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Introdução: O linfoma difuso de grandes células B (LDGCB) é o subtipo mais comum de linfoma não-Hodgkin (LNH) em adultos, correspondendo a 25-30% dos casos. O tratamento baseado em R-CHOP (rituximab, ciclofosfamida, doxorrubicina, vincristina e prednisona) é a terapêutica de primeira linha para o LDGCB, entretanto, cerca de 1/3 dos pacientes sofrem recidivas e/ou são refratários (R/R) a essa primeira linha de tratamento. Objetivos: Descrever os patrões de tratamento e desfechos clínicos de uma coorte brasileira de paciente LDGCB-R/R com dados de mundo real derivados da Plataforma Trinetx. Materiais e métodos: Avaliação de dados de mundo real (demográficos, perfil de comorbidades, informações oncológicas, exames complementares, internações hospitalares, tratamento, resposta terapêutica e mortalidade em 5 anos) através da TriNetX. Foram incluídos pacientes ≥18 anos, com diagnóstico de LDGCB entre Jan/2012 a Dez/2022, tratados com mais de um esquema quimioterápico e com seguimento de pelo menos 3 meses. Resultados: De uma coorte de 1651 pacientes diagnosticados com LDGCB originários de 13 hospitais públicos e privados, 524 (31,7%) pacientes eram R/R. Observamos predominância de homens (58,9%), com idade média de 52 ± 18 anos, 23,6% obesos e 22% hipertensos. Em relação ao LDGCB, 29% dos pacientes possuíam malignidade secundária ao diagnóstico e 77% apresentavam anemia. Sobre o tratamento, 185 (29,6%) receberam 2 linhas de tratamento (LOT) e 235 (44,8%) ≥3 LOT. O tempo mediano entre a 1ª linha de tratamento (R-CHOP) e uma segunda linha foi de 358 dias. A segunda linha mais utilizada foi gemcitabina, dexametasona e cisplatina (GDP) com 37,5%, seguido por R-CHOP na 3ª linha de tratamento (32%) O transplante autólogo de medula óssea (TMO) foi realizado em 9,3% dos pacientes, o alogênico em 1,9% e 21,9% fizeram radioterapia. Ao longo de um tempo de acompanhamento mediano de 782 dias, 402 (76,7%) dos pacientes necessitaram de internação hospitalar, com uma mediana de 4 internações/paciente. Cerca de 30% dessas internações ocorreram por neutropenia febril, 28,8% dos pacientes necessitaram de unidade de terapia intensiva, 25% de droga vasoativa e 7,2% ventilação mecânica. A sobrevida global (SG) dos pacientes R/R da casuística em 5 anos foi de 47,4% e a sobrevida em 5 anos pós-TMO foi de 62,1%. Quando comparamos os pacientes que receberam 2 vs ≥3 LOT, observamos que no segundo grupo os pacientes eram mais velhos (p = 0,006), com maior porcentagem de hipertensos (p = 0,02), obesos (p = 0,004) e doença renal crônica (p = 0,007). Mais pacientes com ≥3 LOT foram submetidos a TMO, tanto alogênico (p = 0,004) quanto autólogo (p = 0,02) e necessitaram de maior número de internações hospitalares (p < 0,001), internações em UTI (p < 0,001), uso de droga vasoativa (p = 0,007) e ventilação mecânica (p = 0,007). A taxa de SG em 5 anos foi 49,7% para pacientes que receberam 2 LOT e 39,4% para pacientes com ≥ 3 LOT, porém sem diferença estatisticamente significante entre os grupos (p = 0,13). Discussão: Dados do mundo real relativos a populações brasileiras e latino-americanas de pacientes com LDGCB R/R são escassos. Informações sobre o perfil epidemiológico, apresentação clínica, padrões de tratamento, complicações associadas ao tratamento e desfechos clínicos são essenciais para a elaboração de políticas públicas referentes ao diagnóstico e tratamento, melhorando assim o manejo do LDGCB no Brasil.

