Search Results (118)

Hyaloserositis, also known as the icing sugar phenomenon, may be commonly observed during autopsies; however, it is not a well-documented topic with varying nomenclature and etiology, which can be generally defined as an organ being covered with a shiny, fibrous hyaline membrane. In our work, we present the case of a 71-year-old female patient with alcohol-induced liver cirrhosis and subsequent ascites and recurrent peritonitis. During the autopsy, a cirrhotic liver and an enlarged spleen were observed, both exhibiting features consistent with hyaloserositis, accompanied by acute fibrinopurulent peritonitis. Histological examination revealed the classical manifestation of hyaloserositis, further proven by Crossmon staining. The cause of death was concluded as hepatic encephalopathy. During our literature review, a total of seven cases were found. It must be emphasized that no publication describing hyaloserositis from the perspective of a pathologist was discovered. Regarding etiology, abdominal presentations were most commonly caused by serohepatic tuberculosis, while pleural manifestation was observed following trauma. Hyaloserositis may prove to be a diagnostic difficulty in imaging findings, as it can mimic malignancy; therefore, a scientific synthesis is necessary. Full article

Background and Objectives: Blood-borne inflammatory ratios have been proposed as inexpensive prognostic tools across a range of diseases, but their role in pulmonary tuberculosis (TB) remains uncertain. In this retrospective case–control analysis, we explored whether composite indices derived from routine haematology—namely the neutrophil-to-lymphocyte ratio (NLR), the platelet-to-lymphocyte ratio (PLR), the systemic immune–inflammation index (SII) and a novel CRP–Fibrinogen Index (CFI)—could enhance risk stratification beyond established cytokine measurements among Romanian adults with culture-confirmed pulmonary T. Materials and Methods: Data were drawn from 80 consecutive TB in-patients and 50 community controls. Full blood counts, C-reactive protein, fibrinogen, and four multiplex cytokines were extracted from electronic records, and composite indices were calculated according to standard formulas. The primary outcomes were in-hospital mortality within 90 days and length of stay (LOS). Results: Among TB patients, the median NLR was 3.70 (IQR 2.54–6.14), PLR was 200 (140–277) and SII was 1.36 × 10⁶ µL⁻¹ (0.74–2.34 × 10⁶), compared with 1.8 (1.4–2.3), 117 (95–140) and 0.46 × 10⁶ µL⁻¹ (0.30–0.60 × 10⁶) in controls. Those with SII above the cohort median exhibited more pronounced acute-phase responses (median CRP 96 vs. 12 mg L⁻¹; fibrinogen 578 vs. 458 mg dL⁻¹), yet median LOS remained virtually identical (29 vs. 28 days) and early mortality was low in both groups (8% vs. 2%). The CFI showed no clear gradient in hospital stay across its quartiles, and composite ratios—while tightly inter-correlated—demonstrated only minimal association with cytokine levels and LOS. Conclusions: Composite cell-count indices were markedly elevated but did not predict early death or prolonged admission. In low-event European cohorts, their chief value may lie in serving as cost-free gatekeepers, flagging those who should proceed to more advanced cytokine or genomic testing. Although routine reporting of NLR and SII may support low-cost surveillance, validation in larger, multicentre cohorts with serial sampling is needed before these indices can be integrated into clinical decision-making. Full article

Background: Acute respiratory distress syndrome (ARDS) secondary to tuberculosis (TB) is rare and associated with high mortality. Management is further complicated by comorbidities and ICU-related complications. Methods: We report a 43-year-old woman with post-polio sequelae and uncontrolled diabetes who developed ARDS due to pulmonary TB, complicated by recurrent nosocomial infections and gastrointestinal bleeding. Early bronchoscopy and GeneXpert MTB/RIF PCR were performed on ICU Day 2, enabling anti-TB therapy initiation by ICU Day 3. The patient received lung-protective ventilation, prone positioning, tailored antibiotics, and multidisciplinary care. Results: The patient’s clinical course was complicated by two episodes of ventilator-associated pneumonia and gastrointestinal bleeding, but with individualized management, she achieved ventilator weaning and functional recovery. Conclusions: Early TB recognition in ARDS is crucial. Multidisciplinary ICU management, including prudent steroid use, improves outcomes. Full article

