Multidimensional Prognostic Index (MPI) score has the major impact on outcome prediction in elderly surgical patients with colorectal cancer: The FRAGIS study.

BACKGROUND: This study aims (I) to evaluate whether the Multidimensional Prognostic Index (MPI) score is associated with postoperative outcomes and (II) to develop a prognostic model for individual complication-risk prediction following colorectal cancer (CRC) surgery. METHOD: This is a prospective multicentric cohort study. Consecutive ≥75-year-old candidates for elective CRC surgery were enrolled from October 2017 to August 2019. Patients underwent standardized preoperative geriatric assessment including the MPI. Patients with MPI score > 0.33 were classified as frail. Logistic regression models were employed to evaluate variables associated with major postoperative complications and mortality, using 10-fold cross-validated LASSO (least absolute shrinkage and selection operator) for model selection. RESULTS: In all, 104 patients were included, 34 (33%) had MPI score > 0.33. Major postoperative complications occurred in 52% of frail versus 16% of fit (MPI score ≤ 0.33) patients (p < .01). Both 30-day (9% vs. 0%; p = .033) and 90-day mortality (18% vs. 1%; p < .01) were higher among frail patients. In multivariate analysis, MPI score was associated with adverse outcomes. A final postoperative complication predictive model was created, including MPI score, gait-speed test, ASA (American Society of Anesthesiology) score, surgical approach, and stoma creation. CONCLUSION: MPI score is strongly associated with postoperative major complications in CRC elderly patients and it is a primary component of an individual prediction model.

Depression and heart failure: an intricate relationship.

In patients with heart failure (HF), depression is common and associated with adverse outcomes such as reduced adherence to treatment, poor quality of life, increased hospitalizations and elevated mortality. Despite these adverse impacts, depression remain underdiagnosed in HF patients. We performed a target review of the literature to identify the association between HF and depression, to examine the mechanisms that link these two conditions and to identify instruments for an accurate diagnosis and treatment of depression in HF patients. Depression is associated with the development and progression of HF, including increased rates of mortality, mediated by behavioral and pathophysiological mechanisms. The overlap of symptoms between depression and HF often makes the diagnosis of depression difficult and late. Currently, specific guidelines for depression screening in HF patients are lacking, partly because evidences showing that depression screening improves cardiac outcomes are insufficient. European guidelines suggest the early use of instruments such as the Beck Depression Inventory (BDI) and the Geriatric Depression Scale (GDS), both characterized by accuracy and administration simplicity. There is limited evidence of pharmacological treatment and psychotherapy efficacy in patients with HF. However, cognitive-behavioral therapy has been shown to improve outcomes HF patients, and selective serotonin reuptake inhibitors appear safe in this cohort.

Antipsychotic prescription and mortality in hospitalized older persons.

BACKGROUND: Recent scientific reports have shown that older persons treated with antipsychotics for dementia-related behavioural symptoms have increased mortality. However, the impact of these drugs prescribed during hospitalization has rarely been assessed. We aimed to investigate whether antipsychotics are associated with an increased risk of mortality during hospitalization and at 3-month follow-up in elderly inpatients. METHODS: We analyzed data gathered during two waves (2010 and 2012) by the REPOSI (Registro Politerapie Società Italiana Medicina Interna). All new prescriptions of antipsychotic drugs during hospitalization, whether maintained or discontinued at discharge, were collected, and logistic regression models were used to analyze their association with in-hospital and 3-month mortality. Covariates were age, sex, the Short Blessed Test (SBT) score, and the Cumulative Illness Rating Scale. RESULTS: Among 2703 patients included in the study, 135 (5%) received new prescriptions for antipsychotic drugs. The most frequently prescribed antipsychotic during hospitalization and eventually maintained at discharge was haloperidol (38% and 36% of cases, respectively). Patients newly prescribed with antipsychotics were older and had a higher Cumulative Illness Rating Scale comorbidity index both at admission and at discharge compared to those who did not receive a prescription. Of those prescribed antipsychotics, 71% had an SBT score ≥10 (indicative of dementia), 12% had an SBT score of 5-9 (indicative of questionable dementia); and 17% had an SBT score <5 (indicative of normal cognition). In-hospital mortality was slightly higher in patients prescribed antipsychotic drugs (14.3% vs 9.4%; P = 0.109), but in multivariate analysis only male sex, older age, and higher SBT scores were significantly related to mortality during hospitalization. At 3-month follow-up, only male sex, older age, and higher SBT scores were associated with mortality. CONCLUSION: We found that the prescription of antipsychotic drugs during hospitalization was not associated with in-hospital or follow-up mortality. Short-term antipsychotic prescriptions (for acutely ill patients) may have a different effect than long-term, repeated prescriptions.

