominis isolates collected between 2014 and 2022. Antibiotic sensitivity was determined using eight different antimicrobial agents (josamycin, pristinamycin, clindamycin, ofloxacin, azithromycin, tetracycline, erythromycin, and doxycycline), with the data analyzed using descriptive statistical methods. Resistance rates to clindamycin and erythromycin increased for both M. hominis and Ureaplasma spp., while remaining relatively low for Tetracycline, Doxycycline, and Ofloxacin. For Ureaplasma spp., high susceptibility was observed to pristinamycin, tetracycline, doxycycline, azithromycin, and josamycin, and intermediate susceptibility to erythromycin. However, the resistance rate for clindamycin dramatically increased from 60% in 2014 to a peak of 98.46% in 2021, and the erythromycin resistance rate increased from 9.54% in 2018 to 22.13% in 2021. M. hominis exhibited consistently high resistance rates to Erythromycin, while Azithromycin resistance significantly increased over time, from 52.78% in 2017 to 97.22% in 2022. The alarming escalation in antibiotic-resistant urogenital mycoplasmas and ureaplasmas in the Greek population is a significant concern. Antibiotic overconsumption may have played a crucial role in increasing resistance trends. The implementation of nationwide surveillance systems, proper antibiotic stewardship policies, and appropriate culture-based therapy policies are necessary to effectively control this emerging risk.

Developing a Tool for Differentiation Between Bacterial and Viral Respiratory Infections Using Myxovirus Resistance Protein A and C-Reactive Protein.

INTRODUCTION: The aim was to assess the performance of a blood assay combining measurements of MxA (myxovirus resistance protein A) and CRP (C-reactive protein) to differentiate viral from bacterial respiratory infections. METHODS: In a prospective study, MxA and CRP were measured in the blood by the AFIAS panel in adults admitted with respiratory infection. Patients were split into discovery and validation cohorts. Final diagnosis was adjudicated by a panel of experts. Microbiology-confirmed cases comprised the discovery cohort, and infections adjudicated as highly probable viral or bacterial comprised the validation cohort. RESULTS: A total of 537 patients were analyzed: 136 patients were adjudicated with definitive viral infections and 131 patients with definitive bacterial infections. Using logistic regression analysis, an equation was developed to calculate the probability for bacterial infection using the absolute value of MxA and CRP. Calculated probability ≥ 0.5 and/or MxA to CRP ratio less than 2 applied as the diagnostic rule for bacterial infections. This rule provided 91.6% sensitivity and 90.4% negative predictive value for the diagnosis of bacterial infections. This diagnostic sensitivity was confirmed in the validation cohort. A MxA/CRP ratio less than 0.15 was associated with unfavorable outcome. CONCLUSION: The calculation of the probability for bacterial infection using MxA and CRP may efficiently discriminate between viral and bacterial respiratory infections.

Impact of Atmospheric Conditions on Epistaxis Incidence.

PURPOSE: A possible correlation between epistaxis occurrence and atmospheric parameters' variation has long been hypothesized. This study aims to determine whether cumulative epistaxis incidence is related to seasonal variation and its relationship to monthly, weekly, and daily recordings of atmospheric measurements in the city of Patras, Greece. METHODS: In this retrospective study, data concerning the patients who presented with active epistaxis at the ED of a tertiary university hospital in Western Greece between January 2020 and December 2021 were collected. Only cases of spontaneous epistaxis were included in the study; patients bleeding secondarily due to a known mechanical cause, i.e., a tumor, trauma, or surgery, were excluded. The measurements of atmospheric parameters were supplied by the Department of Physics, University of Patras. RESULTS: In total, 230 cases of spontaneous, active epistaxis were evaluated in the ED over the course of the study. The median frequency of epistaxis presentations was two cases per week. Most of the patients were male, comprising 62.6% of the cohort, and the median age stood at 70 years, with an interquartile range (IQR) of 54 to 81 years. A minor yet statistically significant negative correlation between the incidence of epistaxis and mean relative humidity was observed both on a daily and weekly basis. Mean relative humidity emerged as a significant predictor for the incidence of epistaxis, both daily and weekly. Significantly lower mean relative humidity values were recorded during weeks with a high incidence of epistaxis cases (57.72% vs. 63.39%, p = 0.02). No discernible seasonality was observed in the frequency of epistaxis presentations to the ED. CONCLUSION: A modest yet statistically significant trend toward fewer epistaxis cases was observed in conditions of higher ambient humidity during the study period in the region of Western Greece.

