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In Vivo (Athens, Greece) 2024The landscape of treatments for hepatocellular carcinoma (HCC), including immune checkpoint inhibitors, has expanded significantly. However, unresectable HCC patients...
Similar Efficacy Between Atezolizumab Plus Bevacizumab Hepatic Arterial Infusion Chemotherapy For Unresectable Hepatocellular Carcinoma With Portal Vein Tumor Thrombus: A Retrospective Cohort Study.
BACKGROUND/AIM
The landscape of treatments for hepatocellular carcinoma (HCC), including immune checkpoint inhibitors, has expanded significantly. However, unresectable HCC patients with portal vein tumor thrombus (PVTT) continue to face a poor prognosis. This investigation examined the survival outcomes and determinants influencing survival rates in advanced HCC patients with PVTT undergoing treatment with atezolizumab plus bevacizumab (ATZ+BEV) or hepatic arterial infusion chemotherapy (HAIC).
PATIENTS AND METHODS
Between December 2003 and June 2023, 48 advanced HCC with PVTT underwent treatment with either ATZ+BEV (16 patients) or HAIC (32 patients).
RESULTS
The analysis revealed no significant disparities in overall survival (OS) or treatment efficacy between the ATZ+BEV and HAIC groups (ATZ+BEV: 10.0 months, HAIC: 15.3 months). Treatment with either ATZ+BEV or HAIC resulted in minimal alterations in the ALBI score and preserved hepatic function. Independent prognostic factors for OS, identified via multivariate logistic regression, included serum α-fetoprotein levels >400 ng/ml [hazard ratio (HR)=1.94; p=0.001], the existence of more than five tumors (HR=1.55; p=0.043), and the Child-Pugh score (HR=2.53; p=0.002).
CONCLUSION
This investigation revealed no significant variance in OS and response rates between patients receiving ATZ+BEV and those treated with HAIC. The survival of advanced HCC patients with PVTT is intricately linked to the preservation of liver function, emphasizing the necessity for additional research to enhance treatment approaches for this patient population.
Topics: Humans; Carcinoma, Hepatocellular; Liver Neoplasms; Bevacizumab; Male; Female; Middle Aged; Antibodies, Monoclonal, Humanized; Portal Vein; Retrospective Studies; Aged; Antineoplastic Combined Chemotherapy Protocols; Infusions, Intra-Arterial; Treatment Outcome; Hepatic Artery; Prognosis; Adult
PubMed: 38936922
DOI: 10.21873/invivo.13639 -
In Vivo (Athens, Greece) 2024Diabetic retinopathy is a leading cause of blindness worldwide, characterized by neurovascular dysfunction. This study aimed to investigate the impact of brimonidine, a...
BACKGROUND/AIM
Diabetic retinopathy is a leading cause of blindness worldwide, characterized by neurovascular dysfunction. This study aimed to investigate the impact of brimonidine, a selective adrenoceptor agonist, on diabetic retinal neurodegeneration, recognizing the critical role of neurodegeneration in diabetic retinopathy.
MATERIALS AND METHODS
Streptozotocin-induced diabetes was established in adult male Sprague-Dawley rats to mimic diabetic retinopathy. Rats, except non-diabetic control rats, received topical applications of 0.15% brimonidine tartrate (treatment group) or balanced salt solution (diabetic control group) twice daily following diabetes induction. Each group comprised six randomly assigned animals. Retinal samples were analyzed using immunofluorescence staining, apoptosis assay, and western blot.
RESULTS
Topical brimonidine treatment reduced apoptosis of retinal ganglion cells at 8 weeks after induction of diabetes (p<0.05). Glial activation induced by diabetes was reduced by brimonidine treatment. Immunoblot and immunofluorescence assay revealed that the decrease in phospho- protein kinase B (AKT) level resulting from diabetes was also attenuated by brimonidine (p<0.05). Furthermore, brimonidine alleviated the decrease in anti-apoptotic proteins [BCL2 apoptosis regulator (BCL2) and BCL-xl] induced by diabetes (p<0.05). Elevation of phospho-p38 mitogen-activated protein kinase (p38MAPK) and p53 in diabetic rats were reduced by brimonidine (p<0.05). Additionally, brimonidine treatment attenuated the upregulation of the pro-apoptotic molecule BCL-2 associated X in retinas of diabetic rats (p<0.05).
