Type 2A Research Articles

HOW DOES VERTICAL LAMINAR FRACTURE IMPACT THE DECISION-MAKING IN THORACOLUMBAR FRACTURES?

Objective Although vertical laminar fracture (VLF) is generally considered a severity marker for thoracolumbar fractures (TLFs), its exact role in decision-making has never been established. This scoping review aims to synthesize the research on VLF’s role in TLF decision-making. Methods A systematic review was conducted following PRISMA guidelines. We searched PubMed, Scopus, and Web of Science from inception to 11 June 2023 for studies examining the association of VLF in thoracolumbar fractures with dural lacerations, neurological deficits, radiographic parameters, or treatment outcomes. Additionally, experimental studies that analyze the biomechanics of burst fractures with VLF were included. The studies extracted key findings, objectives, and patient population. A meta-analysis was performed for the association of VLF with dural laceration and neurological deficit, and ORs were pooled with a 95% confidence interval (CI). Results Twenty-eight studies were included in this systematic review, encompassing 2,021 patients, and twelve were included in the meta-analysis. According to the main subject of the study, the association of VLF with a dural laceration (n=14), neurological deficit (n=4), radiographic parameters (n=3), thoracolumbar fracture classification (n=2), treatment outcome (n=2). Seven studies with a total of 1010 patients reported a significant association between VLF and neurological deficit (OR= 7.35, 95% CI [3.97, 14.25]; P< 0.001). The pooled OR estimates for VLF predicting dural lacerations was 7.75, 95% CI [2.41, 24.87]; P< 0.001). Conclusion VLF may have several important diagnostic and therapeutic implications in managing TLFs. VLF may help to distinguish AO type A3 from A4 fractures. VLF may help to predict preoperatively the occurrence of dural laceration, thereby choosing the optimal surgical strategy. Clinical and biomechanical data suggest VLF may be a valuable modifier to guide the decision-making in burst fractures; however, more studies are needed to confirm its prognostic importance regarding treatment outcomes.

Integral points on a del Pezzo surface over imaginary quadratic fields

Chambert-Loir and Tschinkel constructed a framework for a geometric interpretation of the density of integral points on certain varieties, which was refined by Wilsch. By using harmonic analysis and the circle method, it was proved for some partial equivariant compactifications of vector groups over arbitrary number fields and high-dimensional complete intersections over Q\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$${\\mathbb {Q}}$$\\end{document}. Further, there are some examples of using the torsor method for singular del Pezzo surfaces over Q\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$${\\mathbb {Q}}$$\\end{document}. In this paper, we generalise the torsor method for integral points from Q\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$${\\mathbb {Q}}$$\\end{document} to imaginary quadratic number fields. As a first representative example, we characterise integral points of bounded log-anticanonical height on a quartic del Pezzo surface of singularity type A3\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$${\ extbf{A}}_3$$\\end{document} over imaginary quadratic fields with respect to its singularity and its lines. Furthermore, we count these integral points of bounded height by using universal torsors and interpret the count geometrically to prove an analogue of Manin’s conjecture for the set of integral points with respect to the singularity and to a line. Our results coincide with the predicted framework.

Studies on the Presence of Different Mating Types of<em> Phytophthora infestans</em> in Nuwara Eliya Sri Lanka

Late blight, caused by Phytophthora infestans is one of the most devastating diseases in potato cultivation. It results in direct crop losses but also causes a considerable amount of cost for disease management. The primary objective of this study was to investigate P. infestans mating types in selected areas in Sri Lanka and evaluate the risks associated with mating types. In this experiment potato leaves from a range of late blight severity levels were sampled from infected farmer fields. The pathogen was isolated by leaf culture method and confirmed by microscopic observations. The mating types of each isolate were studied by a Metalaxyl sensitivity test. Mating type A1 has been previously reported in Sri Lanka, but mating type A2 was not reported since 2013. Results of this study reveal that mating type A1 was more prominent than A2 (75% and 50% respectively). A2 was reported only from two fields. These observations prove the presence and emergence of mating type A2 in Sri Lankan potato fields. Gradual increase of detectable A2 mating types suggests a high possibility of pathogen inoculum movement between the locations over time. The presence of both mating types raises the possibility of sexual reproduction and generation of oospores. The ratio of A1: A2: (A1+A2) in the current study was 2:1:1. This could permit genetic recombination with the biological evolution of fungicideresistant types of P. infestans species. This study emphasizes the importance of investigations on the mating types to manage late blight disease in Sri Lankan potato fields.