COVID-19 Pharmacotherapy: A Summary of Key Advances and Insights from the Special Issue.

The COVID-19 pandemic has presented unprecedented challenges for healthcare systems worldwide [...].

Increased Levels of Galectin-3 in Critical COVID-19.

Severe COVID-19 is related to hyperinflammation and multiple organ injury, including respiratory failure, thus requiring intensive care unit (ICU) admission. Galectin-3, a carbohydrate-binding protein exhibiting pleiotropic effects, has been previously recognized to participate in inflammation, the immune response to infections and fibrosis. The aim of this study was to evaluate the relationship between galectin-3 and the clinical severity of COVID-19, as well as assess the prognostic accuracy of galectin-3 for the probability of ICU mortality. The study included 235 COVID-19 patients with active disease, treated in two different Greek hospitals in total. Our results showed that median galectin-3 serum levels on admission were significantly increased in critical COVID-19 patients (7.2 ng/mL), as compared to the median levels of patients with less severe disease (2.9 ng/mL, p = 0.003). Galectin-3 levels of the non-survivors hospitalized in the ICU were significantly higher than those of the survivors (median 9.1 ng/mL versus 5.8 ng/mL, p = 0.001). The prognostic accuracy of galectin-3 for the probability of ICU mortality was studied with a receiver operating characteristic (ROC) curve and a multivariate analysis further demonstrated that galectin-3 concentration at hospital admission could be assumed as an independent risk factor associated with ICU mortality. Our results were validated with galectin-3 measurements in a second patient cohort from a different Greek university hospital. Our results, apart from strongly confirming and advancing previous knowledge with two patient cohorts, explore the possibility of predicting ICU mortality, which could provide useful information to clinicians. Therefore, galectin-3 seems to establish its involvement in the prognosis of hospitalized COVID-19 patients, suggesting that it could serve as a promising biomarker in critical COVID-19.

Investigating the Role of Anti-TPO Antibodies in HIV-Associated Thrombocytopenia before and after Initiation of HAART: A Case-Control Longitudinal Study.

This longitudinal, case-control study aimed to investigate the role of thrombopoietin (TPO) and anti-TPO antibodies in HIV-associated thrombocytopenia, focusing on the changes seen before and after the initiation of highly active antiretroviral therapy (HAART). Patients were assessed before and at least six months after the initiation of HAART. In total, 75 PLWHIV (age/sex-matched and randomized at 2:1, according to thrombocytopenia status) were included in this study. The baseline assessment revealed significantly higher TPO levels in thrombocytopenic patients (140.45 vs. 106.8 mg/mL, p = 0.008). Furthermore, anti-TPO-positive patients displayed lower platelet counts (109,000 vs. 139,000/L, p = 0.002) and TPO levels (114.7 vs. 142.7 mg/mL, p = 0.047). Longitudinally, HAART initiation reduced the frequency of thrombocytopenia from 75.47% to 33.96% (p < 0.001) and elevated the median platelet counts from 131,000 to 199,000 (p < 0.001). No significant difference in median platelet counts was found post-HAART among the anti-TPO subgroups (p = 0.338), a result contrasting with pre-HAART findings (p = 0.043). Changes in anti-TPO status corresponded with significant platelet count alterations (p = 0.036). Notably, patients who became anti-TPO negative showed a median increase of 95,000 platelets (IQR: 43,750-199,500). These marked differences between subgroups underscore the potential role of anti-TPO antibodies in modulating the hematological response to HAART. Further research is needed to elucidate the complex interplay between HIV infection, HAART, and thrombocytopenia.

Epidemiology and Resistance Phenotypes of Carbapenem-Resistant Klebsiella pneumoniae in Corfu General Hospital (2019-2022): A Comprehensive Time Series Analysis of Resistance Gene Dynamics.

