Optimal Duration Of Treatment Research Articles

Duration of antibiotic therapy for multidrug resistant Pseudomonas aeruginosa pneumonia: is shorter truly better?

BackgroundThe 2016 IDSA guideline recommends a treatment duration of at least 7 days for hospital-acquired (HAP)/ventilator-associated pneumonia (VAP). The limited literature has demonstrated higher rates of recurrence for non-glucose fermenting gram-negative bacilli with short course therapy, raising the concern of optimal treatment duration for these pathogens. Therefore, we aimed to compare the outcomes for patients receiving shorter therapy treatment (≤ 8 days) versus longer regimen (> 8 days) for the treatment of multidrug resistant (MDR) Pseudomonas pneumonia.MethodsA single-center, retrospective cohort study was conducted to evaluate adult patients receiving an antimicrobial regimen with activity against MDR Pseudomonas aeruginosa in respiratory culture between 2017 and 2020 for a minimum of 6 consecutive days. Exclusion criteria were inmates, those with polymicrobial pneumonia, community-acquired pneumonia, and infections requiring prolonged antibiotic therapy.ResultsOf 427 patients with MDR P. aeruginosa respiratory isolates, 85 patients were included. Baseline characteristics were similar among groups with a median age of 65.5 years and median APACHE 2 score of 20. Roughly 75% had ventilator-associated pneumonia. Compared to those who received ≤ 8 days of therapy, no difference was seen for clinical success in patients treated for more than 8 days (80% vs. 65.5%, p = 0.16). The number of 30-day and 90-day in-hospital mortality, 30-days relapse, and other secondary outcomes did not significantly differ among the treatment groups.ConclusionsProlonging treatment duration beyond 8 days did not improve patient outcomes for MDR P. aeruginosa HAP/VAP.

IMPACT OF PROLONGED USE OF ANTIDEPRESSANTS ON NEUROPLASTICITY

Antidepressants are widely used in the treatment of depressive and anxiety disorders and are essential for the management of these conditions. However, the impact of prolonged use of these drugs on neuroplasticity - the brain’s ability to reorganize itself, forming new neural connections - has been a topic of growing interest and debate in the scientific community. This abstract addresses the effects of prolonged use of antidepressants on neuroplasticity, considering their implications for long-term mental health. The aim of this paper is to examine and synthesize the scientific evidence on the impact of long-term use of antidepressants on neuroplasticity, with a focus on how these changes can influence the effectiveness of treatment and the long-term prognosis of patients. This study conducts a literature review on the long-term effects of antidepressants on neuroplasticity, investigating both the therapeutic potentials and the associated risks. The review focuses on how neuroplasticity can influence treatment outcomes, tolerance to antidepressants, and the impacts on specific populations, such as the elderly and individuals with hormonal variations. Antidepressants, especially selective serotonin reuptake inhibitors (SSRIs) and serotonin and noradrenaline reuptake inhibitors (SNRIs), have been shown to influence neuroplasticity in several ways. Pre-clinical and clinical studies suggest that prolonged use of these drugs can promote neurogenesis, particularly in the hippocampus, an area of the brain crucial for memory and learning. This neurogenic effect is associated with an improvement in depressive symptoms and the brain’s ability to adapt to new challenges. In addition, antidepressants appear to increase the expression of neurotrophic factors, such as brain-derived neurotrophic factor (BDNF), which plays a vital role in the survival and growth of neurons. The increase in BDNF levels may contribute to the restoration of synaptic connectivity, which is often compromised in patients with depression. However, there is controversy about the long-term effects of continuous use of these drugs on neuroplasticity. Some studies suggest that, despite the initial benefits, prolonged use can lead to a “rigidity” in brain plasticity, making it difficult to adapt to new treatments or therapeutic strategies. In addition, the impact on other areas of the brain, such as the prefrontal cortex, which is involved in decision-making and emotional control, is still poorly understood and requires further research. These findings raise questions about the optimal duration of treatment with antidepressants and the need for continuous monitoring of patients’ long-term mental health. Neuroplasticity may be a crucial factor in individual response to treatment and the possibility of relapse or development of resistance to treatment. Therefore, the prolonged use of antidepressants has a significant impact on neuroplasticity, initially promoting neurogenic effects and an increase in synaptic connectivity, which can improve depressive symptoms. However, the long-term effects still need to be better understood, especially with regard to the possible “rigidity” in brain plasticity and the implications for ongoing treatment. To maximize the benefits and minimize the risks, it is essential that treatment with antidepressants is carefully monitored, with attention to changes in neuroplasticity over time. More research is needed to elucidate the underlying mechanisms and guide clinical practice towards more effective and safer strategies for the management of depression and other related disorders.

