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BACKGROUND: In quantifying left ventricular (LV) diameter, which position for echocardiographic measurements, mitral valve tip level (MV-tip) or LV mid level (LV-mid), more accurately represents the LV volume is unclear. Furthermore, which factor affects the measurement error also has not been elucidated. METHODS: We enrolled 150 patients without myocardial infarction and local asynergy who underwent echocardiography and cardiac magnetic resonance imaging (CMRI). Echocardiographic LV diastolic diameter (LVDD) and LV systolic diameter (LVDS) were measured at both MV-tip and LV-mid, and the LV end-diastolic volume (LVEDV) and end-systolic volume (LVESV) were quantified using CMRI. We quantified the degree of aortic wedging as the angle between the anterior wall of the aorta and the ventricular septal surface (ASA). RESULTS: The average LVDD was smaller and average LVDS larger when measured at the MV-tip than at the LV-mid. In regression analyses, the correlation coefficient between LVDD and LVEDV was larger at LV-mid (R = 0.89) than at MV-tip (R = 0.82), and the correlation coefficient between LVDS and LVESV also larger at LV-mid (R = 0.93) than MV-tip (R = 0.87). ASA, Valsalva diameter, left atrial diameter, patient height, and LV mass significantly affected the echocardiographic measurement error, but no factor affected the measurement error when quantifying LVDD at the LV-mid level. CONCLUSIONS: The echocardiographic LV diameter measured at LV-mid has a stronger correlation with LV chamber size derived from CMRI than measurements at MV-tip. The LVDD measured at the LV-mid level is not affected by other factors.
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Fear of cancer recurrence (FCR) is a common and distressing condition among adolescents and young adults (AYAs). This study aims to investigate the efficacy of digital interventions, including distress screening-based information provision and smartphone problem-solving therapy, on common psychological distress, especially FCR, in AYA patients with cancer. Participants will be 224 AYA outpatients with cancer aged 15-39 years who will be randomly assigned to either an 8-week smartphone-based intervention or a waitlist control group. This intervention includes smartphone-based distress screening, information provision, and psychotherapy (problem-solving therapy). The primary endpoint will be the Fear of Cancer Recurrence Inventory-Short Form score at week 8. This study will be conducted as a fully decentralized, randomized, and multicenter trial. The study protocol was approved by the Institutional Review Board of Nagoya City University on 19 April 2024 (ID: 46-23-0005). Trial registration: UMIN-CTR: UMIN000054583.
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INTRODUCTION: Although the prognosis of Langerhans cell histiocytosis (LCH) is excellent, the high recurrence rate and permanent consequences, such as central diabetes insipidus and LCH-associated neurodegenerative diseases, remain to be resolved. Based on previous reports that patients with high-risk multisystem LCH show elevated levels of inflammatory molecules, we hypothesised that dexamethasone would more effectively suppress LCH-associated inflammation, especially in the central nervous system (CNS). We further hypothesised that intrathecal chemotherapy would effectively reduce CNS complications. We administer zoledronate to patients with multifocal bone LCH based on an efficacy report from a small case series. METHODS AND ANALYSIS: This phase II study (labelled the LCH-19-MSMFB study) is designed to evaluate the significance of introducing dexamethasone and intrathecal chemotherapy for multisystem disease and zoledronate for multifocal bone disease in previously untreated, newly diagnosed children, adolescents (under 20 years) and adults under 40 years. The primary endpoint is the 3-year event-free survival rate by risk group of under 20 years and the 3-year event-free survival rate of 20 years and over. ETHICS AND DISSEMINATION: This study was approved by the Central Review Board of the National Hospital Organisation Nagoya Medical Centre (Nagoya, Japan) on 21 January 2022 and was registered in the Japan Registry of Clinical Trials (https://jrct.niph.go.jp/en-latest-detail/jRCTs041210027). Written informed consent will be obtained from all patients and/or their guardians. TRIAL REGISTRATION NUMBER: jRCTs041210027.
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Dexametasona , Histiocitosis de Células de Langerhans , Ácido Zoledrónico , Humanos , Histiocitosis de Células de Langerhans/tratamiento farmacológico , Histiocitosis de Células de Langerhans/diagnóstico , Histiocitosis de Células de Langerhans/mortalidad , Niño , Adolescente , Japón , Adulto , Dexametasona/uso terapéutico , Dexametasona/administración & dosificación , Adulto Joven , Ácido Zoledrónico/uso terapéutico , Masculino , Femenino , Ensayos Clínicos Fase II como Asunto , Preescolar , Conservadores de la Densidad Ósea/uso terapéuticoRESUMEN
OBJECTIVES: There is a lack of data on the number of surgeries required for endoscopic combined intrarenal surgery (ECIRS). Accordingly, we aimed to identify the learning curve for ECIRS performed by multiple surgeons. METHODS: We included 296 patients who underwent ECIRS at our university hospital between 2016 and 2021. A learning curve for percutaneous nephrolithotomy side was calculated considering urology-resident surgeons. The learning curve was retrospectively analyzed for surgical time, renal puncture time, stone-free rate, and complications and corrected for age, body mass index, stone size, computed tomography value, cumulative number of surgeries, and stone location. RESULTS: This study included cases performed by 32 surgeons, including 30 residents and 2 attending surgeons. The median number of surgeries performed by the residents and attending surgeons prior to this study was 4.5 and 90, respectively. The median number of surgical procedures performed during the training period was seven. The surgical time of the residents decreased as the number of cases increased, reaching a median surgical time of 111 min for the attending surgeons after 16.4 cases. Renal puncture time was achieved in 20.1 cases. Complications related to renal access were observed in 13.0% (34 patients), Clavien-Dindo grade II in 1.9% (5 patients), and grade III or higher in 0.8% (2 patients). Comparing the first to fifth cases with the 21st and subsequent cases, the complication rate improved from 35% to 13%. CONCLUSION: Our study demonstrated that ECIRS training provided 16-20 cases with a learning curve to achieve acceptable surgical outcomes.
