Deprescribing in older patients with advanced cancer referred to palliative care.

OBJECTIVES: This study aimed to explore the prevalence of potentially inappropriate medications (PIMs) in a cohort of older adults with advanced cancer referred to palliative care. Secondary objectives were to describe the categories of identified PIMs and assess risk factors associated with their presence in this population. METHODS: This retrospective, observational study evaluated patients with advanced cancer admitted to a tertiary university hospital in Madrid, Spain and referred to palliative care between 1 January 2020 and 30 June 2020. Demographic, clinical, and pharmacotherapeutic data were obtained from the electronic medical records and regional databases. PIMs were assessed using the Screening Tool of Older Persons Prescriptions in Frail adults (STOPPFrail) criteria, V1. RESULTS: Among 123 patients (median age 80 years (IQR 73.5-87), 64.2% male), 74% presented at least one PIM according to the STOPPFrail criteria. The most common categories of inappropriate medications were lipid-lowering therapies, proton pump inhibitors, calcium supplements, and oral antidiabetics. The number of chronic comedications was significantly associated with PIM presence. CONCLUSIONS: Our study found a high prevalence of PIM among a cohort of older adults with advanced cancer and short life expectancy. This underlines the need for a comprehensive medication review to optimise pharmacotherapy in this population.

Impact of bacterial and fungal inoculants on the resident rhizosphere microbiome and the volatilome of tomato plants under leaf herbivory stress.

Various studies have addressed the impact of microbial inoculants on the composition of the resident microbiome. How microbial inoculants impact plant metabolism and interact with the resident rhizobiota under herbivory stress remains elusive. Here, we investigated the impact of two bacterial and two fungal inoculants, inoculated as single species and as a synthetic community, on the rhizosphere microbiome and volatilome of tomato plants (Solanum lycopersicum) comparing nonstress conditions to exposed to leaf herbivory by Spodoptera exigua. Based on amplicon sequencing analysis, rhizobacterial community composition was significantly affected by all four inoculants and the magnitude of this effect was dependent on herbivory stress. Fungal community composition was altered by the microbial inoculants but independent of herbivory stress. The rhizosphere volatilome was impacted by the microbial inoculation and differences between treatments were evened under herbivory stress. Each microbial inoculant caused unique changes in the volatilome of stressed plants but also shared similar responses, in particular the enhanced production of dimethyl disulfide and benzothiazole. In conclusion, the introduction of microbial inoculants in the tomato rhizosphere caused unique as well as common changes in the rhizosphere microbiome and volatilome, but these changes were minor compared to the microbiome changes induced by herbivory stress.

Prevalence and clinical consequences of Hepatitis C virus infection in patients undergoing hematopoietic stem cell transplantation.

Hepatitis C virus (HCV) infection is a significant cause of morbidity and mortality among hematopoietic stem cell transplant (HCT) recipients. In Brazil, its occurrence in HCT recipients remains undetermined. We now report on HCV prevalence in HCT recipients and its clinical consequences. The medical records of all HCT recipients seen at Hospital das Clinicas, Sao Paulo University Medical School, from January 2010 to January 2020 were reviewed to determine HCV serostatus. A retrospective analysis of medical charts was undertaken on all seropositive cases to determine HCV genotype, presence of liver fibrosis, co-infections with other viruses, previous treatments, and clinical evolution of liver pathology after HCT. Of the 1,293 HCT recipients included in the study, seven (0.54%) were HCV antibody-positive and five (0.39%) were also viremic for HCV-RNA. Four of these individuals had moderate to severe liver fibrosis (METAVIR F2/F3) and one was cirrhotic. Two of the viremic patients developed acute liver dysfunction following transplantation. All patients had their acute episode of liver dysfunction resolved with no further complications. Four of the viremic patients were treated for HCV infection with direct acting agents (DAA). Information regarding HCV treatment was lacking for one of the viremic HCV patients due to loss of follow up. Sustained anti-virologic responses were observed in three cases after the use of DAA. The detection of HCV in hematological adults undergoing HCT and its successful treatment with DAA highlight the necessity of testing for HCV both prior to and following transplantation.

