Medication review and deprescribing in different healthcare settings: a position statement from an Italian scientific consortium.

Recent medical advancements have increased life expectancy, leading to a surge in patients affected by multiple chronic diseases and consequent polypharmacy, especially among older adults. This scenario increases the risk of drug interactions and adverse drug reactions, highlighting the need for medication review and deprescribing to reduce inappropriate medications and optimize therapeutic regimens, with the ultimate goal to improving patients' health and quality of life. This position statement from the Italian Scientific Consortium on medication review and deprescribing aims to describe key elements, strategies, tools, timing, and healthcare professionals to be involved, for the implementation of medication review and deprescribing in different healthcare settings (i.e., primary care, hospital, long-term care facilities, and palliative care). Challenges and potential solutions for the implementation of medication review and deprescribing are also discussed.

Predictors of hospital readmission rate in geriatric patients.

BACKGROUND: Hospital readmissions among older adults are associated with progressive functional worsening, increased institutionalization and mortality. AIM: Identify the main predictors of readmission in older adults. METHODS: We examined readmission predictors in 777 hospitalized subjects (mean age 84.40 ± 6.77 years) assessed with Comprehensive Geriatric Assessment (CGA), clinical, anthropometric and biochemical evaluations. Comorbidity burden was estimated by Charlson Comorbidity Index (CCI). Median follow-up was 365 days. RESULTS: 358 patients (46.1%) had a second admission within 365 days of discharge. Estimated probability of having a second admission was 0.119 (95%C.I. 0.095-0.141), 0.158 (95%C.I. 0.131-0.183), and 0.496 (95%C.I. 0.458-0.532) at 21, 30 and 356 days, respectively. Main predictors of readmission at 1 year were length of stay (LOS) > 14 days (p < 0.001), albumin level < 30 g/l (p 0.018), values of glomerular filtration rate (eGFR) < 40 ml/min (p < 0.001), systolic blood pressure < 115 mmHg (p < 0.001), CCI ≥ 6 (p < 0.001), and cardiovascular diagnoses. When the joint effects of selected prognostic variables were accounted for, LOS > 14 days, worse renal function, systolic blood pressure < 115 mmHg, higher comorbidity burden remained independently associated with higher readmission risk. DISCUSSION: Selected predictors are associated with higher readmission risk, and the relationship evolves with time. CONCLUSIONS: This study highlights the importance of performing an accurate CGA, since defined domains and variables contained in the CGA (i.e., LOS, lower albumin and systolic blood pressure, poor renal function, and greater comorbidity burden), when combined altogether, may offer a valid tool to identify the most fragile patients with clinical and functional impairment enhancing their risk of unplanned early and late readmission.

Evaluation of the impact on hospitalization risk of an electronic pill-box to promote therapeutic adherence in post-acute care setting: a pilot study.

Literature review reveals that adherence to prescribed therapy at hospital discharge averages around 50%. The purpose of this study was to evaluate adherence to prescribed therapy assessing the relationship between re-hospitalization rate at 30 days and degree of therapeutic adherence in a sample of elderly patients discharged from an acute geriatric ward using an Electronic Medication Packaging device, MePill. The study population (n = 56) was divided in 3 groups, a counseling group (A), a counseling + MePill device group (B) and a control group (C). Group A had 98.1% adherence to therapy, Group B had 100%, and control group had 90%. Analyzing the rate of hospitalization by type of intervention for Group A and C the hospitalization rate was 21% and 27.7%, respectively, whilst for Group B no patient was hospitalized. Participants in Group A and C had the shorter hospitalization-free survival as compared with subjects in Group B.

Myocardial Fibrosis and Steatosis in Patients with Aortic Stenosis: Roles of Myostatin and Ceramides.