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Internado y Residencia , Cálculos Renales , Curva de Aprendizaje , Nefrolitotomía Percutánea , Tempo Operativo , Urología , Humanos , Masculino , Femenino , Estudios Retrospectivos , Urología/educación , Persona de Mediana Edad , Adulto , Internado y Residencia/estadística & datos numéricos , Cálculos Renales/cirugía , Nefrolitotomía Percutánea/efectos adversos , Nefrolitotomía Percutánea/métodos , Nefrolitotomía Percutánea/educación , Riñón/cirugía , Riñón/diagnóstico por imagen , Competencia Clínica/estadística & datos numéricos , Anciano , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/epidemiología , Endoscopía/educación , Endoscopía/efectos adversos , Endoscopía/métodosRESUMEN
BACKGROUND: Asthma is characterized by phenotypes of different clinical, demographic, and pathological characteristics. Identifying the profile of exhaled volatile organic compounds (VOCs) in asthma phenotypes may facilitate establishing biomarkers and understanding asthma background pathogenesis. This study aimed to identify exhaled VOCs that characterize severe asthma phenotypes among patients with asthma. METHODS: This was a multicenter cross-sectional study of patients with severe asthma in Japan. Clinical data were obtained from medical records, and questionnaires were collected. Exhaled breath was sampled and subjected to thermal desorption gas chromatography-mass spectrometry (GC/MS). RESULTS: Using the decision tree established in the previous nationwide asthma cohort study, 245 patients with asthma were divided into five phenotypes and subjected to exhaled VOC analysis with 50 healthy controls (HCs). GC/MS detected 243 VOCs in exhaled breath samples, and 142 frequently detected VOCs (50% of all samples) were used for statistical analyses. Cluster analysis assigning the groups with similar VOC profile patterns showed the highest similarities between phenotypes 3 and 4 (early-onset asthma phenotypes), followed by the similarities between phenotypes 1 and 2 (late-onset asthma phenotypes). Comparisons between phenotypes 1-5 and HC revealed 19 VOCs, in which only methanesulfonic anhydride showed p < 0.05 adjusted by false discovery rate (FDR). Comparison of these phenotypes yielded several VOCs showing different trends (p < 0.05); however, no VOCs showed p < 0.05 adjusted by FDR. CONCLUSIONS: Exhaled VOC profiles may be useful for distinguishing asthma and asthma phenotypes; however, these findings need to be validated, and their pathological roles should be clarified.
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INTRODUCTION: Children and adolescents with mature B cell non-Hodgkin lymphoma (B-NHL) are treated with short-intensive chemotherapy. The burden of short-term and long-term toxicity is highly relative to its high cure rate in good-risk patients. Although the addition of rituximab to standard lymphome Malin B (LMB) chemotherapy markedly prolongs event-free survival and overall survival in high-risk patients, the benefit of rituximab in good-risk patients remains to be elucidated. This clinical trial will examine whether the addition of rituximab eliminates anthracyclines in good-risk patients without compromising treatment outcomes. METHODS AND ANALYSIS: We will perform a single-arm, open-label, multicentre phase II study. Low-risk (stage I - completely resected, stage II abdominal) and intermediate-risk (stages I and II - incompletely resected; stage II - resected, other than abdominal; stage III with LDH <2× upper limit of normal) patients with newly diagnosed B-NHL are eligible. Low-risk patients receive two courses of R-COM1P (rituximab, cyclophosphamide, vincristine, methotrexate, prednisolone and intrathecal methotrexate with hydrocortisone), and intermediate-risk patients receive COP (cyclophosphamide, vincristine, prednisolone and intrathecal methotrexate with hydrocortisone) followed by two courses each of R-COM3P and R-CYM (rituximab, cytarabine, methotrexate and intrathecal methotrexate with hydrocortisone). The primary endpoint is a 3-year event-free survival rate in paediatric patients (<18 years) with intermediate-risk disease. 100 patients (10 low-risk and 90 intermediate-risk) will enrol within a 4-year enrolment period and the follow-up period will be 3 years. 108 institutions are participating as of 1 January 2024 (64 university hospitals, 29 general hospitals, 12 children's hospitals and three cancer centres). ETHICS AND DISSEMINATION: This research was approved by the Certified Review Board at NHO Nagoya Medical Center (Nagoya, Japan) on 21 September 2021. Written informed consent is obtained from all patients and/or their guardians. The results of this study will be disseminated through peer-reviewed publications and conference presentations. STUDY REGISTRATION: Japan Registry of Clinical Trials, jRCTs041210104.
