Safety and efficacy of individualised exercise and NAD+ precursor supplementation in patients with Friedreich's ataxia in the USA: a single-centre, 2 × 2 factorial, randomised controlled trial.

Atezolizumab and Stereotactic Body Radiation in Metastatic, Recurrent, or Persistent Cervical Cancer: Results From a Phase 2 Multi-Institutional Study.

Effect of in vitro synergy and additivity of vancomycin or daptomycin plus an antistaphylococcal β-lactam for methicillin-resistant Staphylococcus aureus bacteraemia on mortality: preplanned analysis from CAMERA2.

The combined use of sodium-glucose cotransporter-2 inhibitors (SGLT2is) and glucagon-like peptide-1 receptor agonists (GLP-1RAs) may provide synergistic benefits for liver fibrosis in patients with metabolic dysfunction-associated steatotic liver disease (MASLD) and type 2 diabetes mellitus (T2DM). We evaluated the comparative effectiveness of GLP-1RA plus SGLT2i versus GLP-1RA monotherapy on liver fibrosis progression. We conducted a retrospective cohort study using data from the Mass General Brigham healthcare network (2010-2024). Adults with MASLD and T2DM initiating GLP-1RA therapy were included if their baseline FIB-4 scores indicated low-risk (<1.3) or intermediate-risk (1.3-2.67) categories. Combination therapy was defined as concurrent SGLT2i use for ≥50% of the GLP-1RA treatment period. The primary outcome was fibrosis progression, defined as advancement to a high-risk FIB-4 category. The secondary outcome was hepatic complications (cirrhosis, hepatocellular carcinoma, liver transplantation, or decompensation). Propensity score matching (1:2) was performed to minimize confounding. After matching, 879 combination therapy users were compared with 1690 monotherapy users. Combination therapy was associated with a significantly lower risk of fibrosis progression (3.10 vs. 4.01/100 person-years; HR 0.76, 95% CI 0.61-0.95) and a numerically lower incidence of hepatic complications (1.05 vs. 1.34/100 person-years; HR 0.76, 95% CI 0.53-1.09). Subgroup analyses showed consistent protective associations, with a significant benefit observed among patients with a BMI ≤35. Sensitivity analyses confirmed reduced fibrosis progression in both the ≥90-day and ≥180-day landmark analyses. GLP-1RA plus SGLT2i therapy was associated with reduced fibrosis progression compared with GLP-1RA monotherapy in MASLD and T2DM.

Rhabdomyosarcoma (RMS) is the most common type of soft tissue sarcoma in children. Intensifying chemotherapy has failed to improve patient survival for metastatic or relapsed RMS and RMS survivors often suffer from significant long‑term toxicities. More efficient and less toxic new therapies are critically needed. RMS expresses high levels of anti‑apoptotic protein Bcl‑2 and an oncogenic transcription factor Forkhead box protein M1 (FOXM1), which is also known to inhibit tumor cell apoptosis. The present study used a combination therapy of a recently developed non‑toxic FOXM1 inhibitor, RCM‑1 and the FDA‑approved Bcl2 inhibitor, venetoclax, which is not effective as a monotherapy in solid tumors. Compared with venetoclax alone, the combination therapy efficiently inhibited RMS growth in the animal model by decreasing tumor cell proliferation and inducing tumor cell apoptosis. RNA‑sequencing analysis demonstrated that the combination therapy uniquely decreased expression of ATPase Plasma Membrane Ca2+ Transporting 4 (ATP2B4), a plasma membrane calcium channel that is highly expressed in RMS compared with normal muscle cells. RCM‑1, but not venetoclax treatment, inhibited ATP2B4 and enhanced the sensitivity of RMS cells to apoptosis. Knockdown of ATP2B4 decreased RMS tumor cell proliferation, migration and colony formation in vitro. Furthermore, knockdown of ATP2B4 increased tumor cell apoptosis, while overexpression of ATP2B4 decreased tumor cell apoptosis in vitro. In the animal model of RMS, depletion of ATP2B4 decreased tumor growth. In summary, combining RCM‑1 with venetoclax sensitized RMS cells to apoptosis by decreasing ATP2B4. This made ATP2B4 a promising therapeutic target for RMS and provides a rationale for exploring this combination in early‑stage clinical trials.

Tunable microgel modulars for temporally coordinated combination therapy.

Combination therapy with immune checkpoint inhibitors (ICIs) has become a standard treatment for metastatic renal cell carcinoma (mRCC). However, ICIs may also cause immune-related adverse events. We report a case of mRCC that developed fulminant immune-related enterocolitis. A 79-year-old man received ICIs therapy for mRCC and was urgently hospitalized because of worsening diarrhea. Despite the initiation of steroid therapy, circumferential intestinal necrosis developed, necessitating subtotal colectomy. The patient subsequently developed cytomegalovirus- and Epstein-Barr virus-associated enterocolitis and died from extensive intestinal necrosis caused by severe thrombosis secondary to disseminated intravascular coagulation. Persistent diarrhea during ICIs therapy requires prompt evaluation and specialist consultation, even when symptoms appear mild, as they may signal immune-related enterocolitis. Clinicians should also remain vigilant for infectious complications, which can exacerbate the severity of immune-related enterocolitis and lead to life-threatening outcomes.

Comparative effectiveness of CPAP and isolated or combined non-invasive therapies for obstructive sleep apnea: A network meta-analysis.

Combination therapy with amphotericin B and Ultradiluted Leishmania donovani antigen skews cytokine balance towards protective immunity in visceral leishmaniasis.

A 37-year-old woman with metastatic invasive ductal carcinoma, resistant to anti-HER 2 therapy, underwent [ 177 Lu]Lu-FAPI-2286 radionuclide therapy combined with antibody-drug conjugate chemotherapy. Baseline [ 68 Ga]Ga-FAPI-2286 PET/CT confirmed extensive fibroblast activation protein expression in metastatic sites. After 5 cycles, follow-up imaging showed a significant reduction in FAPI uptake in skin lesions, resolution of bone lesions, and decreased pleural thickening. Clinically, the patient reported pain relief and resolution of lymphedema. However, new metastases emerged in cervical, mediastinal, and abdominopelvic lymph nodes, indicating a heterogeneous response, and biopsy of these newly emerged lymph nodes confirmed disease recurrence.

The role of OX40 in cancer immunotherapy: A comprehensive review from mechanisms to clinical applications.

Dual inhibition of sclerostin and Notum induces synergistic osteoanabolic action in mice.

Design of PROGRESSION-IPF: A pragmatic, open-label, randomized trial of patients with progressive disease in idiopathic pulmonary fibrosis.

Systematic review and meta-analysis of Tongxinluo capsules combined with statins in the treatment of carotid atherosclerosis.

LAMC3 promotes the development of prostate cancer via modulating the cell cycle progression.

Optimal control of Alzheimer's disease model via multi-target combination therapy.

Biomimetic cell membrane-mediated nanodelivery platform based on natural products: Emerging strategies for cancer combination therapy.

Phase Ia/Ib trial of the safety and efficacy of mobocertinib in combination with T-DM1 for patients with HER2-mutant solid tumors (WJOG16022M).

The caspase 11/gasdermin D pathway is a key driver of stress-induced neuroinflammation and behavioral dysfunction in rats.

Physics-informed neural networks enable patient-specific tumor microenvironment modeling: Identifying parameters in combined immune therapy with integer- and fractional-order dynamics