Efficacy Of Treatment Research Articles

Barriers That Interfere with Access to Tuberculosis Diagnosis and Treatment across Countries Globally: A Systematic Review.

This study evaluated the barriers that interfere with access to diagnosis and treatment of tuberculosis (TB) from the perspective of the patient and health professionals globally. Using the PICo acronym, the question we asked was "What are the barriers that interfere with access to tuberculosis diagnosis and treatment (I) from the perspective of patients and/or health professionals (P) across countries globally (Co)?". We searched the following databases: EMBASE, Scopus, MEDLINE, Latin American and Caribbean Literature in Health Sciences (LILACS), and Web of Science. On Rayyan, duplicates were removed and extraction was done afterward by two authors independently, followed by a tiebreaker. Using a Critical Appraisal Tool proposed by the Joanna Briggs Institute, the methodological quality of the article was assessed. From 36 published articles, the barriers to tuberculosis diagnosis as obtained from our study include information scarcity/low TB knowledge, exorbitant cost of transport, sample collection challenges, long distance to health facility, gender limitations, lack of decentralized diagnostic services, payment for diagnosis and testing, medication side effects, multiple visits during therapy, delayed diagnosis, poor human resources, low knowledge of medical practitioners, concerns regarding the efficacy of treatment, poor facility coordination, poor socioeconomic factors, fear and stigmatization of TB, and wrong initial diagnosis. The review of studies on TB diagnosis and treatment barriers evidences the diverse barriers to the eradication of tuberculosis. Eliminating these barriers is an onus that lies on policy makers, citizens, and health workers alike, with the joint aim of reducing the global TB burden.

Technical note: Computational study on thermal management schemes for tumor-treating fields therapy.

The study focuses on thermal management in tumor-treating fields (TTFields) therapy, crucial for patient compliance and therapeutic effectiveness. TTFields therapy, an established treatment for glioblastoma, involves applying alternating electric fields to the brain. However, managing the thermal effects generated by electrodes is a major challenge, impacting patient comfort and treatment efficiency. This research aims to explore methods for controlling temperature increases during TTFields therapy without reducing its duty cycle. The study emphasizes optimizing electrode configurations and array arrangements to mitigate temperature rise, thereby maintaining therapy effectiveness and patient compliance. Using a simplified multi-layer tissue model and finite element analysis, various electrode configurations and array shapes were tested in COMSOL Multiphysics v6.0. Adjustments included changing the electrode gel layer radius from 8 to 12mm, electrode spacing, and transitioning to a more uniform array arrangement, such as a square array or a circular array. The study revealed a strong correlation between high temperatures and edge current density distributions on electrodes. It was found that increasing the electrode gel layer's diameter, enlarging electrode spacing, and adopting a uniform array arrangement markedly mitigated temperature rises. By increasing the gel layer radius from the original 10 to 12mm, a reduction in the peak temperature increases of approximately 0.3°C was observed. Changing the layout from rectangular to circular with the same area further reduced the peak temperature rise by 0.5°C. Additionally, enlarging the spacing between electrodes also contributed to temperature control. By integrating these strategies, we designed a new circular electrode array with an electrode spacing of 45mm and a gel radius of 12mm, successfully reducing the peak temperature from 42.1°C to 40.8°C, effectively achieving temperature control. The research demonstrates that improving electrode and array configurations can effectively manage temperature in TTFields therapy without compromising treatment duration. This strategy is crucial as TTFields therapy relies on prolonged field exposure for effectiveness. The findings offer valuable insights into thermal management in electrode array design and could lead to enhanced patient compliance and treatment efficacy in TTFields therapy.

The efficacy of various interventions as good strategies to reduce pain in botulinum neurotoxin A for wrinkles. A systematic review of the randomized controlled trials (RCTs).

Various topical interventions have been described to minimize botulinum neurotoxin-A (BoNT)-induced pain. The purpose of this study is to conduct a systematic review of relevant randomized controlled trials (RCTs) to compare the efficacy of pain relief methods during BoNT injection. PubMed, Scopus, and Web of Science were searched using "Botox," "Botulinum," or "BTX." We identified RCTs in which BoNT were injected to eliminate wrinkles. The pain score was the study outcome, and pain reduction method was compared with routine one. The meta-analysis was reported using the PRISMA checklist. The Higgins I(I2) statistical model assessed results heterogeneity. Two thousand one hundred and twenty-three articles were identified, thirteen articles eligible. Two hundred and sixty-two healthy volunteers were performed on these RCTs. Meta-analysis evaluated different methods to ease BoNT injection pain, and these methods significantly improved outcomes by 0.23% (95%CI, 0.11-0.46, p = .000). Subgroup analysis based on injection area showed no significant heterogeneity, but heterogeneity decreased when subgroup analysis based on other methods was done (Cochran's Q test = 115.52, p = .0001, I2 = 87.9%). This meta-analysis confirms the effectiveness of pain relief methods during BoNT injection. Evaluation of different methods showed their effectiveness, but finding the best method requires comparative studies, although the role of pH and EMLA has been proven.