Long-term hepatobiliary disorder associated with trastuzumab emtansine pharmacovigilance study using the FDA Adverse Event Reporting System database

Trastuzumab emtansine (T-DM1) is widely utilized as a second-line and subsequent treatment for metastatic HER2+ breast cancer and has shown promise in early breast cancer treatment, particularly in adjuvant settings for residual disease after neoadjuvant chemotherapy. However, concerns have arisen regarding long-term hepatic adverse drug reactions (ADRs) not identified in clinical trials. We investigated potential safety signals of T-DM1 in hepatobiliary disorders and the time-to-onset of ADRs using the FDA Adverse Event Reporting System (FAERS) database. Suspected ADRs were extracted and divided into two groups: T-DM1 (N = 3387) and other drugs (N = 11,833,701). Potential signal for T-DM1 in hepatobiliary disorder were identified (reporting odds ratio [ROR] = 5.66, 95% confidence interval [CI] = 5.11–6.27; information component [IC] = 2.35, 95% Credibility Interval [Crl] = 2.18–2.51). A breast cancer indicated subgroup analysis (2519 T-DM1; 172,329 other drugs) also identified a potential safety signal (ROR = 3.28, 95% CI = 2.92–3.68; IC = 1.53, 95%CrI = 1.35–1.71). The median time-to-onset for T-DM1-associated hepatobiliary disorders was 41 days. For prolonged and chronic hepatobiliary disorders, median times were 322.5 and 301.5 days, respectively. These findings highlight the need for further research to inform clinical decisions on optimal T-DM1 treatment duration, balancing benefits with potential adverse reactions.

Experimental study on H2O2 activation of HSC-T6 and hepatic fibrosis in cholestatic mice by "Yajieshaba"

Ethnopharmacological relevanceYajieshaba (YJSB), approved by the Yunnan Provincial Food and Drug Administration in 2008, are known for their anti-inflammatory, antiviral, and pro-apoptotic properties, effectively treating Hepatic fibrosis (HF). However, its mechanism of action remains unclear. Aim of the studyThe objective of this investigation is to explore how YJSB influences the TGF-β1/Smad signaling pathway as a strategy for reducing HF. MethodsThe establishment of a HF model in mice involved ligation of the common bile duct, followed by administration of YJSB. Body and liver weights were measured, and the liver index calculated. Serum levels of ALT, AST, ALP, TBA, and TBIL were assessed using colorimetric methods. Additionally, liver homogenates were analyzed for PIIINP, Col-IV, LN, HA, and Hyp, as well as TGF-β1 activity, using ELISA. Histological analyses of liver sections, stained with H&E, Ag, and Masson's trichrome, were performed to examine inflammation and the accumulation of collagen and reticular fibers. These studies aimed to elucidate the pharmacodynamic effects of YJSB on HF in mice with bile duct obstruction. The target pathways of YJSB were preliminarily identified through immunofluorescence detection of TGF-β1, P-Smad2L, P-Smad2C, P-Smad3L, P-Smad3C, and Smad4 proteins. In vitro experiments included the induction of hepatic stellate cell (HSC-T6) activation by H2O2. A cell injury model was established for HSC-T6, and the CCK-8 assay was used to determine the optimal YJSB concentration and treatment duration. After pirfenidone (PFD) administration, which inhibits the TGF-β1/Smad pathway, the effects of YJSB on HSC-T6 cell proliferation were observed. ELISA assays quantified Col-III, α-SMA, and Col-I in cell lysates to assess YJSB's impact on collagen synthesis in HSC-T6 cells. Western blot analysis was performed to assess the protein levels within the TGF-β1/Smad signaling cascade. ResultsIn the HF mouse model, administration of YJSB notably augmented the body weight and reduced the liver index. Concurrently, there was an elevation in serum concentrations of ALP, AST, ALT, TBA, and TBIL. Similarly, in the liver homogenates of HF mice, increases were observed in the levels of HA, PIIINP, Col-IV, LN, Hyp, and TGF-β1. Histological assessments using H&E, Ag, and Masson stains indicated a substantial diminution in liver tissue damage. Through immunofluorescence analysis, it was discerned that YJSB modulated the expression of TGF-β1, P-Smad2L, P-Smad2C, and P-Smad3L downwards, while elevating P-Smad3C and Smad4 protein expressions. Additional investigations revealed a significant reduction in α-SMA, Col-I, and Col-III levels in cell culture fluids, suggesting a decrease in collagen synthesis and a protective role against cellular damage. Western blot analyses demonstrated that the TGF-β1/Smad pathway inhibitor, PFD, acted in synergy with YJSB, enhancing its regulatory effects on this pathway, decreasing levels of TGF-β1, P-Smad2L, P-Smad2C, P-Smad3L, and promoting the expression of P-Smad3C. ConclusionsYJSB demonstrates a pharmacodynamic effect against HF, enhancing liver functionality and effectively mitigating the damage associated with bile duct obstruction. The proposed action mechanism of YJSB involves modulation of the TGF-β1/Smad signaling pathway. Research indicates that YJSB might play a role in suppressing the movement, programmed cell death, and activation of HSC-T6, potentially decelerating the advancement of hepatic fibrosis.

Interpretable artificial intelligence to optimise use of imatinib after resection in patients with localised gastrointestinal stromal tumours: an observational cohort study.

