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European Journal of Nuclear Medicine... Jul 2024The study aims to investigate the role of dynamic [F]FDG PET/CT imaging by high-sensitivity PET/CT scanner for assessing patients with locally advanced non-small cell...
Repeated dynamic [F]FDG PET/CT imaging using a high-sensitivity PET/CT scanner for assessing non-small cell lung cancer patients undergoing induction immuno-chemotherapy followed by hypo-fractionated chemoradiotherapy and consolidative immunotherapy: report from a prospective observational study...
OBJECTIVE
The study aims to investigate the role of dynamic [F]FDG PET/CT imaging by high-sensitivity PET/CT scanner for assessing patients with locally advanced non-small cell lung cancer (LA-NSCLC) who undergo induction immuno-chemotherapy, followed by concurrent hypo-fractionated chemoradiotherapy (hypo-CCRT) and consolidative immunotherapy.
METHODS
Patients with unresectable LA-NSCLC are prospectively recruited. Dynamic [F]FDG PET/CT scans are conducted at four timepoints: before treatment (Baseline), after induction immuno-chemotherapy (Post-IC), during hypo-CCRT (Mid-hypo-CCRT) and after hypo-CCRT (Post-hypo-CCRT). The primary lung tumors (PTs) are manually delineated, and the metabolic features, including the Patlak-Ki (Ki), maximum SUV (SUV), metabolic tumor volume (MTV) and total lesion glycolysis (TLG) have been evaluated. The expressions of CD3, CD8, CD68, CD163, CD34 and Ki67 in primary lung tumors at baseline are assayed by immunohistochemistry. The levels of blood lymphocytes at four timepoints are analyzed with flow cytometry.
RESULTS
Fifteen LA-NSCLC patients are enrolled between December 2020 and December 2022. Baseline Ki of primary tumor yields the highest AUC values of 0.722 and 0.796 for predicting disease progression and patient death, respectively. Patients are classified into the High FDG Ki group (n = 8, Ki > 2.779 ml/min/100 g) and the Low FDG Ki group (n = 7, Ki ≤ 2.779 ml/min/100 g). The High FDG Ki group presents better progression-free survival (P = 0.01) and overall survival (P = 0.025). The High FDG Ki group exhibits more significant reductions in Ki after hypo-CCRT compared to the Low FDG Ki group. Patients with a reduction in Ki > 73.1% exhibit better progression-free survival than those with a reduction ≤ 73.1% in Ki (median: not reached vs. 7.33 months, P = 0.12). The levels of CD3 T cells (P = 0.003), CD8 T cells (P = 0.002), CD68 macrophages (P = 0.071) and CD163 macrophages (P = 0.012) in primary tumor tissues are higher in the High FDG Ki group. The High FDG Ki group has higher CD3CD8 lymphocytes in blood at baseline (P = 0.108), post-IC (P = 0.023) and post-hypo-CCRT (P = 0.041) than the Low FDG Ki group.
CONCLUSIONS
The metabolic features in the High FDG Ki group significantly decrease during the treatment, particularly after induction immuno-chemotherapy. The Ki value of primary tumor shows significant relationship with the treatment response and survival in LA-NSCLC patients by the combined immuno-chemoradiotherapy regimen.
TRIAL REGISTRATION
ClinicalTrials.gov. NCT04654234. Registered 4 December 2020.
PubMed: 38953934
DOI: 10.1007/s00259-024-06819-2 -
European Annals of Allergy and Clinical... Jul 2024Papular Urticaria (PU) is a cutaneous hypersensitivity disorder triggered by hematophagous arthropod bites. Despite being a common condition, especially in tropical...
Papular Urticaria (PU) is a cutaneous hypersensitivity disorder triggered by hematophagous arthropod bites. Despite being a common condition, especially in tropical environments, many knowledge gaps are observed for this disease. The main objective of this study was to investigate the patterns of humoral immune response to mosquito antigens in children with PU and establish a correlation between this response and the severity of clinical symptoms. An analytical cross-sectional observational study was carried out. Clinical and sociodemographic data and children's blood samples were collected to measure the specific antibodies from: 1. A. aegypti salivary gland antigens; 2. A. aegypti whole body antigens (both produced in the laboratory of the Center for Health Sciences at the Federal University of Rio de Janeiro). A PU severity score based on clinical data is proposed to correlate disease severity with antibody reactivity signatures. According to the clinical data, 58.9% of children received high severity scores. A significant statistical correlation was found between patients with high PU severity score and the development of symptoms before the age of two (p = 0.0326) and high IgG4 anti-salivary gland antigens concentration (p less than 0.05). It is suggested that PU severity in children is associated with a high concentration of IgG4 anti-salivary gland antigens from Aedes aegypti. Further studies are recommended to deepen the understanding of the mechanisms involved.
