From single to combinatorial therapies in spinal cord injuries for structural and functional restoration

Spinal cord injury results in paralysis, sensory disturbances, sphincter dysfunction, and multiple systemic secondary conditions, most arising from autonomic dysregulation. All this produces profound negative psychosocial implications for affected people, their families, and their communities;the financial costs can be challenging for their families and health institutions. Treatments aimed at restoring the spinal cord after spinal cord injury, which have been tested in animal models or clinical trials, generally seek to counteract one or more of the secondary mechanisms of injury to limit the extent of the initial damage. Most published works on structural/functional restoration in acute and chronic spinal cord injury stages use a single type of treatment: a drug or trophic factor, transplant of a cell type, and implantation of a biomaterial. Despite the significant benefits reported in animal models, when translating these successful therapeutic strategies to humans, the result in clinical trials has been considered of little relevance because the improvement, when present, is usually insufficient. Until now, most studies designed to promote neuroprotection or regeneration at different stages after spinal cord injury have used single treatments. Considering the occurrence of various secondary mechanisms of injury in the acute and sub-acute phases of spinal cord injury, it is reasonable to speculate that more than one therapeutic agent could be required to promote structural and functional restoration of the damaged spinal cord. Treatments that combine several therapeutic agents, targeting different mechanisms of injury, which, when used as a single therapy, have shown some benefits, allow us to assume that they will have synergistic beneficial effects. Thus, this narrative review article aims to summarize current trends in the use of strategies that combine therapeutic agents administered simultaneously or sequentially, seeking structural and functional restoration of the injured spinal cord.

Use of induced pluripotent stem cell-derived brain cells,organoids,assembloids,and blood-brain barrier models in understanding alcohol and anesthetic-induced brain injuries:an emerging perspective

Neurological disorders,including developmental disorders,Alzheimer’s disease(AD),and psychiatric conditions,have significant social and economic impacts globally.Despite extensive research into the underlying mechanisms of these disorders,effective treatments remain elusive,partly due to the complexity of the brain,the limited availability of human brain tissue,and the blood-brain barrier(BBB)’s impermeability to certain drugs.This perspective article discusses the potential of human induced pluripotent stem cell(iPSC)-based models of brain cells,organoids,assembloids,and BBB to advance our understanding of the etiology,progression,and mechanisms of brain injuries induced by alcohol consumption and general anesthesia.These models could also be used to develop protective and therapeutic approaches.

The Role of Age as a Risk Factor for Pickleball-Related Injuries

Pickleball is a popular sport that includes players from many different demographics. The popularity has resulted in not only increases in participation but also in activity related injuries. The purpose of this study was to identify risk factors along with potential mechanisms for injuries related to pickleball and identify effective countermeasures. Methods included the identification of pickleball related injuries from a US National Emergency Room database (NEISS). A narrative section of the database was used to identify and categorize potential mechanisms of injury. Results indicated that the types and mechanisms of injury relate to three specific age groups: younger, middle age, and older players. Injuries to younger players under the age of 26 are likely the result of misuse of sport equipment. Middle aged players from 26 to 50 sustained injuries more related activity overuse. However, there were more concerns with players over 50 years of age with a great percentage resulting in cardia arrest or symptoms leading to more severe cardiovascular conditions. While pickleball activity should be encouraged as it is a beneficial form of physical activity, there should be specific age-group interventions to reduce injury. It should be highly recommended that doctors approve the activity for individual at risk for heart conditions and supervision for adults in that age group.

Resection and reconstruction in high-grade pancreatic head injuries

This study by Chui et al adds further important evidence in the treatment of highgrade pancreatic injuries and endorses the concept of the model of pancreatic trauma care designed to optimize treatment,minimize morbidity and enhance survival in patients with complex pancreatic injuries.Although the authors have demonstrated favorable outcomes based on their limited experience of 5 patients who underwent a pancreaticoduodenectomy(PD),including 2 patients who were“unstable”and did not have damage control surgery(DCS),we would caution against the general recommendations promoting index PD without DCS in“unstable”grade 5 pancreatic head injuries.

