Purpose: Human epidermal growth factor receptor 2 (HER2) is amplified or overexpressed in various malignancies, including breast and gastric cancers, and is associated with poor prognosis. Although HER2-targeted therapies, such as trastuzumab, improve outcomes in HER2-positive tumors, resistance often develops, and HER2-low tumors remain largely untargeted. Trastuzumab deruxtecan (T-DXd; DS-8201a) is a HER2-targeted antibody-drug conjugate with potent activity in HER2-positive and HER2-low tumors. This study evaluates its antitumor mechanisms and efficacy in HER2-positive, HER2-low, and homologous recombination deficiency (HRD)–associated models. Materials and Methods: Effects of T-DXd were assessed in cancer cell lines with diverse HER2 expression and HRD status. In vivo efficacy was evaluated using a xenograft model derived from HER2-low SNU-601 gastric cancer cells. Results: T-DXd reduced HER2 phosphorylation and downstream signaling (AKT, ERK) in HER2-positive cells. It induced DNA damage accumulation, as evidenced by increased γH2AX and p-Chk1 expression, and triggered apoptosis through cleaved poly(ADP-ribose) polymerase and caspase-3 activation, confirmed by annexin V staining. Similar effects were observed in HER2-low cells, with greater sensitivity in HRD cells. In xenografts, T-DXd reduced tumor volume by up to 80% at 4 mg/kg and 10 mg/kg. Histological analyses showed decreased Ki-67 and increased apoptosis. Furthermore, T-DXd induced G2/M cell cycle arrest and nuclear anaplasia, suggesting disruption of chromosomal stability as a potential antitumor mechanism. No significant toxicity, including body weight loss, was observed. Conclusion These findings highlight T-DXd’s effectiveness in HER2-low and HRD tumors, supporting its broader clinical application, including strategies targeting DNA damage repair pathways.

Background/Aims: Shifts in the gut microbiota and metabolites are interrelated with liver cirrhosis progression and complications. However, causal relationships have not been evaluated comprehensively. Here, we identified complication-dependent gut microbiota and metabolic signatures in patients with liver cirrhosis. Methods: Microbiome taxonomic profiling was performed on 194 stool samples (52 controls and 142 cirrhosis patients) via V3-V4 16S rRNA sequencing. Next, 51 samples (17 controls and 34 cirrhosis patients) were selected for fecal metabolite profiling via gas chromatography mass spectrometry and liquid chromatography coupled to timeof-flight mass spectrometry. Correlation analyses were performed targeting the gut-microbiota, metabolites, clinical parameters, and presence of complications (varices, ascites, peritonitis, encephalopathy, hepatorenal syndrome, hepatocellular carcinoma, and deceased). Results: Veillonella bacteria, Ruminococcus gnavus, and Streptococcus pneumoniae are cirrhosis-related microbiotas compared with control group. Bacteroides ovatus, Clostridium symbiosum, Emergencia timonensis, Fusobacterium varium, and Hungatella_uc were associated with complications in the cirrhosis group. The areas under the receiver operating characteristic curve (AUROCs) for the diagnosis of cirrhosis, encephalopathy, hepatorenal syndrome, and deceased were 0.863, 0.733, 0.71, and 0.69, respectively. The AUROCs of mixed microbial species for the diagnosis of cirrhosis and complication were 0.808 and 0.847, respectively. According to the metabolic profile, 5 increased fecal metabolites in patients with cirrhosis were biomarkers (AUROC >0.880) for the diagnosis of cirrhosis and complications. Clinical markers were significantly correlated with the gut microbiota and metabolites. Conclusions Cirrhosis-dependent gut microbiota and metabolites present unique signatures that can be used as noninvasive biomarkers for the diagnosis of cirrhosis and its complications.

Methyl salicylate is widely used in various topical products, including sports creams, ointments, patches, and oral hygiene products. These products are mainly used for localized treatment of musculoskeletal pain. Given their intended topical application, their ingestion can result in salicylic acid poisoning due to their high concentrations of methyl salicylate. Symptoms of salicylic acid poisoning may include dizziness, vomiting, hallucinations, seizures, and, in severe cases, unconsciousness, respiratory failure, and circulatory disorders. We report a case of a 71-year-old male who ingested Mensolatum Lotion to commit suicide and died.