Maintenance Intravenous Immunoglobulin Therapy for Chronic Inflammatory Demyelinating Polyneuropathy: 18-Month Post-marketing Surveillance in 103 Patients.

Objective The efficacy of maintenance intravenous immunoglobulin (IVIg) therapy has been established to prevent relapse in chronic inflammatory demyelinating polyneuropathy (CIDP). This prospective post-marketing surveillance study evaluated the treatment duration, efficacy, and safety of maintenance IVIg therapy in Japanese patients with CIDP. Methods Patients were registered between June 2017 and December 2018. After induction of IVIg therapy (0.4 g/kg/day for 5 consecutive days), patients received maintenance IVIg (1.0 g/kg every 3 weeks). The observation period was 18 months. Efficacy in preventing relapse was assessed using the Inflammatory Neuropathy Cause and Treatment (INCAT) disability score. Relapse was defined as a worsening of the INCAT score by ≥1 from baseline. Patients The efficacy population comprised 103 patients (80 with typical CIDP and 23 with CIDP variants). Results During the observation period, 86 (83%) patients were scheduled to continue maintenance IVIg therapy during the observation period, and the relapse rate was 24% (21/86). In the remaining 17 patients who showed continuous remission, maintenance IVIg therapy was stopped (mean, 136 days after the start), and the relapse rate was 24% (4/17). One serious adverse drug reaction of cardiac failure was reported. Conclusion In this post-marketing surveillance, most (83%) patients with CIDP were scheduled to continue maintenance IVIg for 18 months, with a relapse rate of 24%, indicating long-term efficacy. Maintenance IVIg therapy was rarely withdrawn, and the relapse rate after withdrawal was 24%. Further studies are required to determine the optimal maintenance IVIg dose and duration.

Peripheral blood MR1 tetramer-positive mucosal-associated invariant T-cell function is modulated by mammalian target of rapamycin complex 1 in patients with active tuberculosis.

Tuberculosis (TB) is still an urgent global public health problem. Notably, mucosal-associated invariant T (MAIT) cells play an important role in early anti-TB immune response. Targeted control of them may be an effective method to improve vaccine efficacy and TB treatment. However, the biology and signal regulation mechanisms of MAIT cells in TB patients are still poorly understood. Previous studies have been limited by the lack of reagents to specifically identify MAIT cells. In addition, the use of alternative markers may subsume non-MAIT cell into MAIT cell populations. In this study, the human MR1 tetramer which can specifically identify MAIT cells was used to further explore the effect and mechanism of MAIT cells in anti-TB immune response. Our results showed that the tetramer+ MAIT cells in peripheral blood of TB patients were mainly CD8+ or CD4-CD8- cells, and very few were CD4+ cells. After BCG infecting autologous antigen-presenting cells, MAIT cells in patients produced significantly higher levels of cytokines, lysis and proliferation compared with healthy controls. After suppression of mTORC1 by the mTORC1-specific inhibitor rapamycin, the immune response of MAIT cells in patients was significantly reduced. This study demonstrates that peripheral blood tetramer+ MAIT cells from TB patients have significant anti-TB immune effect, which is regulated by mTORC1. This could provide ideas and potential therapeutic targets for the development of novel anti-TB immunotherapy.

Innovative approaches for coronary heart disease management: integrating biomedical sensors, deep learning, and stellate ganglion modulation.

