Effectiveness of genetic feedback on alcohol metabolism to reduce alcohol consumption in young adults: an open-label randomized controlled trial.

BACKGROUND: It is unclear whether brief interventions using the combined classification of alcohol-metabolizing enzymes aldehyde dehydrogenase 2 (ALDH2) and alcohol dehydrogenase 1B (ADH1B) together with behavioral changes in alcohol use can reduce excessive alcohol consumption. This study aimed to examine the effects of a brief intervention based on the screening of ALDH2 and ADH1B gene polymorphisms on alcohol consumption in Japanese young adults. METHODS: In this open-label randomized controlled trial, we enrolled adults aged 20-30 years who had excessive drinking behavior (average amount of alcohol consumed: men, ≥ 4 drinks/per day and women, ≥ 2 drinks/per day; 1 drink = 10 g of pure alcohol equivalent). Participants were randomized into intervention or control group using a simple random number table. The intervention group underwent saliva-based genotyping of alcohol-metabolizing enzymes (ALDH2 and ADH1B), which were classified into five types. A 30-min in-person or online educational counseling was conducted approximately 1 month later based on genotyping test results and their own drinking records. The control group received traditional alcohol education. Average daily alcohol consumption was calculated based on the drinking diary, which was recorded at baseline and at 3 and 6 months of follow-up. The primary endpoint was average daily alcohol consumption, and the secondary endpoints were the alcohol-use disorder identification test for consumption (AUDIT-C) score and behavioral modification stages assessed using a transtheoretical model. RESULTS: Participants were allocated to the intervention (n = 100) and control (n = 96) groups using simple randomization. Overall, 28 (29.2%) participants in the control group and 21 (21.0%) in the intervention group did not complete the follow-up. Average alcohol consumption decreased significantly from baseline to 3 and 6 months in the intervention group but not in the control group. The reduction from baseline alcohol consumption values and AUDIT-C score at 3 months were greater in the intervention group than in the control group (p < 0.001). In addition, the behavioral modification stages were significantly changed by the intervention (p < 0.001). CONCLUSIONS: Genetic testing for alcohol-metabolizing enzymes and health guidance on type-specific excessive drinking may be useful for reducing sustained average alcohol consumption associated with behavioral modification. TRIAL REGISTRATION: R000050379, UMIN000044148, Registered on June 1, 2021.

Gender differences in changes in alcohol consumption achieved by free provision of non-alcoholic beverages: a secondary analysis of a randomized controlled trial.

BACKGROUND: We recently demonstrated that a 12-week intervention consisting of the provision of free non-alcoholic beverages reduced alcohol consumption in excessive drinkers for 8 weeks after the intervention. However, gender differences in this effect were not explored. Thus, this secondary analysis investigated gender differences in the influence of non-alcoholic beverage provision on alcohol consumption. METHODS: Individuals who frequently drank excessively (at least 40 g/day in men and 20 g/day in women) and who were not diagnosed with alcoholism were recruited. Participants were randomized into the intervention or control group by simple randomization using a random number table. In the intervention group, free non-alcoholic beverages were provided once every 4 weeks for 12 weeks (three times in total). The consumption of alcoholic and non-alcoholic beverages was calculated based on a drinking diary submitted with the previous 4 weeks' of data. In this study, we compared the longitudinal changes in alcohol consumption between genders in both groups. RESULTS: The provision of non-alcoholic beverages significantly reduced alcohol consumption in both genders; however, significant differences in alcohol consumption between the control and intervention groups were observed only in men. The average alcohol consumption during the intervention fell below the level associated with a high risk of non-communicable diseases in men (32.7 g/day), but not in women (24.8 g/day). Correlation coefficient analysis showed that replacing alcoholic beverages with the provided non-alcoholic beverages resulted in different drinking patterns according to gender. The percent changes in the consumption of alcoholic and non-alcoholic beverages relative to baseline levels did not differ between genders. CONCLUSIONS: Our results suggest that the provision of non-alcoholic beverages reduced alcohol consumption irrespective of gender. Of note, providing non-alcoholic beverages might be particularly useful for reducing high-risk alcohol consumption in male excessive drinkers. TRIAL REGISTRATION: UMIN UMIN000047949. Registered 4 June 2022.

