A Retrospective Study of the Efficacy and Safety of Naldemedine for Treatment of Opioid-Induced Constipation in Patients with Hepatobiliary Pancreatic Cancer.

Background and Objectives: Opioid analgesics, which are used for cancer-related pain management, cause opioid-induced constipation (OIC). Naldemedine, a peripheral opioid receptor antagonist, is an OIC-modifying agent, but no focused efficacy and safety analysis has been conducted for its use in hepatobiliary pancreatic cancers. We performed a multi-institutional study on the efficacy and safety of naldemedine in patients with hepatobiliary pancreatic cancer using opioids in clinical practice. Materials and Methods: We retrospectively evaluated patients with hepatobiliary pancreatic cancer (including liver, biliary tract, and pancreatic cancers) treated with opioids and naldemedine during hospitalization at ten institutions in Japan from June 2017 to August 2019. We assessed the frequency of bowel movements before and after the initiation of naldemedine therapy. Responders were defined as patients who defecated ≥3 times/week, with an increase from a baseline of ≥1 defecations/week over seven days after the initiation of naldemedine administration. Results: Thirty-four patients were observed for one week before and one week after starting naldemedine. The frequency of bowel movements increased by one over the baseline frequency or to at least thrice per week in 21 patients. The response rate was 61.7% (95% confidence interval: 45.4-78.0%). The median number of weekly bowel movements before and after naldemedine treatment was 2 (range: 0-9) and 6 (range: 1-17), respectively, in the overall population (n = 34); the increase in the number of bowel movements following naldemedine administration was statistically significant (Wilcoxon signed-rank test, p < 0.0001). Diarrhea was the predominant gastrointestinal symptom, and 10 (29.4%) patients experienced grade 1, grade 2, or grade 3 adverse events. The only other adverse event included fatigue in one patient; grade 2-4 adverse events were absent. Conclusions: Naldemedine is effective, and its use may be safe in clinical practice for patients with hepatobiliary pancreatic cancer receiving opioid analgesics.

Effects of Sex and Seasonal Climatic Changes on the Risk of Incidence of Anti-EGFR Therapy-Induced Rash in Cancer Patients: A Retrospective Study.

Background and Objectives: Seasonal climatic changes may affect the development of the rash that is characteristic of treatment with anti-epidermal growth factor receptor (EGFR) antibodies. We evaluated the association between seasons and rash incidence among patients with cancer. Materials and Methods: Data from patients with colorectal or head and neck cancer treated with cetuximab or panitumumab during summer (S group; n = 34) or winter (W group; n = 37) between June 2014 and February 2019 were collected to retrospectively examine patient characteristics and rash incidence ≤ 8 weeks after treatment initiation. Results: Rashes were observed in 73.5% (n = 25) and 78.4% (n = 29) and grade 3 rashes were observed in 17.6% (n = 6) and 2.7% (n = 1) of the patients in the S and W groups, respectively. The incidence of grade ≥ 2 rashes in males in the S group was higher than that in the rest of the patient groups (p < 0.01). Conclusions: The higher incidence of skin rashes in males during summer might be attributed to the effects of ultraviolet light, lack of skincare, male hormones, and secretion of anti-EGFR antibodies in sweat. These findings highlight the need for research on preventive measures for such rashes.

[Pure red cell aplasia following the rapid reduction and discontinuation of cyclosporine for mixed chimerism after allogeneic bone marrow transplantation].

A 19-year-old male with therapy-related myelodysplastic syndrome underwent allogeneic bone marrow transplantation with reduced-intensity conditioning from his HLA-identical sibling whose ABO blood type exhibited major incompatibility with the patient. After post-transplantation 1 month, chimerism analysis of the bone marrow revealed mixed chimerism with 30% of recipient cells, and after post-transplantation 3 months, complete remission was maintained; however, recipient granulocytes were elevated up to 50% per the chimerism analysis. Next, pancytopenia developed following the rapid discontinuation of the immunosuppressive agent. Although neutrophils and platelets spontaneously recovered, anemia progressed. Based on severe erythroid hypoplasia in the bone marrow and the elevation of anti-ABO isohemagglutinin against donor-derived red blood cells, the patient was diagnosed with pure red cell aplasia (PRCA) following hematopoietic cell transplantation. Because complete chimerism was attained at the PRCA onset even for B cells, we decided to conservatively manage PRCA with only red blood cell transfusion. Notably, after 2 months of the PRCA onset, anemia improved. This case suggests that the therapeutic strategy for PRCA following hematopoietic cell transplantation should be determined by considering the status of each patient, including chimerism.

Utility of the MALDI-TOF MS method to identify nontuberculous mycobacteria.

In comparison to the conventional real-time polymerase chain reaction method (PCR method) or the DNA-DNA hybridization method (DDH method), the utility of NTM identification by the matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) method has seldom been reported. In this study, 75 clinical NTM isolates from our hospital between April 2013 and July 2014 were identified and analyzed using PCR, DDH, and MALDI-TOF MS methods, and the results for the MALDI-TOF MS method were compared with the others. Identification at the species level was in agreement for 71 (94.5%) of the 75 isolates. For further details, identification was possible for 23 (95.8%) of 24 Mycobacterium avium, 11 (100%) of 11 Mycobacterium intracellulare, and 1 (50%) of 2 isolates mixed with M. avium and M. intracellulare. Mycobacterium ksansasii, Mycobacterium abscessus, Mycobacterium fortuitum, Mycobacterium gordonae, and Mycobacterium chelonae identified by DDH method were same result by MALDI-TOF MS. Additionally, Mycobacterium mucogenicum, which could not be identified by the DDH method, was identified by the MALDI-TOF MS method. However, two isolates identified as Mycobacterium terrae by DDH method could not be identified by the MALDI-TOF MS method and were determined to be Mycobacterium arupense by 16S ribosomal RNA (rRNA) sequence analysis. The present findings show that, for rare bacterial species, identification is sometimes not possible, but, in most cases, the results of identification by the MALDI-TOF MS method have a high concordance rate with the results of the PCR and DDH methods.

