Longitudinal Lower Airway Microbial Signatures of Acute Cellular Rejection in Lung Transplantation.

Rationale: Acute cellular rejection (ACR) after lung transplant is a leading risk factor for chronic lung allograft dysfunction. Prior studies have demonstrated dynamic microbial changes occurring within the allograft and gut that influence local adaptive and innate immune responses. However, the lung microbiome's overall impact on ACR risk remains poorly understood. Objectives: To evaluate whether temporal changes in microbial signatures were associated with the development of ACR. Methods: We performed cross-sectional and longitudinal analyses (joint modeling of longitudinal and time-to-event data and trajectory comparisons) of 16S rRNA gene sequencing results derived from lung transplant recipient lower airway samples collected at multiple time points. Measurements and Main Results: Among 103 lung transplant recipients, 25 (24.3%) developed ACR. In comparing samples acquired 1 month after transplant, subjects who never developed ACR demonstrated lower airway enrichment with several oral commensals (e.g., Prevotella and Veillonella spp.) than those with current or future (beyond 1 mo) ACR. However, a subgroup analysis of those who developed ACR beyond 1 month revealed delayed enrichment with oral commensals occurring at the time of ACR diagnosis compared with baseline, when enrichment with more traditionally pathogenic taxa was present. In longitudinal models, dynamic changes in α-diversity (characterized by an initial decrease and a subsequent increase) and in the taxonomic trajectories of numerous oral commensals were more commonly observed in subjects with ACR. Conclusions: Dynamic changes in the lower airway microbiota are associated with the development of ACR, supporting its potential role as a useful biomarker or in ACR pathogenesis.

CandeSpartan Study: Candesartan Spanish Response-prediction and Tolerability study in migraine.

INTRODUCTION: Effectiveness of candesartan in migraine prevention is supported by two randomized controlled trials. We aimed to assess the effectiveness, tolerability, and response predictors of candesartan in the preventive treatment of migraine. METHODS: Observational, multicenter, prospective cohort study. The 50%, 75% and 30% responder rates, between weeks 8-12 and 20-24, were compared with the baseline. Treatment emergent adverse effects were systematically evaluated. Response predictors were estimated by multivariate regression models. RESULTS: Eighty-six patients were included, 79.1% females, aged 39.5 (inter-quartile range [IQR] 26.3-50.3), with chronic migraine (43.0%), medication overuse headache (55.8%) and a median of two (inter-quartile range: 0.75-3) prior preventive treatments. At baseline patients had 14 (10-24) headache and 8 (5-11) migraine days per month. The 30%, 50% and 75% responder rates were 40%, 34.9% and 15.1% between weeks 8-12, and 48.8%, 36%, and 18.6% between weeks 20-24. Adverse effects were reported by 30 (34.9%) and 13 (15.1%) patients between weeks 0-12 and 12-24, leading to discontinuation in 15 (17.4%) patients. Chronic migraine, depression, headache days per month, medication overuse headache, and daily headache at baseline predicted the response between weeks 20-24. CONCLUSION: Candesartan effectiveness and tolerability in migraine prevention was in line with the clinical trials' efficacy.Trial registration: The study protocol is registered in ClinicalTrials.gov (NCT04138316).

Factors related to the development of high antibody titres against SARS-CoV-2 in convalescent plasma donors from the ConPlas-19 trial.

