Clinical implication of megestrol acetate in metastatic gastric cancer: a big data analysis from Health Insurance Review and Assessment (HIRA) database.

OBJECTIVE: Megestrol acetate (MA) is used to manage anorexia and cachexia in patients with advanced cancer. This study investigated the prescription patterns of MA in patients with metastatic gastric cancer, as well as evaluated its impact on survival outcomes and the incidence of venous thromboembolism (VTE). METHODS: A Health Insurance Review and Assessment (HIRA) service database was used to investigate differences in baseline characteristics, survival, and the incidence of VTE according to MA prescription patterns (i.e., prescription vs. no prescription) in patients diagnosed with metastatic gastric cancer from July 2014 to December 2015. RESULTS: A total of 1938 patients were included in this study. In total, 65% of the patients were prescribed MA. Older age, treatment in tertiary hospitals, and palliative chemotherapy were statistically significant predictive factors for MA prescription. Continuous prescription of MA was observed in 37% of patients. There was no statistically significant difference in survival between the MA and non-MA prescription groups on multivariate analysis. Among the 1427 patients included in the analysis for VTE incidence, 4.3% and 2.9% were diagnosed with VTE during the follow-up period in the MA and non-MA prescription groups, respectively. However, there was no statistically significant difference in VTE diagnosis between the groups on multivariate analysis. CONCLUSION: MA is commonly prescribed for metastatic gastric cancer, especially in elderly patients and those undergoing palliative chemotherapy, without significantly affecting survival or VTE risk.

Treatment Patterns and Prognosis of Palliative Chemotherapy Combined With Targeting Agents in Patients With Unresectable Metastatic Colorectal Cancer: CHOICE, A Multicenter Longitudinal Observational Study.

BACKGROUND/AIM: This study investigated the treatment patterns and prognosis of patients with metastatic or unresectable colorectal cancer (mCRC) treated with chemotherapy with targeting agents. PATIENTS AND METHODS: This longitudinal multicenter study included 963 patients with mCRC who were treated in Korea between 2016 and 2020. Treatment patterns and efficacy were compared according to the mutation status and clinical factors. RESULTS: As first-line therapy, most of the patients (83.5%) received FOLFOX plus bevacizumab (35.4%), followed by FOLFIRI plus bevacizumab (18.8%), FOLFIRI plus cetuximab (17.0%), and FOLFOX plus cetuximab (12.3%). Bevacizumab was the most frequent agent (78.8%) combined with chemotherapy in RAS-mutated CRC, while cetuximab (57.2%) in RAS wild-type CRC. Cetuximab was frequently combined with a doublet regimen in patients with left-sided CRC than in those with right-sided CRC (34.4% vs. 16%). As second-line therapy, most patients (63.4%) also received doublet regimens with bevacizumab, and FOLFIRI plus aflibercept was administered in 15.1%. The objective response rate with FOLFIRI plus cetuximab was significantly higher in patients with left-sided CRC than in those with right-sided CRC (59.2% vs. 30.8%, p=0.008) and marginally higher in patients with RAS wild-type CRC than in those with RAS-mutated CRC (55.6% vs. 0.0%, p=0.092). Progression-free survival (PFS) with FOLFOX plus bevacizumab was significantly shorter than that with FOLFIRI plus bevacizumab (p=0.030) in RAS-mutated CRC, whereas there were no significant differences between regimens in RAS wild-type CRC. CONCLUSION: In patients with unresectable metastatic colorectal cancer, doublet chemotherapy with targeting agents is the most common therapy and efficacy depends on the mutation status as well as clinical factors.

Proportion of Non-Medical Opioid Use of Prescription Opioids among Cancer Patients in Korea.

