Surgery As a Trigger for Incident Venous Thromboembolism: Results from a Population-Based Case-Crossover Study

Background Surgery is a major transient risk factor for venous thromboembolism (VTE). However, the impact of major surgery as a VTE trigger has been scarcely investigated using a case-crossover design. Aim To investigate the role of major surgery as a trigger for incident VTE in a population-based case-crossover study while adjusting for other concomitant VTE triggers. Methods We conducted a case-crossover study with 531 cancer-free VTE cases derived from the Tromsø Study cohort. Triggers were registered during the 90 days before a VTE event (hazard period) and in four preceding 90-day control periods. Conditional logistic regression was used to estimate odds ratios (ORs) with 95% confidence intervals (CIs) for VTE according to major surgery and after adjustment for other VTE triggers. Results Surgery was registered in 85 of the 531 (16.0%) hazard periods and in 38 of the 2,124 (1.8%) control periods, yielding an OR for VTE of 11.40 (95% CI: 7.42–17.51). The OR decreased to 4.10 (95% CI: 2.40–6.94) after adjustment for immobilization and infection and was further attenuated to 3.31 (95% CI: 1.83–5.96) when additionally adjusted for trauma, blood transfusion, and central venous catheter. In a mediation analysis, 51.4% (95% CI: 35.5–79.7%) of the effect of surgery on VTE risk could be mediated through immobilization and infection. Conclusions Major surgery was a trigger for VTE, but the association between surgery and VTE risk was in part explained by other VTE triggers often coexisting with surgery, particularly immobilization and infection

Status in Diffuse Large B Cell Lymphoma not otherwise specified: A single center study from Argentina

BackgroundDiffuse large B-cell Lymphoma (DLBCL) is a heterogeneous disease. Based on Hans? algorithm, DLBCL not otherwise specified (NOS) is classified by cell-of-origin into germinal center B-cell (GCB) and non-GCB subtypes. Non-GCB ones have frequently NF-kB pathway activation and worse prognosis compared to GCB cases. MYD88 is an adaptor protein of toll-like and IL-1 receptor signalling, leading downstream NF-kB pathway activation. MYD88 L265P mutation confers the protein constitutional activation. This mutation is present in around 20% of non-GCB subtype, and rarely found in GCB subtype of DLBCL. The prognostic value of MYD88 L265P mutation in DLBCL has been matter of controversy.AimsThe aim of the study was to determine the prevalence of MYD88 L265P mutation in DLBCL NOS cases of Argentina, and compare it with previous reports in the literature.MethodsA retrospective cohort of 73 DLBCL NOS cases diagnosed in the Italian Hospital of Buenos Aires (Argentina) between 2010 and 2016 was studied. Complete clinical records, Hans? algorithm, and available material for molecular testing were inclusion criteria. Patients with prior diagnosis of low-grade lymphoma or diagnosis of immunodeficiency-associated, post-transplant, EBV+, primary mediastinal, primary testicular, primary CNS, primary effusion, leg-type or intravascular DLBCL were excluded. DNA was extracted from tissue blocks using QIAamp mini kit (Qiagen). MYD88 L265P was assessed using an in-house allele-specific probe-based Real-Time PCR assay. Positive (primary testicular DLBCL) and negative controls (tonsil) were added to each run. Every case was checked subsequently using qBiomarker MYD88 L265P Somatic Mutation Assay (Qiagen). Prevalences were expressed as percentage, confident intervals were calculated using Clopper-Pearson exact method. Kaplan Meier curves and Log-rank test were used to evaluate overall survival (OS).Results36 patients (49,31%) were female, and median age at diagnosis was 66 years (range 26-89). 33 patients (45,20%) had extranodal involvement (gastrointestinal tract: 14 cases; liver: 5 cases; bone: 4 cases; other locations: 10 cases). 44 cases (60,27%) were GCB and 29 (39,73%) were non-GCB DLBCLs. MYD88 L265P mutation was present in 2 cases (2,74% ; CI 95%: 0,33-9,55%) among all DLBCLs, including 1 GCB case (2,27% ; CI 95%: 0,06-12,02%) and 1 non-GCB case (3,45% ; CI 95%: 0,09-17.76%). There was no significant association between MYD88 L265P status, Hans´algorithm subtype, sex, age or Ki67 index and OS.ConclusionIn the analyzed population, the prevalence of GCB and non-GCB subtypes among DLBCL NOS cases was similar to international reports, although we did not find significant difference between both groups regarding OS (p=0,712). MYD88 L265P mutation was found only in 2 patients (1 GCB and 1 non-GCB), accounting for 2,74% (CI 95%: 0,33-9,55%) and 2,27% (CI 95%: 0,06-12,02%) of all DLBCL NOS and non-GCB cases, respectively. Both prevalences are significantly lower than those published in 2017 by Lee et al. in a meta-analysis, where they found that MYD88 L265P is present in 16% (CI 95%: 15-18,09%) and 20,63% (CI 95%: 18,41-23%) of patients among all DLBCLs and non-GCB subtype, respectively. However, MYD88 L265P prevalence in primary SNC, testicular and leg-type DLBCLs diagnosed in our institution are similar to the literature (data not shown).Fil: Jauk, Federico. Hospital Italiano; ArgentinaFil: Kohan, Dana. Hospital Italiano; ArgentinaFil: Ortega, Leandro Ismael. Hospital Italiano; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Diaz de Arce, Heidy. Hospital Italiano; ArgentinaFil: Cristaldo, Nancy. Hospital Italiano; ArgentinaFil: RANUNCOLO, Stella Maris. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Oficina de Coordinacion Administrativa Houssay. Instituto de Medicina Traslacional E Ingenieria Biomedica. - Hospital Italiano. Instituto de Medicina Traslacional E Ingenieria Biomedica. - Instituto Universitario Hospital Italiano de Buenos Aires. Instituto de Medicina Traslacional E Ingenieria Biomedica.; ArgentinaFil: Warley, Fernando. Hospital Italiano; ArgentinaFil: Otero, Victoria. Hospital Italiano; ArgentinaFil: Garcia Rivello, Hernan Jorge. Hospital Italiano; Argentina24th Congress of the European Hematology AssociationAmsterdamHolandaEscuela Europea de Hematologí

