Severe acquired hemophilia A associated with COVID-19 vaccination: A case report and literature review.

RATIONALE: Acquired hemophilia A (AHA) is a rare autoimmune disease caused by an antibody that inhibits coagulation factor VIII activity. More than half of patients with AHA cannot identify underlying disorders. The remaining patients are associated with malignancies, autoimmune diseases, skin diseases, infections, and medications. Here, we present a case of 56-year-old Korean man with underlying hypertension, dyslipidemia, and diabetes mellitus who developed AHA following the second dose of BNT162b2 COVID-19 vaccination. PATIENT CONCERNS: He presented with a large 20 × 30 cm-sized hematoma along the psoas muscle and intracranial hemorrhage, necessitating intensive care with mechanical ventilation and continuous renal replacement therapy. Laboratory testing demonstrated that activated partial thromboplastin time and prothrombin times were 74.7 seconds (normal range 29-43 seconds) and 17.2 seconds (normal range 12.5-14.7 seconds), respectively. DIAGNOSES: Laboratory tests confirmed AHA with undetectable factor VIII activity (<1.5%) and a positive factor VIII antibody with a titer of 8.49 Bethesda units/mL. INTERVENTIONS: Recombinant factor VIIa (NovoSeven®) was administered every 2 hours to control the bleeding, alongside immunosuppression with methylprednisolone 1 mg/kg daily and cyclophosphamide 2 mg/kg daily to eliminate the autoantibody. OUTCOMES: Despite the treatments, the patient developed sepsis and succumbed 14 weeks after admission. LESSONS: This rare case underscores the importance of monitoring for AHA following COVID-19 vaccination. Although the benefits outweigh the risks of vaccination, AHA should be considered in the differential diagnosis of unusual bleeding following the vaccinations. Early diagnosis and management before severe bleeding are critical for successfully controlling life-threatening bleeding.

Impact of multidrug resistance on outcomes in hematologic cancer patients with bacterial bloodstream infections.

Despite the improved outcomes in patients with hematological malignancies, infections caused by multidrug-resistant organisms (MDROs) pose a new threat to these patients. We retrospectively reviewed the patients with hematological cancer and bacterial bloodstream infections (BSIs) at a tertiary hospital between 2003 and 2022 to assess the impact of MDROs on outcomes. Among 328 BSIs, 81 (24.7%) were caused by MDROs. MDRO rates increased from 10.3% (2003-2007) to 39.7% (2018-2022) (P < 0.001). The 30-day mortality rate was 25.0%, which was significantly higher in MDRO-infected patients than in non-MDRO-infected patients (48.1 vs. 17.4%; P < 0.001). The observed trend was more pronounced in patients with newly diagnosed diseases and relapsed/refractory disease but less prominent in patients in complete remission. Among MDROs, carbapenem-resistant Gram-negative bacteria exhibited the highest mortality, followed by vancomycin-resistant enterococci, methicillin-resistant Staphylococcus aureus, and extended-spectrum ß-lactamase-producing Enterobacteriaceae. Multivariate analysis identified independent risk factors for 30-day mortality as age ≥ 65 years, newly diagnosed disease, relapsed/refractory disease, MDROs, polymicrobial infection, CRP ≥ 20 mg/L, and inappropriate initial antibiotic therapy. In conclusion, MDROs contribute to adverse outcomes in patients with hematological cancer and bacterial BSIs, with effects varying based on the underlying disease status and causative pathogens. Appropriate initial antibiotic therapy may improve patient outcomes.

Can Older Adult Patients with Hip Fractures Have Their Discharge Destination Predicted by Physical Performance Measures?