Purpose: Limited research has been conducted on the prevalence of non-medical opioid use (NMOU) in Korean cancer patients who have received prescription opioids (PO). This study aimed to identify the potential proportion of NMOU in cancer patients who had been prescribed opioids in Korea. Methods: A retrospective cohort analysis was conducted on 14,728 patients who underwent cancer-related treatment between January 2009 and December 2019, using electronically collected data from a tertiary hospital in Korea. Information regarding the type and duration of opioid use was gathered. A detailed review of medical charts was carried out, focusing on patients who had been prescribed opioids for over 60 days beyond a 12-month period following the completion of their cancer treatment (long-term PO users). Results: Out of the 5,587 patients who were prescribed PO and followed up for at least 12 months, 13 cases of NMOU were identified, representing 0.23% of the patient population. Among the 204 long-term PO users, the rate was 6.37% (13/204). The most commonly misused opioids were oxycodone and fentanyl. For the group confirmed to have NMOU, the median duration of prescription was 1,327 days in total. Of the 13 patients diagnosed with NMOU, 9 reported withdrawal symptoms, 3 exhibited craving behavior for opioids, and 1 experienced both symptoms. Conclusion: This study found that 0.23% of cancer patients who had been prescribed opioids in Korea demonstrated NMOU. Despite this relatively low rate, careful monitoring is necessary to minimize the risk of NMOU in this population, especially among long-term PO users.

Prognostic impact of pretreatment skeletal muscle index and CONUT score in diffuse large B-cell Lymphoma.

BACKGROUND: Although the prognostic value of the Controlling Nutritional Status (CONUT) score in diffuse large B-cell lymphoma (DLBCL) has been reported in several previous studies, its clinical relevance for the presence of sarcopenia has not been assessed. METHODS: In this study, 305 DLBCL patients were reviewed. They were categorized into normal/mild (n = 219) and moderate/severe (n = 86) CONUT groups. Sarcopenia was assessed using the L3-skeletal muscle index measured by baseline computed tomography imaging. Based on CONUT score and sarcopenia, patients were grouped: A (normal/mild CONUT and no sarcopenia), B (either moderate/severe CONUT or sarcopenia, but not both), and C (both moderate/severe CONUT and sarcopenia). RESULTS: The moderate/severe CONUT group showed higher rates of ≥ grade 3 febrile neutropenia, thrombocytopenia, non-hematologic toxicities, and early treatment discontinuation not related to disease progression, compared to the normal/mild CONUT group. The moderate/severe CONUT group had a lower complete response rate (58.1% vs. 80.8%) and shorter median overall survival (18.5 vs. 162.6 months) than the normal/mild group. Group C had the poorest prognosis with a median survival of 8.6 months, while groups A and B showed better outcomes (not reached and 60.1 months, respectively). Combining CONUT score and sarcopenia improved the predictive accuracy of the Cox regression model (C-index: 0.763), compared to the performance of using either CONUT score (C-index: 0.754) or sarcopenia alone (C-index: 0.755). CONCLUSIONS: In conclusion, the moderate/severe CONUT group exhibited treatment intolerance, lower response, and poor prognosis. Additionally, combining CONUT score and sarcopenia enhanced predictive accuracy for survival outcomes compared to individual variables.

Treatment of Opioid Withdrawal Syndrome Triggered by Oxycodone/Naloxone with Dexmedetomidine.

The combination of oxycodone and naloxone is useful for cancer pain management. Naloxone, as a pure opioid antagonist, cannot be used simultaneously with opioids. However, owing to its low bioavailability, it can be used in an oral composite formulation. We present the case of a 55-year-old man with gastric cancer who experienced severe opioid withdrawal syndrome (OWS) triggered by oxycodone/naloxone that was successfully managed with dexmedetomidine. He had been in a stable condition on intravenous morphine to alleviate cancer pain. Intravenous morphine was switched to oral oxycodone/naloxone for discharge from the hospital. The patient suddenly developed restlessness, heartburn, and violent behavior 30 minutes after taking oxycodone/naloxone. We attempted sedation with midazolam and propofol, but paradoxical agitation and desaturation occurred. Next, we tried dexmedetomidine and the patient showed a decreased heart rate and reduced agitation. The patient was eventually stabilized by increasing the dose of dexmedetomidine. This report informs clinicians of the possibility of OWS when switching from opioids to oxycodone/naloxone, which can be overcome with the appropriate use of sedatives and dexmedetomidine depending on the patient's condition.

