A Review and Bibliometric Analysis of Studies on Advances in Peripheral Nerve Regeneration.

Peripheral nerve injuries (PNIs) pose significant clinical challenges due to their complex healing processes and the often incomplete functional recovery. This review and bibliometric analysis aimed to provide a comprehensive overview of advancements in peripheral nerve regeneration research, focusing on trends, influential studies, and emerging areas. By analyzing 2921 publications from the Web of Science Core Collection, key themes such as nerve regeneration, repair, and the critical role of Schwann cells were identified. The study highlights a notable increase in research output since the early 2000s, with China and the United States leading in publication volume and citations. The analysis also underscores the importance of collaborative networks, which are driving innovation in this field. Despite significant progress, the challenge of achieving complete functional recovery from PNIs persists, emphasizing the need for continued research into novel therapeutic strategies. This review synthesizes current knowledge on the mechanisms of nerve regeneration, including the roles of cellular and molecular processes, neurotrophic factors, and emerging therapeutic approaches such as gene therapy and stem cell applications. Additionally, the study revealed the use of nanotechnology, biomaterials, and advanced imaging techniques, which hold promise for improving the outcomes of nerve repair. This bibliometric analysis not only maps the landscape of peripheral nerve regeneration research but also identifies opportunities for future investigation. This study has some limitations, including reliance on the Web of Science Core Collection, which may exclude relevant research from other databases. The analysis is predominantly English-based, potentially overlooking significant non-English studies. Citation trends might be influenced by shifting research priorities and accessibility issues, affecting the visibility of older work. Additionally, geographical disparities and limited collaboration networks may restrict the global applicability and knowledge exchange in this field.

Improving Blood Transfusion Request Form Documentation: A Quality Improvement Project.

BACKGROUND: The transfusion quality improvement project (QIP) serves as a valuable tool for assessing and educating individuals who request blood components. The World Health Organization (WHO) recommends that each institution utilize a blood transfusion request form to ensure the effective conveyance of patient information to the hospital's blood bank. This QIP aimed to implement a transfusion request form and measure compliance with its use. METHODS: A prospective study was conducted at Al Managil Teaching Hospital, Sudan, from May 1 to August 3, 2024, to address the lack of standardized transfusion request forms. The study included three cycles involving pre-intervention analysis, two phases of intervention with training sessions, and post-intervention evaluations. The interventions focused on developing and implementing a new transfusion request form, training clinical physicians, and reinforcing the form's use. Data from 100 randomly selected transfusion request forms were analyzed for completeness and adherence. RESULTS: The study showed significant improvements in the completeness of transfusion request forms across three cycles. In the first cycle, no data were collected, highlighting the absence of standardized forms. During the second cycle, with the introduction of the new form, the completion rates varied: some fields, such as patient information and clinical details, were fully completed in 50 cases (100%), while critical clinical parameters, such as current hemoglobin (Hb) and platelet (PLT) levels, were completed in only four requests (8%). By the third cycle, there was a substantial increase in completion rates across all domains. For example, patient information fields achieved 100% completion in 50 cases, and clinical parameters saw significant improvement, with current Hb and PLT levels documented in 48 cases (96%). The mean percentage completion increased from 68.1% in the second cycle to 97.9% in the third cycle, demonstrating the effectiveness of the interventions and training sessions. Minor decreases were observed in health insurance documentation and certain clinical details, indicating areas for further improvement. CONCLUSION: The systematic implementation and iterative evaluation of transfusion request forms significantly enhanced documentation completeness.

First report of the clinical characteristics and outcomes of cardiac amyloidosis in Saudi Arabia.

