Identification and overcoming rituximab resistance in diffuse large B-cell lymphoma using next-generation sequencing

Background/Aims@#Although rituximab, an antiCD20 monoclonal antibody, has dramatically improved the clinical outcomes of diffuse large B-cell lymphoma, rituximab resistance remains a challenge. @*Methods@#We developed a rituximab-resistant cell line (RRCL) by sequential exposure to gradually increasing concentrations of rituximab in a rituximab-sensitive cell line (RSCL). When the same dose of rituximab was administered, RRCL showed a smaller decrease in cell viability and apoptosis than RSCL. To determine the differences in gene expression between RSCL and RRCL, we performed next-generation sequencing. @*Results@#In total, 1,879 differentially expressed genes were identified, and in the over-representation analysis of Consensus-PathDB, mitogen-activated protein kinase (MAPK) signaling pathway showed statistical significance. MAPK13, which encodes the p38δ protein, was expressed more than four-fold in RRCL. Western blot analysis revealed that phosphop38 expression mainwas increased in RRCL, and when p38 inhibitor was administered, phosphop38 expression was significantly decreased. Therefore, we hypothesized that p38 MAPK activation was associated with rituximab resistance. Previous studies have suggested that p38 is associated with NF-κB activation. Deferasirox has been reported to inhibit NF-κB activity and suppress phosphorylation of the MAPK pathway. Furthermore, it also has cytotoxic effects on various cancers and synergistic effects in overcoming drug resistance. In this study, we confirmed that deferasirox induced dose-dependent cytotoxicity in both RSCL and RRCL, and the combination of deferasirox and rituximab showed a synergistic effect in RRCL at all combination concentrations. @*Conclusions@#We suggest that p38 MAPK, especially p38δ, activation is associated with rituximab resistance, and deferasirox may be a candidate to overcome rituximab resistance.

Periodic Limb Movement Disorder and Mortality / 수면정신생리

Periodic limb movement disorder (PLMD) is a sleep-related movement disorder characterized by involuntary, rhythmic limb movements during sleep. While PLMD itself is not considered life-threatening, its association with certain underlying health conditions raises concerns about mortality risks. PLMD has been found to be associated with cardiovascular diseases such as hypertension and cardiovascular disease. The fragmented sleep caused by the repetitive limb movements and associated arousals may contribute to sympathetic activation, chronic sleep disruption, sleep deprivation, and subsequent cardiovascular problems, which can increase mortality risks. The comorbidities and health factors commonly associated with PLMD, such as obesity, diabetes, and chronic kidney disease, may also contribute to increased mortality risks. PLMD is often observed alongside other neurological disorders, including restless legs syndrome (RLS) and Parkinson's disease. The presence of PLMD in these conditions may exacerbate the underlying health issues and potentially contribute to higher mortality rates. Further research is needed to elucidate the specific mechanisms linking PLMD to mortality risks and to develop targeted interventions that address these risks.

Dietary Carotene Intake and Suicidal Ideation in Korean Females: Analysis of Data From the Korea National Health and Nutrition Examination Survey (2012, 2013, and 2015)

Objective@#The suicide rate in Korea was the highest among countries in the Organisation for Economic Co-operation and Development in 2019. In a previous study, higher intake of vegetables and fruits was associated with a lower risk of suicidal ideation, and carotene-rich fruits and vegetables lowered the risk of depression. This study aimed to examine the direct relationship between carotene intake and suicidal ideation, adjusting for the effect on depression. @*Methods@#This study used data from the Korea National Health and Nutrition Examination Survey (KNHANES) conducted in 2012, 2013, and 2015. Carotene intake was assessed through a food intake frequency survey with a 24-hour recall. Suicidal ideation and depression were assessed using the mental health section of the KNHANES. We applied logistic regression to assess the relationship between carotene intake and suicidal ideation, adjusting for potential confounders. @*Results@#A total of 5,480 females aged 19–64 years were included in this study. Carotene intake was significantly lower in the suicidal ideation group (3,034.5±1,756.4 μg/day) than in the nonsuicidal ideation group (3,225.4±1,795.1 μg/day) (p=0.015). We found a significant inverse association between carotene intake and the risk of suicidal ideation after adjusting for potential confounders (odds ratio=0.934, 95% confidence interval=0.873–0.999). @*Conclusion@#These results suggest that carotene intake may be inversely associated with the risk of suicidal ideation. Our findings may inform the development of new nutritional interventions to prevent increases in the risk of suicide worldwide.

