Efficacy Of Therapy Research Articles

Organelle Targeted Drug Delivery: Key Challenges, Recent Advancements and Therapeutic Implications.

Organelle-specific targeted drug delivery has emerged as a promising approach in the field of drug delivery and therapeutics. This innovative strategy involves the precise delivery of therapeutic agents to specific organelles within cells, such as the nucleus, mitochondria, endoplasmic reticulum, or lysosomes, with the aim of enhancing drug efficacy while minimizing offtarget effects. Despite its tremendous potential, organelle-specific drug delivery faces several key challenges. One major challenge is the development of delivery systems that can accurately navigate the complex intracellular environment and deliver drugs exclusively to the desired organelles. Achieving this level of precision demands advanced nanotechnology and biomaterials engineering. Furthermore, ensuring the safety and biocompatibility of these delivery systems is paramount. Recent advancements in this field include the development of nanocarriers, such as liposomes, nanoparticles, and dendrimers, designed to target specific organelles through ligandreceptor interactions or pH-responsive mechanisms. Additionally, advancements in molecular biology and genetic engineering have enabled the design of genetically encoded organellespecific drug delivery systems. The therapeutic implications of organelle-specific drug delivery are vast. This approach has the potential to revolutionize the treatment of diseases with organelle- specific pathologies, such as neurodegenerative disorders, cancer, and mitochondrial diseases. By precisely targeting the organelles involved in disease progression, the efficacy of therapies can be significantly improved while minimizing collateral damage to healthy tissues.

Theranostic Nanomaterials to Overcome the Challenges in Peptide-based Cancer Therapy

: Globally, the number of cancer cases and death rates are increasing, making it necessary to develop new and improved medications for the treatment of cancer.Owing to a broad range of physio-chemical properties, Antimicrobial Peptides (AMPs) possessing tumoricidal properties and Anticancer Peptides (ACPs) are promising alternatives for enhanced cancer therapy. Recently, biopharmaceuticals have changed the rules of radiation therapy and chemotherapy by introducing peptide therapy for cancer treatments. However, several limitations obstruct the clinical efficacy of peptide-based cancer therapies, which include limited target specificity, oral intake, and half-life payloads. The integration of theranostic nanomaterials could be facilitated as a transformative strategy to address these challenges and enhance the potential of peptide-based cancer therapy. Increasing applications of recent times of peptide-nano hybrids have addressed the crucial issues related to conventional peptide-based drug therapy by enhancing the druggability. This review aims to explore the impact of nano-formulated peptides as an anticancer agent, highlighting the involvement of nanotechnology as an enabling tool.

Synergistic response of PEG coated manganese dioxide nanoparticles conjugated with doxorubicin for breast cancer treatment and MRI application

In this research work, we designed a smart biodegradable PEG-coated MnO2 nanoparticles conjugated with doxorubicin (PMnO2-Dox NPs) for dual chemo-photodynamic therapy and magnetic resonance imaging (MRI) application. This highly sensitive pH-responsive PMnO2-Dox NPs causes effective drug release under acidic pH environment. PMnO2-Dox NPs not only improves the efficacy of chemo-photodynamic therapy due to synergistic response as well as improved MRI imaging via boosting T1 MRI contrast. Manifold characterization techniques have been employed for materials investigation. Crystallography of PMnO2-Dox NPs were performed by using XRD analysis, which confirmed tetragonal crystal structure with an approximate crystallite size of 20–30 nm. Surface morphology was confirmed via SEM analysis, results indicated the spherical and asymmetric agglomerated nanocluster of PMnO2-Dox NPs. In in vitro bioassay, the anticancer activity of PMnO2-Dox NPs were tested against breast cancer (MCF-7) cell line using MTT test. Moreover, it can also inhibit the growth of primary and secondary cancers without light exposure. Results suggested that PMnO2-Dox NPs not only convenient for cancer treatment via combined chemo-photodynamic therapy but also address the way towards a comprehensive strategy for MRI application via bright contrast agent T1 after overcoming the problem of multidrug resistance (MDR) and synergistic response of therapeutic analysis.

The Efficacy of Negative Pressure Wound Therapy (NPWT) on Healing of Diabetic Foot Ulcers: A Literature Review.