Orexin-A Attenuates the Inflammatory Response in Sepsis-Associated Encephalopathy by Modulating Oxidative Stress and Inhibiting the ERK/NF-κB Signaling Pathway in Microglia and Astrocytes.

Oxidative stress-induced inflammation is a major pathogenic mechanism in sepsis-associated encephalopathy (SAE). We hypothesized that regulation of reactive oxygen species (ROS) by the neuropeptide orexin-A could prevent SAE-induced oxidative stress and inflammation. Therefore, the aim of this study was to investigate the effects of orexin-A on oxidative stress and inflammation in SAE in mice. Adult male mice were treated with orexin-A (250 μg/kg, intranasal administration) to establish a cecal ligation perforation (CLP) model. We performed behavioral tests, observed neuronal damage in the hippocampal region, measured the levels of ROS, NOX2, and observed the structure of mitochondria by transmission electron microscopy. We then examined the inflammatory factors TNF-α and IL-1β, the activation of microglia and astrocytes, the expression of ERK/NF-κB, C3, and S100A10, and the presence of A1 type astrocytes and A2 type astrocytes. Orexin-A treatment improved cognitive performance in CLP-induced SAE mice, attenuated neuronal apoptosis in the hippocampal region, ameliorated ROS levels and the extent of mitochondrial damage, and reduced protein expression of NOX2 in hippocampal tissue. In addition, orexin-A treatment significantly reduced microglia and astrocyte activation, inhibited the levels of P-ERK and NF-κB, and reduced the release of IL-1β and TNF-α, which were significantly increased after CLP. Finally, Orexin-A treatment significantly decreased the number of C3/glial fibrillary acidic protein (GFAP)-positive cells and increased the number of S100A10/GFAP-positive cells. Our data suggest that orexin-A reduces ROS expression by inhibiting CLP-induced NOX2 production, thereby attenuating mitochondrial damage and neuronal apoptosis. Its inhibition of microglial and A1-type astrocyte activation and inflammation was associated with the ERK/NF-κB pathway. These suggest that orexin-A may reduce cognitive impairment in SAE by reducing oxidative stress-induced inflammation.

Synergistic effect of Wharton's jelly-derived mesenchymal stem cells and insulin on Schwann cell proliferation in Charcot-Marie-Tooth disease type 1A treatment

Charcot-Marie-Tooth disease type 1A (CMT1A) is a demyelinating disease caused by PMP22 duplication and an exceedingly rare hereditary peripheral neuropathy, with an incidence of 1 in 2500. Currently, no cure exists for CMT1A; however, various therapeutic approaches are under development. Considering the known therapeutic effects of mesenchymal stem cells (MSCs) and the relation of blood sugar levels with nerve damage in CMT, this study aimed to confirm the therapeutic effects of MSCs and insulin on CMT, using both in-vitro and in-vivo models. CMT1A in-vitro models were exposed to Wharton's jelly-derived MSCs (WJ-MSCs) or insulin, and the resulting proliferation changes were measured. CMT1A mice were treated with WJ-MSCs or insulin, and their phenotypic changes were observed. We observed improvements in myelination of Schwann cells in vitro and motor function in vivo. Insulin also showed therapeutic efficacy by promoting Schwann cell proliferation. Furthermore, combination therapy using insulin and WJ-MSCs was more effective than WJ-MSCs or insulin alone. Insulin promoted the proliferation of Schwann cells and WJ-MSCs through activation of the ATK and PI3K-MAPK signaling pathways. Overall, this study is the first to confirm the therapeutic efficacy of WJ-MSCs and insulin in CMT1A, and their synergistic effect without causing insulin resistance.

Characteristics and Management of Neck and Trochanteric Femur Fractures at a Tertiary Hospital in Indonesia: A Retrospective, Single-Center Study

Background: Although hip fractures are common among the elderly population, there are still limited studies on neck-trochanteric fractures, one of the less common types of hip fractures. This study aims to describe the characteristics of patients and their management in patients with neck trochanteric fractures. Methods: This retrospective cross-sectional study analyzed medical records of patients aged >18 years with trochanteric fractures from a tertiary hospital in Central Java, Indonesia, between January and December 2021. Fracture types were identified and classified using the Garden, Pauwels, and AO/OTA classifications. Demographic data, risk factors, fracture locations, and treatment types were also collected. Statistical analysis was performed using SPSS 21.0 to describe patient characteristics. Results: The total sample was 77 patients, most were female (n = 55 (71.4%)) and aged > 60 years. More than a third of diagnosed fractures were neck of the femur fractures in 33 patients (42.9%). Among the most common classification types of fractures were Garden Type 3, Pauwels Type 3, and AO/OTA type A1.1. A total of 33 patients (42.9%) underwent open reduction of the fracture with internal fixation. Conclusions: Our findings show that the prevalence of neck-trochanteric fractures mostly occurs in patients > 60 years of age and in females. Although open reduction with internal fixation is generally performed, there are several cases of fractures that are not classifiable due to limited imaging examinations. Further research on a wider population is needed to confirm the findings of this study.