BACKGROUND AND OBJECTIVES: The efficacy of COVID-19 convalescent plasma (CP) associates with high titres of antibodies. ConPlas-19 clinical trial showed that CP reduces the risk of progression to severe COVID-19 at 28 days. Here, we aim to study ConPlas-19 donors and characteristics that associate with high anti-SARS-CoV-2 antibody levels. MATERIALS AND METHODS: Four-hundred donors were enrolled in ConPlas-19. The presence and titres of anti-SARS-CoV-2 antibodies were evaluated by EUROIMMUN anti-SARS-CoV-2 S1 IgG ELISA. RESULTS: A majority of 80.3% of ConPlas-19 donor candidates had positive EUROIMMUN test results (ratio ≥1.1), and of these, 51.4% had high antibody titres (ratio ≥3.5). Antibody levels decline over time, but nevertheless, out of 37 donors tested for an intended second CP donation, over 90% were still EUROIMMUN positive, and nearly 75% of those with high titres maintained high titres in the second sample. Donors with a greater probability of developing high titres of anti-SARS-CoV-2 antibodies include those older than 40 years of age (RR 2.06; 95% CI 1.24-3.42), with more than 7 days of COVID-19 symptoms (RR 1.89; 95% CI 1.05-3.43) and collected within 4 months from infection (RR 2.61; 95% CI 1.16-5.90). Male donors had a trend towards higher titres compared with women (RR 1.67; 95% CI 0.91-3.06). CONCLUSION: SARS-CoV-2 CP candidate donors' age, duration of COVID-19 symptoms and time from infection to donation associate with the collection of CP with high antibody levels. Beyond COVID-19, these data are relevant to inform decisions to optimize the CP donor selection process in potential future outbreaks.

Incidence and prevalence of headache in influenza: A 2010-2021 surveillance-based study.

BACKGROUND AND PURPOSE: Influenza is a common cause of acute respiratory infection, with headache being one of the symptoms included in the European Commission case definition. The prevalence of headache as a symptom of influenza remains unknown. We aimed to describe the incidence and prevalence of headache in patients with influenza. METHODS: All consecutive patients who met the definition criteria of influenza-like illness during the influenza seasons 2010-2011 through 2021-2022 were included. The seasonal cumulative incidence of influenza per 1000 patients at risk and the prevalence of headache as an influenza symptom were calculated, including the 95% confidence intervals (CIs). Subgroup analyses were done based on patients' sex, age group, microbiological confirmation, vaccination status, and influenza type/subtype/lineage. RESULTS: During the study period, 8171 patients were eligible. The incidence of headache in the context of influenza varied between 0.24 cases per 1000 patients (season 2020-2021) and 21.69 cases per 1000 patients (season 2017-2018). The prevalence of headache was 66.1% (95% CI = 65.1%-67.1%), varying between 49.6% (season 2021-2022) and 80.1% (season 2010-2011). The prevalence of headache was higher in women (67.9% vs. 65.7%, p = 0.03) and higher in patients between 15 and 65 years old. Headache was more prevalent in patients infected with B subtypes than A subtypes (68.7% vs. 56.9%, p < 0.001). There were no notable differences regarding vaccination status or microbiological confirmation of the infection. CONCLUSIONS: Headache is a common symptom in patients with influenza, with a prevalence higher than that observed in other viral infections.

Evaluation of the concomitant use of prophylactic treatments in patients with migraine under anti-calcitonin gene-related peptide therapies: The PREVENAC study.

BACKGROUND AND PURPOSE: Anti-calcitonin gene-related peptide (CGRP) therapies are recent preventive therapies approved for both episodic and chronic migraine. One of the measures of effectiveness is the withdrawal of other preventive treatments. The objective of this study is to quantify the impact of anti-CGRP drugs in concomitant preventive treatment in patients with migraine. METHODS: This was an observational, retrospective, multicenter cohort study with patients from nine national headache units. Patients with migraine undergoing treatment for at least 6 months with anti-CGRP antibodies, who were initially associated with some preventive treatment (oral and/or onabotulinumtoxinA) were included. Demographic and clinical variables were collected, as well as variables related to headache. Differences according to withdrawal or nonwithdrawal were evaluated. RESULTS: A total of 408 patients were included, 86.52% women, 48.79 (SD = 1.46) years old. Preventive treatment was withdrawn in 43.87% (179/408), 20.83% partially and 23.04% totally. In 27.45% (112/408), it was maintained exclusively due to comorbidity and in 28.6% (117/408) due to partial efficacy. The most frequent time of withdrawal was between 3 and 5 months after the start of treatment. The baseline characteristics associated with nonwithdrawal were comorbidities: insomnia, hypertension and obesity, chronic migraine, and medication overuse. In the multivariate analysis, the absence of high blood pressure, a greater number of preventive treatments at the start, and a lower number of migraine days/month after anti-CGRP treatment were independently associated with withdrawal of the treatment (p < 0.05). CONCLUSIONS: Anti-CGRP antibodies allow the withdrawal of associated preventive treatment in a significant percentage of patients, which supports its effectiveness in real-life conditions.

