The growing prevalence of childhood cancer survivors in Australia.

Survivors of childhood cancer have an increased risk of long-term health issues arising mostly from the side effects of treatment. Using population-based data from the Australian Childhood Cancer Registry (ACCR) for children aged 0-14 at diagnosis between 1983 and 2018, there were a total of 17,468 prevalent cases of childhood cancer survivors on 31 December 2018. We also found an 80% increase in the number of 5-year prevalent cases, from 1979 in 1988 to 3566 in 2018. Both short- and long-term prevalence estimates are important for monitoring childhood cancer survivorship and planning for the specific needs of this expanding cohort.

Global patterns of Hodgkin lymphoma incidence and mortality in 2020 and a prediction of the future burden in 2040.

Our study examines global patterns of Hodgkin lymphoma (HL) in 2020 and predicts the future incidence and mortality burden in 2040 using IARC's GLOBOCAN estimates of the number of new cases and deaths of HL in 185 countries. A total of 83 000 new cases of HL and 23 000 deaths from HL were estimated in 2020. In general, incidence and mortality rates were consistently higher in males (50% more cases and deaths than females) across world regions and countries. Incidence rates varied markedly by world region, at least 10-fold in both sexes, with the highest incidence rates observed in Southern Europe. Mortality exhibited an inverse pattern compared to incidence, with rates elevated in Western Asia and Northern Africa. The number of HL incident cases is predicted to rise to around 107 000 cases (a 30% increase) by 2040 due to demographic changes, assuming global rates in 2020 remains unchanged. The findings provide a baseline and impetus for developing strategies that aim to reduce the burden of HL in future decades.

Optimizing screening with faecal immunochemical test for both sexes - Cost-effectiveness analysis from Finland.

A faecal immunochemical test (FIT) screening pilot was introduced in Finland in 2019 with sex-specific screening strategies. This study aims to model cost-effectiveness of sex-specific strategies for the whole population, and to assess whether the current strategies are optimal. We developed separate MISCAN-Colon models, including different FIT performances, for the Finnish men and women using the first-year data of the FIT screening pilot. We evaluated 180 FIT strategies varying in FIT cut-off, screening interval, age to start, and age to stop screening, and compared them to no-screening by sex. We used incremental cost-effectiveness ratios (ICERs) to identify the optimal strategy after combining all male and female strategies and restricting the analysis by costs and referral rate to diagnostic colonoscopies. Offering annual FIT screening with a cut-off of 25 µg/g at 50-79 years in men and with a cut-off of 10 µg/g at 55-69 years in women was optimal. This combined strategy prevented 28% of colorectal cancer (CRC) cases and 55% of CRC deaths with acceptable costs (ICER = 9000€/life-years gained). Screening at the current target age of 60-74 years was suboptimal for both sexes. Among strategies with the same target age and interval for both sexes, expected benefits from optimal screening were lower but still reasonable. Our results support a wider age range of screening in men, and a lower cut-off for a positive test in women when restrictions on colonoscopy capacity and costs are in place. National FIT screening program should start at younger age.

Bioinspired Ether Cyclizations within a π-Basic Capsule Compared to Autocatalysis on π-Acidic Surfaces and Pnictogen-Bonding Catalysts.

While the integration of supramolecular principles in catalysis attracts increasing attention, a direct comparative assessment of the resulting systems catalysts to work out distinct characteristics is often difficult. Herein is reported how the broad responsiveness of ether cyclizations to diverse inputs promises to fill this gap. Cyclizations in the confined, π-basic and Brønsted acidic interior of supramolecular capsules, for instance, are found to excel with speed (exceeding general Brønsted acid and hydrogen-bonding catalysts by far) and selective violations of the Baldwin rules (as extreme as the so far unique pnictogen-bonding catalysts). The complementary cyclization on π-acidic aromatic surfaces remains unique with regard to autocatalysis, which is shown to be chemo- and diastereoselective with regard to product-like co-catalysts but, so far, not enantioselective.