AIMS: Cardiac amyloidosis (CA) is a potentially fatal multisystemic disease that remains significantly underdiagnosed, particularly in the Middle East. This study aims to evaluate the prevalence and clinical characteristics of CA in a high-risk population at a tertiary centre in Saudi Arabia. METHODS: This cross-sectional, retrospective, single-centre study was conducted at a tertiary hospital in Riyadh, Saudi Arabia. We reviewed the medical records of heart failure patients seen between August 2018 and July 2022 who exhibited red flags for CA and subsequently underwent CA screening. Red flags that prompted the workup included at least two of the following factors: the presence of unilateral or bilateral carpal tunnel syndrome, a family history of transthyretin amyloid (ATTR) amyloidosis and specific electrocardiographic features (relative/absolute low QRS voltage, pseudoinfarct pattern and atrioventricular/interventricular conduction abnormalities). Echocardiographic red flags included mainly increased wall thickness (≥12 mm), significant diastolic dysfunction, reduced left ventricular (LV) longitudinal function, right ventricular (RV) dysfunction and elevated right atrial (RA)/pulmonary artery (PA) pressure. Cardiac magnetic resonance (CMR) red flags included aspects similar to those in an echocardiogram as well as a subendocardial or transmural late gadolinium enhancement (LGE) pattern. These patients were assessed for CA through technetium-99m pyrophosphate ([99mTc]Tc-PYP) bone scintigraphy, serum and urine protein electrophoresis with immunofixation and a serum-free light chain assay. RESULTS: A total of 177 patients were screened, of which 21.0 (11.9%) patients were diagnosed with transthyretin amyloid CA (ATTR-CA) and 13 (7.3%) patients were diagnosed with light chain CA (AL-CA). Compared with patients with negative/equivocal [99mTc]Tc-PYP scans (grades 0-1), patients with positive [99mTc]Tc-PYP scans (grades 2-3) were older (78.0 vs. 68.0 years, P < 0.001), had higher levels of troponin (P = 0.003) and N-terminal pro-brain natriuretic peptide (NT-proBNP) (P < 0.001), had a higher LV mass index (P < 0.001), displayed a more depressed global longitudinal strain (GLS) (P < 0.001) with a greater prevalence of a relative apical sparing pattern (P < 0.001) and demonstrated a higher incidence of first-degree atrioventricular block (P = 0.008) and low voltage patterns on electrocardiography (P < 0.001). Patients with ATTR-CA and AL-CA were more likely to have a subendocardial or transmural LGE pattern on CMR (P < 0.001) and had a significantly lower overall survival (P < 0.001) when compared with other heart failure aetiologies. CONCLUSIONS: This is the first study to describe the clinical characteristics and outcomes of CA in the Middle East and Saudi Arabia. The prevalence of CA among screened heart failure patients here aligns with major international studies, suggesting significant underdiagnosis in the region. Therefore, larger multicentric studies and regional screening programmes are urgently needed to accurately characterize the epidemiology and outcomes of CA in the Middle East.

Synergistic Interventions for Silencing Oppositional Defiant Disorder and Dyslexia in a Child With Attention-Deficit/Hyperactivity Disorder: A Case Report From Albania.

To the best of the authors' knowledge, this article is the first of its kind in Albania and neighboring countries to investigate the transformative synergistic intervention approach through cognitive behavioral therapy, parent-child interaction therapy (PCIT), and heavy metal detoxification on a child with attention-deficit/hyperactivity disorder (ADHD) and comorbid oppositional defiant disorder (ODD) and dyslexia. The limited mental health awareness in Albania, particularly regarding PCIT and similar treatments, highlights the importance of the applicability and adaptability of such interventions. This study suggests that the rapid management of comorbidities in ADHD, such as ODD and dyslexia, is better achieved by a combined intervention approach and by investigating the biological aspects. Further research with a large sample size is needed to assess the long-term sustainability and scalability of such an approach.

Relationship between obesity and hypertrophic or dilated cardiomyopathy: The role of sex.

