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.

Long-Term Anatomic and Visual Outcome Following Vitrectomy for Stage 4B and 5 Retinopathy of Prematurity.

BACKGROUND AND OBJECTIVES: Surgical indications in stages 4B and 5 retinopathy of prematurity (ROP) are not universally accepted. The authors' purpose is to evaluate the long-term anatomic and visual outcomes of vitrectomy for retinal detachment (RD) associated with stages 4B and 5 ROP. PATIENTS AND METHODS: Data of patients who consecutively underwent vitrectomy for stages 4B and 5 ROP from 1999 to 2013 were retrospectively reviewed and included grade of retinal attachment and visual acuity (VA) at the last follow-up. RESULTS: Seventy eyes of 38 infants were included: 23 with stage 4B and 47 with stage 5 ROP. Lens-sparing vitrectomy was performed in 11 eyes, combined lensectomy / vitrectomy in 59 eyes. Mean follow-up was 8.5 years. Anatomic success was maintained in 41 eyes (58.5%), and among them, VA greater than 5/200 was achieved in 17 eyes (41.4%). CONCLUSION: The long-term visual and anatomic success rates were encouraging for the surgical correction of RD associated with late stages ROP. [Ophthalmic Surg Lasers Imaging Retina. 2019;50:208-214.].

Prognostic factors in ectopic Cushing's syndrome due to neuroendocrine tumors: a multicenter study.

OBJECTIVE: Evidence is limited regarding outcome of patients with ectopic Cushing's syndrome (ECS) due to neuroendocrine tumors (NETs). DESIGN: We assessed the prognostic factors affecting the survival of patients with NETs and ECS. METHODS: Retrospective analysis of clinicopathological features, severity of hormonal syndrome, treatments from a large cohort of patients with NETs and ECS collected from 17 Italian centers. RESULTS: Our series included 110 patients, 58.2% female, with mean (±s.d.) age at diagnosis of 49.5 ± 15.9 years. The main sources of ectopic ACTH were bronchial carcinoids (BC) (40.9%), occult tumors (22.7%) and pancreatic (p)NETs (15.5%). Curative surgery was performed in 56.7% (70.2% of BC, 11% of pNETs). Overall survival was significantly higher in BC compared with pNETs and occult tumors (P = 0.033) and in G1-NETs compared with G2 and G3 (P = 0.007). Negative predictive factors for survival were severity of hypercortisolism (P < 0.02), hypokalemia (P = 0.001), diabetes mellitus (P = 0.0146) and distant metastases (P < 0.001). Improved survival was observed in patients who underwent NET removal (P < 0.001). Adrenalectomy improved short-term survival. CONCLUSIONS: Multiple factors affect prognosis of ECS patients: type of NET, grading, distant metastases, severity of hypercortisolism, hypokalemia and diabetes mellitus. BCs have the highest curative surgical rate and better survival compared with occult tumors and pNETs. Hypercortisolism plays a primary role in affecting outcome and quality of life; therefore, prompt and vigorous treatment of hormonal excess by NET surgery and medical therapy should be a key therapeutic goal. In refractory cases, adrenalectomy should be considered as it affects outcome positively at least in the first 2 years.

Renal shear wave velocity and estimated glomerular filtration rate in children with chronic kidney disease.

A shear wave velocity (SWV) value obtained by the acoustic radiation force impulse technique depends on tissue elasticity. We investigated the relationship between SWV values and the estimated glomerular filtration rate (eGFR) in children with chronic kidney disease. A total of 29 patients were enrolled in the study. There were 18 primary and 11 secondary cases of vesicoureteral reflux. eGFR was calculated using Schwartz's formulas (2012). Partial eGFR for each kidney was assessed by multiplying the eGFR by the percentage of renal function measured by means of renal (99m)Tc-dimercaptosuccinic acid scintigraphy. All ultrasound tests were done by a single qualified technician using a convex probe (frequency 4 MHz) on an S-2000 system. The mean SWV values of the two kidneys were significantly and negatively correlated with eGFR calculated with both univariate (cystatin C [Cys C] and multivariate (creatinine, Cys C, and nitrogen) equations. Of all the formulae, the strongest correlation was obtained with eGFR (Cys C). SWV of the renal cortex correlates with the eGFR of patients affected by malformative uropathies. Nevertheless, this technique needs standardization and validation.

