Lipid profile after switching from TDF (tenofovir disoproxil)-containing to TAF (tenofovir alafenamide)-containing regimen in virologically suppressed people living with HIV

Background. Tenofovir disoproxil fumarate (TDF) or its prodrug tenofovir alafenamide fumarate (TAF) are currently being recommended in treatment of HIV infection. Distinct pharmacological properties of these two forms of a this drug make TAF treatment less nephrotoxic and lead to better impact on bone density. Nevertheless, there is a rising concern about possible metabolic adverse effects of TAF. The purpose of this study was to evaluate the effects on the lipid profile among ART (antiretroviral therapy)-experienced patients switching from TDF‑containing to TAF‑containing regimen in the first year after the switch. Methods. Demographic and clinical data of HIV‑positive ART‑experienced patients treated in infectious diseases department was retrospectively collected. Changes of lipid profile with regards to baseline BMI, age and time of ART duration were analyzed. Results. In the group of 36 patients there was a significant increase in total cholesterol levels (+18.43 mg/dl, SD = 23.86 mg/dl, p < 0.0001) and LDL levels (+13.75 mg/dl SD = 23.05 mg/dl, p = 0.001) in first 12 months after switching from TDF‑containing to TAF‑containing regimen. There were no statistically significant changes in both HDL and TG levels observed. Analysis of total cholesterol and LDL levels in certain subpopulations revealed a significant increase within first year after the switch in patients younger than 40 years old and in those whose BMI was within normal range. Conclusions. Presented data suggests that switching from TDF to TAF in ART‑experienced patients may be associated with worsening lipid parameters. Early detection and management of dyslipidemias among HIV‑positive patients are needed

Diagnosis and treatment of rhabdomyosarcomas

Rhabdomyosarcoma (RMS) is a soft tissue sarcoma. The primary tumor is most commonly localized in the head and neck, the urogenital system, or the limbs. Classification by the World Health Organization has distinguished four histopathological RMS subtypes: embryonal, alveolar, pleomorphic, and spindle cell/sclerosing. Differential diagnosis of RMS includes melanoma, malignant neoplasm of peripheral nerve sheaths, liposarcoma, and PEComa. Among typical cytogenetic changes in RMS are chromosomal translocations t(2;13)(q35;q14) and t(1;13) (p36;q14). They lead to the formation of fusion genes that have a prognostic value. In the course of RMS, changes may also be present in signaling pathways, including RAS-PI3K, Wnt/b-catenin, receptor tyrosine kinase pathways, and myogenesis regulation. In 30% of patients at the time of diagnosis of RMS, distant metastases are present, most commonly to lungs, lymph nodes, bones, and bone marrow. Treatment of patients with RMS requires a multidisciplinary approach, and steadily perfected diagnostic techniques contribute to the individualization of therapeutic strategies. Optimal treatment of localized RMS is based on surgery combined with radiotherapy and chemotherapy. If distant metastases are present, the basic therapeutic method is multidrug chemotherapy, most frequently based on vincristine, dactinomycin, ifosfamide/cyclophosphamide, and etoposide. Despite intensive treatment, the 5-year survival index for RMS is not greater than 50%. There are still no unequivocal guidelines concerning the treatment in patients with local or distant recurrences

Multicenter registry of Impella-assisted high-risk percutaneous coronary interventions and cardiogenic shock in Poland (IMPELLA-PL)

Background: Impella is a percutaneous mechanical circulatory support device for treatment of cardiogenic shock (CS) and high-risk percutaneous coronary interventions (HR-PCIs). IMPELLA-PL is a national retrospective registry of Impella-treated CS and HR-PCI patients in 20 Polish interventional cardiological centers, conducted from January 2014 until December 2021.Aims: We aimed to determine the efficacy and safety of Impella using real-world data from IMPELLA-PL and compare these with other registries.Methods: IMPELLA-PL data were analyzed to determine primary endpoints: in-hospital mortality and rates of mortality and major adverse cardiovascular and cerebrovascular events (MACCE) at 12 months post-discharge.Results: Of 308 patients, 18% had CS and 82% underwent HR-PCI. In-hospital mortality rates were 76.4% and 8.3% in the CS and HR-PCI groups, respectively. The 12-month mortality rates were 80.0% and 18.2%, and post-discharge MACCE rates were 9.1% and 22.5%, respectively. Any access site bleeding occurred in 30.9% of CS patients and 14.6% of HR-PCI patients, limb ischemia in 12.7% and 2.4%, and hemolysis in 10.9% and 1.6%, respectively.Conclusions: Impella is safe and effective during HR-PCIs, in accordance with previous registry analyses. The risk profile and mortality in CS patients were higher than in other registries, and the potential benefits of Impella in CS require investigation

Dopamine D1 Receptor in Cancer

Dopamine is a biologically active compound belonging to catecholamines. It plays its roles in the human body, acting both as a circulating hormone and neurotransmitter. It acts through G-protein-coupled receptors divided into two subgroups: D1-like receptors (D1R and D5R) and D2-like receptors (D2R, D3R, D4R). Physiologically, dopamine receptors are involved in central nervous system functions: motivation or cognition, and peripheral actions such as blood pressure and immune response modulation. Increasing evidence indicates that the dopamine D1 receptor may play a significant role in developing different human neoplasms. This receptor&rsquo;s value was presented in the context of regulating various signaling pathways important in tumor development, including neoplastic cell proliferation, apoptosis, autophagy, migration, invasiveness, or the enrichment of cancer stem cells population. Recent studies proved that its activation by selective or non-selective agonists is associated with significant tumor growth suppression, metastases prevention, and tumor microvasculature maturation. It may also exert a synergistic anti-cancer effect when combined with tyrosine kinase inhibitors or temozolomide. This review provides a comprehensive insight into the heterogeneity of dopamine D1 receptor molecular roles and signaling pathways in human neoplasm development and discusses possible perspectives of its therapeutic targeting as an adjunct anti-cancer strategy of treatment. We highlight the priorities for further directions in this research area