The Management of Geriatric and Frail HIV Patients. A 2017 Update from the Italian Guidelines for the Use of Antiretroviral Agents and the Diagnostic Clinical Management of HIV-1 Infected Persons.

OBJECTIVE: This article deals with the attempt to join HIV and geriatric care management in the 2017 edition of the Italian guidelines for the use of antiretrovirals and the diagnostic-clinical management of HIV-1 infected persons. METHODS: The outlined recommendations are based on evidence from randomized clinical trials and observational studies published in peer-reviewed journals and/or presented at international scientific conferences in recent years. The principles of starting antiretroviral therapy in elderly patients and the viro-immunological goals are the same as in the general HIV population. However, there are some specificities to consider, related to the host as well as the therapy itself. HIV care in elderly patients must shift from a combined AntiRetroviral Therapy specific approach to a more comprehensive management, and from a disease-based model (list of co-morbidities) to a multi-morbidity and frailty standpoint. The implementation of a geriatric approach, based on the Comprehensive Geriatric Assessment, is essential and consists of a broader evaluation of health status. This multidimensional and multidisciplinary evaluation is focused on the development of a tailored intervention plan. Polypharmacy is a frequent condition in the older population and an independent risk factor for negative health-related outcomes. This can be overcome with a multidisciplinary and cooperative approach involving HIV specialists, geriatricians and primary care physicians. CONCLUSION: The inclusion of geriatric care becomes necessary due to the novel needs of an evolving patient population. It is important to underline that the HIV specialist will continue to lead multidimensional interventions and optimize quality of care for HIV-positive people.

The increasing burden and complexity of multi-morbidity and polypharmacy in geriatric HIV patients: a cross sectional study of people aged 65 - 74 years and more than 75 years.

BACKGROUND: Geriatric Patients Living with HIV/AIDS (GEPPO) is a new prospective observational multicentre cohort consisting of all the HIV-positive geriatric patients being treated at 10 clinics in Italy, and HIV-negative controls attending a single geriatric clinic. The aim of this analysis of the GEPPO cohort was to compare prevalence and risk factors of individual non-communicable diseases (NCD), multi-morbidity (MM) and polypharmacy (PP) amongst HIV positive and HIV negative controls at enrolment into the GEPPO cohort. METHODS: This cross-sectional study was conducted between June 2015 and May 2016. The duration of HIV infection was subdivided into three intervals: < 10, 10-20 and > 20 years. The NCD diagnoses were based on guidelines defined criteria, including cardiovascular disease, hypertension, type 2 diabetes, chronic kidney disease, dyslipidaemia, chronic obstructive pulmonary disease. MM was classified as the presence of two or more co-morbidities. The medications prescribed for the treatment of comorbidities were collected in both HIV positive and HIV negative group from patient files and were categorized using the Anatomical Therapeutic Chemical (ATC) classification. PP was defined as the presence of five or more drug components other than anti-retroviral agents. RESULTS: The study involved a total of 1573 patient: 1258 HIV positive and 315 HIV negative). The prevalence of individual comorbidities was similar in the two groups with the exception of dyslipidaemia, which was more frequent in the HIV-positive patients (p <  0.01). When the HIV-positive group was stratified based on the duration of HIV infection, most of the co-morbidities were significantly more frequent than in control patients, except for hypertension and cardiovascular disease, while COPD was more prevalent in the control group. MM and PP were both more prevalent in the HIV-positive group, respectively 64% and 37%. CONCLUSIONS: MM and PP burden in geriatric HIV positive patients are related to longer duration of HIV-infection rather than older age per se.

Peritonectomy and hyperthermic intraperitoneal chemotherapy: cost analysis and sustainability.

