BACKGROUND: Protein is the most important nutrient for the muscle synthesis and maintenance of muscle mass. However, there have been no studies comparing muscle mass indexes according to protein intake in obese patients. Thus, the present study investigated the hypothesis that high protein intake positively affected muscle mass indexes in obese patients. METHODS: Male (n=50) and female (n=30) obese patients were recruited. Each sex was divided into 2 groups according to their protein intake. Dietary intake, fat-free mass, appendicular skeletal muscle mass, appendicular skeletal muscle mass/height², skeletal muscle index, total bone area, bone mineral count, bone mineral density, total cholesterol, low density lipoprotein cholesterol, high density lipoprotein cholesterol, interleukin-6, tumor necrosis factor α, smoking, alcohol, and exercise were assessed. RESULTS: Fat-free mass, appendicular skeletal muscle mass, and appendicular skeletal muscle mass/height² were significantly higher in obese men in the higher protein intake group, while serum triglyceride was significantly lower in the same group. However, bone indexes and inflammatory cytokines according to protein intake were not significantly different in obese men. Fat-free mass, bone indexes, muscle indexes, blood lipid profiles, and inflammatory cytokines were not significantly different according to protein intake in obese women. CONCLUSION: In this population, increasing protein intake may positively affect fat-free mass, appendicular skeletal muscle mass, appendicular skeletal muscle mass/height², and serum triglyceride in obese men. Therefore, additional studies may be necessary to identify the appropriate level of protein intake required to prevent a decrease in muscle mass, and increase muscle mass in obese patients.
Bone Density ; Cholesterol ; Cholesterol, HDL ; Cholesterol, LDL ; Cytokines ; Female ; Humans ; Interleukin-6 ; Male ; Miners ; Muscle, Skeletal ; Smoke ; Smoking ; Triglycerides ; Tumor Necrosis Factor-alpha

BRAF inhibitors (e.g., vemurafenib) are widely used to treat metastatic melanoma with the BRAF V600E mutation. The initial response is often dramatic, but treatment resistance leads to disease progression in the majority of cases. Although secondary mutations in the mitogen-activated protein kinase signaling pathway are known to be responsible for this phenomenon, the molecular mechanisms governing acquired resistance are not known in more than half of patients. Here we report a genome- and transcriptome-wide study investigating the molecular mechanisms of acquired resistance to BRAF inhibitors. A microfluidic chip with a concentration gradient of vemurafenib was utilized to rapidly obtain therapy-resistant clones from two melanoma cell lines with the BRAF V600E mutation (A375 and SK-MEL-28). Exome and transcriptome data were produced from 13 resistant clones and analyzed to identify secondary mutations and gene expression changes. Various mechanisms, including phenotype switching and metabolic reprogramming, have been determined to contribute to resistance development differently for each clone. The roles of microphthalmia-associated transcription factor, the master transcription factor in melanocyte differentiation/dedifferentiation, were highlighted in terms of phenotype switching. Our study provides an omics-based comprehensive overview of the molecular mechanisms governing acquired resistance to BRAF inhibitor therapy.

BRAF inhibitors (e.g., vemurafenib) are widely used to treat metastatic melanoma with the BRAF V600E mutation. The initial response is often dramatic, but treatment resistance leads to disease progression in the majority of cases. Although secondary mutations in the mitogen-activated protein kinase signaling pathway are known to be responsible for this phenomenon, the molecular mechanisms governing acquired resistance are not known in more than half of patients. Here we report a genome- and transcriptome-wide study investigating the molecular mechanisms of acquired resistance to BRAF inhibitors. A microfluidic chip with a concentration gradient of vemurafenib was utilized to rapidly obtain therapy-resistant clones from two melanoma cell lines with the BRAF V600E mutation (A375 and SK-MEL-28). Exome and transcriptome data were produced from 13 resistant clones and analyzed to identify secondary mutations and gene expression changes. Various mechanisms, including phenotype switching and metabolic reprogramming, have been determined to contribute to resistance development differently for each clone. The roles of microphthalmia-associated transcription factor, the master transcription factor in melanocyte differentiation/dedifferentiation, were highlighted in terms of phenotype switching. Our study provides an omics-based comprehensive overview of the molecular mechanisms governing acquired resistance to BRAF inhibitor therapy.

