Ida Hed Myrberg

Aim: To investigate short‐ and long‐term kidney injury incidence in patients undergoing low anterior resection for rectal cancer, comparing those with and without a defunctioning ileostomy. Method: We identified all Swedish rectal cancer patients ≤80 years old, with ASA fitness grade ≤III and tumour height ≤12 cm from the anal verge, who underwent anterior resection between 2007 and 2021 using CRCBaSe, a nationwide registry linkage. Patients who received a defunctioning ileostomy during surgery were compared with those who did not. Outcomes included chronic kidney failure, chronic kidney disease, acute kidney injury, and dehydration. Cox proportional hazards models were fitted for each outcome, using overlap weights derived from propensity scores for receiving a defunctioning ileostomy. Stoma reversal impact and mediation by anastomotic leakage were also examined. Results: Among 5286 patients, 4623 (87%) received a defunctioning ileostomy and 663 (13%) did not. A defunctioning ileostomy was not significantly associated with chronic kidney failure (HR 1.68, 95% CI: 0.19–15.16) or chronic kidney disease (HR 1.65, 95% CI: 0.91–2.98) but increased risks of acute kidney injury (HR 3.01, 95% CI: 1.61–5.64) and dehydration (HR 4.02, 95% CI: 2.33–6.94). Risks declined after stoma reversal. Stomas reduced anastomotic leakage with negligible mediation effects on short‐term kidney damage. Conclusion: A defunctioning ileostomy after low anterior resection increases the risks of acute kidney injury and dehydration but not chronic kidney failure or chronic kidney disease. These risks decrease following stoma reversal, highlighting the need for careful perioperative management.

Current hemophagocytic lymphohistiocytosis 2004 (HLH-2004)–based diagnostic criteria for familial hemophagocytic lymphohistiocytosis (FHL) are based on expert opinion. Here, we performed a case-control study to test and possibly improve these criteria. We also developed 2 complementary expert opinion–based diagnostic strategies for FHL in patients with signs/symptoms suggestive of HLH, based on genetic and cellular cytotoxicity assays. The cases (N = 366) were children aged <16 years with verified familial and/or genetic FHL (n = 341) or Griscelli syndrome type 2 (n = 25); 276 from the HLH-94/HLH-2004 databases and 90 from the Italian HLH Registry. All fulfilled the HLH-94/HLH-2004 patient inclusion criteria. Controls were 374 children with systemic-onset juvenile idiopathic arthritis (sJIA) and 329 + 361 children in 2 cohorts with febrile infections that could be confused with HLH and sepsis, respectively. To provide complete data sets, multiple imputations were performed. The optimal model, based on 17 variables studied, revealed almost similar diagnostic thresholds as the existing criteria, with accuracy 99.1% (sensitivity 97.1%; specificity 99.5%); the original HLH-2004 criteria had accuracy 97.4% (sensitivity 99.0%; specificity 97.1%). Because cellular cytotoxicity assays here constitute a separate diagnostic strategy, HLH-2004 criteria without natural killer (NK)–cell function was also studied, which showed accuracy 99.0% (sensitivity, 96.2%; specificity, 99.5%). Thus, we conclude that the HLH-2004 criteria (without NK-cell function) have significant validity in their current form when tested against severe infections or sJIA. It is important to exclude underlying malignancies and atypical infections. In addition, complementary cellular and genetic diagnostic guidelines can facilitate necessary confirmation of clinical diagnosis.

Incidence of early-onset (<50 years) colorectal cancer (EOCRC) is increasing in developed countries. The aim was to investigate autoimmune and metabolic conditions as risk factors for EOCRC. In a nationwide nested case–control study, we included all EOCRC cases in Sweden diagnosed during 2007–2016, together with controls, matched for birth year, sex, and county. Information on exposure of autoimmune or metabolic disease was collected from the National Patient Register and Prescribed Drugs Registry. Hazard ratios (HR) as measures of the association between EOCRC and the exposures were estimated using conditional logistic regression. In total, 2626 EOCRC patients and 15,756 controls were included. A history of metabolic disease nearly doubled the incidence hazard of EOCRC (HR 1.82, 95% CI 1.66–1.99). A sixfold increased incidence hazard of EOCRC (HR 5.98, 95% CI 4.78–7.48) was seen in those with inflammatory bowel disease (IBD), but the risk increment decreased in presence of concomitant metabolic disease (HR 3.65, 95% CI 2.57–5.19). Non-IBD autoimmune disease was not statistically significantly associated with EOCRC. IBD and metabolic disease are risk factors for EOCRC and should be considered in screening guidelines.

