Short-Term Outcomes and Cost-Effectiveness between Long-Course Chemoradiation and Short-Course Radiotherapy for Locally Advanced Rectal Cancer

Purpose@#Long-course chemoradiotherapy (LCRT) has been widely recommended in a majority of rectal cancer patients. Recently, encouraging data on short-course radiotherapy (SCRT) for rectal cancer has emerged. In this study, we aimed to compare these two methods in terms of short-term outcomes and cost analysis under the Korean medical insurance system. @*Materials and Methods@#Sixty-two patients with high-risk rectal cancer, who underwent either SCRT or LCRT followed by total mesorectal excision (TME), were classified into two groups. Twenty-seven patients received 5 Gy×5 with two cycles of XELOX (capecitabine 1000 mg/m 2 and oxaliplatin 130 mg/m 2 every 3 weeks) followed by TME (SCRT group). Thirty-five patients received capecitabine-based LCRT followed by TME (LCRT group). Short-term outcomes and cost estimation were assessed between the two groups. @*Results@#Pathological complete response was achieved in 18.5% and 5.7% of patients in the SCRT and LCRT groups, respectively (p=0.223). The 2-year recurrence-free survival rate did not show significant difference between the two groups (SCRT vs. LCRT:91.9% vs. 76.2%, p=0.394). The average total cost per patient for SCRT was 18% lower for inpatient treatment (SCRT vs. LCRT: $18787 vs. $22203, p<0.001) and 40% lower for outpatient treatment (SCRT vs. LCRT: $11955 vs. $19641, p<0.001) compared to LCRT. SCRT was shown to be the dominant treatment option with fewer recurrences and fewer complications at a lower cost. @*Conclusion@#SCRT was well-tolerated and achieved favorable short-term outcomes. In addition, SCRT showed significant reduction in the total cost of care and distinguished cost-effectiveness compared to LCRT.

Tractional Retinal Detachment in Eyes with Vitreous Hemorrhage and Proliferative Diabetic Retinopathy and Posterior Vitreous Detachment in Fellow Eye

Purpose@#To predict the presence of tractional retinal detachment (TRD) in eyes with dense vitreous hemorrhage (VH) and proliferative diabetic retinopathy (PDR) by evaluating the status of posterior vitreous detachment (PVD) in fellow eyes using optical coherence tomography (OCT). @*Methods@#A total of 44 eyes from 22 patients who underwent vitrectomy due to dense VH with PDR were enrolled. Using OCT, the PVD status in the fellow eye was divided into two groups (incomplete and complete PVD). The incomplete PVD group included eyes without PVD and eyes with partial PVD. B-scan ultrasonography was performed on eyes with dense VH to evaluate the presence of TRD. Both OCT and B-scan images were reviewed by four ophthalmologists (two novices and two experienced), and the interobserver agreement was evaluated. @*Results@#There was a difference in the interobserver agreement regarding the presence of TRD in eyes with dense VH evaluated by B scan between novice and experienced ophthalmologists (novice, κ = 0.421 vs. experienced, κ = 0.814), although there was no difference between novice and experienced ophthalmologists in the interobserver agreement regarding the status of PVD in the fellow eye evaluated by OCT (novice, κ = 1.000 vs. experienced, κ = 1.000). All observed TRD during vitrectomy occurred in eyes with incomplete PVD in the fellow eye. Logistic regression analysis revealed a statistically significant relation between TRD and the age of the patient (odds ratio [OR], 0.874; p = 0.047), and between TRD and incomplete PVD in the fellow eye evaluated by OCT (OR, 13.904; p = 0.042). @*Conclusions@#Evaluation of the PVD status in the fellow eye using OCT may be a useful predictor for detecting the presence of TRD in eyes with dense VH and PDR.

