A retrospective analysis of ibrutinib outcomes in relapsed or refractory mantle cell lymphoma.

Background: While treatment strategies for mantle cell lymphoma (MCL) have evolved, patients often experience disease progression and require additional treatment therapies. Ibrutinib presents a promising option for relapsed or refractory MCL (RR-MCL). This study investigated real-world treatment outcomes of ibrutinib in patients with RR-MCL. Methods: A single-center retrospective analysis investigated clinical characteristics and survival outcomes of patients with RR-MCL, treated with ibrutinib. Results: Forty-two patients were included, with 16 received rituximab and bendamustine, and 26 receiving anthracycline-based regimens as front-line treatment. During a median follow-up of 46.0 months, the response rate to ibrutinib was 69%, with 12 CRs and 8 partial responses. Disease progression (54.8%) and adverse events (11.9%) were the primary reasons for discontinuation. Median progression-free survival (PFS) and overall survival (OS) were approximately 16.4 and 50.1 months, respectively. Patients older than 70 years (P=0.044 and P=0.006), those with splenomegaly (P=0.022 and P=0.006), and those with a high-risk simplified Mantle Cell Lymphoma International Prognostic Index (sMIPI) (P＜0.001 and P＜0.001) exhibited siginificantly inferior PFS and OS. Notably, patients with a high-risk sMIPI relapsed earlier. Post-ibrutinib treatment yilded an OS of 12.2 months, while clinical trial participants demonstrated superior survival compared to those receiving chemotherapy alone. Conclusion: This study underscores the importance of considering patient characteristics before administering ibrutinib as salvage therapy. Early relapse was associated with poor outcomes, highlighting the need for novel therapeutic strategies.

Tumor mutation burden in gastro-entero-pancreatic-neuroendocrine neoplasms.

Background: As rare tumors, there are limited treatment options for neuroendocrine neoplasms (NENs). Recently, microsatellite instability (MSI) and tumor mutation burden (TMB) have been emerging as potential biomarkers in various tumors. However, there is a lack of research on the use of these biomarkers in gastro-entero-pancreatic (GEP)-NENs. Methods: We analyzed 31 patients diagnosed with GEP-NEN between 2013 to 2022. The TMB and MSI analyses using next-generation sequencing (NGS) were performed for all patients. The TruSightTM Oncology 500 assay from Illumina was used as the NGS panel. Results: Out of the 31 patients analyzed, the most frequent primary origin was the pancreas (12 patients, 38.7%), followed by the stomach (4 patients, 12.9%), gallbladder (4 patients, 12.9%), rectum (7 patients, 22.6%), small bowel (2 patients, 6.5%), and bile duct (1 patient, 3.2%). Among these patients, 19 (61.3%) were diagnosed with well-differentiated neuroendocrine tumors, with grade 2 being the most common (15 patients, 48.4%), followed by grade 3 (3 patients, 9.7%) and grade 1 (1 patient, 3.2%). Neuroendocrine carcinoma was confirmed in 12 patients (38.7%). The median number of metastases was 2.0 [interquartile range (IQR), 1.0-3.0], and the liver was the most common site of metastasis (23 patients, 74.2%). The median TMB was 4.7 (IQR, 3.1-6.3) mutations/Mb, and all tumors were classified as microsatellite stability (MSS). Only one patient had a high TMB (266.4 mutations/Mb), which was a grade 3 neuroendocrine tumor originating from the pancreas. The TMB value did not vary depending on the primary tumor site or World Health Organization (WHO) grade. Conclusions: This analysis showed that, despite very low incidence, there are GEP-NENs with high TMB. For precision medicine, testing for MSI and TMB is needed for this tumor type.

Effect of ramucirumab plus paclitaxel in advanced gastric cancer according to the status of programmed cell death-ligand 1 (PD-L1) expression.

