Trends in childhood body mass index between 1936 and 2011 showed that underweight remained more common than obesity among 398 970 Danish school children.

AIM: To examine trends in all body mass index (BMI) groups in children from 1936 to 2011. METHODS: We included 197 694 girls and 201 276 boys from the Copenhagen School Health Records Register, born between 1930 and 1996, with longitudinal weight and height measurements (6-14 years). Using International Obesity Task Force criteria, BMI was classified as underweight, normal-weight, overweight and obesity. Sex- and age-specific prevalences were calculated. RESULTS: From the 1930s, the prevalence of underweight was stable until a small increase occurred from 1950 to 1970s, and thereafter it declined into the early 2000s. Using 7-year-olds as an example, underweight changed from 10% to 7% in girls and from 9% to 6% in boys during the study period. The prevalence of overweight plateaued from 1950 to 1970s and then steeply increased from 1970s onwards and in 1990-2000s 15% girls and 11% boys at 7 years had overweight. The prevalence of obesity particularly increased from 1980s onwards and in 1990-2000s 5% girls and 4% boys at 7 years had obesity. These trends slightly differed by age. CONCLUSION: Among Danish schoolchildren, the prevalence of underweight was greater than overweight until the 1980s and greater than obesity throughout the period. Thus, monitoring the prevalence of childhood underweight remains an important public health issue.

The gold standard program (GSP) for smoking cessation: a cohort study of its effectiveness among smokers with and without cancer.

BACKGROUND: Smoking cessation treatment is an important prognostic factor for survival after a cancer diagnosis, especially for tobacco-related cancers. After being diagnosed with lung cancer, approximately 50% of patients continue smoking or frequently relapse after a quit attempt. Given the importance of smoking cessation treatment for cancer survivors, the objective was to compare the effectiveness of a 6-week intensive smoking cessation intervention, the Gold Standard Program (GSP), among cancer survivors compared with smokers without cancer. Second, we compared successful quitting among socioeconomically disadvantaged cancer survivors with that among nondisadvantaged cancer survivors. MATERIALS AND METHODS: This was a cohort study based on 38,345 smokers from the Danish Smoking Cessation Database (2006-2016). Linkage to the National Patient Register was used to identify cancer survivors undergoing the GSP after being diagnosed with cancer (except nonmelanoma skin cancer). Linkage to the Danish Civil Registration System was used to identify participants who died, went missing, or emigrated before the follow-up. Logistic regression models were applied to evaluate effectiveness. RESULTS AND CONCLUSION: Six percent (2438) of the included smokers were cancer survivors at the time they undertook the GSP. Their 6-month successful quitting showed no difference compared to that of smokers without cancer, neither before nor after adjustment; 35% versus 37% in crude rates and an aOR of 1.13 (95% CI: 0.97-1.32). Likewise, the results for disadvantaged compared to nondisadvantaged cancer survivors were not significantly different (32% versus 33% and an adjusted aOR of 0.87 (95% CI 0.69-1.11)). Overall, an intensive smoking cessation program seems effective in helping both people without cancer and cancer survivors become successful quitters.

Birthweight, body size, and growth during childhood and risks of rheumatoid arthritis: a large Danish cohort study.

OBJECTIVES: Adult obesity may be positively associated with risks of rheumatoid arthritis (RA), but associations with early life body size are unknown. We examined whether birthweight, childhood body mass index (BMI), height, and changes in BMI and height were associated with risks of adult RA. METHOD: A cohort of 346 602 children (171 127 girls) from the Copenhagen School Health Records Register, born in 1930-1996, with measured weights and heights from 7 to 13 years of age, were included. Information on RA, including serological status, came from national registers from 1977 to 2017. Cox regressions were performed. RESULTS: During a median of 35.1 years of observation time per person, 4991 individuals (3565 women) were registered with RA. Among girls, per BMI z-score, risks of RA and seropositive RA increased by 4-9% and 6-10%, respectively. Girls with overweight had higher risks of RA than girls without overweight. Girls who became overweight by 13 years of age had increased risks of RA compared to girls without overweight at 7 or 13 years (hazard ratio = 1.40, 95% confidence interval 1.19-1.66). For boys, associations between BMI and RA (including seropositive RA) were not statistically significant. Height was not associated with RA (any type) in girls. Taller boys had higher risks of RA, especially seropositive RA. Birthweight was not associated with RA. CONCLUSIONS: Among women, childhood adiposity was associated with increased risks of RA. Among men, childhood height was positively associated with risks of RA. These findings support the hypothesis that early life factors may be important in the aetiology of RA.

