Upregulated Genes in Atrial Fibrillation Blood and the Left Atrium.

INTRODUCTION: Atrial fibrillation (AF) is a common arrhythmia associated with aging. Many known risk factors are associated with AF, but many senior individuals do not develop AF despite having multiple risk factors. This finding suggests that other factors may be involved in AF onset. This study aimed to identify upregulated genes in the peripheral blood and left atrium of patients with AF. These genes may serve as potential biomarkers to predict AF onset risk and its complications. METHODS: Gene expression data was analyzed from blood (n = 3) and left atrial samples (n = 15) of patients with AF and sinus rhythm. We evaluated the significant genes identified using p-value analysis of weighted average difference to confirm their rankings. We created figures for the genes using GeneMANIA and performed a functional analysis using Cytoscape3.10.1. Hub and bottleneck genes were identified based on degree and betweenness centrality. We used RefEx to confirm the organs in which the extracted genes were expressed. Heatmaps and Gene ontology term evaluation were performed to further elucidate the biological functions of the genes. RESULTS: We identified 12 upregulated genes (CAST, ASAH1, MAFB, VCAN, DDIT4, FTL, HEXB, PROS1, BNIP3L, PABPC1, YBX3, and S100A6) in both the blood and left atrium of patients with AF. We analyzed the gene functions using GeneMANIA and Cytoscape. The identified genes were involved in a variety of pathways, including lysosomal function and lipid and sphingolipid catabolism. Next, we investigated whether the 12 identified genes identified were systemically expressed or had high organ specificity. Finally, Reference expression (RefEx) was used to analyze the gene expression levels in various tissues. Four genes; FTL, ASAH1, S100A6, and PABPC1, were highly expressed in the normal heart tissue. Finally, we evaluated the expression levels of the 12 genes in the blood of patients with AF using a heatmap. Our findings suggest that the 12 genes identified in this study, especially the lysosome-related genes (FTL and ASAH1), may be involved in AF pathogenesis. CONCLUSION: Lysosome-related genes may be important to understand the AF pathophysiology and to develop AF-related future studies.

High signal intensity of the intraaneurysmal sac on T1 CUBE imaging as a predictor of aneurysm stability after coil embolization.

OBJECTIVE: Histopathological studies of aneurysms after coil embolization showed that thrombus formation during the first month after endovascular treatment (EVT) played an important role in the healing process. The authors hypothesized that dedicated T1-weighted imaging may be used to predict stable aneurysms by visualizing the thrombus status within coil-treated aneurysms. Therefore, this study investigated the relationship between the signal intensity (SI) of the intraaneurysmal sac after coil embolization and aneurysm stability. METHODS: The study population included 82 patients with 86 aneurysms who underwent T1-weighted 3D black-blood fast spin-echo (T1 CUBE) imaging within 1 month after coil embolization between 2019 and 2022. The relative SI of a coil-treated aneurysm (RSIcoiled) was calculated as follows: the mean SI of the intraaneurysmal sac/the mean SI of the genu of the corpus callosum. Aneurysms with enlarged remnants on MR angiography (MRA) within 6 months after EVT were defined as recurrence, while a decrease of intraaneurysmal flow on MRA was defined as improved embolization status. Stable aneurysms were defined as improvement or no change in embolization status 6 months after coil embolization. The volume embolization ratio (VER) was calculated as the ratio of the packed coil volume to the aneurysm volume. Differences between stable and recurrent aneurysms were examined. All aneurysms were divided into high and low RSIcoiled groups based on the cutoff value of RSIcoiled, and differences between the two groups were also evaluated. RESULTS: Recurrence was confirmed for 26 of 86 aneurysms. A univariable analysis showed that small aneurysms, high VER, and high RSIcoiled were associated with aneurysm stability. In the receiver operating characteristic curve analysis, the optimal cutoff value for RSIcoiled to differentiate stable from recurrent aneurysms was 0.54. The cutoff value for RSIcoiled was selected as 0.50 (sensitivity 0.77, specificity 0.70) because it was half the value of the SI of the corpus callosum and close to the optimal cutoff value. In a multivariable analysis, RSIcoiled > 0.50 (OR 8.1, 95% CI 2.5-27) remained a significant factor for aneurysm stability. The high RSIcoiled group showed a higher rate of an improved embolization status (26% vs 6.1%, p = 0.022) and stable aneurysms (85% vs 15%, p = 0.0002). CONCLUSIONS: RSIcoiled was associated with postcoiling aneurysm stability. High RSIcoiled might imply intraaneurysmal thrombus formation associated with the healing process of coil-treated aneurysms.