Background: Ramucirumab, an anti-vascular endothelial growth factor receptor (VEGFR) monoclonal antibody (mAb), inhibits angiogenesis and reduces tumor activity. Programmed cell death-ligand 1 (PD-L1) might act upon VEGFR2 to induce cancer cell angiogenesis and metastasis. Herein, we investigated the efficacy of combining ramucirumab and paclitaxel according to the status of PD-L1 expression in patients with advanced gastric cancer (AGC). Methods: This analysis included AGC patients who received ramucirumab plus paclitaxel as 2nd line therapy between December 1, 2018, and February 28, 2022, at Samsung Medical Center. All patient data analyses included an evaluation of PD-L1 expression using the combined positive score (CPS). We analyzed the efficacy and the survival of patients according to their PD-L1 expression. Results: We included 117 patients in this analysis, and 80 patients (68.4%) had a PD-L1 CPS of one or more, 37 (31.6%) had five or more, and 19 (16.2%) had ten or more scores. Progression-free survival (PFS) and overall survival (OS) did not differ significantly between patients with a PD-L1 CPS of less than one and one or more {PD-L1 <1% vs. PD-L1 ≥1%; PFS: median 3.6 months [95% confidence interval (CI): 2.4-4.8 months] vs. median 4.1 months (95% CI: 3.5-4.7 months), P=0.93; PD-L1 <1% vs. PD-L1 ≥1%; OS: median 7.0 months (95% CI: 5.4-8.6 months) vs. median 8.1 months (95% CI: 6.4-9.8 months), P=0.32}. PFS and OS did not differ significantly between patients with a PD-L1 CPS of less than 5 and 5 or more [PD-L1 <5% vs. PD-L1 ≥5%; PFS: 3.9 months (95% CI: 3.3-4.5 months) vs. 4.4 months (95% CI: 3.0-5.8 months), P=0.57; OS: 7.4 months (95% CI: 6.5-8.3 months) vs. 10.0 months (95% CI: 1.1-18.9 months), P=0.07]. Interestingly, with a PD-L1 CPS cutoff of 10, PFS and OS did differ significantly [PD-L1 <10% vs. PD-L1 ≥10%; PFS: 3.8 months (95% CI: 3.3-4.3 months) vs. 5.7 months (95% CI: 4.1-7.3 months), P=0.05; OS: 7.2 months (95% CI: 6.5-7.9 months) vs. 18.9 months (95% CI: 6.5-31.3 months), P=0.04]. Conclusions: No biomarkers have been established to predict survival times after ramucirumab plus paclitaxel treatment. This analysis suggests that a PD-L1 CPS cutoff of 10 might be novel a biomarker to predict the survival of AGC patients treated with ramucirumab and paclitaxel.

Discrete terminal ileal ulcers in patients diagnosed with ulcerative colitis: clinical significance and natural course.

BACKGROUND: Terminal ileal (TI) ulcers are occasionally detected in asymptomatic individuals and mostly resolve without any treatment. In patients with ulcerative colitis (UC), TI ulcers are infrequently observed without evidence of backwash ileitis. However, the clinical significance and natural course of the lesions are unclear. The aim of our study was to evaluate the frequency and clinical implications of TI ulcers in patients with UC. METHODS: We retrospectively reviewed 397 patients with UC via successful TI intubation during colonoscopy. We compared the clinical characteristics of patients manifesting TI ulcers with those who did not. The natural course of TI lesions was also investigated during the follow-up periods. RESULTS: Forty-one patients (10.3%) showed TI ulcers without evidence of inflammation in the right colon. The patients with and without TI ulcers were not different in terms of baseline characteristics, disease activity and extent at the time of the UC diagnosis, proximal extension, Mayo endoscopic score at the last endoscopic examination, medication history, UC-related hospitalization, and relapse during follow-up periods. Of the 30 patients who underwent follow-up colonoscopy in patients with TI ulcers, 23 (76.7%) showed resolution of TI ulcer. In addition, patients with remaining TI ulcers did not differ in disease activity and biopsy results compared with those with resolving TI ulcers. CONCLUSIONS: Discrete TI ulcers are more common in patients with UC, compared with the healthy cohort. No significant clinical impact on disease extension and severity is found.

Immunotherapy for pancreatic cancer.

Pancreatic cancer, a highly lethal cancer, has the lowest 5-year survival rate for several reasons, including its tendency for the late diagnosis, a lack of serologic markers for screening, aggressive local invasion, its early metastatic dissemination, and its resistance to chemotherapy/radiotherapy. Pancreatic cancer evades immunologic elimination by a variety of mechanisms, including induction of an immunosuppressive microenvironment. Cancer-associated fibroblasts interact with inhibitory immune cells, such as tumor-associated macrophages and regulatory T cells, to form an inflammatory shell-like desmoplastic stroma around tumor cells. Immunotherapy has the potential to mobilize the immune system to eliminate cancer cells. Nevertheless, although immunotherapy has shown brilliant results across a wide range of malignancies, only anti-programmed cell death 1 antibodies have been approved for use in patients with pancreatic cancer who test positive for microsatellite instability or mismatch repair deficiency. Some patients treated with immunotherapy who show progression based on conventional response criteria may prove to have a durable response later. Continuation of immune-based treatment beyond disease progression can be chosen if the patient is clinically stable. Immunotherapeutic approaches for pancreatic cancer treatment deserve further exploration, given the plethora of combination trials with other immunotherapeutic agents, targeted therapy, stroma-modulating agents, chemotherapy, and multi-way combination therapies.

Role of Endoscopic Procedures in the Diagnosis of IgG4-Related Pancreatobiliary Disease.

