Not always a miracle - The case of the missing metastasis.

Spontaneous regression of malignant neoplasms is extremely rare, but renal cell carcinomas (RCC) are most often associated with this phenomenon. We report a case of a patient with personal history of RCC, who underwent nephrectomy and no other oncological treatment. One year after nephrectomy, a lung metastasis was detected and kept under follow-up for 3 years. Its size increased over time until a needle biopsy was performed, and its metastatic nature confirmed. Wedge resection of the lung nodule was performed, and no neoplastic cells were found, suggesting its spontaneous regression after biopsy. Different theories have been proposed to explain this phenomenon and, in most cases, the mechanism seems to involve the activation of the immune system. This case supports the importance of reducing tumor burden and the impact of the disturbance of the tumor microenvironment caused by instrumentation, in improving immune system activation and its essential role in neoplasm regression.

Shoulder Pain - Don't Forget First Rib Fractures.

First rib fractures are uncommon, mainly in paediatric population, considering its anatomic features and their skeleton plasticity. Traditional teaching usually characterizes it as a hallmark of severe trauma. Herein, to unfold awareness to an unnoticed diagnosis, we describe two paediatric cases of isolated first rib fracture in adolescents without a clear identifiable cause nor an underlining trauma mechanism. Neurovascular injuries should always be investigated, as fracture of the first rib with ensuing callus formation is a rare but fearing cause of thoracic outlet syndrome. We highlight the scarcity of reports on isolated first rib fractures outside of sports medicine, as well as the importance of considering this otherwise easily missed diagnosis in a common complaint in children.

Knowledge in Inflammatory Bowel Disease: Translation to Portuguese, Validation, and Clinical Application of the IBD-KNOW Questionnaire.

Background/Aims: Inflammatory bowel disease (IBD)-related knowledge empowers patients, providing the development of adaptative coping strategies. Recently, a more comprehensive questionnaire for evaluating IBD-related knowledge was developed, the IBD-KNOW. The main aim of our study was to translate to Portuguese and validate the IBD-KNOW questionnaire. We also explored the predictors of high scores of disease-related knowledge and the effect of knowledge on health-related quality of life (HRQoL) and therapeutic adherence. Methods: This is an observational, unicentric, and cross-sectional study. We translated and adapted the original English version of the IBD-KNOW questionnaire into Portuguese. Afterwards, IBD patients in the outpatient clinics were invited to fill out a multimodal form including the Portuguese version of IBD-KNOW, a visual analogue scale (VAS) of self-perceived knowledge, the Portuguese version of Short IBD Questionnaire (SIBDQ) and the Portuguese version of Morisky Adherence Scale 8-item (MMAS-8). Demographic and disease characteristics were collected. We assessed validity (through discriminate validity among non-IBD volunteers and correlation between IBD-KNOW and VAS) and reliability (through internal consistency, test-retest, and intraclass correlation). Statistical analysis was performed using SPSS version 25.0. Results: The mean IBD-KNOW score was significantly different among non-IBD validation group (doctors: 23, nurses: 18, and non-medical volunteers: 12, p < 0.001). IBD-KNOW showed a high internal consistency (Cronbach's α 0.78) and intraclass correlation (0.90). As expected, the IBD-KNOW score was positively correlated with VAS for self-perceived knowledge (r = 0.45, p < 0.001). One hundred and one patients with IBD (54 with ulcerative colitis and 47 with Crohn's disease) completed the questionnaire at baseline. Multivariate analyses showed that a high IBD-KNOW score was associated with longer disease duration (OR: 2.59 [CI 1.11-5.74]; p = 0.04), previous hospitalization (OR: 3.63 [CI 1.301-9.96]; p = 0.01), current biologic treatment (OR: 3.37 [CI 1.31-8.65]; p = 0.02), and higher educational level (OR: 4.66 [CI 1.74-10.21]; p = 0.02). Moreover, there was no significant correlation between overall IBD-KNOW and SIBDQ, nor between IBD treatment adherence (MMAS-8 = 8) and a higher mean IBD-KNOW score (p = 0.552). Conclusion: The Portuguese version of IBD-KNOW is a simple, valid, and reliable tool for assessing IBD-related knowledge. Longer disease duration, hospitalization, use of biologics, and higher educational level are associated with higher levels of knowledge. Higher patient knowledge was not associated with higher HRQoL and adherence to therapy.

