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For the long-term efficacy of dry eye disease treatment, relieving underlying inflammation is necessary. Imatinib mesylate is a novel ophthalmic formulation of imatinib mesylate, which is expected to alleviate inflammation by inhibiting the discoidin domain receptor 1 activity. This study aims to evaluate the safety and pharmacokinetics of imatinib mesylate in healthy subjects. A randomized, double-blind, placebo-controlled study was conducted. In a single ascending dose, 16 subjects received a single eye drop of imatinib mesylate 0.1%, 0.3%, or matching placebo. In the multiple ascending dose (MAD), subjects received multiple eye drops of imatinib mesylate 0.1%, 0.3%, or matching placebo once daily for 7 days. Safety and tolerability were assessed by ophthalmic examination, including the visual analog scale (VAS) to monitor the burning sensation in the eyes. A total of four treatment-emergent adverse events (TEAEs) occurred during the study. All TEAEs were mildly severe with no serious cases. VAS results in the 0.1% MAD group exhibited highest score of two points, whereas it was less than one point in others. Insignificant difference between the imatinib mesylate and placebo groups in the VAS results was seen. After a single dose administration of imatinib mesylate 0.1%, all plasma concentrations were below the lower limit of quantification. The peak plasma concentrations of imatinib were less than 0.54 µg/L in all groups. In conclusion, a single and multiple topical ophthalmic administration of imatinib mesylate was well-tolerated in healthy subjects. Because there was minimal systemic exposure to imatinib, the adverse effect in the body seems to be insignificant.

Hypertension and hyperlipidemia are often comorbid, requiring combination therapies of antihypertensive drugs and antihyperlipidemia drugs. Taking 1 fixed-dose combination (FDC) may increase patient compliance rather than taking each of the drugs separately. This study aimed to evaluate the pharmacokinetic bioequivalence between an FDC of pitavastatin/valsartan 4/160 mg and the corresponding individual components. Considering that valsartan is a highly variable drug for maximum plasma concentration (C

Background This study prospectively evaluated the risk of relapse according to the status of histologic activity in patients with ulcerative colitis (UC) who achieved deep remission. Methods Patients with UC in clinical remission (partial Mayo score ≤1) and endoscopic remission (ulcerative colitis endoscopic index of severity ≤1) were enrolled. Rectal biopsies were performed in patients, and histologic remission was defined as a Robarts histopathology index of ≤3. Receiver-operating characteristic curve analysis was conducted to determine fecal calprotectin cutoff values for histologic remission. The cumulative risk of relapse was evaluated using the Cox proportional hazards model. Results Among the 187 patients enrolled, 82 (43.9%) achieved histologic remission. The best cutoff value of fecal calprotectin for predicting histologic remission was 80 mg/kg (area under the curve of 0.646, sensitivity of 74%, and specificity of 61%). Among 142 patients who were followed up for >3 months, 56 (39.4%) showed clinical relapse during a median of 42 weeks. The risk of relapse was lower in patients with histologic remission than in those with histologic activity (P = .026). In multivariable analysis, histologic remission (hazard ratio [HR], 0.551; 95% confidence interval [CI], 0.316-0.958; P = .035), elevated C-reactive protein levels (HR, 3.652; 95% CI, 1.400-9.526; P = .008), and history of steroid use (HR, 2.398; 95% CI, 1.196-4.808; P = .014) were significantly associated with clinical relapse. Conclusions In patients with UC who achieved clinical and endoscopic remission, histologic remission was independently associated with a lower risk of clinical relapse.

