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1.
Artigo em Inglês | MEDLINE | ID: mdl-38584083

RESUMO

BACKGROUND: The outcomes after mitral valve transcatheter edge-to-edge repair (M-TEER) for the patients with severe mitral regurgitation (MR) in hemodynamically unstable conditions, such as cardiogenic shock, still remain unclear. We aimed to integrate previous publications regarding M-TEER indicated for life-threatening conditions and indirectly particularly compared the short-term outcomes thereof, with that of other treatments. METHODS: We systematically searched the PubMed, Cochrane, and MEDLINE databases for studies from inception to June 2023, regarding M-TEER in patients with hemodynamic instability and severe MR. The primary outcomes analyzed included the in-hospital and 30-day mortality rates, and peri-procedural complications. RESULTS: Of the initial 820 publications, we conducted a meta-analysis of a total of 25 studies. The relative risk of moderate-to-severe or severe MR was 0.13 (95 % confidence interval [CI]: 0.10-0.18, I2 = 45.2 %). The pooled in-hospital and 30-day mortality rates were 11.8 % (95 % CI: 8.7-15.9, I2 = 96.4 %) and 14.1 % (95 % CI: 10.9-18.3, I2 = 35.5 %), respectively. The 30-day mortality rate was statistically significantly correlated with the residual moderate-to-severe or severe MR, as per the meta-regression analysis (coefficient ß = 3.48 [95 % CI: 0.99-5.97], p = 0.006). Regarding peri-procedural complications, the pooled rates of a stroke or transient ischemic attack, life-threatening or major bleeding, acute kidney injury, and peri-procedural mitral valve surgery were 2.3 % (95 % CI: 1.9-2.6), 7.6 % (95 % CI: 6.8-8.5), 32.9 % (95 % CI: 31.6-34.3), and 1.0 % (95 % CI: 0.8-1.3), respectively. CONCLUSIONS: This meta-analysis demonstrates that the relatively higher rates of procedural complications were observed, nevertheless, M-TEER can potentially provide favorable short-term outcomes even in hemodynamically unstable patients. PROSPERO REGISTRATION NUMBER: CRD42023468946.

2.
Target Oncol ; 19(3): 423-433, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38613731

RESUMO

BACKGROUND: Although osimertinib is a promising therapeutic agent for advanced epidermal growth factor receptor (EGFR) mutation-positive lung cancer, the incidence of pneumonitis is particularly high among Japanese patients receiving the drug. Furthermore, the safety and efficacy of subsequent anticancer treatments, including EGFR-tyrosine kinase inhibitor (TKI) rechallenge, which are to be administered after pneumonitis recovery, remain unclear. OBJECTIVE: This study investigated the safety of EGFR-TKI rechallenge in patients who experienced first-line osimertinib-induced pneumonitis, with a primary focus on recurrent pneumonitis. PATIENTS AND METHODS: We retrospectively reviewed the data of patients with EGFR mutation-positive lung cancer who developed initial pneumonitis following first-line osimertinib treatment across 34 institutions in Japan between August 2018 and September 2020. RESULTS: Among the 124 patients included, 68 (54.8%) patients underwent EGFR-TKI rechallenge. The recurrence rate of pneumonitis following EGFR-TKI rechallenge was 27% (95% confidence interval [CI] 17-39) at 12 months. The cumulative incidence of recurrent pneumonitis was significantly higher in the osimertinib group than in the first- and second-generation EGFR-TKI (conventional EGFR-TKI) groups (hazard ratio [HR] 3.1; 95% CI 1.3-7.5; p = 0.013). Multivariate analysis revealed a significant association between EGFR-TKI type (osimertinib or conventional EGFR-TKI) and pneumonitis recurrence, regardless of severity or status of initial pneumonitis (HR 3.29; 95% CI 1.12-9.68; p = 0.03). CONCLUSIONS: Osimertinib rechallenge after initial pneumonitis was associated with significantly higher recurrence rates than conventional EGFR-TKI rechallenge.