The Factors Affecting Longitudinal Course of Posttraumatic Stress Disorder Symptoms in Sexual Assault Victims

Objective@#This study aimed to identify the factors affecting posttraumatic stress disorder (PTSD) symptom remission prospectively through a 1-year follow-up of sexual assault (SA) victims. @*Methods@#A total 65 female SA victims who visited the crisis intervention center were included. Self-administered questionnaires regarding PTSD symptoms and PTSD related prognostic factors were conducted at both recruitment (T1) and 1 year after recruitment (T2). The multivariate analyses were used to determine the significant predictors of PTSD remissionon-remission state 1 year after SA. @*Results@#In logistic regression analysis, both anxiety and secondary victimization were identified as significant factors explaining the results on PTSD remissionon-remission state at T2 (Beck’s Anxiety Inventory [BAI], p=0.003; Secondary Victimization Questionnaire, p=0.024). In a linear mixed analysis, both depression and anxiety were found to be significant variables leading to changes in Posttraumatic Diagnostic Scale for Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition from T1 to T2 (BAI, p<0.001; Center for Epidemiological Studies Depression Scale, p<0.001). @*Conclusion@#Depression, anxiety symptoms, and secondary victimization after SA were associated with PTSD symptom non-remission 1 year after SA.

Source Investigation and Control of Ralstonia mannitolilytica Bacteremia in a Neonatal Intensive Care Unit: A Case Report

A case of persistent Ralstonia mannitolilytica bacteremia in the neonatal intensive care unit prompted source investigation due to its rarity. After an extensive investigation, a contaminated ultrasonic nebulizer was identified as the source, and the infection was controlled by removing the source. This study emphasizes the importance of further investigations, even in single cases of rare pathogens.

Associations between Maternal sFlt-1/PlGF Ratio and Perinatal and Neonatal Outcomes in Newborns Born to Mothers with Preeclampsia

Purpose@#The ratio of soluble fms-like tyrosine kinase 1 (sFlt-1) to placental growth factor (PlGF) is considered a predictive marker of preeclampsia. However, the relationship between the sFlt-1/PlGF ratio and perinatal and neonatal outcomes remains unknown. This study aimed to determine the associations of the sFlt-1/PlGF ratio with perinatal and neonatal outcomes in newborns born to mothers with preeclampsia. @*Methods@#This retrospective cohort study reviewed singleton neonates born to mothers with preeclampsia who underwent testing for the sFlt-1/PlGF ratio. We investigated the relationship between maternal sFlt-1/PlGF ratios and gestational age (GA), birth weight (Bwt), Bwt z-score, morbidities, and mortality of neonates born to mothers tested for the sFlt-1/PlGF ratio. Maternal sFlt-1/PlGF ratios examined within 30 days before delivery were used for analysis. Neonatal morbidities and mortality were investigated only in preterm infants born earlier than 32 weeks GA. @*Results@#A total of 225 neonates were included, of which 163 (72.4%) were preterm infants. GA (R=– 0.577, p<0.001), Bwt (R=–0.713, p<0.001), and Bwt z-score (R=–0.608, p<0.001) exhibited significant negative correlations with the sFlt-1/PlGF ratios. Among the 50 preterm infants born earlier than 32 weeks GA, neonatal morbidities were not significantly associated with the sFlt-1/PlGF ratio after adjusting for GA and Bwt. @*Conclusion@#In mothers with preeclampsia, a higher sFlt-1/PlGF ratio was associated with the delivery of newborns with lower GA and lower Bwt. However, this ratio was not associated with increased morbidity or mortality in premature infants born earlier than 32 weeks GA.