Effect of initiating biologics compared to intensifying conventional DMARDs on clinical and MRI outcomes in established rheumatoid arthritis patients in clinical remission: Secondary analyses of the IMAGINE-RA trial.

OBJECTIVES: To compare the effect of treat-to-target-based escalations in conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) and biologics on clinical disease activity and magnetic resonance imaging (MRI) inflammation in a rheumatoid arthritis (RA) cohort in clinical remission. METHOD: One-hundred patients with established RA, Disease Activity Score based on 28-joint count-C-reactive protein (DAS28-CRP) < 3.2, and no swollen joints (hereafter referred to as 'in clinical remission') who received csDMARDs underwent clinical evaluation and MRI of the wrist and second to fifth metacarpophalangeal joints every 4 months. They followed a 2 year MRI treatment strategy targeting DAS28-CRP ≤ 3.2, no swollen joints, and absence of MRI osteitis, with predefined algorithmic treatment escalation: first: increase in csDMARDs; second: adding a biologic; third: switch biologic. MRI osteitis and Health Assessment Questionnaire (HAQ) (co-primary outcomes) and MRI combined inflammation and Simplified Disease Activity Index (SDAI) (key secondary outcomes) were assessed 4 months after treatment change and expressed as estimates of group differences. Statistical analyses were based on the intention-to-treat population analysed using repeated-measures mixed models. RESULTS: Escalation to first biologic compared to csDMARD escalation more effectively reduced MRI osteitis (difference between least squares means 1.8, 95% confidence interval 1.0-2.6), HAQ score (0.08, 0.03-0.1), MRI combined inflammation (2.5, 0.9-4.1), and SDAI scores (2.7, 1.9-3.5). CONCLUSIONS: Treat-to-target-based treatment escalations to biologics compared to escalation in csDMARDs more effectively improved MRI inflammation, physical function, and clinical disease activity in patients with established RA in clinical remission. Treatment escalation in RA patients in clinical remission reduces clinical and MRI-assessed disease activity. TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT01656278.

Genomic landscape of treatment refractory metastatic colorectal cancer.

BACKGROUND: Metastatic colorectal cancer (mCRC) is a complex and heterogeneous disease with few standard and targeted treatment options. Next-generation sequencing of tumor tissue was performed to identify cancer driver mutations to discover possible personalized treatment options, as targeted treatment possibilities are limited for this patient population. Results of genomic sequencing in patients with treatment-refractory mCRC are described in this retrospective analysis. MATERIAL AND METHODS: Clinico-pathological characteristics and genomic sequence results of consecutive patients with refractory mCRC, referred to the Experimental Cancer Therapy Unit (ECTU) at Department of Oncology, Herlev & Gentofte Hospital in the period from 1 October 2015 to 14 December 2018 were reviewed in this retrospective analysis. Tumor tissue from the patients was analyzed by next-generation sequencing using the Oncomine Comprehensive primer panel to detect actionable variants of cancer driver mutations and microsatellite instability status. From August 2018 tumor mutational burden was also analyzed. RESULTS: A total of 80 patients with treatment-refractory mCRC and in a fairly good performance were referred to the ECTU during this period. Genomic sequencing of tumor tissue was performed for all 80 patients and a cancer driver mutation was identified in 90% (n = 72) of the patients. A total of 31.3% (n = 25) of the patients received therapy either as targetable therapy outside an available trial (n = 2), FDA approved therapy (n = 2), or treatment in phase 1 or 2 trials, independent of the genomic signature 26.3% (n = 21). CONCLUSION: Most mCRC patients refractory to standard anti-neoplastic therapies, presented with a cancer driver mutation, however, only a few of these mutations gave rise to matched therapies as only 2.5% of the patients from this period received targeted therapy.

Effect of far infrared therapy on arteriovenous fistula maturation, survival and stenosis in hemodialysis patients, a randomized, controlled clinical trial: the FAITH on fistula trial.