Current guidelines recommend use of adjuvant imatinib therapy for many patients with gastrointestinal stromal tumours (GISTs); however, its optimal treatment duration is unknown and some patient groups do not benefit from the therapy. We aimed to apply state-of-the-art, interpretable artificial intelligence (ie, predictions or prescription logic that can be easily understood) methods on real-world data to establish which groups of patients with GISTs should receive adjuvant imatinib, its optimal treatment duration, and the benefits conferred by this therapy. In this observational cohort study, we considered for inclusion all patients who underwent resection of primary, non-metastatic GISTs at the Memorial Sloan Kettering Cancer Center (MSKCC; New York, NY, USA) between Oct 1, 1982, and Dec 31, 2017, and who were classified as intermediate or high risk according to the Armed Forces Institute of Pathology Miettinen criteria and had complete follow-up data with no missing entries. A counterfactual random forest model, which used predictors of recurrence (mitotic count, tumour size, and tumour site) and imatinib duration to infer the probability of recurrence at 7 years for a given patient under each duration of imatinib treatment, was trained in the MSKCC cohort. Optimal policy trees (OPTs), a state-of-the-art interpretable AI-based method, were used to read the counterfactual random forest model by training a decision tree with the counterfactual predictions. The OPT recommendations were externally validated in two cohorts of patients from Poland (the Polish Clinical GIST Registry), who underwent GIST resection between Dec 1, 1981, and Dec 31, 2011, and from Spain (the Spanish Group for Research in Sarcomas), who underwent resection between Oct 1, 1987, and Jan 30, 2011. Among 1007 patients who underwent GIST surgery in MSKCC, 117 were included in the internal cohort; for the external cohorts, the Polish cohort comprised 363 patients and the Spanish cohort comprised 239 patients. The OPT did not recommend imatinib for patients with GISTs of gastric origin measuring less than 15·9 cm with a mitotic count of less than 11·5 mitoses per 5 mm2 or for those with small GISTs (<5·4 cm) of any site with a count of less than 11·5 mitoses per 5 mm2. In this cohort, the OPT cutoffs had a sensitivity of 92·7% (95% CI 82·4-98·0) and a specificity of 33·9% (22·3-47·0). The application of these cutoffs in the two external cohorts would have spared 38 (29%) of 131 patients in the Spanish cohort and 44 (35%) of 126 patients in the Polish cohort from unnecessary treatment with imatinib. Meanwhile, the risk of undertreating patients in these cohorts was minimal (sensitivity 95·4% [95% CI 89·5-98·5] in the Spanish cohort and 92·4% [88·3-95·4] in the Polish cohort). The OPT tested 33 different durations of imatinib treatment (<5 years) and found that 5 years of treatment conferred the most benefit. If the identified patient subgroups were applied in clinical practice, as many as a third of the current cohort of candidates who do not benefit from adjuvant imatinib would be encouraged to not receive imatinib, subsequently avoiding unnecessary toxicity on patients and financial strain on health-care systems. Our finding that 5 years is the optimal duration of imatinib treatment could be the best source of evidence to inform clinical practice until 2028, when a randomised controlled trial with the same aims is expected to report its findings. National Cancer Institute.

The Effect of Vitamin D Supplementation on Thyroid Hormone Levels in Patients With Autoimmune Thyroid Disease: A Systematic Review.

Autoimmune thyroid diseases (AITDs) pose significant challenges in clinical practice, representing one of the most common endocrine abnormalities. Vitamin D deficiency has been linked as one of the contributing factors to the etiology of AITDs. This systematic review evaluates the effects of vitamin D supplementation on thyroid-stimulating hormone (TSH), triiodothyronine (T3), and thyroxine (T4) levels in adults with AITDs. Using a PICO (population, intervention, comparison, and outcome) framework and adhering to thePreferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, seven relevant studies were identified from an initial pool of 1,469 articles. The population comprised individuals with thyroid autoimmunity, as evidenced by at least one elevated positive thyroid autoimmune marker and intervention involved the supplementation of vitamin D, regardless of the dose or method of administration. All randomized clinical trials within the last 10 years, which fit the study criteria, were included. These studies showed varying results based on follow-up duration. Short-term studies (three months or less) demonstrated no significant changes in mean TSH, T3, or T4 levels compared to the control group with vitamin D supplementation. However, all of the long-term studies (greater than three months) indicated significant improvements compared to the controlin mean TSH, T3, and T4 levels. Additionally, all long-term studies that compared TSH, T3, and T4 to baseline levels revealed significant changes by the trial's end. Despite these promising findings, the review highlights limitations, including small sample sizes, short study durations, and the need for further research to establish optimal dosing and treatment duration for vitamin D in AITD management. The overall findings suggest that vitamin D supplementation may play a part in thyroid hormone regulation in AITD, particularly with prolonged administration.

Herbal and Natural Supplements for Improving Sleep: A Literature Review.