Induction of liver transplant immune tolerance in an outbred rat strain model using tacrolimus / 한국실험동물학회지

Background@#Orthotopic liver transplantation is the only option for patients with end-stage liver disease and hepatocellular carcinoma. Post-transplant immunosuppressive therapy is important to prevent graft failure. We investigated the effectiveness of tacrolimus (FK506) and their mechanisms for liver transplant immune tolerance in an outbred rat LT model. @*Results@#To investigate the therapeutic effect of the FK506 on outbred rat LT model, FK506 and postoperative therapy were administered subcutaneously once or twice daily to transplanted rats. Histopathological and immunohistochemical analyses were conducted for all groups. The regulation of inflammatory cytokine signaling in the spleen was analyzed by flow cytometry. FK506 attenuated allograft rejection and increased survival in rat orthotopic liver transplantation models. The FK506-treated group had reduced serum levels of alanine aminotransferase, aspartate aminotransferase and alkaline phosphatase. Furthermore, FK506 decreased the expression of inflammatory cytokines and the activation of pathogenic Th1 and Th17 cells in the liver. @*Conclusions@#Taken together, we revealed that FK506 ameliorated strong allograft rejection in outbred liver transplantation model by anti-inflammatory effect and inhibitory peroperty of pathogenic T cells.

Generative Adversarial Network-Based Image Conversion Among Different Computed Tomography Protocols and Vendors: Effects on Accuracy and Variability in Quantifying Regional Disease Patterns of Interstitial Lung Disease

Objective@#To assess whether computed tomography (CT) conversion across different scan parameters and manufacturers using a routable generative adversarial network (RouteGAN) can improve the accuracy and variability in quantifying interstitial lung disease (ILD) using a deep learning-based automated software. @*Materials and Methods@#This study included patients with ILD who underwent thin-section CT. Unmatched CT images obtained using scanners from four manufacturers (vendors A-D), standard- or low-radiation doses, and sharp or medium kernels were classified into groups 1–7 according to acquisition conditions. CT images in groups 2–7 were converted into the target CT sty le (Group 1: vendor A, standard dose, and sharp kernel) using a RouteGAN. ILD was quantified on original and converted CT images using a deep learning-based software (Aview, Coreline Soft). The accuracy of quantification was analyzed using the dice similarity coefficient (DSC) and pixel-wise overlap accuracy metrics against manual quantification by a radiologist. Five radiologists evaluated quantification accuracy using a 10-point visual scoring system. @*Results@#Three hundred and fifty CT slices from 150 patients (mean age: 67.6 ± 10.7 years; 56 females) were included. The overlap accuracies for quantifying total abnormalities in groups 2–7 improved after CT conversion (original vs. converted: 0.63vs. 0.68 for DSC, 0.66 vs. 0.70 for pixel-wise recall, and 0.68 vs. 0.73 for pixel-wise precision; P < 0.002 for all). The DSCs of fibrosis score, honeycombing, and reticulation significantly increased after CT conversion (0.32 vs. 0.64, 0.19 vs. 0.47, and 0.23 vs. 0.54, P < 0.002 for all), whereas those of ground-glass opacity, consolidation, and emphysema did not change significantly or decreased slightly. The radiologists’ scores were significantly higher (P < 0.001) and less variable on converted CT. @*Conclusion@#CT conversion using a RouteGAN can improve the accuracy and variability of CT images obtained using different scan parameters and manufacturers in deep learning-based quantification of ILD.