CONCLUSION
These findings suggest that topical brimonidine treatment may protect retinal ganglion cells in experimental diabetes by modulating the AKT pathway and reducing pro-apoptotic p38MAPK levels. This presents a potential neuroprotective approach in diabetes, offering the advantage of localized treatment without the added burden of oral medication.
Topics: Animals; Diabetic Retinopathy; Brimonidine Tartrate; Neuroprotective Agents; Rats; Apoptosis; Diabetes Mellitus, Experimental; Male; Retinal Ganglion Cells; Administration, Topical; Disease Models, Animal; Rats, Sprague-Dawley; Proto-Oncogene Proteins c-akt; Retina
PubMed: 38936912
DOI: 10.21873/invivo.13611 -
In Vivo (Athens, Greece) 2024We evaluated the usefulness of prophylactic mini-tracheostomy (PMT) and perioperative administration of tazobactam/piperacillin (TAZ/PIPC) in high-risk patients after...
BACKGROUND/AIM
We evaluated the usefulness of prophylactic mini-tracheostomy (PMT) and perioperative administration of tazobactam/piperacillin (TAZ/PIPC) in high-risk patients after esophagectomy.
PATIENTS AND METHODS
We retrospectively studied 89 consecutive high-risk patients who underwent esophagectomy for esophageal cancer between January 2013 and December 2021. We defined patients with two or more of the following factors as high risk: age ≥70 years, performance status ≥1, respiratory dysfunction, liver dysfunction, cardiac dysfunction, renal dysfunction, diabetes mellitus, albumin <3.5 g/dl, and Brinkman index >600. Standard management was administered to the first 50 patients (standard group). PMT and TAZ/PIPC were administered to the next 39 patients (combination group). Patient characteristics and short-term outcomes were compared before and after propensity-score matching.
RESULTS
Before propensity-score matching, 24-hour urine creatinine clearance, retrosternal route, 3-field lymph node dissection, and open abdominal approach were more common, postoperative pneumonia (13% vs. 36%, p=0.045) and complications of grade ≥3b (2.6% vs. 22%, p=0.01) were less frequent, and the postoperative hospital stay was shorter (median: 23 vs. 28 days, p=0.022) in the combination group than in the standard group. In propensity-score matching, patient characteristics, except for 24-h creatinine clearance and reconstructive route, were matched for 23 paired patients. Postoperative pneumonia (8.7% vs. 39%, p=0.035) and complications of grade ≥3b (0% vs. 26%, p=0.022) were less frequent and postoperative hospital stay was shorter (median: 22 vs. 25 days, p=0.021) in the combination group than in the standard group.
CONCLUSION
PMT with TAZ/PIPC can potentially prevent postoperative pneumonia in high-risk patients after esophagectomy.
Topics: Humans; Male; Female; Aged; Esophagectomy; Esophageal Neoplasms; Pneumonia; Piperacillin, Tazobactam Drug Combination; Middle Aged; Postoperative Complications; Anti-Bacterial Agents; Retrospective Studies; Risk Factors
PubMed: 38936906
DOI: 10.21873/invivo.13630 -
Voprosy Kurortologii, Fizioterapii, I... 2024Functional gastrointestinal disorders, which had an impact on the dentofacial system (pain, loose teeth and falling out of them) in patients who have had COVID-19, drew...
UNLABELLED
Functional gastrointestinal disorders, which had an impact on the dentofacial system (pain, loose teeth and falling out of them) in patients who have had COVID-19, drew the close attention of specialists of different profiles. The pathogenesis of worsening post-COVID edentulism is insufficiently studied, as many issues of adequate therapy remain unsolved, in which the role of non-drug technologies in the treatment of dental patients who have suffered from COVID-19 is extremely high.
OBJECTIVE
To describe the mechanism of action and clinical effectiveness of the developed combined physiotherapy method, including the induced technique of piracetam iontophoresis on the frontooccipital technic and acupuncture laser therapy in dental patients with complaints of edentulism progression after COVID-19 on the basis of the analysis of single studies on the post-COVID loss of teeth treatment.
MATERIAL AND METHODS
A number of patients equal 120 who complained of tooth loss after COVID-19 during the past 6 months were examined. The following initial and end points were considered: dental bleeding and inflammation scores, vascular and endothelial dysfunction markers - levels of intercellular adhesion molecules and their receptors (SlCAM-1, SVCAM-1, VEGF-A, ET-1) before and after treatment.
