Unraveling the influence of surface functionalities on gas Physisorption: A comprehensive study on SBA-15 nanoporous material from Monte Carlo simulation for improved Textural-Energetic characterization.

In this study, we conducted experimental and Monte Carlo simulation studies in the grand canonical ensemble (GCMC) to investigate the role of molecular orientation and surface heterogeneity on the adsorption of N2 at 77 K. Our research focused on a series of ordered nanoporous materials (SBA-15) with varying degrees of oxygen functionalities. Specifically, we examined the effects of surface heterogeneity on the calculation of pore size distribution (PSD) and the Brunauer-Emmett-Teller (BET) area of porous materials. To provide a comprehensive perspective, we compared our results with three levels of surface oxidation, including a pristine case without any surface oxidation. The results from both our experimental and simulation data reveal the importance of chemical heterogeneity in determining equilibrium properties such as molecular packing within the pores, differential enthalpies of adsorption, and N2 orientation distribution. Our findings suggest that accurate characterization of surface heterogeneity is crucial for understanding gas adsorption in nanoporous materials and for developing better models for predicting their performance in various applications. Moreover, our simulations revealed substantial changes in the molecular orientation of adsorbate particles with increasing surface heterogeneity. This insight provides valuable information about the behavior of molecules within the nanoporous materials, further enhancing our understanding of the complex adsorption processes in these systems.

Hepatotoxicity as dose-limiting toxicity of the combination of bosutinib and atezolizumab in patients with chronic myeloid leukemia. Results of the ZEROLMC study.

In the field of chronic myeloid leukemia (CML), new strategies are needed to increase the rate of successful treatment discontinuations, a crucial goal in this disease. Anti-PD-L1 checkpoint inhibitors are a promising therapeutic approach in CML after the demonstration of an increase of these inhibitory molecules in patients with CML. A phase Ib/II (NCT04793399, registration date March 11, 2021) open-label exploratory trial has been conducted to evaluate the safety of atezolizumab, a humanized anti-PD-L1 antibody, in combination with bosutinib in patients with newly diagnosed chronic phase CML. A total of 36 patients were planned to be enrolled, but the study had to be prematurely terminated due to safety concerns. Nine patients were included in the study, and only 8 went on to receive the combination with atezolizumab. There were a total of 44 adverse events (AEs) during the study period. The most frequent were gastrointestinal (50%), mostly mild (86% grade 1-2). The most serious AEs were hepatic. There were 17 hepatic AEs in 5 patients. Of the hepatic AEs 5 were during the bosutinib monotherapy phase and 12 during the combination phase (AST increase x4, ALT increase x4, blood bilirubin increase x1, alkaline phosphatase elevation x2, GGT increase x2), most of them grade 3-4. There were 2 patients who presented a dose-limiting toxicity; a grade 3 elevation of transaminases, that led to premature termination of the study. The combination of atezolizumab with bosutinib presents hepatotoxicity as a dose-limiting effect and therefore we do not recommend to explore this combination in future studies.

Mineral matrix deposition of MC3T3-E1 pre-osteoblastic cells exposed to silicocarnotite and nagelschmidtite bioceramics: In vitro comparison to hydroxyapatite.

This work presents the effect of the silicocarnotite (SC) and nagelschmidtite (Nagel) phases on in vitro osteogenesis. The known hydroxyapatite of biological origin (BHAp) was used as a standard of osteoconductive characteristics. The evaluation was carried out in conventional and osteogenic media for comparative purposes to assess the osteogenic ability of the bioceramics. First, the effect of the material on cell viability at 24 h, 7 and 14 days of incubation was evaluated. In addition, cell morphology and attachment on dense bioceramic surfaces were observed by fluorescence microscopy. Specifically, alkaline phosphatase (ALP) activity was evaluated as an osteogenic marker of the early stages of bone cell differentiation. Mineralized extracellular matrix was observed by calcium phosphate deposits and extracellular vesicle formation. Furthermore, cell phenotype determination was confirmed by scanning electron microscope. The results provided relevant information on the cell attachment, proliferation, and osteogenic differentiation processes after 7 and 14 days of incubation. Finally, it was demonstrated that SC and Nagel phases promote cell proliferation and differentiation, while the Nagel phase exhibited a superior osteoconductive behavior and could promote MC3T3-E1 cell differentiation to a higher extent than SC and BHAp, which was reflected in a higher number of deposits in a shorter period for both conventional and osteogenic media.

