Background: Current international guidelines recommend against deep sedation as it is associated with worse outcomes in the intensive care unit (ICU). However, in Korea the prevalence of deep sedation and its impact on patients in the ICU are not well known. Methods: From April 2020 to July 2021, a multicenter, prospective, longitudinal, noninterventional cohort study was performed in 20 Korean ICUs. Sedation depth extent was divided into light and deep using a mean Richmond Agitation–Sedation Scale value within the first 48 hours. Propensity score matching was used to balance covariables; the outcomes were compared between the two groups. Results: Overall, 631 patients (418 [66.2%] and 213 [33.8%] in the deep and light sedation groups, respectively) were included. Mortality rates were 14.1% and 8.4% in the deep and light sedation groups (P = 0.039), respectively. Kaplan-Meier estimates showed that time to extubation (P < 0.001), ICU length of stay (P = 0.005), and death P = 0.041) differed between the groups. After adjusting for confounders, early deep sedation was only associated with delayed time to extubation (hazard ratio [HR], 0.66; 95% confidence inter val [CI], 0.55– 0.80; P < 0.001). In the matched cohort, deep sedation remained significantly associated with delayed time to extubation (HR, 0.68; 95% 0.56–0.83; P < 0.001) but was not associated with ICU length of stay (HR, 0.94; 95% CI, 0.79–1.13; P = 0.500) and in-hospital mortality (HR, 1.19; 95% CI, 0.65–2.17; P = 0.582). Conclusion In many Korean ICUs, early deep sedation was highly prevalent in mechanically ventilated patients and was associated with delayed extubation, but not prolonged ICU stay or in-hospital death.

Purpose: The introduction of immune checkpoint inhibitors represents a major advance in the treatment of lung cancer, allowing sustained recovery in a significant proportion of patients. Nivolumab is a monoclonal anti–programmed death cell protein 1 antibody licensed for the treatment of locally advanced or metastatic non-small cell lung cancer (NSCLC) after prior chemotherapy. In this study, we describe the demographic and clinical outcomes of patients with advanced NSCLC treated with nivolumab in the Korean expanded access program. Materials and Methods: Previously treated patients with advanced non-squamous and squamous NSCLC patients received nivolumab at 3 mg/kg every 2 weeks up to 36 months. Efficacy data including investigator-assessed tumor response, progression data, survival, and safety data were collected. Results: Two hundred ninety-nine patients were treated across 36 Korean centers. The objective response rate and disease control rate were 18% and 49%, respectively; the median progression-free survival was 2.1 months (95% confidence interval [CI], 1.87 to 3.45), and the overall survival (OS) was 13.2 months (95% CI, 10.6 to 18.9). Patients with smoking history and patients who experienced immune-related adverse events showed a prolonged OS. Cox regression analysis identified smoking history, presence of immune-related adverse events as positive factors associated with OS, while liver metastasis was a negative factor associated with OS. The safety profile was generally comparable to previously reported data. Conclusion This real-world analysis supports the use of nivolumab for pretreated NSCLC patients, including those with an older age.

BACKGROUND: Calcium pyrophosphate dihydrate deposition disease (CPDD) is a rare disease in the temporomandibular joint (TMJ) space. It forms a calcified crystal mass and induces a limitation of joint movement. CASE PRESENTATION: The calcified mass in our case was occupied in the left TMJ area and extended to the infratemporal and middle cranial fossa. For a complete excision of this mass, we performed a vertical ramus osteotomy and resected the mass around the mandibular condyle. The calcified mass in the infratemporal fossa was carefully excised, and the segmented mandible was anatomically repositioned. Scanning electronic microscopy (SEM)/energy-dispersive X-ray spectroscopy (EDS) microanalysis was performed to evaluate the calcified mass. The result of SEM/EDS showed that the crystal mass was completely composed of calcium pyrophosphate dihydrate. This result strongly suggested that the calcified mass was CPDD in the TMJ area. CONCLUSIONS: CPDD in the TMJ is a rare disease and is difficult to differentially diagnose from other neoplasms. A histological examination and quantitative microanalysis are required to confirm the diagnosis. In our patient, CPDD in the TMJ was successfully removed via the extracorporeal approach. SEM/EDS microanalysis was used for the differential diagnosis.
Calcium Pyrophosphate ; Calcium ; Chondrocalcinosis ; Cranial Fossa, Middle ; Diagnosis ; Diagnosis, Differential ; Humans ; Joints ; Mandible ; Mandibular Condyle ; Microscopy ; Osteotomy ; Rare Diseases ; Spectrum Analysis ; Temporomandibular Joint