BACKGROUND: Malignancies of the peritoneum remain a challenge in any hospital that accepts to manage them, due not only to difficulties associated with the complexity of the procedures involved but also the costs, which - in Italy and other countries that use a diagnosis-related group (DRG) system - are not adequately reimbursed. MATERIAL AND METHODS: We analyzed data relative to 24 patients operated on between September 2010 and May 2013 with special regard to operating room expenditure, ICU stay, duration of hospitalization, and DRG reimbursement. The total costs per patient included clinical, operating room, procedure, pathology, imaging, ward care, allied healthcare, pharmaceutical, and ICU costs. RESULTS: Postoperative hospital stay, drugs and materials, and operating room occupancy were the main factors affecting the expenditure for cytoreductive surgery and hyperthermic intraperitoneal chemotherapy. We had a median hospitalization of 14 days, median ICU stay of 2.4 days, and median operating room occupancy of 585 min. The median expenditure for each case was € 21,744; the median reimbursement by the national health system € 8,375. CONCLUSIONS: In a DRG reimbursement system, the economic effort in the management of patients undergoing peritonectomy procedures may not be counterbalanced by adequate reimbursement. Joint efforts between medical and administration parties are mandatory to develop appropriate treatment protocols and keep down the costs.

Guidelines for time-to-event end point definitions in sarcomas and gastrointestinal stromal tumors (GIST) trials: results of the DATECAN initiative (Definition for the Assessment of Time-to-event Endpoints in CANcer trials)†.

BACKGROUND: The use of potential surrogate end points for overall survival, such as disease-free survival (DFS) or time-to-treatment failure (TTF) is increasingly common in randomized controlled trials (RCTs) in cancer. However, the definition of time-to-event (TTE) end points is rarely precise and lacks uniformity across trials. End point definition can impact trial results by affecting estimation of treatment effect and statistical power. The DATECAN initiative (Definition for the Assessment of Time-to-event End points in CANcer trials) aims to provide recommendations for definitions of TTE end points. We report guidelines for RCT in sarcomas and gastrointestinal stromal tumors (GIST). METHODS: We first carried out a literature review to identify TTE end points (primary or secondary) reported in publications of RCT. An international multidisciplinary panel of experts proposed recommendations for the definitions of these end points. Recommendations were developed through a validated consensus method formalizing the degree of agreement among experts. RESULTS: Recommended guidelines for the definition of TTE end points commonly used in RCT for sarcomas and GIST are provided for adjuvant and metastatic settings, including DFS, TTF, time to progression and others. CONCLUSION: Use of standardized definitions should facilitate comparison of trials' results, and improve the quality of trial design and reporting. These guidelines could be of particular interest to research scientists involved in the design, conduct, reporting or assessment of RCT such as investigators, statisticians, reviewers, editors or regulatory authorities.

The management of hip fracture in the older population. Joint position statement by Gruppo Italiano Ortogeriatria (GIOG).

This document is a Joint Position Statement by Gruppo Italiano di OrtoGeriatria (GIOG) supported by Società Italiana di Gerontologia e Geriatria (SIGG), and Associazione Italiana Psicogeriatria (AIP) on management of hip fracture older patients. Orthogeriatric care is at present the best model of care to improve results in older patients after hip fracture. The implementation of orthogeriatric model of care, based on the collaboration between orthopaedic surgeons and geriatricians, must take into account the local availability of resources and facilities and should be integrated into the local context. At the same time the programme must be based on the best available evidences and planned following accepted quality standards that ensure the efficacy of the intervention. The position paper focused on eight quality standards for the management of hip fracture older patients in orthogeriatric model of care. The GIOG promotes the development of a clinic database with the aim of obtaining a qualitative improvement in the management of hip fracture.

Sporadic desmoid-type fibromatosis: a stepwise approach to a non-metastasising neoplasm--a position paper from the Italian and the French Sarcoma Group.

Desmoid-type fibromatosis (DF) is a rare locally aggressive monoclonal proliferation of myofibroblasts lacking metastatic capacity. It may be observed in nearly every part of the body. Considering the variable clinical presentations, anatomic locations, and biologic behaviors, an individualized treatment approach is required. The pathogenesis of DF is not completely understood even if a high prevalence (∼85%) of CTNNB1 mutations discovered in sporadic DF underlies the importance of the Wnt/ß-catenin pathway. No established and evidence-based approach for the treatment of this neoplasm is available as of today. Considering the unpredictable behavior and the heterogeneity of this disease, we propose a treatment algorithm approved by the French and the Italian Sarcoma Group, based on a front-line wait and see approach and subsequent therapy in the case of progression. A careful counseling at a referral center is mandatory and should be offered to all patients affected by sporadic DF from the time of their diagnosis.