Auditory Profile-Based Hearing Aid Fitting: Self-Reported Benefit for First-Time Hearing Aid Users.

Background: Although hearing aids (HAs) can compensate for reduced audibility, functional outcomes and benefits vary widely across individuals. As part of the Danish 'Better hEAring Rehabilitation' (BEAR) project, four distinct auditory profiles differing in terms of audiometric thresholds and supra-threshold hearing abilities were recently identified. Additionally, profile-specific HA-fitting strategies were proposed. The aim of the current study was to evaluate the self-reported benefit of these profile-based HA fittings in a group of new HA users. Methods: A total of 205 hearing-impaired older adults were recruited from two Danish university hospitals. Participants were randomly allocated to one of two treatment groups: (1) NAL-NL2 gain prescription combined with default advanced feature settings ('reference fitting') or (2) auditory profile-based fitting with tailored gain prescription and advanced feature settings ('BEAR fitting'). Two months after treatment, the participants completed the benefit version of the short form of the Speech, Spatial, and Qualities of Hearing Scale (SSQ12-B) and the International Outcome Inventory for Hearing Aids (IOI-HA) questionnaire. Results: Overall, participants reported a clear benefit from HA treatment. However, no significant differences in the SSQ12-B or IOI-HA scores between the reference and BEAR fittings were found. Conclusion: First-time users experience clear benefits from HA treatment. Auditory profile-based HA fitting warrants further investigation.

Amplitude Compression for Preventing Rollover at Above-Conversational Speech Levels.

Hearing aids provide nonlinear amplification to improve speech audibility and loudness perception. While more audibility typically increases speech intelligibility at low levels, the same is not true for above-conversational levels, where decreases in intelligibility ("rollover") can occur. In a previous study, we found rollover in speech intelligibility measurements made in quiet for 35 out of 74 test ears with a hearing loss. Furthermore, we found rollover occurrence in quiet to be associated with poorer speech intelligibility in noise as measured with linear amplification. Here, we retested 16 participants with rollover with three amplitude-compression settings. Two were designed to prevent rollover by applying slow- or fast-acting compression with a 5:1 compression ratio around the "sweet spot," that is, the area in an individual performance-intensity function with high intelligibility and listening comfort. The third, reference setting used gains and compression ratios prescribed by the "National Acoustic Laboratories Non-Linear 1" rule. Speech intelligibility was assessed in quiet and in noise. Pairwise preference judgments were also collected. For speech levels of 70 dB SPL and above, slow-acting sweet-spot compression gave better intelligibility in quiet and noise than the reference setting. Additionally, the participants clearly preferred slow-acting sweet-spot compression over the other settings. At lower levels, the three settings gave comparable speech intelligibility, and the participants preferred the reference setting over both sweet-spot settings. Overall, these results suggest that, for listeners with rollover, slow-acting sweet-spot compression is beneficial at 70 dB SPL and above, while at lower levels clinically established gain targets are more suited.

Neuroimaging and serum biomarkers of neurodegeneration and neuroplasticity in Parkinson's disease patients treated by intermittent theta-burst stimulation over the bilateral primary motor area: a randomized, double-blind, sham-controlled, crossover trial study.

Background and objectives: Intermittent theta-burst stimulation (iTBS) is a patterned form of excitatory transcranial magnetic stimulation that has yielded encouraging results as an adjunctive therapeutic option to alleviate the emergence of clinical deficits in Parkinson's disease (PD) patients. Although it has been demonstrated that iTBS influences dopamine-dependent corticostriatal plasticity, little research has examined the neurobiological mechanisms underlying iTBS-induced clinical enhancement. Here, our primary goal is to verify whether iTBS bilaterally delivered over the primary motor cortex (M1) is effective as an add-on treatment at reducing scores for both motor functional impairment and nonmotor symptoms in PD. We hypothesize that these clinical improvements following bilateral M1-iTBS could be driven by endogenous dopamine release, which may rebalance cortical excitability and restore compensatory striatal volume changes, resulting in increased striato-cortico-cerebellar functional connectivity and positively impacting neuroglia and neuroplasticity. Methods: A total of 24 PD patients will be assessed in a randomized, double-blind, sham-controlled crossover study involving the application of iTBS over the bilateral M1 (M1 iTBS). Patients on medication will be randomly assigned to receive real iTBS or control (sham) stimulation and will undergo 5 consecutive sessions (5 days) of iTBS over the bilateral M1 separated by a 3-month washout period. Motor evaluation will be performed at different follow-up visits along with a comprehensive neurocognitive assessment; evaluation of M1 excitability; combined structural magnetic resonance imaging (MRI), resting-state electroencephalography and functional MRI; and serum biomarker quantification of neuroaxonal damage, astrocytic reactivity, and neural plasticity prior to and after iTBS. Discussion: The findings of this study will help to clarify the efficiency of M1 iTBS for the treatment of PD and further provide specific neurobiological insights into improvements in motor and nonmotor symptoms in these patients. This novel project aims to yield more detailed structural and functional brain evaluations than previous studies while using a noninvasive approach, with the potential to identify prognostic neuroprotective biomarkers and elucidate the structural and functional mechanisms of M1 iTBS-induced plasticity in the cortico-basal ganglia circuitry. Our approach may significantly optimize neuromodulation paradigms to ensure state-of-the-art and scalable rehabilitative treatment to alleviate motor and nonmotor symptoms of PD.

