A Case Study of Stress-Induced Alopecia Areata Treated with Hominis Placenta Pharmacopunture.

The purpose of this study is to report the clinical application of Hominis Placenta Pharmacopunture for Alopecia areata. Patient was diagnosed as stress-induced Alopecia areata 1 years ago. To reduce symptom, we treated a patient 8 times using Hominis Placenta Pharmacopunture. Hominis Placenta was injected subcutaneously into the lesion of head scalp alopecia. According to photographs, the lesion had been replaced with new terminal hair and the size of the lesion had decreased. This case has shown that stress-induced Alopecia areata patient could be treated by Hominis Placenta Pharmacopunture.

Prognosis of subsequent pregnancy in uterine necrosis after uterine artery embolization.

In an 8-year period at two medical center, 138 patients underwent uterine artery embolization, and 11 of them were diagnosed with uterine necrosis. Among them, three were successfully conceived. However, one of them developed an arteriovenous malformation after an artificial abortion, and another experienced complications, including placenta previa and placenta accreta spectrum, which resulted in early preterm delivery and recurrent postpartum hemorrhage, necessitating subtotal hysterectomy. Therefore, it is crucial to prepare for potential adverse pregnancy outcomes in subsequent pregnancies for patients with a history of uterine necrosis.

Association between the COVID-19 pandemic and childhood development aged 30 to 36 months in South Korea, based on the National health screening program for infants and children database.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has had a significant impact on the neurodevelopment of children. However, the precise effects of the virus and the social consequences of the pandemic on pediatric neurodevelopment are not yet fully understood. We aimed to compare the neurodevelopment of children between before and during the COVID-19 pandemic, as well as examine the impact of socioeconomic status (SES) and regional differences on the development. METHODS: The study used the Korean Developmental Screening Test to compare the difference in the risk of neurodevelopmental delay between before and during the COVID-19 pandemic. Multivariable logistic regression analysis was conducted to identify the relationship between experiencing the COVID-19 pandemic and the risk of neurodevelopmental delay. Stratified analyses were performed to determine whether the developmental delays caused by the pandemic's impact varied depending on SES or regional inequality. RESULTS: This study found an association between the experience of COVID-19 and a higher risk of neurodevelopmental delay in communication (adjusted OR [aOR]: 1.21, 95% confidence interval [CI]: 1.19, 1.22; P-value: < 0.0001) and social interaction (aOR: 1.15, 95% CI: 1.13, 1.17; P-value: < 0.0001) domains among children of 30-36 months' ages. Notably, the observed association in the Medicaid group of children indicates a higher risk of neurodevelopmental delay compared to those in the non-Medicaid group. CONCLUSIONS: These findings highlight the need to be concerned about the neurodevelopment of children who experienced the COVID-19 pandemic. The study also calls for increased training and support for Medicaid children, parents, teachers, and healthcare practitioners. Additionally, policy programs focused on groups vulnerable to developmental delays are required.

3D epigenomics and 3D epigenopathies.

Mammalian genomes are intricately compacted to form sophisticated 3-dimensional structures within the tiny nucleus, so called 3D genome folding. Despite their shapes reminiscent of an entangled yarn, the rapid development of molecular and next-generation sequencing technologies (NGS) has revealed that mammalian genomes are highly organized in a hierarchical order that delicately affects transcription activities. An increasing amount of evidence suggests that 3D genome folding is implicated in diseases, giving us a clue on how to identify novel therapeutic approaches. In this review, we will study what 3D genome folding means in epigenetics, what types of 3D genome structures there are, how they are formed, and how the technologies have developed to explore them. We will also discuss the pathological implications of 3D genome folding. Finally, we will discuss how to leverage 3D genome folding and engineering for future studies.

Association between body mass index and results of cryoballoon ablation in Korean patients with atrial fibrillation: an analysis from Korean Heart Rhythm Society Cryoablation registry.

