Need For Treatment Research Articles

Mortality, Clinical Complications, and Healthcare Resource Utilization Associated with Managing Transfusion-Dependent β-Thalassemia and Sickle Cell Disease with Recurrent Vaso-occlusive Crises in Italy.

To examine the clinical burden and healthcare resource utilization (HCRU) among patients with transfusion-dependent β-thalassemia (TDT) and patients with sickle cell disease (SCD) with recurrent vaso-occlusive crises (VOCs) in Italy. Eligible patients were identified from an administrative claims database from 1 January 2010 and 1 February 2019. Patients with TDT had ≥ 1 iron chelation treatment, ≥ 8 red blood cell transfusions (RBCTs) during any 12-month period, and ≥ 12 months of available data pre- and post-index (i.e., first RBCT claim). Patients with SCD with recurrent VOCs had ≥ 2 VOCs/year in ≥ 2 consecutive years and ≥ 12 months of available data pre- and post-index (second VOC claim in the second of 2 consecutive years). Patients were propensity score matched to five controls by age, sex, geographic area, and index year. Clinical and HCRU outcomes were evaluated post-index. In total, 214 patients with TDT and 111 patients with SCD with recurrent VOCs were matched to 1070 and 555 controls, respectively. Both patient groups had substantially higher mortality rates than controls (TDT: 4.8 versus 0.8 deaths per 100 person-years; SCD: 1.6 versus 0.4 deaths per 100 person-years). Clinical complications were prevalent in both patient groups. Compared with controls, both patient groups had significantly higher mean rates of all-cause hospitalizations (TDT: 1.4 versus 0.1; SCD: 2.0 versus 0.1) and outpatient services (TDT: 21.9 versus 1.6; SCD: 6.2 versus 1.0) per patient per year (all: p < 0.05). Management of TDT and SCD in Italy is associated with significant clinical and health system burden, highlighting the need for new treatments that eliminate RBCTs and VOCs.

Predictive power of the eTBI score for 30 day outcome in elderly patients with traumatic brain Injury

Traumatic brain injury (TBI) is a common problem in elderly individuals, with significant morbidity and mortality. The elderly Traumatic Brain Injury (eTBI) score, a novel tool for predicting outcomes in elderly patients with TBI, has shown promising results in previous studies. This study aimed to validate the eTBI score in a larger cohort of elderly patients with TBI in the Middle East. We conducted a retrospective study on 337 TBI patients with a mean age of 73.04 ± 8.73, admitted to a tertiary care hospital between March 2021 and November 2022. Within 30 days of admission, the patients’ conditions, including mortality and entering a vegetative state, were evaluated. The study population was split into three groups based on eTBI score: low, medium, and high risk; then patients were divided into two subgroups based on their Glasgow Outcome Scale (GOS ≤ 2, GOS > 2) in 30 days from hospital admission. Poor outcomes (mortality and entering a vegetative state) occurred in 24.3% of the study population. Within 30 days of hospital admission, 88% of low-risk patients experienced some degree of improvement, while 100% of high-risk patients died or fell into a vegetative state. In the medium-risk group, there was a significant correlation between unresponsive pupil (P = 0.006), initial GCS score (P = 0.003), need for a ventilator device (P = 0.015), need for surgical treatment (P = 0.031) and poor outcomes. Despite having a low sensitivity (21% vs. 57%), the eTBI score performed well in terms of accuracy (81% vs. 88%), specificity (100 vs. 98%), positive predictive value (100% vs. 90%), and negative predictive value (80% vs. 88%) for both eTBI ≤ 0 and eTBI ≤ 3 thresholds. The eTBI score is a reliable tool for predicting outcomes in elderly patients with TBI. This scoring system has a positive predictive value of 100% in the eTBI ≤ 0 group, which shows that 100% of the patients who are predicted by the eTBI score to have a poor outcome will indeed have a poor outcome. Patients in the high-risk group should be closely monitored and provided with intensive care, while those in the low-risk group can be reassured about their prognosis. The eTBI score can also be used in conjunction with other clinical factors to inform treatment decisions for patients in the medium-risk group.