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Linfoma de Células B , Metotrexato , Humanos , Adolescente , Niño , Rituximab/uso terapéutico , Vincristina/uso terapéutico , Metotrexato/uso terapéutico , Antraciclinas , Hidrocortisona , Japón , Doxorrubicina/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Linfoma de Células B/tratamiento farmacológico , Ciclofosfamida/uso terapéutico , Ciclofosfamida/efectos adversos , Resultado del Tratamiento , Antibióticos Antineoplásicos/uso terapéutico , Prednisolona/uso terapéutico , Estudios Multicéntricos como Asunto , Ensayos Clínicos Fase II como AsuntoRESUMEN
BACKGROUND AND OBJECTIVES: We aimed to examine the effect of preoperative three-dimensional (3D) computed tomography (CT)-based resection process map (RPM) imaging on the outcomes of robot-assisted partial nephrectomy (RAPN). METHODS: We retrospectively analyzed 177 patients (RPM group, n = 92; non-RPM group, n = 85) who underwent this surgery between November 2012 and April 2022. Patient-specific contrast-enhanced CT images were used to construct an RPM, a 3D representation of the kidney showing the planned tumor resection and a 5 mm safety margin. Outcome analyses were performed using propensity score matching. The primary endpoint was the trifecta achievement rate. RESULTS: We extracted 90 cases. The trifecta achievement rate showed no significant differences between the RPM (73.3%) and non-RPM groups (73.3%). However, the RPM group had fewer Grade 3 and higher complications (0.0% vs. 13.3%, p = 0.026). The da Vinci Xi (OR 3.38, p = 0.016) and tumor diameter (OR 0.95, p = 0.013) were independent factors affecting trifecta achievement in multivariate analysis. Using RPM imaging was associated with the absence of Grade 3 and higher perioperative complications (OR 5.33, p = 0.036) in univariate analysis. CONCLUSIONS: Using preoperative 3D CT-based RPM images before RAPN may not affect trifecta achievement, but may reduce serious complication occurrence by providing detailed information on tumor resection.
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Imagenología Tridimensional , Neoplasias Renales , Nefrectomía , Puntaje de Propensión , Procedimientos Quirúrgicos Robotizados , Tomografía Computarizada por Rayos X , Humanos , Nefrectomía/métodos , Estudios Retrospectivos , Femenino , Procedimientos Quirúrgicos Robotizados/métodos , Masculino , Neoplasias Renales/cirugía , Neoplasias Renales/diagnóstico por imagen , Neoplasias Renales/patología , Persona de Mediana Edad , Tomografía Computarizada por Rayos X/métodos , Anciano , Estudios de Seguimiento , Carcinoma de Células Renales/cirugía , Carcinoma de Células Renales/diagnóstico por imagen , Carcinoma de Células Renales/patologíaRESUMEN
Introduction: Intractable lymphatic anomalies (LAs) include cystic lymphatic malformation (LM; macrocystic, microcystic, or mixed), generalized lymphatic anomaly, and Gorham-Stout disease. LAs can present with severe symptoms and poor prognosis. Thus, prospective studies for treatments are warranted. We conducted a prospective clinical trial of sirolimus for intractable LAs. Methods: This was an open-label, single-arm, multicenter, prospective trial involving five institutions in Japan. All patients with LAs received oral sirolimus once daily, and the dose was adjusted to ensure that the trough concentration remained within 5-15 ng/mL. We prospectively assessed the drug response (response rate for radiological volumetric change in target lesion), performance state, change in respiratory function, visceral impairment (pleural effusion, ascites, bleeding, pain), laboratory examination data, quality of life (QOL), and safety at 12, 24, and 52 weeks of administration. Results: Eleven patients with LAs (9 generalized lymphatic anomaly, 1 cystic LM, 1 Gorham-Stout disease) were treated with sirolimus, of whom 6 (54.5%; 95% confidence interval: 23.4-83.3%) demonstrated a partial response on radiological examination at 52 weeks of administration. No patients achieved a complete response. At 12 and 24 weeks of administration, 8 patients (72.7%) already showed a partial response. However, patients with stable disease showed minor or no reduction after 12 weeks. Adverse events, such as stomatitis, acneiform dermatitis, diarrhea, and fever, were common with sirolimus. Sirolimus was safe and tolerable. Conclusion: Sirolimus can reduce the lymphatic tissue volume in LAs and may lead to improvements in clinical symptoms and QOL.
