Therapies to eradicate human immunodeficiency virus (HIV) infection, sparing lifelong antiviral therapy, are a still-distant goal. But significant advances have been made to reverse HIV latency while antiretroviral therapy (ART) is maintained to allow targeting of the persistent viral reservoir, to test interventions that could clear cells emerging from latent infection, and to improve HIV cure research assays and infrastructure. Steady progress gives hope that future therapies to clear HIV infection may relieve individuals and society of the burden of HIV.

BACKGROUND: Patients with advanced non-small-cell lung cancer (NSCLC) with activating mutations in the epidermal growth factor receptor (EGFR) gene are a heterogeneous population who often develop brain metastases (BM). The optimal management of patients with asymptomatic brain metastases is unclear given the activity of newer-generation targeted therapies in the central nervous system. We present a protocol for an individual patient data (IPD) prospective meta-analysis to evaluate whether the addition of stereotactic radiosurgery (SRS) before osimertinib treatment will lead to better control of intracranial metastatic disease. This is a clinically relevant question that will inform practice.
METHODS: Randomised controlled trials will be eligible if they include participants with BM arising from EGFR-mutant NSCLC and suitable to receive osimertinib both in the first-line and second-line settings (P); comparisons of SRS followed by osimertinib versus osimertinib alone (I, C) and intracranial disease control included as an endpoint (O). Systematic searches of Medline (Ovid), Embase (Ovid), Cochrane Central Register of Controlled Trials (CENTRAL), CINAHL (EBSCO), PsychInfo, ClinicalTrials.gov and the WHO\'s International Clinical Trials Registry Platform\'s Search Portal will be undertaken. An IPD meta-analysis will be performed using methodologies recommended by the Cochrane Collaboration. The primary outcome is intracranial progression-free survival, as determined by response assessment in neuro-oncology-BM criteria. Secondary outcomes include overall survival, time to whole brain radiotherapy, quality of life, and adverse events of special interest. Effect differences will be explored among prespecified subgroups.
BACKGROUND: Approved by each trial\'s ethics committee. Results will be relevant to clinicians, researchers, policymakers and patients, and will be disseminated via publications, presentations and media releases.
UNASSIGNED: CRD42022330532.

OBJECTIVE: We studied the short- and long-term effects of imatinib in hospitalised COVID-19 patients.
METHODS: Participants were randomised to receive standard of care (SoC) or SoC with imatinib. Imatinib dosage was 400mg daily until discharge (max 14 days). Primary outcomes were mortality at 30 days and 1 year. Secondary outcomes included recovery, quality of life and long COVID symptoms at 1 year. We also performed a systematic review and meta-analysis of randomised trials studying imatinib for 30-day mortality in hospitalised COVID-19 patients.
RESULTS: We randomised 156 patients (73 in SoC and 83 in imatinib). Among patients on imatinib, 7.2% had died at 30 days and 13.3% at 1 year and in SoC 4.1% and 8.2% (adjusted HR 1.35, 95% CI 0.47-3.90). At 1-year, self-reported recovery occurred in 79.0% in imatinib and in 88.5% in SoC (RR 0.91, 0.78-1.06). We found no convincing difference in quality of life or symptoms. Fatigue (24%) and sleep issues (20%) frequently bothered patients at one year. In the meta-analysis, imatinib was associated with a mortality risk ratio of 0.73 (0.32-1.63; low certainty evidence).
CONCLUSIONS: The evidence raises doubts regarding benefit of imatinib in reducing mortality, improving recovery and preventing long COVID symptoms in hospitalised COVID-19 patients.