Comparison of dental plaque flora between intellectually disabled patients and healthy individuals: a cross-sectional study.

Periodontal diseases, including gingivitis, are highly prevalent in individuals with intellectual disability (ID). In particular, gingivitis can be difficult to cure owing to the lack of patient cooperation. Here, we evaluated differences in the oral bacterial flora between individuals with ID (n = 16) and healthy controls (n = 14) to facilitate the development of strategies for the prevention of periodontal disease in people with ID. Our results showed no significant difference in the number of decayed, missing, and filled teeth between the two groups. However, there were significant differences in the median papillary-marginal-attached index, plaque index, and gingival index between groups (P < 0.0001). Additionally, the mean probing depth in the ID group was significantly higher than that in the control group (P < 0.0001). The diversity of oral flora in people with ID and concurrent gingivitis was significantly lower than that of healthy individuals without periodontal disease. The relative abundances of Tannerella spp. and Treponema spp. were significantly higher in the ID group than in the control group at the genus level (P = 0.0383 and 0.0432, respectively), whereas that of Porphyromonas spp. was significantly lower in the ID group (P < 0.0001). Overall, our findings provided important insights into differences in the oral microbiota between patients with ID and healthy controls.

Flow volume mismatch dramatically affects transient neurologic symptoms after direct bypass in Moyamoya disease.

Transient neurological events (TNEs) occur after bypass surgery in Moyamoya disease (MMD); however, their pathology remains unknown. To elucidate the pathophysiology of TNEs, we investigated their relationship with perioperative superficial temporal artery (STA) blood flow volume, which was evaluated using ultrasonography. Forty-nine patients with MMD, who underwent direct bypass surgery, were included and stratified into TNE and non-TNE groups, respectively. The STA blood flow volume was evaluated at four time points (preoperatively and 2-4, 7, and 10-14 days postoperatively), and a change in volume during the postoperative period was defined as a flow volume mismatch. We investigated the association between ultrasonographic findings of flow volume mismatch and TNEs and magnetic resonance imaging findings, such as the cortical hyperintensity belt (CHB) sign, using univariate and path analyses. The STA blood flow volume increased immediately postoperatively, gradually decreasing over time, in both groups. The TNE group showed a significant increase in blood flow volume 2-4 days postoperatively (P = 0.042). Flow volume mismatch was significantly larger in the TNE group than in the non-TNE group (P = 0.020). In the path analysis, STA flow volume mismatch showed a positive association with the CHB sign (P = 0.023) and TNEs (P = 0.000). Additionally, the CHB sign partially mediated the association between STA flow volume mismatch and TNEs. These results suggest that significantly high STA blood flow volume changes occurring during the acute postoperative period after direct bypass surgery in MMD are correlated with TNEs and the CHB sign, suggesting involvement in the pathophysiology of TNEs.

Impact of skeletal muscle volume on patients with BCLC stage-B hepatocellular carcinoma undergoing sorafenib therapy.

AIM: Skeletal muscle volume has been reported to be an important factor that determines overall survival (OS) and post-progression survival (PPS) in patients with hepatocellular carcinoma (HCC). However, the impact of skeletal muscle volume on HCC with Barcelona Clinic Liver Cancer (BCLC) stage B (BCLC-B) remains unclear. We conducted sub-analyses of a previous study on BCLC-B and compared our findings with data on HCC with BCLC stage C (BCLC-C). METHODS: We retrospectively enrolled 356 patients with HCC (BCLC-B, n = 78; and BCLC-C, n = 278) undergoing sorafenib therapy. Prognostic factors were analyzed using various parameters, including skeletal muscle volume. Muscle volume (MV) depletion was designated as less than the median value of the skeletal muscle index for each gender (cutoff value: 45.0 cm2 /m2 for male and 38.0 cm2 /m2 for female participants). RESULTS: Both OS and PPS showed no significant differences in patients with non-MV depletion and those with MV depletion in the BCLC-B group (Median OS [MST] 19.3 vs. 13.5 months [p = 0.348]; median PPS 9.7 vs. 10.8 months [p = 0.578]). In the BCLC-C group, patients with non-MV depletion had a significantly longer OS and PPS compared to patients with MV depletion (MST 12.4 vs. 9.0 months [p = 0.001] and median PPS 7.9 vs. 5.4 months [p = 0.002]). Multivariate analysis revealed that MV depletion was an independent prognostic factor of OS and PPS in the BCLC-C group but not in the BCLC-B group. CONCLUSIONS: Skeletal muscle volume showed little impact on the clinical outcomes of patients with BCLC-B undergoing sorafenib therapy.