A Systematic Review of the Long-Term Outcomes of Surgical Versus Non-surgical Management for Types A3 and A4 Thoracolumbar Spinal Fractures With No Neurological Deficits

A Systematic Review of the Long-Term Outcomes of Surgical Versus Non-surgical Management for Types A3 and A4 Thoracolumbar Spinal Fractures With No Neurological Deficits

Inter-ethnic heterogeneity in valvular morphology and aortopathy of a worldwide bicuspid aortic valve cohort referred for TAVR

Abstract Background Bicuspid aortic valve (BAV) represents one of the most common congenital heart disease. BAV stenosis tipycally occurs in younger, low-surgical risk patients compared to tricuspid aortic valves (TAV). With the predicted expansion of trans-catheter aortic valve replacement (TAVR) into lower-risk patients, the proportion of BAV is expected to rise. Although some observational studies have investigated the characteristics of Asian versus European patients with BAV undergoing TAVR, little is known about the inter-ethnic differences within the large and diverse Asian, African, Russian, and Caucasian population. Purpose To evaluate the inter-ethnic differences of aortic valve morphology, annular size and associated aortopathy, in a worldwide population of patients with severe aortic stenosis referred for TAVR. Methods Cardiovascular multislice computed tomography data of patients with severe aortic valve stenosis referred for TAVR worldwide were obtained from the database of the Meril Life Core Lab. Inter-ethnic and epidemiological differences in terms of valvular phenotype, annular size and aortic morphology were evaluated with particular focus on patients with BAV. Results Among 12,712 patients (59% male), n=3,203 subjects (25%) exhibited a BAV morphology. According to the Siever’s BAV classification, type 1 (71%, n=2,284) was the most prevalent BAV morphology and particularly Type 1a was the most common in almost all population, with 26% exhibiting a type 0 BAV, while only 3% of the patients (n= 92) had a type 2 (Table 1). A significantly higher prevalence of severe calcium score (>1000 mm3) was found in patients with BAV compared with patients exhibiting a TAV morphology (51% vs. 32, p<0.01). Additionally, larger ascending aorta (AA) diameter (AA >40 mm) (BAV: 31% vs TAV 7%, p = 0.04), along with a higher prevalence of horizontal aorta (HA) (BAV: 20% vs TAV: 9%, p<0.01) was found in patients with BAV compared with TAV. As for inter-ethnic characteristics, there was a higher prevalence of BAV in Indian and Asian Pacific populations (respectively 43% and 28%), with the African population exhibiting the lowest prevalence (7%, n= 28, p=0.02) (Table 2). In Indian patients a higher prevalence of BAV was found in an earlier age (61-70 years old) compared to Western countries (p=0.05). Finally, smaller annular size (456±98 mm2 vs 584±99 mm2, p<0.01) and lower coronary ostia height (Asia and India: RCA 14.5±3 mm, LCA 14±2.9mm vs Caucasian and Russian: RCA 16±3.2 mm, LCA 16.9±3.3mm; p<0.01) were found in the Asian and Indian population when compared with Russian, African and Caucasian subjects. Conclusions BAV morphology, aortopathy and annular size resulted widely heterogenous according to the ethnicity and geographical origin of patients referred for TAVR worldwide. These features may lead different therapeutical decision making and outcomes following TAVR in patients with BAV.Table 1Table 2

Risk Factors for Early Implant Failure in Geriatric Intertrochanteric Fractures Treated with Twin Interlocking Derotation and Compression Screw Cephalomedullary Nail (InterTAN).