Aortic stenosis (AS) involves progressive valve obstruction and a remodeling response of the left ventriculum (LV) with systolic and diastolic dysfunction. The roles of interstitial fibrosis and myocardial steatosis in LV dysfunction in AS have not been completely characterized. We enrolled 31 patients (19 women and 12 men) with severe AS undergoing elective aortic valve replacement. The subjects were clinically evaluated, and transthoracic echocardiography was performed pre-surgery. LV septal biopsies were obtained to assess fibrosis and apoptosis and fat deposition in myocytes (perilipin 5 (PLIN5)), or in the form of adipocytes within the heart (perilipin 1 (PLIN1)), the presence of ceramides and myostatin were assessed via immunohistochemistry. After BMI adjustment, we found a positive association between fibrosis and apoptotic cardiomyocytes, as well as fibrosis and the area covered by PLIN5. Apoptosis and PLIN5 were also significantly interrelated. LV fibrosis increased with a higher medium gradient (MG) and peak gradient (PG). Ceramides and myostatin levels were higher in patients within the higher MG and PG tertiles. In the linear regression analysis, increased fibrosis correlated with increased apoptosis and myostatin, independent from confounding factors. After adjustment for age and BMI, we found a positive relationship between PLIN5 and E/A and a negative correlation between septal S', global longitudinal strain (GLS), and fibrosis. Myostatin was inversely correlated with GLS and ejection fraction. Fibrosis and myocardial steatosis altogether contribute to ventricular dysfunction in severe AS. The association of myostatin and fibrosis with systolic dysfunction, as well as between myocardial steatosis and diastolic dysfunction, highlights potential therapeutic targets.

Is handgrip strength a marker of muscle and physical function of the lower limbs? Sex differences in older adults with obesity.

BACKGROUND AND AIMS: In this cross-sectional study we investigate the association between handgrip strength (HGS) and muscle function of the lower limbs and the predictors of the appendicular lean mass index (ALMI) in older adults with obesity of both sexes. METHODS AND RESULTS: Eighty-four older (67 ± 5 years) men (N = 44) and women (N = 40) with obesity (body mass index (BMI) 33 ± 4 kg/m2) performed: the HGS, isokinetic knee extensors (KE) and flexors (KF) muscle strength and power and Short Physical Performance Battery (SPPB). The correlation between HGS and lower limbs muscle function was evaluated, and four multiple hierarchical linear models were built to assess the contribution of each ALMI predictor (i.e., HGS, BMI, SPPB, muscle strength and power). In men, HGS was weakly-to-moderately associated (p < 0.05) with KE, KF muscle function and physical performance. In women, HGS showed a weak association (p < 0.05) with KE muscle function. The significant predictors of ALMI were only the BMI in women, whereas in the group of men BMI, KE maximal strength and power better explain the variance in ALMI than HGS alone. CONCLUSION: Our results suggest that HGS should not be used alone as a marker of lower muscle nor physical function. Sex differences exist with the BMI that is a contributor of ALMI both in men and women. However, at least in the group of men, markers related to strength and power of the lower limbs can better describe variations in ALMI compared to HGS in this kind of population. CLINICAL TRIAL REGISTRATION: NA.

Knee flexor and extensor torque ratio in elderly men and women with and without obesity: a cross-sectional study.

BACKGROUND: With aging and obesity lower limb torque deteriorates. Importantly, the ratio between knee flexor (KF) and extensor (KE) torque is an indicator of joint stability. AIMS: We compared KF torque and KF/KE ratio in older subjects of both sexes with obesity (OB) or without (NOB) obesity. METHODS: The maximal torque during KE and KF isokinetic contractions were evaluated at: 60, 90, 150, 180 and 210 deg/s in 89 elderly (68 ± 5 years) subjects with NOB (BMI < 30 kg/m2) and OB (BMI ≥ 30 kg/m2). Values were normalised for body weight (BW) and leg lean mass (i.e., muscle quality). RESULTS: At all speeds men had higher absolute KF values (P < 0.001). When values were normalised for BW, sex differences remain in favour of men (P < 0.001) with lower values in both groups with OB than NOB (P < 0.001). Muscle quality and KF/KE ratio were lower in OB than NOB (P < 0.001). CONCLUSIONS: The KF torque and KF/KE ratio decline with aging and with OB. In all groups, the KF/KE ratio was below the joint stability threshold. Thus, exercise physiologists should include exercises designed to train both KE and KF in older subjects with OB.

Full characterisation of knee extensors' function in ageing: effect of sex and obesity.

