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Background: Sexual satisfaction is an important dimension of health-related quality of life that needs to be addressed. Various factors may influence sexual satisfaction in women living with HIV (WLHIV); however, research in this area is limited. The aim of this study was to investigate patients’ self-reported sexual satisfaction and its associations with patient-reported outcomes in WLHIV in Sweden. Methods: Data was retrieved from the InfCareHIV registry for the years 2011–2016. The registry includes a self-reported validated 9-item health questionnaire to assess patient-reported outcomes, side effects and adherence. In total, 1292 WLHIV aged ≥18 years were included, corresponding to 42.8% of the female Swedish InfCareHIV cohort 2011–2016. A total of 2444 questionnaires were included in the study. The patient-reported outcomes used were satisfaction with physical health and psychological health, sexual satisfaction, and experiencing side effects from HIV-medication. Associations were tested in univariable and multivariable models. Results: The study shows that there was a significant association between sexual satisfaction and satisfaction with psychological health ( p ≤ 0.0001). There was a lower probability of reporting sexual satisfaction in women who were of an older age when they received an HIV-diagnosis ( p = 0.033), who had lived for more years with HIV ( p = 0.0004), or who had experienced side effects ( p = 0.028). Conclusions: This national register-based study identified that sexual satisfaction in WLHIV is associated with psychological health and with having experienced side-effects. Patient-reported outcomes can provide valuable information so that the care of WLHIV covers all aspects of health and supports sexual satisfaction, which is an important part of quality of life.

Background The widespread nature of coronavirus disease 2019 (COVID-19) has been unprecedented. We sought to analyze its global impact with a survey on colorectal cancer (CRC) care during the pandemic. Methods The impact of COVID-19 on preoperative assessment, elective surgery, and postoperative management of CRC patients was explored by a 35-item survey, which was distributed worldwide to members of surgical societies with an interest in CRC care. Respondents were divided into two comparator groups: 1) ‘delay’ group: CRC care affected by the pandemic; 2) ‘no delay’ group: unaltered CRC practice. Results A total of 1,051 respondents from 84 countries completed the survey. No substantial differences in demographics were found between the ‘delay’ (745, 70.9%) and ‘no delay’ (306, 29.1%) groups. Suspension of multidisciplinary team meetings, staff members quarantined or relocated to COVID-19 units, units fully dedicated to COVID-19 care, personal protective equipment not readily available were factors significantly associated to delays in endoscopy, radiology, surgery, histopathology and prolonged chemoradiation therapy-to-surgery intervals. In the ‘delay’ group, 48.9% of respondents reported a change in the initial surgical plan and 26.3% reported a shift from elective to urgent operations. Recovery of CRC care was associated with the status of the outbreak. Practicing in COVID-free units, no change in operative slots and staff members not relocated to COVID-19 units were statistically associated with unaltered CRC care in the ‘no delay’ group, while the geographical distribution was not. Conclusions Global changes in diagnostic and therapeutic CRC practices were evident. Changes were associated with differences in health-care delivery systems, hospital’s preparedness, resources availability, and local COVID-19 prevalence rather than geographical factors. Strategic planning is required to optimize CRC care., Global changes in both diagnostic and therapeutic practices in colorectal cancer care were evident in this survey conducted to analyze the impact of COVID-19 outbreak. The importance of this finding is that changes were associated with differences in health care delivery systems, hospital’s preparedness, resources availability, and local COVID-19 prevalence rather than geographical variations.

Chronic local inflammation of adipose tissue is an important feature of obesity. Serglycin is a proteoglycan highly expressed by various immune cell types known to infiltrate adipose tissue under obese conditions. To investigate if serglycin expression has an impact on diet-induced adipose tissue inflammation, we subjected Srgn+/+ and Srgn−/− mice (C57BL/6J genetic background) to an 8-wk high-fat and high-sucrose diet. The total body weight was the same in Srgn+/+ and Srgn−/− mice after diet treatment. Expression of white adipose tissue genes linked to inflammatory pathways were lower in Srgn−/− mice. We also noted reduced total macrophage abundance, a reduced proportion of proinflammatory M1 macrophages, and reduced formation of crown-like structures in adipose tissue of Srgn−/− compared with Srgn+/+ mice. Further, Srgn−/− mice had more medium-sized adipocytes and fewer large adipocytes. Differentiation of preadipocytes into adipocytes (3T3-L1) was accompanied by reduced Srgn mRNA expression. In line with this, analysis of single-cell RNA sequencing data from mouse and human adipose tissue supports that Srgn mRNA is predominantly expressed by various immune cells, with low expression in adipocytes. Srgn mRNA expression was higher in obese compared with lean humans and mice, accompanied by an increased expression of immune cell gene markers. SRGN and inflammatory marker mRNA expression was reduced upon substantial weight loss in patients after bariatric surgery. Taken together, this study introduces a role for serglycin in the regulation of obesity-induced adipose inflammation.

Background The success of antiretroviral therapy has normalized pregnancy among women living with HIV (WWH) with a very low risk of perinatal transmission of HIV. Despite these advances, WWH still face complex medical and psychosocial issues during pregnancy and postpartum. The aim of this study was to assess differences in psychosocial health outcomes between pregnant WWH, non-pregnant WWH, and pregnant women without HIV, and further identify factors associated with probable depression in the third trimester and postpartum. Methods In a longitudinal survey study, participants were included from sites in Denmark, Finland, and Sweden during 2019–2020. Data was collected in the 3rd trimester, 3 and 6 months postpartum using standardized questionnaires assessing depression, perceived stress, loneliness, and social support. Mixed regression models were used to assess changes over time within and between groups. Logistic regression models were used to identify factors associated with depression in pregnancy and postpartum. Results A total of 47 pregnant WWH, 75 non-pregnant WWH, and 147 pregnant women without HIV were included. The prevalence of depression was high among both pregnant and non-pregnant WWH. There was no significant difference between pregnant and non-pregnant WWH in depression scores, perceived stress scores, or social support scores at any time point. Compared to pregnant women without HIV, pregnant WWH reported worse outcomes on all psychosocial scales. Social support and loneliness were associated with an increased odds of depressive symptoms in the adjusted analysis. Conclusions A high burden of adverse psychosocial outcomes was observed in both pregnant and non-pregnant women living with HIV compared to pregnant women without HIV. Loneliness and inadequate social support were associated with increased odds of depression in pregnancy and should be a focus in future support interventions.

The European Intergroup for Childhood Non-Hodgkin Lymphoma (EICNHL) was established 25 years ago with the goal to facilitate clinical trials and research collaborations in the field both within Europe and worldwide. Since its inception, much progress has been made whereby major improvements in outcomes have been achieved. In this Review, we describe the different diagnostic entities of non-Hodgkin lymphoma in children and young adults describing key features of each entity and outlining clinical achievements made in the context of the EICNHL framework. Furthermore, we provide an overview of advances in biopathology with an emphasis on the role of biological studies and how they have shaped available treatments. Finally, for each entity, we describe future goals, upcoming clinical trials, and highlight areas of research that require our focus going forward.