PubMed: 38953876
DOI: 10.23822/EurAnnACI.1764-1489.352 -
Blood Cancer Discovery Jul 2024This real-world prospective observational study across 21 Italian centers (CART-SIE) compares axicabtagene ciloleucel (axi-cel) and tisagenlecleucel (tisa-cel) outcomes...
This real-world prospective observational study across 21 Italian centers (CART-SIE) compares axicabtagene ciloleucel (axi-cel) and tisagenlecleucel (tisa-cel) outcomes in 485 relapsed-refractory large B-cell lymphoma patients with baseline characteristics matched by Stabilized Inverse Propensity-Score Weighting. Axi-cel versus tisa-cel had higher all-grade cytokine release syndrome (78.6% vs 89.3%, p=0.0017) and neurotoxicity (9.9% vs 32.2%, p<0.0001), but also superior progression-free survival (PFS) at one year (46.5% vs 34.1%, p=0.0009). Even among patients who failed bridging therapy, axi-cel PFS was superior to tisa-cel (37.5% vs 22.7%, p=0.0059). Differences in overall survival (OS) and high-grade immune toxicities were not significant. The CAR-HEMATOTOX score not only predicted hematologic toxicity but also 1-year survival outcomes (51.5% in CAR-HEMATOTOX high vs. 77.2% in CAR-HEMATOTOX low, p<0.0001). Twenty patients developed second primary malignancies, including two cases of T-cell neoplasms. These findings enable more informed selection of anti-CD19 CAR T-cell therapy balancing bridging, safety and efficacy considerations for individual patients.
PubMed: 38953781
DOI: 10.1158/2643-3230.BCD-24-0052 -
Journal of Bronchology & Interventional... Jul 2024CT-to-body divergence-described as the difference between preprocedural CT scans and intraprocedural lung architecture-is a significant barrier to improving diagnostic... (Observational Study)
Observational Study
BACKGROUND
CT-to-body divergence-described as the difference between preprocedural CT scans and intraprocedural lung architecture-is a significant barrier to improving diagnostic yield during navigational bronchoscopy. A major proposed contributor to CT-to-body divergence is the development of atelectasis, which can confound visualization of peripheral lung lesions via radial probe endobronchial ultrasound (RP-EBUS). High positive end-expiratory pressure (PEEP) ventilatory strategies have been used to decrease atelectasis, allowing the lesion to re-APPEAR on intraprocedure imaging. However, standardized PEEP levels may not be appropriate for all patients due to hemodynamic and ventilatory impacts.
METHODS
We performed a multicenter, prospective observational study in which patients were imaged with RP-EBUS under general anesthesia to determine if subsegmental atelectasis would resolve as incremental increases in PEEP were applied. Resolution of atelectasis was based on the transition from a non-aerated pattern to an aerated appearance on RP-EBUS. RP-EBUS images were reviewed by 3 experienced operators to determine correlation.
RESULTS
Forty-three patients underwent RP-EBUS examination following navigational bronchoscopy. Thirty-seven patients underwent incremental PEEP application and subsequent RP-EBUS imaging. Atelectasis was determined to have resolved in 33 patients (88.2%) following increased PEEP. The intraclass correlation coefficient between reviewers was 0.76. A recruitment maneuver was performed in 7 (16.3%) patients after atelectasis persisted at maximal PEEP. Atelectasis was not identified in the examined subsegments in 6 (10.8%) patients despite zero PEEP.
CONCLUSION
RP-EBUS is an effective tool to monitor what pressure atelectasis within a lung segment has resolved with increasing levels of PEEP.
Topics: Humans; Positive-Pressure Respiration; Pulmonary Atelectasis; Bronchoscopy; Prospective Studies; Male; Female; Aged; Middle Aged; Endosonography; Tomography, X-Ray Computed
PubMed: 38953737
DOI: 10.1097/LBR.0000000000000969 -
Pediatric Pulmonology Jul 2024An inadequate clearance of lung fluid plays a key role in the pathogenesis of transient tachypnea of the newborn (TTN).
