Global herpes zoster burden in adults with asthma: a systematic review and meta-analysis.

BACKGROUND: Asthma is a common respiratory disease, which may be associated with an increased risk of herpes zoster (HZ), often a debilitating disease associated with severe pain. This was the first systematic review with the objective of summarizing evidence on HZ burden in adults with asthma. METHODS: A global systematic literature review (SLR) and meta-analysis was conducted (Medline and Embase, 2003-2024), on HZ burden (incidence, risk, complications) in adults (≥18 years) with asthma. RESULTS: There were 19 studies included on HZ outcomes in adults with asthma. Pooled HZ incidence per 1000 person-years was 5.71 (95% confidence interval [CI] 4.68-6.96) in ≥18-year-olds (4.20 [3.09-5.70] in <60-year-olds versus 10.33 [9.17-11.64] in ≥60-year-olds). The pooled rate ratio for developing HZ was 1.23 [1.11-1.35] in ≥18-year-olds, and 1.36 [1.15-1.61] in ≥50-year-olds. The risk of HZ was higher in people with asthma using systemic corticosteroids; long-acting beta-agonists plus inhaled corticosteroids; and "add-on therapy". Asthma was also associated with an increased risk of post-herpetic neuralgia (odds ratio, OR 1.21 [1.06-1.37]) and HZ ophthalmicus (OR 1.9 [1.1-3.2]).Differences in study design, setting, case definitions, and follow-up durations led to heterogeneity. CONCLUSIONS: This SLR and meta-analysis found that adults with asthma have an increased risk of HZ, with higher risks in older age groups, and in those on certain treatments, such as oral corticosteroids. HZ vaccines are available for adults, including those with comorbidities such as asthma, and can be considered as part of integrated respiratory care.

Powering prescription: Mitochondria as "Living Drugs" - Definition, clinical applications, and industry advancements.

Mitochondria's role as engines and beacons of metabolism and determinants of cellular health is being redefined through their therapeutic application as "Living Drugs" (LDs). Artificial mitochondrial transfer/transplant (AMT/T), encompassing various techniques to modify, enrich, or restore mitochondria in cells and tissues, is revolutionizing acellular therapies and the future of medicine. This article proposes a necessary definition for LDs within the Advanced Therapeutic Medicinal Products (ATMPs) framework. While recognizing different types of LDs as ATMPs, such as mesenchymal stem cells (MSCs) and chimeric antigen receptor T (CAR T) cells, we focus on mitochondria due to their unique attributes that distinguish them from traditional cell therapies. These attributes include their inherent living nature, diverse sources, industry applicability, validation, customizability for therapeutic needs, and their capability to adapt and respond within recipient cells. We trace the journey from initial breakthroughs in AMT/T to the current state-of-the-art applications by emerging innovative companies, highlighting the need for manufacturing standards to navigate the transition of mitochondrial therapies from concept to clinical practice. By providing a comprehensive overview of the scientific, clinical, and commercial landscape of mitochondria as LDs, this article contributes to the essential dialogue among regulatory agencies, academia, and industry to shape their future in medicine.

Asthma and rhinitis control in adolescents and young adults: A real-world MASK-air study.

BACKGROUND: In allergic rhinitis and asthma, adolescents and young adult patients are likely to differ from older patients. We compared adolescents, young adults and adults on symptoms, control levels, and medication adherence. METHODS: In a cross-sectional study (2015-2022), we assessed European users of the MASK-air mHealth app of three age groups: adolescents (13-18 years), young adults (18-26 years), and adults (>26 years). We compared them on their reported rhinitis and asthma symptoms, use and adherence to rhinitis and asthma treatment and app adherence. Allergy symptoms and control were assessed by means of visual analogue scales (VASs) on rhinitis or asthma, the combined symptom-medication score (CSMS), and the electronic daily control score for asthma (e-DASTHMA). We built multivariable regression models to compare symptoms or medication accounting for potential differences in demographic characteristics and baseline severity. RESULTS: We assessed 965 adolescent users (15,252 days), 4595 young adults (58,161 days), and 15,154 adult users (258,796 days). Users of all three age groups displayed similar app adherence. In multivariable models, age groups were not found to significantly differ in their adherence to rhinitis or asthma medication. These models also found that adolescents reported lower VAS on global allergy, ocular, and asthma symptoms (as well as lower CSMS) than young adults and adults. CONCLUSIONS: Adolescents reported a better rhinitis and asthma control than young adults and adults, even though similar medication adherence levels were observed across age groups. These results pave the way for future studies on understanding how adolescents control their allergic diseases.