RIPK3 and kidney disease / RIPK3 y nefropatía

Receptor interacting protein kinase 3 (RIPK3) is an intracellular kinase at the crossroads of cell death and inflammation. RIPK3 contains a RIP homotypic interaction motif (RHIM) domain which allows interactions with other RHIM-containing proteins and a kinase domain that allows phosphorylation of target proteins. RIPK3 may be activated through interaction with RHIM-containing proteins such as RIPK1, TRIF and DAI (ZBP1, DLM-1) or through RHIM-independent mechanisms in an alkaline intracellular pH. RIPK3 mediates necroptosis and promotes inflammation, independently of necroptosis, through either activation of NFκB or the inflammasome. There is in vivo preclinical evidence of the contribution of RIPK3 to both acute kidney injury (AKI) and chronic kidney disease (CKD) and to the AKI-to-CKD transition derived from RIPK3 deficient mice or the use of small molecule RIPK3 inhibitors. In these studies, RIPK3 targeting decreased inflammation but kidney injury improved only in some contexts. Clinical translation of these findings has been delayed by the potential of some small molecule inhibitors of RIPK3 kinase activity to trigger apoptotic cell death by inducing conformational changes of the protein. A better understanding of the conformational changes in RIPK3 that trigger apoptosis, dual RIPK3/RIPK1 inhibitors or repurposing of multiple kinase inhibitors such as dabrafenib may facilitate clinical development of the RIPK3 inhibition concept for diverse inflammatory diseases, including kidney diseases (AU)

La proteína quinasa 3 que interactúa con el receptor (RIPK3) es una quinasa intracelular que se encuentra a medio camino entre la muerte celular y la inflamación. La RIPK3 contiene un dominio motivo de interacción homotípica de RIP (RHIM), que permite las interacciones con otras proteínas que contienen RHIM, y un dominio de quinasa que permite la fosforilación de las proteínas diana. La RIPK3 puede ser activada a través de la interacción con las proteínas que contienen RHIM tales como RIPK1, TRIF y DAI (ZBP1, DLM-1), o a través de mecanismos independientes de RHIM en un pH intracelular alcalino. La RIPK3 media en la necroptosis y promueve la inflamación, independientemente de la necroptosis, bien a través de la activación de NFκB, o del inflamasoma. Existe evidencia preclínica in vivo de la contribución de RIPK3 a la insuficiencia renal aguda (IRA) y la enfermedad renal crónica (ERC), así como a la transición IRA-ERC derivada de ratones con deficiencia de RIPK3 o del uso de pequeñas moléculas inhibidoras de RIPK3. En dichos estudios, el tener a RIPK3 como objetivo redujo la inflamación, pero la nefropatía mejoró solo en algunos contextos. La traducción clínica de estos hallazgos se ha demorado debido al potencial de ciertas pequeñas moléculas inhibidoras de la actividad de la quinasa RIPK3 para activar la muerte celular induciendo cambios conformacionales de la proteína. Comprender mejor los cambios conformacionales de RIPK3 activadores de la apoptosis, los inhibidores duales RIPK3/RIPK1 o la reconversión de múltiples inhibidores de la quinasa tales como dabrafenib podría facilitar el desarrollo clínico del concepto de la inhibición de RIPK3 para diversas enfermedades inflamatorias, incluyendo las enfermedades renales (AU)

An algorithm based on immunotherapy discontinuation and liver biopsy spares corticosteroids in two thirds of cases of severe checkpoint inhibitor-induced liver injury.