Introdução/objetivos: O conhecimento relacionado com a Doença Inflamatória Intestinal (DII) visa capacitar os doentes, proporcionando o desenvolvimento de estratégias adaptativas de coping. Recentemente, foi desenvolvido um questionário mais abrangente para avaliar os conhecimentos relacionados com a DII, o IBD-KNOW. O principal objetivo do nosso estudo foi traduzir para português e validar o questionário IBD-KNOW. Também explorámos os preditores de um elevado nível de conhecimento relacionado com a DII e avaliámos o impacto do conhecimento na qualidade de vida associada a cuidados de saúde (QVACS) e na adesão terapêutica. Métodos: Este é um estudo observacional, unicêntrico e transversal. Traduzimos e adaptámos para português a versão original inglesa do questionário IBD-KNOW. Posteriormente, os doentes com DII de ambulatório foram convidados a preencher um questionário multimodal que incluía, a versão portuguesa do IBD-KNOW, uma escala visual analógica (EVA) de autoperceção do conhecimento, a versão portuguesa do Short IBD Questionnaire (SIBDQ) e a versão portuguesa do Morisky Adherence Scale 8-item (MMAS-8). Foram colhidos dados referentes a aspetos demográficos e da doença. Avaliámos a validade (através da validade discriminatória entre voluntários sem DII e da correlação entre IBD-KNOW e a EVA) e a fiabilidade (através da consistência interna, do teste-reteste e da correlação intraclasse). A análise estatística foi realizada utilizando a versão 25.0 do SPSS. Resultados: A pontuação média do IBD-KNOW foi significativamente diferente entre os voluntários não-DII (médicos: 23, enfermeiros: 18 e voluntários não-médicos: 12, p < 0,001). O IBD-KNOW mostrou uma elevada consistência interna (Cronbach's α 0,78) e uma correlação intraclasse (0,90). Como esperado, a pontuação IBD-KNOW correlacionou-se positivamente com a EVA de autoperceção do conhecimento (r=0,45, p < 0,001). Cento e um doentes com DII (54 com colite ulcerosa e 47 com doença de Crohn) preencheram o questionário. A análise multivariada mostrou valores médios de IBD-KNOW superiores em indivíduos com doença de longa duração (OR: 2,59; [IC 1,11-5,74] p=0,04), hospitalização prévia (OR 3,63 [IC 1,301-9,96]; p=0,01), sob tratamento biológico atual (OR 3,37 [1,31-8,65]; p=0,02) e com nível educacional superior (OR 4,66 [IC 1,74-10,21]; p=0,02). Além disso, não houve correlação significativa entre IBD-KNOW e SIBDQ, nem entre a adesão ao tratamento IBD (MMAS-8=8) e um IBD-KNOW acima da média (p=0,552). Conclusão: A versão portuguesa do IBD-KNOW é uma ferramenta simples, válida e fiável para avaliar os conhecimentos relacionados com a DII. Uma maior duração da doença, hospitalização, utilização de biológicos e um nível de educação mais elevado estão associados a níveis de conhecimento mais elevados. Na nossa coorte, níveis superiores de conhecimento não se associaram a melhor qualidade de vida nem a maior adesão à terapêutica.

Development and Validation of a META-Algorithm to Identify the Indications of Use of Biological Drugs Approved for the Treatment of Immune-Mediated Inflammatory Diseases from Claims Databases: Insights from the VALORE Project.