Dynapenic abdominal obesity as predictor of mortality and disability worsening in older adults: A 10-year prospective study.

UNLABELLED: There are relatively few prospective studies evaluating the combined effect of abdominal obesity and low muscle strength on worsening disability and on mortality. The study aimed at evaluating prospectively the prognostic value of dynapenic abdominal obesity definition on disability worsening in a 5.5-year follow-up and mortality in a 10-year follow-up. METHODS: In 93 men and 169 women aged between 66 and 78 years, leg isometric strength, waist circumference (WC), BMI, glycemia, HOMA, lipid profile, vitamin D3, albumin, fibrinogen, physical activity level, income, smoking status and comorbidities were evaluated at the baseline. Reported disabilities were measured at baseline, 1-y, 2-y, 3-y and 5.5-y follow-up and mortality rate was evaluated during a 10-y follow-up. The study population was categorized in dynapenic abdominal obese (D/AO), nondynapenic abdominal obese (ND/AO), dynapenic nonabdominal obese (D/NAO), nondynapenic nonabdominal obese (ND/NAO) according to muscle strength/WC tertiles. RESULTS: D/NAO subjects presented a disability worsening risk of 1.69 times (95%CI:1.11-2.57), ND/AO subjects showed a 2-fold increase in risk (95%CI:1.34-2.98), while being D/AO more than trebled the risk, even after considering confounding variables (HR:3.39,95%CI:1.91-6.02). Mortality risk after adjustment for other confounding variables was 1.57 (95%CI:1.16-2.13) for ND/AO and 2.46 (95%CI:1.34-4.52) for D/AO. CONCLUSIONS: Dynapenic abdominal obese subjects are at higher risk of worsening disability and mortality than subjects with dynapenia or central fat distribution only.

A 10-Year Follow-Up Study of Subjects Recruited in a Health Campaign for the Early Diagnosis of Cutaneous Melanoma: Suggestions for the Screening Timetable.

BACKGROUND: Cutaneous melanoma affects people at a relatively young age. The possibility of making a screening at the population level is strongly limited because of the high costs and the shortage of well-trained operators. OBJECTIVE: To evaluate the possibility of a sustainable timetable of screening examinations for cutaneous melanoma. METHODS: Subjects who contacted the Lega Italiana per la Lotta contro i Tumori (Italian League against Cancer) between January 2001 and December 2004 were followed up to December 2013 through linkage with the Trento Skin Cancer Registry. The cumulative incidence of cutaneous melanoma was calculated and compared with that observed in the general population. RESULTS: Fifteen newly diagnosed cutaneous melanomas were observed in 3,635 subjects during the screening phase, while 14 new cases were diagnosed within December 2013, in the period of follow-up after the screening. The 95% confidence interval for the cumulative incidence of screened subjects included the cumulative incidence of the general population. No new cutaneous melanomas were detected in a 2-year period, after the first examination, 2 cases within 3 years. CONCLUSIONS: Based on our study, we think that in a selected population a screening programme can be performed every 2-3 years. This could help make a screening possible/sustainable for the early diagnosis of cutaneous melanoma in a public health context.

Heart Fat Infiltration In Subjects With and Without Coronary Artery Disease.

