-
Cancers Dec 2022A tertiary lymphoid structure (TLS) is a special component in the immune microenvironment that is mainly composed of tumor-infiltrating lymphocytes (TILs), including T... (Review)
Review
A tertiary lymphoid structure (TLS) is a special component in the immune microenvironment that is mainly composed of tumor-infiltrating lymphocytes (TILs), including T cells, B cells, DC cells, and high endothelial venules (HEVs). For cancer patients, evaluation of the immune microenvironment has a predictive effect on tumor biological behavior, treatment methods, and prognosis. As a result, TLSs have begun to attract the attention of researchers as a new potential biomarker. However, the composition and mechanisms of TLSs are still unclear, and clinical detection methods are still being explored. Although some meaningful results have been obtained in clinical trials, there is still a long way to go before such methods can be applied in clinical practice. However, we believe that with the continuous progress of basic research and clinical trials, TLS detection and related treatment can benefit more and more patients. In this review, we generalize the definition and composition of TLSs, summarize clinical trials involving TLSs according to treatment methods, and describe possible methods of inducing TLS formation.
PubMed: 36497450
DOI: 10.3390/cancers14235968 -
The European Respiratory Journal Dec 2020https://bit.ly/3o0K9kl
https://bit.ly/3o0K9kl
Topics: COVID-19; Evidence-Based Medicine; Humans; Methylprednisolone; Pandemics; SARS-CoV-2; Steroids
PubMed: 33361452
DOI: 10.1183/13993003.04116-2020 -
Signal Transduction and Targeted Therapy Sep 2023During the ongoing pandemic, providing treatment consisting of effective, low-cost oral antiviral drugs at an early stage of SARS-CoV-2 infection has been a priority for...
During the ongoing pandemic, providing treatment consisting of effective, low-cost oral antiviral drugs at an early stage of SARS-CoV-2 infection has been a priority for controlling COVID-19. Although Paxlovid and molnupiravir have received emergency approval from the FDA, some side effect concerns have emerged, and the possible oral agents are still limited, resulting in optimized drug development becoming an urgent requirement. An oral remdesivir derivative, VV116, has been reported to have promising antiviral effects against SARS-CoV-2 and positive therapeutic outcomes in clinical trials. However, whether VV116 has broad-spectrum anti-coronavirus activity and potential synergy with other drugs is not clear. Here, we uncovered the broad-spectrum antiviral potency of VV116 against SARS-CoV-2 variants of concern (VOCs), HCoV-OC43, and HCoV-229E in various cell lines. In vitro drug combination screening targeted RdRp and proteinase, highlighting the synergistic effect of VV116 and nirmatrelvir on HCoV-OC43 and SARS-CoV-2. When co-administrated with ritonavir, the combination of VV116 and nirmatrelvir showed significantly enhanced antiviral potency with noninteracting pharmacokinetic properties in mice. Our findings will facilitate clinical treatment with VV116 or VV116+nirmatrelvir combination to fight coronavirus infection.
Topics: Humans; Animals; Mice; COVID-19; SARS-CoV-2; Antiviral Agents; Coronavirus OC43, Human
PubMed: 37735468
DOI: 10.1038/s41392-023-01587-1 -
Vascular Health and Risk Management 2007The use of enoxaparin in conjunction with thrombolysis in ST-elevation acute myocardial infarction (STEMI), has been recently investigated in several clinical trials. In... (Review)
Review
The use of enoxaparin in conjunction with thrombolysis in ST-elevation acute myocardial infarction (STEMI), has been recently investigated in several clinical trials. In 8 published open-label studies including about 10,000 patients, in which enoxaparin was compared to either placebo or unfractionated heparin (UFH), a general superiority of enoxaparin on both reinfarction/recurrent angina and patency of the infarct-related artery, was observed. Overall, bleeding rate with enoxaparin was higher than with placebo and comparable to UFH, with the exception of one study where pre-hospital administration induced a doubled incidence of intracranial bleeding in patients older than 75 years. In a recent double-blind, randomized, mega-trial including over 20,000 patients, the superior efficacy on in-hospital and 30-day adverse cardiac events (namely reinfarction), and comparable safety on intracranial bleedings of enoxaparin compared to UFH, was definitively proven. In conclusion, initial intravenous bolus of enoxaparin followed by twice daily subcutaneous administration for about 1 week should be considered instead of intravenous UFH for the treatment of patients with STEMI receiving thrombolysis. Along with its easiness of use, not requiring laboratory monitoring, the subcutaneous administration of enoxaparin allows extended antithrombotic treatment, while permitting early mobilization (and rehabilitation) of patients.
Topics: Clinical Trials as Topic; Enoxaparin; Hemorrhage; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Myocardial Infarction
PubMed: 18078020
DOI: No ID Found -
Psychopharmacology Bulletin Jan 2017Disasters are mega-scale catastrophic events which cause trauma and mental health sequelae. A review of early pharmacological interventions for the prevention of... (Review)
Review
BACKGROUND
Disasters are mega-scale catastrophic events which cause trauma and mental health sequelae. A review of early pharmacological interventions for the prevention of psychiatric disorders following disasters is sorely needed.