The Difference between Serum Vitamin D Level and Depressive Symptoms in Korean Adult Women before and after Menopause: The 5th (2010–2012) Korean National Health and Nutrition Examination Survey

Background@#The relationship between serum vitamin D levels and depressive symptoms has not been consistent in previous studies in Korean women. Menopause is known to be related to depression and vitamin D. @*Methods@#This study included 11,573 women from the 5th Korea National Health and Nutrition Examination Survey. Serum vitamin D levels were divided into four groups according to quartiles, and depressive symptoms were collected into two groups. Multiple logistic regression analysis was conducted in each group of women before and after menopause. @*Results@#Compared with the highest vitamin D group, the lowest vitamin D group did not show significant differences in all females (odds ratio [OR], 0.98; 95% confidence interval [CI], 0.78-1.22). In premenopausal women, compared to the first quartile, ORs were presented in the second quartile (OR, 0.75; 95% CI, 0.53-1.07), third quartile (OR, 0.70; 95% CI, 0.49-1.00) and fourth quartile (OR, 0.62; 95% CI, 0.43-0.92) respectively, and they were statistically significant (P=0.016). In postmenopausal women, compared to the first quartile, ORs were presented in the second quartile (OR, 1.06; 95% CI, 0.78-1.44), third quartile (OR, 1.18; 95% CI, 0.87-1.61), and fourth quartile (OR, 1.27; 95% CI, 0.98-1.66) respectively; however, they were not statistically significant (P=0.057). @*Conclusions@#Depression symptoms increased with a decrease in serum vitamin D in premenopausal women, but the opposite trend was observed in postmenopausal women. In future studies, if the relationship between blood vitamin D and depression is studied, the menopausal status of women can be used as an important criterion.

A study on the effect of denture cleaning utilizing active micro-locomotion of diatom complex / 대한치과재료학회지

This study compared the effectiveness of self-propelling diatom microbubblers to clean dental appliances with commercial denture cleaning agents according to the Ministry of Food and Drug Safety’s guidelines. The microbubbler is made by doping diatoms with MnO2 nanosheets that can decompose hydrogen peroxide to generate oxygen bubbles. Artificial saliva is prepared in accordance with the criteria presented by the American Dental Association, dispensed, and dried in 96 well plates. Experimental groups include 10-15% NaOCl (positive control), distilled water (negative control), diatom microbubbler A (Aulacoseira, MnO2-polydopamine (PDA)-A), diatom microbubbler M (Melosira nummuloids, MnO2-sugar (S)-M), Polident (GlaxoSmithKline, Dungarvan, Ireland), Dentfix-forte (Helago-Phama GmbH&Co, Parchim, Germany). After washing, absorbance (OD 600) was measured. If the absorbance was 70% or higher, the condition was determined to have “cleaning power potency,”Statistical significance was evaluated by one-way ANOVA and Bonferroni correction to compare cleaning effects among groups (p<0.05).The average cleaning rates were 93.8±1.0% in NaOCl (positive control) and 79.1±1.5% in distilled water (negative control).With the diatom microbubbler A, the average cleaning rate was 79.8±4.5% in the 3% H 2O 2 2 mg/mL, 64.7±5.5% in 6% H 2O 2 2 mg/mL, and 81.9±7.9% in 6% H 2O 2 4 mg/mL. The diatom microbubbler M group showed average cleaning rates of 88.5±3.6% in 3% H2O2 2 mg/mL, 75.8±4.0% in 6% H2O2 2 mg/mL, and 84.5±4.5% in 6% H2O2 4 mg/mL. Finally, conventional denture cleaning agents showed average cleaning rates of 88.2±1.2% in Polident and 83.3±3.0% in Dentfix-forte. The positive control group had significant differences from all experimental groups, but the negative control group showed significant differences only in A2 and A3, M1 and M2, M3, Polident, and Dentfix-forte (F=190.141, p<0.001). Among all groups except the positive control group, MnO2 -S-M mixed with 3% H2O2 2 mg/mL showed the highest cleaning rate. As the results of this study show, diatom complexes exhibit cleaning effects compatible with conventional denture cleaning agents. Further studies need to be conducted to narrow down the specific optimal conditions of diatom microbubblers and maximize the cleaning effect.

