A case of needle tract seeding with endoscopic findings of progression over time.

An 83-year-old male underwent three transgastric punctures with endoscopic ultrasound-guided fine-needle aspiration for the examination of a pancreatic body tumor. After a diagnosis of resectable pancreatic cancer and undergoing distal pancreatectomy, the patient was administered postoperative adjuvant chemotherapy with oral S-1 for 6 months, and carcinoembryonic antigen and carbohydrate antigen 19-9 levels were bimonthly evaluated. Carbohydrate antigen 19-9 levels continually increased to 4638.1 U/mL at 45 months post-fine-needle aspiration. Endoscopic ultrasound-guided showed a 25 mm low-echoic, irregularly shaped, and heterogeneous tumor with clear margins protruding from the mucosa outside the gastric wall, and biopsy confirmed adenocarcinoma. Since the immunostaining findings of the specimen matched those of the previously resected specimen, needle tract seeding (NTS) due to puncture of the pancreatic cancer was identified as the cause. After a pylorus-preserving gastrectomy at 46 months post-fine-needle aspiration, postoperative chemotherapy initiation, comprising gemcitabine and nab-paclitaxel, was initiated; however, the patient died despite these interventions as he developed multiple peritoneal dissemination. Although rare, the incidence of NTS will increase in the future owing to the expected extended survival in post-pancreatic cancer resection cases. We suggest regular upper gastrointestinal endoscopy and endoscopic ultrasound-guided evaluations for patients who are at risk for NTS can facilitate early detection. Furthermore, it is extremely relevant to share experiences of encountered NTS cases in practice and extend knowledge of its varying endoscopic appearances.

Fixation devices made of poly-L-lactide composite for rib reconstruction after thoracotomy.

GRAND FIX mesh-type plates and pins (Gunze, Kyoto, Japan) are thin, bioabsorbable fixation devices made of poly-L-lactide (PLLA) composite. These devices are new, and how best to use them in clinical practice remains to be determined. Thus, we describe our approach to rib fixation after thoracotomy in an aortic surgery using GRAND FIX mesh-type plates and pins. The advantage of our approach is that it is easy to perform, but careful attention should be paid to fix the ribs appropriately.

[Establishment of Rapid Simultaneous Analysis Method for Plant Toxins by LC-TOF-MS].

Assuming food poisoning caused by toxic plants, an LC-TOF-MS-based method for the rapid and simultaneous analysis of 16 plant toxins was established. After adding water-methanol (1 : 9) and n-hexane, the samples were homogenized and extracted, and then subjected to centrifugal separation. Without any purification procedures, LC-TOF-MS measurements were performed, and qualitative and quantitative analyses using monoisotopic ion [M+H]+ (m/z) were conducted. The addition-recovery test using curry showed that qualitative analysis was possible under a setting with a retention time of ±0.2 minutes or less and mass accuracy of 5 ppm or lower and that quantitative analysis was possible with a recovery rate of 68-142% and a repeatability of 1.4-10.1%. Furthermore, measurements of the amount of plant toxins in the boiled plants and broths of cooked toxic plants demonstrated the transfer of plant toxins to broths. These suggest that in the event of food poisoning, broths may be used as an analysis sample, even when plants are not available.

A case of disseminated peritoneal metastases after 2-year conservative treatment for intramucosal colon carcinoma due to a perforation during endoscopic submucosal dissection.

A 70-year-old man was admitted to our hospital for the treatment of a large granular-type laterally spreading tumor in the splenic flexure of the descending colon. The preoperative diagnosis was intramucosal colon carcinoma and endoscopic submucosal dissection was performed. During treatment, a small perforation occurred accidentally. After conservative treatment with endoscopic suturing, the patient was discharged without additional surgery. The pathological diagnosis was an intramucosal carcinoma. One year after treatment, no local recurrence was observed on endoscopy, and abdominal computed tomography showed no obvious metastasis. Two years later, fluorodeoxyglucose-positron emission tomography/computed tomography, laparoscopic findings, and histopathologic findings by experimental excision of omentum revealed several disseminated peritoneal metastases from previously treated colon carcinoma. To the best of our knowledge, this is the first report of peritoneal dissemination after a small perforation during endoscopic submucosal dissection and conservative therapy for early-stage colon carcinoma. This report suggests the possibility of tumor dissemination in patients with small perforations during endoscopic procedures. Endoscopists should be aware of these rare potential risks and perform later surveillance carefully.