Poor diagnostic performance of tilt testing in hypertensive patients with unexplained syncope.

Syncope is a common condition. Tilt testing with sublingual nitroglycerin (TT-TNT) provides a test with good specificity and positivity rate in young and old patients. Its use in hypertensive patients with unexplained syncope has not been validated. The aims of this study were to evaluate the positivity rate, specificity and tolerability of TT-TNT in hypertensive patients with unexplained syncope. Five hundred and ten subjects (mean age 55 years) were enrolled, 388 patients with unexplained syncope (73 hypertensive and 315 normotensive) and 122 controls (59 hypertensive and 63 normotensive). All subjects underwent TT-TNT. The responses were classified as positive, negative or exaggerated (aspecific). In hypertensive patients, the usual hypotensive therapy was taken on the day of the test. In hypertensive controls, the positive responses were higher than in normotensives (19% vs 6%, P<0.001). The overall specificity was 81% in hypertensives and 94% in normotensives. The positivity rate was significantly lower in hypertensives (55% vs 72%, P<0.03). There was no significant difference between young patients and patients >65 years. TT was well tolerated, and no serious side effects occurred. TT potentiated with TNT has a lower positivity rate and specificity in hypertensive than in normotensive patients with syncope.

Health care for older people in Italy: The U.L.I.S.S.E. Project (Un link informatico sui servizi sanitari esistenti per l'anziano - a computerized network on health care services for older people).

OBJECTIVES: The U.L.I.S.S.E. study is aimed at describing older patients who are cared for in hospitals, home care or nursing homes in Italy. DESIGN: The U.L.I.S.S.E. study is an observational multicenter prospective 1-year study. SETTING: Overall, 23 acute geriatric or internal medicine hospital units, 11 home care services and 31 nursing homes participated in the study. MEASUREMENTS: The patient's evaluation was performed using comprehensive geriatric assessment instruments, i.e. the interRAI Minimum Data Set, while data on service characteristics were recorded using ad-hoc designed questionnaires. RESULTS: The older subjects who are in need of acute and long term care in Italy have similar characteristics: their mean age is higher than 80 years, they have a high level of disability in ADL, an important multimorbidity, and are treated with several drugs. The prevalence of cognitive impairment is particularly high in nursing homes, where almost 70% of residents suffer from it and 40% have severe cognitive impairment. On the other hand, there is a shortage of health care services, which are heterogeneous and fragmented. CONCLUSIONS: Health care services for older people in Italy are currently inadequate to manage the complexity of the older patients. An important effort should be undertaken to create a more integrated health care system.

Post-imatinib surgery in advanced/metastatic GIST: is it worthwhile in all patients?

BACKGROUND: Surgical indication for metastatic gastrointestinal stromal tumor (GIST) treated with imatinib is not yet established. MATERIALS AND METHODS: We analyzed 80 patients who underwent surgery for metastatic GIST after imatinib therapy from July 2002 to October 2007. Patients were divided into those with surgery at best clinical response (group A, n = 49) and those with surgery at focal progression (group B, n = 31). Primary end points were progression-free survival (PFS) and disease-specific survival (DSS). RESULTS: Two-year postoperative PFS was 64.4% in group A and 9.7% in group B (P < 0.01). In group A, median PFS was not reached; in group B, it was 8 months. Median DSS from the time of imatinib onset was not reached in either group. Five-year DSS was 82.9% in group A and 67.6% in group B (P < 0.01). Multivariate analysis confirmed a significantly shorter PFS and DSS in group B. Surgical morbidity occurred in 13 patients (16.3%). CONCLUSIONS: Surgery for focal progressive lesions could be considered as part of the second-line/third-line armamentarium in selected cases. Surgery of residual disease upon best clinical response seems associated with survival benefit compared with historical controls in similar patient collectives treated with imatinib alone. However, evidence from prospective randomized trials is needed to make definite recommendations.