Sexual satisfaction can be challenging for people living with HIV (PLWH). To investigate self-reported sexual satisfaction in PLWH and its association with HIV-related biomarkers, a retrospective observational cohort study with data on sociodemographic characteristics and changes in PLWH's assessment of their sexual satisfaction over time were retrieved from the Swedish National Quality Assurance Registry (InfCareHIV) where patient-related outcomes are reported annually. PLWH who had assessed self-reported sexual satisfaction 2011-2016 were included. Sexual satisfaction was dichotomized into sexual "satisfaction and dissatisfaction" and associations were analysed. In total, 3798 patients (66% men) answered 8202 questionnaires. Overall, 67% reported sexual satisfaction, with women more satisfied than men (72% vs 64%

Background Cancer treatments may induce side effects and cause eating problems. A gastrostomy tube may be required in order to maintain and optimise the child's nutritional needs. Despite the use of a gastrostomy tube, it is important to maintain a natural and attractive mealtime for the child. The Five Aspect Meal Model is age neutral and originally designed to improve restaurant visits. Its five aspects conceptualise what is necessary to ensure a complete meal experience. To date, there is lack of knowledge to guided model development about mealtimes adapted to children and limited knowledge regarding mealtime experiences for children with a gastrostomy tube. Aim The aim was to investigate whether the Five Aspect Meal Model could be appropriate to be used for children with a gastrostomy tube in caring science and paediatric care. Methods The design followed steps retrieved from Renjith and colleagues. Seven interviews were performed with the Five Aspect Meal Model as a base in the interview guide. The transcripts were analysed by using a qualitative directed content analysis with a deductive approach, which finally passed into a more inductive one. Findings All aspects of the Five Aspect Meal Model were represented in the interviews. There were also experiences related to the gastrostomy tube and the mealtimes that did not fit into any of the five predetermined categories. As a result, the modified version was developed, an adapted prescribing practice model that includes seven aspects, whereof bodily discomfort and time for change and acceptance are specific to children with a gastrostomy tube. Conclusion Based on children and their parent's experiences, the Five Aspect Meal Model has been developed and adapted into a modified version, which includes seven aspects. The modified version seems to be appropriate to use within caring science and paediatric care.

Background Traditionally, perforated diverticulitis has been managed with an open approach, with a Hartmann procedure or a colectomy with primary anastomosis. Minimally invasive surgery is associated with postoperative advantages in the elective setting and may show a benefit in the emergent setting. Objective The aim of this study was to compare postoperative outcomes of open vs minimally invasive approaches for emergent perforated diverticulitis. Design This was a retrospective review of the American College of Surgeons National Surgical Quality Improvement Program targeted colectomy database using propensity score matching. Settings Interventions were performed in hospitals participating in the national database. Patients Patients who underwent emergent colectomy from 2012 to 2017 were included. Procedures were divided into Hartmann procedure and primary anastomosis. Open vs minimally invasive groups were defined by intention to treat. Main outcome measures Outcomes measures included length of stay and overall morbidity and mortality. Results Of 130,616 patients, 7105 met inclusion criteria (4486 Hartmann procedure and 2619 primary anastomosis). A total of 1989 open Hartmann procedure cases were matched to 663 minimally invasive cases. The minimally invasive group underwent longer operations and had lower rates of respiratory failure. There were no differences in overall complications, mortality, length of stay, or home discharge. In the primary anastomosis group, 1027 cases were matched 1:1. The minimally invasive approach was associated with longer operative times, but reduced wound dehiscence, sepsis, bleeding, overall complications, and length of stay. No difference was detected in anastomotic leak, mortality, reoperation, or readmission rates. Limitations Limitations include retrospective nature, data loss, nonuniformity, selection bias, and coding errors. Conclusions Emergent minimally invasive primary anastomosis results in a shorter length of stay and decreased 30-day morbidity in comparison with open primary anastomosis for perforated diverticulitis. Emergent open and minimally invasive Hartmann procedures for perforated diverticulitis have comparable outcomes, perhaps because of a 40% conversion rate. See Video Abstract at http://links.lww.com/DCR/B421. Abordaje abierto versus mnimamente invasivo para colectoma de emergencia en diverticulitis perforada ANTECEDENTES:Tradicionalmente, la diverticulitis perforada se ha tratado con un abordaje abierto, con un procedimiento de Hartmann o una colectomia con anastomosis primaria. La cirugia minimamente invasiva se asocia con ventajas posoperatorias en el escenario electivo y puede mostrar beneficio en el escenario emergente.OBJETIVO:El objetivo de este estudio fue comparar los resultados posoperatorios del abordaje abierto versus el minimamente invasivo para la diverticulitis perforada emergente.DISENO:Esta fue una revision retrospectiva de la base de datos de colectomia dirigida del Programa Nacional de Mejoramiento de la Calidad Quirurgica del Colegio Americano de Cirujanos utilizando el pareamiento por puntaje de propension.ESCENARIO:Las intervenciones se realizaron en los hospitales participantes en la base de datos nacional.PACIENTES:Se incluyeron pacientes que fueron sometidos a colectomia emergente de 2012 a 2017. Los procedimientos se dividieron en procedimiento de Hartmann y anastomosis primaria. Los grupos abierto versus minimamente invasivo se definieron por intencion de tratar.PRINCIPALES MEDIDAS DE RESULTADO:Las medidas de resultado incluyeron la duracion de la estancia, la morbilidad general y la mortalidad.RESULTADOS:De 130,616 pacientes, 7,105 cumplieron los criterios de inclusion (4,486 procedimiento de Hartmann y 2,619 anastomosis primaria). 1,989 casos abiertos de procedimientos de Hartmann se emparejaron con 663 casos minimamente invasivos. El grupo minimamente invasivo se sometio a operaciones mas prolongadas y tuvo tasas mas bajas de insuficiencia respiratoria. No hubo diferencias en las complicaciones generales, la mortalidad, la duracion de la estancia o el alta domiciliaria. En el grupo de anastomosis primaria, 1,027 casos se emparejaron 1: 1. El abordaje minimamente invasivo se asocio con tiempos quirurgicos mas prolongados, pero tambien con tasas reducidas de dehiscencia de herida, sepsis, sangrado, complicaciones generales y la duracion de la estancia. No se detectaron diferencias en las tasas de fuga anastomotica, mortalidad, reintervencion o reingreso.LIMITACIONES:Las limitaciones incluyen la naturaleza retrospectiva, perdida de datos, falta de uniformidad, sesgo de seleccion y errores de codificacion.CONCLUSIONES:La anastomosis primaria minimamente invasiva emergente resulta en una estancia mas corta y una disminucion de la morbilidad a los 30 dias en comparacion con la anastomosis primaria abierta para la diverticulitis perforada. El procedimiento de Hartmann abierto y minimamente invasivo de emergencia para la diverticulitis perforada tiene resultados comparables, quizas debido a una tasa de conversion del 40%. Consulte el Video Resumen en http://links.lww.com/DCR/B421.