Effect of provision of non-alcoholic beverages on alcohol consumption: a randomized controlled study.

BACKGROUND: The use of alcohol-flavored beverages not containing alcohol (hereinafter referred to as non-alcoholic beverages) is recommended to reduce alcohol consumption. However, it is unclear if this reduces excessive drinking. OBJECTIVE: To verify whether non-alcoholic beverages impact the alcohol consumption of excessive drinkers. STUDY DESIGN: Single-center, open-label, randomized, parallel-group study. METHODS: Participants aged 20 years or older who were not diagnosed with alcoholism, who drank at least four times a week, and whose alcohol consumption on those days was at least 40 g in males and 20 g in females, were recruited. Participants were randomized into the intervention or control group by simple randomization using a random number table. In the intervention group, free non-alcoholic beverages were provided once every 4 weeks for 12 weeks (three times in total), and thereafter, the number of alcoholic and non-alcoholic beverages consumed were recorded for up to 20 weeks. The consumption of alcoholic and non-alcoholic beverages was calculated based on a drinking diary submitted with the previous 4 weeks of data. The primary endpoint was the change from baseline in total alcohol consumption during past 4 weeks at week 12. The participants were not blinded to group allocations. RESULTS: Fifty-four participants (43.9%) were allocated to the intervention group and 69 (56.1%) to the control group. None of the participants in the intervention group dropped out, compared to two (1.6%) in the control group. The change in alcohol consumption was - 320.8 g (standard deviation [SD], 283.6) in the intervention group and - 76.9 g (SD, 272.6) in the control group at Week 12, indicating a significant difference (p < 0.001). Even at Week 20 (8 weeks after the completion of the intervention), the change was - 276.9 g (SD, 39.1) in the intervention group, which was significantly greater than - 126.1 g (SD, 41.3) in the control group (p < 0.001). The Spearman rank correlation coefficient between the change in non-alcoholic beverage consumption and alcohol consumption at Week 12 was significantly negative only in the intervention group (ρ = - 0.500, p < 0.001). There were no reports of adverse events during the study. CONCLUSIONS: Providing non-alcoholic beverages significantly reduced alcohol consumption, an effect that persisted for 8 weeks after the intervention. TRIAL REGISTRATION: UMIN UMIN000047949. Registered 4 June 2022.

Classification and regression tree for estimating predictive markers to detect T790M mutations after acquired resistance to first line EGFR-TKI: HOPE-002.

BACKGROUND AND OBJECTIVE: Osimertinib as first-line treatment for patients with non-small cell lung cancer (NSCLC) harboring epidermal growth factor (EGFR) mutations remains controversial. Sequential EGFR-tyrosine kinase inhibitor (TKI) might be superior to the first line osimertinib in patients at risk of developing acquired T790M mutations. METHODS: We enrolled consecutive patients with EGFR-mutated (deletion 19 or L858R) advanced NSCLC treated with first-line drugs and evaluated predictive markers using classification and regression tree (CART) for the detection of T790M mutations based on patient backgrounds prior to initial treatment. RESULTS: Patients without acquired T790M mutations had worse outcomes than those with T790M mutations (median OS: 798 days vs. not reached; HR: 2.70; P < 0.001). CART identified three distinct groups based on variables associated with acquired T790M mutations (age, CYF, WBC, liver metastasis, and LDH; AUROC: 0.77). Based on certain variables, CART identified three distinct groups in deletion 19 (albumin, LDH, bone metastasis, pleural effusion, and WBC; AUROC: 0.81) and two distinct groups in L858R (age, CEA, and ALP; AUROC: 0.80). The T790M detection frequencies after TKI resistance of afatinib and first-generation EGFR-TKIs were similar (35.3% vs. 37.4%, P = 0.933). Afatinib demonstrated longer PFS (398 vs. 279 days; HR: 0.67; P = 0.004) and OS (1053 vs. 956 days; HR: 0.68; P = 0.051) than first-generation EGFR-TKIs. CONCLUSION: Identification of patients at risk of acquiring T790M mutations after EGFR-TKI failure may aid in choice of first-line EGFR-TKI. Furthermore, afatinib may be the more effective 1st-line EGFR-TKI treatment for patients at risk of developing T790M as initial EGFR-TKI resistance.