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Aortic and valvular calcification are well-known risk factors for cardio-cerebrovascular events in patients undergoing hemodialysis. We investigated the clinical impact of an angulated aorto-septal angle as a result of aortic elongation due to aortic calcification on cardio-cerebrovascular outcomes in patients undergoing hemodialysis. We investigated 306 patients (mean age 65.4 years, 68% male) who underwent pre-scheduled routine echocardiography between April and September 2018. The angle between the anterior wall of the aorta and the ventricular septal surface (ASA) was quantified. We determined aortic and mitral valve calcification scores based on calcified cardiac changes; the aortic and mitral valve scores ranged between 0-9 and 0-6, respectively. The primary endpoint was a composite including cardio-cerebrovascular events and cardio-cerebrovascular death. The mean duration of dialysis among the patients in this analysis was 9.6 years. The primary endpoint was observed in 54 patients during the observational period (median 1095 days). Multivariable Cox proportional hazards analyses identified left ventricular ejection fraction (per 10% increase: hazard ratio [HR] 0.67; 95% confidential interval [CI] 0.53-0.84, P = 0.001), left ventricular mass index (per 10 g/m2 increase: HR 1.14; 95% CI 1.05-1.24, P = 0.001), ASA (per 10 degree increase: HR 0.69; 95% CI 0.54-0.88; P = 0.003), and aortic valve calcification score (HR 1.15; 95% CI 1.04-1.26, P = 0.005) as independent determinants of the primary endpoint. Kaplan-Meier analysis showed a higher incidence of the primary endpoint in patients with ASA <119.4 degrees than those with ASA ≥119.4 degrees (Log-rank P < 0.001). An angulated aorto-septal angle is an independent risk factor for cardio-cerebrovascular events and cardio-cerebrovascular death in patients undergoing hemodialysis.
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Estenosis de la Válvula Aórtica , Función Ventricular Izquierda , Humanos , Masculino , Anciano , Femenino , Volumen Sistólico , Diálisis Renal/efectos adversos , Válvula Aórtica/diagnóstico por imagen , Factores de Riesgo , Resultado del TratamientoRESUMEN
Monitoring of hepatitis B virus (HBV)-DNA and HBV-DNA-guided preemptive therapy using nucleos(t)ide analogs (NAs) are recommended to prevent the development of hepatitis due to HBV reactivation after allogeneic hematopoietic stem cell transplantation (allo-HSCT) in recipients with resolved HBV infection. However, little is known about the appropriate duration of NA treatment and the effect of NA cessation on the recurrence of HBV reactivation. This study aimed to clarify the consequences of NA cessation in allo-HSCT recipients with resolved HBV infection who experienced HBV reactivation following transplantation. We retrospectively reviewed the clinical records of recipients with resolved HBV infection (hepatitis B surface antigen [HBsAg]-negative, anti-HBc-positive) before allo-HSCT who had been diagnosed with HBV reactivation (HBsAg-positive and/or HBV-DNA detectable) after allo-HSCT between January 2010 and December 2020. A total of 72 patients from 16 institutions were registered (median age, 60 years; age range, 27 to 73 years; 42 males and 30 females). The day of initial HBV reactivation ranged from day 10 to day 3034 after allo-HSCT (median, 513 days). Anti-HBs were lost in >80% of the patients at the time of HBV reactivation. All 72 patients received preemptive NAs, and no fatal HBV reactivation-related hepatitis was observed. HBV-DNA without hepatitis was continuously detected in 5 patients during the follow-up period. Administration of NAs was discontinued in 24 of 72 patients (33%) by physician decision. Second HBV reactivation occurred in 11 of the 24 patients (46%) in whom administration of NAs was discontinued. The duration of NA treatment did not differ significantly between patients with or without second HBV reactivation. The frequency of further HBV reactivation tended to be lower in patients with an anti-HBs titer of >10 mIU/mL at the time of NA cessation. Multiple reactivations of HBV after NA cessation was common in patients with HBV reactivation who underwent allo-HSCT despite the long duration of NAs. Careful monitoring of HBV-DNA is important even after the discontinuation of NAs in the case with HBV reactivation after allo-HSCT, because multiple reactivations could occur. Active immunization by HB vaccine might be effective for suppressing further HBV reactivation after cessation of NAs.
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Trasplante de Células Madre Hematopoyéticas , Hepatitis A , Hepatitis B , Masculino , Femenino , Humanos , Persona de Mediana Edad , Adulto , Anciano , Virus de la Hepatitis B/genética , Estudios Retrospectivos , Antígenos de Superficie de la Hepatitis B/uso terapéutico , ADN Viral/uso terapéutico , Hepatitis B/prevención & control , Hepatitis B/diagnóstico , Hepatitis B/tratamiento farmacológico , Anticuerpos contra la Hepatitis B/uso terapéutico , Trasplante de Células Madre Hematopoyéticas/efectos adversosRESUMEN
BACKGROUND: Invasive fungal infections (IFIs) represent a potentially fatal complication in patients who undergo allogeneic hematopoietic stem cell transplantation (HSCT) if the initiation of therapy is delayed. Some guidelines recommend antifungal prophylaxis or preemptive therapy for these patients depending on the risk of IFIs following allogeneic HSCT. This retrospective study aimed to identify the group of patients who safely undergo allogeneic HSCT with low-dose fluconazole (FLCZ) prophylaxis (100 mg/day). METHODS: We retrospectively reviewed 107 patients who underwent their first allogeneic HSCT at Nagoya City University Hospital from January 1, 2010, to December 31, 2019. We analyzed the efficacy of low-dose FLCZ prophylaxis and investigated the relationship between major risk factors and antifungal prophylaxis failure (APF) within 100 days post-transplant. RESULTS: Of the 107 patients, 70 received low-dose FLCZ prophylaxis, showing a cumulative incidence of APF of 37.1% and a proven/probable IFI rate of 4.3%. There were no fungal infection-related deaths, including Aspergillus infections, in the FLCZ prophylaxis group. In a multivariable analysis, cord blood transplantation (CBT) (subdistribution hazard ratio (SHR), 3.55; 95% confidence interval (CI), 1.44-8.77; p = 0.006) and abnormal findings on lung CT before transplantation (SHR, 2.24; 95% CI, 1.02-4.92; p = 0.044) were independent risk factors for APF in the FLCZ prophylaxis group. CONCLUSION: Low-dose FLCZ prophylaxis is a useful and safe option for patients receiving allogeneic HSCT, except in those undergoing CBT or having any fungal risk features including history of fungal infections, positive fungal markers, and abnormal findings on lung CT before transplantation.