Diabetes mellitus is a complex disorder that requires continuous management to control blood sugar levels and prevent complications. Diabetic foot ulcers (DFU) are the most common complication in diabetic patients. A popular therapy modality with considerable advantages in the management of diabetic foot ulcers today is negative pressure wound therapy (NPWT). This study aimed to review related articles about the efficacy as well as the complications or adverse effects of using NPWT on the healing of DFUs. Searching English databases from PubMed, Ebscohost, Proquest and Science Direct was done to identify relevant citations published between January 2017 and January 2022. A combination of terms was used with the boolean formulation of "negative pressure wound therapy OR NPWT" OR "vacuum-assisted closure or VAC" AND "diabetic foot ulcers OR diabetic foot wound" AND "wound healing" AND "Conventional dressings" and map terms were also used for the subject heading. Some potentially relevant citations of articles from the bibliographies are also reviewed. This study included 8 related articles consisting of 6 RCTs, 1 cohort study and 1 Quasy experimental study. There were various methodological techniques for using NPWT and outcome measures among studies. The results of this literature review showed that NPWT was more efficacious than the other conventional or advanced moist dressings. This therapy revealed a faster healing time with complete wound healing and formation of granulation tissue and reduction in wound size. The complications or adverse effects of NPWT, such as amputation rate, bleeding and pain, were not different from conventional or advanced moist dressings, though. NPWT was more efficacious than other conventional or advanced moist dressings for the healing of DFUs. However, complications or adverse effects of using this therapy showed no significant difference with other conventional or advanced moist dressings.

Association Between Depressive Symptoms, Cognitive Status, and the Dual-Task Performance Index in Older Adults: A Cross-Sectional Study.

The Performance Index (P-Index) is a measure for evaluating mobility-related dual-task performance in older adults. The identification of specific clinicodemographic factors predictive of P-Index scores, however, remains unclear. This cross-sectional study analyzed data from 120 community-dwelling older adults (average age 71.3 ± 11.23years) to explore clinicodemographic variables that influence P-Index scores during the instrumented timed up and go test. Unadjusted analyses suggested several factors, including age, gender, body mass index, Mini-Mental Status Examination scores, functional reach test performance, history of falls, ethnicity, Geriatric Depression Scale scores, alcohol consumption, and educational levels, as potential predictors of P-Index. However, adjusted multinomial multiple regression analysis revealed Geriatric Depression Scale and Mini-Mental Status Examination scores as the exclusive independent predictors of P-Index classifications, segmented into high, intermediate, or low (percentiles ≤ 25, 26-74, or ≥ 75, respectively). A significant association was observed between the manifestation of depressive symptoms, lower Mini-Mental Status Examination scores, and reduced cognitive-motor performance. The findings implicate depressive symptoms and low cognitive performance as substantial impediments to optimal dual-task mobility within this cohort. Further studies are warranted to examine the efficacy of cognitive stimulation and antidepressant therapy, in augmenting mobility-related dual-task performance among older adults.

Efficacy of pain treatment therapies for chronic pain among clients in assisted living facilities: A systematic review

Background: More than 60% of residents in assisted living homes experience pain, a complex and subjective emotion. Here, we examine the effectiveness of pain management treatments for residents in assisted living facilities who suffer from chronic pain. Method: In this review, the PRISMA Statement was adhered to. Included were intervention studies, whether or not they were randomized. Retrospective studies, studies without a control group, and studies without an intervention were among the studies that were excluded. Subjects having chronic pain who were 60 years of age or older, of any gender, and permanently residing in an institutional environment, such as a assisted living facilities or residential care facility, were included in studies that matched the qualifying requirements. Result: Eight papers total—three non-randomized and five randomized controlled trials—were included in our systematic review. Acupuncture, massage, music therapy, and analgesics are among the interventions employed. Analgesics was the most effective intervention. Exercise had similar effects to social interventions on neuropsychiatric symptoms, pain, and medication intake in older adults with chronic pain; Epsom salt hot fermentation is more effective than regular salt; and acupressure is anticipated to be a beneficial and effective nursing intervention for the elderly with chronic pain. Conclusion: The most beneficial treatment outcome was obtained from the analgesic medication therapy. Alternative therapies without the use of drugs provide modest to significant therapeutic results.