Clinical characteristics and burden of non-obstructive hypertrophic cardiomyopathy: a real-world survey in Italy and Spain

Abstract Background Research describing non-obstructive hypertrophic cardiomyopathy (nHCM) and the associated burden of illness is sparse. Purpose This research aimed to describe the clinical characteristics of patients with nHCM and the associated clinical and societal burden of illness in Italy (IT) and Spain (ES). Methods Data were from the Adelphi HCM Disease Specific Programme (DSP), a cross-sectional survey with retrospective data collection in IT and ES (July 2022–January 2023). Ethics approval was obtained from the Pearl Institutional Review Board. Cardiologists provided data on patient demographics, employment, clinical characteristics, symptoms, support needs and treatment for up to ten consecutively consulting adult HCM patients. Patients voluntarily completed a survey containing the Kansas City Cardiomyopathy Questionnaire-23 (KCCQ). Analyses were descriptive and the mean [SD] was summarized for continuous variables. Results Overall, 112 cardiologists provided data for 483 patients with nHCM from IT (243) and ES (240). The mean age [SD] was 54.3 [14.1] and 58.0 [16.0], with 66.3% and 61.7% of patients being male, in IT and ES respectively. Eighty-four percent and 92.1% of patients were classified as New York Heart Association (NYHA) II, 14.8% and 7.1% were NYHA III, and 1.2% and 0.8% were NYHA IV, in IT and ES respectively. Among patients who completed the KCCQ, the mean [SD] KCCQ-clinical summary score was 84.9 [12.9] in IT and 81.8 [20.7] in ES. Regarding work-related impact, 30.8% (IT) and 16.7% (ES) of patients had taken time off work due to nHCM in the last three months, and 41.6% (IT) and 48.4% (ES) were not working full-time, of which 5.6% (IT) and 11.0% (ES) were not working full time due to nHCM. Additionally, 17.6% and 18.2% of patients experienced a delayed diagnosis in IT and ES respectively, with 24.0% (IT) and 25.0% (ES) having multiple delays to diagnosis. The most common symptoms reported by physicians were dyspnoea when active (83.7%), palpitations (29.3%) and fatigue (25.7%). The most prevalent concomitant conditions were hypertension (20.5%), anxiety (18.6%), and atrial fibrillation (18.4%). In IT and ES, respectively, 77.8% and 74.2% of patients were currently prescribed treatment for nHCM. The most frequently prescribed treatments were beta-blockers (83.3%), diuretics (32.1%) and angiotensin converting enzyme inhibitors (20.5%), alone or in combination. In IT and ES respectively, 14.4% and 18.8% of patients required caregiver support, at a mean [SD] of 46.3 [52.4] and 44.2 [47.5] hours per week. Conclusions While the majority of patients with nHCM were classified as NYHA II, a considerable clinical and societal burden is evident. Burden was demonstrated by the high prevalence of symptoms, comorbidities, disruptions to employment and the requirement for caregiver support among these patients, highlighting the need for new treatment and management approaches to enhance health outcomes and reduce societal impact.

Effect of malocclusion severity on oral health and its correlation with socioeconomical status in Iranian adolescents

BackgroundThis study aimed to assess the effect of malocclusion severity according to the Index of Treatment Need (IOTN) on oral health (dental caries and gingivitis), and its correlation with socioeconomic status (SES) in Iranian adolescents.MethodsThis descriptive cross-sectional study was conducted on adolescents between 10 and 16 years in Tehran city, who underwent clinical dental examination. The Dental Health Component (DHC) of the IOTN was used to assess the severity of malocclusion. The DMFT index was calculated to assess dental caries, and the gingival index (GI) was calculated for gingival health assessment. For oral hygiene assessment, the Oral Hygiene Index-Simplified (OHI-S) was calculated, and a questionnaire was used.ResultsTotally, 306 adolescents participated in this study. The frequency of IOTN grades was 88 (28.8%), 89 (26.1%) ,49 (16%), 60 (19.6%), and 29 (9.5%) for grades 1 to 5, respectively. The multinomial logistic regression showed that by an increase in OHI-S score, the odds of having IOTN grade 4 compared to grade 1 increased. Postgraduate parental level of education decreased the odds of having IOTN grade 4 compared to grade 1. Furthermore, there was an inverse correlation between oral hygiene practice and the odds of having IOTN grade 5 compared to grade 1.ConclusionsMalocclusion may hinder oral hygiene practice, and resultantly increase plaque accumulation. This risk may be amplified in children with lower SES, highlighting the need for preventive and educational oral health programs.

