Incidence of hypocortisolism with long-term budesonide irrigation for chronic rhinosinusitis.

BACKGROUND: Budesonide irrigations (BIs) are commonly used to control inflammation in chronic rhinosinusitis (CRS). In 2016 we reported an analysis of long-term BI with regard to hypothalamic-pituitary-adrenal axis function. We present a follow-up analysis in a larger cohort of patients with longer follow-up. METHODS: Patients were candidates for stimulated cortisol testing after regularly performing BI for CRS at least daily for ≥6 months. We retrospectively evaluated all patients who received stimulated cortisol testing at our center between 2012 and 2022. We correlated cortisol levels with the use of BI and other forms of corticosteroids. RESULTS: We analyzed 401 cortisol test results in 285 patients. The mean duration of use was 34 months. Overall, 21.8% of patients were hypocortisolemic (<18 ug/dL) at first test. In patients who used only BI, the rate of hypocortisolemia was 7.5%, whereas in patients who also used concurrent oral and inhaled corticosteroids, the rate was 40% to 50%. Lower cortisol levels were associated with male sex (p < 0.0001) and concomitant use of oral and inhaled steroids (p < 0.0001). Duration of BI use was not significantly associated with lower cortisol levels (p = 0.701), nor was greater dosing frequency (p = 0.289). CONCLUSION: Prolonged use of BI alone is not likely to cause hypocortisolemia in the majority of patients. However, concomitant use of inhaled and oral steroids and male sex may be associated with hypocortisolemia. Surveillance of cortisol levels may be considered in vulnerable populations who use BI regularly, particularly in patients using other forms of corticosteroids with known systemic absorption.

Sex disparities in parenteral and enteral nutrition societies' leadership worldwide: a 20-year retrospective analysis.

BACKGROUND: Despite advancements in the global dialog surrounding sex and gender equity, an important gap persists with women markedly underrepresented in major roles within health care leadership. OBJECTIVES: We examined the extent of women's representation in prominent positions within parenteral and enteral nutrition (PEN) societies worldwide over a span of 2 decades. DESIGN: This retrospective analysis explored the sex distribution of society chairs, conference presidents, and editor-in-chief positions across 64 PEN societies between 2003 and 2022. Additionally, data on the first and last authors of endorsed clinical guidelines were collected from the 2 leading societies. RESULTS: Over the past 20 y, women held society chair positions in 34.4% of cases. The representation shifted from 30% during the decade from 2003 to 2012 to 40.5% from 2013 to 2022. Throughout these years, the numbers consistently ranged from 0 to 10; however, the median shifted upward from 1 during the first decade to 4 in the subsequent decade (P = 0.04). Of 420 congress presidencies, ∼30% were women. In endorsed guidelines, women were the first authors in 27.1% of cases (P < 0.001) and the last in 28.9% (P < 0.001) compared with men. Of the 123 journal editor-in-chief positions, women occupied 23 (18.7%). CONCLUSION: Over the last 2 decades, women have been consistently underrepresented in prominent leadership roles in PEN societies globally. Although there has been a noticeable shift toward more women in chair positions, true sex equality remains elusive. Moreover, sex disparities are even more pronounced in positions, such as conference presidents, authors of major guidelines, and editors-in-chief of society-affiliated journals. These data underscore the pressing need to enhance efforts toward sex equality across these domains.

Eustachian tube dysfunction symptoms after endonasal skull base surgery.

KEY POINTS: ETD symptoms are present in 16% patients with underlying skull base pathology. Preoperative ETD symptoms improve following surgical treatment of skull base pathology. ETD symptoms may worsen in patients with central, posterior, or malignant skull base pathology.

Surgical Correction of Nasal Obstruction and Its Effect on Eustachian Tube Dysfunction Symptoms.

OBJECTIVES: To investigate how eustachian tube dysfunction symptoms change following surgical treatment of nonsinusitis-related nasal obstruction. STUDY DESIGN: Retrospective chart review. SETTING: Single academic center. METHODS: We assessed patients who underwent septoplasty, turbinate reduction, or both for nasal obstruction. Chronic sinusitis patients were excluded. Eustachian tube dysfunction (ETD) symptoms were studied using the Eustachian Tube Dysfunction Questionnaire (ETDQ-7), collected preoperatively and postoperatively (1 week, 1 month, 3 months, 6 months postop). Patients with preoperative ETDQ-7 > 14.5 were considered to have clinically significant symptoms. Sinonasal outcomes test scores were also assessed. Pre- and postoperative ETDQ-7 scores were compared using t test. Multivariate linear regression analysis identified factors associated with ETDQ-7 change. RESULTS: We analyzed 259 patients. Preoperatively, 37.5% of patients with nasal obstruction had clinically significant ETD symptoms. These patients exhibited significant improvement in ETDQ-7 at all postoperative timepoints from 23.3 ± 7.6 at baseline to 19.1 ± 9.1 at 1 week, 16.5 ± 8.0 at 1 month, 16.2 ± 7.8 at 3 months, and 16.7 ± 10.4 at 6 months (all P < .01). In patients without baseline ETD symptoms, (baseline ETDQ-7: 9.1 ± 2.3) ETDQ-7 scores did not change significantly at postoperative timepoints, except for an acute worsening at 1 week postoperatively (10.7 ± 5.1, P < .001). Regression analysis showed that higher preoperative ETDQ-7 score (ß = -0.84, 95% confidence interval [CI]: -1.10 to -0.59) and postoperative antihistamine spray usage (ß = -8.70, 95% CI: -14.20 to -3.20) were associated with ETDQ-7 improvement, while comorbid GERD (ß = 7.50, 95% CI: 3.42-11.58) and asthma (ß = 5.62, 95% CI: 0.80-10.45) were negatively associated with improvement. CONCLUSION: Surgical correction of nasal obstruction may improve ETD symptoms.

