Frailty is not an independent risk factor for worse clinical outcomes in lumbar spinal surgery: a prospective cohort study.

PURPOSE: Recently, many studies revealed that frailty affects unfavorably on postoperative outcomes in lumbar spinal diseases. This study aimed to investigate the relationship between frailty and clinical outcomes while identifying risk factors associated with worse clinical outcomes following lumbar spinal surgery. METHODS: From March 2019 to February 2021, we prospectively enrolled eligible patients with degenerative lumbar spinal diseases requiring surgery. Frailty was assessed preoperatively. To identify the impact of frailty on lumbar spinal diseases, clinical outcomes, which were measured with patient-reported outcomes (PROs) and postoperative complications, were compared according to the frailty. PROs were assessed preoperatively and one year postoperatively. In addition, risk factors for preoperative and postoperative worse clinical outcomes were investigated. RESULTS: PROs were constantly lower in the frail group than in the non-frail group before and after surgery, and the change of PROs between before and after surgery and postoperative complications were not different between the groups. In addition, frailty was a persistent risk factor for postoperative worse clinical outcome before and after surgery in lumbar spinal surgery. CONCLUSION: Frailty persistently affects the clinical outcome negatively before and after surgery in lumbar spinal surgery. However, as the change of the clinical outcome is not different between the frail group and the non-frail group, it is difficult to interpret whether the frail patients are vulnerable to the surgery. In conclusion, frailty is not an independent risk factor for worse clinical outcome in lumbar spinal surgery.

Phase 1 trial of 4-1BB-based adoptive T-cell therapy targeting human telomerase reverse transcriptase in patients with advanced refractory solid tumors.

BACKGROUND AIMS: Human telomerase reverse transcriptase (hTERT) is an attractive target for anti-cancer therapies. We developed an effective method for generating hTERT-specific CD8+ T cells (hTERT-induced natural T cells [TERTiNTs]) using peripheral blood mononuclear cells (PBMCs) from patients with solid cancers and investigated their feasibility and safety. METHODS: This was a single-center phase 1 trial using a 3 + 3 dose escalation design to evaluate six dose levels of TERTiNTs. PBMCs from each patient were screened using an hTERT peptide panel to select those that stimulated CD8+ T cells. The four most stimulatory peptides were used to produce autologous CD8+ T cells from patients refractory or intolerant to standard therapies. Eligible patients received a single intravenous infusion of TERTiNTs at different dose levels (4 × 108 cells/m2, 8 × 108 cells/m2 and 16 × 108 cells/m2). Pre-conditioning chemotherapy, including cyclophosphamide alone or in combination with fludarabine, was administered to induce lymphodepletion. RESULTS: From January 2014 to October 2019, a total of 24 patients with a median of three prior lines of therapy were enrolled. The most common adverse events were lymphopenia (79.2%), nausea (58.3%) and neutropenia (54.2%), mostly caused by pre-conditioning chemotherapy. The TERTiNT infusion was well tolerated, and dose-limiting toxicities were not observed. None of the patients showed objective responses. Seven patients (30.4%) achieved stable disease with a median progression-free survival of 3.9 months (range, 3.2-11.3). At the highest dose level (16 × 108 cells/m2), four of five patients showed disease stabilization. CONCLUSIONS: The generation of TERTiNTs was feasible and safe and provided an interesting disease control rate in heavily pre-treated cancer patients.

Phase II study of durvalumab monotherapy in patients with previously treated microsatellite instability-high/mismatch repair-deficient or POLE-mutated metastatic or unresectable colorectal cancer.

