Search Results (181)

Visceral disseminated varicella-zoster virus infection (VD-VZV) involves the hematogenous spread of VZV from the skin to the internal organs. Though rare, it is potentially life-threatening, predominantly affecting immunocompromised individuals. Diagnosis is often delayed due to nonspecific symptoms mimicking other viral illnesses. While the vesicular rash is a hallmark sign, it is absent in approximately 5% of cases. Visceral involvement may precede cutaneous lesions, complicate early recognition, and increase the risk of severe complications. This scoping review screened 594 articles of which 153 met the inclusion criteria, yielding 156 individual cases. Patients were predominantly male (53.8%), with a mean age of 42.3 years. The overall mortality rate was 25.0%. Multiple organs were involved in 46.1% of cases. The most frequently affected were the lungs (56%), liver (44%), heart (16%), kidneys (11%), pancreas (11%), stomach (10%), and esophagus (6%). Antivirals were administered in 89.1% of cases, while corticosteroids were used in 22.4%, with no significant impact on outcomes. Early diagnosis, achieved in 65.4% of patients, was significantly associated with survival (p = 0.043). Mortality was significantly associated with underlying comorbidities (p = 0.004), especially autoimmune diseases requiring immunosuppression (p = 0.048). Septic shock or multi-organ dysfunction (MODS), hepatitis, acute kidney injury, and acute liver failure were linked to higher mortality in univariate analysis. Multivariate analysis identified comorbidities (p < 0.001), septic shock/MODS (p = 0.008), and acute liver failure (p = 0.039) as independent predictors of mortality. Patients with septic shock/MODS had over twice the risk of death (OR = 2.24; p = 0.008). This review underscores the diagnostic challenges and high mortality of VD-VZV. Early recognition and timely administration of antiviral treatment appear critical for survival. Greater clinical awareness and further research are needed to guide management. Full article

Polytrauma is a critical global health concern characterized by immune dysregulation and a high risk of multiple organ dysfunction syndrome (MODS). Early molecular mechanisms linking trauma severity to organ injury are poorly understood. We used two rat blast-polytrauma models: a tourniquet-induced ischemia/reperfusion injury (tIRI) model and a non-ischemia/reperfusion injury (non-IRI) model. Naïve animals served as controls. RT-qPCR of 120 inflammatory genes in the lung, kidney, and liver, combined with STRING protein–protein interaction analysis, revealed distinct yet overlapping inflammatory gene signatures across all the organs. A core set of genes (Il6, Lbp, Nos2, and Lcn2) was consistently upregulated, indicating shared inflammatory pathways. Transcriptomic responses were most pronounced in the tIRI group, with greater magnitude and altered temporal dynamics, uniquely amplifying pro-inflammatory cytokines, immune cell activators, chemokines, and tissue damage markers. Lipocalin-2 (Lcn2/NGAL) emerged as a shared hub gene across all the organs within 24 h post-injury. Its expression significantly correlated with MODS activity and adverse outcomes, independent of the injury model. At 168 h, Lcn2 expression correlated with increased liver damage and NGAL levels correlated with tissue trauma severity. These findings elucidate distinct pro-inflammatory mediators and networks underlying secondary organ dysfunction, highlighting NGAL as a potential universal biomarker of trauma-induced inflammation and MODS activity, suggesting it as a therapeutic target. Full article