PURPOSE To analyze the efficacy of a risk-stratified treatment of children with relapsed anaplastic large cell lymphoma (ALCL). The ALCL-Relapse trial (ClinicalTrials.gov identifier: NCT00317408 ) stratified patients according to the time of relapse and CD3 expression to prospectively test reinduction approaches combined with consolidation by allogeneic or autologous hematopoietic stem cell transplantation (SCT) and vinblastine monotherapy. PATIENTS AND METHODS Patients with progression during frontline therapy (very high risk) or a CD3-positive relapse (high risk) were scheduled for allogeneic SCT after reinduction chemotherapy. Patients with a CD3-negative relapse within 1 year after initial diagnosis or prior exposure to vinblastine (intermediate risk) received autologous SCT after carmustine-etoposide-cytarabine-melphalan. This arm was terminated prematurely, and subsequent patients received vinblastine monotherapy instead. Patients with a CD3-negative relapse > 1 year after initial diagnosis (low risk) received vinblastine monotherapy. RESULTS One hundred sixteen patients met the inclusion criteria; 105 evaluable patients with CNS-negative disease had a 5-year event-free survival (EFS) of 53% ± 5% and a 5-year overall survival (OS) of 78% ± 4%. Before termination of autologous SCT, EFS rates of patients in the very-high- (n = 17), high- (n = 26), intermediate- (n = 32), and low- (n = 21) risk groups were 41% ± 12%, 62% ± 10%, 44% ± 9%, and 81% ± 9%; the respective OS rates were 59% ± 12%, 73% ± 9%, 78% ± 7%, and 90% ± 6%. Analyzing only the patients in the intermediate-risk group consolidated per protocol by autologous SCT, EFS and OS of 23 patients were 30% ± 10% and 78% ± 9%, respectively. All 5 patients with intermediate risk receiving vinblastine monotherapy after the amendment experienced relapse again. CONCLUSION Shorter time to relapse was the strongest predictor of subsequent relapse. Allogeneic SCT offers a chance for cure in patients with high-risk ALCL relapse. For early relapsed ALCL autologous SCT was not effective. Vinblastine monotherapy achieved cure in patients with late relapse; however, it was not effective for early relapses.

The amount of research being performed in children, in particular pharmacological research, is lower than in adults, which is in direct contrast to the aims of the UN Convention on the Rights of the Child. A Pediatric Clinical Research Center (PCRC) has been established at Sahlgrenska University Hospital with the aim of supporting clinical research in children and adolescents. The number of inquiries and initiated clinical studies at PCRC has increased since the start in 2016. In addition, there is a need for regional and national infrastructures for paediatric clinical research and a national network for paediatric clinical studies. CONCLUSION: Sahlgrenska University Hospital has established an infrastructure to support paediatric research and to work with national networks and infrastructures.

Sex hormones contribute to differences between males and females in body fat distribution and associated disease risk. Higher concentrations of estrogens are associated with a more gynoid body shape and with more fat storage on hips and thighs rather than in visceral depots. Estrogen-mediated protection against visceral adiposity is shown in post-menopausal women with lower levels of estrogens and the reduction in central body fat observed after treatment with hormone-replacement therapy. Estrogen exerts its physiological effects via the estrogen receptors (ERα, ERβ and GPR30) in target cells, including adipocytes. Studies in mice indicate that estrogen protects against adipose inflammation and fibrosis also before the onset of obesity. The mechanisms involved in estrogen-dependent body fat distribution are incompletely understood, but involve, e.g., increased mTOR signaling and suppression of autophagy and adipogenesis/lipid storage. Estrogen plays a key role in epigenetic regulation of adipogenic genes by interacting with enzymes that remodel DNA methylation and histone tail post-translational modifications. However, more studies are needed to map the differential epigenetic effects of ER in different adipocyte subtypes, including those in subcutaneous and visceral adipose tissues. We here review recent discoveries of ER-mediated transcriptional and epigenetic regulation in adipocytes, which may explain sexual dimorphisms in body fat distribution and obesity-related disease risk.

Background & aims: Visceral adipose tissue (VAT) volume is associated with common lifestyle diseases. Dietary quality, including food matrix and degree of carbohydrate cellularity, as well as the carbohydrate/fat ratio, may influence VAT volume. We aimed to determine the effects of isocaloric diets differing in either “cellularity”, a novel marker of dietary carbohydrate quality, or carbohydrate amount on visceral fat volume and anthropometric measures in adults with obesity. Methods: In a randomized controlled trial of 193 people with obesity/central adiposity, we compared changes in VAT volume after 6 and 12 months, measured by abdominal computed tomography, on three isocaloric eating patterns based on “acellular” carbohydrate sources (e.g., flour-based whole-grain products; comparator arm), “cellular” carbohydrate sources (minimally processed foods with intact cellular structures such as fruits, potatoes/tubers, and rice), or low-carbohydrate high-fat (LCHF) principles. Outcomes were compared by an intention-to-treat (ITT) analysis using constrained linear mixed-effects modelling (cLMM) providing baseline-adjusted change scores and proper missing data handling without imputation. Results: 78 and 57 participants completed 6 and 12 months, respectively, with similar intakes of energy (females: 1820−2060 kcal, males: 2480−2550 kcal) and protein (16–17 energy percent, E%) throughout the intervention, and only modest reductions in energy from baseline. Reported dietary intakes were 42–44, 41–42, and 11–15 E% carbohydrate and 36–38, 37–38, and 66–70 E% fat in the acellular, cellular and LCHF groups, respectively. There were no significant between-group differences in VAT volume after 6 months (cellular vs. acellular [95% CI]: −55 cm³ [−545, 436]; LCHF vs. acellular [95% CI]: −225 cm³ [−703, 253]) or after 12 months (cellular vs. acellular [95% CI]: −122 cm³ [−757, 514]; LCHF vs. acellular [95% CI]: −317 cm³ [−943, 309]). VAT volume decreased significantly within all groups by 14–18% and 12–17% after 6 and 12 months, respectively. Waist circumference was reduced to a significantly greater degree in the LCHF vs. acellular group at 6 months (LCHF vs. acellular [95% CI]: −2.78 cm [−5.54, −0.017]). Conclusions: Despite modest energy restriction, the three isocaloric eating patterns, differing in carbohydrate cellularity and amount, decreased visceral fat volume significantly and to a similar clinically relevant degree. publishedVersion

A chronic low-grade inflammation, originating in the adipose tissue, is considered a driver of obesity-associated insulin resistance. Macrophage composition in white adipose tissue is believed to contribute to the pathogenesis of metabolic diseases, but a detailed characterization of pro- and anti-inflammatory adipose tissue macrophages (ATMs) in human obesity and how they are distributed in visceral- and subcutaneous adipose depots is lacking. In this study, we performed a surface proteome screening of pro- and anti-inflammatory ATMs in both subcutaneous- (SAT) and visceral adipose tissue (VAT) and evaluated their relationship with systemic insulin resistance. From the proteomics screen we found novel surface proteins specific to M1-like- and M2-like macrophages, and we identified depot-specific immunophenotypes in SAT and VAT. Furthermore, we found that insulin resistance, assessed by HOMA-IR, was positively associated with a relative increase in pro-inflammatory M1-like macrophages in both SAT and VAT.

Background/objectives There is limited long-term data comparing the outcomes of sleeve gastrectomy (SG) and Roux-en-Y gastric bypass (RYGB) for severe obesity, both with respect to body weight, quality of life (QOL) and comorbidities. We aimed to determine 7-year trajectories of body mass index (BMI), QOL, obesity-related comorbidities, biomarkers of glucose and lipid metabolism, and early major complications after SG and RYGB. Subjects/methods Patients scheduled for bariatric surgery at two Norwegian hospitals, preferentially performing either SG or RYGB, were included consecutively from September 2011 to February 2015. Data was collected prospectively before and up to 7 years after surgery. Obesity-specific, generic and overall QOL were measured by the Impact of Weight on Quality of Life-Lite, Short-Form 36 and Cantril’s ladder, respectively. Comorbidities were assessed by clinical examination, registration of medication and analysis of glucose and lipid biomarkers. Outcomes were examined with linear mixed effect models and relative risk estimates. Results Of 580 included patients, 543 (75% women, mean age 42.3 years, mean baseline BMI 43.0 kg/m2) were operated (376 SG and 167 RYGB). With 84.2% of participants evaluable after 5–7 years, model-based percent total weight-loss (%TWL) at 7 years was 23.4 after SG versus 27.3 after RYGB (difference 3.9%, p = 0.001). All levels of QOL improved similarly after the two surgical procedures but remained below reference data from the general population at all timepoints. Remission rates for type 2 diabetes, dyslipidemia, obstructive sleep-apnea and gastroesophageal reflux disease (GERD) as well as the rate of de novo GERD significantly favored RYGB. SG had fewer major early complications, but more minor and major late complications combined over follow-up. Conclusion In routine health care, both SG and RYGB are safe procedures with significant long-term weight-loss, improvement of QOL and amelioration of comorbidities. Long-term weight-loss and remission rates of main obesity-related comorbidities were higher after RYGB.