Herbal and natural supplements have gained popularity as alternative treatments to insomnia and sleep disorders due to their perceived safety and potential effectiveness. This literature review summarizes the current evidence on the efficacy, safety, and mechanisms of action of commonly used supplements for sleep, including valerian, hops, kava, German chamomile, cherry, tryptophan, theanine, melatonin, magnesium, and zinc. We conducted literature review of clinical research on herbal and supplements for sleep reported to date. We summarized key findings and reviewed outcomes related to clinical efficacy and side effects. Findings suggest that certain supplements, particularly valerian, hops, and melatonin, could be effective in improving sleep quality and reducing insomnia symptoms through modulation of neurotransmitter systems and regulation of sleep-wake cycles. However, the strength of the evidence varies with unestablished optimal dosages, formulations, and treatment durations. Although generally considered safe, these supplements are not without risks, such as rare but serious adverse effects associated with kava and potential interactions with prescription medications. The quality and purity of supplements also vary widely due to a lack of strict regulations. Healthcare providers should remain informed about the latest research and work closely with patients to develop personalized treatment plans. Herbal and natural supplements may offer promising alternatives or adjunct treatments for insomnia and sleep disorders, but their use should be guided by the best available evidence and individual patient requirements. Larger, well-designed clinical trials are needed to establish the efficacy and safety of these supplements for clinical decision-making.

Immunomodulatory activity of ovotransferrin-chlorogenic acid complexes enhanced by high-intensity ultrasound (HIU): A structure-function relationship study

This study investigated the impact of high-intensity ultrasound (HIU) treatment on the physiochemical, conformational, and immunomodulatory activity of the OVT-CA complex, emphasizing the structure-function relationship. HIU treatment reduced particle size, improved dispersion, and increased electronegativity of the complex. It facilitated binding between OVT and CA, achieving a maximum degree of 45.22 mg/g CA grafting and reducing interaction time from 2 h to 15 min. HIU-induced cavitation and shear promoted the exposure of -SH and unfolding of OVT, leading to increased surface hydrophobicity of the complex and transformation of its structure from β-sheet to α-helix. Additionally, CA binds to OVT in the C-lobe region, and HIU treatment modulates the intermolecular forces governing the complex formation, particularly by reinforcing hydrogen bonding, hydrophobic interactions, and introducing electrostatic interactions. Furthermore, HIU treatment increased the immunomodulatory activity of the complex, which was attributed to complex structural changes facilitating enhanced cell membrane affinity, antigen recognition, and B-cell epitope availability. Hierarchical cluster and Pearson correlation analysis confirmed that HIU treatment duration had a greater impact than power on both the structure and activity of the complex, and an optimal HIU treatment duration within 30 min was found to be crucial for activity enhancement. Moreover, structural changes, including ζ-potential, particle size/turbidity, and surface hydrophobicity, were closely correlated with immunomodulatory activity. This study highlights the potential application of HIU in developing protein–polyphenol immunomodulatory agents for public health and food nutrition.

The Impact of Statins on Disease Severity and Quality of Life in Patients with Psoriasis: A Systematic Review and Meta-Analysis.

Psoriasis, a chronic autoimmune condition, imposes significant burdens on patients' well-being. While corticosteroid medications are commonly used, their prolonged use presents risks. Statins, known for their immunoregulatory and anti-inflammatory properties, have emerged as potential alternatives. Previous reviews indicated that statins might improve psoriasis symptoms but showed inconsistent results and lacked meta-analyses that generated pooled effect estimates. Therefore, this study addresses this gap by providing a comprehensive overview of the impact of statins on psoriasis severity and quality of life (QoL) for patients with psoriasis. A thorough search of four electronic databases (PubMed, Cochrane Central Register of Controlled Trials, Scopus, and Science Direct) was conducted for relevant studies published before April 2024. Seven studies involving 369 patients were included. This meta-analysis showed a statistically significant reduction in PASI scores at week 8 with statin treatment (MD = -1.96, 95% CI [-3.14, -0.77], p = 0.001). However, no statistically significant difference was found between statins and placebo at week 12 (MD = 0.19, 95% CI [-0.18, 0.55]). Additionally, DLQI scores indicated a significant improvement in quality of life with statins compared to placebo (MD = -3.16, 95% CI [-5.55, -0.77]). Statins can improve disease severity and quality of life in psoriasis patients, suggesting the potential benefits of statin therapy. However, further research is needed to determine the optimal treatment duration, address outcome heterogeneity, and explore additional benefits such as cholesterol and triglyceride reduction.

Effects of electrical stimulation with alternating fields on the osseointegration of titanium implants in the rabbit tibia - a pilot study.