Search for Cosmic-Ray Events Using Radio Signals and CNNs in Data from the IceTop Enhancement Prototype Station

Cosmic-ray air showers emit radio waves that can be used to measure the properties of cosmic-ray primary particles. The radio detection technique presents several advantages, such as low cost and year-round duty cycle as well as the ability to provide high sensitivity to Xmax and energy estimation with minimal theoretical uncertainties, making it a promising tool for studying cosmic rays at the highest energies. However, the primary limitation of radio detection is the irreducible background from various sources that obscure the impulsive signals generated by air showers. To address this issue, we investigated the use of Convolutional Neural Networks (CNNs), trained on CoREAS simulations and radio backgrounds measured by a prototype station at the South Pole. We developed two different CNNs: a Classifier that distinguishes between cosmic ray event radio signals and pure background waveforms, and a Denoiser that mitigates background noise to recover the underlying cosmic-ray signal. After training the networks we apply them to the air-shower data to search for radio events. With two months data, we were able to identify 51 candidate events. The event’s arrival direction reconstructed using CNN denoised radio waveforms is found to bein good agreement with the IceTop reconstruction. Finally, our approach demonstrated improved directional reconstruction compared to traditional methods

New genetic loci link adipose and insulin biology to body fat distribution.

Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms

Carotid blowout syndrome in patients with nasopharyngeal carcinoma: three cases

Carotid blowout syndrome (CBS) is a rare complication of radiation therapy for nasopharyngeal carcinoma (NPC), for which angiography is the gold standard for diagnosis and treatment. We report three NPC cases treated with irradiation and complicated by bleeding from the internal carotid artery. The first case presented with multiple episodes of limited nosebleeding followed by massive bleeding. Bleeding was initially stopped by internal carotid artery embolisation. A few months later, meningitis related to skull base osteoradionecrosis occurred and the patient died from sceptic shock. The second case was admitted to the hospital with severe repetitive epistaxis and despite several attempts to manage the bleeding, the patient passed away. The third case presented with a massive epistaxis that resolved itself without any treatment. Spontaneous occlusion of the internal carotid artery occurred without any neurological defects. A nasopharyngeal muscle flap was constructed to prevent meningitis. CBS is a rare but life-threatening complication that requires emergency treatment. Re-irradiation and skull base radioosteonecrosis are strong predisposing factors

SMAD4 Positive Pancreatic Ductal Adenocarcinomas Are Associated with Better Outcomes in Patients Receiving FOLFIRINOX-Based Neoadjuvant Therapy.

SMAD4 is inactivated in 50-55% of pancreatic ductal adenocarcinomas (PDACs). SMAD4 loss of expression has been described as a negative prognostic factor in PDAC associated with an increased rate of metastasis and resistance to therapy. However, the impact of SMAD4 inactivation in patients receiving neoadjuvant therapy (NAT) is not well characterized. The aim of our study was to investigate whether SMAD4 status is a prognostic and predictive factor in patients receiving NAT.info:eu-repo/semantics/publishe

Rapamycin improves lymphoproliferative disease in murine autoimmune lymphoproliferative syndrome (ALPS)

Autoimmune lymphoproliferative syndrome (ALPS) is a disorder of abnormal lymphocyte survival caused by defective Fas-mediated apoptosis, leading to lymphadenopathy, hepatosplenomegaly, and an increased number of double-negative T cells (DNTs). Treatment options for patients with ALPS are limited. Rapamycin has been shown to induce apoptosis in normal and malignant lymphocytes. Since ALPS is caused by defective lymphocyte apoptosis, we hypothesized that rapamycin would be effective in treating ALPS. We tested this hypothesis using rapamycin in murine models of ALPS. We followed treatment response with serial assessment of DNTs by flow cytometry in blood and lymphoid tissue, by serial monitoring of lymph node and spleen size with ultrasonography, and by enzyme-linked immunosorbent assay (ELISA) for anti–double-stranded DNA (dsDNA) antibodies. Three-dimensional ultrasound measurements in the mice correlated to actual tissue measurements at death (r = .9648). We found a dramatic and statistically significant decrease in DNTs, lymphadenopathy, splenomegaly, and autoantibodies after only 4 weeks when comparing rapamycin-treated mice with controls. Rapamycin induced apoptosis through the intrinsic mitochondrial pathway. We compared rapamycin to mycophenolate mofetil, a second-line agent used to treat ALPS, and found rapamycin's control of lymphoproliferation was superior. We conclude that rapamycin is an effective treatment for murine ALPS and should be explored as treatment for affected humans