Characteristics and Therapeutic Needs of Older Patients with Oropharyngeal Dysphagia Admitted to a General Hospital.

BACKGROUND: Oropharyngeal dysphagia (OD) is a prevalent geriatric syndrome causing severe nutritional and respiratory complications. OBJECTIVE: We aimed to describe the characteristics and therapeutic needs of older patients with OD admitted to a general hospital. DESIGN, PARTICIPANTS AND MEASUREMENTS: Prospective cohort study with patients (≥70 years) with OD consecutively admitted to a general hospital. OD was clinically assessed with the Volume-Viscosity Swallowing Test and nutritional status with the Mini Nutritional Assessment-short form. Oral health (OH) and periodontal diseases were evaluated by dentists. Functionality, frailty, sarcopenia, comorbidities, dehydration, quality of life (QoL) and mortality were also assessed. RESULTS: We included 235 patients (87.3±5.5 years) with OD hospitalized for acute diseases (9.6±7.6 days). On admission, they had low functionality (Barthel: 51.3±25.1), frailty (Fried: 3.9±0.9; Edmonton: 10.3±2.7, 87.2-91.1% frail) and high comorbidities (Charlson: 3.7±2.0). Moreover, 85.1% presented signs of impaired safety and 84.7% efficacy of swallow. Up to 48% required fluid adaptation with a xanthan gum-based thickener (89.4% at 250 mPa·s; 10.6% at 800 mPa·s) and 93.2% a texture-modified diet (TMD) (74.4%, fork-mashable; 25.6%, pureed). A total of 98.7% had nutritional risk, 32.3% sarcopenia and 75.3% dehydration. OH was moderate (Oral Hygiene Index-simplified: 2.0±1.3) and 67.4% had periodontitis. QoL self-perception was 62.2% and 5.5% of patients died during hospitalization. CONCLUSION: Hospitalized older OD patients have impaired safety of swallow, frailty, malnutrition, dehydration, low functional capacity and poor OH and high risk of respiratory infections. They need a multimodal intervention including fluid thickening, TMD, thickened oral nutritional supplementation and OH care to improve health status and reduce OD-associated complications.

Association between biochemical control and comorbidities in patients with acromegaly: an Italian longitudinal retrospective chart review study.

PURPOSE: Achieving biochemical control (normalization of insulin-like growth factor-1 [IGF-1] and growth hormone [GH]) is a key goal in acromegaly management. However, IGF-1 and GH fluctuate over time. The true potential impact of time-varying biochemical control status on comorbidities is unclear and relies on multiple, longitudinal IGF-1 and GH measurements. This study assessed the association between time-varying biochemical control status and onset of selected comorbidities in patients with acromegaly. METHODS: Medical charts of adults with confirmed acromegaly and ≥ 6 months of follow-up at an Italian endocrinology center were reviewed. Patients were followed from the first diagnosis of acromegaly at the center until loss to follow-up, chart abstraction, or death. Biochemical control status was assessed annually and defined as IGF-1 ≤ the upper limit of normal, or GH ≤ 2.5 µg/L in the few cases where IGF-1 was unavailable. Time-varying Cox models were used to assess the association between biochemical control status and comorbidities. RESULTS: Among 150 patients, 47% were female, average age at diagnosis was 43.1, and mean length of follow-up was 10.4 years. Biochemical control was significantly associated with a lower hazard of diabetes (HR = 0.36, 95% CI 0.15; 0.83) and cardiovascular system disorders (HR = 0.54, 95% CI 0.31; 0.93), and a higher hazard of certain types of arthropathy (HR = 1.68, 95% CI 1.04; 2.71); associations for other comorbidities did not reach statistical significance. CONCLUSION: Results further support the importance of achieving biochemical control, as this may reduce the risk of high-burden conditions, including diabetes and cardiovascular system disorders. The association for arthropathy suggests irreversibility of this impairment. Due to limitations, caution is required when interpreting these results.

Leading edge or tumor core: Intratumor cancer stem cell niches in oral cavity squamous cell carcinoma and their association with stem cell function.

