Safety of Pediatric rhGH Therapy: An Overview and the Need for Long-Term Surveillance

Growth hormone (GH) therapy dates back to 1958 and, though has shown an excellent safety profile in the short-term, has never ceased to raise concern about potential long-term side effects. In the last decade, a number of observational studies in different cohorts of young adult patients treated with GH during childhood have yielded conflicting results. The attention has mainly focused on three major potential risks associated with GH therapy: cancer, cardio and cerebrovascular diseases and diabetes. This review intends to provide a detailed overview of the main studies reporting long-term safety in subjects treated with rhGH therapy during childhood, highlighting the evidence for or against the risk of cancer, cardio and cerebrovascular diseases and diabetes.

Giving Oncolytic Viruses a Free Ride: Carrier Cells for Oncolytic Virotherapy

Oncolytic viruses (OVs) are an emerging class of therapeutics which combine multiple mechanisms of action, including direct cancer cell-killing, immunotherapy and gene therapy. A growing number of clinical trials have indicated that OVs have an excellent safety profile and provide some degree of efficacy, but to date only a single OV drug, HSV-1 talimogene laherparepvec (T-Vec), has achieved marketing approval in the US and Europe. An important issue to consider in order to accelerate the clinical advancement of OV agents is the development of an effective delivery system. Currently, the most commonly employed OV delivery route is intratumoral; however, to target metastatic diseases and tumors that cannot be directly accessed, it is of great interest to develop effective approaches for the systemic delivery of OVs, such as the use of carrier cells. In general, the ideal carrier cell should have a tropism towards the tumor microenvironment (TME), and it must be susceptible to OV infection but remain viable long enough to allow migration and finally release of the OV within the tumor bed. Mesenchymal stem cells (MSCs) have been heavily investigated as carrier cells due to their inherent tumor tropism, in spite of some disadvantages in biodistribution. This review focuses on the other promising candidate carrier cells under development and discusses their interaction with specific OVs and future research lines.

Hepatic and Renal Safety of Remdesivir in COVID-19 Patients Observational prospective study

Background: SARS-CoV-2 has been demonstrated to be inhibited by Remdesivir, a broad-spectrum antiviral medication. Remdesivir has been tried for a compassionate use in severe COVID-19 in the absence of any viable treatment for SARS-CoV-2 infection (COVID-19). Methods: In 50 patients with SARSCoV-2 infection who were given Remdesivir as part of their institutional treatment plan, we conducted an observational prospective analysis. Remdesivir 100 mg was given daily for7 days during the therapy period. The results of liver and kidney function tests were compared before and after Remdesivir administration. Results: With the administration of Re%) exhibited an improvement in their oxygen needs. Patients reported only a few minor side effects. Serious side effects, on the other hand, were rare. Conclusion: Remdesivir seems to have an excellent safety profile, while its efficacy in the treatment of COVID-19 is currently inconclusive. Remdesivir use in patients was shown to be safe, with no serious side effects or significant changes in normal test results for liver and kidney functions. Keywords: Adverse events, Covid-19, liver function, remdesivir, renal function

Chemoselective reduction of tertiary amides by 1,3-diphenyldisiloxane (DPDS)

A convenient procedure for the chemoselective reduction of tertiary amides at room temperature in the presence of air and moisture using 1,3-diphenyldisiloxane (DPDS) has been developed. The reaction conditions are tolerant of a great number of functional groups including esters, nitriles, secondary amides, carbamates, sulfoxides, sulfones, sulfonyl fluorides, halogens, aryl-nitro groups, and arylamines. The conditions reported are the mildest to date and utilize EtOAc, a preferred solvent given its excellent safety profile and lower environmental impact. The ease of set up and broad chemoselectivity make this method attractive for organic synthesis. These results further demonstrate the utility of DPDS as a selective reducing agent.

Combined Echo and Fluoroscopy-Guided Pulmonary Valvuloplasty in Neonates and Infants: Efficacy and Safety

Percutaneous balloon pulmonary valvuloplasty (PBPV) is the treatment of choice for isolated pulmonary valve stenosis. While this procedure is highly efficacious and has an excellent safety profile, as currently practiced, patients are obligatorily exposed to the secondary risks of ionizing radiation and contrast media. To mitigate these risks, we developed a protocol which utilized echo guidance for portions of the procedure which typically require fluoroscopy and/or angiography. Ten cases of echo-guided pulmonary valvuloplasty (EG-PBPV) for isolated pulmonary stenosis in children less than a year of age were compared to a historical cohort of nineteen standard cases using fluoroscopy/angiography alone, which demonstrated equivalent procedural outcomes and safety, while achieving a median reduction in radiation (total dose area product) and contrast load of 80% and 84%, respectively. Our early experience demonstrates that EG-PBPV in neonates and infants has results equivalent to standard valvuloplasty but with less radiation and contrast.