Purpose: This research aimed to develop and validate a META-algorithm combining individual immune-mediated inflammatory disease (IMID)-specific algorithms to identify the exact IMID indications for incident biological drug users from claims data within the context of the Italian VALORE project. Methods and Patients: All subjects with at least one dispensing of TNF-alpha inhibitors, anti-interleukin agents, and selective immunosuppressants approved for IMIDs were identified from claims databases of Latium region in Italy (observation period: 2010-2020). Validated coding algorithms for identifying individual IMIDs from claims databases were found from published literature and combined into a META-algorithm. Positive predictive value (PPV), sensitivity (Se), negative predictive value (NPV), specificity (Sp), and accuracy (Acc) were estimated for each indication against the electronic therapeutic plans (ETPs) of the Latium region as the reference standard. Lastly, the frequency of the indication of use across individual biologic drugs was compared with that reported in three other Italian regions (Lombardy, Apulia, and the Veneto region). Results: In total, 9755 incident biological drug users with a single IMID indication were identified. Using the newly developed META-algorithm, an indication of use was detected in 95% (n=9255) of the total cohort. The estimated Acc, Se, Sp, PPV, and NPV, against the reference standard were as follows: 0.96, 0.86, 0.97, 0.82, and 0.98 for Crohn's disease, 0.96, 0.80, 0.98, 0.85, and 0.97 for ulcerative colitis, 0.93, 0.76, 0.99, 0.95, and 0.92 for rheumatoid arthritis, 0.97, 0.75, 0.99, 0.85, and 0.98 for spondylarthritis, and 0.91, 0.92, 0.91, 0.88, and 0.94 for psoriatic arthritis/psoriasis, respectively. Additionally, no substantial difference was observed in the frequency of indication of use by active ingredient among Latium and the other three Italian regions included in the study. Conclusion: The newly developed META-algorithm demonstrated high validity estimates in the Italian claims data and was capable of discriminating with good performance among the most frequent IMID indications.

In the claims database, the lack of information on the indication of use represents a well-known limitation for the conduct of observational studies. This study was conducted to develop and validate a META-algorithm that accurately identifies the exact indication for the use of biological drugs in treating various immune-mediated inflammatory diseases. Using claims databases from the Latium region, we developed and validated a META-algorithm. The META-algorithm combines disease-specific algorithms for different immune-mediated inflammatory diseases (ie, Crohn's disease, ulcerative colitis, rheumatoid arthritis, spondyloarthritis, psoriasis, and psoriatic arthritis) and was tested against a reference standard (electronic therapeutic plans of the Lazio region). The META-algorithm reported high validity estimates and was able to distinguish with a good performance among the most frequent IMIDs as indications for use. Applying this META-algorithm may facilitate post-marketing surveillance of biological drugs such as TNF-alpha inhibitors, anti-interleukin, and selective immunosuppressants in specific therapeutic areas in an Italian setting.

Exploring the potential of cell-derived vesicles for transient delivery of gene editing payloads.

Gene editing technologies have the potential to correct genetic disorders by modifying, inserting, or deleting specific DNA sequences or genes, paving the way for a new class of genetic therapies. While gene editing tools continue to be improved to increase their precision and efficiency, the limited efficacy of in vivo delivery remains a major hurdle for clinical use. An ideal delivery vehicle should be able to target a sufficient number of diseased cells in a transient time window to maximize on-target editing and mitigate off-target events and immunogenicity. Here, we review major advances in novel delivery platforms based on cell-derived vesicles - extracellular vesicles and virus-like particles - for transient delivery of gene editing payloads. We discuss major findings regarding packaging, in vivo biodistribution, therapeutic efficacy, and safety concerns of cell-derived vesicles delivery of gene editing cargos and their potential for clinical translation.

Switching patterns of biological drugs in patients with psoriasis and psoriatic arthritis: insight from the VALORE database network.