Оценка эффективности и безопасности применения антиоксидантного комплекса «Спермаферт»

Reactive oxygen species negatively affect the indicators of ejaculate and spermatogenesis in general. This study evaluated the efficacy and safety of combination antioxidant therapy with respect to the treatment of male infertility. The general indicators of the ejaculate and the sperm DNA fragmentation index were assessed. Men with a high sperm DNA fragmentation index were recommended to take 1 capsule and 5 ml of liquid (1 scoop) once a day with meals. The liquid contains L-carnitine – 900 mg; 1 capsule contains: lipoic acid - 96 mg, vitamin C – 72 mg, zinc citrate – 56 mg, vitamin B6 – 2.4 mg, folic acid – 0.48 mg, 9-phenyl-symmetric octahydroselenoxanthene – 0.34 mg. Results. After three months of treatment with the antioxidant complex "Spermafert", ejaculate valuesimproved, as evidenced by a decrease in the sperm DNA fragmentation index from 21.6 ± 3.2% to 12.8 ± 3.3%; an increase in sperm concentration from 29.7× 106 /ml to 35.7 × 106 /ml an increase in the totalsperm count from 72.1 × 106 to 95.5 × 106 . Findings. Taking antioxidants can improve overall ejaculate counts and lowersperm DNA fragmentation index levelsin men in infertile marriages. The conclusions of thisstudy coincide with general trendsin this direction. Keywords: male infertility, antioxidants, Spermafert, DNA fragmentation

A clinical randomized controlled study on the psycho-cardiological therapy for patients with coronary atherosclerosis disease

Objective: To explore the prognosis efficacy of psycho-cardiological therapy and management on patients with coronary atherosclerosis disease (CAD). Methods: This was a clinical randomized controlled study. This study included inpatients with CAD at the cardiology department in Beijing Anzhen Hospital, Capital Medical University from August 2021 to January 2024. The patients enrolled in this study were asked for basic information, and received measurements for depression, anxiety, sleep quality and living quality by the scales of Patient Health Questionnaire-9 (PHQ-9), General Anxiety Disorder scale-7 (GAD-7), Athens Insomnia Scale (AIS), EuroQol 5-dimension 5-level (EQ-5D-5L) respectively. The patients were randomly grouped into a regular treatment group and a psycho-cardiological treatment group which included WeChat management or antidepressant/antianxiety medical therapy according to the situation. After the patients discharging from hospital for 2, 4, 12, 24, 48, 72, and 96 weeks, professional cardiovascular doctors would follow up by telephone, WeChat, and outpatient department, including scales (2-48 weeks), and cardiac events (2-96 weeks). Kaplan-Meier survival curve and multivariate Cox proportional hazards model were used for analyzing the association between psycho-cardiological treatment and cardiac events. Results: This study recruited a total of 552 patients with CAD, aged 61.0(54.0, 67.0) years, and 379 (68.7%) were male. There were 279(50.5%) in the regular treatment group and 273(49.5%) in the psycho-cardiological treatment group. After treatment for 4, 12 and 48 weeks, the PHQ-9 score in psycho-cardiological was significantly lower than the regular treatment group; After treatment for 12 weeks, the EQ-5D-5L effective value in psycho-cardiological group was higher than the regular treatment group; After treatment for 2, 4, 12, 24 and 48 weeks, the EQ-5D-5L VAS score in psycho-cardiological group was higher than the regular therapy group (all P<0.05). The Kaplan-Meier survival curve showed that, during the different follow-up periods, the rate of cardiac events in psycho-cardiological treatment group was lower than regular treatment group (log-rank P<0.001). The multivariate Cox proportional hazards model adjusted the factor of age, the psycho-cardiological treatment contributed to reducing the cardiac events rate by 80.3% (HR=0.197, 95%CI: 0.067-0.582, P=0.003). Conclusion: Psycho-cardiological treatment is beneficial for improving psychological stress, living quality, and reducing cardiac events, and helps to improve prognosis and psycho-cardiological rehabilitation in CAD patients.

Hydroxyurea: An Old Drug in Need of New Clinical Trials in Myeloproliferative Neoplasms?