The aim of this study was to elucidate the diatomological investigation and the forensic role of spleen tissue in cases of drowning or non-drowning. Specimens of spleen tissue and other organ tissue from 136 drowning cases, as well as 21 cases where death resulted from causes other than drowning (acting as controls), were examined for the presence of diatoms. The diatom test was performed on all cases using the acid digestion method, involving fumed nitric acid on a hot sand bath. The presence of diatoms in spleen tissue was observed in drowning cases but not in non-drowning cases. Diatoms in spleen tissue showed a positive association with drowning (P=0.011). Among the 136 drowning cases, diatoms were most frequently found in lung tissue (n=134, 99%), followed by spleen (n=33, 24%), kidney (n=28, 21%), liver (n=27, 20%), and heart (n=22, 16%) tissues. Moreover, in 95 cases where putrefaction did not progress, diatoms were detected in spleen tissues in 14 cases, indicating that the highest detection rate among other enclosed organ tissues, excluding lung tissues. Furthermore, a significant correlation was observed between the presence of diatoms in spleen tissue and those in enclosed organs, including the liver, kidney, and heart, but not in lung tissues. Our results revealed a significant correlation between the presence of diatoms in spleen tissue and drowning. Thus, the present study provides evidence that the presence of diatoms in spleen tissue may be a reliable indicator of death by drowning.

Objective: We used paclitaxel and cisplatin, known to be effective in intraperitoneal chemotherapy, in a novel prototype of rotational intraperitoneal pressurized aerosol chemotherapy (RIPAC) and evaluated the pharmacokinetics, tissue concentrations, and toxicities in a pig model. Methods: We developed RIPAC, including the nozzle with the conical pendulum motion, and used 10% of intravenous doses of paclitaxel and cisplatin. We used high-performance liquid chromatography followed by tandem mass spectrometry to analyze serum and tissue concentrations. We applied a non-compartment model to study pharmacokinetics to analyze the time-dependent serum concentrations measured before RIPAC to 48 hours. We evaluated the difference in tissue concentrations between twelve peritoneal regions by the modified peritoneal cancer index. For evaluating toxicities, we observed hepatic and renal function until 4 days after RIPAC. Results: Six pigs underwent RIPAC using paclitaxel (n=3) and cisplatin (n=3). The peak serum concentration (Cmax) and the area under the curve were higher for cisplatin, while the time to the peak serum concentration (Tmax) was longer for paclitaxel. Moreover, the parietal peritoneum showed higher tissue concentrations than the visceral peritoneum, and the ratio of tissue to serum concentrations using Cmax was higher for paclitaxel (172.2–6,237.9) than for cisplatin (0.1–9.3). However, there were no renal and hepatic toxicities after RIPAC with paclitaxel or cisplatin. Conclusion Delayed absorption of paclitaxel sprayed by RIPAC into the peritoneum to the bloodstream may lead to higher tissue concentrations at different regions and lower serum concentrations than cisplatin.

Forensic autopsy is performed to investigate a death. However, this is difficult in some cases, particularly in putrefied bodies. Pulmonary ossification is a rare pathological process, characterized by progressive and metaplastic ossification, which leads to the formation of small bony fragments in the pulmonary tissue. This condition can develop within the pulmonary tissues that are injured due to various causes. Metastatic and dystrophic calcification occur in normal tissues in conditions of deranged calcium metabolism and dead or degenerative tissue, respectively. Here, we describe the case of a 54-year-old man who lived alone and whose putrefied body was discovered by his landlord. A forensic pathologist identified needle-like sharp materials in both the lower lobes of the lungs during autopsy. Microscopic examination revealed dendriform pulmonary ossification with calcification. After autopsy, his medical history, including chronic kidney disease, was recorded by forensic pathologist. A review of his past medical history and comprehensive postmortem examination findings of the gross dissection, microscopic examination, and postmortem laboratory tests led to the determination of the cause of death as renal problems.

Recently, increasing evidence suggests that neuroinflammation may be a critical factor in the development of Parkinson’s disease (PD) in addition to the ratio of acetylcholine/dopamine because dopaminergic neurons are particularly vulnerable to inflammatory attack. In this study, we investigated whether botulinum neurotoxin A (BoNT-A) was effective for the treatment of PD through its anti-neuroinflammatory effects and the modulation of acetylcholine and dopamine release. We found that BoNT-A ameliorated MPTP and 6-OHDA-induced PD progression, reduced acetylcholine release, levels of IL-1β, IL-6 and TNF-α as well as GFAP expression, but enhanced dopamine release and tyrosine hydroxylase expression. These results indicated that BoNT-A had beneficial effects on MPTP or 6-OHDA-induced PD-like behavior impairments via its anti-neuroinflammation properties, recovering dopamine, and reducing acetylcholine release.