Introduction: Electrical stimulation has been used as a promising approach in bone repair for several decades. However, the therapeutic use is hampered by inconsistent results due to a lack of standardized application protocols. Recently, electrical stimulation has been considered for the improvement of the osseointegration of dental and endoprosthetic implants. Methods: In a pilot study, the suitability of a specifically developed device for electrical stimulation in situ was assessed. Here, the impact of alternating electric fields on implant osseointegration was tested in a gap model using New Zealand White Rabbits. Stimulation parameters were transmitted to the device via a radio transceiver, thus allowing for real-time monitoring and, if required, variations of stimulation parameters. The effect of electrical stimulation on implant osseointegration was quantified by the bone-implant contact (BIC) assessed by histomorphometric (2D) and µCT (3D) analysis. Results: Direct stimulation with an alternating electric potential of 150mV and 20Hz for three times a day (45min per unit) resulted in improved osseointegration of the triangular titanium implants in the tibiae of the rabbits. The ratio of bone area in histomorphometry (2D analysis) and bone volume (3D analysis) around the implant were significantly increased after stimulation compared to the untreated controls at sacrifice 84days after implantation. Conclusion: The developed experimental design of an electrical stimulation system, which was directly located in the defect zone of rabbit tibiae, provided feedback regarding the integrity of the stimulation device throughout an experiment and would allow variations in the stimulation parameters in future studies. Within this study, electrical stimulation resulted in enhanced implant osseointegration. However, direct electrical stimulation of bone tissue requires the definition of dose-response curves and optimal duration of treatment, which should be the subject of subsequent studies.

Curcumin and nano-curcumin applications in psychiatric disorders.

Psychiatric disorders cause long-lasting disabilities across different age groups. While various medications are available for mental disorders, some patients do not fully benefit from them or experience treatment resistance. The pathogenesis of psychiatric disorders involves multiple mechanisms, including an increase in the inflammatory response. Targeting inflammatory mechanisms has shown promise as a therapeutic approach for these disorders. Curcumin, known for its anti-inflammatory properties and potential neuroprotective effects, has been the subject of studies investigating its potential as a treatment option for psychiatric disorders. This review comprehensively examines the potential therapeutic role of curcumin and its nanoformulations in psychiatric conditions, including major depressive disorder (MDD), bipolar disorder, schizophrenia, and anxiety disorders. There is lack of robust clinical trials across all the studied psychiatric disorders, particularly bipolar disorder and schizophrenia. More studies have focused on MDD. Studies on depression indicate that curcumin may be effective as an antidepressant agent, either alone or as an adjunct therapy. However, inconsistencies exist among study findings, highlighting the need for further research with improved blinding, optimized dosages, and treatment durations. Limited evidence supports the use of curcumin for bipolar disorder, making its therapeutic application challenging. Well-designed clinical trials are warranted to explore its potential therapeutic benefits. Exploring various formulations and delivery strategies, such as utilizing liposomes and nanoparticles, presents intriguing avenues for future research. More extensive clinical trials are needed to assess the efficacy of curcumin as a standalone or adjunctive treatment for psychiatric disorders, focusing on optimal dosages, formulations, and treatment durations.

P-093 The effect of antioxidant supplementation on sperm quality in infertile men: a randomized placebo-controlled clinical trial

Abstract Study question Is sperm quality improved in infertile men after administration for three months of a combination of antioxidants as compared to placebo? Summary answer Administration in infertile men for three months of a combination of antioxidants as compared to placebo does not improve sperm quality. What is known already In infertile men, limited evidence exists to support treatment with a combination of antioxidants for improving sperm quality. A recent Cochrane meta-analysis suggested that treatment of these patients with combinations of antioxidants as compared to placebo or no treatment results in an increase in sperm motility (MD + 12.71 95%CI +11.33 to + 14.08, 7 studies, 684 patients), while no beneficial effect was observed on DNA fragmentation index (DFI) and on the probability of live birth. Nevertheless, combinations of antioxidants are widely used in clinical practice at present. Study design, size, duration This randomized placebo-controlled trial evaluated the effect of a combination of antioxidants on sperm motility (primary outcome). Secondary outcomes were sperm concentration, morphology, DFI and levels of reactive oxygen species (ROS). For this purpose, 79 infertile men, were randomized, using a computer-generated randomization list, between 2019-2022, to receive either a combination of antioxidants (n = 40) or placebo (n = 39) for three months. This was a quadruple-blind trial (participants, clinicians, outcome assessors, data analyst). Participants/materials, setting, methods Sperm variables were evaluated according to WHO criteria, ROS levels by the detection of 8-hydroxy-2-deoxy-guanosine peroxidation product on sperm and DFI by flow cytometry. For all outcomes, the changes between treatment initiation and completion were assessed in both the antioxidant and the placebo groups and compared statistically. Values are expressed as mean (95%CI of the mean) and statistical significance was set at p = 0.05. Main results and the role of chance Nine patients dropped out from the study, since they did not perform the second sperm analysis for personal reasons and thus did not complete the study process. No differences were observed between the antioxidants and the placebo group regarding male age {mean difference (MD) -1.3 years, 95%CI -1.4 to + 4.1}, smoking (antioxidants: 41.6%, 95%CI 25.5 to 59.2 vs placebo: 43.5%, 95%CI 27.8 to 60.3), exercise (antioxidants: 45.4%, 95%CI 28.1 to 63.6 vs placebo: 16.1%, 95%CI 5.4 to 33.7) and primary infertility (antioxidants: 82.3%, 95%CI 65.4 to 93.2 vs placebo: 85.7%, 95%CI 69.7 to 95.1). No statistically significant differences were observed in infertile men who received a combination of antioxidants or placebo, between the changes of pre and post treatment values, regarding sperm motility (-3.5%, 95%CI: -13 to + 5.9, p = 0.742), concentration (-1.9%, 95%CI: -15.7 to + 11.8, p = 0.0.77), morphology (-0.10%, 95%CI: -0.8 to 0.6, p = 0.793), DFI (0.2%, 95%CI: -3.8 to + 4.4, p = 0.891) and levels of ROS (-1.2%, 95%CI: -3.2 to + 0.8, p = 0.231). No side effects were reported in antioxidants combination treated patients for the duration of follow-up. Limitations, reasons for caution The current RCT did not explicitly include men with abnormal DFI, limiting the extrapolation of the results obtained in this group of patients. Moreover, it was not designed to evaluate the probability of pregnancy either spontaneously or after Medically Assisted Reproduction (MAR). Wider implications of the findings The current study does not support the use of antioxidants for enhancing male infertility. Future relevant studies should focus on identifying the optimal population and duration of treatment. Trial registration number NCT04256278

