L-glutamic acid-g-poly hydroxyethyl methacrylate nanoparticles: acute and sub-acute toxicity and biodistribution potential in mice

The aim of this safety study in mice was to determine in vivo toxicity and biodistribution potential of a single and multiple doses of L-glutamic acid-g-p(HEMA) polymeric nanoparticles as a drug delivery system. The single dose did not cause any lethal effect, and its acute oral LD₅₀ was >2.000 mg/kg body weight (bw). Multiple doses (25, 50, or 100 mg/kg bw) given over 28 days resulted in no significant differences in body and relative organ weights compared to control. These results are supported by biochemical and histological findings. Moreover, nanoparticle exposure did not result in statistically significant differences in micronucleus counts in bone marrow cells compared to control. Nanoparticle distribution was time-dependent, and they reached the organs and even bone marrow by hour 6, as established by ex vivo imaging with the IVIS^® spectrum imaging system. In conclusion, L-glutamic acid-g-p(HEMA) polymeric nanoparticles appear biocompatible and have a potential use as a drug delivery system.KEY WORDS: biocompatibility, blood biochemistry, genotoxicity, histology, in vivo toxicity, micronucleus test, polymers     

Pre-COVID-19 Social Determinants of Health Among Mexican Migrants in Los Angeles and New York City and Their Increased Vulnerability to Unfavorable Health Outcomes During the COVID-19 Pandemic

Journal of Immigrant and Minority Health - COVID-19 has disproportionally affected underrepresented minorities (URM) and low-income immigrants in the United States. The aim of the study is to...     

Pain in desmoid-type fibromatosis: Prevalence,determinants and prognosis value

The aim of this study is to evaluate the prevalence, determinants and prognostic value of pain at diagnosis in patients with desmoid-type fibromatosis (DF). We selected patients from the ALTITUDES cohort (NCT02867033), managed by surgery, active surveillance or systemic treatments, with pain assessment at diagnosis. Patients were invited to fill QLQ-C30 questionnaire and Hospital Anxiety Depression Scale. Determinants were identified using logistic models. Prognostic value on event-free survival (EFS) was evaluated using the Cox model. Overall, 382 patients were included in the current study (median age: 40.2 years; 117 men). The prevalence of pain was 36%, without significant difference according to first-line treatment (P = .18). In the multivariate analysis, pain was significantly associated with tumor size >50 mm (P = .013) and tumor site (P < .001); pain was more frequent in the neck and shoulder locations (odds ratio: 3.05 [1.27-7.29]). Pain at baseline was significantly associated with poor quality of life (P < .001), depression (P = .02), lower performance status (P = .03) and functional impairment (P = .001); we also observed a nonsignificant association with anxiety (P = .10). In the univariate analysis, baseline pain was associated with poor EFS; the 3-year EFS was 54% in patients with pain compared to 72% in those without pain. After adjustment for sex, age, size and line of treatment, pain was still associated with poor EFS (hazard ratio: 1.82 [1.23-2.68], P = .003). One third of recently diagnosed patients with DF experienced pain, especially those with larger tumors and neck/shoulder locations. Pain was associated with unfavorable EFS after adjustment for the confounders.     

Drezotomía en el tratamiento del dolor por desaferentización: revisión de resultados y análisis de factores predictores de éxito

Background and objectivesThe treatment of deafferentation pain by spinal DREZotomy is a proven therapeutic option in the literature. In recent years, use of DREZotomy has been relegated to second place due to the emergence of neuromodulation therapies. The objectives of this study are to demonstrate that DREZotomy continues to be an effective and safe treatment and to analyse predictive factors for success.Patients and methodsA retrospective study was conducted of all patients treated in our department with spinal DREZotomy from 1998 to 2018. Bulbar DREZotomy procedures were excluded. A visual analogue scale (VAS) and the reduction of routine medication were used as outcome variables. Demographic, clinical and operative variables were analysed as predictive factors for success.ResultsA total of 27 patients (51.9% female) with a mean age of 53.7 years underwent DREZotomy. The main cause of pain was brachial plexus injury (BPI) (55.6%) followed by neoplasms (18.5%). The mean time of pain evolution was 8.4 years with a mean intensity of 8.7 according to the VAS, even though 63% of the patients had previously received neurostimulation therapy. Favourable outcome (≥ 50% pain reduction in the VAS) was observed in 77.8% of patients during the postoperative period and remained in 59.3% of patients after 22 months average follow-up (mean reduction of 4.9 points). This allowed for a reduction in routine analgesic treatment in 70.4% of them. DREZotomy in BPI-related pain presented a significantly higher success rate (93%) than the other pathologies (41.7%) (p = .001). No association was observed between outcome and age, gender, DREZ technique, duration of pain or previous neurostimulation therapies. There were six neurological complications, four post-operative transient neurological deficits and two permanent deficits.ConclusionDorsal root entry zone surgery is effective and safe for treating patients with deafferentation pain, especially after brachial plexus injury. It can be considered an alternative treatment after failed neurostimulation techniques for pain control. However, its indication should be considered as the first therapeutic option after medical therapy failure due to its good long-term results.     