BACKGROUND: Switch patterns among different biologics and from originators to biosimilars (and vice versa) can be complex in patients with psoriasis (PsO) and psoriatic arthritis (PsA). OBJECTIVE: The aim of this study was to describe switching patterns of biological drugs in PsO/PsA patients and to explore predictors of multiple switches and switch-back. RESEARCH DESIGN AND METHODS: A large-scale retrospective cohort study was conducted using the Italian VALORE database. Bio-naïve users treated for PsO/PsA during 2010-2022 were included. Time to switch/swap and predictors of multiple switches and switch-back were analyzed. RESULTS: Thirty-thousand seven hundred bio-naïve users were included. At 3 and 5 years of follow-up, patients with at least one switch/swap were 37.1% and 47.8%, respectively. The median time to first switch/swap was significantly shorter (p< 0.001) for TNF-α inhibitors (2,068 days) than anti-IL (2,780 days). At 1 year of follow-up patients starting with IL-23 switched/swapped biological therapy less frequently than those with anti-IL-12/23 and anti-IL-17 (4.9% vs. 8.7% and 9.4%, respectively). Patients starting with anti-IL-12/23 reported a significantly lower risk of multiple switches and switch-back (0.74, 95% CI, 0.67-0.83; 0.58, 95% CI, 0.44-0.77, respectively) than those with TNF-α inhibitors. CONCLUSIONS: Patients with PsO/PsA starting with TNF-α inhibitors switch/swap more rapidly and frequently than those with anti-IL, which are also associated with a reduced risk of multiple switches during follow-up.

Revisiting the utility of identifying nuclear grooves as unique nuclear changes by an object detector model.

BACKGROUND: Among other structures, nuclear grooves are vastly found in papillary thyroid carcinoma (PTC). Considering that the application of artificial intelligence in thyroid cytology has potential for diagnostic routine, our goal was to develop a new supervised convolutional neural network capable of identifying nuclear grooves in Diff-Quik stained whole-slide images (WSI) obtained from thyroid fineneedle aspiration. METHODS: We selected 22 Diff-Quik stained cytological slides with cytological diagnosis of PTC and concordant histological diagnosis. Each of the slides was scanned, forming a WSI. Images that contained the region of interest were obtained, followed by pre-formatting, annotation of the nuclear grooves and data augmentation techniques. The final dataset was divided into training and validation groups in a 7:3 ratio. RESULTS: This is the first artificial intelligence model based on object detection applied to nuclear structures in thyroid cytopathology. A total of 7,255 images were obtained from 22 WSI, totaling 7,242 annotated nuclear grooves. The best model was obtained after it was submitted 15 times with the train dataset (14th epoch), with 67% true positives, 49.8% for sensitivity and 43.1% for predictive positive value. CONCLUSIONS: The model was able to develop a structure predictor rule, indicating that the application of an artificial intelligence model based on object detection in the identification of nuclear grooves is feasible. Associated with a reduction in interobserver variability and in time per slide, this demonstrates that nuclear evaluation constitutes one of the possibilities for refining the diagnosis through computational models.

Colorectal cancer screening: A review of current knowledge and progress in research.

Colorectal cancer (CRC) is one of the most prevalent malignancies worldwide, being the third most commonly diagnosed malignancy and the second leading cause of cancer-related deaths globally. Despite the progress in screening, early diagnosis, and treatment, approximately 20%-25% of CRC patients still present with metastatic disease at the time of their initial diagnosis. Furthermore, the burden of disease is still expected to increase, especially in individuals younger than 50 years old, among whom early-onset CRC incidence has been increasing. Screening and early detection are pivotal to improve CRC-related outcomes. It is well established that CRC screening not only reduces incidence, but also decreases deaths from CRC. Diverse screening strategies have proven effective in decreasing both CRC incidence and mortality, though variations in efficacy have been reported across the literature. However, uncertainties persist regarding the optimal screening method, age intervals and periodicity. Moreover, adherence to CRC screening remains globally low. In recent years, emerging technologies, notably artificial intelligence, and non-invasive biomarkers, have been developed to overcome these barriers. However, controversy exists over the actual impact of some of the new discoveries on CRC-related outcomes and how to effectively integrate them into daily practice. In this review, we aim to cover the current evidence surrounding CRC screening. We will further critically assess novel approaches under investigation, in an effort to differentiate promising innovations from mere novelties.