BACKGROUND/OBJECTIVES: Muscle function is a marker of current and prospective health/independence throughout life. The effects of sex and obesity (OB) on the loss of muscle function in ageing remain unresolved, with important implications for the diagnosis/monitoring of sarcopenia. To characterise in vivo knee extensors' function, we compared muscles torque and power with isometric and isokinetic tests in older men (M) and women (W), with normal range (NW) of body mass index (BMI) and OB. SUBJECTS/METHODS: In 70 sedentary older M and W (69 ± 5 years), NW and OB (i.e. BMI < 30 kg m-2 and ≥30 kg m-2, respectively) we tested the right knee's extensor: (i) isometric torque at 30°, 60°, 75° and 90° knee angles, and (ii) isokinetic concentric torque at 60, 90, 150, 180 and 210° s-1 angular speeds. Maximal isometric T-angle, maximal isokinetic knee-extensor torque-velocity, theoretical maximal shortening velocity, maximal power, optimal torque and velocity were determined in absolute units, normalised by body mass (BM) and right leg lean mass (LLMR) and compared over sex, BMI categories and angle or angular speeds by three-way ANOVA. RESULTS: In absolute units, relative to BM and LLMR, sex differences were found in favour of M for all parameters of muscle function (main effect for sex, p < 0.05). OB did not affect either absolute or relative to LLMR isometric and isokinetic muscle function (main effect for BMI, p > 0.05); however, muscle function indices, when adjusted for BM, were lower in both M and W with OB compared to NW counterparts (p < 0.05). CONCLUSIONS: We confirmed sex differences in absolute, relative to BM and LLMR muscle function in favour of men. While overall muscle function and muscle contractile quality is conserved in individuals with class I OB, muscle function normalised for BM, which defines the ability to perform independently and safely the activities of daily living, is impaired in comparison with physiological ageing.

Impact of different patterns of metastasis in non-small-cell lung cancer patients.

Aim: The aim of this study was to evaluate the frequency and median time for the development of metastases and prognosis by metastatic site after the diagnosis of non-small-cell lung cancer (NSCLC). Patients & methods: This cohort study was conducted with 1096 patients diagnosed with NSCLC between 2006 and 2014. Results: The most prevalent site of NSCLC metastases was the respiratory system. The nervous and adrenal systems presented the longest median time for the development of metastases. The 6-month survival varied from 68.2% for liver to 79.9% for the nervous system. Bone metastases were associated with a higher risk of death. Conclusion: The respiratory system was the most prevalent site of metastases. OS and risk of death varied according to the metastatic site.

Prolonged unsupervised Nordic walking and walking exercise following six months of supervision in adults with overweight and obesity: A randomised clinical trial.

BACKGROUND AND AIMS: This study is a randomized trial that examined the effects of 6 months of unsupervised Nordic walking (NW) and walking (W) exercise following 6 months of supervised training in overweight/obese adults. METHODS AND RESULTS: After a 6-month program of diet and supervised training participants (n = 27) of NW (66 ± 7 yrs, body mass index (BMI) 34 ± 5) and W (66 ± 8 yrs, BMI 32 ± 5) group continue the training without supervision for other 6 months. Steps count and mean heart rate (HRmean) were performed in each session; anthropometric and body composition, aerobic capacity and strength of the upper and lower limbs were evaluated at baseline, after 6 months of supervised and 6 months of unsupervised training. In the unsupervised training, monthly sessions and steps count decreased over time in both groups (p < 0.05), with no significant changes in HRmean. Compared to the supervised phase, adherence decreased significantly only in the W group in the last 3 months of unsupervised training. Compared to baseline in both groups BMI did not change, but W group lost total fat; only the NW group maintained (p < 0.05) the gains in arm curl (33%) and chair stand (31%); both groups improved in six-minute walking test (p < 0.05). CONCLUSION: Despite unsupervised training was not effective for a further increase in performance, participants, especially in NW, maintained some of the improvements achieved during the supervision. However, the presence of instructor that guides training, may enhance adherence and health benefits of NW and W exercise. CLINICAL TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT03212391 (July 11, 2017).

Obesity as a risk factor for unfavourable outcomes in critically ill patients affected by Covid 19.