INTRODUCTION: Since the beginning of COVID-19 pandemic, it is known that the severe course of the disease occurs mostly among the elderly, whereas it is rare among children and young adults. Comorbidities, in particular, diabetes and hypertension, clearly associated with age, besides obesity and smoke, are strongly associated with the need for intensive treatment and a dismal outcome. A weaker immunity of the elderly has been proposed as a possible explanation of this uneven age distribution. Thus, there is concern that children treated for cancer may allso be at risk for an unfavourable course of infection. Along the same line, anecdotal information from Wuhan, China, mentioned a severe course of COVID-19 in a child treated for leukaemia. AIM AND METHODS: We made a flash survey on COVID-19 incidence and severity among children on anticancer treatment. Respondents were asked by email to fill in a short Web-based survey. RESULTS: We received reports from 25 countries, where approximately 10,000 patients at risk are followed up. At the time of the survey, more than 200 of these children were tested, nine of whom were positive for COVID-19. Eight of the nine cases had asymptomatic to mild disease, and one was just diagnosed with COVID-19. We also discuss preventive measures that are in place or should be taken and treatment options in immunocompromised children with COVID-19. CONCLUSION: Thus, even children receiving anticancer chemotherapy may have a mild or asymptomatic course of COVID-19. While we should not underestimate the risk of developing a more severe course of COVID-19 than that observed here, the intensity of preventive measures should not cause delays or obstructions in oncological treatment.

Background Anal squamous cell carcinoma (SCC) generally carries a favorable prognosis, as most tumors are highly sensitive to standard of care chemoradiation. However, outcomes are poor for the 20–30% of patients who are refractory to this approach, and many will require additional invasive procedures with no guarantee of disease resolution. Methods To identify the patients who are unlikely to respond to the current standard of care chemoradiation protocol, we explored a variety of objective clinical findings as a potential predictor of treatment failure and/or mortality in a single center retrospective study of 42 patients with anal SCC. Results Patients with an increase in total peripheral white blood cells (WBC) and/or neutrophils (ANC) had comparatively poor clinical outcomes, with increased rates of death and treatment failure, respectively. Using pre-treatment biopsies from 27 patients, tumors with an inflamed, neutrophil dominant stroma also had poor therapeutic responses, as well as reduced overall and disease-specific survival. Following chemoradiation, we observed uniform reductions in nearly all peripheral blood leukocyte subtypes, and no association between peripheral white blood cells and/or neutrophils and clinical outcomes. Additionally, post-treatment biopsies were available from 13 patients. In post-treatment specimens, patients with an inflamed tumor stroma now demonstrated improved overall and disease-specific survival, particularly those with robust T-cell infiltration. Conclusions Combined, these results suggest that routinely performed leukocyte subtyping may have utility in risk stratifying patients for treatment failure in anal SCC. Specifically, pre-treatment patients with a high WBC, ANC, and/or a neutrophil-dense tumor stroma may be less likely to achieve complete response using the standard of care chemoradiation regimen, and may benefit from the addition of a subsequent line of therapy.

Purpose To evaluate the feasibility of oral cryotherapy (OC) in children and to investigate if OC reduces the incidence of severe oral mucositis (OM), oral pain, and opioid use in children undergoing hematopoietic stem cell transplantation (HSCT). Methods Fifty-three children, 4–17 years old, scheduled for HSCT in Sweden were included and randomized to OC or control using a computer-generated list. OC instructions were to cool the mouth with ice for as long as possible during chemotherapy infusions with an intended time of ≥ 30 min. Feasibility criteria in the OC group were as follows: (1) compliance ≥ 70%; (2) considerable discomfort during OC Results Forty-nine children (mean age 10.5 years) were included in analysis (OC = 26, control = 23). The feasibility criteria were not met. Compliance was poor, especially for the younger children, and only 15 children (58%) used OC as instructed. Severe OM (WHO-OTS ≥ 3) was recorded in 26 children (OC = 15, control = 11). OC did not reduce the incidence of severe OM, oral pain, or opioid use. Conclusion The feasibility criteria were not met, and the RCT could not show that OC reduces the incidence of severe OM, oral pain, or opioid use in pediatric patients treated with a variety of conditioning regimens for HSCT. Trial registration ClinicalTrials.gov id: NCT01789658

Adipose tissue macrophages (ATMs) orchestrate low-grade chronic adipose tissue inflammation, linking obesity and insulin resistance. Whereas factors contributing to macrophage accumulation in adipose tissue are established, little is known regarding signals that link adipocyte stress to proinflammatory activation of macrophages. Natural killer (NK) cells are specialized innate lymphocytes that identify and respond to stressed cells. In this Opinion, we discuss the possibility of NK cells to function as sensors recognizing adipose tissue stress. We further summarize recent literature suggesting NK cells to play an important role in development of insulin resistance via secretion of cytokines that stimulate proinflammatory polarization of ATMs. This suggests adipose tissue-resident NK cells as a pharmacological target for the treatment of obesity-induced insulin resistance.

Immune reconstitution after hematopoietic stem cell transplantation (HSCT) is a complex process. Impacts of the reconstitution of different immune cells over time are complex and difficult to understand. New mathematical models are needed to better understand this process. In this study, we used principal component analysis to better analyze the process of immune reconstitution after HSCT. Forty-six consecutive patients receiving HSCT for malignant and nonmalignant disorders were included in the study. All patients were followed for at least 24 months after transplantation with regular blood sampling for analysis of lymphocyte subset numbers and function. Exponentially transformed lymphocyte subset counts and lymphocyte functional markers were analyzed to identify major trends in the reconstitution process. Using our multivariate model for mapping immune reconstitution after HSCT, we showed that dysfunctional reconstitution patterns precede severe complications, such as chronic graft-versus-host disease, relapse, and death.

The objective of this study was to compare the biochemical changes related to glucose tolerance and lipid metabolism in non-diabetic patients shortly after vertical sleeve gastrectomy (SG) or Roux-en-Y gastric bypass (RYGB). Non-diabetic women and men with morbid obesity were studied the day before and six days after SG (N = 15) or RYGB (N = 16). Patients completed an oral glucose tolerance test (OGTT; 75 g glucose) at both visits. SG and RYGB similarly improved fasting glucose homeostasis six days after surgery, with reduced glucose and insulin concentrations. The OGTT revealed differences between the two surgery groups that were not evident from the fasting serum concentrations. Postprandial (120 min) glucose and insulin concentrations were lower after RYGB but not after SG, whereas concentrations of glucagon-like peptide-1, peptide YY, glucagon and non-esterified fatty acids were elevated after both SG and RYGB. Fasting triacylglycerol concentration did not change after surgery, but concentrations of high density lipoprotein and low density lipoprotein cholesterols were reduced in both surgery groups, with no differences between the groups. To conclude, RYGB induced a more pronounced improvement in postprandial glucose homeostasis relative to SG, possibly due to improved insulin sensitivity rather than augmented insulin concentration.