Impact of COVID-19 Pandemic on Cancer-Related Hospitalizations in Brazil.

BACKGROUND: Alongside the SARS-CoV-2 (COVID-19) pandemic, Brazil also faces an ongoing rise in cancer burden. In 2020, there were approximately 592 000 new cancer cases and 260 000 cancer deaths. Considering the heterogeneities across Brazil, this study aimed to estimate the impact of the COVID-19 pandemic on cancer-related hospital admissions at a national and regional level. METHODS: The national, regional, and state-specific monthly average of cancer-related hospital admission rates per 100 000 inhabitants and 95% confidence intervals (95% CIs) were calculated from March to July (2019: pre-COVID-19; and 2020: COVID-19 period). Thematic maps were constructed to compare the rates between periods and regions. RESULTS: Cancer-related hospital admissions were reduced by 26% and 28% for clinical and surgical purposes, respectively. In Brazil, the average hospitalization rates decreased from 13.9 in 2019 to 10.2 in 2020 per 100,000 inhabitants, representing a rate difference of -3.7 (per 100,000 inhabitants; 95% CI: -3.9 to -3.5) for cancer-related (clinical) hospital admissions. Surgical hospital admissions showed a rate decline of -5.8 per 100,000 (95% CI: -6.0 to -5.5). The reduction in cancer-related admissions for the surgical procedure varies across regions ranging between -2.2 and -10.8 per 100 000 inhabitants, with the most significant decrease observed in the south and southeastern Brazil. CONCLUSIONS: We observed a substantial decrease in cancer-related hospital admissions during the COVID-19 pandemic with marked differences across regions. Delays in treatment may negatively impact cancer survival in the future; hence, cancer control strategies to mitigate the impact are needed.

Pnictogen-Bonding Catalysis: An Interactive Tool to Uncover Unorthodox Mechanisms in Polyether Cascade Cyclizations.

Pnictogen-bonding catalysis and supramolecular σ-hole catalysis in general is currently being introduced as the non-covalent counterpart of covalent Lewis acid catalysis. With access to anti-Baldwin cyclizations identified as unique characteristic, pnictogen-bonding catalysis appeared promising to elucidate one of the hidden enigmas of brevetoxin-type epoxide opening polyether cascade cyclizations, that is the cyclization of certain trans epoxides into cis-fused rings. In principle, a shift from SN 2- to SN 1-type mechanisms could suffice to rationalize this inversion of configuration. However, the same inversion could be explained by a completely different mechanism: Ring opening with C-C bond cleavage into a branched hydroxy-5-enal and the corresponding cyclic hemiacetal, followed by cascade cyclization under conformational control, including stereoselective C-C bond formation. In this report, a pnictogen-bonding supramolecular SbV catalyst is used to demonstrate that this unorthodox polyether cascade cyclization mechanism occurs.

Cost Effectiveness of Screening Individuals With Cystic Fibrosis for Colorectal Cancer.