BACKGROUND: Pulmonary vein isolation using cryoablation is effective and safe in patients with atrial fibrillation (AF). Although both obesity and underweight are associated with a higher risk for incident AF, there is limited data on the efficacy and safety following cryoablation according to body mass index (BMI) especially in Asians. METHODS: Using the Korean Heart Rhythm Society Cryoablation registry, a multicenter registry of 12 tertiary hospitals, we analyzed AF recurrence and procedure-related complications after cryoablation by BMI (kg/m2) groups (BMI<18.5, underweight, UW; 18.5-23, normal, NW; 23-25, overweight, OW; 25-30, obese Ⅰ, OⅠ; ≥30, obese Ⅱ, OⅡ). RESULTS: A total of 2,648 patients were included (median age 62.0 years; 76.7% men; 55.6% non-paroxysmal AF). Patients were categorized by BMI groups; 0.9% UW, 18.7% NW, 24.8% OW, 46.1% OI, and 9.4% OII. UW patients were the oldest, and had least percentage of non-paroxysmal AF (33.3%). During a median follow-up of 1.7 years, atrial arrhythmia recurred in 874 (33.0%) patients (incidence rate, 18.9 per 100 person-year). After multivariable adjustment, the risk of AF recurrence was higher in UW group compared to NW group (adjusted hazard ratio, 95% confidence interval; 2.55, 1.18-5.50, p=0.02). Procedure-related complications occurred in 123 (4.7%) patients and the risk was higher for UW patients (odds ratio, 95% confidence interval; 2.90, 0.94-8.99, p=0.07), mainly due to transient phrenic nerve palsy. CONCLUSION: UW patients showed a higher risk of AF recurrence after cryoablation compared to NW patients. Also, careful attention is needed on the occurrence of phrenic nerve palsy in UW patients.

Functional Outcomes Associated With Blood Pressure Decrease After Endovascular Thrombectomy.

Importance: The associations between blood pressure (BP) decreases induced by medication and functional outcomes in patients with successful endovascular thrombectomy remain uncertain. Objective: To evaluate whether BP reductions induced by intravenous BP medications are associated with poor functional outcomes at 3 months. Design, Setting, and Participants: This cohort study was a post hoc analysis of the Outcome in Patients Treated With Intra-Arterial Thrombectomy-Optimal Blood Pressure Control trial, a comparison of intensive and conventional BP management during the 24 hours after successful recanalization from June 18, 2020, to November 28, 2022. This study included 302 patients who underwent endovascular thrombectomy, achieved successful recanalization, and exhibited elevated BP within 2 hours of successful recanalization at 19 stroke centers in South Korea. Exposure: A BP decrease was defined as at least 1 event of systolic BP less than 100 mm Hg. Patients were divided into medication-induced BP decrease (MIBD), spontaneous BP decrease (SpBD), and no BP decrease (NoBD) groups. Main Outcomes and Measures: The primary outcome was a modified Rankin scale score of 0 to 2 at 3 months, indicating functional independence. Primary safety outcomes were symptomatic intracerebral hemorrhage within 36 hours and mortality due to index stroke within 3 months. Results: Of the 302 patients (median [IQR] age, 75 [66-82] years; 180 [59.6%] men), 47 (15.6%)were in the MIBD group, 39 (12.9%) were in the SpBD group, and 216 (71.5%) were in the NoBD group. After adjustment for confounders, the MIBD group exhibited a significantly smaller proportion of patients with functional independence at 3 months compared with the NoBD group (adjusted odds ratio [AOR], 0.45; 95% CI, 0.20-0.98). There was no significant difference in functional independence between the SpBD and NoBD groups (AOR, 1.41; 95% CI, 0.58-3.49). Compared with the NoBD group, the MIBD group demonstrated higher odds of mortality within 3 months (AOR, 5.15; 95% CI, 1.42-19.4). The incidence of symptomatic intracerebral hemorrhage was not significantly different among the groups (MIBD vs NoBD: AOR, 1.89; 95% CI, 0.54-5.88; SpBD vs NoBD: AOR, 2.75; 95% CI, 0.76-9.46). Conclusions and Relevance: In this cohort study of patients with successful endovascular thrombectomy after stroke, MIBD within 24 hours after successful recanalization was associated with poor outcomes at 3 months. These findings suggested lowering systolic BP to below 100 mm Hg using BP medication might be harmful.