This study investigates whether optical coherence tomography (OCT) could add useful information in the examination of children with optic pathway glioma (OPG) at high risk of developing vision loss. For this purpose, the relationship between ganglion cell-inner plexiform layer (GC-IPL) thickness and visual function, evaluated with tests of visual acuity (VA) and visual field (VF), as well as tumor site according to magnetic resonance imaging (MRI), were examined in a geographically defined group of children with OPG. Methods: Children aged p < 0.001). The GC-IPL pattern loss corresponded in 95% to VF defects and in 92% to MRI findings. Conclusions: Our study indicates that GC-IPL measures could serve as an early marker of vision-threatening changes related to OPG and as a valuable link between MRI and visual function tests. Thinning of GC-IPL and differences in topography between eyes are strong indicators of and predictive of vision loss related to OPG.

Purpose: The blood sampling procedure is complex and prone to failure, as reflected by preanalytical errors in pediatric hospital care. The primary aim was to evaluate if the risk of preanalytical errors was higher with capillary blood sampling than with venous blood sampling, and secondary, explore specific factors associated with preanalytical errors, both overall and stratified by capillary and venous blood sampling.Design and Methods: This observational pediatric hospital study collected outcomes from medical records and blood sampling surveys from year 2014 to 2016. The risk of preanalytical errors was analyzed with adjusted‐odds ratio (adj‐OR) by multivariable logistic regression with 95% confidence intervals (CIs).Results: Overall, 128 (13%) preanalytical errors were identified among 951 blood samples. The proportion and adj‐OR of errors was significantly higher in capillary compared with venous blood samples, 72 (20%) of 354 versus 56 (9.4%) of 597, p = .001, adj‐OR 2.88 (CI 1.79–4.64). Blood collection with multiple sample tubes was significantly associated with increased risk of preanalytical errors (n = 97 of 601, 16%), while log weight (kg) significantly decreased the risk of preanalytical errors adj‐OR 0.66 (CI 0.50–0.86), indicating a protective effect of increasing weight. However, stratified analyses indicated a protective effect of increasing log weight for venous blood sampling adj‐OR 0.52 (CI 0.38–0.72), but not capillary blood sampling, adj‐OR 1.08 (CI 0.76–1.55).Conclusion: This study indicates that capillary blood sampling collection increases the risk of preanalytical errors. Further, a child's increasing body weight reduced the risk of preanalytical errors, while multiple sample tube collections significantly increased the risk of preanalytical errors.Practice Implications: This new information may help nurses improve their knowledge concerning blood sampling collection in pediatrics. Altogether, this study also indicates that implementing more venous blood sampling and improve the cases of capillary sampling could reduce the number of preanalytical errors in pediatric hospitals.

Sequence variants in genes involved in the immune system have previously been linked to neutropenia as well as infections in cancer patients. Sequence variants in genes coding for TLR4, MBL, and IL-1Ra were investigated in relation to clinical utility of identifying severe episodes of febrile neutropenia (FN) in a cohort of children undergoing treatment for acute lymphoblastic leukemia. The study included 122 children, where data on FN and microbiological findings were retrospectively collected from medical records. Sequence variants in genes coding for MBL, TLR4, and IL-1Ra were identified by pyrosequencing, TaqMan SNP genotyping assay, and gel electrophoresis. A total of 380 episodes of FN were identified and in 139 episodes, there was a microbiological defined infection. Age and treatment intensity were all associated with the risk of developing FN. No sequence variant was associated to increased numbers of FN episodes. Two sequence variants in the TLR4 gene increased the risk of viral infection, whilst sequence variants in the IL-1Ra gene were associated to a decreased risk of bacterial blood-stream infection (BSI). The investigated sequence variants did not associate with increased risk for FN or to severe infections, as to why the clinical utility as a risk-stratification tool is low. Most episodes of FN were classified as fever with unknown origin, emphasizing the need for improved microbial detection methods.