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Fluconazol , Trasplante de Células Madre Hematopoyéticas , Humanos , Fluconazol/efectos adversos , Estudios Retrospectivos , Antifúngicos/efectos adversos , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Factores de RiesgoRESUMEN
Objective Skeletal muscle weakness and cardiomyopathy can be seen in carriers of dystrophinopathy. Therefore, the health management of caregivers of Duchenne/Becker muscular dystrophy (DMD/BMD) patients who are themselves carriers is an important issue. However, few studies have focused on caregivers who have dystrophin mutations. Methods In this cross-sectional study conducted at five hospitals, the daily living, situation medical treatment status, genetic testing, physical assessment, care burden, and quality of life of caregivers of DMD/BMD patients were surveyed. Results The subjects were 36 main caregivers (mean age 55.7±8.4 years old), of whom 52.8% were diagnosed as carriers, 8.3% were noncarriers, and 38.9% were not confirmed. In addition, half of the caregivers were not examined regularly at medical institutions. Of all caregivers, 54.3% had muscle or cardiac symptoms, and 75% had elevated serum creatine kinase levels. The mean Zarit Caregiver Burden Interview (ZBI) total score of current caregivers was 20.9±13.1. The frequency of a ZBI total score ≥25 was significantly higher in caregivers diagnosed as carriers than in caregivers unexamined as carriers (p=0.04). The health-related quality of life score (Short Form 36; SF-36) in caregivers was slightly lower than the Japanese standard scores in the sections of physical functioning, role limitations-physical, bodily pain, and social functioning. Conclusion Some caregivers of DMD/BMD patients can themselves have muscular or cardiac symptoms and a heavy care burden. It is therefore necessary for carrier caregivers, especially women, to undergo regular health checkups and receive appropriate health management.
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Distrofia Muscular de Duchenne , Humanos , Femenino , Persona de Mediana Edad , Distrofia Muscular de Duchenne/genética , Carga del Cuidador , Japón/epidemiología , Calidad de Vida , Estudios TransversalesRESUMEN
PURPOSE: We aimed to elucidate whether postinduction hypotension (PIH), defined as hypotension between anesthesia induction and skin incision, and intraoperative hypotension (IOH) are associated with postoperative mortality. METHODS: We conducted a retrospective cohort study of adult patients with an ASA Physical Status I-IV who underwent noncardiac and nonobstetric surgery under general anesthesia between 2015 and 2021 at Nagoya City University Hospital. The primary and secondary outcomes were 30-day and 90-day postoperative mortality, respectively. We calculated four hypotensive indices (with time proportion of the area under the threshold being the primary exposure variable) to evaluate the association between hypotension (defined as a mean blood pressure < 65 mm Hg) and mortality using multivariable logistic regression models. We used propensity score matching and RUSBoost (random under-sampling and boosting), a machine-learning model for imbalanced data, for sensitivity analyses. RESULTS: Postinduction hypotension and IOH were observed in 82% and 84% of patients, respectively. The 30-day and 90-day postoperative mortality rates were 0.4% (52/14,210) and 1.0% (138/13,334), respectively. Postinduction hypotension was not associated with 30-day mortality (adjusted odds ratio [aOR], 1.03; 95% confidence interval [CI], 0.93 to 1.13; P = 0.60) and 90-day mortality (aOR, 1.01; 95% CI, 0.94 to 1.07; P = 0.82). Conversely, IOH was associated with 30-day mortality (aOR, 1.19; 95% CI, 1.12 to 1.27; P < 0.001) and 90-day mortality (aOR, 1.12; 95% CI, 1.06 to 1.19; P < 0.001). Sensitivity analyses supported the association of IOH but not PIH with postoperative mortality. CONCLUSION: Despite limitations, including power and residual confounding, postoperative mortality was associated with IOH but not with PIH.