Pemetrexed-carboplatin salvage therapy in advanced thyroid cancers.

The overall survival of patients with advanced thyroid cancers that have progressed following targeted therapies is limited, indicating a strong need for salvage treatments. We retrospectively analyzed patients with refractory advanced thyroid cancer treated with pemetrexed-carboplatin (PC) at Mayo Clinic since 2019. Eleven patients, three with anaplastic thyroid cancer (ATC), seven with differentiated or poorly differentiated thyroid cancer (DTC), and one with oncocytic carcinoma of the thyroid, were treated with novel salvage PC. Patients with DTC (n = 7) had durable responses with a median progression-free survival of 29 months. One responder included a patient with ATC whose disease progressed following pembrolizumab/axitinib, lenvatinib, and dabrafenib/trametinib. On this fourth line treatment, the patient remains on therapy to date, over 12 months after initial response. This case series reinforces prior published phase I clinical trial data and shows that pemetrexed can have potent efficacy in the treatment of the most advanced thyroid cancers.

Study the Antifungal Effects of Green Synthesized Silver Nanoparticles on the Aspergillus niger, Microsporum canis, and Candida albicans

: The increasing prevalence of drug-resistant fungal pathogens and the limitations of current antifungal therapies underscore the need for novel alternative treatments. This study aimed to evaluate the antifungal effects of green-synthesized silver nanoparticles (Ag NPs) on three clinically significant fungi: Aspergillus niger, Microsporum canis, and Candida albicans. Silver nanoparticles were synthesized using plant-based extracts to ensure eco-friendly production methods. The synthesized Ag NPs were characterized using UV spectrophotometry, Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), dynamic light scattering (DLS), zeta potential measurements, scanning electron microscopy (SEM), and transmission electron microscopy (TEM). Characterization assays revealed spherical particles with colloidal stability, an average size of approximately 80 nm, a Polydispersity Index of 0.4, and a surface charge of 62.3 mV. Minimum inhibitory concentration (MIC) values demonstrated effective suppression of fungal growth at low nanoparticle concentrations. In conclusion, our study highlights the potential of green-synthesized Ag NPs as a promising alternative to conventional antifungal agents, emphasizing their significant advantages in biocompatibility and eco-friendliness. These findings could pave the way for a new era in treating fungal infections, particularly those caused by drug-resistant strains.

Effect of Neoadjuvant Therapy on Endoluminal Vacuum-Assisted Closure Therapy (EVAC) for Anastomotic Leakage After Oesophagectomy.

Anastomotic leakage (AL) is a dreaded complication after oesophagectomy. Endoluminal vacuum-assisted closure therapy (EVAC) has been increasingly used as a first-line treatment for AL. We aimed to identify any potential adverse effects of a neoadjuvant therapy (chemotherapy (CT) or radiochemotherapy (RCT)) on EVAC. We performed a retrospective cohort study at our tertiary centre between 2013 and 2024. All patients who underwent EVAC for AL after oesophagectomy were included in this study. Parameters such as success rate, length of therapy, number of sponges needed, changes in treatment, and survival were analysed. A total of 29 patients were included, 19 of whom received CT/RCT and 10 of whom received no neoadjuvant treatment (NT). There was no significant difference in patient survival (30-day survival rate CT/RCT n = 1 (5.3%) vs. NT n = 1 (10%), p = 0.632), success rate (CT/RCT n = 15 (78.9%) vs. NT n = 9 (90%), p = 0.454), and length of therapy (CT/RCT vs. NT 24.11 vs. 23.8, p = 0.681), the number of sponges required (CT/RCT vs. NT 6.26 vs. 6.6, p = 0.835), and the need for changing treatment (CT/RCT n = 5 (26.3%) vs. NT n = 1 (10%), p = 0.303). NT did not affect the success rate or length of therapy. Thus, we found no significant influence of CT/RCT on EVAC for AL after oesophagectomy.

