Early Detection Screening of Cognitive Decline in Patients Over 60 Years: ELDERCARE Study.

Background: Dementia is the fourth leading cause of death in people >  65 years old in western countries.

Objective: This cross-sectional assisted survey aimed to evaluate a multidisciplinary team approach of specialists of the Associazione Geriatri Extraospedalieri a favore di Anziani Svantaggiati and pharmacists to facilitate progress in the early identification and management of cognitive decline in patients >  60 years.

Methods: A multidisciplinary team conducted this cross-sectional assisted survey.

Pre-exposure Prophylaxis Use History in People With Antiretroviral Resistance at HIV Diagnosis: Findings From New York City HIV Surveillance and Partner Services, 2015-2022.

Background: Drug resistance may be acquired in people starting human immunodeficiency virus (HIV) preexposure prophylaxis (PrEP) during undiagnosed infection. Population-based estimates of PrEP-related resistance are lacking.

Methods: We used New York City surveillance and partner services data to measure the effect of PrEP use (tenofovir disoproxil fumarate/tenofivir alafenamide fumarate with emtricitabine) history on the baseline prevalence of M184I/V mutations in people with HIV diagnosed in 2015-2022.

Genomic alterations in cholangiocarcinoma: clinical significance and relevance to therapy.

Improving the survival of patients with cholangiocarcinoma (CCA) has long proved challenging, although the treatment of this disease nowadays is on advancement. The historical invariability of survival outcomes and the limited number of agents known to be effective in the treatment of this disease has increased the number of studies designed to identify genetic targetable hits that can be efficacious for novel therapies. In this respect, the increasing feasibility of molecular profiling starting either from tumor tissue or circulating cell-free DNA (cfDNA) has led to an increased understanding of CCA biology.

Low Impact of Clonal Hematopoiesis on the Determination of RAS Mutations by Cell-Free DNA Testing in Routine Clinical Diagnostics.

Targeted sequencing of circulating cell-free DNA (cfDNA) is used in routine clinical diagnostics for the identification of predictive biomarkers in cancer patients in an advanced stage. The presence of KRAS mutations associated with clonal hematopoiesis of indeterminate potential (CHIP) might represent a confounding factor. We used an amplicon-based targeted sequencing panel, covering selected regions of 52 genes, for circulating cell-free total nucleic acid (cfTNA) analysis of 495 plasma samples from cancer patients.

Using molecular epidemiology to trace the history of the injection-related HIV epidemic in New York City, 1985-2019.

Objective: Unintentional drug poisoning and overdose deaths in New York City (NYC) increased 175% between 2010 and 2017, partly due to the transition from noninjectable opioids to heroin injection. This transition has led to concern of a resurgent HIV epidemic among persons who inject drugs (PWID) in NYC. Thus, we sought to characterize HIV transmission dynamics in PWID.

Dynamics of RAS/BRAF Mutations in cfDNA from Metastatic Colorectal Carcinoma Patients Treated with Polychemotherapy and Anti-EGFR Monoclonal Antibodies.

Analysis of plasma-derived cell-free DNA (cfDNA) might allow for the early identification of resistance in metastatic colorectal carcinoma (mCRC) patients receiving anti-EGFR monoclonal antibodies. We tested plasma samples from the Erbitux Metastatic Colorectal Cancer Strategy (ERMES) phase III trial of FOLFIRI+Cetuximab in first-line treatment of RAS/BRAF wild-type mCRC. Samples were collected at baseline ( = 37), at 8 weeks of treatment ( = 32), progressive disease (PD; = 36) and 3 months after PD ( = 21).

Sorting by Race/Ethnicity Across HIV Genetic Transmission Networks in Three Major Metropolitan Areas in the United States.

An important component underlying the disparity in HIV risk between race/ethnic groups is the preferential transmission between individuals in the same group. We sought to quantify transmission between different race/ethnicity groups and measure racial assortativity in HIV transmission networks in major metropolitan areas in the United States. We reconstructed HIV molecular transmission networks from viral sequences collected as part of HIV surveillance in New York City, Los Angeles County, and Cook County, Illinois.