T/myeloid mixed-phenotype acute leukemia treated with venetoclax and decitabine: A case report.

BACKGROUND: Mixed-phenotype acute leukemia (MPAL) is characterized by acute undifferentiated leukemia with blasts co-expressing myeloid and lymphoid antigens. However, consensus regarding the ideal management strategy for MPAL is yet to be established, owing to its rarity. CASE SUMMARY: A 55-year-old male was diagnosed with T/myeloid MPAL. Vincristine, prednisolone, daunorubicin, and L-asparaginase were administered as induction chemotherapy. Septic shock occurred 10 days after induction, and bone marrow examination following recovery from sepsis revealed refractory disease. Venetoclax and decitabine were administered as chemotherapy-free induction therapy to reduce the infection risk. There were no serious infections, including febrile neutropenia, at the end of the treatment. After receiving two additional cycles of venetoclax/decitabine, the patient underwent haploidentical peripheral blood stem-cell transplantation and achieved complete response (CR) to treatment. CONCLUSION: CR was maintained in a patient with MPAL who underwent haploidentical peripheral blood stem-cell transplantation after additional venetoclax/decitabine cycles.

A Multicenter, Prospective, Observational Study to Evaluate Ethanol-Induced Symptoms in Patients Receiving Docetaxel Chemotherapy.

PURPOSE: Several previous studies and case reports have reported ethanol-induced symptoms in patients receiving anticancer drugs containing ethanol. Most docetaxel formulations contain ethanol as a solvent. However, there are insufficient data on ethanol-induced symptoms when docetaxel-containing ethanol is administered. The primary purpose of this study was to investigate the frequency and pattern of ethanol-induced symptoms during and after docetaxel administration. The secondary purpose was to explore the risk factors for ethanol-induced symptoms. MATERIALS AND METHODS: This was a prospective, multicenter, observational study. The participants filled out ethanol-induced symptom questionnaire on the day of chemotherapy and the following day. RESULTS: Data from 451 patients were analyzed. The overall occurrence rate of ethanol-induced symptoms was 44.3% (200/451 patients). The occurrence rate of facial flushing was highest at 19.7% (89/451 patients), followed by nausea in 18.2% (82/451 patients), and dizziness in 17.5% (79/451 patients). Although infrequent, unsteady walking and impaired balance occurred in 4.2% and 3.3% of patients, respectively. Female sex, presence of underlying disease, younger age, docetaxel dose, and docetaxel-containing ethanol amount were significantly associated with the occurrence of ethanol-induced symptoms. CONCLUSION: The occurrence of ethanol-induced symptoms was not low in patients receiving docetaxel-containing ethanol. Physicians need to pay more attention to the occurrence of ethanol-induced symptoms and prescribe ethanol-free or low-ethanol-containing formulations to high-risk patients.

Endothelial activation and stress index (EASIX) as a predictive biomarker in small cell lung cancer.

BACKGROUND: Endothelial activation and insult may contribute to the aggressive clinical course of small-cell lung cancer (SCLC); however, no predictive biomarker for this pathogenesis has been identified. OBJECTIVE: To evaluate the clinical impact of the endothelial activation and stress index (EASIX) in SCLC. METHODS: In this retrospective study, the EASIX was calculated from measurements of serum lactate dehydrogenase, creatinine, and platelet levels. A total of 264 patients with SCLC treated with platinum-based chemotherapy were stratified into high and low EASIX groups. RESULTS: Complete and objective response rates in the limited-stage (LD) were 19.5% vs. 33.3% (P= 0.050) and 85.4% vs. 97.9% (P= 0.028) in the high and low EASIX groups, respectively. There was no significant difference in the response rate between the two groups in the extensive-stage (ED). The median overall survival was 9.8 vs. 40.5 months in LD (P< 0.001) and 7.2 vs. 11.9 months in ED (P< 0.001) in the high and low EASIX groups, respectively. In multivariate analyses, a high EASIX level was an independent prognostic factor for worse progression-free and overall survival irrespective of stage. CONCLUSION: EASIX may be a potential predictive biomarker of SCLC.

