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The Journal of Dermatological Treatment Dec 2024Mycosis fungoides (MF) is the most common type of cutaneous T-cell lymphoma. This study was conducted to evaluate efficacy and safety of interferon (IFN) α-2a...
Mycosis fungoides (MF) is the most common type of cutaneous T-cell lymphoma. This study was conducted to evaluate efficacy and safety of interferon (IFN) α-2a combined with phototherapy for early-stage MF. Thirteen patients with early-stage MF received subcutaneous injections of IFN α-2a at 3 million IU combined with phototherapy three times per week for 6 months. Treatment efficacy was measured by changes in body surface area (BSA) score and modified severity-weighted assessment tool (mSWAT) score at 1, 3, and 6 months after treatment. Histopathologic examinations of skin lesions were performed before and after treatment. After 3 months of treatment, all 13 patients achieved a partial response, and BSA and mSWAT scores were significantly lower than those at baseline ( < 0.001). After 6 months, BSA and mSWAT scores were significantly lower than those at baseline ( < 0.001) and after 3 months ( < 0.05). Eleven patients achieved complete remission and two patients achieved a partial response (overall response rate, 100%). Histopathologic examination showed a significant decrease in the number of atypical lymphocytes in both epidermis and dermis. No severe adverse effects occurred. IFN α-2a in combination with phototherapy may be an effective and safe alternative modality for early-stage MF.
Topics: Humans; Mycosis Fungoides; Male; Middle Aged; Female; Prospective Studies; Skin Neoplasms; Adult; Interferon alpha-2; Treatment Outcome; Aged; Injections, Subcutaneous; Interferon-alpha; Combined Modality Therapy; Phototherapy; Neoplasm Staging; Recombinant Proteins
PubMed: 38754985
DOI: 10.1080/09546634.2024.2350231 -
Stroke and Vascular Neurology May 2024Remnant cholesterol (RC) is considered to be one of the most significant and important risk factors for atherosclerotic cardiovascular disease (ASCVD). Nonetheless, the...
BACKGROUND
Remnant cholesterol (RC) is considered to be one of the most significant and important risk factors for atherosclerotic cardiovascular disease (ASCVD). Nonetheless, the association between RC and unstable carotid plaque remains unclear. Our primary objective is to ascertain whether RC exhibits an independent and significant association with unstable carotid plaque in a neurologically healthy population.
METHODS
In the cross-sectional study, we enrolled neurologically healthy participants who visited our centre for health checkups between 2021 and 2022. All eligible participants underwent a standardised questionnaire, physical examinations and laboratory testing. The carotid plaque was evaluated with a standard carotid ultrasound and an advanced ultrasound imaging technique called superb microvascular imaging. The correlation between lipids and unstable carotid plaque was primarily assessed utilising univariate and multivariate logistic regression.
RESULTS
The study totally enrolled 1100 participants who had an average age of 57.00 years (IQR: 49.00-63.00), with 67.55% being men. Among the participants, 321 (29.18%) had unstable carotid plaque. In the multivariate logistic regression analysis, higher RC had an independent association with an elevated incidence of unstable carotid plaque compared with the lowest concentrations of RC (OR=1.673, 95% CI 1.113 to 2.515, p=0.0134), but not other lipids. In addition, apolipoprotein A1 was negatively related to unstable carotid plaque (OR=0.549, 95% CI 0.364 to 0.830, p=0.0045).
CONCLUSIONS
Elevated concentrations of RC are independently and excellently correlated with unstable carotid plaque within a neurologically healthy population.
PubMed: 38754970
DOI: 10.1136/svn-2023-002888 -
Journal For Immunotherapy of Cancer May 2024Chimeric antigen receptor (CAR) T cell therapies specific for the CD19 and B-cell maturation antigen have become an approved standard of care worldwide for relapsed and...
BACKGROUND
Chimeric antigen receptor (CAR) T cell therapies specific for the CD19 and B-cell maturation antigen have become an approved standard of care worldwide for relapsed and refractory B-cell malignancies. If CAR-T cell therapy for non-hematological malignancies is to achieve the same stage of clinical development, then iterative early-phase clinical testing can add value to the clinical development process for evaluating CAR-T cell products containing different CAR designs and manufactured under differing conditions.