Background: The MeMed BV^® BV score is a novel, promising host-protein score, differentiating bacterial from viral infections, that combines the expression levels of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), interferon gamma-induced protein-10 (IP-10), and C-reactive protein (CRP). The aim of our study was to determine its diagnostic accuracy in hospitalized febrile children. Methods: A prospective study was performed from December 2023 to April 2024 in two pediatric clinics at “Aghia Sophia” Children’s Hospital, Athens, Greece. Patients > 3 months old, presenting with fever, clinical suspicion of acute infection, and symptoms onset up to 7 days prior were considered eligible. Patients with cancer, Human Immunodeficiency Virus (HIV), Hepatitis B Virus (HBV), Hepatitis C Virus (HCV), Tuberculosis (TB), and immunodeficiency were excluded. Two pediatricians reviewed the clinical, laboratory, microbiological, and radiological data and assigned the final diagnosis. The experts were blinded to the BV scores. Results: One hundred and thirty-five patients were enrolled. The predominant medical condition was respiratory tract infection (59.3% lower, 26.7% upper). Twenty-nine (21.5%) patients were diagnosed with bacterial infections. The BV score demonstrated a sensitivity of 96.2%, specificity of 88.7%, and negative predictive value (NPV) of 98.9% for bacterial infections. Equivocal BV scores were reported in 8.9% of cases and were excluded from calculations. The area under the curve was 0.96 (95% CI: 0.93–0.99). A ROC curve analysis was performed, and the optimal cut-off score was estimated at 60, providing a sensitivity of 93.1%, specificity of 88.7%, and NPV of 97.9%. Conclusions: In our study population, the BV score showed high sensitivity and NPV in bacterial infection diagnosis. Further studies are needed to assess the possibility of replacing the “equivocal” range with a narrower one or a specific cut-off value. Full article

Background/Objectives: Before the Coronavirus disease 2019 (COVID-19) era, the global prevalence of pulmonary arterial hypertension (PAH) was between 0.4 and 1.4 per 100,000 people. The long-term effects of protracted COVID-19 associated with pulmonary vascular disease (PVD) risk factors may increase this prevalence. According to preliminary data, the exact prevalence of early estimates places the prevalence of PVD in patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection at 22%, although its predictive value remains unknown. PVD caused by COVID-19 co-infections is understudied and underreported, and its future impact is unclear. However, due to COVID-19/co-infection pathophysiological effects on pulmonary vascularization, PVD mortality and morbidity may impose a genuine concern—both now and in the near future. Based on reported studies, this literature review focused on the potential link between COVID-19, parasitic co-infection, and PVD. This review article also highlights hypothetical pathophysiological mechanisms between COVID-19 and parasitic co-infection that could trigger PVD. Methods: We conducted a systematic literature review (SLR) searching peer-reviewed articles, including link between COVID-19, parasitic co-infection, and PVD. Results: This review hypothesized that multiple pathways associated with pathogens such as underlying schistosomiasis, human immunodeficiency virus (HIV), pulmonary tuberculosis (PTB), pulmonary aspergillosis, Wuchereria bancrofti, Clonorchis sinensis, paracoccidioidomycosis, human herpesvirus 8, and scrub typhus coupled with acute or long COVID-19, may increase the burden of PVD and worsen its mortality in the future. Conclusions: Further experimental studies are also needed to determine pathophysiological pathways between PVD and a history of COVID-19/co-infections. Full article

Drug-induced liver injury (DILI) is one of the main causes of acute liver failure in children. Its incidence is probably underestimated, as specific diagnostic tools are currently lacking. Over 1000 known drugs cause DILI, and the list is expanding. The aim of this review is to describe DILI pathogenesis and emphasize the drugs accountable for child DILI in order to aid its recognition. Intrinsic DILI is well described in terms of mechanism, incriminated drugs, and toxic dose. Conversely, idiosyncratic DILI (iDILI) is unpredictable, occurring as a result of a particular response to drug administration, and its occurrence cannot be foreseen in clinical studies. Half of pediatric iDILI cases are linked to antibiotics, mostly amoxicillin–clavulanate, in the immune-allergic group, while autoimmune DILI is the hallmark of minocycline and nitrofurantoin. Secondly, antiepileptics are responsible for 20% of pediatric iDILI cases, children being more prone to iDILI caused by these agents than adults. A similar tendency was observed in anti-tuberculosis drugs, higher incidences being reported in children below three years old. Current data show growing cases of iDILI related to antineoplastic agents, atomoxetine, and albendazole, so that it is advisable for clinicians to maintain a high index of suspicion regarding iDILI. Full article