Evidence suggests an association between obesity and the risk for cardiomyopathy development; however, robust evidence is still lacking. In this study we sought to explore the relationship of obesity with hypertrophic cardiomyopathy (HCM) and dilated cardiomyopathy (DCM) and possible interactions with sex using large-scale epidemiological real-world data. We analysed data from the Nationwide Inpatient Sample of US hospitalisations for the years 2015-2019. There were a total of 46 934 admissions with diagnosis of HCM and 170 924 with DCM. There was a significant interaction between cardiomyopathies' diagnosis with sex and age subgroups; the rates of both DCM and HCM increased with age (p < .001 for both); DCM diagnosis was significantly higher in males compared with females (0.85% vs. 0.35%, p < .001). After adjustment for age, sex, race and presence of arterial hypertension there was a significant stepwise positive association between obesity and the population rates of both cardiomyopathy subtypes. For hospitalised patients with a body mass index (BMI) ≥30 kg/m2 there was an odds ratio (OR) of 1.68 (95% CI: 1.55-1.81, p < .001) for HCM and OR = 1.82 (95% CI: 1.79-1.84, p < .001) for DCM. More importantly, the positive relationship between a cardiomyopathy diagnosis (HCM or DCM) with increasing BMI was driven by the male sex (p < .001 for both) and it was non-significant in females. The findings from this nationwide observational analysis support a sexual dimorphism in the relationship between obesity and HCM or DCM, which should be further investigated.

Modeling Highly Repetitive Low-level Blast Exposure in Mice.

Exposure to explosive blasts is a significant risk factor for brain trauma among exposed persons. Although the effects of large blasts on the brain are well understood, the effects of smaller blasts such as those that occur during military training are less understood. This small, low-level blast exposure also varies highly according to military occupation and training tempo, with some units experiencing few exposures over the course of several years whereas others experience hundreds within a few weeks. Animal models are an important tool in identifying both the injury mechanisms and long-term clinical health risks following low-level blast exposure. Models capable of recapitulating this wide range of exposures are necessary to inform acute and chronic injury outcomes across these disparate risk profiles. Although outcomes following a few low-level blast exposures are easily modeled for mechanistic study, chronic exposures that occur over a career may be better modeled by blast injury paradigms with repeated exposures that occur frequently over weeks and months. Shown here are methods for modeling highly repetitive low-level blast exposure in mice. The procedures are based on established and widely used pneumatic shocktube models of open-field blast exposure that can be scaled to adjust the overpressure parameters and the number or interval of the exposures. These methods can then be used to either enable mechanistic investigations or recapitulate the routine blast exposures of clinical groups under study.

Intradermal Syringocystadenoma Papilliferum on the Popliteal Fossa: A Rare Dermal Variant in an Atypical Location.

Syringocystadenoma papilliferum (SCAP) is a benign adnexal tumor commonly found on the scalp and face, and often associated with nevus sebaceous, with about half of cases appearing in early childhood. SCAP exhibits cystic invaginations with papillary structures and a double-layered glandular epithelium linked to the epidermal surface and stromal plasma cells. We are reporting a rare instance of intradermal SCAP in a 55-year-old male. He sought evaluation for a long-standing asymptomatic dark-pink papule in his left popliteal fossa, measuring 0.7 x 0.5 x 0.4 cm. A shave biopsy revealed papillary dermal fibrosis, glandular epithelium with apocrine secretion, and papillary projections without an epidermal connection. Infundibulofollicular keratinization was observed, along with stromal plasma cells. The patient chose local excision as the treatment option. This case highlights the rarity of intradermal SCAP, especially in the left popliteal fossa, with only one other reported case in the literature.

Successful prediction of left bundle branch block-induced cardiomyopathy and treatment effect by artificial intelligence-enabled electrocardiogram.

BACKGROUND: Left bundle branch block (LBBB) induced cardiomyopathy is an increasingly recognized disease entity.  However, no clinical testing has been shown to be able to predict such an occurrence. CASE REPORT: A 70-year-old male with a prior history of LBBB with preserved ejection fraction (EF) and no other known cardiovascular conditions presented with presyncope, high-grade AV block, and heart failure with reduced EF (36%). His coronary angiogram was negative for any obstructive disease. No other known etiologies for cardiomyopathy were identified. Artificial intelligence-enabled ECGs performed 6 years prior to clinical presentation consistently predicted a high probability (up to 91%) of low EF. The patient successfully underwent left bundle branch area (LBBA) pacing with correction of the underlying LBBB. Subsequent AI ECGs showed a large drop in the probability of low EF immediately after LBBA pacing to 47% and then to 3% 2 months post procedure. His heart failure symptoms markedly improved and EF normalized to 54% at the same time. CONCLUSIONS: Artificial intelligence-enabled ECGS may help identify patients who are at risk of developing LBBB-induced cardiomyopathy and predict the response to LBBA pacing.