Impact of the early phase of the COVID-19 pandemic on emergency department-to-intensive care unit admissions in Korea: an interrupted time-series analysis.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic resulted in significant disruptions to critical care systems globally. However, research on the impact of the COVID-19 pandemic on intensive care unit (ICU) admissions via the emergency department (ED) is limited. Therefore, this study evaluated the changes in the number of ED-to-ICU admissions and clinical outcomes in the periods before and during the pandemic. METHODS: We identified all adult patients admitted to the ICU through level 1 or 2 EDs in Korea between February 2018 and January 2021. February 2020 was considered the onset point of the COVID-19 pandemic. The monthly changes in the number of ED-to-ICU admissions and the in-hospital mortality rates before and during the COVID-19 pandemic were evaluated using interrupted time-series analysis. RESULTS: Among the 555,793 adult ED-to-ICU admissions, the number of ED-to-ICU admissions during the pandemic decreased compared to that before the pandemic (step change, 0.916; 95% confidence interval [CI] 0.869-0.966], although the trend did not attain statistical significance (slope change, 0.997; 95% CI 0.991-1.003). The proportion of patients who arrived by emergency medical services, those transferred from other hospitals, and those with injuries declined significantly among the number of ED-to-ICU admissions during the pandemic. The proportion of in-hospital deaths significantly increased during the pandemic (step change, 1.054; 95% CI 1.003-1.108); however, the trend did not attain statistical significance (slope change, 1.001; 95% CI 0.996-1.007). Mortality rates in patients with an ED length of stay of ≥ 6 h until admission to the ICU rose abruptly following the onset of the pandemic (step change, 1.169; 95% CI 1.021-1.339). CONCLUSIONS: The COVID-19 pandemic significantly affected ED-to-ICU admission and in-hospital mortality rates in Korea. This study's findings have important implications for healthcare providers and policymakers planning the management of future outbreaks of infectious diseases. Strategies are needed to address the challenges posed by pandemics and improve the outcomes in critically ill patients.

Development of a multiplex droplet digital PCR method for detection and monitoring of Mycobacterium tuberculosis and drug-resistant tuberculosis.

BACKGROUND: The prevalence of multidrug-resistant tuberculosis (MDR-TB) among Korean tuberculosis patients is about 4.1%, which is higher than the OECD average of 2.6%. Inadequate drug use and poor patient compliance increase MDR-TB prevalence through selective pressure. Therefore, prompt detection of drug resistance in tuberculosis patients at the time of diagnosis and quantitative monitoring of these resistant strains during treatment are crucial. METHODS: A multiplex droplet digital PCR (ddPCR) assay was developed and assessed using DNA material of nine Mycobacterium tuberculosis strains with known mutation status that were purchased from the Korean National Tuberculosis Association. We collected a total of 18 MDR-TB residual samples referred for PCR analysis. Total DNA was extracted from the samples and subjected to the quadruplex ddPCR assay. Their results were compared to those of known resistance phenotypes. RESULTS: The analytical sensitivity and specificity of the multiplex ddPCR assay for detecting INH, RIF, EMB, FQ, and SM resistance-causing mutations ranged from 71.43 to 100% and 94.12-100%, respectively. Follow-up sample results showed that the quadruplex ddPCR assay was sensitive enough to detect IS6110 and other mutations even after onset of treatment. CONCLUSIONS: We developed a sensitive and accurate multiplex ddPCR assay that can detect the presence of tuberculosis quantitatively and resistance-conveying mutations concurrently. This tool could aid clinicians in the diagnosis and treatment monitoring of tuberculosis.

The Potential Role of Aripiprazole Augmentation for Major Depressive Disorder with Anxious Distress in Naturalistic Treatment Setting.

Objective: : This study tried to observe clinical benefit of aripiprazole augmentation (ARPA) treatment for major depressive disorder with anxious distress (MDDA) in routine practice. Methods: : Retrospective chart review (n = 41) was conducted for clinical benefit of ARPA in patients with MDDA in routine practice. The primary endpoint was the mean change of Hamilton Anxiety Rating scale (HAMA) total scores from baseline to the endpoint. Additional secondary endpoints were also retrieved. Results: : The changes of primary endpoint HAMA (t = 5.731, -4.6, p = 0.001), and secondary endpoints including Hamilton Depression Rating scale (HAMD, t = 4.284, -3.4, p ＜ 0.001), Clinical Global Impression-Clinical Benefit (CGI-CB, -0.9, t = 1.821, p = 0.026), and Clinical Global Impression Score-Severity (CGI-S, t = 3.556, -0.4, p ＜ 0.001) scores were also significantly improved during the study. No significant adverse events were observed. Conclusion: : This study has shown additional benefit of ARPA treatment for MDDA patients in routine practice. However, adequately-powered and well-controlled studies are necessary for generalization of the present findings.

