Kobe City Medical Center General Research Articles

Risk stratification and prognosis prediction using cardiac biomarkers in COVID-19: a single-centre retrospective cohort study

ObjectiveThere is a need for a robust tool to stratify the patient’s risk with COVID-19. We assessed the prognostic values of cardiac biomarkers for COVID-19 patients.MethodsThis is a single-centre retrospective...

Correlation Between Dosimetric Parameters and Local Control in Definitive Radiotherapy for Head and Neck Cancers.

Radiotherapy (RT) outcomes are generally reported based on stage, patient background, and concomitant chemotherapy. This study aimed to investigate the effects of the prescribed dose to gross tumor volume (GTV) and the calculation algorithm on local control in definitive RT for head and neck (H&N) cancers using follow-up images after RT. This study included 154 patients with H&N cancers treated by Volumetric Modulated Arc Therapy at the Kobe City Medical Center General Hospital. Patients were classified into those receiving definitive RT (70 Gy of irradiation) and those not receiving it. Follow-up images were used to categorize the patients into the responders and non-responders groups. In the non-responders group, follow-up images were imported into the treatment planning system, and the contours of the residual or recurrent areas (local failure) were extracted and fused with computed tomography-simulated images for treatment planning. Dose evaluation parameters included maximum dose, dose administered to 1% of the volume, dose administered to 50% of the volume, dose administered to 99% of the volume (D99%), and minimum dose (Dmin) administered to the GTV. The doses to the GTV were compared between responders and non-responders. D99% exhibited significant differences between local failure and responders and between local failure and non-responders. Dmin showed significant differences between responders and non-responders and between responders and local failure. This study emphasizes the importance of verifying dose distribution in all slices of treatment planning, highlighting the need for precise assessment of the dose to the GTV in head and neck cancers.

Safety and blood levels of daratumumab after switching from intravenous to subcutaneous administration in patients with multiple myeloma.

The intravenous administration (IV) of daratumumab sometimes causes an infusion reaction and needs a long infusion time. Recently, a subcutaneous formulation (SC) of daratumumab, which has fewer infusion reactions and shorter administration time, was approved. However, because SC has a fixed dose, overdosing is a concern for patients with low body weights. In this study, we investigated the safety and blood levels of daratumumab after switching from IV to SC in patients with multiple myeloma (MM). Patients who switched from IV to SC of daratumumab between June 2021 and May 2022 at Kobe City Medical Center General Hospital were included in the study. Blood daratumumab levels were measured using liquid chromatography-tandem mass spectrometry. Safety after switching from IV to SC was evaluated for six months and graded according to the Common Terminology Criteria for Adverse Events, version 5.0. The median body weight of ten patients included in the analysis was 57.4kg (range: 45.0-74.4). Blood daratumumab levels were significantly increased after switching to SC (p = 0.002); median through concentration at the last IV dose was 403.6μg/mL (range: 96.3-776.3) and that at the third SC dose was 557.1μg/mL (range: 288.3-997.2). Grade 1-2 injection site reactions were observed in six patients (60.0%) after switching to SC. A new grade 3 adverse event was observed in only one patient (neutropenia). The blood levels of daratumumab were significantly increased after switching from IV to SC in patients with MM; however, the dosage was tolerable.

Reliability of the respiratory rate and oxygenation index for successful high-flow nasal cannula support in coronavirus disease pneumonia: a retrospective cohort study