RESULTS
Negative correlation between VEGF-A (pg/ml) concentration in peripheral blood serum and sVCAM-1 (ng/ml) level in the examined patients (=0.4830, <0.05) and strong inverse correlation between slCAM-1 (ng/ml) level and sVCAM-1 (=0.7696, <0.01) have been established. More significant effects after application of the combined induced method on the head's structures and laser acupuncture have been noted than after acupuncture laser exposure and after inducing technique separately, namely in the form of dental inflammation score correction by 1.76 times (<0.001), decrease of bleeding score by 2.6 (<0.05), decrease of concentration of SVCAM-1 by 1.7 times and SlCAM-1 by 2 times (<0.001), increase of endothelin level by 1.7 times as well as the initial low VEGF-A (pg/ml) by 1.5 times (<0.01).
CONCLUSION
The developed physiotherapeutic complex, which includes laser acupuncture physiotherapy and induced technique of 5% piracetam iontophoresis, can potentially be considered as a physioprophylactic and therapeutic model of post-COVID edentulism.
Topics: Humans; COVID-19; Female; Male; Middle Aged; Physical Therapy Modalities; Iontophoresis; SARS-CoV-2; Adult; Acupuncture Therapy; Combined Modality Therapy; Aged
PubMed: 38934954
DOI: 10.17116/kurort202410103118 -
Immunity, Inflammation and Disease Jun 2024Particulate β-glucans (WGP) are natural compounds with regulatory roles in various biological processes, including tumorigenesis and inflammatory diseases such as...
BACKGROUND
Particulate β-glucans (WGP) are natural compounds with regulatory roles in various biological processes, including tumorigenesis and inflammatory diseases such as allergic asthma. However, their impact on mast cells (MCs), contributors to airway hyperresponsiveness (AHR) and inflammation in asthma mice, remains unknown.
METHODS
C57BL/6 mice underwent repeated OVA sensitization without alum, followed by Ovalbumin (OVA) challenge. Mice received daily oral administration of WGP (OAW) at doses of 50 or 150 mg/kg before sensitization and challenge. We assessed airway function, lung histopathology, and pulmonary inflammatory cell composition in the airways, as well as proinflammatory cytokines and chemokines in the bronchoalveolar lavage fluid (BALF).
RESULTS
The 150 mg/kg OAW treatment mitigated OVA-induced AHR and airway inflammation, evidenced by reduced airway reactivity to aerosolized methacholine (Mch), diminished inflammatory cell infiltration, and goblet cell hyperplasia in lung tissues. Additionally, OAW hindered the recruitment of inflammatory cells, including MCs and eosinophils, in lung tissues and BALF. OAW treatment attenuated proinflammatory tumor necrosis factor (TNF)-α and IL-6 levels in BALF. Notably, OAW significantly downregulated the expression of chemokines CCL3, CCL5, CCL20, CCL22, CXCL9, and CXCL10 in BALF.
CONCLUSION
These results highlight OAW's robust anti-inflammatory properties, suggesting potential benefits in treating MC-dependent AHR and allergic inflammation by influencing inflammatory cell infiltration and regulating proinflammatory cytokines and chemokines in the airways.
Topics: Animals; Asthma; Mast Cells; Mice; Disease Models, Animal; Administration, Oral; Mice, Inbred C57BL; beta-Glucans; Cytokines; Inflammation; Ovalbumin; Respiratory Hypersensitivity; Bronchoalveolar Lavage Fluid; Lung
PubMed: 38934407
DOI: 10.1002/iid3.1333 -
Current Protein & Peptide Science 2024'Structure determines function' is a consensus in the current biological community, but the structural characteristics corresponding to a certain function have always... (Review)
Review
'Structure determines function' is a consensus in the current biological community, but the structural characteristics corresponding to a certain function have always been a hot field of scientific exploration. A peptide is a bio-active molecule that is between the size of an antibody and a small molecule. Still, the gastrointestinal barrier and the physicochemical properties of peptides have always limited the oral administration of peptides. Therefore, we analyze the main ways oral peptide conversion strategies of peptide modification and permeation enhancers. Based on our analysis of the structure of natural oral peptides, which can be absorbed through the gastrointestinal tract, we believe that the design strategy of natural stapled peptides based on disulfide bonds is good for oral peptide design. This cannot only be used to identify anti-gastrointestinal digestive structural proteins in nature but also provide a solid structural foundation for the construction of new oral peptide drugs.