A Mycobacteriophage-Based Vaccine Platform: SARS-CoV-2 Antigen Expression and Display

The explosion of SARS-CoV-2 infections in 2020 prompted a flurry of activity in vaccine development and exploration of various vaccine platforms, some well-established and some new. Phage-based vaccines were described previously, and we explored the possibility of using mycobacteriophages as a platform for displaying antigens of SARS-CoV-2 or other infectious agents. The potential advantages of using mycobacteriophages are that a large and diverse variety of them have been described and genomically characterized, engineering tools are available, and there is the capacity to display up to 700 antigen copies on a single particle approximately 100 nm in size. The phage body may itself be a good adjuvant, and the phages can be propagated easily, cheaply, and to high purity. Furthermore, the recent use of these phages therapeutically, including by intravenous administration, suggests an excellent safety profile, although efficacy can be restricted by neutralizing antibodies. We describe here the potent immunogenicity of mycobacteriophage Bxb1, and Bxb1 recombinants displaying SARS-CoV-2 Spike protein antigens.

Changes in Treatment Patterns and Globe Salvage Rate of Advanced Retinoblastoma in Korea: Efficacy of Intra-Arterial Chemotherapy

(1) Background: To analyze changes in treatment patterns for advanced retinoblastoma over time and differences in globe salvage rates; (2) Methods: Retrospective, observational case-control study of 97 eyes of 91 patients with advanced retinoblastoma (Group D and E).; (3) Results: Patients were divided into two groups based on whether they were treated before or after intraarterial chemotherapy (IAC) was introduced in our center in 2010. Before 2010, primary treatment pattern was enucleation, which was performed in 57.6% of cases, whereas primary treatment pattern after 2010 was IAC combined with intravenous chemotherapy (IVC), which was performed in 78.1%. Intravitreal chemotherapy (IVitC) has been performed to treat vitreous and subretinal seeding since 2015. The 5-year globe salvage rate of IVC alone was 24.0% for Group D and 0% for Group E, whereas that of IVC–IAC was 50.4% for Group D and 49.7% for Group E. Whether IVitC was performed or not did not significantly contribute to globe salvage rate. There was one metastatic death in the IVC alone group.; (4) Conclusions: Primary treatment pattern changed from enucleation to IAC-based treatment, which can now save nearly half of eyes with advanced retinoblastoma with excellent safety profile and survival rate.

Wide-Awake Brachioplasty: A Safe and Effective Technique for Local Anesthesia

Brachioplasty is a popular body contouring surgery which treats upper arm deformity related to both aging and massive weight loss. Demand for brachioplasty is growing, as the volume of bariatric surgery performed in the United States has doubled in the last decade.1 Local anesthesia offers multiple benefits for both patients and providers: it avoids anesthetic risks and anesthesia costs, decreases operating room time, and facilitates a more rapid recovery for patients. Brachioplasty is typically performed under general anesthesia or moderate sedation; this study details a successful technique to perform brachioplasty under wide-awake local anesthesia with high patient satisfaction and an excellent safety profile.

Benefits of Vaccination

Vaccines in routine use around the world have been shown to be clinically well-tolerated and in double-blind randomized prospective controlled field trials – to be efficacious. Furthermore, they have been proven to be effective in routine vaccination programmes worldwide. They have had an excellent safety profile. Vaccinated individuals will face a greatly reduced danger of contracting the targeted disease with a minimal risk of serious side-effects. Should the vaccine fail to give complete protection, the severity of the "breakthrough" disease and its accompanying complications will, in most cases, be less than among the unvaccinated. Mortality, if a possible outcome, will also be greatly reduced. Mass vaccination of children in developed nations have brought many vaccine-preventable diseases under control or even eliminated them. Vaccines have made erstwhile lethal infectious diseases so rare that they have become "victims of their own success" to the point that uninformed people query the necessity of continuing to use them. Unless a disease is eradicated on a global scale – as has been achieved for smallpox and will soon be for poliomyelitis – vaccination cannot cease since the pathogen will quickly reappear and spread with dire consequences. Elimination of disease has many socio-economic, educational, and geo-political advantages. Healthy children grow to become well-educated and productive citizens that live longer. Increased life-expectancy brings prosperity and wealth buys health. Reduced infant mortality will put a brake on population growth in less developed countries and ease pressure on land and food – a determinant of belligerence. Vaccines are a powerful tool to foster equity and peace in the world.

H-Wave® Device Stimulation: A Critical Review

Pain treatments have historically centered on drugs, but an “opioid crisis” has necessitated new standards of care, with a paradigm shift towards multi-modal pain management emphasizing early movement, non-narcotics, and various adjunctive therapies. Electrotherapies remain understudied and most lack high-quality clinical trials, despite a desperate need for effective adjunctive options. A systematic search of human clinical studies on H-Wave® device stimulation (HWDS) was conducted as well as a comprehensive review of articles articulating possible HWDS mechanisms of action. Studies unrelated to H-Wave were excluded. Data synthesis summarizes outcomes and study designs, categorized as pre-clinical or clinical. Pre-clinical studies demonstrated that HWDS utilizes a biphasic waveform to induce non-fatiguing muscle contractions which positively affect nerve function, blood and lymph flow. Multiple clinical studies have reported significant benefits for diabetic and non-specific neuropathic pain, where function also improved, and pain medication usage substantially dropped. In conclusion, low- to moderate-quality HWDS studies have reported reduced pain, restored functionality, and lower medication use in a variety of disorders, although higher-quality research is needed to verify condition-specific applicability. HWDS has enough reasonable evidence to be considered as an adjunctive component of non-opioid multi-modal pain management, given its excellent safety profile and relative low cost. Level of Evidence: III.