The aim of our study is to evaluate the clinical efficacy of durvalumab in patients with microsatellite instability-high/mismatch repair-deficient (MSI-H/dMMR) or polymerase epsilon (POLE)-mutated metastatic or unresectable colorectal cancer (mCRC) who had disease progression after standard chemotherapy. This prospective, open-label, multicenter, phase II study enrolled patients with mCRC harboring MSI-H/dMMR or POLE mutations treated with at least one prior line of therapy. The participants received durvalumab (1500 mg) every 4 weeks intravenously. The primary endpoint was the objective response rate (ORR). Of the 33 patients, 30 had MSI-H/dMMR and 3 had POLE-mutated microsatellite stable (MSS) CRC. With a median follow-up duration of 11.2 months (95% confidence interval [CI]: 7.3-15.0), the ORR was 42.4% (95% CI: 25.5-60.8). Among three patients with POLE-mutated CRC, one patient who had an exonuclease domain mutation (EDM) achieved an objective response, but the others with mutations in the non-exonuclease domain had progressive disease. Overall, the median duration of response was not reached and 85.7% of the responses were ongoing at data cutoff. The progression-free survival rate of 12 months was 58.2% (95% CI: 39.0-73.1) and the 12-month overall survival rate was 68.3% (95% CI: 48.8-81.7). Grade 3 treatment-related adverse events occurred in 36.4% of the patients and were manageable. In conclusion, durvalumab showed promising clinical activity with encouraging response rates and satisfactory survival outcomes in mCRC patients with MSI-H/dMMR or POLE EDM. In patients with POLE-mutated mCRC, clinical response to durvalumab may be restricted to those with EDM.

Sphingomyelin synthase 1 mediates hepatocyte pyroptosis to trigger non-alcoholic steatohepatitis.

OBJECTIVE: Lipotoxic hepatocyte injury is a primary event in non-alcoholic steatohepatitis (NASH), but the mechanisms of lipotoxicity are not fully defined. Sphingolipids and free cholesterol (FC) mediate hepatocyte injury, but their link in NASH has not been explored. We examined the role of free cholesterol and sphingomyelin synthases (SMSs) that generate sphingomyelin (SM) and diacylglycerol (DAG) in hepatocyte pyroptosis, a specific form of programmed cell death associated with inflammasome activation, and NASH. DESIGN: Wild-type C57BL/6J mice were fed a high fat and high cholesterol diet (HFHCD) to induce NASH. Hepatic SMS1 and SMS2 expressions were examined in various mouse models including HFHCD-fed mice and patients with NASH. Pyroptosis was estimated by the generation of the gasdermin-D N-terminal fragment. NASH susceptibility and pyroptosis were examined following knockdown of SMS1, protein kinase Cδ (PKCδ), or the NLR family CARD domain-containing protein 4 (NLRC4). RESULTS: HFHCD increased the hepatic levels of SM and DAG while decreasing the level of phosphatidylcholine. Hepatic expression of Sms1 but not Sms2 was higher in mouse models and patients with NASH. FC in hepatocytes induced Sms1 expression, and Sms1 knockdown prevented HFHCD-induced NASH. DAG produced by SMS1 activated PKCδ and NLRC4 inflammasome to induce hepatocyte pyroptosis. Depletion of Nlrc4 prevented hepatocyte pyroptosis and the development of NASH. Conditioned media from pyroptotic hepatocytes activated the NOD-like receptor family pyrin domain containing 3 inflammasome (NLRP3) in Kupffer cells, but Nlrp3 knockout mice were not protected against HFHCD-induced hepatocyte pyroptosis. CONCLUSION: SMS1 mediates hepatocyte pyroptosis through a novel DAG-PKCδ-NLRC4 axis and holds promise as a therapeutic target for NASH.

Retreatment of Irinotecan in Later Lines of Therapy for Metastatic Colorectal Cancer: A Retrospective Study.

BACKGROUND: Due to few efficacious options in later lines of therapy in metastatic colorectal cancer (mCRC), there has been considerable interest in the possibility of retreatment with previously administered agents. This study investigated the efficacy and safety of irinotecan retreatment (IRI2) in patients with refractory mCRC. METHODS: We performed a retrospective analysis of patients with mCRC who were retreated with irinotecan-based regimens. The retreatment regimens with anti-epidermal growth factor receptor therapies were excluded. RESULTS: A total of 64 patients were included. Patients had a median age of 56 years and were offered mainly in the setting of third- or fourth-line therapy with IRI2. The disease control rate was 78.2% including an objective response of 23.5%. Median progression-free survival and overall survival were 5.5 and 19.3 months, respectively. The most frequent grade 3 or higher toxicities were nausea/vomiting (27.9%) and neutropenia (25%). CONCLUSION: IRI2 might be a reasonable option for heavily pretreated patients with mCRC who achieved disease control with prior irinotecan therapy.