Relation of neurocardiovascular instability to cognitive, emotional and functional domains.

There is bulk of evidence suggesting that blood pressure dysregulation, as low blood pressure (LBP) or hypotension, orthostatic hypotension (OH) and high blood pressure (HPB) or hypertension are associated with alterations in cognitive and emotional domains. Some studies suggest that LBP, neurocardiovascular instability, like the OH, and atherosclerosis resulting from long standing HBP, reduces cerebral blood flow, increasing the risk of cognitive impairment, morbidity and mortality. This study aims to evaluate whether patients with cognitive impairment and cardiovascular disease would show any differences in some anamnestic indicators and/or psychometric measures of cognitive performance and affective symptoms. We recruited 36 patients over 65 years of age admitted to both psycho- and cardio-geriatric ambulatories of our hospital during the last year. The population (mean age of 80.5 years, 72.2% females, 27.8% males) was divided in 2 groups, with OH (25%), and without OH (75%). The first group was subdivided in subgroups: patients with HBP, normal BP and LBP, respectively. Cognitive and depressive domains were assessed with the mini mental state examination (MMSE) and the Italian "scala di valutazione del benessere emotivo nell' anziano" (SVEBA). Information about the present status, comorbidities (cumulative illness rating scale=CIRS), functional ability (activities of daily living=ADL, instrumental ADL=IADL) and drugs were collected during clinical examination. BP was measured 4 times, at the beginning of examination, then with the patient in clinostatic and orthostatic position (1st and 3rd minute). Data were analyzed by MANCOVA, considering age and gender as covariates, MMSE, SVEBA, CIRS, ADL, IADL and drugs as dependent variables, and presence/absence of OH as factor. Covariates were not significant sources of variance, as well as overall factor. Due to the heuristic aim of the study, we considered of interest the results of subsequent ANOVAs showing significant differences in SVEBA and ADL with respect to the factor. These data give us the basis to develop a longitudinal study to confirm the detrimental effect of OH on a wide range of health domains.

Frailty of older age: the role of the endocrine--immune interaction.

The so-called demographic transition has changed the age structure of the population worldwide, with profound effects on societal organization. The growing number and percentage of old and very old people has compelled the scientific community to focus on age related diseases and peculiar consequences of aging itself such as disability and frailty. Understanding the pathophysiology of frailty, a syndrome characterized by a reduced functional reserve and impaired adaptive capacity that results from cumulative declines of multiple subsystems, and causes increased vulnerability to adverse outcomes, is a major topic in aging research. Aging processes induce multiple changes in the hormones network (menopause, andropause, somatopause and adrenopause), in the immune system, and can modulate their efficiency and effectiveness in determining a response to stressors. These triggering events can unmask frailty in older people. Starting from these assumptions, we analyzed the relationship of the endocrine and immune networks in aging and in the different domains that are characteristically associated with the frailty syndrome, such as disability and sarcopenia, as well as in diseases related to aging such as Alzheimer's dementia and Congestive Heart Failure.

Palliative surgery for recurrent bowel obstruction due to advanced ovarian cancer.

AIM: Intestinal obstruction is a frequent event in patients affected by ovarian carcinoma. Little data on repeat palliative surgery for recurrent bowel obstruction are available. The aim of this study was to analyze postoperative and long term outcomes of ovarian cancer patients who underwent reoperation for recurrent intestinal obstruction. METHODS: We retrospectively evaluated the records of these patients treated at our Department between 1992 and 2002. RESULTS: Nine women with a mean age of 56 years (range 37-72) were identified. All patients had undergone previous abdominal surgery for bowel obstruction from ovarian cancer. All patients underwent exploratory laparotomy. In 4 patients (Group A) because of advanced disease, only exploratory surgery was carried out. A surgical correction was achieved in the other 5 patients (Group B), but only 3 patients had a successful palliation, defined as the ability to tolerate an oral intake for at least 60 days postoperatively. Postoperative mortality was nil, morbidity was 44.4%; particularly 2 patients developed an enterocutaneous fistula. Mean survival of Group A and B patients were 36.7 and 96.2 days respectively. The 3 successful palliated patients died of disease after 3.5, 4 and 5 months, in 2 cases for recurrent bowel obstruction. CONCLUSIONS: Repeat surgery for recurrent bowel obstruction in advanced ovarian carcinoma may achieve successful palliation in few cases and is associated with high postoperative morbidity and limited survival. In these patients non surgical approaches based on medical treatment, percutaneous endoscopic gastrostomy and stent placement should be considered.