Association of Nutritional Indices With Adverse Effects and Time-to-Treatment-Failure in Triple Therapy for Lung Cancer.

BACKGROUND/AIM: Recent lung cancer treatments include an immune checkpoint inhibitor (ICI) pembrolizumab, platinum-based agents, plus an additional cytotoxic anticancer agent. Nutritional indices, such as the geriatric nutritional risk index (GNRI) and the prognostic nutritional index (PNI), are known to correlate with the prognosis of cancer chemotherapy. Several previous studies have investigated the relationship between PNI and treatment response in non-small cell lung cancer patients, reporting significantly increased OS and PFS in the high PNI group before treatment. However, the relationship between the three-drug combination and GNRI/PNI is unclear. The current study aimed to investigate the association of nutritional indices with duration of treatment success and occurrence of side effects in triple therapy. PATIENTS AND METHODS: Seventy-two patients with non-small cell lung cancer, treated with combination of carboplatin, pemetrexed, and pembrolizumab from November 2019 to September 30, 2022, were classified into two groups (High and Low) for GNRI and PNI, and a retrospective study was performed. RESULTS: In terms of time-to-treatment-failure (TTF), univariate and multivariate Cox proportional hazards regression analysis showed the Low-PNI group to have significantly shorter TTF than the High-PNI group (p=0.006); multivariate analysis results also showed PNI as a factor affecting TTF (HR=2.791, 95%CI=1.362-5.721, p=0.005). On the other hand, GNRI was not shown to be a factor affecting TTF. CONCLUSION: PNI at the start of treatment was an independent prognostic factor affecting treatment success time (TTF) in non-small cell lung cancer patients receiving triple therapy. However, PNI was not shown to be a prognostic predictor of irAE development.

Association of Geriatric Nutritional Risk Index With Adverse Event and Treatment Duration in Adjuvant Chemotherapy for Patients With Colorectal Cancer.

BACKGROUND/AIM: In recent years, the Geriatric Nutritional Risk Index (GNRI) has been reported as a predictor of prognosis in many patients with cancer. This study investigated the association of preoperative GNRI with the occurrence of adverse events and duration of treatment with capecitabine plus oxaliplatin (CAPOX), a postoperative adjuvant chemotherapy, in 59 patients with colorectal cancer from September 2019 to April 2022. PATIENTS AND METHODS: A cut-off value of 100.9 was used to categorize patients into high and low GNRI groups. RESULTS: The incidence of grade ≥2 leukopenia (p=0.03), and all grades peripheral neuropathy (p=0.04) were significantly more frequent in the low GNRI group. Analysis of factors influencing treatment duration by univariate and multivariate Cox regression proportional hazards models showed a significant difference in GNRI (p=0.0097). CONCLUSION: GNRI, a nutritional indicator assessed before the start of treatment, influences the occurrence of adverse events and duration of treatment with CAPOX as adjuvant chemotherapy. To complete CAPOX therapy, preoperatively, it is important to assess the patients' nutritional status using the GNRI and to actively intervene in nutritional therapy.

Association of Geriatric Nutritional Risk Index With Immune Checkpoint Inhibitor Treatment Duration and Adverse Events in Lung Cancer.

