Timed up and go test and long-term survival in older adults after oncologic surgery

BACKGROUND: Physical performance tests are a reflection of health in older adults. The Timed Up and Go test is an easy-to-administer tool measuring physical performance. In older adults undergoing oncologic surgery, an impaired TUG has been associated with higher rates of postoperative complications and increased short term mortality. The objective of this study is to investigate the association between physical performance and long term outcomes. METHODS: Patients aged ≥65 years undergoing surgery for solid tumors in three prospective cohort studies, ‘PICNIC’, ‘PICNIC B-HAPPY’ and ‘PREOP’, were included. The TUG was administered 2 weeks before surgery, a score of ≥12 seconds was considered to be impaired. Primary endpoint was 5-year survival, secondary endpoint was 30-day major complications. Survival proportions were estimated using Kaplan-Meier curves. Cox- and logistic regression analysis were used for survival and complications respectively. Hazard ratios (aHRs) and Odds ratios (aOR) were adjusted for literature-based and clinically relevant variables, and 95% confidence intervals (95% CIs) were estimated using multivariable models. RESULTS: In total, 528 patients were included into analysis. Mean age was 75 years (SD 5.98), in 123 (23.3%) patients, the TUG was impaired. Five-year survival proportions were 0.56 and 0.49 for patients with normal TUG and impaired TUG respectively. An impaired TUG was an independent predictor of increased 5-year mortality (aHR 1.43, 95% CI 1.02-2.02). The TUG was not a significant predictor of 30-day major complications (aOR 1.46, 95% CI 0.70-3.06). CONCLUSIONS: An impaired TUG is associated with increased 5-year mortality in older adults undergoing surgery for solid tumors. It requires further investigation whether an impaired TUG can be reversed and thus improve long-term outcomes. TRIAL REGISTRATION: The PICNIC studies are registered in the Dutch Clinical Trial database at www.trialregister.nl: NL4219 (2010-07-22) and NL4441 (2014-06-01). The PREOP study was registered with the Dutch trial registry at www.trialregister.nl: NL1497 (2008-11-28) and in the United Kingdom register (Research Ethics Committee reference 10/H1008/59). https://www.hra.nhs.uk/planning-and-improving-research/application-summaries/research-summaries/?page=15&query=preop&date_from=&date_to=&research_type=&rec_opinion=&relevance=true. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12877-022-03585-4

Long-Term Survival and Risk of Institutionalization in Onco-Geriatric Surgical Patients:Long-Term Results of the PREOP Study

OBJECTIVES: To evaluate long-term survival and institutionalization in onco-geriatric surgical patients, and to analyze the association between these outcomes and a preoperative risk score. DESIGN: Prospective cohort study with long-term follow-up. SETTING: International and multicenter locations. PARTICIPANTS: Patients aged 70 years or older undergoing elective surgery for a malignant solid tumor at five centers (n = 229). MEASUREMENTS: We assessed long-term survival and institutionalization using the Preoperative Risk Estimation for Onco-geriatric Patients (PREOP) score, developed to predict the 30-day risk of major complications. The PREOP score collected data about sex, type of surgery, and the American Society for Anesthesiologists classification, as well as the Timed Up & Go test and the Nutritional Risk Screening results. An overall score higher than 8 was considered abnormal. RESULTS: We included 149 women and 80 men (median age = 76 y; interquartile range = 8). Survival at 1, 2, and 5 years postoperatively was 84%, 77%, and 56%, respectively. Moreover, survival at 1 year was worse for patients with a PREOP risk score higher than 8 (70%) compared with 8 or lower (91%). Of those alive at 1 year, 43 (26%) were institutionalized, and by 2 years, almost half of the entire cohort (46%) were institutionalized or had died. A PREOP risk score higher than 8 was associated with increased mortality (hazard ratio = 2.6; 95% confidence interval [CI] = 1.7-4.0), irrespective of stage and age, but not with being institutionalized (odds ratios = 1 y, 1.6 [95% CI =.7-3.8]; 2 y, 2.2 [95% CI =.9-5.5]). CONCLUSION: A high PREOP score is associated with mortality but not with remaining independent. Despite acceptable survival rates, physical function may deteriorate after surgery. It is imperative to discuss treatment goals and expectations preoperatively to determine if they are feasible. Using the PREOP risk score can provide an objective measure on which to base decisions. J Am Geriatr Soc 68:1235–1241, 2020

A scan of all coding region variants of the human genome, identifies 13q12.2-rs9579139 and 15q24.1-rs2277598 as novel risk loci for pancreatic ductal adenocarcinoma

Coding sequence variants comprise a small fraction of the germline genetic variability of the human genome. However, they often cause deleterious change in protein function and are therefore associated with pathogenic phenotypes. To identify novel pancreatic ductal adenocarcinoma (PDAC) risk loci, we carried out a complete scan of all common missense and synonymous SNPs and analysed them in a case control study comprising four different populations, for a total of 14,538 PDAC cases and 190,657 controls. We observed a statistically significant association between 13q12.2-rs9581957-T and PDAC risk (P=2.46x10 -9), that is in linkage disequilibrium (LD) with a deleterious missense variant (rs9579139) of the URAD gene. Recent findings suggest that this gene is active in peroxisomes. Considering that peroxisomes have a key role as molecular scavengers, especially in eliminating reactive oxygen species, a malfunctioning URAD protein might expose the cell to a higher load of potentially DNA damaging molecules and therefore increase PDAC risk. The association was observed in individuals of European and Asian ethnicity. We also observed the association of the missense variant 15q24.1-rs2277598-T, that belongs to BBS4 gene, with increased PDAC risk (P=1.53x10 -6). rs2277598 is associated with body mass index and is in LD with diabetes susceptibility loci. In conclusion, we identified two missense variants associated with the risk of developing PDAC independently from the ethnicity highlighting the importance of conducting reanalysis of GWAS studies in light of functional data