Analysis of Probiotic Role in Non-Alcoholic Fatty Liver Disease (NAFLD) Management: A Meta-Analysis

Background: Non-alcoholic fatty liver disease (NAFLD) is an increasing global health problem. Probiotics have emerged as a potential therapy for NAFLD, but evidence for their efficacy remains mixed. This meta-analysis aims to evaluate the effectiveness of probiotics in the management of NAFLD. Methods: A comprehensive literature search was performed on PubMed, Embase, Cochrane Library, and Web of Science databases until December 2023. Randomized controlled trials (RCTs) evaluating the effects of probiotics in NAFLD patients were included. The main outcomes evaluated were changes in liver enzymes (ALT, AST), insulin resistance index (HOMA-IR), and hepatic steatosis score. Meta-analysis was performed using a random effects model, and heterogeneity was assessed using the I² statistic. Results: Twenty-five RCTs involving 1845 patients met inclusion criteria. Meta-analysis showed that probiotics significantly reduced ALT (MD -8.45; 95% CI -12.67 to -4.23; p&lt;0.0001) and AST (MD -6.89; 95% CI -10.11 to -3.67; p&lt;0.0001) levels compared with placebo. Significant reductions were also observed in HOMA-IR (MD -0.68; 95% CI -1.02 to -0.34; p&lt;0.0001) and hepatic steatosis scores (SMD -0.45; 95% CI -0.71 to -0.19; p=0.0008). Subgroup analysis showed that the effects of probiotics were more pronounced in patients with NAFLD non-alcoholic steatohepatitis (NASH) and those receiving multi-strain probiotics. Conclusion: This meta-analysis provides strong evidence that probiotics have beneficial effects on biochemical and imaging parameters in NAFLD patients. Probiotics may be considered as an adjunct therapy for NAFLD, especially in patients with NASH. However, more research is needed to determine the optimal probiotic strain, dosage, and duration of treatment.

Short-Term Statin Treatment Reduces, and Long-Term Statin Treatment Abolishes, Chronic Vascular Injury by Radiation Therapy.

The incidental use of statins during radiation therapy has been associated with a reduced long-term risk of developing atherosclerotic cardiovascular disease. We examined whether irradiation causes chronic vascular injury and whether short-term administration of statins during and after irradiation is sufficient to prevent chronic injury compared with long-term administration. C57Bl/6 mice were pretreated with pravastatin for 72 hours and then exposed to 12 Gy X-ray head-and-neck irradiation. Pravastatin was then administered either for an additional 24 hours or for 1 year. Carotid arteries were tested for vascular reactivity, altered gene expression, and collagen deposition 1 year after irradiation. Treatment with pravastatin for 24 hours after irradiation reduced the loss of endothelium-dependent vasorelaxation and protected against enhanced vasoconstriction. Expression of markers associated with inflammation (NFκB p65 [phospho-nuclear factor kappa B p65] and TNF-α [tumor necrosis factor alpha]) and with oxidative stress (NADPH oxidases 2 and 4) were lowered and subunits of the voltage and Ca2+ activated K+ BK channel (potassium calcium-activated channel subfamily M alpha 1 and potassium calcium-activated channel subfamily M regulatory beta subunit 1) in the carotid artery were modulated. Treatment with pravastatin for 1 year after irradiation completely reversed irradiation-induced changes. Short-term administration of pravastatin is sufficient to reduce chronic vascular injury at 1 year after irradiation. Long-term administration eliminates the effects of irradiation. These findings suggest that a prospective treatment strategy involving statins could be effective in patients undergoing radiation therapy. The optimal duration of treatment in humans has yet to be determined.

Current management of giant cell arteritis and its complications.

