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Wiener Klinische Wochenschrift Jul 2024Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired hematologic disorder characterized by a loss of glycosyl-phosphatidyl-inositol-linked (GPI) proteins on various...
Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired hematologic disorder characterized by a loss of glycosyl-phosphatidyl-inositol-linked (GPI) proteins on various hematopoietic cells. Some GPI proteins are involved in the regulation of the complement system, and their absence renders erythrocytes susceptible to complement-mediated lysis. Current standard of care in PNH is to block the complement system at the level of C5 using ravulizumab or eculizumab; however, some patients with PNH may develop extravascular hemolysis (EVH) during treatment with C5 inhibitors. The proximal complement inhibitor iptacopan has recently been shown to be efficacious in patients with PNH. This article reports on a 43-year-old female patient with PNH who was successfully treated with iptacopan. The patient had received ravulizumab for several years and developed a clinically relevant EVH. After obtaining informed consent, the patient received oral iptacopan 200 mg twice daily and ravulizumab was discontinued. Over the next few weeks hemoglobin levels and reticulocyte counts normalized. The patient reported mild flushes with erythema, chills, and mild muscle pain, all of which resolved during follow-up. No breakthrough hemolysis occurred, and no severe adverse events were recorded.
PubMed: 38954058
DOI: 10.1007/s00508-024-02390-w -
Cancer Immunology, Immunotherapy : CII Jul 2024Oral squamous cell carcinoma (OSCC), while common and with a favorable prognosis in early stages, presents a marked reduction in survival rate upon metastasis to lymph...
INTRODUCTION
Oral squamous cell carcinoma (OSCC), while common and with a favorable prognosis in early stages, presents a marked reduction in survival rate upon metastasis to lymph nodes. Early detection of lymph node metastasis via biomarkers could enhance the therapeutic strategy for OSCC. Here, we explored dendritic cells (DCs) and cytotoxic T-cells in tumour-draining lymph nodes (TDLNs) as potential biomarkers.
METHOD
Dendritic cells and cytotoxic T-cells in 33 lymph nodes were analyzed with multi-parameter flow cytometry in TDLNs, regional non-TDLNs surgically excised from 12 OSCC patients, and compared to 9 lymph nodes from patients with benign conditions.
RESULTS
Our results displayed a higher proportion of conventional cDC1s with immunosuppressive features in TDLN. Further, high PD-L1 expression on cDC1 in TDLNs was associated with metastasis and/or recurrent disease risk. Also, elevated levels of memory CD8 T-cells and terminally exhausted PD-1TCF-1CD8 T-cells were observed in TDLNs and non-TDLNs compared to healthy lymph nodes.
CONCLUSIONS
We conclude that TDLNs contain cells that could trigger an anti-tumor adaptive response, as evidenced by activated cDC1s and progenitor-like TCF-1 T-cells. The detection of high PDL1 expression on cDC1s was indicative of TDLN metastasis and an adverse prognosis, proposing that PD-L1 on dendritic cells in TDLN could serve as a predictive biomarker of OSCC patients with a worse prognosis.
Topics: Humans; Dendritic Cells; Mouth Neoplasms; Prognosis; Female; Male; Lymph Nodes; B7-H1 Antigen; Middle Aged; Aged; Lymphatic Metastasis; Carcinoma, Squamous Cell; Biomarkers, Tumor; Adult
PubMed: 38954023
DOI: 10.1007/s00262-024-03754-x -
International Orthopaedics Jul 2024Trigger finger (TF) is a common hand condition that can be treated with surgery. We conducted a systematic review and meta-analysis to assess whether ultrasound-guided...
PURPOSE
Trigger finger (TF) is a common hand condition that can be treated with surgery. We conducted a systematic review and meta-analysis to assess whether ultrasound-guided (US-guided) percutaneous surgery is superior to other conventional surgical methods.
METHODS
We conducted a comprehensive search in Medline, Embase, and the Cochrane Library to identify relevant studies. We included randomized clinical trials (RCTs) and observational studies comparing US-guided TF release with blind percutaneous or open approaches. We combined Risk Ratios (RR) and Mean Differences (MD) with 95% Confidence Intervals (CI) across studies. Data processing and analysis were conducted using R software, version 4.3.1.