BACKGROUND: There are few data on corticosteroids (CS)-sparing strategies for checkpoint inhibitor (ICI)-induced liver injury (ChILI). AIM: We aimed to assess the performance of a 2-step algorithm for severe ChILI, based on ICI temporary discontinuation (step-1) and, if lack of biochemical improvement, CS based on the degree of necroinflammation at biopsy (step-2). METHODS: Prospective study that included all subjects with grade 3/4 ChILI. Peripheral extended immunophenotyping was performed. Indication for CS: severe necroinflammation; mild or moderate necroinflammation with later biochemical worsening. RESULTS: From 111 subjects with increased transaminases (January 2020 to August 2023), 44 were diagnosed with grade 3 (N = 35) or grade 4 (N = 9) ChILI. Main reason for exclusion was alternative diagnosis. Lung cancer (13) and melanoma (12) were the most common malignancies. ICI: 23(52.3%) anti-PD1, 8(18.2%) anti-PD-L1, 3(6.8%) anti-CTLA-4, 10(22.7%) combined ICI. Liver injury pattern: hepatocellular (23,52.3%) mixed (12,27.3%) and cholestatic (9,20.5%). 14(32%) presented bilirubin >1.2 mg/dL. Overall, 30(68.2%) patients did not require CS: 22(50.0%) due to ICI discontinuation (step-1) and 8/22 (36.4%) based on the degree of necroinflammation (step-2). Biopsy mainly impacted on grade 3 ChILI, sparing CS in 8 out of 15 (53.3%) non-improvement patients after ICI discontinuation. CD8+ HLA-DR expression (p = 0.028), central memory (p = 0.046) were lower in CS-free managed subjects, but effector-memory cells (p = 0.002) were higher. Time to transaminases normalisation was shorter in those CS-free managed (overall: p < 0.001, grade 3: p < 0.001). Considering our results, a strategy based on ICI discontinuation and biopsy for grade 3 ChILI is proposed. CONCLUSIONS: An algorithm based on temporary immunotherapy discontinuation and biopsy allows CS avoidance in two thirds of cases of severe ChILI.

Beyond the acute phase: a comprehensive literature review of long-term sequelae resulting from infectious diseases.

Infectious diseases have consistently served as pivotal influences on numerous civilizations, inducing morbidity, mortality, and consequently redirecting the course of history. Their impact extends far beyond the acute phase, characterized by the majority of symptom presentations, to a multitude of adverse events and sequelae that follow viral, parasitic, fungal, or bacterial infections. In this context, myriad sequelae related to various infectious diseases have been identified, spanning short to long-term durations. Although these sequelae are known to affect thousands of individuals individually, a comprehensive evaluation of all potential long-term effects of infectious diseases has yet to be undertaken. We present a comprehensive literature review delineating the primary sequelae attributable to major infectious diseases, categorized by systems, symptoms, and duration. This compilation serves as a crucial resource, illuminating the long-term ramifications of infectious diseases for healthcare professionals worldwide. Moreover, this review highlights the substantial burden that these sequelae impose on global health and economies, a facet often overshadowed by the predominant focus on the acute phase. Patients are frequently discharged following the resolution of the acute phase, with minimal long-term follow-up to comprehend and address potential sequelae. This emphasizes the pressing need for sustained vigilance, thorough patient monitoring, strategic health management, and rigorous research to understand and mitigate the lasting economic and health impacts of infectious diseases more fully.

Structural and mechanical anisotropy in plant-based meat analogues.

The rising demand for plant-based meat analogues as alternatives to animal products has sparked interest in understanding the complex interplay between their structural and mechanical properties. The ability to manipulate the processing parameters and protein blend composition offers fundamental insights into the texturization process and holds economic and sustainable implications for the food industry. Consequently, the correlation between mechanical and structural properties in meat analogues is crucial for achieving consumer satisfaction and successful market penetration, providing comprehensive insights into the textural properties of meat analogues and their potential to mimic traditional animal produce. Our study delves into the relationship between structural and mechanical anisotropy in meat analogues produced using high moisture extrusion cooking, which involves blending protein, water, and other ingredients, followed by a controlled heating and cooling process to achieve a fibrous texture akin to traditional meat. By employing techniques such as scanning small-angle X-ray scattering, scanning electron microscopy, and mechanical testing we investigate the fibrous structure and its impact on the final texture of meat analogues. We show that textural and structural anisotropy is reflected on the mechanical properties measured using tensile and dynamic mechanical techniques. It is demonstrated that the calculated anisotropy indexes, a measure for the degree of textural and structural anisotropy, increase with increasing protein content. Our findings have significant implications for the understanding and development of plant-based meat analogues with structures that can be tuned to closely resemble the animal meat textures of choice, thereby enabling consumers to transition to more sustainable dietary choices while preserving familiar eating habits.