CONTEXT: Fat may accumulate around the heart in epicardial adipose tissue or inside the heart as lipid droplets (LDs). OBJECTIVE: To compare myocardial steatosis between subjects with and without coronary artery disease (CAD and non-CAD) and to identify which cells contain LDs. DESIGN: Body mass index, waist circumference, glucose, insulin, homeostasis model assessment index, leptin, adiponectin, and high-sensitivity C-reactive protein were evaluated in CAD and non-CAD subjects. Biopsies were collected from right atrial myocardium. Immunohistochemistry for perilipin (PLIN) 1 and 2 was used to characterize LDs and their localization in adipocytes or myocardial cells, respectively. Cardiomyocytes apoptosis and hypoxia inducible factor 1 alpha were obtained in a subgroup of subjects. SETTING: The study took place in a hospital. PATIENTS: Male subjects consecutively undergoing elective cardiac surgery either for coronary bypass grafting (CAD, n = 23) or for valve replacement (non-CAD, n = 18). MAIN OUTCOMES AND MEASURES: The study was designed to compare myocardial steatosis between subjects with and without coronary artery disease. RESULTS: PLIN1 and PLIN2 resulted significantly higher in CAD than in non-CAD subjects, as did apoptosis. PLIN1 was positively associated with circulating leptin, high-sensitivity C-reactive protein, and apoptosis, and negatively with adiponectin. PLIN2 was positively associated with body mass index, waist circumference, and leptin and negatively with adiponectin. After taking into account the absence/presence of hypertension, diabetes, and CAD/non-CAD, adiponectin was negatively associated with PLIN1 (r(2) = 0.532); waist circumference and adiponectin were associated with PLIN2 (r(2) = 0.399). CONCLUSIONS: Myocardial steatosis is greater in CAD than non-CAD subjects, depending on both metabolically active adipocytes interspersed among cardiomyocytes and higher fat deposition inside cardiomyocytes; serum adiponectin and waist circumference are independent predictors of myocardial steatosis.

Myosteatosis and myofibrosis: relationship with aging, inflammation and insulin resistance.

The mechanisms impairing muscle quality and leading to myofibrosis (MF) and myosteatosis (MS) are incompletely known. In biopsies of paraspinous muscle (PM) of 16 elderly men undergoing elective vertebral surgery, we histologically determined the area of MF and MS expressed as muscle quality index (MQI), in order to investigate the relation between them, as well as the main predictors of muscle quality. Total PM area and intermuscular adipose tissue (IMAT) were evaluated by MRI and body composition by DXA. Circulating fasting glucose, insulin, hs-CRP, leptin, adiponectin and IL-6 were measured and HOMA index calculated. Quantification of gene expression in PM and in subcutaneous adipose tissue (SAT) overlying the muscle was performed by rt-PCR. The degree of MS and MF was significantly and positively related to each other and positively associated with BMI, waist, FM and FM% as well as with IMAT. The area of PM was negatively related with MF even after adjustment for weight. Leptin was positively associated with MF and MS, whereas hs-CRP to MF. In backward regression analyses, larger waist and smaller PM area explained 90% of MF variance, whereas leptin about 80% of MS variance. IL-6 expression in SAT was significantly higher in participants with higher MQI values. In PM biopsies we found significantly higher expression of SOCS-3 and a trend toward higher expression of myostatin with greater degrees of MQI. MS and MF are related phenomena that concur to alter muscle quality and both should be considered in further studies on the evolution of sarcopenia.

Determining the oncological risk of autologous lipoaspirate grafting for post-mastectomy breast reconstruction.

This study compares the incidence of local and regional recurrence of breast cancer between two contiguous time windows in a homogeneous population of 137 patients who underwent fat tissue transplant after modified radical mastectomy. Median follow-up time was 7.6 years and the follow-up period was divided into two contiguous time windows, the first starting at the date of the radical mastectomy and ending at the first lipoaspirate grafting session and the second beginning at the time of the first lipoaspirate grafting session and ending at the end of the total follow-up time. Although this study did not employ an independent control group, the incidence of local recurrence of breast cancer was found to be comparable between the two periods and in line with data from similar patient populations enrolled in large multicenter clinical trials and who did not undergo postsurgical fat tissue grafting. Statistical comparison of disease-free survival curves revealed no significant differences in relapse rate between the two patient subgroups before fat grafting and after fat grafting. Although further confirmation is needed from multicenter randomized clinical trials, our results support the hypothesis that autologous lipoaspirate transplant combines striking regenerative properties with no or marginal effects on the probability of post-mastectomy locoregional recurrence of breast cancer.