Urinary Biomarkers for Lupus Nephritis: A Systems Biology Approach.

Systemic lupus erythematosus (SLE) is the prototypical systemic autoimmune disorder. Kidney involvement, termed lupus nephritis (LN), is seen in 40-60% of patients with systemic lupus erythematosus (SLE). After the diagnosis, serial measurement of proteinuria is the most common method of monitoring treatment response and progression. However, present treatments for LN-corticosteroids and immunosuppressants-target inflammation, not proteinuria. Furthermore, subclinical renal inflammation can persist despite improving proteinuria. Serial kidney biopsies-the gold standard for disease monitoring-are also not feasible due to their inherent risk of complications. Biomarkers that reflect the underlying renal inflammatory process and better predict LN progression and treatment response are urgently needed. Urinary biomarkers are particularly relevant as they can be measured non-invasively and may better reflect the compartmentalized renal response in LN, unlike serum studies that are non-specific to the kidney. The past decade has overseen a boom in applying cutting-edge technologies to dissect the pathogenesis of diseases at the molecular and cellular levels. Using these technologies in LN is beginning to reveal novel disease biomarkers and therapeutic targets for LN, potentially improving patient outcomes if successfully translated to clinical practice.

Avoidable emergency department visits among palliative care cancer patients: novel insights from Saudi Arabia and the Middle East.

BACKGROUND: Several studies emerging from developed countries have highlighted a significant number of potentially avoidable emergency department (ED) visits by cancer patients during the end-of-life period. However, there is a paucity of information from developing nations regarding palliative care practices and the utilization of the ED by palliative care patients. Herein, we aim to characterize ED admissions among patients receiving palliative care at our tertiary center in Saudi Arabia. METHODS: This is a retrospective, cross-sectional study evaluating ED visits amongst adult patients with advanced cancer who were receiving treatment under the palliative care department. This study took place over a period of 12 months from July 2021 through to July 2022. Three palliative care specialist physicians independently and blindly reviewed each patient's ED visits and determined whether the visit was avoidable or unavoidable. RESULTS: A total of 243 patients were included in the final analysis, of which 189 (78.1%) patients had unavoidable visits and 53 (21.9%) patient visits were classified as avoidable. A significantly higher proportion of breast cancer patients presented with unavoidable admissions (14.3% vs. 3.8%, P = 0.037) compared to other cancer types. The incidence of dyspnea (23.8% vs. 5.7%, P < 0.001) and fevers/chills (23.3% vs. 5.7%, P = 0.005) was significantly higher in patients with unavoidable visits. Patients with avoidable visits had a significantly greater proportion of visits for dehydration (13.2% vs. 2.1%, P = 0.002). Notably, although hospital stay was significantly longer in the unavoidable group (P = 0.045), mortality for palliative care patients-regardless of whether their ED visit was avoidable or unavoidable-was not statistically different (P=-0.069). CONCLUSION: To our knowledge, this is the largest and most comprehensive study from Saudi Arabia and the Middle East providing insights into the utilization of palliative care services in the region and the propensity of advanced cancer patients towards visiting the ED. Future studies ought to explore interventions to reduce the frequency of avoidable ED visits.

Ethnobotanical study on medicinal plants in Melit area (North Darfur), Western Sudan.