Antimicrobial resistance is a significant global health challenge, with Klebsiella pneumoniae being one of the most common antibiotic-resistant pathogens. This study provides an in-depth analysis of the prevalence and resistance patterns of antibiotic-resistant Klebsiella pneumoniae in the General Hospital of Corfu, Greece, between 2019 and 2022, with the aim of understanding the potential impact of the COVID-19 pandemic on the epidemiology of this bacterium. Utilizing a retrospective epidemiological approach, this study analyzed 212 isolates obtained from the hospital's Microbiology Department. These isolates were subjected to genotypic and phenotypic identification, with resistance genes (bla-KPC, bla-NDM, bla-VIM, bla-OXA-48, and mcr-1) and antibiotic resistance patterns as the primary focus. The results revealed a significant shift in resistance gene prevalence, with a notable increase in bla-KPC from 16.67% in 2021 to 58.46% in 2022, and a decrease in bla-NDM from 81.48% in 2021 to 38.46% in 2022. In terms of antibiotic resistance patterns, there was a consistent increase in resistance to amikacin and a significant decrease in resistance to ceftazidime/avibactam. These findings underscore the dynamic nature of carbapenem-resistant Klebsiella pneumoniae (CRKP) resistance and highlight the need for ongoing surveillance and adaptive therapeutic strategies in the face of evolving resistance patterns.

Understanding and Implementing Diagnostic Stewardship: A Guide for Resident Physicians in the Era of Antimicrobial Resistance.

Antimicrobial resistance (AMR) poses a significant global health challenge, exacerbated by the COVID-19 pandemic. Antimicrobial stewardship programs (ASPs) are crucial in managing this crisis, with diagnostic stewardship (DS) emerging as a key component. DS refers to the appropriate use of diagnostic tests to optimize patient outcomes, improve antimicrobial use, and combat multi-drug-resistant (MDR) organisms. Despite its potential, understanding and application of DS remain ambiguous in multiple respects, which, however, do not directly implicate the implementation of such initiatives. DS is particularly important for resident physicians who are often at the forefront of patient care and can significantly influence future AMR strategies. This review provides a comprehensive overview of DS, discussing its importance, potential challenges, and future directions. It emphasizes the need for resident physicians to understand DS principles and integrate them into their clinical practice from the beginning of their careers. The review also highlights the role of various stakeholders in implementing DS and the importance of continuous education and training. Ultimately, DS is not just a clinical tool but a philosophy of care, essential for a more responsive, humane, and effective healthcare system.

Patterns, Cost, and Immunological Response of MDR vs. Non MDR-Bacteremia: A Prospective Cohort Study.

BACKGROUND: Antimicrobial resistance (AMR) is a significant global health concern, posing a critical challenge for the effective management of infectious diseases. This study aimed to compare the immunological response, clinical outcomes, and associated costs in patients with bacteremia due to antibiotic-resistant vs. susceptible bacterial microorganisms. METHODS: This study was a single-center, prospective cohort study conducted from May 2017 to November 2019. The study population consisted of patients admitted with a confirmed diagnosis of bacteremia. RESULTS: A total of 116 patients were included, with 53 (45.7%) harboring non-multidrug-resistant (non-MDR) bacterial isolates and 63 (54.3%) harboring multidrug-resistant (MDR) bacterial isolates. Patients with MDR bacteremia had more severe clinical presentations, as indicated by higher SOFA and APACHE II scores. Results revealed higher all-cause mortality rates (39.7% vs. 17%) and median healthcare costs (€4791 vs. €2843.5) in the MDR bacteremia group. Moreover, MDR bacteremia was linked to higher levels of TNF-a, indicating a differential immune response. Furthermore, MDR bacteremia was found to be an independent predictor of mortality (OR = 3.216, 95% CI: 1.338-7.730, p = 0.009) and increased healthcare costs (effect size of approximately 27.4%). CONCLUSION: These findings underscore the significant impact of antimicrobial resistance in healthcare settings, highlighting the urgency of addressing the challenges posed by MDR microorganisms.