Circulating Tumor DNA Testing Opens New Perspectives in Melanoma Management.

Malignant melanoma accounts for about 1% of all skin cancers, but it causes most of the skin cancer-related deaths. Circulating tumor DNA (ctDNA) testing is emerging as a relevant tool for the diagnosis and monitoring of cancer. The availability of highly sensitive techniques, including next generation sequencing (NGS)-based panels, has increased the fields of application of ctDNA testing.

Targeted sequencing analysis of cell-free DNA from metastatic non-small-cell lung cancer patients: clinical and biological implications.

Background: Sequencing artifacts, clonal hematopoietic mutations of indeterminate potential (CHIP) and tumor heterogeneity have been hypothesized to contribute to the low concordance between tissue and cell-free DNA (cfDNA) molecular profiling with targeted sequencing.

Methods: We analyzed by targeted sequencing cfDNA from 30 healthy individuals, and cfDNA and matched tumor samples from 30 EGFR-mutant and 77 EGFR wild-type metastatic non-small-cell lung cancer (mNSCLC) patients. Discordant cases were solved by droplet digital PCR (ddPCR).

Estimating the probability of diagnosis within 1 year of HIV acquisition.

Background: Early diagnosis of HIV is important for the prevention of ongoing transmission and development of HIV-related illness. The purpose of this study is to develop an outcome indicator to monitor the progress in early HIV diagnosis.

Methods: Persons diagnosed with HIV in New York City and their first CD4 test results were used to estimate the distribution of HIV diagnosis delay, based on a CD4 count depletion model.

Colorectal cancer genomic biomarkers in the clinical management of patients with metastatic colorectal carcinoma.

Colorectal carcinoma (CRC) is an heterogeneous disease in which different genetic alterations play a role in its pathogenesis and progression and offer potential for therapeutic intervention. The research on predictive biomarkers in metastatic CRC (mCRC) mainly focused on the identification of biomarkers of response or resistance to anti-epidermal growth factor receptor monoclonal antibodies. In this respect, international guidelines suggest testing mCRC patients only for , and mutations and for microsatellite instability.

The role of circulating free DNA in the management of NSCLC.

Circulating cell-free DNA (cfDNA) testing has emerged as an alternative to tumor tissue analyses for the management of metastatic non-small-cell lung cancer (NSCLC) patients. Analysis of cfDNA is a minimally invasive procedure that might better reflect tumor heterogeneity and allows repeated testing over the time. Areas covered: This review article covers the different applications of cfDNA testing in NSCLC: early diagnosis of the disease; detection of minimal residual disease in early lung cancer; identification of predictive and prognostic markers in advanced NSCLC patients; monitoring the response to therapy; assessment of tumor mutation burden.

Growth of HIV-1 Molecular Transmission Clusters in New York City.

Background: HIV-1 genetic sequences can be used to infer viral transmission history and dynamics. Throughout the United States, HIV-1 sequences from drug resistance testing are reported to local public health departments.

Methods: We investigated whether inferred HIV transmission network dynamics can identify individuals and clusters of individuals most likely to give rise to future HIV cases in a surveillance setting.

RAS testing of liquid biopsy correlates with the outcome of metastatic colorectal cancer patients treated with first-line FOLFIRI plus cetuximab in the CAPRI-GOIM trial.

Background: Liquid biopsy is an alternative to tissue for RAS testing in metastatic colorectal carcinoma (mCRC) patients. Little information is available on the predictive role of liquid biopsy RAS testing in patients treated with first-line anti-EGFR monoclonal antibody-based therapy.

Patients And Methods: In the CAPRI-GOIM trial, 340 KRAS exon-2 wild-type mCRC patients received first-line cetuximab plus FOLFIRI.

Clinical utility of circulating tumor cells in patients with non-small-cell lung cancer.