RE-START: Exploring the effectiveness of anti-calcitonin gene-related peptide resumption after discontinuation in migraine.

BACKGROUND AND PURPOSE: According to the latest European guidelines, discontinuation of monoclonal antibodies against calcitonin gene-related peptide (anti-CGRP MAb) may be considered after 12-18 months of treatment. However, some patients may worsen after discontinuation. In this study, we assessed the response following treatment resumption. METHODS: This was a prospective study conducted in 14 Headache Units in Spain. We included patients with response to anti-CGRP MAb with clinical worsening after withdrawal and resumption of treatment. Numbers of monthly migraine days (MMD) and monthly headache days (MHD) were obtained at four time points: before starting anti-CGRP MAb (T-baseline); last month of first treatment period (T-suspension); month of restart due to worsening (T-worsening); and 3 months after resumption (T-reintroduction). The response rate to resumption was calculated. Possible differences among periods were analysed according to MMD and MHD. RESULTS: A total of 360 patients, 82% women, with a median (interquartile range [IQR]) age at migraine onset of 18 (12) years. The median (IQR) MHD at T-baseline was 20 (13) and MMD was 5 (6); at T-suspension, the median (IQR) MHD was 5 (6) and MMD was 4 (5); at T-worsening, the median (IQR) MHD was 16 (13) and MMD was 12 (6); and at T-reintroduction, the median (IQR) MHD was 8 (8) and MHD was 5 (5). In the second period of treatment, a 50% response rate was achieved by 57.4% of patients in MHD and 65.8% in MMD. Multivariate models showed significant differences in MHD between the third month after reintroduction and last month before suspension of first treatment period (p < 0.001). CONCLUSION: The results suggest that anti-CGRP MAb therapy is effective after reintroduction. However, 3 months after resumption, one third of the sample reached the same improvement as after the first treatment period.

Factors associated to the presence of headache in patients with influenza infection and its consequences: a 2010-2020 surveillance-based study.

Headache is a common symptom of influenza infection; however, its causes and consequences remain uncertain. In this manuscript, we analyzed which demographic and clinical factors were associated with the presence of headache during the course of influenza infection and whether patients with headache had a different prognosis, evaluated by need of hospitalization, sick leave or school absenteeism. The influence study (NCT05704335) was an observational study that analyzed data routinely collected from the Health Sentinel Network between 2010 and 2020. During the study period, 7832 cases were considered, among which, 5275 (67.4%) reported headache. The presence of headache was independently associated with myalgia (2.753; 95%CI: 2.456-3.087, P < 0.001), asthenia (OR: 1.958; 95%CI: 1.732-2.214, P < 0.001), shivering (OR: 1.925; 95%CI: 1.718-2.156, P < 0.001), nasopharyngeal erythema (OR: 1.505; 95%CI: 1.293-1.753, P < 0.001), fever (OR: 1.469; 95%CI: 1.159-1.861; P = 0.001), sudden onset of symptoms (OR: 1.380; 95%CI: 1.120-1.702, p = 0.004), female sex (OR: 1.134; 95%CI: 1.023-1.257, P = 0.018), and gastrointestinal symptoms (OR: 1.169; 95%CI: 1.039-1.315; P = 0.01). Patients with headache had a sex and age adjusted lower odds of being referred to the hospital (OR: 0.463; 95%CI: 0.264-0.812, P = 0.007) and a higher odd of having a sick leave and/or school absenteeism (absenteeism (OR: 1.342; 95%CI: 1.190-1.514, P < 0.001). In conclusion, the presence of headache seems associated with symptoms caused by the innate immune response. These findings support a headache pathophysiology linked with the innate immune response. Due to the potential negative consequences and its treatable nature, clinicians should systematically evaluate it and, whenever necessary, treat it too.

