“Real world” eligibility for aducanumab Canevelli, Marco; Rossi, Paolo Dionigi; Astrone, Paolo ...
Journal of the American Geriatrics Society (JAGS),
October 2021, 2021-10-00, 20211001, Letnik:
69, Številka:
10
Journal Article
Frailty is a geriatric syndrome that results from multisystem impairment caused by age-associated accumulation of deficits. The frailty index is used to define the level of frailty. Several studies ...have searched for molecular biomarkers associated with frailty, to meet the needs for personalized care. Cyclase-associated protein 2 (CAP2) is a multifunctional actin-binding protein involved in various physiological and pathological processes, that might reflect frailty's intrinsic complexity. This study aimed to investigate the association between frailty index and circulating CAP2 concentration in 467 community-dwelling older adults (median age: 79; range: 65-92 years) from Milan, Italy. The selected robust regression model showed that circulating CAP2 concentration was not associated with chronological age, as well as sex and education. However, circulating CAP2 concentration was significantly and inversely associated with the frailty index: a 0.1-unit increase in frailty index leads to ~0.5-point mean decrease in CAP2 concentration. Furthermore, mean CAP2 concentration was significantly lower in frail participants (i.e., frailty index ≥0.25) than in non-frail participants. This study shows the association between serum CAP2 concentration and frailty status for the first time, highlighting the potential of CAP2 as a biomarker for age-associated accumulation of deficits.
Vitamin D exerts a role in the maintenance of cognitive abilities and in frailty. Although several studies evaluated the interactions between vitamin D and cognitive impairment, results were ...conflicting. In a cohort of community-dwelling older persons, we described the association between vitamin D levels and cognitive decline and all-cause dementia evaluating frailty's contribution. Our cohort included 509 adults, aged 64-92 years: 176 patients with mild cognitive impairment (MCI), 59 with Alzheimer's Disease (AD), 26 with idiopathic Normal Pressure Hydrocephalus (iNPH), 133 with mixed dementia (MD) and 115 without cognitive decline. Frailty was measured by frailty index, and serum 25-hydroxyvitamin D concentrations through electrochemiluminescence immunoassays. We found a significant association between vitamin D levels and Mini Mental State Examination independently of cognitive impairment, age, sex and frailty. The patients with dementia (AD and MD) showed the lowest vitamin D levels, while MCI patients showed higher levels than the other groups. The most severe deficiency was observed in MD patients, the most aged as well as cognitively and functionally impaired. In conclusion, in our community-dwelling older persons investigated for a suspected cognitive impairment, we observed an association between vitamin D levels and cognitive decline, regardless of the frailty status.
Idiopathic normal pressure hydrocephalus (iNPH) is a potentially reversible neurological disease, causing motor and cognitive dysfunction and dementia. iNPH and Alzheimer’s disease (AD) share similar ...molecular characteristics, including amyloid deposition, t-tau and p-tau dysregulation; however, the disease is under-diagnosed and under-treated. The aim was to identify a panel of sphingolipids and proteins in CSF to diagnose iNPH at onset compared to aged subjects with cognitive integrity (C) and AD patients by adopting multiple reaction monitoring mass spectrometry (MRM-MS) for sphingolipid quantitative assessment and advanced high-resolution liquid chromatography–tandem mass spectrometry (LC–MS/MS) for proteomic analysis. The results indicated that iNPH are characterized by an increase in very long chains Cer C22:0, Cer C24:0 and Cer C24:1 and of acute-phase proteins, immunoglobulins and complement component fragments. Proteins involved in synaptic signaling, axogenesis, including BACE1, APP, SEZ6L and SEZ6L2; secretory proteins (CHGA, SCG3 and VGF); glycosylation proteins (POMGNT1 and DAG1); and proteins involved in lipid metabolism (APOH and LCAT) were statistically lower in iNPH. In conclusion, at the disease onset, several factors contribute to maintaining cell homeostasis, and the protective role of very long chains sphingolipids counteract overexpression of amyloidogenic and neurotoxic proteins. Monitoring specific very long chain Cers will improve the early diagnosis and can promote patient follow-up.
Microglia performs a variety of functions during brain development designed to maintain brain homeostasis. Triggering receptor expressed on myeloid cells 2 (TREM2) is expressed in microglial cells ...modulating phagocytosis, cytokine production, cell proliferation, and cell survival. Interestingly, the levels of soluble TREM2 (the secreted ectodomain of TREM2, sTREM2) were higher in cerebrospinal fluid (CSF) from Alzheimer's disease (AD) patients than subjects without cognitive decline. It is noteworthy that, while CSF sTREM2 levels have been extensively studied, few studies have investigated sTREM2 in blood producing conflicting results. We aimed to investigate the levels of sTREM2 in CSF and blood from a cohort of well-characterized AD comparing the results to those obtained in patients suffering from idiopathic normal pressure hydrocephalus (iNPH), a potentially reversible cognitive impairment. Our findings underlined a significantly lower plasma sTREM2 concentration in AD patients compared to iNPH subjects 39.1 ng/mL (standard deviation (SD), 15.0) and 47.2 ng/mL (SD, 19.5), respectively;
= 0.01, whereas no difference was revealed between the two groups in the CSF sTREM2 levels. The adjusted regression analyses evidenced in AD patients an association between plasma and CSF sTREM2 levels
= 0.411; 95% confidence interval (CI), 0.137-0.685,
= 0.004, as well as β-amyloid concentrations (
= 0.035; 95% CI, 0.007-0.063,
= 0.01) and an association between CSF sTREM2 and phospho-Tau concentrations (
= 0.248; 95% CI, 0.053-0.443;
= 0.01). No significant relation was found in iNPH patients. In conclusion, these differences in sTREM2 profiles between AD and iNPH reinforce the notion that this receptor has a role in neurodegeneration.
