Delays in cancer diagnosis: challenges and opportunities in Europe

Background and aim: Early cancer diagnosis is a public health priority, but large proportions of patients are diagnosed with advanced disease or as an emergency, even in countries with universal healthcare coverage. The study aimed at examining factors contributing to diagnostic delays and inequalities in cancer care, discussing challenges and opportunities for improving the diagnosis of cancer. // Methods: We performed a critical review of the literature examining factors contributing to delays and inequalities in cancer diagnosis, published between 2019-2023, in Europe with a specific focus on Italy. // Results: Disparities in screening, cancer diagnosis and treatment have been reported in many European countries, with poorer outcomes for some population sub-groups. For example, some Northern regions in Italy have six-times higher screening participation versus Southern regions. In 2019 36% of the Italian population aged 50-74 reported colorectal cancer screening, higher than the EU average (33%), but lower than in countries like Denmark (>60%). In Italy, the EU country with the largest percentage of people aged 65+, incident cancers are expected to rise by 19.6% over two decades. Older age is also associated with multimorbidity, with physical and mental health morbidities possibly affecting cancer diagnostic pathways. For example, colon cancer patients with pre-existing mental health conditions were 28% less likely to have a prompt colonoscopy when presenting with red-flag symptoms, according to recent UK research. Covid-19 has exacerbated pre-existing inequalities, with reductions in scheduled surgery and oncological treatments, especially affecting women, older and less educated individuals. // Conclusions: For ensuring appropriate care, it is crucial to better understand how different factors, including physical and mental health morbidities, impact cancer diagnosis. The “NextGenerationEU” program and the “National Recovery and Resilience Plan” (PNNR in Italy) following the Covid-19 pandemic offer opportunities for reducing inequalities, improving cancer care and chronic disease management for ageing populations

Isolated Left Ventricular Noncompaction in a Case of Sotos Syndrome: A Casual or Causal Link?

A 16-year-old boy affected by Sotos syndrome was referred to our clinic for cardiac evaluation in order to play noncompetitive sport. Physical examination was negative for major cardiac abnormalities and rest electrocardiogram detected only minor repolarization anomalies. Transthoracic echocardiography showed left ventricular wall thickening and apical trabeculations with deep intertrabecular recesses, fulfilling criteria for isolated left ventricular noncompaction (ILVNC). Some sporadic forms of ILVNC are reported to be caused by a mutation on CSX gene, mapping on chromosome 5q35. To our knowledge, this is the first report of a patient affected simultaneously by Sotos syndrome and ILVNC

Perfluorinated compounds (pfcs) in river waters of central Italy. Monthly variation and ecological risk assessment (era)

Perfluorinated compounds (PFCs) are a wide class of emerging pollutants. In this study, we applied the US EPA method 533 for the determination of 21 PFCs in river water samples. In particular, this method was used to investigate the presence of the target PFCs in six rivers in central Italy during a 4-month-long monitoring campaign. In 73% of the analyzed samples, at least some of the target PFCs were detected at concentrations higher than the limit of detection (LOD). The sum of the 21 target analytes ( n-ary sumation 21PFCs) ranged from 4.3 to 68.5 ng L-1, with the highest concentrations measured in the month of June, probably due to a minor river streamflow occurring in the warmer summer months. Considering the individual congeners, PFBA and PFPeA, followed by PFHxA and PFOA, were the predominantly detected compounds. Short- and medium-chain PFCs (C4-C9) prevail over the long-chain PFCs (C10-C18), likely due to the increased industrial use and the higher solubility of short-chain PFCs compared to long-chain PFCs. The ecological risk assessment, conducted by using the risk quotient method, highlighted that the risk for aquatic environments associated with PFBA, PFPeA, PFBS, PFHxA and PFOA was low or negligible. Only for PFOA, there was a medium level of risk in two rivers in the month of June. With regard to PFOS, 54% of the river water samples were classified as "high risk" for the aquatic environment. The remaining 46% of the samples were classified as "medium risk.