Despite the high prevalence of latent Kaposi’s sarcoma-associated herpesvirus (KSHV) infections in patients from endemic areas with a high human immunodeficiency virus (HIV) prevalence, KSHV lytic reactivation in the context of other co-infections is not well understood. Lytic KSHV infections can contribute to severe inflammatory symptoms and KSHV-associated pathogenesis. We have previously reported on KSHV reactivation upon severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) exposure in a non-hospitalised cohort of people living with HIV (PLWH). From this cohort, we identified a 34-year-old male who presented for routine HIV care in May 2021 with an unusually high KSHV viral load (VL) of 189,946.3 copies/10⁶ cells, before SARS-CoV-2 infection. The patient was invited into a 2-year follow-up study where his peripheral blood was analysed for selected virological, clinical, and inflammatory parameters every 6 months. He remained highly viremic for KSHV throughout the 2-year study period, during which he was infected with SARS-CoV-2 and developed disseminated tuberculosis, with steadily increasing levels of the inflammatory markers C-reactive protein (CRP), and interleukin-6 (IL-6). His HIV VL remained controlled (<1000 copies/mL) and his CD4 count bordered immunosuppression (±200 cells/µL), suggesting some responsiveness to antiretroviral treatment (ART). However, the patient’s uncontrolled lytic KSHV infection may increase his risk for developing a KSHV-associated pathology manifesting with inflammation which should be closely monitored beyond the study period. Full article

Background/Objectives: Tuberculosis (TB) remains a major global health issue, further complicated by the COVID-19 pandemic. This study assesses the clinical outcomes of TB-COVID-19-coinfected patients compared to those with TB disease alone at an Italian infectious disease hospital during the pandemic’s first two years. Methods: Retrospective data analysis was conducted on TB patients hospitalized from March 2020 to June 2022. Data included demographics, comorbidities, clinical characteristics, and outcomes. Coinfection was defined as concurrent TB disease and SARS-CoV-2 infection. Statistical methods included Fisher’s exact test and Mann–Whitney statistics. Results: Of 267 TB patients, 25 (9.4%) had concurrent COVID-19 infection. The TB-COVID-19 group showed higher rates of diabetes and cough. Acute respiratory failure was more prevalent in coinfected patients (odds ratio, 5.99), and coinfection was associated with worse outcomes compared to TB alone (odds ratio, 0.15). Despite similar socio-demographic factors, the coexistence of TB and COVID-19 led to exacerbated respiratory failure and increased mortality. Conclusions: Coinfection with TB and COVID-19 significantly increases the risk of acute respiratory failure and poor outcomes. Clinicians should be aware of this risk, especially in patients with pulmonary involvement. Although specific protocols are unavailable, prompt diagnosis and management may enhance outcomes. Additional research is necessary to understand the long-term effects of TB-COVID-19 coinfection, particularly as COVID-19 becomes endemic. Full article

Background and Objectives: Atlantoaxial tuberculosis (TB) is rare, and its diagnosis is difficult. Herein, we present a rare case with a challenging diagnostic journey of atlantoaxial TB spanning over two years. Materials and Methods: A 70-year-old immunocompetent female patient presented with a four-week history of nuchal pain, stiffness, and headache. She did not have any TB-associated constitutional symptoms. The result of the initial biopsy indicated only a nonfermenting Gram-negative bacillus and the histopathological report revealed concurrent acute and chronic inflammation. Posterior fusion with bilateral C1 lateral mass and C2 transpedicular screw fixation was performed after a five-week course of antibiotics. Results: However, the atlantoaxial abscess progressed and led to myelopathy two years later. Tuberculous spondylitis was not confirmed until the second biopsy. We chose the transoral approach for prompt abscess evacuation and to prevent unnecessary damage to the nearby vital neurovascular structures. The sputum culture and chest radiograph did not reveal concurrent pulmonary TB. Conclusions: Spinal TB has a greater likelihood of presenting with a cold abscess without the typical constitutional symptoms of pulmonary TB. Distinctive magnetic resonance imaging (MRI) features, such as a thin and smooth abscess wall, subligamentous spread, severe vertebral body destruction, and heterogenous vertebral wall enhancement, might help to differentiate between tuberculous and pyogenic spondylitis. We hope to offer meaningful insights to clinicians facing similar intricate scenarios, including subtle clues that may lead to a quicker diagnosis and the considerations we made while designing a treatment plan. Full article

