Clinical Study of Metabolic Parameters, Leptin and the SGLT2 Inhibitor Empagliflozin among Patients with Obesity and Type 2 Diabetes.

Obesity is a major public health problem worldwide, and it is associated with many diseases and abnormalities, most importantly, type 2 diabetes. The visceral adipose tissue produces an immense variety of adipokines. Leptin is the first identified adipokine which plays a crucial role in the regulation of food intake and metabolism. Sodium glucose co-transport 2 inhibitors are potent antihyperglycemic drugs with various beneficial systemic effects. We aimed to investigate the metabolic state and leptin level among patients with obesity and type 2 diabetes mellitus, and the effect of empagliflozin upon these parameters. We recruited 102 patients into our clinical study, then we performed anthropometric, laboratory, and immunoassay tests. Body mass index, body fat, visceral fat, urea nitrogen, creatinine, and leptin levels were significantly lower in the empagliflozin treated group when compared to obese and diabetic patients receiving conventional antidiabetic treatments. Interestingly, leptin was increased not only among obese patients but in type 2 diabetic patients as well. Body mass index, body fat, and visceral fat percentages were lower, and renal function was preserved in patients receiving empagliflozin treatment. In addition to the known beneficial effects of empagliflozin regarding the cardio-metabolic and renal systems, it may also influence leptin resistance.

Involvement of Mitochondrial Mechanisms and Cyclooxygenase-2 Activation in the Effect of Desethylamiodarone on 4T1 Triple-Negative Breast Cancer Line.

Novel compounds significantly interfering with the mitochondrial energy production may have therapeutic value in triple-negative breast cancer (TNBC). This criterion is clearly fulfilled by desethylamiodarone (DEA), which is a major metabolite of amiodarone, a widely used antiarrhythmic drug, since the DEA previously demonstrated anti-neoplastic, anti-metastasizing, and direct mitochondrial effects in B16F10 melanoma cells. Additionally, the more than fifty years of clinical experience with amiodarone should answer most of the safety concerns about DEA. Accordingly, in the present study, we investigated DEA's potential in TNBC by using a TN and a hormone receptor positive (HR+) BC cell line. DEA reduced the viability, colony formation, and invasive growth of the 4T1 cell line and led to a higher extent of the MCF-7 cell line. It lowered mitochondrial transmembrane potential and induced mitochondrial fragmentation. On the other hand, DEA failed to significantly affect various parameters of the cellular energy metabolism as determined by a Seahorse live cell respirometer. Cyclooxygenase 2 (COX-2), which was upregulated by DEA in the TNBC cell line only, accounted for most of 4T1's DEA resistance, which was counteracted by the selective COX-2 inhibitor celecoxib. All these data indicate that DEA may have potentiality in the therapy of TNBC.

Involvement of Mitochondrial Mechanisms in the Cytostatic Effect of Desethylamiodarone in B16F10 Melanoma Cells.

Previously, we showed that desethylamiodarone (DEA), a major metabolite of the widely used antiarrhythmic drug amiodarone, has direct mitochondrial effects. We hypothesized that these effects account for its observed cytotoxic properties and ability to limit in vivo metastasis. Accordingly, we examined DEA's rapid (3-12 h) cytotoxicity and its early (3-6 h) effects on various mitochondrial processes in B16F10 melanoma cells. DEA did not affect cellular oxygen radical formation, as determined using two fluorescent dyes. However, it did decrease the mitochondrial transmembrane potential, as assessed by JC-1 dye and fluorescence microscopy. It also induced mitochondrial fragmentation, as visualized by confocal fluorescence microscopy. DEA decreased maximal respiration, ATP production, coupling efficiency, glycolysis, and non-mitochondrial oxygen consumption measured by a Seahorse cellular energy metabolism analyzer. In addition, it induced a cyclosporine A-independent mitochondrial permeability transition, as determined by Co2+-mediated calcein fluorescence quenching measured using a high-content imaging system. DEA also caused outer mitochondrial membrane permeabilization, as assessed by the immunoblot analysis of cytochrome C, apoptosis inducing factor, Akt, phospho-Akt, Bad, and phospho-Bad. All of these data supported our initial hypothesis.

Amiodarone's major metabolite, desethylamiodarone inhibits proliferation of B16-F10 melanoma cells and limits lung metastasis formation in an in vivo experimental model.