Epidemiological analysis of pediculosis and the distribution of kdr mutation frequency in head lice populations in Torbat Heydarieh city of Khorasan Razavi Province, Northeastern Iran

Head lice infestations are the most prominent ectoparasitic infection in the world, including Iran, particularly among school children. Recently, numerous cases of infestation have been reported in various provinces of the country. This study aimed to investigate the prevalence of head louse infestations and analyze kdr gene sequences in terms of resistance mutations in the Torbat-e Heydarieh, Mahvelat, and Zaveh cities of Khorasan Razavi Province, Northeast Iran. The data related to the epidemiological and demographic history of head lice populations were extracted from their medical records and analyzed in Excel software. After extracting the genomic DNA, the kdr fragment was amplified using specific primers. The sequences were also analyzed using bioinformatics software. The prevalence of head louse infestations was 1.59% and 1.7% during 2016 and 2017, respectively. Sequence analysis revealed the frequency distribution of two kdr haplotypes, I and V, in the study areas. The increase in head louse infestations in recent years and the simultaneous presence of kdr mutations indicate the need for new treatments and monitoring/controlling resistance to head louse insecticides.

Patients with Diabetes Mellitus and Comorbid Mental Disorders - Is there a Psychotherapeutic Undertreatment? - Results of the DiMPS Study

Diabetes mellitus is associated with an increased likelihood of mental disorders, especially depression. Despite a frequently postulated underprovision, the actual need for psychotherapeutic treatment in this patient group has hardly been investigated. The aim of this study is to analyze the care situation of diabetes patients with mental comorbidities in Germany. 240 consecutively treated patients with type 1 or type 2 diabetes were examined cross-sectionally and longitudinally in a tertiary diabetological center. After a screening and diagnostic examination, 94 patients with comorbid mental disorders were included in the study. Patients then decided on the treatment of their mental disorder according to a standardized shared decision-making process. At the 6-month follow-up, 77 of the 94 patients (81.9%) provided information about the realization of their treatment decision and the obstacles they encountered. 39.2% of patients with diabetes had a mental disorder. Of these, 44.2% were already receiving psychotherapy or medication. After six months, 46.8% were able to implement their treatment decision. Only 7.1% did not receive any treatment despite their efforts. The 6-month follow-up showed a significant reduction in diabetes-related distress (PAID; p<0.05) and an increase in psychological well-being in all subgroups, regardless of treatment initiation (WHO-5; p<0.05). Contrary to the widespread notion of a lack of access to psychotherapy for people with diabetes and mental disorders in Germany, this assumption could not be confirmed in this study. Equating the frequency of mental disorders with the need for psychotherapeutic and/or psychopharmacological treatment without considering the specific treatment needs and preferences of patients may lead to an overestimation of the need for care.

Disease Overlap, Healthcare Resource Utilization, and Costs in Patients with Eosinophilic Granulomatosis with Polyangiitis: A REVEAL Sub-study.

Eosinophilic granulomatosis with polyangiitis (EGPA) is an eosinophil-associated disease (EAD) characterized by inflammation in small- to medium-sized blood vessels. Inthe REal-world inVestigation of Eosinophilic-Associated disease overLap (REVEAL) study, overlap among 11 EADswas assessed. In the present sub-study, we evaluated EGPA overlapwith other EADs, all-cause EAD- and EGPA-related healthcare resource utilization (HCRU) and costs, and their relationship with blood eosinophil count and treatments received. REVEAL, a retrospective study, used Optum's de-identified Clinformatics® Data Mart Database. In this sub-study, eligibility criteria included an age of ≥ 12years, ≥ 1 EAD, continuous health-plan eligibility, and compliance with the EGPA/GPA case definition per International Classification of Diseases Ninth/Tenth Revision diagnosticcodes between 1 January 2015 and 30 June 2018. Patients were grouped based on whether they had received immunomodulators/cyclophosphamide/mepolizumab (ICM) or not (non-ICM). Of 701 patients with EGPA, 29.5% were in the ICM group. Overall, 72.2% had ≥ 1 overlapping EAD. The number of overlaps was similar for the ICM and non-ICM groups. In patients with blood eosinophil counts ≥ 300 cells/µL, 22.8% had ≥ 1 overlapping EAD. The mean annual all-cause cost was $98,644, 54.1% of which was from outpatients and 33.6% from inpatients. The mean annual EAD- and EGPA-related costs were $23,820 and $9,306, respectively. Patients in the non-ICM groupversus the ICM group had higher all-cause ($101,560 vs $91,684) but lower EAD-related ($22,733 vs $26,412) and EGPA-related ($6,171 vs $16,786) costs. All-cause HCRU and costs increased with increasing overlap. EGPA was associated with substantial HCRU and costs, driven by outpatient and inpatient settings. More overlapping EADs were associated with higher HCRU and costs, highlighting the need for treatment to reduce healthcare expenditure in these patients. Infographic available for this article.