Assuntos
Acrilamidas , Compostos de Anilina , Receptores ErbB , Neoplasias Pulmonares , Pneumonia , Inibidores de Proteínas Quinases , Humanos , Acrilamidas/uso terapêutico , Acrilamidas/farmacologia , Masculino , Feminino , Compostos de Anilina/uso terapêutico , Compostos de Anilina/farmacologia , Compostos de Anilina/efeitos adversos , Idoso , Pneumonia/induzido quimicamente , Estudos Retrospectivos , Neoplasias Pulmonares/tratamento farmacológico , Inibidores de Proteínas Quinases/efeitos adversos , Inibidores de Proteínas Quinases/uso terapêutico , Inibidores de Proteínas Quinases/farmacologia , Pessoa de Meia-Idade , Idoso de 80 Anos ou mais , Japão , Indóis , Pirimidinas
3.
JAMA Oncol ; 10(4): 439-447, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38451530

RESUMO

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


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Masculino , Humanos , Idoso , Feminino , Antígeno B7-H1 , Estudos Retrospectivos , Recidiva Local de Neoplasia , Imunoterapia
4.
Clin Cancer Res ; 30(6): 1104-1110, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38165684

RESUMO

PURPOSE: Concurrent chemoradiotherapy (CCRT) followed by durvalumab consolidation for up to 12 months is the standard of care for patients with unresectable stage III non-small cell lung cancer (NSCLC). However, exactly when to initiate durvalumab therapy after chemoradiation completion remains unknown. We evaluated the efficacy and safety of durvalumab, administered immediately after CCRT completion, for patients with unresectable stage III NSCLC. PATIENTS AND METHODS: This study was a prospective, single-arm, open-label phase II clinical trial. Patients without disease progression after definitive CCRT (two cycles of platinum-based doublet chemotherapy with 60 Gy/30 Fr radiotherapy) received durvalumab (every 2 weeks for up to 12 months) from the next day (up to 5 days) after the final radiation dose. The primary endpoint was the 1-year progression-free survival (PFS) from registration before the start of CCRT. RESULTS: From January 2020 to August 2020, 47 of 50 enrolled patients were evaluable for treatment efficacy and safety. The 1-year PFS from registration was 75.0% [60% confidence interval (CI), 69.0-80.0 and 95% CI, 59.4-85.3]. The objective response rate throughout the study treatment and median PFS from registration were 78.7% and 14.2 months (95% CI, 13.4 to not reached), respectively. Grade 3/4 pneumonitis and febrile neutropenia were each 4.3%. CONCLUSIONS: Our study met the primary endpoint. The incidence of pneumonitis was similar to that of a Japanese subset in the PACIFIC study. Our data support the efficacy and safety of durvalumab administered immediately after the completion of CCRT for patients with unresectable stage III NSCLC.


Assuntos
Anticorpos Monoclonais , Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Pneumonia , Humanos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Estudos Prospectivos , Estadiamento de Neoplasias , Quimiorradioterapia/efeitos adversos
5.
Clin Lung Cancer ; 25(1): 85-90, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-37981477

RESUMO

BACKGROUND: According to the results of the KEYNOTE-407 trial, pembrolizumab plus platinum-based chemotherapy is the standard of care for patients with previously untreated advanced squamous non-small-cell lung cancer (NSCLC). Ubenimex, a potent aminopeptidase inhibitor, is an oral drug with immunostimulatory and antitumor activities. We aim to assess the safety and efficacy of ubenimex in combination with pembrolizumab, nab-paclitaxel, and carboplatin in patients with previously untreated advanced squamous NSCLC. PATIENTS AND METHODS: This prospective, single-arm, multicenter, phase II clinical trial is conducted to confirm the tolerability and efficacy of the tested drugs. Patients with previously untreated advanced squamous NSCLC will receive a predetermined daily dose of ubenimex orally plus 4 cycles of pembrolizumab, nab-paclitaxel, and carboplatin, followed by continuous administration of ubenimex and pembrolizumab for a maximum of 2 years. To confirm tolerability, the daily dose of ubenimex will begin at level 1 (30 mg), which will be increased to levels 2 (60 mg) and 3 (120 mg) according to the escalation criteria, with a standard 3 + 3 design for achieving the target dose-limiting toxicity rate of 33%. The efficacy, safety, and tolerability of ubenimex at the determined dose level will be analyzed. The primary endpoint of the efficacy evaluation will be the objective response rate assessed by an independent review committee. CONCLUSIONS: This is the first study to evaluate the efficacy and safety of ubenimex combined with pembrolizumab, nab-paclitaxel, and carboplatin in patients with previously untreated advanced squamous NSCLC. The results will help devise future treatment strategies.