BACKGROUND/AIM: Compared to conventional cytotoxic anticancer agent-based therapy, treatment with immune checkpoint inhibitors (ICI) significantly prolongs overall survival. The Geriatric Nutritional Risk Index (GNRI) has been used as a new prognostic indicator in cancer. As nutritional status is associated with prognosis and indicates treatment response, we investigated the effect of the pretreatment GNRI on the (1) occurrence of ICI-induced immune-related adverse events (ir-AE) and (2) association with time to treatment failure (TTF) in ICI monotherapy for lung cancer. PATIENTS AND METHODS: In this study, 127 patients with lung cancer who were treated with ICI monotherapy were retrospectively enrolled. Based on a cutoff value of 92 for the GNRI, we investigated intergroup differences in the occurrence of adverse events and their association with TTF in the High-GNRI (≥92) and Low-GNRI (<92) groups. For intergroup comparisons, we used the Student's t-test, Welch's t-test, Fisher's direct probability test, and Mann-Whitney's U-test, and factors with p<0.05 in the intergroup comparison were extracted as explanatory variables. RESULTS: Based on the pretreatment GNRI, the median TTF was 5.1 months (95%CI=2.4-7.9 months) in the High-GNRI group and 2.3 months (95%CI=1.6-3.1 months) in the Low-GNRI group, with the High-GNRI group having a significantly longer TTF (p<0.01). The incidence of skin rash (p=0.0129) and pruritus (p<0.01) was significantly higher in the High-GNRI group. CONCLUSION: Pretreatment GNRI influences the continuation of ICI monotherapy. The High-GNRI group demonstrated a significantly higher frequency of skin lesions, which may have influenced the prolongation of TTF.

Case Report: Case series: association between blood concentration and side effects of sotorasib.

Introduction: Sotorasib is a crucial therapeutic agent for patients with non-small cell lung cancer (NSCLC) harboring the KRAS p.G12C mutation. Despite its efficacy, the relationship between blood sotorasib concentrations and side effects remains largely unexplored. Methods: This study enrolled five patients with KRAS p.G12C-positive NSCLC treated with sotorasib (LUMAKRAS® Tablets, Amgen, Japan) between July 2022 and February 2023 at Asahikawa Medical University Hospital. Blood sotorasib levels were monitored, and their association with adverse events was examined, with no adjustments made to drug dosages based on these levels. Results: Variable blood sotorasib levels were observed among the participants. Notably, one patient developed interstitial pneumonitis, although a definitive attribution to sotorasib was uncertain due to prior pembrolizumab treatment. The study revealed no consistent association between blood sotorasib levels and adverse events or therapeutic outcomes, with some patients experiencing severe side effects at higher concentrations, while others did not. Conclusion: Preliminary findings suggested that monitoring blood sotorasib levels may aid in anticipating adverse events in this small cohort. However, future studies with larger sample sizes and extended follow-up periods are required to validate these initial observations. Such studies could potentially offer insights into personalized dosing strategies, thereby mitigating adverse effects and enhance patient care for individuals with KRAS p.G12C-positive NSCLC.

An experimental study on the addition of bacteria to residual anticancer drugs: evaluation of the effect on bacterial growth.

Using anticancer drugs as an example, we examined the possibility of reusing residual drugs. The use of residual drugs is not widespread because of concerns regarding bacterial contamination. We mixed anticancer drugs with bacteria and investigated their effects on bacterial growth. The anticancer drugs carboplatin, paclitaxel, etoposide, irinotecan, methotrexate, and 5-fluorouracil (5-FU) were mixed with Staphylococcus aureus, Enterococcus faecalis, Serratia marcescens, and Escherichia coli. After a certain period, the number of bacteria was counted. Irinotecan showed no antibacterial activity, whereas 5-FU showed high antibacterial activity against the bacteria tested. The 5-FU also showed a minimum inhibitory concentration value in the range of 8-80 µg/mL, depending on the bacterial species. The 5-FU dose-dependently inhibited S. aureus growth at more than 0.8 µg/mL. Since protein synthesis systems are reportedly antibiotic targets, we used a cell-free protein synthesis system to confirm the mechanism of the anticancer agent's antibacterial activity. The 5-FU and methotrexate had direct inhibitory effects on protein synthesis. It is suggested that even if the residual drugs are contaminated with bacteria, there will be no microbial growth or microbes will be killed by the drug. With careful monitoring, the 5-FU could potentially be used for antimicrobial purposes.

The Relationship Between Efficacy and Safety of Osimertinib Blood Concentration in Patients With EGFR Mutation-positive Lung Cancer: A Prospective Observational Study.