Analysis of self-monitoring of blood glucose metrics in gestational diabetes mellitus and their association with infants born large for gestational age: A historical observational cohort study of 879 pregnancies.

Self-monitoring of blood glucose (SMBG) is the standard of care for women with gestational diabetes mellitus (GDM). This study aimed to review SMBG profiles in women with GDM and to examine how glucose metrics derived from SMBG relate to fetal overgrowth and infants born large for gestational age (LGA, >90th percentile). This was a single-center, historical, observational cohort study of 879 GDM pregnancies in Sweden. The diagnosis of GDM was based on a universal 75 g oral glucose tolerance test at gestational week 28 or 12 in high-risk women. The glucose metrics derived from the SMBG profiles were calculated. Treatment targets for glucose were <5.3 mmol/L fasting, and ≤7.8 mmol/L 1-h postprandial. The median (interquartile range) number of glucose measurements in the analysis for each woman was 318 (216-471), including 53 (38-79) fasting glucose measurements. Associations between glucose metrics and LGA were analyzed using binary logistic regression analysis adjusted for maternal age, body mass index, smoking, nulliparity, and European/non-European origin. Receiver operating characteristic (ROC) curves were used to evaluate glucose levels for LGA prediction. Differences in means were tested using analysis of variance. The proportion of LGA infants was 14.6%. Higher mean glucose levels and smaller proportion of readings in target (glucose 3.5-7.8 mmol/L) were significantly associated with LGA (odds ratio [95% confidence interval]: 3.06 [2.05-4.57] and 0.94 [0.92-0.96], respectively). The strongest association was found with mean fasting glucose (3.84 [2.55-5.77]). The ability of mean fasting glucose and overall mean glucose to predict LGA infants in the ROC curves was fair, with areas under the curve of 0.738 and 0.697, respectively (p < 0.001). The corresponding discriminating thresholds were 5.3 and 6.1 mmol/L, respectively. Mean glucose levels increased and readings in target decreased with increasing body mass index category and at each step of adding pharmacological treatment, from diet alone to metformin and insulin (p < 0.001). Higher mean glucose levels and a smaller proportion of readings within the target range were associated with an increased risk of LGA. Suboptimal glucose control is associated with obesity and the need for pharmacological treatment.

A retrospective study on biotinidase deficiency: analysis of the Eastern Anatolia region patient cohort

ABTRACT This study retrospectively reviews individuals diagnosed with biotinidase deficiency in Eastern Anatolia to analyze the genetic variants and their relationship with biotinidase activity levels. The research focuses on determining the percentage impact of different variants on enzyme activity. The study included 357 patients who presented to Erzurum City Hospital with symptoms of biotinidase deficiency between 2018 and 2023 and were referred to the medical genetics department. Biotinidase enzyme levels were determined using spectrophotometric and colorimetric techniques, while Sanger sequencing analyzed the four exons and intron boundaries of the BTD gene. In the analysis of 357 patients (181 boys, 176 girls), the most frequent variant was c.1270G > C | p.Asp424His. Biotinidase enzyme activity was above 30% in 97.3% of patients with a homozygous p.D424His mutation. The mutations that caused the most significant decrease in enzyme activity were c.410G > A p.Arg137His, c.38_delinsTCC p.Cys13phefs*36, and c.1535C > T p.Thr512Met. Hearing loss (4 patients) and optic atrophy (1 patient) were mainly observed in patients with the c.38_delinsTCC mutation (homozygous or heterozygous). Most patients were asymptomatic, and mild symptoms were effectively prevented with biotin treatment. This study provides a detailed analysis of genetic diversity and clinical presentation in biotinidase deficiency cases in Eastern Anatolia, demonstrating the efficacy of biotin treatment. It highlights the significant role of genetic variants in phenotypic diversity and the need for personalized treatment, calling for further genetic research to enhance understanding of variant diversity and its impact on enzyme activity.