Previously, we demonstrated the in vitro anti-tumor effects of desethylamiodarone (DEA) in bladder and cervix cancer cell lines. In the present study, we intended to establish its potentiality in B16-F10 metastatic melanoma cells in vitro and in vivo. We assessed cell proliferation, apoptosis and cell cycle by using sulforhodamine B assay, Muse™ Annexin V & Dead Cell and Muse® Cell Cycle assays, respectively. We determined colony formation after crystal violet staining. For studying mechanistic aspects, immunoblotting analysis was performed. We used a C57BL/6 experimental lung metastasis model for demonstrating in vivo anti-metastatic potential of DEA. DEA inhibited in vitro proliferation and colony formation, and in vivo lung metastasizing properties of B16-F10 cells. It arrested the cells in G0/G1 phase of their cycle likely via p21 in a p53-dependent fashion, and induced caspase mediated apoptosis likely via inversely regulating Bcl-2 and Bax levels, and reducing Akt and ERK1/2 activation. In this study, we provided in vitro and in vivo experimental evidences for DEA's potentiality in the therapy of metastatic melanomas. Since DEA is the major metabolite of amiodarone, a worldwide used antiarrhythmic drug, safety concerns could be resolved more easily for it than for a novel pharmacological agent.

Muslim nursing homes in the United States: barriers and prospects.

Historically, many nursing homes in the United States have been established by religious groups. This was done to provide care for the elderly when care could not be furnished in other venues. Despite several attempts reported in the literature, there are currently no Muslim nursing homes in the United States. In the Arab and Muslim world, the acceptance and success of such an institution has been somewhat variable. As the Arab Muslim population in the United States ages and becomes more frail, the Muslim community will have to evaluate the need to establish nursing homes to provide care for elderly.

Challenges and opportunities in the management of the aging voice.

Presbyphonia, or age-related dysphonia, is a diagnosis of exclusion, and other comorbidities must be considered in a complete evaluation of elderly patients with dysphonia. The aging voice can have a significant effect on the quality of life of the patient. In addition to the molecular effects of aging on the laryngeal tissues, the etiology of presbyphonia is often multifactorial because of comorbidities in the other organ systems involved in phonation. After a comprehensive evaluation, presbyphonia may be treated conservatively with voice therapy or with a range of interventions. Research into tissue engineering and electrical reanimation offers future options for treatment of presbyphonia. Currently, a multidisciplinary approach offers the most complete improvement in the vocal quality of life in this patient population.

A comparative study of community- and nursing home-acquired empyema thoracis.

OBJECTIVES: To compare the clinical presentation, microbiological features, and outcomes of patients with community-acquired empyema (CAE) with those of patients with nursing home-acquired empyema (NHAE). DESIGN: A retrospective observational study. SETTING: Three tertiary care centers. PARTICIPANTS: One hundred fourteen patients admitted from the community and 55 patients transferred from nursing homes. MEASUREMENTS: Baseline sociodemographic information, activities of daily living, Charlson Comorbidity Index score, and clinica, and microbiologic data were obtained. Outcome was assessed at hospital discharge and 6 months postdischarge. RESULTS: Patients admitted from nursing homes had a delayed presentation, with dyspnea, weight loss, and anemia as the predominant manifestation. Patients with CAE presented more acutely, with fever, cough, and chest pain. Anaerobic organisms were more commonly isolated from patients with NHAE. The success rate of nonsurgical intervention was significantly lower for the NHAE patients than for the CAE group (39% vs 63; P=.01). In-hospital mortality was not significantly different between the two groups (NHAE, 18%; CAE, 8%; P=.09). In a Cox regression analysis, preadmission functional status (hazard ratio (HR)=1.26, 95% confidence interval (CI)=1.19-1.4; P<.001) and surgical intervention (HR=0.47, 95% CI=0.24-0.92; P=.03) were the only variables highly correlated with long-term outcome. CONCLUSION: Patients admitted with NHAE have distinctly different clinical and microbiological presentation from that of patients with CAE. Because of the delayed presentation in patients with NHAE, medical treatment alone may be associated with higher rate of failure. Surgical therapy should be considered for selected cases, with the aim of improving long-term survival.

Overview of respiratory failure in older adults.

Older adults comprise 48% of the critically ill population in intensive care units and will continue to represent a substantial proportion of patients requiring intensive care for decades to come. Aging both decreases the reserve capacity of vital organs and increases the risk of concurrent illnesses that challenge the respiratory system, such as pneumonia, renal failure, or heart diseases. Because respiratory failure is one of the leading causes of death in intensive care units, implementation of strategies to prevent the need for reintubation should be considered early in the course of respiratory decompensation. For those who require mechanical ventilation, protocols to identify patients who are ready to wean should facilitate liberation from respiratory support and reduce complications of mechanical ventilation. Finally, allocation of potentially limited health care resources necessitates knowing about the risk-benefit of mechanical ventilation and other treatment for respiratory failure in this population.