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.

Early Fluvoxamine Reduces the Risk for Clinical Deterioration in Symptomatic Outpatients with COVID-19: A Real-World, Retrospective, before-after Analysis.

Fluvoxamine, a selective serotonin reuptake inhibitor with anti-inflammatory properties, has gained attention as a repurposed drug to treat COVID-19. We aimed to explore the potential benefit of fluvoxamine on outpatients with early SARS-CoV-2 infection. We performed a retrospective study of fluvoxamine adult outpatients with symptomatic COVID-19 disease of early onset (<5 days), in the context of an infectious diseases private practice, between September-December 2021, in Greece. Patients with disease duration ≥5 days, dyspnea and/or hypoxemia with oxygen saturation <94% in room air and pregnancy were excluded from the analysis. In total, 103 patients, 54 males/49 females with a median age of 47 years (39-56), were included in this study. Patient characteristics were balanced before and after the introduction of fluvoxamine. Two patients in the fluvoxamine arm (3.8%; 95% CI 0.4-13) had clinical deterioration compared to 8 patients in the standard of care group (16%; 95% CI 7.2-29.1, p < 0.04). After controlling for age, sex, body mass index > 30 and vaccination status, fluvoxamine was independently associated with a lower risk of clinical deterioration (adj. OR 0.12; 95% CI 0.02-0.70, p < 0.02). Adding on fluvoxamine to treatment for early symptomatic COVID-19 patients may protect them from clinical deterioration and hospitalization, and it is an appealing low-cost, low-toxicity option in the community setting and warrants further investigation.

Preventing Multidrug-Resistant Bacterial Transmission in the Intensive Care Unit with a Comprehensive Approach: A Policymaking Manual.

Patients referred to intensive care units (ICU) commonly contract infections caused by multidrug-resistant (MDR) bacteria, which are typically linked to complications and high mortality. There are numerous independent factors that are associated with the transmission of these pathogens in the ICU. Preventive multilevel measures that target these factors are of great importance in order to break the chain of transmission. In this review, we aim to provide essential guidance for the development of robust prevention strategies, ultimately ensuring the safety and well-being of patients and healthcare workers in the ICU. We discuss the role of ICU personnel in cross-contamination, existing preventative measures, novel technologies, and strategies employed, along with antimicrobial surveillance and stewardship (AMSS) programs, to construct effective and thoroughly described policy recommendations. By adopting a multifaceted approach that combines targeted interventions with broader preventive strategies, healthcare facilities can create a more coherent line of defense against the spread of MDR pathogens. These recommendations are evidence-based, practical, and aligned with the needs and realities of the ICU setting. In conclusion, this comprehensive review offers a blueprint for mitigating the risk of MDR bacterial transmission in the ICU, advocating for an evidence-based, multifaceted approach.

Radiologic Features of T10 Paravertebral Muscle Sarcopenia: Prognostic Factors in COVID-19.