Phase angle is related to oxidative stress and antioxidant biomarkers in breast cancer patients undergoing chemotherapy.

PURPOSE: The study aimed to analyze the influence of chemotherapy on health biomarkers and examine the relationship between phase angle (PhA) and oxidative stress. METHODS: A prospective study was performed. Women who were starting chemotherapy were recruited. Also, this study included a control group of women without cancer. Bioelectrical impedance multiple-frequency (BIS) analysis, 24h food recall, and blood samples were collected at 2-time points: diagnosis (T0) and after one month of completion of therapy (T1) for the main study group and one-time point for the control group. T-tests or Mann-Whitney Wilcoxon Test was used to compare variables. Linear regression analysis was conducted to test if PhA is related to the dependent variables after adjusting for age and body mass index. RESULTS: 119 women were included (61 with breast cancer and 58 healthy). There was no difference between the groups concerning anthropometrics, fat mass, and fat-free mass. Breast cancer patients had a worsening in PhA (p<0.001) after chemotherapy completion. PhA was positive statistically correlated with extracellular water, albumin, and the antioxidant markers at both times. The linear model showed that PhA was significantly predicted by C reactive protein, 2,2-Diphenyl-1-picrylhydrazyl (DPPH), Malondialdehyde (MDA), total body water/extracellular water, and body mass index fat mass. This model explained 58% of PhA variability (p<0.001). CONCLUSION: Our findings show that PhA is an easy and affordable tool that correlates oxidative stress markers in breast cancer patients, regardless of age or body mass index.

Proteomic profiling of Klebsiella pneumoniae carbapenemase (KPC)-producer Klebsiella pneumoniae after induced polymyxin resistance.

Aim: To elucidate the changes in protein expression associated with polymyxin resistance in Klebsiella pneumoniae, we profiled a comparative proteomic analysis of polymyxin B-resistant mutants KPC-2-producing K. pneumoniae, and of its susceptible counterparts. Material & methods: Two-dimensional reversed phase nano ultra-performance liquid chromatography mass spectrometry was used for proteomic analysis. Results: Our results showed that the proteomic profile involved several biological processes, and we highlight the downregulation of outer membrane protein A (OmpA) and the upregulation of SlyB outer membrane lipoprotein (conserved protein member of the PhoPQ regulon) and AcrA multidrug efflux pump in polymyxin B-resistant strains. Conclusion: Our results highlight the possible participation of the SlyB, AcrA and OmpA proteins in the determination of polymyxin B heteroresistance in KPC-2-producing K. pneumoniae.

Synthesis of Novel Methyl 3-(hetero)arylthieno[3,2-b]pyridine-2-carboxylates and Antitumor Activity Evaluation: Studies In Vitro and In Ovo Grafts of Chick Chorioallantoic Membrane (CAM) with a Triple Negative Breast Cancer Cell Line.

A series of novel functionalized methyl 3-(hetero)arylthieno[3,2-b]pyridine-2-carboxylates 2a-2h were synthesized by C-C Pd-catalyzed Suzuki-Miyaura cross-coupling of methyl 3-bromothieno[3,2-b]pyridine-2-carboxylate with (hetero)aryl pinacol boranes, trifluoro potassium boronate salts or boronic acids. Their antitumoral potential was evaluated in two triple negative breast cancer (TNBC) cell lines-MDA-MB-231 and MDA-MB-468, by sulforhodamine B assay. Their effects on the non-tumorigenic MCF-12A cells were also evaluated. The results demonstrated that three compounds caused growth inhibition in both TNBC cell lines, with little or no effect against the non-tumorigenic cells. The most promising compound was further studied concerning possible effects on cell viability (by trypan blue exclusion assay), cell proliferation (by bromodeoxyuridine assay) and cell cycle profile (by flow cytometry). The results demonstrated that the GI50 concentration of compound 2e (13 µM) caused a decreased in MDA-MB-231 cell number, which was correlated with a decreased in the % of proliferating cells. Moreover, this compound increased G0/G1 phase and decreased S phases, when compared to control cells (although was not statistic significant). Interestingly, compound 2e also reduced tumor size using an in ovo CAM (chick chorioallantoic membrane) model. This work highlights the potential antitumor effect of a novel methyl 3-arylthieno[3,2-b]pyridine-2-carboxylate derivative.