Beyond Chronological Age: Frailty and Multimorbidity Predict In-Hospital Mortality in Patients With Coronavirus Disease 2019.

BACKGROUND: We evaluated whether frailty and multimorbidity predict in-hospital mortality in patients with COVID-19 beyond chronological age. METHOD: A total of 165 patients admitted from March 8th to April 17th, 2020, with COVID-19 in an acute geriatric ward in Italy were included. Predisease frailty was assessed with the Clinical Frailty Scale (CFS). Multimorbidity was defined as the co-occurrence of ≥2 diseases in the same patient. The hazard ratio (HR) of in-hospital mortality as a function of CFS score and number of chronic diseases in the whole population and in those aged 70+ years were calculated. RESULTS: Among the 165 patients, 112 were discharged, 11 were transferred to intensive care units, and 42 died. Patients who died were older (81.0 vs 65.2 years, p < .001), more frequently multimorbid (97.6 vs 52.8%; p < .001), and more likely frail (37.5 vs 4.1%; p < .001). Less than 2.0% of patients without multimorbidity and frailty, 28% of those with multimorbidity only, and 75% of those with both multimorbidity and frailty died. Each unitary increment in the CFS was associated with a higher risk of in-hospital death in the whole sample (HR = 1.3; 95% CI = 1.05-1.62) and in patients aged 70+ years (HR = 1.29; 95% CI = 1.04-1.62), whereas the number of chronic diseases was not significantly associated with higher risk of death. The CFS addition to age and sex increased mortality prediction by 9.4% in those aged 70+ years. CONCLUSIONS: Frailty identifies patients with COVID-19 at risk of in-hospital death independently of age. Multimorbidity contributes to prognosis because of the very low probability of death in its absence.

Impact of low dose tocilizumab on mortality rate in patients with COVID-19 related pneumonia.

BACKGROUND: Pneumonia with respiratory failure represents the main cause of death in COVID-19, where hyper inflammation plays an important role in lung damage. This study aims to evaluate if tocilizumab, an anti-soluble IL-6 receptor monoclonal antibody, reduces patients' mortality. METHODS: 85 consecutive patients admitted to the Montichiari Hospital (Italy) with COVID-19 related pneumonia and respiratory failure, not needing mechanical ventilation, were included if satisfying at least one among: respiratory rate ≥ 30 breaths/min, peripheral capillary oxygen saturation ≤ 93% or PaO2/FiO2<=300 mmHg. Patients admitted before March 13th (n=23) were prescribed the standard therapy (hydroxychloroquine, lopinavir and ritonavir) and were considered controls. On March 13th tocilizumab was available and patients admitted thereafter (n=62) received tocilizumab once within 4 days from admission, plus the standard care. RESULTS: Patients receiving tocilizumab showed significantly greater survival rate as compared to control patients (hazard ratio for death, 0.035; 95% confidence interval [CI], 0.004 to 0.347; p = 0.004), adjusting for baseline clinical characteristics. Two out of 62 patients of the tocilizumab group and 11 out of 23 in the control group died. 92% and 42.1% of the discharged patients in the tocilizumab and control group respectively, recovered. The respiratory function resulted improved in 64.8% of the observations in tocilizumab patients who were still hospitalized, whereas 100% of controls worsened and needed mechanical ventilation. No infections were reported. CONCLUSIONS: Tocilizumab results to have a positive impact if used early during Covid-19 pneumonia with severe respiratory syndrome in terms of increased survival and favorable clinical course.