Accuracy of eight-polar bioelectrical impedance analysis for the assessment of total and appendicular body composition in peritoneal dialysis patients.

OBJECTIVE: To establish the accuracy of bioelectrical impedance analysis (BIA) for the assessment of total and appendicular body composition in peritoneal dialysis (PD) patients. DESIGN: Cross-sectional study. SETTING: University Nephrology Clinic. SUBJECTS: In all, 20 PD patients and 77 healthy controls matched for gender, age and body mass index. METHODS: Whole-body fat-free mass (FFM) and appendicular lean tissue mass (LTM) were measured by dual-energy X-ray absorptiometry. Resistance (R) of arms, trunk and legs was measured by eight-polar BIA at frequencies of 5, 50, 250 and 500 kHz. Whole-body resistance was calculated as the sum of R of arms, trunk and legs. The resistance index (RI) was calculated as the ratio between squared height and whole-body or segmental R. RESULTS: RI at 500 kHz was the best predictor of FFM, LTM(arm) and LTM(leg) in both PD patients and controls. Equations developed on controls overestimated FFM and LTM(arm) and underestimated LTM(leg) when applied to PD patients. Specific equations were thus developed for PD patients. Using these equations, the percent root mean-squared errors of the estimate for PD patients vs controls were 5 vs 6% for FFM, 8 vs 8% for LTM(arm) and 7 vs 8% for LTM(leg). CONCLUSION: Eight-polar BIA offers accurate estimates of total and appendicular body composition in PD patients, provided that population-specific equations are used.

Gastrointestinal carcinoids. Prognosis and survival.

BACKGROUND: Gastrointestinal carcinoid tumors are rare and little is known about factors related to prognosis in patients with carcinoid disease. Aim of this study is to determine the impact of clinical presentation variables on the management and survival. METHODS: We have evaluated 31 consecutive patients with gastrointestinal carcinoid tu-mours who underwent surgical intervention at the I Department of Surgery of Milano-Bicocca University over 15 years (1985-1999). Tumor distribution, hormone production, prognostic factors and survival were analysed. RESULTS: Carcinoid syndrome was the only clinical pattern diagnostic of carcinoid tumour. Most common symptoms were abdominal pain (64%), nausea and vomiting (48%). High levels of urinary 5-hydroxyindolacetic acid were significantly associated with carcinoid syndrome and metastatic disease. Tumor size, depth and gender were significant predictors of metastases. Age, gender, tumor size, metastatic spread and location were statistically significant predictors of death. CONCLUSIONS: Clinical presentation was non specific except for those patients affected by carcinoid syndrome. Ten years overall survival was 43%, with 52% metastatic spread incidence. The extent of surgical resection should be modulated on patient related risk factors. Poor prognostic factors affecting survival were: age, gender, metastatic disease, depth of invasion and tumour size.

Alteration of hypothalamus-pituitary-adrenal gland axis in colorectal cancer patients. Preliminary report.