A novel rat model for longitudinal electrophysiological evaluation after cold-induced brain injury.

OBJECTIVE: Cerebral contusion models of cold-induced injury are widely used in animal studies. However, owing to the difficulty of longitudinal recording of electrical stimulation transcranial motor evoked potential (tcMEP) in brain injury models of incomplete paralysis, to the authors' knowledge there have been no multimodal evaluations of cold-induced brain injury models that have included motor function and electrophysiological and histological evaluations. Therefore, in this study the authors aimed to perform a multimodal evaluation of a rat model of brain injury. METHODS: A brain injury model in female rats and a tcMEP recording technique based on the authors' previous study were established to enable multifaceted analysis, including longitudinal electrophysiological evaluation. RESULTS: The model showed incomplete paralysis of the right forelimb. Motor function showed recovery over time, and histological evaluation showed tissue changes associated with cerebral contusion. In addition, stable tcMEP waveforms were recorded before and after surgery and up to 4 weeks after injury. The tcMEP amplitude decreased significantly after injury and recovered over time. Furthermore, the amplitudes at 1, 7, and 14 days after injury were significantly lower than those at preinjury (p < 0.0006, p < 0.0007, and p < 0.0067, respectively). CONCLUSIONS: In the present study, the authors established a novel cold-induced brain injury rat model and technique that allowed for the evaluation of longitudinal tcMEP recording and demonstrated that multimodal evaluation for brain injury can be performed. This model can potentially be applied in future investigations of various therapies for brain injury.

Headache characteristics to screen for cervicocerebral artery dissection in patients with acute onset unusual headache.

OBJECTIVES: The aim of this preplanned primary analysis was to investigate the clinical manifestations of headache to screen for CAD patients with acute onset headache only. BACKGROUND: Spontaneous cervicocerebral artery dissection (CAD) with acute onset headache is not rare in clinical practice; however, it is underdiagnosed. On the other hand, subsequent infarction or subarachnoid hemorrhage mainly occurs within 1 week of headache onset. METHODS: Between April 2017 and January 2022, we conducted a single-center, cross-sectional retrospective study on 197 consecutive referred patients from neurosurgical outpatient clinics with acute onset unusual headache (stronger or longer headache than usual). All patients underwent magnetic resonance imaging to screen for secondary headache and were diagnosed based on the diagnostic protocol. We examined patient background data and the following headache characteristics: distribution, condition at the onset of headache, accompanying vomiting or nausea, worsening headache, and analgesic effects against headache. These factors were analyzed to identify independent diagnostic predictors of CAD. In this study, the rate of missing data was 41% for improvement of headache by analgesia and multiple imputation by chained equations was performed. RESULTS: A total of 93 patients (46 men and 47 women; mean age: 48 years, range: 25-73 years) were diagnosed with CAD. Univariate logistic regression analysis showed CAD was associated with current smoking, systolic blood pressure >140 mmHg, unilateral headache, worsening headache, and no headache improvement by analgesia. Unilateral, worsening headache and no headache improvement by analgesia remained independent diagnostic predictors in multivariable logistic regression after multiple imputation. No headache improvement by analgesia had the highest sensitivity (86%), while worsening headache had the highest specificity (84%). CONCLUSIONS: CAD needs to be considered in patients with unilateral, worsening headache and no headache improvement by analgesia.

Effect of Lacticaseibacillus rhamnosus L8020 on the abundance of periodontal pathogens in individuals with intellectual disability: a randomized clinical trial.