RESULTS
Our analysis included eight RCTs and two observational studies with 555 patients. US-guided surgery significantly reduced postoperative DASH scores (MD -3.75 points; 95% CI = -7.48, -0.02; p < 0.01), shortened time to resume activities (MD -11.52 days; 95% CI = -16.13, -6.91; p < 0.01), hastened discontinuation of oral analgesics (MD -4.44 days; 95% CI = -8.01, -0.87; p < 0.01), and improved patient satisfaction scores (RR 1.13; 95% CI = 1.04, 1.23; p = 0.75). There were no significant differences in VAS scores, time to movement recovery, or surgical success rate.
CONCLUSION
Ultrasound-guided percutaneous release is a safe, effective, and superior alternative for treating TF compared to other methods, leading to improved DASH scores, quicker recovery, faster cessation of oral analgesics, and enhanced patient satisfaction.
PubMed: 38953949
DOI: 10.1007/s00264-024-06243-z -
Osteoporosis International : a Journal... Jul 2024Long-term glucocorticoids (GCs) treatment is associated with osteoporosis and fractures. We investigated whether low-dose GC treatment also increased the risk of...
UNLABELLED
Long-term glucocorticoids (GCs) treatment is associated with osteoporosis and fractures. We investigated whether low-dose GC treatment also increased the risk of osteoporotic fractures, and the results showed that even low-dose GC treatment increased the risk of osteoporotic fractures, especially spine fractures.
PURPOSE
The effect of low-dose glucocorticoid (GC) therapy on the fracture risk in postmenopausal women with low bone mass was investigated.
METHODS
119,790 66-year-old postmenopausal women with low bone mass based on bone mineral density (BMD) results were included. GC group consisted of patients who had been prescribed oral GCs within 6 months of BMD testing. In GC group, GCs dosage was calculated by a defined daily dose (DDD), and divided into five groups according to GC usage (Group 1[G1]; < 11.25 DDDs, G2; ≥ 11.25, < 22.5 DDDs, G3; ≥ 22.5, < 45 DDDs, G4; ≥ 45, < 90 DDDs, G5; ≥ 90 DDDs). The risk of major osteoporotic fractures (MOF) and non-MOF was analyzed and compared with that of the control group during the 1-year follow-up.
RESULTS
The risk of total fracture was higher in G3-G5 than in the control group (G3, hazard ratio (HR) 1.25, 95% confidence interval [CI] 1.07-1.46; G4, 1.37 [1.13-1.66]; G5 1.45 [1.08-1.94]). The risk of MOF was higher in all groups except G2 than in the control group (G1, 1.23 [1.05-1.45]; G3, 1.37 [1.11-1.68]; G4, 1.41 [1.09-1.83]; G5, 1.66 [1.14-2.42]). The risk of spine fracture was significantly higher in all GC groups except G2 than in the control group. The risk of non-MOF was higher only in G4 than in the control group (G4, 1.48 [1.13-1.94]).
CONCLUSION
Low-dose GC therapy can increase the risk of osteoporotic fractures, particularly spine fractures, in postmenopausal women with low bone mass.
PubMed: 38953946
DOI: 10.1007/s00198-024-07159-5 -
Journal of Molecular Medicine (Berlin,... Jul 2024Diabetes mellitus (DM), an important public health problem, aggravates the global economic burden. Diabetic encephalopathy (DE) is a serious complication of DM in the...
Diabetes mellitus (DM), an important public health problem, aggravates the global economic burden. Diabetic encephalopathy (DE) is a serious complication of DM in the central nervous system. Metformin has been proven to improve DE. However, the mechanism is still unclear. In this study, the db/db mice, a common model used for DE, were employed to explore and study the neuroprotective effect of metformin and related mechanisms. Behavioral tests indicated that metformin (100 or 200 mg/kg/day) could significantly improve the learning and memory abilities of db/db mice. The outcomes from the oral glucose tolerance test (OGTT) and insulin tolerance test (ITT) demonstrate that metformin effectively modulates glucose and insulin signaling pathways in db/db mice. The results of body weight and blood lipid panel (total cholesterol, triglycerides, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol) show that metformin promotes the level of lipid metabolism in db/db mice. Furthermore, data from oxidative stress assays, which measured levels of malondialdehyde, superoxide dismutase, catalase, and glutathione peroxidase, suggest that metformin suppresses oxidative stress-induced brain damage in db/db mice. In addition, western blot, Nissl staining, and immunofluorescence results showed that metformin increased the expressions of nerve growth factor and postsynaptic density 95 and repaired neuronal structural damage. For the mechanism study, metformin activated SIRT1 and inhibited the expression of NLRP3 inflammasome (NLRP3, ASC, caspase-1, IL-1β, and IL-18) and inflammatory cytokines (TNFα and IL-6). In conclusion, metformin could ameliorate cognitive dysfunction through the SIRT1/NLRP3 pathway, which might be a promising mechanism for DE treatment.