BackgroundHigh-flow nasal cannula (HFNC) therapy is an important non-invasive respiratory support in acute respiratory failure, including coronavirus disease (COVID-19) pneumonia. Although the respiratory rate and oxygenation (ROX) index is a simple and useful predictor for HFNC failure and mortality, there is limited evidence for its use in patients with COVID-19 pneumonia. We aimed to evaluate the ROX index as a predictor for HFNC failure in patients with COVID-19 pneumonia. We also evaluated the ROX index as a predictor for 28-day mortality.MethodsIn this single-center, retrospective, cohort study, 248 patients older than 18 years of age with COVID-19 pneumonia received HFNC therapy for acute respiratory failure. The ROX index was evaluated within 4 h from the start of HFNC therapy. Past medical history, laboratory data, and the ROX index were evaluated as predictors for HFNC failure and 28-day mortality.ResultsThe ROX index < 4.88 showed a significantly high risk ratio for HFNC failure (2.13 [95% confidence interval [CI]: 1.47 – 3.08], p < 0.001). The ROX index < 4.88 was significantly associated with 28-day mortality (p = 0.049) in patients with COVID-19 pneumonia receiving HFNC therapy. Age, chronic hypertension, high lactate dehydrogenase level, and low ROX index showed significantly high risk ratio for HFNC failure. C-reactive protein level and low ROX index were predictors of 28-day morality.ConclusionThe ROX index is a useful predictor for HFNC success and 28-day mortality in patients with COVID-19 pneumonia receiving HFNC therapy.Trial registrationAn independent ethics committee approved the study (Research Ethics Review Committee of Kobe City Medical Center General Hospital [number: zn220303; date: February 21, 2022]), which was performed in accordance with the Declaration of Helsinki, Guidelines for Good Clinical Practice.

Pharmacist-Urologist Collaborative Management for Patients with Renal Cell Carcinoma Receiving Pazopanib Monotherapy.

Pazopanib is one of recommended treatment for metastatic renal cell carcinoma (RCC). Despite its effectiveness, patients often difficult to continue pazopanib treatment due to adverse events (AEs). We established an ambulatory care pharmacy practice that enables pharmacist-urologist collaboration to manage patients with RCC. This study evaluated the usefulness of this collaborative management. We retrospectively reviewed the medical records of 51 consecutive patients with metastatic RCC receiving pazopanib at the Kobe City Medical Center General Hospital between April 2014 and December 2020. Our collaborative management was implemented in October 2016. The time to pazopanib discontinuation was compared between patients who started pazopanib before (n = 30) and after (n = 21) the implementation of the collaborative management. A multivariate Cox regression analysis was performed to analyze the factors associated with pazopanib discontinuation. In the collaborative management, the oncology pharmacists had a total of 245 face-to-face patient consultations, and provided 286 suggestions [according to supportive care in pazopanib treatment (214 suggestions) were most frequent], and 236 (82.5%) were accepted by urologists. The median time to discontinuation (6.1 months vs. 2.4 months, p = 0.024) was significantly longer in the after group. Multivariate analysis showed that collaborative management (hazard ratio (HR) 0.49, 95% confidence interval (CI) 0.26-0.88, p = 0.017), and Eastern Cooperative Oncology Group performance status (ECOG PS) ≥2 at pazopanib initiation (HR 3.87, 95% CI 1.47-9.13, p = 0.008) were significantly associated with pazopanib discontinuation. These results suggested that, compared to conventional management, collaborative management is effective at prolonging the time to pazopanib discontinuation.

Postoperative nausea and vomiting after artificial joint replacement surgery: comparison between remimazolam and sevoflurane, a propensity score analysis.

Remimazolam, a newly synthesized ultrashort-acting benzodiazepine, has not been previously compared with sevoflurane with regard to postoperative nausea and vomiting (PONV). The aim of this study is to investigate the incidence of PONV between remimazolam and sevoflurane among patients undergoing artificial joint replacement surgery. We conducted a retrospective analysis of the electronic medical records of patients who underwent artificial joint replacement surgery at Kobe City Medical Center General Hospital from 2020 to 2022, with a focus on comparing the incidence of PONV among those who received sevoflurane versus remimazolam anesthesia. To control for confounding factors, we employed a propensity score-matching technique to pair patients who received sevoflurane anesthesia with those who received remimazolam anesthesia. The records of 292 patients receiving general anesthesia for artificial joint replacement surgery were collected and categorized into group sevoflurane (n = 241) or group remimazolam (n = 51). Before propensity score matching, age and ASA-PS exhibited significant differences between two groups. There was no significant difference in the incidence of PONV between them (p = 0.461). After matching, there were 51 patients in each group. However, there is no significant difference in the incidence of PONV between the two matched cohorts (p = 0.243). This study demonstrated that there was no difference in the prevalence of PONV between remimazolam and sevoflurane anesthesia in patients undergoing artificial joint replacement surgery.

