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Cureus Nov 2023The spike protein of SARS-CoV-2 has been found to exhibit pathogenic characteristics and be a possible cause of post-acute sequelae after SARS-CoV-2 infection or... (Review)
Review
The spike protein of SARS-CoV-2 has been found to exhibit pathogenic characteristics and be a possible cause of post-acute sequelae after SARS-CoV-2 infection or COVID-19 vaccination. COVID-19 vaccines utilize a modified, stabilized prefusion spike protein that may share similar toxic effects with its viral counterpart. The aim of this study is to investigate possible mechanisms of harm to biological systems from SARS-CoV-2 spike protein and vaccine-encoded spike protein and to propose possible mitigation strategies. We searched PubMed, Google Scholar, and 'grey literature' to find studies that (1) investigated the effects of the spike protein on biological systems, (2) helped differentiate between viral and vaccine-generated spike proteins, and (3) identified possible spike protein detoxification protocols and compounds that had signals of benefit and acceptable safety profiles. We found abundant evidence that SARS-CoV-2 spike protein may cause damage in the cardiovascular, hematological, neurological, respiratory, gastrointestinal, and immunological systems. Viral and vaccine-encoded spike proteins have been shown to play a direct role in cardiovascular and thrombotic injuries from both SARS-CoV-2 and vaccination. Detection of spike protein for at least 6-15 months after vaccination and infection in those with post-acute sequelae indicates spike protein as a possible primary contributing factor to long COVID. We rationalized that these findings give support to the potential benefit of spike protein detoxification protocols in those with long-term post-infection and/or vaccine-induced complications. We propose a base spike detoxification protocol, composed of oral nattokinase, bromelain, and curcumin. This approach holds immense promise as a base of clinical care, upon which additional therapeutic agents are applied with the goal of aiding in the resolution of post-acute sequelae after SARS-CoV-2 infection and COVID-19 vaccination. Large-scale, prospective, randomized, double-blind, placebo-controlled trials are warranted in order to determine the relative risks and benefits of the base spike detoxification protocol.
PubMed: 38024037
DOI: 10.7759/cureus.49204 -
Indian Dermatology Online Journal 2023Melasma is an acquired disorder, which presents with well-demarcated, brown-colored hyperpigmented macules, commonly involving the sun-exposed areas such as the face. It... (Review)
Review
INTRODUCTION
Melasma is an acquired disorder, which presents with well-demarcated, brown-colored hyperpigmented macules, commonly involving the sun-exposed areas such as the face. It is a chronic and distressing condition, affecting the patients' quality of life, and has been conventionally treated with "first-line" agents including hydroquinone (HQ) alone or as a part of a triple combination cream (TCC), while "second-line" options include chemical peels, and third line options include laser therapy.
MATERIALS AND METHODS
A systematic search was performed for all topical and systemic treatments for melasma up till May 4, 2021, using the PubMed and EMBASE databases, according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) protocol. The search terms "melasma" and "treatment" were used to search for the relevant articles on both these databases, and a total of 4020 articles were identified. After removing the duplicate entries and screening the titles, abstracts, and full-text articles, we identified 174 randomized controlled trials (RCTs) or controlled clinical trials.
RESULTS
Based on our review, HQ, TCCs, sunscreens, kojic acid (KA), and azelaic acid receive grade A recommendation. Further large-scale studies are required to clearly establish the efficacy of topical vitamin C, resorcinol, and topical tranexamic acid (TXA). Several newer topical agents may play a role only as an add-on or second-line drugs or as maintenance therapy. Oral TXA has a strong recommendation, provided there are no contraindications. Procyanidins, Polypodium leucotomos (PL), and even synbiotics may be taken as adjuncts.
DISCUSSION
Several newer topical and systemic agents with multimodal mechanisms of action have now become available, and the balance seems to be tipping in favor of these innovative modalities. However, it is worth mentioning that the choice of agent should be individualized and subject to availability in a particular country.
PubMed: 38099013
DOI: 10.4103/idoj.idoj_490_22 -
Blood Cancer Discovery Nov 2023In the past year, three new bispecific antibodies have received accelerated FDA approval for the treatment of relapsed/refractory multiple myeloma. In this article, we... (Review)
Review
In the past year, three new bispecific antibodies have received accelerated FDA approval for the treatment of relapsed/refractory multiple myeloma. In this article, we review the available data for these three agents, teclistamab, elranatamab, and talquetamab, and discuss practical considerations for their use in clinical settings while the medical community awaits randomized phase III clinical trial datasets comparing them to standard-of-care regimens.