Birt-Hogg-Dubé syndrome (BHDS) is a rare disease with autosomal dominant inheritance that manifests through skin tumors, pulmonary cystic lesions, and renal tumors. A mutation of FLCN located on chromosome 17p11.2, which encodes a tumor-suppressor protein (folliculin), is responsible for the development of BHDS. We report the case of a patient presenting with spontaneous pneumothorax, in whom a familial genetic study revealed a novel nonsense mutation: p.(Arg379*) in FLCN.
Birt-Hogg-Dube Syndrome* ; Codon, Nonsense ; Estrone* ; Humans ; Pneumothorax* ; Rare Diseases ; Skin ; Thoracic Surgery, Video-Assisted ; Thoracoscopy ; Wills

Birt-Hogg-Dubé syndrome (BHDS) is a rare disease with autosomal dominant inheritance that manifests through skin tumors, pulmonary cystic lesions, and renal tumors. A mutation of FLCN located on chromosome 17p11.2, which encodes a tumor-suppressor protein (folliculin), is responsible for the development of BHDS. We report the case of a patient presenting with spontaneous pneumothorax, in whom a familial genetic study revealed a novel nonsense mutation: p.(Arg379*) in FLCN.
Birt-Hogg-Dube Syndrome* ; Codon, Nonsense ; Estrone* ; Humans ; Pneumothorax* ; Rare Diseases ; Skin ; Thoracic Surgery, Video-Assisted ; Thoracoscopy ; Wills

The structures of the intact synaptosomal plasma membrane vesicles (SPMVs) isolated from bovine cerebral cortexs, and the outer and the inner monolayer separately, were evaluated with 1,6-diphenyl-1,3,5-hexatriene (DPH) and 1,3-di(1-pyrenyl)propane (Py-3-Py) as fluorescent reporters and trinitrophenyl groups as quenching agents. The methanol increased bulk rotational and lateral mobilities of SPMVs lipid bilayers. The methanol increased the rotational and lateral mobilities of the outer monolayers more than of the inner monolayers. n-(9-Anthroyloxy)stearic acid (n-AS) were used to evaluate the effect of the methanol on the rotational mobility at the 16, 12, 9, 6, and 2 position of aliphatic chains present in phospholipids of the SPMVs outer monolayers. The methanol decreased the anisotropy of the 16-(9-anthroyloxy)palmitic acid (16-AP), 12-(9-anthroyloxy)stearic acid (12-AS), 9-(9-anthroyloxy)stearic acid (9-AS), and 6-(9-anthroyloxy)stearic acid (6-AS) in the SPMVs outer monolayer but it increased the anisotropy of 2-(9-anthroyloxy)stearic acid (2-AS) in the monolayers. The magnitude of the increased rotational mobility by the methanol was in the order at the position of 16, 12, 9, and 6 of aliphatic chains in phospholipids of the outer monolayers. Furthermore, the methanol increased annular lipid fluidity and also caused membrane proteins to cluster. The important finding is that was far greater increase by methanol in annular lipid fluidity than increase in lateral and rotational mobilities by the methanol. Methanol alters the stereo or dynamics of the proteins in the lipid bilayers by combining with lipids, especially with the annular lipids. In conclusion, the present data suggest that methanol, in additions to its direct interaction with proteins, concurrently interacts with membrane lipids, fluidizing the membrane, and thus inducing conformational changes of proteins known to be intimately associated with membranes lipids.
Anisotropy ; Cell Membrane ; Cerebral Cortex ; Diphenylhexatriene ; Lipid Bilayers ; Membrane Lipids ; Membrane Proteins ; Membranes ; Methanol ; Neurons ; Palmitic Acids ; Phospholipids ; Proteins ; Stearic Acids