Several different studies have addressed the role of the circulating tumor cells (CTC) in non-small-cell lung cancer (NSCLC). In particular, the potential of CTC analysis in the early diagnosis of NSCLC and in the prediction of the outcome of patients with early and advanced NSCLC have been explored. A major limit of these studies is that they used different techniques for CTC isolation and enumeration, they employed different thresholds to discriminate between high- and low-risk patients, and they enrolled heterogeneous and often small cohort of patients.

Social and Genetic Networks of HIV-1 Transmission in New York City.

Background: Sexually transmitted infections spread across contact networks. Partner elicitation and notification are commonly used public health tools to identify, notify, and offer testing to persons linked in these contact networks. For HIV-1, a rapidly evolving pathogen with low per-contact transmission rates, viral genetic sequences are an additional source of data that can be used to infer or refine transmission networks.

Estimated HIV Incidence in the United States, 2003-2010.

Objective: To estimate HIV incidence in the United States using a newly developed method.

Methods: The analysis period (2002-2011) was broken down into 3-year periods with overlaps, and HIV incidence was estimated based on the relationship between number of new diagnoses and HIV incidence in each of these 3-year periods, by assuming that all HIV infections would eventually be diagnosed and within each 3-year period HIV incidence and case finding were stable.

Results: The estimated HIV incidence in the United States decreased from 52,721 (range: 47,449-57,993) in 2003 to 39,651 (range: 35,686-43,617) in 2010, among males from 38,164 (range: 35,051-42,840) to 33,035 (range: 29,088-35,553), and among females from 13,557 (range: 12,133-14,830) to 6616 (range: 5825 to 7120).

Assessment of high-sensitive methods for the detection of EGFR mutations in circulating free tumor DNA from NSCLC patients.

Aim: We assessed the ability of the Therascreen(®) kit (plasma-Therascreen) and of a peptide nucleic acids (PNA)-clamp approach to detect EGFR mutations in plasma-derived circulating-free tumor DNA (cftDNA) from non-small-cell lung cancer patients.

Materials & Methods: cftDNA from 96 patients was analyzed for exon 19 deletions and the p.L858R mutation, using both plasma-Therascreen and PNA-clamp-based assays.

EGFR mutations in lung cancer: from tissue testing to liquid biopsy.

ABSTRACT  The presence of EGFR mutations predicts the sensitivity to EGF receptor (EGFR)-tyrosine kinase inhibitors in a molecularly defined subset of non-small-cell lung carcinoma (NSCLC) patients. For this reason, EGFR testing of NSCLC is required to provide personalized treatment options and better outcomes for NSCLC patients. As surgery specimens are not available in the majority of NSCLC, other currently available DNA sources are small biopsies and cytological samples, providing however limited and low-quality material.

Retrospective study on the benefits of combined Memantine and cholinEsterase inhibitor treatMent in AGEd Patients affected with Alzheimer's Disease: the MEMAGE study.

Background: Combined therapy of memantine and acetylcholinesterase inhibitors (AChEIs) in patients with Alzheimer's disease (AD) may be associated with higher benefits than either monotherapy.

Objective: This retrospective multicentric study conducted in seven Italian Ambulatory Centers for Dementia assessed the efficacy and safety of memantine 20 mg/day administered for 6 months in addition to an AChEI in AD patients with worsened cognitive functions and behavioral disorders.

Methods: A total number of 240 patients (61.

The S492R EGFR ectodomain mutation is never detected in KRAS wild-type colorectal carcinoma before exposure to EGFR monoclonal antibodies.

The activity of the epidermal growth factor receptor (EGFR) antibodies cetuximab and panitumumab in metastatic colorectal carcinoma (mCRC) is significantly limited by molecular mechanisms leading to intrinsic or acquired resistance. The S492R mutation of the EGFR, which is caused by either the 1476C>A or the 1474A>C substitution, interferes with binding to cetuximab but not to panitumumab, and has been detected in mCRC with acquired resistance to cetuximab. Since mechanisms of acquired and intrinsic resistance to EGFR monoclonal antibodies in CRC significantly overlap, we evaluated the frequency of the S492R mutation in a series of KRAS-exon 2 wild-type CRC patients.