Search Results (228)

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

Plasmodium falciparum malaria remains a major cause of morbidity and mortality, particularly in endemic regions. We report the case of a 21-year-old male with recent travel to an endemic area (Guapi, Colombia), who presented with febrile symptoms, severe respiratory distress, and oxygen saturation below 75%, necessitating orotracheal intubation. During the procedure, he developed pulseless electrical activity cardiac arrest, achieving return of spontaneous circulation after advanced resuscitation. Diagnosis was confirmed by thick blood smear, demonstrating P. falciparum infection. The patient progressed to multiorgan failure, including acute respiratory distress syndrome with capillary leak pulmonary edema, refractory distributive shock, acute kidney injury with severe hyperkalemia, and consumptive thrombocytopenia. Management included invasive mechanical ventilation, vasopressor support, sedation-analgesia, neuromuscular blockade, methylene blue, unsuccessful hemodialysis due to hemorrhagic complications, and platelet transfusions. Despite these interventions, the patient experienced a second cardiac arrest and died. This case highlights the severity and rapid progression of severe malaria with multisystem involvement, underscoring the critical importance of early diagnosis and intensive multidisciplinary management. It also emphasizes the need for preventive strategies for travelers to endemic areas and the development of clinical protocols to improve outcomes in complicated malaria. Full article

Background and Objectives: Neonatal respiratory distress syndrome (NRDS), resulting from a deficiency of pulmonary surfactant (PS), can cause alveoli to collapse. Glucocorticoids reduce inflammation and are effective in reducing pulmonary swelling. This study aims to assess the effectiveness of the combination of PS and budesonide in the management of NRDS. Materials and Methods: Publications between 21 May and 24 November were screened through PubMed, Cochrane and Embase. Data analysis was performed on RevMan 5.3 software. Subgroup analysis was performed to evaluate the routes of administrations. Results: The use of budesonide along with pulmonary surfactant for treating NRDS revealed the following results: (1) a reduced duration of invasive mechanical ventilation (standardized mean difference (SMD) = −1.06, 95% confidence interval (CI) = −1.55 to −0.56, p < 0.0001); (2) reduced rate of bronchopulmonary dysplasia (BPD) occurrence (relative risk (RR) = 0.72, 95% CI = 0.60 to 0.86, p = 0.0003); (3) reduced duration for hospital admittance (SMD = −0.38, 95% CI = −0.64 to −0.11, p = 0.005). The occurrence of complications, i.e., sepsis, pneumothorax, retinopathy of prematurity (ROP), necrotizing enterocolitis (NEC), rate of mortality, hyperglycemia and intraventricular hemorrhage (IVH), was not significantly different among the intervention and comparison group except for patent ductus arteriosus (PDA) and pulmonary hemorrhage, with their incidence being higher in the control group (p = 0.002 and p = 0.05, respectively). Conclusions: The combination of pulmonary surfactant and budesonide decreases the occurrence of BPD, duration of mechanical ventilation, length of hospital stay and risk of pulmonary hemorrhage and PDA. It does not increase the risk of complications and death and is clinically safe. Full article

Pulmonary hemorrhage (PH) is a life-threatening complication predominantly affecting preterm infants, particularly those with very low birth weight (VLBW) and fetal growth restriction (FGR). Typically occurring within the first 72 h of life, PH is characterized by acute respiratory deterioration and significant morbidity and mortality. This review synthesizes current evidence on the multifactorial pathogenesis of PH, highlighting the roles of immature pulmonary vasculature, surfactant-induced hemodynamic shifts, and left ventricular diastolic dysfunction. Key risk factors include respiratory distress syndrome (RDS), hemodynamically significant patent ductus arteriosus (hsPDA), sepsis, coagulopathies, and genetic predispositions. Diagnostic approaches incorporate clinical signs, chest imaging, lung ultrasound, and echocardiography. Management strategies are multifaceted and include ventilatory support—particularly high-frequency oscillatory ventilation (HFOV)—surfactant re-administration, blood product transfusion, and targeted hemostatic agents. Emerging therapies such as recombinant activated factor VII and antifibrinolytics show promise but require further investigation. Preventive measures like antenatal corticosteroids and early indomethacin prophylaxis may reduce incidence, particularly in high-risk populations. Despite advancements in neonatal care, PH remains a major contributor to neonatal mortality and long-term neurodevelopmental impairment. Future research should focus on individualized risk stratification, early diagnostic tools, and optimized treatment protocols to improve outcomes. Multidisciplinary collaboration and innovation are essential to advancing care for this vulnerable population. Full article