Open Platform Cameras Based Bio-Imaging Evaluation System.

With the active development of mobile devices, a variety of ultra-small, high-definition, and open platform-based cameras are being mass-produced. In this paper, we established an emulation system to verify the bio-imaging performance of the bulky and expensive high-performance cameras and various smartphone cameras that have been used in bio-imaging devices. In the proposed system, the linearity of the brightness gradient change of four types of cameras was compared and analyzed. Based on these results, three cameras were selected in order of excellent linearity, and gel image analysis results were compared.

Comparison of Two Electronic Physical Performance Batteries by Measurement Time and Sarcopenia Classification.

The Short Physical Performance Battery (SPPB) is a widely accepted test for measuring lower extremity function in older adults. However, there are concerns regarding the examination time required to conduct a complete SPPB consisting of three components (walking speed, chair rise, and standing balance tests) in clinical settings. We aimed to assess specific examination times for each component of the electronic Short Physical Performance Battery (eSPPB) and compare the ability of the original three-component examinations (eSPPB) and a faster, two-component examination without a balance test (electronic Quick Physical Performance Battery, eQPPB) to classify sarcopenia. The study was a retrospective, cross-sectional study which included 124 ambulatory outpatients who underwent physical performance examination at a geriatric clinic of a tertiary, academic hospital in Seoul, Korea, between December 2020 and March 2021. For eSPPB, we used a toolkit containing sensors and software (Dyphi, Daejeon, Korea) developed to measure standing balance, walking speed, and chair rise test results. Component-specific time stamps were used to log the raw data. Duration of balance examination, 5 times sit-to-stand test (5XSST), and walking speed examination were calculated. Sarcopenia was determined using the 2019 Asian Working Group for Sarcopenia (AWGS) guideline. The median age was 78 years (interquartile range, IQR: 73,82) and 77 subjects (62.1%) were female. The total mean eSPPB test time was 124.8 ± 29.0 s (balance test time 61.8 ± 12.3 s, 49.5%; gait speed test time 34.3 ± 11.9 s, 27.5%; and 5XSST time 28.7 ± 19.1 s, 23.0%). The total mean eQPPB test time was 63.0 ± 25.4 s. Based on the AWGS criteria, 34 (27.4%) patient's results were consistent with sarcopenia. C-statistics for classifying sarcopenia were 0.83 for eSPPB and 0.85 for eQPPB (p = 0.264), while eQPPB took 49.5% less measurement time compared with eSPPB. Breakdowns of eSPPB test times were identified. Omitting balance tests may reduce test time without significantly affecting the classifying ability of eSPPB for sarcopenia.

Polypharmacy, Inappropriate Medication Use, and Drug Interactions in Older Korean Patients with Cancer Receiving First-Line Palliative Chemotherapy.