METHODS
A literature search of "Psychiatric Sequelae AND Disasters", "Disaster mental health/Disaster psychiatry", "Psychotropics AND Disasters", and "Drug therapy AND Disasters" yielded 213 articles, 38 of which were included in the review.
RESULTS
Common post-disaster psychiatric conditions are: posttraumatic stress disorder (PTSD), depressive and anxiety disorders, substance use disorders and medically-unexplained psychological symptoms. Early psychopharmacological interventions to prevent PTSD provide promising evidence for hydrocortisone in medically ill trauma populations. Less robust benefits were noted for other pharmacological interventions. No reported trials have explored prevention of depression or other common post-disaster psychiatric conditions.
CONCLUSION
Hydrocortisone shows promise in preventing and reducing the psychiatric sequelae of PTSD following disasters. Further evaluation of hydrocortisone and other potentially beneficial psychopharmacological interventions are needed.
Topics: Anxiety Disorders; Depression; Disasters; Humans; Hydrocortisone; Mental Disorders; Mental Health; Stress Disorders, Post-Traumatic; Substance-Related Disorders; Survivors
PubMed: 28138200
DOI: No ID Found -
Kardiologia Polska 2023Percutaneous coronary intervention in high-risk patients (HRPCI) is associated with increased risk of complications. Mechanical circulatory support devices, including... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Percutaneous coronary intervention in high-risk patients (HRPCI) is associated with increased risk of complications. Mechanical circulatory support devices, including intra-aortic balloon pump (IABP) may bridge patient safely throughout the procedure.
AIM
We aimed to describe hemodynamic effects of larger (MEGA) compared to standard (STRD) volume IABP or no balloon control group (CTRL) during HRPCI.
METHODS
In this single-center, open-label randomized controlled trial HRPCI were randomly assigned to three groups according to planned hemodynamic support: MEGA, STDR and CTRL in a 1:1:1 scheme. Screening failure patients formed registry (REG). We analyzed data from pulmonary artery catheter especially cardiac output and cardiac power output (CPO) with Fick method and pulmonary artery wedge pressure (PCWP), as well as left ventricle systolic pressure (LVSP) with PIGTAIL catheter. We also calculated endocardial viability ratio (EVR) and analyzed pressure tracings from the IABP console. We compared baseline and on-support values. Final hemodynamic analysis was done on per-treatment basis, including REG patients.
RESULTS
A total of 47 patients were analyzed (16 MEGA, 10 STRD and 21 CTRL). Compared to CTRL we found significant increase from baseline to on-support value for cardiac output and CPO in the MEGA, but not in the STRD group. The change in EVR (increase) and in LVSP (decrease) was significant equally in MEGA and STRD vs. CTRL group, but PCWP did not change significantly for both balloons vs. CTRL. Diastolic augmented pressure with IABP was higher in MEGA than STRD and was positively correlated with systolic unloading.
CONCLUSIONS
We observed more favorable hemodynamic effects of larger compared to standard volume balloon.
Topics: Humans; Hemodynamics; Cardiac Output; Heart; Cardiac Catheters; Percutaneous Coronary Intervention
PubMed: 38189506
DOI: 10.33963/v.kp.98410 -
BMJ Open Ophthalmology 2022The current grading of retinopathy of prematurity (ROP) does not sufficiently discriminate disease severity for evaluation of trial interventions. The published ROP... (Randomized Controlled Trial)
Randomized Controlled Trial
Evaluation of the Retinopathy of Prematurity Activity Scale (ROP-ActS) in a randomised controlled trial aiming for prevention of severe ROP: a substudy of the Mega Donna Mega trial.
OBJECTIVE
The current grading of retinopathy of prematurity (ROP) does not sufficiently discriminate disease severity for evaluation of trial interventions. The published ROP Activity Scales (original: ROP-ActS and modified: mROP-ActS), describing increasing severity of ROP, versus the categorical variables severe ROP, stage, zone and plus disease were evaluated as discriminators of the effect of an ROP preventive treatment.
METHODS AND ANALYSIS
The Mega Donna Mega trial investigated ROP in infants born <28-week gestational age (GA), randomised to arachidonic acid (AA) and docosahexaenoic acid (DHA) supplementation or no supplementation. Of 207 infants, 86% with finalised ROP screening were included in this substudy. ROP-ActS versus standard variables were evaluated using Fisher's non-parametric permutation test, multivariable logistic and linear regression and marginal fractional response models.
RESULTS
The AA:DHA group (n=84) and the control group (n=93) were well balanced. The maximum ROP-ActS measurement was numerically but not significantly lower in the AA:DHA group (mean: 4.0 (95% CI 2.9 to 5.0)) versus the control group (mean: 5.3 (95% CI 4.1 to 6.4)), p=0.11. In infants with any ROP, the corresponding scale measurements were 6.8 (95% CI 5.4 to 8.2) and 8.7 (95% CI 7.5 to 10.0), p=0.039. Longitudinal profiles of the scale were visually distinguished for the categories of sex and GA for the intervention versus control.