PubMed: 38953935
DOI: 10.1007/s00109-024-02465-1 -
Microbial Biotechnology Jul 2024Porcine epidemic diarrhoea virus (PEDV) infects pigs of all ages by invading small intestine, causing acute diarrhoea, vomiting, and dehydration with high morbidity and...
Porcine epidemic diarrhoea virus (PEDV) infects pigs of all ages by invading small intestine, causing acute diarrhoea, vomiting, and dehydration with high morbidity and mortality among newborn piglets. However, current PEDV vaccines are not effective to protect the pigs from field epidemic strains because of poor mucosal immune response and strain variation. Therefore, it is indispensable to develop a novel oral vaccine based on epidemic strains. Bacillus subtilis spores are attractive delivery vehicles for oral vaccination on account of the safety, high stability, and low cost. In this study, a chimeric gene CotC-Linker-COE (CLE), comprising of the B. subtilis spore coat gene cotC fused to the core neutralizing epitope CO-26 K equivalent (COE) of the epidemic strain PEDV-AJ1102 spike protein gene, was constructed. Then recombinant B. subtilis displaying the CLE on the spore surface was developed by homologous recombination. Mice were immunized by oral route with B. subtilis 168-CLE, B. subtilis 168, or phosphate-buffered saline (PBS) as control. Results showed that the IgG antibodies and cytokine (IL-4, IFN-γ) levels in the B. subtilis 168-CLE group were significantly higher than the control groups. This study demonstrates that B. subtilis 168-CLE can generate specific systemic immune and mucosal immune responses and is a potential vaccine candidate against PEDV infection.
Topics: Porcine epidemic diarrhea virus; Animals; Bacillus subtilis; Spores, Bacterial; Mice; Antibodies, Viral; Swine; Viral Vaccines; Coronavirus Infections; Swine Diseases; Antigens, Viral; Administration, Oral; Cytokines; Immunoglobulin G; Mice, Inbred BALB C; Female; Cell Surface Display Techniques; Spike Glycoprotein, Coronavirus
PubMed: 38953907
DOI: 10.1111/1751-7915.14518 -
Journal of Public Health Dentistry Jul 2024American Indian and Alaska native (AI/AN) individuals report distrust of the healthcare system. This study explored associations between having either high levels of...
OBJECTIVE
American Indian and Alaska native (AI/AN) individuals report distrust of the healthcare system. This study explored associations between having either high levels of dental distrust or high levels of dental care-related fear and anxiety ("dental anxiety") and oral health outcomes in AI/AN adults.
METHODS
The 2022 State of Oral Health Equity in America survey included the Modified Dental Anxiety Scale and asked to what extent respondents agreed with the statement, "At my last oral health visit, I trusted the oral health provider I saw", and asked about self-rated oral health and presence of a dental home.
RESULTS
AI/AN individuals (N = 564) who reported low dental trust (n = 110) or with high dental anxiety (MDAS≥19; n = 113) reported significantly worse overall and oral health and were significantly less likely to have a dental home (p < 0.05 used for each analysis).
CONCLUSION
Dental distrust and dental anxiety can significantly impact oral health and dental utilization in AI/AN communities and are important intervention targets to improve AI/AN oral health.
PubMed: 38953889
DOI: 10.1111/jphd.12633 -
Future Oncology (London, England) Jul 2024This is a summary describing the results from a phase 3 clinical trial called SUNLIGHT. The study looked at treatment with orally administered trifluridine/tipiracil...
WHAT IS THIS SUMMARY ABOUT?
This is a summary describing the results from a phase 3 clinical trial called SUNLIGHT. The study looked at treatment with orally administered trifluridine/tipiracil plus intravenously administered bevacizumab in people with metastatic colorectal cancer (mCRC) that is refractory to treatment.This study included people whose cancer had grown or spread beyond its original location after no more than two previous treatments. People in the study received either the combination of trifluridine/tipiracil plus bevacizumab or they received trifluridine/tipiracil alone. The aims of the study were to see how long people lived after treatment with trifluridine/tipiracil plus bevacizumab compared with trifluridine/tipiracil alone and to find out how well the combination of trifluridine/tipiracil plus bevacizumab worked at slowing down the spread of the cancer. Researchers also looked at side effects from taking the medicines and at how treatment affected people's physical functioning.