Background/Objectives: Our work was designed to study the physicochemical properties, safety profile, pharmacokinetics, and prophylactic efficacy of an original iodine–dextrin-based pharmaceutical formulation (PA), both alone and in combination with azithromycin (AZ), in a murine model of LPS-induced sepsis. Methods/Results: UV–vis and ¹H-NMR spectroscopy confirmed the formation of a stable iodine–dextrin complex, with triiodide anions stabilized by hydrogen bonding and donor–acceptor interactions. No clinical signs of acute toxicity were observed at doses up to 5000 mg/kg, and subacute administration (62.5 and 125 mg/kg) showed no adverse effects on hematological or biochemical parameters. A mild, non-pathological enlargement of thyrocytes and parallel increases in TSH, T3, and T4 levels were observed at 125 mg/kg, consistent with physiological adaptation to iodine. Pharmacokinetic analysis revealed high oral bioavailability (~92%), prolonged half-life (~21 h), and wide tissue distribution with low clearance. In the sepsis model, pretreatment with AZ+PA alleviated clinical symptoms, maintained body weight, and significantly improved hematological parameters, reducing WBCs and CRP levels. The combination also decreased plasma IL-6 and TNF-α concentrations more effectively than either agent alone, indicating a synergistic anti-inflammatory effect. Histological analysis confirmed that PA, particularly in combination with AZ, mitigated LPS-induced tissue injury in the liver, kidney, and lungs. Conclusions: These findings suggest that PA is a safe, bioavailable compound with immunomodulatory properties that enhance azithromycin’s protective effects during systemic inflammation. This supports its potential use as a prophylactic agent in clinical settings, such as preoperative immune modulation to prevent sepsis-related complications. Full article

Hypothermia-related deaths present significant diagnostic challenges due to non-specific and often inconsistent autopsy findings. This study investigated the histological and immunohistochemical alterations associated with primary and secondary hypothermia in an experimental Rattus norvegicus model, focusing on the effects of benzodiazepine and alcohol ingestion. Twenty-one male rats were divided into three groups: control (K), benzodiazepine-treated (B), and alcohol-treated (A). After two weeks of substance administration, hypothermia was induced and multiple organ samples were analyzed. Histologically, renal tissue showed hydropic and vacuolar degeneration, congestion, and acute tubular injury across all groups, with no significant differences in E-cadherin expression. Lung samples revealed congestion, emphysema, and hemorrhage, with more pronounced vascular congestion in the alcohol and benzodiazepine groups. Cardiac tissue exhibited vacuolar degeneration and protein denaturation, particularly in substance-exposed animals. The spleen showed preserved architecture but increased erythrocyte infiltration and significantly elevated myeloperoxidase (MPO)-positive granulocytes in the intoxicated groups. Liver samples demonstrated congestion, focal necrosis, and subcapsular hemorrhage, especially in the alcohol group. Immunohistochemical analysis revealed statistically significant differences in MPO expression in both lung and spleen tissues, with the highest levels observed in the benzodiazepine group. Similarly, CK7 and CK20 expression in the gastroesophageal junction was significantly elevated in both alcohol- and benzodiazepine-treated animals compared to the controls. In contrast, E-cadherin expression in the kidney did not differ significantly among the groups. These findings suggest that specific histological and immunohistochemical patterns, particularly involving pulmonary, cardiac, hepatic, and splenic tissues, may help differentiate primary hypothermia from substance-related secondary hypothermia. The study underscores the value of integrating toxicological, histological, and molecular analyses to enhance the forensic assessment of hypothermia-related fatalities. Future research should aim to validate these markers in human autopsy series and explore additional molecular indicators to refine diagnostic accuracy in forensic pathology. Full article