Background and Objectives: The majority of patients who undergo hip fracture surgery do not recover their former level of physical function; hence, it is essential to establish a specific rehabilitation strategy for maximal functional recovery of patients after a hip fracture. Knowing which indicators of physical function in hip fracture patients have a significant impact on the decision regarding the place or timing of discharge would make it possible to plan and prepare for discharge as soon as possible. Therefore, this study aimed to investigate the relationship between physical function and discharge destination for older adult patients with hip fracture. Materials and Methods: In this retrospective cohort study, 150 hip fracture patients (mean age 78.9 ± 10.6 years) between January 2019 and June 2021 were enrolled. Patients were categorized into two groups according to their discharge destination, either home or facility. Demographic and disease-related characteristic data were collected from the medical records. All the patients completed performance-based physical function tests including the 10 Meter Walk Test (10MWT), Timed Up and Go test (TUG), Koval's grade, and Berg Balance Scale (BBS) at the start of rehabilitation and at discharge. A backward stepwise binary logistic regression analysis was then performed to determine the independent factors of the discharge destination. Results: The home discharge group had a significantly lower Koval's grade, lower TUG, higher BBS both at baseline and discharge, and younger age. Backward stepwise logistic binary regression analysis showed that TUG, BBS, and 10MWT at baseline and discharge were significant variables affecting the discharge destination after hip fracture. Conclusions: These results demonstrate that balance and gait in older adult patients with hip fractures are highly influential factors in the determining the discharge destination.

Poly(l-threonine-co-l-threonine Succinate) Thermogels for Sustained Release of Lixisenatide.

Negatively charged poly(l-Thr-co-l-Thr succinate) (PTTs) was developed as a new thermogel. Aqueous PTT solutions underwent thermogelation over a concentration range of 6.0-8.3 wt %. Dynamic light scattering, FTIR, 1H NMR, and COSY spectra revealed the partial strengthening of the ß-sheet conformation and the dehydration of PTTs during the transition. Extendin-4 was released from the PTTs thermogel with a large initial burst release, whereas positively charged lixisenatide significantly reduced its initial burst release to 25%, and up to 77% of the dose was released from the gel over 14 days. In vivo study revealed a high plasma concentration of lixisenatide over 5 days and hypoglycemic efficacy was observed for type II diabetic rats over 7-10 days. The biocompatible PTTs were degraded by subcutaneous enzymes. This study thus demonstrates an effective strategy for reducing the initial burst release of protein drugs from thermogels with the introduction of electrostatic interactions between the drug and the thermogel.

Cardiovascular disease risk and associated physical activity factors in gastrointestinal cancer survivors.

INTRODUCTION: Although the risk of CVD is increased in cancer survivors, few studies have investigated the CVD risk in survivors of gastrointestinal (GI) cancer. Therefore, we evaluated the CVD risk using the 10-year atherosclerotic cardiovascular disease (ASCVD) risk score for GI cancer survivors and associated physical activity factors. METHODS: Using the 2014-2019 Korean National Health and Nutrition Examination Surveys, data were collected for 262 GI cancer survivors and 1,310 cancer-free controls matched at a 1:5 ratio based on age and sex. The International Physical Activity Questionnaire Short-Form was used to assess physical activity, and the Euro QoL Questionnaire 5-Dimensional Classification (EQ-5D) was used to assess the health-related quality of life. RESULTS: A multiple logistic regression analysis demonstrated a lower risk of ASCVD in GI cancer survivors than in controls (adjusted odds ratio [aOR] = 0.73, 95% confidence interval [CI] = 0.55-0.97). Moreover, the risk of having a high ASCVD score was significantly lower in individuals who performed sufficient aerobic physical activity (aOR = 0.59, 95% CI = 0.47-0.75) and those with an EQ-5D score 1 or 2 (aOR = 0.36, 95% CI = 0.20-0.65 and aOR = 0.31, 95% CI = 0.16-0.58, respectively). CONCLUSIONS: This population-based study demonstrated that engaging in sufficient physical activity can reduce the ASCVD risk among GI cancer survivors.

Stimulator of Interferon Gene Agonists Induce an Innate Antiviral Response against Influenza Viruses.