BACKGROUND: Polypharmacy is an important issue in the care of older patients with cancer, as it increases the risk of unfavorable outcomes. We estimated the prevalence of polypharmacy, potentially inappropriate medication (PIM) use, and drug-drug interactions (DDIs) in older patients with cancer in Korea and their associations with clinical outcomes. SUBJECTS, MATERIALS, AND METHODS: This was a secondary analysis of a prospective observational study of geriatric patients with cancer undergoing first-line palliative chemotherapy. Eligible patients were older adults (≥70 years) with histologically diagnosed solid cancer who were candidates for first-line palliative chemotherapy. All patients enrolled in this study received a geriatric assessment (GA) at baseline. We reviewed the daily medications taken by patients at the time of GA before starting chemotherapy. PIMs were assessed according to the 2015 Beers criteria, and DDIs were assessed by a clinical pharmacist using Lexi-comp Drug Interactions. We evaluated the association between polypharmacy and clinical outcomes including treatment-related toxicity, and hospitalization using logistic regression and Cox regression analyses. RESULTS: In total, 301 patients (median age 75 years; range, 70-93) were enrolled; the most common cancer types were colorectal cancer (28.9%) and lung cancer (24.6%). Mean number of daily medications was 4.7 (±3.1; range, 0-14). The prevalence of polypharmacy (≥5 medications) was 45.2% and that of excessive polypharmacy (≥10 medications) was 8.6%. PIM use was detected in 137 (45.5%) patients. Clinically significant DDIs were detected in 92 (30.6%) patients. Polypharmacy was significantly associated with hospitalization or emergency room (ER) visits (odds ratio: 1.73 [1.18-2.55], p < .01). Neither polypharmacy nor PIM use showed association with treatment-related toxicity. CONCLUSION: Polypharmacy, PIM use, and potential major DDIs were prevalent in Korean geriatric patients with cancer. Polypharmacy was associated with a higher risk of hospitalization or ER visits during the chemotherapy period. IMPLICATIONS FOR PRACTICE: This study, which included 301 older Korean patients with cancer, highlights the increased prevalence of polypharmacy in this population planning to receive palliative chemotherapy. The prevalence of polypharmacy and excessive polypharmacy was 45.2% and 8.6%, respectively. The prescription of potentially inappropriate medications (PIMs) was detected in 45.5% and clinically significant drug-drug interaction in 30.6% of patients. Given the association of polypharmacy with increased hospitalization or emergency room visits, this study points to the need for increased awareness and intervention to minimize polypharmacy in the geriatric cancer population undergoing chemotherapy. Moreover, specific criteria for establishing PIMs should be adopted for the treatment of older adults with cancer.

Autophagic flux defect in diabetic kidney disease results in megamitochondria formation in podocytes.

Podocyte injury is an important factor in the pathogenesis of diabetic nephropathy. Podocytes are characterized by large numbers of mitochondria. However, mitochondrial dysfunction as it relates to kidney pathology remains poorly understood. The present study found that podocyte mitochondria in different animal models of diabetes mellitus became elongated with the development of albuminuria, suggesting a change in mitochondrial dynamics. We then treated cells with a combination of glucose, fatty acids, and angiotensin II (GFA) to mimic the diabetic milieu. Cultured podocytes exposed to GFA showed megamitochondria formation and decreased autophagosome degradation. We also found that GFA treatment decreased the binding of the autophagosome to the lysosome. Our results suggest that megamitochondria are common in podocytes during diabetic nephropathy and that insufficient autophagy flux may underlie this effect. These findings have expanded our understanding of the pathogenesis of diabetic nephropathy and identified a potential pharmacological target for treatment.

Analysis of metachronous colorectal neoplasms and survival following segmental or extended resection in patients with hereditary non-polyposis colorectal cancer.

PURPOSE: The high incidence of metachronous colorectal tumours in patients with hereditary non-polyposis colorectal cancer (HNPCC) encourages extended resection (ER); however, the optimal surgical approach remains unclear. We evaluated the incidences of metachronous colorectal neoplasms following curative colorectal cancer segmental resection (SR) vs ER in patients with HNPCC and investigated patients' oncologic outcomes according to surgical modality and mismatch repair status. METHODS: We retrospectively investigated medical records of patients with HNPCC (per the Amsterdam II criteria) treated for primary colon cancer at our institution between 2001 and 2017. All patients underwent intensive endoscopic surveillance. RESULTS: We included 87 patients (36 who underwent SR and 51 who underwent ER). The cumulative incidence of metachronous adenoma was higher in the SR group. One patient in the SR group (2.8%) and 3 in the ER group (5.9%) developed metachronous colon cancer; the difference was not significant (P = 0.693). Four patients in the SR group (11.1%) and 1 in the ER group (2.0%) developed distant recurrences; again, the difference was not significant (P = 0.155). Moreover, no significant differences were observed in the 5-year overall survival rates of patients in the SR and ER groups (88.2% vs 95.5%, P = 0.446); the same was true for 5-year disease-free survival rates (79.5% vs 91.0%, P = 0.147). CONCLUSION: The incidence of metachronous cancer was not significantly different between the ER and SR groups; however, that of cumulative metachronous adenoma was higher in the SR group. Hence, intensive surveillance colonoscopy may be sufficient for patients with HNPCC after non-extensive colon resection.