Background and Objectives: Acute kidney injury (AKI) is common in intensive-care unit (ICU) patients and is associated with increased mortality. Elderly patients tend to have more comorbid chronic diseases and are more prone to AKI than younger populations, resulting in higher rates of hospitalization and a higher incidence of AKI. Our aim in this study was to investigate the prognostic utility of BUN/albumin ratio (BAR) in predicting mortality in elderly critically ill patients with AKI. Materials and Methods: This study was conducted retrospectively on 154 elderly patients with AKI who were admitted to the ICU between October 2023 and September 2024.Data on the following demographic, clinical, and laboratory parameters were retrospectively collected from medical cards and electronic records. Results: In the non-survivor group, among comorbidities, lung disease was higher (p < 0.05), GCS was lower, and APACHE II was higher among clinical scores (p < 0.001). In the non-survivor group, diuretic use (p = 0.03), oliguria, RRT, vasopressor requirement, sepsis, and MV rates (p < 0.001),as well as BUN, phosphate, LDH, Crp, APTT, INR, and BAR rates, were higher (all p < 0.05) and albumin was lower (p = 0.01). Cut-off values of BUN, albumin, and BAR variables according to mortality status were determined by an ROC curve analysis, as follows:48.4 for BUN (p = 0.013), 31.5 for albumin (p = 0.001), and 1.507 for BAR (p = 0.001).According to the results of the ROC analysis performed to predict in-hospital mortality, the BAR level reached an AUC value of 0.655. A BAR value above 1.507 increases mortality by 3.944 times (p = 0.023). Conclusions: BAR is a simple and accessible biomarker that may serve as a predictor of in-hospital mortality in elderly patients with AKI. Its use may aid early risk stratification and decisionmaking in the ICU. Full article

In this study, pharmacotherapies of abdominal compartment syndrome (ACS) and intra-abdominal hypertension (IAH) in animal studies were reviewed from the perspective of ACS/IAH as failed cytoprotection issues, as non-specific injuries, and from the point of view of the cytoprotection concept as resolution. Therefore, this review challenges the unresolved theoretical and practical issues of severe multiorgan failure, acknowledged significance in clinics, and resolving outcomes (i.e., open abdomen). Generally, the reported agents not aligned with cytoprotection align with current pharmacotherapy limitations and have (non-)confirmed effectiveness, mostly in only one organ, mild/moderate IAH, prophylactic application, and provide only a tentative resolution. Contrarily, stable gastric pentadecapeptide BPC 157 therapy, as a novel and relevant cytoprotective mediator having pleiotropic beneficial effects, simultaneously resolves many targets, resolving established disturbances, specifically compression/ischemia (grade III and grade IV), and decompression/advanced reperfusion. BPC 157 therapy rapidly activates collateral bypassing pathways, and, in ACS and IAH, and later, in reperfusion, there is a “bypassing key” (i.e., azygos vein direct blood flow delivery). This serves to counteract multiorgan and vessel failure, including lesions and hemorrhages in the brain, heart, lung, liver, kidney and gastrointestinal tract, thrombosis, peripherally and centrally, intracranial (superior sagittal sinus), portal and caval hypertension and aortal hypotension, occlusion/occlusion-like syndrome, advanced Virchow triad circumstances, and free radical formation acting as a membrane stabilizer and free radical scavenger. Likewise, not only in ACS/IAH resolving, but also in other occlusion/occlusion-like syndromes, this “bypassing key” could be an effect of the essential endothelial cytoprotective capacity of BPC 157 and a particular modulatory effect on the NO-system, and a rescuing impact on vasomotor tone. Full article

Snakebite is a significant global public health challenge, and the limited application of antivenom has driven the exploration of novel therapies. Combination therapy using small-molecule drugs targeting phospholipases A₂ (PLA2) and metalloproteinases (SVMP) in venom shows great potential. Although Rhamnetin and RXP03 exhibit notable anti-phospholipase and anti-metalloproteinase activities, respectively, their antiophidic potential remains poorly explored. This study aims to evaluate the inhibitory effects of Rhamnetin and RXP03 on snake venom toxicity. Methodologically, we conducted in vitro enzymatic assays to quantify PLA₂/SVMP inhibition, murine models of envenomation (subcutaneous/intramuscular venom injection) to assess local tissue damage and systemic toxicity, and histopathological/biochemical analyses. In vitro experiments demonstrated that Rhamnetin effectively inhibited PLA₂ activity while RXP03 showed potent suppression of SVMP activity, with their combination significantly reducing venom-induced hemorrhagic activity. In murine models, the combined therapy markedly alleviated venom-triggered muscle toxicity and ameliorated oxidative stress. Furthermore, the combination enhanced motor performance and survival rate in mice, improved serum biochemical parameters, corrected coagulation disorders, and attenuated pathological damage in liver, kidney, heart, and lung tissues. This research demonstrates that dual-targeted therapy against metalloproteinases and phospholipases in snake venom can effectively prevent a series of injuries caused by snake venom. Collectively, the combined application of Rhamnetin and RXP03 exhibits significant inhibitory effects on a variety of venom-induced toxicities, providing pharmacological evidence for the development of antivenom therapies. However, the efficacy validation in this study was limited to murine models, and there is a discrepancy with clinical needs for delayed treatment in real-world envenomation scenarios. Despite these limitations, the findings provide robust preclinical evidence supporting the Rhamnetin–RXP03 combination therapy as a cost-effective, broad-spectrum antivenom strategy. Future studies are required to optimize dosing regimens and evaluate clinical translatability. Full article