Incidental finding of intraductal papillary mucinous tumor with adenocarcinoma focus after variceal bleeding.

Case of a young female patient with reflux symptoms. During gastroscopy, the patient presented an episode of gastrointestinal bleeding after biopsy of a fundic lesion. Imaging tests were requested, showing a 8cm pancreatic cyst causing obstruction of the splenic vein with presence of portal hypertension and secondary gastric varices.

The Relevance of Implementing the Systematic Screening of Perioperative Myocardial Injury in Noncardiac Surgery Patients.

Perioperative myocardial injury (PMI) is a common cardiac complication. Recent guidelines recommend its systematic screening using high-sensitivity cardiac troponin (hs-cTn). However, there is limited evidence of local screening programs. We conducted a prospective, single-center study aimed at assessing the feasibility and outcomes of implementing systematic PMI screening. Hs-cTn concentrations were measured before and after surgery. PMI was defined as a postoperative hs-cTnT of ≥14 ng/L, exceeding the preoperative value by 50%. All patients were followed-up during the hospitalization, at one month and one year after surgery. The primary outcome was the incidence of death and major cardiovascular and cerebrovascular events (MACCE). The secondary outcomes focused on the individual components of MACCE. We included two-thirds of all eligible high-risk patients and achieved almost complete compliance with follow-ups. The prevalence of PMI was 15.7%, suggesting a higher presence of cardiovascular (CV) antecedents, increased perioperative CV complications, and higher preoperative hs-cTnT values. The all-cause death rate was 1.7% in the first month, increasing up to 11.2% at one year. The incidence of MACCE was 9.5% and 8.6% at the same time points. Given the observed elevated frequencies of PMI and MACCE, implementing systematic PMI screening is recommendable, particularly in patients with increased cardiovascular risk. However, it is important to acknowledge that achieving optimal screening implementation comes with various challenges and complexities.

Surface-acoustic-wave-driven graphene plasmonic sensor for fingerprinting ultrathin biolayers down to the monolayer limit.

Surface plasmon polaritons in graphene can enhance the performance of mid-infrared spectroscopy, which is key for the study of both the composition and the conformation of organic molecules via their vibrational resonances. In this paper, a plasmonic biosensor using a graphene-based van der Waals heterostructure on a piezoelectric substrate is theoretically demonstrated, where far-field light is coupled to surface plasmon-phonon polaritons (SPPPs) through a surface acoustic wave (SAW). The SAW creates an electrically-controlled virtual diffraction grating, suppressing the need for patterning the 2D materials, that limits the polariton lifetime, and enabling differential measurement schemes, which increase the signal-to-noise ratio and allow a quick commutation between reference and sample signals. A transfer matrix method has been used for simulating the SPPPs propagating in the system, which are electrically tuned to interact with the vibrational resonances of the analytes. Furthermore, the analysis of the sensor response with a coupled oscillators model has proven its capability of fingerprinting ultrathin biolayers, even when the interaction is too weak to induce a Fano interference pattern, with a sensitivity down to the monolayer limit, as tested with a protein bilayer or a peptide monolayer. The proposed device paves the way for the development of advanced SAW-assisted lab-on-chip systems combining the existing SAW-mediated physical sensing and microfluidic functionalities with the chemical fingerprinting capability of this novel SAW-driven plasmonic approach.

Impact of the COVID-19 Pandemic in Spain in the Successive Pandemic Waves on Hemodialysis Patients and Healthcare Personnel.