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Fatigue is a common physiological state that affects normal human activities. Prolonged fatigue induces a variety of diseases and seriously affects human health, so it is imperative to discover nutritional dietary supplements and treatments without side effects, among which natural anti-fatigue polysaccharides have shown great potential. Polysaccharides, a class of biomolecules produced by a variety of organisms such as plants, animals, bacteria and algae, have attracted much attention in recent years due to their anti-fatigue activity and fewer side effects. This review summarizes the classification, dosage and experimental models of polysaccharides with anti-fatigue activity obtained from different natural sources. We also review the fatigue-relieving effects of these polysaccharides through mechanisms such as modulating oxidative damage, regulating energy metabolism and influencing intestinal flora, as well as the effects of molecular weights, monosaccharide compositions, structural features and chemical modifications of the polysaccharides on their anti-fatigue activities to support their potential application value in functional foods and pharmaceuticals. New valuable insights for future research on natural polysaccharides are also presented in the field of natural production of bio-based functional materials, functional foods and therapeutic agents.

The COVID-19 pandemic has resulted in many therapies, of which many are repurposed and used for other diseases in the last decade such in Influenza and Ebola. We intend to provide a robust foundation for cardiovascular outcomes of the therapies to better understand the rationale for the clinical trials that were conducted during the COVID-19 pandemic, and to gain more clarity on the steps moving forward should the repurposing provide clinical benefit in pandemic situations. With this state-of-the-art review, we aim to improve the understanding of the cardiovascular involvement of the therapies prior to, during, and after the COVID-19 pandemic to provide meaningful findings to the cardiovascular specialists and clinical trials for therapies, moving on from the period of pandemic urgency.

Currently, cervical cancer (CC) is the fourth recorded widespread cancer among women globally. There are still many cases of metastatic or recurring disease discovered, despite the incidence and fatality rates declining due to screening identification and innovative treatment approaches. Palliative chemotherapy continues to be the standard of care for patients who are not contenders for curative therapies like surgery and radiotherapy. This article seeks to provide a thorough and current summary of therapies that have been looked into for the management of CC. The authors emphasize the ongoing trials while reviewing the findings of clinical research. Agents that use biological mechanisms to target different molecular pathways such as epidermal growth factor receptor (EGFR), vascular endothelial growth factor (VEGF), mammalian target of rapamycin (mTOR), poly ADP-ribosepolymerase (PARP), and epigenetic biological mechanisms epitomize and offer intriguing research prospects.

BACKGROUND: Assisted partner services (APS) is an effective strategy for increasing HIV testing, new diagnosis, and linkage to care among sexual partners of people living with HIV (PLWH). APS can be resource intensive as it requires community tracing to locate each partner named and offer them testing. There is limited evidence for the effectiveness of offering HIV self-testing (HIVST) as an option for partner testing within APS.
METHODS: We conducted a cluster randomized controlled trial comparing provider-delivered HIV testing (Standard APS) versus offering partners the option of provider-delivered testing or HIVST (APS+HIVST) at 24 health facilities in Western Kenya. Facilities were randomized 1:1 and we conducted intent-to-treat analyses using Poisson generalized linear mixed models to estimate intervention impact on HIV testing, new HIV diagnoses, and linkage to care. All models accounted for clustering at the clinic level and new diagnoses and linkage models were adjusted for individual-level age, sex, and income a priori.
RESULTS: From March to December 2021, 755 index clients received APS and named 5054 unique partners. Among these, 1408 partners reporting a prior HIV diagnosis were not eligible for HIV testing and were excluded from analyses. Of the remaining 3646 partners, 96.9% were successfully contacted for APS and tested for HIV: 2111 (97.9%) of 2157 in the APS+HIVST arm and 1422 (95.5%) of 1489 in the Standard APS arm. In the APS+HIVST arm, 84.6% (1785/2111) tested via HIVST and 15.4% (326/2111) received provider-delivered testing. Overall, 16.7% of the 3533 who tested were newly diagnosed with HIV (APS+HIVST = 357/2111 [16.9%]; Standard APS = 232/1422 [16.3%]). Of the 589 partners who were newly diagnosed, 90.7% were linked to care (APS+HIVST = 309/357 [86.6%]; Standard APS = 225/232 [97.0%]). There were no significant differences between the two arms in HIV testing (relative risk [RR]: 1.02, 95% CI: 0.96-1.10), new HIV diagnoses (adjusted RR [aRR]: 1.03, 95% CI: 0.76-1.39) or linkage to care (aRR: 0.88, 95% CI: 0.74-1.06).
CONCLUSIONS: There were no differences between APS+HIVST and Standard APS, demonstrating that integrating HIVST into APS continues to be an effective strategy for identifying PLWH by successfully reaching and HIV testing >95% of elicited partners, newly diagnosing with HIV one in six of those tested, >90% of whom were linked to care.
BACKGROUND: NCT04774835.