Intertrochanteric hip fractures in elderly patients are a significant cause of morbidity and mortality, with increasing incidence due to the aging population. Despite advancements in intramedullary nailing (IMN) technology, fixation failure remains a concern. This study aims to evaluate pre-and postoperative radiographic risk factors for varus collapse in geriatric intertrochanteric fractures treated with twin interlocking derotation and compression screw cephalomedullary nail (InterTAN, Smith & Nephew). This retrospective study included patients over 60 years with AO 31A1 and 31A2 intertrochanteric femur fractures treated with InterTAN at a tertiary referral center from August 2012 to August 2017. Patients with high-energy fractures, AO 31A3 fractures, or those requiring open reduction were excluded. Data on demographics, fracture classification, implant sizes, imaging studies, and follow-up were collected. Radiographic assessments included Chang's medial cortical support concept, tip-apex distance (TAD), calcar-referenced TAD (CalTAD), neck-shaft angles (NSA), and screw placement according to Cleveland zones. Varus collapse was defined as a >5° change in NSA within three months postoperatively. Multivariate logistic regression analysis was used to identify risk factors for varus collapse. The study included 136 patients with a mean age of 79.8 years, of whom 38.2% were male. The early postoperative tipapex distance (TAD) averaged 21.9mm, with 30.1% of patients experiencing varus collapse greater than 5°. Positive medial cortical support (PMCS) or neutral position (NP) type reduction was highly protective against varus collapse (p < 0.001), as well as TAD less than 25mm (p < 0.001). Additionally, the placement of screws in the central-central or central-inferior zones provided a protective effect against varus collapse (p = 0.031). Conversely, having an OTA/AO type A2.2 or A2.3 fracture significantly increased the risk of varus collapse (p = 0.030). Other factors, such as CalTAD and the nail width to medullary canal ratio, did not significantly predict varus collapse (p = 0.831 and p = 0.952, respectively). Our findings align with previous studies highlighting TAD and screw placement as critical factors in preventing fixation failure. The protective effect of PMCS or NP reduction and the increased risk associated with OTA/AO type A2.2 and A2.3 fractures are noteworthy. Unlike previous studies, CalTAD was not significantly associated with varus collapse in our cohort. The study underscores the importance of surgical technique and radiographic parameters in optimizing outcomes for elderly patients with intertrochanteric fractures. In elderly patients treated with InterTAN nails, varus collapse is influenced by fracture type, TAD, reduction quality, and screw placement. Ensuring a TAD <25mm, achieving PMCS or NP reduction, and placing screws in central-central or central-inferior zones are crucial for minimizing varus collapse. These findings highlight the importance of meticulous surgical technique and radiographic assessment in managing intertrochanteric fractures in the elderly. hip fractures, intertrochanteric fractures, internal Fixation, geriatrics, cephalomedullary nail.

Single-centre results of a randomised controlled trial comparing the Gamma3 nail and a sliding hip screw to treat AO type 31-A1 and 31-A2 trochanteric fractures.

The primary goal of this randomised controlled trial was to investigate whether there are differences in the outcome between the Gamma3 nail and a sliding hip screw (SHS) regarding quality of life 1 year after surgery. In a controlled randomised trial, we compared the Gamma3 nail (Stryker) and a SHS(Omega, Stryker) in the treatment of 193 patients with pertrochanteric fractures. The follow-up period was 12 months. The outcomes included the surgical duration, health-related quality of life measured with the EQ-5D Index and a Visual Analogue Scale (VAS), the living situation and use of walking aid before trauma and 52 weeks after surgery; the Parker Mobility Score; the Harris Hip Score; and the revision, complication and mortality rates. The Gamma3 group had a significantly shorter surgical duration than the SHS group (p < 0.0001). Implant-related complications were significantly lower in the Gamma3 group (p > 0.05). The revision rate was significantly lower in the Gamma3 group based on intention-to-treat (p = 0.0336) as well as as-treated (p = 0.0302) analyses. Otherwise, we did not find significant difference between the two groups regarding the EQ-5D Index and VAS scores, the Parker Mobility Score, the Harris Hip Score, the mortality rate, the use of walking aids and the living situation. There were no detectable differences between the groups in terms of quality of life and clinical scores 12 months after surgery. The surgical duration and revision rate were superior for the Gamma3 group.

Effect of screw insertion depth into fractured vertebrae in the treatment of thoracolumbar fractures

PurposeThe study’s objective was to assess the effect of the screw insertion depth into fractured vertebrae in treating thoracolumbar fractures.Materials and methodsThis was a retrospective analysis of 92 patients with thoracolumbar fractures from December 2018 to February 2020. Patients had AO type A2, A3 thoracolumbar fractures. The patients were divided into two groups according to the screw insertion depth. The vertebral wedge angle (VWA), Cobb angle (CA), anterior vertebral body height (AVBH), middle vertebral body height (MVBH), visual analog scale (VAS) score, and Oswestry Disability Index (ODI) were compared preoperatively and at one week and 12 months postoperatively. The correlation between Vertebral height loss and potential risk factors, such as sex, age, BMD and BMI was evaluated.ResultsCompared with the preoperative data, the postoperative clinical and radiographic findings were significantly different in both groups, But no significant difference between the two groups at 1 week. At 1 year postoperatively, there was a significant difference in the CA (p < 0.0001), VWA (p = 0.047), AVBH (p < 0.0001), MVBH (p < 0.0001), VAS score (p < 0.0001), and ODI (p < 0.0001) between the two groups, Except for age, bone density and other influencing factors the long screw group had better treatment results than the short screw group.ConclusionA longer screw provides greater grip on the fractured vertebral body and stronger support to the vertebral plate. The optimal screw placement depth exceeds 60% of the vertebral body length on the lateral view.