BACKGROUND: The documentation of ethnobotanical knowledge in Sudan is restricted to specific regions, and there is a far-reaching lack of written information on the traditional use of medicinal plants in other places like Darfur State, in western Sudan. The present study was designed to document the medicinal plants used in traditional medicine of Melit area in North Darfur State. METHOD: Ethnomedicinal information was collected from 135 local informants through semi-structured questionnaires. Data were analysed for use value (UV), informant consensus factor (ICF) and fidelity level. RESULTS: A total of 59 medicinal plants, belonging to 32 families and 55 genera, were recorded for their traditional uses in Melit area. Fabaceae were represented by highest number of species (13) followed by Asteraceae and Malvaceae (4 each) and Poaceae (3). Herbs comprise the main sources (50.8%) of traditional remedies. Fruits and stem bark (17.9% each) were the major plant parts used. Decoction (36.5%) is the most mode of preparation used. Geigeria alata was most commonly used species with UV of 2.37. The highest ICF values were recorded for swellings (ICF = 1.00) and respiratory system (ICF = 0.95) categories. Ten plants, namely Carica papaya, Corchorus trilocularis, Eragrostis cilianensis, Heliotropium sudanicum, Mollugo cerviana, Psiadia punctulate, Rhynchosia minima, Solanum coagulans, Solanum forskalii and Tephrosia purpurea, were cited for the first time as medicinal plants used in Sudan traditional medicine. Resins of Boswellia papyrifera, seeds of Nigella sativa, pods of Vachellia nilotica (syn. Acacia nilotica) and clove of Syzygium aromticum were used to make different preparations for the treatment of the corona virus. CONCLUSION: This is the first ethnobotanical survey conducted in this region which is always suffering from security issues, and results indicated that Melit area harbours high diversity of plants used traditionally to cure different health conditions. The present study aids in conserving such rich heritage, and it is recommended that the newly reported species worth further studying over their phytochemical and biological properties.

Cellular senescence in brain aging and cognitive decline.

Cellular senescence is a biological aging hallmark that plays a key role in the development of neurodegenerative diseases. Clinical trials are currently underway to evaluate the effectiveness of senotherapies for these diseases. However, the impact of senescence on brain aging and cognitive decline in the absence of neurodegeneration remains uncertain. Moreover, patient populations like cancer survivors, traumatic brain injury survivors, obese individuals, obstructive sleep apnea patients, and chronic kidney disease patients can suffer age-related brain changes like cognitive decline prematurely, suggesting that they may suffer accelerated senescence in the brain. Understanding the role of senescence in neurocognitive deficits linked to these conditions is crucial, especially considering the rapidly evolving field of senotherapeutics. Such treatments could help alleviate early brain aging in these patients, significantly reducing patient morbidity and healthcare costs. This review provides a translational perspective on how cellular senescence plays a role in brain aging and age-related cognitive decline. We also discuss important caveats surrounding mainstream senotherapies like senolytics and senomorphics, and present emerging evidence of hyperbaric oxygen therapy and immune-directed therapies as viable modalities for reducing senescent cell burden.

Brain uptake pharmacokinetics of albiglutide, dulaglutide, tirzepatide, and DA5-CH in the search for new treatments of Alzheimer's and Parkinson's diseases.

BACKGROUND: A number of peptide incretin receptor agonists (IRAs) show promise as therapeutics for Alzheimer's disease (AD) and Parkinson's disease (PD). Transport across the blood-brain barrier (BBB) is one way for IRAs to act directly within the brain. To determine which IRAs are high priority candidates for treating these disorders, we have studied their brain uptake pharmacokinetics. METHODS: We quantitatively measure the ability of four IRAs to cross the BBB. We injected adult male CD-1 mice intravenously with 125I- or 14C-labeled albiglutide, dulaglutide, DA5-CH, or tirzepatide and used multiple-time regression analyses to measure brain kinetics up to 1 hour. For those IRAs failing to enter the brain 1 h after intravenous injection, we also investigated their ability to enter over a longer time frame (i.e., 6 h). RESULTS: Albiglutide and dulaglutide had the fastest brain uptake rates within 1 hour. DA5-CH appears to enter the brain rapidly, reaching equilibrium quickly. Tirzepatide does not appear to cross the BBB within 1 h after iv injection but like albumin, did so slowly over 6 h, presumably via the extracellular pathways. CONCLUSIONS: We find that IRAs can cross the BBB by two separate processes; one that is fast and one that is slow. Three of the four IRAs investigated here have fast rates of transport and should be taken into consideration for testing as AD and PD therapeutics as they would have the ability to act quickly and directly on the brain as a whole.

Non-Mixture Cure Model Estimation in Bladder Cancer Patients: A Novel Approach with Exponentiated Weibull Exponential Distribution.