Isolation of Adeno-associated Viral Vectors Through a Single-step and Semi-automated Heparin Affinity Chromatography Protocol.

Adeno-associated virus (AAV) has become an increasingly valuable vector for in vivo gene delivery and is currently undergoing human clinical trials. However, the commonly used methods to purify AAVs make use of cesium chloride or iodixanol density gradient ultracentrifugation. Despite their advantages, these methods are time-consuming, have limited scalability, and often result in vectors with low purity. To overcome these constraints, researchers are turning their attention to chromatography techniques. Here, we present an optimized heparin-based affinity chromatography protocol that serves as a universal capture step for the purification of AAVs. This method relies on the intrinsic affinity of AAV serotype 2 (AAV2) for heparan sulfate proteoglycans. Specifically, the protocol entails the co-transfection of plasmids encoding the desired AAV capsid proteins with those of AAV2, yielding mosaic AAV vectors that combine the properties of both parental serotypes. Briefly, after the lysis of producer cells, a mixture containing AAV particles is directly purified following an optimized single-step heparin affinity chromatography protocol using a standard fast protein liquid chromatography (FPLC) system. Purified AAV particles are subsequently concentrated and subjected to comprehensive characterization in terms of purity and biological activity. This protocol offers a simplified and scalable approach that can be performed without the need for ultracentrifugation and gradients, yielding clean and high viral titers.

Referral for liver transplant following acute variceal bleeding: a multicenter cohort study.

OBJECTIVES: Referral for liver transplant (LT) following acute variceal bleeding (AVB) varies widely. We aimed to characterize and assess its impact on clinical outcomes. METHODS: Observational retrospective cohort including cirrhosis patients with AVB from 3 hospitals in Lisbon, Portugal, from 2018 to 2019. Primary exposure was referral for LT and primary endpoint was all-cause mortality within 2 years of index hospital admission. RESULTS: Among 143 patients, median (IQR) age was 59 (52-72) years and 90 (62.9%) were males. Median (IQR) MELDNa scores on hospital admission and discharge were 15 (11-21) and 13 (10-16), respectively. Overall, 30 (21.0%) patients were assessed for LT, 13 (9.1%) prior to and 17 (11.9%) within 2 years of hospital admission. Overall, 58 (40.6%) patients had at least one potential contra-indication for transplant. LT was performed in 3 (2.1%) patients (among 5 listed). Overall, 34 (23.8%) and 62 (43.4%) patients died at 6 weeks and 2 years post hospital admission, respectively. Following adjustment for confounders, referral for LT was associated with lower 2-year mortality (aHR (95% CI) = 0.20 (0.05-0.85)). CONCLUSION: In a multicenter cohort of cirrhosis patients with AVB, less than a quarter underwent formal LT evaluation. Improved referral for LT following AVB may benefit cirrhosis patients' longer-term mortality.

Lamin A/C and PI(4,5)P2-A Novel Complex in the Cell Nucleus.

Lamins, the nuclear intermediate filaments, are important regulators of nuclear structural integrity as well as nuclear functional processes such as DNA transcription, replication and repair, and epigenetic regulations. A portion of phosphorylated lamin A/C localizes to the nuclear interior in interphase, forming a lamin A/C pool with specific properties and distinct functions. Nucleoplasmic lamin A/C molecular functions are mainly dependent on its binding partners; therefore, revealing new interactions could give us new clues on the lamin A/C mechanism of action. In the present study, we show that lamin A/C interacts with nuclear phosphoinositides (PIPs), and with nuclear myosin I (NM1). Both NM1 and nuclear PIPs have been previously reported as important regulators of gene expression and DNA damage/repair. Furthermore, phosphorylated lamin A/C forms a complex with NM1 in a phosphatidylinositol-4,5-bisphosphate (PI(4,5)P2)-dependent manner in the nuclear interior. Taken together, our study reveals a previously unidentified interaction between phosphorylated lamin A/C, NM1, and PI(4,5)P2 and suggests new possible ways of nucleoplasmic lamin A/C regulation, function, and importance for the formation of functional nuclear microdomains.

