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Background Children with cancer are not at increased risk of severe SARS-CoV-2 infection; however, adults with haematological malignancies have increased risk of severe infections compared with non-haematological malignancies. Methods We compared patients with haematological and non-haematological malignancies enrolled in the UK Paediatric Coronavirus Cancer Monitoring Project between 12 March 2020 and 16 February 2021. Children who received stem cell transplantation were excluded. Results Only 2/62 patients with haematological malignancy had severe/critical infections, with an OR of 0.5 for patients with haematological compared with non-haematological malignancies. Interpretation Children with haematological malignancies are at no greater risk of severe SARS-CoV-2 infection than those with non-haematological malignancies., Children have a very low risk of developing severe SARS-CoV-2 infections. Early in the pandemic it became clear from the experiences in China, Italy and Spain that this was also true for children with cancer. Not so for adult patients particularly those with haematological malignancies who were considered to be 'extremely vulnerable'. The recommendation however, from the UK's national Childhood Cancer and Leukaemia group (CCLG) in 2020 was that, other than particularly high risk patients (those with multiply relapsed disease or undergoing bone marrow transplant or CAR-T therapy) children with cancer, including those with haematological malignancies, need not be considered extremely vulnerable. This clearly written, concise paper by Millen et al compares patients with haematological and non-haematological malignancies enrolled on the UK Paediatric Coronavirus Cancer Monitoring Project from March 2020 until Feb 2021 and supports that recommendation.

Little is known about the long-term neurological development of children diagnosed with congenital Zika infection at birth. Here, we report the imaging and clinical outcomes up to three years of life of a cohort of 129 children exposed to Zika virus in utero. Eighteen of them (14%) had a laboratory confirmed congenital Zika infection at birth. Infected neonates have a higher risk of adverse neonatal and early infantile outcomes (death, structural brain anomalies or neurologic symptoms) than those who tested negative: 8/18 (44%) vs 4/111 (4%), aRR 10.1 [3.5-29.0]. Neurological impairment, neurosensory alterations or delays in motor acquisition are more common in infants with a congenital Zika infection at birth: 6/15 (40%) vs 5/96 (5%), aRR 6.7 [2.2-20.0]. Finally, infected children also have an increased risk of subspecialty referral for suspected neurodevelopmental delay by three years of life: 7/11 (64%) vs 7/51 (14%), aRR 4.4 [1.9-10.1]. Infected infants without structural brain anomalies also appear to have an increased risk, although to a lesser extent, of neurological abnormalities. It seems paramount to offer systematic testing for congenital ZIKV infection in cases of in utero exposure and adapt counseling based on these results.

Summary Background The number of individuals with vision impairment worldwide is increasing because of an ageing population. We aimed to systematically identify studies describing the association between vision impairment and mortality, and to assess the association between vision impairment and all-cause mortality. Methods For this systematic review and meta-analysis, we searched MEDLINE (Ovid), Embase, and Global Health database on Feb 1, 2020, for studies published in English between database inception and Feb 1, 2020. We included prospective and retrospective cohort studies that measured the association between vision impairment and all-cause mortality in people aged 40 years or older who were followed up for 1 year or more. In a protocol amendment, we also included randomised controlled trials that met the same criteria as for cohort studies, in which the association between visual impairment and mortality was independent of the study intervention. Studies that did not report age-adjusted mortality data, or that focused only on populations with specific health conditions were excluded. Two reviewers independently assessed study eligibility, extracted the data, and assessed risk of bias. We graded the overall certainty of the evidence using the Grading of Recommendations, Assessment, Development and Evaluations framework. We did a random-effects meta-analysis to calculate pooled maximally adjusted hazard ratios (HRs) for all-cause mortality for individuals with a visual acuity of