CONCLUSIONS
The preventive effect of AA:DHA supplementation versus no supplementation was better discriminated by the trial's primary outcome, severe ROP, than by ROP-ActS. The sensitivity and the linear qualities of ROP-ActS require further validations on large data sets and perhaps modifications.
TRIAL REGISTRATION NUMBER
NCT03201588.
Topics: Arachidonic Acid; Docosahexaenoic Acids; Gestational Age; Humans; Infant; Infant, Low Birth Weight; Infant, Newborn; Infant, Premature, Diseases; Retinopathy of Prematurity
PubMed: 35495419
DOI: 10.1136/bmjophth-2021-000923 -
British Journal of Clinical Pharmacology Apr 1997The reliable detection of moderate differences in major health outcomes that arise as a result of treatment requires large-scale randomized evidence (and the appropriate... (Review)
Review
The reliable detection of moderate differences in major health outcomes that arise as a result of treatment requires large-scale randomized evidence (and the appropriate interpretation of this evidence once it has been generated). This may take the form of a single mega-trial or, exceptionally, a meta-analysis of many smaller randomized trials may provide worthwhile information. Small or non-randomized studies cannot generally be trusted to distinguish reliably between a moderate benefit, a moderate hazard, and a negligible difference in major outcomes. Simple design, streamlined data collection, and use of the "uncertainty principle' to guide eligibility would all encourage the recruitment of larger samples in randomized trials. Future trials need to adopt these methods in order to detect any moderate improvements in major outcomes that may await discovery.
Topics: Clinical Trials, Phase III as Topic; Ethics, Medical; Humans; Meta-Analysis as Topic; Outcome Assessment, Health Care; Randomized Controlled Trials as Topic; Reproducibility of Results; Risk Factors; Sample Size; Selection Bias; Treatment Outcome
PubMed: 9146845
DOI: 10.1046/j.1365-2125.1997.00569.x -
Biomedicines Mar 2023Schizophrenia is among the fifteen most disabling diseases worldwide. Negative symptoms (NS) are highly prevalent in schizophrenia, negatively affect the functional... (Review)
Review
Schizophrenia is among the fifteen most disabling diseases worldwide. Negative symptoms (NS) are highly prevalent in schizophrenia, negatively affect the functional outcome of the disorder, and their treatment is difficult and rarely specifically investigated. Serotonin-dopamine activity modulators (SDAMs), of which aripiprazole, cariprazine, brexpiprazole, and lumateperone were approved for schizophrenia treatment, represent a possible therapy to reduce NS. The aim of this rapid review is to summarize the evidence on this topic to make it readily available for psychiatrists treating NS and for further research. We searched the PubMed database for original studies using SDAM, aripiprazole, cariprazine, brexpiprazole, lumateperone, schizophrenia, and NS as keywords. We included four mega-analyses, eight meta-analyses, two post hoc analyses, and 20 clinical trials. Aripiprazole, cariprazine, and brexpiprazole were more effective than placebo in reducing NS. Only six studies compared SDAMs with other classes of antipsychotics, demonstrating a superiority in the treatment of NS mainly for cariprazine. The lack of specific research and various methodological issues, related to the study population and the assessment of NS, may have led to these partial results. Here, we highlight the need to conduct new methodologically robust investigations with head-to-head treatment comparisons and long-term observational studies on homogeneous groups of patients evaluating persistent NS with first- and second-generation scales, namely the Brief Negative Symptom Scale and the Clinical Assessment Interview for Negative Symptoms. This rapid review can expand research on NS therapeutic strategies in schizophrenia, which is fundamental for the long-term improvement of patients' quality of life.
PubMed: 36979900
DOI: 10.3390/biomedicines11030921 -
Stem Cells International 2015Induced pluripotent stem cells (iPSCs) could be employed in the creation of patient-specific stem cells, which could subsequently be used in various basic and clinical... (Review)
Review
Induced pluripotent stem cells (iPSCs) could be employed in the creation of patient-specific stem cells, which could subsequently be used in various basic and clinical applications. However, current iPSC methodologies present significant hidden risks with respect to genetic mutations and abnormal expression which are a barrier in realizing the full potential of iPSCs. A chemical approach is thought to be a promising strategy for safety and efficiency of iPSC generation. Many small molecules have been identified that can be used in place of exogenous transcription factors and significantly improve iPSC reprogramming efficiency and quality. Recent studies have shown that the use of small molecules results in the generation of chemically induced pluripotent stem cells from mouse embryonic fibroblast cells. These studies might lead to new areas of stem cell research and medical applications, not only human iPSC by chemicals alone, but also safe generation of somatic stem cells for cell based clinical trials and other researches. In this paper, we have reviewed the recent advances in small molecule approaches for the generation of iPSCs.
PubMed: 25922608
DOI: 10.1155/2015/794632