Multiple basal infusion rates in open-loop insulin delivery systems: is there a metabolic benefit?

Objective: To evaluate glycemic control according to the number of daily basal rates (BRs) in type 1 diabetes patients using continuous subcutaneous insulin infusion (CSII). Subjects and methods: Cross-sectional study of patients treated with an open-loop CSII for at least 6 months and using a flash glucose monitoring system. Patients were divided into 2 groups: group 1 (G1) and group 2 (G2), with ≤4 and >4 BRs/24h, respectively. The groups were compared regarding HbA1c, time in range (TIR), time above range (TAR), time below range (TBR), glucose management indicator (GMI), glucose variability and data related to hypoglycemia. Regression models were performed. Results: The study included 99 patients (n = 55 in G1; n = 44 in G2). Median (Interquartile range) overall age was 30 (17) years, with 19.5 (48) and 51 (77) months of CSII use, respectively. The median number of different BRs was 3 (2) for G1 and 6 (2) for G2. There were no differences concerning age, sex, educational stage, weight, and insulin analog used. G2 had longer disease duration, longer CSII use, and higher total basal daily dose/kg. No significant differences regarding HbA1c, median glucose, GMI, TIR, TAR, and CV were found. G2 patients had more hypoglycemia, more asymptomatic hypoglycemia, and higher TBR. After adjusting for potential confounders, G1 maintained a lower risk of asymptomatic hypoglycemia. Conclusion: Programming open-loop CSII devices with more than 4 BRs does not improve metabolic control. Additionally, it seems to be a risk factor for hypoglycemia and was an independent predictor for asymptomatic hypoglycemia.

Bridging the Gap between Field Experiments and Machine Learning: The EC H2020 B-GOOD Project as a Case Study towards Automated Predictive Health Monitoring of Honey Bee Colonies.

Honey bee colonies have great societal and economic importance. The main challenge that beekeepers face is keeping bee colonies healthy under ever-changing environmental conditions. In the past two decades, beekeepers that manage colonies of Western honey bees (Apis mellifera) have become increasingly concerned by the presence of parasites and pathogens affecting the bees, the reduction in pollen and nectar availability, and the colonies' exposure to pesticides, among others. Hence, beekeepers need to know the health condition of their colonies and how to keep them alive and thriving, which creates a need for a new holistic data collection method to harmonize the flow of information from various sources that can be linked at the colony level for different health determinants, such as bee colony, environmental, socioeconomic, and genetic statuses. For this purpose, we have developed and implemented the B-GOOD (Giving Beekeeping Guidance by computational-assisted Decision Making) project as a case study to categorize the colony's health condition and find a Health Status Index (HSI). Using a 3-tier setup guided by work plans and standardized protocols, we have collected data from inside the colonies (amount of brood, disease load, honey harvest, etc.) and from their environment (floral resource availability). Most of the project's data was automatically collected by the BEEP Base Sensor System. This continuous stream of data served as the basis to determine and validate an algorithm to calculate the HSI using machine learning. In this article, we share our insights on this holistic methodology and also highlight the importance of using a standardized data language to increase the compatibility between different current and future studies. We argue that the combined management of big data will be an essential building block in the development of targeted guidance for beekeepers and for the future of sustainable beekeeping.

The lucky polyp: an unusual manifestation of chronic schistosomiasis.

A 23-year-old male from Brazil presented with bright red hematochezia. Proctological examination revealed grade II internal hemorrhoids, but flexible sigmoidoscopy uncovered a 6 mm-pedunculated polyp in the sigmoid colon, which was found to result from inflammatory reaction to Schistosoma mansoni egg deposition. The patient had no signs of portal hypertension and was successfully treated with praziquantel. This case underscores a rare presentation of chronic intestinal schistosomiasis and emphasizes the role of early diagnosis in preventing severe hepatic sequelae of chronic Schistosoma infection.

