Background: and Purpose We delineated the association between otolithic dysfunction and blood pressure (BP) variability. Methods: We prospectively recruited 145 consecutive patients (age=71 [59–79] years, median [interquartile range]; 76 females) with orthostatic intolerance between December 2021 and December 2023 at a tertiary hospital in South Korea. Each patient underwent evaluations of cervical and ocular vestibular-evoked myogenic potentials (oVEMPs), 24-h noninvasive ambulatory BP monitoring (ABPM), and a head-up tilt-table test using the Finometer device. As measures of BP variability, the standard deviations (SDs) of the systolic BP (SBP SD) and the diastolic BP were calculated based on serial ABPM recordings. Patients were divided into those with orthostatic hypotension (OH, n=68) and those with a normal head-up tilt-table test despite orthostatic intolerance (NOI, n=77) groups. Results: A multivariable logistic regression analysis showed that OH was associated with bilateral oVEMP abnormalities (p=0.021), SBP SD (p=0.012), and female sex (p=0.004). SBP SD was higher in patients with OH than in those with NOI (p<0.001), and was not correlated with n1–p1 amplitude (p=0.491) or normalized p13–n23 amplitude (p=0.193) in patients with OH.The sensitivity and specificity for differentiating OH from NOI were 72.1% and 67.5%, respectively, at a cutoff value of 12.7 mm Hg for SBP SD, with an area under the receiver operating characteristic curve of 0.73. Conclusions Bilaterally deficient oVEMP responses may be associated with OH regardless of 24-h BP variability, reflecting the integrity of the otolith-autonomic reflex during orthostasis. Alternatively, 24-h BP variability is predominantly regulated by the baroreflex, which also participates in securing orthostatic tolerance complementary to the vestibulo-autonomic reflex.

Background: and Purpose We delineated the association between otolithic dysfunction and blood pressure (BP) variability. Methods: We prospectively recruited 145 consecutive patients (age=71 [59–79] years, median [interquartile range]; 76 females) with orthostatic intolerance between December 2021 and December 2023 at a tertiary hospital in South Korea. Each patient underwent evaluations of cervical and ocular vestibular-evoked myogenic potentials (oVEMPs), 24-h noninvasive ambulatory BP monitoring (ABPM), and a head-up tilt-table test using the Finometer device. As measures of BP variability, the standard deviations (SDs) of the systolic BP (SBP SD) and the diastolic BP were calculated based on serial ABPM recordings. Patients were divided into those with orthostatic hypotension (OH, n=68) and those with a normal head-up tilt-table test despite orthostatic intolerance (NOI, n=77) groups. Results: A multivariable logistic regression analysis showed that OH was associated with bilateral oVEMP abnormalities (p=0.021), SBP SD (p=0.012), and female sex (p=0.004). SBP SD was higher in patients with OH than in those with NOI (p<0.001), and was not correlated with n1–p1 amplitude (p=0.491) or normalized p13–n23 amplitude (p=0.193) in patients with OH.The sensitivity and specificity for differentiating OH from NOI were 72.1% and 67.5%, respectively, at a cutoff value of 12.7 mm Hg for SBP SD, with an area under the receiver operating characteristic curve of 0.73. Conclusions Bilaterally deficient oVEMP responses may be associated with OH regardless of 24-h BP variability, reflecting the integrity of the otolith-autonomic reflex during orthostasis. Alternatively, 24-h BP variability is predominantly regulated by the baroreflex, which also participates in securing orthostatic tolerance complementary to the vestibulo-autonomic reflex.