Topics: Humans; Multiple Myeloma; Antibodies, Bispecific; Embarrassment; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols
PubMed: 37824758
DOI: 10.1158/2643-3230.BCD-23-0176 -
BMJ Open Jul 2023Reanalyse the patient-level data set of the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study with fidelity to the original research protocol and...
What are the treatment remission, response and extent of improvement rates after up to four trials of antidepressant therapies in real-world depressed patients? A reanalysis of the STAR*D study's patient-level data with fidelity to the original research protocol.
OBJECTIVE
Reanalyse the patient-level data set of the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study with fidelity to the original research protocol and related publications.
DESIGN
The study was open label and semirandomised examining the effectiveness of up to four optimised and increasingly aggressive, antidepressant therapies in depressed adults. Patients who failed to gain adequate relief from their level 1 trial on the SSRI citalopram could receive up to three additional treatment trials in levels 2-4.
SETTING
41 North American psychiatry and primary care treatment centres.
PARTICIPANTS
4041 adults screened positive for major depressive disorder. In contrast to most clinical trials, STAR*D enrolled patients seeking care (vs recruited) and included patients with a wide range of common comorbid medical and psychiatric conditions to enhance the generalisability of findings to real-world clinical practice.
INTERVENTIONS
STAR*D evaluated the relative effectiveness of 13 antidepressants therapies in treatment levels 2-4 for depressed patients who failed to gain adequate benefit from their level 1 medication trial.
MAIN OUTCOME MEASURES
According to the STAR*D protocol, the primary outcome was remission, defined as a score <8 on the blinded Hamilton Rating Scale for Depression (HRSD). Response was a secondary outcome defined as ≥50% reduction in HRSD scores. STAR*D's protocol specifically excluded all non-blinded clinic-administered assessments from use as research outcome measures.
RESULTS
STAR*D investigators did not use the protocol-stipulated HRSD to report cumulative remission and response rates in their summary article and instead used a non-blinded clinic-administered assessment. This inflated their report of outcomes, as did their inclusion of 99 patients who scored as remitted on the HRSD at study outset as well as 125 who scored as remitted when initiating their next-level treatment. These patients should have been excluded from data analysis. In contrast to the STAR*D-reported 67% cumulative remission rate after up to four antidepressant treatment trials, the rate was 35.0% when using the protocol-stipulated HRSD and inclusion in data analysis criteria.
CONCLUSION
STAR*D's cumulative remission rate was approximately half of that reported.
Topics: Adult; Humans; Depressive Disorder, Major; Treatment Outcome; Antidepressive Agents; Citalopram; Psychotherapy
PubMed: 37491091
DOI: 10.1136/bmjopen-2022-063095 -
American Journal of Hematology Aug 2023Intensive chemotherapy with cytarabine and anthracycline (7&3) remains the standard therapy for patients medically fit for induction, but the assessment of fitness...
Intensive chemotherapy with cytarabine and anthracycline (7&3) remains the standard therapy for patients medically fit for induction, but the assessment of fitness remains controversial. Venetoclax and hypomethylating agent (ven/HMA) combination therapy has improved outcomes in unfit patients but no prospective study has assessed ven/HMA versus 7&3 as initial therapy in older, fit patients. Given no studies and expectation of ven/HMA use in patients outside of trial criteria, we evaluated retrospective outcomes among newly diagnosed patients. A nationwide electronic health record (EHR)-derived database and the University of Pennsylvania EHR identified 312 patients receiving 7&3 and 488 receiving ven/HMA who were 60-75 years old without history of organ failure. Ven/HMA patients were older and more likely to have secondary AML, adverse cytogenetics, and adverse mutations. Median overall survival (OS) for patients receiving intensive chemotherapy was 22 versus 10 months for ven/HMA (HR 0.53, 95% CI 0.40-0.60). Controlling for measured baseline characteristic imbalances reduced survival advantage by half (HR 0.71, 95% CI 0.53-0.94). A sub-group of patients with equipoise, likelihood at least 30%-70% of receiving either treatment, had similar OS outcomes (HR 1.10, 95% CI 0.75-1.6). Regarding safety outcomes, 60-day mortality was higher for ven/HMA (15% vs. 6% at 60 days) despite higher documented infections and febrile neutropenia for 7&3. In this multicenter real-word dataset, patients selected for intensive chemotherapy had superior OS but a large group had similar outcomes with ven/HMA. Prospective randomized studies, controlling for both measured and unmeasured confounders, must confirm this outcome.
Topics: Humans; Aged; Middle Aged; Retrospective Studies; Cytarabine; Bridged Bicyclo Compounds, Heterocyclic; Leukemia, Myeloid, Acute; Antineoplastic Combined Chemotherapy Protocols
PubMed: 37334852
DOI: 10.1002/ajh.26991