Management of Traumatic Brain Injuries at the Kara Regional Hospital

Introduction: Traumatic Brain Injury (TBI) is a major public health problem causing significant morbidity and mortality in young adults. This study aimed to describe the epidemiological, diagnostic, therapeutic, and evolutionary aspects of TBI. Materials and Methods: This was a prospective, descriptive study conducted from 1 April 2022 to 31 March 2023 on patients admitted to and treated for cranioencephalic trauma in the General Surgery department of Kara Regional Hospital. Results: Eighty-three (83) patients with cranioencephalic trauma were managed out of 773 patients admitted to the department during the study period. The mean age was 34 ± 14.98 years and the sex ratio was 3.6 in favour of men. Motorbike taxi drivers were the social group most affected (n = 33, 40%). The causes of trauma were dominated by public road accidents (n = 80;96%). TBI was mild (n = 40;48%), moderate (n = 35;42%) and severe (n = 8;10%). Cerebral CT scans were performed in 19 patients (23%). Cerebral contusion (n = 4) was the most frequent cerebral lesion. Six patients (7%) with severe head injuries were transferred to Kara University Hospital. Six deaths (7%) occurred in patients with severe head injuries. The main sequelae were intermittent headaches in all patients reviewed, and memory problems (6%). Conclusion: Traumatic brain injuries are common at Kara Regional Hospital. Severe cranial trauma is less frequent but leads to death because of financial difficulties and limited technical facilities.

Crosstalk among mitophagy,pyroptosis,ferroptosis,and necroptosis in central nervous system injuries

Central nervous system injuries have a high rate of resulting in disability and mortality;however,at present,effective treatments are lacking.Programmed cell death,which is a genetically determined fo rm of active and ordered cell death with many types,has recently attra cted increasing attention due to its functions in determining the fate of cell survival.A growing number of studies have suggested that programmed cell death is involved in central nervous system injuries and plays an important role in the progression of brain damage.In this review,we provide an ove rview of the role of programmed cell death in central nervous system injuries,including the pathways involved in mitophagy,pyroptosis,ferroptosis,and necroptosis,and the underlying mechanisms by which mitophagy regulates pyroptosis,ferroptosis,and necro ptosis.We also discuss the new direction of therapeutic strategies to rgeting mitophagy for the treatment of central nervous system injuries,with the aim to determine the connection between programmed cell death and central nervous system injuries and to identify new therapies to modulate programmed cell death following central nervous system injury.In conclusion,based on these properties and effects,interventions targeting programmed cell death could be developed as potential therapeutic agents for central nervous system injury patients.

Decision-Making and Management of Self-Care in Persons with Traumatic Spinal Cord Injuries: A Preliminary Study

Patients and physicians understand the importance of self-care following spinal cord injury (SCI), yet many individuals with SCI do not adhere to recommended self-care activities despite logistical supports. Neurobehavioral determinants of SCI self-care behavior, such as impulsivity, are not widely studied, yet understanding them could inform efforts to improve SCI self-care. We explored associations between impulsivity and self-care in an observational study of 35 US adults age 18 - 50 who had traumatic SCI with paraplegia at least six months before assessment. The primary outcome measure was self-reported self-care. In LASSO regression models that included all neurobehavioral measures and demographics as predictors of self-care, dispositional measures of greater impulsivity (negative urgency, lack of premeditation, lack of perseverance), and reduced mindfulness were associated with reduced self-care. Outcome (magnitude) sensitivity, a latent decision-making parameter derived from computationally modeling successive choices in a gambling task, was also associated with self-care behavior. These results are preliminary;more research is needed to demonstrate the utility of these findings in clinical settings. Information about associations between impulsivity and poor self-care in people with SCI could guide the development of interventions to improve SCI self-care and help patients with elevated risks related to self-care and secondary health conditions.