Hypocomplementemic Urticarial Vasculitis Syndrome

From the Department of General Internal Medicine, Kobe City Medical Center General Hospital, Kobe City, Hyogo, Japan. The authors declare no conflict of interest. Informed consent was obtained from the patient. This work did not receive any specific grants from funding agencies in the public, commercial, or not-for-profit sectors. Author contributions: D.U. collected the data and wrote the first draft of the manuscript. D.U. and H.N. reviewed the literature. H.N. supervised the manuscript writing, editing, and review. Correspondence: Hiroaki Nishioka, MD, PhD, Department of General Internal Medicine, Kobe City Medical Center General Hospital, 2-1-1 Minami-Machi, Minatojima, Chuo-ku, Kobe, Hyogo, 650-0047, Japan. E-mail: [email protected].

Pharmacokinetic Study of Antiviral Drugs in Patients with COVID-19

The Faculty of Pharmaceutical Sciences, Kobe Gakuin University has collaborated in clinical research with Kobe City Medical Center General Hospital. In this university-medical institution collaboration, university faculty members discuss clinical problems with on-site pharmacists and doctors, and carry out clinical research to resolve these problems. During the coronavirus disease 2019 (COVID-19) pandemic, many patients with COVID-19 were treated at Kobe City Medical Center General Hospital. In February 2020, during the first increase in the number of patients with COVID-19 in Japan, treatment for COVID-19 was not established, and some existing anti-viral drugs, such as favipiravir, were experimentally used for COVID-19 treatment. However, since these drugs were not developed specifically for treating COVID-19, their pharmacokinetics have not been sufficiently studied. In particular, the pharmacokinetics of favipiravir in critically ill patients with COVID-19 was of concern, because critically ill patients have an urgent need for life-saving anti-viral drug treatment. Therefore, we conducted a collaborative clinical study to evaluate the pharmacokinetics of favipiravir in patients with COVID-19. The blood concentration of favipiravir in patients with COVID-19 at Kobe City Medical Center General Hospital was measured by lipid chromatography-tandem mass spectrometry at Kobe Gakuin University. Population pharmacokinetics analysis was then performed. In this symposium review, we introduce our pharmacokinetic study of antiviral drugs in patients with COVID-19, focusing on the university-medical institution collaboration. We believe collaborative clinical research will be useful for solving clinical issues and ensuring the effectiveness and safety of pharmacotherapies.

Effects of Low-Dose Tolvaptan for Fluid Management After Cardiovascular Surgery.

Background: Perioperative management of body fluid levels after cardiovascular surgery with cardiopulmonary bypass is essential. Fluid management using tolvaptan with conventional diuretics is effective in maintaining urine output without worsening renal function. This study aimed to improve the in-out balance in the early perioperative phase using low-dose tolvaptan (3.75 mg/day). Methods and Results: This prospective, single-center, randomized, open-label study included 199 patients who underwent cardiovascular surgery with cardiopulmonary bypass in Kobe City Medical Center General Hospital between September 2018 and December 2020. Treatment with tolvaptan and loop diuretics (tolvaptan group; 99 patients) was compared with treatment with loop diuretics alone (control group; 100 patients) to evaluate achievement of preoperative body weight as the primary outcome. Secondary outcomes were urine volume, the incidence of worsening renal function (WRF), and postoperative paroxysmal atrial fibrillation (POAF). There was no significant difference between groups in the return to preoperative body weight on postoperative Day 6. The tolvaptan group had significantly increased urine volume (2,530 vs. 2,150 mL/day) and decreased total furosemide dose (24 vs. 32 mg) compared with the control group. No significant differences were observed in the development of WRF and POAF between the 2 groups. Conclusions: Although low-dose tolvaptan administration did not shorten the time to achieving preoperative body weight, it did significantly increase urine volume without WRF and POAF.