Distraction osteogenesis in the treatment of transverse malocclusions in children

Relevance. Malocclusions accounts for 37% to 89% of all maxillofacial conditions in children aged 3 to 18 across various regions of Russia. These malocclusions can present as isolated issues in a single plane or as combined anomalies across multiple planes. Jaw narrowing or underdevelopment is influenced by various endogenous and exogenous factors. The choice of treatment depends on the severity of the malocclusion. While literature indicates several effective methods for treating transverse malocclusions, some aspects remain insufficiently explored.Materials and methods. A statistical analysis was conducted on 271 patient records of individuals with transverse malocclusions who received treatment in the Department of Pediatric Maxillofacial Surgery at A.I. Evdokimov Moscow State University of Medicine and Dentistry, Ministry of Health of the Russian Federation, between 2013 and 2023.Results. There was an almost equal distribution of patients by gender, with a noticeable increase in medical consultations from 2013 to 2023. The majority of surgically treated patients were between 15 and 17 years old. Isolated transverse malocclusions were significantly less common than cases combined with other pathologies, with mesial occlusion being the most frequent comorbidity.Conclusion. The findings demonstrate a significant need for surgical treatment in pediatric patients with transverse malocclusions through distraction osteogenesis. This underscores the importance of continually improving treatment methods for children, including enhancing diagnostics, refining treatment indications, optimizing distraction protocols, and adjusting treatment courses. These efforts aim to improve the quality of rehabilitation for children, ensuring better outcomes into adulthood and facilitating their social adaptation.

Optimizing Allocation to Telehealth and In-Person Prolonged Exposure for Women Veterans with Military Sexual Trauma: A Precision Medicine Approach

Military sexual trauma-related post-traumatic stress disorder (PTSD) is highly prevalent and costly among women veterans, making the need for effective and accessible treatment of critical importance. Access to care is a key mechanism of mental health disparities and might affect differential response to treatment. The goal of this study was to estimate an individualized treatment rule based on readily available individual characteristics related to access to care to optimize allocation to in-person vs. telehealth delivery of prolonged exposure for PTSD in military sexual trauma survivors. The following variables were used as prescriptive factors: age, race, disability status, socioeconomic status, rural vs. urban status, and baseline PTSD level. The rule was estimated using a machine-learning approach, Outcome Weighted Learning. The estimated optimal rule outperformed a one-size-fits-all rule where everyone is universally assigned to telehealth; it led to markedly lower mean PTSD levels following 6 months from treatment (Vdopt − VTelehealth = −14.55, 95% CI: −27.24, −1.86). However, the rule did not significantly discriminate for in-person therapy (Vdopt − VIn-person = −11.86, 95% CI: −25.83, 2.12). Upon further validation with larger and more diverse samples, such a rule may be applied in practice settings to aid clinical decision-making and personalization of treatment assignment.

Low-Energy extracorporeal shockwave therapy improves locomotor functions, tissue regeneration and modulating the inflammation induced FGF1 and FGF2 signaling to protect damaged tissue in spinal cord injury of rat model: An experimental animal study.

Spinal cord injury (SCI) is a debilitating condition that results in severe motor function impairments. Current therapeutic options remain limited, underscoring the need for novel treatments. Extracorporeal shockwave therapy (ESWT) has emerged as a promising noninvasive approach for treating musculoskeletal disorders and nerve regeneration. This study explored the effects of low-energy ESWT on locomotor function, tissue regeneration, inflammation, and mitochondrial function in a rat SCI model. Experiments were performed using locomotor function assays, CatWalk gait analysis, histopathological examination, immunohistochemical and immunofluorescence staining. The findings demonstrated that low-energy ESWT had a dose-dependent effect, with three treatment sessions (ESWT3) showing superior outcomes compared to a single session. ESWT3 significantly improved motor functions (run patterns, run average speed, and maximum variation, as well as the Basso, Beattie, and Bresnahan (BBB) score) and promoted tissue regeneration while reducing inflammation. ESWT3 significantly decreased levels of IL-1β, IL6 and macrophages (CD68) while increasing leucocyte (CD45) infiltration. Additionally, ESWT3 upregulated NueN and mitofusin 2 (MFN2), suggesting enhanced neuronal health and mitochondrial function. Moreover, ESWT3 modulated the expression of fibroblast growth factor 1 (FGF1), FGF2, their receptor FGFR1 and phosphorylation of ERK, aiding tissue repair and regeneration in SCI. This study highlights the potential of low-energy ESWT as an effective noninvasive treatment for SCI, demonstrating significant improvements in motor recovery, tissue regeneration, anti-inflammatory effects, and mitochondrial protection. These findings provide valuable insights into the mechanisms of ESWT and its therapeutic application for SCI recovery.

