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ImportanceMaternal infection is common during pregnancy and is an important potential cause of fetal genetic and immunological abnormalities. Maternal infection has been reported to be associated with childhood leukemia in previous case-control or small cohort studies.ObjectiveTo evaluate the association of maternal infection during pregnancy with childhood leukemia among offspring in a large study.Design, Setting, and ParticipantsThis population-based cohort study used data from 7 Danish national registries (including the Danish Medical Birth Register, the Danish National Patient Registry, the Danish National Cancer Registry, and others) for all live births in Denmark between 1978 and 2015. Swedish registry data for all live births between 1988 and 2014 were used to validate the findings for the Danish cohort. Data were analyzed from December 2019 to December 2021.ExposuresMaternal infection during pregnancy categorized by anatomic locations identified from the Danish National Patient Registry.Main Outcomes and MeasuresThe primary outcome was any leukemia; secondary outcomes were acute lymphoid leukemia (ALL) and acute myeloid leukemia (AML). Offspring childhood leukemia was identified in the Danish National Cancer Registry. Associations were first assessed in the whole cohort using Cox proportional hazards regression models, adjusted for potential confounders. A sibling analysis was performed to account for unmeasured familial confounding.ResultsThis study included 2 222 797 children, 51.3% of whom were boys. During the approximately 27 million person-years of follow-up (mean [SD], 12.0 [4.6] years per person), 1307 children were diagnosed with leukemia (ALL, 1050; AML, 165; or other, 92). Children born to mothers with infection during pregnancy had a 35% increased risk of leukemia (adjusted hazard ratio [HR], 1.35 [95% CI, 1.04-1.77]) compared with offspring of mothers without infection. Maternal genital and urinary tract infections were associated with a 142% and 65% increased risk of childhood leukemia, with HRs of 2.42 (95% CI, 1.50-3.92) and 1.65 (95% CI, 1.15-2.36), respectively. No association was observed for respiratory tract, digestive, or other infections. The sibling analysis showed comparable estimates to the whole-cohort analysis. The association patterns for ALL and AML were similar to that for any leukemia. No association was observed for maternal infection and brain tumors, lymphoma, or other childhood cancers.Conclusions and RelevanceIn this cohort study of approximately 2.2 million children, maternal genitourinary tract infection during pregnancy was associated with childhood leukemia among offspring. If confirmed in future studies, our findings may have implications for understanding the etiology and developing preventive measures for childhood leukemia.

Additional file 1 S1 Introduction, S2 Mathematical Model, S3 Model fitting, S4 Parameters, S5 Results.

In many centers, Stage I-II melanoma patients are considered "cured" after 10 years of disease-free survival and follow-up visits are interrupted. However, melanoma may relapse also later. We retrospectively analyzed a cohort of 1,372 Stage I-II melanoma patients who were disease-free 10 years after diagnosis. The aim of this study was to characterize patients who experienced a late recurrence and to compare them to those who remained disease-free to identify possible predictive factors. Multivariate Cox proportional-hazards regression analyses were carried out to evaluate the influence of different factors on the risk of recurrence. Seventy-seven patients out of 1,372 (5.6%) relapsed, 52 in regional sites and 25 in distant ones. The majority of patients (31 out of 52) experienced late recurrence in regional lymph nodes. Brain and lung were the most common site of single distant recurrence (24% each). Patients with multiple distant metastases showed a brain and lung involvement in, respectively, 40 and 48% of cases. A Cox proportional-hazards regression model analysis showed the independent role of age under 40 years, Breslow thickness2 mm, and Clark Level IV/V in increasing the risk of Late Recurrence. These patients should be followed-up for longer than 10 years. The pattern of recurrence suggests that melanoma cells can be dormant preferentially in lymph nodes, brain and lung. A particular attention should be reserved to these anatomic sites during the follow-up after 10 years of disease-free.