A longitudinal study of idiopathic exudative lymphocytic pleural effusion in older people.

OBJECTIVES: To assess the long-term prognosis of older patients with idiopathic exudative lymphocytic pleural effusion. DESIGN: Prospective observational study. SETTING: A university-affiliated tertiary care center. PARTICIPANTS: Forty-seven consecutive patients (aged 74.9+/-5.4) with idiopathic exudative lymphocytic pleural effusion were enrolled over a 42-month period. MEASUREMENTS: Baseline sociodemographic information, clinical data, and Charlson Comorbidity Index score were obtained. After an exhaustive examination, clinical evaluation and periodic chest radiographs were taken until one of the endpoints was met: complete resolution of the pleural effusion, death from all causes, or the end of the study period. RESULTS: The mean follow-up period was 16.3+/-17.0 months. During the course of the study, complete resolution of the pleural effusion occurred in 17% of the patients, whereas it remained stable in 45%, and progressed in 38%. In seven cases, the cause of the effusion was established after an average of 84 days, and in another two, the diagnosis was made postmortem. Malignancy was documented in eight of the nine cases. Although the burden of comorbidities and cardiac function at baseline were similar in the three categories, the 3-year survival rate was 63%, 5%, and 0%, respectively. None of the patients developed active tuberculosis, although 15% had positive tuberculin test. CONCLUSION: By categorizing the presence of idiopathic effusion into resolving, persistent, or progressive, this study may provide a more practical approach to the long-term prognosis of older patients with idiopathic exudative lymphocytic effusion who refuse or are considered too frail to undergo an invasive procedure.

A multifactorial intervention to reduce prevalence of delirium and shorten hospital length of stay.

OBJECTIVES: To improve outcomes for cognitively impaired and delirious older adults. DESIGN: Pretest, posttest. SETTING: A university-affiliated hospital. PARTICIPANTS: Physicians and nurses in the emergency department (ED) and on an acute geriatric unit (AGU). INTERVENTION: Multifactorial and targeted to the processes of care for cognitively impaired and delirious older adults admitted to medicine service from the ED. MEASUREMENTS: Prevalence of delirium, admission to AGU, psychotropic medication use, hospital length of stay. RESULTS: Patient characteristics did not differ between baseline and the two outcome cohorts 4 and 9 months postintervention. Prevalence of delirium was 40.9% at baseline, 22.7% at 4 months (P<.002), and 19.1% at 9 months (P<.001). More delirious patients were admitted to the AGU than to non-AGU units at 4 months (P<.01) and 9 months (P<.01). Postintervention medication use in the hospital differed from baseline. Antidepressant use was greater at 4 months (P<.05). Benzodiazepine and antihistamine use were lower at 9 months (P>.01). Antidepressant and neuroleptic use were higher (P<.02) and antihistamine use was lower (P<.02) at 4 months on the AGU than for the baseline group. Benzodiazepine (P<.01) and antihistamine (P<.05) use were lower at 9 months. Each case of delirium prevented saved a mean of 3.42 hospital days. CONCLUSION: A multifactorial intervention designed to reduce delirium in older adults was associated with improved psychotropic medication use, less delirium, and hospital savings.

Radiographic resolution of community-acquired bacterial pneumonia in the elderly.

OBJECTIVES: To investigate the radiographic clearance of proven community-acquired nontuberculous bacterial pneumonia in nonimmunocompromised older patients to provide working estimates of the rate of radiographic resolution as a function of the patient cumulative comorbidities, extent of initial radiographic involvement, functional status, and causative pathogens. DESIGN: A prospective study. PARTICIPANTS: Seventy-four patients aged 70 and older, consecutively admitted to a hospital for community-acquired bacterial pneumonia. SETTING: A university-affiliated teaching hospital. MEASUREMENTS: Chest radiographs were performed every 3 weeks from the date of admission for a total period of 12 weeks or until all radiographic abnormalities had resolved or returned to baseline. RESULTS: Sixty-four patients (86%) completed the study. The rate of radiographic clearance was estimated at 35.1% within 3 weeks, 60.2% within 6 weeks, and 84.2% within 12 weeks. Radiographic resolution was significantly slower for those with high comorbidity index, bacteremia, multilobar involvement, and enteric gram-negative bacilli pneumonias. Multivariate regression analysis demonstrated that the comorbidity index (relative risk for clearance=0.67 per class index, P<.001) and multilobar disease (relative risk for clearance=0.24 for more than one lobe, P<.001) had independent predictive value (Cox proportional hazards regression model) on the rate of resolution. CONCLUSION: The radiographic resolution of nontuberculous bacterial pneumonia in the elderly should take into account the extent of lobar disease and the burden of underlying illnesses. A waiting period of 12 to 14 weeks is recommended for slowly resolving pneumonia to be considered nonresolving.