Artificial intelligence and its clinical application in Anesthesiology: a systematic review.

PURPOSE: Application of artificial intelligence (AI) in medicine is quickly expanding. Despite the amount of evidence and promising results, a thorough overview of the current state of AI in clinical practice of anesthesiology is needed. Therefore, our study aims to systematically review the application of AI in this context. METHODS: A systematic review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. We searched Medline and Web of Science for articles published up to November 2022 using terms related with AI and clinical practice of anesthesiology. Articles that involved animals, editorials, reviews and sample size lower than 10 patients were excluded. Characteristics and accuracy measures from each study were extracted. RESULTS: A total of 46 articles were included in this review. We have grouped them into 4 categories with regard to their clinical applicability: (1) Depth of Anesthesia Monitoring; (2) Image-guided techniques related to Anesthesia; (3) Prediction of events/risks related to Anesthesia; (4) Drug administration control. Each group was analyzed, and the main findings were summarized. Across all fields, the majority of AI methods tested showed superior performance results compared to traditional methods. CONCLUSION: AI systems are being integrated into anesthesiology clinical practice, enhancing medical professionals' skills of decision-making, diagnostic accuracy, and therapeutic response.

Multiple basal infusion rates in open-loop insulin delivery systems: is there a metabolic benefit?

ABSTRACT Objective: To evaluate glycemic control according to the number of daily basal rates (BRs) in type 1 diabetes patients using continuous subcutaneous insulin infusion (CSII). Subjects and methods: Cross-sectional study of patients treated with an open-loop CSII for at least 6 months and using a flash glucose monitoring system. Patients were divided into 2 groups: group 1 (G1) and group 2 (G2), with ≤4 and >4 BRs/24h, respectively. The groups were compared regarding HbA1c, time in range (TIR), time above range (TAR), time below range (TBR), glucose management indicator (GMI), glucose variability and data related to hypoglycemia. Regression models were performed. Results: The study included 99 patients (n = 55 in G1; n = 44 in G2). Median (Interquartile range) overall age was 30 (17) years, with 19.5 (48) and 51 (77) months of CSII use, respectively. The median number of different BRs was 3 (2) for G1 and 6 (2) for G2. There were no differences concerning age, sex, educational stage, weight, and insulin analog used. G2 had longer disease duration, longer CSII use, and higher total basal daily dose/kg. No significant differences regarding HbA1c, median glucose, GMI, TIR, TAR, and CV were found. G2 patients had more hypoglycemia, more asymptomatic hypoglycemia, and higher TBR. After adjusting for potential confounders, G1 maintained a lower risk of asymptomatic hypoglycemia. Conclusion: Programming open-loop CSII devices with more than 4 BRs does not improve metabolic control. Additionally, it seems to be a risk factor for hypoglycemia and was an independent predictor for asymptomatic hypoglycemia.

Sustainable trehalose lipid production by Rhodotorula sp.: a promising bio-based alternative.

Global environmental concerns drive research toward the development of new eco-friendly compounds to replace pollutant chemicals. This study focuses on optimizing the production of trehalose lipids (TLs), which are glycolipid biosurfactants (BS) with various applications like antimicrobial or surface tension reduction. New microorganism sources, growth conditions, medium composition, purification conditions, and physicochemical properties of TLs are studied. Addressing a microscale approach, TLs production was successfully achieved using Rhodotorula sp. and Rhodococcus erythropolis to compare, with different media compositions including glucose-based and salt media supplemented with glycerol, glucose, n-hexadecane, n-dodecane. Liquid-liquid extraction using ethyl acetate and methanol was employed for compound extraction, followed by characterization using analytical methods such as Thin layer chromatography (TLC), High performance liquid chromatography (HPLC), and UHPLC. The produced TLs exhibited a minimum surface tension of 47 mN/m and a critical micellar concentration of 4.4 mg/mL. This study also identified Rhodotorula sp. as a new sustainable producer of TLs with improved productivity.

Severe Acute Liver Injury due to Secondary Hemophagocytic Lymphohistiocytosis: A Case Report.