BACKGROUND AND AIMS: Recent studies show that obesity is a risk factor for hospital admission and for critical care need in patients with coronavirus disease 2019 (COVID-19). The aim was to determine whether obesity is a risk factor for unfavourable health outcomes in patients affected by COVID-19 admitted to ICU. METHODS AND RESULTS: 95 consecutive patients with COVID-19 (78 males and 18 females) were admitted to ICU and included in the study. Height, weight, BMI, Sequential Organ Failure Assessment (SOFA) and Acute Physiology and Chronic Health Evaluation II (APACHE II) scores, CRP, CPK, ICU and hospital length of stay and comorbidities were evaluated. Participants with obesity had a lower 28 day survival rate from ICU admission than normal weight subjects. Cox proportional hazard model-derived estimates, adjusted for age, gender and comorbidity, confirmed the results of the survival analysis (HR:5.30,95%C.I.1.26-22.34). Obese subjects showed longer hospital and ICU stay as compared with normal weight counterpart.Subjects with obesity showed significantly higher CRP and CPK levels than normal weight subjects. CONCLUSION: In individuals with obesity, careful management and prompt intervention in case of suspected SARS-CoV-2 infection is necessary to prevent the progression of the disease towards severe outcomes and the increase of hospital treatment costs.

Predictors of overall survival in non-small-cell lung cancer patients with metastatic spinal cord compression treated with short-course radiotherapy.

Metastatic spinal cord compression (MSCC) is a condition that impacts directly on the patient's prognosis. OBJECTIVE: The study purpose was to identify predictors of overall survival in non-small-cell lung cancer (NSCLC) patients with MSCC. METHODS: A cohort study involving NSCLC patients enrolled between 2008 and 2017 was performed. Sixty-four patients treated with short-course radiotherapy were included. Clinical and socio-demographic data were extracted from medical records. Data were analysed using survival analysis and Cox proportional hazard regression analysis. RESULTS: The median survival time was 2.5 months (95% CI: 1.6-3.5). Patients >60 years had shorter survival than younger patients (HR 1.85; 95% CI 1.06-3.24; p = 0.02), and patients with performance status (PS) >2 had shorter survival than those with PS≤2 (HR 1.93; 95% CI 1.12-3.33; p = 0.01). CONCLUSION: This study found worse PS and higher age are independent predictors of overall survival in NSCLC patients with MSCC treated with short-course radiotherapy after adjusting the potential confounding factors (PS, age and target therapy).

The Mini Sarcopenia Risk Assessment (MSRA) Questionnaire score as a predictor of skeletal muscle mass loss.

BACKGROUND: Previous studies showed a strong relationship between reduction of appendicular muscle mass and worsening disability; hence, accuracy in assessing muscle mass is considered a key feature for a sarcopenia screening tool. AIM: The aim of the study was to evaluate if the 7 items of Mini Sarcopenia Risk Assessment (MSRA) questionnaire predict muscle mass loss in a population of community-dwelling elderly subjects over a 5.5-y follow-up. METHODS: The study included 159 subjects, 92 women and 67 men aged 71.5 ± 2.2 years and with mean body mass index of 26.7 ± 4.0 kg/m2. Appendicular skeletal muscle mass (ASMM) as measured with Dual-Energy X-ray absorptiometry (DXA), was obtained at baseline and after 2 and 5.5 years of follow-up where the skeletal muscle index (SMI) was calculated. RESULTS: A significant reduction of ASMM and SMI was observed at two and 5.5 years of follow-up, in both, men and women. Repeated-measures analysis of variance (ANOVA) found a significant time effect on ASMM for both subjects with MSRA > 30 and ≤ 30 (P < 0.01 and P < 0.001). The group × time interaction was significant (P < 0.001), after even considering separately subjects with normal muscle mass and low muscle mass at baseline (P < 0.05 and P = 0.005). Similar results were obtained for SMI. Considering only the subjects with normal SMI at baseline, subjects with MSRA questionnaire ≤ 30 showed 5.7 (95% CI 1.73-19.03) higher risk of exceeding the low muscle mass threshold. CONCLUSION: In a population of community-dwelling elderly men and women, MSRA score of 30 is predictive of a steeper decline in ASMM and SMI and of a higher risk of exceeding the low muscle mass EWGSOP threshold.