BACKGROUND: An arteriovenous fistula (AVF) is the preferred vascular access for hemodialysis treatment. After creation many of the AVFs will never mature or if functioning will need an intervention within 1 year due to an AVF stenosis. Studies investigating possible therapies that improves the AVF maturation and survival are scarce. Far infrared therapy (FIR) has shown promising results. In minor single centre and industry supported trials FIR has shown improved AVF maturation and survival. There is a need of a randomized multicentre controlled trial to examine the effect of FIR on the AVF maturation and survival and to explore the possible AVF protective mechanism induced by the FIR treatment. METHODS: This investigator initiated, randomized, controlled, open-labeled, multicenter clinical trial will examine the effect of FIR on AVF maturation in patients with a newly created AVF (incident) and AVF patency rate after 1 year of treatment in patients with an existing AVF (prevalent) compared to a control group. The intervention group will receive FIR to the skin above their AVF three times a week for 1 year. The control group will be observed without any treatment. The primary outcome for incident AVFs is the time from surgically creation of the AVF to successful cannulation. The primary outcome for the prevalent AVFs is the difference in number of AVFs without intervention and still functioning in the treatment and control group after 12 months. Furthermore, the acute changes in inflammatory and vasodilating factors during FIR will be explored. Arterial stiffness as a marker of long term AVF patency will also be examined. DISCUSSION: FIR is a promising new treatment modality that may potentially lead to improved AVF maturation and survival. This randomized controlled open-labelled trial will investigate the effect of FIR and its possible mechanisms. TRIAL REGISTRATION: Clinicaltrialsgov NCT04011072 (7th of July 2019).

Evaluating effects of different control strategies for Infectious Salmon Anaemia (ISA) in marine salmonid farming by scenario simulation using a disease transmission model.

Infectious salmon anaemia (ISA) is an important viral disease causing economic losses and reduced welfare in farmed Atlantic salmon. Here, we present a spatio-temporal stochastic model for the spread of ISA between and within marine aquaculture farms. The model is estimated on historical production data for all marine salmonid farms in Norway from 2004 to February 2019. In this time 142 outbreaks of ISA occurred. We find that transmission from infected neighbouring farms accounts for around 50% of the infections, whereas transmission from "non-specified sources" accounts for around 40%. We hypothesise that the most important of the latter are viruses mutating from the non-virulent ISAV HPR0 to the virulent ISAV HPRdel. The model is used for scenario simulation, or what-if analysis, to investigate the effects of potential strategies to combat ISA, including screening, vaccination and culling. Changing from the current strategy of culling farms with detected ISA-outbreaks to mandatory screening and culling when virus is detected will reduce the fraction of cohorts with a clinical ISA outbreak from 3.8 to 0.36%. Introducing mandatory vaccination would have approximately the same effect as the current stamping-out strategy. The scenario simulation is a useful tool for deciding on appropriate mitigation measures.

[Oro- and Nasopharyngeal Swab for Detection of SARS-CoV-2 - Step-by-step Approach]. / Oro- und nasopharyngealer Abstrich ­ Schritt für Schritt.

Oro- and nasopharyngeal swab specimens by quantitative reverse-transcriptase polymerase chain reaction (RT-PCR) to detect SARS-CoV-2 is currently the main diagnostic tool during the ongoing COVID-19 pandemia. Accurate performance of the procedure to avoid false negative results, adequate personal protective equipment and material sparing algorithms are mandatory while obtaining swab specimens. In the current stey-by-step review a feasible approach will be presented.

Torque Teno Virus plasma level as novel biomarker of retained immunocompetence in HIV-infected patients.

PURPOSE: To predict the course of immune recovery (IR) in HIV-1-infected patients after initiation of combined antiretroviral therapy (cART) by determination of the plasma concentration of Torque Teno Virus (TTV). TTV has been identified as marker for risk assessment in immunosuppressed patients after transplantation procedures. Here, TTV was analyzed in HIV-1-infected therapy-naïve patients to evaluate its use as predictor of the course of IR for guidance of individualized treatment. METHODS: TTV DNA was quantified in plasma samples of 301 therapy-naïve HIV-1-infected patients and correlated to CD4+ cell count, HIV viral load, presence of the herpes viruses CMV, EBV and HHV-8, age and sex. Patients were classified according to their initial CD4+ cell count and to the extent of CD4+ T-cell increase within the first year of cART. RESULTS: TTV DNA was detectable in 96% of the patients' plasma samples with a median TTV plasma concentration of 5.37 log10 cop/ml. The baseline CD4+ cell count was negatively correlated with TTV plasma concentration (p = 0.003). In patients with a CD4+ cell recovery < 50 cells/µl, the median TTV plasma concentration was significantly higher compared to patients with a CD4+ cell recovery of > 200 CD4+ cells/µl (5.68 log10 cop/ml versus 4.99 log10 cop/ml; p = 0.011). TTV plasma concentration in combination with baseline CD4+ cell count were significantly correlated to CD4+ cell recovery (p = 0.004). For all other parameters considered, no significant correlation for CD4+ cell recovery was found. CONCLUSION: Within the cohort, the significantly elevated TTV plasma concentration in patients with diminished CD4+ cell recovery indicates a more profound immune defect. Baseline TTV plasma concentrations and CD4+ cell count are predictive for the course of immune recovery in HIV-1-infected patients with severe immunodeficiency.