RéSUMé: OBJECTIF: Nous avons cherché à déterminer si l'hypotension post-induction (HPI), définie comme une hypotension entre l'induction de l'anesthésie et l'incision cutanée, et l'hypotension peropératoire (HPO) étaient associées à la mortalité postopératoire. MéTHODE: Nous avons mené une étude de cohorte rétrospective de patient·es adultes ayant un statut physique I-IV selon l'ASA et ayant bénéficié d'une chirurgie non cardiaque et non obstétricale sous anesthésie générale entre 2015 et 2021 à l'Hôpital universitaire de la ville de Nagoya. Les critères d'évaluation principal et secondaire étaient la mortalité postopératoire à 30 et 90 jours, respectivement. Nous avons calculé quatre indices d'hypotension (la proportion temporelle de la zone sous le seuil étant la principale variable d'exposition) pour évaluer l'association entre l'hypotension (définie comme une tension artérielle moyenne < 65 mm Hg) et la mortalité à l'aide de modèles de régression logistique multivariée. Nous avons utilisé l'appariement par score de propension et le RUSBoost (sous-échantillonnage et boosting aléatoire), un modèle d'apprentissage automatique pour les données déséquilibrées, pour les analyses de sensibilité. RéSULTATS: Une HPI et une HPO ont été observées chez 82 % et 84 % des patient·es, respectivement. Les taux de mortalité postopératoire à 30 et 90 jours étaient respectivement de 0,4 % (52/14 210) et de 1,0 % (138/13 334). L'hypotension post-induction n'était pas associée à la mortalité à 30 jours (rapport de cotes ajusté [RCa], 1,03; intervalle de confiance [IC] à 95 %, 0,93 à 1,13; P = 0,60) et à la mortalité à 90 jours (RCa, 1,01; IC 95 %, 0,94 à 1,07; P = 0,82). À l'inverse, l'HPO était associée à une mortalité à 30 jours (RCa, 1,19; IC 95 %, 1,12 à 1,27; P < 0,001) et à la mortalité à 90 jours (RCa, 1,12; IC 95 %, 1,06 à 1,19; P < 0,001). Les analyses de sensibilité ont confirmé l'association de l'HPO, mais pas de l'HPI, avec la mortalité postopératoire. CONCLUSION: Malgré les limitations, y compris la puissance et persistance de facteurs confondants, la mortalité postopératoire était associée à l'hypotension peropératoire mais pas à l'hypotension post-induction seule.
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Hipotensión , Complicaciones Intraoperatorias , Adulto , Humanos , Estudios Retrospectivos , Complicaciones Posoperatorias/epidemiología , Hipotensión/epidemiología , Presión ArterialRESUMEN
BACKGROUND: Actionable tumor genomic alterations, primarily EGFR mutations, occur in nearly 70% of Japanese advanced nonsquamous non-small cell lung cancer (NSCLC) patients. Standard assessment of tumor tissue includes rapid testing for EGFR mutations, ALK fusions and ROS1 fusions. We conducted a prospective observational study (WJOG13620L) of follow-on next-generation sequencing of circulating tumor DNA (ctDNA) in patients without driver alterations after EGFR testing. METHODS: Patients with untreated advanced (Stage IIIB-IV or relapsed) nonsquamous NSCLC without EGFR mutations according to single-plex testing of tumor tissue, were enrolled into this study. Patients with other known driver mutations or who underwent comprehensive genomic profiling were excluded. Plasma was analyzed by Guardant360, and the primary endpoint was the proportion of patients with pathogenic gene alterations in at least one of nine genes. RESULTS: Among the 72 patients enrolled, ALK and ROS1 fusions were tested in 86.1% and 65.2%, respectively. Alterations in pre-defined genes were detected in 21 patients (29.2%; 95% confidence interval: 19.0-41.1, p < 0.001 [one-sided null hypothesis proportion of 10%]), including RET fusion (n = 1) and mutations in KRAS (n = 11), EGFR (n = 5), ERBB2 (n = 3), and BRAF (n = 1). Median time from sample submission to results was 8 days (range, 5-17 days). CONCLUSION: Rapid follow-on comprehensive testing of ctDNA should be considered prior to first-line treatment for patients with advanced nonsquamous NSCLC when no alterations are detected after single-plex tissue testing.
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Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Humanos , Carcinoma de Pulmón de Células no Pequeñas/diagnóstico , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/patología , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patología , Proteínas Tirosina Quinasas/genética , Proteínas Proto-Oncogénicas/genética , Mutación , Genómica , Biopsia Líquida , Receptores ErbB/genéticaRESUMEN
OBJECTIVE: This study sought to elucidate the molecular impacts of belimumab (BEL) treatment on T-cell immune profiling in SLE. METHODS: We used mass cytometry with 25 marker panels for T-cell immune profiling in peripheral blood T cells (CD3+) from 22 patients with BEL-treated SLE and 20 controls with non-BEL-treated SLE. An unsupervised machine-learning clustering, FlowSOM, was used to identify 39 T-cell clusters (TCLs; TCL01-TCL39). TCLs (% of CD3+) showing significant (p<0.05) associations with BEL treatment (BEL-TCL) were selected by a linear mixed-effects model for comparing groups of time-series data. Furthermore, we analysed the association between BEL treatment and variations in regulatory T-cell (Treg) phenotypes, and the ratio of other T-cell subsets to Treg as secondary analysis. RESULTS: Clinical outcomes: BEL treatment was associated with a decrease in daily prednisolone use (coef=-0.1769, p=0.00074), and an increase in serum CH50 (coef=0.4653, p=0.003), C3 (coef=1.1047, p=0.00001) and C4 (coef=0.2990, p=0.00157) levels. Molecular effects: five distinct BEL-TCLs (TCL 04, 07, 11, 12 and 27) were identified. Among these, BEL-treated patients exhibited increased proportions in the Treg-like cluster TCL11 (coef=0.404, p=0.037) and two naïve TCLs (TCL04 and TCL07). TCL27 showed increased levels (coef=0.222, p=0.037) inversely correlating with baseline C3 levels. Secondary analyses revealed associations between BEL treatment and an increase in Tregs (coef=1.749, p=0.0044), elevated proportions of the fraction of Tregs with inhibitory function (fTregs, coef=0.7294, p=0.0178) and changes in peripheral helper T cells/fTreg (coef=-4.475, p=0.0319) and T helper 17/fTreg ratios (coef=-6.7868, p=0.0327). Additionally, BEL was linked to variations in T-cell immunoglobulin and mucin domain-containing protein-3 expression (coef=0.2422, p=0.039). CONCLUSIONS: The study suggests an association between BEL treatment and variations in T cells, particularly Tregs, in SLE pathologies involving various immune cells.