COVID-19 infection control education for medical students undergoing clinical clerkship: a mixed-method approach.

BACKGROUND: Coronavirus disease (COVID-19) has induced an urgent need to train medical students not only in infection prevention control but also in the treatment of infectious diseases, including COVID-19. This study evaluates the impact of simulated clinical practice with peer role-plays and a lecture on clinical education for COVID-19. METHODS: The sample for the study included 82 fourth- and fifth-year medical students undergoing clinical clerkship in respiratory medicine. They answered questionnaires and participated in semi-structured focus group interviews (FGIs) regarding the advantages of simulated clinical practice with peer role-plays and lectures on clinical education for COVID-19. RESULTS: A total of 75 students participated in the COVID-19 education program between January and November 2021. The responses to the questionnaire revealed that the satisfaction level of students with COVID-19 education was high. No significant change was found among students concerning fear of COVID-19 before and after the program. The degree of burden of handling information on COVID-19 reduced significantly, while the degree with respect to the use of personal protective equipment (PPE), including appropriate wearing and removing of PPE, and care of patients with confirmed COVID-19 while taking steps to prevent infection, exhibited a decreasing trend. Nine FGIs were conducted (n = 74). The advantages of simulated clinical practice were segregated into five categories (infection prevention control, educational methods, burden on healthcare providers, self-reflection, and fear of COVID-19); and that of the lecture were segregated into four categories (information literacy, knowledge of COVID-19, educational methods, and self-reflection). CONCLUSIONS: Simulated clinical practice with peer role-plays and the lecture pertaining to COVID-19 can prove to be efficient and safe methods for learning about COVID-19 infection and prevention control for medical students. They can reduce the burden of COVID-19 patients' care. Moreover, they can also provide an opportunity for self-reflection, realize the burden of medical care, and acquire relevant information.

Risk factors for skeletal-related events in non-small cell lung cancer patients treated with bone-modifying agents.

PURPOSE: The risk factors for skeletal-related events (SREs) among non-small cell lung cancer (NSCLC) patients during treatment with bone-modifying agents (BMAs) are not yet well-understood. METHODS: The medical records of 238 consecutive NSCLC patients treated with BMAs, including zoledronic acid and denosumab, at the Chiba University Hospital from 2012 to 2016 were reviewed in the present study. SREs were defined as either pathologic fractures, spinal cord compression, the need for bone irradiation or surgery, or hypercalcemia. The risk factors for earlier occurrence of the first SRE from the time of the first bone metastasis diagnosis after the initiation of BMA treatment were identified. RESULTS: Of the 238 included patients, 92% (n = 220) had a performance status (PS) of 0-2 at diagnosis of bone metastasis. Forty-eight (20%) patients developed at least one SRE. The most common first SRE was the need for bone irradiation surgery (n = 27, 56%). Significant risk factors included poor PS (hazard ratio [HR]: 4.36; p = .024), male sex (HR: 2.17; p = .022), and the use of zoledronic acid (HR: 1.91; p = .032). The overall survival (OS) from the first bone metastasis diagnosis was 394 days (95% confidence interval [CI]: 331-465). The OS of patients with PS 3 and 4 at the diagnosis of bone metastasis (median: 36 days; 95% CI: 13-50) was significantly (p < 0.0001) shorter than that of patients with PS 0-2 (median: 411 days; 95% CI: 354-558) (HR: 4.53; 95% CI: 2.62-7.35). CONCLUSIONS: Careful observation is needed for patients with the identified risk factors, which include poor PS and male sex, despite the BMA treatment.

Optimal Cutoff Values of the Alcohol Use Disorders Identification Test and its Short Version for Detecting Excessive Alcohol Use in Japanese College Students.