Assessment of Welfare Problems in Broilers: Focus on Musculoskeletal Problems Associated with Their Rapid Growth.

The growth of the broiler industry has been accompanied with concerns over the environmental and social impacts on intensive production systems, as well as the welfare of the animals themselves. As a result, since the 2000s, there has been growing interest in alternative production systems that improve animal welfare and sustainability. In this context, it is important to prioritize the welfare of broilers in commercial production systems and to use reliable welfare indicators to provide consumers with information about the welfare of the animals they consume. Resource-based measures (RBM) are based on assessing the resources available to the birds in terms of their housing, environment, and management practices, such as stocking density, litter quality, lighting and air quality, etc. Outcome-based measures (OBM), also known as animal-based measures, focus on assessing the actual welfare outcomes for the birds, such as footpad dermatitis, hock burn, contamination or damage to feathers, gait score, mortality, etc. These OBM-based measures are one of the more direct indicators of welfare and can help identify any welfare issues. The present review highlighted the factors that affect animal welfare indicators focused on OBMs which can be used in the commercial broiler farms.

Unusual US Findings of Diffuse Large B-Cell Lymphoma of the Breast: A Case Report.

Lymphoma is an uncommon type of breast malignancy, with low prevalence. The ultrasonographic findings of breast lymphoma have been described as nonspecific. Breast lymphoma most commonly appears as a solitary hypoechoic mass on US, and usually shows hypervascularity on color Doppler US. Herein, we report an unusual case of breast lymphoma that presented as multiple bilateral hyperechoic nodules on US.

Risk factors for progressing to critical illness in patients with hospital-acquired COVID-19.

Background/Aims: Risk factors for progression to critical illness in hospital-acquired coronavirus disease 2019 (COVID-19) remain unknown. Here, we assessed the incidence and risk factors for progression to critical illness and determined their effects on clinical outcomes in patients with hospital-acquired COVID-19. Methods: This retrospective cohort study analyzed patients admitted to the tertiary hospital between January 2020 and June 2022 with confirmed hospital-acquired COVID-19. The primary outcome was the progression to critical illness of hospital- acquired COVID-19. Patients were stratified into high-, intermediate-, or low-risk groups by the number of risk factors for progression to critical illness. Results: In total, 204 patients were included and 37 (18.1%) progressed to critical illness. In the multivariable logistic analysis, patients with preexisting respiratory disease (OR, 3.90; 95% CI, 1.04-15.18), preexisting cardiovascular disease (OR, 3.49; 95% CI, 1.11-11.27), immunocompromised status (OR, 3.18; 95% CI, 1.11-9.16), higher sequential organ failure assessment (SOFA) score (OR, 1.56; 95% CI, 1.28-1.96), and higher clinical frailty scale (OR, 2.49; 95% CI, 1.62-4.13) showed significantly increased risk of progression to critical illness. As the risk of the groups increased, patients were significantly more likely to progress to critical illness and had higher 28-day mortality. Conclusions: Among patients with hospital-acquired COVID-19, preexisting respiratory disease, preexisting cardiovascular disease, immunocompromised status, and higher clinical frailty scale and SOFA scores at baseline were risk factors for progression to critical illness. Patients with these risk factors must be prioritized and appropriately isolated or treated in a timely manner, especially in pandemic settings.

A phase Ib/II trial of capmatinib plus spartalizumab vs. spartalizumab alone in patients with pretreated hepatocellular carcinoma.