Topics: Disulfides; Administration, Oral; Humans; Cyclization; Peptides; Animals; Drug Design
PubMed: 38934364
DOI: 10.2174/0113892037280719231214095428 -
Current Pediatric Reviews Jun 2024An off-label medication involves the use of an approved drug for an unapproved indication, population, route of administration, or dosage.The physiological state of...
Awareness, Practice, and Views of Pediatricians, General Physicians, and Pharmacists about Prescribing Off-label Medication in Pediatric Patients in Eastern Province, Saudi Arabia.
BACKGROUND
An off-label medication involves the use of an approved drug for an unapproved indication, population, route of administration, or dosage.The physiological state of children differs from that of adults, making the adult formulation potentially dangerous to children. Off-label prescribing is quite common in children due to challenges in the development of pediatric formulations. The current study was conducted to determine the awareness, practice, and views of pediatricians, general physicians, and pharmacists about prescribing Off-label medication to pediatric patients in Eastern Province, Saudi Arabia.
METHODS
A cross-sectional study based on a questionnaire was conducted among pediatricians, general physicians, and pharmacists (clinical and community) in Eastern Province, Saudi Arabia. Statistical analysis was conducted using the data exported from Google Forms (Mountain View, California, USA) and Microsoft Excel (Version 2016) and then exported into Statistical Package for Social Sciences (SPSS) version 26.0 (IBM, Inc., Armonk, NY, USA). Chi-square was deemed suitable. The level of significance was set at 0.05.
RESULTS
Among the study participants, 53(35.09%) were pharmacists, followed by 24(15.89%) others, 22(14.565) pediatricians, 19(12.58%) other specialists, 17(11.25%) general physicians, and 16(10.59%) were clinical pharmacist. About 73(48.34%) described the definition of off-label correctly. About 114(75.49%) believed that parents and guardians must be informed about off-label medicine prescribed to their children. About 52(34.43%) had concerns about the safety of the medication, and 98(64.90%) believed they should be tested in pediatrics during clinical trials. Further, 97(64.23%) considered themselves not enough knowledgeable about off-label medications. The barriers reported by the participants were as follows: 89(58.945%) said lack of information resources, 71(47.01%) said lack of training, 56(37.08%) said lack of information on the safety of excipients used in pediatrics, 47(31.12%) said lack of formulary, 44(29.13%) said lack of guidelines, and 58(5.29%) said lack of information related to the safety of excipient concentration in pediatrics. The proportion of healthcare professionals who agreed that excipients in adult medication may be harmful to pediatrics was 103(68.21%). The drugs most often prescribed as off-label were paracetamol 54(21.68%), followed by Phenobarbital 35(14%), and Amoxicillin 33(13.25%).
CONCLUSION
There are a considerable number of healthcare professionals unaware of the description of off-label medication. The majority have concerns over the safety and efficacy of the off-label drugs and believe that most frequently used off-label drugs in pediatrics must be tested in pediatrics during clinical trials. In addition, excipient safety data are of considerable importance to ensure off-label drug safety in pediatrics, who believe their knowledge is inadequate and need proper guidelines and training on this issue.
PubMed: 38934287
DOI: 10.2174/0115733963298903240614072717 -
Frontiers in Immunology 2024Allergic sensitization is an essential step in the development of allergic airway inflammation to birch pollen (BP); however, this process remains to be fully...
INTRODUCTION & OBJECTIVE
Allergic sensitization is an essential step in the development of allergic airway inflammation to birch pollen (BP); however, this process remains to be fully elucidated. Recent scientific advances have highlighted the importance of the allergen context. In this regard, microbial patterns (PAMPs) present on BP have attracted increasing interest. As these PAMPs are recognized by specialized pattern recognition receptors (PRRs), this study aims at investigating the roles of intracellular PRRs and the inflammasome regulator NLRP3.
METHODS
We established a physiologically relevant intranasal and adjuvant-free sensitization procedure to study BP-induced systemic and local lung inflammation.
RESULTS
Strikingly, BP-sensitized -deficient mice showed significantly lower IgE levels, Th2-associated cytokines, cell infiltration into the lung, mucin production and epithelial thickening than their wild-type counterparts, which appears to be independent of inflammasome formation. Intriguingly, bone-marrow chimera revealed that expression of NLRP3 in the hematopoietic system is required to trigger an allergic response.
CONCLUSION
Overall, this study identifies NLRP3 as an important driver of BP-induced allergic immune responses.