Alcohol use disorder is a serious health problem in college students. Alcohol Use Disorders Identification Test (AUDIT) is a 10-item screening tool to assess alcohol consumption, drinking behaviors, and alcohol-related problems. AUDIT-C is a short version of AUDIT, consisting of consumption items 1-3. However, the optimal cutoff values of AUDIT and AUDIT-C for detecting excessive drinking are not available for Japanese college students. The aim of this study was to evaluate the validity of cutoff points of AUDIT and AUDIT-C for detecting moderate drinking, heavy drinking and binge drinking among Japanese college students. The cross-sectional study was based on an anonymous, self-administered questionnaire. In January 2017, we sampled college students and graduate students aged 20 years or older during annual health examinations at Mie University in Japan. Two thousand students underwent health examinations, and the eligible subjects were 1,600, including 152 (9.5%) moderate drinkers, 58 (3.6%) heavy drinkers and 666 (41.6%) binge drinkers. ROC (receiver operating characteristic) curve analysis showed that the optimal cutoff values for moderate drinking, heavy drinking and binge drinking were 5, 8 and 5 for men and 4, 7 and 4 for women in AUDIT; and 4, 7 and 4 for men and 4, 7 and 4 for women in AUDIT-C, respectively. Moderate drinking is considered unsafe drinking. Therefore, the optimal cutoff values for moderate drinking (5 for men and 4 for women in AUDIT and 4 for both sexes in AUDIT-C) are important parameters for prevention of alcohol use disorder in Japanese college students.

Alternative approaches for clinical clerkship during the COVID-19 pandemic: online simulated clinical practice for inpatients and outpatients-A mixed method.

BACKGROUND: The COVID-19 pandemic has created a need for educational materials and methods that can replace clinical clerkships (CCs) for online simulated clinical practice (online-sCP). This study evaluates the impact of using simulated electronic health records (sEHR) for inpatients, and electronic problem-based learning (e-PBL) and online virtual medical interviews (online-VMI) for outpatients, for an online-sCP using a learning management system (LMS) and online meeting system facilitated by a supervising physician. METHODS: The sEHR was reviewed by medical students and subsequently discussed with a supervising physician using an online meeting system. In the e-PBL, medical students reviewed the simulated patients and discussed on the LMS. For the online-VMI, a faculty member acted as an outpatient and a student acted as the doctor. Small groups of students discussed the clinical reasoning process using the online meeting system. A mixed-method design was implemented. Medical students self-assessed their clinical competence before and after the online-sCP. They answered questionnaires and participated in semi-structured focus group interviews (FGIs) regarding the advantages and disadvantages of the practice. RESULTS: Forty-three students completed the online-sCP during May and June 2020. All students indicated significant improvement in all aspects of self-evaluation of clinical performance after the online-sCP. Students using sEHR reported significant improvement in writing daily medical records and medical summaries. Students using e-PBL and online-VMI reported significant improvement in medical interviews and counseling. Students also indicated CCs as more useful for learning associated with medical interviews, physical examinations, and humanistic qualities like professionalism than the online-sCP. Eight FGIs were conducted (n = 42). The advantages of online-sCP were segregated into five categories (learning environment, efficiency, accessibility, self-paced learning, and interactivity); meanwhile, the disadvantages of online-sCP were classified into seven categories (clinical practice experience, learning environment, interactivity, motivation, memory retention, accessibility, and extraneous cognitive load). CONCLUSIONS: Online-sCP with sEHR, e-PBL, and online-VMI could be useful in learning some of the clinical skills acquired through CC. These methods can be implemented with limited preparation and resources.

The Use of All-You-Can-Drink System, Nomihodai, Is Associated with the Increased Alcohol Consumption among College Students: A Cross-Sectional Study in Japan.

Excessive drinking by college students is a major public health problem in Japan. However, data on heavy episodic drinking (HED) and nomihodai, a several-hour all-you-can-drink system, are scarce. We surveyed the drinking behavior of undergraduate and graduate students at 35 colleges, and examined the association between HED and use of nomihodai. The study used a cross-sectional design conducted by a self-administered questionnaire. From December 2016 to March 2017, we sampled undergraduate and graduate students aged 20 or older at 35 colleges in the Kanto area, including Tokyo. The following items were measured: 1) frequency of drinking; 2) frequency of binge drinking in the past year; 3) nomihodai use; 4) the number of drinks consumed when using or not using nomihodai; and 5) sex and age for demographic data. Paired t-test was used to compare means between use and non-use state of nomihodai. The Fisher's exact test was used to evaluate the significance of the distribution difference between the two types of states. A total of 511 subjects completed the questionnaire, including 274 men and 237 women. The amount of drinking was increased 1.8-fold (85.9 ± 49.7 g vs. 48.2 ± 29.5 g) among men and 1.7-fold (63.7 ± 39.3 g vs. 36.5 ± 26.7 g) among women during nomihodai use, comapred with non-use states. Among them, 109 (39.8%) men and 71 (30.3%) women reported HED only at nomihodai states. These data suggest that the use of nomihodai system may lead to excessive drinking among college students.