Background & aims: This phase Ib/II trial evaluated the safety and efficacy of capmatinib in combination with spartalizumab or spartalizumab alone in patients with advanced hepatocellular carcinoma (HCC). Methods: Eligible patients who had progressed or were intolerant to sorafenib received escalating doses of capmatinib 200 mg, 300 mg, and 400 mg twice a day (bid) plus spartalizumab 300 mg every 3 weeks (q3w) in the phase Ib study. Once the recommended phase II dose (RP2D) was determined, the phase II study commenced with randomised 1:1 treatment with either capmatinib + spartalizumab (n = 32) or spartalizumab alone (n = 30). Primary endpoints were safety and tolerability (phase Ib) and investigator-assessed overall response rate per RECIST v1.1 for combination vs. single-agent arms using a Bayesian logistic regression model (phase II). Results: In phase Ib, the RP2D for capmatinib in combination with spartalizumab was determined to be 400 mg bid. Dose-limiting toxicity consisting of grade 3 diarrhoea was reported in one patient at the capmatinib 400 mg bid + spartalizumab 300 mg q3w dose level. The primary endpoint in the phase II study was not met. The observed overall response rate in the capmatinib + spartalizumab arm was 9.4% vs. 10% in the spartalizumab arm. The most common any-grade treatment-related adverse events (TRAEs, ≥20%) were nausea (37.5%), asthenia and vomiting (28.1% each), diarrhoea, pyrexia, and decreased appetite (25.0% each) in the combination arm; TRAEs ≥10% were pruritus (23.3%), and rash (10.0%) in the spartalizumab-alone arm. Conclusion: Capmatinib at 400 mg bid plus spartalizumab 300 mg q3w was established as the RP2D, with manageable toxicities and no significant safety signals, but the combination did not show superior clinical activity compared with spartalizumab single-agent treatment in patients with advanced HCC who had previously been treated with sorafenib. Impact and implications: Simultaneous targeting of MET and programmed cell death protein 1 may provide synergistic clinical benefit in patients with advanced HCC. This is the first trial to report a combination of capmatinib (MET inhibitor) and spartalizumab (programmed cell death protein 1 inhibitor) as second-line treatment after sorafenib for advanced HCC. The combination did not show superior clinical activity compared with spartalizumab single-agent treatment in patients with advanced HCC who had previously been treated with sorafenib. The results indicate that there is a clear need to identify a reliable predictive marker of response for HCC and to identify patients with HCC that would benefit from the combination of checkpoint inhibitor +/- targeted therapy. Clinical trial number: NCT02795429.

Acupuncture-Induced Abscess in the Retroperitoneal Cavity and Thigh Muscle: A Case Report.

Acupuncture is increasingly being used in Asian countries and is generally considered a relatively safe procedure. However, adverse events have been reported consistently. Therefore, clinicians should be aware of the possibility of acupuncture-related complications and should actively treat serious cases. We report a case of an acupuncture-induced large abscess in the retroperitoneal cavity and thigh muscles treated with percutaneous catheter drainage, surgical incision, and drainage.

Network analysis of stroke systems of care in Korea.

Background: The landscape of stroke care has shifted from stand-alone hospitals to cooperative networks among hospitals. Despite the importance of these networks, limited information exists on their characteristics and functional attributes. Methods: We extracted patient-level data on acute stroke care and hospital connectivity by integrating national stroke audit data with reimbursement claims data. We then used this information to transform interhospital transfers into a network framework, where hospitals were designated as nodes and transfers as edges. Using the Louvain algorithm, we grouped densely connected hospitals into distinct stroke care communities. The quality and characteristics in given stroke communities were analysed, and their distinct types were derived using network parameters. The clinical implications of this network model were also explored. Results: Over 6 months, 19 113 patients with acute ischaemic stroke initially presented to 1009 hospitals, with 3114 (16.3%) transferred to 246 stroke care hospitals. These connected hospitals formed 93 communities, with a median of 9 hospitals treating a median of 201 patients. Derived communities demonstrated a modularity of 0.904, indicating a strong community structure, highly centralised around one or two hubs. Three distinct types of structures were identified: single-hub (n=60), double-hub (n=22) and hubless systems (n=11). The endovascular treatment rate was highest in double-hub systems, followed by single-hub systems, and was almost zero in hubless systems. The hubless communities were characterised by lower patient volumes, fewer hospitals, no hub hospital and no stroke unit. Conclusions: This network analysis could quantify the national stroke care system and point out areas where the organisation and functionality of acute stroke care could be improved.