Purpose. For individualized follow-up, accurate prediction of locoregional recurrence (LRR) and second primary (SP) breast cancer risk is required. Current prediction models employ regression, but with large data sets, machine-learning techniques such as Bayesian Networks (BNs) may be better alternatives. In this study, logistic regression was compared with different BNs, built with network classifiers and constraint- and score-based algorithms. Methods. Women diagnosed with early breast cancer between 2003 and 2006 were selected from the Netherlands Cancer Registry (NCR) ( N = 37,320). BN structures were developed using 1) Bayesian network classifiers, 2) correlation coefficients with different cutoffs, 3) constraint-based learning algorithms, and 4) score-based learning algorithms. The different models were compared with logistic regression using the area under the receiver operating characteristic curve, an external validation set obtained from the NCR from 2007 and 2008 ( N = 12,308), and subgroup analyses for a high- and low-risk group. Results. The BNs with the most links showed the best performance in both LRR and SP prediction (c-statistic of 0.76 for LRR and 0.69 for SP). In the external validation, logistic regression generally outperformed the BNs in both SP and LRR (c-statistic of 0.71 for LRR and 0.64 for SP). The differences were nonetheless small. Although logistic regression performed best on most parts of the subgroup analysis, BNs outperformed regression with respect to average risk for SP prediction in low- and high-risk groups. Conclusions. Although estimates of regression coefficients depend on other independent variables, there is no assumed dependence relationship between coefficient estimators and the change in value of other variables as in the case of BNs. Nonetheless, this analysis suggests that regression is still more accurate or at least as accurate as BNs for risk estimation for both LRRs and SP tumors.

New-onset atrial fibrillation (AF) is frequently observed following esophagectomy and may predict other complications. The aim of the current study was to determine the association between, and the possible predictive value of, new-onset AF and infectious complications following esophagectomy. Consecutive patients who underwent elective esophagectomy with curative intent for esophageal cancer between 2004 and 2016 in the University Medical Center Utrecht were included from a prospective database. The date of diagnosis of the complications included in the current analysis was retrospectively collected from the computerized medical record. The association between new-onset AF and infectious complications was studied in univariable and multivariable logistic regression analyses. A total of 455 patients were included. In 93 (20.4%) patients new-onset AF was encountered after esophagectomy. There were no significant differences in patient and treatment-related characteristics between the patients with and without AF. In 9 (9.7%) patients, AF was the only adverse event following surgery. In multivariable analyses, AF was significantly associated with infectious complications in general (OR 3.00, 95% CI: 1.73-5.21). More specifically, AF was associated with pulmonary complications (OR 2.06, 95% CI: 1.29-3.30), pneumonia (OR 2.41, 95% CI: 1.48-3.91) and anastomotic leakage (OR 3.00, 95% CI: 1.80-4.99). In patients who underwent esophagectomy, new-onset AF was highly associated with infectious complications. AF may serve as an early clinical warning sign for anastomotic leakage. Therefore, further evaluation of patients who develop new-onset AF after esophagectomy is warranted.

BACKGROUND:Genome-wide association studies have identified at least 15 independent common genetic variants associated with colorectal cancer (CRC) risk. The aim of this study was to investigate whether 11 of these variants are associated with CRC risk for carriers of germline mutations in DNA mismatch repair (MMR) genes.METHODS:A total of 927 MMR gene mutation carriers (360 MLH1, 442 MSH2, 85 MSH6 and 40 PMS2) from 315 families enrolled in the Colon Cancer Family Registry, were genotyped for the single nucleotide polymorphisms (SNPs): rs16892766 (8q23.3), rs6983267 (8q24.21), rs719725 (9p24), rs10795668 (10p14), rs3802842 (11q23.1), rs4444235 (14q22.2), rs4779584 (15q13.3), rs9929218 (16q22.1), rs4939827 (18q21.1), rs10411210 (19q13.1) and rs961253 (20p12.3). We used a weighted Cox regression to estimate CRC risk for homozygous and heterozygous carriers of the risk allele compared with homozygous non-carriers as well as for an additive per allele model (on the log scale).RESULTS:Over a total of 40,978 person-years observation, 426 (46%) carriers were diagnosed with CRC at a mean age of 44.3 years. For all carriers combined, we found no evidence of an association between CRC risk and the total number of risk alleles (hazard ratio [HR] per risk allele=0.97, 95% confidence interval [CI]=0.88-1.07, p=0.52).CONCLUSIONS:We found no evidence that the SNPs associated with CRC in the general population are modifiers of the risk for MMR gene mutation carriers overall, and therefore any evidence of proven clinical utility in Lynch syndrome.