Reasons for Drinking among College Students in Japan: A Cross-Sectional Study.

Binge drinking by college students is a problematic behavior. However, data on binge drinking and the reasons for drinking by college students in Japan are scarce. We explored the reasons for drinking among college students. The study used a cross-sectional design and a self-administered questionnaire. From December 2016 to March 2017, we sampled undergraduate and graduate students aged 20 or older at 35 colleges in the Kanto region of Japan. The questionnaire addressed 1) frequency of drinking alcohol, 2) amount of drinking per day, 3) frequency of binge drinking in the past year, and 4) reasons for drinking (with 12 possible responses). The t-test was used to compare the means between binge drinkers and non-binge drinkers. Logistic regression analysis was conducted on binge drinking and the reasons for drinking. The participants included 303 men and 260 women. Significant differences between men and women included the presence of binge drinking (men: 74.9%; women: 59.6%). Among male students, the statistically significant reasons given for binge drinking were "to feel happy or be in a good mood" and "to relieve stress," whereas among female students, the reasons were "to feel happy or be in a good mood," "to facilitate interpersonal relationships," "to forget something bad," and "to relieve stress." The reasons for drinking associated with binge drinking were identified. It is important to incorporate these results into preventive education about binge drinking aimed at college students in Japan.

Association between Excessive Alcohol Use and Alcohol-Related Injuries in College Students: A Multi-Center Cross-Sectional Study in Japan.

Alcohol-related injuries in college students are a major public health problem worldwide. We clarified the association between excessive drinking and alcohol-related injuries in Japanese college students. This was a cross-sectional study with a self-administered questionnaire. From January to March 2013, we sampled all college students and graduate students aged 20 years or older during annual health examinations at three colleges in Mie Prefecture in Japan. The questionnaire assessed the frequency of alcohol drinking, amount of alcohol consumed per day, binge drinking during the past year, alcohol-related injuries during the past year, and demographic data. Logistic regression analysis was conducted on the association between excessive alcohol use and alcohol-related injuries. A total of 2,842 students underwent health examinations, of whom 2,177 (76.6%) completed the questionnaire. Subjects included 1,219 men (56.0%) and 958 women (44.0%). Eighty-eight men (7.2%) and 93 women (9.7%) were classified as excessive weekly drinkers, while 693 men (56.8%) and 458 women (47.8%) were determined to be binge drinkers. Eighty-one men (6.6%) and 26 women (2.7%) had experienced alcohol-related injuries during the past year. In the logistic regression analysis, binge drinkers (odds ratio 25.6 [8.05-81.4]) and excessive weekly drinkers (odds ratio 3.83 [2.41-6.09]) had a history of significantly more alcohol-related injuries, even after adjusting for age and sex. In conclusion, alcohol-related injuries in college students in Japan were strongly associated with excessive drinking. As a strategy for preventing such injuries in this population, an interventional study is required to identify effective methods for reducing excessive alcohol use.

Calcium pyrophosphate crystal arthritis associated with immune checkpoint inhibitor successfully treated with intra-articular glucocorticoid: A case report.