[Optimization of microbial diagnostics by introduction of a blood culture standard operating procedure in the emergency department]. / Optimierung der mikrobiellen Diagnostik durch Einführung einer Standard Operating Procedure "Blutkulturen" in der zentralen Notaufnahme.

INTRODUCTION: The emergency department (ED) is the main port of entry for patients with infectious diseases, the place where a number of diagnostic procedures are performed and treatment is often initiated. The aim of this retrospective study was to estimate the influence of the establishment and introduction of a blood culture standard operating procedure (BC-SOP) and of the subsequent training of microbial diagnostics in an ED. METHODS: In a before and after study over a study period of 3 months each (November 2017-January 2018 and November 2018-January 2019), the number of blood cultures taken, the rate of blood cultures per 1000 patients, the number of positive blood cultures and the frequency of typical skin pathogens were evaluated. In the interim time between the two study periods, a BC-SOP was developed in collaboration with the hospital's antibiotic stewardship team and subsequently introduced with staff training in the ED. The study was approved by the local ethics committee of the medical faculty of the Heinrich Heine University (2019-392-RetroDEuA). RESULTS: In total 92% of the nursing personnel and 93% of the medical personnel received training. The total number of blood cultures increased from 1757 to 2872 (64% increase) and the rate of blood cultures per 1000 patients from 287 to 481 (68% increase). The number of positive blood cultures decreased from 18.6% to 13.7% (p < 0.05). Typical skin pathogens were found in 34.4% and 26.4% of the cases, respectively (p < 0.05). CONCLUSION: The development, introduction and training of a BC-SOP in the ED can make a relevant contribution to the microbial diagnostics and increase the quantity as well as the quality.

Sweet Corn Sentinel Monitoring for Lepidopteran Field-Evolved Resistance to Bt Toxins.

As part of an insect resistance management plan to preserve Bt transgenic technology, annual monitoring of target pests is mandated to detect susceptibility changes to Bt toxins. Currently Helicoverpa zea (Boddie) monitoring involves investigating unexpected injury in Bt crop fields and collecting larvae from non-Bt host plants for laboratory diet bioassays to determine mortality responses to diagnostic concentrations of Bt toxins. To date, this monitoring approach has not detected any significant change from the known range of baseline susceptibility to Bt toxins, yet practical field-evolved resistance in H. zea populations and numerous occurrences of unexpected injury occur in Bt crops. In this study, we implemented a network of 73 sentinel sweet corn trials, spanning 16 U.S. states and 4 Canadian provinces, for monitoring changes in H. zea susceptibility to Cry and Vip3A toxins by measuring differences in ear damage and larval infestations between isogenic pairs of non-Bt and Bt hybrids over three years. This approach can monitor susceptibility changes and regional differences in other ear-feeding lepidopteran pests. Temporal changes in the field efficacy of each toxin were evidenced by comparing our current results with earlier published studies, including baseline data for each Bt trait when first commercialized. Changes in amount of ear damage showed significant increases in H. zea resistance to Cry toxins and possibly lower susceptibility to Vip3a. Our findings demonstrate that the sentinel plot approach as an in-field screen can effectively monitor phenotypic resistance and document field-evolved resistance in target pest populations, improving resistance monitoring for Bt crops.

Phase angle and vector analysis from multifrequency segmental bioelectrical impedance analysis: new reference data for older adults.