(1) Background: The impact of SARS-CoV-2 has been variable over the time course of the pandemic and in different populations. The aim was to analyze the impact of COVID-19 infection in a known population of hemodialysis (HD) patients and professionals in Spain at different times of the pandemic. (2) Methods: We conducted an observational, descriptive study with a follow-up from 3 March 2020 to 23 April 2022 (776 days), using in average of 414 professionals and 1381 patients from 18 HD units in Spain. The data from the positive PCR or the rapid antigen detection test (RADT) subject were analyzed and segmented into six periods (waves). (3) Results: Of 703 positive COVID-19 tests, 524 were HD patients (74.5%), and 179 were HD professionals (25.5%). Overall, 38% of staff and 43% of patients were affected. Differences were observed in regard to incidence (21% vs. 13%), mortality (3.5% vs. 0%), and symptomatology between the patients and professionals and throughout the pandemic. (4) Conclusions: COVID-19 severity varied during different pandemic waves, with a greater impact seen in the first wave. HD professionals and patients had similar infection rates, but patients had higher mortality rates. Community transmission was the primary route of infection.

Application of IPSET-thrombosis in 1366 Patients Prospectively Followed From the Spanish Registry of Essential Thrombocythemia.

The International Prognostic Score of thrombosis in Essential Thrombocythemia (IPSET-thrombosis) and its revised version have been proposed to guide thrombosis prevention strategies. We evaluated both classifications to prognosticate thrombosis in 1366 contemporary essential thrombocythemia (ET) patients prospectively followed from the Spanish Registry of ET. The cumulative incidence of thrombosis at 10 years, taking death as a competing risk, was 11.4%. The risk of thrombosis was significantly higher in the high-risk IPSET-thrombosis and high-risk revised IPSET-thrombosis, but no differences were observed among the lower risk categories. Patients allocated in high-risk IPSET-thrombosis (subdistribution hazard ratios [SHR], 3.7 [95% confidence interval, CI, 1.6-8.7]) and high-risk revised IPSET-thrombosis (SHR, 3.2 [95% CI, 1.4-7.45]) showed an increased risk of arterial thrombosis, whereas both scoring systems failed to predict venous thrombosis. The incidence rate of thrombosis in intermediate risk revised IPSET-thrombosis (aged >60 years, JAK2-negative, and no history of thrombosis) was very low regardless of the treatment administered (0.9% and 0% per year with and without cytoreduction, respectively). Dynamic application of the revised IPSET-thrombosis showed a low rate of thrombosis when patients without history of prior thrombosis switched to a higher risk category after reaching 60 years of age. In conclusion, IPSET-thrombosis scores are useful for identifying patients at high risk of arterial thrombosis, whereas they fail to predict venous thrombosis. Controlled studies are needed to determine the appropriate treatment of ET patients assigned to the non-high-risk categories.

Hybrid-APC treatment for gastric vascular ectasia of atypical location after failed radiofrequency ablation.

A 76-year-old woman was being followed up for chronic anemia secondary to bleeding from vascular ectasias at the gastric antrum and the cardial and subcardial region. On several occasions the patient required fulguration of these lesions with conventional APC, which resulted in no clear improvement. Radiofrequency ablation of these lesions was then attempted using a 90-degree probe, which was successful on antral angiodysplasias but failed to remove lesions in the cardial and subcardial region since anatomy there prevented proper apposition of the probe onto the target mucosa. Given the absence of any improvement, it was decided to use fulguration for angiectasias at the cardial and subcardial level by means of Hybrid-APC, which consists of lifting the mucosa with an injection through the APC probe and then fulgurating in the pulsedAPC® mode, thus achieving a broader ablation area in a shorter time. During the subsequent review a clear reduction of vascular ectasias was observed.

Projected clinical benefits of dapagliflozin in patients with heart failure with preserved ejection fraction.

Aims: To address the projected clinical benefits of dapagliflozin among patients with heart failure (HF) with mildly reduced ejection fraction (HFmrEF) and preserved ejection fraction (HFpEF). Methods: A multicenter, prospective, cohort study of patients ≥50 years admitted with HF to Spanish internal medicine departments. The projected clinical benefits of dapagliflozin were calculated from the DELIVER trial. Results: A total of 4049 patients were included; 3271 (80.8%) were eligible for dapagliflozin treatment, according to DELIVER criteria. Within 1 year after discharge, 22.2% were rehospitalized for HF and 21.6% died. Implementation of dapagliflozin would translate into an absolute risk reduction of 1.3% for mortality and 5.1% for HF readmission. Conclusion: HF patients with preserved or mildly reduced ejection fraction have a high risk of events. The use of dapagliflozin could substantially reduce the HF burden.