The devastating effects of COVID-19 have highlighted the importance of prophylactic and therapeutic strategies to combat respiratory diseases. Stimulator of interferon gene (STING) is an essential component of the host defense mechanisms against respiratory viral infections. Although the role of the cGAS/STING signaling axis in the innate immune response to DNA viruses has been thoroughly characterized, mounting evidence shows that it also plays a key role in the prevention of RNA virus infections. In this study, we investigated the role of STING activation during Influenza virus (IFV) infection. In both mouse bone marrow-derived macrophages and monocytic cell line THP-1 differentiated with PMA, we found that dimeric amidobenzimidazole (diABZI), a STING agonist, had substantial anti-IFV activity against multiple strains of IFV, including A/H1N1, A/H3N2, B/Yamagata, and B/Victoria. On the other hand, a pharmacological antagonist of STING (H-151) or the loss of STING in human macrophages leads to enhanced viral replication but suppressed IFN expression. Furthermore, diABZI was antiviral against IFV in primary air-liquid interface cultures of nasal epithelial cells. Our data suggest that STING agonists may serve as promising therapeutic antiviral agents to combat IFV.

Predictive Value of Ultrasound-Measured Quadriceps Depth and Frailty Status for Hypotension in Older Patients Undergoing Reverse Total Shoulder Arthroplasty in the Beach Chair Position under General Anesthesia.

The beach chair position (BCP) is widely used in shoulder surgery; however, it frequently leads to hypotension. Hypotension in BCP is prevalent among older patients who are at risk of secondary complications such as ischemic injuries. Therefore, this prospective study aimed to investigate the association and predictive value of frailty, as assessed by ultrasound-measured quadriceps depth and questionnaire, in patients aged ≥65 years undergoing elective shoulder surgery under general anesthesia. A multivariable logistic regression analysis was performed to identify independent risk factors for hypotension in BCP under general anesthesia. Receiver operating characteristic curves were constructed to assess the predictive values of various parameters. The results indicated that a quadriceps depth < 2.3 cm and BCP for an extended period significantly increased the risk of hypotension. The combined consideration of quadriceps depth < 2.3 cm and frailty demonstrated markedly superior predictive power compared with each factor individually. In conclusion, the study findings facilitate the screening and identification of risk factors for older patients undergoing surgery in BCP, thereby enhancing perioperative management.

Assessment of malignant potential for HPV types 16, 52, and 58 in the uterine cervix within a Korean cohort.

High-risk human papillomavirus (HR-HPV) is the primary carcinogen in uterine cervical carcinoma. While genotype-specific carcinogenic risks have been extensively studied in Western populations, data from Korean are sparse. This study evaluates the malignant potential of the three most prevalent HR-HPVs in Korea: HPV16, HPV52, and HPV58. We analyzed 230 patients who underwent cervical conization and had been tested for HPV within a year prior to the procedure, excluding those with multiple infections. This analysis was confined to patients with single HPV infections and assessed outcomes of CIN3+, which includes carcinoma in situ (CIN3) and invasive carcinoma. The incidence of invasive cervical cancer was 6.7% for HPV16, 1.7% for HPV52, and 2.0% for HPV58; however, these differences were not statistically significant (p = 0.187). The rate of CIN3+ for HPV16, HPV52, and HPV58 were 70.6%, 51.7%, and 58.8%, respectively. Despite the small sample size, which may limit the robustness of statistical analysis, the data suggest a higher observed risk with HPV16. These findings highlight the need for vigilant clinical management tailored to specific HPV genotypes and support the implementation of a nine-valent vaccine in Korea. Physicians should be aware of these genotype-specific risks when treating patients.

Primary Solid Pseudopapillary Tumor of the Ovary: A Case Report and Review of the Literature.

INTRODUCTION: Solid pseudopapillary neoplasms (SPNs) are rare and mainly originate from the pancreas. SPNs originating from the ovary (SPN-O) are extremely rare, and only 13 cases have been reported in the English literature since 2010. CASE: We report a 31-year-old woman with SPN-O accompanied by multiple metastases in the abdominal cavity. The patient underwent staging surgery and cytoreduction. Furthermore, the multidisciplinary board decided on adjuvant chemotherapy with an FP regimen (fluorouracil plus cisplatin) because a microscopic metastasis was discovered in the peritoneum near the appendix. Next-generation sequencing showed some pathologic mutations of oncogenes/cancer-associated genes, including CTNNB1 and TP53. This is the fourteenth case of SPN-O and the first one to demonstrate the TP53 pathogenic mutant variant in SPN-O. The patient showed 8 months of disease-free survival until February 2024. CONCLUSION: The combination of R0 cytoreduction with FOLFIRI chemotherapy appears to be an effective and feasible treatment option.