Background: Despite suppressive antiretroviral therapy (ART), many HIV-infected individuals have low-level persistent immune activation in the central nervous system (CNS). There have been ...

Objective: Hepatitis E virus (HEV) genotype 3 is endemic in Northern Europe and despite a high seroprevalence of anti-HEV IgG antibodies among blood donors (≈17%), few clinical cases are notified in Sweden. Low awareness of hepatitis E and its possible symptoms may contribute to this discrepancy. The aim of this study was to investigate the prevalence of acute HEV infection among hospital admitted patients with abdominal pain and elevated liver enzymes.Materials and methods: During 2016-2017, 148 adult patients with serum alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > twice normal levels were prospectively enrolled at surgical wards at three Swedish hospitals. Serum samples were analyzed for HEV RNA as well as anti-HEV IgM and IgG, and medical records were reviewed.Results: Six (6/148, 4.1%) patients were HEV infected confirmed by detectable HEV RNA, but only one of these patients had detectable anti-HEV antibodies. Four of the HEV infected patients were diagnosed with gallstone-related disease: three with biliary pancreatitis and one with biliary colic. The remaining two were diagnosed with bowel obstruction and pancreatic malignancy. Four HEV strains were typed by sequencing to genotype 3.Conclusions: This study identified acute HEV3 infection in 4% of the patients with elevated liver enzymes admitted to a surgical ward. HEV infection was not the solitary disease leading to hospitalization, instead it was found to be associated with other surgical conditions such as gallstone-related disease including biliary pancreatitis. Additionally, HEV RNA might be the preferential diagnostic tool for detecting ongoing HEV infection.

Objectives Despite progress in the treatment of childhood acute lymphoblastic leukemia, severe complications are common, and the need of supportive care is high. We explored the cumulative prevalence, clinical risk factors, and outcomes of children with acute lymphoblastic leukemia, on first-line leukemia treatment in the ICUs in Sweden. Design A nationwide prospective register and retrospective chart review study. Setting Children with acute lymphoblastic leukemia were identified,and demographic and clinical data were obtained from the Swedish Childhood Cancer Registry. Data on intensive care were collected from the Swedish Intensive Care Registry. Data on patients with registered ICU admission in the Swedish Childhood Cancer Registry were supplemented through questionnaires to the pediatric oncology centers. Patients All 637 children 0-17.9 years old with acute lymphoblastic leukemia diagnosed between June 2008 and December 2016 in Sweden were included. Interventions None. Measurements and main results Twenty-eight percent of the children (178/637) were admitted to an ICU at least once. The Swedish Intensive Care Registry data were available for 96% of admissions (241/252). An ICU admission was associated with poor overall survival (hazard ratio, 3.25; 95% CI, 1.97-5.36; p ≤ 0.0001). ICU admissions occurred often during early treatment; 48% (85/178) were admitted to the ICU before the end of the first month of acute lymphoblastic leukemia treatment (induction therapy). Children with T-cell acute lymphoblastic leukemia or CNS leukemia had a higher risk of being admitted to the ICU in multivariable analyses, both for early admissions before the end of induction therapy and for all admissions during the study period. Conclusions The need for intensive care in children with acute lymphoblastic leukemia, especially for children with T cell acute lymphoblastic leukemia and CNS leukemia, is high with most admissions occurring during early treatment.

Data on stem cell transplantation (SCT) for Diamond-Blackfan Anemia (DBA) is limited. We studied patients transplanted for DBA and registered in the EBMT database. Between 1985 and 2016, 106 DBA patients (median age, 6.8 years) underwent hematopoietic stem cell transplantation from matched-sibling donors (57%), unrelated donors (36%), or other related donors (7%), using marrow (68%), peripheral blood stem cells (20%), both marrow and peripheral blood stem cells (1%), or cord blood (11%). The cumulative incidence of engraftment was 86% (80% to 93%), and neutrophil recovery and platelet recovery were achieved on day +18 (range, 16 to 20) and +36 (range, 32 to 43), respectively. Three-year overall survival and event-free survival were 84% (77% to 91%) and 81% (74% to 89%), respectively. Older patients were significantly more likely to die (hazard ratio, 1.4; 95% confidence interval, 1.06 to 1.23; P < .001). Outcomes were similar between sibling compared to unrelated-donor transplants. The incidence of acute grades II to IV of graft-versus-host disease (GVHD) was 30% (21% to 39%), and the incidence of extensive chronic GVHD was 15% (7% to 22%). This study shows that SCT may represent an alternative therapeutic option for transfusion-dependent younger patients. (C) 2021 Published by Elsevier Inc. on behalf of The American Society for Transplantation and Cellular Therapy.

BACKGROUND Hemorrhoids are common and affect mainly the young and middle-aged populations. Current guidelines recommend treating grade I and II hemorrhoids with office-based procedures. These therapies usually require multiple applications. Hemorrhoid energy therapy treats the hemorrhoids at 1 treatment session. OBJECTIVE The purpose of this study was to evaluate the safety and efficacy of hemorrhoid energy therapy. DESIGN This was a prospective pilot study evaluating patients with symptomatic grade I and II internal hemorrhoids. SETTINGS The study was conducted at a tertiary academic center. PATIENTS Patients over the age of 18 years with chronic, symptomatic grade I and II internal hemorrhoids who failed 2 weeks of conservative therapy were enrolled between July 2015 and January 2019. Exclusion criteria included patients with grade III or IV internal hemorrhoids, external hemorrhoids, nonhemorrhoidal GI bleeding, active proctitis, and IBD. INTERVENTIONS Hemorrhoid energy therapy was administered in clinic, and 2 postprocedure visits were completed. A pretreatment hemorrhoid symptom score was obtained from each patient. A visual analog score was assessed posttreatment. MAIN OUTCOME MEASURES The primary end point was to evaluate the effect of hemorrhoid energy therapy on hemorrhoid symptoms and its safety. The secondary end point was evaluation of postprocedural pain. RESULTS A total of 35 patients were enrolled. The mean duration of hemorrhoid symptoms was 3.3 ± 6.4 years, and rectal bleeding and hemorrhoidal prolapse were the most common symptoms. After the procedure, patient hemorrhoid symptom scores decreased from mean 5.5 to 1.4. The mean immediate postprocedural visual analog score was 2.4 ± 2.1 and decreased to

Summary Skeletal and glycemic traits have shared etiology, but the underlying genetic factors remain largely unknown. To identify genetic loci that may have pleiotropic effects, we studied Genome-wide association studies (GWASs) for bone mineral density and glycemic traits and identified a bivariate risk locus at 3q21. Using sequence and epigenetic modeling, we prioritized an adenylate cyclase 5 (ADCY5) intronic causal variant, rs56371916. This SNP changes the binding affinity of SREBP1 and leads to differential ADCY5 gene expression, altering the chromatin landscape from poised to repressed. These alterations result in bone- and type 2 diabetes-relevant cell-autonomous changes in lipid metabolism in osteoblasts and adipocytes. We validated our findings by directly manipulating the regulator SREBP1, the target gene ADCY5, and the variant rs56371916, which together imply a novel link between fatty acid oxidation and osteoblast differentiation. Our work, by systematic functional dissection of pleiotropic GWAS loci, represents a framework to uncover biological mechanisms affecting pleiotropic traits., Graphical abstract, Highlights • 3q21 variants are associated with type 2 diabetes and increased bone mineral density • 3q21 variants affect chromatin accessibility in mesenchymal cells • rs56371916 is a 3q21 causal variant and ADCY5 its target in adipocytes and osteoblasts • ADCY5 and rs56371916 affect lipid oxidation processes in adipocytes and osteoblasts, Nasa Sinnott-Armstrong and colleagues identify a pleiotropic risk locus at 3q21 that is associated with type 2 diabetes (T2D) and greater bone mineral density (BMD) and its associated cell-autonomous mechanisms in adipocytes and osteoblasts. Together, these findings provide a possible explanation for the perplexing finding that individuals with T2D have higher BMD but greater susceptibility to bone fracture.