BACKGROUND/AIM: Osimertinib blood levels and their impact on treatment continuation in patients with EGFR mutation-positive lung cancer is not known. This study investigated the drug blood levels and risk factors affecting treatment continuation. PATIENTS AND METHODS: Fifty-six patients with recurrent and inoperable epidermal growth factor receptor (EGFR) mutation-positive non-small cell lung cancer who received Osimertinib (80 mg once daily, daily dose) between October 1, 2016, and August 31, 2021, were included. Patients were classified into two groups using a cutoff blood level of 155 ng/ml. The primary endpoint was the relationship between Osimertinib exposure and efficacy, and secondary endpoints were the relationship between Osimertinib exposure and side effects, and the effect of covariates on efficacy and blood levels. RESULTS: The median progression-free survival (PFS) for evaluable patients in the steady-state trough concentration (Cmin ss) ≥155 ng/ml and Cmin ss <155 ng/ml groups was 18.7 months and 31.2 months. Serum albumin (Alb) levels were 3.73±0.40 g/dl and 3.93±0.28 g/dl (p=0.030), respectively, and in multivariate analysis, Alb <3.7 g/dl was associated with a hazard ratio of 5.304 (95%CI=1.431-19.66; p=0.013), indicating that Alb <3.7 g/dl significantly shortened PFS. CONCLUSION: Free blood concentration of Osimertinib may have been increased by a combination of factors, including decreased hepatic metabolic function and decreased albumin production caused by systemic inflammation in patients with cancer. However, there was no effect of Osimertinib Cmin ss on PFS.

Serum Albumin Affects the Time-to-treatment Failure of Alectinib: A Multicenter Retrospective Study.

BACKGROUND/AIM: Alectinib is recommended for anaplastic lymphoma kinase fusion gene-positive non-small cell lung cancer. We have experienced early alectinib discontinuation due to disease progression and adverse effects in real world. Because alectinib has a high protein-binding rate of >99%, low serum albumin may increase the concentration of free drug and affect efficacy and adverse events. However, no association between serum albumin and the clinical impact of alectinib has been reported. The purpose of this study was to determine the effect of serum albumin on time-to-treatment failure (TTF) in alectinib. PATIENTS AND METHODS: Fifty-six patients who were admitted to four hospitals (National Hospital Organization Hokkaido Cancer Center, Sapporo Minami-Sanjo Hospital, KKR Sapporo Medical Center, Otaru General Hospital) between October 2014 and September 2020 were retrospectively evaluated to identify those treated with alectinib. RESULTS: The multivariate analysis showed that the risk of discontinuation was significantly higher with serum albumin <3.6 g/dl compared to ≥3.6 g/dl at the start of alectinib administration (hazard ratio=3.00; 95% confidence interval=1.36-6.66; p<0.01). On Kaplan-Meier curves, TTF for serum albumin <3.6 was significantly shorter than that for ≥3.6. (median TTF: 12.1 months vs. not reach, p<0.01). CONCLUSION: To the best of our knowledge, this study is the first to report that serum albumin <3.6 g/dl at alectinib induction is associated with poor TTF. Low serum albumin is a poor prognostic factor in cancer patients. Thus, serum albumin levels must be measured before treatment.

Effect of the Minimum Inhibitory Concentration of Vancomycin on the Clinical Outcome of Enterococcus faecium Bacteremia.

BACKGROUND/AIM: Vancomycin (VCM) is an antibiotic widely used in the treatment of resistant bacteria. In patients with methicillin-resistant Staphylococcus aureus (MRSA) infection, the clinical outcome differs according to the VCM minimum inhibitory concentration (MIC) of isolates. However, the effect of VCM MIC on the clinical outcome is unclear for bacterial species other than MRSA. This study evaluated the relationship between the VCM MIC and clinical outcomes in patients with Enterococcus faecium bacteremia. PATIENTS AND METHODS: This study included patients who had E. faecium detected in at least one set of blood cultures between April 2011 and March 2022. The study assessed the outcome according to the VCM MIC. The primary outcome was the 30-day mortality rate. Measures of interest included the initial serum concentration of VCM, MIC, the area under the curve (AUC), and the AUC over 24-48 hours (AUC24-48 h). RESULTS: A total of 26 patients were included in the study, of whom 5 died and 21 survived. The 30-day mortality was higher in patients with higher MICs and lower serum albumin levels. Patients with a serum albumin level <2.0 mg/dl and a MIC ≥1 µg/ml had significantly shorter survival than those who did not (p=0.013, log-rank test). CONCLUSION: The 30-day mortality rate of patients with E. faecium bacteremia is associated with the VCM MIC of E. faecium isolates and the patient's nutritional status. Patients with albumin <2 mg/dl and MIC ≥1 µg/ml may have a poor outcome and require careful clinical monitoring.