Design of Fluorescent Carbon Dots (CDs) for the Selective detection of Metal-Containing Ions.

The pollution caused by heavy metals (HMs) may occur through both natural processes and anthropogenic activities and is found in complex media. The purpose of this review is to summarize the state-of-art of fluorescent CDs and the sensing applications in a systematic manner. This review intends to provide clues on the origin on the observed selectivity in chemiluminiscence sensors, which was until now a stated but unaddressed question, and still remains open for debate. Indeed, it is tempting to think that CDs possessing functional groups with soft bases at the surface are able to detect soft metal acids, while the opposite is to be suspected for hard acid-base pairs. However, the literature shows several examples where this trend does not hold. We found that such observation is explained by the involvement of dynamic quenching, which does not involve the formation of a non-fluorescent complex, as in the case of static quenching. We have provided an interpretation of published data that was not provided by the original authors and offer guidelines to enable the design of CDs to target ions in solution.

Long-term outcomes of nummular headache: A series of 168 patients and 1198 patient-years of follow-up.

BACKGROUND: Since the first description of nummular headache (NH), more than 500 cases have been described, delineating its clinical phenotype and response to treatment. However, data on the natural history of NH and outcomes during long-term follow-up are not currently available. The present study aimed to describe the long-term outcomes and follow-up of a large series of patients with NH. METHODS: A descriptive observational ambisective study with a series of cases was conducted. The study population included adult patients with primary NH and a minimum of 12 months of follow-up. Demographic variables, previous medical history, clinical phenotype, diagnosis and treatment of NH, temporal pattern, and long-term evolution were analysed. RESULTS: In total, 168 patients were enrolled and followed for a median [interquartile range (IQR)] of 80.5 (55-118.5) months. The temporal pattern after NH onset was chronic in 67.9% and, at diagnosis, the median (IQR) number of pain days per month was 20 [10-30] days with 138 (82.1%) patients with ≥8 days of pain per month. Preventive treatment was needed by 112 (66.7%) patients. The most frequently used drugs were gabapentin (69/112; 61.6%), onabotulinumtoxinA (38/112; 33.9%), amitriptyline (31/112; 27.7%) and lamotrigine (21/112; 18.7%). Response to preventive treatment was at least partial in 91/112 (81.3%) patients. At the end of follow-up, 81 (48.2%) patients had inactive NH. Of patients with active NH, the median (IQR) number of headache days per month was 3 (1-12) days and patients had ≥8 days of pain in 35 (20.8%) cases. CONCLUSIONS: Long-term outcomes of NH were positive in most patients. After a median of 6.7 years of follow-up, 48% of cases were inactive. Two-thirds of patients required preventive treatment, and 80% of them were treatment-responsive. In NH cases that remained symptomatic, the headache frequency was lower, and the proportion of patients with chronic NH decreased from 68% to 11%.

InfluenCEF study: Clinical phenotype and duration of headache attributed to influenza infection.

INTRODUCTION: Headache is a frequent symptom of infections. We aimed to characterize the clinical phenotype and duration of headache attributed to influenza infection. METHODS: Prospective cohort study done in 53 primary care centers between January and April 2023. Patients were included if they had a confirmed influenza diagnosis, were older than 15 years and had a new-onset headache. Patients' demographics, prior medical history, headache phenotype and duration, associated symptoms and patients' outcomes were assessed. The International Classification of Headache Disorders criteria for headache attributed to a systemic viral infection, migraine and tension-type headache were assessed. RESULTS: Of the 478 patients 75 fulfilled eligibility criteria. The mean age was 43, 56% were men, and 27% had a prior headache history. The headache phenotype was a bilateral headache (52%), with frontal topography (48%), pressing quality (61%), moderate intensity, rhinorrhea (79%), nasal congestion (76%), and photophobia (59%). All patients fulfilled headache attributed to acute systemic viral infection criteria, 43% fulfilled migraine criteria and 31% tension-type headache criteria. The median duration of the headache was four (Inter-quartile range: two-six) days. CONCLUSION: The clinical phenotype of headache attributed to influenza infection was similar to other infections, with more pronounced cranial autonomic symptoms. The headache was an early symptom and was self-limited within a few days.Trial Registration: The study protocol is registered in ClinicalTrial.gov (NCT05704335).