Assuntos
Anticorpos Monoclonais Humanizados , Carcinoma Pulmonar de Células não Pequenas , Carcinoma de Células Escamosas , Leucina/análogos & derivados , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/patologia , Carboplatina , Neoplasias Pulmonares/patologia , Estudos Prospectivos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Paclitaxel , Albuminas , Carcinoma de Células Escamosas/tratamento farmacológico
7.
Transl Cancer Res ; 12(4): 873-886, 2023 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-37180670

RESUMO

Background: Currently, only a few treatment options exist for performance status (PS) 2 patients with advanced non-small cell lung cancer (NSCLC), whereas the carboplatin/nab-paclitaxel (CBDCA/nab-PTX) regimen is attracting attention as a standard of care for PS 0-1 patients because of its wide suitability and modest risk of peripheral neuropathy. However, the treatment dose and schedule should be optimized for PS 2 patients. Therefore, we planned a single-arm phase II study to characterize the efficacy and tolerability of our modified CBDCA/nab-PTX regimen for untreated PS 2 patients with advanced NSCLC. Methods: Enrolled patients were treated with CBDCA (area under the curve 5 on day 1) plus nab-PTX (70 mg/m2 on days 1, 8, and 15) every 4 weeks for up to six cycles. The primary endpoint was the progression-free survival (PFS) rate at 6 months. As exploratory analyses, the reasons for PS 2 (disease burden versus comorbidities/indeterminant) and the Charlson Comorbidity Index (CCI) were evaluated as efficacy indicators. Results: This study was terminated early because of slow accrual. Seventeen patients [median age, 68 years (range, 50-73 years)] received a median of three cycles. The 6-month PFS rate, median PFS, and median overall survival were 20.8% [95% confidence interval (CI): 0-41.6], 3.0 months (95% CI: 1.7-4.3), and 9.5 months (95% CI: 5.0-14.0), respectively. Exploratory analyses suggested better overall survival in patients whose PS was not attributable to the disease burden (median, 9.5 vs. 7.2 months) or whose CCI was ≤3 (median, 15.5 vs. 7.2 months). Grade 3-4 adverse events occurred in 12 (71%) patients, and grade 5 pleural infection occurred in one (6%) patient. Meanwhile, only one (6%) patient each experienced grade 1 peripheral neuropathy and grade 2 interstitial pneumonitis. Conclusions: No conclusion could be drawn from this study because of its early termination. However, our modified CBDCA/nab-PTX regimen might be useful for PS 2 patients who hesitate to use regimens other than nab-PTX, and particularly patients concerned about peripheral neuropathy or interstitial pneumonitis. The potential role of PS 2 and CCI as efficacy predictors for this regimen should be further examined.

9.
Acta Med Okayama ; 77(2): 199-201, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37094958

RESUMO

Meningitis-retention syndrome (MRS) is the combination of aseptic meningitis and acute urinary retention that occurs in the absence of other neurological diseases. The cause(s) of MRS remain unclear. A 57-year-old Japanese woman was referred to our hospital for the evaluation of persistent fever and headache. The fever's cause was initially unclear, but the presence of urinary retention raised concern about possible aseptic meningitis despite no physical indications of meningeal irritation. Only typical cases of MRS have been reported thus far to our knowledge, and it is important that clinicians are aware of MRS when it presents in this atypical form.


Assuntos
Meningite Asséptica , Meningite , Retenção Urinária , Feminino , Humanos , Pessoa de Meia-Idade , Meningite Asséptica/complicações , Meningite Asséptica/diagnóstico , Retenção Urinária/diagnóstico , Retenção Urinária/etiologia , Síndrome , Hospitais
10.
Cureus ; 15(2): e34846, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36923181