Temperament and Character Associated With Resilience in Patients With Bipolar Disorder / 생물치료정신의학

Objectives@#The aim of this study was to investigate temperament and character associated with resilience in patients with bipolar disorder (BD). @*Methods@#A total of 55 outpatients diagnosed with BD according to the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition (DSM-IV), and 55 healthy controls matched by age and sex with the BD group were recruited.All participants completed the Connor-Davidson Resilience Scale (CD-RISC) and Temperament and Character Inventory (TCI). Multiple linear regression analysis was performed by controlling for age, length of education, age of onset, number of depressive episodes, and number of hospitalizations to determine factors related to resilience. In addition, multiple regression analysis was performed using the interaction term to investigate whether temperament and character associated with resilience differed between the two groups. @*Results@#Patients with BD showed higher harm avoidance (p<0.001) and lower self-directedness (p<0.001) among the TCI dimensions compared to the control group. In multiple regression analysis, harm avoidance (β=-0.274, p=0.025) and self-directedness (β=0.431, p=0.002) were associated with resilience in patients with BD, while harm avoidance (β=-0.411, p=0.008), persistence (β=0.244, p=0.031), and cooperativeness (β=0.264, p=0.037) were associated with resilience in the control group. Self-directedness had a different relationship with resilience between the two groups (β=0.212, p=0.001). @*Conclusions@#The findings suggest that BD patients’ particular temperament and character are associated with resilience.Furthermore, temperament and character related to resilience differed between the BD group and the control group.

Choroidal Vascularity Index and Treatment Outcomes in Branch Retinal Vein Occlusion Patients with Macular Edema

Purpose@#To explore the association between the visual and anatomical outcomes and the choroidal vascularity index (CVI) post-intravitreal injection in patients with macular edema associated with branch retinal vein occlusion (BRVO). @*Methods@#We conducted a retrospective review of medical records of 50 patients (27 eyes treated with anti-vascular endothelial growth factor and 23 eyes treated with a dexamethasone implant) with BRVO and macular edema who underwent intravitreal injections from January 2017 to October 2020. We measured the central macular thickness (CMT), subfoveal choroidal thickness, and CVI of the BRVO eyes and the fellow eyes using optical coherence tomography and then analyzed the correlation between these measurements and visual and anatomical outcomes. @*Results@#After six months of treatment, the best corrected visual acuity improved, and CMT decreased. Multiple linear regression analysis revealed that factors associated with best corrected visual acuity improvement at six months were fellow eye CVI (standardized β = 0.346, p = 0.008), ellipsoid zone integrity (standardized β = 0.398, p = 0.001), and initial best corrected visual acuity (standardized β = 0.590, p < 0.001). Initial CMT (standardized β = 0.563, p < 0.001) was the only factor associated with the decrease in CMT at six months. @*Conclusions@#In cases of severe macular edema, accurate evaluation of choroidal vessels can be challenging due to shadowing. We discovered that a larger CVI in the fellow eye was associated with greater visual improvement in patients with BRVO and macular edema. CVI could be a prognostic factor for predicting treatment outcomes in BRVO patients, suggesting that the choroidal vascular status may play a role in the pathophysiology of BRVO.