Changes of Immune Cell Fractions in Patients Treated with Immune Checkpoint Inhibitors.

BACKGROUND: With the development of immunology, immune checkpoint inhibitors (ICIs) have been widely used in various cancer treatments. Although some patients can benefit from ICIs, other patients have no response to ICIs or suffer from hyperprogression. There has been no biomarker for predicting the efficacy of ICIs. Thus, the objective of this study was to find biomarkers for predicting the efficacy of ICIs using peripheral blood. METHODS: Adults patients planned to be treated with ICIs were enrolled in this study. Blood sampling was carried out before and after administration of ICIs. Changes of immune cell fraction were analyzed for each patient. RESULTS: Among 182 patients enrolled, immune cell analysis was performed for 90 patients. The objective response rate was 14.4% (n = 13/90). The median progression-free survival (PFS) was 6.0 months (95% CI: 3.1-8.9 months), and the median overall survival (OS) was 13.9 months (95% CI: 5.6-22.2 months). Significant benefits in ORR and OS were shown for patients with increased NKp46-/CD56+ NK cells (p = 0.033 and p = 0.013, respectively). The PFS tended to be longer in these patients, although the difference was not statistically significant (p = 0.050). CONCLUSION: Changes of immune cell fraction before and after administration of ICIs could be a novel biomarker for predicting the efficacy of immunotherapy.

Prognostic implication of serum AFP in patients with hepatocellular carcinoma treated with regorafenib.

Background: This multicenter study investigated the predictive value of baseline AFP and on-treatment AFP response for survival in hepatocellular carcinoma (HCC) patients with regorafenib. Materials & methods: A total of 578 patients with HCC treated with regorafenib from 12 institutions in South Korea and Italy were included. Baseline AFP (cutoff, 400 ng/ml) and AFP response (20% reduction from baseline) were analyzed for overall survival (OS) and progression-free survival (PFS). Results: Baseline AFP below 400 ng/ml was a significant factor that was independently associated with longer OS and PFS. AFP response was also a significant factor independently associated with longer OS and PFS. Conclusion: Baseline AFP and AFP response may be used as prognostic factors for survival in HCC treated with regorafenib.

Regorafenib is standard second-line therapy for patients with hepatocellular carcinoma (HCC) who show failure to sorafenib treatment, but there is no reliable factor to predict survival. In this multicenter, retrospective study with patients from South Korea and Italy, we have found that both baseline AFP level and on-treatment AFP response have independent predictive value for survival in patients with HCC under regorafenib treatment. We observed similar results when the patients were divided according to their nationality (South Korea vs Italy), despite the fact that the baseline characteristics of the patients from the two cohorts were significantly different.

Oxaliplatin (3 months v 6 months) With 6 Months of Fluoropyrimidine as Adjuvant Therapy in Patients With Stage II/III Colon Cancer: KCSG CO09-07.

PURPOSE: The combination of oxaliplatin and fluoropyrimidine for 6 months is one of the standard options for adjuvant therapy for high-risk stage II and III colorectal cancers (CRCs). The optimal duration of oxaliplatin to diminish neurotoxicity without compromising efficacy needs to be clarified. PATIENTS AND METHODS: This open-label, randomized, phase III, noninferiority trial randomly assigned patients with high-risk stage II and III CRC to 3 and 6 months of oxaliplatin with 6 months of fluoropyrimidine groups (3- and 6-month arms, respectively). The primary end point was disease-free survival (DFS), and the noninferiority margin was a hazard ratio (HR) of 1.25. RESULTS: In total, 1,788 patients were randomly assigned to the 6-month (n = 895) and 3-month (n = 893) arms, and 83.6% in the 6-month arm and 85.7% in the 3-month arm completed the treatment. The neuropathy rates with any grade were higher in the 6-month arm than in the 3-month arm (69.5% v 58.3%; P < .0001). The 3-year DFS rates were 83.7% and 84.7% in the 6-month and 3-month arms, respectively, with an HR of 0.953 (95% CI, 0.769 to 1.180; test for noninferiority, P = .0065) within the noninferiority margin. Among patients with stage III CRC treated by capecitabine plus oxaliplatin, the 3-year DFS of the 3-month arm was noninferior as compared with that of the 6-month arm with an HR of 0.713 (95% CI, 0.530 to 0.959; P = .0009). However, among patients with high-risk stage II and stage III CRC treated by infusional fluorouracil, leucovorin, and oxaliplatin, the noninferiority of the 3-month arm compared with the 6-month arm was not proven. CONCLUSION: This study suggests that adding 3 months of oxaliplatin to 6 months of capecitabine could be considered an alternative adjuvant treatment for stage III CRC (ClinicalTrials.gov identifier: NCT01092481).