Ultrasound-guided peripheral intravenous canulation by emergency nurses: A systematic review and meta-analysis.

BACKGROUND: Peripheral intravenous cannulation is a common procedure in the emergency department. Nevertheless, failure rates during the first attempt are as high as 40% in adults and 65% in children. Evidence suggests that physician performed ultrasound-guided peripheral intravenous cannulation (USG-PIVC) is an effective alternative to the traditional method; however, there is insufficient data on the efficacy of the technique performed by nurses. OBJECTIVE: To examine the efficacy of the USG-PIVC technique performed by emergency department nurses. METHODS: A literature review with meta-analysis was performed. The databases used were PubMed, Scopus and CINAHL. The search was conducted in March 2023. Two meta-analysis one of clinical trials about the effectiveness and one about the succession rate were performed. RESULTS: 20 studies were selected and analysed. The studies showed that USGPIVC performed by emergency nurses increased the probability of both the overall success and a successful first attempt compared to the standard technique. In addition, patients showed high satisfaction and lower complication rates. However, the procedure had no significant effect on the time or number of attempts required. A lower probability of success was obtained as regards peripheral intravenous cannulation when the standard technique was used, OR = 0.42 (95 %CI 0.25-0.70p < 0,05). CONCLUSIONS: Ultrasound-guided peripheral intravenous cannulation performed by emergency nurses is a safe and effective technique.

Outcomes and factors associated with relapse of vaccine-induced liver injury after SARS CoV-2 immunization: A nationwide study.

INTRODUCTION AND OBJECTIVES: Different patterns of liver injury have been reported in association with the SARS-CoV-2 vaccines. The aim of this study was to describe a nationwide cohort of patients with SARS CoV-2 vaccine-induced liver injury, focusing on treatment and the evolution after further booster administration. PATIENTS AND METHODS: multicentre, retrospective-prospective study, including subjects who developed abnormal liver tests within 90 days after administration of SARS-CoV-2 vaccination. RESULTS: 47 cases were collected: 17 after prime dose and 30 after booster. Age was 57 years, 30 (63.8 %) were female, and 7 (14.9 %) had a history of prior autoimmune hepatitis (AIH). Most cases were non-severe, though 9 (19.1 %) developed acute liver injury or failure (ALF). Liver injury tended to be more severe in those presenting after a booster (p=0.084). Pattern of liver injury was hepatocellular (80.9 %), mixed (12.8 %) and 3 (6.4 %) cholestatic. Liver biopsy was performed on 33 patients; 29 showed findings of AIH. Forty-one (87.2 %) patients received immunosuppressants, mostly corticosteroids (35/41). One required liver transplantation and another died due to ALF. Immunosuppression was discontinued in 6/41 patients without later rebound. Twenty-five subjects received at least one booster and 7 (28.0 %) relapsed from the liver injury, but all were non-severe. Recurrence was less frequent among patients on immunosuppressants at booster administration (28.6 % vs. 88.9 %, p=0.007). CONCLUSIONS: SARS CoV-2 vaccine-induced liver injury is heterogeneous but mostly immune-mediated. Relapse of liver injury after re-exposure to vaccine is frequent (28.0 %) but mild. Immunosuppression at booster administration is associated with a lower risk of liver injury.

The perspectives of people with dementia and their supporters on advance care planning: A qualitative study with the European Working Group of People with Dementia.