Hydroxyurea (Hu) has been a front-line therapeutic agent for myeloproliferative neoplasms (MPN) for many years and still enjoys the endorsement of experts in the field. However, several publications have reported sub-optimal response, the need for treatment interruption because of cytopenias and lack of sustained response. In all these studies, Hu was used as continuous therapy at a daily dose ranging from 500mg to 3000mg. At our Centre we have used Hu as intermittent therapy (akin to schedules used in patients with solid tumours) at 20-30mg/Kg doses, given as a single dose, twice or thrice weekly. We have consistently observed sustained responses without troublesome cytopenias. Concurrent anti-platelet therapy was given on the basis of the results of whole blood platelet aggregation studies, achieving effective thromboprophylaxis. In this report we present our experience in 118 patients treated with intermittent Hu during the past 30 years (median follow-up 8.5 yrs): polycythemia vera – 29; essential thrombocythemia – 84; primary myelofibrosis – 5. Based on the pharmacokinetics of Hu and our experience, we speculate that the efficacy of intermittent Hu therapy without troublesome myelotoxicity over long periods of time is attributable to the following: i) higher plasma level from intake of Hu as a single dose; ii) higher uptake of Hu by cells with higher mitotic activity (i.e. the abnormal clone); and iii) unhindered, normal haemopoiesis on the drug free days each week. We hope that this article will generate interest and contemplation, leading to further publications from Centres using intermittent Hu therapy and randomized clinical studies to compare the two dosage schedules (Continuous Vs Intermittent) in MPN patients.

Virtual reality in telepsychiatry is a new horizon for immersive mental health therapy

AbstractThe use of virtual reality (VR) in telepsychiatry signifies a paradigm shift in mental health care. VR provides realistic, interactive environments for therapies like exposure therapy and cognitive behavioral therapy, resulting in reliable and reproducible scenarios that improve treatment effectiveness. This technology enhances accessibility for those with geographical or physical limitations, lowers stigma, and boosts patient engagement and adherence by making treatment activities more pleasurable and interesting. Furthermore, VR may emulate social interactions and circumstances that are difficult to replicate in typical treatment settings, providing useful practice for people with social anxiety or autism spectrum disorders (ASD). Despite its great potential, integrating VR into telepsychiatry offers problems such as high VR equipment costs, assuring clinical effectiveness and safety, and securing patient data. Future research should prioritize large-scale, randomized controlled trials to determine the efficacy of VR-based therapy, investigate long-term consequences, and offer cost-effective solutions. By tackling these issues and investing in novel research, VR has the potential to greatly improve telepsychiatry, making mental health care more effective, engaging, and easily available to people all over the world.

Engineered Tools to Advance Cell Transplantation in the Nervous System Towards a Clinical Reality

Abstract Purpose of the Review The goal of this review is to highlight engineered tools for overcoming challenges in cell survival and engraftment for tissue regeneration and mitigation of neuropathic pain following cell transplantation for neural applications. Recent Findings There is a growing body of evidence supporting the safety of cell transplantation for the treatment of injuries to the brain, spinal cord, and peripheral nerves. However, the efficacy of these cell therapies is inconclusive, and the path forward remains unclear due to a lack of evidence of transplant survival and engraftment. Engineered biomaterials offer promising pre-clinical evidence of enhanced survival and engraftment of cells transplanted within the nervous system. Biomaterials have been used alone or in combination with drug and gene delivery to direct cell transplant outcomes and represent a future direction for clinical evaluation given pre-clinical survival rates that may eliminate reliance on systemic immunosuppression. Summary Biomaterial approaches under pre-clinical evaluation can support cell survival, localize cells in the injured tissue where they are needed, and enable tissue engraftment, yet have not advanced towards the clinic. Existing biomaterials provide passive support of survival during delivery and/or place a premium on supporting cell engraftment, but active remediation of tissue-local inflammation that inhibits transplant survival and leads to neuropathic pain has seen very little advancement in recent years. Combinatorial approaches capable of addressing challenges in both survival and engraftment of cell transplants in the nervous system represent an area for significant growth in the coming years.