Background: Sarcopenia, defined as a small cross-sectional area (CSA) in computed tomography (CT) measurements of skeletal muscles, serves as a disease severity marker in various clinical scenarios, including pulmonary conditions and critical illness. Another parameter of sarcopenia, the level of myosteatosis, reflected by the tissue's radiodensity, in the thoracic skeletal muscles group, has been linked to disease progression in coronavirus disease 2019 (COVID-19) patients. We hypothesize that CT-derived measurements of the skeletal muscle density (SMD) and the CSA of thoracic skeletal muscles can predict outcomes in COVID-19 pneumonia. Methods: We retrospectively reviewed the CT scans of 84 patients with COVID-19 pneumonia admitted to two of Greece's largest academic teaching hospitals between April 2020 and February 2021. CSA and SMD at the level of the T10 vertebra were measured using computational imaging methods. The patient population was stratified according to survival status and CT severity score (CT-SS). Correlations were drawn between the radiologic features of sarcopenia, CT severity subgroups, serum inflammatory markers, and adverse events, e.g., death and intubation. Results: Thoracic muscles' CSA measurements correlate with CT-SS and prominent inflammatory markers, such as white blood cell (WBC), C-reactive protein (CRP), fibrinogen, and D-dimers. Moreover, according to linear regression analysis, CSA seems to predict CT-SS variation significantly (ß = -0.266, P = 0.018). CSA proved to differ significantly across survivors (P = 0.027) but not between CT severity categories and intubation subgroups. The AUC (area under the curve) of the receiver operating characteristic (ROC) curve for the predictive value of thoracic muscles' CSA in mortality is 0.774 (95% confidence interval (CI): 0.66 - 0.83, P < 0.000). The optimal cut-off value (Youden index = 0.57) for mortality prognosis, with a sensitivity of 66.7% and a specificity of 88.9%, is 15.55. Thoracic muscles' SMD analyses did not reveal any significant correlations. Conclusions: Easy to obtain and accurately calculated, radiologic features can provide a reliable alternative to laboratory methods for predicting survival in COVID-19. Thoracic muscles' CSA measurement in the level of the T10 vertebra, an acclaimed prognostic imaging assessment that relates directly to CT-SS and inflammatory markers in COVID-19 pneumonia, is a fairly specific tool for survival prognosis.

COVID-19 Outcomes and Diabetes Mellitus: A Comprehensive Multicenter Prospective Cohort Study.

The link between type 2 diabetes (T2D) and the severe outcomes of COVID-19 has raised concerns about the optimal management of patients with T2D. This study aimed to investigate the clinical characteristics and outcomes of T2D patients hospitalized with COVID-19 and explore the potential associations between chronic T2D treatments and adverse outcomes. This was a multicenter prospective cohort study of T2D patients hospitalized with COVID-19 in Greece during the third wave of the pandemic (February-June 2021). Among the 354 T2D patients included in this study, 63 (18.6%) died during hospitalization, and 16.4% required ICU admission. The use of DPP4 inhibitors for the chronic management of T2D was associated with an increased risk of in-hospital death (adjusted odds ratio (adj. OR) 2.639, 95% confidence interval (CI) 1.148-6.068, p = 0.022), ICU admission (adj. OR = 2.524, 95% CI: 1.217-5.232, p = 0.013), and progression to ARDS (adj. OR = 2.507, 95% CI: 1.278-4.916, p = 0.007). Furthermore, the use of DPP4 inhibitors was significantly associated with an increased risk of thromboembolic events (adjusted OR of 2.249, 95% CI: 1.073-4.713, p = 0.032) during hospitalization. These findings highlight the importance of considering the potential impact of chronic T2D treatment regiments on COVID-19 and the need for further studies to elucidate the underlying mechanisms.

High-Dose Nebulized Colistin Methanesulfonate and the Role in Hospital-Acquired Pneumonia Caused by Gram-Negative Bacteria with Difficult-to-Treat Resistance: A Review.

Hospital-acquired pneumonia, including ventilator-associated pneumonia (VAP) due to difficult-to-treat-resistant (DTR) Gram-negative bacteria, contributes significantly to morbidity and mortality in ICUs. In the era of COVID-19, the incidences of secondary nosocomial pneumonia and the demand for invasive mechanical ventilation have increased dramatically with extremely high attributable mortality. Treatment options for DTR pathogens are limited. Therefore, an increased interest in high-dose nebulized colistin methanesulfonate (CMS), defined as a nebulized dose above 6 million IU (MIU), has come into sight. Herein, the authors present the available modern knowledge regarding high-dose nebulized CMS and current information on pharmacokinetics, clinical studies, and toxicity issues. A brief report on types of nebulizers is also analyzed. High-dose nebulized CMS was administrated as an adjunctive and substitutive strategy. High-dose nebulized CMS up to 15 MIU was attributed with a clinical outcome of 63%. High-dose nebulized CMS administration offers advantages in terms of efficacy against DTR Gram-negative bacteria, a favorable safety profile, and improved pharmacokinetics in the treatment of VAP. However, due to the heterogeneity of studies and small sample population, the apparent benefit in clinical outcomes must be proven in large-scale trials to lead to the optimal use of high-dose nebulized CMS.