Impact of Neoadjuvant Chemotherapy (NAC) on Biomarker Expression in Breast Cancer.

Background and Objectives: This study aimed to explore biomarker change after NAC (neoadjuvant chemotherapy) and to investigate biomarker expression as a prognostic factor in patients with residual disease (RD) after NAC. Materials and Methods: We retrospectively evaluated 104 patients with invasive breast cancer, who underwent NAC and surgery at Pusan National University Hospital from 2015 to July 2022. The expression of the biomarker was assessed, and the overall survival (OS) and disease-free survival (DFS) were investigated. Results: After NAC, 24 patients (23.1%) out of 104 total patients had a pathological complete response (pCR). We found that changes in at least one biomarker were observed in 41 patients (51.2%), among 80 patients with RD. In patients with RD after NAC (n = 80), a subtype change was identified in 20 patients (25.0%). Any kind of change in the HER2 status was present 19 (23.7%) patients. The hormone receptor (HR)+/HER2+ subtype was significantly associated with better disease-free survival (DFS) (HR, 0.13; 95% CI, 0.02-0.99; p = 0.049). No change in p53 was associated with better DFS, and negative-to-positive change in p53 expression after NAC was correlated with worse DFS (p < 0.001). Negative-to-positive change in p53 was an independent, worse DFS factor in the multivariate analysis (HR,18.44; 95% CI, 1.86-182.97; p = 0.013). Conclusions: Biomarker change and subtype change after NAC were not infrequent, which can affect the further treatment strategy after surgery. The expression change of p53 might have a prognostic role. Overall, we suggest that the re-evaluation of biomarkers after NAC can provide a prognostic role and is needed for the best decision to be made on further treatment.

A survey of current practices in post-polypectomy surveillance in Korea.

BACKGROUND/AIMS: We investigated the clinical practice patterns of post-polypectomy colonoscopic surveillance among Korean endoscopists. METHODS: In a web-based survey conducted between September and November 2021, participants were asked about their preferred surveillance intervals and the patient age at which surveillance was discontinued. Adherence to the recent guidelines of the U.S. Multi-Society Task Force on Colorectal Cancer (USMSTF) was also analyzed. RESULTS: In total, 196 endoscopists completed the survey. The most preferred first surveillance intervals were: a 5-year interval after the removal of 1-2 tubular adenomas < 10 mm; a 3-year interval after the removal of 3-10 tubular adenomas < 10 mm, adenomas ≥ 10 mm, tubulovillous or villous adenomas, ≤ 20 hyperplastic polyps < 10 mm, 1-4 sessile serrated lesions (SSLs) < 10 mm, hyperplastic polyps or SSLs ≥ 10 mm, and traditional serrated adenomas; and a 1-year interval after the removal of adenomas with highgrade dysplasia, >10 adenomas, 5-10 SSLs, and SSLs with dysplasia. In piecemeal resections of large polyps ( > 20 mm), surveillance colonoscopy was mostly preferred after 1 year for adenomas and 6 months for SSLs. The mean USMSTF guideline adherence rate was 30.7%. The largest proportion of respondents (40.8%-55.1%) discontinued the surveillance at the patient age of 80-84 years. CONCLUSIONS: A significant discrepancy was observed between the preferred post-polypectomy surveillance intervals and recent international guidelines. Individualized measures are required to increase adherence to the guidelines.

Preadipocytes potentiate melanoma progression and M2 macrophage polarization in the tumor microenvironment.

Melanoma, the deadliest skin cancer, originates from epidermal melanocytes. The influence of preadipocytes on melanoma is less understood. We co-cultured mouse melanoma B16 cells with 3T3L1 preadipocytes to form mixed spheroids and observed increased melanoma proliferation and growth compared to B16-only spheroids. Metastasis-related proteins YAP, TAZ, and PD-L1 levels were also higher in mixed spheroids. Treatment with exosome inhibitor GW4869 halted melanoma growth and reduced expression of these proteins, suggesting exosomal crosstalk between B16 and 3T3L1 cells. MiR-155 expression was significantly higher in mixed spheroids, and GW4869 reduced its levels. Additionally, co-culturing with Raw264.7 macrophage cells increased M2 markers IL-4 and CD206 in Raw264.7 cells, effects that were diminished by GW4869. These results indicate that preadipocytes may enhance melanoma progression and metastasis via exosomal interactions.