OBJECTIVE: Cure models are frequently used in survival analysis to account for a cured fraction in the data. When there is a cure rate present, researchers often prefer cure models over parametric models to analyse the survival data. These models enable the ability to define the probability distribution of survival durations for patients who are at risk. Various distributions can be considered for the survival times, such as Exponentiated Weibull Exponential (EWE), Exponential Exponential (EE), Weibull and lognormal distribution. The objective of this research is to choose the most appropriate distribution that accurately represents the survival times of patients who have not been cured. This will be accomplished by comparing various non-mixture cure models that are based on the EWE distribution with its sub-distributions, and distributions distinct from those belonging to the EWE distribution family. MATERIAL AND METHODS: A sample of 85 patients diagnosed with superficial bladder tumours was selected to be used in fitting the non-mixture cure model. In order to estimate the parameters of the suggested model, which takes into account the presence of a cure rate, censored data, and covariates, we utilized the maximum likelihood estimation technique using R software version 3.5.7. RESULT: Upon conducting a comparison of various parametric models fitted to the data, both with and without considering the cure fraction and without incorporating any predictors, the EE distribution yields the lowest AIC, BIC, and HQIC values among all the distributions considered in this study, (1191.921/1198.502, 1201.692/1203.387, 1195.851/1200.467). Furthermore, when considering a non-mixture cure model utilizing the EE distribution along with covariates, an estimated ratio was obtained between the probabilities of being cured for placebo and thiotepa groups (and its 95% confidence intervals) were 0.76130 (0.13914, 6.81863). CONCLUSION: The findings of this study indicate that EE distribution is the optimal selection for determining the duration of survival in individuals diagnosed with bladder cancer.

Neutrophil extracellular traps and long COVID.

Post-acute COVID-19 sequelae, commonly known as long COVID, encompasses a range of systemic symptoms experienced by a significant number of COVID-19 survivors. The underlying pathophysiology of long COVID has become a topic of intense research discussion. While chronic inflammation in long COVID has received considerable attention, the role of neutrophils, which are the most abundant of all immune cells and primary responders to inflammation, has been unfortunately overlooked, perhaps due to their short lifespan. In this review, we discuss the emerging role of neutrophil extracellular traps (NETs) in the persistent inflammatory response observed in long COVID patients. We present early evidence linking the persistence of NETs to pulmonary fibrosis, cardiovascular abnormalities, and neurological dysfunction in long COVID. Several uncertainties require investigation in future studies. These include the mechanisms by which SARS-CoV-2 brings about sustained neutrophil activation phenotypes after infection resolution; whether the heterogeneity of neutrophils seen in acute SARS-CoV-2 infection persists into the chronic phase; whether the presence of autoantibodies in long COVID can induce NETs and protect them from degradation; whether NETs exert differential, organ-specific effects; specifically which NET components contribute to organ-specific pathologies, such as pulmonary fibrosis; and whether senescent cells can drive NET formation through their pro-inflammatory secretome in long COVID. Answering these questions may pave the way for the development of clinically applicable strategies targeting NETs, providing relief for this emerging health crisis.

Bispecific Antibodies in Hematological Malignancies: A Scoping Review.

Bispecific T-cell engagers (BiTEs) and bispecific antibodies (BiAbs) have revolutionized the treatment landscape of hematological malignancies. By directing T cells towards specific tumor antigens, BiTEs and BiAbs facilitate the T-cell-mediated lysis of neoplastic cells. The success of blinatumomab, a CD19xCD3 BiTE, in acute lymphoblastic leukemia spearheaded the expansive development of BiTEs/BiAbs in the context of hematological neoplasms. Nearly a decade later, numerous BiTEs/BiAbs targeting a range of tumor-associated antigens have transpired in the treatment of multiple myeloma, non-Hodgkin's lymphoma, acute myelogenous leukemia, and acute lymphoblastic leukemia. However, despite their generally favorable safety profiles, particular toxicities such as infections, cytokine release syndrome, myelosuppression, and neurotoxicity after BiAb/BiTE therapy raise valid concerns. Moreover, target antigen loss and the immunosuppressive microenvironment of hematological neoplasms facilitate resistance towards BiTEs/BiAbs. This review aims to highlight the most recent evidence from clinical trials evaluating the safety and efficacy of BiAbs/BiTEs. Additionally, the review will provide mechanistic insights into the limitations of BiAbs whilst outlining practical applications and strategies to overcome these limitations.