Eight-Month Follow-up After the Third Dose of BNT162b2 Vaccine in Healthcare Workers: The Question of a Fourth Dose

Background@#A fourth dose of vaccination is known to help reduce the severity and mortality rate of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. The South Korean vaccination guidelines for the fourth dose do not include healthcare workers (HCWs) as priority candidates. We investigated the necessity of the fourth dose in South Korean HCWs based on an 8-month follow-up period after the third vaccination. @*Methods@#Changes in the surrogate virus neutralization test (sVNT) inhibition (%) score were measured at one month, four months and eight months after the third vaccination. The sVNT values were analyzed between infected and uninfected groups, and their trajectories were compared. @*Results@#A total of 43 HCWs were enrolled in this study. In total, 28 cases (65.1%) were confirmed to be infected with SARS-CoV-2 (presumed omicron variant), and all had mild symptoms. Meanwhile, 22 cases (78.6%) were infected within four months of the third dose (median, 97.5 days). Eight months after the third dose, the SARS-CoV-2 (presumed omicron variant)-infected group showed significantly higher sVNT inhibition than that in the uninfected group (91.3% vs. 30.7%; P < 0.001). The antibody response due to hybrid immunity, provided by a combination of infection and vaccination, was maintained at sufficient levels for more than four months. @*Conclusion@#For HCWs who had coronavirus disease 2019 infection after completing a third vaccination, a sufficient antibody response was maintained until eight months after the third dose. The recommendation of the fourth dose may not be prioritized in subjects with hybrid immunity.

Retrospective Cohort Study on the Long-term Oncologic Outcomes of Sentinel Lymph Node Mapping Methods (Dye-Only versus Dye and Radioisotope Mapping) in Early Breast Cancer: A Propensity Score-Matched Analysis / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#In sentinel lymph node (SLN) biopsy (SLNB) during breast cancer surgery, SLN mapping using dye and isotope (DUAL) may have lower false-negative rates than the dye-only (DYE) method. However, the long-term outcomes of either method are unclear. We aimed to compare long-term oncological outcomes of DYE and DUAL for SLNB in early breast cancer. @*Materials and Methods@#This retrospective single-institution cohort study included 5,795 patients (DYE, 2,323; DUAL, 3,472) with clinically node-negative breast cancer who underwent SLNB and no neoadjuvant therapy. Indigo carmine was used for the dye method and Tc99m-antimony trisulfate for the isotope. To compare long-term outcomes, pathologic N0 patients were selected from both groups, and propensity score matching (PSM), considering age, pT category, breast surgery, and adjuvant treatment, was performed (1,441 patients in each group). @*Results@#The median follow-up duration was 8.7 years. The median number of harvested sentinel nodes was 3.21 and 3.12 in the DYE and DUAL groups, respectively (p=0.112). The lymph node–positive rate was not significantly different between the two groups in subgroups of similar tumor sizes (p > 0.05). Multivariate logistic regression revealed that the mapping method was not significantly associated with the lymph node–positive rate (p=0.758). After PSM, the 5-year axillary recurrence rate (DYE 0.8% vs. DUAL 0.6%, p=0.096), and 5-year disease-free survival (DYE 93.9% vs. DUAL 93.7%, p=0.402) were similar between the two groups. @*Conclusion@#Dye alone for SLNB was not inferior to dual mapping regarding long-term oncological outcomes in early breast cancer.

Feasibility and reliability of various morphologic features on magnetic resonance imaging for iliotibial band friction syndrome

Background@#To evaluate the feasibility, inter-reader reliability, and intra-reader reliability for various morphological features reported to be related to iliotibial band friction syndrome (ITBFS) on knee magnetic resonance imaging (MRI). @*Methods@#A total of 145 patients with a clinical diagnosis and knee MRI findings consistent with ITBFS were included in the “study group” and 232 patients without knee pathology on both physical examination and MRI were included in the “control group”. Various morphologic features on knee MRI were assessed including the patella shape, patella height, lateral epicondyle anterior-posterior (AP) width, lateral epicondyle height, ITB diameter (ITB-d), and ITB area (ITB-a). @*Results@#Patients in the study group had significantly higher lateral epicondyle height (13.9 mm vs. 12.92 mm, P = 0.003), ITB-d (2.9 mm vs. 2.0 mm, P = 0.022), and ITB-a (38.5 mm2 vs. 23.8 mm2 , P < 0.001) than the control group. ITB-a showed higher area under the curve index (0.849 with 74.1% sensitivity and 72.4% specificity at a 30.3 mm2 cutoff) than ITB-d (0.710 with 70.8% sensitivity and 61.2% specificity at 2.4 mm cutoff) and lateral epicondyle height (0.776 with 72.4% sensitivity and 67.8% specificity at 13.4 mm cutoff). However, only the interreader agreement for ITB-a (intraclass correlation coefficient = 0.65) was moderate, while the agreements for other morphologic features were good or excellent. @*Conclusions@#Lateral epicondyle height seems to be a reliable and feasible morphologic feature for diagnosis of ITBFS.