Background: and Purpose We delineated the association between otolithic dysfunction and blood pressure (BP) variability. Methods: We prospectively recruited 145 consecutive patients (age=71 [59–79] years, median [interquartile range]; 76 females) with orthostatic intolerance between December 2021 and December 2023 at a tertiary hospital in South Korea. Each patient underwent evaluations of cervical and ocular vestibular-evoked myogenic potentials (oVEMPs), 24-h noninvasive ambulatory BP monitoring (ABPM), and a head-up tilt-table test using the Finometer device. As measures of BP variability, the standard deviations (SDs) of the systolic BP (SBP SD) and the diastolic BP were calculated based on serial ABPM recordings. Patients were divided into those with orthostatic hypotension (OH, n=68) and those with a normal head-up tilt-table test despite orthostatic intolerance (NOI, n=77) groups. Results: A multivariable logistic regression analysis showed that OH was associated with bilateral oVEMP abnormalities (p=0.021), SBP SD (p=0.012), and female sex (p=0.004). SBP SD was higher in patients with OH than in those with NOI (p<0.001), and was not correlated with n1–p1 amplitude (p=0.491) or normalized p13–n23 amplitude (p=0.193) in patients with OH.The sensitivity and specificity for differentiating OH from NOI were 72.1% and 67.5%, respectively, at a cutoff value of 12.7 mm Hg for SBP SD, with an area under the receiver operating characteristic curve of 0.73. Conclusions Bilaterally deficient oVEMP responses may be associated with OH regardless of 24-h BP variability, reflecting the integrity of the otolith-autonomic reflex during orthostasis. Alternatively, 24-h BP variability is predominantly regulated by the baroreflex, which also participates in securing orthostatic tolerance complementary to the vestibulo-autonomic reflex.

Colorectal cancer is the third most common cancer in Korea and the third leading cause of death from cancer. Treatment outcomes for colon cancer are steadily improving due to national health screening programs with advances in diagnostic methods, surgical techniques, and therapeutic agents.. The Korea Colon Cancer Multidisciplinary (KCCM) Committee intends to provide professionals who treat colon cancer with the most up-to-date, evidence-based practice guidelines to improve outcomes and help them make decisions that reflect their patients’ values and preferences. These guidelines have been established by consensus reached by the KCCM Guideline Committee based on a systematic literature review and evidence synthesis and by considering the national health insurance system in real clinical practice settings. Each recommendation is presented with a recommendation strength and level of evidence based on the consensus of the committee.

Objective: This study investigated the associations between paraspinal muscle measurements on chest computed tomography and clinical outcomes of elderly patients with community-acquired pneumonia (CAP). Methods: This single-center, retrospective, observational study analyzed elderly patients (≥65 years) with CAP hospitalized through an emergency department between March 2020 and December 2022. We collected their baseline characteristics and laboratory data at the time of admission. The paraspinal muscle index and attenuation were calculated at the level of the 12th thoracic vertebra using chest computed tomography taken within 48 hours before or after admission. Univariable and multivariable logistic regression analyses were conducted to evaluate the association between paraspinal muscle measurements and 28-day mortality. Receiver operating characteristic (ROC) curve and area under the curve (AUC) analyses were used to evaluate the prognostic predictive power. Results: Of the 338 enrolled patients, 60 (17.8%) died within 28 days after admission. A high paraspinal muscle index was associated with low 28-day mortality in elderly patients with CAP (adjusted odds ratio, 0.994; 95% confidence interval, 0.992–0.997). The area under the ROC curve for the muscle index was 0.75, which outperformed the pneumonia severity index and the CURB-65 (confusion, urea, respiratory rate, blood pressure, age ≥65 years) metric, both of which showed an AUC of 0.64 in predicting mortality. Conclusion A high paraspinal muscle index was associated with low 28-day mortality in patients aged 65 years or older with CAP.