Treat-to-target strategy in patients with rheumatoid arthritis: Audit of adherence from real world clinical data

IntroductionThe current paradigm of the management of rheumatoid arthritis (RA) recommends achieving a state of remission or low disease activity through the treat-to-target strategy. Our study assesses adherence to this strategy.MethodPatients with RA (ACR-EULAR 2010 criteria) were included. From each centre, 19 patients were randomly selected. Clinical histories (CH) were assessed by independent auditors, checking compliance with predefined quality criteria. The study was approved by ethics committees.ResultsWe included 856 patients (mean age 54 years; 71% women). The use of a combined index (CI) was recorded in 61% of cases. Visits were recorded every 4 weeks using a CI in 4% of CH while attempts were made to achieve remission. Monitoring of disease activity every 6–8 months after reaching the target was recorded in 73% of cases.ConclusionsThe implementation of the treat-to-target strategy is barely recorded in patients with RA in routine clinical practice.     

Outcomes of patients with non-small cell lung cancer and poor performance status treated with immune checkpoint inhibitors in the real-world setting

International Journal of Clinical Oncology - Immune-checkpoint inhibitors (ICIs) are standard treatments for metastatic non-small cell lung cancer (NSCLC). Patients with poor performance status...     

Deep Inspiration Breath Hold Reduces the Mean Heart Dose in Left Breast Cancer Radiotherapy

BackgroundPatients with left breast cancer who undergo radiotherapy have a non-negligible risk of developing radiation-induced cardiovascular disease (CVD). Cardioprotection can be achieved through better treatment planning protocols and through respiratory gating techniques, including deep inspiration breath hold (DIBH). Several dosimetric studies have shown that DIBH reduces the cardiac dose, but clinical data confirming this effect is limited. The aim of the study was to compare the mean heart dose (MHD) in patients with left breast cancer who underwent radiotherapy at our institution as we transitioned from non-gated free-breathing (FB) radiotherapy to gated radiotherapy (FB-GRT), and finally to DIBH.Patients and methodsRetrospective study involving 2022 breast cancer patients who underwent radiotherapy at West Pomeranian Oncology Center in Szczecin from January 1, 2014 through December 31, 2017. We compared the MHD in these patients according to year of treatment and technique.ResultsOverall, the MHD for patients with left breast cancer in our cohort was 3.37 Gy. MHD values in the patients treated with DIBH were significantly lower than in patients treated with non-gated FB (2.1 vs. 3.48 Gy, p < 0.0001) and gated FB (3.28 Gy, p < 0.0001). The lowest MHD values over the four-year period were observed in 2017, when nearly 85% of left breast cancer patients were treated with DIBH. The proportion of patients exposed to high (> 4 Gy) MHD values decreased every year, from 40% in 2014 to 7.9% in 2017, while the percentage of patients receiving DIBH increased.ConclusionsCompared to free-breathing techniques (both gated and non-gated), DIBH reduces the mean radiation dose to the heart in patients with left breast cancer. These findings support the use of DIBH in patients with left breast cancer treated with radiotherapy.Key words: breast cancer, gated radiotherapy, deep inspiration breath hold, free breathing gated radiotherapy, mean heart dose     

Recent insights into the characteristics and role of peritoneal macrophages from ascites of cirrhotic patients

Macrophages are a diverse myeloid cell population involved in innate and adaptive immune responses, embryonic development, wound repair, and regulation of tissue homeostasis. These cells link the innate and adaptive immunities and are crucial in the development and sustainment of various inflammatory diseases. Macrophages are tissue-resident cells in steady-state conditions; however, they are also recruited from blood monocytes after local pathogen invasion or tissue injury. Peritoneal macrophages vary based on their cell complexity, phenotype, and functional capabilities. These cells regulate inflammation and control bacterial infections in the ascites of decompensated cirrhotic patients. Our recent work reported several phenotypic and functional characteristics of these cells under both healthy and pathological conditions. A direct association between cell size, CD14/CD16 expression, intracellular level of GATA-6, and expression of CD206 and HLA-DR activation/maturation markers, indicate that the large peritoneal macrophage CD14^highCD16^high subset constitutes the mature phenotype of human resident peritoneal macrophages during homeostasis. Moreover, elevated expression of CD14/CD16 is related to the phagocytic capacity. The novel large CD14^highCD16^high peritoneal subpopulation is increased in the ascites of cirrhotic patients and is highly sensitive to lipopolysaccharide (LPS)-induced activation, thereby exhibiting features of inflammatory priming. Thus, phosphorylation of ERK1/2, PKB/Akt, and c-Jun is remarkably increased in response to LPS in vitro, whereas that of p38 MAPK is reduced compared with the monocyte-derived macrophages from the blood of healthy controls. Furthermore, in vitro activated monocyte-derived macrophages from ascites of cirrhotic patients secreted significantly higher levels of IL-6, IL-10, and TNF-α and lower amounts of IL-1β and IL-12 than the corresponding cells from healthy donor’s blood. Based on these results, other authors have recently reported that the surface expression level of CD206 can be used to identify mature, resident, inflammatory peritoneal macrophages in patients with cirrhosis. Soluble CD206 is released from activated large peritoneal macrophages, and increased concentrations in patients with cirrhosis and spontaneous bacterial peritonitis (SBP) indicate reduced odds of survival for 90 d. Hence, the level of soluble CD206 in ascites might be used to identify patients with SBP at risk of death. In conclusion, peritoneal macrophages present in ascites of cirrhotic patients display multiple phenotypic modifications characterized by reduced ratio of cells expressing several membrane markers, together with an increase in the ratios of complex and intermediate subpopulations and a decrease in the classic-like subset. These modifications may lead to the identification of novel pharmaceutical targets for prevention and treatment of hepatic damage.