Efficacy and safety of naldemedine for opioid-induced constipation in older patients with cancer: a retrospective study.

BACKGROUND: Opioids are pain relievers that are often associated with opioid-induced constipation (OIC) that worsens with age. We performed a multicenter, retrospective analysis on the efficacy and safety of naldemedine, an opioid receptor antagonist, in treating OIC in patients with cancer (age >75 years). METHODS: The electronic medical records of cancer patients who received naldemedine at 10 Japanese institutions between 7 June 2017 and August 31, 2019, were retrieved. Patients aged ≥75 years who were treated with naldemedine for the first time and hospitalized for at least 7 days before and after initiating naldemedine therapy were included in this analysis. RESULTS: Sixty patients were observed for at least 7 days before and after starting naldemedine. The response rate was 68.3%, and the frequency of bowel movements increased significantly after naldemedine administration in the overall population ( P  < 0.0001) and among those who defecated <3 times/week before naldemedine administration ( P  < 0.0001). Diarrhea was the most frequent adverse event in all grades, observed in 45% of patients, of which 92.6% were Grade 1 or 2. Grade 4 or higher adverse events, including death, were not observed. CONCLUSION: Naldemedine exhibits significant efficacy and safety in OIC treatment in older patients with cancer.

Efficacy and Safety of Naldemedine Administration for Opioid-Induced Constipation in Cancer Patients with Poor Performance Status.

Background: Constipation is a concern among patients with Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 3 and 4. Objectives: To assess naldemedine's efficacy and safety in cancer patients on opioids with poor PS. Design: Multicenter, retrospective study. Setting/Subjects: Japanese cancer patients with ECOG performance status 3 or 4 who received naldemedine. Measurements: Frequency of defecations before/after naldemedine use. Responders were patients whose defecation frequency increased to ≥3 times/week, from baseline ≥1 defecations/week over seven days after naldemedine administration. Results: Seventy-one patients were analyzed; 66.1% were responders (95% confidence interval: 54.5%-76.1%). Defecation frequency increased significantly after naldemedine in the overall population (6 vs. 2, p < 0.0001) and among those who defecated <3 times/week before naldemedine (4.5 vs. 1, p < 0.0001). Diarrhea (38.0%) of all grades was the most common adverse event; 23 (85.2%) events were classified as Grade 1 or 2. Conclusion: Naldemedine is effective and safe among cancer patients with poor PS.

Use of the Japanese Version of the Montreal Cognitive Assessment to Estimate Cognitive Decline in Patients Aged 75 Years or Older with and without Type 2 Diabetes Mellitus.

BACKGROUND: The number of people diagnosed with dementia worldwide is set to increase significantly. Patients with dementia often have comorbidities, particularly diabetes, and patients with type 2 diabetes mellitus (T2DM) have a high risk of cognitive decline. This study investigated whether older people with T2DM have disease-specific cognitive deficits. METHODS: The Montreal Cognitive Assessment is a well-known tool for examining mild cognitive impairment, and the modified Japanese version (MoCA-J) has been confirmed as effective. Using the MoCA-J, we assessed the cognitive function of Japanese adults aged ≥75 years with and without T2DM and analyzed the results. RESULTS: Thirty-three patients with T2DM and 23 non-DM patients completed the examination, and MoCA-J total scores differed between these groups (T2DM mean, 21.4 ± 3.5; non-DM mean, 23.5 ± 3.6). Only 9% of patients with T2DM and 39% of those with non-DM had scores ≥26, which is the cutoff point for mild cognitive impairment, although all patients were capable of self-care. Additionally, delayed recall scores were significantly lower for the older patients with T2DM had for the non-DM group. CONCLUSIONS: Patients aged ≥75 years with T2DM might have worse cognition than those without T2DM; the inability to perform delayed recall in T2DM patients suggests a decline in cognitive function. Therefore, patients aged ≥75 years with T2DM should receive explanations of their care that are individualized in relation to their cognitive status.

Clinical Efficacy and Safety of Arbekacin against Pneumonia in Febrile Neutropenia: A Retrospective Study in Patients with Hematologic Malignancies.

BACKGROUND: Arbekacin (ABK) is an aminoglycoside that exhibits anti-methicillin-resistant Staphylococcus aureus (MRSA) and anti-Pseudomonas aeruginosa activities. Therefore, for patients with febrile neutropenia (FN) and concurrent pneumonia suspected to be caused by MRSA, ABK may be sufficiently effective even as a single agent. MATERIALS AND METHODS: Patients with hematologic malignancies treated with ABK who met the following criteria were included: 1) fever during neutropenia or functional neutropenia, 2) FN complicated by pneumonia, and 3) possible infection by antimicrobial-resistant Gram-positive cocci. RESULTS: This study encompassed 22 episodes involving 19 patients, of which, 15 (68.2%) were successfully treated with ABK. Of the nine episodes showing inadequate response to other anti-MRSA drugs, eight were successfully treated with ABK. Grade 2 or worse adverse events included acute kidney injury (13.6%) and increased transaminase levels (9.1%). CONCLUSION: The present study demonstrated that ABK is effective and safe in patients with FN and concurrent pneumonia caused by antimicrobial-resistant Gram-positive cocci. ABK may also be effective in patients who are unresponsive to other anti-MRSA drugs. Therefore, ABK may be beneficial in the treatment of pneumonia caused by antimicrobial-resistant Gram-positive cocci in patients with FN.