Background: Diabetes is an alarming health problem affecting more than half a billion people globally. Diabetes is one of the most psychologically demanding illnesses and is frequently associated with anxiety and depression. The present study aimed to estimate the prevalence of depression and anxiety among diabetic patients and comparison of mental health assessment tools among diabetic and nondiabetic participants. Methodology: A comparative study of 80 diabetic patients attending the diabetology outpatient department and 80 age-matched nondiabetic attendees/relatives of patients attending the medicine outpatient department were randomly selected after fulfilling inclusion and exclusion criteria. After confirming their disease status, informed consent was obtained. Data were collected using a pretested questionnaire, mini international neuropsychiatric interview scale, beck depression inventory (BDI) for depression, and Hamilton Rating Scale for Anxiety scale (HAM-A) for anxiety. Results: Majority of the study participants in both groups (n = 35, 43.8%) were of 46–50 years old. About 52.5% of diabetic and 17.5% of nondiabetic participants were having depression and 51.3% of diabetic and 18.3% of nondiabetics were having anxiety as per BDI and HAM-A scores, respectively. Although major differences in sociodemographic variables such as socioeconomic class, gender, and place of residence, etc., between the two groups, it was not statistically significant. Conclusion: The present study shows depression and anxiety were more common among diabetic patients than nondiabetic participants. The risk for depression and anxiety is more among male patients, urban population, and those in low-socioeconomic status.

Nuclear reaction cross-sections are an essential ingredient to reliable deterministic and stochastic radiation transport codes used for radiation protection in space and heavy-ion therapy applications. A recent study compared the existing literature data compiled within the open-access GSI-ESA-NASA cross-section database to the models implemented in the transport codes most commonly used for radiation protection in space and heavy-ion therapy applications. The outcome of the comparison was that none of the models fit well the experimental data for all projectile-target systems at all energy ranges. Therefore, the literature data were exploited to optimise the Tripathi–Cucinotta–Wilson model as reported in this work. This model is used as default in FLUKA, TRiP, and SpaceTRiP, it is part of the hybrid-Kurotama (HK) model used in particle and heavy ion transport code (PHITS), and it is implemented in Geant4. The consequences of using the proposed Tripathi–Cucinotta–Wilson optimisation in the HK model are also analysed.

Realistic nuclear reaction cross-section models are an essential ingredient of reliable heavy-ion transport codes. Such codes are used for risk evaluation of manned space exploration missions as well as for ion-beam therapy dose calculations and treatment planning. Therefore, in this study, a collection of total nuclear reaction cross-section data has been generated within a GSI-ESA-NASA collaboration. The database includes the experimentally measured total nucleus–nucleus reaction cross-sections. The Tripathi, Kox, Shen, Kox–Shen, and Hybrid-Kurotama models are systematically compared with the collected data. Details about the implementation of the models are given. Literature gaps are pointed out and considerations are made about which models fit best the existing data for the most relevant systems to radiation protection in space and heavy-ion therapy.

A stable isotope dilution gas chromatography chemical ionization mass spectrometry (GC-CI-MS) method was developed for the quantitative profiling of plasma acylcarnitines. The clean-up procedure was comprised of a solid-phase cation exchange extraction using PRS-columns from which the acylcarnitines were eluted with a barium chloride solution. Isolated acylcarnitines were transformed into acyloxylactones and analyzed by positive GC-CI-MS using isobutane as reactant gas. The selected monitoring of a common ion at m/z [85]+ and the protonated molecular ion enabled a selective and sensitive detection of all C2-C18 acylcarnitines. An accurate quantitation was achieved by the use of stable isotope-labeled internal standards (C2-C18) and acylcarnitines could be analyzed in the sub-nanomolar range. Control values for C2-C18 acylcarnitines in plasma were established. Concentrations ranged from 0.02 micromol/L for C14-acylcarnitine to 4.90 micromol/L for C2-acylcarnitine. The diagnostic suitability of the method was demonstrated for patients with medium-chain acyl-CoA dehydrogenase deficiency and very long-chain acyl-CoA dehydrogenase deficiency.

A novel point mutation in the 3-hydroxy-3methyl-glutaryl coenzyme A lyase gene was found in a Turkish patient with homozygous 3-hydroxy-3-methylglutaric acidemia. Amplification by RT-PCR of the mRNA using a six different pairs of oligonucleotides produced no differences in four of the fragments amplified with respect to the control, but generated two fragments of different size. One was representative of a deletion of 126 bp and the other of an insertion of 78 bp. These abnormal mRNAs resulted from a G–>C transversion at the nucleotide +1 of an intron, which changed the invariant GT dinucleotide of the 5' donor splice site. This was associated with the occurrence of an alternative splicing, which led to the skipping of the whole exon of 126 bp, and also with the activation of one cryptic donor splice site in the same intron. These aberrant spliced mRNAs are predicted to encode two abnormal HMG-CoA lyase proteins: the first results in a protein with an internal deletion of 42 amino acids, whose enzyme activity is largely abolished, as the catalytic site was completely removed; the second contains 17 missense amino acids that precede a stop codon. Northern blot analysis showed that the overall content of these aberrantly spliced mRNAs in proband fibroblasts was the same as that found in control fibroblasts. However, hardly any transcript was observed corresponding to the inserted mutated mRNA when it was examined by a specific probe. To quantify the relative proportion of the two mRNAs, a quantitative RT-PCR (the DNA-mimic PCR reaction) was carried out. Results show that the proportion of the inserted mRNAs with respect to the deleted mRNA is only 1.2%. The father, mother, and two brothers of the proband were heterozygous in the G–>C mutation in the +1 nucleotide of the intron considered, while the two alleles of another brother were free of the mutation.