Association Between Depressed Mood Changes and Physical Activity Among Adolescents Post COVID-19 Pandemic

Objectives@#Following the coronavirus disease 2019 (COVID-19) pandemic, adolescents have experienced decreased physical activity and a decline in mental health. This study analyzed the association between changes in depressed mood after the COVID-19 pandemic and physical activity among adolescents. @*Methods@#The analysis was based on the results of the 17th Youth Health Behavior Online Survey conducted in 2021, which included 54848 middle and high school students in South Korea. Information on physical activity included low-intensity physical activity lasting >60 min/day, high-intensity physical activity, and strength training exercises. A logistic regression analysis was performed to evaluate the association between physical activity and changes in depression after the COVID-19 pandemic. @*Results@#After adjusting for sociodemographic characteristics and previous depression, adolescents who performed strength training exercises more than once per week had a 0.95-fold lower risk (odds ratio [OR]=0.948, 95% confidence interval [CI]=0.905–0.994, p= 0.027) of increasing depression after the COVID-19 pandemic, while the risk of decreasing depression increased by 1.22-fold (OR=1.215, 95% CI=1.131–1.305, p60 min/day and high-intensity physical activity. @*Conclusion@#Strength-training exercises are significantly associated with the prevention of depression among adolescents following the COVID-19 pandemic.

High Mean Platelet Volume Is Associated with Cerebral White Matter Hyperintensities in Non-Stroke Individuals

Purpose@#The mean platelet volume (MPV) is regarded as a marker for thrombosis, atherosclerosis, and inflammation in various vascular diseases. However, it still remains unclear whether plasma MPV is associated with cerebral white matter hyperintensities (WMH) and cerebral microvascular pathology in the elderly population. @*Materials and Methods@#We examined whether MPV level is associated with the presence of cerebral WMH on brain magnetic resonance imaging from 870 non-stroke outpatient subjects. The subjects were divided into three groups according to the consecutive level of MPV (low T1, middle T2, and high T3 MPV tertile groups). To determine the association of MPV levels with the WMH, logistic regression and receiver operating characteristic curve analyses were conducted. @*Results@#Subjects with higher MPV level were older and more likely to have hypertension, diabetes mellitus, and low renal function. Cerebral WMH were more prevalent in subjects with higher MPV level. After adjusting for confounding factors, moderate to severe cerebral WMH were significantly associated with high MPV tertile level. This association remained significant after adjusting for other cerebral vascular pathologies. T2 [odds ratio (OR): 1.49, 95% confidence interval (CI): 1.03–2.15] and T3 MPV tertile groups (OR: 1.51, 95%CI: 1.04–2.20) had more cerebral WMH lesions compared to T1 MPV tertile group. In addition, the subjects with higher Fazekas scores showed higher MPV level (p=0.020). @*Conclusion@#We found that high MPV level is independently associated with cerebral WMH. This result suggests that platelet activation plays a role in the development of cerebral WMH.

Clinical Outcomes of Moderately Hypofractionated Concurrent Chemoradiotherapy for Newly Diagnosed Glioblastoma

Purpose@#Hypofractionated radiotherapy (HypoRT) has recently been implemented in patients with glioblastoma (GBM) receiving concurrent temozolomide. Lymphopenia during treatment (LDT) is considered an important prognostic factor of clinical outcomes for GBM. We aimed to investigate the outcomes of HypoRT. @*Materials and Methods@#Among 223 patients with GBM, 145 and 78 were treated with conventionally fractionated RT (ConvRT, 60 Gy in 30 fractions) and HypoRT (58.5 Gy in 25 fractions), respectively. To balance characteristics between the two groups, propensity score matching (PSM) was performed. @*Results@#Patients in the HypoRT group were older and had smaller tumors than those in the ConvRT group (p0.05). Multivariable analysis before PSM revealed that ≥grade 2 LDT at 6 months was associated with inferior outcomes. Subsequent analysis demonstrated that HypoRT significantly reduced the rate of ≥grade 2 LDT at 6 months post-RT before and after PSM. @*Conclusion@#HypoRT with 58.5 Gy in 25 fractions could provide comparable oncologic outcomes and significantly reduce the ALC changes. In addition, HypoRT decreased the LDT. Further investigation should be warranted to suggest the significance of reduced LDT through HypoRT affecting survival outcomes.