BACKGROUND: Advance care planning has been defined in an international consensus paper, supported by the European Association for Palliative Care. There are concerns that this definition may not apply to dementia. Moreover, it is not informed by input from people with dementia. AIM: To gather the perspective of the European Working Group of People with Dementia and their supporters on how advance care planning is defined and develop recommendations for changes to the definition. DESIGN: An in-depth qualitative study was conducted, analysing online focus groups and interviews using thematic analysis. SETTING/PARTICIPANTS: We included 12 people with dementia and 9 supporters. RESULTS: Participants suggested several changes to the current advance care planning definition: mentioning people with decreasing decisional capacity; better reflecting the role of family and/or trust-based relationships; reducing focus on end-of-life/medical decisions; strengthening focus on social aspects of care. Elements of the current definition that participants suggested keeping and highlighting include the framing of advance care planning as a continuous process, that is also optional; mention of communication next to documentation of decisions; and the importance of proxy decision makers. Based on this input, we developed three overarching and 16 specific recommendations for a modified definition of advance care planning that is inclusive of people with dementia. CONCLUSIONS: The perspectives of the European Working Group of People with Dementia and their supporters highlighted the need for a person-centred and dementia-inclusive advance care planning definition. We provide tangible recommendations for future adaptations of the definition that reflect these perspectives.

Potentially inappropriate prescriptions and potential prescription omissions in older people living with HIV.

OBJECTIVES: This study aimed to determine the prevalence of potentially inappropriate prescriptions (PIPs) and potential prescription omissions (PPOs) in a Spanish cohort of people living with HIV (PLWH) aged ≥65 years and to identify risk factors for the presence of PIPs and PPOs. METHODS: This retrospective cross-sectional study was conducted across 10 public hospitals in the Autonomous Community of Madrid, Spain. Clinical and demographic data were cross-checked against hospital and community pharmacy dispensation registries. PIPs and PPOs were assessed using the American Geriatrics Society (AGS)/Beers and Screening Tool of Older Persons' Prescriptions (STOPP)/Screening Tool to Alert Doctors to Right Treatment (START) criteria. Risk factors for PIPs and PPOs and agreement between AGS/Beers and STOPP/START criteria were statistically analysed. RESULTS: This study included 313 PLWH (median age 72 years), of whom 80.5% were men. PIP prevalence rates were 29.4% and 44.4% based on the AGS/Beers and STOPP criteria, respectively. The concordance between AGS/Beers and STOPP criteria was moderate. Benzodiazepines and proton pump inhibitors were the chronic comedications most commonly involved in PIPs. PPOs were observed in 61.4% of the patients. The leading omissions were insufficient influenza and pneumococcal vaccine coverage and inadequate bone health-related treatments. The number of chronic comedications, female sex, neuropsychiatric disorders, and cancer diagnosis were risk factors for PIPs, whereas osteopenia and osteoporosis were risk factors for PPOs. CONCLUSIONS: A high prevalence of PIPs and PPOs was observed in our cohort of older PLWH. These findings emphasize the importance of comprehensive medication reviews in this population to reduce inappropriate medication use and address their specific and underserved therapeutic needs.

Stability of meropenem in portable elastomeric infusion devices: which protocol should be implemented in clinical practice?

Meropenem has an excellent activity against gram-positive and gram-negative bacteria, including multi-resistant microorganisms. Even though meropenem is a great candidate for outpatient parenteral antimicrobial therapy (OPAT), its physicochemical stability is a major challenge. This work aimed to demonstrate the suitability of including meropenem in OPAT by elucidating its physicochemical stability in a range of commonly prescribed concentrations within portable elastomeric infusion devices. Physical and chemical stability were evaluated at two concentrations commonly used in clinical practice (2 and 25 mg/mL), and three temperatures (2°C-8°C, 25°C, and 32°C) using Accufuser portable elastomeric infusion devices. Drug adsorption onto portable elastomeric infusion devices was also determined at the end of the experiment. Meropenem stability significantly decreased at higher temperatures and when higher drug solution concentrations were used. Meropenem solutions at 2 mg/mL kept the drug content above 95% over 24 h at 2°C-8°C but just for 8 h at 25°C. Nevertheless, solutions containing 25 mg/mL of meropenem showed a dramatic decrease in chemical stability after 8 h 2°C-8°C and just after 4 h at 25°C or 32°C. However, physical stability was kept favorable during this period. The drug adsorption on the material of the elastomeric infusion device was below 1%, indicating the suitability of the chosen device. We propose several administration protocols for meropenem in portable elastomeric infusion devices in clinical practice, according to the results obtained in our study. The results obtained in this study open up the possibility of administering meropenem in an OPAT setting despite its short stability.IMPORTANCEAlthough outpatient parenteral antibiotic therapy can be a good approach to treating infections, a lack of data regarding antibiotic stability in portable elastomeric infusion devices restricts its safe and effective use. Actually, meropenem is used for prolonged periods above 24 h, and it is not physicochemically stable, which can compromise efficacy and toxicity. This work is of high importance to show the clinicians the real shelf life of meropenem when administered in portable elastomeric infusion devices. We propose several administration protocols for meropenem in portable elastomeric infusion devices in clinical practice, according to the stability drug results obtained in our study.