BACKGROUND: Despite the low-risk nature of participation in most clinical anesthesia trials, subject recruitment on the same day as surgery is often restricted due to the concerns of researchers and local research ethics boards that same-day consent may not afford adequate time and opportunity for patients to weigh and make decisions, as well as perceptions of patient vulnerability immediately prior to surgery that could impact the voluntary nature and the rigor of the informed consent process. However, specialties such as anesthesiology, critical care, interventional radiology, and emergency medicine have a varied pattern of practice and patient acquaintance that does not typically afford the luxury of time or, in many cases, advance consent for participation in research. Indeed, the initial encounter between anesthesiologists and patients undergoing elective procedures routinely occurs on the day of surgery. Concerns of coercion related to same-day consent for clinical anesthesia research trials have not been borne out in the literature, and represent a significant obstacle to clinical researchers, as well as to the patients who are denied opportunities for potential benefit through participation in research studies.
METHODS: We describe the protocol for a prospective randomized controlled trial examining the voluntariness of patient consent, solicited either in advance of surgery or on the same day, to participate in an anesthesia research study at Women\'s College Hospital. One hundred fourteen patients scheduled to undergo ambulatory anterior cruciate ligament repair facilitated by general anesthesia with an adductor canal block will be randomized for recruitment either (a) in the pre-operative assessment clinic before the day of surgery or (b) on the day of surgery, to be approached for consent to participate in a fabricated research study of adjunct medications in adductor canal blocks. Regardless of allocation, patients in both groups will receive the same routine standard of care and will complete a post-operative questionnaire to signal perceptions of undue influence in the process of providing informed consent for the fabricated trial.
CONCLUSIONS: This study will inform trial design and practice guidelines surrounding the amount of time patients ought to be afforded in order to make durable decisions to participate (or not) in clinical research studies. This is expected to impact trial recruitment in a variety of clinical settings where researchers have only brief opportunities to interface with patients.
BACKGROUND: The trial was registered prospectively on the Open Science Framework (OSF), registration #46twc, on 2023-Mar-17.

Despite several small-molecule drugs that have revolutionized the current treatment strategy for acute myeloid leukemia (AML), hematopoietic stem cell transplantation remains the only curative treatment in most cases to date. Chimeric antigen receptor (CAR)-T cell therapy is one of the most promising next-generation cancer therapies for hematological malignancies and is clinically available for treatment of AML. However, developing AML-targeted CAR-T therapy is challenging because of the heterogeneity of target antigen expression across leukemic cells and patients, the difficulty in excluding on-/off-target tumor effects, and the immunosuppressive tumor microenvironment. To date, various targets, including CD33, NKG2D, CD123, CLL-1, and CD7, have been actively studied for CAR-T cells. Although no CAR-T cell products are close to practical use, several clinical trials have shown promising results, particularly for CAR-T cells targeting CLL-1 or CD123. Meanwhile, research exploring the ideal target for AML-targeted CAR-T therapy continues. Furthermore, as collecting autologous lymphocytes from patients with AML is difficult, development of off-the-shelf CAR-T products is being actively pursued. This review discusses the challenges in AML-targeted CAR-T cell therapy development from the perspectives of target antigen characteristics and AML-specific on-target/off-tumor toxicity. Moreover, it discusses the clinical development and prospects of AML-targeting CAR-T cells.