Correlates of behavioral disturbances and pattern of psychotropic medication use in five skilled nursing facilities.

There are several treatment options for behavioral disturbances (BDs) in dementia. However, the choice of a specific psychotropic agent is directed by personal preferences and local community practice patterns. We examined the relationship between common clusters of BDs and the use of different classes of psychotropic agents in our community. A cross-sectional study of 430 long-term care residents from 5 nursing homes was undertaken. The Behavior Measurement Scale (BMS) was used to measure the frequency of BDs grouped in 4 categories. Residents with > 4 BD episodes in at least one category during a 2-week observation period were the behavior group and were considered to have clinically significant BDs. A sample of patients who had < 4 BDs in all BMS categories during the same observation period defined the nonbehavior group. A BD cluster was defined as > 4 BDs occurring in one or more BMS categories during the 2-week observation. Data on functional status, comorbidity, use of benzodiazepines, antidepressants, and neuroleptic agents were collected with chart review. The chi-square test was used to examine the correlation between variables. Clinically significant BDs were identified in 27.2% (117/430) of the residents in the sample. Five of 15 behavior clusters accounted for 73% of all clinically significant BDs. The 5 clusters were verbally nonaggressive behaviors (cluster 1, 20.5%), behaviors from all 4 categories (cluster 2, 17.9%), verbally and physically nonaggressive behaviors (cluster 3, 14.5%), physically nonaggressive behaviors (cluster 4, 12.8%), and verbally aggressive and nonaggressive behaviors (cluster 5, 7.7%). Cluster 5 had a negative correlation with functional impairment (P = .009). There was a significant correlation between cluster 2 and benzodiazepine use (P = .014). No other significant correlation was found between any of the 5 clusters and demographic variables, comorbidity status, and use of antidepressant or neuroleptic medications. Residents in the behavior group had higher impairment in self-feeding (P = .036) and bathing (P < .001) and were more likely to be treated with benzodiazepines (P = .004) and neuroleptic agents (P = .009) than residents in the nonbehavior group (n = 116). The higher use of neuroleptics and benzodiazepines in the behavior group compared with the nonbehavior group indicates that BDs are being identified for treatment, but the medications used may not be efficacious. The lack of association between specific classes of psychotropic medications and distinct behavior clusters indicates that clinicians are not using a standardized approach to target the neurochemical abnormalities that may underlie certain behavior clusters. Some behavior clusters correlate with impairment in specific activities of daily living categories such as bathing and feeding, making room for nonpharmacologic interventions.

Impact of invasive strategy on management of antimicrobial treatment failure in institutionalized older people with severe pneumonia.

The aim of the study was to investigate the etiology and the impact of invasive quantitative sampling on the management of severe pneumonia in institutionalized older people with antimicrobial treatment failure. Fifty-two institutionalized patients aged 70 years and older hospitalized with a presumptive diagnosis of severe pneumonia and failure to respond to treatment after 72 hours of initiation of outpatient antimicrobial therapy were enrolled. Microbial investigation included blood culture, serology, pleural fluid, and bronchoalveolar samples. A definite etiology could be established in 24 of 52 (46%) patients. Methicillin-resistant Staphylococcus aureus (33%), enteric Gram-negative bacilli (24%), and Pseudomonas aeruginosa (14%) accounted for most isolates. Atypical infections (2%) were uncommon. Invasive bronchial sampling directed a change of microbial therapy in 8 (40%) and discontinuation of antibiotics in 2 of 20 cases (10%) of definite pneumonia. Overall hospital mortality was 42%. There was no difference in mortality among definite or unverified cases or those who had invasive bronchial sampling-guided change in therapy. We conclude that antimicrobial therapy should be targeted toward "nosocomial" pathogens in those institutionalized patients who received prior antibiotic treatment. When combined with microbial investigation, direct visualization of the tracheobronchial tree might be useful in determining the presence of bacterial pneumonia.