Quantification of intermuscular adipose tissue in the erector spinae muscle by MRI: agreement with histological evaluation.

Deposition of fat between skeletal muscle bundles and beneath the muscle fascia, recently called intermuscular adipose tissue (IMAT), is gaining attention as potential contributor to insulin resistance, metabolic syndrome, muscle function impairment, and disability. The aim of this study was to compare IMAT as measured at the erector spinae level by magnetic resonance imaging (MRI), a well-recognized gold standard method to evaluate fat content inside muscles, and histology estimates. In 18 healthy elderly men and women with a wide range of BMI (25.05-35.58 kg/m(2)), undergoing elective vertebral surgery, IMAT within the erector spinae muscle was evaluated by MRI, by body composition using dual-energy X-ray absorptiometry and histological evaluation of intraoperative biopsy sample. The concordance between IMAT/total area (TA) ratio evaluated by MRI and histological examination was analyzed employing Lin's concordance correlation coefficient and the procedure proposed by Bland and Altman. Two thresholds to distinguish between muscle and IMAT calculated, respectively, by 20 and 10% reduction of the gray-level intensity evaluated by MRI from surrounding subcutaneous adipose tissue (SAT) were used. With a 20% reduction, calculated IMAT/TA as evaluated by MRI on average exceeds histological evaluation by 21.79%, whereas by reducing the threshold by 10% agreement between MRI and histology improved with a 12.42% difference. Our data show a good degree of concordance between IMAT assessment by MRI and histology and seems to show that agreement between the two methods could be improved by using a more restrictive threshold between muscle and fat.

Leptin and its receptor are overexpressed in brain tumors and correlate with the degree of malignancy.

Although leptin and its receptor (ObR) have emerged as important cancer biomarkers, the role of the leptin system in brain tumor development remains unknown. We screened 87 human brain tumor biopsies using immunohistochemistry and detected leptin and ObR in 55.2% and 60.9% cases, respectively. In contrast, leptin and ObR were absent in 14 samples of normal brain tissue. The presence of leptin correlated with ObR with overall concordance 80.5%. The leptin/ObR system was highly expressed in glioblastomas and anaplastic astrocytomas, while lower expression of both markers was noted in low-grade astrocytomas and gangliogliomas. The association between leptin/ObR and the degree of tumor malignancy was highly significant (P < 0.001). Using double immunofluorescence of glioblastoma tissues, we found co-expression of leptin with ObR and with the proliferation marker Ki-67 in 87% and 64% of cells, respectively. The leptin/ObR-positive tissues also expressed activated forms of STAT3 and Akt. In line with this finding, ObR-positive glioblastoma cells responded to leptin with cell growth and induction of the STAT3 and Akt pathways as well as inactivation of the cell cycle suppressor Rb. In summary, our data demonstrate that the leptin/ObR system is expressed in malignant brain tumors and might be involved in tumor progression.

Clinical relevance of sentinel lymph node status examined with conventional histology and molecular biology.

AIMS AND BACKGROUND: The presence of nodal metastases in patients with primary cutaneous melanoma adversely affects the biological behavior and is related to a poor prognosis. The role of sentinel lymph node biopsy is still debated. The aim of this study was to evaluate the prognostic role of sentinel lymph node biopsy with respect to disease-free period and overall survival. PATIENTS AND METHODS: Patients with invasive cutaneous melanoma who underwent sentinel lymph node biopsy in the Santa Chiara Hospital of Trento between October 1997 and December 2002 were evaluated. The lymph nodes were examined with conventional histology, S100 and tyrosinase in immunohistochemistry, and tyrosinase in molecular biology. RESULTS: There were 144 patients with 198 sentinel lymph nodes. A significant association was found in conventional histology with Clark level and Breslow thickness. The prognostic role of sentinel lymph node status was independent of the other considered variables. However, no significant association was found with the molecular biology test. A significant excess of positive results at molecular biology was found. CONCLUSIONS: Sentinel lymph node biopsy is an important independent prognostic factor for invasive cutaneous melanoma, but only when evaluated with conventional histology. As a result of this study, we stopped performing the tyrosinase test in molecular biology.