Clinical Experience of Allogeneic Hematopoietic Stem Cell Transplantation in Elderly Patients Aged 60 Years and Older in South Korea

Purpose@#The purpose of this study is to share our outcomes and experiences on allogeneic hematopoietic stem cell transplantation (HSCT) in elderly patients aged 60 years and older with myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML) in South Korea, and to compare them with other studies. @*Materials and Methods@#We analyzed the clinical outcomes of 116 patients with AML or MDS aged 60 years and older who underwent allogeneic HSCT. We also analyzed which pretreatment factors affect the overall survival (OS) after allogeneic HSCT. @*Results@#Neutrophil and platelet engraftment were achieved at median day +11 [interquartile range (IQR) 10–15] and +14 (IQR 11–19), respectively. A complete donor chimerism was confirmed in 65 (56.0%) patients at 3 weeks and in 63 (54.3%) patients at 3 months after HSCT. The estimated incidence of grade II–IV acute graft-versus-host disease (GVHD) at day 100 was 13.7%. The estimated incidence of chronic GVHD at 2 years was 38.8%. Within a median follow-up of 14 months after HSCT, OS was 64% at 1 year and 55% at 2 years, and non-relapse mortality (NRM) was 20% at 1 year and 28% at 2 years. Multivariate analysis revealed that male sex and Hematopoietic Cell Transplantation-Specific Comorbidity Index ≥3 were associated with poor OS. @*Conclusion@#This study showed that allogeneic HSCT in elderly adults aged 60 and older can be performed with successful engraftment and acceptable NRM and OS are expected given the generally known survival of patients with higher risk MDS and poor risk AML.

Factors predicting meaningful suicide attempts: multiple attempts and index methods

Purpose@#This study investigated the association of the index method, defined as the method used in the first suicide attempt (SA), with the outcome of SAs among adolescents. @*Methods@#The study analyzed medical records of 227 adolescents aged 10-18 years with clear SAs who visited the emergency department of Severance Hospital in Seoul, Korea from January 2007 through February 2021, focusing on the index methods and meaningful SAs defined as hospitalization, death or transfer to another hospital for psychiatric hospitalization. The association of the index method with the meaningful SAs was quantified using logistic regression. @*Results@#Among the 227 adolescents, 80 underwent the meaningful SAs (35.2%). The adolescents with the meaningful SA chose drug intoxication, fall, and hanging as the index methods more frequently than those without the outcome, whereas they showed a reverse pattern in cutting (P < 0.001). The association of fall or cutting with the meaningful SAs remained significant after adjustment (fall: adjusted odds ratio, 6.93 [95% confidence interval, 1.70-28.26]; cutting: 0.39 [0.17-0.91]; compared with those undergoing drug intoxication). Multiple SAs were also associated with the meaningful SA (1.76 [1.04-3.13]). @*Conclusion@#This study identifies the index method and multiple SAs as factors associated with the meaningful SA among adolescents in the emergency department. This finding may be helpful in interviewing adolescents with SAs.

Short-term Changes in Thyroid-Stimulating Hormone Level after Body Fat Reduction via Partial Meal Replacement / 가정의학회지

Background@#Serum thyroid-stimulating hormone (TSH) levels change during body weight reduction. However, the changes that occur during short-term body weight control interventions remain controversial. Thus, this study aimed to evaluate the changes in TSH levels according to body fat reduction. @*Methods@#We performed a 3-month intervention study involving partial meal replacement. Forty-nine participants completed the study. Correlations between changes in TSH levels and other body composition parameters were determined. The subjects were divided into two groups according to their body fat reduction (>1 kg, n=20; 1 kg, can reduce serum TSH concentrations in subjects with metabolic syndrome after short-term body weight intervention.