RESUMO

Pulmonary endarterectomy (PEA) is the standard treatment for chronic thromboembolic pulmonary hypertension (CTEPH). However, repeating surgery in recurrent cases is generally deemed high-risk. Balloon pulmonary angioplasty (BPA), an alternative treatment for organized thrombotic lesions of the peripheral pulmonary artery, has also shown a good prognosis in cases of inoperable CTEPH. Here, we report the case of a 65-year-old woman who presented with dyspnea. She had been admitted to our hospital in 2015 and diagnosed with University of San Diego (USD)-California classification CTEPH of level II. PEA had been performed, which resolved her respiratory discomfort, and her WHO functional class had improved from IV to I. Post-surgery pulmonary angiography had shown several residual lesions; nonetheless, pulmonary hypertension had not been noted, and the patient had not experienced dyspnea thereafter. We had decided to continue medical therapy; however, the patient stopped taking anticoagulation and pulmonary vasodilators due to the absence of symptoms. In 2021, dyspnea recurred, and she was hospitalized for examination. Chest radiography showed no cardiomegaly, and heart failure and tricuspid regurgitation were absent on echocardiography. The six-minute walk test distance was 565 m, and the lowest oxygen saturation during the test was 92%. Right heart catheterization demonstrated a mean pulmonary arterial pressure (PAP) of 15 mmHg without pulmonary hypertension; however, pulmonary angiography showed new organized thrombotic lesions in the left segments of the lower lobe. Based on the advancement of the lesions, we speculated that they were the cause of the symptoms even without concurrent pulmonary hypertension. Therefore, we performed two additional BPA procedures. Subsequently, the mean PAP decreased further to 13 mmHg. The patient's symptoms improved, the six-minute walk test distance increased to 656 m, and the WHO functional class returned to I. In conclusion, BPA for recurrent lesions after surgery for CTEPH can improve the patient's symptoms and exercise tolerance.

11.
Eur Heart J Case Rep ; 7(3): ytad106, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36949868

RESUMO

Background: Chronic thromboembolic pulmonary hypertension (CTEPH) is a rare thromboembolic disease, with occasional critical consequences. Essential thrombocythaemia (ET) is associated with an increased incidence of venous and arterial thrombotic events. In addition, the JAK2-V617F mutation increases the risk of thrombosis. Few reports have evaluated the utility of balloon pulmonary angioplasty (BPA) for worsening CTEPH with ET and the JAK2-V617F mutation. Case Summary: A 76-year-old woman, diagnosed with ET and the JAK2-V617F mutation, presented with dyspnoea. Echocardiography showed severe tricuspid regurgitation with a flattened interventricular septum. Contrast-enhanced computed tomography showed an eccentric thrombus in the right main pulmonary artery (PA) and thrombi in bilateral peripheral PAs. Acute pulmonary embolism (PE) was initially diagnosed, and heparinization was initiated; however, her oxygen saturation gradually worsened despite continued anticoagulation therapy. Her oxygen saturation level decreased to 90% (under a reservoir mask of 10 L). Her haemodynamics suggested CTEPH comorbidity. We decided to perform emergency right heart catheterization (RHC) and pulmonary angiography (PAG). RHC showed severe pulmonary hypertension. PAG showed fresh and organized thrombi and web regions in several segmental PAs. These findings indicated a combination of acute PE and CTEPH. Rescue BPA was performed on the right A1, A3, A8, and A9 segments. After BPA, the patient's oxygen saturation showed marked improvement. The patient was discharged 18 days after hospitalization without complications. Discussion: Rescue BPA could be an effective treatment for worsening CTEPH in severely impaired conditions, even with ET and the JAK2-V617F mutation.

13.
Eur Heart J Case Rep ; 7(2): ytad040, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36761282

RESUMO

A 77-year-old man presented with dyspnoea and was diagnosed with chronic thromboembolic pulmonary hypertension. Balloon pulmonary angioplasty was attempted; however, the balloons could not be advanced to the total occlusion lesion in the right A3 segment. The obstruction was overcome using a microcatheter Corsair (AsahiKASEI). This technique may be useful in managing a total occlusion lesion.

14.
Clin Case Rep ; 10(12): e6738, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36523383

RESUMO

The standard treatment of chronic thromboembolic pulmonary hypertension (CTEPH) is pulmonary endarterectomy (PEA); however, it may be unsuitable in the presence of comorbidities such as cardiac shock and severe hypoxia. We describe a successful case of emergent balloon pulmonary angioplasty performed before PEA in a patient with deteriorating central-type CTEPH.