Phase angle (PA) and bioelectrical impedance vector analysis (BIVA) have been recommended as useful prognostic markers in various clinical settings. However, reference data for older adults measured by the novel segmental multifrequency bioelectrical impedance analysis (SMF-BIA) technique are currently lacking. This study examined 567 (286 men, 281 women) healthy older adults (65 - 97 years) and new SMF-BIA-based PA and BIVA reference values were generated stratified according to gender and 3 age groups (65 - 75 years, 76 - 85 years, > 85 years). Mean PA-values (women: 4.30 ± 0.6°, men: 4.77 ± 0.7°) were significantly lower than those previously reported for a younger reference population. Age and gender were significant determinants of PA and BIVA. PA showed a significant decrease with increasing age in both genders. The greatest changes occurred in the age group > 85 years. Men had higher Pas compared to women (except for the oldest age group), but showed a substantially steeper decline in PA, possibly due to a more pronounced reduction of muscle mass. Compared to published reference data for younger adults, there was a clear downward migration of the BIVA vector points in older adults, indicating an age-related reduction of body cell mass. Accordingly, the equation for the BIVA chart generation was modified by adding the factor age. In conclusion, this is the first study to present SMF-BIA-determined PA and BIVA reference data for healthy subjects aged ≥ 65 years. These data can be used for clinical purposes to identify individuals at increased risk for adverse health events or to monitor treatment responses.

Future directions for the concept of salutogenesis: a position article.

Aaron Antonovsky advanced the concept of salutogenesis almost four decades ago (Antonovsky, Health, Stress and Coping. Jossey-Bass, San Francisco, CA, 1979; Unravelling the Mystery of Health. Jossey-Bass, San Francisco, CA, 1987). Salutogenesis posits that life experiences shape the sense of coherence (SOC) that helps to mobilize resources to cope with stressors and manage tension successfully (determining one's movement on the health Ease/Dis-ease continuum). Antonovsky considered the three-dimensional SOC (i.e. comprehensibility, manageability, meaningfulness) as the key answer to his question about the origin of health. The field of health promotion has adopted the concept of salutogenesis as reflected in the international Handbook of Salutogenesis (Mittelmark et al., The Handbook of Salutogenesis. Springer, New York, 2016). However, health promotion mostly builds on the more vague, general salutogenic orientation that implies the need to foster resources and capacities to promote health and wellbeing. To strengthen the knowledge base of salutogenesis, the Global Working Group on Salutogenesis (GWG-Sal) of the International Union of Health Promotion and Education produced the Handbook of Salutogenesis. During the creation of the handbook and the regular meetings of the GWG-Sal, the working group identified four key conceptual issues to be advanced: (i) the overall salutogenic model of health; (ii) the SOC concept; (iii) the design of salutogenic interventions and change processes in complex systems; (iv) the application of salutogenesis beyond health sector. For each of these areas, we first highlight Antonovsky's original contribution and then present suggestions for future development. These ideas will help guide GWG-Sal's work to strengthen salutogenesis as a theory base for health promotion.

Scoring magnetic resonance imaging (MRI) inflammation and structural lesions in sacroiliac joints of patients with axial spondyloarthritis: assessment of all MRI slices of the cartilaginous compartment versus standardized six or five slices.

Objectives: The Spondyloarthritis Research Consortium of Canada (SPARCC) sacroiliac joint (SIJ) scoring system assesses six or five (6/5) semicoronal magnetic resonance imaging (MRI) slices for inflammation/structural lesions in patients with axial spondyloarthritis (axSpA). However, the cartilaginous SIJ compartment may be visible in a few additional slices. The objective was to investigate interreader reliability, sensitivity to change, and classification of MRI scans as positive or negative for various lesion types using an 'all slices' approach versus standard SPARCC scoring of 6/5 slices.Method: Fifty-three axSpA patients were treated with the tumour necrosis factor inhibitor golimumab and followed with serial MRI scans at weeks 0, 4, 16, and 52. The most anterior and posterior slices covering the cartilaginous compartment and the transitional slice were identified. Scores for inflammation, fat metaplasia, erosion, backfill, and ankylosis in the cartilaginous SIJ compartment were calculated for the 'all slices' approach and the 6/5 slices standard.Results: By the 'all slices' approach, three readers scored mean 7.2, 7.7, and 7.0 slices per MRI scan. Baseline and change scores for the various lesion types closely correlated between the two approaches (Pearson's rho ≥ 0.95). Inflammation score was median 13 (interquartile range 6-21, range 0-49) for 6/5 slices versus 14 (interquartile range 6-23, range 0-69) for all slices at baseline. Interreader reliability, sensitivity to change, and classification of MRI scans as positive or negative for various lesion types were similar.Conclusion: The standardized 6/5 slices approach showed no relevant differences from the 'all slices' approach and, therefore, is equally suited for monitoring purposes.