Abstract Objectives Surgical excision is the standard strategy for managing liver metastases from colorectal carcinoma. The achievement of negative (R0) margins is a major determinant of disease-free ...survival in these patients. Current imaging techniques are of limited value in achieving this goal. A new approach to the intraoperative detection of colorectal liver metastatic tissue based on the emission of indocyanine green (ICG) fluorescence was evaluated. Methods A total of 25 consecutive patients with liver metastases from primary colorectal cancers who were eligible for liver resection received a bolus of ICG (0.5 mg/kg body weight) 24 h before surgery. During surgery, ICG fluorescence, which accumulates around lesions as a result of defective biliary clearance, was detected with a near-infrared camera system, the Photodynamic Eye (PDE). Numbers of lesions detected by, respectively, PDE + ICG, intraoperative ultrasound (IOUS) and preoperative computed tomography (CT) were recorded. Results The near-infrared camera plus ICG revealed a total of 77 metastatic liver nodules. Preoperative CT demonstrated 45 (58.4%) and IOUS showed 55 (71.4%). Preoperative CT and IOUS alone were inferior to the combined use of PDE + ICG and IOUS in the detection of lesions of ≤3 mm in size. Conclusions This experience suggests that PDE + ICG, combined with IOUS, may represent a safe and effective tool for ensuring the complete surgical eradication of liver metastases from colorectal cancer.
Vascular alterations often overlap with neurodegeneration, resulting in mixed forms of dementia (MD) that are hard to differentiate from Alzheimer's Disease (AD). The 26 bp intergenic polymorphism of
..., a key component of SNARE complex, as well as its mRNA and protein levels are associated with neurological diseases. We evaluated
and
26 bp Ins/Del genotype distribution in 177 AD, 132 MD, 115 Mild Cognitive Impairment (MCI) and 250 individuals without cognitive decline (CT), as well as
gene expression in a subset of 73 AD, 122 MD, 103 MCI and 140 CT. Forty-two MCI evolved to AD (22 MCI-AD) or MD (20 MCI-MD) over time.
mRNA was higher in MD compared to AD (
= 0.0013) and CT (
= 0.0017), and in MCI-MD compared to MCI-AD (
< 0.001) after correcting for age, gender, MMSE and
+/- covariates (
= 0.004). A higher
expression was observed in subjects carrying the minor allele Del compared to those carrying the Ins/Ins genotype (
= 0.012). Finally, Del/Del genotype was more frequently carried by MD/MCI-MD compared to CT (
= 0.036). These results suggest that
mRNA expression can discriminate mixed form of dementia from AD, possibly being a biomarker of AD evolution in MCI patients.
Sacral chordoma (SC) is a neoplasm arising from residual notochordal cells degeneration. SC is difficult to manage mainly because of anatomic location and tendency to extensive spread. Carbon ion ...radiotherapy (CIRT) is highly precise to selectively deliver high biological effective dose to the tumor target sparing the anatomical structure on its path even if when SC is contiguous to the intestine, and a surgical spacer might be an advantageous tool to create a distance around the target volume allowing radical curative dose delivery with a safe dose gradient to the surrounding organs. This paper describes a double approach-open and hand-assisted laparoscopic-for a silicon spacer placement in patients affected by sacral chordoma undergoing carbon ion radiotherapy.
Six consecutive patients have been enrolled for surgical spacer placement-open (three) or hand-assisted (three)-prior carbon ion radiotherapy treatment in order to increase efficacy of carbon ion radiotherapy minimizing its side effects.
Results showed that silicon spacer placement for SC treatment is feasible both via laparoscopic and laparotomic approach.
Its use might improve CIRT safety and thus efficacy for SC treatment.
Abstract Frontotemporal Dementia (FTD) and Alzheimer's Disease (AD) share the accumulation of fibrillar aggregates of misfolded proteins. To better understand these neurodegenerative diseases and ...identify biomarkers in easily accessible cells, we investigated DNA methylation at Pin1 gene promoter and its expression in peripheral blood mononuclear cells of FTD patients. We found a lower gene expression of Pin1 with a higher DNA methylation in three CpG sites at Pin1 gene promoter analysed in FTD subjects, in contrast to a higher gene expression with a lower methylation in AD subjects and controls. These data suggest an important and distinct involvement of Pin1 in these two types of dementia.
Surgical site infection (SSI) remains the most frequent complication after colorectal resection. The role of sutures coated with antimicrobial agents such as triclosan in reducing SSI is ...controversial.
This was a multi-center randomized controlled trial with patients and outcome assessors blinded to treatment. The study was performed in four university referral hospitals. Patient candidates for elective colorectal resection were assigned randomly to abdominal incision closure with polyglactin 910 triclosan-coated sutures (triclosan group) or with polyglactin 910 without triclosan (control group). The primary outcome was the rate of SSI within 30 d after hospital discharge. The secondary outcomes were the overall rate of incision complications and length of hospital stay (LOS).
Two hundred eighty-one patients (triclosan group: 140; control group: 141) were analyzed after randomization. The rate of SSI was 12.9% (18/140) in the triclosan group versus 10.6% (15/141) in the control group (odds ratio: 1.24; 95% confidence interval: 0.60-2.57; p=0.564). Secondary outcome analysis showed an overall incision complication rate of 38.3% in the control group versus 45.7% in the triclosan group (odds ratio: 1.36; 95% confidence interval: 0.84-2.18; p=0.208). Median LOS was 11 d in both groups (p=0.55).
Surgical sutures coated with triclosan do not appear to be effective in reducing the rate of SSI.
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