METHODS
We conducted a phase 1 trial of third-generation GD2-specific CAR-T cell therapy, which has previously been tested in neuroblastoma patients. In this study, the GD2-CAR-T therapy was evaluated for the first time in metastatic melanoma patients in combination with BRAF/MEK inhibitor therapy, and as a monotherapy in patients with colorectal cancer and a patient with fibromyxoid sarcoma. Feasibility and safety were determined and persistence studies, multiplex cytokine arrays on sera and detailed immune phenotyping of the original CAR-T products, the circulating CAR-T cells, and, in select patients, the tumor-infiltrating CAR-T cells were performed.
RESULTS
We demonstrate the feasibility of manufacturing CAR-T products at point of care for patients with solid cancer and show that a single intravenous infusion was well tolerated with no dose-limiting toxicities or severe adverse events. In addition, we note significant improvements in CAR-T cell immune phenotype, and expansion when a modified manufacturing procedure was adopted for the latter 6 patients recruited to this 12-patient trial. We also show evidence of CAR-T cell-mediated immune activity and in some patients expanded subsets of circulating myeloid cells after CAR-T cell therapy.
CONCLUSIONS
This is the first report of third-generation GD2-targeting CAR-T cells in patients with metastatic melanoma and other solid cancers such as colorectal cancer, showing feasibility, safety and immune activity, but limited clinical effect.
TRIAL REGISTRATION NUMBER
ACTRN12613000198729.
Topics: Humans; Melanoma; Immunotherapy, Adoptive; Receptors, Chimeric Antigen; Male; Female; Middle Aged; Gangliosides; Adult; Aged; T-Lymphocytes; Treatment Outcome
PubMed: 38754916
DOI: 10.1136/jitc-2023-008659 -
BMJ Global Health May 2024Africa is experiencing a gradual demographic shift due to rising life expectancy and increasing urbanisation. In sub-Saharan Africa, elderly individuals typically reside...
INTRODUCTION
Africa is experiencing a gradual demographic shift due to rising life expectancy and increasing urbanisation. In sub-Saharan Africa, elderly individuals typically reside with their children. The rise in life expectancy by almost a decade and the prevalence of precarious living conditions raise concerns about the sustainability of the healthcare system, which has traditionally relied on intergenerational solidarity.
METHODS
The research aims to analyse the evolving role of older adults in Cameroonian society and to examine the potential impact of this change on intergenerational relationships and the health of older adults. A qualitative methodology was employed, using intergenerational focus groups in Cameroon.
RESULTS
Traditionally, older adults held a central role in knowledge transmission through discourse. However, the modernisation of society is challenging this position.The emergence of new technologies, particularly communication tools, is leading to a questioning of older adults' experiential knowledge. Societal changes are contributing to a decline in respect for older adults in discourse. Older adults deplore these societal changes and fear for their place in society while young people are questioning the central role of older people in society.
DISCUSSION
These changes could reduce the sense of usefulness of older people, with negative consequences for their health. Several studies have highlighted the impacts of ageism on the health of older adults in industrialised countries. However, there are little data on the impact of the marginalisation of older adults on their health in industrialising societies. Further research is needed to study the impact on the health of older adults.
Topics: Humans; Cameroon; Intergenerational Relations; Aged; Male; Female; Focus Groups; Qualitative Research; Middle Aged; Aged, 80 and over; Ageism; Health Status
PubMed: 38754898
DOI: 10.1136/bmjgh-2023-014678 -
BMJ Paediatrics Open May 2024This study aimed to identify predictors of sepsis-associated in-hospital mortality from readily available laboratory biomarkers at onset of illness that include... (Observational Study)
Observational Study
BACKGROUND AND OBJECTIVES
This study aimed to identify predictors of sepsis-associated in-hospital mortality from readily available laboratory biomarkers at onset of illness that include haematological, coagulation, liver and kidney function, blood lipid, cardiac enzymes and arterial blood gas.