A long-term survey of Serratia spp. bloodstream infections revealed an increase of antimicrobial resistance involving adult population.

Serratia spp. is a well-recognized pathogen in neonates; however, limited data are available in adults. We studied microbiological and clinical characteristics of Serratia spp. causing bloodstream infections (BSI) in our institution (January 2005-July 2020). Overall, 141 BSI episodes affecting 139 patients were identified and medical records reviewed. Antimicrobial susceptibility was recovered from our informatics system and 118 isolates from 116 patients were available for further microbiological studies. Whole genome sequencing (WGS) was completed in 107 isolates. Incidence of Serratia BSI was 0.3/1000 overall admissions (range 0.12-0.60), with maximum prevalence (27 episodes, 19.1%) during 2017-2018. Relevant patients' clinical characteristics were 71.9% ≥60 years (n = 100), with high comorbidity rates (49%, ≥2), 23 (74.2%) of them died within 1 month of the BSI episode. WGS identified all isolates as Serratia marcescens when Kraken bioinformatics taxonomic tool was used despite some which were identified as Serratia nematodiphila (32/118) or Serratia ureilytica (5/118) by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Nevertheless, when using MASH distance, Serratia nevei (63/107), S. ureilytica (38/107), and S. marcescens (6/107) were assigned. Carbapenemase (blaVIM-1) and extended-spectrum ß-lactases (ESBL) (blaSHV-12) genes were found in seven and three isolates, respectively, one of them expressing both genes. The worldwide-disseminated IncL/M scaffold plasmid was identified in six VIM producers. Four genotypes were established based on their virulence factors and resistome. Serratia spp. emerged as a relevant nosocomial pathogen causing BSI in elderly patients in our hospital, particularly in recent years with a remarkable increase in antibiotic resistance. ESBL and carbapenemases production related to plasmid dissemination are particularly noteworthy.IMPORTANCESerratia spp. is the third most frequent pathogen involved in outbreaks at neonatal facilities and is primarily associated with bacteremia episodes. In this study, we characterized all causing bloodstream infection (BSI) in patients admitted to our hospital during a 16-year period (2005-2020). Despite having no neonatal intensive care unit in our hospital, this study revealed that Serratia spp. is a relevant pathogen causing BSI in elderly patients with high comorbidity rates. A significant increase of antimicrobial resistance was detected over time, particularly in 2020 and coinciding with the coronavirus disease (COVID-19) pandemic and nosocomial spread of multidrug-resistant Serratia spp. isolates. extended-spectrum ß-lactases and carbapenemases genes associated with plasmid dissemination, typically detected in other Enterobacterales species, were also identified, reinforcing the role of Serratia spp. in the antimicrobial resistance landscape. Additionally, this work highlights the need to reclassify the species of Serratia, since discrepancies were observed in the identification when using different tools.

Numerical and biomass growth study of Bulimulus bonariensis (Rafinesque, 1833) (Gastropoda: Bulimulidae) under laboratory conditions.