Simulation of Vancomycin Exposure Using Trough and Peak Levels Achieves the Target Area under the Steady-State Concentration-Time Curve in ICU Patients.

The therapeutic drug monitoring (TDM) of vancomycin (VCM) in critically ill patients often results in the estimated area being under the concentration-time curve (AUC) values that deviate from individual observations. In this study, we investigated the factors influencing the achievement of the target AUC of VCM at steady-state in critically ill patients. We retrospectively collected data from patients treated with VCM in an intensive care unit (ICU). Multivariate analysis was used to adjust for significant factors with p < 0.05 and identify new factors affecting the achievement of the target AUC at steady-state for VCM. Among the 113 patients included in this study, 72 (64%) were in the 1-point group (trough only), whereas 41 (36%) were in the 2-point group (trough/peak). The percentage of patients achieving the target AUC at the follow-up TDM evaluation was significantly higher in the two-point group. Multivariate analysis showed that being in the 2-point group and those with a 20% or more increase (or decrease) in creatinine clearance (CCr) were both significantly associated with the success rate of achieving the target AUC at the follow-up TDM. Novel findings revealed that in patients admitted to the ICU, changes in renal function were a predictor of AUC deviation, with a 20% or more increase (or decrease) in CCr being an indicator. We believe the indicators obtained in this study are simple and can be applied clinically in many facilities. If changes in renal function are anticipated, we recommend an AUC evaluation of VCM with a two-point blood collection, close monitoring of renal function, and dose adjustment based on reanalyzing the serum concentrations of VCM.

[Association of Geriatric Nutritional Risk Index with Adverse Events and Time to Treatment Failure in Malignant Lymphoma Patients Treated with(R-)EPOCH].

To date, there are no reports that examine the relationship between geriatric nutritional risk index(GNRI)at the start of chemotherapy for malignant lymphoma and adverse effects. In this study, we investigated the relationship between GNRI at the start of chemotherapy and the incidence of side effects and time to treatment failure(TTF)in(R-)EPOCH-treated patients with relapsed or refractory malignant lymphoma. A significant difference in the incidence of Grade 3 or higher thrombocytopenia was observed between high and low GNRI groups(p=0.043). The GNRI may be an indicator of hematologic toxicity in malignant lymphoma patients treated with(R-)EPOCH. There was a statistically significant difference in TTF between the high and low GNRI groups(p=0.025), suggesting that nutritional status at the start of(R-)EPOCH may affect treatment continuation.

Association between Area under the Curve Estimated from Carboplatin Dose and Incidence of Severe Thrombocytopenia in Patients with Non-Hodgkin's Lymphoma on DeVIC Therapy.

BACKGROUND: The degrees of adverse effects with carboplatin (CBDCA) are influenced by interindividual differences in the area under the curve (AUC), whereas renal function is not considered in the CBDCA dose design for dexamethasone, etoposide, ifosfamide, and CBDCA (DeVIC) therapy. We conducted this study to evaluate the association between the AUC and incidence of severe thrombocytopenia in patients treated with DeVIC with or without rituximab (DeVIC ± R). METHODS: We retrospectively analyzed clinical data for 36 patients with non-Hodgkin's lymphoma who received DeVIC ± R between May 2013 and January 2021 at the National Hospital Organization Hokkaido Cancer Center. The AUC of CBDCA (AUCactual) was calculated backward using a variant of the Calvert formula. RESULTS: The median AUCactual was 4.6 (interquartile range: 4.3-5.3) min mg/mL and AUCactual was negatively correlated with the nadir platelet count (r = -0.45; P < 0.01). Multivariate analysis showed that AUCactual ≥ 4.3 versus < 4.3 was an independent factor predictive of severe thrombocytopenia (odds ratio: 19.3, and 95% confidence interval: 1.45-258; P = 0.02). CONCLUSION: This study suggests that the CBDCA dosing design considering renal function can reduce the risk of severe thrombocytopenia in DeVIC ± R therapy.