The Role of Digital Surgical Planning and Surgical Guides in the Treatment of Unilateral Condylar Hyperplasia.

Unilateral condylar hyperplasia (UCH) results in facial asymmetry, malocclusion, and temporomandibular joint dysfunction. Treatment consists of both surgical and orthodontic intervention. A review was performed for 4 patients with UCH who underwent digital surgical planning (DSP)-assisted condylectomy. All patients were female, aged 14 to 35 years at the time of operation with facial asymmetry and class III malocclusion. None of the patients had prior treatment and all had perioperative orthodontic appliances to provide fixation and postoperative elastic therapy. All patients underwent DSP-guided condylectomy, and intraoperative surgical cutting guides were used for 3 of the patients. All had significant improvement in facial symmetry and occlusion. None had recurrence, and additional intervention has not been required. If UCH is recognized before marked secondary changes in the maxilla, mandible, and occlusion, future orthognathic surgery may be potentially obviated. Craniomaxillofacial surgeons should consider using DSP and surgical guides in the treatment of UCH.

Biomarkers in Thyroid Cancer: Emerging Opportunities from Non-Coding RNAs and Mitochondrial Space.

Thyroid cancer diagnosis primarily relies on imaging techniques and cytological analyses. In cases where the diagnosis is uncertain, the quantification of molecular markers has been incorporated after cytological examination. This approach helps physicians to make surgical decisions, estimate cancer aggressiveness, and monitor the response to treatments. Despite the availability of commercial molecular tests, their widespread use has been hindered in our experience due to cost constraints and variability between them. Thus, numerous groups are currently evaluating new molecular markers that ultimately will lead to improved diagnostic certainty, as well as better classification of prognosis and recurrence. In this review, we start reviewing the current preoperative testing methodologies, followed by a comprehensive review of emerging molecular markers. We focus on micro RNAs, long non-coding RNAs, and mitochondrial (mt) signatures, including mtDNA genes and circulating cell-free mtDNA. We envision that a robust set of molecular markers will complement the national and international clinical guides for proper assessment of the disease.

Imaging Tumor-Targeting Bacteria Using 18F-Fluorodeoxysorbitol Positron Emission Tomography.

BACKGROUND: Microbial-based cancer treatments are an emerging field, with multiple bacterial species evaluated in animal models and some advancing to clinical trials. Noninvasive bacteria-specific imaging approaches can potentially support the development and clinical translation of bacteria-based cancer treatments by assessing the tumor and off-target bacterial colonization. METHODS: 18F-Fluorodeoxysorbitol (18F-FDS) positron emission tomography (PET), a bacteria-specific imaging approach, was used to visualize an attenuated strain of Yersinia enterocolitica, currently in clinical trials as a microbial-based cancer treatment, in murine models of breast cancer. RESULTS: Y. enterocolitica demonstrated excellent 18F-FDS uptake in in vitro assays. Whole-body 18F-FDS PET demonstrated a significantly higher PET signal in tumors with Y. enterocolitica colonization compared to those not colonized, in murine models utilizing direct intratumor or intravenous administration of bacteria, which were confirmed using ex vivo gamma counting. Conversely, 18F-fluorodeoxyglucose (18F-FDG) PET signal was not different in Y. enterocolitica colonized versus uncolonized tumors. CONCLUSIONS: Given that PET is widely used for the management of cancer patients, 18F-FDS PET could be utilized as a complementary approach supporting the development and clinical translation of Y. enterocolitica-based tumor-targeting bacterial therapeutics.

Visualizing Bacterial Infections With Novel Targeted Molecular Imaging Approaches.

Although nearly a century has elapsed since the discovery of penicillin, bacterial infections remain a major global threat. Global antibiotic use resulted in an astounding 42 billion doses of antibiotics administered in 2015 with 128 billion annual doses expected by 2030. This overuse of antibiotics has led to the selection of multidrug-resistant "super-bugs," resulting in increasing numbers of patients being susceptible to life-threatening infections with few available therapeutic options. New clinical tools are therefore urgently needed to identify bacterial infections and monitor response to antibiotics, thereby limiting overuse of antibiotics and improving overall health. Next-generation molecular imaging affords unique opportunities to target and identify bacterial infections, enabling spatial characterization as well as noninvasive, temporal monitoring of the natural course of the disease and response to therapy. These emerging noninvasive imaging approaches could overcome several limitations of current tools in infectious disease, such as the need for biological samples for testing with their associated sampling bias. Imaging of living bacteria can also reveal basic biological insights about their behavior in vivo.