Bulimulus bonariensis is considered a species of relevance to agribusiness, having been declared a pest with indirect damage because of its negative effects on several crops such as soybeans, chickpeas, and corn in central and northern Argentina. The objective of this work was to analyze the growth pattern of a population born under laboratory conditions, to explore population aspects such as survival and mortality, to estimate the age and size at gonadal maturity and first reproduction, and to contribute to the knowledge of the reproductive biology of this gastropod. From the clutches obtained, the basic biologic parameters were calculated and the individuals hatched under laboratory conditions counted and measured every two weeks. The clutches contained an average of 44 eggs, which took about 13.7 days to hatch at a birth rate of 41.82%. The growth pattern in the five clutches was analyzed individually, and the logistic model used was the one with the highest degree of fit to that observed growth pattern, followed by the Gompertz model, and finally the von Bertalanffy model. In addition, the models were applied to the 102 specimens analyzed together as a cohort, where the best fitting model was also proved to be the logistic growth model. A concave type III survival curve was obtained from the horizontal life table. The cohort was reduced by 48% during the first 50 days after birth. Beyond one month of hatching, life expectancy gradually increased and remained high between 65-302 days of life. After day 330, life expectancy decreased and only 13.72% exceeded one year of birth, with an average length of 16.68 mm. The last specimen died after 23 months at a total length of 20.24 mm, and the life expectancy was estimated at almost three years. In addition, it was inferred that gonadal maturity, when these gastropods reach 12 mm of total shell length, is reached after 200 days of life. Therefore, the individuals that are born are able to reproduce for the first time a year after birth, when they have the approximate size of 16.68 mm.

Design of mobile and website health application devices for drug tolerability in hereditary fructose intolerance.

BACKGROUND: Hereditary fructose intolerance (HFI) is a rare metabolic disease caused by aldolase B deficiency. The aim of our study was to analyse excipient tolerability in patients with HFI and other related diseases and to design mobile and website health applications to facilitate the search for drugs according to their tolerance. RESULTS: A total of 555 excipients listed in the Spanish Medicines Agency database (July 2023) were classified as suitable for HFI patients, suitable with considerations ((glucose and glucose syrup, intravenous sucrose, oral mannitol, polydextrose, gums and carrageenans, ethanol, sulfite caramel and vanilla), not recommended (intravenous mannitol) and contraindicated (fructose, oral sucrose, invert sugar, sorbitol, maltitol, lactitol, isomaltitol, fruit syrups, honey, sucrose esters and sorbitol esters). Glucose and glucose syrup were classified as suitable with considerations due to its possible fructose content and their potential endogenous fructose production. For other related intolerances, wheat starch was contraindicated and oatmeal was not recommended in celiac disease; oral lactose and lactose-based coprocessed excipient (Cellactose®) were not recommended in lactose intolerance; and glucose, invert sugar and oral sucrose were not recommended in diabetes mellitus. The applications were named IntoMed®. Results are listed in order of tolerability (suitable drugs appear first and contraindicated drugs at the end), and they are accompanied by a note detailing their classified excipients. If a drug contains excipients within different categories, the overall classification will be the most restrictive. The apps are also able to classify substances with the same criteria if they act as active ingredients. The tools exhibited good usability (82.07 ± 13.46 points on the System Usability Scale [range: 0-100]) on a sample of HFI patients, their families and health care professionals. CONCLUSIONS: IntoMed® is a tool for finding information about the tolerability of drugs according to excipients for patients with HFI and other related intolerances, with good usability. It is a fast and reliable system that covers the current excipient legislation and expands on it with other specific information: HFI patients should be alert for excipients such as mannitol (especially in intravenous drugs), fruit syrups, honey, sulfite caramel or vanilla. Glucose might contain or produce fructose, and special precaution is needed because of potential errors in their composition.

Bilateral Digitally Aided Tooth Autotransplantation: A 2-Year Case Report.