Magnetic Resonance Imaging-Detected Extramural Venous Invasion in Rectal Cancer before and after Preoperative Chemoradiotherapy: Diagnostic Performance and Prognostic Significance.

OBJECTIVES: We evaluated the diagnostic performance of magnetic resonance imaging (MRI) in terms of identifying extramural venous invasion (EMVI) in rectal cancer patients with preoperative chemoradiotherapy (CRT) and its prognostic significance. METHODS: During 2008-2010, 200 patients underwent surgery following preoperative CRT for rectal cancer. Two radiologists independently reviewed all pre- and post-CRT MRI retrospectively. We investigated diagnostic performance of pre-CRT MR-EMVI (MR-EMVI) and post-CRT MR-EMVI (yMR-EMVI), based on pathological EMVI as the standard of reference. We assessed correlation between MRI findings and patients' prognosis, such as disease-free survival (DFS) and overall survival (OS). Additionally, subgroup analysis in MR- or yMR-EMVI-positive patients was performed to confirm the significance of the severity of EMVI in MRI on patient's prognosis. RESULTS: The sensitivity and specificity of yMR-EMVI were 76.19% and 79.75% (area under the curve: 0.830), respectively. In univariate analysis, yMR-EMVI was the only significant MRI factor in DFS (P = 0.027). The mean DFS for yMR-EMVI (+) patients was significantly less than for yMR-EMVI (-) patients: 57.56 months versus 72.46 months. CONCLUSION: yMR-EMVI demonstrated good diagnostic performance. yMR-EMVI was the only significant EMVI-related MRI factor that correlated with patients' DFS in univariate analysis; however, it was not significant in multivariate analysis. KEY POINTS: • Diagnostic performance of MRI for EMVI after preoperative chemoradiotherapy is good. • The mean DFS was lower in yMR-EMVI-positive than yMR-EMVI-negative patients. • MRI can facilitate prognosis prediction of rectal cancer patients with preoperative chemoradiotherapy.

Association between diabetes and asthma: Evidence from a nationwide Korean study.

BACKGROUND: Type 2 diabetes and asthma share a common pathophysiology: "chronic inflammation." However, it is unclear whether patients with type 2 diabetes are at increased risk of asthma. OBJECTIVE: To investigate the effect of type 2 diabetes on asthma using data from a large population-based study in Korea. METHODS: Data from the Korean National Health Insurance Service identified 13,154,348 participants who underwent regular health checkups from 2005 to 2008. Subjects were classified according to status of diabetes mellitus (DM) and diabetic retinopathy (DR), and followed until the date of asthma development, death, or December 31, 2013. Cox proportional hazard regression analysis was used to evaluate the effect of diabetes, with or without retinopathy, on asthma development. RESULTS: The incidences of asthma in the non-DM, DM without DR, and DR groups were 27.1, 30.1, and 38.4 per 1,000 person-years, respectively. Cox proportional hazard multiple regression models revealed that diabetic patients without retinopathy had a significantly lower risk of developing asthma than non-DM subjects (hazard ratio, 0.943; 95% confidence interval, 0.939-0.948). By contrast, diabetic patients with retinopathy had a higher risk of developing asthma (hazard ratio, 1.067; 95% confidence interval, 1.053-1.081). CONCLUSION: Type 2 diabetes without retinopathy is not a risk factor for asthma development. However, patients with DR are at a greater risk of incident asthma, supporting the notion that the lung is a target organ for diabetic injury. Future studies will address whether proper glycemic control mitigates the risk of asthma.

Analysis of unexplained carcinoembryonic antigen elevation after curative treatment of locally advanced rectal cancer.