Late-onset sepsis (LOS) affects a large proportion of pre-term neonates in neonatal intensive care units (NICUs) worldwide, with high morbidity and related mortality, and frequent occurrence of severe late neurodevelopmental impairment. Due to the frequency, severity and difficulties in early diagnosis and prompt therapy, prevention is crucial for decreasing the burden of infection-related complications in NICUs. It is well known that feeding with fresh maternal milk, hygiene measures and the cautious use of H2-blockers are related with a decreased risk of developing sepsis. However, evidence from randomised clinical trials exists only for fluconazole in the prevention of fungal infections in the NICU. Lactoferrin is the main whey protein in mammalian milk, and is involved in innate immune host defences. Notably, human lactoferrin can be found at increased concentrations in colostrum and in milk from mothers of premature neonates. Human (hLF) and bovine lactoferrin (bLF) share a high (77%) amino-acid homology, and the same N-terminal peptide responsible for antimicrobial activity, called lactoferricin. In vitro, bLF shows potent direct antimicrobial activity against all types of pathogens, which occurs via anti-cell wall actions and leads to disintegration of the micro-organism's membranes. bLF is also synergistic with many antimicrobials and antifungals, and promotes growth and differentiation of the immature gut. Based on this background data, a randomised clinical trial was recently conducted in very low birth weight pre-term neonates given bLF alone or with the probiotic Lactobacillus GG. The aim of the trial was to assess the ability of bLF to prevent late-onset sepsis of any origin in the studied infants during their stay in the NICU. This article discusses the preliminary data from this study, along with the proposed mechanisms of action of bLF in pre-term infants.

Upper airway inflammation and narrowing are characteristics of obstructive sleep apnoea (OSA). Inflammatory markers have been found to be increased in exhaled breath and induced sputum of patients with OSA.The aim of this study was to investigate if the measurement of exhaled nitric oxide (F(ENO) ), as marker of airway inflammation, together with the forced mid-expiratory/mid-inspiratory airflow ratio (FEF(50) /FIF(50) ), as marker of upper airway narrowing, may help to predict OSA.Two hundred one consecutive outpatients with suspected OSA were prospectively studied between January 2004 and December 2005. All patients underwent clinical examination, spirometry with measurement of FEF(50) /FIF(50) , maximum inspiratory pressure, arterial blood gas analysis, exhaled nitric oxide (F(ENO) ) and overnight polysomnography. Linear regression models were used to evaluate the effect of measured variables on the apnoea-hypopnoea index (AHI). Models were cross-validated by bootstrapping.Most of the patients were obese and had severe OSA. FEF(50) /FIF(50) , F(ENO) and an interaction term between smoking and F(ENO) contributed significantly to the predictive model for AHI, in addition to age, neck circumference, body mass index and carboxyhaemoglobin saturation. A nomogram to predict AHI was obtained, which converted the effect of each covariate in the model to a 0-100 scale. The nomogram showed a good predictive ability for AHI values between 25 and 64.The measurement of F(ENO) and of FEF(50) /FIF(50) improves the ability to predict OSA and may be used to identify patients who require a sleep study.

The population-based Childhood Cancer Registry of Piedmont (CCRP) has collected data on incidence since 1967. The occurrence of early death (i.e. within 30 days of diagnosis) was investigated in 3006 cases of childhood cancer diagnosed during the period 1967-1998. The proportion of early deaths (178 of the 3006 cases) was analysed by period of diagnosis (three decennial periods), age group, major diagnostic group and hospital category, with univariate statistics and logistic regression. The proportion of children with cancer who died within 1 month of diagnosis was 10.8%, 5.3% and 1.8% for cases diagnosed during 1967-1978, 1979-1988 and 1989-1998, respectively. This trend may reflect earlier diagnosis, improved diagnosis, more effective therapy or more frequent referral to specialised centres. The risk factors for early death were: age1 year and diffuse disease at diagnosis, diagnosis during 1967-1978, a diagnosis of acute non lymphocytic leukaemia, non-Hodgkin lymphoma, central nervous system tumour or hepatic tumour. Early death was not related to the sex of the child. Care in an extra-regional specialised centre was associated with lower risk of early death.No temporal changes in early mortality were found among children with acute non lymphocytic leukaemia diagnosed in the first, second or third decade of activity of the CCRP, the percentages of children dying within 1 month being 12.8%, 10.7% and 12.8%, respectively. This pattern clearly differed from the corresponding trend for acute lymphoid leukaemia (6.4%, 2.0%, 0.4%).