Tooth autotransplantation is an effective treatment to replace missing teeth. Digital planning can facilitate successful autotransplantation. Guiding templates are highly recommended when performing cases in healed ridges in the posterior area to reduce excessive bone loss and increase the chances of fitting the donor tooth in the new socket. This case report highlights the use of 3D planning tools and fully guided drilling templates for successful tooth autotransplantation in the posterior area. Two tooth autotransplantations were performed in a 51-year-old patient using mandibular third molars to replace hopeless mandibular first and second molars. Root canal treatments were carried out before the surgeries, and different alveoloplasty techniques were used in each recipient area. The prosthetic phase was carried out after 9 months. Both teeth were asymptomatic, functional, and exhibited no signs of resorption or apical radiolucency and showed complete regeneration of the periodontal apparatus at the 2-year follow-up.

Sub-millisecond microfluidic mixers coupled to time-resolved in situ photonics to study ultra-fast reaction kinetics: the case of ultra-small gold nanoparticle synthesis.

We report a continuous microreactor platform achieving sub-millisecond homogeneous reagent mixing (∼300 µs) for a time-resolved study on the synthesis of ultra-small gold nanoparticles (NPs). The microreactor (coupled with small angle X-ray scattering, UV-vis, and X-ray absorption spectroscopy for in situ and in operando characterizations), operates within mixing time frames below system characteristic times, providing a unique opportunity to deepen the comprehension of reaction and phase transition pathways with unprecedented details. The microreactor channel length can be approximated to a given reaction time when operated in continuous mode and steady state. As a result, the system can be statically investigated, eliminating technique-dependent probing time constraints and local inhomogeneities caused by mixing issues. We have studied Au(0) NP formation kinetics from Au(III) precursors complexed with oleylamine in organic media, using triisopropylsilane as a reducing agent. The existence of Au(III)/Au(I) prenucleation clusters and the formation of a transient Au(I) lamellar phase under certain conditions, before the onset of Au(0) formation, have been observed. Taking advantage of the high frequency time-resolved information, we propose and model two different reaction pathways associated with the presence or absence of the Au(I) lamellar phase. In both cases, non-classical pathways leading to the formation of NPs are discussed.

Stability of meropenem in portable elastomeric infusion devices: which protocol should be implemented in clinical practice?

IMPORTANCE: Although outpatient parenteral antibiotic therapy can be a good approach to treating infections, a lack of data regarding antibiotic stability in portable elastomeric infusion devices restricts its safe and effective use. Actually, meropenem is used for prolonged periods above 24 h, and it is not physicochemically stable, which can compromise efficacy and toxicity. This work is of high importance to show the clinicians the real shelf life of meropenem when administered in portable elastomeric infusion devices. We propose several administration protocols for meropenem in portable elastomeric infusion devices in clinical practice, according to the stability drug results obtained in our study.

Prevalence and clinical consequences of Hepatitis C virus infection in patients undergoing hematopoietic stem cell transplantation

ABSTRACT Hepatitis C virus (HCV) infection is a significant cause of morbidity and mortality among hematopoietic stem cell transplant (HCT) recipients. In Brazil, its occurrence in HCT recipients remains undetermined. We now report on HCV prevalence in HCT recipients and its clinical consequences. The medical records of all HCT recipients seen at Hospital das Clinicas, Sao Paulo University Medical School, from January 2010 to January 2020 were reviewed to determine HCV serostatus. A retrospective analysis of medical charts was undertaken on all seropositive cases to determine HCV genotype, presence of liver fibrosis, co-infections with other viruses, previous treatments, and clinical evolution of liver pathology after HCT. Of the 1,293 HCT recipients included in the study, seven (0.54%) were HCV antibody-positive and five (0.39%) were also viremic for HCV-RNA. Four of these individuals had moderate to severe liver fibrosis (METAVIR F2/F3) and one was cirrhotic. Two of the viremic patients developed acute liver dysfunction following transplantation. All patients had their acute episode of liver dysfunction resolved with no further complications. Four of the viremic patients were treated for HCV infection with direct acting agents (DAA). Information regarding HCV treatment was lacking for one of the viremic HCV patients due to loss of follow up. Sustained anti-virologic responses were observed in three cases after the use of DAA. The detection of HCV in hematological adults undergoing HCT and its successful treatment with DAA highlight the necessity of testing for HCV both prior to and following transplantation.