Influence of Geriatric Nutritional Risk Index on Occurrence of Adverse Events and Duration of Treatment in Patients With Lymphoma Receiving R-CHOP Therapy.

BACKGROUND/AIM: No studies have examined the association between the Geriatric Nutritional Risk Index (GNRI) at the initiation of chemotherapy for malignant lymphoma and the occurrence of adverse events. Therefore, we investigated the impact of GNRI at treatment initiation on the occurrence of side effects and time to treatment failure (TTF) in patients with malignant lymphoma undergoing initial rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) therapy. PATIENTS AND METHODS: This study included 131 patients who underwent initial R-CHOP therapy between March 2016 and October 2021. Patients were stratified into those with high (GNRI ≥92; n=56) or low (GNRI <92; n=75) GNRI status. RESULTS: Comparing the High GNRI group and Low GNRI group, the incidence of febrile neutropenia (FN) and Grade ≥3 creatinine increase, alkaline phosphatase (ALP) increase, albumin decrease, hemoglobin decrease, neutropenia, and thrombocytopenia were significantly higher in the Low GNRI group. TTF in the High GNRI group was significantly longer than that in the Low GNRI group (p=0.045). Multivariate analysis showed that the factors influencing the duration of treatment were PS (≥2) at the start of treatment, serum albumin level, and GNRI. CONCLUSION: In patients undergoing R-CHOP therapy, GNRI <92 at regimen initiation increased the risks of developing FN and hematologic toxicity. Multivariate analysis revealed that performance status, albumin levels, and GNRI at regimen initiation were the factors influencing treatment duration. Nutritional status at treatment initiation may influence the development of hematologic toxicity and TTF.

Impact of Unexpected In-House Major COVID-19 Outbreaks on Depressive Symptoms among Healthcare Workers: A Retrospective Multi-Institutional Study.

The coronavirus disease 2019 (COVID-19) has significantly affected the mental health of healthcare workers (HCWs). The authors have provided psychosocial support to HCWs working in typical hospitals and nursing homes in Fukushima Prefecture, Japan, where major COVID-19 outbreaks have occurred since December 2020. This study retrospectively examines depressive symptoms before psychosocial interventions among HCWs working at typical hospitals and nursing homes experiencing in-house major COVID-19 outbreaks. We have offered psychosocial support in eight hospitals and nursing homes, obtaining data on the mental health status of 558 HCWs using the Patient Health Questionnaire-9. The study's results indicate that 29.4% of HCWs have exhibited moderate or higher depressive symptoms, and 10.2% had suicidal ideation. Multiple logistic regression analysis showed that being a nurse was associated with higher depressive symptoms and suicidal ideation compared to other HCWs. In addition, multiple logistic regression analysis of Polymerase Chain Reaction-positive HCWs showed that being a nurse and the number of COVID-19-related symptoms was associated with high depressive symptoms. These results suggest that HCWs in typical hospitals and nursing homes experiencing major COVID-19 outbreaks are more likely to exhibit severe depressive symptoms, which may worsen if infected with COVID-19. This study's findings expand the current understanding of HCWs' depressive symptoms and the importance of psychosocial support during unexpected major outbreaks in healthcare facilities.

Effect of Different Approaches to Antimicrobial Therapy with Cefmetazole and Meropenem on the Time to Defervescence in Non-Severe Extended-Spectrum ß-Lactamase-Producing Escherichia coli Bacteremia.

Carbapenems are antimicrobial agents commonly used to treat extended-spectrum ß-lactamase (ESBL)-producing bacteria. Although cefmetazole (CMZ) is considered effective for ESBL-producing Escherichia coli (ESBL-EC) bacteremia, previous studies showed its limitations, including the influence of the initial antimicrobial agent. Here, we examined the effects of different approaches to antimicrobial therapy with CMZ and meropenem (MEPM) on the time to defervescence in ESBL-EC bacteremia. Notably, the influence of previous antimicrobial agents was excluded. Inpatients with ESBL-EC detected in blood cultures between April 2018 and March 2023 were included and assigned to CMZ (n = 14), MEPM (n = 8), de-escalation to CMZ (dCMZ; n = 9), or escalation to MEPM (eMEPM; n = 11) groups. The median time to defervescence was 3.5, 1.0, 2.0, and 4.0 days in the CMZ, MEPM, dCMZ, and eMEPM groups, respectively, with no significant differences. Cox proportional hazards analysis showed a significant difference in the hazard ratio (95% confidence interval) of 0.378 (0.145-0.984) for the time to defervescence with CMZ versus MEPM (p = 0.046). The extent of a delayed time to defervescence is greater with early CMZ administration than with MEPM administration in patients with non-severe ESBL-EC bacteremia.