Interleukin-1 receptor-associated kinase 4 (IRAK4) is a pivotal enzyme in the Toll-like receptor (TLR)/MYD88 dependent signaling pathway, which is highly activated in rheumatoid arthritis tissues and activated B cell-like diffuse large B-cell lymphoma (ABC-DLBCL). Inflammatory responses followed by IRAK4 activation promote B-cell proliferation and aggressiveness of lymphoma. Moreover, proviral integration site for Moloney murine leukemia virus 1 (PIM1) functions as an anti-apoptotic kinase in propagation of ABC-DLBCL with ibrutinib resistance. We developed a dual IRAK4/PIM1 inhibitor KIC-0101 that potently suppresses the NF-κB pathway and proinflammatory cytokine induction in vitro and in vivo. In rheumatoid arthritis mouse models, treatment with KIC-0101 significantly ameliorated cartilage damage and inflammation. KIC-0101 inhibited the nuclear translocation of NF-κB and activation of JAK/STAT pathway in ABC-DLBCLs. In addition, KIC-0101 exhibited an anti-tumor effect on ibrutinib-resistant cells by synergistic dual suppression of TLR/MYD88-mediated NF-κB pathway and PIM1 kinase. Our results suggest that KIC-0101 is a promising drug candidate for autoimmune diseases and ibrutinib-resistant B-cell lymphomas.

Purpose: The activity and safety of neoadjuvant nivolumab plus gemcitabine/cisplatin (N+GC) were tested in patients with muscle-invasive bladder urothelial carcinoma (MIBC). Materials and Methods: In a prospective phase II trial, patients with cT2-T4a N0 MIBC who were eligible for cisplatin and medically appropriate to undergo radical cystectomy (RC) were enrolled. Treatment with nivolumab 3 mg/kg on days 1 and 15 plus GC (cisplatin 70 mg/m2 on day 1, and gemcitabine 1,000 mg/m2 on days 1, 8, and 15) was repeated every 28 days up to 3 or 4 cycles, depending on the surgery schedules. The primary endpoint was pathologic complete response (pCR, ypT0). Secondary endpoints included pathologic downstaging (≤ ypT1), disease-free survival (DFS), and safety. Results: Between September 2019 and October 2020, 51 patients were enrolled. Neoadjuvant N+GC was well tolerated. Among 49 patients who completed neoadjuvant N+GC, clinical complete response (cCR) was achieved in 59% of intent-to-treat (ITT) population. RC was performed in 34 (69%) patients. pCR was achieved in 24% (12/49) of ITT population and 35% (12/34) of RC patients. Median DFS was not reached. Over a median follow-up of 24 months, 12 patients experienced disease recurrence and were treated with palliative therapy or surgery. Although 12 patients declined surgery and were treated with concurrent chemoradiotherapy, DFS was longer in patients with cCR after neoadjuvant therapy than those without. Preoperative programmed death-ligand 1 (PD-L1) did not correlate with pCR or pathologic downstaging rates. Conclusion Neoadjuvant N+GC was feasible and provided meaningful pathologic responses in patients with MIBC, regardless of baseline PD-L1 expression (ONO-4538-X41; CRIS.nih.go.kr, KCT0003804).

Objective: : The association between boule (BOLL) and endothelin receptor type A (EDNRA) loci and intracranial aneurysm (IA) formation has been reported via genome-wide association studies. We sought to identify genome-wide interactions involving BOLL and EDNRA loci for IA in a Korean adult cohort. Methods: : Genome-wide pairwise interaction analyses of BOLL and EDNRA involving 250 patients with IA and 296 controls were performed using the additive effect model after adjusting for confounding factors. Results: : Among 512575 single-nucleotide polymorphisms (SNPs), 23 and 11 common SNPs suggested a genome-wide interaction threshold (p<1.25×10-8) involving rs700651 (BOLL) and rs6841581 (EDNRA). Rather than singe SNP effect of BOLL or EDNRA on IA development, they showed a synergistic effect on IA formation via multifactorial pair-wise interactions. The rs1105980 of PTCH1 gene showed the most significant interaction with rs700651 (natural log-transformed odds ratio [lnOR], 1.53; p=6.41×10-11). The rs74585958 of RYK gene interacted strongly with rs6841581 (lnOR, -19.91; p=1.64×10-9). Although, there was no direct interaction between BOLL and EDNRA variants, two EDNRA-interacting gene variants of TNIK (rs11925024 and rs1231) and FTO (rs9302654), and one BOLL-interacting METTL4 gene variant (rs549315) exhibited marginal interaction with BOLL gene. Conclusion : BOLL or EDNRA may have a synergistic effect on IA formation via multifactorial pair-wise interactions.