Early use of low dose tocilizumab in patients with COVID-19: A retrospective cohort study with a complete follow-up.

BACKGROUND: Pneumonia with severe respiratory failure represents the principal cause of death in COVID-19, where hyper-inflammation plays an important role in lung damage. An effective treatment aiming at reducing the inflammation without preventing virus clearance is thus urgently needed. Tocilizumab, an anti-soluble IL-6 receptor monoclonal antibody, has been proposed for treatment of patients with COVID-19. METHODS: A retrospective cohort study at the Montichiari Hospital, Brescia, Italy, was conducted. We included consecutive patients with COVID-19 related pneumonia at the early stage of respiratory failure, all treated with a standard protocol (hydroxychloroquine 400 mg daily, lopinavir 800 mg plus ritonavir 200 mg per day). We compared survival rate and clinical status in a cohort of patients who received additional treatment with tocilizumab once (either 400 mg intravenous or 324 mg subcutaneous) with a retrospective cohort of patients who did not receive tocilizumab (referred to as the standard treatment group). All outcomes were assessed at the end of the follow-up, that correspond to death or complete recovery and discharge from the hospital. FINDINGS: 158 patients were included, 90 of which received tocilizumab. 34 out of 68 (50%) patients in the standard treatment group and 7 out of 90 (7.7%) in the tocilizumab group died. Tocilizumab significantly improved survival compared to standard care (multivariate HR: 0.057; 95% C.I = 0.017- 0.187, p < 0.001). No differences between the two administration routes of tocilizumab were observed. No tocilizumab-related infections and/or side effects were observed. INTERPRETATION: Early treatment with tocilizumab could be helpful to prevent excessive hyper-inflammation and death in COVID-19 related pneumonia. Low dose administration of tocilizumab is not associated with adverse events. FUNDING: none.

Tocilizumab for the treatment of severe COVID-19 pneumonia with hyperinflammatory syndrome and acute respiratory failure: A single center study of 100 patients in Brescia, Italy.

A hyperinflammatory syndrome (HIS) may cause a life-threatening acute respiratory distress syndrome (ARDS) in patients with COVID-19 pneumonia. A prospective series of 100 consecutive patients admitted to the Spedali Civili University Hospital in Brescia (Italy) between March 9th and March 20th with confirmed COVID-19 pneumonia and ARDS requiring ventilatory support was analyzed to determine whether intravenous administration of tocilizumab (TCZ), a monoclonal antibody that targets the interleukin 6 (IL-6) receptor, was associated with improved outcome. Tocilizumab was administered at a dosage of 8 mg/kg by two consecutive intravenous infusions 12 h apart. A third infusion was optional based on clinical response. The outcome measure was an improvement in acute respiratory failure assessed by means of the Brescia COVID Respiratory Severity Score (BCRSS 0 to 8, with higher scores indicating higher severity) at 24-72 h and 10 days after tocilizumab administration. Out of 100 treated patients (88 M, 12 F; median age: 62 years), 43 received TCZ in the intensive care unit (ICU), while 57 in the general ward as no ICU beds were available. Of these 57 patients, 37 (65%) improved and suspended noninvasive ventilation (NIV) (median BCRSS: 1 [IQR 0-2]), 7 (12%) patients remained stable in NIV, and 13 (23%) patients worsened (10 died, 3 were admitted to ICU). Of the 43 patients treated in the ICU, 32 (74%) improved (17 of them were taken off the ventilator and were discharged to the ward), 1 (2%) remained stable (BCRSS: 5) and 10 (24%) died (all of them had BCRSS≥7 before TCZ). Overall at 10 days, the respiratory condition was improved or stabilized in 77 (77%) patients, of whom 61 showed a significant clearing of diffuse bilateral opacities on chest x-ray and 15 were discharged from the hospital. Respiratory condition worsened in 23 (23%) patients, of whom 20 (20%) died. All the patients presented with lymphopenia and high levels of C-reactive protein (CRP), fibrinogen, ferritin and IL-6 indicating a HIS. During the 10-day follow-up, three cases of severe adverse events were recorded: two patients developed septic shock and died, one had gastrointestinal perforation requiring urgent surgery and was alive at day 10. In conclusion, our series showed that COVID-19 pneumonia with ARDS was characterized by HIS. The response to TCZ was rapid, sustained, and associated with significant clinical improvement.