Developed proteome-scale ortholog and paralog prediction methods are mainly based on sequence similarity. However, it is known that even the closest BLAST hit often does not mean the closest neighbor. For this reason, we added conserved interaction information to find orthologs. We propose a genome-scale, automated ortholog prediction method, named OrthoInterBlast. The method is based on both sequence and interaction similarity. When we applied this method to fly and yeast, 17% of the ortholog candidates were different compared with the results of Inparanoid. By adding protein-protein interaction information, proteins that have low sequence similarity still can be selected as orthologs, which can not be easily detected by sequence homology alone.
Diptera ; Proteins ; Sequence Homology ; Yeasts

BACKGROUND: Though leptin, the adipocytes-derived hormone, plays an important role in obesity, it can act as a growth factor for several cancers including gastrointestinal malignancies. Based on this background, we investigated whether leptin expression correlated with the clinicopathological characteristics or disease outcome in patients with colon cancer. We immunohistochemically analyzed the expression of leptin in a "colon adenoma-carcinoma sequence" in the normal colon mucosa, an adenomatous polyp and adenocarcinoma tissue, from a surgical resection for each patient. METHODS: We collected samples from 24 patients with a colorectal adenocarcinoma that was removed in either a total colectomy or hemicolectomy, and who presented with an adenomoatous polyp and an adenocarcinoma in the same surgical specimen. Leptin expression was assessed using immunohistochemical methods and was evaluated by grading the staining intensity as 0, +1, +2, +3. RESULTS: Whereas leptin expression was observed in 4.2% (1/24) of the normal colon mucosa, adenomatous polyps and adenocarcinomas showed 33.3% (8/24) and 50.0% (12/24) expression of leptin, respectively (p<0.05), suggesting that leptin expression in the adenomatous polyps and adenocarcinomas was higher than in the normal colon mucosa (p<0.05). There was no significant difference in leptin expression between the adenomatous polyps and adenocarcinomas, statistically. There was no relationship between leptin expression and patients age, sex, BMI (body mass index), cancer stage, and lymph node metastasis. However, the tumor size in the positive leptin expression group was larger than in the negative leptin expression group (5.6+/-2.2 cm vs 3.9+/-1.4 cm; p<0.05) CONCLUSIONS: Since leptin expression in adenomatous polyps and adenocarcinomas was higher than in the normal colon mucosa and leptin expression significantly correlated with the tumor size, leptin might play a role in the development of an adenomatous polyp and an adenocarcinoma in the colon. However, leptin does not contribute to the progression of colon adenoma, and further evaluation studies will be required.
Adenocarcinoma* ; Adenoma ; Adenomatous Polyps* ; Colectomy ; Colon* ; Colonic Neoplasms* ; Humans ; Leptin* ; Lymph Nodes ; Mucous Membrane ; Neoplasm Metastasis ; Obesity ; Polyps

This is the first report of papillary thyroid carcinoma combined with multiple endocrine neoplasia type 1 (MEN 1). It is an hereditary syndrome characterized by neoplastic disorders such as pituitary adenoma, parathyroid adenoma or hyperplasia and pancreatic neuroendocrine tumor, such as gastrinoma just like in our case. But sometimes pheochromocytoma, mucosal ganglioneuromas, lipoma, forgut carcinoid and thyroid disease could be accompany the disease, but coincidental papillary thyroid carcinoma was never reported before in Korea. Herein we represent a 39-year-old woman who manifested typical features of MEN 1 with coincidental papillary thyroid carcinoma. Despite with definite family history of MEN 1, her genetic analysis of DNA had not found any germline mutation in MEN 1 gene. Unidentified culprit gene unable further genetic study of finding LOH (loss of heterogeneity) in 11q13, the possible explanation of papillary thyroid carcinoma as a new component of MEN 1. As we have experienced a case of MEN 1 combined with papillary thyroid carcinoma, we report it with the review of literature.
Adult ; Carcinoid Tumor ; DNA ; Female ; Ganglioneuroma ; Gastrinoma ; Germ-Line Mutation ; Humans ; Hyperplasia ; Korea ; Lipoma ; Multiple Endocrine Neoplasia Type 1* ; Multiple Endocrine Neoplasia* ; Neuroendocrine Tumors ; Parathyroid Neoplasms ; Pheochromocytoma ; Pituitary Neoplasms ; Prolactinoma ; Thyroid Diseases ; Thyroid Gland* ; Thyroid Neoplasms*

No abstract available.