Evaluating the Performance of Pathogen-Targeted Positron Emission Tomography Radiotracers in a Rat Model of Vertebral Discitis-Osteomyelitis.

BACKGROUND: Vertebral discitis-osteomyelitis (VDO) is a devastating infection of the spine that is challenging to distinguish from noninfectious mimics using computed tomography and magnetic resonance imaging. We and others have developed novel metabolism-targeted positron emission tomography (PET) radiotracers for detecting living Staphylococcus aureus and other bacteria in vivo, but their head-to-head performance in a well-validated VDO animal model has not been reported. METHODS: We compared the performance of several PET radiotracers in a rat model of VDO. [11C]PABA and [18F]FDS were assessed for their ability to distinguish S aureus, the most common non-tuberculous pathogen VDO, from Escherichia coli. RESULTS: In the rat S aureus VDO model, [11C]PABA could detect as few as 103 bacteria and exhibited the highest signal-to-background ratio, with a 20-fold increased signal in VDO compared to uninfected tissues. In a proof-of-concept experiment, detection of bacterial infection and discrimination between S aureus and E coli was possible using a combination of [11C]PABA and [18F]FDS. CONCLUSIONS: Our work reveals that several bacteria-targeted PET radiotracers had sufficient signal to background in a rat model of S aureus VDO to be potentially clinically useful. [11C]PABA was the most promising tracer investigated and warrants further investigation in human VDO.

Acute Chagas Disease Outbreak among Military Personnel, Colombia, 2021.

We report an acute Chagas disease outbreak among soldiers in Colombia. Trypanosoma cruzi infection was confirmed through parasitology, serology, and molecular methods. Among 9 affected soldiers, 2 died; 7 were hospitalized and received benznidazole treatment, which produced favorable outcomes. Personnel patrolling rural areas in Colombia could be at increased risk for Chagas disease.

Serologic Evidence of Orientia Infection among Rural Population, Cauca Department, Colombia.

We assessed serum samples collected in Cauca Department, Colombia, from 486 persons for Orientia seroreactivity. Overall, 13.8% showed reactive IgG by indirect immunofluorescence antibody assay and ELISA. Of those samples, 30% (20/67) were confirmed to be positive by Western blot, showing >1 reactive band to Orientia 56-kD or 47-kD antigens.

Bartonella spp. and Typhus Group Rickettsiae among Persons Experiencing Homelessness, São Paulo, Brazil.

Persons experiencing homelessness in São Paulo, Brazil, were seropositive for Bartonella spp. (79/109, 72.5%) and typhus group rickettsiae (40/109, 36.7%). Bartonella quintana DNA was detected in 17.1% (14/82) body louse pools and 0.9% (1/114) blood samples. Clinicians should consider vectorborne agents as potential causes of febrile syndromes in this population.

Consistent trajectories of rhinitis control and treatment in 16,177 weeks: The MASK-air® longitudinal study.

INTRODUCTION: Data from mHealth apps can provide valuable information on rhinitis control and treatment patterns. However, in MASK-air®, these data have only been analyzed cross-sectionally, without considering the changes of symptoms over time. We analyzed data from MASK-air® longitudinally, clustering weeks according to reported rhinitis symptoms. METHODS: We analyzed MASK-air® data, assessing the weeks for which patients had answered a rhinitis daily questionnaire on all 7 days. We firstly used k-means clustering algorithms for longitudinal data to define clusters of weeks according to the trajectories of reported daily rhinitis symptoms. Clustering was applied separately for weeks when medication was reported or not. We compared obtained clusters on symptoms and rhinitis medication patterns. We then used the latent class mixture model to assess the robustness of results. RESULTS: We analyzed 113,239 days (16,177 complete weeks) from 2590 patients (mean age ± SD = 39.1 ± 13.7 years). The first clustering algorithm identified ten clusters among weeks with medication use: seven with low variability in rhinitis control during the week and three with highly-variable control. Clusters with poorly-controlled rhinitis displayed a higher frequency of rhinitis co-medication, a more frequent change of medication schemes and more pronounced seasonal patterns. Six clusters were identified in weeks when no rhinitis medication was used, displaying similar control patterns. The second clustering method provided similar results. Moreover, patients displayed consistent levels of rhinitis control, reporting several weeks with similar levels of control. CONCLUSIONS: We identified 16 patterns of weekly rhinitis control. Co-medication and medication change schemes were common in uncontrolled weeks, reinforcing the hypothesis that patients treat themselves according to their symptoms.