The coronavirus disease 2019 (COVID-19) pandemic resulted from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Variants of SARSCoV-2 have caused distinct COVID-19 surges worldwide. The Omicron variant has replaced other variants as a cause of COVID-19 in the Republic of Korea. Fortunately, COVID-19 patients infected with Omicron have a decreased disease severity. Tuberculosis (TB) remains a major public health threat worldwide, and the incidence of TB is still high in the Republic of Korea. We report the case of a deceased illegal migrant who died at home. An autopsy revealed fatal pneumonia with pulmonary TB caused by the Omicron subvariant BA.2 of SARS-CoV-2. We assumed that a superimposed SARS-CoV-2 infection caused this fatal pneumonia with a previous TB infection. After a comprehensive postmortem (PM) examination, including gross dissection, microscopic studies, PM computed tomography, and PM laboratory tests, the cause of death was determined to be pneumonia, and the death manner was natural. We present this case with a comprehensive PM examination from the perspective of forensic pathology and the public healthcare system.

Background: There is currently a lack of evidence-based postresuscitation or postmortem guidelines for patients with out-of-hospital cardiac arrest (OHCA) in the setting of an emerging infectious disease. This study aimed to develop and validate a multimodal screening tool that aids in predicting the disease confirmation in emergency situations and patients with OHCA during a coronavirus disease 2019 (COVID-19) outbreak. Materials and Methods: We conducted a retrospective, multicenter observational study of adult patients with OHCA in Daegu, Korea. To identify the potential predictors that could be used in screening tools in the emergency department, we applied logistic regression to data collected from March 1 to March 14. The prediction performance of the screening variables was then assessed and validated on the data of patients with OHCA who were treated between February 19 and March 31, 2020. General patient characteristics and hematological findings of the COVID-19-negative and COVID-19-positive groups were compared. We also evaluated confirmation test criteria as predictors for COVID-19 positivity in patients with OHCA. Results: Advanced age, body temperature, and abnormal chest X-ray (CXR) revealed significant predictive ability in the derivation cohort. Of the 184 adult patients with OHCA identified in the validation cohort, 80 patients were included in the analysis. Notably, 9 patients were positive and 71 were negative on the COVID-19 reverse transcription polymerase chain reaction test. Five patients (55.6%) in the COVID-19-positive group had a fever before OHCA, and 12 (16.9%) of the COVID-19-negative group had a fever before OHCA (P = 0.018).Eight patients (88.9%) in the COVID-19-positive group had a CXR indicating pneumonic infiltration. Of the criteria for predicting COVID-19, fever or an abnormal CXR had a sensitivity of 100% (95% confidence interval [CI]: 65.4 – 100) and a specificity of 22.5% (95% CI: 13.5 – 34.0). Conclusion The screening tools that combined fever or abnormal CXR had a good discriminatory ability for COVID-19 infection in adult patients with OHCA. Therefore, during the COVID-19 outbreak period, it is recommended to suspect COVID-19 infection and perform COVID-19 test if patients present with a history of fever or show abnormal findings in postmortem CXR

Background: There is currently a lack of evidence-based postresuscitation or postmortem guidelines for patients with out-of-hospital cardiac arrest (OHCA) in the setting of an emerging infectious disease. This study aimed to develop and validate a multimodal screening tool that aids in predicting the disease confirmation in emergency situations and patients with OHCA during a coronavirus disease 2019 (COVID-19) outbreak. Materials and Methods: We conducted a retrospective, multicenter observational study of adult patients with OHCA in Daegu, Korea. To identify the potential predictors that could be used in screening tools in the emergency department, we applied logistic regression to data collected from March 1 to March 14. The prediction performance of the screening variables was then assessed and validated on the data of patients with OHCA who were treated between February 19 and March 31, 2020. General patient characteristics and hematological findings of the COVID-19-negative and COVID-19-positive groups were compared. We also evaluated confirmation test criteria as predictors for COVID-19 positivity in patients with OHCA. Results: Advanced age, body temperature, and abnormal chest X-ray (CXR) revealed significant predictive ability in the derivation cohort. Of the 184 adult patients with OHCA identified in the validation cohort, 80 patients were included in the analysis. Notably, 9 patients were positive and 71 were negative on the COVID-19 reverse transcription polymerase chain reaction test. Five patients (55.6%) in the COVID-19-positive group had a fever before OHCA, and 12 (16.9%) of the COVID-19-negative group had a fever before OHCA (P = 0.018).Eight patients (88.9%) in the COVID-19-positive group had a CXR indicating pneumonic infiltration. Of the criteria for predicting COVID-19, fever or an abnormal CXR had a sensitivity of 100% (95% confidence interval [CI]: 65.4 – 100) and a specificity of 22.5% (95% CI: 13.5 – 34.0). Conclusion The screening tools that combined fever or abnormal CXR had a good discriminatory ability for COVID-19 infection in adult patients with OHCA. Therefore, during the COVID-19 outbreak period, it is recommended to suspect COVID-19 infection and perform COVID-19 test if patients present with a history of fever or show abnormal findings in postmortem CXR