Impact of alternative materials to plasticized PVC infusion tubings on drug sorption and plasticizer release.

Medical tubings in plasticized polyvinylchloride (PVC) are widely used for the infusion of medications but are known in some cases to cause content-container interactions (drug sorption and plasticizer release). The aim of this study was to assess interactions between drugs and five alternative materials to a reference plasticized PVC intravenous (IV) infusion tubing: three were PVC coextruded with polyethylene (PE), polyurethane (PU) or a thermoplastic elastomer (Styrene-EthyleneButadiene-Styrene (SEBS)) and two were SEBS or thermoplastic olefin (TPO) monolayer tubings. Diazepam and insulin were chosen as respective reference of absorption and adsorption while paracetamol acted as a negative control. The concentration of each drug was quantified with liquid chromatography to evaluate a potential loss after a static contact condition and simulated infusion at 1 mL/h and 10 mL/h dynamic condition by an electric syringe pump. A characterization of each material's surface was performed by Fourier transform infrared spectroscopy in attenuated total reflection mode (ATR-FTIR) and by measurement of surface zeta potential. Plasticizer release was quantified by gas chromatography coupled with mass spectrometry (GC-MS). For all tubings except PVC/PU, no loss of paracetamol was observed in any condition. Diazepam sorption appeared to be less important with PVC/PE, PVC/SEBS, SEBS and TPO tubings than with PVC, but was more important when using PVC/PU tubings. PVC tubings induced the least loss of insulin amongst all the studied materials. Surface analysis by ATR-FTIR highlighted the presence of a plasticizer (that could be attributed to Tris (2-Ethylhexyl) Trimellitate (TOTM)) in the coextruded SEBS layer of PVC/SEBS, which could have influenced drug sorption, probably as a consequence of a migration from the PVC layer. Coextruded PVC/SEBS and PVC/PE presented the lowest zeta potential of all studied materials with respective values of -39 mV and -36 mV and were related to the highest sorption of insulin while PVC/PU with the highest zeta potential (about -9 mV) presented the highest absorption of diazepam. Coextruded layered materials appeared to have a lower plasticizer release than PVC alone. As a conclusion, PVC/PE and thermoplastic elastomers alone or coextruded with PVC could be interesting alternatives to PVC tubings with regards to sorption phenomena and plasticizer release.

Detonation synthesis of carbon nano-onions via liquid carbon condensation.

Transit through the carbon liquid phase has significant consequences for the subsequent formation of solid nanocarbon detonation products. We report dynamic measurements of liquid carbon condensation and solidification into nano-onions over ∽200 ns by analysis of time-resolved, small-angle X-ray scattering data acquired during detonation of a hydrogen-free explosive, DNTF (3,4-bis(3-nitrofurazan-4-yl)furoxan). Further, thermochemical modeling predicts a direct liquid to solid graphite phase transition for DNTF products ~200 ns post-detonation. Solid detonation products were collected and characterized by high-resolution electron microscopy to confirm the abundance of carbon nano-onions with an average diameter of ∽10 nm, matching the dynamic measurements. We analyze other carbon-rich explosives by similar methods to systematically explore different regions of the carbon phase diagram traversed during detonation. Our results suggest a potential pathway to the efficient production of carbon nano-onions, while offering insight into the phase transformation kinetics of liquid carbon under extreme pressures and temperatures.

Tratamiento quirúrgico de la endometriosis pélvica profunda con compromiso colorrectal / Surgical treatment of deep pelvic endometriosis with colorectal involvement

