Providence Hospital

Neurodegenerative diseases, including multiple sclerosis, amyotrophic lateral sclerosis, Huntington's disease, retinal degenerative diseases, Alzheimer's disease, and Parkinson's disease, continue to pose a significant clinical challenge due to the progressive loss of neural tissue structure and function. Stem cell-based therapies are gaining attention for the treatment of neurodegenerative diseases. Mesenchymal stem cells, particularly those derived from perinatal tissues, exhibit remarkable plasticity, along with immunomodulatory, neurotrophic, and regenerative capabilities. Mesenchymal stem cells primarily influence their environment through paracrine signaling and can also differentiate into neural lineages, aiding in neuronal repair. Tissue-specific progenitor cells, such as neural stem cells and retinal progenitor cells, offer greater therapeutic precision. This review examines advancements in mesenchymal stem cell-based therapies for neurodegenerative diseases, discusses relevant clinical trials, and highlights the challenges, while proposing that personalized regenerative treatments utilizing lineage-restricted progenitors may improve patient outcomes in these complex disorders.

The VDA 238-100 tight radius bend test has gained widespread acceptance for plane strain fracture characterization of sheet metals in proportional loading without necking. The VDA test features a 60 × 60 mm2 square blank with a 0.2 mm or 0.4 mm radius punch to provide plane strain bending where the fracture limit of the material is lowest. However, the through-thickness gradients that suppress necking and promote fracture on the convex surface in tension can be exploited to efficiently characterize the fracture strain from uniaxial to plane strain tension by varying the sample width. In this study, V-bend tests were conducted for various sample widths for four advanced high-strength steels: 980GEN3, DP1180, MP800-V1, and MP800-V2 with the local fracture strains measured using digital image correlation. Reducing the width-to-thickness ratio below five altered the stress state at the failure location, with an aspect ratio of one providing edge fractures under uniaxial tension. This aspect ratio was then applied to 980GEN3 and MP800 steel samples with punched edges as it provides an efficient method for sheared edge fracture characterization that is not susceptible to necking as with common sheared edge tensile tests. To mitigate strain averaging inherent in DIC near surfaces, a geometric-based arc length methodology was proposed. The sheared edge fracture limits from the V-bend tests were then compared with the results from conical hole expansion and in-plane bend tests. The sheared edge formability was observed to have a material-dependent sensitivity to the test method. MP800-V2, with centerline segregation, exhibited a pronounced sensitivity to the applied deformation mode with absolute differences in fracture strains of 0.13 while the MP800-V1 and 980GEN3 did not.

Background: Traumatic brain injury (TBI) imposes a substantial public health burden through long-term physical, cognitive, and psychiatric effects. This includes substance use disorders (SUDs) for which TBI is a demonstrated risk factor; however, prior studies have not comprehensively compared relative incidences of SUD subtypes post-TBI or differences between intracranial hemorrhage (ICH) and non-ICH TBI in patients without prior SUD history. This global retrospective analysis using the TriNetX database aims to quantify new-onset SUD incidence post-TBI in the largest cohort of patients evaluated to date, with cohorts stratified by SUD subtype and ICH versus non-ICH TBI, to highlight opportunities for post-injury care models to mitigate SUD risk. Methods: De-identified data from the TriNetX Research Network were used to select patients with TBI (n = 1,889,112) and define distinct cohorts based upon the presence (n = 420,868) or absence (n = 1,471,592) of ICH. Patients with previously diagnosed SUD before the date of TBI were excluded. Patient demographics and medical comorbidities were calculated for each group. The incidence of new SUD diagnosis over the lifetime and at 1-, 3-, and 5-years post-TBI were calculated and compared. Subtypes of SUD were defined and calculated based on the specific substance used. Propensity scores were calculated to create balanced matched ICH and non-ICH cohorts (n = 331,812 each) were used for comparisons of 5-year SUD incidence. Results: In the full TBI cohort, 5-year new SUD incidence was 4.2% overall, with nicotine (2.4%) and alcohol (1.1%) predominating, followed by cannabis (0.9%) and opioids (0.4%). Rates of SUDs increased over time, but attenuated beyond 5 years, with approximately 50% of those who would ultimately be diagnosed with SUD manifesting (lifetime) by 3 years post-TBI. After propensity matching, non-ICH TBI showed higher 5-year risk for any SUD (4.2% vs. 3.6%; risk difference −0.65%, p < 0.0001) and all subtypes (p < 0.05) except inhalants (p = 0.53). Conclusions: This largest-to-date analysis of new-onset SUD post-TBI demonstrates significantly higher rates of SUD in TBI patients; rates of nicotine, alcohol, cannabis, and opioid use disorders were most common. Non-ICH TBI patients demonstrated greater rates of SUD after injury than patients with ICH-associated TBI. Of patients suffering from TBI without ICH who would eventually be diagnosed with SUD, approximately 50% had obtained that diagnosis within 3 years of the injury. Taken together, these findings demonstrate the clinical need for routine SUD screening in post-TBI care, especially for 3 years post-injury. Such an intervention has the potential to significantly alleviate the public health burden and associated cost of care for TBI-associated substance use disorder patients.