BACKGROUND & AIMS: Individuals with cystic fibrosis are at increased risk of colorectal cancer (CRC) compared with the general population, and risk is higher among those who received an organ transplant. We performed a cost-effectiveness analysis to determine optimal CRC screening strategies for patients with cystic fibrosis. METHODS: We adjusted the existing Microsimulation Screening Analysis-Colon model to reflect increased CRC risk and lower life expectancy in patients with cystic fibrosis. Modeling was performed separately for individuals who never received an organ transplant and patients who had received an organ transplant. We modeled 76 colonoscopy screening strategies that varied the age range and screening interval. The optimal screening strategy was determined based on a willingness to pay threshold of $100,000 per life-year gained. Sensitivity and supplementary analyses were performed, including fecal immunochemical test (FIT) as an alternative test, earlier ages of transplantation, and increased rates of colonoscopy complications, to assess if optimal screening strategies would change. RESULTS: Colonoscopy every 5 years, starting at an age of 40 years, was the optimal colonoscopy strategy for patients with cystic fibrosis who never received an organ transplant; this strategy prevented 79% of deaths from CRC. Among patients with cystic fibrosis who had received an organ transplant, optimal colonoscopy screening should start at an age of 30 or 35 years, depending on the patient's age at time of transplantation. Annual FIT screening was predicted to be cost-effective for patients with cystic fibrosis. However, the level of accuracy of the FIT in this population is not clear. CONCLUSIONS: Using a Microsimulation Screening Analysis-Colon model, we found screening of patients with cystic fibrosis for CRC to be cost effective. Because of the higher risk of CRC in these patients, screening should start at an earlier age with a shorter screening interval. The findings of this study (especially those on FIT screening) may be limited by restricted evidence available for patients with cystic fibrosis.

Double Cu-Catalyzed Direct Csp3 -H Azidation/CuAAC Reaction: A Direct Approach towards Demanding Triazole Conjugates.

The first one-pot procedure for the double copper(I)-catalyzed oxidative Csp3 -H azidation-CuAAC process, implying unstable azide intermediates and easy-to-remove reagents under water-tolerant conditions, is presented. The combination of tert-butyl hydroperoxide as oxidant and TMSN3 as azide source for the C-H bond azidation, which produces harmless side-products such as tBuOH and H2 O, probed to be perfectly compatible with the following cycloaddition step. Highly demanding 1,2,3-triazoles could be then directly obtained in good overall yields by extraction or simple crystallization, thus avoiding chromatography purifications. The potential of this methodology, has also being highlighted by the successful reaction of alkynes presenting interesting complex biological moieties based for example on biotin, DNA base or cinchona alkaloid units.

Direct C-H Bond Imidation with Benzoyl Peroxide as a Mild Oxidant and a Reagent.

A simple and mild Cu-catalyzed oxidative three-component oxidative Ugi-type method for the synthesis of a variety of substituted imides has been developed. In this direct imidation approach, benzoyl peroxide serves as both the oxidant and the carboxylate source, allowing not only the functionalization of C(sp3)-H bonds in α-position to an amine but also benzylic substrates. This procedure presents a wide substrate-type and functional group tolerance. Moreover, the mildness of the method permitted us to extend its application to the late stage functionalization of complex natural products such as the alkaloids brucine and strychnine, leading to interesting highly functionalized imide derivatives. On the basis of experimental and computational studies, a plausible mechanism has been proposed.

Cost-Effectiveness of Screening Individuals With Cystic Fibrosis for Colorectal Cancer.

BACKGROUND & AIMS: Individuals with cystic fibrosis are at increased risk of colorectal cancer (CRC) compared to the general population, and risk is higher among those who received an organ transplant. We performed a cost-effectiveness analysis to determine optimal CRC screening strategies for patients with cystic fibrosis. METHODS: We adjusted the existing Microsimulation Screening Analysis-Colon microsimulation model to reflect increased CRC risk and lower life expectancy in patients with cystic fibrosis. Modeling was performed separately for individuals who never received an organ transplant and patients who had received an organ transplant. We modeled 76 colonoscopy screening strategies that varied the age range and screening interval. The optimal screening strategy was determined based on a willingness to pay threshold of $100,000 per life-year gained. Sensitivity and supplementary analyses were performed, including fecal immunochemical test (FIT) as an alternative test, earlier ages of transplantation, and increased rates of colonoscopy complications, to assess whether optimal screening strategies would change. RESULTS: Colonoscopy every 5 years, starting at age 40 years, was the optimal colonoscopy strategy for patients with cystic fibrosis who never received an organ transplant; this strategy prevented 79% of deaths from CRC. Among patients with cystic fibrosis who had received an organ transplant, optimal colonoscopy screening should start at an age of 30 or 35 years, depending on the patient's age at time of transplantation. Annual FIT screening was predicted to be cost-effective for patients with cystic fibrosis. However, the level of accuracy of the FIT in population is not clear. CONCLUSIONS: Using a Microsimulation Screening Analysis-Colon microsimulation model, we found screening of patients with cystic fibrosis for CRC to be cost-effective. Due to the higher risk in these patients for CRC, screening should start at an earlier age with a shorter screening interval. The findings of this study (especially those on FIT screening) may be limited by restricted evidence available for patients with cystic fibrosis.