Knowledge, Attitude, and Practice of Using Helmets in Children amongst Parents to Prevent Head Injuries: A Cross-Sectional Study in Riyadh, Saudi Arabia

Objectives: The primary objective was to characterize the range of Knowledge, Attitude, and Practice (KAP) of Helmet use in children amongst parents to prevent head injuries and death. Methods: This is a cross-sectional study, done by online survey using a snowball sampling technique, the number of included responses were 386 parents (Male and female) living in Riyadh Aged 21 - 60 years old or above. Results: The study showed that there is a difference in Parents’ belief in the importance of helmet use while riding a Bicycle vs Motorcycle/Quad bike and that was affected by parents’ education level, almost all the people who answered the survey (76.7%) agree that it is important for their children to wear a helmet when riding both a Bicycle and a Motorcycle or Quadbike with a cumulative percentage of (93.8%). And almost all agreed on multiple approaches to help increase helmet use be it by forcing rental shops to give out helmets, forcing sellers to recommend the use of helmets, increasing awareness campaigns, and imposing fines for not wearing helmets. Conclusions: This study is the first to explore Family helmet use while riding Bicycles and Motorcycles/Quad bikes. Although Parent’s belief in the importance of helmet use for their children was high, it is clear that the level of practice is low. With that the risk of head injuries might be high, our findings suggest that safety interventions for increasing pediatric helmet use are needed to increase helmet use and reduce the risk of head injury and hospitalization.

Upper extremity vascular injuries:Etiology,management and outcome

BACKGROUND Vascular injuries of the upper extremities are considered relatively rare injuries affecting mostly the young population.They often are complex injuries accompanied by other musculoskeletal trauma or trauma in other anatomic locations.Their management is challenging since they can lead to disabilities with major socioeconomic effects.AIM To analyze data about the mechanism of injury,the management algorithm and functional outcomes of vascular injuries of the upper extremity.METHODS One hundred and fifteen patients(96 males and 19 females)with arterial injuries of the upper extremity treated in a tertiary trauma center from January 2003 to December 2022 was conducted.Mean patients’age was 33.7 years and the mean follow up time was 7.4 years.Patients with Mangled Extremity Severity Score≥7 and Injury Severity Score≥20,previous upper limb surgery or major trauma and any neuromuscular or psychiatric disease were excluded,from the study.RESULTS A penetrating trauma was the most common cause of injury.The radial artery was the artery injured in most of the cases(37.4%)followed by the ulnar(29.5%),the brachial(12.1%)and the axillary(6%).A simultaneous injury of both of the forearm’s arteries was in 15.6%of the cases.In 93%of the cases there were other concomitant musculoskeletal injuries of the extremity.Tendon lacerations were the most common,followed by nerve injuries.The postoperative functional scores(full Disabilities of the Arm,Shoulder,and Hand and VAS)had very satisfactory values.CONCLUSION Although vascular injuries of the upper extremity are rare,they may occur in the context of major combined musculoskeletal trauma.Although a multidisciplinary approach is essential to optimize outcome,the ability of trained hand surgeons to repair all injuries in combined vascular and musculoskeletal upper extremity trauma,excluding isolated vascular injuries,ensures shorter operative times and better functional outcomes.

Is there a place for endoscopic management in postcholecystectomy iatrogenic bile duct injuries?

In this editorial we comment on the article by Emara et al published in the recent issue of the World Journal of Gastrointestinal Surgery.Previously,surgery was the primary treatment for bile duct injuries(BDI).The treatment of BDI has advanced due to technological breakthroughs and minimally invasive procedures.Endoscopic and percutaneous treatments have largely supplanted surgery as the primary treatment for most instances in recent years.Patient management,including the specific technique,is typically impacted by local knowledge and the kind and severity of the injury.Endoscopic therapy is a highly successful treatment for postoperative benign bile duct stenosis and offers superior long-term outcomes compared to surgical correction.Based on the damage features of BDI,therapeutic options include endoscopic duodenal papillary sphincterotomy,endoscopic nasobiliary drainage,and endoscopic biliary stent implantation.

Relationships between Quadriceps:Hamstring Strength Ratio and Lower Extremity Injuries in Netball Players

Background: Netball is a popular sport. Due to high impact and quick movement, there is an enormous load on the lower extremities which increases the risk for injury. Aim: The aim of this study was to investigate the relationship between the quadricep and hamstring strength and the prevalence of lower extremity injuries in netball players. Setting: Twenty-five female netball players (age: 20.8 ± 1.4 years) voluntarily participated. Methods: The Cybex Isokinetic dynamometer was used to determine concentric knee torques. Quadriceps:hamstring strength ratio was determined. Occurrence of lower extremity injuries was documented bi-weekly. Results: Medium effect sizes were noted for flexion torque:work for the left leg and for the quadriceps:hamstring ratio (≥60%) for the right leg. All the other measured variables have a small effect size. 18.75% of lower extremity injuries and ConQ:ConH of Conclusion: Injuries to the ankle and knee are especially common among netball players. Hamstring and quadriceps muscle asymmetry (>10%) were found to be a potential indicator of lower extremity injury. Contribution: This study highlights awareness on lower extremity injuries and the strength ratio between the quadriceps and hamstrings. This can aid coaches and netball players to lower the risk for injuries and thus improve individual- and team performance.