15.
Oncologist ; 27(9): 720-e702, 2022 09 02.
Artigo em Inglês | MEDLINE | ID: mdl-35759340

RESUMO

BACKGROUND: Interstitial pneumonia (IP) is a poor prognostic comorbidity in patients with non-small cell lung cancer (NSCLC) and is also a risk factor for pneumonitis. The TORG1936/AMBITIOUS trial, the first known phase II study of atezolizumab in patients with NSCLC with comorbid IP, was terminated early because of the high incidence of severe pneumonitis. METHODS: This study included patients with idiopathic chronic fibrotic IP, with a predicted forced vital capacity (%FVC) of >70%, with or without honeycomb lung, who had previously been treated for NSCLC. The patients received atezolizumab every 3 weeks. The primary endpoint was the 1-year survival rate. RESULTS: A total of 17 patients were registered; the median %FVC was 85.4%, and 41.2% had honeycomb lungs. The 1-year survival rate was 53.3% (95% CI, 25.9-74.6). The median overall and progression-free survival times were 15.3 months (95% CI, 3.1-not reached) and 3.2 months (95% CI, 1.2-7.4), respectively. The incidence of pneumonitis was 29.4% for all grades, and 23.5% for grade ≥3. Tumor mutational burden and any of the detected somatic mutations were not associated with efficacy or risk of pneumonitis. CONCLUSION: Atezolizumab may be one of the treatment options for patients with NSCLC with comorbid IP, despite the high risk of developing pneumonitis. This clinical trial was retrospectively registered in the Japan Registry of Clinical Trials on August 26, 2019, (registry number: jRCTs031190084, https://jrct.niph.go.jp/en-latest-detail/jRCTs031190084).


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Pneumonias Intersticiais Idiopáticas , Neoplasias Pulmonares , Pneumonia , Anticorpos Monoclonais Humanizados , Carcinoma Pulmonar de Células não Pequenas/complicações , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Humanos , Pneumonias Intersticiais Idiopáticas/complicações , Pneumonias Intersticiais Idiopáticas/tratamento farmacológico , Neoplasias Pulmonares/complicações , Neoplasias Pulmonares/tratamento farmacológico
16.
Int J Clin Oncol ; 27(7): 1139-1144, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35534642

RESUMO

BACKGROUND: The role of pembrolizumab in the treatment of poor performance status (PS) patients remains unclear. PATIENTS AND METHODS: We conducted a phase II trial to investigate the efficacy and safety of pembrolizumab as first-line therapy for non-small-cell lung cancer (NSCLC) patients with PSs of 2-3 and programmed cell death ligand 1 (PD-L1) expression ≥ 50%. The primary endpoint of this study was the objective response rate (ORR). RESULTS: Fourteen patients treated at eight institutions were enrolled. Most patients had PS 2 (12/14; 86%) and others had PS 3 (2/14; 14%). The ORR was 57.1% (95% confidence interval 28.9-82.3%), which met the primary endpoint. The median progression-free survival (PFS) and 1-year PFS rates were 5.8 months and 20.0%, respectively. At the time of data cut-off, one patient had received treatment for more than 1 year; another patient had received treatment for more than 2 years. Nine patients had improved PS with treatment (Wilcoxon signed-rank test, p = 0.003). Two patients had immune-related adverse events ≥ grade 3: grades 5 and 3 elevation in alanine and aspartate aminotransferases. Two PS 3-stage patients were diagnosed with clinically progressive disease prior to initial computed tomography; both died within 2 months. CONCLUSION: Pembrolizumab was effective for the treatment of NSCLC patients with a poor PS and PD-L1 level ≥ 50%. However, given the poor outcomes of the PS 3 patients, the drug is not indicated for such patients. Adverse events, including liver dysfunction, should be carefully monitored. REGISTRATION ID: UMIN000030955.


Assuntos
Anticorpos Monoclonais Humanizados , Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Anticorpos Monoclonais Humanizados/efeitos adversos , Antígeno B7-H1/metabolismo , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/patologia , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia
17.
Heart ; 108(5): 382-387, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-34415851

RESUMO

OBJECTIVE: Therapeutic strategies for atrial septal defect (ASD) with severe pulmonary arterial hypertension (PAH) are controversial. This study aimed to evaluate the efficacy of PAH-specific medications and subsequent transcatheter closure (ie, treat-and-repair strategy) on clinical outcomes. METHODS: We enrolled 42 patients who were referred to 13 institutions for consideration of ASD closure with concomitant PAH and underwent the treat-and-repair strategy. The endpoint was cardiovascular death or hospitalisation due to heart failure or exacerbated PAH. RESULTS: At baseline prior to PAH-specific medications, pulmonary to systemic blood flow ratio (Qp:Qs), pulmonary vascular resistance (PVR), and mean pulmonary artery pressure (PAP) were 1.9±0.8, 6.9±3.2 Wood units and 45±15 mm Hg. Qp:Qs was increased to 2.4±1.2, and PVR and mean PAP were decreased to 4.0±1.5 Wood units and 35±9 mm Hg at the time of transcatheter ASD closure after PAH-specific medications. Transcatheter ASD closure was performed without any complications. During a median follow-up period of 33 months (1-126 months) after transcatheter ASD closure, one older patient died and one patient was hospitalised due to heart failure, but the other patients survived with an improvement in WHO functional class. PAP was further decreased after transcatheter ASD closure. CONCLUSIONS: The treat-and-repair strategy results in low complication and mortality rates with a reduction in PAP in selected patients with ASD complicated with PAH who have a favourable response of medical therapy.