Novel Oxidative Ugi Reaction for the Synthesis of Highly Active, Visible-Light, Imide-Acridinium Organophotocatalysts.

A newly designed class of acridinium-based organophotocatalysts bearing an imide group at the C9-position is presented. To achieve these unprecedented structures, a synthetic strategy based on a novel straightforward oxidative Ugi-type reaction at the benzylic position of C9-unsubstituted acridanes was developed. The introduction of the imide-unit affords a notable photocatalytic activity enhancement, allowing efficient transformations in different oxidative and reductive visible-light catalytic reactions.

Recent progress in mild Csp3-H bond dehydrogenative or (mono-) oxidative functionalization.

Over the past few years, the development of oxidative methodologies towards efficient and selective direct Csp3-H bond functionalization processes has attracted tremendous attention from synthetic chemists. However, only a little attention has been given to the key role of the nature of the oxidant. This review aims at providing a brief summary of the recent advances in mild and more benign oxidative Csp3-H bond functionalization reactions, which are classified according to the type of oxidation system employed.

Pd(OAc)2/Ph3P-catalyzed dimerization of isoprene and synthesis of monoterpenic heterocycles.

The palladium-catalyzed dimerization of isoprene is a practical approach of synthesizing monoterpenes. Though several highly selective methods have been reported, most of them still required pressure or costly ligands for attaining the active system and desired selectivity. Herein, we present a simple and economical procedure towards the tail-to-tail dimer using readily available Pd(OAc)2 and inexpensive triphenylphosphine as ligand. Furthermore, simple screw cap vials are employed, allowing carrying out the reaction at low pressure. In addition, the potential of the dimer as a chemical platform for the preparation of heterocyclic terpenes by subsequent (hetero)-Diels-Alder or [4 + 1]-cycloadditions with nitrenes is also depicted.

Dietary inflammatory index and prostate cancer survival.

Systemic inflammatory status has been reported to impact survival of prostate cancer (PCa) patients; however, evidence is lacking on whether the inflammatory potential of diet can influence prognosis of PCa patients. To investigate the association between a dietary inflammatory index (DII) and PCa survival, we conducted a retrospective cohort study including 726 men with PCa originally enrolled, between 1995 and 2002, in an Italian case-control study. Information on diet and Gleason score was collected at PCa diagnosis. DII was derived from a food frequency questionnaire using a validated algorithm. Adjusted hazard ratios (HRs) of death with 95% confidence intervals (CIs) were estimated using a Fine-Gray model. DII scores were not significantly associated with all-cause mortality of PCa patients (HR highest vs. lowest DII tertile = 1.25; 95% CI: 0.86-1.83). However, considerable heterogeneity emerged according to Gleason score (p < 0.01): no associations emerged among men with Gleason score 2-6 PCa; whereas, among patients with Gleason score 7-10 PCa, DII was directly associated with both all-cause and PCa-specific mortality (HR highest vs. lowest DII tertile: 2.78; 95% CI: 1.41-5.48; and 4.01; 95% CI: 1.25-12.86; respectively). Among patients with Gleason score 7-10 PCa, ten-year all-cause survival probabilities were 58% (95% CI: 47-67%) for highest and 78% (95% CI: 67-86%) for lowest DII tertile. Study findings support the hypothesis that diet, through its inflammatory potential, may influence the prognosis of patients with more aggressive PCa. Dietary interventions aimed at decreasing inflammation may be considered to improve survival of men with PCa.