57Fe Mössbauer and DFT study of the electronic and spatial structures of the iron(II) (pseudo)clathrochelates: the effect of ligand field strength.

Combined experimental 57Fe Mössbauer and theoretical DFT study of a series of iron(II)-centered (pseudo)macrobicyclic analogs and homologs was performed. The field strength of the corresponding (pseudo)encapsulating ligand was found to affect both the spin state of a caged iron(II) ion and the electron density at its nucleus. In a row of the iron(II) tris-dioximates, passing from the non-macrocyclic complex to its monocapped pseudomacrobicyclic analog caused an increase both in the ligand field strength and in the electron density at the Fe2+ ion, and, therefore, a decrease in the isomer shift (IS) value (so-called "semiclathrochelate effect"). Its macrobicyclization, giving the quasiaromatic cage complex, caused a further increase in the two former parameters and a decrease in IS (so-called "macrobicyclic effect"). The trend of their IS values was successfully predicted using the performed quantum-chemical calculations and the corresponding linear correlation with the electron density at their 57Fe nuclei was plotted. A variety of different functionals can be successfully used for such excellent prediction. The slope of this correlation was found to be unaffected by the used functional. In contrast, the predictions of both the sign and the values of quadrupole splitting (QS) for them, based on the theoretical calculations of EFG tensors, were found to be a real great challenge, which could not be solved at the moment even in the case of these C3-pseudosymmetric iron(II) complexes with known XRD structures. The latter experimental data allowed us to deduce a sign of the QSs for them. The straightforwarded molecular design of a (pseudo)encapsulating ligand is proposed to control both the spin state and the redox characteristics of an encapsulated metal ion.

Precise Fingerprint Determination of Vibrational Infrared Spectra in a Series of Co(II) Clathrochelates through Experimental and Theoretical Analyses.

The energetic demands of modern society for clean energy vectors, such as H2, have caused a surge in research associated with homogeneous and immobilized electrocatalysts that may replace Pt. In particular, clathrochelates have shown excellent electrocatalytic properties for the hydrogen evolution reaction (HER). However, the actual mechanism for the HER catalyzed by these d-metal complexes remains an open debate, which may be addressed via Operando spectroelectrochemistry. The prediction of electrochemical properties via density functional theory (DFT) needs access to thermodynamic functions, which are only available after Hessian calculations. Unfortunately, there is a notable lack in the current literature regarding the precise evaluation of vibrational spectra of such complexes, given their structural complexity and the associated tangled IR spectra. In this work, we have performed a detailed theoretical and experimental analysis in a family of Co(II) clathrochelates, in order to establish univocally their IR pattern, and also the calculation methodology that is adequate for such predictions. In summary, we have observed the presence of multiple common bands shared by this clathrochelate family, using the B3LYP functional, the LANL2DZ basis, and effective core potentials (ECP) for heavy atoms. The most important issue addressed in this article was therefore related to the detailed assignment of the fingerprint associated with cobalt(II) clathrochelates, which is a challenging endeavor due to the crowded nature of their spectra.

Potential Predictors of Response to CGRP Monoclonal Antibodies in Chronic Migraine: Real-World Data.

PURPOSE OF REVIEW: Real-world data (RWD) has identified potential predictors of response to anti-CGRP therapies in patients with chronic migraine (CM). This review aims to synthesize the most remarkable findings published to date regarding this topic. RECENT FINDINGS: Migraine features such as unilateral pain and positive triptan response and chronic features such as daily headache or medication overuse (MO) emerge as predictors of positive outcomes, potentially linked to elevated baseline serum anti-calcitonin gene-related peptide (anti-CGRP) levels. Demographic and baseline characteristics, encompassing obesity, psychiatric comorbidities, and prior refractoriness to prophylactic treatments, are associated with poor responses in both treatment-naïve patients and after-switch scenarios. Nevertheless, the consistency of these predictors across diverse populations requires further investigation. Recent RWD literature highlights emerging predictors of response of different sources among patients with CM receiving anti-CGRP therapies. Comprehending these predictors and identifying novel biomarkers of response hold the potential to refine treatment strategies for CM patients, enhancing their management and therapeutic outcomes.