Coronary heart disease (CHD) is a significant global health concern, necessitating continuous advancements in treatment modalities to improve patient outcomes. Traditional Chinese medicine (TCM) offers alternative therapeutic approaches, but integration with modern biomedical technologies remains relatively unexplored. This study aimed to assess the efficacy of a combined treatment approach for CHD, integrating traditional Chinese medicinal interventions with modern biomedical sensors and stellate ganglion modulation. The objective was to evaluate the impact of this combined treatment on symptom relief, clinical outcomes, hemorheological indicators, and inflammatory biomarkers. A randomized controlled trial was conducted on 117 CHD patients with phlegm-turbidity congestion and excessiveness type. Patients were divided into a combined treatment group (CTG) and a traditional Chinese medicinal group (CMG). The CTG group received a combination of herbal decoctions, thread-embedding therapy, and stellate ganglion modulation, while the CMG group only received traditional herbal decoctions. The CTG demonstrated superior outcomes compared to the CMG across multiple parameters. Significant reductions in TCM symptom scores, improved clinical effects, reduced angina manifestation, favorable changes in hemorheological indicators, and decreased serum inflammatory biomarkers were observed in the CTG post-intervention. The combination of traditional Chinese medicinal interventions with modern biomedical sensors and stellate ganglion modulation has shown promising results in improving symptoms, clinical outcomes, and inflammatory markers in CHD patients. This holistic approach enhances treatment efficacy and patient outcomes. Further research and advancements in sensor technology are needed to optimize this approach.

Combining [177Lu]Lu-DOTA-TOC PRRT with PARP inhibitors to enhance treatment efficacy in small cell lung cancer.

Small cell lung cancer (SCLC) is a highly aggressive tumor with neuroendocrine origin. Although SCLC frequently express somatostatin receptor type 2 (SSTR2), a significant clinical benefit of SSTR2-targeted radionuclide therapies of SCLC was not observed so far. We hypothesize that combination treatment with a PARP inhibitor (PARPi) could lead to radiosensitization and increase the effectiveness of SSTR2-targeted therapy in SCLC. SSTR2-ligand uptake of the SCLC cell lines H69 and H446 was evaluated in vitro using flow cytometry, and in vivo using SPECT imaging and cut-and-count biodistribution. Single-agent (Olaparib, Rucaparib, [177Lu]Lu-DOTA-TOC) and combination treatment responses were determined in vitro via cell viability, clonogenic survival and γH2AX DNA damage assays. In vivo, we treated athymic nude mice bearing H69 or H446 xenografts with Olaparib, Rucaparib, or [177Lu]Lu-DOTA-TOC alone or with combination treatment regimens to assess the impact on tumor growth and survival of the treated mice. H446 and H69 cells exhibited low SSTR2 expression, i.e. 60 to 90% lower uptake of SSTR2-ligands compared to AR42J cells. In vitro, combination treatment of [177Lu]Lu-DOTA-TOC with PARPi resulted in 2.9- to 67-fold increased potency relative to [177Lu]Lu-DOTA-TOC alone. We observed decreased clonogenic survival and higher amounts of persistent DNA damage compared to single-agent treatment for both Olaparib and Rucaparib. In vivo, tumor doubling times increased to 1.6-fold (H446) and 2.2-fold (H69) under combination treatment, and 1.0 to 1.1-fold (H446) and 1.1 to 1.7-fold (H69) in monotherapies compared to untreated animals. Concurrently, median survival was higher in the combination treatment groups in both models compared to monotherapy and untreated mice. Fractionating the PRRT dose did not lead to further improvement of therapeutic outcome. The addition of PARPi can markedly improve the potency of SSTR2-targeted PRRT in SCLC models in SSTR2 low-expressing tumors. Further evaluation in humans seems justified based on the results as novel treatment options for SCLC are urgently needed.

Mechanistic in silico explorations of the immunogenic and synergistic effects of radiotherapy and immunotherapy: a critical review.

Immunotherapy is a rapidly evolving field, with many models attempting to describe its impact on the immune system, especially when paired with radiotherapy. Tumor response to this combination involves a complex spatiotemporal dynamic which makes either clinical or pre-clinical in vivo investigation across the resulting extensive solution space extremely difficult. In this review, several in silico models of the interaction between radiotherapy, immunotherapy, and the patient's immune system are examined. The study included only mathematical models published in English that investigated the effects of radiotherapy on the immune system, or the effect of immuno-radiotherapy with immune checkpoint inhibitors. The findings indicate that treatment efficacy was predicted to improve when both radiotherapy and immunotherapy were administered, compared to radiotherapy or immunotherapy alone. However, the models do not agree on the optimal schedule and fractionation of radiotherapy and immunotherapy. This corresponds to relevant clinical trials, which report an improved treatment efficacy with combination therapy, however, the optimal scheduling varies between clinical trials. This discrepancy between the models can be attributed to the variation in model approach and the specific cancer types modeled, making the determination of the optimum general treatment schedule and model challenging. Further research needs to be conducted with similar data sets to evaluate the best model and treatment schedule for a specific cancer type and stage.