The prognostic value of comprehensive geriatric assessment on the management of older patients with small cell lung cancer

Background/Aims@#The prognostic value of a comprehensive geriatric assessment (CGA) for the management of older small cell lung cancer (SCLC) patients remains to be established. @*Methods@#A retrospective cohort enrolled 21 SCLC patients over 65 years from March 2018 to 2019 at the Yonsei Cancer Center. The CGA included the following instruments: frailty, body mass index, sarcopenia (circumference of arm and calf, Timed Up and Go test, grip strength), comorbidity, polypharmacy, activities of daily living (ADL), Instrumental ADL, nutrition, depression, and cognitive function. The correlations of oncological and geriatric variables with overall survival (OS) were determined. The log-rank test with Cox model and Kaplan-Meier method were used for the analysis. @*Results@#The median age was 75 years (range, 67 to 85). All patients had the Eastern Cooperative Oncology Group performance status 0–2. The median survival was 9.93 months (range, 1.53 to 36.30). Among CGA parameters, ADL and nutritional status had significant differences in OS in univariate analysis. In multivariate analysis, only nutritional status was independently associated with survival (hazard ratio, 0.17; 95% confidence interval, 0.05 to 0.57). Median OS for low nutritional status was 5.63 months and the normal nutrition group was 15.5 months (p = 0.004). @*Conclusions@#Pre-treatment nutritional status measured by CGA appears to be a predictor of OS in older SCLC patients. However, for further generalization of the implication of CGA in SCLC, a larger scale study with prospective design is strongly needed.

Analysis of Judicial Precedents on Drug Eruption in South Korea / 대한피부과학회지

Background@#Both medicolegal disputes and the incidence of cutaneous drug eruptions are increasing in Korea. We were unable to find research that surveyed the legal disputes involving drug eruption cases. @*Objective@#This study investigates medical litigation associated with drug eruption cases in Korea. @*Methods@#Judicial precedents on drug eruption cases were searched using the Supreme Court of South Korea’s Written Judgement Management System. General characteristics, results, suspected agents, and recognized negligence were analyzed. @*Results@#From the search results, 50 cases were selected. Of these, 34 cases had severe cutaneous adverse reactions, including Stevens-Johnson syndrome/toxic epidermal necrolysis (n=25, 50.0%), and drug rash with eosinophilia and systemic symptoms syndrome (n=9, 18.0%). Antimicrobial agents (n=17, 34.0%), non-steroidal anti-inflammatory drugs (n=6, 12.0%), and anticonvulsants (n=6, 12.0%) were the most common drugs implicated. Death was reported in 15 patients (30.0%). In this sample, 22 cases (47.0%) were awarded to the plaintiff, and violation of the duty to inform patients of risks was the most common legal issue cited. @*Conclusion@#Clinicians should be aware of and advise patients of the potential for severe adverse reactions that can lead to negative outcomes and medicolegal disputes.

Atypical Ischemic Cranial Nerve Palsy in a Diabetic Patient

Purpose@#We report an atypical case of ischemic oculomotor palsy occurring sequentially in both eyes and then improving, followed by a new abducens palsy in a diabetic patient with poor blood sugar control.Case summary: A 51-year-old woman presented with diplopia, dizziness, and pain in the right eye and was diagnosed with oculomotor palsy in the right eye. Magnetic resonance imaging of her brain was normal but glycated hemoglobin concentration was 13.4%. After 2 months, the third nerve palsy in the right eye had recovered completely but a new third nerve palsy occurred in the left eye. 1 month later, the symptoms had improved, and the patient did not return to our clinic until 18 months later, when she returned with new diplopia. This time, she was diagnosed with a sixth nerve palsy in the left eye and was observed while controlling her blood sugar. She recovered after 4 months. @*Conclusions@#Generally, cranial nerve palsies occur unilaterally in situations that can cause ischemia, such as diabetes, high blood pressure, and hyperlipidemia. Rarely, they occur bilaterally, or two or more cranial nerve palsies occur simultaneously. However, it is very rare that cranial nerve palsy occurs sequentially in both eyes under the same systemic blood sugar control. Diabetic patients with poor blood sugar control require long-term monitoring, considering the possibility of symptoms developing in both eyes with a time lag or other forms of ischemic cranial nerve palsy.