WHAT ARE THE KEY TAKEAWAYS?
People in the combination group lived longer (a median of 10.8 months) than people who received trifluridine/tipiracil alone (7.5 months). In addition, the time it took for the cancer to worsen was longer for those who received the combination treatment (a median of 5.6 months) compared with those who received trifluridine/tipiracil alone (2.4 months). People's physical functioning took longer to worsen with combination therapy (a median of 9.3 months) than it did with trifluridine/tipiracil alone (6.3 months), as measured by the impact of treatment on people's ability to carry out daily living activities. The most common side effects in both treatment groups were low levels of white blood cells, known as neutrophils (neutropenia), nausea, and low levels of healthy red blood cells (anemia).
WHAT WERE THE MAIN CONCLUSIONS REPORTED BY THE RESEARCHERS?
The results from the study suggest that treatment with oral trifluridine/tipiracil plus intravenous (IV) bevacizumab could help people with refractory mCRC live longer and maintain good physical functioning, and it could slow the worsening of their cancer. NCT04737187 (SUNLIGHT) (ClinicalTrials.gov).
PubMed: 38953855
DOI: 10.1080/14796694.2024.2366100 -
Nanomedicine (London, England) Jul 2024This study focused on developing a topical gel incorporating lornoxicam-loaded poly(lactic-co-glycolic acid) and polyethylene glycol (PLGA-PEG) blend nanoparticles to...
This study focused on developing a topical gel incorporating lornoxicam-loaded poly(lactic-co-glycolic acid) and polyethylene glycol (PLGA-PEG) blend nanoparticles to mitigate gastrointestinal (GIT) side effects and enhance therapeutic efficacy. Synthesized nanoparticles were subjected to characterization, permeation studies, and acute oral toxicity analysis post-incorporation into the gel using a S/O/W double emulsion solvent. The nanoparticles displayed a smooth, spherical morphology (170-321 nm) with increased entrapment efficiency (96.2%). LOX exhibited a permeation rate of 70-94% from the nanoparticle-infused gel, demonstrating favorable biocompatibility at the cellular level. The formulated gel, enriched with nanoparticles, holds promising prospects for drug-delivery systems and promising improved therapeutic outcomes for LOX.
PubMed: 38953843
DOI: 10.1080/17435889.2024.2359356 -
Indian Journal of Public Health Apr 2024With increasing importance being given to preexposure prophylaxis (PrEP) for human immunodeficiency virus prevention among men who have sex with men (MSM) and... (Meta-Analysis)
Meta-Analysis
Human Immunodeficiency Virus Preexposure Prophylaxis Awareness and Acceptability among Men Who Have Sex with Men and Transgender Persons in India: Systematic Review and Meta-analysis.
With increasing importance being given to preexposure prophylaxis (PrEP) for human immunodeficiency virus prevention among men who have sex with men (MSM) and transgender persons (TG), we undertook a systematic review and meta-analysis of PrEP awareness and acceptability among these key populations in India, and their sociodemographic and behavioral determinants. The systematic review was registered with PROSPERO (CRD42023390508). Studies were included if they provided quantitative data on PrEP awareness or acceptability among MSM or TG in India. MEDLINE, Scopus, Web of Science, and Embase were searched from inception to February 29, 2024, using keywords and database-specific terms. Relevant websites were also searched. Critical appraisal was done using the Joanna Briggs Institute Checklist for Prevalence Studies. Random-effects meta-analysis was done for common outcomes reported by the studies. Reporting was as per the Preferred Reporting Items for Systematic Reviews and Meta-analyses 2020 statement. Ten studies providing cross-sectional data, mostly from South West India, were included for qualitative synthesis. All were conducted in settings where PrEP was not available. The pooled prevalence among MSM and TG was 18.7% (95% confidence interval [CI] 8.7%, 28.7%) for awareness and 79.8% (95% CI 57.4%, 100.0%) for willingness to use daily oral PrEP. This review highlights the felt need for PrEP among MSM and TG in India. Further research is needed to understand user attitudes in different parts of the country.
Topics: Humans; Male; India; HIV Infections; Pre-Exposure Prophylaxis; Transgender Persons; Homosexuality, Male; Health Knowledge, Attitudes, Practice; Patient Acceptance of Health Care
PubMed: 38953814
DOI: 10.4103/ijph.ijph_1027_23