Review and update on the management of triangular fibrocartilage complex injuries in professional athletes

Triangular fibrocartilage complex injuries are common in amateur and professional sports.These injuries are mainly caused by acute or chronic repetitive axial loads on the wrist,particularly on the ulnar side and in association with rotations or radial/ulnar deviations.In order to treat professional athletes,a detailed specific knowledge of the pathology is needed.Moreover,the clinician should fully understand the specific and unique environment and needs of the athletes,their priorities and goals,the type of sport,the time of the season,and the position played.An early diagnosis and appropriate management with the quickest possible recovery time are the uppermost goals for both the athlete and the surgeon.A compromise between conservative vs surgical indications,athletes’needs and expectations,and financial implications should be achieved.Arthroscopic procedures should be timely planned when indicated as they could allow early diagnosis and treatment at the same time.Conservative measures are often used as first line treatment when possible.Peripheral lesions are treated by arthroscopic repair,whilst central lesions are treated by arthroscopic debridement.Further procedures(such as the Wafer procedure,ulnar osteotomies,etc.)have specific indications and great implications with regard to rehabilitation.

Network pharmacology investigation of the mechanism underlying the therapeutic action of Shikang granules in retinal ischemia-reperfusion injuries

Background:Retinal ischemia/reperfusion(I/R)injury often results in vision loss,and effective clinical management options are currently lacking.Shikang granules(SKG)are traditional Chinese medicine-based preparations commonly used in clinical practice for treating optic atrophy.Methods:Despite decades of clinical use,the precise mechanism of action(MoA)of SKG remains elusive.Here,we employ a network pharmacological approach to elucidate its MoA by identifying active ingredients and relevant targets using the Traditional Chinese Medicine System Pharmacology Database and Analytical Platform.Targets associated with retinal I/R injury were sourced from GeneCards,Online Mendelian Inheritance in Man,and DisGeNET.Venny software facilitated the identification of intersecting targets,which were then subjected to gene ontology functional analysis and Kyoto Encyclopedia of Genes and Genomes pathway analysis.To validate the protective effect and explore the MoA of SKG in retinal I/R injuries,we conducted experiments using rat models.Results:Our animal experiments demonstrated that SKG mitigated apoptosis following retinal I/R injury by upregulating the expression of the anti-apoptotic protein Bcl-2 and downregulating the expression of BAX,Caspase-9,Caspase-3,PARP,and cytochrome C.Additionally,SKG was found to increase the expression of PI3K and AKT.Conclusions:SKG may exert its protective effects by inhibiting apoptosis through modulation of pro-apoptotic and anti-apoptotic protein expression,as well as activation of the PI3K/AKT pathway.

Otorhinolaryngological (ORL) and Cervicofacial Injuries Resulting from Road Accidents within the Otorhinolaryngology (ORL) Department of the Regional Hospital of Mamou

Introduction: Otorhinolaryngological (ORL) and cervicofacial traumas encompass injuries affecting the neck, face, and ORL region, resulting from external influence. The objective of this study was to conduct an epidemiological and clinical analysis of ORL and cervicofacial injuries observed in victims of road accidents treated at the Otorhinolaryngology (ORL) department of the Regional Hospital of Mamou. Materials and Methods: This prospective and descriptive study was conducted over a period of 12 months, from January 1st to December 31st, 2021, within the Otorhinolaryngology (ORL) department of the Regional Hospital of Mamou. It included patients hospitalized for ORL and/or cervicofacial traumas resulting from road accidents during the study period. Results: A total of 348 cases were included, representing 36.22% of all traumas related to road accidents (AVP) within the Regional Hospital of Mamou. The average age of the patients was 26.44 years, with a sex ratio of 3.83, favoring males. The dominant socio-professional category was students, encompassing 32.47% of cases. Road accidents were mainly associated with motorcycle use (31.32% motorcycle-to-motorcycle, 24.43% motorcycle skidding, 13.51% motorcycle-pedestrian). Facial region injuries were the most common, accounting for 69.03% of cases, followed by rhinological injuries (17.28%) and otological injuries (13.69%). Associated injuries were predominantly closed head traumas (52.55%) and lower limb fractures (20.41%). Imaging was underutilized. Regarding surgical interventions, reconstructive surgery was the most predominant, accounting for 52.51% of cases, with a management timeframe of 30 minutes to 12 hours for 99.72% of patients. Conclusion: Road traffic accidents remain a serious public health issue, primarily affecting young males. Emphasis should be placed on road safety measures to reduce the frequency of these accidents.