Background Guidelines recommending additional imaging for adrenal nodules lack relevant epidemiologic evidence. Purpose To measure the prevalence of adrenal nodules detected at staging CT in patients with potentially resectable gastric cancer and the proportion of patients with malignant nodules among them. Materials and Methods This retrospective study included 10 250 consecutive patients (median age, 63 years; interquartile range, 53-71 years; 6884 men) who underwent staging CT and had potentially resectable gastric cancer in a tertiary center (May 2003 to December 2018). All 10 250 CT studies were retrospectively reviewed, and patients with adrenal nodules (or thickening ≥10 mm) were identified to measure the prevalence of adrenal nodules. Among patients with adrenal nodules, the per-patient proportions of malignant nodules, adrenal metastasis from gastric cancer, and additional adrenal examinations were measured. A secondary analysis was performed by using data from the original CT reports. The same metrics that were used in the retrospective review were assessed. Results The prevalence of adrenal nodules was 4.5% (95% CI: 4.1, 4.9; 462 of 10 250). The proportions of malignant nodules and adrenal metastasis from gastric cancer were 0.4% ( 95% CI: 0.1, 1.6; two of 462) and 0% (95% CI: 0.0, 0.8; 0 of 462), respectively. A total of 27% of the patients (95% CI: 23, 31; 123 of 462) underwent additional adrenal examination. According to original CT reports, the prevalence of adrenal nodules and the proportions of malignant nodules, adrenal metastases from gastric cancer, and additional adrenal examination were 2.7% (95% CI: 2.4, 3.0; 272 of 10 250), 0.7% (95% CI: 0.1, 2.6; two of 272), 0% (95% CI: 0.0, 1.4; 0 of 272), and 42.6% (95% CI: 36.7, 48.8; 116 of 272), respectively. Conclusion Although adrenal nodules were detected frequently on staging CT images of patients with otherwise resectable gastric cancer, these nodules were rarely malignant. ©RSNA, 2021

Tertiary drug information resources are frequently consulted for the optimal antimicrobial dosing in intermittent hemodialysis (IHD) patients. Yet, significant discrepancy may exist in dosing recommendations between resources. This study was to evaluate the consistency of antimicrobial dosing recommendations in IHD among four different drug information resources and the relevance of referenced pharmacokinetic studies.Dosing recommendations of 29 commonly prescribed antimicrobials in IHD patients were collected from Micromedex, LexiComp, Clinical Pharmacology and Drug Prescribing in Renal Impairment to compare dosing categorization and the total daily dose (TDD). Significant dosing discrepancies were defined as ≥30% difference. Referenced pharmacokinetic studies were evaluated for their relevance in current practice, using sample size, hemodialyzer types, the use of optimal pharmacodynamic targets and the consideration of different interdialytic dosing periods.A significant variation was found both in dosing categorization and recommended doses between resources. Seventeen drugs were compared for TDD with significant dosing discrepancy in 8 drugs. Among 42 referenced pharmacokinetic studies, 40 were evaluated. Mean patient numbers of pharmacokinetic studies were 13 ranging from 3 to 70. Sixty per cent of studies utilized contemporary hemodialyzers (e.g., high-flux and/or high efficiency). The optimal pharmacodynamic targets and the impact of different interdialytic intervals were assessed only in 27.5% and 7.5% respectively.Inconsistent antimicrobial dosing recommendations for IHD patients exist among four well-established resources. Many referenced pharmacokinetic studies utilized outdated or less pharmacodynamically relevant study methods. Newer studies are warranted to reflect contemporary dialysis practice and assess its impact on optimal antimicrobial dosing.

Conventionally, Te has primarily been used to improve the machinability of steel and its alloys. In this work, Te was used to refine the grains of an oxide-dispersion-strengthened (ODS) steel produced by additive manufacturing (AM) with fixed processing parameters. Addition of Te to the raw powder produced an ODS steel with a fine-grained microstructure, in contrast to the ODS steel manufactured without Te. Moreover, the addition of Te resulted in superior yield strength and ultimate tensile strength, which was attributed to the combined effects of grain refinement and the finer nanoparticles (NPs) composed of Te-rich composite NPs and Cr-rich NPs. For the first time, the AM technique was used to obtain grain and nanoparticle sizes of ~3.4 µm and 6 nm, respectively, from the Te-added ODS steel

Although angiomyolipoma (AML) is commonly found in the kidney, its appearance in the liver is rare. The first hepatic AML was reported by Ishak in 1976. Since then, there have been various reports of AML. An AML is a tumour affecting adipocytes, muscle tissues, and blood vessels. Hepatic AML has been associated with tuberous sclerosis. Its spontaneous occurrence has also been noticed. It can have a varied presentation with some being asymptomatic, others presenting with a dull aching pain, while some with disastrous consequences due to rupture and torrential bleeding intra-abdominally. Herein, we present a case of a 47-year-old female with a large hepatic AML having an internal hemorrhage that caused changes in hepatic arteries. In our case, magnetic resonance imaging was unable to establish a diagnosis. Intraoperatively, AML caused dilatation and engorgement of vessels around the porta. Immediately post resection, vessel dilatation and engorgement were reduced on table. Another notable feature was that these changes caused no intra-operative or post-operative hemodynamic changes. We report a case of a huge hepatic AML with internal hemorrhage associated with perihepatic vascular changes having a successful surgical treatment.