Assuntos
Insuficiência Cardíaca , Comunicação Interatrial , Hipertensão Pulmonar , Hipertensão Arterial Pulmonar , Cateterismo Cardíaco/efeitos adversos , Hipertensão Pulmonar Primária Familiar , Insuficiência Cardíaca/etiologia , Comunicação Interatrial/complicações , Comunicação Interatrial/terapia , Humanos , Hipertensão Pulmonar/diagnóstico , Hipertensão Pulmonar/etiologia , Hipertensão Pulmonar/terapia , Hipertensão Arterial Pulmonar/diagnóstico , Hipertensão Arterial Pulmonar/etiologia , Hipertensão Arterial Pulmonar/terapia , Resultado do Tratamento
20.
Eur J Cancer ; 149: 73-81, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33838391

RESUMO

BACKGROUND: Immune checkpoint inhibitors (ICIs) are essential for treatment of various malignancies, including non-small-cell lung cancer (NSCLC). Recently, several studies have shown that the gut microbiome plays an important role in ICI treatment of solid cancers, and antibiotic (ATB) use had a negative impact on the outcomes of ICI treatment via dysbiosis in the gut. However, whether this is applicable to NSCLC remains unclear. The impact of ATBs based on PD-L1 expression also remains unclear. METHODS: We retrospectively reviewed the medical records of patients with NSCLC who received ICI monotherapy (anti-PD-1 or anti-PD-L1 antibody) at nine institutions from December 2015 to May 2018. Outcomes with use of ATBs during the 2 months before or a month after initiation of ICI treatment, including progression-free survival (PFS) and overall survival (OS), were investigated using the Kaplan-Meier method. Multivariate analysis was also conducted using a Cox proportional hazards model. RESULTS: A total of 531 patients were included in this study, among whom 98 (18.5%) received ATBs before or after ICI treatment. ATB use was significantly associated with a shorter median OS (11.7 months in the ATB group vs. 16.1 months in the non-ATB group; p = 0.028), whereas the difference in PFS was not significant (3.5 months in both the groups; p = 0.287). We next investigated the association based on PD-L1 expression in the 265 patients for whom PD-L1 expression was determined. There was no significant difference in the median OS or PFS between patients with NSCLC and PD-L1 expression <50% receiving ATBs and those not receiving ATBs (PFS: 3.3 vs. 2.8 months, p = 0.88; OS: 9.5 vs. 17.1 months, p = 0.24). Conversely, patients with NSCLC and PD-L1 expression ≥50% receiving ATBs showed significantly shorter median PFS and OS (PFS: 4.2 vs. 9.4 months, p = 0.012; OS: 11.9 vs. 28.4 months, p = 0.011). The impact of ATBs in patients with NSCLC and PD-L1 expression ≥50% was more significant than that in the entire cohort. CONCLUSIONS: Our results indicate that the impact of ATB use on the efficacy of ICIs differed based on PD-L1 expression in patients with advanced NSCLC. A negative impact of ATB use was found in patients with NSCLC and PD-L1 expression ≥50% but not in those with PD-L1 expression <50%.


Assuntos
Antibacterianos/uso terapêutico , Antígeno B7-H1/antagonistas & inibidores , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Inibidores de Checkpoint Imunológico/uso terapêutico , Neoplasias Pulmonares/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Antibacterianos/efeitos adversos , Antígeno B7-H1/imunologia , Carcinoma Pulmonar de Células não Pequenas/imunologia , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma Pulmonar de Células não Pequenas/patologia , Interações Medicamentosas , Disbiose , Feminino , Microbioma Gastrointestinal/efeitos dos fármacos , Humanos , Inibidores de Checkpoint Imunológico/efeitos adversos , Japão , Neoplasias Pulmonares/imunologia , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Polimedicação , Intervalo Livre de Progressão , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Fatores de Tempo
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