Cultivation of a naturally resilient Chlorella sp.: A bioenergetic strategy for valorization of cheese whey for high nutritional biomass production

This study investigated Chlorella's capacity to treat cheese whey (CW) effluent and produce a high-nutritional value biomass, by using a systematic sequential experimental design. Physicochemical analysis of CW revealed its high pollution load, characterized by elevated levels of lactose, phosphorus, and nitrogen, as well as high turbidity due to the presence of whey solids. Screening experiments demonstrated that trace mineral addition and continuous air supply are essential factors for Chlorella biomass production in CW (>800 mg·mL−1). Furthermore, whey solids did not hinder Chlorella growth, with notable biomass production observed even in undiluted CW, demonstrating this microalga's ability to adapt metabolically to the complex environment. Laboratory-scale photobioreactor experiments confirmed Chlorella's ability to produce biomass in CW, outperforming controls (>800 mg·mL−1). Bioremediation potential assessment exhibited significant reductions in organic pollutants (>14 g·L−1 COD), nitrogen (>400 mg·L−1), phosphorus (>140 mg·L−1) and sodium (>650 mg·L−1). CW solids were also removed with Chlorella harvesting (>99 %). Harvested algal biomass was enriched with proteins (>40 g·100 g−1), polyunsaturated fatty acids (>9 % TFA) and pigments, offering potential applications in nutraceutical and pharmaceutical industries. Overall, this study highlights Chlorella's efficacy in CW treatment and biomass valorization, offering a sustainable solution for dairy wastewater management while producing valuable resources.

Paediatric Uveitis - the uniqueness in clinical presentation and the efficacy of biologics treatment

AimsTo evaluate unique clinical characteristics of paediatric uveitis in our locality and treatment outcomes especially the efficacy of biologics.MethodsThis was a retrospective cohort.Results37 paediatric uveitis cases involving 67 eyes were included. Male-to-female ratio was 1:1.3. Mean age of uveitis onset was 11 ± 3.7 (4–18). 81.1% cases suffered from bilateral uveitis. 75.7% cases were chronic uveitis. Nearly half of the cases (40.5%) presented with anterior uveitis. The predominant diagnosis of uveitis in our cohort was idiopathic. Unlike studies from other populations, the associated systemic conditions in this mostly Chinese cohort were Behçet’s disease (8.1%), tubulointerstitial nephritis and uveitis (8.1%) and HLA-B27 associated uveitis (8.1%). Steroid response was a common phenomenon, observed in 40.5% of cases. The most common complication was posterior synechiae (45.9%), followed by cataract (37.8%), glaucoma (27.0%), band keratopathy (18.9%) and macular oedema (13.5%). 3/37 patients encountered either first attack of uveitis or flare after receiving COVID-19 vaccine. 54.1% of patients required systemic steroid for disease control. The majority required steroid sparing immunotherapy, including Methotrexate (43.2%), Mycophenolate Mofetil (24.3%), Cyclosporine A (8.1%), Azathioprine (5.4%) and Tacrolimus (2.7%). Resistant cases required biologics including tumour necrosis factor alpha inhibitors (Adalimumab 32.4%, Infliximab 2.7%) and interleukin-6 inhibitors (Tocilizumab 2.7%).ConclusionsClinical presentation of the local paediatric uveitis differs from previously described features in Caucasian and other populations. According to our experience as a tertiary eye centre, Behçet’s disease, tubulointerstitial nephritis and uveitis and HLA-B27 associated uveitis were more often encountered than Juvenile Idiopathic Arthritis associated uveitis. Our report evaluated the efficacy of immunomodulatory therapy and biologics in controlling uveitis and reducing ocular complications.

Differential functionality of fluoropyrimidine nucleosides for safe cancer therapy.

Chemotherapies are standard care for most cancer types. Pyrimidine analogs including 5-fluorouracil, cytosine arabinoside, 5-azacytidine, and gemcitabine are effective drugs that are utilized as part of a number of anticancer regimens. However, their lack of cell-specificity results in severe side effects. Therefore, there is a capacity to improve the efficacy of such therapies, while decreasing unwanted side effects. Here, we report that while 5-fluorocytosine is not chemotherapeutic in itself, incorporated into a ribonucleoside and more importantly into an RNA oligonucleotide, it induces cytotoxic effects on cancer cells in vitro. Interestingly, these effects are rescued by both uridine and thymidine. Similarly, in-vitro 2'-deoxy-5-fluorocytidine inhibits the growth of tumor cells but has the advantage of being less toxic to human primary cells compared with 5-fluorocytidine, suggesting that the deoxyribonucleoside could exhibit less side-effects in vivo. Thus, this work indicates that the potency of 5-fluorocytidine and 2'-deoxy-5-fluorocytidine should be further explored. In particular, oligonucleotides incorporating 5-fluorocytosine could be novel chemotherapeutic drugs that could be formulated in cancer-specific particles for safe and efficacious cancer treatments.