Cardiotonic steroids modulate various aspects of the inflammatory response. The synthetic cardiotonic steroid γ-benzylidene digoxin 15 (BD-15), a digoxin derivative, has emerged as a promising candidate with potential immunomodulatory effects. However, its biological activity remains largely unexplored. This study investigated the anti-mycobacterial and anti-inflammatory effects of BD-15 in an in vitro macrophage infection model with Mycobacterium spp. Unlike digoxin, which showed significant toxicity at higher concentrations, BD-15 exhibited no cytotoxicity in RAW 264.7 cells (a murine macrophage cell line). Both compounds were evaluated in Mycobacterium smegmatis-infected RAW 264.7 cells, reducing bacterial burden without direct bactericidal activity. Additionally, both modulated pro-inflammatory cytokine levels, notably by decreasing tumor necrosis factor alpha (TNF-α) and interleukin-1 beta (IL-1β) levels. BD-15 specifically reduced NOD-, LRR-, and pyrin-domain-containing protein 3 (NLRP3) inflammasome expression and increased interleukin-10 (IL-10) production. Notably, BD-15 reduced colony-forming unit (CFU) counts in Mycobacterium tuberculosis-infected RAW 264.7 cells. Toxicity assays in HepG2 cells (a human liver cancer cell line) showed that BD-15 had minimal hepatotoxicity compared to digoxin, and both demonstrated negligible acute toxicity in an Artemia salina bioassay. These findings revealed the immunomodulatory effects of cardiotonic steroids in a bacterial infection model and highlighted BD-15 as a safer alternative to digoxin for therapeutic applications. Full article

mRNA vaccines represent a milestone in the history of vaccinology, because they are safe, very effective, quick and cost-effective to produce, easy to adapt should the antigen vary, and able to induce humoral and cellular immunity. Methods: To date, only two COVID-19 mRNA and one RSV vaccines have been approved. However, several mRNA vaccines are currently under development for the prevention of human viral (influenza, human immunodeficiency virus [HIV], Epstein–Barr virus, cytomegalovirus, Zika, respiratory syncytial virus, metapneumovirus/parainfluenza 3, Chikungunya, Nipah, rabies, varicella zoster virus, and herpes simplex virus 1 and 2), bacterial (tuberculosis), and parasitic (malaria) diseases. Results: RNA viruses, such as severe acute respiratory syndrome coronavirus (SARS-CoV)-2, HIV, and influenza, are characterized by high variability, thus creating the need to rapidly adapt the vaccines to the circulating viral strain, a task that mRNA vaccines can easily accomplish; however, the speed of variability may be higher than the time needed for a vaccine to be adapted. mRNA vaccines, using lipid nanoparticles as the delivery system, may act as adjuvants, thus powerfully stimulating innate as well as adaptive immunity, both humoral, which is rapidly waning, and cell-mediated, which is highly persistent. Safety profiles were satisfactory, considering that only a slight increase in prognostically favorable anaphylactic reactions in young females and myopericarditis in young males has been observed. Conclusions: The COVID-19 pandemic determined a shift in the use of RNA: after having been used in medicine as micro-RNAs and tumor vaccines, the new era of anti-infectious mRNA vaccines has begun, which is currently in great development, to either improve already available, but unsatisfactory, vaccines or develop protective vaccines against infectious agents for which no preventative tools have been realized yet. Full article

The hospital-at-home (HaH) model delivers hospital-level acute care, including diagnostics, monitoring, and treatments, in a patient’s home. It is particularly effective for managing conditions such as pneumonia. Point-of-care ultrasonography (PoCUS) is a key diagnostic tool in the HaH model, and it often serves as a substitute for imaging-based diagnosis in the HaH setting. Both standard and handheld ultrasound equipment are suitable for lung ultrasound (LUS) evaluation. Curvelinear and linear probes are typically used. Patient positioning depends on their clinical condition and specific diagnostic protocols. To enhance sensitivity, we recommend using at least 10-point protocols supported by studies for pneumonia. Five essential LUS patterns should be identified, including A-line, multiple B-lines (alveolar-interstitial syndrome), confluent B-lines, subpleural consolidation, and consolidation with air bronchogram. Pleural effusion is common, and its internal echogenicity can indicate severity and the need for invasive procedures. The current evidence on various etiologies and types of pneumonia is limited, but LUS demonstrates good sensitivity in detecting abnormal sonographic patterns in atypical pneumonia, tuberculosis, and ventilator-associated pneumonia. Further LUS studies in the HaH setting are required to validate and generalize the findings. Full article