The efficacy of programmed death ligand (PD-L)-1/PD-1 checkpoint blockade in renal cell carcinoma (RCC) remains unknown. The effects of mTOR inhibitors are uncertain, and patients may develop resistance to them. The limited understanding of cancer cell-intrinsic mTOR-mediated pathways remains a challenge in developing effective treatments. Whether transcription factor (TF)-E3 regulates PD-L1 expression and the tumor microenvironment was investigated, and the effects of an mammalian target of rapamycin (mTOR) inhibitor on translocation RCC were explored. TFE3 was overexpressed in clear cell RCC cell lines, and PD-L1 expression was analyzed by Western blot analysis. PD-L1 activity in translocation RCC was analyzed in relation to TFE3 expression via TFE3 knockdown and treatment with an mTOR inhibitor. The results were correlated with the gene expression profile, evaluated using digital multiplex analysis. TFE3 and PD-L1 expression were positively correlated in RCC cells. TFE3 overexpression was associated with the expression of PD-L1 in RCC. Furthermore, mTOR inhibition was associated with enhanced PD-L1 expression via TFE3 activation in translocation RCC. These data support the feasibility of combination therapy based on mTOR inhibition and PD-L1 blockade as a novel strategy for the treatment of patients with translocation RCC.

Chemical short-range order in disordered solid solutions often emerges with specific heat treatments. Unlike thermally activated ordering, mechanically derived short-range order (MSRO) in a multi-principal-element Fe40Mn40Cr10Co10 (at%) alloy originates from tensile deformation at 77 K, and its degree/extent can be tailored by adjusting the loading rates under quasistatic conditions. The mechanical response and multi-length-scale characterisation pointed to the minor contribution of MSRO formation to yield strength, mechanical twinning, and deformation-induced displacive transformation. Scanning and high-resolution transmission electron microscopy and the anlaysis of electron diffraction patterns revealed the microstructural features responsible for MSRO and the dependence of the ordering degree/extent on the applied strain rates. Here, we show that underpinned by molecular dynamics, MSRO in the alloys with low stacking-fault energies forms when loaded at 77 K, and these systems that offer different perspectives on the process of strain-induced ordering transition are driven by crystalline lattice defects (dislocations and stacking faults).

The authors report a rare case of sequentially developed bilateral internal carotid artery (ICA) fusiform giant aneurysms in a patient with pathologically confirmed intimal fibroplasia. Both ICA fusiform aneurysms were treated with multiple flow diverter insertion and were well-managed over the past 5.5 years of follow-up. The development of aneurysms in this rare disease entity appears to be a lifelong process based on the authors’ observations in serial angiographic follow-up studies. Reconstruction therapy using flow-diverting stents in this unique condition may be a safe and effective treatment modality.

Objectives: This study aims to investigate patterns of visual attention on a target object in VSDs (Visual Scene Displays) when they are designed with/without an action of usage of the object. We used eye-tracking technology to evaluate how the action of usage of an object in still photographs influenced the visual attention of adults without disabilities. We tried to examine visual attention on the contents of visual scene displays (VSDs).Methods: 25 college students participated in the study. Eye-tracking technology recorded point-of-gaze while participants viewed 20 photographs. Data from eye-tracking provided information on where participants were visually fixated and paid more attention on the presented VSDs including a target object.Results: Both total fixation duration and average fixation count were statistically significant. Participants visually fixated on the target object longer and more often when the object was being used in the presented VSDs. For AOI (Area Of Interest) time of the first fixation, after analyzing only a partial group that had the data match due to the difference in gaze pattern per subject, the average AOI time of the first fixation was shown to be faster when using an object in 6 out of 10 objects.Conclusion: This study supports the inclusion of an action of an object usage in VSDs suggesting that the act of object usage can partially influence the visual attention pattern of a user.

We identified nine Verona integron-encoded metallo-β-lactamase-2 (VIM-2)-producing Acinetobacter nosocomialis (n = 8) and Acinetobacter seifertii (n = 1) isolates from South Korea and performed who...