The electromagnetic momentum loss approach is applied to predict the plasmon drag effect in profile-modulated gold films at different amplitudes of surface modulations. Direct proportionality of energy and momentum transfer in interactions of plasmons and free electrons in metal is proven to be valid for surfaces with relatively low height modulation amplitudes. An equivalent circuit model is discussed, which can provide qualitative description of the plasmon-induced electrical effects in modulated surfaces and surfaces with random roughness.

Diffuse signal changes in the liver on MRI often represent a depositional process with decreased signal when iron or copper is deposited or increased signal with fatty deposition. We present a 68y male with myelodysplasia requiring multiple blood transfusion, resulting in such signal changes.

(1) Scant information is available concerning the characteristics that may favour the acquisition of COVID-19 in patients with inflammatory bowel disease (IBD). Therefore, the aim of this study was to assess these differences between infected and noninfected patients with IBD. (2) This nationwide case−control study evaluated patients with inflammatory bowel disease with COVID-19 (cases) and without COVID-19 (controls) during the period March−July 2020 included in the ENEIDA of GETECCU. (3) A total of 496 cases and 964 controls from 73 Spanish centres were included. No differences were found in the basal characteristics between cases and controls. Cases had higher comorbidity Charlson scores (24% vs. 19%; p = 0.02) and occupational risk (28% vs. 10.5%; p < 0.0001) more frequently than did controls. Lockdown was the only protective measure against COVID-19 (50% vs. 70%; p < 0.0001). No differences were found in the use of systemic steroids, immunosuppressants or biologics between cases and controls. Cases were more often treated with 5-aminosalicylates (42% vs. 34%; p = 0.003). Having a moderate Charlson score (OR: 2.7; 95%CI: 1.3−5.9), occupational risk (OR: 2.9; 95%CI: 1.8−4.4) and the use of 5-aminosalicylates (OR: 1.7; 95%CI: 1.2−2.5) were factors for COVID-19. The strict lockdown was the only protective factor (OR: 0.1; 95%CI: 0.09−0.2). (4) Comorbidities and occupational exposure are the most relevant factors for COVID-19 in patients with IBD. The risk of COVID-19 seems not to be increased by immunosuppressants or biologics, with a potential effect of 5-aminosalicylates, which should be investigated further and interpreted with caution.

We aim to describe the incidence and source of contagion of COVID-19 in patients with IBD, as well as the risk factors for a severe course and long-term sequelae. This is a prospective observational study of IBD and COVID-19 included in the ENEIDA registry (53,682 from 73 centres) between March-July 2020 followed-up for 12 months. Results were compared with data of the general population (National Centre of Epidemiology and Catalonia). A total of 482 patients with COVID-19 were identified. Twenty-eight percent were infected in the work environment, and 48% were infected by intrafamilial transmission, despite having good adherence to lockdown. Thirty-five percent required hospitalization, 7.9% had severe COVID-19 and 3.7% died. Similar data were reported in the general population (hospitalisation 19.5%, ICU 2.1% and mortality 4.6%). Factors related to death and severe COVID-19 were being aged ≥ 60 years (OR 7.1, 95% CI: 1.8-27 and 4.5, 95% CI: 1.3-15.9), while having ≥2 comorbidities increased mortality (OR 3.9, 95% CI: 1.3-11.6). None of the drugs for IBD were related to severe COVID-19. Immunosuppression was definitively stopped in 1% of patients at 12 months. The prognosis of COVID-19 in IBD, even in immunosuppressed patients, is similar to that in the general population. Thus, there is no need for more strict protection measures in IBD.