Botch improves cognitive impairment after cerebral ischemia associated with microglia-induced A1-type astrocyte activation

Vascular cognitive impairment (VCI) is a clinical syndrome that arises from cerebrovascular issues and associated risk factors, resulting in difficulties in at least one area of cognitive function. VCI has emerged as the second most prevalent type of dementia following Alzheimer's disease, yet there is no effective clinical treatment. Botch, an endogenous Notch1 antagonist, demonstrates neuroprotective effects by inhibiting neuroinflammatory responses mediated through the Notch pathway. While its role in stroke-induced neuroinflammation is well-established, its involvement in VCI remains largely unexplored. This study investigates the role and potential mechanisms of Botch in a rat model of cognitive impairment caused by bilateral common carotid artery occlusion (BCCAO). Firstly, we observed that Botch levels were down-regulated in BCCAO rats, which correlated with increased release of inflammatory cytokines and neuronal damage. Microglia in BCCAO rats released interleukin-1α (IL-1α), tumor necrosis factor-α (TNF-α), and complement component 1q (C1q), leading to the activation of neurotoxic C3+ A1 reactive astrocytes. Then, the down-regulation of Botch exacerbated microglia-mediated inflammation, activated C3+ A1 astrocytes, worsened neuronal damage, and led to a decline in cognitive function. Conversely, the re-expression of Botch alleviated C3+ astrocyte activation, inhibited neuronal damage, and improved mental function. In conclusion, Botch plays a crucial role in inhibiting neuroinflammation induced by type A1 reactive astrocytes. It achieves this by blocking the activation of microglia triggered by the Notch pathway. Ultimately, it inhibits neuronal damage to play a neuroprotective role. These findings suggest that Botch may represent a novel potential target for treating VCI.

Approach to the patient with thyroid nodules: considering GLP-1 receptor agonists.

Glucagon-like peptide 1 receptor agonists (GLP1RA) have rapidly changed the landscape of diabetes and obesity treatment. Enthusiasm for their use is tempered with concerns regarding their risk for inducing C-cell tumors based on preclinical studies in rodents. A black-box warning from the United States Food and Drug Administration (USFDA) recommends against using GLP1RA in patients with a personal or family history of medullary thyroid carcinoma (MTC) or multiple endocrine neoplasia syndrome type 2A or 2B (MEN2), providing clear guidance regarding this cohort of patients. However, emerging data also suggest an increased incidence of differentiated thyroid cancer (DTC) in patients treated with these agents. Other studies, though, have not confirmed an association between GLP1RA and DTC. With conflicting results concerning thyroid cancer risk, there is no clear consensus regarding the optimal approach to screening patients prior to initiating the medications and/or evaluating for thyroid cancer during GLP1RA treatment. Within the context of patient cases, this review will summarize the existing data, describe ongoing controversies, and outline future areas for research regarding thyroid cancer risk with GLP1RA use.

Exome Sequencing of Consanguineous Pashtun Families With Familial Epilepsy Reveals Causative and Candidate Variants in TSEN54, MOCS2, and OPHN1.

Next-generation sequencing is advancing in low- and middle-income countries, but accessibility remains limited. In Pakistan, many members of the Pashtun population practice familial marriage and maintain distinct socio-cultural traditions, isolating them from other ethnic groups. As a result, they may harbor genetic variants that could unveil new gene-disease associations. To investigate the genetic basis of epilepsy in the Pashtun community we recently established a collaboration between Bannu University and the University of Tuebingen. Here we report our first results of exome sequencing of four families with presumed monogenetic epilepsy and Mendelian inheritance pattern. In Family #201, we identified distinct disease-causing variants. One had a homozygous pathogenic missense variant in TSEN54 (c.919G > T, p.(Ala307Ser)), linked to Pontocerebellar Hypoplasia Type 2A. The second individual had a homozygous class IV missense variant in MOCS2 (c.226G > A, p.(Gly76Arg)) which is associated with Molybdenum cofactor deficiency. In family EP02, one affected individual carried a heterozygous class III variant in OPHN1 (c.1490G > A, p.(Arg497Gln)), related to syndromic X-linked intellectual disability with epilepsy. Our small study demonstrates the promise of next-generation sequencing in genetic epilepsies among the Pashtun population. Diagnostic next-generation sequencing should be established in Pakistan as soon as possible, and if not feasible, genetic research projects may pioneer this path.