Predictors of histologic remission in patients with biologic-naïve, moderate-to-severe ulcerative colitis treated with first-line biologic agents and small-molecule drugs: a single-center, retrospective cohort study.

Background/Aims: The prevalence and incidence of ulcerative colitis (UC) in Korea is increasing. Each patient has a different disease course and treatment response. Recently, with the development of biologic agents, histological remission has become a treatment goal. In this study, we aimed to identify the predictors of histological remission after first-line biologic agent treatment in patients with biologic agent-naïve UC. Methods: We retrospectively analyzed the medical records of 92 patients who had been diagnosed with UC and treated with first-line biologic agent treatment at our center, between 2015 and 2022. The clinical characteristics, laboratory test results, and endoscopic and biopsy findings were analyzed. Histological remission was defined as the absence of cryptitis, crypt abscesses, and inflammatory cells on histology. Univariate and multivariate logistic regression analyses were performed to identify the predictors of histological remission after first-line treatment. Results: Of the total 92 patients, 25 (27.2%) achieved histological remission. Each cohort had a varied body mass index (BMI) distribution, with a statistically significant overweight ratio, as defined by the Asian-Pacific BMI category of 23-25 kg/m2, of 48.0% in the histological remission cohort (P= 0.026). A causal correlation between the overweight category and histological remission was confirmed (odds ratio, 3.883; 95% confidence interval, 1.141-13.212; P= 0.030). Conclusions: We confirmed that the overweight category was a predictor of histological remission after first-line treatment with a biological agent. However, as BMI does not account for skeletal muscle mass, future studies are required to confirm the correlation between skeletal muscle mass and histological remission.

Recent trends in the epidemiology and clinical outcomes of inflammatory bowel disease in South Korea, 2010-2018.

BACKGROUND: Inflammatory bowel disease (IBD) was previously regarded as a Western disease; however, its incidence is increasing in the East. The epidemiology of IBD in Asia differs significantly from the patterns in the West. AIM: To comprehensively investigate the epidemiology of IBD in South Korea, including its incidence, prevalence, medication trends, and outcomes. METHODS: We analyzed claims data from the Health Insurance Review and Assessment Service and Rare and Intractable Diseases (RIDs), operated by the National Health Insurance Service of South Korea. Patients with IBD were identified based on the International Classification of Diseases, Tenth Revision, and RID diagnostic codes for Crohn's disease (CD) and ulcerative colitis (UC) from 2010 to 2018. RESULTS: In total, 14498 and 31409 patients were newly diagnosed with CD and UC, respectively, between 2010 and 2018. The annual average incidence of CD was 3.11 cases per 105 person-years, and that of UC was 6.74 cases per 105 person-years. Since 2014, the incidence rate of CD has been stable, while that of UC has steadily increased, shifting the peak age group from 50-year-olds in 2010 to 20-year-olds in 2018. The CD and UC prevalence increased consistently over the study period; the use of 5-aminosalicylates and corticosteroids gradually decreased, while that of immunomodulators and biologics steadily increased in both CD and UC. The clinical outcomes of IBD, such as hospitalization and surgery, decreased during the study period. CONCLUSION: The CD incidence has been stable since 2014, but that of UC has increased with a shift to a younger age at peak incidence between 2010 and 2018. IBD clinical outcomes improved over time, with increased use of immunomodulators and biologics.

TFE3/PI3K/Akt/mTOR Axis in Renal Cell Carcinoma Affects Tumor Microenvironment.