Tackling social disconnection: an umbrella review of RCT-based interventions targeting social isolation and loneliness

BackgroundSocial isolation and loneliness are urgent public health concerns associated with negative physical and mental health outcomes. Understanding effective remedies is crucial in addressing these problems. This umbrella review aimed to synthesize and critically appraise scientific evidence on the effectiveness of social isolation and loneliness interventions overall and across subgroups. We focused on systematic reviews (SRs) of randomized controlled trials (RCTs).MethodsWe searched seven databases (June 2022 and updated June 2023) and supplemented the search with grey literature and reference screening to identify SRs published since 2017. Screening, data extraction, and quality assessment using the AMSTAR2 tool were conducted independently by author pairs, with disagreements resolved through discussion.ResultsWe included 29 SRs, 16 with meta-analysis and 13 with narrative synthesis. All SRs focused on loneliness, with 12 additionally examining social isolation. Four SRs focused on young people, 11 on all ages, and 14 on older adults. The most frequently examined intervention types were social (social contact, social support), psychological (therapy, psychoeducation, social skills training), and digital (e.g., computer use and online support). Meta-analyses indicated small-to-moderate beneficial effects, while narrative synthesis demonstrated mixed or no effect. Social interventions for social isolation and psychological interventions for loneliness were the most promising. However, caution is warranted due to the effects’ small magnitude, significant heterogeneity, and the variable quality of SRs. Digital and other interventions showed mixed or no effect; however, caution is advised in interpreting these results due to the highly diverse nature of the interventions studied.ConclusionsThis overview of SRs shows small to moderate effectiveness of social interventions in reducing social isolation and psychological ones in tackling loneliness. Further rigorously conducted RCTs and SRs are needed to guide policy decisions regarding the implementation of efficacious and scalable interventions. Evaluation should focus on both preventive structural interventions and tailored mitigating strategies that address specific types and causes of loneliness.

Clinical impact of drug-drug interactions on abemaciclib in the real-world experience of AB-ITALY study

Abemaciclib demonstrated clinical benefit in women affected by HR+/HER2− advanced breast cancer (aBC). Drug-drug interactions (DDIs) can lead to reduced treatment efficacy or increased toxicity. This retro-prospective study aimed to evaluate outcomes, DDIs’ impact, and toxicities of abemaciclib combined with endocrine therapy in a real-world setting. Patients from 12 referral Italian hospitals with HR+/HER2− aBC who received abemaciclib were included. Clinical data about comorbidities, concurrent medications, outcomes, and adverse events (AE) were collected. Drug-PIN® (Personalized Interactions Network) is a tool recognizing the role of multiple interactions between active and/or pro-drug forms combined with biochemical and demographic patient data. The software was used to define the Drug-PIN score and Drug-PIN tier (green, yellow, dark yellow, and red) for each patient. Univariate and multivariate analyses were performed to identify predictors of patients’ PFS or toxicity. One hundred seventy-three patients were included. 13% of patients had >75years. The overall response rate (ORR) was 63%. The general population’s median PFS (mPFS) was 22 months (mo), while mOS were not reached. Patients treated with abemaciclib in combination with AI and fulvestrant had a mPFS of 36 and 19 mo, respectively. The most common toxicities were diarrhea, asthenia, and neutropenia detected in 63%,49%, and 49% of patients. The number of concomitant medications and comorbidities were not associated with survival outcomes (22 vs 17 mo, p = 0.068, p = 0.99). Drug-PIN tier from dark yellow to red and Drug-PIN score >12 were associated with shorter PFS compared to no/low-risk DDIs and score <12 (15 vs 23, p = 0.005, p = 0.0017). Drug interaction was confirmed as an independent biomarker in a multivariate model (p = 0.02). No difference in any grade AE, severe toxicities, and diarrhea were detected among different age subgroups. No association was found between Drug-PIN score or Drug-PIN tier and overall toxicity (p = 0.44), severe AEs (p = 0.11), or drug reduction (p = 0.27). The efficacy and safety of abemaciclib plus ET were confirmed in a real-world setting, even in the elderly population and patients with comorbidities. Evaluation of DDIs with Drug-PIN appears to be an independent predictor of PFS.

Macrophage Migration Inhibitory Factor (MIF) Upregulates CXCR7 and Contributes to Chemotherapy Resistance in Colorectal Cancer.