Leptin/HER2 crosstalk in breast cancer: in vitro study and preliminary in vivo analysis.

BACKGROUND: Obesity in postmenopausal women is associated with increased breast cancer risk, development of more aggressive tumors and resistance to certain anti-breast cancer treatments. Some of these effects might be mediated by obesity hormone leptin, acting independently or modulating other signaling pathways. Here we focused on the link between leptin and HER2. We tested if HER2 and the leptin receptor (ObR) can be coexpressed in breast cancer cell models, whether these two receptors can physically interact, and whether leptin can transactivate HER2. Next, we studied if leptin/ObR can coexist with HER2 in breast cancer tissues, and if presence of these two systems correlates with specific clinicopathological features. METHODS: Expression of ObR, HER2, phospho-HER2 was assessed by immunoblotting. Physical interactions between ObR and HER2 were probed by immunoprecipitation and fluorescent immunostaining. Expression of leptin and ObR in breast cancer tissues was detected by immunohistochemistry (IHC). Associations among markers studied by IHC were evaluated using Fisher's exact test for count data. RESULTS: HER2 and ObR were coexpressed in all studied breast cancer cell lines. In MCF-7 cells, HER2 physically interacted with ObR and leptin treatment increased HER2 phosphorylation on Tyr 1248. In 59 breast cancers, the presence of leptin was correlated with ObR (the overall association was about 93%). This result was confirmed both in HER2-positive and in HER2-negative subgroups. The expression of leptin or ObR was numerically more frequent in larger (> 10 mm) tumors. CONCLUSION: Coexpression of HER2 and the leptin/ObR system might contribute to enhanced HER2 activity and reduced sensitivity to anti-HER2 treatments.

Incidence and mortality data from cutaneous melanoma in Trentino: registry-based study.

BACKGROUND: The province of Trento has been the target of health campaigns for early diagnosis of cutaneous melanoma for 30 years. OBJECTIVE: To evaluate incidence and mortality data of skin melanoma in the province from January 1992 to December 2001. METHODS: The study is based on the provincial skin cancer registry and the regional mortality registry. Standardized incidence and mortality rates were computed, and time trends were evaluated. Incidence rates were modeled using Poisson regression. RESULTS: Five hundred fifty-four melanomas were diagnosed (226 in males and 328 in females). No period effect was revealed. Incidence rates in females were about 1.24 times those in males. No significant trend in mortality rates was observed. CONCLUSION: We examined incidence and mortality data of cutaneous melanoma during a 10-year period and failed to find any significant trend. It seems we have reached a plateau after many years of continuous, intensive health campaigns.

Bone Marrow Micrometastases in Breast Cancer Patients: A Long-Term Follow-up Study.

In 125 early breast cancer patients who underwent multiple bone marrow aspirates, there was no significant difference in terms of disease-free and overall survival after a median follow-up of 163 months between the patients with or without micrometastasis at the time of primary surgery. However, when the time-dependent evolution of the bone marrow aspirates was taken into account, some evidence for a longer disease-free and overall survival was found for the patients with negative bone marrow.

Gemcitabine (GEM) and vindesine (VDS) in advanced non-small cell lung cancer (NSCLC): a phase II study in elderly or poor performance status patients.