IntroductionSince early 2020, the COVID-19 pandemic has challenged societies and revealed the built-in fragility and dependencies in complex adaptive systems, such as healthcare. The pandemic has placed healthcare providers and systems under unprecedented amounts of strain with potential consequences that have not yet been fully elucidated. This multilevel project aims to explore resilient performance with the purpose of improving the understanding of how healthcare has adapted during the pandemic’s rampage, the processes involved and the consequences on working conditions, ethics and patient safety.MethodsAn emerging explorative multilevel design based on grounded theory methodology is applied. Open and theoretical sampling is performed. Empirical data are gathered over time from written narratives and qualitative interviews with staff with different positions in healthcare organisations in two Swedish regions. The participants’ first-person stories are complemented with data from the healthcare organisations’ internal documents and national and international official documents.AnalysisExperiences and expressions of resilient performance at different system levels and times, existing influencing risk and success factors at the microlevels, mesolevels and macrolevels and inter-relationships and consequences in different healthcare contexts, are explored using constant comparative analysis. Finally, the data are complemented with the current literature to develop a substantive theory of resilient performance during the pandemic.Ethics and disseminationThis project is ethically approved and recognises the ongoing strain on the healthcare system when gathering data. The ongoing pandemic provides unique possibilities to study system-wide adaptive capacity across different system levels and times, which can create an important basis for designing interventions focusing on preparedness to manage current and future challenges in healthcare. Feedback is provided to the settings to enable pressing improvements. The findings will also be disseminated through scientific journals and conferences.

Purpose: Adolescents with cerebral palsy may need a feeding tube due to feeding challenges, since nutritional intake and mealtimes may be negatively affected. The purpose of the study was to describe and better understand how one adolescent with cerebral palsy and her parents experienced mealtimes before and after a nasogastric and gastrostomy tube insertion and how the use of these feeding tubes was experienced in daily life. Methods: Individual interviews were performed with one adolescent and each of her parents. In total, six interviews were conducted on two separate occasions. The qualitative approach known as Interpretive Description was used during the analysis. Results: Four thematic patterns were identified within the data: (i) struggling with nutritional intake, (ii) the paradox of using an aid, (iii) being different, and (iv) challenges of public mealtimes. Conclusions: The results showed that four themes influenced daily mealtimes in adolescents with cerebral palsy and a gastrostomy tube. Nutritional intake and mealtimes may be difficult, which is why using a gastrostomy tube can be a relief. However, the gastrostomy tube can also pose a challenge and a paradox. Time of change and acceptance seems necessary in order to meet these challenges.

Context Currently there are no assays that can simultaneously quantify serum levels of the third-generation aromatase inhibitors (AIs): letrozole, anastrozole, and exemestane, and the ultra-low levels of estrogens in postmenopausal breast cancer patients on AI treatment. Such measurements may be pivotal for the determination of optimal and individualized treatment regimens. We aimed at developing a liquid chromatography–tandem mass spectrometry (MS/MS) method for simultaneous assessment of letrozole, anastrozole, exemestane, and 17-hydroxyexemestane as well as subpicomolar levels of estradiol and estrone. Methods Internal standards, calibrators, serum samples, and quality controls were in fully automated steps transferred to a deep-well plate for a 2-step liquid-liquid extraction. The extracts were reconstituted and analytes were separated chromatographically using 2 serially coupled columns, then subject to MS/MS in electrospray ionization mode. The method was thoroughly validated and is traceable to 2 accredited estrogen methods. Results The measurement range for estrone and estradiol was 0.2 to 12 000 pmol/L and 0.8 to 13 000 pmol/L, and covered the expected therapeutic range for the AIs. All analytes had a precision of less than or equal to 13%, and accuracies within 100 ± 8%. As proof of concept, AI and estrogen levels were determined in serum samples from postmenopausal breast cancer patients under treatment. Conclusion We present here an assay suitable for the simultaneous measurement of serum levels of all third-generation AIs and ultra-low levels of estrogens, providing a powerful new tool to study drug efficacy and compliance. The method is highly valuable for postmenopausal patients whose pretreatment estradiol levels are below the threshold of detection for most routine assays, but still require suppression.

Introduction The use of patient-reported outcomes (PROs) to systematically quantify adverse events (AE) will assist in the improvement of medical care and the QoL of patients living with HIV (PLWH). The aim of this study was to investigate the associations between self-reported side effects and other PROs, demographics and laboratory data, and further evaluate the Health Questionnaire (HQ) as a tool for following trends in patient-reported side effects over time in relation to trends in prescribed third agent in ART. Materials and methods The Swedish National Registry InfCareHiv includes an annual self-reported nine-item HQwhich is used in patient-centered HIV care in all Swedish HIV units. In this study, the experience of side effects was addressed. We analyzed 9,476 HQs completed by 4,186 PLWH together with details about their prescribed ART and relevant biomarkers collected during 2011–2017. Data were analyzed using descriptive statistics, Pearson’s correlation coefficient and mixed logistic regression. Results The cross-sectional analysis of the HQs showed that the frequency of reported side effects decreased from 32% (2011) to 15% (2017). During the same period, there was a shift in ART prescription from efavirenz (EFV) to dolutegravir (DTG) (positive correlation coefficient r = 0.94, p = 0.0016). Further, PLWH who reported being satisfied with their physical health (OR: 0.47, p = Conclusions Self-reported side effects were found to have a close relationship with the patient’s ratings of their overall health situation and demonstrated a strong correlation with the sharp decline in use of EFV and rise in use of DTG, with reported side effects being halved. This study supports the feasibility of using the HQ as a tool for longitudinal follow up of trends in PROs.

In this investigation performed in pediatric patients in Västra Götalandsregionen in Sweden we concluded that as many as 20 % of the children had long-term and/or more extensive contact with the health care system. We used two different methods, combining professional clinical judgement with data from the health care production register in Västra Götalandsregionen, to define the incidence of chronic diseases among the pediatric population. The spectrum of diseases observed is broad, spanning up to 20 different diagnostic areas. Furthermore, the number of children with special health care needs increases over time. The high incidence and definition of chronic illness and complex needs amongst our children and adolescents need to be taken into consideration.