Circulating methylated DNA to monitor the dynamics of RAS mutation clearance in plasma from metastatic colorectal cancer patients

The clearance of RAS mutations in plasma circulating tumor DNA (ctDNA) from originally RAS-mutant metastatic colorectal cancer (mCRC) has been recently demonstrated. Clinical trials investigating whether RAS mutant mCRC who “convert” to wild-type in plasma might benefit from EGFR blockade are ongoing. Detection of tumor-specific DNA methylation alterations in ctDNA has been suggested as a specific tool to confirm the tumoral origin of cell-free DNA. We monitored RAS clearance in plasma from patients with RAS-mutant mCRC at baseline (pre-treatment) (T0); after 4 months of first-line therapy (T1); at the time of first (T2) and second (T3) progression. A five-gene methylation panel was used to confirm the presence of ctDNA in samples in which RAS mutation clearance was detected. At T1 ctDNA analysis revealed wild-type RAS status in 83% of samples, all not methylated, suggesting at this time point the lack of ctDNA shedding. At T2 ctDNA analysis revealed wild-type RAS status in 83% of samples, of which 62.5% were found methylated. At T3 50% of wild-type-RAS samples were found methylated. Non-methylated samples were found in patients with lung or brain metastases. This five-gene methylation test might be useful to confirm the presence of ctDNA in RAS wild-type plasma samples

Genomic landscape and survival analysis of ctDNA “neo-RAS wild-type” patients with originally RAS mutant metastatic colorectal cancer

Background: The term “neo-RAS wild-type” refers to the switch to RAS wild-type disease in plasma circulating tumor DNA (ctDNA) from originally RAS mutant colorectal cancers. Consistently, the hypothesis to re-determine RAS mutational status in ctDNA at disease progression in RAS mutant mCRC opened to a new perspective for clinically-based selection of patients to be treated with EGFR inhibitors. Currently, the genomic landscape of “neo-RAS wild-type” is unknown. This is a prospective study aimed to investigate clinical and genomic features associated with RAS mutation clearance in a large cohort of RAS mutant mCRC patients who converted to RAS wild- type in liquid biopsy at failure of first-line treatments. Secondary aim was to investigate the long term prognostic significance of “true neo-RAS wild- type”. Patients and methods: 70 patients with stage IV RAS mutant colorectal cancer were prospectively enrolled. Plasma samples were collected at progression from first-line treatment. RAS/BRAF mutations in plasma were assessed by RT-PCR. In RAS/BRAF wild-type samples, ctDNA was used to generate libraries using a 17 genes panel whose alteration has clinical relevance. To investigate the prognostic significance of RAS mutation clearance, test curves for PFS and OS were represented by Kaplan-Meier estimator plot and Log-rank test. Results: The most commonly detected actionable mutations in “neo-RAS wild-type” were: PIK3CA (35.7%); RET (11.9%); IDH1 (9.5%); KIT (7%); EGFR (7%); MET (4.7%); ERBB2 (4.7%); FGFR3 (4.7%). Both OS and post-progression survival were longer in patients with “neo-RAS wild-type” compared to those who remained RAS mutant (p<0.001 for both). Conclusions: De-novo-targetable mutations occured in a large percentage of “neo-RAS wild-type”, being PIK3CA the most commonly detected. RAS mutation clearance in ctDNA is associated with long- term improvement of overall survival

Impact of different exposure models and spatial resolution on the long-term effects of air pollution.