Survey of Opioid Risk Tool Among Cancer Patients Receiving Opioid Analgesics.

BACKGROUND: The risk of opioid-related aberrant behavior (OAB) in Korean cancer patients has not been previously evaluated. The purpose of this study is to investigate the Opioid Risk Tool (ORT) in Korean cancer patients receiving opioid treatment. METHODS: Data were obtained from a multicenter, cross-sectional, nationwide observational study regarding breakthrough cancer pain. The study was conducted in 33 South Korean institutions from March 2016 to December 2017. Patients were eligible if they had cancer-related pain within the past 7 days, which was treated with strong opioids in the previous 7 days. RESULTS: We analyzed ORT results of 946 patients. Only one patient in each sex (0.2%) was classified as high risk for OAB. Moderate risk was observed in 18 males (3.3%) and in three females (0.7%). Scores above 0 were primarily derived from positive responses for personal or familial history of alcohol abuse (in men), or depression (in women). In patients with an ORT score of 1 or higher (n = 132, 14%), the score primarily represented positive responses for personal history of depression (in females), personal or family history of alcohol abuse (in males), or 16-45 years age range. These patients had more severe worst and average pain intensity (proportion of numeric rating scale ≥ 4: 20.5% vs. 11.4%, P < 0.001) and used rescue analgesics more frequently than patients with ORT scores of 0. The proportion of moderate- or high-risk patients according to ORT was lower in patients receiving low doses of long-acting opioids than in those receiving high doses (2.0% vs. 6.6%, P = 0.031). Moderate or high risk was more frequent when ORT was completed in an isolated room than in an open, busy place (2.7% vs. 0.6%, P = 0.089). CONCLUSIONS: The score of ORT was very low in cancer patients receiving strong opioids for analgesia. Higher pain intensity may associate with positive response to one or more ORT item.

Modified FOLFIRINOX as a Second-Line Treatment for Patients with Gemcitabine-Failed Advanced Biliary Tract Cancer: A Prospective Multicenter Phase II Study.

BACKGROUND: After the publication of the ABC-02 trial, gemcitabine and cisplatin combination therapy (GP) became the standard first-line treatment for advanced biliary tract cancer (BTC). Despite GP therapy, most patients suffer from disease progression. The ABC-06 trial recommended FOLFOX as a second-line treatment, but its efficacy was modest. In this phase II study, we looked at the efficacy and safety of a second-line modified dose of FOLFIRINOX (mFOLFIRINOX) for patients who had failed first-line gemcitabine-based treatment. METHODS: From January 2020 to January 2021, 34 patients with advanced BTC who failed first-line gemcitabine-based chemotherapy were enrolled. We evaluated the clinical efficacy and safety outcomes of mFOLFIRINOX. RESULTS: With a median follow-up duration of 13.4 months, the median progression-free survival and overall survival was 2.8 months (95% confidence interval (CI): 1.6-4.0 months) and 6.2 months (95% CI: 5.0-7.4 months), respectively. The objective response rate was 14.7% with no complete response. The disease control rate was 61.7%, with a disease control duration of 4.2 months. Due to the rapid progression of the disease, approximately half of all patients received less than three cycles of treatment. The most common type of adverse event (AEs) was hematopoietic AEs. The incidence of non-hematopoietic AEs was relatively low. CONCLUSIONS: The efficacy of mFOLFIRINOX as a second-line treatment in advanced BTC patients after the failure of gemcitabine-based first-line treatment was replicated, albeit with slightly shorter survival results compared to previous studies. Long-term administration of mFOLFIRINOX with toxicity management might offer a survival benefit.