PRRSV continues to evolve, complicating its epidemiological landscape in China. In this study, we isolated a novel PRRSV strain, GZ2022, from a swine farm in Guizhou Province. Subsequent analyses performed on this isolate included complete genome sequencing, phylogenetic analysis, recombination assessment, and characterization of its biological properties. Phylogenetic analysis revealed that GZ2022 clusters within Lineage 1 (NADC30-like) and features a 131-amino-acid deletion in NSP2, consistent with NADC30-derived strains. Recombination analysis identified NADC30 as the major parental strain (75% genomic contribution), with a minor recombinant region (25%) derived from the highly pathogenic HuN4 strain. In vitro growth kinetics revealed peak viral titers in Marc-145 cells at 72 h post infection (hpi). Pathogenicity was evaluated in 21-day-old piglets infected with GZ2022, the highly pathogenic PRRSV strain WUH3, or negative controls. Both infected groups exhibited typical PRRS clinical signs (fever, respiratory distress) and histopathological lesions (interstitial pneumonia, pulmonary consolidation). However, GZ2022-infected piglets exhibited attenuated virulence compared to WUH3, with reduced pulmonary hemorrhage and 0% mortality compared to 80% in the WUH3 group. Seroconversion (N-protein antibodies) was observed at 14 dpi (days post inoculation) in GZ2022-infected animals, persisting throughout the 28-day trial. Viral shedding dynamics aligned with moderate pathogenicity. These findings classify GZ2022 as a moderately virulent NADC30-like recombinant strain with partial HuN4-derived genomic regions. The emergence of such strains underscores the need for sustained surveillance of PRRSV genetic diversity and systematic evaluation of the biological properties of novel variants to refine control measures and inform vaccine development. Full article

Background/Objectives: To identify the risk factors and clinical outcomes of persistent pulmonary hypertension of the newborn (PPHN) in very low birth weight (VLBW) infants in a resource-limited setting. Methods: We conducted a 1:4 matched case–control study in a Thai neonatal unit between 2014 and 2023. Neonates born at a gestational age (GA) < 32 weeks and with a birth weight (BW) < 1500 g were included. Neonates who died in the delivery room or had major congenital anomalies were excluded. Matching was based on GA, BW, year of birth, and endotracheal intubation at birth. Conditional logistic regression analysis was performed. Results: Over the 10-year study period, the incidence of PPHN among VLBW neonates was 4.6% (31/667). After matching, there were 31 cases and 124 controls. In univariable analysis, PPHN was significantly associated with lower 1 min and 5 min Apgar scores; however, no significant association remained in multivariable analysis. PPHN was significantly associated with composite adverse outcomes—including mortality and major morbidities (adjusted odds ratio [aOR] = 7.51, 95% confidence interval [CI]: 2.41–23.40), mortality alone (aOR = 2.88, 95% CI: 1.06–7.63), major morbidities (aOR = 2.99; 95% CI: 1.29–6.95), and severe neurological injury (aOR = 4.44, 95% CI: 1.56–12.59). Daily hospital costs were also higher in PPHN cases, with an average increase of 97.1 USD. Conclusions: In VLBW infants, PPHN was associated with a lower Apgar score and surfactant administration. PPHN was significantly linked to adverse outcomes, particularly mortality, major morbidities, and severe neurological injury. Full article

Background: Hypothermia, occurring when core temperature drops below 35 °C, can lead to death when the body’s heat loss exceeds its heat production. This study investigates two hypothermia-related deaths, exploring the utility of immunohistochemistry, specifically focusing on chromogranin A (CgA) as a potential diagnostic tool. The aim is to assess whether CgA expression in neuroendocrine tissues can be considered a reliable indicator of premortem stress response in fatal hypothermia cases. Case Presentation: In the first case, a 67-year-old man was found on a snowy road 24 h after his disappearance. The autopsy revealed cold-induced skin lesions, gastric hemorrhages, and cerebral and pulmonary edema. Positive CgA immunostaining was observed in the pancreatic islets and adrenal medulla. In the second case, a 49-year-old man was found dead in a wooded area with indications of suicide. Both cases were examined with attention to macroscopic findings and histological samples from major neuroendocrine organs. As in previous cases, CgA immunostaining was positive in the pancreatic islets and adrenal medulla. Staining intensity was moderate to strong, consistent with heightened neuroendocrine activity, supporting the hypothesis of systemic stress prior to death. Conclusions: Although CgA is a potentially valuable adjunct in hypothermia diagnosis, careful consideration of cadaveric preservation is emphasized, particularly when bodies are preserved before autopsy. Further studies with larger sample sizes are needed to confirm its diagnostic specificity and to distinguish true pathological patterns from postmortem artifacts. Full article