Background: There is increasing recognition that health care providers need to focus attention, and be judged against, the impact they have on the health outcomes experienced by patients. The measurement of health outcomes as a routine part of clinical documentation is probably the only scalable way of collecting outcomes evidence, since secondary data collection is expensive and error-prone. However, there is uncertainty about whether routinely collected clinical data within electronic health record (EHR) systems includes the data most relevant to measuring and comparing outcomes and if those items are collected to a good enough data quality to be relied upon for outcomes assessment, since several studies have pointed out significant issues regarding EHR data availability and quality., Objective: In this paper, we first describe a practical approach to data quality assessment of health outcomes, based on a literature review of existing frameworks for quality assessment of health data and multistakeholder consultation. Adopting this approach, we performed a pilot study on a subset of 21 International Consortium for Health Outcomes Measurement (ICHOM) outcomes data items from patients with congestive heart failure., Methods: All available registries compatible with the diagnosis of heart failure within an EHR data repository of a general hospital (142,345 visits and 12,503 patients) were extracted and mapped to the ICHOM format. We focused our pilot assessment on 5 commonly used data quality dimensions: completeness, correctness, consistency, uniqueness, and temporal stability., Results: We found high scores (>95%) for the consistency, completeness, and uniqueness dimensions. Temporal stability analyses showed some changes over time in the reported use of medication to treat heart failure, as well as in the recording of past medical conditions. Finally, the investigation of data correctness suggested several issues concerning the characterization of missing data values. Many of these issues appear to be introduced while mapping the IMASIS-2 relational database contents to the ICHOM format, as the latter requires a level of detail that is not explicitly available in the coded data of an EHR., Conclusions: Overall, results of this pilot study revealed good data quality for the subset of heart failure outcomes collected at the Hospital del Mar. Nevertheless, some important data errors were identified that were caused by fundamentally different data collection practices in routine clinical care versus research, for which the ICHOM standard set was originally developed. To truly examine to what extent hospitals today are able to routinely collect the evidence of their success in achieving good health outcomes, future research would benefit from performing more extensive data quality assessments, including all data items from the ICHOM standards set and across multiple hospitals., (©Hannelore Aerts, Dipak Kalra, Carlos Sáez, Juan Manuel Ramírez-Anguita, Miguel-Angel Mayer, Juan M Garcia-Gomez, Marta Durà-Hernández, Geert Thienpont, Pascal Coorevits. Originally published in JMIR Medical Informatics (https://medinform.jmir.org), 04.08.2021.)

Introduction: sleep disorders are common in the general population and have obvious repercussions on quality of life. Poor sleep quality is associated to inflammatory activity and fatigue in inflammatory bowel disease (IBD) patients. This study aimed to analyze the prevalence of poor sleep quality and the factors associated with it, in IBD outpatients., Methods: an observational and prospective study was performed in which epidemiological, clinical and laboratory data were collected from clinical records and patients who consecutively attended an outpatient clinic. Pittsburgh Sleep Quality index (PSQI), Hospital Anxiety and Depression Scale (HADS) and International Physical Activity Questionnaire (IPAQ) were used to measure sleep quality, anxiety, depression and physical activity, respectively. Treatment optimizations, hospital admissions or surgery were prospectively verified three months after the baseline visit., Results: one hundred and two patients were included and 54.9 % had poor sleep quality (PSQI score > 5). No association was found between poor sleep quality and IBD-related variables such as type of disease, ulcerative colitis (UC) extent, Crohn's disease (CD) location or behavior, time from diagnosis, treatment, prior admissions or surgery and laboratory values. Rotating night shift job (OR 6.116, 95 % CI: 1.312-28.514), HAD score for depression (OR 1.125, 95 % CI: 1.062-1.490) and frequency (days per week) of vigorous physical activity (OR 0.783, 95 % CI: 0.619-0.991) were independent predictors of poor sleep quality. A Pittsburgh questionnaire score higher than 5 was not significantly associated to treatment optimization in the total patient cohort (15.2 % vs 18.2 %, p = 0.451), in UC patients (18.2 % vs 10.7 %, p = 0.362) or CD patients (12.5 % vs 25.9 %, p = 0.198)., Conclusions: poor sleep quality is present in more than half of IBD patients. Aspects not directly related to IBD are associated to poor sleep quality.

A 43-year-old female presented to our department with hemoglobin of 3.4 g/dl. She denied gastrointestinal bleeding or weight loss. An upper endoscopy revealed an ulcerative lesion on the greater curvature of the gastric body with two visible clots. Two hemoclips were needed to attain hemostasis, as one of the biopsies of the tumor caused active spurting bleeding. An abdominal computed tomography (CT) demonstrated a well-circumscribed intramural mass arising in the gastric wall, measuring 65 x 50 x 90 mm, with marked internal vascularity and extraluminal component associated. The biopsies identified areas of mature and immature plasmocytes.

