Definition of therapeutic effect

Non-junctional connexin43 (Cx43) plasma membrane hemichannels have been implicated in several inflammatory diseases, particularly playing a role in ATP release that triggers activation of the inflammasome. Therapies targeting the blocking of the hemichannels to prevent the pathological release or uptake of ions and signalling molecules through its pores are of therapeutic interest. To date, there is no close-to-native, high-definition documentation of the impact of Cx43 hemichannel-mediated inflammation on cellular ultrastructure, neither is there a robust account of the ultrastructural changes that occur following treatment with selective Cx43 hemichannel blockers such as Xentry-Gap19 (XG19)...

Anterior cutaneous nerve entrapment syndrome (ACNES) is a cause of moderate to severe chronic pain, hyperesthesia/hypoesthesia, and altered perception of heat/cold in a specific region of the anterior abdominal wall, referable to the territory of innervation of one or more anterior branches of the intercostal nerves. None of the therapeutic options currently available has proved to be effective in the long term or decisive. In recent years, we have begun to treat purely sensory neuropathies, such as this, with the implantation of wireless peripheral nerve stimulators (PNS), achieving the safety of modular and personalized analgesia...

This case study reports a patient with Myosin Heavy Chain 9 (MYH9)-related disorder (MYH9-RD) which is characterized by congenital macrothrombocytopenia, Döhle-like bodies, sensorineural hearing loss, cataracts, and glomerulopathy. Often misdiagnosed as idiopathic thrombocytopenic purpura (ITP), MYH9-RD requires accurate identification to avoid inappropriate treatments like steroids, rituximab, or splenectomy. Platelet transfusions were traditionally the only therapeutic option, but thrombopoietin receptor agonists (TPO-RA), specifically eltrombopag, have shown success in MYH9-RD treatment...

BACKGROUND: Aggressive care near patients' end-of-life (EOL) entails limited therapeutic values, high costs, and compromised quality of life (QoL). In this study, we aimed to estimate the global prevalence of aggressive care in patients with cancer and explore potential subgroup differences. METHODS: We searched PubMed, Embase, and the Cochrane Library from database inception to Feb 16, 2024. Eligible studies reported the prevalence of aggressive EOL care using at least one quantifiable measure...

BACKGROUND: Aortic Aneurysm and Dissection (AAD) are severe cardiovascular conditions with potentially lethal consequences such as aortic rupture. Existing studies suggest that liraglutide, a long-acting glucagon-like peptide receptor (GLP-1R) agonist, offers protective benefits across various cardiovascular diseases. However, the efficacy of liraglutide in mitigating AAD development is yet to be definitively elucidated. METHODS: Ang II (Angiotension II) infusion of APOE-/- mouse model with intraperitoneal injection of liraglutide (200ug/kg) to study the role of GLP-1R in AAD formation...

OBJECTIVES: Health technology assessment (HTA) does not systematically account for the circumstances and needs of children and youth. To supplement HTA processes, we aimed to develop a child-tailored value assessment framework using a multi-criteria decision analysis (MCDA) approach. METHODS: We constructed an MCDA-based model in multiple phases to create the Comprehensive Assessment of Technologies for Child Health (CATCH) framework. Using a modified Delphi process with stakeholders having broad disciplinary and geographic variation (n=23), we refined previously generated criteria and developed rank-based weights...

Radiation toxicities may be underestimated after treatment of transitional cell carcinoma in dogs' lower urinary tract. Assessing acute and late toxicities and differentiating them from progressive disease (PD) impacts further therapeutic approach. We retrospectively assessed dogs treated with definitive-intent chemoradiotherapy (12 × 3.8 Gy, various first-line chemotherapeutics). Local tumour control, radiation toxicities and survival were evaluated. We classified radiation toxicities according to the previously published radiation toxicity scheme "VRTOG" as well as the updated version, "VRTOG_v2...

Vitiligo is a complex skin disorder that involves oxidative stress and inflammatory responses and currently lacks a definitive cure. Transcutaneous auricular vagus nerve stimulation (taVNS) is a noninvasive method for targeting the auricular branch of the vagus nerve and has gained widespread attention for potential intervention in the autonomic nervous system. Although previous research has suggested that vagus nerve stimulation can potentially inhibit inflammatory responses, its specific role and mechanisms in vitiligo treatment remain unknown...

In all mammals, the circulating pool of MLTs is synthesized in the pineal gland during the night's darkness hours. Its main function is synchronizing the organism in the photoperiod. In contrast, extra-pineal MLT is synthesized in peripheral organs, does not follow any circadian rhythm or circulate, and plays a detoxifying and cytoprotective role. Circulating MLT may stimulate both innate and acquired immune responses through its circadian action and by activating high-affinity receptors on immunocompetent cells...

Therapeutic recombinant proteins are powerful tools used for the treatment of many detrimental diseases such as diabetes, cancer, multiple sclerosis, rheumatoid arthritis, hepatitis, and many more. Their importance in disease therapy is growing over small molecule drugs because of their advantages like specificity and reduced side effects. However, the large-scale production of certain recombinant proteins is still challenging despite impressive advancements in biomanufacturing. The complement cascade is considered a rich source of drug targets and natural regulator proteins with great therapeutic potential...