Proper Depth of Percutaneous Central Venous Catheter via the Great Saphenous Vein for Very Low Birth Weight Infants: A Single-Center, Prospective Cohort Study

Background@#A proper depth of percutaneous central venous catheter (PCVC) is very important to reduce procedural time and prevent various complications in very low birth weight (VLBW) infants who require minimal handling or have a sensitive skin. The objective of this study was to suggest a formula for faster and proper insertion of PCVC in VLBWIs to prevent unintended consequences of patients’ conditions. @*Methods@#Prospective data of VLBW infants admitted from June 2015 to January 2018 who had PCVC inserted via the great saphenous vein within seven days after birth were analyzed.Correlations of length of inserted PCVC with body weight, body length, and postmenstrual age at the date of PCVC insertion were determined with a linear regression analysis. Using results of this analysis, a formula to determine the optimal insertion length of PCVC was derived. Coefficient of determination was used to assess how well outcomes were replicated by the formula. @*Results@#The formula to predict the proper insertion length of PCVC via the great saphenous vein at popliteal crease level was obtained as follows: Optimal Length (cm) = 3.8 × Body Weight (kg) + 11.1. With everyday movements such as flexion and extension of the lower extremities, the mean difference in catheter tip position was 7.0 ± 3.9 mm, which was not significant enough to escalate the risk of catheter tip displacement. The rate of catheterrelated complications was as low as 4.9% in this study. @*Conclusions@#The formula derived from this study to predict the optimal PCVC insertion length could benefit VLBW infants by reducing procedural time and lowering the risk of complications.

Effects of Omicron Infection and Changes in Serum Antibody Response to Wild-Type, Delta, and Omicron After a Booster Dose With BNT163b2 Vaccine in Korean Healthcare Workers

Background@#Although the primary vaccine coverage rate for coronavirus disease 2019 (COVID-19) in South Korea has exceeded 80%, the coronavirus continues to spread, with reports of a rapid decline in vaccine effectiveness. South Korea is administering booster shots despite concerns about the effectiveness of the existing vaccine. @*Methods@#Neutralizing antibody inhibition scores were evaluated in two cohorts after the booster dose. For the first cohort, neutralizing activity against the wild-type, delta, and omicron variants after the booster dose was evaluated. For the second cohort, we assessed the difference in neutralizing activity between the omicron infected and uninfected groups after booster vaccination. We also compared the effectiveness and adverse events (AEs) between homologous and heterologous booster doses for BNT162b2 or ChAdOx1 vaccines. @*Results@#A total of 105 healthcare workers (HCWs) that were additionally vaccinated with BNT162b2 at Soonchunhyang University Bucheon Hospital were enrolled in this study.Significantly higher surrogate virus neutralization test (sVNT) inhibition (%) was observed for the wild-type and delta variants compared to sVNT (%) for the omicron after the booster dose (97%, 98% vs. 75%; P < 0.001). No significant difference in the neutralizing antibody inhibition score was found between variants in the BNT/BNT/BNT group (n = 48) and the ChA/ChA/BNT group (n = 57). Total AEs were not significantly different between the ChA/ ChA/BNT group (85.96%) and the BNT/BNT group (95.83%; P = 0.11). In the second cohort with 58 HCWs, markedly higher sVNT inhibition to omicron was observed in the omicroninfected group (95.13%) compared to the uninfected group (mean of 48.44%; P < 0.001) after four months of the booster dose. In 41 HCWs (39.0%) infected with the omicron variant, no difference in immunogenicity, AEs, or effectiveness between homogeneous and heterogeneous boosters was observed. @*Conclusion@#Booster vaccination with BNT162b2 was significantly less effective for the neutralizing antibody responses to omicron variant compared to the wild-type or delta variant in healthy population. Humoral immunogenicity was sustained significantly high after 4 months of booster vaccine in the infected population after booster vaccination.Further studies are needed to understand the characteristics of immunogenicity in these populations.