Comparison of ustekinumab, infliximab and combination therapy in moderately to severely active ulcerative colitis – a study protocol of a randomized, multicenter, head-to-head COMBO-UC trial

BackgroundUlcerative colitis (UC) is a chronic inflammatory bowel disease with a complex etiology that affects the large intestine. Characterized by chronic, bloody diarrhea, UC can lead to severe complications, including an increased risk of colorectal cancer. Despite advancements in conservative treatment, including biologics like anti-TNF agents and ustekinumab (UST), many patients do not achieve full remission. Dual targeted therapy (DTT) combining infliximab (IFX) and UST is a promising approach to improve treatment outcomes.MethodsThis prospective, randomized, multicenter, head-to-head controlled trial will evaluate the efficacy and safety of UST, IFX, and combination therapy (UST + IFX) in 172 patients with moderate to severe active UC across eight gastroenterology centers in Poland. The study includes a 14–16 week remission induction period followed by a 52-week maintenance phase. Patients will be randomly assigned to one of three treatment arms: IFX monotherapy, UST monotherapy, or IFX + UST combination therapy. Primary endpoint is clinical and endoscopic remission post-induction. Secondary endpoints include clinical response, biochemical remission, histological remission, and quality of life assessments using the Inflammatory Bowel Diseases Questionnaire and 36-Item Short Form Survey. Safety will be monitored through adverse event and serious adverse event reporting.DiscussionThis trial aims to determine whether combining IFX and UST can achieve higher remission rates and better long-term outcomes compared to monotherapy. The results could provide crucial insights into the optimal use of biologic agents in UC treatment, potentially establishing DTT as a standard therapy. The study’s design, including extensive follow-up and robust endpoint measures, will contribute to understanding the therapeutic potential and safety profile of this combination therapy.

Oral versus intravenous antibiotic therapy for Staphylococcus aureus bacteremia or endocarditis: a systematic review and meta-analysis of randomized controlled trials.

We conducted a systematic review of randomized controlled trials (RCTs) to generate more precise estimates of the efficacy and safety of oral versus intravenous antibiotic therapy for S. aureus bacteremia or endocarditis. MEDLINE, EMBASE, the Cochrane Library, and Web of Science database were searched through February 21st, 2024. RCTs were included if they compared oral versus intravenous antibiotic therapy for S. aureus bacteremia or endocarditis, and appropriately reported outcomes for each group. Risk of bias was assessed using the revised Cochrane tool for assessing risk of bias in randomized trials. Heterogeneity between studies was evaluated with the Cochran's Q-statistic and I2 test. Treatment effects were summarized with pooled risk ratios using a random effects model meta-analysis. (PROSPERO CRD42024481512). Only four RCTs met criteria for inclusion in meta-analysis. Among participants assessed for treatment failure, there was no difference between the oral and intravenous therapy groups (RR 0.99; 95% CI, 0.63-1.57; I2 = 0%). There was also no significant difference in adverse events between oral and intravenous therapy groups (RR 0.65; 95% CI, 0.07-5.94; I2 = 74%); however, the confidence interval is wide, and heterogeneity was high. In this systematic review of RCTs comparing oral to intravenous antibiotic therapy for S. aureus bacteremia or endocarditis, few studies met eligibility criteria for inclusion. Meta-analysis of these studies suggests that transitioning from intravenous to oral therapy is likely effective in a subgroup of carefully selected patients. Additional randomized trials are necessary before transition to oral therapy can be routinely recommended.

Electroconvulsive therapy response and remission in moderate to severe depressive illness: a decade of national Scottish data.

Despite strong evidence of efficacy of electroconvulsive therapy (ECT) in the treatment of depression, no sensitive and specific predictors of ECT response have been identified. Previous meta-analyses have suggested some pre-treatment associations with response at a population level. Using 10 years (2009-2018) of routinely collected Scottish data of people with moderate to severe depression (n = 2074) receiving ECT we tested two hypotheses: (a) that there were significant group-level associations between post-ECT clinical outcomes and pre-ECT clinical variables and (b) that it was possible to develop a method for predicting illness remission for individual patients using machine learning. Data were analysed on a group level using descriptive statistics and association analyses as well as using individual patient prediction with machine learning methodologies, including cross-validation. ECT is highly effective for moderate to severe depression, with a response rate of 73% and remission rate of 51%. ECT response is associated with older age, psychotic symptoms, necessity for urgent intervention, severe distress, psychomotor retardation, previous good response, lack of medication resistance, and consent status. Remission has the same associations except for necessity for urgent intervention and, in addition, history of recurrent depression and low suicide risk. It is possible to predict remission with ECT with an accuracy of 61%. Pre-ECT clinical variables are associated with both response and remission and can help predict individual response to ECT. This predictive tool could inform shared decision-making, prevent the unnecessary use of ECT when it is unlikely to be beneficial and ensure prompt use of ECT when it is likely to be effective.