Current status and issues of oral and maxillofacial surgery during the infection epidemic period −COVID-19 countermeasures at Kobe City Medical Center General Hospital−

Current status and issues of oral and maxillofacial surgery during the infection epidemic period −COVID-19 countermeasures at Kobe City Medical Center General Hospital−

Prediction of clinical outcomes in patients with coronavirus disease 2019 using high-sensitive troponin I and N-terminal pro-B-type natriuretic peptide

Abstract Background Several comorbidities, including cardiovascular diseases or myocardial injury, are reported to be associated with poor prognosis in patients with Coronavirus disease 2019 (COVID-19). However, detailed prognostic analysis of myocardial injury by various biomarkers in COVID-19 patients is limited. Purpose This study aims to explore the prognostic values of high-sensitive Troponin I (hsTnI) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) for COVID-19 patients using Japanese real-world data. Methods The COVID-MI study is a retrospective cohort study that enrolls consecutive laboratory-confirmed COVID-19 patients admitted to the hospital from July 2020 to September 2021. We collected clinical data, including cardiac biomarker values, by chart review. If the prespecified biomarkers in concern were not available, we measured them using the institutional serum blood bank, which enrolled patients prospectively from July 2020. Patients with available biomarkers were analyzed according to the values of hsTnI or NT-proBNP, using the clinically relevant thresholds (hsTnI: 5 ng/L and 99th percentile of the upper reference limit [99%ile URL], and NT-proBNP: 125 pg/mL and 900 pg/mL). The primary outcome measure was all-cause death. Secondary outcome measures included acute respiratory distress syndrome, myocardial infarction, myocarditis/pericarditis, venous thromboembolism, cerebral infarction, and bleeding events. Results We enrolled 917 patients with COVID-19 confirmed by viral nucleic acid amplification test. The mean age was 61 years, and 591 patients (64%) were men. On admission, the number of patients classified as severe or critical COVID-19 was 515 (56%) and 85 (8.7%), respectively. Among the 544 patients with hsTnI values, 365 (67%) patients had elevated hsTnI of ≥5 ng/L, and 134 patients (25%) had TnI of ≥99%ile URL. Besides, among 546 patients with NT-proBNP values, 295 patients (54%) had elevated NT-pro-BNP of ≥125 pg/mL, and 93 patients (17%) had NT-proBNP of ≥900 pg/mL. The median follow-up period was 31 days (interquartile range: 11–90 days). In cumulative incidence analysis, higher levels of hsTnI and NT-proBNP were associated with significantly higher mortality (hsTnI: &amp;lt;5 ng/L group; 8.8%, 5 ng/L to 99%ile URL group; 19%, and ≥99%ile URL group; 37%, P&amp;lt;0.001, and NT-proBNP: &amp;lt;125 pg/mL group; 7.8%, 125 to 900 pg/mL group; 21%, and ≥900 pg/mL group; 45%, P&amp;lt;0.001). The adjusted risk for all-cause death remained significant for each threshold of cardiac biomarkers (hsTnI ≥99%ile URL: hazard ratio [HR] 1.98, 95% confidence interval [CI] 1.11–3.54, P=0.02, and NT-proBNP ≥900 pg/mL: HR 3.60, 95% CI 1.86–6.98, P&amp;lt;0.001). Conclusion Elevation of hsTnI or NT-proBNP was associated with poor prognosis in the current relatively severely ill COVID-19 patients. Measuring hsTnI or NT-proBNP can be an attractive option for risk stratification and deciding appropriate management in patients with COVID-19. Funding Acknowledgement Type of funding sources: Public hospital(s). Main funding source(s): Institutional Research Fund at Kobe City Medical Center General Hospital

Psychological impact of the COVID-19 pandemic on hospital workers in Kobe: A cross-sectional survey.

AimMany health‐care workers exposed to coronavirus disease 2019 (COVID‐19) are psychologically distressed. This study aimed to investigate the psychological impact of the COVID‐19 pandemic on hospital workers under the emergency declaration in Japan.MethodsThis cross‐sectional, survey‐based study collected sociodemographic data and responses to 19 stress‐related questions and the Impact of Event Scale‐Revised (IES‐R), which measures post‐traumatic stress disorder (PTSD) symptoms, from all 3217 staff members at Kobe City Medical Center General Hospital from April 16, 2020 to June 8, 2020. Exploratory factor analysis was applied to the 19 stress‐related questions. Multiple regression models were used to evaluate the association of personal characteristics with each score of the four factors and the IES‐R.ResultsWe received 951 valid responses; 640 of these were by females, and 311 were by respondents aged in their 20s. Nurses accounted for the largest percentage of the job category. Women, those aged in their 30s–50s, nurses, and frontline workers had a high risk of experiencing stress. The prevalence of stress (IES‐R ≥ 25) was 16.7%. The psychological impact was significantly greater for those aged in their 30s–50s and those who were not medical doctors.ConclusionsThis is the first study to examine the stress of hospital workers, as measured by the IES‐R, under the emergency declaration in Japan. It showed that women, those aged in their 30s–50s, nurses, and frontline workers have a high risk of experiencing stress. Health and medical institutions should pay particular attention to the physical and psychological health of these staff members.