Sarcopenia and obesity.

PURPOSE OF REVIEW: Together with age-related body composition changes, the increased prevalence of obesity observed in the past few decades in older individuals has led to a condition called sarcopenic obesity, characterized by a mismatch between muscle mass and fat mass. The operative definition of sarcopenic obesity is still under discussion and creates difficulties in clinical practice. Muscle weakness, rather than low muscle mass, was previously proposed as an alternative criterion and, more recently, the dynapenic abdominal obese phenotype is of increasing interest because of its unfavorable health consequences and usability in clinical practice. RECENT FINDINGS: This review focuses on the most recent findings of pathogenic inter-relationships between adipose tissue and muscle. Recent studies on health consequences of sarcopenic obesity and dynapenic abdominal obesity are also examined. Despite the lack of consensus on a definition for sarcopenic obesity, progress has been made in the delineation of the treatment principles for this condition. SUMMARY: Further research is needed to compare different definitions of sarcopenic/dynapenic obesity to clarify the relationship between obesity and the most important adverse outcomes in the elderly. The next step will be the definition of best possible therapeutic approaches for this condition.

Sarcopenia: revised European consensus on definition and diagnosis.

Background: in 2010, the European Working Group on Sarcopenia in Older People (EWGSOP) published a sarcopenia definition that aimed to foster advances in identifying and caring for people with sarcopenia. In early 2018, the Working Group met again (EWGSOP2) to update the original definition in order to reflect scientific and clinical evidence that has built over the last decade. This paper presents our updated findings. Objectives: to increase consistency of research design, clinical diagnoses and ultimately, care for people with sarcopenia. Recommendations: sarcopenia is a muscle disease (muscle failure) rooted in adverse muscle changes that accrue across a lifetime; sarcopenia is common among adults of older age but can also occur earlier in life. In this updated consensus paper on sarcopenia, EWGSOP2: (1) focuses on low muscle strength as a key characteristic of sarcopenia, uses detection of low muscle quantity and quality to confirm the sarcopenia diagnosis, and identifies poor physical performance as indicative of severe sarcopenia; (2) updates the clinical algorithm that can be used for sarcopenia case-finding, diagnosis and confirmation, and severity determination and (3) provides clear cut-off points for measurements of variables that identify and characterise sarcopenia. Conclusions: EWGSOP2's updated recommendations aim to increase awareness of sarcopenia and its risk. With these new recommendations, EWGSOP2 calls for healthcare professionals who treat patients at risk for sarcopenia to take actions that will promote early detection and treatment. We also encourage more research in the field of sarcopenia in order to prevent or delay adverse health outcomes that incur a heavy burden for patients and healthcare systems.

Predictors of self-reported adherence to direct oral anticoagulation in a population of elderly men and women with non-valvular atrial fibrillation.

There is a general lack of studies evaluating medication adherence with self-report scales for elderly patients in treatment with direct oral anticoagulants (DOACs). The aim of the study was to assess the degree of adherence to DOAC therapy in a population of elderly outpatients aged 65 years or older affected by non-valvular atrial fibrillation (NVAF), using the 4-item Morisky Medication Adherence Scale, and to identify potential factors, including the geriatric multidimensional evaluation, which can affect adherence in the study population. A total of 103 subjects, anticoagulated with DOACs for NVAF in primary or secondary prevention, were eligible; 76 showed adequate adhesion to anticoagulant therapy, while 27 showed inadequate adherence. Participants underwent biochemical assessment and Morisky Scale, Instrumental Activities of Daily Living, CHA2DS2-VASc, HAS-BLED, mental status and nutritional evaluations were performed. 2% of subjects assumed Dabigatran at low dose, while 7.8% at standard dose, 9.7% assumed low-dose of Rivaroxaban and 30.1% at standard dose, 6.8% assumed Apixaban at low dose and 39.7% at standard dose, and finally 1% assumed Edoxaban at low dose and 2.9% at standard dose. Most subjects took the DOACs without help (80.6%), while 16 subjects were helped by a family member (15.5%) and 4 were assisted by a caregiver (3.9%). Binary logistic regression considered inappropriate adherence as a dependent variable, while age, male sex, polypharmacotherapy, cognitive decay, caregiver help for therapy assumption, duration of DOAC therapy and double daily administration were considered as independent variables. The double daily administration was an independent factor, determining inappropriate adherence with an OR of 2.88 (p = 0.048, CI 1.003-8.286).