Anthropometric measures of central adiposity are highly concordant with predictors of cardiovascular disease risk in HIV patients.

Background: Body fat redistribution and metabolic abnormalities found in HIV patients receiving highly active antiretroviral therapy (HAART) contribute to an atherogenic profile, increasing cardiovascular disease risk. Objective: We aimed to evaluate adiposity measures/indexes and propose cutoffs associated with predictors of cardiovascular disease risk in HIV patients on HAART. Design: To evaluate cardiovascular disease risk in this cross-sectional study, we conducted electrocardiogram exams and stress electrocardiography, measured the ankle brachial index and blood pressure arterial hypertension, conducted lipid biochemical tests, and measured blood glucose. We measured circumferences [waist (WC), hip, thigh, calf, neck, trunk] and skinfold thicknesses (biceps, triceps, subscapular, suprailiac), conducted bioelectrical impedance analysis (BIA), and calculated indexes [body mass index, waist-to-hip ratio, waist-to-thigh ratio, waist-to-calf ratio, waist-to-height ratio (WHtR), trunk-to-arm ratio, body mass index corrected for body fat mass, Body Adiposity Index, conicity index, body shape index, fat mass (percentage), and phase angle]. For evaluating the performance of all adiposity measures/indexes, we used receiver operating characteristic (ROC) curves. Results: Measures of central adiposity WC and WHtR showed the best performances-WC area under the curve (AUC) for men: 0.83 (95% CI: 0.78, 0.89; P < 0.05); WC AUC for women: 0.86 (95% CI: 0.81, 0.91; P < 0.05); WHtR AUC for men: 0.83 (95% CI: 0.78, 0.88; P < 0.05); and WHtR AUC for women: 0.85 (95% CI: 0.80, 0.91; P < 0.05). All adiposity measures/indexes presented different cutoffs from those proposed for the HIV seronegative population. The cutoffs for WC were 87.75 cm (sensitivity: 82.2%; specificity: 75.5%) for men and 90.5 cm (sensitivity: 84.0%; specificity: 73.0%) for women. Conclusions: The measures/indexes of central adiposity presented excellent associations with predictors of cardiovascular disease risk, and the use of the cutoffs proposed in the present study aims to contribute to the early identification of increasing risk of cardiovascular diseases, enabling interventions. This trial was registered at the Brazilian clinical trials registry Registro brasileiro de ensaios clínicos (Rebec) as RBR-9rcxbq.

Cutoff Points of BMI for Classification of Nutritional Status Using Bioelectrical Impedance Analysis.

The objective of this study was to improve the cutoff points of the traditional classification of nutritional status and overweight / obesity based on the BMI in a Brazilian sample. A cross-sectional study was conducted on 1301 individuals of both genders aged 18 to 60 years. The subjects underwent measurement of weight and height and bioelectrical impedance analysis. Simple linear regression was used for statistical analysis, with the level of significance set at p < 0.05. The sample consisted of 29.7% men and 70.3% women aged on averaged 35.7 ± 17.6 years; mean weight was 67.6 ± 16.0 kg, mean height was 164.9 ± 9.5 cm, and mean BMI was 24.9 ± 5.5 kg/m2. As expected, lower cutoffs were found for BMI than the classic reference points traditionally adopted by the WHO for the classification of obesity, i.e., 27.15 and 27.02 kg/m2 for obesity for men and women, respectively. Other authors also follow this tendency, Romero-Corral et al. (2008) suggested 25.8 to 25.5 kg/m2 for American men and women as new values for BMI classification of obesity. Gupta and Kapoor (2012) proposed 22.9 and 28.8 kg/m2 for men and women of North India. The present investigation supports other literature studies which converge in reducing the BMI cutoff points for the classification of obesity. Thus, we emphasize the need to conduct similar studies for the purpose of defining these new in populations of different ethnicities.

Is there any relationship between gene expression of tumor antigens and CD4+ T cells in multiple myeloma?

AIM: The present study aimed at correlating the expression of cancer/testis antigens (CTAs) with the expression of genes related to tumor-infiltrating T cells. MATERIALS & METHODS: MAGE-C1/CT-7, MAGEA3/6, NY-ESO-1, LAGE-1 and GAGE expression were evaluated in 46 bone marrow multiple myeloma (MM) aspirates by RT-PCR. Expression of FOXP3/CTLA4 and RORyt, as markers for Tregs and Th17 cells, respectively, was investigated by quantitative PCR. RESULTS: MAGEC1/CT7 was expressed in 66% of MM samples. We did not find correlation between the presence of single CTA and expression of CTLA4 or RORyt neither expression of CD4(+) T-cell markers and the number of CTA simultaneously expressed in the tumor. However, we did observe a correlation between the percentage of plasma cells and the number of CTAs expressed in the patients' bone marrow. CONCLUSION: Although CTAs and immunomodulatory CD4(+) T cells represent potential targets for immunotherapy in MM, we did not find association among expression of such genes in MM.