Association of Myosteatosis with Nonalcoholic Fatty Liver Disease, Severity, and Liver Fibrosis Using Visual Muscular Quality Map in Computed Tomography

Background@#The association of myosteatosis measured using visual muscular quality map in computed tomography (CT) with nonalcoholic fatty liver disease (NAFLD), its severity, and fibrosis was analyzed in a large population. @*Methods@#Subjects (n=13,452) with abdominal CT between 2012 and 2013 were measured total abdominal muscle area (TAMA) at L3 level. TAMA was segmented into intramuscular adipose tissue and skeletal muscle area (SMA), which was further classified into normal attenuation muscle area (NAMA) and low attenuation muscle area (LAMA). The following variables were adopted as indicators of myosteatosis: SMA/body mass index (BMI), NAMA/BMI, NAMA/TAMA, and LAMA/BMI. NAFLD and its severity were assessed by ultrasonography, and liver fibrosis was measured by calculating the NAFLD fibrosis score (NFS) and fibrosis-4 index (FIB-4) scores. @*Results@#According to multiple logistic regression analyses, as quartiles of SMA/BMI, NAMA/BMI, and NAMA/TAMA increased, the odds ratios (ORs) for NAFLD decreased in each sex (P for trend <0.001 for all). The ORs of moderate/severe NAFLD were significantly higher in the Q1 group than in the Q4 group for SMA/BMI, NAMA/BMI, and NAMA/TAMA in men. The ORs of intermediate/high liver fibrosis scores assessed by NFS and FIB-4 scores increased linearly with decreasing quartiles for SMA/BMI, NAMA/BMI, and NAMA/TAMA in each sex (P for trend <0.001 for all). Conversely, the risk for NAFLD and fibrosis were positively associated with LAMA/BMI quartiles in each sex (P for trend <0.001 for all). @*Conclusion@#A higher proportion of good quality muscle was associated with lower risks of NAFLD and fibrosis.

Posterior Rotator Cuff Tears: Is Extracorporeal Shockwave Therapy a Risk Factor?

Background@#Negative effects of extracorporeal shock wave therapy (ESWT) on vulnerable tendon structures have been reported. Meanwhile, tears of the posterior rotator cuff tendon, which is thinner than the anterior, are not common, and the clinical features remain poorly understood. Therefore, we evaluated the relationship between ESWT and posterior rotator cuff tears (RCTs) by investigating the risk factors. @*Methods@#Of 294 patients who underwent rotator cuff repair between October 2020 and March 2021, a posterior RCT more than 1.5 cm from the biceps tendon or an isolated infraspinatus tear was identified in 24 (8.1%, group P). Sixty-two patients (21%) with an anterior RCT within 1.5 cm of the biceps tendon were analyzed as a control group (group A). Preoperative clinical characteristics were assessed to determine the risk factors of posterior RCTs. @*Results@#Calcific deposits were more frequently observed in group P (n = 7, 29.2%) than group A (n = 6, 9.7%, p= 0.024). Further, those in group P were more likely to undergo ESWT (n = 18, 75.0%) than those in group A (n = 15, 24.2%, p < 0.001). Of these, 7 patients experiencing calcific tendinitis from group P (29.2%) and 4 from group A (6.5%, p= 0.005) underwent ESWT for calcification removal. Furthermore, 11 patients experiencing tendinopathy from group P (45.8%), and 11 from group A (17.7%,p = 0.007) underwent ESWT for pain relief. The mean level of fatty infiltration of the supraspinatus was significantly higher in group A than group P (1.8 vs. 1.0, p < 0.001). @*Conclusions@#Since a high prevalence rate of posterior RCTs was related to ESWT, it should be carefully considered when treating calcific tendinitis or pain in patients experiencing tendinopathy.

Is Treosulfan-Based Conditioning Attractive as a Reduced-Intensity Conditioning Regimen in Korea?