Patient-centered digital biomarkers for allergic respiratory diseases and asthma: The ARIA-EAACI approach - ARIA-EAACI Task Force Report.

Biomarkers for the diagnosis, treatment and follow-up of patients with rhinitis and/or asthma are urgently needed. Although some biologic biomarkers exist in specialist care for asthma, they cannot be largely used in primary care. There are no validated biomarkers in rhinitis or allergen immunotherapy (AIT) that can be used in clinical practice. The digital transformation of health and health care (including mHealth) places the patient at the center of the health system and is likely to optimize the practice of allergy. Allergic Rhinitis and its Impact on Asthma (ARIA) and EAACI (European Academy of Allergy and Clinical Immunology) developed a Task Force aimed at proposing patient-reported outcome measures (PROMs) as digital biomarkers that can be easily used for different purposes in rhinitis and asthma. It first defined control digital biomarkers that should make a bridge between clinical practice, randomized controlled trials, observational real-life studies and allergen challenges. Using the MASK-air app as a model, a daily electronic combined symptom-medication score for allergic diseases (CSMS) or for asthma (e-DASTHMA), combined with a monthly control questionnaire, was embedded in a strategy similar to the diabetes approach for disease control. To mimic real-life, it secondly proposed quality-of-life digital biomarkers including daily EQ-5D visual analogue scales and the bi-weekly RhinAsthma Patient Perspective (RAAP). The potential implications for the management of allergic respiratory diseases were proposed.

Nomenclature of allergic diseases and hypersensitivity reactions: Adapted to modern needs: An EAACI position paper.

The exponential growth of precision diagnostic tools, including omic technologies, molecular diagnostics, sophisticated genetic and epigenetic editing, imaging and nano-technologies and patient access to extensive health care, has resulted in vast amounts of unbiased data enabling in-depth disease characterization. New disease endotypes have been identified for various allergic diseases and triggered the gradual transition from a disease description focused on symptoms to identifying biomarkers and intricate pathogenetic and metabolic pathways. Consequently, the current disease taxonomy has to be revised for better categorization. This European Academy of Allergy and Clinical Immunology Position Paper responds to this challenge and provides a modern nomenclature for allergic diseases, which respects the earlier classifications back to the early 20th century. Hypersensitivity reactions originally described by Gell and Coombs have been extended into nine different types comprising antibody- (I-III), cell-mediated (IVa-c), tissue-driven mechanisms (V-VI) and direct response to chemicals (VII). Types I-III are linked to classical and newly described clinical conditions. Type IVa-c are specified and detailed according to the current understanding of T1, T2 and T3 responses. Types V-VI involve epithelial barrier defects and metabolic-induced immune dysregulation, while direct cellular and inflammatory responses to chemicals are covered in type VII. It is notable that several combinations of mixed types may appear in the clinical setting. The clinical relevance of the current approach for allergy practice will be conferred in another article that will follow this year, aiming at showing the relevance in clinical practice where various endotypes can overlap and evolve over the lifetime.

Susceptibility of Cu(I) transport ATPases to sodium dodecyl sulfate. Relevance of the composition of the micellar phase.

Sodium dodecyl sulfate (SDS) is a well-known protein denaturing agent. A less known property of this detergent is that it can activate or inactivate some enzymes at sub-denaturing concentrations. In this work we explore the effect of SDS on the ATPase activity of a hyper-thermophilic and a mesophilic Cu(I) ATPases reconstituted in mixed micelles of phospholipids and a non-denaturing detergent. An iterative procedure was used to evaluate the partition of SDS between the aqueous and the micellar phases, allowing to determine the composition of micelles prepared from phospholipid/detergent mixtures. The incubation of enzymes with SDS in the presence of different amounts of phospholipids reveals that higher SDS concentrations are required to obtain the same degree of inactivation when the initial concentration of phospholipids is increased. Remarkably, we found that, if represented as a function of the mole fraction of SDS in the micelle, the degree of inactivation obtained at different amounts of amphiphiles converges to a single inactivation curve. To interpret this result, we propose a simple model involving active and inactive enzyme molecules in equilibrium. This model allowed us to estimate the Gibbs free energy change for the inactivation process and its derivative with respect to the mole fraction of SDS in the micellar phase, the latter being a measure of the susceptibility of the enzyme to SDS. Our results showed that the inactivation free energy changes are similar for both proteins. Conversely, susceptibility to SDS is significantly lower for the hyperthermophilic ATPase, suggesting an inverse relation between thermophilicity and susceptibility to SDS.

