Medicines, Volume 7, Issue 5 (May 2020) – 8 articles

Background: The pharmacologic management of heart failure with preserved ejection fraction (HFpEF) involves far fewer options with demonstrated additional benefit. Therefore, we examined the effect of combination of multiple classes of HF medication in the 30-day hospital readmission in patients with HFpEF. Methods: All adult patients discharged with a diagnosis of HFpEF and a left ventricular ejection fraction (LVEF) of ≥ 50% reported during the admission or within the previous six months from our institution were retrospectively studied for a 30-day hospital readmission risk. Individual as well as combination drug therapy at the time of hospital discharge were evaluated using Pearson chi² test and multivariate logistic regression. Results: The overall 30-day readmission rate in this HFpEF cohort of 445 discharges was 29%. Therapy with loop diuretics (p = 0.011), loop diuretics and angiotensin receptor blocker (p = 0.043) and loop diuretics and beta blockers (p = 0.049) were associated with a lower risk of 30-day hospital readmission. Multivariate logistic regression revealed only loop diuretics to be associated with a lower risk of hospital readmission in patients with HFpEF (OR 0.59; 95% CI, 0.39-0.90; p = 0.013). Conclusions: Our study revealed that loop diuretics at discharge decreases early readmission in patients with HFpEF. Further, our study highlights the implication of a lack of guidelines and treatment challenges in HFpEF patients and emphasizes the importance of a conservative approach in preventing early readmission in patients with HFpEF. Full article

Background: The prognosis of children with diffuse intrinsic pontine glioma (DIPG) remains dismal despite radio- and chemotherapy or molecular-targeted therapy. Immunotherapy is a powerful and promising approach for improving the overall survival (OS) of children with DIPG. Methods: A retrospective analysis for feasibility, immune responsiveness, and OS was performed on 41 children treated in compassionate use with multimodal therapy consisting of Newcastle disease virus, hyperthermia, and autologous dendritic cell vaccines as part of an individualized combinatorial treatment approach for DIPG patients. Results: Patients were treated at diagnosis (n = 28) or at the time of progression (n = 13). In the case of 16 patients, histone H3K27M mutation was confirmed by analysis of biopsy (n = 9) or liquid biopsy (n = 9) specimens. PDL1 mRNA expression was detected in circulating tumor cells of ten patients at diagnosis. Multimodal immunotherapy was feasible as scheduled, until progression, in all patients without major toxicity. When immunotherapy was part of primary treatment, median PFS and OS were 8.4 m and 14.4 m from the time of diagnosis, respectively, with a 2-year OS of 10.7%. When immunotherapy was given at the time of progression, median PFS and OS were 6.5 m and 9.1 m, respectively. A longer OS was associated with a Th1 shift and rise in PanTum Detect test scores. Conclusions: Multimodal immunotherapy is feasible without major toxicity, and warrants further investigation as part of a combinatorial treatment approach for children diagnosed with DIPG. Full article

Background: Implant-assisted breast augmentation is among the most performed surgeries performed by plastic surgeons today. This prospective study evaluated the patient satisfaction and complication rates using high-profile round silicone implant alone (traditional breast augmentation) Group A versus the high-profile round silicone implant assisted with stromal enriched lipograft (composite breast augmentation) Group B. Methods: A total of 50 female patient candidates to undergo breast augmentation between January to September 2017 were randomly assigned to either group. The periareolar technique for breast augmentation and the subfascial plane were used in both groups for the insertion of the high-profile round silicone implants. The stromal enriched lipograft (SEL) was used in Group B for the preparation of the autologous fat grafting to the breast. The satisfaction of each patient with body appearance following breast augmentation was rated using an already published scale of 1–5. The rate of complications was analysed. Results: AS performed all the surgeries. In Group A, the age range was between 19 and 48 years (mean of 22.5 years). In Group B, the age range was between 20 and 47 years (mean of 24.1 years). The average BMI of Group A was 24 m/kg² and 23 m/kg² of Group B. Patient satisfaction meta-analysis for Group A and B at 12 months shows that patients in Group B expressed a satisfaction that is superior when compared to Group A patients. The ability to camouflage the implant could explain the higher satisfaction rates in Group B. The rate of complications appears similar in both groups. Conclusions: Composite breast augmentation using a combination of round high-profile implants and SEL in breast augmentation can achieve a higher patient satisfaction and aesthetic outcome as compared to the round high-profile breast augmentation alone. The technique is safe, simple and fast with low complication rates. Large multicentre, controlled, prospective studies need to be performed to further confirm the favourable results that were observed in this study. Full article