INTRODUCCIÓN: En la endometriosis el compromiso intestinal afecta hasta al 12% de las pacientes, comprometiendo al recto y a la unión rectosigmoidea en el 90% de los casos. OBJETIVO: Describir la experiencia del equipo de Coloproctología y Ginecología de Clínica Alemana de Santiago en el tratamiento quirúrgico de la endometriosis pélvica profunda con compromiso colorrectal. MATERIAL Y MÉTODOS: Estudio retrospectivo a partir de la base de datos de pacientes con endometriosis tratados entre enero del año 2015 y abril de 2018. Los criterios de inclusión fueron pacientes con clínica de endometriosis pélvica profunda, que tuviesen compromiso colorrectal y hayan sido tratados con shaving rectal, resección discoide o resección segmentaria. Se revisaron fichas clínicas electrónicas, protocolos operatorios y biopsias definitivas. RESULTADOS: Se reclutaron 25 pacientes con una mediana de edad de 35 años. El síntoma principal de consulta fue dismenorrea y el síntoma digestivo más frecuente fue disquecia. En 8 pacientes se realizó un shaving rectal, en 7 una sigmoidectomía, en 9 una resección discoide y en 1 paciente una tiflectomía. La complicación posoperatoria reportada fue la hemorragia digestiva baja en 4 pacientes (Clavien-Dindo I y IIIa). Con una mediana de seguimiento de 13 meses, a la fecha 3 pacientes se les ha diagnosticado algún tipo de recidiva. CONCLUSIÓN: Es importante que la cirugía a realizar, garantice una morbilidad y recurrencia baja. Los resultados en nuestro centro son alentadores, lo que nos hace creer que el tratamiento quirúrgico podría ser una buena alternativa en la endometriosis pélvica profunda con compromiso colorrectal.

INTRODUCTION: In endometriosis, intestinal involvement affects up to 12% of patients, compromising the rectum and the rectosigmoid junction in 90% of cases. AIM: Describe the experience of the Coloproctolgy and Gynecology Team of the Clínica Alemana de Santiago in the surgical treatment of deep pelvic endometriosis with colorectal involvement. MATERIAL AND METHODS: Retrospective study based on the database of patients with endometriosis treated between January 2015 and April 2018. The inclusion criteria were patients with deep pelvic endometriosis clinic, who had colorectal involvement and who had been treated with rectal shaving, discoid resection or segmental resection. Electronic clinical records, operative protocols and definitive biopsies were reviewed. RESULTS: Twenty-five patients with a median age of 35 years were recruited. The main symptom of consultation was dysmenorrhoea and the most frequent digestive symptom was dyschezia. In 8 patients a rectal shaving was performed, in 7 a sigmoidectomy, in 9 a discoid resection and in 1 patient a tiflectomy. The only reported post-operative complication was low gastrointestinal bleeding in 4 of the 25 patients (Clavien-Dindo I and IIIa). A median follow-up of 13 months was achieved, to date 3 patients have been diagnosed with some type of recurrence. CONCLUSION: It is important that the surgery to be performed guarantees low morbidity and recurrence. The results in our center are encouraging, which makes us believe that surgical treatment could be a good alternative in deep pelvic endometriosis with colorectal involvement.

Paneth cell α-defensins HD-5 and HD-6 display differential degradation into active antimicrobial fragments.

Antimicrobial peptides, in particular α-defensins expressed by Paneth cells, control microbiota composition and play a key role in intestinal barrier function and homeostasis. Dynamic conditions in the local microenvironment, such as pH and redox potential, significantly affect the antimicrobial spectrum. In contrast to oxidized peptides, some reduced defensins exhibit increased vulnerability to proteolytic degradation. In this report, we investigated the susceptibility of Paneth-cell-specific human α-defensin 5 (HD-5) and -6 (HD-6) to intestinal proteases using natural human duodenal fluid. We systematically assessed proteolytic degradation using liquid chromatography-mass spectrometry and identified several active defensin fragments capable of impacting bacterial growth of both commensal and pathogenic origins. Of note, incubation of mucus with HD-5 resulted in 255-8,000 new antimicrobial combinations. In contrast, HD-6 remained stable with consistent preserved nanonet formation. In vivo studies demonstrated proof of concept that a HD-5 fragment shifted microbiota composition (e.g., increases of Akkermansia sp.) without decreasing diversity. Our data support the concept that secretion of host peptides results in an environmentally dependent increase of antimicrobial defense by clustering in active peptide fragments. This complex clustering mechanism dramatically increases the host's ability to control pathogens and commensals. These findings broaden our understanding of host modulation of the microbiome as well as the complexity of human mucosal defense mechanisms, thus providing promising avenues to explore for drug development.