Colorectal cancer is one of the most common malignant tumors worldwide, with high incidence and mortality rates making it a focus of research. Chemotherapy is a primary treatment modality for colon cancer, but chemotherapy resistance severely impacts treatment efficacy. MIF has been found to promote tumor progression and resistance in various cancers. This study aims to investigate the role of MIF in chemotherapy resistance in colon cancer and its potential mechanisms, particularly through the upregulation of CXCR7 expression, affecting the metabolism and drug sensitivity of colon cancer cells. The expression levels of MIF in colon cancer tissues and its association with patient prognosis were evaluated by analyzing TCGA and HPA data. Subsequently, the expression levels of MIF in colon cancer cell lines and resistant cell lines were detected by qRT-PCR and immunohistochemistry, and the effect of MIF on oxaliplatin sensitivity was assessed. The impact of MIF on the metabolic activity of colon cancer cells was measured using a cellular energy metabolism analyzer. Further experiments explored the mechanism by which MIF affects the metabolic activity of colon cancer cells through the upregulation of CXCR7 expression, and the role of CTCF in regulating CXCR7 transcription was validated by silencing CTCF. Finally, the effect of MIF on drug sensitivity of colon cancer cells was verified in a mouse xenograft tumor model. In this study, we found that the expression of MIF in colon cancer tissues was significantly higher than in normal tissues, and high MIF expression was associated with poor prognosis in patients. The expression levels of MIF in resistant colon cancer cell lines were significantly higher than in parental cell lines, and MIF overexpression significantly increased the resistance of colon cancer cells to oxaliplatin. Conversely, silencing MIF significantly reduced the IC50 value of resistant cells and increased apoptosis. MIF overexpression significantly increased the ECAR and OCR levels of colon cancer cells, while MIF knockdown significantly reduced these metabolic indicators. Further studies indicated that MIF affects the metabolic activity of colon cancer cells by upregulating CXCR7 expression. CTCF binding peaks at the CXCR7 promoter region and luciferase activity assays indicated that CTCF regulates CXCR7 transcription, and silencing CTCF significantly enhanced the sensitivity of colon cancer cells to oxaliplatin. In vivo experiments in mice showed that MIF silencing combined with oxaliplatin treatment significantly inhibited tumor growth and increased the necrotic area of tumor tissues. In conclusion, this study reveals the crucial role of MIF in chemotherapy resistance in colon cancer through the upregulation of CXCR7 expression, with CTCF playing an important regulatory role in this process. Our findings provide new theoretical insights and potential therapeutic targets for overcoming chemotherapy resistance in colon cancer. Future research should further explore the roles of MIF and CXCR7 in other types of cancers and the potential of MIF and CXCR7 as therapeutic targets.

Efficacy, safety, tolerability and treatment durability of microneedling plus topical tranexamic acid in combination with topical modified Kligman lightening formula for melasma: A four-arm assessor and analyst blinded randomized controlled clinical trial.

The challenging management of melasma highlights the inadequacies of conventional therapies and their high risk of recurrence. Integrating microneedling for device-assisted drug delivery with tranexamic acid (TA), recognized for its melanin synthesis inhibition, presents a novel approach that warrants further investigation to fully assess its potential in enhancing melasma treatment efficacy. Fifty moderate to severe melasma patients participated in this randomized outcome-assessor-blinded controlled trial. Patients were randomly allocated into two main groups. Group A received a modified Kligman formula on one hemi-face on alternate nights for 2 months (A1) and three sessions of microneedling with 10% topical TA on the other hemi-face at 1-month intervals (A2). Group B used the same modified Kligman formula on both sides of the face, with one side additionally receiving three sessions of microneedling with 4% TA (B1) and the opposite side with 10% TA (B2). Primary outcomes were % Modified Melasma Area and Severity Index (mMASI) and % visual analogue scale (VAS) change during 6 month follow-up. Adverse events including post-inflammatory hyperpigmentation (PIH) and treatment tolerability were recorded. Compared to baseline, the mean mMASI reduction immediately after the final session was higher in A1, B1, and B2 (56.84%, 50.88%, and 55.87%, respectively) than in A2, which saw only a 13.16% reduction. Efficacy notably declined after the cessation of treatment across all groups. While the efficacy within groups A1, B1, and B2 was comparable, microneedling with 4% or 10% TA combined with the topical modified Kligman formula proved more potent in patients at a lower risk of PIH. Overall, 22% of patients reported PIH, particularly in the A2 group (28% of hemi-faces), with its occurrence significantly associated with treatment during warmer seasons and in darker skin phototypes. Other adverse events were not observed in any patient. Patient satisfaction was highest in groups B1 and B2, where approximately 72% reported 'excellent' satisfaction. The lowest durability rate (16%) was observed in group A2, while the highest (72%) was seen in group B2, comparable with groups A1 and B1. Treatment tolerability was reported 100% in all groups. It was found that the modified Kligman formula outperformed microneedling-TA alone. However, with optimal patient selection, particularly targeting those at lower risk for PIH with lighter skin phototypes and scheduling treatments during less-sunny seasons, combining microneedling with 4% or 10% TA and the modified Kligman formula significantly enhanced efficacy and satisfaction rates compared to conventional topical treatment.