Combined effect of tobacco smoking and alcohol drinking in the risk of head and neck cancers: a re-analysis of case-control studies using bi-dimensional spline models.

The synergistic effect of tobacco smoking and alcohol consumption on the risk of head and neck cancers has been mainly investigated as a cross-product of categorical exposure, thus leading to loss of information. We propose a bi-dimensional logistic spline model to investigate the interacting dose-response relationship of two continuous exposures (i.e., ethanol intake and tobacco smoking) on the risk of head and neck cancers, representing results through three-dimensional graphs. This model was applied to a pool of hospital-based case-control studies on head and neck cancers conducted in Italy and in the Vaud Swiss Canton between 1982 and 2000, including 1569 cases and 3147 controls. Among never drinkers and for all levels of ethanol intake, the risk of head and neck cancers steeply increased with increasing smoking intensity, starting from 1 cigarette/day. The risk associated to ethanol intake increased with incrementing exposure among smokers, and a threshold effect at approximately 50 g/day emerged among never smokers. Compared to abstainers from both tobacco and alcohol consumption, the combined exposure to ethanol and/or cigarettes led to a steep increase of cancer risk up to a 35-fold higher risk (95 % confidence interval 27.30-43.61) among people consuming 84 g/day of ethanol and 10 cigarettes/day. The highest risk was observed at the highest levels of alcohol and tobacco consumption. Our findings confirmed a combined effect of tobacco smoking and alcohol drinking on head and neck cancers risk, providing evidence that bi-dimensional spline models could be a feasible and flexible method to explore the pattern of risks associated to two interacting continuous-exposure variables.

The negative impact of tobacco smoking on survival after prostate cancer diagnosis.

PURPOSE: Tobacco smoking has been found to increase prostate cancer (PCa) mortality in cohorts of healthy men, but its effects on prognosis of men with PCa are still unclear. This study investigated the role of smoking on long-term survival after PCa diagnosis. METHODS: A retrospective cohort including 780 men with incident PCa previously enrolled (between 1995 and 2002) as cases in an Italian case-control study. Information on vital status up to 2013 (median follow-up 13 years) and cause of death were retrieved through health archives. Hazard ratios (HRs) of all-cause and PCa-specific death, and corresponding 95 % confidence intervals (CIs), were calculated using Cox models, adjusting for Gleason score and major confounders. RESULTS: Out of 263 PCa deceased patients, 81 died because of PCa. Smokers at PCa diagnosis reported increased risks of all-cause (HR = 1.5, 95% CI 1.1-2.2) and PCa death (HR = 2.0, 95% CI 1.0-3.8), as compared to never smokers. Dose-response effects emerged according to smoking intensity (HRs for >15 cigarettes/day: 1.9, 95% CI 1.3-3.0, for all causes and 2.3, 95% CI 1.1-4.9, for PCa) and duration (HRs for >45 years: 1.7, 95% CI 1.1-2.6, for all causes and 2.6, 95% CI 1.2-5.5, for PCa). Conversely, former smokers at PCa diagnosis showed no statistically significant higher risks of PCa death. The effects of smoking were consistent in strata of Gleason score. CONCLUSIONS: Current smoking at PCa diagnosis negatively impacted PCa-specific, long-term survival, regardless of Gleason score. Our findings suggest that smoking could be a modifiable risk factor to improve prognosis of men diagnosed with PCa.

Dehydrogenative TEMPO-Mediated Formation of Unstable Nitrones: Easy Access to N-Carbamoyl Isoxazolines.