The emergence of the disease entity of glucocorticoid-responsive systemic immunoglobulin G4 (IgG4)-related pancreatobiliary disease has generated substantial attention among the international gastroenterology society. IgG4-related pancreatobiliary disease includes type 1 autoimmune pancreatitis (AIP) and IgG4-related sclerosing cholangitis (IgG4-SC). The typical manifestations of IgG4-related pancreatobiliary disease are cholestatic liver dysfunction, obstructive jaundice, and weight loss, although it may present with no clinical symptoms. Since it mimics tumors on imaging, AIP/IgG4-SC may often be misdiagnosed as pancreatic or biliary cancer. The endoscopic armamentarium for the diagnosis of IgG4-related pancreatobiliary disease includes endoscopic ultrasonography, intraductal ultrasonography, endoscopic retrograde cholangiopancreatography, and cholangioscopy. The role of endoscopic tissue acquisition is two-fold in the diagnosis of IgG4-related pancreatobiliary disease: exclusion of cancer and procurement of histopathological proof for diagnosis of AIP/IgG4-SC, which can also be achieved by adding the immunohistochemistry for IgG4. Our review article addresses the role of various endoscopic examinations in diagnosing IgG4-related pancreatobiliary disease, focusing on the differentiation of this condition from pancreatobiliary malingnancies.

Electrochemical Properties According to the Particle Size Effect of Poly(ethylene oxide)-Poly(propylene oxide)-Poly(ethylene oxide) Triblock Copolymer Electrolyte.

The electrolyte of lithium secondary batteries is an important component. Among lithium secondary batteries, the lithium polymer battery, which has similar performance to the lithium secondary battery, is made of a solid polymer electrolyte. Lithium ions in a solid polymer electrolyte exist in the form of a solution by a polar group in a polymer matrix. Lithium ions in the solid polymer electrolyte migrate via the segmental motion of the polymer. That is, the properties of a polymer matrix in a solid polymer electrolyte can affect the conduction of lithium ions. Therefore, this study focused on the electrochemical properties of poly(ethylene oxide)-block-poly(propylene oxide)-blockpoly( ethylene oxide) copolymer-based solid polymer electrolyte. For this, poly(ethylene oxide)-blockpoly( propylene oxide)-block-poly(ethylene oxide) copolymer-based solid polymer electrolytes, which have spherical micelles, and various sizes of poly(ethylene oxide)-block-poly(propylene oxide)-block-poly(ethylene oxide) copolymer micelle, were prepared. Amino acids were added to the poly(ethylene oxide)-block-poly(propylene oxide)-block-poly(ethylene oxide) copolymer-based solid polymer electrolyte as an ion dissociator to assist in the dissociation of a lithium salt and increase the ionic conductivity of the solid polymer electrolyte. The copolymer-based solid polymer electrolytes was characterized by Fourier transform infrared spectroscopy, transmission electron microscopy, impedance analysis, cyclic voltammetry, and linear sweep voltammetry.

Effects of footrest heights on muscle fatigue, kinematics, and kinetics during prolonged standing work.

BACKGROUND: Among the tools for relieving lower back pain, footrests are commonly recommended. Few studies have investigated the effects of footrest and the proper application of footrest height. OBJECTIVE: The purpose of this study was to compare the effects of the normalized footrest height on muscle fatigue, kinematics, kinetics, and pain intensity. METHODS: In total, 13 males who had a history of non-specific lower back pain during prolonged standing were recruited. The experimental conditions were 2-hour prolonged standing with no footrest and with footrests of 5%, 10%, and 15% of body height. Muscle fatigue was investigated through measurements of the median frequency ratio and the muscle activity ratio (post/pre) in lumbar erector spinae. The lumbo-pelvic angles, and the external moment in the lumbar region were investigated. A visual analog scale was used to investigate the intensity of the pain. RESULTS: The footrests at 10% and 15% of the body height caused a lower change in the median frequency ratio and the muscle activity ratio than the other conditions. The footrest at 10% of the body height placed the lowest external moment on the lumbar region among all the conditions. The pain intensity was significantly lower in with footrest conditions than with no footrest condition. CONCLUSIONS: The results suggests that a footrest height of 10% of the body height can be recommended as a normalized height for prolonged standing work in subjects with a history of non-specific lower back pain during prolonged standing.

Disulfide-Containing Crosslinked Polyaniline Cathode for Rechargeable Battery.

Polymer electrodes have had several advantages like being environment friendly, mechanically flexible and more inexpensive than lithium metal which is used as lithium metal oxide-based cathode. But polymer electrodes generally have had lower charge/discharge capacity. Sulfur compounds with organothiol (-SH) or disulfide (S-S) group have advantages about high theoretical capacity but they have poor electronic conductivity. Then in this study, focusing on the enhancement of electrical performance of polymer electrode, disulfide bonds are linked to the side chain of polyaniline (PANI) and conjugated crosslinking between polymer chains is formed. As a result, crosslinked poly(9-amino-5,8-dihydro-1H,4H-2,3,6,7-tetrathia-anthracene) (PADTTAA)-co-PANI electrodes with different ratio of ADTTAA were successfully synthesized. Elemental and compositional analysis on the surface of the polymer sample was measured by using X-ray photoelectron spectroscopy (XPS). And the electrochemical property of disulfide-containing crosslinked PANI based cathode was investigated by confirming cyclic voltammetry and charge-discharge capacity. As the contents of ADTTAA increased, the charge/discharge capacity increased but the conductivity and cycle life decreased.