SUMMARYOBJECTIVES. Subjective sleep complaints have been reported in up to 80% of patients with end stage renal disease (ESRD). In these patients, sleep disturbances manifesting as insomnia, sleep apnea syndrome, restless leg syndrome (RLS), periodic limb movement disorder and excessive daytime sleepiness (EDS) have been frequently reported. Moreover, studies about the role of dialysis shift on sleep abnormalities, morbidity and mortality are still scarce. The aim of this study was to investigate the influence of dialysis shift on the quality of sleep and sleep abnormalities in patients with ESRD. MÉTHODS. We studied one hundred consecutive patients from a dialysis center. Quality of sleep was assessed by the Pittsburgh Sleep Quality Index and subjective EDS by the Epworth Sleepiness Scale. Restless leg syndrome was diagnosed using the four minimum criteria defined by the International Restless Legs Syndrome Study Group. Clinical and laboratory parameters were obtained by interview and chart review. Adequacy of dialysis was evaluated by the Kt/V index. RESULTS. Poor quality sleep (PSQI>6) was found in 75% of cases and was associated with RLS (p=0.004) and with snoring (p=0.016). EDS (ESS>10) was present in 28% of cases. Patients with EDS (1.33±0.29) had lower values of the Kt/v index (P=0.01) than those without EDS (1.52±0.32). RLS was present in 48% of cases. Irrespective of dialysis shift, poor quality sleep, EDS and RLS were not different among patients. CONCLUSION. Poor quality sleep, EDS and RLS were common and not related to dialysis shift.
Glutamine or alanyl-glutamine accelerated the mucosal recovery increasing mucosal tissue glutathione stores, reducing inflammatory parameters and speeding reepithelization.
A 22-year-old male was admitted to the emergency department with a sore throat, dysphagia, hemoptysis, and retrosternal pain. He had attempted suicide by ingesting 50 mL of a paraquat solution four days prior to admission and had been treated, at another facility, with gastric lavage and administration of activated charcoal. It is of note that he had attempted suicide previously, on more than one occasion.
SummaryThis research investigated the effect of glutamine (Gln) depletion on leucocyte-dependent inflammatory events. Rats were treated intraperitoneally, 16 hr prior to the peak of every parameter evaluated, with either 0Á9% NaCl, methionine-sulphoximine (MSO, an inhibitor of endogenous Gln synthesis, 25 mg/kg) or with MSO + Gln (MSO as above plus Gln 3 g/kg in three doses). MSO-induced Gln depletion increased paw oedema induced both by carrageenan (Cg) and by Clostridium difficile toxin A (TxA) (66Á2% and 45Á5%, respectively; P < 0Á05). In dextran-injected animals, oedema and myeloperoxidase (MPO) activity were not modified by Gln depletion. In Cg-treated paws, Gln depletion increased MPO activity by 44% (P < 0Á05), interleukin-1b (IL-1b) and tumour necrosis factor-a (TNF-a) concentrations by 47% and 52%, respectively (P < 0Á05), and immunostaining for TNF-a in paw tissue. In TxA-injected paws, Gln depletion increased MPO activity (46%; P < 0Á05). Gln depletion increased Cg-and TxA-induced neutrophil migration to subcutaneous air pouches by 56% and 77% (P < 0Á05), respectively, but did not affect migration induced by N-formyl-methionyl-leucyl-phenylalanine (fMLP). Gln infusions reversed all the effects of MSO. Leucocyte counts did not differ between groups. Gln depletion potentiates acute inflammation, possibly by increasing neutrophil migration through resident cell activation and production of IL-1b and TNF-a. Gln supplementation reverses these effects and may be useful during inflammatory catabolic stress.
Background: Recent studies in murine models and humans suggest that modulation of the gut microbiome may enhance response to immune checkpoint blockade in different cancer types. However, little is known about the landscape of gut microbiome in pts with HR+ MBC and its influence on response to chemotherapy and immunotherapy.Methods: A randomized phase 2 trial of E +/- P for pts with HR+ MBC (n= 88) was conducted. The results of this study have been previously presented and found the addition of P did not result in an improvement in progression-free survival (PFS). Fecal samples were prospectively collected (baseline (BL), after 2 cycles of therapy (C2), and end of treatment (EOT)) in a subset of pts (E+P, n = 12; E, n = 11) in order to evaluate if microbiome was associated with response (partial response [PR], stable disease [SD], and progressive disease [PD]), PFS, and overall survival (OS). 16S rRNA gene sequencing was performed to characterize the diversity and composition of fecal microbiome. Results: A total 23 pts provided 23 BL, 22 C2, and 5 EOT fecal specimens for microbiome profiling. 16S(v3-4) rRNA gene data was successfully generated for all samples and the dataset was rarefied to 24,743 reads for analysis. Overall, the variability in the composition and structure of the fecal microbiome was significantly driven by each individual (p<0.001) more than any other variable studied. This effect was observed across all timepoints collected. At BL, subjects randomized to receive E+P and E did not show any differences in composition (p = 0.715) and structure (p = 0.457) of the fecal microbiome. The major genera identified in E+P and E groups were Bacteroides, 37.9% vs. 41.56%; Faecalibacterium 9.9% vs. 4.4%, and Blautia 4.9% vs. 2.9%, respectively. These abundances were observed at a similar level in the C2 sample. Overall, subjects receiving E had a marked increase in Faecalibacterium from 6.4% at BL to 21.2% at C2 and a decrease in Akkermansia from BL (8.5%) to C2 (<1%). Among those pts receiving E who achieved a PR, the abundance of Faecalibacterium increased from BL (4.3%) to C2 (13.9%), while the levels remained unchanged in those achieving SD. These shifts in abundance were not observed