Palliative Sedation in End-of-Life Patients in Eastern Asia: A Narrative Review.

Although palliative sedation (PS) is a common practice in the palliative care of cancer patients in Western countries, there is little related research on the practice in Korea. PS can be classified into several categories according to sedation level and continuity. PS is clearly distinct from euthanasia. While euthanasia is illegal and regarded as unethical in Korea, there is little ethical and legal controversy about PS in terms of the doctrine of double effect. Most studies have asserted that PS does not shorten the survival of terminal cancer patients. Since preference for PS heavily depends on stakeholder value, it should be preceded by shared decision-making through full communication among the patient, family members, and medical team. This is a narrative review article analyzing previous studies, especially from the three Eastern Asian countries, Korea, Japan and Taiwan, which share similar cultures compared with Western countries. Practical issues concerning PS-for example, prevalence, type and dosage of medications, salvage medication, timing of its initiation, and assessment-are described in detail.

The Positive Effects of Cancer Survivor Support Service on Distress in South Korea: A Nationwide Prospective Study.

BACKGROUND AND AIM: Cancer survivors are gradually increasing, however, they suffer from various difficulties. We aimed to investigate the characteristics of cancer survivors and the effects of the services of the Korean Cancer Survivorship Center Pilot Project launched by the South Korean government on distress. METHODS: A prospective observational cohort study was performed on cancer survivors who completed primary treatment. Cancer survivors' distress and symptoms such as fatigue, pain, depressive mood, anxiety, and insomnia were evaluated by well-trained nurses. Regarding their needs, medical and psychosocial support services were provided. RESULTS: This study included 1,921 cancer survivors, with a mean age of 57.3 years (68.7% females). Breast cancer was most common, followed by stomach and colorectal cancer. Psychosocial and medical support decreased the percentage of the high-distress group from 50.9 to 30.5% and decreased the percentage of cancer survivors with high scores in fatigue, pain, anxiety, depressive mood, and insomnia. The independent predictors of a low distress level after the use of the services were older age, the relief of fatigue, pain, and insomnia. CONCLUSION: This study showed that psychosocial and medical support is associated with the lower distress and physical and mental symptoms of cancer survivors. Psychosocial and medical support could contribute to distress relief in cancer survivors. Further management strategies for fatigue, pain and insomnia are required.

Beliefs and Attitudes toward Physician-assisted Suicide among Korean Adults.

Purpose: To grasp public opinion accurately, we conducted an opinion poll on beliefs and attitudes toward physician-assisted suicide (PAS). Methods: A randomized telephone survey ensuring a representative sample was conducted, 1,007 participants aged 18 years or older (response rate, 9.5%). Results: The main results are as follows i) 61.1% of participants thought that the current social support system for terminally ill patients and their families is insufficient; ii) 60% of participants did not recognize the term "hospice and palliative care"; iii) 81.7% of participants would not like to receive life-sustaining treatment if there is no possibility of recovery; iv) 58.4% of participants would like to receive hospice and palliative care if they are diagnosed with a terminal illness; v) the priorities for dignified dying were preparing a support system to reduce the burden of care (28.6%), economic support including reduction of medical expenses (26.7%), expansion of hospice and palliative care services (25.4%), and legalization of PAS (13.6%); and vi) 58.3% of participants agreed that the expansion of hospice and palliative care should precede the legalization of PAS. Conclusion: Koreans currently want other efforts, including expansion of hospice and palliative care services, instead of the legalization of PAS.

Cachexia index as a potential biomarker for cancer cachexia and a prognostic indicator in diffuse large B-cell lymphoma.