N-carbamoyl nitrones represent an important class of reagents for the synthesis of a variety of natural and biologically active compounds. These compounds are generally converted into valuable 4-isoxazolines upon cyclization reaction with dipolarophiles. However, these types of N-protected nitrones are highly unstable, which limits their synthesis, storage and practical use, enforcing alternative lengthy or elaborated synthetic routes. In this work, a 2,2,6,6-tetramethylpiperidin-1-oxyl (TEMPO)-mediated formal "dehydrogenation" of N-protected benzyl-, allyl- and alkyl-substituted hydroxylamines followed by in situ trapping of the generated unstable nitrones into N-carbamoyl 4-isoxazolines is presented. A plausible mechanism is also proposed, in which the dipolarophile shows an important assistant role in the generation of the active nitrone intermediate. This simple protocol avoids the problematic isolation of N-carbamoyl protected nitrones, providing new synthetic possibilities in isoxazoline chemistry.

Changes in cervical cancer incidence following the introduction of organized screening in Italy.

OBJECTIVE: To quantify the impact of organized cervical screening programs (OCSPs) on the incidence of invasive cervical cancer (ICC), comparing rates before and after activation of OCSPs. METHODS: This population-based investigation, using individual data from cancer registries and OCSPs, included 3557 women diagnosed with ICC at age 25-74years in 1995-2008. The year of full-activation of each OCSP was defined as the year when at least 40% of target women had been invited. Incidence rate ratios (IRRs) with 95% confidence intervals (95% CIs) were calculated as the ratios between age-standardized incidence rates observed in periods after full-activation of OCSPs vs those observed in the preceding quinquennium. RESULTS: ICC incidence rates diminished with time since OCSPs full-activation: after 6-8years, the IRR was 0.75 (95% CI: 0.67-0.85). The reduction was higher for stages IB-IV (IRR=0.68, 95% CI: 0.58-0.80), squamous cell ICCs (IRR=0.74, 95% CI: 0.64-0.84), and particularly evident among women aged 45-74years. Conversely, incidence rates of micro-invasive (stage IA) ICCs increased, though not significantly, among women aged 25-44years (IRR=1.34, 95% CI: 0.91-1.96). Following full-activation of OCSPs, micro-invasive ICCs were mainly and increasingly diagnosed within OCSPs (up to 72%). CONCLUSION(S): Within few years from activation, organized screening positively impacted the already low ICC incidence in Italy and favored down-staging.

Prevalence of childhood cancer survivors in Europe: a scoping review.

Childhood cancer survivors (CCS) require specialized follow-up throughout their lifespan to prevent or manage late effects of cancer treatment. Knowing the size and structure of the population of CCS is crucial to plan interventions. In this scoping review we reviewed studies that reported prevalence of CCS in Europe. We searched Medline, Web of Science, and Embase using permutations of terms referring to childhood, cancer, survivors, prevalence, registries, and Europe. We followed PRISMA-ScR guidelines to select studies and The Joanna Briggs Institute Prevalence Critical Appraisal Tool to evaluate their quality. From 979 unique studies published between 1989 and 2022, 12 were included. Limited-duration prevalence (LDP) for all childhood cancers, assessed in three studies using counting method, varied between 450 and 1240 persons per million. Complete prevalence (CP) of survivors of any childhood cancer except skin carcinomas, reported in three studies using observed data complemented with modelled data for the unobserved period, varied between 730 and 1110 persons per million. CP of survivors of an embryonal tumour was estimated by completeness index method in six studies. In four of them CP ranged from 48 to 95 persons per million for all embryonal tumours, while CP for those occurring in central nervous system was 43 per million in one study and CP for rhabdomyosarcoma was 17 per million in another. Information on prevalence of CCS in Europe is fragmented and inconsistent. The large variations in LDP and CP estimates were linked to differences in data availability, the selection of populations, prevalence measure, statistical method, incidence period, index date, age at diagnosis and prevalence, cancer types, sex, and, for LDP, also the length of follow-up. Standardisation of methodology and reporting are needed to systematically monitor and compare CCS prevalence in Europe and provide data to help address survivors' needs.