Postnatal Overfeeding during Lactation Induces Endothelial Dysfunction and Cardiac Insulin Resistance in Adult Rats.

Early overnutrition is associated with cardiometabolic alterations in adulthood, likely attributed to reduced insulin sensitivity due to its crucial role in the cardiovascular system. This study aimed to assess the long-term effects of early overnutrition on the development of cardiovascular insulin resistance. An experimental childhood obesity model was established using male Sprague Dawley rats. Rats were organized into litters of 12 pups/mother (L12-Controls) or 3 pups/mother (L3-Overfed) at birth. After weaning, animals from L12 and L3 were housed three per cage and provided ad libitum access to food for 6 months. L3 rats exhibited elevated body weight, along with increased visceral, subcutaneous, and perivascular fat accumulation. However, heart weight at sacrifice was reduced in L3 rats. Furthermore, L3 rats displayed elevated serum levels of glucose, leptin, adiponectin, total lipids, and triglycerides compared to control rats. In the myocardium, overfed rats showed decreased IL-10 mRNA levels and alterations in contractility and heart rate in response to insulin. Similarly, aortic tissue exhibited modified gene expression of TNFα, iNOS, and IL-6. Additionally, L3 aortas exhibited endothelial dysfunction in response to acetylcholine, although insulin-induced relaxation remained unchanged compared to controls. At the molecular level, L3 rats displayed reduced Akt phosphorylation in response to insulin, both in myocardial and aortic tissues, whereas MAPK phosphorylation was elevated solely in the myocardium. Overfeeding during lactation in rats induces endothelial dysfunction and cardiac insulin resistance in adulthood, potentially contributing to the cardiovascular alterations observed in this experimental model.

Gene Characterization of Nocturnin Paralogues in Goldfish: Full Coding Sequences, Structure, Phylogeny and Tissue Expression.

The aim of this work is the full characterization of all the nocturnin (noc) paralogues expressed in a teleost, the goldfish. An in silico analysis of the evolutive origin of noc in Osteichthyes is performed, including the splicing variants and new paralogues appearing after teleostean 3R genomic duplication and the cyprinine 4Rc. After sequencing the full-length mRNA of goldfish, we obtained two isoforms for noc-a (noc-aa and noc-ab) with two splice variants (I and II), and only one for noc-b (noc-bb) with two transcripts (II and III). Using the splicing variant II, the prediction of the secondary and tertiary structures renders a well-conserved 3D distribution of four α-helices and nine ß-sheets in the three noc isoforms. A synteny analysis based on the localization of noc genes in the patrilineal or matrilineal subgenomes and a phylogenetic tree of protein sequences were accomplished to stablish a classification and a long-lasting nomenclature of noc in goldfish, and valid to be extrapolated to allotetraploid Cyprininae. Finally, both goldfish and zebrafish showed a broad tissue expression of all the noc paralogues. Moreover, the enriched expression of specific paralogues in some tissues argues in favour of neo- or subfunctionalization.

Long-term effectiveness and tolerability of galcanezumab in patients with migraine excluded from clinical trials: real world evidence of 1055 patients with 1 year follow-up from the Galca-Only registry.