Immune checkpoint inhibitors (ICIs) sometimes induce immune-related adverse events (irAEs), and arthritis is one of the irAE symptoms. Recently, crystal-induced arthritis, such as calcium pyrophosphate (CPP) crystal deposition disease and gout, has been reported to occur after ICI administration. However, the distinction between ICI-associated crystal arthritis and ICI-induced non-crystal arthritis is difficult because their symptoms are similar. Besides, optimal treatment for ICI-associated crystal arthritis has not been established. Here, we report a patient who developed CPP crystal arthritis twice after pembrolizumab (ICI) administration and was successfully treated with intra-articular glucocorticoid injection. He suffered arthritis and acute interstitial nephritis simultaneously after ICI administration. Musculoskeletal ultrasound of his affected joint suggests that his arthritis was crystal-induced arthritis, and arthrocentesis detected CPP crystal in synovial fluid. Thus, we diagnosed his arthritis as ICI-associated cystal arthritis. Therefore, our case encourages the use of musculoskeletal ultrasound in patients with arthritis after treatment with ICI because it may distinguish between ICI-associated crystal arthritis and ICI-induced non-crystal arthritis. Besides, ICI-associated crystal arthritis could be treatable by intra-articular glucocorticoid injection.

Effect of a workplace-based learning program on clerkship students' behaviors and attitudes toward evidence-based medicine practice.

In clinical clerkship (CC), medical students can practice evidence-based medicine (EBM) with their assigned patients. Although CC can be a valuable opportunity for EBM education, the impact of EBM training, including long-term behavioral changes, remains unclear. One hundred and nine fourth- and fifth-year medical students undergoing CC at a medical school in Japan attended a workplace-based learning program for EBM during CC (WB-EBM), which included the practice of the five steps of EBM. The program's effect on the students' attitudes toward EBM in CC was assessed through questionnaires. A total of 88 medical students participated in the program. Responses to the questionnaire indicated high satisfaction with the WB-EBM program. The most common theme in students' clinical problems with their assigned patients was the choice of treatment, followed by its effect. Based on the responses in the post-survey for the long-term effects of the program, the frequency of problem formulation and article reading tended to increase in the 'within six months' group comprising 18 students who participated in the WB-EBM program, compared with the control group comprising 34 students who did not. Additionally, the ability to self-assess problem formulation was significantly higher, compared with the control group. However, among 52 students who participated in the WB-EBM program more than six months later, EBM-related behavioral habits in CC and self-assessments of the five steps of EBM were not significantly different from those in the control group. The WB-EBM program was acceptable for medical students in CC. It motivated them to formulate clinical questions and enhanced their critical thinking. Moreover, the WB-EBM program can improve habits and self-evaluations about EBM. However, as its effects may not last more than six months, it may need to be repeated across departments throughout CC to change behavior in EBM practice.

Immunotherapy or Chemoimmunotherapy in Older Adults With Advanced Non-Small Cell Lung Cancer.

Importance: Immune checkpoint inhibitor (ICI) plus chemotherapy combination treatment (ICI-chemotherapy) is now a standard treatment for non-small cell lung cancer (NSCLC) without targetable oncogene alterations, but there are few data on ICI-chemotherapy for patients 75 years and older. Objective: To inform the choice of first-line drugs in clinical practice and assess the safety and efficacy of ICI-chemotherapy combination treatment in older adult patients with previously untreated advanced NSCLC. Design, Setting, and Participants: This retrospective cohort study included 58 centers in Japan. The cohort consisted of patients 75 years and older with clinical stage IIIB, IIIC, IV, postoperative or radiotherapy recurrent NSCLC. Patients started first-line systemic therapy between December 2018 and March 2021. Those receiving first-line molecular targeted drugs were excluded. The data were analyzed from February 2022 to October 2022. Exposures: Systemic therapy. Main Outcomes and Measures: The main outcomes were overall survival (OS), progression-free survival (PFS), and safety. Results: A total of 1245 patients (median [range] age, 78 [75-95] years; 967 [78%] male) with NSCLC were included in the cohort. Programmed death ligand-1 (PD-L1) expression of less than 1% occurred in 268 tumors (22%); 1% to 49% in 387 tumors (31%); 50% and higher in 410 tumors (33%), and unknown expression in 180 tumors (14%). Median OS was 20.0 (95% CI, 17.1-23.6) months for the 354 patients receiving ICI-chemotherapy (28%); 19.8 (95% CI, 16.5-23.8) months for the 425 patients receiving ICI alone (34%); 12.8 (95% CI, 10.7-15.6) months for the 311 patients receiving platinum-doublet chemotherapy (25%); and 9.5 (95% CI, 7.4-13.4) months for the 155 patients receiving single-agent chemotherapy (12%). After propensity score matching, no differences in OS and PFS were found between the patients receiving ICI-chemotherapy vs ICI alone. Each group consisted of 118 patients. For PD-L1 expression of 1% and higher the OS hazard ratio (HR) was 0.98 (95% CI, 0.67-1.42; P = .90), and the PFS HR was 0.92 (95% CI, 0.67-1.25; P = .59). Significance was also not reached when separately analyzed for lower or higher PD-L1 expression (1%-49% or ≥50%). However, grade 3 or higher immune-related adverse events occurred in 86 patients (24.3%) treated with ICI-chemotherapy and 76 (17.9%) with ICI alone (P = .03). Conclusions and Relevance: In this study, ICI-chemotherapy combination treatment did not improve survival and increased the incidence of grade 3 and higher immune-related adverse events compared with ICI alone in patients 75 years and older. Based on these results, ICI alone may be recommended for older adult patients with PD-L1-positive NSCLC.