A case report involving suppressed nuclear receptor transcription factors 4a1 and Stevens-Johnson syndrome induced by a single dose of pembrolizumab and successfully treated with early steroid administration, resulting in complete remission of stage III lung cancer.

BACKGROUND: Immunotherapy with immune checkpoint inhibitors is associated with immune-related adverse events (irAEs). A positive correlation between treatment efficacy and irAEs has been reported. Clinical indicators are required for appropriate interventions, such as steroid administration, to prevent fatal outcomes. Nuclear receptor transcription factor 4a (Nr4a), which is involved in T-cell anergy, exhaustion, and regulatory T cells, were observed not only in thymocytes but in peripheral blood mononuclear cells. We describe a case of Stevens-Johnson syndrome (SJS) that was induced by a single dose of pembrolizumab and successfully treated with steroids, leading to complete remission of lung cancer during the monitoring of immune response indices, including Nr4a1 mRNA. CASE PRESENTATION: A 68-year-old male with squamous cell lung cancer (cT2aN3M0, stage IIIb) received a single dose of pembrolizumab (200 mg). On Day 21 of treatment, SJS appeared, and the patient was treated with prednisolone 60 mg/day, which was gradually tapered off. After the disappearance of the SJS symptoms, complete remission of cancer was achieved and was maintained for more than 1 year. Acute increases in the plasma IFN-γ and IL-17 concentrations and a decrease in IL-10 concentrations were observed at the onset of SJS. Simple regression analysis showed that these changes in IL-17, IFN-γ and IL-10 were significantly influenced by the decreased expression of Nr4a1 mRNA. The pembrolizumab levels and prednisolone doses significantly influenced the suppression of Nr4a1 mRNA levels. Although Nr4a1 mRNA levels in the current case fluctuated during the observation period, they were significantly lower than those in a nonresponding progressive-disease case, as well as a pembrolizumab-responding case with non-SJS but similar background. The suppression of Nr4a1 in current case, might result in upregulation of cytotoxic T cells and a reduction in functional regulatory T cells, promoting favorable antitumor immunity. CONCLUSION: The immune responses involving Nr4a1 suppression might relate to complete remission of lung cancer in this case, despite causing SJS, which may be attributed to synergistic effects from pembrolizumab treatment and intervention with steroids. The current case indicates the preliminarily clinical benefit of evaluating Nr4a expression-related indices as the possible clinical covariates and may serve as a milestone for appropriate future chemotherapy interventions.

Long-Term, Community-based Approach for Affected People Having Problems With Mental Health and Lifestyle Issues After the 2011 Fukushima Disaster: the Fukushima Health Management Survey.

A Mental Health and Lifestyle Survey (MHLS) has been conducted yearly as part of the Fukushima Health Management Survey since 2012, in order to monitor different health issues related to long-term evacuation of affected people after the 2011 Fukushima disaster. This survey is a mail-based one of nearly 210,000 affected people living in the evacuation zone at the time of the disaster. Another purpose of the MHLS is to provide efficient interventions by telephone based on the results of the survey. Significant findings contributing to understanding of non-radiological health effects caused by long-term evacuation were obtained from the MHLS, directly connecting to telephone-based interventions for over 3,000 respondents per year. In this article, the mental health outcomes of the MHLS, including depressive symptoms and posttraumatic responses, are reviewed, and the usefulness of telephone-based interventions is discussed. The evidence showed that, despite improvement of core mental health outcomes, the prevalence of respondents at high risk of some psychiatric problems remained high compared to that among the general population in Japan. In particular, several mental health consequences of respondents staying outside of Fukushima Prefecture were higher than those staying inside Fukushima. Along with further efforts to increase the response rate, we need to continue and modify the MHLS to meet the requirements of the affected people and communities.