Background A laparoscopic approach is widely used in abdominal surgery. Although several studies have compared surgical and oncological outcomes between laparoscopic surgery (LS) and open surgery (OS) in rectal cancer patients, there have been few studies on postoperative renal outcomes. Methods We conducted a retrospective cohort study involving 1,633 patients who underwent rectal cancer surgery between 2003 and 2017. Postoperative acute kidney injury (AKI) was diagnosed according to the serum creatinine criteria of the Kidney Disease: Improving Global Outcomes classification. Results Among the 1,633 patients, 1,072 (65.6%) underwent LS. After matching propensity scores, 395 patients were included in each group. The incidence of postoperative AKI in the LS group was significantly lower than in the OS group (9.9% vs. 15.9%; p = 0.01). Operation time, estimated blood loss, and incidence of transfusion in the LS group were significantly lower than those in the OS group. Cox proportional hazard models revealed that LS was associated with decreased risk of postoperative AKI (hazard ratio [HR], 0.599; 95% confidence interval [CI], 0.402-0.893; p = 0.01) and postoperative transfusion was associated with increased risk of AKI (HR, 2.495; 95% CI, 1.529-4.072; p < 0.001). In the subgroup analysis, the incidence of postoperative AKI in patients with middle or high rectal cancer who underwent LS was much lower than in those who underwent OS (HR, 0.373; 95% CI, 0.197-0.705; p = 0.002). Conclusion This study showed that LS may have a favorable effect on the development of postoperative AKI in patients with rectal cancer.

A malignancy is a fatal condition that could occur through various mechanisms. Forensic pathologists sometimes find unexpected findings during autopsy and post-mortem (PM) tests. Colorectal cancer is one of the leading causes of cancer-related deaths worldwide. The deceased was a 64-year-old man with a medical history of right hemicolectomy due to colon cancer approximately two years earlier. He was found dead at his home. He was admitted to the hospital due to subdural hemorrhage (SDH) two days prior to his demise and was discharged without the permission of the doctor after one day of hospitalization. An autopsy was performed within two days of his death. After gross dissection, the cause and manner of death were assumed to be SDH and unnatural death, respectively. Microscopic examination revealed fresh SDH and dural metastasis of signet-ring cell carcinoma. Furthermore, metastasis was identified in the heart, stomach, and peritoneum. Immunohistochemical examination revealed cancer cells to originate from the colon. After meticulous PM examination, including gross dissection, microscopic examination, PM computed tomography, and PM laboratory tests, the cause and manner of death were determined as SDH and natural death, respectively. This case report highlights the importance of comprehensive PM evaluation for investigating death.

Omeprazole blocks the gastric H+ /K+ adenosine triphosphatase, thus inhibiting gastric acid secretion, and is metabolized by cytochrome P450 (CYP) 2C19. Due to the physiological changes in the elderly, there are different pharmacokinetic consequences compared to young people. The aim of this study was to evaluate the pharmacokinetic profiles of omeprazole in 15 elderly participants according to the CYP2C19 genotype. The concentration-time profiles of omeprazole and its metabolites, 5-hydroxy (5-OH) omeprazole and omeprazole sulfone, were similar between the CYP2C19 extensive metabolizer (EM) and intermediate metabolizer groups. In contrast, when comparing the EM group and CYP2C19 poor metabolizer (PM) group, the EM/PM geometric mean ratio (95% confidence interval) of area under the plasma concentration-time curve from time of dosing to the last measurable concentration was 0.52 (0.27-1.01) and that of the IM group was 0.71 (0.32-1.59), indicating that the exposure of omeprazole in the PM group was increased. The exposure of 5-OH omeprazole was significantly decreased in the PM group when compared to the EM group, with an EM/PM geometric mean ratio (95% confidence interval) of 2.20 (1.50-3.22). In conclusion, the tendency of drug exposure according to the CYP2C19 genotype in the elderly and young adults was similar in that the exposure level was highest in the PM group. However, when compared to young adults, the difference between the genotype groups was smaller in the elderly.