Association of blood pressure and genetic background with white matter lesions in patients with mild cognitive impairment.

Background. White matter lesions (WMLs) may contribute to cognitive deficits in patients with mild cognitive impairment (MCI), but their pathogenesis is complex. Fluctuations of blood pressure (BP) over 24 hours and genetic predisposition to develop vascular damage have been implicated. Methods. In 63 MCI patients 65 years old or older, BP was measured both clinically and with ambulatory BP monitoring. Patients were classified in two groups: no/very mild (n = 34) and mild to severe (n = 29) WMLs, based on a visual scale on magnetic resonance (mean age 71.8 +/- 4.7 vs 74.6 +/- 5.1, and female gender 53% vs 66%, respectively). The volume of WMLs was measured by a semi-automatic method, separately for periventricular caps and rim, periventricular confluent, subcortical punctate, and subcortical confluent. Polymorphisms of cystatin C (CST3) and cholesterol 24-hydroxylase (CYP46) genes, putative risk factors for cerebrovascular disease, were determined. Results. The prevalence of cerebrovascular risk factors was similar in the two MCI groups of different WML severity, as well as clinic and ambulatory BP. In patients with mild to severe, but not in those with no/very mild WMLs, the volume of periventricular confluent WMLs increased with increasing daytime systolic BP (regression coefficient.47, 95% confidence interval [CI],.13 to.71 vs.02, 95% CI, -.32 to.36, p =.003 for the difference between slopes). The volume of other WML subtypes was not associated with ambulatory BP. Participants carrying both CST3*B and CYP46*T alleles were overrepresented in the MCI group with mild to severe WMLs (43% vs 17%, p.03). Conclusions. BP and gene putative risk factors for cerebrovascular disease are differentially associated with WMLs in two MCI groups of different WML severity. WMLs might develop for the convergence of innate with acquired factors.

Increased prevalence of silent myocardial ischaemia and severe ventricular arrhythmias in untreated patients with Alzheimer's disease and mild cognitive impairment without overt coronary artery disease.

OBJECTIVE: To assess the prevalence and the characteristics of silent myocardial ischaemia (SMI) and ventricular arrhythmias (VA) in subjects with Alzheimer's disease (AD) and mild cognitive impairment (MCI) and their relationships with QT interval dispersion (QTD). METHODS: Thirty-three subjects with AD, 39 subjects with MCI, and 29 cognitive healthy control subjects matched for demographic characteristics, hypertensive condition, smoking habits, and laboratory parameters were enrolled. Each subject underwent clinical and cognitive examination, a structural brain imaging study, electrocardiogram (ECG), 24-h ECG recording, 24-h blood pressure monitoring, and echocardiogram. Detection and characterization of QT dispersion, SMI and VA were performed. RESULTS: The three groups were comparable regarding demographic and basal cardiovascular characteristics: notwithstanding this, SMI episodes were observed only in AD and MCI patients (19 and 14, respectively). A significantly greater prevalence of repetitive ventricular premature beats was observed in AD (mean 8.56+/-13.1) and in MCI (1.8+/-7.2) vs. control (0.7+/-1.7). The QTD, the ischaemic burden and the number of repetitive ventricular beats revealed to be significantly related. CONCLUSIONS: Increased prevalence of SMI and potentially ominous VA were found in AD and, to a lesser extent, in MCI. SMI and repetitive VA were significantly related with QTD. These findings could be related to an increased risk of sudden cardiac death in AD and MCI patients.