Topics: Animals; NLR Family, Pyrin Domain-Containing 3 Protein; Pollen; Betula; Mice; Mice, Knockout; Administration, Intranasal; Allergens; Disease Models, Animal; Inflammasomes; Mice, Inbred C57BL; Cytokines; Hypersensitivity; Plant Extracts; Immunoglobulin E
PubMed: 38933263
DOI: 10.3389/fimmu.2024.1393819 -
Obesity (Silver Spring, Md.) Jul 2024The objective of this study was to evaluate the efficacy and safety of semaglutide 2.4 mg, a glucagon-like peptide-1 receptor agonist, by race and ethnicity, across... (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVE
The objective of this study was to evaluate the efficacy and safety of semaglutide 2.4 mg, a glucagon-like peptide-1 receptor agonist, by race and ethnicity, across three phase 3 trials.
METHODS
The Semaglutide Treatment Effect in People with Obesity (STEP) clinical trials evaluated the efficacy and safety of once-weekly subcutaneous semaglutide 2.4 mg. Here, STEP 1 and 3 data were pooled for analysis; STEP 2 data were examined separately. All analyses were conducted using data from racial and ethnic subgroups. The primary outcome was the estimated treatment difference in percent body weight change for semaglutide 2.4 mg versus placebo.
RESULTS
Participants reported race as White (STEP 1 and 3, 75.3%; STEP 2, 59.4%), Black (8.8%; 8.9%), Asian (10.6%; 27.3%), or other racial group (5.3%; 4.4%); and ethnicity as Hispanic or Latino (13.9%; 11.9%) or not Hispanic or Latino (83.9%; 88.1%). There were no significant interactions between treatment effect and race (STEP 1 and 3: p ≥ 0.07; STEP 2: p ≥ 0.15) or ethnicity (p ≥ 0.40; p ≥ 0.85). The safety of semaglutide 2.4 mg was consistent across subgroups.
CONCLUSIONS
The treatment effect of semaglutide was statistically significant versus placebo and clinically relevant across all racial and ethnic subgroups in STEP 1 and 3 and STEP 2. All subgroups across both samples demonstrated good tolerability.
Topics: Humans; Glucagon-Like Peptides; Male; Female; Adult; Middle Aged; Obesity; Treatment Outcome; Weight Loss; Injections, Subcutaneous; Double-Blind Method; Glucagon-Like Peptide-1 Receptor; White People; Hispanic or Latino; Anti-Obesity Agents; Ethnicity; Hypoglycemic Agents
PubMed: 38932728
DOI: 10.1002/oby.24042 -
Skin Research and Technology : Official... Jul 2024The delicate periorbital region is susceptible to skin dehydration, wrinkles, and loss of elasticity. Thus, targeted and effective anti-aging interventions are necessary... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
The delicate periorbital region is susceptible to skin dehydration, wrinkles, and loss of elasticity. Thus, targeted and effective anti-aging interventions are necessary for the periorbital area.
AIM
To evaluate the efficacy and safety of a new anti-aging eye cream formulated with the active complex (Yeast/rice fermentation filtrate, N-acetylneuraminic acid, palmityl tripeptide-1, and palmitoyl tetrapeptide-7).
METHODS
The cell viability and expressions of key extracellular matrix (ECM) components of the active complex were evaluated using a human skin fibroblast model. In the 12-week clinical trial, skin hydration, elasticity, facial photographs, and collagen density following eye cream application were assessed using Corneometer, Cutometer, VISIA, and ultrasound device, respectively. Dermatologists and participants evaluated clinical efficacy and safety at baseline, and after 4, 8, and 12 weeks.
RESULTS
PCR and immunofluorescent analyses revealed that the active complex significantly stimulated fibroblast proliferation (p < 0.05) and markedly promote the synthesis of collagen and elastin. Clinical findings exhibited a substantial enhancement in skin hydration (28.12%), elasticity (18.81%), and collagen production (54.99%) following 12 weeks of eye cream application. Dermatological evaluations and participants' assessments reported a significant improvement in skin moisture, roughness, elasticity, as well as fine lines and wrinkles by week 8.
CONCLUSION
The new anti-aging eye cream, enriched with the active complex, demonstrates comprehensive rejuvenating effects, effectively addressing aging concerns in the periorbital area, coupled with a high safety profile.
Topics: Humans; Skin Aging; Fibroblasts; Female; Middle Aged; Skin Cream; Adult; Elasticity; Collagen; Cell Survival; Elastin; Male; Skin; Treatment Outcome; Administration, Topical; Cell Proliferation; Aged
PubMed: 38932444
DOI: 10.1111/srt.13790