INTRODUCTION
An inadequate clearance of lung fluid plays a key role in the pathogenesis of transient tachypnea of the newborn (TTN).
OBJECTIVES
To evaluate if left ventricular diastolic dysfunction contributes to reduced clearance of lung fluid in TTN.
MATERIALS AND METHODS
This was a prospective, observational study. Echocardiography and lung ultrasound were performed at 2, 24 and 48 h of life (HoL) to assess biventricular function and calculate lung ultrasound score (LUS). Left atrial strain reservoir (LASr) provided surrogate measurement of left ventricular diastolic function.
RESULTS
Twenty-seven neonates with TTN were compared with 27 controls with no difference in gestation (36.1 ± 2 vs. 36.9 ± 2 weeks) or birthweight (2508 ± 667 vs. 2718 ± 590 g). Biventricular systolic function was normal in both groups. LASr was significantly lower in cases at 2 (21.0 ± 2.7 vs. 38.1 ± 4.4; p < 0.01), 24 (25.2 ± 4.5 vs. 40.6 ± 4.0; p < 0.01) and 48 HoL (36.5 ± 5.8 and 41.6 ± 5.2; p < 0.01), resulting in a significant group by time interaction (p < 0.001), after adjusting for LUS and gestational diabetes. A logistic regression model including LUS, birth weight and gestational diabetes as covariates, showed that LASr at 2 HoL was a predictor of respiratory support at 24 HoL, with an adjusted odds ratio of 0.60 (CI 0.36-0.99).
CONCLUSIONS
LASr was reduced in neonates with TTN, suggesting diastolic dysfunction, that may contribute to the delay in lung fluid clearance.
PubMed: 38953730
DOI: 10.1002/ppul.27156 -
Clinical Cardiology Jul 2024The DESyne novolimus-eluting coronary stent (NES) is a new-generation drug-eluting stent (DES) that is widely used, but clinical data are rarely reported for this stent.... (Observational Study)
Observational Study Comparative Study
INTRODUCTION
The DESyne novolimus-eluting coronary stent (NES) is a new-generation drug-eluting stent (DES) that is widely used, but clinical data are rarely reported for this stent. We compared the safety and effectiveness of the DESyne NES and the Orsiro bioresorbable polymer sirolimus-eluting stent (SES) in patients undergoing percutaneous coronary intervention (PCI).
METHODS
This was a retrospective, single-center, observational study. Between July 2017 and December 2022, patients who presented with chronic or acute coronary syndrome undergoing PCI with DESyne NES or Orsiro SES were consecutively enrolled in the present study. The primary endpoint, major adverse cardiovascular event (MACE), was a composite of cardiovascular death, target-vessel myocardial infarction, or clinically driven target-lesion revascularization.
RESULTS
A total of 776 patients (age 68.8 ± 12.2; 75.9% male) undergoing PCI were included. Overall, 231 patients with 313 lesions received NES and 545 patients with 846 lesions received SES. During a follow-up duration of 784 ± 522 days, the primary endpoint occurred in 10 patients (4.3%) in the NES group and in 36 patients (6.6%) in the SES group. After multivariate adjustment, the risk of MACE did not significantly differ between groups (NES vs. SES, hazard ratio 0.74, 95% CI, 0.35-1.55, p = 0.425). The event rate of individual components of the primary endpoint was comparable between the two groups.
CONCLUSIONS
Favorable and similar clinical outcomes were observed in patients undergoing PCI with either NES or SES in a medium-term follow-up duration. Future studies with adequately powered clinical endpoints are required for further evaluation.
Topics: Humans; Drug-Eluting Stents; Male; Female; Sirolimus; Retrospective Studies; Aged; Percutaneous Coronary Intervention; Treatment Outcome; Prosthesis Design; Coronary Artery Disease; Time Factors; Follow-Up Studies; Acute Coronary Syndrome; Risk Factors; Middle Aged; Coronary Angiography; Macrolides
PubMed: 38953595
DOI: 10.1002/clc.24317 -
Lung India : Official Organ of Indian... Jul 2024Lung transplant (LTx) is a potential treatment option for all patients with chronic, end-stage respiratory disease, who are refractory to optimal medical therapy or...