Severe acute liver injury (ALI) is mostly triggered by viral infections and hepatotoxic drugs; however, it can also be seen in systemic diseases. Hemophagocytic lymphohistiocytosis (HLH) is a rare, immune-mediated syndrome that presents as a life-threatening inflammatory disorder affecting multiple organs. Secondary causes occur mainly in the set of malignancy, infection, and autoimmune disease, and are seldom triggered by vaccination. Although liver involvement is common, presentation as severe ALI is rare. We describe a case of a 65-year-old male with history of low-risk chronic lymphocytic leukemia and rheumatoid arthritis treated with prednisolone who presented with persistent fever and jaundice 1 week after COVID-19 vaccination. The diagnosis was challenging given the predominant liver impairment, characterized by hyperbilirubinemia, transaminases over 1,000 U/L, and prolonged INR, which prompted an extensive investigation and exclusion of autoimmune, toxic, and viral causes of hepatitis. Laboratory workup revealed bicytopenia, hyperferritinemia, which together with organ failure and evidence of hemophagocytosis in bone marrow suggested the diagnosis of HLH. After excluding infectious etiologies, flare of rheumatological disease, and the progression of hematological disease, HLH was diagnosed. He was successfully treated with etoposide and corticosteroids, with dramatic improvement of liver tests. After exclusion of other causes of secondary HLH, the recent vaccination for COVID-19 was the likely trigger. We report a case of double rarity of HLH, as it presented with severe liver dysfunction which was probably triggered by vaccination. In this case, the predominant liver involvement urged extensive investigation of liver disease, so a high index of suspicion was required to make an early diagnosis. Clinicians should consider HLH in patients with unexplained signs and symptoms of systemic inflammatory response and multiorgan involvement, including severe liver involvement as the first presentation.

A lesão hepática aguda (LHA) grave é desencadeada principalmente por infeções virais e hepatotóxicos; contudo, pode ocorrer em condições com envolvimento sistémico. A linfohistiocitose hemofagocítica (LHH) é uma síndrome inflamatória, rara, imunomediada, potencialmente fatal, que pode afetar múltiplos órgãos. A LHH secundária ocorre em contexto de neoplasias, infeções e doenças autoimunes, podendo raramente ser precipitada pela vacinação. Embora seja frequente o envolvimento hepático na LHH, a apresentação como LHA grave é rara. Os autores descrevem o caso de um homem de 65 anos com história de leucemia linfocítica crónica de baixo risco e artrite reumatóide sob prednisolona de 65 anos, que se apresentou com febre persistente e icterícia uma semana após a primeira dose da vacina COVID-19. O diagnóstico constituiu um desafio dado o envolvimento hepático predominante, caracterizado por hiperbilirrubinemia, transaminases acima de 1000 U/L e INR prolongado, o que condicionou uma extensa investigação e exclusão das causas autoimunes, tóxicas, e virais de doença hepática. A presença de bicitopenia e hiperferritinemia, conjuntamente com o desenvolvimento de falências de órgão e evidência de hemofagocitose na medula óssea sugeriram o diagnóstico de LHH. Após exclusão infeções, agudização da doença reumatológica e progressão da doença hematológica, foi feito o diagnóstico de LHH.O doente foi tratado com etoposido e corticosteróides com sucesso, verificando-se uma melhoria dramática das provas hepáticas. Após a exclusão de outras causas de LHH secundária, a recente vacinação foi assumida como provável fator desencadeante. Relatamos um caso raro de LHH, quer pela apresentação com lesão hepática grave, quer pela vacinação como presumível desencadeante. Neste caso, o envolvimento hepático predominante promoveu a uma investigação extensa da doença hepática, tendo sido necessário um elevado índice de suspeição para um diagnóstico atempado. Os médicos devem considerar o diagnóstico de LHH em doentes com sinais e sintomas de resposta inflamatória sistémica, inexplicados que se acompanham por disfunção multiorgânica, nomeadamente disfunção hepática grave como apresentação clínica.