Molecular Main Group Metal Hydrides.

This review serves to document advances in the synthesis, versatile bonding, and reactivity of molecular main group metal hydrides within Groups 1, 2, and 12-16. Particular attention will be given to the emerging use of said hydrides in the rapidly expanding field of Main Group element-mediated catalysis. While this review is comprehensive in nature, focus will be given to research appearing in the open literature since 2001.

Another case of preventable death from asthma.

INTRODUCTION: Asthma prevalence is 262 million globally, with more than 1,000 deaths each day, most of them preventable. We were performing a longitudinal study, in Brazil, with the objective to following up patients who had a severe asthma attack and attended an emergency room (ATTACK Study). Here we present a case of a 28-year-old woman presenting what was considered moderate asthma, enrolled in ATTACK, who subsequently died of asthma. CASE STUDY: The patient was initially evaluated at an emergency room (ER) with uncontrolled asthma and no regular treatment. She had an asthma diagnosis just before this visit to the ER, despite presenting symptoms of asthma since childhood. She was subsequently evaluated by a specialist, who prescribed a treatment with regular inhaled corticosteroid and an inhaled bronchodilator, if necessary. The patient was systematically monitored by telephone for six months. RESULTS: The patient did not adhere to the treatment, in spite of repeated warnings, and 6 months later had an asthma attack resulting in her death. CONCLUSION: It is important to prioritize asthma in primary health care, including building capacity health care professionals for early diagnosis, asthma management, and to educate patients with asthma patients for the identification of worsening and signs of severity, to manage the exacerbations according to a written asthma plan. This may reduce the number of premature and preventable asthma deaths.

A Point-Based Risk Calculator for Mortality After Hepatectomy.

BACKGROUND: Preoperative risk stratification for hepatectomy patients can aid clinical decision making. The objective of this retrospective cohort study was to determine postoperative mortality risk factors and develop a score-based risk calculator using a limited number of preoperative predictors to estimate mortality risk in patients undergoing hepatectomy. METHODS: Data were collected from patients that underwent hepatectomy from the National Surgical Quality Improvement Program dataset from 2014 to 2020. Baseline characteristics were compared between survival and 30-day mortality cohorts using the χ 2 test. Next, the data were split into a training set to build the model and a test set to validate the model. A multivariable logistic regression model modeling 30-day postoperative mortality was trained on the training set using all available features. Next, a risk calculator using preoperative features was developed for 30-day mortality. The results of this model were converted into a score-based risk calculator. A point-based risk calculator was developed that predicted 30-day postoperative mortality in patients who underwent hepatectomy surgery. RESULTS: The final dataset included 38,561 patients who underwent hepatectomy. The data were then split into a training set from 2014 to 2018 (n = 26,397) and test set from 2019 to 2020 (n = 12,164). Nine independent variables associated with postoperative mortality were identified and included age, diabetes, sex, sodium, albumin, bilirubin, serum glutamic-oxaloacetic transaminase (SGOT), international normalized ratio, and American Society of Anesthesiologists classification score. Each of these features were then assigned points for a risk calculator based on their odds ratio. A univariate logistic regression model using total points as independent variables were trained on the training set and then validated on the test set. The area under the receiver operating characteristics curve on the test set was 0.719 (95% confidence interval, 0.681-0.757). CONCLUSIONS: Development of risk calculators may potentially allow surgical and anesthesia providers to provide a more transparent plan to support patients planned for hepatectomy.

Melatonin associated with a high-fat diet during pregnancy and lactation prevents liver changes in the offspring.

In the present study, we set out to determine whether melatonin combined with a high-fat diet during pregnancy and lactation can prevent liver disorders in offspring. Forty rats were divided into four groups: DC - pregnant rats submitted to the standard diet; DC + Mel - pregnant rats submitted to the standard diet combined with melatonin; HFD - pregnant rats submitted to a high-fat diet; HFD + Mel - pregnant rats submitted to a high-fat diet combined with melatonin. Morphophysiological and biochemical parameters were analyzed. Melatonin (5 mg/kg) was administered intraperitoneally. The HFD group offspring showed an increase in AST, ALT, alkaline phosphatase, cholesterol, triglycerides, LDL and glucose levels, and a reduction in HDL and lipase levels. In the liver obseved steatosis, hepatocellular ballooning, increased lobular parenchyma and reduced non-lobular parenchyma, beside reduced liver glycogen and fibrosis. These changes were not observed in the HFD + Mel group. In conclusion, melatonin combined with a high-fat diet preserves the liver architecture and function in the offspring.