Frailty predicts short-term survival even in older adults without multimorbidity.

BACKGROUND: Frailty and multimorbidity are both strongly associated with poor health-related outcomes, including mortality. Being multimorbidity one of the major determinants of frailty, we aimed to explore whether, and to what extent, frailty without multimorbidity plays an independent role in shortening life. METHODS: We used data from the Swedish National Study on Aging and Care in Kungsholmen (SNAC-K). Among the 3363 adults aged 60+ enrolled at baseline, those without multimorbidity (i.e.: less than two chronic diseases) (N = 1115) have been characterized according to Fried's frailty phenotype (i.e. robust, prefrail, and frail). The association between frailty and mortality was estimated using piecewise proportional hazard regression models in three five-year time periods. RESULTS: Among participants without multimorbidity, 424 (38%) were prefrail and 19 (2%) were frail. During the 15-year follow-up, 263 (24%) participants died: 19%, 29%, and 63% of those who were robust, prefrail, and frail at baseline, respectively. Within the first 5 years of follow-up, prefrail and frail participants had more than doubled mortality risk in comparison to robust ones (HR for pre-frailty 2.08, 95% CI 1.15-3.76; HR for frailty 2.69, 95% CI 1.22-5.97). Beyond 5 years, a trend of increased mortality rate was still detectable for prefrail and frail subjects in comparison to robust ones. CONCLUSIONS: Physical frailty and pre-frailty are associated with short-term mortality in a cohort of older adults free from multimorbidity. Frailty could be a clinical indicator of increased risk of negative health outcomes even among subjects without multiple chronic conditions.

Role of rehabilitation in the elderly after an acute event: insights from a real-life prospective study in the subacute care setting.

BACKGROUND: Any acute event, either primary or secondary to a chronic disease, is generally followed by some degree of physical impairment. Subacute care (SAC) represents one of the inpatient intermediate care settings aimed at completing recovery and restoring functional capacity. Debate exists on the role of the rehabilitation treatment in the SAC setting. AIM: The aim of this study was to compare the outcomes of patients managed in two different SAC Units where A) patients undergo an individualized rehabilitation program on top of optimal medical therapy (OMT) B) patients receive OMT only. DESIGN: Real-life prospective study. SETTING: SAC units. POPULATION: Seventy-five chronic heart failure (CHF) and chronic obstructive pulmonary disease (COPD) patients transferred after an acute hospitalization. METHODS: Upon SAC admission, the following scales were obtained: cumulative illness rating scale comorbidity and severity (CIRSC and CIRSS), mini mental state examination (MMSE), Performance-Oriented Mobility Assessment (POMA), Barthel Index (BI), the 10-meter walking test (10MWT). Pre-admission BI was also collected based on history. Upon SAC discharge, BI, POMA, and 10MWT were repeated. RESULTS: Patients (44 in Group A, 31 in Group B) were similar with regard to age, gender, MMSE, clinical complexity, pre-admission BI, admission 10MWT, POMA, and bedrest conditions. Admission BI was lower in Group A. In both groups BI was lower when compared to the respective pre-admission score. Upon discharge, Group A patients were characterized by a higher BI and POMA compared to Group B. Indeed, BI and POMA improved at discharge only in Group A patients. Only this latter group reached the pre-morbid BI. Upon discharge the number of bedrest patients decreased only in Group A. The percentage of patients discharged home was also much higher in Group A, while a greater number of Group B patients were transferred to a rehabilitation ward or were enrolled in an integrated home care assistance program. CONCLUSIONS: In a real-life prospective experience, a better outcome is demonstrated in elderly CHF and COPD patients undergoing a rehabilitative approach during their in-hospital SAC stay. CLINICAL REHABILITATION IMPACT: An individualized rehabilitation program should integrate medical treatment of CHF and BPCO patients in the SAC setting. This approach demonstrates a better cost-effectiveness management of these patients.