Emergence of Artificial Intelligence Art Therapies (AIATs) in Mental Health Care: A Systematic Review.

The application of artificial intelligence art therapies (AIATs) in mental health care represents an innovative merger between digital technology and the therapeutic potential of creative arts. This systematic review aimed to assess the effectiveness and ethical considerations of AIATs, incorporating robots, AI painting and AI Chatbots to augment traditional art therapies. Aligning with the Preferred Reporting Items for systematic reviews (PRISMA) guidelines, we meticulously searched PubMed, Cochrane Library, Web of Science and CNKI, resulting in 15 selected articles for detailed analysis. To ensure methodological quality, we applied the Joanna Briggs Institute (JBI) criteria for quality assessment and extracted data using the PICO(S) format, specifically targeting randomised controlled trials (RCTs). Our findings suggest that AIATs can profoundly enhance the therapeutic experience by providing new creative outlets and reinforcing existing methods, despite possible drawbacks and ethical challenges. This examination underscores AIATs' potential to enrich mental health therapies, emphasising the critical importance of ethical considerations and the responsible application of AI as the field evolves. With a focus on expanding treatment efficacy and patient expressiveness, the promise of AIATs in mental health care necessitates a careful balance between innovation and ethical responsibility. Trial Registration: PROSPERO: CRD42024504472.

Treatment approaches, outcomes and prognostic indicators in patients with tinnitus and temporomandibular disorders evaluated with DC/TMD: A systematic review and Meta-analysis.

This systematic review summarised the results reported in randomised controlled trials (RCTs) aimed at evaluating the different treatment approaches in patients with tinnitus associated with temporomandibular disorders (TMD) evaluated with the diagnostic criteria of temporomandibular disorders (DC/TMD), and the possible predictive factors influencing treatment outcomes. The electronic databases Medline, Web of Science, Latin American and Caribbean Health Sciences Literature (LILACs) were searched systematically up to March 2023. Only RCTs with full texts were included in this study. The eligibility of the RCTs selected was based on the PICO model (participants, intervention, comparators, outcomes), and subjects of any age, sex or ethnicity, were included when showing both tinnitus and TMD, diagnosed through DC/TMD criteria. From a total of 635 articles, only five RCTs were included and the data from a total of 329 participants were examined. Two RCTs focused on the efficacy of the multidisciplinary approach among people with tinnitus who have TMD; two RCTs examined prognostic indicators predicting a positive outcome after multidisciplinary orofacial treatment; one RCT analysed low-level laser therapy's effectiveness with Nd:YAG laser. A multidisciplinary non-invasive approach is the most efficacious treatment for tinnitus in patients diagnosed with TMD. Baseline tinnitus severity, gender, quality of life, age, and tinnitus duration were considered predictive factors of clinical outcomes in patients diagnosed with DMTs and referring tinnitus.

Efficacy of acupuncture for allergic rhinitis in children: Systematic review and meta‑analysis with trial sequential analysis.

Acupuncture has been shown for the treatment of allergic rhinitis in previous studies. Nevertheless, relevant evidence was lacked for paediatric patients with allergic rhinitis. We aim to validate the efficacy of acupuncture for allergic rhinitis in children by meta-analysis and trial sequence analysis. Comprehensive search of eight databases were conducted until August 27, 2023. Randomized controlled trials comparing acupuncture alone or in combination with drugs versus medication in children with AR were included. The primary outcome was total nasal symptom score (TNSS). The secondary outcomes were serum immunoglobulin E levels, and relapse rates. Thirteen studies involving 1186 participants were included. In results, acupuncture group (AC group) versus medication group (Med group) shows no significant difference in the treatment of AR in children (risk ratio [RR] = 1.10, 95% CI = 0.97 to 1.24, p = 0.13), while TSA suggested the included sample size did not exceed required information size (RIS). Significant differences were found between the AC + Med group versus the Med group (RR = 1.29, 95% CI = 1.17 to 1.42, p < 0.00001), with sufficient sample size. Results in serum IgE after treatment which favored the Med group (MD = 51.94, 95% CI [22.24, 81.65], p = 0.0006). In terms of relapse rate, The AC group had a lower relapse rate than the Med group (RR = 0.40, 95% CI = 0.26-0.63, p < 0.0001). Acupuncture is an efficacious treatment for allergic rhinitis in children, but this conclusion might be limited by the generally low quality of evidence. TSA suggested additional high-quality trials with larger sample sizes and longer treatment durations were needed.