Monocytes and dendritic cells are crucial mediators of innate and adaptive immune responses during viral infection, but misdirected responses by these cells might contribute to immunopathology. A comprehensive map of the mononuclear phagocyte (MNP) landscape during SARS-CoV-2 infection and concomitant COVID-19 disease is lacking. We performed 25-color flow cytometry-analysis focusing on MNP lineages in SARS-CoV-2 infected patients with moderate and severe COVID-19. While redistribution of monocytes towards intermediate subset and decrease in circulating DCs occurred in response to infection, severe disease associated with appearance of Mo-MDSC-like cells and a higher frequency of pre-DC2. Furthermore, phenotypic alterations in MNPs, and their late precursors, were cell-lineage specific and in select cases associated with severe disease. Finally, unsupervised analysis revealed that the MNP profile, alone, could identify a cluster of COVID-19 non-survivors. This study provides a reference for the MNP response to clinical SARS-CoV-2 infection and unravel myeloid dysregulation associated with severe COVID-19.

The deoxycytidine analogue cytarabine (ara‐C) remains the backbone treatment of acute myeloid leukaemia (AML) as well as other haematological and lymphoid malignancies, but must be combined with other chemotherapeutics to achieve cure. Yet, the underlying mechanism dictating synergistic efficacy of combination chemotherapy remains largely unknown. The dNTPase SAMHD1, which regulates dNTP homoeostasis antagonistically to ribonucleotide reductase (RNR), limits ara‐C efficacy by hydrolysing the active triphosphate metabolite ara‐CTP. Here, we report that clinically used inhibitors of RNR, such as gemcitabine and hydroxyurea, overcome the SAMHD1‐mediated barrier to ara‐C efficacy in primary blasts and mouse models of AML, displaying SAMHD1‐dependent synergy with ara‐C. We present evidence that this is mediated by dNTP pool imbalances leading to allosteric reduction of SAMHD1 ara‐CTPase activity. Thus, SAMHD1 constitutes a novel biomarker for combination therapies of ara‐C and RNR inhibitors with immediate consequences for clinical practice to improve treatment of AML.

Background: Children with central nervous system (CNS) toxicity during therapy for acute lymphoblastic leukaemia (ALL) are at risk for treatment modifications, long‐term sequelae and even higher mortality. A better understanding of CNS symptoms and their complications improves the potential to prevent and treat them.Methods: Patient files from 649 children treated with Nordic Society of Pediatric Hematology and Oncology ALL92 and ALL2000 protocols in Finland were reviewed retrospectively for any acute CNS symptom. Detailed data on symptoms, examinations and treatment of the underlying CNS complications were collected from the medical records. Disease‐related and outcome data were retrieved from the Nordic leukaemia registry.Results: Altogether, 13% (86) of patients with ALL had acute CNS symptoms. Most symptoms (64%) occurred during the first 2 months of therapy. Posterior reversible encephalopathy syndrome was the most frequent complication (4.5%). Cerebrovascular events were diagnosed in 10 cases (1.6%), while methotrexate‐related stroke‐like syndrome (SLS) was observed in only one patient (0.2%). CNS symptoms due to systemic or unclear conditions, especially sepsis, were important for differential diagnosis. CNS leukaemia was associated with CNS symptoms (hazard ratio [HR] = 4.03; P = .003), and epilepsy was a common sequel of CNS complications (19%).Conclusions: Acute CNS symptoms are common during ALL therapy, occurring mainly during the first 2 months of treatment. Patients with CNS leukaemia at diagnosis are at a higher risk for CNS toxicity. Despite intensive CNS‐directed methotrexate treatment, SLS was diagnosed extremely rarely in our series.