Ambient ozone (O₃) pollution, which has become a global problem, is associated with damage to various biological systems, as determined by many studies. However, there is limited experimental evidence regarding the systemic damage induced by O₃ exposure, and there are few associated studies on mice. In the present investigation, we constructed a subacute C57BL/6J female mouse model involving exposure to 0, 0.5, 1, or 2 ppm O₃ for 28 days (3 h/day). Body weights, pulmonary function, hematology, serum biochemistry, inflammatory factors, and injuries to various organs were assessed for O₃-exposed mice. After O₃ exposure, especially to 2 ppm O₃, mice showed a loss of body weight, abnormal glucose and lipid metabolism, respiratory and nervous system injuries, an inflammatory response, and pathological changes, which supported the data reported for epidemiology studies. In addition, the IL-6 levels in bronchoalveolar lavage fluid (BALF), the lungs, the livers, the kidneys, and the brains were increased, which indicated that IL-6 was associated with the damage to various organs induced by O₃ exposure. The present report highlights the pathological injury to various organs and provides a basis for further studies of the molecular mechanisms associated with O₃ exposure. Full article

Background: Systemic sclerosis (SSc) is a rare connective tissue disease characterized by vasculopathy, autoimmunity, and fibrosis. Due to its low prevalence and heterogeneous clinical presentation, early diagnosis remains challenging, often delaying appropriate treatment. The disease progresses from microvascular dysfunction, manifesting as Raynaud’s phenomenon, to systemic fibrosis affecting multiple organs, including the lungs, gastrointestinal tract, heart, and kidneys. There have been considerable advancements in understanding the pathophysiology of the disease during the last few years and this has already resulted in the improvement of the therapeutic approaches used to control organ-specific manifestations. However, the underlying cause of the disease still remains incompletely elucidated. Methods: Here, we summarize the current knowledge on the SSc pathogenesis. Results: The pathophysiology involves an interplay of chronic inflammation, impaired vascular function, and excessive extracellular matrix deposition, leading to progressive organ damage. Endothelial dysfunction in SSc is driven by immune-mediated injury, oxidative stress, and the imbalance of vasoconstrictors and vasodilators, leading to capillary loss and chronic hypoxia. Autoantibodies against endothelial cells or other toxic factors induce apoptosis and impair angiogenesis, further exacerbating vascular damage. Despite increased angiogenic factor levels, capillary repair mechanisms are defective, resulting in progressive ischemic damage. Dysregulated immune responses involving Th2 cytokines, B cells, and macrophages contribute to fibroblast activation and excessive collagen deposition. Transforming growth factor-beta (TGF-β) plays a central role in fibrotic progression, while fibroblasts resist apoptosis, perpetuating tissue scarring. The extracellular matrix in SSc is abnormally stiff, reinforcing fibroblast activation and creating a self-perpetuating fibrotic cycle. Conclusions: Advances in molecular and cellular understanding have facilitated targeted therapies, yet effective disease-modifying treatments remain limited. Future research should focus on precision medicine approaches, integrating biomarkers and novel therapeutics to improve patient outcomes. Full article