OBJECTIVES: To describe differences in cancer stem cell (CSC) presence and behavior associated with their intratumor compartment of origin using a patient-derived xenograft (PDX) model of oral cavity squamous cell carcinoma (OCSCC). MATERIALS AND METHODS: Four HPV-negative OCSCC PDX cases were selected (CUHN004, CUHN013, CUHN096, CUHN111) and the percentage of CSCs (ALDH+CD44high) was measured in the tumor Leading Edge (LE) and Core compartments of each PDX tumor case via fluorescence activated cell sorting (FACS). The fraction of cells in the proliferative phase was measured by Ki-67 labelling index of paraffin embedded tissue. The proliferation and invasion of LE versus Core CSCs were compared using sphere and Matrigel invasion assays, respectively. RESULTS: Both CUHN111 and CUHN004 demonstrate CSC enrichment in their LE compartments while CUHN013 and CUHN096 show no intratumor difference. Cases with LE CSC enrichment demonstrate greater Ki-67 labelling at the LE. CSC proliferative potential, assessed by sphere formation, reveals greater sphere formation in CUHN111 LE CSCs, but no difference between CUHN013 LE and Core CSCs. CUHN111 CSCs do not demonstrate an intratumor difference in invasiveness while CUHN013 LE CSCs are more invasive than Core CSCs. CONCLUSION: A discrete intratumor CSC niche is present in a subset of OCSCC PDX tumors. The CSC functional phenotype with regard to proliferation and invasion is associated with the intratumor compartment of origin of the CSC: LE or Core. These individual functional characteristics appear to be modulated independently of one another and independently of the presence of an intratumor CSC niche.

Effects of selenium on short-term control of hyperthyroidism due to Graves' disease treated with methimazole: results of a randomized clinical trial.

OBJECTIVE: In spite of previous conflicting results, an adjuvant role of selenium in the treatment of Graves' disease (GD) hyperthyroidism has been proposed. To address this issue, a randomized clinical trial was carried out aimed at investigating whether selenium is beneficial on the short-term control of GD hyperthyroidism treated with methimazole (MMI). METHODS: Thirty newly diagnosed hyperthyroid GD patients were randomly assigned to treatment with: (i) MMI or (ii) MMI plus selenium. Primary outcomes were: control of hyperthyroidism and clinical and biochemical manifestations of hyperthyroidism [heart rate, cholesterol, sex hormone-binding globulin (SHBG), hyperthyroidism symptoms] at 90 days. RESULTS: Baseline features of the two groups did not differ. Serum selenium at baseline was similar in the two groups and within the recommended range to define selenium sufficiency. Selenium increased with treatment in the MMI-selenium group and became significantly higher than in the MMI group. Serum malondialdehyde, a marker of oxidative stress, was similar in the two groups and decreased significantly with treatment, with no difference between groups. Administration of MMI was followed by a reduction of FT3 and FT4, with no difference between groups. Heart rate, SHBG and symptoms of hyperthyroidism decreased, whereas total cholesterol increased in both groups with no difference between groups. CONCLUSIONS: Our study, carried out in a selenium-sufficient cohort of GD patients, failed to show an adjuvant role of selenium in the short-term control of hyperthyroidism. However, selenium might be beneficial in patients from selenium-deficient areas, as well as in the long-term outcome of antithyroid treatment.

Influence of stromal-epithelial interactions on androgen action.

Androgen receptor (AR) signaling is vital to the development and function of the prostate and is a key pathway in prostate cancer. AR is differentially expressed in the stroma and epithelium, with both paracrine and autocrine control throughout the prostate. Stromal-epithelial interactions within the prostate are commonly dependent on AR signaling and expression. Alterations in these pathways can promote tumorigenesis. AR is also expressed in normal and malignant mammary tissues. Emerging data indicate a role for AR in certain subtypes of breast cancer that has the potential to be exploited therapeutically. The aim of this review is to highlight the importance of these interactions in normal development and tumorigenesis, with a focus on the prostate and breast.

Does optical coherence tomography identify arterial healing after stenting? An in vivo comparison with histology, in a rabbit carotid model.

OBJECTIVE: To verify whether optical coherence tomography (OCT) can accurately monitor the occurrence of arterial healing after stenting. SETTING: Delayed stent endothelialisation may predispose to stent thrombosis. OCT is a high-resolution intravascular imaging technique that accurately identifies stent struts and arterial tissues. DESIGN AND INTERVENTIONS: Eight New Zealand white rabbits underwent the implantation of single bare metal stents (diameter 2-2.5 mm, length 8-13 mm) in the right common carotid artery through the external carotid artery. After a median of 11 days (range 2-28), the stented arteries were visualised by OCT, with images acquired at a pull-back speed of 0.5 mm/sec. The rabbits were then euthanised, vessels were formalin-fixed and finally processed for histopathology. RESULTS: We analysed 32 cross-sections from eight stented carotid arteries, for a total of 384 stent struts. OCT detected all of the stent struts in 30 of 32 cross-sections (93.7%), and correctly identified the presence/absence of tissue for every strut. Histological and OCT measurements of mean neointima thickness (0.135 (SD 0.079) mm and 0.145 (SD 0.085) mm, respectively, p = NS) were similar and closely related (r = 0.85, p<0.001). Neointima area progressively increased with longer time intervals from stent deployment to sacrifice; histological and OCT measurements were similar for each time interval. The intra-observer and interobserver reproducibility of OCT neointima measurements were excellent (R2 = 0.90 and 0.88, respectively). CONCLUSIONS: OCT is a promising means for monitoring stent strut coverage and vessel wall healing in vivo, the relevance of which will become even more significant with the increasing use of drug-eluting stents.

