Attenuated initial serum ferritin concentration in critically ill coronavirus disease 2019 geriatric patients with comorbid psychiatric conditions.

We examined the effects of psychiatric comorbidity, sex, and ICU admission on serum ferritin concentration in 628 elderly patients (79.7 ± 8.5 years) with positive SARS-CoV-2 PCR test. Hospitalization was required in 96% of patients and 17% required ICU admission. Patients with COVID-19 and psychiatric comorbidities (n = 212) compared to patients without psychiatric comorbidities (n = 416) had significantly lower ferritin concentration (570.4 ± 900.1 vs. 744.1 ± 965, P = 0.029), a greater incidence of delirium (22.6 vs. 14.4%, P = 0.013) and higher mortality (35.3 vs. 27.6%, P = 0.015). Furthermore, we found significant effects for sex (P = 0.002) and ICU admission (P = 0.007). Among patients without comorbid psychiatric conditions, males had significantly higher ferritin compared to females (1,098.3 ± 78.4 vs. 651.5 ± 94.4, P < 0.001). ICU patients without comorbid psychiatric conditions had significantly higher serum ferritin compared to ICU patients with comorbid psychiatric conditions: (1,126.6 ± 110.7 vs. 668.6 ± 156.5, P < 0.001). Our results suggest that the presence of comorbid psychiatric conditions in elderly patients with COVID-19 is associated with higher rates of delirium and mortality and lower ferritin levels during severe illness. Whether high serum ferritin is protective during severe infection requires further investigation.

Bioengineered optogenetic model of human neuromuscular junction.

Functional human tissues engineered from patient-specific induced pluripotent stem cells (hiPSCs) hold great promise for investigating the progression, mechanisms, and treatment of musculoskeletal diseases in a controlled and systematic manner. For example, bioengineered models of innervated human skeletal muscle could be used to identify novel therapeutic targets and treatments for patients with complex central and peripheral nervous system disorders. There is a need to develop standardized and objective quantitative methods for engineering and using these complex tissues, in order increase their robustness, reproducibility, and predictiveness across users. Here we describe a standardized method for engineering an isogenic, patient specific human neuromuscular junction (NMJ) that allows for automated quantification of NMJ function to diagnose disease using a small sample of blood serum and evaluate new therapeutic modalities. By combining tissue engineering, optogenetics, microfabrication, optoelectronics and video processing, we created a novel platform for the precise investigation of the development and degeneration of human NMJ. We demonstrate the utility of this platform for the detection and diagnosis of myasthenia gravis, an antibody-mediated autoimmune disease that disrupts the NMJ function.

In vitro models of neuromuscular junctions and their potential for novel drug discovery and development.

Introduction: Neuromuscular Junctions (NMJs) are the synapses between motor neurons and skeletal muscle fibers, and they are responsible for voluntary motor function. NMJs are affected at early stages of numerous neurodegenerative and neuroimmunological diseases. Due to the difficulty of systematically studying and manipulating NMJs in live subjects, in vitro systems with human tissue models would provide a powerful complement to simple cell cultures and animal models for mechanistic and drug development studies.Areas covered: The authors review the latest advances in in vitro models of NMJs, from traditional cell co-culture systems to novel tissue culture approaches, with focus on disease modeling and drug testing.Expert opinion: In recent years, more sophisticated in vitro models of human NMJs have been established. The combination of human stem cell technology with advanced tissue culture systems has resulted in systems that better recapitulate the human NMJ structure and function, and thereby allow for high-throughput quantitative functional measurements under both healthy and diseased conditions. Although they still have limitations, these advanced systems are increasingly demonstrating their utility for evaluating new therapies for motoneuron and autoimmune neuromuscular diseases, and we expect them to become an integral part of the drug discovery process in the near future.

Minimal Invasive Fixation Can Decrease Infection Rates in Diabetic and Obese Patients With Severe Ankle Fracture and Syndesmotic Injury.

BACKGROUND: Ankle fractures involving syndesmosis disruption cause severely unstable joint conditions. Traditional invasive operations put certain patient groups at an increased risk of infection. There is limited literature discussing the outcomes of minimally invasive fixation of severe ankle fractures including syndesmotic injury, as clinicians may be tempted to treat these difficult cases with open reduction internal fixation (ORIF). METHODS: A retrospective case-control study was conducted on patients treated at a level one trauma center. Patients were divided into 2 groups based on presence of diabetes and/or obesity (body mass index ≥30.0 kg/m2). Those with either comorbidity were defined as high infection risk patients and placed in a comorbidity group. Patients were further divided into subgroups based on the operation's invasiveness; either traditional ORIF or percutaneous cannulated screw fixation. RESULTS: Comorbid patients (N = 67) were more likely to sustain Weber C fractures compared to noncomorbid patients (N = 43) (59.70% to 37.21%, P = .019). Additionally, patients receiving minimally invasive fixation procedures experienced fewer infections than those receiving ORIF (0 vs 11 incidences, P = .01), without effect on union rates, fracture reduction, pain, need for revision surgery, or time to full weightbearing. CONCLUSIONS: Diabetic and obese patients are at an increased risk of experiencing severe ankle fractures. The use of minimally invasive fixation methods can reduce the risk of postoperative infection without sacrificing other surgical outcomes, even with fractures involving syndesmotic injury. LEVELS OF EVIDENCE: Therapeutic, Level III: Retrospective comparative study.