Background: Immunosuppressive therapies are vital for solid organ transplant (SOT) recipients to ensure graft survival, but long-term use can lead to complications. This study aimed to comprehensively evaluate the complications associated with immunosuppressive agents across different types of major SOTs. Methods: In a retrospective cohort study using a national claims database, we analyzed adult SOT recipients who began immunosuppressive therapy from 2007 to 2018. We identified complications such as infections, acute kidney injury, hypertensive emergencies, chronic kidney disease, hypertension, diabetes, dyslipidemia, and osteoporosis. These outcomes were determined through diagnostic codes, medication usage data, and hospital or emergency department visits. Results: Among 30,997 transplants with three-year follow up, complication rates varied by transplant type. Pancreatic transplant recipients had the lowest complication rate (225.9 per 1000 patient-years), while lung transplant recipients experienced the highest rate (823.9 per 1000 patient-years). Serious infections and chronic kidney disease were most common 2 to 6 months post transplant. Other complications, like acute kidney injury, hypertensive emergencies, hypertension, diabetes, dyslipidemia, and osteoporosis, were predominantly observed in the first month. Opportunistic infections peaked between 7 months and 1 year after transplantation. Conclusions: This study emphasizes the varied complications related to immunosuppressive therapy among different SOT recipients, delineating specific timeframes for each complication and maintenance regimen. Full article

Acute pancreatitis (AP) an inflammatory condition caused by the premature activation of pancreatic proteases, leads to organ damage, systemic inflammation, and multi-organ failure. Severe acute pancreatitis (SAP) has high morbidity and mortality, affecting the liver, kidneys, and lungs. Autophagy maintains pancreatic homeostasis, with VMP1-mediated selective autophagy (zymophagy) preventing intracellular zymogen activation and acinar cell death. This study examines the protective role of VMP1 (Vacuole Membrane Protein 1)-induced autophagy using ElaI-VMP1 transgenic mice in a necrohemorrhagic SAP model (Hartwig’s model). ElaI-VMP1 mice show significantly reduced pancreatic injury, including lower necrosis, edema, and inflammation, compared to wild-type (WT) mice. Biochemical markers (lactate dehydrogenase-LDH-, amylase, and lipase) and histopathology confirm that VMP1 expression mitigates pancreatic damage. Increased zymophagy negatively correlates with acinar necrosis, reinforcing its protective role. Beyond the pancreas, ElaI-VMP1 mice exhibit preserved liver, kidney, and lung histology, indicating reduced systemic organ damage. The liver maintains normal architecture, kidneys show minimal tubular necrosis, and lung inflammation features are reduced compared to WT mice. Our results confirm that zymophagy functions as a protective pathophysiological mechanism against pancreatic and extrapancreatic tissue injury in SAP. Further studies on the mechanism of VMP1-mediated selective autophagy in AP are necessary to determine its relevance and possible modulation to prevent the severity of AP. Full article

Background and Objectives: Eosinophilic lung diseases (ELD) encompass disorders with an abnormally high number of polymorphonuclear eosinophils in the lungs. Presentation severity can range from low-grade fever and cough to life-threatening acute respiratory distress syndrome (ARDS). Due to the rarity of these conditions, no large sample studies have been performed to assess the characteristics of patients with pulmonary eosinophilia. Materials and Methods: Patients admitted with a diagnosis of pulmonary eosinophilia between the years 2016 and 2020 were extracted from the largest inpatient US database, the Nationwide Inpatient Sample (NIS). Patients under the age of eighteen and those with diabetic ketoacidosis were excluded. Baseline demographic characteristics and medical comorbidities were evaluated for individuals admitted with pulmonary eosinophilia depending on intubation requirement. The primary outcomes included in-hospital mortality, intubation, and length of stay (LOS). Results: 3784 records were extracted, among which 384 patients required intubation. Patients who required intubation had higher rates of in-hospital mortality (23.9% vs. 1.2% p < 0.0001%) and a significantly more prolonged hospital stay (19 days vs. 6 days p < 0.001) compared to patients who did not need intubation. Factors associated with mortality in the intubated group included increasing age (OR: 1.022, 95% CI 1.002–1.042), duration of intubation superior to 96 h (OR: 2.705, 95% CI 1.235–5.927), and AKI (OR: 2.964, 95% CI 1.637–5.366). Conclusions: Our findings suggest that ELD patients requiring intubation experience significantly higher rates of in-hospital mortality, acute kidney injury, deep venous thrombosis, and ARDS. Full article