Zoonotic viral diseases have continued to threaten global public health in recent decades, with rodent-borne viruses being significant contributors. Infection by rodent-carried hantaviruses (HV) can result in hemorrhagic fever with renal syndrome (HFRS) and hantavirus pulmonary syndrome (HPS) in humans, with varying degrees of morbidity and mortality. However, no Food and Drug Administration (FDA) vaccines or therapeutics have been approved for the treatment of these diseases. In an effort to identify antiviral bioactive molecules, we isolated four oligomeric phloroglucinols from Callistemon rigidus leaves, including two new phloroglucinol trimers, callistemontrimer A and B, along with two previously characterized phloroglucinol dimers, rhodomyrtosone B and rhodomyrtone. We evaluated the anti-Hantaan virus (HTNV) activity of these compounds. Notably, callistemontrimer A demonstrated higher anti-HTNV activity compared to ribavirin. Mechanistic studies revealed that callistemontrimer A exerted its antiviral effects by inhibiting viral replication, likely through interaction with RNA-dependent RNA polymerase (RdRp) of HTNV, as supported by molecular docking analysis. These results highlight oligomeric phloroglucinols as promising lead candidates for the development of anti-HV therapeutics. Full article

Background and Clinical Significance: Fulminant pulmonary embolism (PE) leading to an out-of-hospital cardiac arrest (OHCA) is associated with a high mortality rate and cardiopulmonary resuscitation (CPR) frequently failing to achieve return of spontaneous circulation (ROSC). Extracorporeal CPR (eCPR) has emerged as a potential life-saving intervention. Case Presentation: A 66-year-old woman suffered an OHCA due to massive PE, presenting with pulseless electrical activity (PEA). After 90 min of pre- and in-hospital CPR without sustained ROSC, venoarterial extracorporeal membrane oxygenation (va-ECMO) was initiated as eCPR upon arrival at the hospital. Even after implantation of the va-ECMO, there was initially a pronounced acidosis (pH 6.9) with a high elevated lactate level (>30 mmol/L); these factors, together with the prolonged low-flow period, indicated a poor prognosis. Further diagnostic tests revealed intracranial hemorrhage (subdural hematoma), and systemic lysis was not possible. With persistent right heart failure, surgical thrombectomy was performed during hospitalization. Intensive multidisciplinary management finally led to successful therapy and weaning from mechanical ventilation, as well as to complete neurological recovery (CPC-Score 1-2). Conclusions: This case illustrates that eCPR can facilitate survival with good favorable neurological outcomes despite initially poor prognostic predictors. It underscores the importance of refining patient selection criteria and optimizing management strategies for eCPR in refractory cardiac arrest secondary to PE. Full article

Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant vascular disorder caused by pathogenic variants in ENG (HHT1) and ACVRL1 (HHT2), with distinct phenotypic expressions. Background/Objectives: This study investigates the genotype–phenotype correlations, including comparing the quality of life by phenotype, conducting a cardiovascular risk assessment, and evaluating the impact of mutation type on its clinical manifestations and prognosis. Methods: A cross-sectional study was conducted on 85 HHT patients, stratified into HHT1 (ENG, n = 43) and HHT2 (ACVRL1, n = 42). Their clinical and biochemical parameters, arteriovenous malformations (AVMs), epistaxis severity, quality of life, and cardiovascular risk were assessed. Genetic variants were classified as truncating or non-truncating. The statistical analyses included logistic regression and survival analysis. Results: The onset of epistaxis occurred earlier in HHT1 (log-rank p = 0.011), whereas its severity (p = 0.006) and iron deficiency were greater in HHT2 (p = 0.043). Pulmonary AVMs were significantly more frequent in HHT1 (58.1% vs. 9.5%, p < 0.01), contributing to a potential decrease in survival, despite the greater hemorrhagic burden in HHT2. Truncating mutations were independently associated with anemia (p < 0.05). Cardiovascular risk (measured using the SCORE2 scale) was low to moderate, and quality of life (measured using the EQ-5D-5L scale) was most impaired in patients with severe epistaxis (p = 0.031) or anemia (p = 0.026). Truncating mutations influence the severity of anemia independently of genotype. Limitations: The principal limitations include the small sample size and the bias generated by this being a paper based on another prospective study with a methodology designed for different objectives. Conclusions: These findings underscore the need for personalized management strategies based on genotype and mutation type. Further prospective studies are warranted to validate these associations and optimize the risk stratification in HHT. Full article