BACKGROUND: To analyze the causes and patterns of unexplained carcinoembryonic antigen (CEA) elevation after curative treatment in locally advanced rectal cancer patients. METHODS: Among the 1309 locally advanced rectal cancer patients treated with curative resection and radiotherapy between January 2001 and June 2011, 325 patients who postoperatively developed abnormal CEA elevation were reviewed. The unexplained CEA elevation was defined as a CEA level higher than 5 ng/mL with no evidence of cancer recurrence at the time of elevation. RESULTS: Of the 325 patients, 143 (44%) had unexplained CEA elevations. The causes were categorized as delayed recurrence (n = 29, 20%), non-colorectal malignancy (n = 10, 7%), and non-malignancy-related conditions (n = 104, 73%). Shorter intervals between treatment and the first CEA elevation, and a higher peak CEA level, were observed in the delayed recurrence group compared with the non-colorectal malignancy or non-malignancy-related group (intervals of 6.8 vs. 44.9 vs. 23.2 months, respectively, p = 0.002; and peak CEA levels of 9.9 vs. 7.1 vs. 6.2 ng/mL, respectively, p = 0.034). In patients who showed delayed recurrence, the interval between the first CEA elevation and diagnosis of recurrence was a median of 13.0 months (range 3.8-60.6 months). Smoking was the most common cause for non-malignancy-related conditions. The patterns of unexplained CEA elevations were defined as sporadic (n = 78, 55%), stationary (n = 37, 26%), and increasing (n = 28, 20%). The patterns were significantly different depending on the cause (p < 0.001). CONCLUSIONS: Analysis of the patterns of unexplained CEA elevations is a reasonable approach to predict the cause of the cancer.

Can chemoradiation allow for omission of lateral pelvic node dissection for locally advanced rectal cancer?

OBJECTIVES: We evaluated the relationship between pretreatment clinical parameters and lateral pelvic node (LPN) recurrence in patients with rectal cancer treated with a combination of curative resection and chemoradiotherapy (CRT) and attempted to identify the patients who might benefit from LPN dissection. METHODS: This study involved 900 patients between June 2001 and June 2009. Pretreatment clinical parameters including radiological size of LPN were analyzed to identify risk factors associated with long-term outcomes. RESULTS: Locoregional recurrence developed in 65 patients (7.2%); 42 (64.6%) had LPN recurrence, 20 (47.6%) of which had no distant metastasis. Multivariate analysis showed that LPN short-axis diameter (<5, 5-<10, and ≥10 mm) was significantly associated with LPN recurrence-free survival (5-year survival rate (5YSR), 98.2, 91.7, and 40.1%, respectively, P < 0.05), locoregional recurrence-free survival (5YSR, 95.5, 87.6, and 40.1%, respectively, P < 0.05), relapse-free survival (5YSR, 76.8, 72.5, and 30.3, respectively, P < 0.05), and overall survival (5YSR, 86.3, 83.0, and 57.5%, respectively, P < 0.05). CONCLUSIONS: Patients with an LPN short-axis diameter ≥10 mm represent a potential subgroup at a high risk of LPN recurrence, even after CRT. Further study is needed to confirm whether LPN dissection is beneficial for these patients.

Clinical outcomes of laparoscopic versus open surgery for primary tumor resection in patients with stage IV colorectal cancer with unresectable metastasis.

PURPOSE: The aim of this study was to compare the clinical outcomes of laparoscopic surgery with those of open surgery in patients with colorectal cancer and unresectable metastasis. METHODS: We retrospectively reviewed the medical records of patients who underwent primary tumor resection of colorectal cancer with unresectable metastasis between January 2001 and December 2010. RESULTS: Of 280 patients, 61 underwent laparoscopic surgery and 219 underwent open surgery. Regarding the short-term outcomes, the amount of blood loss was lower in the laparoscopic group (P = 0.014), although the operation was longer in the laparoscopic group (P = 0.003). The times to flatus (P < 0.001), liquid food intake (P < 0.001), and the duration of hospital stay (P < 0.001) were shorter in the laparoscopic group. The complication rate was lower in the laparoscopic group than in the open group (P = 0.043). Although the overall survival was significantly better in the laparoscopic group in a univariate analysis, there was no significant difference in the overall survival between the two groups in a multivariate analysis (P = 0.482). CONCLUSIONS: Laparoscopic surgery seems to be a safe and feasible option, with short-term benefit for primary tumor resection in patients with stage IV colorectal cancer with unresectable metastasis.