Adrenal-Permissive Germline HSD3B1 Allele and Prostate Cancer Outcomes.

Importance: The adrenal androgen-metabolizing 3ß-hydroxysteroid dehydrogenase-1 enzyme, encoded by the HSD3B1 gene, catalyzes the rate-limiting step necessary for synthesizing nontesticular testosterone and dihydrotestosterone production. The common adrenal-permissive HSD3B1(1245C) allele is responsible for encoding the 3ß-HSD1 protein with decreased susceptibility to degradation resulting in higher extragonadal androgen synthesis. Retrospective studies have suggested an association of the HSD3B1 adrenal-permissive homozygous genotype with androgen deprivation therapy resistance in prostate cancer. Objective: To evaluate differences in mortality outcomes by HSD3B1 genetic status among men with prostate cancer. Design, Setting, and Participants: This cohort study of patients with prostate cancer who were enrolled in the Million Veteran Program within the Veterans Health Administration (VHA) system between 2011 and 2023 collected genotyping and phenotyping information. Exposure: HSD3B1 genotype status was categorized as AA (homozygous adrenal-restrictive), AC (heterozygous adrenal-restrictive), or CC (homozygous adrenal-permissive). Main Outcomes and Measures: The primary outcome of this study was prostate cancer-specific mortality (PCSM), defined as the time from diagnosis to death from prostate cancer, censored at the date of last VHA follow-up. Secondary outcomes included incidence of metastases and PCSM in predefined subgroups. Results: Of the 5287 participants (median [IQR] age, 69 [64-74] years), 402 (7.6%) had the CC genotype, 1970 (37.3%) had the AC genotype, and 2915 (55.1%) had the AA genotype. Overall, the primary cause of death for 91 patients (1.7%) was prostate cancer. Cumulative incidence of PCSM at 5 years after prostate cancer diagnosis was higher among men with the CC genotype (4.0%; 95% CI, 1.7%-6.2%) compared with the AC genotype (2.1%; 95% CI, 1.3%-2.8%) and AA genotype (1.9%; 95% CI, 1.3%-2.4%) (P = .02). In the 619 patients who developed metastatic disease at any time, the cumulative incidence of PCSM at 5 years was higher among patients with the CC genotype (36.0%; 95% CI, 16.7%-50.8%) compared with the AC genotype (17.9%; 95% CI, 10.5%-24.7%) and AA genotype (18.5%; 95% CI, 12.0%-24.6%) (P = .01). Conclusions and Relevance: In this cohort study of US veterans undergoing treatment for prostate cancer at the VHA, the HSD3B1 CC genotype was associated with inferior outcomes. The HSD3B1 biomarker may help identify patients who may benefit from therapeutic targeting of 3ß-hydroxysteroid dehydrogenase-1 and the androgen-signaling axis.

Ionizing radiation­induced modification of nialamide as an anti­inflammatory agent against lipopolysaccharide­induced RAW 264.7 and DH82 cells.

Nialamide is a non-selective monoamine oxidase inhibitor that was widely used as an antidepressant. However, it has been prohibited for decades in the depressive medicine market due to the adverse hepatotoxic side effects. The re-use of drugs that have been withdrawn from the market represents a promising approach for the development of novel incrementally modified drugs and, in this context, ionizing radiation can serve as a powerful tool for producing new drug candidates. The present study exposed nialamide to γ radiation at 50 kGy to obtain the novel cyclized benzylamide, nialaminosin (compound 2), along with five known compounds, 3-amino-N-benzylpropanamide (compound 3), 3-methoxy-N-benzylpropanamide (compound 4), 3-hydroxy-N-benzylpropanamide (HBPA; compound 5), N-benzylpropanamide (compound 6) and isonicotinamide (compound 7). Among the isolated compounds, HBPA was established to inhibit the lipopolysaccharide-induced overproduction of pro-inflammatory mediators, including nitric oxide (NO) and prostaglandin E2 and cytokines including TNF-α, IL-6 and IL-10, without causing cytotoxicity to both RAW 264.7 and DH82 cells. Furthermore, HBPA was found to reduce the protein expression of inducible NO synthase and cyclooxygenase-2 in macrophages and compared with nialamide, it was established to have more potent radical scavenging activity. The present study therefore suggested the application of HBPA for the improvement of anti-inflammatory properties using ionizing radiation technology on the withdrawn drug nialamide.