Background/Objectives: Right ventricular (RV) dysfunction and circulatory collapse are considered to play a major role in mortality in patients suffering from pulmonary embolism (PE). Catheter-based therapies (CBTs) have been shown to improve RV hemodynamics. The aim of this study was to present available data for CBTs in acute PE and investigate whether CBTs offer mortality benefit and better safety outcomes over anticoagulation (AC) in patients with intermediate-risk PE. Methods: PubMed was searched from inception until February 2024 for studies that investigated treatment strategies in patients with confirmed PE. We initially investigated the crude incidence of mortality and major bleeding for individual interventions in patients with either intermediate or high-risk PE. We then directly compared CBT to AC for intermediate-risk PE, for which the effectiveness endpoint was comparative short-term (30-day or in-hospital) and midterm (90-day or 1-year) all-cause mortality and the safety outcomes included minor bleeding, major bleeding, and intracranial hemorrhage (ICH). Results: In all, 59 studies (4457 patients) were eventually included in our study. For the prevalence study, we described the crude incidence for mortality and major bleeding for interventions like catheter-directed thrombolysis (CDT), mechanical thrombectomy (MT), AC, and systemic thrombolysis (ST) in patients with either intermediate or high-risk PE. Our data synthesis comparing CBT to AC included 1657 patients (11 studies) with intermediate-risk PE. Our results indicate that CBT is associated with a lower risk of both short-term (RR 0.43; 95% CI [0.24–0.79], I² = 0%) and midterm all-cause mortality (RR 0.38; 95% CI [0.23–0.62], I² = 0%) compared to AC. Major bleeding and ICH did not differ between the two groups. Conclusions: In patients with intermediate-risk PE, our meta-analysis of the current literature suggests that CBT offers better outcomes in terms of short-term and midterm mortality compared to AC alone, with no difference in safety outcomes. Further RCTs are needed to explore and validate these findings. Full article

Background: Since clazosentan was approved for insurance coverage in Japan, the postoperative management of delayed cerebral ischemia (DCI) after subarachnoid hemorrhage (SAH) has changed as each facility gains experience. Here, we investigate the prevention, treatment, and management of DCI after SAH throughout Japan in 2023. Methods: In 2024, we conducted an anonymous questionnaire survey—emailed to certified neurosurgeons in hospitals across Japan—regarding management for preventing DCI after aneurysmal SAH. Of them, 78 hospitals responded and were included in this study. These results were compared with the findings of a survey conducted prior to the approval of clazosentan in Japan (2022). Results: The proportion of institutions with a standardized protocol for DCI after aneurysmal SAH at a level of ≥50% was 93.0%. For both craniotomy and endovascular surgery, clazosentan was used most frequently, followed by cilostazol, fasudil, and statins. The most common drug for both direct and endovascular procedures was clazosentan. The predominant reason for discontinuing clazosentan was respiratory complications—such as pulmonary edema—followed by cardiac complications. However, 62.1% of facilities felt that the number of cases wherein clazosentan was discontinued was deceasing. While 77.5% of respondents felt that clazosentan was effective for preventing DCI after aneurysmal SAH, only 49.3% felt that it improved outcomes. Conclusions: Since its approval, clazosentan has been the most common treatment for DCI prevention after aneurysmal SAH. The impression of the effectiveness in preventing DCI and the outcomes of clazosentan have been mixed. As data accumulate, clazosentan use and management protocols will be refined and developed. Full article