This review provides an update on current management strategies for giant cell arteritis (GCA), emphasizing the need for alternative therapies to reduce disease relapses and mitigate glucocorticoid (GC)-related morbidity. The standard of care for GCA has traditionally involved prolonged use of GC, and recent studies are exploring faster GC tapering regimens in an effort to reduce adverse effects while maintaining disease control. Randomized clinical trials have highlighted the efficacy of tocilizumab (TCZ), an interleukin-6 receptor inhibitor, in reducing disease flares and sparing GCs. However, the optimal treatment duration with TCZ is unknown and patients remain at risk of relapse after treatment discontinuation. An unmet therapeutic need persists for patients who are not candidates for TCZ, and for those who have inadequate response to this biologic. Therefore, investigations into alternative therapies such as targeting interleukin-17A, blocking T-cell activation or inhibiting the Janus kinase-signal transducer and activator of transcription pathway, showcase potential avenues for tailored treatments. While GCs remain the cornerstone of therapy, TCZ emerges as a promising GC-sparing agent. Ongoing research targeting different pathways implicated in GCA pathogenesis have led to encouraging results. However, the preliminary nature of these findings necessitates larger randomized controlled trials to establish their efficacy conclusively.

A Study on Optimal Frequency and Duration of PRP in Androgenic Alopecia

Background: Platelet-rich plasma (PRP) therapy has emerged as a promising treatment for androgenetic alopecia (AA), addressing the need for effective hair restoration with minimal invasiveness. However, questions remain regarding the optimal frequency and duration of PRP treatment. Objective: This study aimed to assess the impact of PRP therapy on hair density and diameter in AGA patients, considering variations in treatment response across different AGA grades and alopecia durations. Method: A 6-month open-labeled pilot study was conducted on 30 male participants with AGA Grades III-VII. PRP was administered every 15 days for six sessions, and hair parameters were evaluated using trichoscan. Results: The study demonstrated a significant increase in both hair diameter and density over six months of platelet-rich plasma (PRP) therapy for androgenetic alopecia (AGA). Initially, the mean hair diameter was 0.055 mm, rising to 0.075 mm by the study's end, with a substantial increase of 0.021 mm at six months, equating to a 39.85% improvement. Similarly, hair density increased notably from 6.13 to 8.43 hairs per 10 mm², with the most significant rise at the six-month mark, showing a mean increase of 2.3 hairs per 10 mm², reflecting a 39.73% enhancement. All AGA grades experienced increased hair diameter and density, with Grade 5 showing the highest diameter increase (0.03 mm), and Grade 4A exhibiting the highest density increase (3.0 hairs per 10 mm²). Statistical analysis confirmed significant improvements across all grades (p = 0.0446 for diameter; p = 0.0196 for density). Additionally, patients with alopecia durations up to five years experienced the highest improvements in both diameter (0.026 mm) and density (2.68 hairs per 10 mm²), while longer durations showed lower enhancements (p = 0.0485 for diameter; p = 0.0096 for density). Conclusion: PRP therapy demonstrated efficacy across all AGA grades and durations, suggesting its potential as a promising treatment option for AGA. Further research is needed to validate these findings and establish PRP therapy as a standard AGA treatment.

Safety and efficacy of Kaffes intraductal self-expanding metal stents in the management of post-liver transplant anastomotic strictures.

Endoscopic management is the first-line therapy for post-liver-transplant anastomotic strictures. Although the optimal duration of treatment with plastic stents has been reported to be 8-12 months, data on safety and duration for metal stents in this setting is scarce. Due to limited access to endoscopic retrograde cholangiopancreatography (ERCP) during the coronavirus disease 2019 pandemic in our centre, there was a change in practice towards increased usage and length-of-stay of the Kaffes biliary intraductal self-expanding stent in patients with suitable anatomy. This was mainly due to the theoretical benefit of Kaffes stents allowing for longer indwelling periods compared to the traditional plastic stents. To compare the safety and efficacy profile of different stenting durations using Kaffes stents. Adult liver transplant recipients aged 18 years and above who underwent ERCP were retrospectively identified during a 10-year period through a database query. Unplanned admissions post-Kaffes stent insertion were identified manually through electronic and scanned medical records. The main outcome was the incidence of complications when stents were left indwelling for 3 months vs 6 months. Stent efficacy was calculated via rates of stricture recurrence between patients that had stenting courses for ≤ 120 d or > 120 d. During the study period, a total of 66 ERCPs with Kaffes insertion were performed in 54 patients throughout their stenting course. In 33 ERCPs, the stent was removed or exchanged on a 3-month interval. No pancreatitis, perforations or deaths occurred. Minor post-ERCP complications were similar between the 3-month (abdominal pain and intraductal migration) and 6-month (abdominal pain, septic shower and embedded stent) groups - 6.1% vs 9.1% respectively, P = 0.40. All strictures resolved at the end of the stenting course, but the stenting course was variable from 3 to 22 months. The recurrence rate for stenting courses lasting for up to 120 d was 71.4% and 21.4% for stenting courses of 121 d or over (P = 0.03). There were 28 patients that were treated with a single ERCP with Kaffes, 21 with removal after 120 d and 7 within 120 d. There was a significant improvement in stricture recurrence when the Kaffes was removed after 120 d when a single ERCP was used for the entire stenting course (71.0% vs 10.0%, P = 0.01). Utilising a single Kaffes intraductal fully-covered metal stent for at least 4 months is safe and efficacious for the management of post-transplant anastomotic strictures.

NIR-II Absorption/Emission Dual Function Based 2D Targeted Nanotheranostics for Tunable Hydrogenothermal Therapy.