Deciphering the landscape of triple negative breast cancer from microenvironment dynamics and molecular insights to biomarker analysis and therapeutic modalities.

Triple negative breast cancer (TNBC) displays a notable challenge in clinical oncology due to its invasive nature which is attributed to the absence of progesterone receptor (PR), estrogen receptor (ER), and human epidermal growth factor receptor (HER-2). The heterogenous tumor microenvironment (TME) of TNBC is composed of diverse constituents that intricately interact to evade immune response and facilitate cancer progression and metastasis. Based on molecular gene expression, TNBC is classified into four molecular subtypes: basal-like (BL1 and BL2), luminal androgen receptor (LAR), immunomodulatory (IM), and mesenchymal. TNBC is an aggressive histological variant with adverse prognosis and poor therapeutic response. The lack of response in most of the TNBC patients could be attributed to the heterogeneity of the disease, highlighting the need for more effective treatments and reliable prognostic biomarkers. Targeting certain signaling pathways and their components has emerged as a promising therapeutic strategy for improving patient outcomes. In this review, we have summarized the interactions among various components of the dynamic TME in TNBC and discussed the classification of its molecular subtypes. Moreover, the purpose of this review is to compile and provide an overview of the most recent data about recently discovered novel TNBC biomarkers and targeted therapeutics that have proven successful in treating metastatic TNBC. The emergence of novel therapeutic strategies such as chemoimmunotherapy, chimeric antigen receptor (CAR)-T cells-based immunotherapy, phytometabolites-mediated natural therapy, photodynamic and photothermal approaches have made a significant positive impact and have paved the way for more effective interventions.

Evaluations of the deterioration characteristics of thermally treated wood samples from Corymbia citriodora and Eucalyptus urophylla caused by marine wood borers

The low natural durability properties of some types of wood indicate the need for treatments to enhance the resistance of these materials to biological decay. In the sea, this resistance is necessary due to the actions of wood-boring mollusks and crustaceans. These treatments must be effective without harming the environment. Wood thermal treatment should be evaluated for this purpose. Therefore, the aim of this study was to evaluate the deterioration characteristics of thermally treated wood samples from Corymbia citriodora and Eucalyptus urophylla under the actions of marine wood borers. A method was proposed to aid in this assessment. Ten samples of these woods, both untreated and thermally treated, were submerged in the sea, each at a depth of 2.5 meters, for five months. After this period, the external borehole number, mass loss, and central flat lesion parameters of the samples were evaluated. Both the thermally treated and untreated wood samples of C. citriodora showed less deterioration than those of E. urophylla, with fewer boreholes, smaller lesioned areas, and lower mass losses. Compared with untreated wood and E. urophylla wood, thermally treated C. citriodora wood exhibited some resistance to marine wood borers. It was concluded that C. citriodora wood was naturally more resistant to marine wood borers than E. urophylla wood. Moreover, thermal treatment increased the boring resistance of C. citriodora wood while increasing the susceptibility of E. urophylla wood. The digital measurement of flat lesions was proven to be an auxiliary and promising method for evaluating the deterioration process.