BACKGROUND: Cancer cachexia is known to adversely affect the clinical course in patients with malignant lymphoma. The cachexia index (CXI) is a potential biomarker of cancer cachexia, and its implications for the prognosis and treatment outcome of lung cancer and aggressive lymphoma has been assessed in previous studies. METHODS: A total of 267 patients diagnosed with diffuse large B-cell lymphoma who were treated with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) immunochemotherapy were retrospectively reviewed. The CXI was calculated as the skeletal muscle index (SMI) × serum albumin/neutrophil-lymphocyte ratio (NLR). Although previous studies measured the SMI using the muscles of the L3 vertebral level, the present study used both the L3 vertebral muscles and the pectoralis muscles (PM) at the T4 vertebral level to measure the SMI. Depending on the type of muscles used, the CXI was termed the L3-CXI or PM-CXI. Using sex-specific cutoff values for CXI, the patients were categorized as follows: (i) high-CXI group (high L3-CXI and high PM-CXI), (ii) intermediate-CXI group (high L3-CXI and low PM-CXI), and (iii) low-CXI group (low L3-CXI and low PM-CXI). RESULTS: Complete responses to R-CHOP were obtained in 145/173 (83.8%), 25/36 (69.4%), and 27/57 (47.4%) patients in the high-CXI, intermediate-CXI, and low-CXI groups, respectively (P < 0.001). Treatment-related anaemia (15.6%, 30.6%, and 26.3%, P = 0.038), thrombocytopenia (21.4%, 36.1%, and 43.9%, P < 0.001), febrile neutropenia (23.7%, 44.4%, and 36.8%, P = 0.022), and any nonhaematologic toxicity (31.2%, 44.4%, and 54.4%, P = 0.001) of Grade 3 or more were more common in the lower CXI groups than in the higher-CXI groups. Early treatment discontinuation for reasons other than lymphoma progression also occurred more frequently in the low-CXI group (24/57, 42.1%) compared with the intermediate-CXI (5/36, 13.9%) and high-CXI (18/173, 10.4%) groups (P < 0.001). Median overall survival in the high-CXI, intermediate-CXI, and low-CXI groups was not reached, 50.6 months, and 14.5 months, respectively (p < 0.001). Multivariable analysis showed that low CXI was an independent negative prognostic factor for overall survival (hazard ratio 2.103, 95% confidence interval 1.278-3.460, P = 0.003). CONCLUSIONS: We suggest that in patients with diffuse large B-cell lymphoma, the CXI is a biomarker for cancer cachexia that can predict survival, treatment response, treatment-related toxicity, and compliance with R-CHOP. Patients were more clearly stratified by this new CXI category compared with the classifications described in previous studies.

In vitro antimicrobial activity of cold atmospheric microwave plasma against bacteria causing canine skin and ear infections.

BACKGROUND: Cold atmospheric plasma (CAP) is a new generation medical therapeutic option for bacterial infections. CAP causes physical cell wall rupture and DNA damage, therefore making it highly useful in the treatment of various conditions such as skin infections. HYPOTHESIS/OBJECTIVES: The antimicrobial activity of cold atmospheric microwave plasma (CAMP) against major strains in canine skin infections was tested and the difference in antimicrobial activity between the antibiotic-resistant and antibiotic-susceptible strains of Staphylococcus pseudintermedius was evaluated. METHODS AND MATERIALS: American Type Culture Collection (ATCC) strains (Staphylococcus aureus, Pseudomonas aeruginosa and Escherichia coli) and clinical isolates identified as methicillin-resistant S. pseudintermedius (n = 27) and methicillin-susceptible S. pseudintermedius (n = 13) were exposed to CAMP for 10 s, 30 s and 60 s. Afterwards, the bacterial survival rate was confirmed. RESULTS: Gram-negative bacteria (P. aeruginosa and E. coli) were more susceptible than Gram-positive bacteria (S. aureus and S. pseudintermedius) for the same duration of CAMP exposure. Only the Gram-negative bacteria were completely killed after 60 s exposure. In S. pseudintermedius isolates, CAMP exposure had similar antibacterial effects regardless of antibiotic resistance. CONCLUSIONS AND CLINICAL IMPORTANCE: CAMP has sufficient antimicrobial activity against major bacterial strains that cause pyoderma and otitis externa in dogs, and may be an alternative therapeutic option for S. pseudintermedius skin infections, for which antibiotics often are ineffective because of antimicrobial resistance in clinical veterinary medicine.