COVID-19 related liver injuries in pregnancy

While severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)quickly spread across the globe,our understanding of its pathogenic mechanisms evolved.Importantly,coronavirus disease 2019(COVID-19)is now considered a syndromic multisystem inflammatory disease involving not only the respiratory system but also the cardiovascular,excretory,nervous,musculoskeletal,and gastrointestinal systems.Moreover,a membrane-bound form of angiotensin-converting enzyme 2,the entry receptor for SARS-CoV-2,is expressed on the surface of cholangiocytes and hepatocytes,suggesting the potential of COVID-19 to involve the liver.With the widespread distribution of SARS-CoV-2 throughout the population,infection during pregnancy is no longer a rare occurrence;however,little is known about the course of hepatic injuries and related outcomes in pregnant SARS-CoV-2-positive women.Thus,the understudied topic of COVID-related liver disease during pregnancy poses a great challenge for the consulting gynecologist and hepatologist.In this review,we aim to describe and summarize potential liver injuries in pregnant women with COVID-19.

Epidemiology of animal bite injuries in North of Fars province in Iran

Objective:To investigate the epidemiological situation of animal bites in Rostam city of Fars province.Methods:This is a cross-sectional study.Cases of animal bites registered in health centers of Rostam city of Fars province from the beginning of 2014 to 2020 were analyzed using the census method.The tool for collecting information was the portal of the Ministry of Health and the registration offices of people who were referred to the rabies center.Results:A total of 628 cases of animal bites registered in health centers of Rostam city of Fars province from the beginning of 2014 to 2020.The mean age of the injured was(31.3±20.2)years.Of the total injured cases,414(65.9%)were male,and 491(78.2%)lived in villages.Most of the cases were bitten by dogs(n=420,66.8%)and the upper limb was involved in 280(55.2%)cases.In addition,an increasing trend was observed in the incidence of animal bites from 2015 to 2020.Conclusions:The incidence of animal bites in Rostam City is high,and most of the cases occur in rural areas.Considering the injuries caused by animal bites,the risk of rabies transmission,and the high costs of vaccination and serum therapy,it is necessary to hold control,educational,and vaccination programs.

Surgical management of high-grade pancreatic injuries: Insights from a high-volume pancreaticobiliary specialty unit

BACKGROUND The management of high-grade pancreatic trauma is controversial.AIM To review our single-institution experience on the surgical management of blunt and penetrating pancreatic injuries.METHODS A retrospective review of records was performed on all patients undergoing surgical intervention for high-grade pancreatic injuries [American Association for the Surgery of Trauma(AAST) Grade Ⅲor greater] at the Royal North Shore Hospital in Sydney between January 2001 and December 2022. Morbidity and mortality outcomes were reviewed, and major diagnostic and operative challenges were identified.RESULTS Over a twenty-year period, 14 patients underwent pancreatic resection for highgrade injuries. Seven patients sustained AAST Grade Ⅲinjuries and 7 were classified as Grades Ⅳ or Ⅴ. Nine underwent distal pancreatectomy and 5 underwent pancreaticoduodenectomy(PD). Overall, there was a predominance of blunt aetiologies(11/14). Concomitant intra-abdominal injuries were observed in 11 patients and traumatic haemorrhage in 6 patients. Three patients developed clinically relevant pancreatic fistulas and there was one in-hospital mortality secondary to multi-organ failure. Among stable presentations, pancreatic ductal injuries were missed in two-thirds of cases(7/12) on initial computed tomography imaging and subsequently diagnosed on repeat imaging or endoscopic retrograde cholangiopancreatography. All patients who sustained complex pancreaticoduodenal trauma underwent PD without mortality. The management of pancreatic trauma is evolving. Our experience provides valuable and locally relevant insights into future management strategies.CONCLUSION We advocate that high-grade pancreatic trauma should be managed in high-volume hepatopancreato-biliary specialty surgical units. Pancreatic resections including PD may be indicated and safely performed with appropriate specialist surgical, gastroenterology, and interventional radiology support in tertiary centres.