Bone ultrasonometric features and growth hormone secretion in asthmatic patients during chronic inhaled corticosteroid therapy.

BACKGROUND: Quantitative ultrasound bone densitometry (QUBD) is a new method to assess bone mineral density and bone microarchitecture. Corticosteroid (CS) therapy may diminish bone mass, alter bone quality and may influence growth hormone (GH) secretion and bone metabolism markers. Therefore, the aim of this study was to evaluate the effects of long-term therapy with inhaled CSs (ICSs) on structural bone characteristics and their correlations with GH secretion and bone markers in asthmatic patients. METHODS: In a cross-sectional study, we enrolled 60 adult patients with mild to moderate persistent asthma: 22 on chronic (>1 year) ICS therapy, 10 naive to ICSs treatment and 28 healthy control subjects. The groups were matched for age and BMI. Each subject underwent to QUBD at the phalanxes to assess bone microarchitecture by ultrasound bone profile index (UBPI), bone density by amplitude-dependent speed of sound (AdSos); test with GH-releasing hormone (GHRH) injection with calculation of peak GH and the Delta GH (peak GH-basal GH); and hormonal and bone markers measurements. RESULTS: Asthmatics treated with long-term ICS therapy showed a lower UBPI (P < 0.01) compared to controls (49.8 +/- 19.3 vs. 77.0 +/- 10.1, respectively) and to asthmatics never taking ICSs (73.2 +/- 9.6). In ICS-treated asthmatics, DeltaGH and GH-peak showed a significant correlation with UBPI. A significant difference was observed comparing asthmatics treated with ICSs to controls and asthmatics naive to ICSs in GH response to GHRH iv bolus. Serum osteocalcin was significantly reduced in asthmatic patients treated with ICSs. CONCLUSIONS: In asthmatic patients, long-term ICSs treatment produces negative effects on bone quality assessed by QUBD, and such effects are associated to an impaired GH secretion.

[Pneumonia: state-of-art and perspectives]. / Polmoniti: oggi e domani.

Pneumonia is a constellation of symptoms and signs in combination with at least one opacity on chest radiography. Pneumonia affects 4 million adults per year in the USA (with the highest rates at the extremes of age and during the winter months), about 20% of whom are admitted to a hospital for treatment; in fact pneumonia is the sixth leading cause of death and the most common lethal infectious disease with an annual cost of 10 billion. Pneumonia can be broadly categorized as: community acquired pneumonia, health -care associated, hospital acquired (nosocomial) pneumonia and ventilator-associated. These categories provide a rough guide as to likely pathogens, disease severity and treatment. In light of the significant morbidity and potential mortality of pneumonia, appropriate measures of prevention should be instituted as: smoking cessation, optimising the patient's nutritional status and current pneumococcal and flu vaccines. Because the microbiological etiology of pneumonia is frequently unknown, initial antibiotic therapy is often empirical. There are currently three sets of North American guidelines for empirical antibiotic treatment of pneumonia. Under current guidelines, patients are stratified with respect to where treatment is initiated, the presence of underlying cardiopulmonary disease and other modifying factors such as whether the patient is likely to be infected with drug resistant S. pneumoniae, gram negative enteric bacilli or P. aeruginosa.

Influence of type 2 diabetes on functional and structural properties of coronary artery bypass conduits.