METHODS
Children with sepsis were enrolled consecutively in a prospective observational study involving paediatric intensive care units (PICUs) of two hospitals in Beijing, between November 2016 and January 2020. The data on demographics, laboratory examinations during the first 24 hours after PICU admission, complications and outcomes were collected. We screened baseline laboratory indicators using the Least Absolute Shrinkage and Selection Operator (LASSO) analysis, then we constructed a mortality risk model using Cox proportional hazards regression analysis. The ability of risk factors to predict in-hospital mortality was evaluated by receiver operating characteristic (ROC) curves.
RESULTS
A total of 266 subjects were enrolled including 44 (16.5%) deaths and 222 (83.5%) survivors. Those who died showed a shorter length of hospitalisation, and a higher proportion of mechanical ventilation, complications and organ failure (p<0.05). LASSO analysis identified 13 clinical parameters related to prognosis, which were included in the final Cox model. An elevated triglyceride (TG) remained the most significant risk factor of death (HR=1.469, 95% CI: 1.010 to 2.136, p=0.044), followed by base excess (BE) (HR=1.131, 95% CI: 1.046 to 1.223, p=0.002) and pH (HR=0.95, 95% CI: 0.93 to 0.97, p<0.001). The results of the ROC curve showed that combined diagnosis of the three indicators-TG+BE+pH-has the best area under the curve (AUC) (AUC=0.77, 95% CI: 0.69 to 0.85, p<0.001), with a 68% sensitivity and 80% specificity.
CONCLUSION
Laboratory factors of TG, BE and pH during the first 24 hours after intensive care unit admission are associated with in-hospital mortality in PICU patients with sepsis. The combination of the three indices has high diagnostic value.
Topics: Humans; Male; Prospective Studies; Female; Hospital Mortality; Sepsis; Child, Preschool; Infant; Intensive Care Units, Pediatric; Biomarkers; Predictive Value of Tests; Child; Risk Factors; Community-Acquired Infections; ROC Curve; Prognosis
PubMed: 38754894
DOI: 10.1136/bmjpo-2023-002329 -
BMJ Open Ophthalmology May 2024Lipid profiles have been changed in numerous chronic conditions. The impact of uveitis on lipid metabolism remains unclear.
BACKGROUND/AIMS
Lipid profiles have been changed in numerous chronic conditions. The impact of uveitis on lipid metabolism remains unclear.
METHODS
This is a cross-sectional study included 416 patients with non-infectious uveitis (NIU) and 416 healthy subjects. Standard techniques were used to measure total cholesterol (TC), triglycerides (TG), high-density lipoprotein-cholesterol (HDLc), low-density lipoprotein-cholesterol (LDLc) levels. Quantitative optical coherence tomography angiography (OCTA) parameters were obtained from 500 eyes in each group. Correlation analysis examined the relationship between lipid profile and OCTA parameters.
RESULTS
Patients with NIU exhibited significantly elevated TC, TG and LDLc levels compared with controls (p=0.003; p<0.001; p<0.001, respectively). Subgroup analysis revealed that HDLc was significantly lower in Behçet's disease (p=0.024) compared with controls. Vascular density (VD) in the superficial capillary plexus (SCP), deep capillary plexus (DCP), choriocapillaris and optic disk were significantly decreased in NIU eyes (p<0.05, respectively) compared with controls. HDLc exhibited a significant negative correlation with VDs in the whole and parafovea SCP (r=-0.489, p=0.008; r=-0.480, p=0.0026, respectively), while LDLc showed a significant positive correlation with VDs in the whole and parafovea DCP in NIU patients (r=0.576, p=0.032; r=0.267, p=0.034, respectively).
CONCLUSIONS
The lipid profile is altered in NIU, and there are correlations between HDLc and LDLc levels and VD as measured by OCTA. Lipid profile analysis may offer valuable insights into evaluating vascular and metabolic aspects of NIU.