Reduction of Multispecies Biofilms on an Acrylic Denture Base Model by Antimicrobial Photodynamic Therapy Mediated by Natural Photosensitizers

Objectives: The aim of this study is to investigate the antimicrobial efficacy of antimicrobial photodynamic therapy (PDT) using natural photosensitizers (curcumin, riboflavin, and phycocyanin) and light-emitting diode (LED) irradiation against multispecies biofilms in an acrylic denture base model. Materials and Methods: Forty-five acrylic specimens were fabricated using heat-curing acrylic resin. The specimens were then infected with a mixed culture of bacterial and fungal species (including Streptococcus mutans, Streptococcus sanguinis, Candida albicans, and Candida glabrata) for 4 days. The acrylic discs were divided into nine groups, with each group containing five discs: control, 0.2% chlorhexidine, 5.25% sodium hypochlorite, curcumin, riboflavin, phycocyanin alone or along with LED. After treatment, the number of colony-forming units (CFUs) per milliliter was counted. In addition, the extent of biofilm degradation was assessed using the crystal violet staining method and scanning electron microscopy. Results: All experimental groups exhibited a significant reduction in colony numbers for both bacterial and fungal species compared to the control (p &lt; 0.001). The PDT groups exhibited a statistically significant reduction in colony counts for both bacteria and fungi compared to the photosensitizer-only groups. Conclusions: The results of this in vitro study show that PDT with natural photosensitizers and LED devices can effectively reduce the viability and eradicate the biofilm of microorganisms responsible for causing denture infections.

Update on Clinical Trial Endpoints in Gene Therapy Trials for Inherited Retinal Diseases

Inherited retinal diseases (IRDs) encompass a wide spectrum of rare conditions characterized by diverse phenotypes associated with hundreds of genetic variations, often leading to progressive visual impairment and profound vision loss. Multiple natural history studies and clinical trials exploring gene therapy for various IRDs are ongoing. Outcomes for ophthalmic trials measure visual changes in three main categories—structural, functional, and patient-focused outcomes. Since IRDs may range from congenital with poor central vision from birth to affecting the peripheral retina initially and progressing insidiously with visual acuity affected late in the disease course, typical outcome measures such as central visual acuity and ocular coherence tomography (OCT) imaging of the macula may not provide adequate representation of therapeutic outcomes including alterations in disease course. Thus, alternative unique outcome measures are necessary to assess loss of peripheral vision, color vision, night vision, and contrast sensitivity in IRDs. These differences have complicated the assessment of clinical outcomes for IRD therapies, and the clinical trials for IRDs have had to design novel specialized endpoints to demonstrate treatment efficacy. As genetic engineering and gene therapy techniques continue to advance with growing investment from industry and accelerated approval tracks for orphan conditions, the clinical trials must continue to improve their assessments to demonstrate safety and efficacy of new gene therapies that aim to come to market. Here, we will provide an overview of the current gene therapy approaches, review various endpoints for measuring visual function, highlight those that are utilized in recent gene therapy trials, and provide an overview of stage 2 and 3 IRD trials through the second quarter of 2024.

Effect of extracorporeal shock wave combined with autologous platelet-rich plasma injection on rotator cuff calcific tendinitis: study protocol for a randomized controlled trial

BackgroundRotator cuff calcific tendinitis (RCCT) is a common shoulder disease whose main symptoms include shoulder pain, limited mobility, and calcification deposits in the shoulder. Traditional treatment methods have certain limitations, so finding new treatment methods has become the focus of research. Extracorporeal shock wave (ESW) and platelet-rich plasma (PRP) treatments have attracted much attention due to their non-invasive and tissue repair-promoting properties; however, the efficacy of their combined treatment in RCCT remains unclear.MethodsThis study is designed as a single-center, assessment-blind, randomized controlled clinical trial with three parallel groups. Sixty subjects will be recruited and randomly divided into the ESW group, PRP group, and ESW combined with PRP group, in a 1:1:1 ratio. The entire intervention period is 4 weeks, and the follow-up period is 4 weeks. Outcomes will be measured at baseline (T0), after 1 week of intervention (T1), after 2 weeks of intervention (T2), after 4 weeks of intervention (T3), and after an additional 4 weeks of follow-up period (T4). The primary endpoint is the VAS score. Secondary endpoints are ASES, CMS, UCLA, and the location and size of calcified areas.DiscussionThis study aims to evaluate the efficacy of ESW therapy combined with PRP in treating RCCT. We compare the effects of single and combined treatments to explore their impact on disease symptoms, functional improvement, and calcification regression. This provides a scientific basis for identifying more effective treatment options.Trial registrationClinicalTrials.gov NCT06372600. Registered on April 17, 2024; version 1.