Purpose: In 2015, the South Korean government legislated the Act for the Improvement of Training Conditions and Status of Medical Residents (Medical Resident Act). This study investigated changes in the working and learning environment pre- and post-implementation of the Medical Resident Act in 2017, as well as changes in training conditions by year post-implementation. Methods: An annual cross-sectional voluntary survey was conducted by the Korean Intern Resident Association (KIRA) between 2016 and 2019. The learning and working environment, including extended shift length, rest time, learning goals, and job satisfaction, were compared by institution type, training year, and specialty. Results: Of the 55,727 enrollees in the KIRA, 15,029 trainees took the survey, and the number of survey participants increased year by year (from 2,984 in 2016 to 4,700 in 2019). Overall working hours tended to decrease; however, interns worked the most (114 hours in 2016, 88 hours in 2019; P<0.001). Having 10 hours or more of break time has gradually become more common (P<0.001). Lunch breaks per week decreased from 5 in 2017 to 4 in 2019 (P<0.001). Trainees’ sense of educational deprivation due to physician assistants increased from 17.5% in 2016 to 25.6% in 2018 (P<0.001). Awareness of tasks and program/work achievement goals increased from 29.2% in 2016 to 58.3% in 2018 (P<0.001). Satisfaction with the learning environment increased over time, whereas satisfaction with working conditions varied. Conclusion The Medical Resident Act has brought promising changes to the training of medical residents in Korea, as well as their satisfaction with the training environment.

Purpose: In 2015, the South Korean government legislated the Act for the Improvement of Training Conditions and Status of Medical Residents (Medical Resident Act). This study investigated changes in the working and learning environment pre- and post-implementation of the Medical Resident Act in 2017, as well as changes in training conditions by year post-implementation. Methods: An annual cross-sectional voluntary survey was conducted by the Korean Intern Resident Association (KIRA) between 2016 and 2019. The learning and working environment, including extended shift length, rest time, learning goals, and job satisfaction, were compared by institution type, training year, and specialty. Results: Of the 55,727 enrollees in the KIRA, 15,029 trainees took the survey, and the number of survey participants increased year by year (from 2,984 in 2016 to 4,700 in 2019). Overall working hours tended to decrease; however, interns worked the most (114 hours in 2016, 88 hours in 2019; P<0.001). Having 10 hours or more of break time has gradually become more common (P<0.001). Lunch breaks per week decreased from 5 in 2017 to 4 in 2019 (P<0.001). Trainees’ sense of educational deprivation due to physician assistants increased from 17.5% in 2016 to 25.6% in 2018 (P<0.001). Awareness of tasks and program/work achievement goals increased from 29.2% in 2016 to 58.3% in 2018 (P<0.001). Satisfaction with the learning environment increased over time, whereas satisfaction with working conditions varied. Conclusion The Medical Resident Act has brought promising changes to the training of medical residents in Korea, as well as their satisfaction with the training environment.

Catastrophic antiphospholipid syndrome (APS) is defined as a rare, life-threatening autoimmune disorder leading to multiorgan failure. Probable APS, with clinical manifestations similar to APS without antiphospholipid antibodies, was suggested to be seronegative catastrophic APS. The triggering factors of catastrophic APS are various, including infection, trauma, malignancy, and surgery. In approximately 40% of patients, catastrophic APS develops from an unknown cause. We report a case of seronegative catastrophic APS due to an unknown origin. A 20-year-old man presented with cough, abdominal pain, skin lesions, tunnel vision, and watery diarrhea without fever. His symptoms and laboratory test suggested disseminated intravascular coagulation. Considering seronegative catastrophic APS, we treated with intravenous steroid and intravenous immunoglobulin, but the effects were limited. After weekly treatment with rituximab, an immune-modulating agent, his laboratory findings including thrombocytopenia and coagulation tests, returned to normal. We conclude that rituximab can be an effective treatment for seronegative catastrophic APS.
Abdominal Pain ; Antibodies, Antiphospholipid* ; Antiphospholipid Syndrome ; Autoimmune Diseases ; Cough ; Diarrhea ; Disseminated Intravascular Coagulation* ; Fever ; Humans ; Immunoglobulins ; Skin ; Thrombocytopenia ; Young Adult ; Rituximab