OBJECTIVES: Gingivitis refers to inflammation of the gingiva and its connective tissues. Research has revealed a higher prevalence of gingivitis in individuals with intellectual disability than in healthy individuals. Milk fermented with Lacticaseibacillus rhamnosus L8020 (L8020 yogurt) inhibits the accumulation of periodontal disease-related pathogens in vitro and alleviates the symptoms of periodontal disease. The aim of this study was to investigate the influence of L8020 yogurt on oral microbiota and the abundance of four periodontal pathogens (Tannerella forsythia, Porphyromonas gingivalis, Prevotella intermedia, and Treponema denticola) and on the microbiota in individuals with intellectual disability and gingivitis. METHOD AND MATERIALS: Forty-one outpatients with intellectual disability participated in this study. To examine the effects of daily consumption of L8020 yogurt, the patients were randomly divided into L8020 (test group, n = 21) and placebo (n = 20) yogurt groups. All patients consumed 80 g of yogurt for 12 weeks. Oral examination was performed before the first intake of yogurt and dental plaque was collected before and after the intake of yogurt. DNA was extracted from dental plaque and subjected to next-generation sequencing. RESULTS: The relative abundance of T forsythia was significantly lower in the test group than in the placebo group. Additionally, the relative abundance of the four pathogens reduced after 84 days of consuming L8020 yogurt compared with that after consuming placebo yogurt. CONCLUSION: Mixing L rhamnosus L8020 with probiotic products that are consumed daily would be effective in suppressing the increase in periodontal disease-causing bacteria and beneficial for individuals with intellectual disability.

Bioelectrical impedance analysis in patients with breast cancer-related lymphedema before and after lymphaticovenular anastomosis.

OBJECTIVE: Bioelectrical impedance analysis (BIA) as a measure of lymphedema has been gaining popularity because of its measurement simplicity and noninvasiveness. This study was performed to investigate the effectiveness of BIA for assessment of the outcomes of lymphaticovenular anastomosis (LVA) in patients with breast cancer-related lymphedema. METHODS: This study involved 25 patients with unilateral breast cancer-related lymphedema who underwent LVA. Segmental multifrequency BIA and conventional circumferential volume measurement were performed preoperatively and 6 months postoperatively from June 2018 to June 2021 at Hiroshima University Hospital International Center for Lymphedema. The patients' clinicopathological data, operative details, and preoperative and postoperative BIA results were investigated. RESULTS: Segmental multifrequency BIA and circumferential volume measurement were strongly correlated in the lymphedema-affected upper limb both before and after LVA. The interlimb volume, interlimb extracellular water ratio (r = 0.784; P < .001), and interlimb extracellular water/total body water ratio were positively correlated (r = 0.612; P < .01), whereas the phase angle was negatively associated (r = -0.556; P < .01). CONCLUSIONS: Segmental multifrequency BIA can be a useful tool for assessing the severity of lymphedema and monitoring the outcomes of LVA.

Evaluation of Inappropriate Positioning of Dosimeters in Medical Workers Based on Dose Equivalent Hp(10).

ABSTRACT: This report presents a new method to characterize the inappropriate positioning of dosimeters based on the dose equivalent Hp(10). The Hp(10) values of medical workers were measured monthly for 12 mo using two personal dosimeters. Using the ratio between the values of Hp(10) recorded from dosimeters worn over and under protective aprons [Hp(10) over and Hp(10) under , respectively], 670 pairs of dosimeter readings were categorized into a proper use group [Hp(10) over /Hp(10) under ≥ 5] and a misuse group [Hp(10) over /Hp(10) under < 5]. Following personal interviews, the readings in the misuse group were classified into the following six subgroups: "reversed," "sometimes reversed," "both under," "both over," "without apron," and "not specified." Ultimately, the scatter plot of "Hp(10) over - Hp(10) under " vs. Hp(10) over was identified as the most promising tool for clarifying the misuse patterns of dosimeters, as individual readings were mapped to the locations of the corresponding subgroups in the obtained graphs. Our results are expected to facilitate efficient and accurate usage of dosimeters by medical workers.

Differential diagnosis of infectious diseases, drug-induced lung injury, and pulmonary infiltration due to underlying malignancy in patients with hematological malignancy using HRCT.