11 Is emergency department transfer always required following anaphylaxis and epinephrine use?

Abstract Background Patients known for anaphylaxis are advised to always carry 2 epinephrine auto-injectors (EAI) with them. With epinephrine being the first-line treatment for anaphylaxis, current guidelines recommend prompt EAI administration, followed by observation in the emergency department (ED) for 4 hours. Data supporting transfer to the ED in all cases after epinephrine are sparse. Recent North American allergy guidelines no longer suggest that ED presentation after EAI use is required for all cases of anaphylaxis. Objectives We aimed to describe the need for additional ED treatment in children known for food-triggered anaphylaxis who received at least 1 EAI pre-hospital. Design/Methods Data on children under 18 years with food-induced anaphylaxis who received at least one dose of pre-hospital epinephrine was collected from the Cross-Canada Anaphylaxis REgistry (C-CARE) from seven hospitals. A standardized questionnaire obtained information on symptoms, allergens, comorbidities, and pre-hospital and in-hospital management. Multivariable logistic regression was performed to identify factors associated with ED management, among children who received 1, 2 or 3 or more doses of epinephrine pre-hospital. Results From 2011 to 2023, 1054 children with known food-triggered anaphylaxis and who used one or more EAIs pre-hospital were enrolled in C-CARE. The mean age at reaction was 8.2 (standard deviation [SD] 5.3) years, 648 (60.8%) were male and 82 (7.8%) of reactions were severe (defined as loss of bowel control, cyanosis, respiratory arrest, hypotension and/or circulatory collapse, dysrhythmia, severe bradycardia and/or cardiac arrest, confusion, and loss of consciousness). Primary triggers included peanuts (n=280; 26.6%) followed by tree nuts (n=173; 16.4%). 193 patients (18.3%) had known asthma and 201 received additional dose(s) of epinephrine in the ED, the majority of whom (177, 88.1%) received one dose. Only 2.9% of patients required admission. Among all patients, reactions to egg were less likely to require additional epinephrine (aOR 0.90; 95% CI 0.83, 0.99), and more likely with severe reactions (aOR 1.24; 95% CI 1.14-1.35). Among patients who received only one EAI pre-hospital, severe reactions (adjusted odds ratio [aOR] 1.19; 95% confidence interval [CI] 1.08-1.31) and reactions to tree nuts (aOR 1.12; 95% CI 1.04-1.20) were associated with increased odds of an additional dose of epinephrine in hospital. Conclusion One-fifth of anaphylaxis cases that used EAI require an additional dose of epinephrine in ED. Children with severe reactions and reactions to tree nuts are more likely to require additional doses; these cases should be considered for ED transfer and treatment following pre-hospital EAI use.

A non-melting additive approach to structural repair of aluminum aircraft fastener holes

The damage to fastener holes in aerospace aluminum structures presents significant challenges for aircraft durability, and conventional bushing methods for repairing oversized holes often fall short due to the lack of metallurgical bonding and limited edge distance availability. This study investigates additive friction stir deposition, a non-melting additive process, as a viable alternative for the structural repair of aerospace fastener holes. The repair process, demonstrated on AA7050 (Al-Zn-Mg-Cu-Zr) hole structures, involves filling oversized holes with new material and machining to restore the original hole size. The repaired hole coupons are defect-free and exhibit good fatigue performance under fully reversed tension-compression loading (R = -1). At a nominal stress amplitude of 123.5 MPa, the average number of cycles to failure is 12,666 for unrepaired baseline coupons and 17,372 for effectively repaired coupons. Restoring complex geometries without compromising fatigue performance has been difficult in aerospace applications; this study marks the first demonstration of additive repair that consistently outperforms the unrepaired baseline coupons. Notably, the result is achieved through a low-energy, cost-effective solution without the need for post-repair heat treatment. Except for a few outliers, the post-repair fatigue performance generally remains inferior to that of undamaged, pristine coupons, likely due to precipitate evolution in AA7050 caused by the thermomechanical processing nature of additive friction stir deposition. This evolution weakens the repair region and the adjacent base material, leading to faster crack initiation and growth compared to the properly aged base material, AA7050-T7451.

Unveiling the Promise: Navigating Clinical Trials 1978-2024 for PDAC.

Despite many decades of research, pancreatic ductal adenocarcinoma (PDAC) remains one of the most difficult cancers to diagnose and treat effectively. Although there have been improvements in the 5-year overall survival rate, it is still very low at 12.5%. The limited efficacy of current therapies, even when PDAC is detected early, underscores the aggressive nature of the disease and the urgent need for more effective treatments. Clinical management of PDAC still relies heavily on a limited repertoire of therapeutic interventions, highlighting a significant gap between research efforts and available treatments. Over 4300 clinical trials have been or are currently investigating different treatment modalities and diagnostic strategies for PDAC, including targeted therapies, immunotherapies, and precision medicine approaches. These trials aim to develop more effective treatments and improve early detection methods through advanced imaging techniques and blood-based biomarkers. This review seeks to categorize and analyze PDAC-related clinical trials across various dimensions to understand why so few chemotherapeutic options are available to patients despite the numerous trials being conducted. This review aims to provide a comprehensive and nuanced understanding of the landscape of PDAC-related clinical trials, with the overarching goal of identifying opportunities to accelerate progress in drug development and improve patient outcomes in the fight against this devastating disease.