Bullous pemphigoid (BP) is a chronic and recurrent bullous disorder that may be associated with the administration of certain drugs. Recently, bullous cutaneous adverse events after immunotherapy (IT) or targeted therapy have been increasingly reported. Here, we report a case of BP in a patient diagnosed with metastatic melanoma after treatment with pembrolizumab, dabrafenib, and trametinib. Histopathological examination showed a subepidermal blister with perivascular lymphocytic and eosinophilic infiltration; the accompanying findings of linear immunoglobulin G and C3 deposition by immunofluorescence microscopy were consistent with BP. Since IT agents may initiate immune dysregulation and pathologic autoantibody production, which are required for the pathogenesis of BP, the lesions were thought to be cutaneous adverse events caused by IT.

PURPOSE: Hereditary leiomyomatosis and renal cell carcinoma (HLRCC) is a rare genetic syndrome resulting from germline mutations in fumarate hydratase. The combination of bevacizumab plus erlotinib showed promising interim results for HLRCC-associated RCC. Based on these results, we analyzed the outcome of bevacizumab plus erlotinib in Korean patients with HLRCC-associated RCC. MATERIALS AND METHODS: We retrospectively reviewed the efficacy and safety of bevacizumab plus erlotinib in patients with HLRCC-associated RCC who were confirmed to have germline mutations in fumarate hydratase. The primary endpoint was the objective response rate (ORR), while the secondary endpoints were progression-free survival (PFS) and overall survival (OS). RESULT: We identified 10 patients with advanced HLRCC-associated RCC who received bevacizumab plus erlotinib. Median age at diagnosis was 41 years, and five of the patients had received the combination as first- or second-line treatments. The ORR was 50% and the median PFS and OS were 13.3 and 14.1 months, respectively. Most adverse events were predictable and manageable by conventional measures, except for one instance where a patient died of gastrointestinal bleeding. CONCLUSION: This is the first real-world outcome of the treatment of advanced HLRCC-associated RCC. Bevacizumab plus erlotinib therapy showed promising activity with moderate toxicity. We should be increasingly aware of HLRCC-associated RCC and bevacizumab plus erlotinib should be a first-line treatment for this condition, unless other promising data are published.
Bevacizumab ; Carcinoma, Renal Cell ; Diagnosis ; Disease-Free Survival ; Erlotinib Hydrochloride ; Fumarate Hydratase ; Germ-Line Mutation ; Hemorrhage ; Humans ; Leiomyomatosis ; Retrospective Studies

Objectives: . This study aimed to evaluate long-term changes after balloon dilation of the Eustachian tube (BDET) in chronic otitis media (COM) patients with Eustachian tube (ET) dysfunction that persisted after tympanomastoidectomy (TM). Methods: . We retrospectively reviewed the medical records of consecutive patients who were diagnosed with COM and ET dysfunction and underwent TM at our tertiary hospital from 2016 to 2017. The tympanic membrane status, the presence of a ventilation tube, ability to perform the Valsalva maneuver, and audiologic changes after dilation of the ET were analyzed. Results: . This study included 20 patients (with 21 ears) who underwent TM but could not perform the Valsalva maneuver, showed a persistent air-bone gap, and eventually underwent BDET (male:female, 8:13; right:left, 11:10). Four ears showed perforation of the tympanic membrane after TM. Among the remaining 17 ears, 15 ears underwent ventilation tube insertion before BDET, while two ears underwent ventilation tube insertion and BDET simultaneously. Although none of the patients were capable of the Valsalva maneuver before BDET, 13 (62%) were able to perform the Valsalva maneuver successfully after BDET. When evaluating the tympanic membrane status at the latest follow-up, ventilation tubes were still present in eight ears. In the other 13 ears, intact tympanic membranes were present in nine out of 11 ears n the successful Valsalva group, whereas none of them were intact in the unsuccessful Valsalva group (P=0.014). The successful Valsalva group after BDET showed an improved air-bone gap of 8.9±12.4 dB, while the unsuccessful Valsalva group showed an aggravated air-bone gap of 3.8±11.8 dB at 1 year after BDET; this difference was statistically significant (P=0.031). Conclusion The Valsalva maneuver could be performed successfully after BDET by 62% of patients with COM and ET dysfunction. BDET is helpful for successful hearing improvement and improved tympanic aeration in COM patients with ET dysfunction.

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