PURPOSE: To differentiate among infectious diseases, drug-induced lung injury (DILI) and pulmonary infiltration due to underlying malignancy (PIUM) based on high-resolution computed tomographic (HRCT) findings from patients with hematological malignancies who underwent chemotherapy or hematopoietic stem cell transplantation. MATERIALS AND METHODS: A total of 221 immunocompromised patients with hematological malignancies who had proven chest complications (141 patients with infectious diseases, 24 with DILI and 56 with PIUM) were included. Two chest radiologists evaluated the HRCT findings, including ground-glass opacity, consolidation, nodules, and thickening of bronchovascular bundles (BVBs) and interlobular septa (ILS). After comparing these CT findings among the three groups using the χ2test, multiple logistic regression analyses (infectious vs noninfectious diseases, DILI vs non-DILI, and PIUM vs non-PIUM) were performed to detect useful indicators for differentiation. RESULTS: Significant differences were detected in many HRCT findings by the χ2 test. The results from the multiple logistic regression analyses identified several indicators: nodules without a perilymphatic distribution [p = 0.012, odds ratio (95% confidence interval): 4.464 (1.355-11.904)], nodules with a tree-in-bud pattern [p = 0.011, 8.364 (1.637-42.741)], and the absence of ILS thickening[p = 0.003, 3.621 (1.565-8.381)] for infectious diseases, the presence of ILS thickening [p = 0.001, 7.166 (2.343-21.915)] for DILI, and nodules with a perilymphatic distribution [p = 0.011, 4.256 (1.397-12.961)] and lymph node enlargement (p = 0.008, 3.420 (1.385-8.441)] for PIUM. CONCLUSION: ILS thickening, nodules with a perilymphatic distribution, tree-in-bud pattern, and lymph node enlargement could be useful indicators for differentiating among infectious diseases, DILI, and PIUM in patients with hematological malignancies.

Adoptive immunotherapy with natural killer cells from peripheral blood CD34+ stem cells to prevent hepatocellular carcinoma recurrence after curative hepatectomy: a study protocol for an open-label, single-arm phase I study.

INTRODUCTION: Hepatocellular carcinoma (HCC) remains a major clinical problem as more than half of these cases recur after radical resection. Natural killer (NK) cells are at the forefront of the innate immune system and attack microcarcinomas and circulating tumour cells. The objective of this study was to evaluate the feasibility and toxicity of peripheral blood CD34+ stem cell-derived NK cell infusion after radical hepatectomy for HCC. METHODS AND ANALYSIS: This is an open-label, single-arm, single-centre phase I study. Patients who have undergone initial hepatectomy for HCC with three or more risk factors for recurrence (≥10 ng/mL of Alpha fetoprotein (AFP), ≥360 mAU/mL of PIVKA-II, multiple tumours and ≥3 peripheral blood circulating tumour cells) will be enrolled and be treated with three peripheral blood CD34+ stem cell-derived NK cell infusions every 3 months. The primary endpoint will be safety assessment including the type and severity of adverse events, frequency of occurrence and duration of occurrence. The secondary endpoints will include survival, effect of immune response and clinical laboratory test results. ETHICS AND DISSEMINATION: Ethical approval of the trial was obtained from the Certified Committee for Regenerative Medicine Hiroshima University in Japan. The trial results will be shared with the scientific community at international conferences and by publication in a peer-reviewed journal. TRIAL REGISTRATION NUMBER: jRCTb060200020.

Diagnostic accuracy of MR vessel wall imaging at 2 weeks to predict morphological healing of vertebral artery dissection.