Can we reliably predict the level of anticoagulation after enoxaparin injection in elderly patients with renal failure?

OBJECTIVES: The aim of this study was to evaluate the activity of anti-activated factor X (anti-Xa) in patients with different degrees of chronic renal failure (CRF), treated with therapeutic doses of low molecular weight heparin. DESIGN: This prospective study evaluated the effect of age, renal function, BMI, gender, in determining the efficacy and safety of treatment with enoxaparin, evaluated by assessing the anti-Xa. The therapeutic anticoagulant range was set between 0.20 and 0.70 U/mL. SETTING: Two hospital geriatric units. PARTICIPANTS: 98 patients (64 men, 34 women, mean age 82 years) with CRF, treated with enoxaparin at therapeutic dosage, for deep vein thrombosis or acute coronary syndrome. MEASUREMENTS: Anti-Xa was assessed 4 h after the third administration of LMWH using Chromogenix test. Renal function was assessed by calculating creatinine clearance according to Cockcroft formula. RESULTS: The dose of enoxaparin ranged between 53 and 200 U/kg; total 4000-16000 U/day. The mean anti-Xa was 0.41 U/mL (95% CI 0.36-0.45). Multiple regression analysis selected only the dose of enoxaparin, but not age, creatinine clearance, BMI, gender, as a predictor of anti-Xa serum levels. In seven patients anti-Xa was above the range but none of them received more than 150 U/Kg enoxaparin (100 U/kg if creatinine clearance <30 mL/min). Ten patients (eight men, two women) showed suboptimal levels of anti-Xa, regardless enoxaparin dose or creatinine clearance. CONCLUSION: Enoxaparin dose reduction according to renal function decreases the risk of overdosing and potentially the risk of bleeding. The risk of under dosing seems less predictable; therefore, anti-Xa assay may be useful in severe clinical situations that require higher anticoagulant activity.

Models of lipid droplets growth and fission in adipocyte cells.

Lipid droplets (LD) are spherical cellular inclusion devoted to lipids storage. It is well known that excessive accumulation of lipids leads to several human worldwide diseases like obesity, type 2 diabetes, hepatic steatosis and atherosclerosis. LDs' size range from fraction to one hundred of micrometers in adipocytes and is related to the lipid content, but their growth is still a puzzling question. It has been suggested that LDs can grow in size due to the fusion process by which a larger LD is obtained by the merging of two smaller LDs, but these events seems to be rare and difficult to be observed. Many other processes are thought to be involved in the number and growth of LDs, like the de novo formation and the growth through additional neutral lipid deposition in pre-existing droplets. Moreover the number and size of LDs are influenced by the catabolism and the absorption or interaction with other organelles. The comprehension of these processes could help in the confinement of the pathologies related to lipid accumulation. In this study the LDs' size distribution, number and the total volume of immature (n=12), mature (n=12, 10-days differentiated) and lipolytic (n=12) 3T3-L1 adipocytes were considered. More than 11,000 LDs were measured in the 36 cells after Oil Red O staining. In a previous work Monte Carlo simulations were used to mimic the fusion process alone between LDs. We found that, considering the fusion as the only process acting on the LDs, the size distribution in mature adipocytes can be obtained with numerical simulation starting from the size distribution in immature cells provided a very high rate of fusion events. In this paper Monte Carlo simulations were developed to mimic the interaction between LDs taking into account many other processes in addition to fusion (de novo formation and the growth through additional neutral lipid deposition in pre-existing droplets) in order to reproduce the LDs growth and we also simulated the catabolism (fission and the decrease through neutral lipid exit from pre-existing droplets) to reproduce their size reduction observed in lipolytic conditions. The results suggest that each single process, considered alone, can not be considered the only responsible for the size variation observed, but more than one of them, playing together, can quite well reproduce the experimental data.

Lipid droplets fusion in adipocyte differentiated 3T3-L1 cells: a Monte Carlo simulation.