The Safety and Efficacy of Peptide Receptor Radionuclide Therapy for Gastro-Entero-Pancreatic Neuroendocrine Tumors: A Single Center Experience

The aim of the present study was to evaluate the safety and efficacy of radionuclide therapy with [177Lu]Lu-DOTA-TATE according to our single center experience at the University of Naples Federico II. For the present analysis, we considered 21 patients with progressive, advanced, well-differentiated G1 and G2 in patients with gastro-entero-pancreatic (GEP) neuroendocrine tumors (NETs) treated with [177Lu]Lu-DOTA-TATE according to the decisions of a multidisciplinary team. All patients underwent four cycles of 7–8 GBq of [177Lu]Lu-DOTA-TATE every 8 weeks. A whole-body scan (WBS) was performed 4, 48, and 168 h after each treatment. The dosimetry towards the organ at risk and target lesions was calculated. For each patient, renal and bone marrow parameters were evaluated before, during, and 3 months after the end of the treatment. Follow-up data were obtained and RECIST criteria were considered as the endpoint. Among 21 patients enrolled (mean age 65 ± 9 years); 17 (81%) were men and the small intestine was the most frequent location of disease (n = 12). A mild albeit significant variation (p &lt; 0.05) in both platelets and white blood cell counts among all time points was observed, despite it disappearing 3 months after the end of the therapy. According to the RECIST criteria, 11 (55%) patients had a partial response to therapy and 8 (40%) had stable disease. Only one (5%) patient had disease progression 4 months after treatment. Our data confirm that [177Lu]Lu-DOTA is safe and effective in controlling the burden disease of G1/G2 GEP-NETs patients.

Correction to "Comments on: Increasing Enzyme Mannose-6-Phosphate Levels but Not Miglustat Coadministration Enhances the Efficacy of Enzyme Replacement Therapy in Pompe Mice".

Correction to "Comments on: Increasing Enzyme Mannose-6-Phosphate Levels but Not Miglustat Coadministration Enhances the Efficacy of Enzyme Replacement Therapy in Pompe Mice".

UM171 enhances fitness and engraftment of gene modified hematopoietic stem cells from sickle cells disease patients

Hematopoietic stem cell transplantation with lentiviral vector (LVV) transduced autologous cells has proven an effective therapeutic strategy for sickle cell disease (SCD). However, ex vivo culture or proliferative stress associated with in vivo reconstitution may amplify any underlying genetic risk of leukemia. We aimed to minimize culture-induced stress and reduce genomic damage during ex vivo culture, enhance stem cell fitness and reconstitution of SCD CD34+ cells transduced with BCL11A shmiR-encoding LVV currently in clinical trials (NCT NCT03282656). UM171, a pyrimidoindole derivative can expand normal hematopoietic stem cells (HSCs) during in vitro culture and has been shown to be safe and effective in clinical trials using umbilical cord blood (NCT02668315). We examined the effect of UM171 during ex vivo LVV transduction of SCD HSCs. Culture of SCD CD34+ HSCs with UM171 during transduction reduced DNA damage and reactive oxygen species (ROS), decreased apoptosis, and was associated with increased numbers of immunophenotypically defined long-term HSCs. UM171 increased the engraftment of LVV transduced human HSCs in immunodeficient mice and barcode tracing revealed increased clonal diversity of engrafting cells. In competitive transplantation assays, analysis of BM showed that cells transduced in the presence of UM171 consistently outcompeted those transduced under control conditions. In summary, exposure of SCD peripheral blood CD34+ cells to UM171 during LVV transduction enhances stem cell fitness. These findings suggest manufacturing of genetically modified HSCs in the presence of UM171 may improve efficacy, safety and sustainability of gene therapy utilizing ex vivo approaches.