Neuroendocrine neoplasms (NENs) such as small cell lung cancer (SCLC) and large cell neuroendocrine carcinoma (LCNEC) have characteristic histologies, but immunohistochemistry using neuroendocrine markers is still desirable to confirm diagnosis. CD56 is the most sensitive marker, but also stains various normal tissues and other tumors. Recently, we reported that nucleolar protein 4 (NOL4) is present in the blood of SCLC patients and found it was stained in the SCLC nuclei. In this study, we compared expressions of NOL4 and CD56, using 64 cases of SCLC, 18 cases of LCNEC, 6 cases of atypical carcinoid tumor, 7 cases of typical carcinoid tumor, 68 cases of lung adenocarcinoma, and 62 cases of lung squamous cell carcinoma. For primary lung NENs, sensitivity, specificity, positive predictive value (PPV) and negative predictive value of NOL4 were 77.5%, 95.8%, 93.2%, and 85.1%, respectively, while those of CD56 were 92.1%, 93.3%, 91.1%, and 94.1%. The specificity and PPV of NOL4 were higher than those of CD56, although the differences were not statistically significant. However, NOL4 retains its nuclear immunoreactivity in areas of crush artifact or necrosis. Furthermore, NOL4 was not expressed in adjacent normal tissues including bronchial cells and pneumocytes. Therefore, a combination of NOL4 staining with other cytoplasmic or membranous neuroendocrine markers might enhance diagnostic utility for SCLC and other NENs.

Tujuan dari penelitian kualitatif ini adalah untuk mengeksplorasi transformasi holistik siswa yang mengikuti kelas taekwondo di tiga lembaga pendidikan olahraga di Jakarta. Transformasi holistik diartikan sebagai perubahan aspek fisik, mental, dan spiritual siswa. Oleh karena itu, pendekatan holistik terhadap kesehatan dan kebugaran melalui pendidikan olahraga Kristen dianggap penting. Penelitian ini mengeksplorasi pertanyaan-pertanyaan berikut: apa tujuan kepemimpinan Kristen dalam pendidikan olahraga; bagaimana mengajarkan nilai-nilai Kristen melalui kelas taekwondo; apa peran master taekwondo sebagai pemimpin; dan bagaimana transformasi kepribadian holistik pada siswa melalui kelas taekwondo? Untuk menjawab pertanyaan tersebut, dilakukan wawancara semi terstruktur dan diskusi kelompok terfokus. Para peserta termasuk Pendeta, pemimpin olahraga Kristen, guru olahraga, master Taekwondo, siswa Taekwondo dan orang tua. Setting penelitian ini adalah tiga organisasi pendidikan olahraga berbasis Kristen di Jakarta yang menawarkan kelas taekwondo untuk anak-anak dan remaja, baik Kristen dan non-Kristen: K-art Studio, New G, dan tim Somang Taekwondo.

Treatment for early colon cancer has progressed rapidly, with endoscopic resection and minimally invasive surgery. It is important to select patients without risk of lymph node metastasis before deciding on endoscopic resection for early colon cancer treatment. Pathological risk factors include histologic grade of cancer cell differentiation, lymphovascular invasion, perineural invasion, tumor budding, and deep submucosal invasion. These risk factors for predicting lymph node metastasis are crucial for determining the treatment strategy of endoscopic excision and radical resection for early colon cancer. A multidisciplinary approach is emphasized to establish a treatment strategy for early colon cancer to minimize the risk of complications and obtain excellent oncologic outcomes by selecting an appropriate treatment optimized for the patient's stage and condition. Therefore, we aimed to review the optimal multidisciplinary treatment strategies, including endoscopy and surgery, for early colon cancer.

Due to the extremely indolent behavior, a subset of noninvasive encapsulated follicular variant papillary thyroid carcinomas has been classified as “noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP)” since 2016 and is no longer considered carcinoma. Since the introduction of this new terminology, changes and refinements have been made in diagnostic criteria. Initially, the incidence of NIFTP was estimated substantial. However, the reported incidence of NIFTP varies greatly among studies and regions, with higher incidence in North American and European countries than in Asian countries. Thus, the changes in the risk of malignancy (ROM) in the Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) differ inevitably among regions. Because more conservative surgery is recommended for NIFTPs, distinguishing NIFTPs from papillary thyroid carcinomas in preoperative fine-needle aspiration cytology became one of the major concerns. This review will provide comprehensive overview of updates on diagnostic criteria, actual incidence and preoperative cytologic diagnoses of NIFTP, and its impact on the ROM in TBSRTC.