Several human worldwide diseases like obesity, type 2 diabetes, hepatic steatosis, atherosclerosis and other metabolic pathologies are related to the excessive accumulation of lipids in cells. Lipids accumulate in spherical cellular inclusions called lipid droplets (LDs) whose sizes range from fraction to one hundred of micrometers in adipocytes. It has been suggested that LDs can grow in size due to a fusion process by which a larger LD is obtained with spherical shape and volume equal to the sum of the progenitors' ones. In this study, the size distribution of two populations of LDs was analyzed in immature and mature (5-days differentiated) 3T3-L1 adipocytes (first and second populations, respectively) after Oil Red O staining. A Monte Carlo simulation of interaction between LDs has been developed in order to quantify the size distribution and the number of fusion events needed to obtain the distribution of the second population size starting from the first one. Four models are presented here based on different kinds of interaction: a surface weighted interaction (R2 Model), a volume weighted interaction (R3 Model), a random interaction (Random model) and an interaction related to the place where the LDs are born (Nearest Model). The last two models mimic quite well the behavior found in the experimental data. This work represents a first step in developing numerical simulations of the LDs growth process. Due to the complex phenomena involving LDs (absorption, growth through additional neutral lipid deposition in existing droplets, de novo formation and catabolism) the study focuses on the fusion process. The results suggest that, to obtain the observed size distribution, a number of fusion events comparable with the number of LDs themselves is needed. Moreover the MC approach results a powerful tool for investigating the LDs growth process.

Important prognostic factors for survival in patients with malignant pleural effusion.

BACKGROUND: The approach to palliative treatment of malignant pleural effusion (MPE) should be individualized because these patients generally have poor survival. Our study aimed to develop a model to identify prognostic factors or survival time in patients diagnosed with MPE. METHODS: This is a retrospective, descriptive, observational study to identify prognostic factors related to MPE in patients with a confirmed cancer diagnosis. Cox regression analysis was used to determine significant potential prognostic factors with respect to survival time. Survival time was defined as the time from pathological diagnosis to death. RESULTS: One hundred and sixty-five patients were included; 77 were men (47%) and 88 were women (53%). The median age was 60 years, and all of the patients were pathologically proven to have MPE. Non-small-cell lung cancer (36.0%), breast carcinoma (26%), and lymphoma (13.0%) were the most frequently diagnosed tumors. The median overall survival of patients from the initial diagnosis was 5 months (range: 1.0-96.0 months). Kaplan-Meier univariate analysis showed that survival was significantly related to the following prognostic factors: ECOG PS (hazard ratio [HR] 10.0, 95% confidence interval [95% CI] 5.96 to 18.50, p < 0.0001), primary cancer site (HR 1.99, 95% CI 1.23 to 3.22, p < 0.01), positive pleural cytology (HR 1.25, 95% CI 0.88 to 1.78, p = 0.04), and positive histology (HR 1.33, 95% CI 0.97 to 1.81, p = 0.04). Other potential independent diagnostic factors that were examined did not affect survival. Cox regression analysis showed that only the ECOG PS was highly predictive of survival (HR 73.58, 95% CI 23.44 to 230.95, p < 0.0001). CONCLUSIONS: ECOG PS is an independent predictor of survival in patients with MPE at initial diagnosis. This prognostic factor can help physicians select patients for appropriate palliative treatment of this syndrome.

The pathogenetic bases of sarcopenia.

Aging is accompanied by involuntary loss of skeletal muscle mass, strength and function, called sarcopenia. The mechanisms underlying the development of sarcopenia are not completely understood and most likely multi-factorial, but significant progress has been made over the past few years to identify some of the major contributors. Besides life style-related factors, as diet and physical activity, sarcopenia seems to be also determined by hormonal dysregulation, chronic inflammatory status, ectopic adipose tissue accumulation, neurological and vascular changes associated with aging. The present mini-review focused on the basic factors that primarily impact muscle homeostasis in older subjects. A better understanding of cellular mechanism leading to sarcopenia is required to establish evidence-based intervention in order to prevent onset of symptoms associated with sarcopenia and to extend the time free from disability in older adults.