Excitation-contraction coupling inhibitors potentiate the actions of botulinum neurotoxin type A at the neuromuscular junction.

Botulinum neurotoxin type A1 (BoNT/A) is one of the most potent neurotoxins known. At the same time, it is also one of the safest therapeutic agents used for the treatment of several human disorders and in aesthetic medicine. Notwithstanding great effectiveness, strategies to accelerate the onset and prolong BoNT/A action would significantly ameliorate its pharmacological effects with beneficial outcomes for clinical use. Here, we combined BoNT/A with two fast-acting inhibitors of excitation-contraction coupling inhibitors (ECCI), either the μ-conotoxin CnIIIC or dantrolene, and tested the effect of their co-injection on a model of hind-limb paralysis in rodents using behavioural, biochemical, imaging and electrophysiological assays. The BoNT/A-ECCI combinations accelerated the onset of muscle relaxation. Surprisingly, they also potentiated the peak effect and extended the duration of the three BoNT/A commercial preparations OnabotulinumtoxinA, AbobotulinumtoxinA and IncobotulinumtoxinA. ECCI co-injection increased the number of BoNT/A molecules entering motoneuron terminals, which induced a faster and greater cleavage of SNAP-25 during the onset and peak phases, and prolonged the attenuation of nerve-muscle neurotransmission during the recovery phase. We estimate that ECCI co-injection yields a threefold potentiation in BoNT/A pharmacological activity. Overall, our results show that the pharmacological activity of BoNT/A can be combined and synergized with other bioactive molecules and uncover a novel strategy to enhance the neuromuscular effects of BoNT/A without altering the neurotoxin moiety or intrinsic activity, thus maintaining its exceptional safety profile.

ANALYSIS OF THE EFFECTIVENESS OF INDIRECT SPINAL CANAL DECOMPRESSION IN THE TREATMENT OF BURST FRACTURES AT THE THORACOLUMBAR JUNCTION

Indirect decompression of the spinal canal through ligamentotaxis is one of the methods for remodeling the spinal canal in traumatic stenosis. Objective: To evaluate the effectiveness of indirect decompression of the spinal canal for different morphological types of burst fractures of vertebral bodies at the thoracolumbar junction. Methods. A preoperative and postoperative analysis of computed tomography scans was performed on 59 patients who were treated at the«Romodanov Neurosurgery Institute, National Academy of Medical Sciences of Ukraine» for burst fractures at the thoracolumbar junction. The criterion for the effectiveness of indirect decompression was the area of the spinal canal, measured at the level of injury in the zone of maximum compression. The grading of burst fractures was performed using the classification by F. Magerl et al. (1994). Results. In the preoperative period, the median degree of stenosis in the group of patients was 43.47 % (95 % confidence interval (CI): 37.53–46.22 %). For damage type A3.1, it was 36.9 % (95 % CI: 28.1‒40.5 %), for type A3.2 — 46.1 % (95 % CI: 32.1‒54.5 %), and for type A3.3 — 47.6 % (95 % CI: 37.5‒56.5 %). After surgical treatment, the degree of stenosis decreased by 20.14 % (95 % CI: 15.93‒21.56 %). For type A3.1, the effectiveness was 20.1 % (95 % CI: 9.5‒22.7 %), for type A3.2 — 15.2 % (95 % CI: 7.51‒17.3 %), and for type A3.3 — 21.7 % (95 % CI: 20.8‒26.4 %). The difference between types A3.2 and A3.3 was statistically significant (p = 0.0018). It was found that indirect decompression is most effective with higher degrees of stenosis. For Grade I by D. Wolter (1988), the canalexpansion achieved was 7.07 % (95 % CI: 5.69‒8.65 %), for Grade II — 21.6 % (95 % CI: 20.4‒22.7 %), and for Grade III — 30.3 % (95 % CI: 27.0‒33.6 %). Conclusions. Closed remodeling of the spinal canal with transpedicular fixation and the effect of ligamentotaxis is an effective method for correcting traumatic spinal canal stenosis at the thoracolumbar junction. The effectiveness of the technique is determined by many factors, including the type of burst fracture, the initial degree of stenosis, and the level of injury.

Subtyping of pancreatic neuroendocrine tumors by transcription factors, hormones, histology, and patient outcome.