An Antibody-CRISPR/Cas Conjugate Platform for Target-Specific Delivery and Gene Editing in Cancer.

The CRISPR/Cas system has been introduced as an innovative tool for therapy, however achieving specific delivery to the target has been a major challenge. Here, an antibody-CRISPR/Cas conjugate platform that enables specific delivery and target gene editing in HER2-positive cancer is introduced. The CRISPR/Cas system by replacing specific residues of Cas9 with an unnatural amino acid is engineered, that can be complexed with a nanocarrier and bioorthogonally functionalized with a monoclonal antibody targeting HER2. The resultant antibody-conjugated CRISPR/Cas nanocomplexes can be specifically delivered and induce gene editing in HER2-positive cancer cells in vitro. It is demonstrated that the in vivo delivery of the antibody-CRISPR/Cas nanocomplexes can effectively disrupt the plk1 gene in HER2-positive ovarian cancer, resulting in substantial suppression of tumor growth. The current study presents a useful therapeutic platform for antibody-mediated delivery of CRISPR/Cas for the treatment of various cancers and genetic diseases.

Patient Perception on Osteoporosis in Korean Female Patients with Osteoporosis.

BACKGROUND: Patient perception is a key element in improving compliance with medications for osteoporosis. This study evaluated the awareness, perception, sources of information, and knowledge of osteoporosis among Korean women with osteoporosis. METHODS: A questionnaire survey was conducted from July 22, 2021 to 13 August 2021. Patients who were followed up in endocrinology (Endo), orthopedic surgery (OS), and gynecology (GY) were recruited (N=40, 40, and 20 in each group). Patients were allocated according to their age, as follows: 15, 15, and 10 patients in their 60s, 70s, and 80s for Endo and OS, and 10 and 10 patients in their 60s and 70s for GY. The questionnaire was composed of the following topics: patient journey to the hospital, drug-related issues, communication with medical doctors, patient knowledge, and sources of information about osteoporosis. RESULTS: The results of medical check-ups were the most common reason for patient visits to the hospital for an initial diagnosis of osteoporosis (61%). A knowledge gap regarding mortality, refracture, and drug-induced osteoporosis was observed. Doctors were the most preferred and trustful source of information, while health-related TV shows were the second most common source of information. Patients with OS reported lower perceived severity and higher drug discontinuation, along with a higher proportion of fractures, as the initial reasons for hospital visits for osteoporosis. CONCLUSIONS: Variations in perceptions according to the issue and group were identified. These should be considered during patient consultations to improve compliance with osteoporosis treatment.

Rapidly growing distal choroidal artery aneurysm re-rupture following revascularization for hemorrhagic Moyamoya disease: A case report.

Intracranial hemorrhage is the leading cause of neurological deficits and poor prognosis in adult patients with Moyamoya disease (MMD). Intracranial hemorrhage is occasionally accompanied by MMD-associated aneurysm and requires additional treatment. To date, direct or indirect bypass surgery or endovascular treatment, such as coil embolization, has been adopted and has achieved successful outcomes. The rapid growth of MMD-associated aneurysms and rebleeding after direct bypass surgery via superficial temporal artery-middle cerebral artery (STA-MCA) anastomosis has rarely been reported. We report a case of a rapidly growing fragile arterial pseudoaneurysm in a patient with MMD. A 45-year-old female was admitted with a headache and decreased mental status. Radiological evaluation, including distal subtraction angiography, revealed intraventricular hemorrhage with a left posterior choroidal artery pseudoaneurysm. Within 4 days after revascularization surgery via STA-MCA direct bypass, the size of the pseudoaneurysm rapidly increased and rebleeding occurred, requiring coil embolization. After endovascular therapy and a second STA-MCA bypass surgery, the patient recovered well and was discharged 8 days later. Follow-up radiological imaging revealed an obliterated pseudoaneurysm without rebleeding or complications. In this case, the rapid growth of an MMD-associated pseudoaneurysm was observed after revascularization surgery because of temporary hemodynamic instability. This report raises questions regarding the causes and management of unstable postbypass hemodynamics.