Background@#Allogeneic hematopoietic stem cell transplantation (HSCT) was not actively performed in elderly acute myeloid leukemia (AML) or myelodysplastic syndrome patients who are at a high-risk based on hematopoietic cell transplantation-specific comorbidity index (HCT-CI). The advent of reduced-intensity conditioning (RIC) regimens has made HSCT applicable in this population. However, the selection of appropriate conditioning is a major concern for the attending physician. The benefits of combination of treosulfan and fludarabine (Treo/Flu) have been confirmed through many clinical studies. Korean data on treosulfan-based conditioning regimen are scarce. @*Methods@#A retrospective study was conducted to compare the clinical outcomes of allogeneic HSCT using RIC between 13 patients receiving Treo/Flu and 39 receiving busulfan/ fludarabine (Bu/Flu). @*Results@#In terms of conditioning-related complications, the frequency of ≥ grade 2 nausea or vomiting was significantly lower and the duration of symptoms was shorter in the Treo/ Flu group than in the Bu/Flu group. The incidence of ≥ grade 2 mucositis tended to be lower in the Treo/Flu group. In the analysis of transplant outcomes, all events of acute graft versus host disease (GVHD) and ≥ grade 2 acute GVHD occurred more frequently in the Treo/ Flu group. The frequency of Epstein-Barr virus reactivation was significantly higher in the Treo/Flu group (53.8% vs. 23.1%, P = 0.037). Non-relapse mortality (NRM) at 12 months was higher in the Treo/Flu group (30.8% vs. 7.7%, P = 0.035). Significant prognostic factors included disease type, especially secondary AML, disease status and high-risk based on HCT-CI, ≥ grade 2 acute GVHD, and cases requiring ≥ 2 immunosuppressive drugs for treating acute GVHD. In the comparison of survival outcomes according to conditioning regimen, the Bu/Flu group seemed to show better results than the Treo/Flu group (60% vs.46.2%, P = 0.092 for overall survival; 56.4% vs. 38.5%, P = 0.193 for relapse-free survival). In additional analysis for only HCT-CI high-risk groups, there was no difference in transplant outcomes except that the Treo/Flu group tended to have a higher NRM within one year after transplantation. Survival outcomes of both groups were similar. @*Conclusion@#This study suggests that Treo/Flu conditioning may be an alternative to Bu/Flu regimen in elderly patients with high-risk who are not suitable for standard conditioning.

Life-Threatening Hematoma in an Elderly Breast Cancer Patient Undergoing Chemotherapy / 한국유방암학회지

The use of neoadjuvant chemotherapy in older patients is increasing. However, chemotherapy should be administered considering the medical comorbidities of the patients and the toxicity of chemotherapeutic agents. Here, we present a case of abdominal wall hematoma with spontaneous inferior epigastric artery injury caused by coughing in a 70-year-old woman who was treated with neoadjuvant chemotherapy. Abdominal computed tomography demonstrated an abdominal wall hematoma with active bleeding. However, angiography with selective embolization of the right inferior epigastric artery and the right internal mammary artery was performed successfully. Scheduled chemotherapy was discontinued over concerns of rebleeding and breast-conserving surgery was performed. When deciding on chemotherapy for older patients, attention should be paid to the various complications.

Development and External Validation of a Machine Learning Model to Predict Pathological Complete Response After Neoadjuvant Chemotherapy in Breast Cancer / 한국유방암학회지

Purpose@#Several predictive models have been developed to predict the pathological complete response (pCR) after neoadjuvant chemotherapy (NAC); however, few are broadly applicable owing to radiologic complexity and institution-specific clinical variables, and none have been externally validated. This study aimed to develop and externally validate a machine learning model that predicts pCR after NAC in patients with breast cancer using routinely collected clinical and demographic variables. @*Methods@#The electronic medical records of patients with advanced breast cancer who underwent NAC before surgical resection between January 2017 and December 2020 were reviewed. Patient data from Seoul National University Bundang Hospital were divided into training and internal validation cohorts. Five machine learning techniques, including gradient boosting machine (GBM), support vector machine, random forest, decision tree, and neural network, were used to build predictive models, and the area under the receiver operating characteristic curve (AUC) was compared to select the best model. Finally, the model was validated using an independent cohort from Seoul National University Hospital. @*Results@#A total of 1,003 patients were included in the study: 287, 71, and 645 in the training, internal validation, and external validation cohorts, respectively. Overall, 36.3% of the patients achieved pCR. Among the five machine learning models, the GBM showed the highest AUC for pCR prediction (AUC, 0.903; 95% confidence interval [CI], 0.833–0.972).External validation confirmed an AUC of 0.833 (95% CI, 0.800–0.865). @*Conclusion@#Commonly available clinical and demographic variables were used to develop a machine learning model for predicting pCR following NAC. External validation of the model demonstrated good discrimination power, indicating that routinely collected variables were sufficient to build a good prediction model.