Prominent crista terminalis mimicking a right atrial mixoma: cardiac magnetic resonance aspects.

A 68-year-old woman came to our observation with a clinical history of isolated systolic hypertension poorly controlled by the combination of ramipril 5 mg and hydrochlorothiazide 12.5 mg o.d. The ECG showed sinus rhythm with heart rate of 68 beats per minute and signs of left ventricular hypertrophy without strain. Further investigation included an echocardiogram that showed normal left and right cavities and normal cardiac valves. At the level of the posterior wall of the right atrial (RA) an apparent smooth, bean-like tumor, having a thin pedicle, was identified as a RA mixoma. Cardiac MRI was requested and showed in two sequential slices a muscular ridge, identified as a prominent crista terminalis. Some para-physiological structures sited in the RA may have the appearance of tumors, as crista terminalis, Eustachian valve extending into the RA chambers and Chiari network. The multiplain projections of MRI allow the cardiologist to identify the presence of intracardiac masses and to make a differential diagnosis between neoplasms and variant anatomic structures.

Cooperation and competition between the binding of COUP-TFII and NF-Y on human epsilon- and gamma-globin gene promoters.

The nuclear receptor COUP-TFII was recently shown to bind to the promoter of the epsilon- and gamma-globin genes and was identified as the nuclear factor NF-E3. Transgenic experiments and genetic evidence from humans affected with hereditary persistence of fetal hemoglobin suggest that NF-E3 may be a repressor of adult epsilon and gamma expression. We show that, on the epsilon-promoter, recombinant COUP-TFII binds to two sites, the more downstream of which overlaps with an NF-Y binding CCAAT box. Binding occurs efficiently to either the 5' or the 3' COUP-TFII site but not to both sites simultaneously. However, adding recombinant NF-Y induces the formation of a stable COUP-TFII.NF-Y-promoter complex at concentrations of COUP-TFII that would not give significant binding in the absence of NF-Y. Mutations of the promoter indicate that COUP-TFII cooperates with NF-Y when bound to the 5' site, whereas binding at the 3' site is mutually exclusive. Likewise, in the gamma-promoter, COUP-TFII binds to a site overlapping the distal member of a duplicated CCAAT box, competing with NF-Y binding. Transfections in K562 cells show that both the mutation of the 5' COUP-TFII or of the NF-Y site on the epsilon-promoter decrease the activity of a luciferase reporter; the mutation of the 3' COUP-TFII site has little effect. These results, together with transgenic experiments suggesting a repressive activity of COUP-TFII on the epsilon-promoter and the observation that, on the 3' site, COUP-TFII and NF-Y binding is mutually exclusive, suggest that COUP-TFII may exert different effects on epsilon transcription depending on whether it binds to the 5' or to the 3' site. At the 5' site, COUP-TFII might cooperate with NF-Y, forming a stable complex, and stimulate transcription; at the 3' site, COUP-TFII might compete for binding with NF-Y and, directly or indirectly, decrease gene activity.

Attention versus avoidance: attributional search and denial after myocardial infarction.

OBJECTIVE: In this study the focus was on two strategies: denial (an avoidant strategy) and causal thinking (an attention strategy) and their relationships to affect after myocardial infarction. DESIGN: Descriptive, correlational. SETTING: Large rural medical center. SAMPLE: The sample comprised 152 recently hospitalized patients with first-time myocardial infarction. MEASURES: A denial scale, a question about causal thinking, and an affect adjective checklist measuring anxiety, hostility, and depression. RESULTS: Denial had a weak but significant negative correlation with anxiety (r = -0.18, p < 0.05). However, denial was not significantly related to either depression or hostility. Regression analysis indicated that both denial (F = 4.84, p = 0.02) and the interaction of denial with causal search (f = 4.77, p = 0.009) were predictors of affect. The interaction indicated that those with high denial who had not searched for a cause were least anxious. A large number of subjects used both attention and avoidant strategies. CONCLUSIONS: The main effect for denial suggests that avoidance is a more effective strategy for reducing anxiety after myocardial infarction than causal search, an attention strategy. However, the fact that many subjects used both strategies suggests that they are not mutually exclusive in the process of adaptation after a heart attack.