The role of the phosphatidylinositol 3-kinase (PI3K)/Akt pathway in renal cell carcinoma (RCC) progression, metastasis, and resistance to therapies has not been investigated thoroughly. Transcription factor E3 (TFE3) expression is related to a poorer prognosis and tumor microenvironment in patients with RCC. This study aimed to determine the relationship between TFE3 and the PI3K/Akt pathway. TFE3 down-regulation was achieved by transient transfection of siRNA and shRNA in UOK146 cells. TFE3 overexpression was induced by transient transfection with pcDNA3.1 encoding the constitutively active form of TFE3. The cells were treated with mammalian target of rapamycin (mTOR) and PI3K inhibitors. Western blot was performed to detect TFE3, programmed death-ligand 1, phospho-Akt, and Akt. Phospho-Akt expression increased significantly upon TFE3 down-regulation, and decreased significantly upon up-regulation. When RCC cells were treated with a PI3K inhibitor (LY294002), TFE3 expression increased and phospho-Akt expression decreased. Data from this study indicate that TFE3 plays a role in the PI3K/Akt pathway in RCC. The results of this study suggest that PI3K/Akt inhibitors may aid in the treatment of patients with RCC by affecting the tumor microenvironment.

Pericardiocentesis versus window formation in malignant pericardial effusion: trends and outcomes.

OBJECTIVES: Malignant pericardial effusion (MPE) in patients with cancer is associated with poor prognosis. This study aimed to compare clinical outcomes in patients with cancer who underwent pericardiocentesis versus pericardial window formation. METHODS: In the present study, 765 consecutive patients with cancer (mean age 58.4 years, 395 men) who underwent pericardial drainage between 2003 and 2022 were retrospectively analysed. All-cause death and MPE recurrence were compared based on the drainage method (pericardiocentesis vs pericardial window formation) and time period (period 1: 2003-2012; period 2: 2013-2022). RESULTS: Pericardiocentesis was performed in 639 (83.5%) patients and pericardial window formation in 126 (16.5%). There was no difference in age, sex distribution, proportion of metastatic or relapsed cancer, and chemotherapy status between the pericardiocentesis and pericardial window formation groups. Difference was not found in all-cause death between the two groups (log-rank p=0.226) regardless of the period. The pericardial window formation group was associated with lower MPE recurrence than the pericardiocentesis group (6.3% vs 18.0%, log-rank p=0.001). This advantage of pericardial window formation was more significant in period 2 (18.1% vs 1.3%, log-rank p=0.005). In multivariate analysis, pericardial window formation was associated with lower MPE recurrence (HR: 0.31, 95% CI: 0.15 to 0.63, p=0.001); younger age, metastatic or relapsed cancer, and positive malignant cells in pericardial fluid were associated with increased recurrence. CONCLUSION: In patients undergoing pericardial drainage for MPE, pericardial window formation showed mortality outcomes comparable with pericardiocentesis and was associated with lower incidence of MPE recurrence.

Migraine is associated with the development of adult patients with inflammatory bowel disease: a nationwide, population-based study.

It has been reported that migraine is more common in patients with inflammatory bowel disease (IBD) than in general. However, the impact of migraine on the development of IBD has not yet been elucidated. The aim of this study was to determine the association between migraine and the development of IBD. This nationwide population-based cohort study was conducted using the Korean National Health Insurance Service (NHIS) database. A total of 10,628,070 people aged 20 years or older who had undergone a national health examination conducted by the NHIS in 2009 were followed up until 2017. The study population was divided into two groups according to the presence or absence of migraine. We analyzed the incidence of newly developed IBD, Crohn's disease (CD), or ulcerative colitis (UC) during the follow-up period. The incidence of IBD was significantly higher in patients with migraine (adjusted hazard ratio [aHR] with 95% confidence interval [95%CI] of 1.31 [1.173-1.468], p < 0.001), CD (aHR with 95%CI of 1.58 [1.237-2.013], p < 0.001) and UC (aHR with 95%CI of 1.26 [1.106-1.424], p < 0.001) than in those without migraine. After 5 years of follow-up, those with migraine showed curves implying cumulative incidences of IBD with a steep increase, especially for CD. In subgroup analysis, migraine was associated with the risk of UC in males (aHR, 1.431 vs. 1.117; interaction p = 0.042). Migraine is significantly associated with the development of IBD. Patients with migraine should be monitored carefully for the development of IBD.