Association between 25-hydroxyvitamin D levels and COVID-19 severity.

Background and aimsDespite reports on the impact of vitamin D status on coronavirus disease 2019 (COVID-19) severity, the association between low vitamin D status and severe COVID-19 remains unclear. Moreover, researchers have not determined the aforementioned association in Japanese patients. This study aimed to investigate the association between 25-hydroxyvitamin D [25(OH)D] levels and COVID-19 severity in Japanese patients.MethodsThis retrospective observational study included 117 consecutive patients with COVID-19 admitted to the Kobe City Medical Center General Hospital between October 01, 2020, and January 31, 2021. We measured the serum 25(OH)D levels using blood specimens collected within 5 days of hospital admission using liquid chromatography-tandem mass spectrometry.ResultsThere were 21 (17.9%), 73 (62.4%), 19 (16.2%) and 4 (3.4%) patients with severe deficiency (<10 ng/mL), deficiency (10–<20 ng/mL), insufficiency (20–<30 ng/mL), and sufficiency (≥30 ng/mL) of vitamin D, respectively. In univariate logistic regression analyses, lower serum 25(OH)D levels [odds ratio (OR) 1.18 per 1 ng/mL decrease, 95% confidence interval (CI) 1.04–1.33, p = 0.007] were significantly associated with invasive mechanical ventilation (IMV) or death. In a multivariate logistic regression analysis, low serum 25(OH)D levels [OR 1.22 per 1 ng/mL decrease, 95% CI 1.06–1.40, p = 0.005] were significantly associated with IMV or death. The cut-off value of serum 25(OH)D levels was 10.4 ng/mL, calculated by the receiver operating characteristic curve to detect the requirement for IMV or death.ConclusionsTo the best of our knowledge, this is the first study to assess the association between vitamin D status and COVID-19 severity in Japanese patients. Low serum 25(OH)D level was detected as an independent risk factor for severe COVID-19 among Japanese patients.

Ringed fluorodeoxyglucose uptake predicted poor prognosis after resection of pulmonary pleomorphic carcinoma

BackgroundPulmonary pleomorphic carcinoma (PPC) is a relatively rare and poorly differentiated non-small cell carcinoma. This study aimed to investigate the clinicopathological features including programmed cell death ligand 1 (PD-L1) expression status in patients with PPC who underwent curative resection.MethodsWe retrospectively studied 29 consecutive patients who had undergone anatomical lung resections for PPC. Perioperative and pathological variables, including radiological findings, were investigated to define prognostic factors.ResultsOverall survival (OS) rates were 71.8% at 1 year and 60.0% at 5 years. Disease-free survival (DFS) rates were 54.8% at 1 year and 43.6% at 5 years. Univariate analysis revealed that ringed fluorodeoxyglucose (FDG) uptake on positron emission tomography/computed tomography (PET/CT) (p = 0.003), a cavity in the tumor on CT (p = 0.004), and tumor size (> 40 mm) (p = 0.014) were poor prognostic factors for OS. Regarding DFS, ringed FDG uptake (p = 0.002), a cavity on CT (p < 0.001), tumor size (p = 0.007), and pleural invasion (p = 0.014) were poor prognostic factors. PD-L1 expression was not a prognostic factor.ConclusionThis study showed for the first time that ringed FDG uptake on PET/CT is a poor prognostic factor of PPC. PD-L1 expression status was not related to the prognosis.Trial registration The study was approved by the Kobe City Medical Center General Hospital’s ethics board (No. 20112) on August 20, 2020.

Incidence of Adverse Events Associated With the In-Hospital Transport of Critically Ill Patients.