The role of coronary computed tomography angiography (CCTA) in diagnostic cardiology is steadily increasing. Normal CCTAs successfully reclassify patients to a low-to-intermediate risk category with marked reduction in cardiovascular events. However, hepatic steatosis has been associated with adverse cardiovascular events and can be routinely evaluated on non-contrast CCTAs. The prevalence of hepatic steatosis in the setting of normal CCTAs is not known and may be of clinical significance. We conducted a retrospective, single-center analysis to evaluate for the presence and incidence of hepatic steatosis in the setting of normal CCTAs. Non-contrast images were used to identify/measure the presence or absence of hepatic steatosis. The presence of hepatic steatosis was defined based on attenuation measurements in Hounsfield units (HU), by comparing the liver and spleen. Of 297 patients screened, a cohort of 99 patients were identified with a coronary calcium score of zero. Ten patients (10%) were found to have non-calcified plaque on CCTAand were excluded from the study population. Of the remaining 89 patients, 13 patients (14%) were found to have evidence of hepatic steatosis. Patients with normal CCTAs are often reassured, supported by data predicting an improved prognosis with low rates of cardiovascular events. Wepropose that evaluating and identifying patients with underlying hepatic steatosis, a known associated marker of atherosclerosis, even in patients with "normal"CCTAs is important, as this correlates with higher cardiovascular risk.

A 78-year-old man with type 2 diabetes and spinal stenosis complicated by chronic neuropathy suffered an open medial malleolus fracture with proximal tendon rupture after fall from height. Fracture fixation was achieved with cannulated screws. Meticulous repair of the proximal tibialis posterior and flexor digitorum longus tendon avulsions required tunneling into the deep posterior compartment. Postoperatively, the patient was non-weight bearing, responsive to therapy, and discharged home. This unique case illustrates the importance of maintaining a high index of suspicion for tendinous injury. A careful physical examination, understanding of injury mechanisms, and a high index of suspicion for these associated injuries should be maintained to maximize patient outcomes.

Total knee arthroplasty is one of the most common and successful orthopedic surgeries for the treatment of osteoarthritis. While infection is a common postoperative complication, periprosthetic joint infection is a rarer type of infection requiring aggressive treatment. This case report reviews the clinical course of a 71-year-old female with a history of recurrent prosthetic joint infections and osteomyelitis of the left knee and femur following a left total knee arthroplasty. Ten years after the index procedure, she developed a soft tissue ulcer and non-healing wound that led to exposure of her knee joint hardware at the level of the skin. Due to her complicated medical history, it was decided she would undergo an above-knee amputation. This report discusses a unique patient history of recurrent periprosthetic joint infections requiring extensive surgical and medical management, ultimately leading to an above-knee amputation. It also highlights the importance of a multidisciplinary team in the setting of complex patient care.