Background: Although many therapeutic approaches have been attempted to treat spinal cord injury, cellular transplantation offers the greatest promise in reconstituting the architecture of the damaged cord. Methods: A literature review was conducted to search for clinical trials investigating stem cells as treatment for spinal cord injury in the United States. Results: Overall, eight studies met inclusion criteria. Of the included studies, four were identified as being terminated, suspended, or not yet recruiting. Two studies were identified as currently recruiting, including one phase one trial evaluating stereotactic injections of human spinal cord-derived neural stem cells in patients with chronic spinal cord injuries, and one trial of transplantation of autologous bone marrow derived stem cells via paraspinal injections, intravenous injections, and intranasal placement. One study was identified as an active study, a phase one trial of intrathecal injection of 100 million autologous, ex-vivo expanded, adipose-derived mesenchymal stem cells. One trial that was listed as completed is a phase 1/2a, dose escalation study, investigating stereotactic injection of human embryonic stem cell derived oligodendrocyte progenitor cells. Conclusions: Although few significant publications have emerged to this point, current trial results are promising. Full article

The present editorial serves as an introduction to the Special Issue “Antioxidant and Anti-aging Action of Plant Polyphenols”. It also provides a summary of the polyphenols, their biological properties and possible functions as medicines, the importance of traditional medicines as a source of inspiration, the rationalization of new uses of plant extracts which lead to applications in modern medicine, the status of modern green-chemistry extraction methods, and some reflections on future prospects. Here, the articles from this Special Issue, and the main aspects of the antioxidant and anti-aging effects of plant polyphenols are discussed in the form of seven questions. Full article

Background: Hypomyelinating leukodystrophy 3 (HLD3), previously characterized as a congenital diseases associated with oligodendrocyte myelination, is increasingly regarded as primarily affecting neuronal cells. Methods: We used N1E-115 cells as the neuronal cell model to investigate whether HLD3-associated mutant proteins of cytoplasmic aminoacyl-tRNA synthase complex-interacting multifunctional protein 1 (AIMP1) aggregate in organelles and affect neuronal differentiation. Results: 292CA frame-shift type mutant proteins harboring a two-base (CA) deletion at the 292th nucleotide are mainly localized in the lysosome where they form aggregates. Similar results are observed in mutant proteins harboring the Gln39-to-Ter (Q39X) mutation. Interestingly, the frame-shift mutant-specific peptide specifically interacts with actin to block actin fiber formation. The presence of actin with 292CA mutant proteins, but not with wild type or Q39X ones, in the lysosome is detectable by immunoprecipitation of the lysosome. Furthermore, expression of 292CA or Q39X mutants in cells inhibits neuronal differentiation. Treatment with ibuprofen reverses mutant-mediated inhibitory differentiation as well as the localization in the lysosome. Conclusions: These results not only explain the cell pathological mechanisms inhibiting phenotype differentiation in cells expressing HLD3-associated mutants but also identify the first chemical that restores such cells in vitro. Full article

A current research topic of great interest is the study of the therapeutic properties of plants and of their bioactive secondary metabolites. Plants have been used to treat all types of health problems from allergies to cancer, in addition to their use in the perfumery industry and as food. Hedychium species are among those plants used in folk medicine in several countries and several works have been reported to verify if and how effectively these plants exert the effects reported in folk medicine, studying their essential oils, extracts and pure secondary metabolites. Hedychium coronarium and Hedychium spicatum are the most studied species. Interesting compounds have been identified like coronarin D, which possesses antibacterial, antifungal and antitumor activities, as well as isocoronarin D, linalool and villosin that exhibit better cytotoxicity towards tumor cell lines than the reference compounds used, with villosin not affecting the non-tumor cell line. Linalool and α-pinene are the most active compounds found in Hedychium essential oils, while β-pinene is identified as the most widespread compound, being reported in 12 different Hedychium species. Since only some Hedychium species have been investigated, this review hopes to shed some light on the uncharted territory that is the Hedychium genus. Full article