Recent studies have reported a high incidence of postoperative unfavorable cardiac-related events in patients with diabetes who underwent coronary artery bypass grafting (CABG). Structural and functional characteristics of CABG conduits, which have been shown to play an important role in patient outcome after myocardial revascularization, have not been fully investigated in diabetic subjects. Therefore, we sought to determine the influence of adult-onset diabetes on vasoreactivity and morphological profile of venous and arterial grafts. Of the 160 consecutive patients enrolled in the study, 90 were diagnosed with type 2 diabetes and 70 did not have diabetes (control group). All patients underwent evaluation of glucose control before surgery. Tissue specimens were collected from left internal thoracic artery (LITA) and saphenous vein (SV) grafts harvested during elective CABG. Functional tests were performed to assess contractile and vasodilative responses of bypass conduits. Histological evaluation was carried out to examine vessel wall structure. Univariate and multivariate analyses were performed to correlate the preoperative factors related to the control of the endocrine disorder with histological findings. Patient medical history and demographics did not differ between the groups. Diabetic patients showed significant microalbuminuria and higher plasma levels of C-peptide and GHb as compared with nondiabetic subjects. Functional tests of the LITA segments revealed no difference between groups with regard to contractile and vasodilative responses. In contrast, significant impairment in the endothelium-related vasodilation of the SV grafts was observed in diabetic subjects. Histological studies showed structural preservation of the arterial conduits in both groups. However, marked intimal abnormalities (also atherosclerotic calcified plaques) were detected in SV grafts harvested from diabetic patients. Logistic regression analysis showed that high levels of proteinuria and GHb were independent predictors of advanced structural degeneration of SV conduits. Treatment modality, duration of diabetes, and other demographic or metabolic factors were found to have no influence on the morphological characteristics of SV conduits. In conclusion, biological properties of LITA conduits for CABG were preserved in diabetic patients. However, these patients frequently showed impairment of the endothelium-dependent vasorelaxation and intimal degeneration of SV grafts. The extent of structural abnormalities of SV grafts was inversely correlated with the efficacy of the metabolic control of the endocrine disorder. Further studies are required to conclusively correlate preoperative SV graft abnormalities with postoperative conduit patency rate and the occurrence of adverse cardiac-related events in diabetic subjects.

QT dispersion and heart rate variability abnormalities in Alzheimer's disease and in mild cognitive impairment.

OBJECTIVES: To investigate the effect of cardiovascular changes (i.e., QT interval, QT dispersion (QTD), heart rate variability (HRV), and other cardiovascular measures) in subjects with Alzheimer's disease (AD) and mild cognitive impairment (MCI). DESIGN: Each subject underwent clinical and cognitive examination, a structural brain imaging study, echocardioDoppler, electrocardiogram (ECG), HRV analysis using 24-hour ECG monitoring, and 24-hour blood pressure monitoring. SETTING: Community population-based sample of patients admitted to an AD center for investigation of cognitive disturbances. PARTICIPANTS: Thirty-three subjects with AD, 39 subjects with MCI, and 29 cognitive healthy subjects (controls) matched for demographic characteristics, hypertensive condition, smoking habits, and laboratory parameters were enrolled consecutively. MEASUREMENTS: Clinical and cognitive examination, structural brain imaging study, echocardioDoppler, ECG, HRV analysis using 24-hour ECG monitoring, and 24-hour blood pressure monitoring. RESULTS: QTD and QT corrected dispersion mean values were significantly higher in patients with AD than in patients with MCI and controls and higher in patients with MCI than in controls. HRV time and domain parameters were lower in patients with AD than in patients with MCI and controls. No difference in other cardiovascular measures was found. QTD and HRV were found to be significantly correlated with the degree of cognitive impairment. CONCLUSION: These findings support the presence of a peculiar neuroanatomic dysfunction in patients with AD and MCI that parallels the disease progression. These noninvasive parameters might prove to be powerful predictive tools in the worsening of cognitive function and mortality risk.

Microvascular damage and platelet abnormalities in early Alzheimer's disease.

Accumulating evidence from epidemiological and clinical studies suggests that vascular risk factors may be involved in Alzheimer disease (AD). Although the precise contribution of vascular disturbances to the pathogenesis of AD is still unclear, various biochemical and neuropathological data strengthen the view that cerebrovascular deficiencies such as reduced blood supply to the brain and disrupted microvascular integrity in brain parenchyma play a direct or intermediate role in the chain of events ending with a dementia syndrome. The present review focuses on platelet abnormalities and hemostatic alterations in AD. In particular, data from our group, along with current literature, are discussed with regard to the evidence of platelets amyloid precursor protein (APP) processing disturbances in early AD as well as to the recent observations of increased serum levels of thrombomodulin and sE-selectin, which are sensitive markers of endothelial dysfunction. These findings strongly indicate that platelet dysfunction and microvasculature deficiencies occur rather early during the course of AD, thus suggesting a further link between AD-related processes and vascular disorders.