Background Serum histamine, immunoglobulin E, and tryptase are markers of allergic diseases. Despite the reported association between migraine and allergic diseases, differences in these marker levels between episodic and chronic migraines remain unelucidated. Methods We investigated serum histamine, immunoglobulin E, and tryptase levels in 97 and 96 participants with episodic migraine and chronic migraine, respectively, and 56 controls according to the presence of allergic diseases. Results Serum histamine levels in episodic migraine (median and interquartile ranges, 0.78 [0.65–1.25] ng/mL, p Conclusions Altered serum histamine and immunoglobulin E levels in episodic migraine and chronic migraine and different profiles concerning allergic diseases suggest the involvement of allergic mechanisms in migraine pathogenesis.

The use of sodium nitrite in suicide has become more common among young adults in the Republic of Korea. This report details the case of a 28-year-old man; the man had posted on a social network service detailing his attempt at suicide at 13:45. In the posted article, he stated that he had ingested 84 g of sodium nitrite. A post-mortem (PM) inspection was performed at 21:00, and peripheral blood (PB) was collected. An autopsy was performed approximately 44 h after death. The victim's face was dark brown in color, but the color of his oral mucosa was bright red. Toxicological analyses revealed 33% and 26% methemoglobinemia in the PB collected during PM inspection and autopsy, respectively. The concentration of nitrate in the PB collected during PM inspection, and PB and cardiac blood collected during the autopsy were 220.6 mg/L, 220.0 mg/L, and 218.5 mg/L, respectively. Nitrate was also detected in the pericardial fluid and cerebrospinal fluid at levels of 91.7 mg/L and 50.5 mg/L, respectively. The cause of death was determined to be methemoglobinemia-induced hypoxia due to sodium nitrite ingestion. This intoxication case informs some novel points about nitrite intoxication; the concentration of methemoglobin decreased during the PM period, while the concentration of nitrate was stable. There was no difference in the concentration of nitrate between cardiac and peripheral blood. Nitrate could be detected in the pericardial fluid and cerebrospinal fluid. This new information is helpful for better identifying future cases of nitrite intoxication.

Purpose: Current understanding of COVID-19 disease progression suggests a major role for the “cytokine storm” as an important contributor to COVID-19 mortality. To prevent an exaggerated immune response and improve COVID-19 patient endpoints, anti-inflammatory therapeutics have been proposed as clinically useful in severe patients with COVID-19. The purpose of this study was to propose a clinical trial design for the development of anti-inflammatory agents for the treatment of COVID-19, taking into account the physiological and immunological process of COVID-19 and the treatment mechanism of anti-inflammatory agents.Methods: We reviewed and analyzed the guidelines for the development of COVID-19 treatments and the treatment of COVID-19 by regulatory agencies and previously conducted clinical trials on anti-inflammatory drugs for COVID-19. Finally, after discussing with an advisory group, a synopsis was presented for an example protocol for a COVID-19 anti-inflammatory agent phase 2 or 3 study that considers the drug mechanism and the disease progression of COVID-19.Results: A randomized, placebo-controlled, double-blind parallel-group design was suggested as a phase 2 or 3 trial design for developing an anti-inflammatory agent as a COVID-19 treatment. A key item of the example protocol specific to anti-inflammatory agents was the inclusion and exclusion criteria, taking into account the immunosuppressive effects of the drug, clinical time course of COVID-19 disease, and treatment guidelines for COVID-19. Time to recovery is the primary endpoint associated with clinical efficacy and is generally well accepted by many experts.Conclusion: Through this suggested phase 2 or 3 study design of an anti-inflammatory drug for COVID-19, we provide a basis for a study design that can be utilized in clinical development by pharmaceutical companies which are developing a potential anti-inflammatory agent for COVID-19.