Abstract Long-term exposure to air pollution has been related to mortality in several epidemiological studies. The investigations have assessed exposure using various methods achieving different accuracy in predicting air pollutants concentrations. The comparison of the health effects estimates are therefore challenging. This paper aims to compare the effect estimates of the long-term effects of air pollutants (particulate matter with aerodynamic diameter less than 10 μm, PM10, and nitrogen dioxide, NO2) on cause-specific mortality in the Rome Longitudinal Study, using exposure estimates obtained with different models and spatial resolutions. Annual averages of NO2 and PM10 were estimated for the year 2015 in a large portion of the Rome urban area (12 × 12 km2) applying three modelling techniques available at increasing spatial resolution: 1) a chemical transport model (CTM) at 1km resolution; 2) a land-use random forest (LURF) approach at 200m resolution; 3) a micro-scale Lagrangian particle dispersion model (PMSS) taking into account the effect of buildings structure at 4 m resolution with results post processed at different buffer sizes (12, 24, 52, 100 and 200 m). All the exposures were assigned at the residential addresses of 482,259 citizens of Rome 30+ years of age who were enrolled on 2001 and followed-up till 2015. The association between annual exposures and natural-cause, cardiovascular (CVD) and respiratory (RESP) mortality were estimated using Cox proportional hazards models adjusted for individual and area-level confounders. We found different distributions of both NO2 and PM10 concentrations, across models and spatial resolutions. Natural cause and CVD mortality outcomes were all positively associated with NO2 and PM10 regardless of the model and spatial resolution when using a relative scale of the exposure such as the interquartile range (IQR): adjusted Hazard Ratios (HR), and 95% confidence intervals (CI), of natural cause mortality, per IQR increments in the two pollutants, ranged between 1.012 (1.004, 1.021) and 1.018 (1.007, 1.028) for the different NO2 estimates, and between 1.010 (1.000, 1.020) and 1.020 (1.008, 1.031) for PM10, with a tendency of larger effect for lower resolution exposures. The latter was even stronger when a fixed value of 10 μg/m3 is used to calculate HRs. Long-term effects of air pollution on mortality in Rome were consistent across different models for exposure assessment, and different spatial resolutions

Operative management of acute abdomen after bariatric surgery in the emergency setting: the OBA guidelines

Background: Patients presenting with acute abdominal pain that occurs after months or years following bariatric surgery may present for assessment and management in the local emergency units. Due to the large variety of surgical bariatric techniques, emergency surgeons have to be aware of the main functional outcomes and long-term surgical complications following the most performed bariatric surgical procedures. The purpose of these evidence-based guidelines is to present a consensus position from members of the WSES in collaboration with IFSO bariatric experienced surgeons, on the management of acute abdomen after bariatric surgery focusing on long-term complications in patients who have undergone laparoscopic sleeve gastrectomy and laparoscopic Roux-en-Y gastric bypass. Method: A working group of experienced general, acute care, and bariatric surgeons was created to carry out a systematic review of the literature following the Preferred Reporting Items for Systematic Review and Meta-analysis Protocols (PRISMA-P) and to answer the PICO questions formulated after the Operative management in bariatric acute abdomen survey. The literature search was limited to late/long-term complications following laparoscopic sleeve gastrectomy and laparoscopic Roux-en-Y gastric bypass. Conclusions: The acute abdomen after bariatric surgery is a common cause of admission in emergency departments. Knowledge of the most common late/long-term complications (> 4 weeks after surgical procedure) following sleeve gastrectomy and Roux-en-Y gastric bypass and their anatomy leads to a focused management in the emergency setting with good outcomes and decreased morbidity and mortality rates. A close collaboration between emergency surgeons, radiologists, endoscopists, and anesthesiologists is mandatory in the management of this group of patients in the emergency setting

Multi-messenger searches via IceCube’s high-energy neutrinos and gravitational-wave detections of LIGO/Virgo

We summarize initial results for high-energy neutrino counterpart searches coinciding with gravitational-wave events in LIGO/Virgo\u27s GWTC-2 catalog using IceCube\u27s neutrino triggers. We did not find any statistically significant high-energy neutrino counterpart and derived upper limits on the time-integrated neutrino emission on Earth as well as the isotropic equivalent energy emitted in high-energy neutrinos for each event