Pancreatic neuroendocrine tumors (PanNETs) show pronounced heterogeneity in terms of hormone and transcription factor (TF) expression. TFs such as ARX and PDX1 are related to alpha- and beta-cell-type features, respectively, and partly associate with patient outcome. However, detailed studies correlating hormone expression, histology, and clinical data are lacking. The aim of this study was to identify subtypes of PanNETs that associate with histological, hormonal, and prognostic findings. Atotal of 185resected PanNETs were divided into five subtypes (types A1, A2, B, C, and D) by cluster analysis based on expression of four TFs (ARX, PDX1, ISL1, and CDX2) and correlated to the expression of hormones and DAXX/ATRX as well as ALT activation status, histology, and progression-free survival. Subgroup A1 (ISL1+/ARX+/PDX-/CDX2-) was most frequent (46%), followed by typeB (18%; ISL1+/ARX-/PDX+/CDX2-), A2 (15%; ISL1+/ARX+/PDX+/CDX2-), C(15%; ISL1-/ARX-/PDX-/CDX2-), and D(5%; ISL1-/ARX-/PDX+/CDX2+). Subgroups A1 and A2 showed astrong association with atrabecular growth pattern and glucagon and pancreatic polypeptide (PP) expression (p < 0.001), while A2 was in addition associated with gastrin expression. SubgroupB was associated with insulin production (p < 0.001) and included all 17insulinomas. SubgroupC was associated with solid morphology and expression of serotonin, calcitonin, and adrenocorticotropic hormone (ACTH). SubgroupD showed solid morphology, expression of ACTH, somatostatin, or serotonin and had the shortest disease-free survival (p < 0.01). ALT positivity was associated with poorer outcome in types A1 and A2 but not in other types. PanNETs can be categorized into five subgroups based on different TF signatures, which associate strongly with histology, hormone production, functionality, and patient outcome.

Structural Study on Alkali‐Carboxylate Functionalized Late‐Transition Metal Bis(dithiocarbamate) Complexes

AbstractLithium, sodium, and potassium derivatives of amino‐acid derived bis(dithiocarbamate) complexes of bivalent nickel, palladium, platinum, and copper are readily available by treatment of the carboxylic‐acid functionalized complexes with the respective alkali metal hydroxide. Representative derivatives of the types A4[M(L1)2], A2[M(HL1)2], A[M(HL1)(H2L1)] (N‐dithioato‐iminodiacetate, L1), and A2[M(L2,3)2] (N‐dithioato‐l‐prolinate, L2, and ‐N‐benzylglycinate, L3; A=Li, Na, K; M=Ni, Pd, Pt, Cu) were isolated and characterized by spectroscopic and thermal methods. Six entries were accessible to single‐crystal X‐ray structure determination, revealing the presence of different coordination‐polymeric structures and hydrogen‐bonded assemblies comprising solvent‐separated cations in the solid state. While the transition metal always retains its all‐sulfur coordination with defined geometry, the alkali metals are structurally more flexible. The latter are usually coordinated by carboxylate and water, but additional interactions with sulfur donors are also relevant in some cases.

6874 A Rare Case Of Hereditary 1,25 (OH)2D Resistant Rickets

Abstract Disclosure: G. Umarji: None. F. Thelmo: None. S.A. Jabbour: None. Vitamin D-dependent rickets type 2A (VDDR2A) also known as hereditary 1,25 (OH)2D resistant rickets is due to biallelic loss-of-function mutations in the gene encoding vitamin D receptor on chromosome 12q13.11, thus, it represents a true form of tissue resistance to vitamin D. It is a scarce form of rickets with approximately only 120 cases reported. A 37-year-old male was referred to endocrinology by neurosurgery for evaluation of metabolic bone disease. Seven years ago, he was in a car accident which resulted in a lumbar spine injury causing radiculopathy and severe low back pain leading to lumbar spine decompression/fusion. However, he suffered from nonunion of bones and had to undergo another surgery a year later with recurrent postoperative nonunion of bones. During the operation, the surgeon noticed that his spine seemed demineralized. He had a history of multiple minor fractures in childhood, decreased hearing in left ear for two years, fragile teeth for many years, and some hair loss since age 30. Physical exam showed a height of 1.82 m, weight 89.3 kg with body mass index of 26 kg/m2, broken teeth, no leg bowing and normal stance. Laboratory results showed normal renal function, thyroid function tests and testosterone level, corrected calcium 8.3 mg/dL (8.7-10.2), 25-OH-vitamin D 54 ng/mL (30-100), phosphorus 2.8 mg/dL (2.8-4.1), intact parathyroid hormone 65 pg/mL (15-65), bone-specific alkaline phosphatase 21 mcg/L (4-27), 24-hour urine calcium 156 mg/day (100-300), 24-hour urine phosphorus 1,752 mg/day (390-1,425), FGF-23: 93 RU/mL (44-215) and 1,25 (OH)2D 92 pg/mL (24-81.5). Dual absorptiometry of the lumbar spine and hip showed osteopenia with Z scores of -2.2 and -1.2 respectively. Genetic testing for metabolic bone disease panel showed heterozygous mutation in VDR gene at nucleotide position c.146+9dup associated with autosomal recessive VDDR2A. We present a very rare form of vitamin D resistant rickets. As many patients with VDDR2A are unable to respond to any form of vitamin D, it is suggested that VDDR2 be more appropriately described as hereditary 1,25 (OH)2D resistant rickets (HVDRR), hereditary resistance to 1,25 (OH)2D, or even pseudovitamin D-deficiency type IIA (PDDR IIA). Clinical features include severe rickets, bone pain, hypotonia, dental caries and alopecia. Biochemical features include hypocalcemia, hypophosphatemia, normal to elevated alkaline phosphatase, normal 25(OH)D and importantly, elevated 1,25-(OH)2D levels. Management is with high doses of calcium and vitamin D therapy. While rare, this disease highlights the need for a comprehensive evaluation of metabolic bone diseases and a thorough understanding of calcium and vitamin D metabolism. Presentation: 6/2/2024