The aim of the study was to assess the activity and tolerability of the combination of gemcitabine (GEM) and vindesine (VDS) in elderly or poor performance patients with advanced non-small cell lung cancer. Forty four patients (36 males and 8 females with a median age of 70 years and a median Karnofsky performance score of 60) were recruited between January 1998 and June 2001; 9 (20.5%) were stage IIIB patients and 35 (79.5%) were stage IV patients; 20 (45.5%) had squamous carcinoma and 24 (54.5%) non-squamous carcinoma. The patients received GEM 1000 mg/m(2) and VDS 3mg/m(2) (max 5mg) on days 1 and 8 every 3 weeks, and were all evaluable for response and toxicity: 17 (38.6%) were partial responders, 17 (38.6%) experienced stable disease, and 10 (22.3%) progressive disease. Grade 3-4 anemia, neutropenia and thrombocytopenia were observed in, respectively, 6.8, 9.1 and 2.3% of the patients, and grade 2-3 fatigue, paresthesias and skin toxicity in, respectively, 11.4, 20.4 and 2.3%. After a median follow-up of 54 months, 43/44 patients died; median survival was 12 months, and a clinical benefit was observed in 54.5% of cases. GEM plus VDS is an active and well-tolerated schedule.

Unbalanced serum leptin and ghrelin dynamics prolong postprandial satiety and inhibit hunger in healthy elderly: another reason for the "anorexia of aging".

BACKGROUND: In healthy elderly, a reduction from the appetite and food intake of younger years has been defined as the "anorexia of aging," which may cause malnutrition. Leptin and ghrelin may alter the control of hunger and satiety and thus lead to anorexia. OBJECTIVE: The aim of this study was to investigate how aging affects serum leptin and ghrelin concentrations in response to a meal and the relation of those hormones to hunger and satiety sensations. DESIGN: We studied 8 community-dwelling elderly (x +/- SD age: 78 +/- 1 y) subjects and 8 younger (29.5 +/- 1 y) control subjects. Under fasting conditions and for 4 h after an 800-kcal mixed meal, satiety and hunger were evaluated at intervals, by using a visual analogic scale. Blood samples for leptin, ghrelin, and insulin measurements were collected at the following times: 30 min before and immediately and 30, 60, 120, and 240 min after the meal. RESULTS: Postprandial satiety lasted significantly longer in the elderly than in the control subjects, and hunger was suppressed in the elderly throughout the observation. Fasting leptin was higher in the elderly than in the young (x +/- SE: 4.3 +/- 1.9 and 1.3 +/- 0.4 ng/mL, respectively; P < 0.05), and postprandial fluctuation was not significant. Fasting insulin also was significantly higher in the elderly than in the young (6.8 +/- 1.3 and 3.5 +/- 0.6 mU/L, respectively; P < 0.05), and the postprandial insulin rise was greater in the elderly. Fasting and postprandial ghrelin values did not differ significantly between the 2 groups. Insulin was inversely correlated with hunger and directly correlated with satiety scores. CONCLUSIONS: In healthy elderly, anorexigenic signals prevail over orexigenic signals, and they contribute to prolonged satiety and inhibition of hunger. This condition may lead to a calorie deficit and finally to malnutrition in the elderly.

Pathological, biological and clinical characteristics, and surgical management, of elderly women with breast cancer.

For this retrospective study, we divided 3814 patients with invasive operable breast cancer into five groups based on their age at diagnosis. Univariate analysis showed that the elderly women had larger tumours with more axillary node involvement and lymphovascular invasion, more estrogen- and progesterone-positive tumours, lower grades and proliferative indices, and were less likely to be c-erbB2 positive. They were more likely to have been diagnosed in a symptomatic state and to have undergone mastectomy, and less likely to have undergone mammary reconstruction or axillary dissection, or to have a family history of breast cancer. The multinomial regression model showed that pT, pN, ER, PgR, the type of diagnosis, and a family history were independently associated with each other. The results of this study show that elderly women are more likely to have larger and more frequently N+ tumours, but these are biologically less aggressive and usually seem to receive less invasive surgical treatment.