Background: The management of renal injuries in hemodynamically stable adult patients is moving toward more conservative methods, even in cases of severe grade and/or penetrating trauma. The objective of this study was to analyze the patterns of injury, management, and complications in renal trauma patients at a Polish trauma center. Methods: Patients diagnosed with renal trauma at the trauma center between January 2019 and December 2023 were identified based on the ICD-10 codes. The information was gathered from digitalized medical records, while imaging data were classified by Radiologists. Results: During a period of 4 years, a total of 81 patients with renal trauma were admitted to the trauma center. 76% of these patients were males, with a mean age of 44.61 ± 16.8 years. The most common concomitant conditions, both among men and women, included retroperitoneal hematoma, rib fractures, as well as chest and lung injuries. Surgical intervention within 8 h of admission was mainly performed on patients with grade IV and V kidney damage, which included a total of 22 people. In deferred treatment, 31 patients underwent surgical intervention. Conclusions: Hemodynamically stable patients, even with penetrating and/or high-grade blunt trauma, were mostly managed non-operatively, with a low rate of complications. Full article

In a rapidly changing technology landscape, “Clinical Decision Support” (CDS) has become an important tool to improve patient management. CDS systems offer medical professionals new insights to improve diagnostic accuracy, therapy planning, and personalized treatment. In addition, CDS systems provide cost-effective options to augment conventional screening for secondary prevention. This review aims to (i) describe the purpose and mechanisms of CDS systems, (ii) discuss different entities of algorithms, (iii) highlight quality features, and (iv) discuss challenges and limitations of CDS in clinical practice. Furthermore, we (v) describe contemporary algorithms in oncology, acute care, cardiology, and nephrology. In particular, we consolidate research on algorithms across diseases that imply a significant disease and economic burden, such as lung cancer, colorectal cancer, hepatocellular cancer, coronary artery disease, traumatic brain injury, sepsis, and chronic kidney disease. Full article

Background/Objectives: Acute kidney injury (AKI) is a serious and prevalent complication of COVID-19. This study examines the prevalence, risk factors, and outcomes of AKI in hospitalized COVID-19 patients. Methods: We analyzed the data of 1223 adult COVID-19 hospitalized patients from a single district hospital during three pandemic periods: 3 November 2020–31 December 2020, 17 March 2021–8 May 2021, and 4 November 2021–21 February 2022. The analysis included demographic data, comorbidities, laboratory results, chest radiographs (CT lung scans), and outcomes. Results: We found an overall AKI incidence of 29.02%. AKI patients versus non-AKI ones were significantly older (median age 76.0 vs. 71.0, p < 0.001) and had more comorbidities, especially previous renal diseases, heart failure, coronary artery disease, and hypertension; they also significantly more often used diuretics, angiotensin receptor blockers (ARBs), and angiotensin-converting enzyme inhibitors (ACE-Is). AKI patients more frequently presented with abnormal CT lung scans and had higher white blood cell counts, lower lymphocytes percentages, higher C-reactive protein (CRP) levels, and lower platelet counts. They more often required oxygen therapy, more days of hospitalization, and had higher mortality rates. Conclusions: Older age, comorbidities, the use of diuretics, and renin-angiotensin system inhibitors (RASI) are key risk factors for AKI, which is consequently linked to a more severe disease course and poorer prognosis. Full article