OBJECTIVES: The spontaneous healing of non-hemorrhagic intracranial vertebral artery dissection (VAD) may be associated with the stabilization of intramural hematoma (IMH). We previously suggested that the signal intensity of IMH increases until approximately 2 weeks in VAD with spontaneous healing. We herein investigated the diagnostic accuracy of the signal intensity of IMH at 2 weeks to predict the spontaneous healing of VAD. METHODS: From April 2017 to April 2021, we prospectively investigated patients with non-hemorrhagic VAD who underwent vessel wall imaging (VWI). Morphological healing of VAD was evaluated by MR angiography three months after its onset. The relative signal intensity (RSI) of IMH against the posterior cervical muscle on VWI was calculated. Univariate and multivariate analyses were performed on factors associated with the spontaneous healing of VAD among patient baseline data, vascular morphology at the diagnosis, and RSI parameters. RESULTS: Forty-eight patients (23 men and 25 women; mean age: 51 years, range: 34-73 years) with 50 non-hemorrhagic VAD were included in the present study. Spontaneous healing was observed in 28 VAD (56%). RSI two weeks after the onset of VAD (RSI2w) and morphological feature such as the string sign were associated with spontaneous healing, respectively. The multivariate logistic regression analysis identified RSI2w as an independent predictive factor of spontaneous healing (OR: 7.3; 95% CI, 1.9-28, p = 0.004). The cut-off value for RSI2w to predict spontaneous healing was 1.22 (AUC = 0.90, sensitivity: 91%, specificity: 82%). CONCLUSION: RSI2w predicted the spontaneous healing of non-hemorrhagic VAD 3 months after its onset.

Effectiveness of a Virtual Program on Nurses' Pain-Related Knowledge and Pain-Measurement Skills.

BACKGROUND: Aim: To test whether a comprehensive virtual program for using pain scales to manage neonatal pain improved nurses' knowledge and skill acquisition. METHODS: This non-blind randomized controlled trial included 64 participants who were randomly divided into intervention and control groups; changes in scores between pre- and posttests were compared. Certified neonatal intensive care nurses were recruited from across Japan. The learning intervention group received online training in pain measurement using structured scales, such as the Face Scale for Pain Assessment of Preterm Infants and the Japanese version of the Premature Infant Pain Profile. The control group received no training. Independent t tests and χ2 tests were used to compare the baseline scores. The outcome measure was score change on a 40-point test (20 for knowledge and 20 for skill) before and after the e-learning program. RESULTS: No differences in baseline data were found between the groups. Generalized linear regression models yielded a significant difference in the least squared means (95% confidence interval [CI]) for the amount of change in the total, knowledge, and skill scores between groups: 6.22 (4.18, 8.26; p < .001) for total score, 4.66 (3.37, 5.95; p < .001) for knowledge score, and 1.53 (0.06, 3.00; p = .041) for skill score. CONCLUSIONS: The results showed that the e-learning program improved nurses' neonatal pain knowledge and pain-measurement skills compared with no training.

Acene Size-Dependent Transition of The Radical Centers From the Metal to The Acene Parts In Monocationic Dinuclear (Diethynylacene)diyl Complexes.

Controlling radical localization/delocalization is important for functional materials. The present paper describes synthesis and results of electrochemical, spectroscopic, and theoretical studies of diruthenium (p-diethynylacene)diyl complexes, Me3 Si-(C≡C)2 -Ru(dppe)2 -C≡C-Ar-C≡C-Ru(dppe)2 -(C≡C)2 -SiMe3 (1-6) (dppe: 1,2-bis(diphenylphosphino)ethane), and their monocationic radical species ([1]+ -[6]+ ). The HOMO-LUMO energy gaps can be finely tuned by the acene rings in the bridging ligands installed, as indicated by the absorption maxima of the electronic spectra of 1-6 ranging from the UV region even to the NIR region. The cationic species [1]+ -[6]+ show two characteristic NIR bands, which are ascribed to the charge resonance (CR) and π-π* transition bands, as revealed by spectroelectrochemistry. Expansion of the acene rings in [1]+ -[6]+ causes (1) blue shifts of the CR bands and red shifts of the π-π* transition bands and (2) charge localization on the acene parts as evidenced by the ESR, DFT and TD-DFT analyses. Notably, the monocationic complexes of the larger acene derivatives are characterized as the non-classical acene-localized radicals.

Prognosis following an extended duration of adjuvant gemcitabine plus S-1 chemotherapy in patients with pancreatic ductal adenocarcinoma: Analysis using inverse probability of treatment weighting.