INTRODUCTION
Lung transplant (LTx) is a potential treatment option for all patients with chronic, end-stage respiratory disease, who are refractory to optimal medical therapy or where no medical therapy exists. In India, LTx is still in its evolving stages and published literature is sparse. The current study was carried out to study the selection criteria for lung transplant and to evaluate the clinical and socio-economic profile of patients referred for the same at a tertiary health care facility.
METHODS
The study was a descriptive, prospective, observational study. All adults referred for lung transplant were evaluated for clinical and laboratory profiles. All enrolled patients were assessed for presence of referral criteria, listing criteria, contraindications, and willingness for lung transplant. These patients were followed up for 2 years for transplant-free survival, and the Cox proportional hazards model was used to determine independent predictors of all-cause mortality.
RESULTS
A total of 103 were included in study. The most common diagnosis was interstitial lung disease (57.2%), followed by bronchiectasis (17.5%) and COPD (13.6%). Most patients were referred for LTx at an advanced stage as 90% met listing criteria. Fifty-four (52.4%) patients had an absolute or relative contraindication to transplant; however, the majority of those contraindications were modifiable. Patients with a lower socio-economic status were less likely to be willing for LTx. The median survival was 757 days. A 6-minute walk distance (6MWD) lesser than 250 m was found to be an independent predictor of mortality.
CONCLUSION
Making patients aware about lung transplant early in their treatment may give them sufficient time to come to terms with their disease and understand the risk and benefits associated. Efforts should be focused on screening and early treatment of reversible contraindications for the eligible patients. Patients with 6MWD < 250 m are at increased risk of mortality.
PubMed: 38953189
DOI: 10.4103/lungindia.lungindia_515_23 -
Otolaryngology--head and Neck Surgery :... Jul 2024The development of acquired middle ear cholesteatoma is associated with a single nucleotide polymorphism, 538G>A, in the human adenosine triphosphate-binding cassette...
OBJECTIVE
The development of acquired middle ear cholesteatoma is associated with a single nucleotide polymorphism, 538G>A, in the human adenosine triphosphate-binding cassette transporter C11 (ABCC11) gene, which is a determinant of the earwax morphotype, such as wet- and dry-type earwax; however, the mechanism underlying this association is unclear. We focused on the earwax pH and aimed to elucidate the mechanism between ABCC11 genotypes and acquired middle ear cholesteatoma.
STUDY DESIGN
Prospective observational study.
SETTING
Single-center, academic hospital.
METHODS
We recruited 40 patients with acquired middle ear cholesteatoma who underwent surgery and 115 controls with no history of middle ear cholesteatoma. We assessed the earwax pH and ABCC11 genotypes in all participants. Clinical information was collected from the patients with cholesteatoma.
RESULTS
The earwax pH was significantly less acidic in patients with cholesteatoma and those carrying wet earwax genotypes (ABCC11 538G/G or 538G/A) than in the controls and those carrying the dry earwax genotype (ABCC11 538A/A), respectively. Furthermore, earwax pH was significantly positively correlated with high preoperative cholesteatoma stages in the patients with cholesteatoma.
CONCLUSION
Our results show that the less acidic earwax pH was significantly related to the development and progression of acquired middle ear cholesteatoma. The less acidic earwax pH may play an important role in the mechanism underlying the association between acquired middle ear cholesteatoma and the ABCC11 gene at site 538.
PubMed: 38953179
DOI: 10.1002/ohn.888 -
Frontiers in Immunology 2024Unbalanced inflammatory response is a critical feature of sepsis, a life-threatening condition with significant global health burdens. Immune dysfunction, particularly... (Observational Study)
Observational Study
BACKGROUND
Unbalanced inflammatory response is a critical feature of sepsis, a life-threatening condition with significant global health burdens. Immune dysfunction, particularly that involving different immune cells in peripheral blood, plays a crucial pathophysiological role and shows early warning signs in sepsis. The objective is to explore the relationship between sepsis and immune subpopulations in peripheral blood, and to identify patients with a higher risk of 28-day mortality based on immunological subtypes with machine-learning (ML) model.