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Lupus Eritematoso Sistémico , Humanos , Subgrupos de Linfocitos T/metabolismo , Linfocitos T Reguladores , Anticuerpos Monoclonales Humanizados/uso terapéuticoRESUMEN
BACKGROUND: Carfilzomib is a selective proteasome inhibitor approved for treating relapsed or refractory multiple myeloma (RRMM). Carfilzomib improves overall survival (OS) and progression-free survival (PFS); however, treatment with carfilzomib results in a higher incidence of cardiovascular and renal toxicity. More than 70% of patients with RRMM in clinical practice do not meet the eligibility criteria for randomized clinical trials (RCT). OS and PFS are negatively influenced by complications, concomitant medications and prior treatments. Therefore, we assessed the risk factors influencing the OS and time to next treatment (TTNT) in the real world. TTNT has emerged as a relevant alternative clinical endpoint to PFS. METHODS: A retrospective analysis of a large claims database prepared during the post-marketing stages in Japan was performed. The patients treated with carfilzomib for the first time were identified. Multivariable Cox proportional hazards regression analysis was performed to evaluate the risk factors influencing OS and TTNT following carfilzomib treatment. RESULTS: A total of 732 patients with RRMM who received carfilzomib-containing chemotherapy between April 2014 and September 2021 were identified. Multivariable Cox regression analysis for OS and TTNT showed a significantly higher hazard ratio (HR) of 1.48 (95% confidence interval [Cl]: 1.10-2.00; p = 0.010) and 1.38 (95% Cl: 1.15-1.65; p < 0.001), respectively, for patients with renal impairment compared to those without renal impairment. Multivariable Cox regression analysis for OS and TTNT showed a significantly higher HR of 1.80 (95% Cl: 1.27-2.55; p = 0.0010) and 1.38 (95% Cl: 1.14-1.66; p < 0.001), respectively, for patients with prior lenalidomide treatment compared to those without prior lenalidomide treatment. CONCLUSION: Complication of renal impairment and prior lenalidomide treatment could be risk factors influencing OS and TTNT during carfilzomib treatment.
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Mieloma Múltiple , Humanos , Mieloma Múltiple/tratamiento farmacológico , Mieloma Múltiple/epidemiología , Lenalidomida , Japón/epidemiología , Estudios Retrospectivos , Dexametasona , Factores de Riesgo , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversosRESUMEN
PURPOSE: Mammography screening has increased the detection of subcentimeter breast cancers. The prognosis for estrogen receptor (ER)-positive and human epidermal growth factor receptor 2 (HER2)-negative T1a/bN0M0 breast cancers is excellent; however, the necessity of adjuvant endocrine therapy (ET) is uncertain. METHODS: We evaluated the effectiveness of adjuvant ET in patients with ER-positive and HER2-negative T1a/bN0M0 breast cancer who underwent surgery from 2008 to 2012. Standard ET was administrated after surgery. The primary endpoint was the cumulative incidence of distant metastasis. All statistical tests were 2-sided. RESULTS: Adjuvant ET was administered to 3991 (83%) of the 4758 eligible patients (1202 T1a [25.3%] and 3556 T1b [74.7%], diseases). The median follow-up period was 9.2 years. The 9-year cumulative incidence of distant metastasis was 1.5% with ET and 2.6% without ET (adjusted subdistribution hazard ratio [sHR], 0.54; 95% CI, 0.32-0.93). In multivariate analysis, the independent risk factors for distant metastasis were no history of ET, mastectomy, high-grade, and lymphatic invasion. The 9-year overall survival was 97.0% and 94.4% with and without ET, respectively (adjusted HR, 0.57; 95% CI, 0.39-0.83). In addition, adjuvant ET reduced the incidence of ipsilateral and contralateral breast cancer (9-year rates; 1.1% vs. 6.9%; sHR, 0.17, and 1.9% vs. 5.2%; sHR, 0.33). CONCLUSIONS: The prognosis was favorable in patients with ER-positive and HER2-negative T1a/bN0M0 breast cancer. Furthermore, adjuvant ET reduced the incidence of distant metastasis with minimal absolute risk difference. These findings support considering the omission of adjuvant ET, especially for patients with low-grade and no lymphatic invasion disease.
