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.

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.

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.

Targeting CMV Reactivation to Optimize Care for Critically Ill COVID-19 Patients: A Review on the Therapeutic Potential of Antiviral Treatment.

Cytomegalovirus (CMV) reactivation has been linked to adverse clinical outcomes in critically ill patients, with emerging evidence suggesting a potential connection with severe COVID-19. Mechanisms driving this association may include primary lung injury, amplification of systemic inflammation, and secondary immunosuppression. Diagnostic challenges in detecting and assessing CMV reactivation necessitate a comprehensive approach to improve accuracy and inform treatment decisions. Currently, there is limited evidence on the efficacy and safety of CMV pharmacotherapy in critically ill COVID-19 patients. Although insights from non-COVID-19 critical illness studies suggest a potential role for antiviral treatment or prophylaxis, the risks and benefits must be carefully balanced in this vulnerable patient population. Understanding the pathophysiological role of CMV in the context of COVID-19 and exploring the advantages of antiviral treatment are crucial for optimizing care in critically ill patients. This review provides a comprehensive synthesis of available evidence, emphasizing the need for additional investigation to establish the role of CMV treatment or prophylaxis in the management of severe COVID-19 and to develop a framework for future research on this topic.

Remdesivir Use in the Real-World Setting: An Overview of Available Evidence.

In the years of Coronavirus Disease 2019 (COVID-19), various treatment options have been utilized. COVID-19 continues to circulate in the global population, and the evolution of the Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus has posed significant challenges to the treatment and prevention of infection. Remdesivir (RDV), an anti-viral agent with in vitro efficacy against coronaviruses, is a potent and safe treatment as suggested by a plethora of in vitro and in vivo studies and clinical trials. Emerging real-world data have confirmed its effectiveness, and there are currently datasets evaluating its efficacy and safety against SARS-CoV-2 infections in various clinical scenarios, including some that are not in the SmPC recommendations according for COVID-19 pharmacotherapy. Remdesivir increases the chance of recovery, reduces progression to severe disease, lowers mortality rates, and exhibits beneficial post-hospitalization outcomes, especially when used early in the course of the disease. Strong evidence suggests the expansion of remdesivir use in special populations (e.g., pregnancy, immunosuppression, renal impairment, transplantation, elderly and co-medicated patients) where the benefits of treatment outweigh the risk of adverse effects. In this article, we attempt to overview the available real-world data of remdesivir pharmacotherapy. With the unpredictable course of COVID-19, we need to utilize all available knowledge to bridge the gap between clinical research and clinical practice and be sufficiently prepared for the future.

Immune-mediated liver injury following COVID-19 vaccination.

Liver injury secondary to vaccination is a rare adverse event that has recently come under attention thanks to the continuous pharmacovigilance following the widespread implementation of coronavirus disease 2019 (COVID-19) vaccination protocols. All three most widely distributed severe acute respiratory syndrome coronavirus 2 vaccine formulations, e.g., BNT162b2, mRNA-1273, and ChAdOx1-S, can induce liver injury that may involve immune-mediated pathways and result in autoimmune hepatitis-like presentation that may require therapeutic intervention in the form of corticosteroid administration. Various mechanisms have been proposed in an attempt to highlight immune checkpoint inhibition and thus establish causality with vaccination. The autoimmune features of such a reaction also prompt an in-depth investigation of the newly employed vaccine technologies. Novel vaccine delivery platforms, e.g., mRNA-containing lipid nanoparticles and adenoviral vectors, contribute to the inflammatory background that leads to an exaggerated immune response, while patterns of molecular mimicry between the spike (S) protein and prominent liver antigens may account for the autoimmune presentation. Immune mediators triggered by vaccination or vaccine ingredients per se, including autoreactive antibodies, cytokines, and cytotoxic T-cell populations, may inflict hepatocellular damage through well-established pathways. We aim to review available data associated with immune-mediated liver injury associated with COVID-19 vaccination and elucidate potential mechanisms underlying its pathogenesis.

COVID-19 Pharmacotherapy in Pregnancy: A Literature Review of Current Therapeutic Choices.

The clinical management of COVID-19 in pregnant women, who are considered a vulnerable population, remains uncertain even as the pandemic subsides. SARS-CoV-2 affects pregnant individuals in multiple ways and has been associated with severe maternal morbidity and mortality, as well as neonatal complications. The unique anatomy and physiology of gestation make managing COVID-19 in this population a complex and challenging task, emphasizing the importance of spreading knowledge and expertise in this area. Therapeutic interventions require distinct clinical consideration, taking into account differences in pharmacokinetics, vertical transmission, drug toxicities, and postnatal care. Currently, there is limited data on antiviral and immunomodulating COVID-19 pharmacotherapy in pregnancy. Some medication has been shown to be safe and well tolerated among pregnant women with COVID-19; however, the lack of randomized clinical trials and studies in this patient population is evident. Available vaccines are considered safe and effective, with no evidence of harm to the fetus, embryo development, or short-term postnatal development. Pregnant women should be counseled about the risks of SARS-CoV-2 infection and informed of available ways to protect themselves and their families. Effective treatments for COVID-19 should not be withheld from pregnant individuals, and more research is needed to ensure the best outcomes.

COVID-19 Vaccination in Patients with Chronic Liver Disease.

Vaccination against SARS-CoV-2 has become a central public health issue, primarily for vulnerable populations such as individuals with Chronic Liver Disease (CLD). Increased COVID-19-related mortality and disease severity has been noted in this subgroup of patients. Severe COVID-19 tends to further deregulate liver function in patients with chronic liver failure or cirrhosis and even reactivate hepatitis in people living with HBV or HCV. In addition, impaired hepatic function leads to several limitations in possible therapeutic interventions. Chronic hepatic dysregulation, along with the underlying cirrhosis-associated immune dysfunction (CAID), leads to a decreased immune response to vaccination that, in turn, may result in reduced efficacy rates and lowered lasting protection. According to current guidelines, timely vaccination and frequent booster shot administration are deemed necessary in this context. Vaccination-related adverse events are mostly mild in nature and similar to those reported in the general population, whereas the incidence of liver injury following vaccination is relatively rare. We aimed to review available evidence and recommendations associated with COVID-19 vaccination in patients with chronic liver disease, and provide insight to current issues and future directions.