AIM: In advanced cancer patients a cell-mediated immunological impairment, both at baseline and during postoperative period, is often found and is associated with poor prognosis. Cortisol is strictly involved in the response to major surgical stress, is an immunosuppressor and causes a redistribution of immunological population cells in different tissues. The aim of the study was to verify serum levels and circadian rhythm of cortisol in patients with colorectal cancer at baseline before surgery and in the postoperative period, and relate it to the immune status. METHODS: In 21 patients with colorectal cancer undergoing surgery we evaluated the assessment of total lymphocytes, CD4+, cortisolemia, circadian rhythm of cortisol (11 p.m. and 8 a.m.) at baseline and in 3(rd) and 7(th) postoperative days. RESULTS: Increase of cortisolemia, as decrease of total and CD4+ lymphocytes in the postoperative period versus baseline was statistically significant. Patients with an altered circadian rhythm were 47% and 36% at 3rd and 7th postoperative days, respectively. At baseline 19% of patients had an altered cortisol circadian rhythm and it was more frequent in patients with nodal involvement (p<0.05) and with metastasis (p<0.01). No relations between lymphocytopenia and alteration of cortisolemia and cortisol circadian rhythm were found, either at baseline or postoperatively (p<0.05). CONCLUSION: Lymphocytopenia in cancer patients seems not to be associated with cortisol level and circadian rhythm alteration, either at baseline or after surgical stress. An impairment of circadian rhythm of cortisol was found at baseline in 19% of patients. It was significantly associated with the presence of metastatic disease.

Cross-calibration of eight-polar bioelectrical impedance analysis versus dual-energy X-ray absorptiometry for the assessment of total and appendicular body composition in healthy subjects aged 21-82 years.

AIM: To calibrate eight-polar bioelectrical impedance analysis (BIA) against dual-energy X-ray absorptiometry (DXA) for the assessment of total and appendicular body composition in healthy adults. RESEARCH DESIGN: A cross-sectional study was carried out. SUBJECTS: Sixty-eight females and 42 males aged 21-82 years participated in the study. METHODS: Whole-body fat-free mass (FFM) and appendicular lean tissue mass (LTM) were measured by DXA; resistance (R) of arms, trunk and legs was measured by eight-polar BIA at frequencies of 5, 50, 250 and 500 kHz; whole-body resistance was calculated as the sum R of arms, trunk and legs. RESULTS: The resistance index (RI), i.e. the height(2)/resistance ratio, was the best predictor of FFM and appendicular LTM. As compared with weight (Wt), RI at 500 kHz explained 35% more variance of FFM (vs 0.57), 45% more variance of LTM(arm) (vs 0.48) and 36% more variance of LTM(leg) (vs 0.50) (p < 0.0001 for all). The contribution of age to the unexplained variance of FFM and appendicular LTM was nil or negligible and the RI x sex interactions were either not significant or not important on practical grounds. The percent root mean square error of the estimate was 6% for FFM and 8% for LTM(arm) and LTM(leg). CONCLUSION: Eight-polar BIA offers accurate estimates of total and appendicular body composition. The attractive hypothesis that eight-polar BIA is influenced minimally by age and sex should be tested on larger samples including younger individuals.

Accuracy of an eight-point tactile-electrode impedance method in the assessment of total body water.

OBJECTIVE: To establish the accuracy of an eight-polar tactile-electrode impedance method in the assessment of total body water (TBW). DESIGN: Transversal study. SETTING: University department. SUBJECTS: Fifty healthy subjects (25 men and 25 women) with a mean (s.d.) age of 40 (12) y. METHODS: TBW measured by deuterium oxide dilution; resistance (R) of arms, trunk and legs measured at frequencies of 5, 50, 250 and 500 kHz with an eight-polar tactile-electrode impedance-meter (InBody 3.0, Biospace, Seoul, Korea). RESULTS: An algorithm for the prediction of TBW from the whole-body resistance index at 500 kHz (height (2)/R(500) where R is the sum of the segmental resistances of arms, trunk and legs) was developed in a randomly chosen subsample of 35 subjects. This algorithm had an adjusted coefficient of determination (r2(adj)) of 0.81 (P<0.0001) and a root mean square error (RMSE) of 3.6 l (9%). Cross-validation of the predictive algorithm in the remaining 15 subjects gave an r2(adj) of 0.87 (P<0.0001) and an RMSE of 3.0 l (8%). The precision of eight-polar BIA, determined by measuring R three times a day for five consecutive days in a fasting subject, was < or =2.8% for all segments and frequencies. CONCLUSION: Eight-polar BIA is a precise method that offers accurate estimates of TBW in healthy subjects. This promising method should undergo further studies of precision and its accuracy in assessing extracellular water and appendicular body composition should be determined. SPONSORSHIP: Modena and Reggio Emilia University.