Marine-derived omega-3 (n-3) polyunsaturated fatty acids (PUFAs), mainly eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), lower circulating levels of triacylglycerols (TAGs), and the plant-derived omega-6 (n-6) PUFA linoleic acid (LA) may reduce cholesterol levels. Clinical studies on effects of these dietary or supplemental PUFAs on other blood fat fractions are few and have shown conflicting results. This study aimed to determine effects of high-dose supplemental n-3 (EPA + DHA) and n-6 (LA) PUFAs from high-quality oils on circulating lipoprotein subfractions and standard lipids (primary outcomes), as well as apolipoproteins, fatty acids, and glycemic control (secondary outcomes), in females and males with abdominal obesity.This was a randomized double-blind crossover study with two 7-wk intervention periods separated by a 9-wk washout phase. Females (n = 16) were supplemented with 3 g/d of EPA + DHA (TAG fish oil) or 15 g/d of LA (safflower oil), while males (n = 23) received a dose of 4 g/d of EPA + DHA or 20 g/d of LA. In fasting blood samples, we investigated lipoprotein particle subclasses by nuclear magnetic resonance spectroscopy, as well as standard lipids, apolipoproteins, fatty acid profiles, and glucose and insulin. Data were analyzed by linear mixed-effects modeling with 'subjects' as the random factor.The difference between interventions in relative change scores was among the lipoprotein subfractions significant for total very-low-density lipoproteins (VLDLs) (n-3 vs. n-6: -38%∗ vs. +16%, p 0.001; ∗: significant within-treatment change score), large VLDLs (-58%∗ vs. -0.91%, p 0.001), small VLDLs (-57%∗ vs. +41%∗, p 0.001), total low-density lipoproteins (LDLs) (+5.8%∗ vs. -4.3%∗, p = 0.002), large LDLs (+23%∗ vs. -2.1%, p = 0.004), total high-density lipoproteins (HDLs) (-6.0%∗ vs. +3.7%, p 0.001), large HDLs (+11%∗ vs. -5.3%, p = 0.001), medium HDLs (-24%∗ vs. +6.2%, p = 0.030), and small HDLs (-9.9%∗ vs. +9.6%∗, p = 0.002), and among standard lipids for TAGs (-16%∗ vs. -2.6%, p = 0.014), non-esterified fatty acids (-19%∗ vs. +5.5%, p = 0.033), and total cholesterol (-0.28% vs. -4.4%∗, p = 0.042). A differential response in relative change scores was also found for apolipoprotein (apo)B (+0.40% vs. -6.0%∗, p = 0.008), apoA-II (-6.0%∗ vs. +1.5%, p = 0.001), apoC-II (-11%∗ vs. -1.7%, p = 0.025), and apoE (+3.3% vs. -3.8%, p = 0.028).High-dose supplementation of high-quality oils with n-3 (EPA + DHA) or n-6 (LA) PUFAs was followed by reductions in primarily TAG- or cholesterol-related markers, respectively. The responses after both interventions point to changes in the lipoprotein-lipid-apolipoprotein profile that have been associated with reduced cardiometabolic risk, also among people with TAG or LDL-C levels within the normal range.Registered under ClinicalTrials.gov Identifier: NCT02647333.Registered at https://clinicaltrials.gov/ct2/show/NCT02647333.

Background The pneumococcal conjugate vaccine PCV7 was introduced in Southwest Sweden in the child vaccination program in 2009, followed by PCV13 in 2010 and PCV10 in 2015. In this retrospective cohort study we assessed the pneumococcal serotype distribution in relation to predisposing factors, clinical manifestations and outcome during seven years after PCV introduction. Methods Clinical data from 1278 patients with 1304 episodes of invasive pneumococcal disease (IPD) between January 2009 and December 2015 in Region Västra Götaland, Sweden, were retrospectively collected from medical records. Pneumococcal isolates were serotyped by gel diffusion and/or Quellung reactions performed at the Public Health Agency in Sweden. Associations between serotypes and clinical characteristics were statistically evaluated by use of Fisher’s exact test, Mann-Whitney U test and Logistic regression analysis, whereas IPD episodes caused by serotypes over time were analyzed by Mantel-Haenszel chi-square test. Results With the exception of serotype 3, the prevalence of PCV13 serotypes decreased during the study period, from 76% (n = 157) of all IPD episodes in 2009 to 25% (n = 42) in 2015 (p p Conclusions Non-PCV13 serotypes caused the majority of IPD cases in Southwest Sweden, especially in patients ≥65 years and in patients with predisposing factors. Serotype 3, included in PCV13, was prevalent and often caused severe disease.

Purpose Primarily, to investigate the effect of high intake of cod (lean fish) or salmon (fatty fish) on serum concentration of total neopterin, a marker of cellular immune activation that is associated with cardiovascular disease. Second, to investigate effects of high cod/salmon intake on antioxidant vitamins and elements essential for activity of antioxidant enzymes. Methods In this randomised clinical trial, 63 participants with overweight/obesity consumed 750 g/week of either Atlantic cod (N = 22) or Atlantic salmon (N = 22) or were instructed to continue their normal eating habits but avoid fish intake (Control group, N = 19) for 8 weeks. Food intake was recorded, and fasting serum were collected at baseline and endpoint. Results Serum total neopterin concentration was reduced in the Cod group (median change − 2.65 (25th, 75th percentiles − 3.68, − 0.45) nmol/l, P = 0.018) but not in the Salmon group (median change 0.00 (25th, 75th percentiles − 4.15, 3.05) nmol/l, P = 0.59) when compared with the Control group after 8 weeks. The estimated daily intake of selenium, iron, magnesium and zinc were similar between all groups. Increased serum concentration of selenium was observed only after cod intake when compared to the Control group (P = 0.017). Changes in serum concentrations of copper, iron, magnesium, all-trans retinol, α-tocopherol and γ-tocopherol were similar between the groups. Conclusion A high intake of cod, but not of salmon, lowered serum total neopterin concentration when compared to the Control group. Clinical trial registration This trial was registered at clinicaltrials.gov as NCT02350595

Concentrations of active tamoxifen metabolites may be predictive of tamoxifen efficacy, and several therapeutic thresholds have been reported. This study of 406 ER+ breast cancer patients replicated an association between a previously reported active tamoxifen threshold (Z‐4OHtam ≤ 3.26 nm) and adverse BC outcome. The association was identified in early‐stage premenopausal patients using tamoxifen alone without sequential aromatase inhibitor use., Low steady‐state levels of active tamoxifen metabolites have been associated with inferior treatment outcomes. In this retrospective analysis of 406 estrogen receptor‐positive breast cancer (BC) patients receiving adjuvant tamoxifen as initial treatment, we have associated our previously reported thresholds for the two active metabolites, Z‐endoxifen and Z‐4‐hydroxy‐tamoxifen (Z‐4OHtam), with treatment outcomes in an independent cohort of BC patients. Among all patients, metabolite levels did not affect survival. However, in the premenopausal subgroup receiving tamoxifen alone (n = 191) we confirmed an inferior BC ‐specific survival in patients with the previously described serum concentration threshold of Z‐4OHtam ≤ 3.26 nm (HR = 2.37, 95% CI = 1.02–5.48, P = 0.039). The ‘dose–response’ survival trend in patients categorized to ordinal concentration cut‐points of Z‐4OHtamoxifen (≤ 3.26, 3.27–8.13, > 8.13 nm) was also replicated (P‐trend log‐rank = 0.048). Z‐endoxifen was not associated with outcome. This is the first study to confirm the association between a published active tamoxifen metabolite threshold and BC outcome in an independent patient cohort. Premenopausal patients receiving 5‐year of tamoxifen alone may benefit from therapeutic drug monitoring to ensure tamoxifen effectiveness.

Background Breast cancer represents the most frequent neoplasm diagnosed in women of childbearing age. When the tumour is oestrogen receptor-positive, tamoxifen is among the recommended endocrine treatments. Lactating women are advised not to breastfeed while receiving tamoxifen. However, information about tamoxifen transfer into breast milk is lacking. Methods We measured the concentration of tamoxifen and its metabolites by liquid chromatography-tandem mass spectrometry in the milk of a nursing mother that was treated for pregnancy-associated breast cancer diagnosed a few months after delivery. She was advised not to breastfeed her child and she collected milk samples for 23 days while the baby was fed with formula. Results Tamoxifen concentrations in milk increased reaching a maximum of 214 nM. The two active metabolitesZ-4-hydroxy-tamoxifen and Z-endoxifen, could not be quantified in milk the first days after tamoxifen intake, but increased over time and reached clinically significant levels after day 18. Conclusion This study demonstrates for the first time in human that tamoxifen and its metabolites transfer into milk. Since tamoxifen has a complete oral bioavailability, a long half-life (>7 days) and may interfere with the normal development of the infant, mothers should not breastfeed during tamoxifen treatment.