Background and Objectives: The needle path is crucial for preoperative localization of deep thoracic pulmonary nodules using CT-guided patent blue dye (PBD) injection. This study aimed to evaluate the efficacy and safety of four categorized needle approach paths tailored to the anatomical location of the nodules. Materials and Methods: We retrospectively evaluated data from 50 consecutive patients (50 deep pulmonary nodules), who underwent CT-guided localization with PBD injection, between November 2015 and May 2023 at our hospital. The nodules could be divided into four categories: (1) perifissural nodules, (2) paravertebral nodules, (3) paramediastinal nodules, and (4) deep parenchymal nodules, according to their location relative to the thoracic organs and the visceral pleura. Needle approach methods and needle pathway lengths were recorded. Clinical and radiological features, technical information, pathological results, and procedure-related complications were analyzed. Results: All 50 dyes were successfully identified by thoracoscopy and then resected without major complication. The mean nodule diameter and the nodular depth were 10.3 (range, 4.7–21.0) mm and 16.1 (range, 0.1–52.2) mm. The needle pathway length was 7.7 (range, 4.5–11.7) cm. The mean procedure time was 16 (range, 8–26) minutes. Asymptomatic pneumothorax developed in twenty-four patients (48.0%), and focal parenchymal hemorrhage occurred in four patients (8.0%) after localization. No patients required chest tube insertion or resuscitation. Conclusions: Strategic needle approach paths provide precise localization of deep thoracic pulmonary nodules with minimal complications. These methods offer a practical framework for improving thoracoscopic surgery in challenging deep thoracic cases. Full article

Pulmonary arteriovenous malformations (PAVMs) are abnormal communications between a pulmonary artery and pulmonary vein that bypass the capillary bed, resulting in right-to-left shunting. The majority of PAVMs are associated with hereditary hemorrhagic telangiectasia (HHT), an autosomal dominant disease. Asymptomatic children with either a confirmed diagnosis of HHT or who are at risk of HHT from positive family history, as well as those with signs or symptoms concerning for HHT and/or PAVMs, should undergo screening for PAVMs at the time of clinical presentation or diagnosis. Screening in children can use a conservative approach (pulse oximetry, exercise intolerance testing, and chest radiograph) or transthoracic contrast echocardiography with agitated saline (TTCE). Pediatric patients with large or physiologically significant PAVMs should be treated with transcatheter embolization. Close follow-up is required after treatment to evaluate for interval growth of other PAVMs or reperfusion of the treated PAVMs. Full article

Background/Objectives: Pathogenic variants in the growth differentiation factor 2 (GDF2) gene have been linked to a hereditary hemorrhagic telangiectasia (HHT)-like syndrome, yet their clinical significance remains under investigation. This study reports seven pediatric patients with GDF2 variants from a single center. Methods: We identified children with GDF2 pathogenic variants and variants of uncertain significance (VUS) from the Children’s Hospital of Philadelphia Comprehensive HHT Program and cross-referenced the list with a full-text query by GDF2 gene name on >53,000,000 visits to ensure complete ascertainment. Medical records were reviewed retrospectively, and variables of interest were abstracted. Results: The median age at genetic testing was 12 years (range 1.75–16). Reasons for genetic testing included telangiectasias, pulmonary hypertension, familial testing, respiratory symptoms, seizures, developmental disabilities, and lung arteriovenous malformations (AVMs). Four patients had missense VUS, including two novel VUS (c.34C>G; p.Leu12Val, c.41C>T; p.Ser14Phe), while three had pathogenic deletions. All patients experienced epistaxis, starting at a median age of 6 years (range 2–12). Three had telangiectasias. One patient had both a GDF2 VUS and a de novo partial endoglin (ENG) gene deletion. While this patient’s symptoms of HHT are likely related to her ENG variant, synergy cannot be excluded, and two first-degree family members with clinically significant epistaxis also have the same GDF2 VUS. Notably, two patients had visceral AVMs—one with a lung AVM and another with a vein of Galen malformation. Conclusions: Interpretation of GDF2 VUS and their relationship to clinical symptoms is challenging given the rarity of these genetic variants and the inadequate diagnostic utility of the current clinical criteria for HHT in the pediatric population. Further research with larger cohorts is necessary to improve the genotype–phenotype correlation in GDF2-related HHT. Carefully collected clinical information with longitudinal follow-up may also assist in refining classification of GDF2 VUS as benign or pathogenic in the future. Full article