in the group receiving E+P. Subjects with PFS below the median had comparable alpha-diversity scores to those above the median in both arms of the study. Specifically, the number of Operational Taxonomic Units (OTUs) observed at BL in pts receiving E+P with PFS above and below the median were 563 and 663, respectively. When looking at the differences between BL and C2, OTUs decreased slightly to 513 and 637, respectively. Similar results were observed in pts receiving E. Among pts with PFS time below the median receiving E, there was a decrease in Akkermansia from BL (5.7%) to C2 (<1%). Pts with OS below the median had comparable alpha-diversity scores at BL to those above the median OS in both arms of the study. Pts with OS above the median receiving E experienced a decrease in the abundance of Akkermansia from BL (5.3%) to C2 (2.4%). Conclusion: The composition and structure of the fecal microbiome identified in this study were found to be associated primarily with the pt rather than with any of the variables studied including type of treatment and outcome. Although the fecal microbiome from all pts randomized were indistinguishable at BL, shifts in the abundance of certain types of bacteria like Faecalibacterium and Akkermansia were observed from BL to C2. These shifts were characteristic of pts receiving E but not of those receiving E+P. Although this study is limited by the small sample size in each arm, these findings warrant further evaluation in a larger population to interrogate if the composition and metabolic potential of the fecal microbiome can be used as a predictor of benefit to treatment. Citation Format: Romualdo Barroso de Sousa, Nadim Ajami, Tanya E Keenan, Chelsea Andrews, Jessica L Pittenger, Gerburg Wulf, Laura Spring, Ian E Krop, Eric P Winer, Elizabeth A Mittendorf, Sara M Tolaney. Fecal microbiome and association with outcomes among patients (pts) receiving eribulin (E) +/- pembrolizumab (P) for hormone receptor positive (HR+) metastatic breast cancer (MBC) [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P3-09-16.
Objective: This study aims to investigate the adherence rates to adjuvant hormone therapy in patients with early-stage breast cancer. Methods: Breast cancer patients with early invasive disease who are being treated with adjuvant hormone therapy for at least 6 months in a private oncology service were evaluated for adherence rates. Data collection was done using the RedCap software. The MMAS-8 scale was used to assess adherence to treatment, dividing patients into three groups as follows: low (<6 points), medium (6–8 points), or high adherence (8 points). Demographic and clinical characteristics were assessed for the three adherence groups. Results: From June to December 2021, a total of 60 patients were recruited. The median age was 60.3 years, and 23.3% were premenopause. About demographic statistics, 80% have a college degree, 35% live alone, and 30% have comorbidities. About breast cancer, 50% were in stage I, 50% received chemotherapy, 10% received HER2 blockade, and 26 patients (43.3%) used letrozole. Analyzing adherence, 45% had low/medium adhesion and 55% had high adhesion. There was no association between adherence rates and demographics, clinical and pathological characteristics, except for ECOG Performance Status (PS). All patients with PS ECOG 1 had low/medium adherence (p=0.036). More patients who live alone had low or medium adherence, whereas more patients who live together had high adherence. There was no difference in the type of hormonal treatment and adherence. Conclusion: Preliminary results show high adherence in only 55% of patients, lower than reported in previous studies. This result draws attention because it can compromise survival. We will continue the recruitment of patients in the private service and start in the public service to assess the rate of adherence in a larger population and the relationship with demographic characteristics.
Objective: The lack of financial resources challenges the inclusion of genetic testing in the Brazilian Public Health System. This study aims to describe the detection rate of germline pathogenic variants (GPVs) in patients at risk of hereditary breast cancer (BC) in the public hospitals of Brasilia, DF, as well as the clinical and demographic profile of patients (pts). Methods: Hereditary cancer risk assessment based on the National Comprehensive Cancer Network Criteria, version 1.2020 was performed on patients with a personal history of BC who were being followed in a public hospital (DF) between January 2021 and January 2022. Results: Among 217 female pts eligible for this study, 78 pts performed germline multigene panel testing out of pocket. Panels included 26–84 cancer susceptibility genes. Patients in this cohort were mainly from the center-west (46%) and northeast (31%) of Brazil. The median age of BC diagnosis was 42 years. Invasive ductal carcinoma represented 88% of the tumors. From a total of 78 BC, 52% were hormone receptor-positive, 23% HER2 positive, and 24% triple-negative. Most patients presented with locally advanced disease: 50% (n=39) IIB-IIIC and 8% (n=6) had metastatic disease. The detection rate of GPVs was 20% (n=16). Among these 16 patients, the most frequently mutated genes were BRCA1/2 (n=11, 68.5%) and TP53 (n=2, 12.5%). Conclusion: The overall detection rate of GPVs was similar to other worldwide studies. In comparison with other Brazilian studies, GPVs in TP53 were at lower rates, possibly because this cohort was enriched by patients from Brazilian center-west and northeast. Higher rates of advanced disease at BC diagnosis may impact treatment outcomes. The lack of access to genetic testing in the public health system takes away the opportunity for cancer prevention, more effective treatments, and proper family risk assessment.
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