IMPORTANCE:Despite various reports on the incidence of adverse events related to the in-hospital transport of critically ill patients, there is little verification of the correlation between the occurrence of adverse events and the use of checklists. The risk factors for the occurrence of adverse events during transport based on the use of checklists have not been well studied. Understanding them can contribute to making patient transport safer.OBJECTIVES:We aimed to investigate the frequency of adverse events and risk factors related to the in-hospital transport of critically ill patients in a hospital that uses a checklist for transporting patients.DESIGN, SETTING, AND PARTICIPANTS:This single-center, prospective, observational study was conducted between February 1, 2020, and July 31, 2020, at Kobe City Medical Center General Hospital, Japan. Patients greater than or equal to 18 years old who were admitted to the ICU and were transported for examination or procedures were included.MAIN OUTCOMES AND MEASURES:The transport member recorded patient information and any adverse events that occurred and filled out an information collection form. We then applied multivariate analysis to identify risk factors.RESULTS:A total of 117 transports for 117 patients were evaluated in this study. Twenty-two adverse events occurred in 20 transports (17.1%). There were nine transports (7.7%) in which the patients required treatment, all of which were related to patient instability. Multivariate logistic regression analysis showed that the use of sedative drugs was related to adverse events (odds ratio, 2.9; 95% CI, 1.0–8.5; p = 0.04). We were not able to show a relationship of either the severity of the illness or body mass index with the occurrence of adverse events.CONCLUSIONS AND RELEVANCE:This study revealed that the frequency of adverse events related to the in-hospital transportation of critically ill patients based on the use of a checklist was 17.1% and that the use of sedatives was associated with adverse events.

Risk Factors of Proteinuria in Patients with Hepatocellular Carcinoma Receiving Lenvatinib.

Proteinuria is one of the most frequently reported adverse events leading to the discontinuation of lenvatinib treatment in patients with advanced hepatocellular carcinoma (HCC). However, there are no reports regarding the risk factors of proteinuria in patients with HCC or patients receiving lenvatinib. We retrospectively reviewed the medical records of patients with HCC receiving lenvatinib at the Kobe City Medical Center General Hospital between April 2018 and December 2020. The severity of proteinuria was graded based on the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. A multivariate Cox proportional hazards model was employed to identify the risk factors of developing grade ≥2 proteinuria. Among the 37 patients included, 3 patients had grade-1 proteinuria at baseline and 10 patients had estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2 at baseline. Grades 1, 2, and 3 proteinuria were observed in 15 (40.5%), 10 (27.0%), and 2 (5.4%) patients, respectively, during lenvatinib treatment. The median value of eGFR was significantly lower in patients who developed grade ≥2 proteinuria than those with grade ≤1 proteinuria (59.6 vs. 78.1 mL/min/1.73 m2, p = 0.045). Multivariate analysis revealed that pre-existing proteinuria at baseline (hazard ratio (HR), 9.72; 95% confidence interval (CI), 1.29-52.21; p = 0.030), and eGFR <60 mL/min/1.73 m2 at baseline (HR, 4.49; 95% CI, 1.32-16.07; p = 0.017) were significantly associated with developing grade ≥2 proteinuria. These patients should be monitored carefully, and our preliminary data should be confirmed by further studies.

Clinical features and outcomes of duodenal-type follicular lymphoma: A single-center retrospective study.

Duodenal‐type follicular lymphoma (FL) is a rare and newly recognized disease. Few data are available on the outcomes and treatment strategies for patients with duodenal‐type FL. We aimed to investigate the clinical features and outcomes of duodenal‐type FL. We defined duodenal‐type FL as involvement of the duodenum, without nodal or extranodal lesions other than intestinal lesions, pathologically diagnosed as FL. We reviewed 26 patients with duodenal‐type FL between January 2011 and December 2020 at Kobe City Hospital Organization, Kobe City Medical Center General Hospital. In particular, patients were selected for the watch and wait (WW) strategy and followed up with regular esophagogastroduodenoscopy about once a year at our institution. The patient characteristics were as follows: median age 63.5 years (range: 42–78), sex (male, 15; female, 11), stage (I, 26), and grade (I, 26). Regarding treatment strategies, 23 patients were selected for the WW strategy, and three patients received initial rituximab therapy. The median follow‐up period was 65.5 months (range: 0.2–109). Five‐year progression‐free survival and 5‐year overall survival rates were 86.3% and 100%, respectively. Among the 23 patients selected for the WW strategy, six had spontaneous complete regression, and 14 had stable disease, and three had progressive disease, including one with histologic transformation. The WW strategy for patients with duodenal‐type FL could be an appropriate and safe treatment option. However, in several cases, disease progression was documented, and regular follow‐up is important.