METHODS
Patients were enrolled according to the sepsis-3 criteria in this retrospective observational study, along with age- and sex-matched healthy controls (HCs). Data on clinical characteristics, laboratory tests, and lymphocyte immunophenotyping were collected. XGBoost and k-means clustering as ML approaches, were employed to analyze the immune profiles and stratify septic patients based on their immunological subtypes. Cox regression survival analysis was used to identify potential biomarkers and to assess their association with 28-day mortality. The accuracy of biomarkers for mortality was determined by the area under the receiver operating characteristic (ROC) curve (AUC) analysis.
RESULTS
The study enrolled 100 septic patients and 89 HCs, revealing distinct lymphocyte profiles between the two groups. The XGBoost model discriminated sepsis from HCs with an area under the receiver operating characteristic curve of 1.0 and 0.99 in the training and testing set, respectively. Within the model, the top three highest important contributions were the percentage of CD38CD8T cells, PD-1NK cells, HLA-DRCD8T cells. Two clusters of peripheral immunophenotyping of septic patients by k-means clustering were conducted. Cluster 1 featured higher proportions of PD1 NK cells, while cluster 2 featured higher proportions of naïve CD4T cells. Furthermore, the level of PD-1NK cells was significantly higher in the non-survivors than the survivors (15.1% vs 8.6%, <0.01). Moreover, the levels of PD1 NK cells combined with SOFA score showed good performance in predicting the 28-day mortality in sepsis (AUC=0.91,95%CI 0.82-0.99), which is superior to PD1 NK cells only(AUC=0.69, sensitivity 0.74, specificity 0.64, cut-off value of 11.25%). In the multivariate Cox regression, high expression of PD1 NK cells proportion was related to 28-day mortality (aHR=1.34, 95%CI 1.19 to 1.50; <0.001).
CONCLUSION
The study provides novel insights into the association between PD1NK cell profiles and prognosis of sepsis. Peripheral immunophenotyping could potentially stratify the septic patients and identify those with a high risk of 28-day mortality.
Topics: Humans; Sepsis; Male; Female; Programmed Cell Death 1 Receptor; Middle Aged; Aged; Killer Cells, Natural; Retrospective Studies; Biomarkers; Prognosis; Immunophenotyping; ROC Curve; Machine Learning
PubMed: 38953031
DOI: 10.3389/fimmu.2024.1426064 -
Iranian Journal of Medical Sciences Jun 2024Children with Congenital Adrenal Hyperplasia (CAH) have a higher chance of hypertension. The likelihood of hypertension is higher in CAH children who get fludrocortisone... (Observational Study)
Observational Study
BACKGROUND
Children with Congenital Adrenal Hyperplasia (CAH) have a higher chance of hypertension. The likelihood of hypertension is higher in CAH children who get fludrocortisone medication and have an over-suppression. Plasma renin activity (PRA) is a sensitive indicator when the fludrocortisone dose is insufficient. The objective of this study is to assess the relationship between plasma renin activity with hypertension in 21-hydroxylase-deficient (21-OHD) CAH children.
METHODS
This cross-sectional observational analytical study was conducted in 2019 at the Pediatric Endocrinology Outpatient Clinic in Dr. Cipto Mangunkusumo Hospital (RSCM), Jakarta, Indonesia. The subjects were 21-OHD CAH children, aged >6 months to 18 years who had already taken hydrocortisone with or without fludrocortisone for at least 6 months, and were divided into hypertension and non-hypertension groups. The subjects were selected by a consecutive sampling method. Data was analyzed using SPSS software (version 23.0) with unpaired test analysis and multiple logistic regression test. Statistical significance was achieved if P<0.05.
RESULTS
Forty 21-OHD CAH patients were included, and 20 subjects (50%) had hypertension. A higher incidence of hypertension was found in salt-wasting CAH than in simple virilizing types (59.3% vs 30.8%). There was a significant mean difference in PRA levels between hypertension and non-hypertension groups in salt-wasting patients (P=0.016). A significant difference between the last dose of hydrocortisone with the number of hypertension patients in salt-wasting patients (P=0.032) was found, and low PRA levels showed a 1.09 times higher risk of hypertension.
CONCLUSION
Children with salt-wasting CAH with low PRA levels had a higher risk of getting hypertension.
Topics: Humans; Adrenal Hyperplasia, Congenital; Renin; Child; Hypertension; Female; Male; Cross-Sectional Studies; Child, Preschool; Adolescent; Hydrocortisone; Infant; Indonesia; Fludrocortisone
PubMed: 38952640
DOI: 10.30476/ijms.2023.98508.3058