BACKGROUND AND AIMS Although C1q nephropathy (C1QN) was introduced three decades ago, the clinical significance and renal outcomes of C1QN remain unclear. Furthermore, it is uncertain whether the diagnosis of C1QN could be a new pathologic entity with clinical meanings. This study aimed to compare the clinical characteristics of the GN reclassified into C1QN based on the criteria described by Jennette and Falk (Pediatr Nephrol 2010: 25: 1385–1396) and corresponding GN not included in C1QN. METHOD We enrolled 21 212 patients with native kidney biopsy between 1979 and 2018 from 18 hospitals throughout Korea, retrospectively. We primarily adopted the findings and diagnosis by the pathologist in each hospital and then reclassified into C1q nephropathy (C1QN) on the basis of the criteria as follows: (i) presence of ≥ 2 + C1q in the mesangium on immunofluorescence (IF), (ii) corresponding mesangial or para-mesangial electron dense deposits on electron microscopy (EM), and (iii) lack of clinical and pathological evidence of systemic lupus erythematosus. Among 21212 patients, 77 patients were selected as C1QN with the criteria; however, six patients were excluded because of presence of primary diseases, such as renal amyloidosis, Henoch-Schölein Nephritis and systemic vasculitis, and myeloma cast nephropathy. The data of final outcomes, incidences of end-stage renal disease (ESRD) and death, were gathered from each hospital’s data registry, from the ESRD registry of the Korean Society of Nephrology, and from the Statistics of Korea, and were merged based on the identifier of Koreans. The follow-up duration for ESRD was 69.1 ± 67.8 months and, for mortality, 77.9 ± 65.5 months. RESULTS There were pathologic findings of 71 patients reclassified into C1QN including 41 (57.7%) males. Mean age of patients were 42.9 ± 18.9 years. There were 9 (12.7%) patients with DM and 39 (54.9%) hypertensive patients. The levels of creatinine, eGFR, and UPCR were 1.24 ± 0.92 mg/dL, 84 ± 43 mL/min/1.73 m2 and 2.58 ± 2.80 g/g creatinine, respectively. There were 22 (31.0%) patients with eGFR < 60 mL/min/1.73 m2 and 22 (31.0%) patients with UPCR ≥ 3.5 g/g creatinine. There were various pathologic diagnoses classified into C1QN, such as, original C1QN (21), IgA nephropathy (IGAN) (21), membranous nephropathies (MN) (11), focal segmental glomerulosclerosis (7), mesangial glomerulopathy (6), diabetic nephropathy (3), minimal change lesion (1), and acute tubulointerstitial nephritis (1). We compared the characteristics among the pathologic finding classified into C1QN, the pathologic finding without C1q stain, and the pathologic finding with non-dominant C1q stain which did not fulfill the criteria of C1QN. The identified GNs, which included enough number of patients to compare, were FSGS, IGAN and MN. Some differences of clinico-pathologic findings and incidence of ESRD were not evident after re-analysis with groups matched age and gender with 1:3 manner between the GN re-categorized into C1QN and the corresponding GN without C1q staining. The only difference was lesser amount of proteinuria in MN patients re-classified into C1QN compared with MN patients without C1q staining. Immunoglobulins showed higher intensity in IF staining of C1QN compared with non-C1QN of the corresponding GN. Intensity of C3 was also higher in IGAN and MN re-categorized into C1QN compared with the corresponding IGAN and MN not included in C1QN, respectively. CONCLUSION Reclassification into C1QN with the pre-defined criteria did not indicate a different clinico-pathologic identity based on comparison with the original diagnosis of GN. Activation of C1q, presumed activation of classical complement pathway in kidney tissues, in so-called C1QN could not be classified into new disease entity. Further studies on this topic are needed.

Fecal microbiota transplantation (FMT) is considered as an effective treatment for Clostridioides difficile infection. However, the precise mechanism of FMT is yet to be determined. Human stool consists of the gut microbiota, bacterial debris, and metabolic products. Of these, the intestinal microbiota is the most important factor that exerts therapeutic efficacy in FMT. Fresh donor stool, blended with normal saline, has been employed for traditional FMT. Nevertheless, stool processing is a major impediment in FMT. Frozen stool and capsule formulations have similar efficacy to that of fresh stool. In addition, several novel stool products have been identified. A stool bank that provides stool products with pre-screened donor stool has been established to help physicians and thereby facilitate FMT. Recent next-generation sequencing techniques have been key in facilitating the detailed analysis of the microbiota and gut environment of individual donors and recipients.