Topics: Humans; Cross-Sectional Studies; Tomography, Optical Coherence; Male; Uveitis; Female; Adult; Fluorescein Angiography; Lipids; Middle Aged; Retinal Vessels; Fundus Oculi; Lipid Metabolism; Triglycerides
PubMed: 38754892
DOI: 10.1136/bmjophth-2024-001641 -
BMJ Open May 2024Continuous theta burst stimulation (cTBS), a form of repetitive transcranial magnetic stimulation (rTMS), targeting the language network in the right hemisphere of...
INTRODUCTION
Continuous theta burst stimulation (cTBS), a form of repetitive transcranial magnetic stimulation (rTMS), targeting the language network in the right hemisphere of post-stroke aphasia (PSA) patients shows promising results in clinical trials. However, existing PSA studies have focused on single-target rTMS, leaving unexplored the potential benefits of multitarget brain stimulation. Consequently, there is a need for a randomised clinical trial aimed to evaluate the efficacy and safety of cTBS targeting on multiple critical nodes in the language network for PSA.
METHODS AND ANALYSIS
This is a prospective, multicentre, double-blind, two-arm parallel-group, sham-controlled randomised trial. The study will include a total of 60 participants who will be randomly assigned in a 1:1 ratio to either the active cTBS group or the sham cTBS group. Using precision resting-state functional MRI for each participant, we will map personalised language networks and design personalised targets in the inferior frontal gyrus, superior temporal gyrus and superior frontal gyrus. Participants will undergo a 3-week cTBS intervention targeting the three personalised targets, coupled with speech and language therapy. The primary outcome is the change in the Western Aphasia Battery-Revised aphasia quotient score among participants after a 3-week treatment. Secondary outcomes include Boston Diagnostic Aphasia Examination severity ratings, Token Test and the Chinese-version of the Stroke and Aphasia Quality of Life Scale 39-generic version.
ETHICS AND DISSEMINATION
The study has been approved by the ethics committees of Affiliated Hospital of Hebei University, Hebei General Hospital and Affiliated Hospital of Chengde Medical University. The findings of this study will be reported in peer-reviewed scientific journals.
TRIAL REGISTRATION NUMBER
The study has been registered on ClinicalTrials.gov (NCT05957445).
Topics: Humans; Aphasia; Transcranial Magnetic Stimulation; Double-Blind Method; Stroke; Prospective Studies; Magnetic Resonance Imaging; Randomized Controlled Trials as Topic; Female; Male; Middle Aged; Adult; Stroke Rehabilitation; Multicenter Studies as Topic
PubMed: 38754874
DOI: 10.1136/bmjopen-2023-081847 -
Bone & Joint Research May 2024To assess the alterations in cell-specific DNA methylation associated with chondroitin sulphate response using peripheral blood collected from Kashin-Beck disease (KBD)...
AIMS
To assess the alterations in cell-specific DNA methylation associated with chondroitin sulphate response using peripheral blood collected from Kashin-Beck disease (KBD) patients before initiation of chondroitin sulphate treatment.
METHODS
Peripheral blood samples were collected from KBD patients at baseline of chondroitin sulphate treatment. Methylation profiles were generated using reduced representation bisulphite sequencing (RRBS) from peripheral blood. Differentially methylated regions (DMRs) were identified using MethylKit, while DMR-related genes were defined as those annotated to the gene body or 2.2-kilobase upstream regions of DMRs. Selected DMR-related genes were further validated by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) to assess expression levels. Tensor composition analysis was performed to identify cell-specific differential DNA methylation from bulk tissue.
RESULTS
This study revealed 21,060 hypermethylated and 44,472 hypomethylated DMRs, and 13,194 hypermethylated and 22,448 hypomethylated CpG islands for differential global methylation for chondroitin sulphate treatment response. A total of 12,666 DMR-related genes containing DMRs were identified in their promoter regions, such as (false discovery rate (FDR) = 2.11 × 10), (FDR = 7.05 × 10), and (FDR = 1.43 × 10). Additionally, and were hypermethylated in responders, while was hypomethylated in responders, all showing decreased gene expression. The patterns of cell-specific differential global methylation associated with chondroitin sulphate response were observed. Specifically, we found that DMRs located in and exhibited differential DNA methylation between responders and non-responders in granulocytes, monocytes, and B cells.