Association between a polymorphic variant in the CDKN2B-AS1/ANRIL gene and pancreatic cancer risk

Genes carrying high-penetrance germline mutations may also be associated with cancer susceptibility through common low-penetrance genetic variants. To increase the knowledge on genetic pancreatic ductal adenocarcinoma (PDAC) aetiology, the common genetic variability of PDAC familial genes was analysed in this study. We conducted a multi-phase study analysing 7,745 single nucleotide polymorphisms (SNPs) from 29 genes reported to harbour a high-penetrance PDAC-associated mutation in at least one published study. To assess the effect of the SNPs on PDAC risk, a total of 14,666 PDAC cases and 221,897 controls across five different studies were analysed. The T allele of the rs1412832 polymorphism, that is situated in the CDKN2B-AS1/ANRIL, showed a genome-wide significant association with increased risk of developing PDAC (OR=1.11, 95%CI=1.07-1.15, P=5.25×10-9 ). CDKN2B-AS1/ANRIL is a long non-coding RNA, situated in 9p21.3, and regulates many target genes, among which CDKN2A (p16) that frequently shows deleterious somatic and germline mutations and deregulation in PDAC. Our results strongly support the role of the genetic variability of the 9p21.3 region in PDAC aetiopathogenesis and highlight the importance of secondary analysis as a tool for discovering new risk loci in complex human diseases. This article is protected by copyright. All rights reserved

Correction: "Timed Up & Go":A Screening Tool for Predicting 30-Day Morbidity in Onco-Geriatric Surgical Patients? A Multicenter Cohort Study (vol 9, e0086863, 2014)

<p>Correction: "Timed Up & Go": A Screening Tool for Predicting 30-Day Morbidity in Onco-Geriatric Surgical Patients? <i>A Multicenter Cohort Study</i></p

Meconium microbiome analysis and its effects on weight at birth and response to non-pharmacologic analgesic therapy in newborns

In the last decade several studies indicated the first thousand days of life as a critical time-window in which the basis for health, growth and neurodevelopment are established, triggering both short-term effects and long-term effects. One of the most important clinical parameters to consider in the first stage of life is birth weight, which has been proven to play a key role in healthy growth and correct development, since many studies showed that small for gestational age (SGA) and large for gestational age (LGA) newborns had a higher risk to develop cardiovascular diseases, diabetes, obesity and other several pathologies at infant and adult stages. Another important aspect in post-natal period is pain. The experience of pain in newborns has been associated with behavioural disorders and long-term complications arising in later ages, such as anxiety spectrum disorders, sleep disorders, reduced post-natal growth and poor neurological outcomes. This study aims to investigate clinical and anthropometric measures, the microbiome composition in relation to weight at birth and in the variability of an analgesic non-pharmacological treatment response. The study population was made of 95 newborns (Apgar score>7 and gestational age of at least 37 weeks. Clinical and anthropometric data) were collected by the Neonatology Division of Santa Chiara Hospital. The ABC score was used to assess whether the analgesic therapy effectiveness. Bacterial DNA was extracted from meconium, then, V3-V4 regions belonging to 16S rRNA gene were amplified and finally, purified sequences were sequenced by NGS on a MiSeq platform. Taxonomical classification of OTUs was carried out at each taxonomic level using SILVA database and QIIME2 platform. Microbiome composition was explored from phylum to species level considering each taxon as a continuous variable in terms of its relative abundance. Alpha diversity metrics such as richness, Shannon index and Inverse Simpson index were calculated. The effects of alpha diversity indexes on weight at birth were assessed by using a generalized linear model corrected for covariates. The effects of alpha diversity indexes on ABC score were evaluated by using a logistic regression model (corrected for covariates). Then, Tax4Fun2 tool was used to infer metabolic pathways from 16S sequences. Furthermore, the effects of most relevant anthropometric and clinical variables on alpha diversity indexes were considered. In addition, taxa distribution among samples was evaluated comparing taxa’s abundances by each level of single dichotomic factors (such as sex, delivery mode, maternal use of drugs, maternal diabetes and so on). So, correction for multiple testing was introduced to assess the significance of results. As expected, meconium microbiome showed a high degree of variability in terms of composition, sharing some similarities with the human adult gut microbiome. For the association between clinical and anthropometric factors and alpha diversity, it was found that Rh factor had a significant effect on both Shannon and observed richness indexes. On the other side, observed richness was significantly associated to ABC score (OR=0.974, p=0.011), while if considering weight at birth as outcome variable, both Shannon and Inverse Simpson index had a significant effect on weight (p=0.011 and p=0.012 respectively). For metabolic pathways, no significant difference was observed, as all samples showed a quite identical bacterial metabolic composition (in contrast with the higher variability of taxonomical composition). In conclusion these preliminary results seem to support the involvement of the microbiome composition in two key aspect of newborns well-being

Saint Louis du Sénégal. Strategie urbane e progetti per la ricostruzione di una metropoli regionale africana

Il testo riporta gli esiti di una ricerca progettuale che ha riguardato la città di Saint Louis du Sénégal. Il lavoro è stato svolto nell'ambito di un progetto europeo intitolato "Acqua come Patrimonio" e il gruppo di ricerca dopo una fase analisi e luttura della città e del contesto paesaggistico del delta del fiume Sénégal ha definito delle linee strategiche per la pianificazione delle città e ha approfondito alcuni temi di rigenerazione legati al rapporto tra la città e il fiume