A disease risk index (DRI) that was developed for adults with hematologic malignancy who were undergoing hematopoietic cell transplantation is also being used to stratify children and adolescents by disease risk. Therefore, to develop and validate a DRI that can be used to stratify those with AML and ALL by their disease risk, we analyzed 2569 patients aged 8) risk groups was 78%, 53%, 40%, and 25%, respectively (P < .0001). For ALL, 3 risk groups were identified based on age and disease status, including minimal residual disease status at transplantation. The 5-year leukemia-free survival for low (0 points), intermediate (2-4), and high (≥5) risk groups was 68%, 51%, and 33%, respectively (P < .0001). We confirmed that the risk groups could be applied to overall survival, with 5-year survival ranging from 80% to 33% and 73% to 42% for AML and ALL, respectively (P < .0001). This validated pediatric DRI, which includes age and residual disease status, can be used to facilitate prognostication and stratification of children with AML and ALL for allogeneic transplantation.

The impact of conditioning regimen prior to hematopoietic cell transplant (HCT) in pediatric AML-patients is not well studied. We retrospectively analyzed the impact of Busulfan-Cyclophosphamide (BuCy), Busulfan-Cyclophosphamide-Melphalan (BuCyMel) and Clofarabine-Fludarabine-Busulfan (CloFluBu) in pediatric AML-patients, with similar upfront leukemia treatment (NOPHO-DBHconsortium), receiving an HCT between 2010 and 2015. Outcomes of interest were LFS, relapse, TRM and GvHD. 103 patients were included; 30 received BuCy, 37 BuCyMel, and 36 CloFluBu. The 5-years LFS was 43.3% (SE ± 9.0) in the BuCy group, 59.2 % (SE ± 8.1) after BuCyMel, and 66.7 % (SE ± 7.9) after CloFluBu. Multivariable Cox regression analysis showed a trend to lower LFS after BuCy compared to CloFluBu (p = 0.07). BuCy was associated with a higher relapse incidence compared to the other regimens (p = 0.06). Younger age was a predictor for relapse (p = 0.02). A strong correlation between Busulfan Therapeutic Drug Monitoring (TDM) and lower incidence of aGvHD (p 0.001) was found. In conclusion, LFS after BuCyMel and CloFluBu was comparable, lower LFS was found after BuCy, due to higher relapse incidence. CloFluBu was associated with lower incidence of aGvHD, suggesting lower toxicity with this type of conditioning. This finding is also explained by the impact of Busulfan monitoring.

Pediatric-type follicular (PTFL), marginal zone (MZL), and peripheral T-cell lymphoma (PTCL) account each for

Background Children with cancer often suffer side effects from their treatment, for example nausea and vomiting, which can lead to malnutrition. If a child cannot eat orally, a percutaneous endoscopic gastrostomy (PEG) can improve his or her well-being, psychosocial development and growth by enabling the supply of nourishment and facilitating the administration of necessary medicines. Few data exist on children’s comfort when using a PEG. The aim of this study was firstly to develop three versions of a web-based assessment tool in which children, families, and healthcare professionals would be able to register their observations and assessments for evaluating the meal situation when a child has a PEG and secondly to validate the content of the tool. Methods A qualitative design was chosen with purposive sampling of participants. Five children with cancer, five parents, five registered nurses and five paediatricians participated first in an interview and then in a member check of the web-based tool. The data were analysed with manifest qualitative content analysis. Results The results highlighted four categories of issues which needed to be revised in the web-based tool: words which were difficult for the participants to understand, items which contained several questions, items which needed to be split into more items to be answerable and the layout of the questionnaire. The web-based tool was revised according to the categories, and then a member check evaluated and finally confirmed the revisions. Conclusions A web-based tool may be able to evaluate the meal situation when a child with cancer has a PEG. The tool may be able to detect early failures of the PEG, facilitating early action from the healthcare professionals in supporting the child and his or her parents in their care of the PEG. In the long run, this web-based tool may also be able to increase the quality of care of children living with a PEG. Electronic supplementary material The online version of this article (10.1186/s12887-019-1447-1) contains supplementary material, which is available to authorized users.

PurposeTo explore whether high intake of cod or salmon would affect gut microbiota profile, faecal output and serum concentrations of lipids and bile acids.MethodsSeventy-six adults with overweight/obesity with no reported gastrointestinal disease were randomly assigned to consume 750 g/week of either cod or salmon, or to avoid fish intake (Control group) for 8 weeks. Fifteen participants from each group were randomly selected for 72 h faeces collection at baseline and end point for gut microbiota profile analyses using 54 bacterial DNA probes. Food intake was registered, and fasting serum and morning urine were collected at baseline and end point.ResultsSixty-five participants were included in serum and urine analyses, and gut microbiota profile was analysed for 33 participants. Principal component analysis of gut microbiota showed an almost complete separation of the Salmon group from the Control group, with lower counts for bacteria in theBacteroidetesphylum and theClostridialesorder of theFirmicutesphyla, and higher counts for bacteria in theSelenomonadalesorder of theFirmicutesphylum. The Cod group showed greater similarity to the Salmon group than to the Control group. Intake of fibres, proteins, fats and carbohydrates, faecal daily mass and output of fat, cholesterol and total bile acids, and serum concentrations of cholesterol, triacylglycerols, non-esterified fatty acids and total bile acids were not altered in the experimental groups.ConclusionA high intake of cod or salmon fillet modulated gut microbiota but did not affect faecal output or serum concentrations of lipids and total bile acids.Clinical trial registrationThis trial was registered at clinicaltrials.gov as NCT02350595.

Pediatric-type follicular (PTFL), marginal zone (MZL), and peripheral T-cell lymphoma (PTCL) account each for

Vitamin D (Vit-D), an essential nutrient, interacts with different drugs including chemotherapeutic agents like busulphan, an alkylating agent used for conditioning prior to stem cell transplantation. The correlation between Vit-D plasma levels and busulphan clearance was investigated in an uncontrolled prospective study in patients and mice. Plasma 25(OH)D levels were measured and busulphan pharmacokinetics calculated in 81 patients. Adults received oral busulphan (n = 34) while children received busulphan orally (n = 19) or intravenously (n = 28). Patients received no Vit-D supplementation. To confirm our findings, pharmacokinetics after a single dose of busulphan (oral or intravenous) were evaluated in two groups of mice (n = 60) receiving high or standard-level Vit-D supplementation. Both busulphan clearance (P 0.0001) and 25(OH)D levels (P = 0.0004) were significantly higher in adults compared to children. A significant negative correlation (P = 0.041) was found between busulphan clearance and 25(OH)D levels in children treated orally. No such correlation was observed in adults or in children receiving intravenous busulphan. In addition, no significant effect of Vit-D levels on busulphan pharmacokinetics in mice regardless of the administration route. In conclusion, 25(OH)D can affect oral busulphan pharmacokinetics in children and its level should be considered when personalizing oral busulphan treatment. Further studies are warranted to confirm the underlying mechanisms.