From Lab Bench to Hope: Emerging Gene Therapies in Clinical Trials for Alzheimer's Disease.

Alzheimer's disease is a progressive neurodegenerative disorder that affects memory and cognitive abilities, affecting millions of people around the world. Current treatments focus on the management of symptoms, as no effective therapy has been approved to modify the underlying disease process. Gene therapy is a promising approach that can offer disease-modifying treatment for AD, targeting various aspects of the pathophysiology of the disease. This review presents a comprehensive overview of the current state of gene therapy research for AD, with a specific focus on clinical trials and preclinical studies that have used nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), apolipoprotein E2 (APOE2), and human telomerase reverse transcriptase (hTERT) as therapeutic gene therapy approaches. These gene targets have shown potential to alleviate the neuropathology of AD in animal studies and have demonstrated feasibility and safety in non-human primates. Despite the failure of the NGF gene therapy approach in clinical trials, we have reviewed and highlighted the reported findings and evaluations from the trials. Furthermore, the review included the conclusions of postmortem brain tissue analysis of AD patients who received NGF gene therapy. The goal is to learn from the failed trials and improve the approach in the future. Although gene therapy shows promise, it faces several challenges and limitations, including optimizing gene delivery methods, enhancing safety and efficacy profiles, and determining long-term results. This review contributes to the growing body of literature on innovative treatments for AD and highlights the need for more research and development to advance gene therapy as a viable treatment option for AD.

Unexpected Airway Collapse: A Rare Case of Spontaneous Postoperative Tracheobronchomalacia in the Absence of Identifiable Risk Factors.

We report the case of a 53-year-old female who developed tracheobronchomalacia immediately following an uncomplicated robotic hysterectomy with bilateral salpingo-oophorectomy to treat postmenopausal bleeding. Induction of anesthesia was notable for moderately difficult intubation, managed with applied cricothyroid pressure and a small 6.5 endotracheal tube placement via GlideScope. The surgical course was uneventful. The patient remained intubated in the post-anesthesia care unit but was not providing end-tidal volumes. Attempts to replace the endotracheal tube with a larger tube were unsuccessful and the patient was temporarily unable to ventilate. Rapid troubleshooting discovered that a laryngeal mask airway (LMA) could sufficiently ventilate the patient. An otolaryngologist was able to perform direct bronchoscopy, which revealed more than 50% dynamic anterior-posterior collapse of the trachea and bronchi. The patient was subsequently awakened from anesthesia and monitored in the intensive care unit, ventilating with an LMA. After a couple of hours, it was determined that the patient's airway was protected, and the LMA was removed.

Basivertebral nerve ablation with concurrent lumbar laminotomy.

Lumbar radiculopathy due to impingement of nerve roots from facet hypertrophy and/or disc herniation can often coincide with vertebrogenic low back pain. This is demonstrated on MRI with foraminal stenosis and Modic changes. We examine the potential of using a combination of basivertebral nerve ablation (BVNA) and lumbar laminotomy as an alternative to traditional spinal fusion in specific patient populations. This unique combination of surgical techniques has not been previously reported in the medical literature. We report a man in his late 30s with chronic low back pain and lumbar radiculopathy, treated with BVNA and concurrent laminotomy. The patient reported progressive improvements in his mobility and pain over the next 2 years. We discuss the advantages of using this technique for lumbar radiculopathy and Modic changes compared with conventional surgical modalities.

Benign Acute Childhood Myositis in a Pediatric Patient Post Influenza B Infection.

Benign acute childhood myositis (BACM) is a mild and self-limited sudden onset of lower extremity pain during or following recovery from a viral illness. It is characterized by difficulty walking due to severe bilateral calf pain, which usually resolves in three days. It is typically appreciated during times of large influenza outbreaks and epidemics. The most severe complication can be rhabdomyolysis without proper treatment and can lead to renal damage and potential renal failure. There are limited reported cases of BACM and therefore no clear guidelines in the treatment or management of the condition. This case is unique in the sense that the patient had leg pain the entire month prior to presentation in the absence of trauma or injury, and it is believed that the pre-existing myalgia may have been exacerbated by an upper respiratory infection (URI) that started a few weeks after the leg pain onset. In addition, this patient's creatine kinase peaked at over 13,000 U/L, which is three to five times higher than the average of other reported children with this condition. The patient is a five-year-old male who presented to the emergency department with bilateral leg pain and difficulty ambulating. His guardian reported that the leg pain began one month prior to presentation and worsened to the point where he could no longer ambulate, following a fever and cough that began one week prior to presentation. A respiratory viral panel was positive for influenza B, and initial creatine kinase (CK) levels were greater than 10,000. A diagnosis of BACM was made, and supportive care was initiated. BACM is an infrequent complication following a viral infection that is typically treatable with hydration management and routine CK monitoring. Symptoms of BACM are usually limited to muscle pain and weakness, but it can progress to rhabdomyolysis and renal failure if not managed properly. It is therefore crucial that physicians monitor CK values daily until a downtrend is noticed and symptoms begin to resolve.

Minimally Invasive Procedures, Perioperative Telemedicine, and Decreased Hospital Stays Following Covid-19 Surgical Restrictions: Spinal Surgery.

The 2019 severe acute respiratory syndrome coronavirus 2 pandemic had devastating impacts on healthcare system operations. Disruption of this delicate system led to international healthcare challenges with new policy changes that affected all specialties, including the global spine surgery community. The pandemic disrupted normal spine surgery proceedings, restricting, and postponing elective procedures, which comprise a large proportion of spine surgeries. This disruption may have contributed to significant economic losses for providers and resulted in the prolonged impairment of patients who were forced to postpone their procedures. However, response to the pandemic precipitated new procedural guidelines and practices that prioritize health outcomes and satisfaction. These new changes and innovations are positioned to provide lasting economic and procedural impacts in favor of both providers and patients. Thus, the objective of our review is to explore how spinal surgical practices and post-op recovery changed following COVID-19 and highlight some lasting impacts the pandemic created for future patients.