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OBJECTIVES: Balloon pulmonary angioplasty (BPA) and medical therapy, such as soluble guanylate cyclase stimulators, are recommended treatments for patients with chronic thromboembolic pulmonary hypertension (CTEPH) who are ineligible for pulmonary endarterectomy (PEA). However, monotherapy with BPA or medical therapy cannot always eliminate symptoms such as exertional dyspnoea. Thus, this study aims to clarify the efficacy of continuous treatment with riociguat in inoperable CTEPH patients with normalised haemodynamics after BPA. METHODS AND ANALYSIS: This is a double-blind, multicentre, randomised, placebo-controlled trial. Participants with CTEPH who are ineligible for PEA will receive riociguat followed by BPA. Subsequently, participants will be randomised (1:1) into either riociguat continuing or discontinuing groups and will be observed for 16 weeks after randomisation. The primary endpoint will be the change in peak cardiac index (CI) during the cardiopulmonary exercise test. In the primary analysis, the least square mean differences and 95% CIs for the change in peak CI at 16 weeks between the groups will be estimated by a linear mixed-effects model with baseline value as a covariate, treatment group as a fixed effect and study institution as a random effect. ETHICS AND DISSEMINATION: National Hospital Organisation Review Board for Clinical Trials (Nagoya) and each participating institution approved this study and its protocols. Written informed consent will be obtained from all participants. The results will be disseminated at medical conferences and in journal publications. REGISTRATION DETAILS: Japan Registry of Clinical Trials: jRCT no. 041200052. CLINICALTRIALS: gov by National Library of Medicine Registry ID: NCT04600492. TRIAL REGISTRATION NUMBER: NCT04600492.
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Angioplastia de Balón , Hipertensión Pulmonar , Embolia Pulmonar , Humanos , Hipertensión Pulmonar/tratamiento farmacológico , Hipertensión Pulmonar/etiología , Embolia Pulmonar/complicaciones , Embolia Pulmonar/terapia , Embolia Pulmonar/diagnóstico , Enfermedad Crónica , Ensayos Clínicos Controlados Aleatorios como Asunto , Estudios Multicéntricos como AsuntoRESUMEN
Introduction: In the CAPITAL study, a randomized phase 3 study, wherein carboplatin plus nab-paclitaxel treatment was compared with docetaxel treatment for older patients with squamous-cell lung cancer, the former became the new standard of care for such patients. Our study aimed to evaluate whether the efficacy of second-line immune checkpoint inhibitors (ICIs) affected the primary analysis of overall survival (OS). Methods: Herein, we performed a post hoc analysis of the impact of second-line ICIs on OS, safety in each group of participants aged more than 75 years, and intracycle nab-paclitaxel skip status. Results: Patients were randomly allocated to the carboplatin plus nab-paclitaxel (nab-PC) arm (n = 95) or the docetaxel (D) arm (n = 95). Of these patients, 74 of 190 (38.9%) were transferred to ICIs for second-line treatment (nab-PC arm: 36, D arm: 38). A survival benefit was numerically observed only for patients for whom first-line therapy was terminated owing to disease progression (median OS [nab-PC arm]: with and without ICIs, 321 and 142 d, respectively; median OS [D arm]: with and without ICIs, 311 and 256 d, respectively). The OS among patients who received ICI after adverse events was similar in the two arms. In the D arm, a significantly higher frequency of grade greater than or equal to 3 adverse events was observed among patients aged more than or equal to 75 years (86.2%) than among those aged less than 75 years (65.6%, p = 0.041), including a significantly higher frequency of neutropenia (84.6% versus 62.5%, p = 0.032); no such differences were observed in the nab-PC arm. Conclusions: We found that second-line ICI treatment seemed to have a little impact on OS.
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STUDY OBJECTIVE: The combined use of the ProSeal laryngeal mask airway and a bronchial blocker may reduce postoperative hoarseness and sore throat. We aimed to test the feasibility and efficacy of this combination technique in thoracoscopic surgery. DESIGN: A single-center, patient-assessor blinded, randomized controlled trial. SETTING: Nagoya City University Hospital (between November 2020 and April 2022). PATIENTS: A total of 100 adult patients undergoing lobectomy or segmentectomy by video- or robotic-assisted thoracoscopic surgery. INTERVENTIONS: Patients were randomly assigned to either group using a combination of the ProSeal laryngeal mask airway and a bronchial blocker (pLMA+BB group) or a double-lumen endobronchial tube (DLT group). MEASUREMENTS: The primary outcome was the hoarseness incidence on 1-3 postoperative days. Secondary outcomes included sore throat, intraoperative complications (hypoxemia, hypercapnia, surgical interruption, malposition of devices, unintended lung expansion, and ventilatory difficulty), lung collapse, device placement-related outcomes, and coughing during emergence. MAIN RESULTS: A total of 100 patients underwent randomization (51 to the pLMA+BB group and 49 to the DLT group). After drop outs, a total of 49 patients in each group were analyzed per-protocol. The incidences of hoarseness in the pLMA+BB and DLT groups were 42.9% and 53.1% (difference, -10.2%; 95% confidence interval, -30.1% to 10.3%; p = 0.419), 18.4% vs. 32.7%, and 20.4% vs. 24.5% on postoperative day 1, 2, and 3, respectively. The incidences of sore throat in the pLMA+BB and DLT groups were 16.3% vs. 34.7% (difference, -18.4%; 95% confidence interval, -35.9% to -0.9%; p = 0.063) on postoperative day 1. In the pLMA+BB group, more intraoperative complications and less coughing during emergence were observed compared to the DLT group. Lung collapse and placement-related outcomes were comparable between the groups. CONCLUSIONS: The combination of ProSeal laryngeal mask airway and bronchial blocker did not significantly reduce hoarseness compared to the double-lumen endobronchial tube.