Ex vivo liver resection and auto-transplantation as an alternative for the treatment of liver malignancies: Progress and challenges

Hepatectomy is still the major curative treatment for patients with liver malignancies.However,it is still a big challenge to remove the tumors in the central posterior area,especially if their location involves the retrohepatic inferior vena cava and hepatic veins.Ex vivo liver resection and auto-transplantation(ELRA),a hybrid technique of the traditional liver resection and transplantation,has brought new hope to these patients and therefore becomes a valid alternative to liver transplantation.Due to its technical difficulty,ELRA is still concentrated in a few hepatobiliary centers that have experienced surgeons in both liver resection and liver transplantation.The efficacy and safety of this technique has already been demonstrated in the treatment of benign liver diseases,especially in the advanced alveolar echinococcosis.Recently,the application of ELRA for liver malignances has gained more attention.However,standardization of clinical practice norms and international consensus are still lacking.The prognostic impact in these oncologic patients also needs further evaluation.In this review,we summarized the principles and recent progresses on ELRA.

Liver transplantation as an alternative for the treatment of neuroendocrine liver metastasis: Appraisal of the current evidence

Background:Liver transplantation(LT)for neuroendocrine liver metastases(NELM)is still in debate.Studies comparing LT with liver resection(LR)for NELM are scarce,as patient selection is heterogeneous and experience is limited.The goal of this review was to provide a critical analysis of the evidence on LT versus LR in the treatment of NELM.Data sources:A scoping literature search on LT and LR for NELM was performed with PubMed,including English articles up to March 2023.Results:International guidelines recommend LR for NELM in resectable,well-differentiated tumors in the absence of extrahepatic metastatic disease with superior results of LR compared to systemic or liver-directed therapies.Advanced liver surgery has extended resectability criteria whilst entailing increased perioperative risk and short disease-free survival.In highly selected patients(based on the Milan criteria)with unresectable NELM,oncologic results of LT are promising.Prognostic factors include tumor biology(G1/G2)and burden,waiting time for LT,patient age and extrahepatic spread.Based on low-level evi-dence,LT for low-grade NELM within the Milan criteria resulted in improved disease-free survival and overall survival compared to LR.The benefits of LT were lost in patients beyond the Milan NELM-criteria.Conclusions:With adherence to strict selection criteria especially tumor biology,LT for NELM is becoming a valuable option providing oncologic benefits compared to LR.Recent evidence suggests even stricter selection criteria with regard to tumor biology.

Liver transplantation as an alternative for the treatment of intrahepatic cholangiocarcinoma: Past, present, and future directions

Intrahepatic cholangiocarcinoma(iCCA)is a rare biliary tract cancer with high mortality rate.Complete resection of the iCCA lesion is the first choice of treatment,with good prognosis after margin-negative resection.Unfortunately,only 12%-40% of patients are eligible for resection at presentation due to cirrhosis,portal hypertension,or large tumor size.Liver transplantation(LT)offers margin-negative iCCA extirpation for patients with unresectable tumors.Initially,iCCA was a contraindication for LT until size-based selection criteria were introduced to identify patients with satisfied post-LT outcomes.Recent studies have shown that tumor biology-based selection can yield high post-LT survival in patients with locally advanced iCCA.Another selection criterion is the tumor response to neoadjuvant therapy.Patients with response to neoadjuvant therapy have better outcomes after LT compared with those without tumor response to neoadjuvant therapy.Another index that helps predict the treatment outcome is the biomarker.Improved survival outcomes have also opened the door for living donor LT for iCCA.Patients undergoing LT for iCCA now have statistically similar survival rates as patients undergoing resection.The combination of surgery and locoregional and systemic therapies improves the prognosis of iCCA patients.