LentiGlobin Administration to Sickle Cell Disease Patients: Effect on Serum Markers and Vaso-Occlusive Crisis.

LentiGlobin, an innovative gene therapy, introduces a modified beta-globin gene that yields an anti-sickling hemoglobin variant. It boosts total hemoglobin levels, mitigates hemolysis, curtails inflammation, and addresses iron overload by reducing transfusion requirements. These changes, in turn, provide insights into disease mechanisms and treatment outcomes. Alterations in serum markers, such as hemoglobin levels and inflammatory biomarkers, can illuminate the therapeutic effectiveness of LentiGlobin and its impact on mitigating complications such as vaso-occlusive crises. Therefore, the purpose of this narrative review is to discuss the effects of LentiGlobin administration on diverse serum biomarkers and its correlation with vaso-occlusive crises in individuals with sickle cell disease (SCD).

Anchoring on Hyperglycemia and Sepsis in the Presence of an Unforeseen Thyroid Storm.

Thyroid storm (TS) is a relatively rare but life-threatening complication of an overactive thyroid that can manifest in a myriad of ways due to its multisystem involvement. Due to its relatively high mortality rate, it is essential that TS is recognized and treated promptly. TS can occur due to trauma, drugs, and sepsis. Identifying TS as a diagnosis is challenging to pinpoint due to its similar presentation to more common pathologies like sepsis and diabetic ketoacidosis (DKA). Here, we present a case of a 31-year-old African-American woman with type 2 diabetes mellitus following sepsis secondary to Escherichia coli pyelonephritis and DKA. Despite standard sepsis treatment, which included appropriate intravenous fluids and antibiotics, the patient did not improve. Further workup, utilizing the Burch-Wartofsky score, helped identify TS as the underlying cause of the patient's hospitalization, despite no history of underlying thyroid disease. The inclusion of thyroid pathology as part of the differential diagnosis and workup of a patient with a sepsis-like presentation to avoid anchoring bias warrants further investigation.

Severe COVID-19 Infection in an Infant With 8p Inverted Duplication/Deletion Syndrome: Is Vaccination Still a Debate?

Despite having a milder course of coronavirus disease 2019 (COVID-19) in comparison to adults, children are at risk for more significant complications, including acute neurological, renal, respiratory, and cardiovascular complications. Acute complications can manifest as encephalopathy, renal injury, interstitial pneumonia, and heart failure. However, the most severe complication is multisystem inflammatory syndrome in children, which often requires intensive care to manage the subsequent respiratory failure. Moreover, children with comorbidities such as chronic lung disease, neurological disorders, and cardiovascular disease are at an elevated risk of morbidity and mortality. Here, we present the case of an 11-month-old white female patient, previously unvaccinated against COVID-19, with chronic lung disease and the 8p inverted duplication/deletion (Inv dup del (8p)) syndrome who suffered from a severe COVID-19 infection. Initially presenting to the pediatric clinic with nasal congestion and respiratory distress, the patient's condition rapidly deteriorated which necessitated immediate transfer to the nearest pediatric tertiary center. There, she was mechanically ventilated, received dexamethasone and remdesivir, and was hospitalized for 26 days, nine of which were in the pediatric intensive care unit. To date, there is no current literature on Inv dup del (8p) syndrome as a predisposing factor for severe COVID-19 infection. Therefore, further investigation is needed to determine if Inv dup del (8p) can predispose a patient to having a severe COVID-19 course.

Anticoagulation Options for Cranial Procedures: A Comparative Review of Aspirin, Plavix, and Aggrastat.

Anticoagulation therapy is critical to avoiding thrombotic events in patients following cranial surgery. Although Aspirin, Plavix, and Aggrastat are used as anticoagulants for this purpose, there is no consensus on which agent is the most effective and safe. In this comparative study, we analyze the current evidence on the efficacy and safety of these three anticoagulants in the context of cranial surgeries. This review focuses on the advantages and disadvantages of each anticoagulant, such as its pharmacokinetics, indications, contraindications, and possible consequences. The outcomes of this study will help physicians choose the best anticoagulant for their patients based on individual patient characteristics and the kind of cranial procedure. Aggrastat's potential to be included as a recommended anticoagulant for cranial procedures warrants further study.

Recent Advancements in Epidural Etanercept for Pain Management in Radiculopathy: A Literature Review.