Heart failure (HF) with preserved ejection fraction is frequent in clinical practice, particularly in the elderly. In HF with preserved ejection fraction, the heart still pumps a similar proportion of blood, but the heart muscle has become thicker. This means there is less space inside the heart to fill with blood, so too little is pumped out each time. Until very recently, no drugs had been shown to provide significant benefits on the outcome of the condition or the chance of recovery for these patients. Fortunately, recent clinical trials have demonstrated that treatment with drugs called SGLT2 inhibitors (e.g., dapagliflozin) could reduce the chance of being admitted to hospital or dying from HF. We investigated the benefits for patients who took dapagliflozin after being admitted to hospital and had HF with mildly reduced or preserved ejection fraction. We saw substantial benefits in this population.

Pediatric Intraoperative Neurophysiological Monitoring and Long-Term Outcomes in a Developing Country.

PURPOSE: Pediatric intraoperative neurophysiological monitoring (IONM) has been shown to be effective in preventing and reversing postoperative neurological deficits in developed countries. There are currently no published studies from developing countries that describe neurophysiological findings and postoperative outcomes. Our study aims to address these gaps in children undergoing neurosurgical procedures in a single center. METHODS: We conducted a retrospective study of case series of children who underwent IONM (2014-2020) in the State of Mexico, Mexico. Sociodemographic characteristics, IONM modalities, changes during procedures, and short-term and long-term postoperative results were recorded. Descriptive statistics were used. RESULTS: We included 35 patients (≤18 years of age), 57% (20/35) boys. A relative increase of up to 5 times in the use of IONM is observed from 2014 (5.7%) to 2020 (25.7%) in our center. The most frequent preoperative pathologies were located at the infratentorial cranium (40%), followed by the spine and spinal cord (37.1%). The IONM modalities were as follows: free-running EMG 94.3%, transcranial electrical stimulation motor-evoked potentials 91.4%, somatosensory-evoked potentials 85.7%, triggered EMG 28.6%, EEG 25.7%, and visual-evoked potentials 5.7%. Only in 8.3%, we did not obtain sufficient evoked potential baseline signals. At 24 hours postoperatively true negatives were 100%. Long-term follow-up was completed in 22/35 (63%) at 3 months, 12/35 (34.2%) at 6 months, and 5/35 (14.3%) at 12 months with progressive motor and sensory improvement. CONCLUSIONS: Pediatric multimodal IONM in neurosurgeries from a single center in a developing country is mainly used in pathologies of the posterior fossa, spine, and spinal cord, with true negatives in 100% of those monitored, preventing and avoiding postoperative sequelae.

Early biochemical analysis of COVID-19 patients helps severity prediction.

COVID-19 pandemic has put the protocols and the capacity of our Hospitals to the test. The management of severe patients admitted to the Intensive Care Units has been a challenge for all health systems. To assist in this challenge, various models have been proposed to predict mortality and severity, however, there is no clear consensus for their use. In this work, we took advantage of data obtained from routine blood tests performed on all individuals on the first day of hospitalization. These data has been obtained by standardized cost-effective technique available in all the hospitals. We have analyzed the results of 1082 patients with COVID19 and using artificial intelligence we have generated a predictive model based on data from the first days of admission that predicts the risk of developing severe disease with an AUC = 0.78 and an F1-score = 0.69. Our results show the importance of immature granulocytes and their ratio with Lymphocytes in the disease and present an algorithm based on 5 parameters to identify a severe course. This work highlights the importance of studying routine analytical variables in the early stages of hospital admission and the benefits of applying AI to identify patients who may develop severe disease.

Comparison of hearing aid fitting effectiveness with audiograms from either user-operated or traditional audiometry in a clinical setting: a study protocol for a blinded non-inferiority randomised controlled trial.