Globally, widespread tuberculosis is one of the acute problems of healthcare. Drug-resistant forms of tuberculosis require a personalized approach to treatment. Currently, rapid methods for detecting drug resistance of Mycobacterium tuberculosis (MTB) to some antituberculosis drugs are often used and involve optical, electrochemical, or PCR-based assays. Despite the large number of these assays, it is necessary to develop new tests (for drug-resistant MTB strains) that are structurally simple and do not require specialized equipment. Colorimetric assays involving a colloidal solution of gold nanoparticles (AuNPs) have good potential for the development of the needed diagnostic tools. Here, conditions were found for the formation of tandem duplexes between DNA probes and DNA targets, representing a part of MTB gene gyrA, either wildtype or containing a single-nucleotide polymorphism associated with fluoroquinolone resistance of MTB. Adsorption of the duplexes on AuNPs allowed to distinguish the two targets owing to the formation of nano-constructs of different structures. Interaction of DNA with AuNPs was analyzed by optical spectroscopy, dynamic light scattering, and transmission electron microscopy. A scheme is proposed for direct colorimetric detection of the fluoroquinolone-resistance-associated single-nucleotide polymorphism at a 2 nM concentration in a liquid system based on a shift of AuNPs’ optical absorption maximum. Full article

Ursolic acid (UA) and oleanolic acid (OA) are hydrophobic triterpenoid isomers with demonstrated anti-mycobacterial (Mtb) and immune-regulatory properties, although their poor solubility limits clinical use. We report the development of solid lipid microparticles (SLMs) as delivery vehicles for UA and OA and evaluate their anti-Mtb efficacy in vitro and in vivo, as well as their acute toxicity. SLMs measured 0.7–0.89 µM in size, with complete in vitro release of OA and UA at 40 and 32 h, respectively. The minimum inhibitory concentration (MIC) of SLMs loaded with OA and UA was 40 µg/mL SLMs + 20 µg/mL OA + 20 µg/mL UA for drug-sensitive Mtb and 80 µg/mL SLMs + 40 µg/mL OA + 40 µg/mL UA for multidrug-resistant (MDR) Mtb. These SLMs showed an efficient reduction in Mtb burden in infected alveolar macrophages. In a murine model of late-stage progressive MDR-TB, aerosolized delivery of SLMs containing OA and UA via a metered-dose inhaler significantly reduced pulmonary bacterial loads and extended survival. In vivo, acute toxicity studies revealed no mortality or signs of toxicity. These findings demonstrate that SLMs are an optimal delivery system for terpenoids, providing potent in vitro and in vivo anti-TB activity with an excellent safety profile. Full article

Background/Objectives: The diagnosis of encephalitis is a challenging problem due to the heterogeneity of clinical presentations. The objective was to determine the etiology, clinical features, laboratory parameters, radiological findings, and in-hospital outcome of acute encephalitis syndrome (AES) cases in Myanmar. Methods: A prospective descriptive study was conducted at the Neuromedical Ward of Yangon General Hospital from March to August 2023. Eighty-one AES cases were enrolled, and cerebrospinal fluid (CSF) samples were collected. A Qiastat ME Panel was used to detect viral, bacterial, and fungal pathogens. Results: Seventeen out of eighty-one (21%) cases were non-encephalitis with alternative definite diagnosis. Among the remaining 64 encephalitis cases, the exact infectious and immune etiologies were identified in 31 of 64 cases (48.4%); 26 of these (83.9%) were due to infectious causes and 5 (16.1%) were immune encephalitis. Among the infectious causes, six Herpes Simplex Virus-1-, one bacteriologically confirmed and seven probable Mycobacterium tuberculosis-, three Haemophilus influenzae-, two Streptococcus pneumoniae-, one Streptococcus pyogenes-, one Varicella-Zoster Virus (Ramsay Hunt Syndrome with meningoencephalitis)-, and two Cryptococcus neoformans-infected patients and rare causes such as Listeria monocytogenes, Burkholdelria cepacia, Sphingomonas paucimobilis, and Aspergillus were identified. One case was a dual infection with Haemophilus influenzae and Cryptococcus neformans. Abnormal protein levels and CSF pleocytosis were significantly higher among bacterial causes (p < 0.05). In total, 6.45% (2/31) of encephalitis patients with identified causes and 12.12% (4/33) of those without an identified organism had poor outcome. Conclusions: Herpes encephalitis and tuberculous meningoencepalitis were the commonest. This study highlighted that molecular testing with a multidisciplinary approach is required to ensure the right treatment on time. Full article