CONCLUSION
Our study identified cell-specific changes in DNA methylation associated with chondroitin sulphate response in KBD patients.
PubMed: 38754865
DOI: 10.1302/2046-3758.135.BJR-2023-0271.R1 -
Animal Bioscience May 2024Pine needles are rich in many nutrients and exhibit antibacterial and antioxidant biological activities; however, the effects of different production methods of pine...
OBJECTIVE
Pine needles are rich in many nutrients and exhibit antibacterial and antioxidant biological activities; however, the effects of different production methods of pine needle additives on the growth performance and intestinal flora of broiler chickens are not known.
METHODS
Normal diets were supplemented with PNF (Pine Needle Fermentation juice), PNS (Pine Needle Soaking juice), or PNP (Pine Needle Powder), and the associated effects on growth performance, relative organ weights, intestinal development, intestinal histological morphology, intestinal flora, meat quality, and serum indicators in broiler chickens were observed.
RESULTS
The results showed that PNF, PNS, and PNP all significantly improved feed utilisation and promoted the growth and development of broilers. All three additives also significantly improved the structure of the intestinal flora, specifically increasing the diversity of bacteria; increasing the abundance of beneficial bacteria, such as Faecalibacterium, Rikenella, and Blautia; and decreasing the abundance of harmful bacteria, such as Staphylococcus. The antioxidant properties of pine needles were also found to intensify lipid metabolic reactions in the blood, thus leading to lower TG and TCHO. Meanwhile, high doses of PNF reduced jejunum and ileum weights and also increased meat yellowness. Lastly, none of PNF, PNS, or PNP had an effect on relative organ weights or intestinal histological morphology.
CONCLUSION
In conclusion, the addition of pine needles to the diet of broiler chickens can effectively promote their growth performance as well as improve their intestinal flora and serum status without side effects; in particular, the dose of 0.2% of either PNF and PNS is expected to have the capacity to replace growth-promoting antibiotics as diet additives.
PubMed: 38754853
DOI: 10.5713/ab.24.0042 -
Animal Bioscience May 2024Coat color is an important characteristic and economic trait in domestic sheep. In this study, we explored the potential mechanisms and the signaling pathways involved...
OBJECTIVE
Coat color is an important characteristic and economic trait in domestic sheep. In this study, we explored the potential mechanisms and the signaling pathways involved in coat color regulation for sheep.
METHODS
Isobaric tags for relative and absolute quantification (iTRAQ) technology was used to catalog global protein expression profiles in skin of sheep with black versus white coat color. Immunofluorescence was used to observe the expression localization of differential protein. Western blot and quantitative real time polymerase chain reaction (qRT-PCR) were used to evaluate their role in the coat color formation of sheep.
RESULTS
A total of 136 differential proteins were obtained in different coat colors, including 101 up-regulated and 35 down-regulated. Pigmentation function entries were enriched through GO annotation. Tyrosine metabolism and platelet activation signaling pathway were extracted by KEGG analysis. APOA1 (Apolipoprotein A-1) and FGA (Fibrinogen alpha chain) were found to be critical differential proteins by the interaction of differential proteins in the direct-interaction network diagram. Strikingly, twenty candidate differential proteins were screened, from which ACTB (Beta-actin) protein showed higher expression in white sheep skin, while ALB (albumin), APOA1 MAOA (Amine oxidase) and FGA proteins showed higher expression in black sheep skin, which validated by immunofluorescence, western blot and qRT-PCR.
CONCLUSION
Our studies identified several novel proteins that may involved in the coat color formation of sheep. The white and black sheep skin proteome profiles obtained provide a valuable resource for future research to understand the network of protein expression controlling skin physiology and melanogenesis in sheep.
PubMed: 38754850
DOI: 10.5713/ab.24.0014