Diagnostic imaging of intrathoracic extramedullary haematopoiesis.

Although intrathoracic extramedullary haematopoiesis (EMH) is rare, its nodular lesions should be differentiated from malignancy. 111In-bone marrow scintigraphy can be useful for the non-invasive diagnosis of intrathoracic EMH because extramedullary accumulation of 111In can be determined as EMH.

Novel anti-reflux biliary metal stent with a distal tapered end for distal malignant biliary obstruction: a feasibility study.

Background and study aims We developed a self-expandable metallic stent (SEMS) with a distal tapered end to reproduce the physiological bile flow with a pressure gradient due to the difference in the diameter. We aimed to evaluate the safety and efficacy of the newly developed distal tapered covered metal stent (TMS) for distal malignant biliary obstruction (DMBO). Patients and methods This single-center, prospective, single-arm study was conducted in patients with DMBO. The primary endpoint was time to recurrent biliary obstruction (TRBO), and the secondary endpoints were the survival time and incidence of adverse events (AEs). Results Thirty-five patients (15 men, 20 women; median age, 81 years [range: 53-92]) were enrolled between December 2017 and December 2019. The primary diseases were pancreatic head cancer in 25 cases, bile duct cancer in eight cases, and ampullary cancer in two cases. TMS was successfully placed in all cases. Acute cholecystitis occurred as an early AE (within 30 days) in two cases (5.7 %). The median TRBO was 503 days, median survival time was 239 days. RBO was observed in 10 cases (28.6 %), and the causes were distal migration in six cases, proximal migration in two cases, biliary sludge in one case, and tumor overgrowth in one case. Conclusions Endoscopic placement of the newly developed TMS in patients with DMBO is technically feasible and safe, and the TRBO was remarkably long. The anti-reflux mechanism based on the difference in diameter may be effective, and a randomized controlled trial with a conventional SEMS is required.

Outcomes of Chemoimmunotherapy Among Patients With Extensive-Stage Small Cell Lung Cancer According to Potential Clinical Trial Eligibility.

Importance: Chemoimmunotherapy is the standard first-line therapy for patients with extensive-stage small cell lung cancer (ES-SCLC). However, whether findings from pivotal trials can be extrapolated to the clinical practice setting remains unclear. Objective: To compare treatment outcome gaps following first-line chemoimmunotherapy for patients with ES-SCLC between those who met and did not meet the eligibility criteria used in previous clinical trials. Design, Setting, and Participants: A prospective cohort study was conducted from September 1, 2019, to September 30, 2020, at 32 hospitals in Japan, with at least 12 months of follow-up. Participants included consecutive patients with ES-SCLC who received carboplatin and etoposide with atezolizumab as first-line therapy. Exposures: Patients who met eligibility criteria for pivotal phase 3 clinical trials were considered trial-eligible. Main Outcomes and Measures: The primary outcome was 6-month progression-free survival. The secondary outcomes were differences in progression-free survival, overall survival, and safety according to whether key clinical trial eligibility criteria were met. Results: A total of 207 patients were analyzed (median age, 72 years; range, 46-87 years; 170 [82%] were male). Sixty-four patients (31%) were older adults (age ≥75 years), and most (184 [89%]) had an Eastern Cooperative Oncology Group performance status of 0 or 1. There were 132 (64%) trial-eligible patients. The 6-month progression-free survival rate for all patients was 38.8% (95% CI, 32.4%-45.7%). The median progression-free survival was 5.1 months in trial-eligible patients and 4.7 months in trial-ineligible patients (hazard ratio, 0.72; 95% CI, 0.53-0.97; P = .03). The proportion of patients who achieved disease control was 93% (118 of 127) in trial-eligible patients and 77% (55 of 71) in trial-ineligible patients (P = .002). The median overall survival was 15.8 months in trial-eligible patients and 13.1 months in trial-ineligible patients (hazard ratio, 0.73; 95% CI, 0.51-1.07; P = .10). The rate of severe adverse events was numerically higher among trial-ineligible patients than among trial-eligible patients (39% vs 27%; P = .07). Conclusions and Relevance: In this cohort study, the overall treatment outcome was comparable to that reported in pivotal clinical trials. However, treatment outcomes after chemoimmunotherapy might differ between trial-eligible and trial-ineligible patients. These findings suggest that trial-eligibility criteria may be useful in clinical practice, and further studies using data from clinical practice settings are required to inform regulatory approval and clinical decision-making.