Serpin B5 is a CEA-interacting biomarker for colorectal cancer.

Serpin B5 is a candidate tumour suppressor, but its oncogenic activity has also been reported. Its function may be affected by protein interactions. The aim of this study was to assess the relationship between serpin B5 and carcinoembryonic antigen (CEA) expression in colorectal cancer (CRC). We also analysed the clinicopathological significance of serpin B5 expression in patients with CRC. Downregulation of serpin B5 was identified in a CEA-suppressed LoVo cell line using two-dimensional gel electrophoresis (2-DE) and matrix-associated laser desorption ionisation-mass spectrometry (MALDI-MS). The specific interaction and co-localisation of serpin B5 with CEA were confirmed by co-immunoprecipitation and confocal microscopy. Western blot analysis and ELISAs revealed significant positive correlations between levels of serpin B5 and CEA in human colon cancer cell lines and in the blood of patients with CRC. Tissue expression of serpin B5 in 377 patients with CRC was significantly associated with serum CEA, histological grade, stage, lymph node metastasis, lymphatic and perineural invasion, and infiltrative border. Strong expression of serpin B5 was also associated with a reduced DFS (p = 0.001) and OS (p = 0.017). Together, these findings describe a relationship between serpin B5 and CEA expression in CRC. Strong expression of serpin B5 was associated with a worse prognosis in patients with CRC and its expression may correlate with CEA levels in CRC.

S-1 plus oxaliplatin versus capecitabine plus oxaliplatin for the first-line treatment of patients with metastatic colorectal cancer: updated results from a phase 3 trial.

BACKGROUND: We report updated progression-free survival (PFS) and overall survival (OS) data from a trial that compared capecitabine plus oxaliplatin (CapeOX) versus S-1 plus oxaliplatin (SOX) for the first-line treatment of metastatic colorectal cancer. METHODS: This trial was a randomized, two-armed, non-inferiority phase 3 comparison of CapeOX (capecitabine 1000 mg/m2 twice daily on days 1-14 and oxaliplatin 130 mg/m2 on day 1) versus SOX (S-1 40 mg/m2 twice daily on days 1-14 and oxaliplatin 130 mg/m2 on day 1). The primary end point was to show non-inferiority of SOX relative to CapeOX in terms of PFS. Thus, a follow-up exploratory analysis of PFS and OS was performed. RESULTS: The intention to treat (ITT) population was comprised of 340 patients (SOX arm: 168 and CapeOX arm: 172). The updated median PFS was 7.1 months (95% CI 6.4-8.0) in the SOX group and 6.3 months (95% CI 4.9-6.7) in the CapeOX group (hazard ratio [HR], 0.83 [0.66-1.04], p = .10). The median OS was 19.0 months (95% CI 15.3-23.0) in the SOX group and 18.4 months (95% CI 14.1-20.7) in the CapeOX group (HR, 0.86 [0.68-1.08], p = .19). Subgroup analyses according to principal demographic factors such as sex, age, ECOG (Eastern Cooperative Oncology Group) performance status, primary tumor location, measurability, previous adjuvant therapy, number of metastatic organs, and liver metastases showed no interaction between any of these characteristics and the treatment. CONCLUSIONS: Updated survival analysis shows that SOX is similar to CapeOX, confirming the initial PFS analysis. Therefore, the SOX regimen could be an alternative first-line doublet chemotherapy strategy for patients with metastatic colorectal cancer. TRIAL REGISTRATION: NCT00677443 and May 12 2008.

Phenotype validation of the Korean working group on sarcopenia guideline.