Real-World Data of Trifluridine/Tipiracil for Patients With Advanced Gastric Cancer: A Multi-Institutional Retrospective Study.

A trial with trifluridine/tipiracil (FTD/TPI) versus placebo in patients with heavily pretreated metastatic gastric cancer showed that FTD/TPI is effective with manageable toxicity in these patients. However, real-world data on the effects of FTD/TPI in patients with advanced gastric cancer (AGC) are limited. We retrospectively collected and analyzed the clinicopathological data of patients with AGC who received FTD/TPI monotherapy at our institutions (Kobe City Medical Center General Hospital, Osaka Red Cross Hospital, Himeji Red Cross Hospital, and Kansai Medical University Hospital) between September 2019 and July 2021. Tumor responses were evaluated based on the Response Evaluation Criteria in Solid Tumors, version 1.1. Overall survival (OS) and progression-free survival were estimated using the Kaplan-Meier method. A total of 53 patients were included in the study. The median age was 70 (range, 37-85) years; 39 patients (74%) were men; the numbers of patients with Eastern Cooperative Oncology Group performance status scores of 0, 1, and 2 were 10 (19%), 39 (74%), and 4 (8%), respectively; and 27 patients (51%) had diffuse-type histology. A total of 29 patients (56%) had ascites. Prior nivolumab therapy was administered to 49 patients (92%). The response rate and disease control rate (DCR) were 2% and 35%, respectively. The median progression-free survival was 2.4 months, and OS was 5.8 months. Patients with ascites exhibited significantly shorter OS (8.6 vs 4.7 months, P = .0291) than those without ascites, and DCR (54% vs 18%, P = .0055) was significantly worse in patients with ascites. There was no significant difference in the frequency of adverse events of grade 3 or higher between patients with and without ascites. In a real-world setting, FTD/TPI has similar effectiveness as late-line chemotherapy for patients with AGC, including those who previously had received nivolumab.

The Prognostic Significance of the Complete IgH Rearrangement Pattern Using the BIOMED-2 Protocol in Diffuse Large B-Cell Lymphoma