Modified FOLFIRINOX versus S-1 as second-line chemotherapy in gemcitabine-failed metastatic pancreatic cancer patients: A randomised controlled trial (MPACA-3).

BACKGROUND: The efficacy of modified FOLFIRINOX (mFOLFIRINOX) as a second-line chemotherapy treatment for metastatic pancreatic adenocarcinoma (mPAC), remains unclear. This multi-center randomised phase III trial aimed to elucidate the efficacy of mFOLFIRINOX as a second-line chemotherapy treatment for mPAC patients with good performance status. PATIENTS AND METHODS: Eighty mPAC patients (age, 19-75 years) refractory to first-line gemcitabine-based chemotherapy were randomly selected to receive mFOLFIRINOX or S-1. mFOLFIRINOX comprised oxaliplatin (65 mg/m2), irinotecan (135 mg/m2), and leucovorin (400 mg/m2) on day 1 and continuous 5-FU infusion (1000 mg/m2) over 24 h on days 1-2 every 2 weeks. S-1 comprised body surface area-dependent oral S-1, divided into two doses per day on days 1-28 every 6 weeks. RESULTS: Overall survival was the primary endpoint. The objective response and disease control rates were higher in the mFOLFIRINOX than in the S-1 group (15% versus 2%; p = .04 and 67% versus 37%; p = .007). The median progression-free survival rates were 5.2 and 2.2 months in the mFOLFIRINOX and S-1 groups, respectively (adjusted hazard ratio [HR]: .4; 95% confidence interval [CI]: .2-.6; p < .001). The median overall survival rates were 9.2 and 4.9 months in the mFOLFIRINOX and S-1 groups, respectively (adjusted HR: .4; 95% CI: .2-.7; p = .002). Grade 3-4 adverse events occurred in 56% and 17% of the patients in the mFOLFIRINOX and S-1 groups, respectively (p < .001). CONCLUSION: Administration of mFOLFIRINOX as a second-line chemotherapy treatment for mPAC patients refractory to gemcitabine-based chemotherapy resulted in increased survival rates than S-1 treatment alone.

Relationship between heavy metal exposure and type 2 diabetes: a large-scale retrospective cohort study using occupational health examinations.

OBJECTIVES: To investigate the associations between heavy metal exposure and serum ferritin levels, physical measurements and type 2 diabetes mellitus (DM). DESIGN: A retrospective cohort study. SETTING: Changwon, the location of this study, is a Korean representative industrial city. Data were obtained from medical check-ups between 2002 and 2018. PARTICIPANTS: A total of 34 814 male subjects were included. Of them, 1035 subjects with lead exposure, 200 subjects with cadmium exposure and the 33 579 remaining were assigned to cohort A, cohort B and the control cohort, respectively. Data including personal history of alcohol and smoking, age, height, weight, the follow-up duration, haemoglobin A1c (HbA1c), fasting blood sugar (FBS), ferritin levels, and lead and cadmium levels within 1 year after exposure were collected. PRIMARY OUTCOME MEASURE: In subjects without diabetes, changes in FBS and HbA1c were analysed through repeated tests at intervals of 1 year or longer after the occupational exposure to heavy metals. RESULTS: In Cohort A, DM was diagnosed in 33 subjects. There was a significant difference in lead concentrations between the subjects diagnosed with DM and those without DM during the follow-up period (3.94±2.92 mg/dL vs 2.81±2.03 mg/dL, p=0.002). Simple exposure to heavy metals (lead and cadmium) was not associated with DM in Cox regression models (lead exposure (HR) 1.01, 95% CI: 0.58 to 1.77, p 0.971; cadmium exposure HR 1.48, 95% CI: 0.61 to 3.55, p=0.385). Annual changes in FBS according to lead concentration at the beginning of exposure showed a positive correlation (r=0.072, p=0.032). CONCLUSION: Our findings demonstrated that simple occupational exposure to heavy metals lead and cadmium was not associated with the incidence of DM. However, lead concentrations at the beginning of the exposure might be an indicator of DM and glucose elevations.