BACKGROUND: This study aimed to validate the proposed Korean Working Group on Sarcopenia (KWGS) guideline, which introduces the concept of functional sarcopenia, in older Korean adults. METHODS: Data from the Aging Study of Pyeongchang Rural Area, a longitudinal cohort of community-dwelling older adults, were utilized to compare frailty status and institutionalization-free survival among participants according to sarcopenia status. Based on the KWGS guideline, severe sarcopenia was defined as low muscle mass and strength with slow gait speed; sarcopenia (not severe) was defined as low muscle mass with low muscle strength or slow gait speed; and functional sarcopenia was defined as low muscle strength and slow gait speed without low muscle mass. RESULTS: Among the 1302 participants, 329 (25.3 %) had severe sarcopenia, 147 (11.3 %) had sarcopenia (not severe), and 277 (21.3 %) had functional sarcopenia. Frailty was significantly greater in participants with any phenotype of sarcopenia than in those without sarcopenia. Additionally, participants with functional sarcopenia were frailer than those with sarcopenia (not severe). Furthermore, the rates of institutionalization and mortality were higher in participants with any phenotype of sarcopenia than in those without sarcopenia. There was no statistical difference between the rates of sarcopenia (not severe) and those with functional sarcopenia. These findings remained consistent after adjusting for age and sex. CONCLUSIONS: Each phenotype according to the KWGS guideline was associated with significantly greater frailty and increased risk of institutionalization and mortality. Functional sarcopenia was associated with greater frailty and had comparable prognosis with sarcopenia (not severe).

Sarcopenia as the Mobility Phenotype of Aging: Clinical Implications.

Sarcopenia, which is characterized by an age-related decline in muscle mass and function, poses significant challenges to geriatric care. Its definition has evolved from muscle-specific criteria to include muscle mass, muscle function, and physical performance, recognizing sarcopenia as a physical frailty. Sarcopenia is associated with adverse outcomes, including mortality, falls, fractures, cognitive decline, and admission to long-term care facilities. Neuromechanical factors, protein-energy balance, and muscle protein synthesis-breakdown mechanisms contribute to its pathophysiology. The identification of sarcopenia involves screening tests and a comprehensive assessment of muscle mass, strength, and physical function. Clinical approaches aligned with the principles of comprehensive geriatric assessment prioritize patient-centered care. This assessment aids in identifying issues related to activities of daily living, cognition, mood, nutrition, and social support, alongside other aspects. The general approach to factors underlying muscle loss and functional decline in patients with sarcopenia includes managing chronic diseases and evaluating administered medications, with interventions including exercise and nutrition, as well as evolving pharmacological options. Ongoing research targeting pathways, such as myostatin-activin and exercise mimetics, holds promise for pharmacological interventions. In summary, sarcopenia requires a multifaceted approach, acknowledging its complex etiology and tailoring interventions to individual patient needs.

Circulating lumican as a potential biomarker for osteosarcopenia in older adults.

In vitro and animal experiments demonstrated that lumican exerts anabolic effects on bone and muscle by stimulating osteoblastogenesis, suppressing osteoclastogenesis and increasing myogenesis. However, the relationship between circulating lumican and musculoskeletal phenotypes in humans remains unclear. We aimed to analyze the relationship between serum lumican levels and osteosarcopenia in older adults. Blood samples were collected from 134 participants (age: 65 years and older) who underwent comprehensive assessment of bone and muscle phenotypes. Osteoporosis and sarcopenia were diagnosed based on World Health Organization and Asian consensus guidelines, respectively. Osteosarcopenia was defined as the simultaneous presence of osteoporosis and sarcopenia. After adjusting for sex, age, and body mass index, older adults with osteosarcopenia had 20.2 % lower serum lumican levels than those without (P = 0.010). The odds ratio (OR) for osteosarcopenia per standard deviation decrease in serum lumican level was 4.17 (P = 0.003). Consistently, higher serum lumican levels were correlated with higher bone mass at all measured sites (P = 0.004 to 0.045) and higher grip strength (P = 0.023). Furthermore, participants in the lowest tertile (T1) had 7.56-fold higher OR for osteosarcopenia (P = 0.024) than those in the highest lumican tertile (T3). In conclusion, these findings clinically validate previous experimental data showing the musculoskeletal protective effects of lumican and suggest that blood lumican levels could be used as a potential biomarker to assess the risk of not only osteosarcopenia but also osteoporosis or sarcopenia in older adults.