Respuesta del tumor primario a la quimioterapia en cáncer colorrectal etapa IV con metástasis hepáticas sincrónicas: serie de casos / Response of the primary tumor to chemotherapy in stage IV colorectal cancer with synchronous liver metastases: serie of cases

Resumen Introducción: El cáncer colorrectal se ha convertido en el tercer cáncer a nivel mundial en cuanto a incidencia y cuarto en mortalidad. Al diagnóstico, aproximadamente el 25% de los pacientes tendrán metástasis hepáticas. Con tratamiento adecuado el pronóstico de los pacientes etapa IV alcanza una sobrevida de 40% a 5 años. Con nuestro trabajo queremos evaluar la respuesta del tumor primario de colon desde el punto de vista imagenológico y anatomopatológico en pacientes con cáncer colorrectal con metástasis hepáticas tratados con quimioterapia y que luego fueron a resección del colon. Materiales y Método: Se trata un estudio retrospectivo y descriptivo, de pacientes con cáncer colorrectal con metástasis hepáticas. Los criterios de inclusión fueron que presentaran cáncer de colon o recto superior, con metástasis hepáticas sincrónicas, recibieran al menos 4 ciclos de quimioterapia neoadyuvante y que posteriormente fueran a resección del tumor primario. Resultados: Se reclutaron 9 pacientes, 4 hombres y 5 mujeres. Todos recibieron 4 o más ciclos de quimioterapia previo a la cirugía del tumor primario. De ellos, 8 tuvieron control imagenológico posquimioterapia. Según criterios RECIST, 3 pacientes presentaron respuesta completa, 1 paciente respuesta parcial y 4 enfermedad estable. El estudio anatomopatológico del colon resecado mostró desaparición tumoral macroscópica en 2 pacientes y microscópica en 1 paciente. Conclusiones: La regresión patológica completa en nuestros casos tratados con quimioterapia neoadyuvante es un hecho poco frecuente. Esto nos permite indicar la resección del sitio del tumor colorrectal en todos estos casos.

Introduction: Colorectal cancer has become the third cancer worldwide in terms of incidence and fourth in mortality. At diagnosis approximately 25% of patients will have liver metastases. With adequate treatment, the prognosis of stage IV patients reaches a survival of 40% at 5 years. We want to evaluate the response of the primary tumor of the colon from imaging and anatomopathological point of view in patients with colorectal cancer with liver metastases treated with chemotherapy and who then went to colon resection. Materials and Method: It is a retrospective and descriptive study of patients with stage IV colorectal cancer. The inclusion criteria were that they had cancer of the colon or upper rectum, with synchronous liver metastases, who have received at least 4 cycles of neoadjuvant chemotherapy and that subsequently went to resection of the primary tumor. Results: We recruited 9 patients, 4 men and 5 women. All received 4 or more cycles of chemotherapy prior to primary surgery. Of these, 8 had imaging control after chemotherapy. According to RECIST criteria, 3 patients presented complete response, 1 patient partial response and 4 stable disease. The anatomopathological study of the resected colon showed a macroscopic tumor disappearance in 2 patients, and microscopic in 1 patient. Conclusions: The complete pathological regression in our cases treated with neoadjuvant chemotherapy is a rare occurrence. This allows us to indicate the resection of the colorectal tumor site in all these cases.

Germline BRCA2 K3326X and CHEK2 I157T mutations increase risk for sporadic pancreatic ductal adenocarcinoma.

Rare truncating BRCA2 K3326X (rs11571833) and pathogenic CHEK2 I157T (rs17879961) variants have previously been implicated in familial pancreatic ductal adenocarcinoma (PDAC), but not in sporadic cases. The effect of both mutations in important DNA repair genes on sporadic PDAC risk may shed light on the genetic architecture of this disease. Both mutations were genotyped in germline DNA from 2,935 sporadic PDAC cases and 5,626 control subjects within the PANcreatic Disease ReseArch (PANDoRA) consortium. Risk estimates were evaluated using multivariate unconditional logistic regression with adjustment for possible confounders such as sex, age and country of origin. Statistical analyses were two-sided with p values <0.05 considered significant. K3326X and I157T were associated with increased risk of developing sporadic PDAC (odds ratio (ORdom ) = 1.78, 95% confidence interval (CI) = 1.26-2.52, p = 1.19 × 10-3 and ORdom = 1.74, 95% CI = 1.15-2.63, p = 8.57 × 10-3 , respectively). Neither mutation was significantly associated with risk of developing early-onset PDAC. This retrospective study demonstrates novel risk estimates of K3326X and I157T in sporadic PDAC which suggest that upon validation and in combination with other established genetic and non-genetic risk factors, these mutations may be used to improve pancreatic cancer risk assessment in European populations. Identification of carriers of these risk alleles as high-risk groups may also facilitate screening or prevention strategies for such individuals, regardless of family history.