Background and Aims: The prevalence of the non-alcoholic fatty liver disease (NAFLD) in developed countries is up to 30% of the general population, and 50% of patients present type 2 diabetes mellitus (DM2). Fibrosis is the most important prognostic factor in NAFLD. The aim of this study was to search evidence for an early diagnosis of liver fibrosis in subjects with DM2 and to evaluate potential risk and protective factors., Methods: This study was conducted among 160 diabetic patients with NAFLD proven biopsy. Anthropometric assessments, laboratory test, liver histological features and follow-up of a Mediterranean diet were evaluated., Results: Diabetic patients with liver fibrosis showed a greater number of positive metabolic criteria than diabetic patients without liver fibrosis. Patients with hepatic fibrosis have a lower score on the PREDIMED test (9.0 (2.4) vs. 6.2 (2.3); p < 0.05). Diabetic patients with liver fibrosis showed higher glucose levels (delta: 10.1 (4.5) mg/dl), fasting insulin levels (delta: 3.1 (1.5) UI/L), HOMA-IR (delta: 2.1 (0.3) units) and HbA1c (delta: 0.6 (0.2)%). Non-invasive tests showed a higher score (non-alcoholic fatty liver disease fibrosis score and fibrosis-4) in liver fibrosis subjects than no liver fibrosis subjects. A logistic regression analysis adjusted by age, gender, HbA1c and body mass index showed independent significant direct association between liver fibrosis and homeostatic model assessment of insulin resistance as indicator of insulin resistance (odds ratio (OR) = 1.53: 95% confidence interval (CI): 1.1-2.2; p = 0.026) and inverse association with PREDIMED score as an indicator of adherence to Mediterranean diet (OR = 0.6; 95% CI: 0.4-0.8; p = 0.01)., Conclusion: In patients with DM2, insulin resistance is an independent risk factor associated with liver fibrosis, and the adherence of a Mediterranean diet is a protective factor associated with absence of liver fibrosis.

Background and Aims: non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disorder in the western world. Although NAFLD prevalence is higher in patients with a BMI > 25 kg /m2, it is unclear if there are differences between overweight and obese patients. The associated biochemical, dietary and genetic parameters were compared between overweight and obese patients with NAFLD., Methods: patients with biopsy-proven NAFLD (n = 203) were enrolled in a cross-sectional study. The MEDAS questionnaire was used to assess adherence to the Mediterranean diet. Biochemical, anthropometrical parameters and the I148M variant (rs738409) of the PNPLA3 gene and rs180069 of the TNF-α gene were evaluated., Results: overweight patients had higher serum adiponectin levels (22.5 ± 21.9 vs 11.2 ± 18.1 ng/ml; p < 0.05) and lower resistin (3.3 ± 1.7 vs 8.1 ± 8 ng/ml; p < 0.001) and leptin concentrations (22.9 ± 21.9 vs 55.8 ± 45 ng/ml; p < 0.001) than obese patients. Non-alcoholic steatohepatitis (NASH) was more frequent in the obese group (59.3% vs 41.3%; p = 0.02). The multivariate analysis showed adherence to the Mediterranean diet to be an independent protective factor for NASH and liver fibrosis in overweight patients (OR 0.7, 95% CI 0.5-0.8)., Conclusions: NASH was more prevalent in obese patients than in overweight subjects. HOMA-IR and adherence to the Mediterranean diet provided protection against fibrosis in overweight patients. Adherence to the Mediterranean diet was the only independent factor associated with NASH in these patients.

Background: non-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in developed countries. Lifestyle changes are the pillar of the treatment, although a pharmacological approach is sometimes required in the case of a failure to respond/adhere to the diet., Objective: the aim of this study was to evaluate the effect of silymarin and the influence of the patatin-like phospholipase domain-containing protein 3 (PNPLA3) variant on the response to treatment in patients with NAFLD in a pilot study., Methods: a total of 54 patients with a NAFLD proven biopsy were enrolled in an open prospective study and were treated with Eurosil 85® (silymarin + vitamin E) for six months. Biochemical parameters and cardiovascular risk factors (diabetes mellitus, dyslipidemia, hypertriglyceridemia, arterial hypertension and HOMA-IR > 2.5) were recorded before and after six months of treatment. Non-invasive indexes (fatty liver index, lipid accumulation product and NAFLD-fibrosis score) were also calculated. The rs738409 PNPLA3 gene polymorphism status was also determined., Results: significant statistical changes from baseline values after six months of treatment were observed in transaminases levels but not in non-invasive index markers. Twenty patients (37.1%) were G allele carriers and had a higher percentage of lobular inflammation and ballooning on the basal liver biopsy. Patients with the G allele had a smaller decrease in transaminases levels after treatment with silymarin + vitamin E than non-G-allele carriers., Conclusions: treatment with silymarin + vitamin E produced a decrease in transaminases after six months of treatment without an accompanying weight loss. PNPLA3 G-allele carriers responded poorly to the treatment.