BACKGROUND: Galcanezumab has shown efficacy and effectiveness in the treatment of episodic and chronic migraine (CM), however, the population represented in randomized clinical trials (RCTs) differs from the population observed in real-world setting. To describe the long-term effectiveness and tolerability of galcanezumab in clinical practice in patients excluded from RCTs. METHODS: Multicenter prospective cohort study of consecutive patients with chronic and high-frequency episodic migraine (HFEM) with prior failure to three or more migraine preventive drugs, treated with galcanezumab and followed up for 12 months. RESULTS: We enrolled 1055 patients, aged 50 (IQR: 42-58), 82.9% female, 76.4% chronic migraine, 69% with at least one exclusion criteria for RCTs, including age > 65 (n = 121), concomitant use of onabotulinumtoxinA (n = 185), daily headache at baseline (n = 347), chronic painful syndromes (n = 206), fibromyalgia (n = 101) or treatment resistance (n = 957). The median number of prior preventive treatments was 4 (IQR: 3-5). The retention rate was 90.8%, 76.8% and 71.4% at 3, 6 and 12 months. The main reasons for treatment discontinuation were lack of effectiveness (21.1%) and inadequate tolerability (6.6%). The 30%, 50% and 75% responder rates were 62.6%, 49.8% and 24.2% between weeks 8-12; 60.9%, 48.8% and 24.6% between weeks 20-24; and 59.7%, 48.3% and 24.6% between weeks 44-48. Daily headache at baseline (OR: 0.619; 95%CI: 0.469-0.817) and patient's age (OR: 1.016; 95%CI: 1.005-1.026) were associated with 50% response at weeks 20-24. The variables that were associated with a higher reduction of headache days between weeks 20-24 were patient's age (0.068; 95% CI: 0.018-0.119) and headache days per month at baseline (0.451; 95% CI: 0.319-0.583), while psychiatric comorbidity (-1.587; 95% CI: -2.626-0.538) and daily headache at baseline (-2.718; 95% CI: -4.58-0.869) were associated with fewer reduction in the number of headache days between weeks 20-24. CONCLUSION: This study provides class III evidence of effectiveness and tolerability of galcanezumab in patients with HFEM and CM with comorbidities that would result in exclusion of the pivotal RCTs. Nonetheless, the clinical results over a 12-month period were similar to the efficacy observed in randomized controlled trials. Few patients discontinued the drug due to inadequate tolerability.

Sensitivity of the SNNOOP10 list in the high-risk secondary headache detection.

AIM: To evaluate the diagnostic accuracy of the SNNOOP10 list in the detection of high-risk headaches. METHODS: Patients that visited the Hospital Clínico San Carlos (Madrid) emergency department due to headache that were allocated to a Manchester Triage System level between critical and urgent were prospectively included but retrospectively analysed. A researcher blind to the patients' diagnosis administered a standardised questionnaire and afterwards a neurologist blind to the questionnaire results diagnosed the patient according to the International Classification of Headache Disorders. The primary endpoint was to assess the sensitivity of the SNNOOP10 list in the detection of high-risk headaches. Secondary endpoints included the evaluation of the sensitivity, specificity, positive predictive value, negative predictive value and area under the curve of each SNNOOP10 item. RESULTS: Between April 2015 and October 2021, 100 patients were included. Patients were 44 years old (inter-quartile range: 33.6-64.7) and 57% were female. We identified 37 different diagnoses. Final diagnosis was a primary headache in 33%, secondary headache in 65% and cranial neuralgia in 2%. There were 46 patients that were considered as having high-risk headache. Patients from the primary headache group were younger and more frequently female. Sensitivity of SNNOOP10 list was 100% (95% confidence interval: 90.2%-100%). The items with higher sensitivity were neurologic deficit or disfunction (75.5%), pattern change or recent onset of the headache (64.4%), onset after 50 years (64.4%). The most specific items were posttraumatic onset of headache (94.5%), neoplasm in history (89.1%) and systemic symptoms (89%). The area under the curve of the SNNOOP10 list was 0.66 (95% CI: 0.55-0.76). CONCLUSION: The red flags from the SNNOOP10 list showed a 100% sensitivity in the detection of high-risk headache disorders.

Machine-learning-based approach for predicting response to anti-calcitonin gene-related peptide (CGRP) receptor or ligand antibody treatment in patients with migraine: A multicenter Spanish study.