7109 "My Stomach hurts": A Rare Case of Adrenal Cortical Carcinoma

Abstract Disclosure: R.C. Attah: None. I. Sirisena: None. Pheochromocytoma/Paragangliomas are rare neurogenic tumors that arise from chromaffin cells present in the adrenal medulla or extra-adrenal paraganglia, these cells produce catecholamines. Typically, these tumors are discovered as incidentalomas. They can be hereditary as seen in genetic syndromes like multiple endocrine neoplasia type 2A or 2B, neurofibromatosis type 1 or Von Hippel Lindau syndrome but can occur sporadically. Patients typically present with hormonal hypersecretion signs or symptoms like abdominal pain, episodic headaches, sweating, hypertension and tachycardia, but some patients are asymptomatic. Patient is a 37-year-old female with past medical history of hypertension, type 2 diabetes mellitus and fatty liver who presented to the ED with abdominal pain for a few weeks. On arrival, her vitals were BP 205/124, HR 102, RR 14 and SpO2 100% on room air. CT abdomen was obtained which showed a 7.6 x 4.7 x 5.7 cm mass replacing left adrenal gland with small left retroperitoneal hemorrhage worrisome for adrenal cortical carcinoma, metastatic disease or pheochromocytoma. Hormonal workup revealed elevated 24-hr urine cortisol 124.2mcg (ref 4.0-50.0mcg/24h), normal aldosterone/renin ratio 10.63ng/dL (ref &amp;lt;30ng/dl), failed low dose dexamethasone suppression test with post-dex AM cortisol 7.20ug/dL (ref &amp;lt;1.8ug/dL), slightly elevated serum total catecholamine 1256pg/mL (242-1125 pg/mL), norepinephrine 1155pg/mL (ref 217-1109 pg/mL), total metanephrine and normetanephrine 341pg/mL (reg &amp;lt;205 pg/mL), normetanephrine 244.1 (ref &amp;lt;210.1pg/mL), elevated 24-hr urine normetanephrine 700ug/L (ref 131-612ug/L), metanephrine 136ug/L (ref 36-209ug/L) and DHEA-s level 285ug/dl (ref 23-266ug/dL). Due to elevation in cortisol, adrenal cortical carcinoma was suspected as these tumors are frequently associated with cortisol secretion. However, pheochromocytoma with co-secretion of ACTH could not be excluded. She was started on doxazosin for alpha blockade and eventually started on beta blockade with Metoprolol. She underwent a left adrenalectomy and was started on steroid taper post-op due to concern of cortisol co-secretion. Surgical pathology was positive for Left adrenal malignant pheochromocytoma and ganglioneuroma. Genetic panel was negative with no mutation identified in the 54 gene Hereditary paraganglioma-pheochromocytoma panel. This patient had a large adrenal tumor (&amp;gt;4cm mass) but mildly elevated catecholamines which could have led to misdiagnosis as her catecholamine levels were less than 2-3x ULN which is unusual for pheochromocytomas. Roughly 25% of people with pheochromocytoma are undiagnosed throughout their lifespan. This condition can be life-threatening, hence early diagnosis and intervention can be lifesaving. Prognosis of malignant pheochromocytoma is dependent on tumor size, presence of SDHB gene mutation or visceral metastases. Presentation: 6/1/2024