Cisplatin-based chemotherapy has been the standard of care in metastatic urothelial cancer (mUC) for more than two decades. However, many patients with comorbidities cannot receive cisplatin or its alternative, carboplatin. 'Cisplatin-ineligible' and 'platinum-ineligible' patients lacked effective therapy options. However, the recent combination of enfortumab vedotin (EV), an antibody-drug conjugate targeting Nectin-4, with pembrolizumab (P), an antibody targeting the programmed death-1 (PD-1) immune checkpoint, is changing the status quo of frontline mUC treatment, with potential synergy seen in the EV-103 and EV-302 clinical trials...

The placebo effect is now generally defined widely as an individual's response to the psychosocial context of a clinical treatment, as distinct from the treatment's characteristic physiological effects. Some researchers, however, argue that such a wide definition leads to confusion and misleading implications. In response, they propose a narrow definition restricted to the therapeutic effects of deliberate placebo treatments. Within the framework of modern medicine, such a scope currently leaves one viable placebo treatment paradigm: the non-deceptive and non-concealed administration of "placebo pills" or open-label placebo (OLP) treatment...

BACKGROUND: While observation studies have shown a positive correlation between inflammatory bowel disease (IBD) and the risk of nonmalignant digestive system diseases, a definitive causal relationship has not yet been clearly established. METHODS: Mendelian randomization (MR) was employed to investigate the potential causal association between genetic susceptibility to IBD and nonmalignant gastrointestinal diseases. Genetic variants were extracted as instrumental variables (IVs) from a genome-wide association study (GWAS) meta-analysis, which included 12,194 cases of Crohn's disease (CD) and 28,072 control cases of European ancestry...

BACKGROUND: Severe aplastic anemia (SAA) is a syndrome of bone marrow failure which is life-threatening. Recent studies have demonstrated that CD4 + T cell subsets, including T regulatory (Treg) and T helper 17 (Th17) cells, play a pivotal role in the pathogenesis of SAA. Formononetin (FMN) is a natural compound extracted from the traditional Chinese medicine Huangqi, which has the ability to regulate the imbalance of Treg/Th17 cells in some inflammatory diseases. Nevertheless, the therapeutic effect of FMN in SAA has yet to be definitively established...

Superiority trials are designed to test the hypothesis that a given diagnostic or therapeutic strategy is better than (i.e. "superior to") placebo or an active control. Conversely, non-inferiority trials test the hypothesis that a newer (i.e. alternative) strategy is not "unacceptably worse" than a control (i.e. "traditional", or "older") strategy. Non-inferiority trials are increasingly conducted in clinical medicine more often when a "newer" strategy is supposed to offer a relevant advantage in terms other than clinical efficacy (i...

INTRODUCTION: Lichen planopilaris (LPP) is one of the most common causes of scarring hair loss caused by immune-mediated inflammation resulting in atrophy and scaling. The key to preventing this irreversible hair loss is diagnosing and starting treatment at the earliest possible stage. As there is no definite cure for LPP, the therapy could be challenging. In the study, we conducted a single-blinded randomized clinical trial to evaluate the therapeutic effects, safety, and tolerability of platelet-rich plasma versus topical clobetasol in the treatment of LPP...

BACKGROUND: Neuromyelitis optica spectrum disorder (NMOSD) is a rare and debilitating disease that has become more widely recognized in China. Legislative measures have been implemented by the government to improve treatment access for rare diseases. OBJECTIVES: To investigate the diagnostic journey, treatment status, treatment accessibility, and treatment satisfaction of the NMOSD patients on disease-modifying therapies (DMTs) in China. DESIGN: A patient online survey...

The opioid crisis is an international public health concern. Treatments for opioid use disorder centre largely on the management of opioid withdrawal, an aversive collection of signs and symptoms that contribute to opioid use disorder. Whereas in the past 50 years more than 90 medications have been developed for depression, only five medications have been developed for opioid use disorder during this period. We posit that underinvestment has occurred in part due to an underdeveloped understanding of opioid withdrawal syndrome...

Metabolic dysfunction-associated steatotic liver disease (MASLD), previously known as nonalcoholic fatty liver disease (NAFLD), is the main cause of chronic liver disease in children and adolescents. Indeed, epidemiological studies have shown that MASLD affects up to 40% of children with obesity. Despite the recent approval of medications that target weight loss in adolescents that could have benefits on pediatric MASLD, lifestyle interventions, such as diet and exercise, remain the mainstay of our therapeutic approach...

BACKGROUND: White matter hyperintensities (WMHs) are associated with higher anxiety or depression (A/D) incidence. We investigated associations of WMHs with A/D, cerebrovascular reactivity (CVR), and functional connectivity (FC) to identify potential pathomechanisms. METHODS: Participants with WMH (n = 239) and normal controls (NCs, n = 327) were assessed for A/D using the Hamilton Anxiety Rating Scale (HAMA) and Hamilton Depression Rating Scale (HAMD)...