BACKGROUND/PURPOSE: The aim of this study was to assess whether the duration of adjuvant gemcitabine plus S-1 (GS) chemotherapy has any effect on survival in patients with pancreatic ductal adenocarcinoma (PDAC). METHODS: Of the 290 patients who received adjuvant GS chemotherapy, 100 (34%) received the standard duration (20-29 weeks) and 190 (66%) received an extended duration (≥30 weeks). To reduce selection bias, the prognostic impact (recurrence-free survival [RFS] and overall survival [OS]) based on the duration of adjuvant GS chemotherapy was analyzed using inverse probability of treatment weighting (IPTW). Moreover, to reduce immortal time bias, time-dependent multivariate analyses in which implementation of adjuvant GS chemotherapy was treated as time-varying covariate was also performed. RESULTS: Extended duration of adjuvant GS chemotherapy was significantly correlated with prolonged RFS (P < .001) and OS (P < .001) after IPTW adjustment. Time-dependent multivariate analyses revealed that extended duration of adjuvant GS chemotherapy was an independent prognostic factor for prolonged RFS (hazard ratio [HR], 0.58, P = .002) and OS (HR, 0.56, P = .005). CONCLUSION: Extended duration (≥30 weeks) of adjuvant GS chemotherapy in patients with PDAC was associated with an improved prognosis. These findings warrant a further prospective trial on PDAC to investigate the survival benefit of extended adjuvant chemotherapy.

Phase 2 study of first-line pembrolizumab monotherapy in elderly patients with non-small-cell lung cancer expressing high PD-L1.

BACKGROUND: Pembrolizumab is the recommended first-line therapy for patients with advanced non-small-cell lung cancer (NSCLC) and a programmed death ligand-1 (PD-L1) tumor proportion score (TPS) of ≥50% without driver mutations. However, its efficacy and safety for patients ≥75 years have not been prospectively investigated; this was the aim of this study. METHODS: This multicenter and open-label single-arm phase II study was conducted at 12 institutions. Chemotherapy-naïve patients with advanced NSCLC and a PD-L1 TPS of ≥50% without EGFR mutations or translocation of the ALK received pembrolizumab every 3 weeks. The primary endpoint was progression-free survival (PFS) with a threshold of 4.3 months. The secondary endpoints were overall survival (OS), objective response rate (ORR), disease control rate (DCR), safety, and quality of life. RESULTS: Twenty-six patients were enrolled between October 2017 and March 2020. The median PFS was 9.6 (95% confidence interval [CI] 2.1-20.6) months. The lower limit of the 95% CI did not exceed the target. The median OS was 21.6 months. The ORR and DCR were 41.7% and 70.8%, respectively. The proportion of patients with grade ≥3 treatment-related adverse events was 15.4%. The quality of life score did not change significantly during treatment. CONCLUSION: While this study showed that pembrolizumab was a tolerable treatment for elderly patients, the safety requires further confirmation in a larger study. Although the primary endpoint, the median PFS (9.6 months), was slightly shorter than that (10.3 months) of the previous phase III study (KEYNOTE-024 study), the median PFS did not achieve the expected value.

High-resolution CT findings of pulmonary infections in patients with hematologic malignancy: comparison between patients with or without hematopoietic stem cell transplantation.

PURPOSE: To evaluate the high-resolution CT (HRCT) findings of pulmonary infections in patients with hematologic malignancy and compare them between patients with or without hematopoietic stem cell transplantation (HSCT). MATERIALS AND METHODS: A total of 128 patients with hematologic malignancy and pulmonary infection were included in this study. The diagnoses of the patients consisted of bacterial pneumonia (37 non-HSCT cases and 14 HSCT cases), pneumocystis pneumonia (PCP) (29 non-HSCT cases and 11 HSCT cases), and fungal infection other than PCP (20 non-HSCT cases and 17 HSCT cases). Two chest radiologists retrospectively evaluated the HRCT criteria and compared them using chi-squared tests and a multiple logistic regression analysis. RESULTS: According to the multiple logistic regression analysis, nodules were an indicator in HSCT patients with PCP (p = 0.025; odds ratio, 5.8; 95% confidence interval, 1.2-26.6). The centrilobular distribution of nodules was the most frequent (n = 4, 36%) in HSCT patients with PCP. A mosaic pattern was an indicator of PCP in both HSCT and non-HSCT patients. There were no significant differences in other infections. CONCLUSION: The mosaic pattern could be an indicator of PCP in both HSCT and non-HSCT patients. Nodules with centrilobular distribution might be relatively frequent HRCT findings of PCP in HSCT patients.