Background The incidence and mortality rates of colorectal cancer (CRC) has been reported to be strongly associated to sex/gender difference. CRC shows sexual dimorphism, and sex hormones have been shown to affect the tumor immune microenvironment. This study aimed to investigate location-dependent sex differences in tumorigenic molecular characteristics in patients with colorectal tumors, including adenoma and CRC. Methods A total of 231 participants, including 138 patients with CRC, 55 patients with colorectal adenoma, and 38 healthy controls, were recruited between 2015 and 2021 at Seoul National University Bundang Hospital. All patients underwent colonoscopy and acquired tumor lesion samples were further analyzed for programmed death-ligand 1 (PD-L1), epidermal growth factor receptor (EGFR) expression, deficient mismatch repair (dMMR), and microsatellite instability (MSI) status. This study was registered with ClinicalTrial.gov, number NCT05638542. Results The average of combined positive score (CPS) was higher in serrated lesions and polyps (lesions/polyps) compared to conventional adenomas (5.73 and 1.41, respectively, P < 0.001). No significant correlation was found between sex and PD-L1 expression within the groups, regardless of histopathological diagnosis. In multivariate analysis where each sex was further stratified by tumor location due to their interaction in CRC, PD-L1 expression was inversely correlated with males having proximal CRC with a CPS cutoff of 1 (Odds ratio (OR) 0.28, P = 0.034). Females with proximal CRC showed a significant association with dMMR/MSI-high (OR 14.93, P = 0.032) and high EGFR expression (OR 4.17, P = 0.017). Conclusion Sex and tumor location influenced molecular features such as PD-L1, MMR/MSI status and EGFR expression in CRC, suggesting a possible underlying mechanism of sex-specific colorectal carcinogenesis.

Although type I IFNs (IFN-I) are important for the innate and adaptive immune responses to suppress viral replication, prolonged IFN-I signaling in macrophages suppresses the immune response. Nuclear receptor estrogen-related receptor γ (ERRγ) regulates the transcription of genes involved in endocrine and metabolic functions. However, the role of ERRγ in macrophage immune responses to viruses remains largely unknown. ERRγ expression was significantly induced in mouse bone marrow-derived macrophages (BMDMs) treated with polyinosinic-polycytidylic acid (poly(I:C)). Our results indicated that the induction of ERRγ expression by poly(I:C) is mediated through activation of the cytoplasmic dsRNA receptors, retinoic acid-inducible gene I and melanoma differentiation-associated protein 5. In BMDMs, overexpression of ERRγ significantly increased gene expression and secretion of the IFN-I genes, IFN-α and IFN-β, whereas abolition of ERRγ significantly attenuated poly(I:C)-mediated IFN-I secretion. Chromatin immunoprecipitation assays and mutation analyses of the IFN-I promoters revealed that ERRγ regulates the transcription of IFN-α and IFN-β by binding to a conserved ERR response element in each promoter region. Finally, GSK5182 significantly suppressed poly(I:C)-mediated induction of IFN-I gene expression and secretion in BMDMs. Taken together, these findings reveal a previously unrecognized role for ERRγ in the transcriptional control of innate and adaptive immune response to dsRNA virus replication.

Purpose To examine the relationships of body dysmorphic disorder (BDD) with psychiatric symptoms and quality of life in dermatological patients. Patients and Methods A total of 154 female patients with dermatological disease underwent a comprehensive clinical assessment that included the Body Dysmorphic Disorder Examination-Self Report (BDDE-SR), Symptom Checklist 90-Revised (SCL-90-R), and Skindex-29. Dermatological disease was categorized as follows: inflammatory dermatoses (reference category), isolated lesions, and unclassified dermatoses. The BDDE-SR and SCL-90-R scores were used to evaluate BDD and psychiatric symptoms, respectively. Dermatological quality of life was measured with the Skindex-29. Results The BDDE-SR score was significantly associated with the SCL-90-R and Skindex-29 total and subscores, even after controlling for age, body mass index, and dermatological diagnosis. The variables that contributed most to the BDDE-SR score were the SCL-90-R depression score and Skindex-29 emotion scores. Additional analyses revealed that the BDDE-SR score was higher in participants with unclassified dermatoses, but neither the SCL-90-R score nor Skindex-29 score was related to any dermatological diagnosis. Conclusion The BDD symptoms were especially prominent in the unclassified dermatoses group and were highly related to psychiatric symptoms and a poor quality of life in our dermatological patients. Further research including studies involving psychiatric interviews to confirm the BDD diagnosis and symptoms will improve our understanding of BDD in dermatological patients.