Antidiabetic effects of water extracts of mulberry (Morus alba L.) twig by inhibition of disaccharidase activity in streptozotocin-induced diabetic mice / 한국영양학회지

Purpose@#The prevalence of diabetes mellitus (DM) continues to increase worldwide, and blood glucose control may reduce mortality from diabetic complications and healthcare costs. Mulberry twig (MT) has been used as a herbal medicine in Asia, and its antidiabetic efficacy has recently been reported, but research in this area is still limited. This study examined the antidiabetic effects of water extracts of MT in diabetic animals. @*Methods@#Six weeks old male ICR mice were divided randomly into three groups; normal control (NC, n = 10), DM control (DC, n = 10), and MT (n = 10). Streptozotocin (STZ, 50 mg/ kg/day) was injected intraperitoneally into mice in the DC and MT groups for 5 consecutive days. After 10 days of the last STZ injection, the mice in the MT group were administered orally with MT water extracts (5 g/kg body weight) for 16 days. @*Results@#The MT water extracts ameliorated the swelling of the liver in the diabetic mice and reduced the elevated levels of fasting blood and plasma glucose, total cholesterol (T-CHO), low density lipoprotein-CHO, and the ratio of high density lipotrotein (HDL)-CHO/T-CHO. The liver triglyceride (TG) and glycogen contents were also significantly lower in the MT group mice than in the DC group. The small intestine disaccharidase activity was analyzed to understand the therapeutic effects and the mechanism of MT water extracts in diabetic animals. MT group mice showed reduced lactase and sucrase activity in the proximal part of the small intestine. On the other hand, body weight, plasma insulin, TG, HDL-CHO, and hepatic T-CHO levels were similar in the DC and MT groups. @*Conclusion@#These results suggest that MT water extracts have antidiabetic effects and can be developed as a functional source to reduce the postprandial blood glucose or to prevent DM incidence.

Effect of Bevacizumab Treatment in Cerebral Radiation Necrosis : Investigation of Response Predictors in a Single-Center Experience

Objective@#: Bevacizumab is a feasible option for treating cerebral radiation necrosis (RN). We investigated the clinical outcome of RN after treatment with bevacizumab and factors related to the initial response and the sustained effect. @*Methods@#: Clinical data of 45 patients treated for symptomatic RN between September 2019 and February 2021 were retrospectively collected. Bevacizumab (7.5 mg/kg) was administered at 3-week intervals with a maximum four-cycle schedule. Changes in the lesions magnetic resonance image (MRI) scans were examined for the response evaluation. The subgroup analysis was performed based on the initial response and the long-term maintenance of the effect. @*Results@#: Of the 45 patients, 36 patients (80.0%) showed an initial response, and eight patients (17.8%) showed delayed worsening of the corresponding lesion. The non-responders showed a significantly higher incidence of diffusion restriction on MRI than the responders (100.0% vs. 25.0%, p<0.001). The delayed worsening group showed a significantly higher proportion of glioma pathology than the maintenance group (87.5% vs. 28.6%, p=0.005). Cumulative survival rates with sustained effect were significantly higher in the groups with non-glioma pathology (p=0.019) and the absence of diffusion restriction (p<0.001). Pathology of glioma and diffusion restriction in MRI were the independent risk factors for non-response or delayed worsening after initial response. @*Conclusion@#: The initial response of RN to bevacizumab was favorable, with improvement in four-fifths of the patients. However, a certain proportion of patients showed non-responsiveness or delayed exacerbations. Bevacizumab may be more effective in treating RN in patients with non-glioma pathology and without diffusion restriction in the MRI.