▪Introduction: In several B-cell malignancies, such as chronic lymphocytic leukemia and mantle cell lymphoma, the somatic hypermutation (SHM) status of immunoglobulin heavy chain (IgH) variable region (VH) significantly correlates with clinical outcome. Diffuse large B-cell lymphoma (DLBCL) usually contains a number of VH SHMs, with considerably variable frequency. However, there have been few reports about the association between VHSHM frequency and clinical outcome in DLBCL.The BIOMED-2 multiplex PCR protocol is one of the standardized methods for detecting IgH gene rearrangements, and has been used to prove clonality in B-cell lymphomas. VH SHMs in the germinal center prevent proper annealing of the applied PCR primers, rendering clonal VH rearrangements undetectable by this protocol. Thus, the complete IgH rearrangement pattern produced by the BIOMED-2 protocol is expected to reflect the frequency of VH SHMs. In this study, we investigated the prognostic impact of complete IgH rearrangement pattern on patients with DLBCL, and analyzed the correlation between complete IgH rearrangement pattern and VH SHM frequency by Sanger sequencing.Materials and Methods: We retrospectively identified 386 patients diagnosed with de novo DLBCL that received anthracycline-based immunochemotherapy at Kobe City Medical Center General Hospital from January 2005 to June 2015. We excluded 83 patients because fresh samples were not available for PCR analysis, and a total of 303 patients were enrolled. Based on the BIOMED-2 protocol, complete IgH rearrangement was detected by three PCR reactions using three VH forward primer sets: framework region (FR) 1, FR2, and FR3. The primary endpoint was 5-year overall survival (5-yr OS). The secondary endpoint was 5-year progression-free survival (5-yr PFS). OS and PFS were estimated using the log-rank test. Multivariate analysis using the Cox proportional hazard ratio was performed for 5-yr OS. For VH sequencing analysis, the cryopreserved PCR products of 42 available samples were sequenced directly using both forward and reverse primers, and for each sequenced sample, the percentage of VH identity to the closest germline gene was calculated, using the immunoglobulin gene database (IMGT/V-QUEST).Results: Of the 303 patients enrolled (median age: 69 years old), 183 patients (60.3%) had advanced stage disease and 148 (48.8%) had a high-intermediate or high International Prognostic Index (IPI) score. The median follow-up was 60.6 months (2.0-133.8 months). Complete IgH rearrangement was detected in 176 (58.1%), 172 (56.8%), and 113 (37.2%) of patients using the FR1, FR2, and FR3 primer sets, respectively. In total, 80 patients (26.4%) were positive for all three PCR reactions, 82 (27.1%) for two, 57 (18.8%) for one, and 84 (27.7%) had completely negative results. We compared the 5-yr OS and PFS among these subgroups (Figure 1), and observed that the probability of survival decreased with accumulation of positive PCR results. As shown in Figure 2, both the 5-yr OS and PFS were significantly worse for patients with all three reactions positive for complete IgH rearrangement (OS: 54.2% vs 73.2% p=0.002; PFS: 34.4% vs. 59.3%, p<0.001). In multivariate analysis adjusted by IPI score, complete IgH rearrangement detected by all three PCR reactions was significantly correlated with poor prognosis (hazard ratio: 2.13; 95% CI: 1.38-3.26; p<0.001).This classification also allowed subgroups with unfavorable prognosis to be identified, even among patients with a high-intermediate or high IPI score (5-yr OS: 28.0% vs. 62.9%, p<0.001). Moreover, VH sequencing analysis of 42 available samples confirmed that patients with complete IgH rearrangement in all three PCR reactions had significantly lower VH gene SHMs than other groups (median value of VH identity; 91.9% vs 84.0%, p<0.001).Conclusion: Complete IgH rearrangement detected by all three primer sets in the BIOMED-2 PCR protocol was associated with poor prognosis in patients with DLBCL. Combined with the additional sequencing analysis, this suggests that the lower levels of VH SHMs may be associated with unfavorable prognosis in DLBCL. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Effect of early intensive rehabilitation on the clinical outcomes of patients with acute stroke.

Intensive rehabilitation effectively improves physical functions in patients with acute stroke, but the frequency of intervention and its cost-effectiveness are poorly studied. This study aimed to examine the effect of early high-frequency rehabilitation intervention on inpatient outcomes and medical expenses of patients with stroke. The study retrospectively included 1759 patients with acute stroke admitted to the Kobe City Medical Center General Hospital between 2013 and 2016. Patients with a transient ischemic attack, subarachnoid hemorrhage, and those who underwent urgent surgery were excluded. Patients were divided into two groups according to the frequency of rehabilitation intervention: the high-frequency intervention group (>2 times/day, n=1105) and normal-frequency intervention group (<2 times/day, n=654). A modified Rankin scale score ≤2 at discharge, immobility-related complications and medical expenses were compared between the groups. The high-frequency intervention group had a significantly shorter time to first rehabilitation (median [interquartile range], 19.0 h [13.1-38.4] vs. 24.7 h [16.1-49.4], P < 0.001) and time to first mobilization (23.3 h [8.7-47.2] vs. 22.8 h [5.7-62.3], P=0.65) than the normal-frequency intervention group. Despite higher disease severity, the high-frequency intervention group exhibited favorable outcomes at discharge (modified Rankin scale, ≤2; adjusted odds ratio, 1.89; 95% confidence interval, 1.25-2.85; P=0.002). No significant differences were observed between the two groups concerning the rate of immobility-related complications and total medical expenses during hospitalization. High-frequency intervention was associated with improved outcomes and decreased medical expenses in patients with stroke. Our results may contribute to reducing medical expenses by increasing the efficiency of care delivery. Geriatr Gerontol Int 2021; 21: 623-628.