Osimertinib as first-line treatment for elderly patients with advanced EGFR mutation-positive non-small cell lung cancer in a real-world setting (OSI-FACT-EP).

OBJECTIVES: Osimertinib is the primary treatment for patients with epidermal growth factor receptor (EGFR) mutation-positive advanced non-small cell lung cancer. However, evidence of the outcomes of osimertinib treatment in patients over 75 years of age in the real-world setting is limited. MATERIALS AND METHODS: This retrospective study analyzed the data of 538 patients (203 elderly and 335 non-elderly) with EGFR mutation-positive lung cancer in whom osimertinib was initiated as first-line treatment between August 2018 and December 2019. Patients over 75 years of age were classified as elderly. The data cut-off date was February 28, 2022. RESULTS: The progression-free survival (PFS) did not significantly differ between the elderly and non-elderly groups [elderly group: median PFS, 16.9 months (95 % confidence interval (CI), 14.3-20.2); non-elderly group: median PFS, 22.1 months (95 % CI: 19.5-26.3); hazard ratio (HR) for the elderly against the non-elderly: 1.21 (95 % CI: 0.98-1.50), p = 0.079]. However, the time to treatment failure (TTF) was significantly shorter in the elderly than in the non-elderly [elderly group: median TTF, 14.0 months (95 % CI: 0.98-1.50); non-elderly group: median TTF, 21.8 months (95 % CI: 18.2-24.6); HR for the elderly against the non-elderly: 1.46 (95 % CI: 1.20-1.77), p < 0.001]. Furthermore, the rate of treatment discontinuation because of adverse events was 28.6 % in the elderly and 14.9 % in the non-elderly (p < 0.001). Among patients who discontinued treatment, the conversion rate to second-line treatment was 39.6 % in the elderly and 72.8 % in the non-elderly. In addition, the median overall survival was 30 months (95 % CI: 25.8-37.7) in the elderly and not reached (NR) (95 % CI: NR-NR) in the non-elderly (p < 0.001). CONCLUSION: In a real-world clinical setting, elderly patients receiving osimertinib as first-line treatment should be aware of the frequent inability to transition to second-line treatment due to adverse events.

Histologic transformation in lung cancer: when one door shuts, another opens.

Histologic transformation (HT) is a major cause of drug resistance to therapy in patients with lung cancer. HTs to small-cell lung cancer (SCLC) have been reported frequently in patients with epidermal growth factor receptor (EGFR)-mutated lung cancer. Although HTs have an impact on the clinical outcomes in patients owing to a high refractoriness to treatments, there is limited data on the prevalence, causes, mechanisms, treatment efficacy, and future treatment strategies. In this review, we assess the literature regarding HTs comprehensively, including those describing EGFR-tyrosine kinase inhibitors, other molecular targeted drugs, and immune checkpoint inhibitors. Furthermore, we discuss the mechanisms of HTs and the lineage plasticity to SCLC and squamous cell carcinoma in lung cancer. In addition, we summarize the treatment efficacy and future perspectives of HTs in patients with lung cancer, and propose better management strategies for this group of patients.