Cognitive performance is impaired in coeliac patients on gluten free diet: a case-control study in patients older than 65 years of age.

INTRODUCTION: Retrospective studies and case reports suggest an association between coeliac disease and impaired cognitive function. AIM: To evaluate functional and cognitive performances in coeliac disease vs. control patients older than 65 years. METHOD: Eighteen coeliac disease patients (75±4 years, group A) on gluten free diet since 5.5±3 years and 18 age-sex matched controls (76±4 years, group B) were studied using a battery of neuropsychological tests. Results of functional and cognitive tests are expressed as "row scores" and as "equivalent scores" by relating "raw scores" to reference rank categories. RESULTS: Barthel Index of functional performance was similar in the 2 groups. "Raw score" was significantly lower in coeliac disease than controls for Mini Mental Test Examination (p=0.02), Trail Making Test (p=0.001), Semantic Fluency (p=0.03), Digit Symbol Test (p=0.007), Ideo-motor apraxia (p<0.001) and Bucco-facial apraxia (p<0.002). "Equivalent score" was also lower in coeliac disease than controls for Semantic memory (p<0.01) and for Ideo-motor apraxia (p=0.007). CONCLUSION: Cognitive performance is worse in elderly coeliac disease than control patients, despite prolonged gluten avoidance in coeliacs. Awareness on the increasing phenomenon of late-onset coeliac disease is important to minimize diagnostic delay and prolonged exposure to gluten that may adversely and irreversibly affect cognitive function.

Hypoglycemia, an atypical early sign of hepatocellular carcinoma.

BACKGROUND: Hypoglycemia is extremely uncommon as the first presentation of hepatocellular carcinoma, and it occurs predominantly as a paraneoplastic manifestation. METHODS: We report a case of a 38-year-old-man positive for hepatitis B surface antigen with high-serum viremia who presented with symptoms of acute severe hypoglycemia. RESULTS: Laboratory tests confirmed hypoglycemia (serum glucose 1.54 mmol/L) with undetectable serum-C peptide (<0.5 µIU/mL) and slightly increased serum insulin concentration (35 µIU/mL). Alpha-fetoprotein serum level was 75,625 ng/mL. Abdominal ultrasonography and computed tomography revealed a big vascularized mass of 13 cm in diameter occupying most of the right lobe of the liver and an (18)F-fluoro-2-deoxy-D-glucose positron-emission tomography revealed a predominant uptake of glucose by the tumor mass. CONCLUSIONS: These findings indicate that hepatocellular carcinoma-associated hypoglycemia may be due exclusively to increased glucose utilization by the tumor mass.

Cardiac autonomic dysfunction is associated with white matter lesions in patients with mild cognitive impairment.

BACKGROUND: Cardiac autonomic dysfunction has been associated with cognitive impairment, but the underlying pathogenesis is complex and cerebral white matter lesions (WMLs) might be implicated. METHODS: Time and frequency heart rate variability (HRV) and visual rating of WMLs were carried out in 42 patients with mild cognitive impairment. RESULTS: After adjustment for relevant demographic and clinical characteristics, including left ventricular mass, reduced HRV indices of parasympathetic (root mean square of successive difference of RR intervals, RMSSD) and sympathetic modulation (low-frequency [LF] power) were associated with increased WML score (RMSSD: B -0.30, 95% CI -0.52 to -0.08, p = .01; LF: B -0.24, 95% CI -0.46 to -0.02, p = .05). In a multiple-adjusted model, RMSSD was the major independent predictor of WMLs (B -0.35, 95% CI -0.57 to -0.13, p = .002). CONCLUSION: The evidence for an independent association of cardiac autonomic dysfunction with WMLs might suggest its role in the pathogenesis of WMLs.