Photothermal therapy (PTT) is a promising approach for treating tumors that offers multiple advantages. Nevertheless, its practical use in clinical settings faces several limitations, such as suboptimal delivery efficiency, uneven heat distribution, and challenges in predicting optimal treatment duration. In addition, the localized hyperthermia generated by the PTT method to induce cell apoptosis can result in the production of excessive reactive oxygen species (ROS) and the release of inflammatory cytokines, which can pose a threat to the healthy tissues surrounding the tumor. To address the above challenges, this work designs an integrated H2 delivery nanoplatform for multimodal imaging H2 thermal therapy. The combination of the second near-infrared window (NIR-II) fluorescence imaging (FL) agent (CQ4T) and the photothermal and photoacoustic (PA) properties of Ti3C2 (TC) enables real-time monitoring of the tumor area and guides photothermal treatment. Simultaneously, due to the acid-responsive H2 release characteristics of the nanoplatform, H2 can be utilized for synergistic photothermal therapy to eradicate tumor cells effectively. Significantly, acting as an antioxidant and anti-inflammatory agent, Ti3C2-BSA-CQ4T-H2 (TCBCH) protects peritumoral normal cells from damage. The proposed technique utilizing H2 gas for combination therapies and multimodal imaging integration exhibits prospects for effective and secure treatment of tumors in future clinical applications.

A retrospective study to evaluate the safety and efficacy of intrapleural alteplase in pediatric empyema.

Medical treatment of pediatric empyema consists of appropriate antibiotics, chest tube insertion, and intrapleural fibrinolytic drugs to facilitate pleural drainage. There is a lack of consensus about the drug of choice for fibrinolytic therapy, so this study was designed to evaluate the safety and efficacy of intrapleural alteplase in pediatric empyema. The medical records of all children with empyema treated with intrapleural alteplase at a university hospital between January 2016 and December 2020 were retrospectively reviewed. Efficacy outcomes were assessed by chest tube output before and after the first dose of alteplase, pleural fluid volume before and after therapy, a need for surgical intervention, and length of hospital stay. Safety was assessed by the frequency and severity of side effects. 40 children aged 2 months to 9 years hospitalized with empyema received intrapleural alteplase. Thirty patients (75%) experienced full recovery after three doses of intrapleural alteplase. The median length of hospital stay was 16 days. Chest tube output increased significantly after the first dose of alteplase. Pleural fluid volume decreased significantly after treatment. The most common side effect was pain (30%). Two patients experienced severe complications: 1 had a pulmonary hemorrhage and the other experienced a bronchopleural fistula. These patients recovered fully spontaneously. According to our results, the administration of intrapleural alteplase was safe and effective in facilitating pleural drainage in pediatric patients with empyema. However, further clinical trials will be needed to determine the optimal dose, frequency, and duration of intrapleural alteplase treatment.

The Effects of Longer Use of Teriparatide on Clinical and Radiographic Outcomes after Spinal Fusion in Geriatric Patients.

Background: Teriparatide is an anabolic agent for osteoporosis and is believed to improve the bone healing process. Previous studies showed that teriparatide could enhance not only fracture healing but also spine fusion. It has been reported that use of teriparatide could promote the spine fusion process and decrease mechanical complications. However, there was no consensus regarding optimal treatment duration. The purpose of this study was to compare surgical outcomes between short-duration and long-duration teriparatide treatment after lumbar fusion surgery in elderly patients. Materials and Methods: All consecutive patients older than 60 years who underwent 1-level lumbar fusion surgery for degenerative diseases between January 2015 and December 2019 were retrospectively reviewed. Based on the duration of teriparatide treatment (daily subcutaneous injection of 20 µg teriparatide), patients were subdivided into two groups: a short-duration (SD) group (<6 months) and a long-duration (LD) group (≥6 months). Mechanical complications, such as screw loosening, cage subsidence, and adjacent vertebral fractures, were investigated. Postoperative 1-year union rate was also evaluated on computed tomography. Clinical outcomes were recorded using visual analog scale (VAS) and Oswestry Disability Index (ODI). Between-group differences for these radiographic and clinical outcomes were analyzed. Results: Ninety-one patients were reviewed in this study, including sixty patients in the SD group and thirty-one patients in the LD group. Their mean age was 72.3 ± 6.2 years, and 79 patients were female. Mean T-score was -3.3 ± 0.8. Cage subsidence (6.7% vs. 3.2%), screw loosening (28.3% vs. 35.5%), and adjacent vertebral fracture (6.7% vs. 9.7%) were not significantly different between the SD and LD groups. Union rate at 1-year postoperative was 65.0% in the SD group and 87.1% in the LD group (p = 0.028). Both groups showed improvement in VAS and ODI after surgery. However, the differences of VAS from preoperative to 6 months and 1 year postoperative were significantly higher in the LD group. Conclusions: Longer teriparatide treatment after lumbar fusion surgery resulted in a higher union rate at 1-year postoperative than the shorter treatment. Also, it could be more beneficial for clinical outcomes.