The most common etiology of low back and neck pain is associated with spinal cord pathologies. Regardless of origin, low back and neck pain are some of the most common causes of disability worldwide. Mechanical compression due to spinal cord diseases, such as degenerative disc disorders, can lead to radiculopathy, which manifests as numbness or tingling and can progress to loss of muscle function. Conservative management, such as physical therapy, has not been proven effective in treating radiculopathy, and surgical treatments have more risks than benefits for most patients. Epidural disease-modifying medications, such as Etanercept, have been recently explored due to their minimal invasiveness and direct effects on inhibiting tumor necrosis factor-α (TNF-α). Therefore, this literature review aims to evaluate epidural Etanercept's effect on radiculopathy caused by degenerative disc diseases. Epidural Etanercept has been shown to improve radiculopathy in patients with lumbar disc degeneration, spinal stenosis, and sciatica. Further research is needed to compare the effectiveness of Etanercept with commonly used treatments such as steroids and analgesia.

The Potential Role of Etanercept in the Management of Post-stroke Pain: A Literature Review.

Strokes are the second leading cause of death and disability worldwide. The brain injury resulting from stroke produces a persistent neuroinflammatory response in the brain, resulting in a spectrum of neurologic dysfunction affecting stroke survivors chronically, also known as post-stroke pain. Excess production of tumor necrosis factor alpha (TNF alpha) in the cerebrospinal fluid (CSF) of stroke survivors has been implicated in post-stroke pain. Therefore, this literature review aims to assess and review the role of perispinal etanercept in the management of post-stroke pain. Several studies have shown statistically significant evidence that etanercept, a TNF alpha inhibitor, can reduce symptoms present in post-stroke syndrome by targeting the excess TNF alpha produced in the CSF. Studies have also shown improvements in not only post-stroke pain but also in traumatic brain injury and dementia. Further research is needed to explore the effects of TNF alpha on stroke prognosis and determine the optimal frequency and duration of etanercept treatment for post-stroke pain.

A Scoping Review of the Impact of COVID-19 on Kidney Transplant Patients in the United States.

SARS-CoV-2, responsible for the COVID-19 pandemic, is a highly infectious virus that quickly became and continues to be a public health emergency, given the severe international implications. Immunocompromised patients, such as those undergoing kidney transplantation, are at an increased risk for severe illness from COVID-19 and require hospitalization for more aggressive treatment to ensure survival. COVID-19 has been infecting kidney transplant recipients (KTRs), affecting their treatment protocols, and threatening their survival. The objective of this scoping review was to summarize the published literature regarding the impact of COVID-19 on KTRs in the United States in terms of prevention, various treatment protocols, COVID-19 vaccination, and risk factors. The databases such as PubMed, MEDLINE/Ebsco, and Embase were used to search for peer-reviewed literature. The search was restricted to articles that were published on KTRs in the United States from January 1, 2019, to March 2022. The initial search yielded 1,023 articles after removing duplicates, leading to a final selection of 16 articles after screening with inclusion and exclusion criteria. Four domains emerged from the review: (1) impacts of COVID-19 on performing kidney transplants, (2) impacts of COVID-19 vaccinations on KTRs, (3) outcomes of treatment regiments for KTRs with COVID-19, and (4) risk factors associated with an increased mortality rate of COVID-19 in KTRs. Waitlisted patients for kidney transplants had a higher risk of mortality compared to nontransplant patients. COVID-19 vaccinations in KTRs are found to be safe, and the immune response can be improved by placing patients on a low dose of mycophenolate before vaccination. Withdrawal of immunosuppressants showed a mortality rate of 20% without increasing the rate of acute kidney injury (AKI). There is evidence to support that kidney transplantation with the accompanying immunosuppressant regimen can provide KTRs with better COVID-19 infection outcomes compared to waitlisted patients. Hospitalization, graft dysfunction, AKI, and respiratory failure were the most common risk factors that increased the risk of mortality in COVID-19-positive KTRs. Withdrawing KTRs from immunosuppressive drugs increased the mortality rate. Further studies are needed to investigate the effects of specific drugs and dosages on the severity and mortality rate of COVID-19 in KTRs.

Acquired Thrombotic Thrombocytopenic Purpura in the Presence of a Urinary Tract Infection: A Rare Pediatric Case.