INTRODUCTION: There is a worldwide need to enhance the capacity of audiometry testing. The objective of this study is to compare the User-operated Audiometry (UAud) system with traditional audiometry in a clinical setting, by investigating if hearing aid effectiveness based on UAud is non-inferior to hearing aid effectiveness based on traditional audiometry, and whether thresholds obtained with the user-operated version of the Audible Contrast Threshold (ACT) test correlates to traditional measures of speech intelligibility. METHODS AND ANALYSIS: The design will be a blinded non-inferiority randomised controlled trial. 250 adults referred for hearing aid treatment will be enrolled in the study. Study participants will be tested using both traditional audiometry as well as the UAud system and they will answer the questionnaire Speech, Spatial and Qualities of Hearing Scale (SSQ12) at baseline. Participants will be randomly divided to receive hearing aids fitted based on either UAud or traditional audiometry. Three months after participants have started using their hearing aids, they will undergo a hearing in noise test with hearing aids to measure their speech-in-noise performance and answer the following questionnaires: SSQ12, the Abbreviated Profile of Hearing Aid Benefit and the International Outcome Inventory for Hearing Aids. The primary outcome is a comparison of the change in SSQ12 scores from baseline to follow-up between the two groups. Participants will undergo the user-operated ACT test of spectro-temporal modulation sensitivity as part of the UAud system. The ACT results will be compared with measures of speech intelligibility from the traditional audiometry session and follow-up measurements. ETHICS AND DISSEMINATION: The project was evaluated by the Research Ethics Committee of Southern Denmark and judged not to need approval. The findings will be submitted to an international peer-reviewed journal and presented at national and international conferences. TRIAL REGISTRATION NUMBER: NCT05043207.

Sensbio: an online server for biosensor design.

Allosteric transcription factor (aTF) based biosensors can be used to engineer genetic circuits for a wide range of applications. The literature and online databases contain hundreds of experimentally validated molecule-TF pairs; however, the knowledge is scattered and often incomplete. Additionally, compared to the number of compounds that can be produced in living systems, those with known associated TF-compound interactions are low. For these reasons, new tools that help researchers find new possible TF-ligand pairs are called for. In this work, we present Sensbio, a computational tool that through similarity comparison against a TF-ligand reference database, is able to identify putative transcription factors that can be activated by a given input molecule. In addition to the collection of algorithms, an online application has also been developed, together with a predictive model created to find new possible matches based on machine learning.

Toxicity of Asciminib in Real Clinical Practice: Analysis of Side Effects and Cross-Toxicity with Tyrosine Kinase Inhibitors.

(1) Background: Despite the prognostic improvements achieved with tyrosine kinase inhibitors (TKIs) in chronic myeloid leukemia (CML), a minority of patients still fail TKIs. The recent introduction of asciminib may be a promising option in intolerant patients, as it is a first-in-class inhibitor with a more selective mechanism of action different from the ATP-competitive inhibition that occurs with TKIs. Therefore, our goal was to analyze toxicities shown with asciminib as well as to study cross-toxicity with previous TKIs. (2) Methods: An observational, multicenter, retrospective study was performed with data from 77 patients with CML with therapeutic failure to second-generation TKIs who received asciminib through a managed-access program (MAP) (3) Results: With a median follow-up of 13.7 months, 22 patients (28.5%) discontinued treatment: 32% (7/22) due to intolerance and 45% (10/22) due to resistance. Fifty-five percent of the patients reported adverse effects (AEs) with asciminib and eighteen percent grade 3-4. Most frequent AEs were: fatigue (18%), thrombocytopenia (17%), anemia (12%), and arthralgias (12%). None of the patients experienced cardiovascular events or occlusive arterial disease. Further, 26%, 25%, and 9% of patients required dose adjustment, temporary suspension, or definitive discontinuation of treatment, respectively. Toxicities under asciminib seemed lower than with prior TKIs for anemia, cardiovascular events, pleural/pericardial effusion, diarrhea, and edema. Cross-toxicity risk was statistically significant for thrombocytopenia, anemia, neutropenia, fatigue, vomiting, and pancreatitis. (4) Conclusion: Asciminib is a molecule with a good safety profile and with a low rate of AEs. However, despite its new mechanism of action, asciminib presents a risk of cross-toxicity with classical TKIs for some AEs.

Disseminated multidrug-resistant tuberculosis and SARS-CoV-2 co-infection in a child with IL-12Rß1 deficiency.

Mendelian Susceptibility to Mycobacterial Disease describes a spectrum of inherited defects, of which complete deficiency of the interleukin-12 receptor ß subunit 1 (IL-12Rß1) is the most common cause. This condition results in a predisposition to severe disease caused by mycobacteria. We report a case of disseminated multidrug-resistant tuberculosis with extensive central nervous system affection with SARS-CoV-2 co-infection, in a 4-year-old child with IL-12Rß1 complete deficiency.