Background: Recent reports have suggested that pneumonitis is a rare complication following vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).However, its clinical features and outcomes are not well known. The aim of this study was to identify the clinical characteristics and outcomes of patients with vaccine-associated pneumonitis following vaccination against SARS-CoV-2. Methods: In this nationwide multicenter survey study, questionnaires were distributed to pulmonary physicians in referral hospitals. They were asked to report cases of development or exacerbation of interstitial lung disease (ILD) associated with the coronavirus disease 2019 vaccine. Vaccine-associated pneumonitis was defined as new pulmonary infiltrates documented on chest computed tomography within 4 weeks of vaccination and exclusion of other possible etiologies. Results: From the survey, 49 cases of vaccine-associated pneumonitis were identified between February 27 and October 30, 2021. After multidisciplinary discussion, 46 cases were analyzed. The median age was 66 years and 28 (61%) were male. The median interval between vaccination and respiratory symptoms was 5 days. There were 20 (43%), 17 (37%), and nine (19%) patients with newly identified pneumonitis, exacerbation of pre-diagnosed ILD, and undetermined pre-existing ILD, respectively. The administered vaccines were BNT162b2 and ChAdOx1 nCov-19/AZD1222 each in 21 patients followed by mRNA-1273 in three, and Ad26.COV2.S in one patient. Except for five patients with mild disease, 41 (89%) patients were treated with corticosteroid. Significant improvement was observed in 26 (57%) patients including four patients who did not receive treatment. However, ILD aggravated in 9 (20%) patients despite treatment. Mortality was observed in eight (17%) patients. Conclusion These results suggest pneumonitis as a potentially significant safety concern for vaccines against SARS-CoV-2. Clinical awareness and patient education are necessary for early recognition and prompt management. Additional research is warranted to identify the epidemiology and characterize the pathophysiology of vaccine-associated pneumonitis.

Purpose: The benefit of adjuvant chemotherapy following curative-intent surgery in pancreatic ductal adenocarcinoma (PDAC) patients who had received neoadjuvant FOLFIRINOX is unclear. This study aimed to assess the survival benefit of adjuvant chemotherapy in this patient population. Materials and Methods: This retrospective study included 218 patients with localized non-metastatic PDAC who received neoadjuvant FOLFIRINOX and underwent curative-intent surgery (R0 or R1) between January 2017 and December 2020. The association of adjuvant chemotherapy with disease-free survival (DFS) and overall survival (OS) was evaluated in overall patients and in the propensity score matched (PSM) cohort. Subgroup analysis was conducted according to the pathology-proven lymph node status. Results: Adjuvant chemotherapy was administered to 149 patients (68.3%). In the overall cohort, the adjuvant chemotherapy group had significantly improved DFS and OS compared to the observation group (DFS: median, 13.8 months [95% confidence interval (CI), 11.0 to 19.1] vs. 8.2 months [95% CI, 6.5 to 12.0]; p < 0.001; and OS: median, 38.0 months [95% CI, 32.2 to not assessable] vs. 25.7 months [95% CI, 18.3 to not assessable]; p=0.005). In the PSM cohort of 57 matched pairs of patients, DFS and OS were better in the adjuvant chemotherapy group than in the observation group (p < 0.001 and p=0.038, respectively). In the multivariate analysis, adjuvant chemotherapy was a significant favorable prognostic factor (vs. observation; DFS: hazard ratio [HR], 0.51 [95% CI, 0.36 to 0.71; p < 0.001]; OS: HR, 0.45 [95% CI, 0.29 to 0.71; p < 0.001]). Conclusion Among PDAC patients who underwent surgery following neoadjuvant FOLFIRINOX, adjuvant chemotherapy may be associated with improved survival. Randomized studies should be conducted to validate this finding.