Thrombotic thrombocytopenic purpura (TTP) is a type of microangiopathic hemolytic anemia that rarely presents in the pediatric population. This life-threatening disorder manifests as severe consumptive thrombocytopenia and disseminated micro-thromboemboli, leading to organ ischemia. Here, we present a case of an acute first-time episode of acquired TTP in a 17-year-old African American female with a past medical history of obesity, recurrent urinary tract infections, and dysfunctional uterine bleeding managed with oral contraceptives. The disorder's insidious onset was only preceded by a urinary tract infection managed as an outpatient with oral cefdinir for four days before symptoms worsened. The patient was admitted to the pediatric intensive care unit with microangiopathic hemolytic anemia, severe thrombocytopenia, low von Willebrand factor-cleaving protease (ADAMTS13) activity, hypofibrinogenemia, gross hematuria, and acute kidney injury. Further workup was significant for a positive urine culture for Escherichia coli. Her hospital course was complicated by an acute ischemic stroke. The patient's TTP was managed by five sessions of plasmapheresis (PLEX), two once-weekly doses of rituximab, five doses of caplacizumab, three doses of high-dose solumedrol, and six days of high-dose prednisone. This regimen led to an overall uptrend in platelet counts toward normal and resolved her kidney injury. Currently, the patient continues to recover as an outpatient with no disability, managed with rituximab and caplacizumab as relapse prophylaxis. This case highlights the need for further investigation into the consideration of TTP as part of the differential diagnosis for pediatric patients presenting with severe thrombocytopenia and acute kidney injury in the absence of a significant medical history. Additionally, the utilization of rituximab, caplacizumab, steroids, and PLEX for TTP in the pediatric population should be further investigated.

Ethical Perspectives of Therapeutic Human Genome Editing From Multiple and Diverse Viewpoints: A Scoping Review.

Human genome editing has been increasingly explored to determine if it can be used to eradicate genetic diseases like sickle cell disease, but it has also been surrounded by a wide variety of ethical dilemmas. The purpose of this review was to conduct a scoping review of the ethics of therapeutic human genome editing in terms of philosophy, theology, public perspectives, and research ethics. A systemized search of PubMed, Embase, Ovid MEDLINE, and Web of Science was conducted. The initial search resulted in 4,445 articles, and after removing 1,750 duplicates and screening the remaining 2,695 articles, 27 final articles were selected for the final analysis. From a philosophical and theological standpoint, therapeutic human genome editing was generally ethically acceptable. Worldwide public perspectives were also in agreement except for the Oceanic region, which disagreed mainly due to the possible effects on future generations. Lastly, human research ethics revealed that women were not always included in informed consent, and that child autonomy needs to be preserved. Further research is needed to determine adverse effects on the mother, fetus, and future generations.

Osteopathic Manipulative Treatment and the Management of Headaches: A Scoping Review.

Headaches have been studied and treated since nearly 7,000 BC because of their significant global impact. Current headache treatment modalities are various and have a wide variety of targets, but medications are the most common. Since conventional medical treatments have several side effects, alternative remedies such as osteopathic manipulative treatment (OMT) should be considered. OMT can assist in the management of various health conditions, such as low back pain, neck pain, and headaches. The purpose of this scoping review is to evaluate recent findings regarding the efficacy of OMT modalities in the management of headaches such as tension-type headaches (TTH) and migraines. This study was designed as a scoping review to gather evidence on the efficacy of OMT modalities in the management of headaches. Following PRISMA guidelines, four databases were used to search for articles published between 2010 and 2022 that reported the use of OMT and manual therapy for TTH and migraines. Databases used include Embase, PubMed, Medline, and Web of Science. The following keywords were used: treatment, therapy, Headache, migraine, craniosacral, muscle energy, myofascial release, trigger point, osteopathic, and manipulation. The initial search yielded 473 unique articles after removing duplicates. After screening based on the inclusion and exclusion criteria, and after further analysis, 15 articles were selected. Data reports of OMT and manual therapy efficacy and/or effectiveness in treating TTH and migraine were analyzed. Articles included were randomized control studies (13 of 15, 86.6%), one pilot study (one of 15, 6.7%), and one case series (one of 15, 6.7%), which were divided into TTH (nine of 15, 60%) and Migraine Headaches (six of 15, 40%). All articles reported significant headache improvement in at least one measurement. Of all treatments analyzed, single technique interventions (seven of 15, 47%) and multiple technique interventions (eight of 15, 53%) were identified. Among the techniques used, Myofascial Release was the most common (nine of 15, 60%). The articles presented provide evidence of the significant benefits of manual therapy. Because of the limitations of traditional medicine, OMT can be used either as an alternative or adjuvant therapy for headaches. Evidence suggests the positive impact it can provide on headache management, but the number of randomized control trials and population samples should be increased to support its recommendation. This demonstrates how different osteopathic techniques can provide therapeutic effects on TTH, MH, and potentially other types of headaches. A preference for myofascial release was observed, which can be due to the fast relief from the physiologic effect on tissue movement. This review study demonstrates the benefits OMT has on decreasing headache frequency, intensity, and duration in TTH and migraines. OMT has shown to be beneficial, especially for patients seeking alternative non-pharmaceutical and non-invasive treatments. Further studies are needed to evaluate the effects of different OMT techniques, and different combinations of treatments, on other types of headaches.