BACKGROUND AND PURPOSE: Several variables have been reported to be associated with anti-calcitonin gene-related peptide (CGRP) receptor or ligand antibody response, but with differing results. Our objective was to determine whether machine-learning (ML)-based models can predict 6-, 9- and 12-month responses to anti-CGRP receptor or ligand therapies among migraine patients. METHODS: We performed a multicenter analysis of prospectively collected data from patients with migraine receiving anti-CGRP therapies. Demographic and clinical variables were collected. Response rates in the 30% to 50% range, or at least 30%, in the 50% to 75% range, or at least 50%, and response rate of at least 75% regarding the reduction in the number of headache days per month at 6, 9 and 12 months were calculated. A sequential forward feature selector was used for variable selection and ML-based predictive models for the response to anti-CGRP therapies at 6, 9 and 12 months, with model accuracy not less than 70%, were generated. RESULTS: A total of 712 patients were included, 93% were women, and the mean (SD) age was 48 (11.6) years. Eighty-four percent of patients had chronic migraine. ML-based models using headache days/month, migraine days/month and the Headache Impact Test (HIT-6) yielded predictions with an F1 score range of 0.70-0.97 and an area under the receiver-operating curve score range of 0.87-0.98. SHAP (SHapley Additive exPlanations) summary plots and dependence plots were generated to evaluate the relevance of the factors associated with the prediction of the above-mentioned response rates. CONCLUSIONS: Our results show that ML models can predict anti-CGRP response at 6, 9 and 12 months. This study provides a predictive tool that can be used in a real-world setting.

Multimodal opioid-sparing pain management after lung transplantation and the impact of liposomal bupivacaine intercostal nerve block.

Opioid analgesics are commonly used post-lung transplant, but have many side effects and are associated with worse outcomes. We conducted a retrospective review of all lung transplant recipients who were treated with a multimodal opioid-sparing pain protocol. The use of liposomal bupivacaine intercostal nerve block was variable due to hospital restrictions. The primary objective was to describe opioid requirements and patient-reported pain scores early post-lung transplant and to assess the impact of intraoperative liposomal bupivacaine intercostal nerve block. We treated 64 lung transplant recipients with our protocol. Opioid utilization decreased to a mean of 43 milligram oral morphine equivalents by postoperative day 4. Median pain scores peaked at 4 on postoperative day 1 and decreased thereafter. Only three patients were discharged home with opioids, all of whom were taking opioid agonist therapy pre-transplant for opioid use disorder. Patients who received liposomal bupivacaine intercostal nerve block in the operating room had a significant reduction in opioid consumption over postoperative day 1 through 4 (228 mg vs. 517 mg, P= .032). A multimodal opioid-sparing pain management protocol is feasible and resulted in weaning of opioids prior to hospital discharge.

One-year immunologic outcomes of lung transplantation utilizing hepatitis C-viremic donors.

Little is known about the effects of hepatitis C viremia on immunologic outcomes in the era of direct-acting antivirals. We conducted a prospective, single-arm trial of lung transplantation from hepatitis C-infected donors into hepatitis C-naïve recipients (n = 21). Recipients were initiated on glecaprevir-pibrentasvir immediately post-transplant and were continued on therapy for a total of 8 weeks. A control group of recipients of hepatitis C-negative lungs were matched 1:1 on baseline variables (n = 21). The primary outcome was the frequency of acute cellular rejection over 1-year post-transplant. Treatment with glecaprevir-pibrentasvir was well tolerated and resulted in viremia clearance after a median of 16 days of therapy (IQR 10-24 days). At one year, there was no difference in incidence of acute cellular rejection (71.4% vs. 85.7%, P = .17) or rejection requiring treatment (33.3% vs. 57.1%, P = .12). Mean cumulative acute rejection scores were similar between groups (.46 [SD ± .53] vs. .52 [SD ± .37], P = .67). Receipt of HCV+ organs was not associated with acute rejection on unadjusted Cox regression analysis (HR .55, 95% CI .28-1.11, P = .09), or when adjusted for risk factors known to be associated with acute rejection (HR .57, 95% CI .27-1.21, P = .14). Utilization of hepatitis C infected lungs with immediate treatment leads to equivalent immunologic outcomes at 1 year.