Gut microbiome on immune checkpoint inhibitor therapy and consequent immune-related colitis: a review

Immune checkpoint inhibitors have dramatically revolutionized the therapeutic landscape for patients with advanced malignancies. Recently, convincing evidence has shown meaningful influence of gut microbiome on human immune system. With the complex link between gut microbiome, host immunity and cancer, the variations in the gut microbiota may influence the efficacy of immune checkpoint inhibitors. Indeed, some bacterial species have been reported to be predictive for cancer outcome in patients treated with immune checkpoint inhibitors. Although immune checkpoint inhibitors are currently proven to be an effective anti-tumor treatment, they can induce a distinct form of toxicity, termed immune-related adverse events. Immune-related colitis is one of the common toxicities from immune checkpoint inhibitors, and it might preclude the cancer therapy in severe or refractory cases. The manipulation of gut microbiome by fecal microbiota transplantation or probiotics administration has been suggested as one of the methods to enhance anti-tumor effects and decrease the risk of immune-related colitis. Here we review the role of gut microbiome on immune checkpoint inhibitor therapy and consequent immune-related colitis to provide a new insight for better anti-cancer therapy.

Strategic Application of Epigenetic Regulators for Efficient Neuronal Reprogramming of Human Fibroblasts

Background and Objectives@#Cellular reprogramming in regenerative medicine holds great promise for treating patients with neurological disorders. In this regard, small molecule-mediated cellular conversion has attracted special attention because of its ease of reproducibility, applicability, and fewer safety concerns. However, currently available protocols for the direct conversion of somatic cells to neurons are limited in clinical application due of their complex nature, lengthy process, and low conversion efficiency. @*Methods@#and Results: Here, we report a new protocol involving chemical-based direct conversion of human fibroblasts (HF) to matured neuron-like cells with a short duration and high conversion efficiency using temporal and strategic dual epigenetic regulation. In this protocol, epigenetic modulation by inhibition of histone deacetylase and bromodomain enabled to overcome “recalcitrant” nature of adult fibroblasts and shorten the duration of neuronal reprogramming. We further observed that an extended epigenetic regulation is necessary to maintain the induced neuronal program to generate a homogenous population of neuron-like cells. @*Conclusions@#Therefore, our study provides a new protocol to produce neurons-like cells and highlights the need of proper epigenetic resetting to establish and maintain neuronal program in HF.

Arthroscopic transosseous anchorless rotator cuff repair reduces bone defects related to peri-implant cyst formation: a comparison with conventional suture anchors using propensity score matching

Background@#The transosseous anchorless repair (ToR) technique was recently introduced to avoid suture anchor-related problems. While favorable outcomes of the ToR technique have been reported, no previous studies on peri-implant cyst formation with the ToR technique exist. Therefore, this study compared the clinical outcomes and prevalence of peri-implant cyst formation between the ToR technique and the conventional transosseous equivalent technique using suture anchors (SA). @*Methods@#Cases with arthroscopic rotator cuff repair (ARCR) between 2016 and 2018 treated with the double-row suture bridge technique were retrospectively reviewed. Patients were divided into ToR and SA groups. To compare clinical outcomes, 19 ToR and 57 SA cases without intraoperative implant failure were selected using propensity score matching (PSM). While intraoperative implant failure rate was analyzed before PSM, retear rate, peri-implant cyst formation rate, and functional outcomes were compared after PSM. @*Results@#The intraoperative implant failure rate (ToR, 8% vs. SA, 15.3%) and retear rate (ToR, 5.3% vs. SA, 19.3%) did not differ between the two groups (all P>0.05). However, peri-implant cysts were not observed in the ToR group, while they were observed in 16.7% of the SA group (P=0.008). Postoperative functional outcomes were not significantly different between the two groups (all P>0.05). @*Conclusions@#The ToR technique produced comparable clinical outcomes to conventional techniques. Considering the prospect of potential additional surgeries, the absence of peri-implant cyst formation might be an advantage of ToR. Furthermore, ToR might reduce the medical costs related to suture anchors and, thereby, could be a useful option for ARCR.Level of evidence: III.