Effect of body mass index on survival in patients with metastatic colorectal cancer receiving chemotherapy plus bevacizumab: a systematic review and meta-analysis

AimThis systematic review and meta-analysis was to evaluate the relationship between body mass index (BMI) and the clinical outcomes in patients with metastatic colorectal cancer (mCRC) undergoing treatment with bevacizumab plus chemotherapy.MethodsThe search for relevant literature was conducted across PubMed, Embase, Cochrane Library, and Web of Science, with the final search date being October 4, 2023. We utilized the weighted mean differences (WMDs), risk ratios (RRs), or Hazard ratios (HRs) as the metric for effect sizes, which were accompanied by 95% confidence intervals (CIs).ResultsA total of 9 studies were included for analysis. The results indicated that non-obese patients with mCRC undergoing treatment with bevacizumab experienced a reduced overall survival (OS) at the six-month compared to their obese counterparts (RR: 0.97, 95% CI: 0.94 to 1.00, p = 0.047). Furthermore, no significant differences in one-year, two-year, and five-year OS, as well as PFS and median OS, were observed between obese and non-obese mCRC patients undergoing treatment with bevacizumab plus chemotherapy.ConclusionThese findings suggest that obesity may play a role in the short-term OS of patients with mCRC undergoing bevacizumab treatment. The clinical implications of these findings underscore the importance of considering patients’ BMI in the context of mCRC care. This study may also help guide personalized treatment strategies and further research into the interplay between obesity, treatment efficacy, and patient survival in mCRC. However, further investigation is warranted to substantiate the findings of this study.

Role of Brown Adipose Tissue in Metabolic Health and Efficacy of Drug Treatment for Obesity

(1) Background: Brown adipose tissue (BAT) is responsible for non-shivering thermogenesis, and its activation has become a new object as both a determinant of metabolic health and a target for therapy. This study aimed to identify the relationships between the presence of BAT, parameters that characterize metabolic health (glucose, lipids, blood pressure (BP)), and the dynamics of body mass index (BMI) during weight-reducing therapy. (2) Methods: The study included 72 patients with obesity. We investigated metabolic parameters, anthropometric parameters, and BP. Dual-energy X-ray absorptiometry (DXA) and positron emission tomography and computed tomography (PET/CT) imaging with 18F-fluorodeoxyglucose (18F-FDG) were performed. (3) Results: Before weight-reducing therapy, BAT was revealed only in 19% patients with obesity. The presence of BAT was associated with a lower risk of metabolic deviations that characterize metabolic syndrome: shorter waist circumference (WC) (p = 0.02) and lower levels of glucose (p = 0.03) and triglycerides (p = 0.03). Thereafter, patients were divided into four groups according to the type of therapy (only lifestyle modification or with Liraglutide or Reduxin or Reduxin Forte). We did not find a relationship between the presence of BAT and response to therapy: percent weight reduction was 10.4% in patients with BAT and 8.5% in patients without BAT (p = 0.78) during six months of therapy. But we noted a significant positive correlation between the volume of BAT and the effectiveness of weight loss at 3 months (r = 0.52, p = 0.016). The dynamic analysis of BAT after 6 months of therapy showed a significant increase in the volume of cold-induced metabolically active BAT, as determined by PET/CT with 18F-FDG in the Liraglutide group (p = 0.04) and an increase in the activity of BAT standardized uptake value (SUV mean and SUV max) in the Reduxin (p = 0.02; p = 0.01, respectively) and Liraglutide groups (p = 0.02 in both settings). (4) Conclusions: The presence of brown adipose tissue is associated with a lower risk of metabolic abnormalities. In general, our study demonstrated that well-established drugs in the treatment of obesity (Liraglutide and Reduxin) have one more mechanism for implementing their effects. These drugs have the ability to increase the activity of BAT. A significant positive relationship between the total volume of BAT and the percentage of weight loss may further determine the priority mechanism of the weight-reducing effect of these medicaments.