Association of Visceral Fat Obesity, Sarcopenia, and Myosteatosis with Non-Alcoholic Fatty Liver Disease without Obesity

Background/Aims@#To investigate whether non-alcoholic fatty liver disease (NAFLD) in individuals without generalized obesity is associated with visceral fat obesity (VFO), sarcopenia, and/or myosteatosis. @*Methods@#This cross-sectional analysis included 14,400 individuals (7,470 men) who underwent abdominal computed tomography scans during routine health examinations. The total abdominal muscle area (TAMA) and skeletal muscle area (SMA) at the 3rd lumbar vertebral level were measured. The SMA was divided into the normal attenuation muscle area (NAMA) and low attenuation muscle area, and the NAMA/TAMA index was calculated. VFO was defined by visceral to subcutaneous fat ratio, sarcopenia by body mass index-adjusted SMA, and myosteatosis by the NAMA/TAMA index. NAFLD was diagnosed with ultrasonography. @*Results@#Of the 14,400 individuals, 4,748 (33.0%) had NAFLD, and the prevalence of NAFLD among non-obese individuals was 21.4%. In regression analysis, both sarcopenia (men: odds ratio [OR] 1.41, 95% confidence interval [CI] 1.19–1.67, P<0.001; women: OR=1.59, 95% CI 1.40–1.90, P<0.001) and myosteatosis (men: OR=1.24, 95% CI 1.02–1.50, P=0,028; women: OR=1.23, 95% CI 1.04–1.46, P=0.017) were significantly associated with non-obese NAFLD after considering for VFO and other various risk factors, whereas VFO (men: OR=3.97, 95% CI 3.43–4.59 [adjusted for sarcopenia], OR 3.98, 95% CI 3.44–4.60 [adjusted for myosteatosis]; women: OR=5.42, 95% CI 4.53–6.42 [adjusted for sarcopenia], OR=5.33, 95% CI 4.51–6.31 [adjusted for myosteatosis]; all P<0.001) was strongly associated with non-obese NAFLD after adjustment with various known risk factors. @*Conclusions@#In addition to VFO, sarcopenia and/or myosteatosis were significantly associated with non-obese NAFLD.

Clinical Practice Guideline: Clinical Efficacy of Nasal Surgery in the Treatment of Obstructive Sleep Apnea

Obstructive sleep apnea (OSA) is a common disorder characterized by upper airway obstruction during sleep. To reduce the morbidity of OSA, sleep specialists have explored various methods of managing the condition, including manifold positive airway pressure (PAP) techniques and surgical procedures. Nasal obstruction can cause significant discomfort during sleep, and it is likely that improving nasal obstruction would enhance the quality of life and PAP compliance of OSA patients. Many reliable studies have offered evidence to support this assumption. However, few comprehensive guidelines for managing OSA through nasal surgery encompass all this evidence. In order to address this gap, the Korean Society of Otorhinolaryngology-Head and Neck Surgery (KORL-HNS) and the Korean Society of Sleep and Breathing designated a guideline development group (GDG) to develop recommendations for nasal surgery in OSA patients. Several databases, including OVID Medline, Embase, the Cochrane Library, and KoreaMed, were searched to identify all relevant papers using a predefined search strategy. The types of nasal surgery included septoplasty, turbinate surgery, nasal valve surgery, septorhinoplasty, and endoscopic sinus surgery. When insufficient evidence was found, the GDG sought expert opinions and attempted to fill the evidence gap. Evidence-based recommendations for practice were ranked according to the American College of Physicians’ grading system. The GDG developed 10 key action statements with supporting text to support them. Three statements are ranked as strong recommendations, three are only recommendations, and four can be considered options. The GDG hopes that this clinical practice guideline will help physicians make optimal decisions when caring for OSA patients. Conversely, the statements in this guideline are not intended to limit or restrict physicians’ care based on their experience and assessment of individual patients.