Severe Events Research Articles

The Climate-Changing Context of Inflation: Fossilflation, Climateflation, and the Environmental Politics of Green Central Banks

Abstract In this forum, I seek to demonstrate how the growing confluence of climate change and inflation offers a fruitful research agenda for environmental politics scholars. It develops two independent, yet interrelated, concepts first proposed by Schnabel: first, fossilflation, the legacy cost of the dependency on fossil energy sources, which has not been reduced forcefully enough over the past decades, and second, climateflation, the growing impact of natural disasters and severe weather events on economic activity and prices. With the subject of inflation often considered to be a contextual or descriptive feature of environmental issues, the economic implications of climate change have come to challenge the conventional understanding of the inflationary phenomenon. This article seeks to foster an interdisciplinary dialogue between scholars from different disciplinary backgrounds on the subject of climate change–induced inflation and the questions it presents for notions of “green” central banking.

The Platform Trial In COVID-19 Priming and BOOsting (PICOBOO): The immunogenicity, reactogenicity, and safety of different COVID-19 vaccinations administered as a second booster (fourth dose) in AZD1222 primed individuals aged 50-

PICOBOO is a randomised, adaptive trial evaluating the immunogenicity, reactogenicity, and safety of COVID-19 booster strategies. We report data for second boosters among individuals 50-<70 years old primed with AZD1222 (50-<70y-AZD1222) until Day 84. Immunocompetent adults who received any first booster ≥three months prior were eligible. Participants were randomly allocated to BNT162b2, mRNA-1273 or NVX-CoV2373 1:1:1. The concentrations of ancestral anti-spike immunoglobulin were summarised as the geometric mean concentrations (GMC). Reactogenicity and safety outcomes were captured. Additional analyses including neutralising antibodies were performed on a subset. ACTRN12622000238774. Between Mar 2022 and Aug 2023, 743 participants were recruited and had D28 samples; 155 belonged to the 50-<70y-AZD1222 stratum. The mean adjusted GMCs (95% credible intervals) were 20,690 (17 555-23 883), 23,867 (20 144-27 604) and 8654 (7267-9962) U/mL at D28 following boosting with BNT162b2, mRNA-1273 and NVX-CoV2372, respectively, and 10,976 (8826-13 196), 15,779 (12 512-19 070) and 6559 (5220-7937) U/mL by D84. IgG against Omicron BA.5 was 2.7-2.9 times lower than the ancestral strain. Limited neutralisation against Omicron subvariants was found following all vaccines. Severe reactogenicity events were <4%. All vaccines were immunogenic with more rapid waning after mRNA vaccines. These data support boosting with vaccines with greater specificity for circulating Omicron subvariants.

Cryptogenic stroke and seronegative antiphospholipid syndrome: a case series of patients with positivity for "non-criteria" antiphospholipid antibodies.

Cerebrovascular events (CE) are one of the most common and severe events in antiphospholipid syndrome (APS), a condition characterized by thrombosis and circulating anti-phospholipid antibodies (aPL). Seronegative APS (SN-APS) refers to a group of patients with clinical features of APS but persistently negative tests for "criteria aPL": anti-cardiolipin antibodies (aCL) and anti-β2glycoprotein I antibodies detected by enzyme-linked immunosorbent assay (ELISA), and the lupus anticoagulant detected by clotting assays. We report a series of five cases of SN-APS in young or middle-aged patients who tested positive for "non-criteria" aPL. We retrospectively collected cases of SN-APS patients who experienced CE without an identified cause despite an extensive diagnostic work-up and tested negative for criteria aPL. All the patient sera were tested for aCL by immunostaining on thin-layer chromatography (TLC) and anti-vimentin/cardiolipin (aCL/Vim) by ELISA. We identified five cases of female patients aged 21 to 58 years, evaluated at the Rheumatology Unit and/or Stroke Unit/Emergency Department of the Sapienza University Hospital of Rome, "Policlinico Umberto I". All patients presented a clinical history suggestive of APS. All the patients tested positive for aCL by TLC-immunostaining, and one patient was positive for aCL/Vim. In young or middle-aged patients with cryptogenic CE and a clinical history suggestive of APS, the use of new diagnostic tools for identifying aPL, if validated in future studies, could represent an important step in the prompt diagnosis of APS.

Automated Insulin Delivery for Young People with Type 1 Diabetes and Elevated A1c

BackgroundAutomated insulin delivery is the treatment of choice in adults with type 1 diabetes. Data are needed on the efficacy and safety of automated insulin delivery for children and youth with diabetes and elevated glycated hemoglobin levels.MethodsIn this multicenter, open-label randomized controlled trial, we assigned patients with type 1 diabetes in a 1:1 ratio either to use an automated insulin delivery system (MiniMed 780G) or to receive usual diabetes care of multiple daily injections or non-automated pump therapy (control). The patients were children and youth (defined as 7 to 25 years of age) with elevated glycemia (glycated hemoglobin ≥8.5% with no upper limit). The primary outcome was the baseline-adjusted between-group difference in glycated hemoglobin at 13 weeks.ResultsA total of 80 patients underwent randomization (37 to automated insulin delivery and 43 to control) and all patients completed the trial. At 13 weeks, the mean (±SD) glycated hemoglobin decreased from 10.5±1.9% to 8.1±1.8% in the automated insulin delivery group but remained relatively consistent in the control group, changing from 10.4±1.6% to 10.6±1.8% (baseline-adjusted between-group difference, −2.5 percentage points; 95% confidence interval [CI], −3.1 to −1.8; P<0.001). Patients in the automated insulin delivery group spent on average 8.4 hours more in the target glucose range of 70 to 180 mg/dl than those in the control group. One severe hypoglycemia event and two diabetic ketoacidosis events occurred in the control group, with no such events in the automated insulin delivery group.ConclusionsIn this trial of 80 children and youth with elevated glycated hemoglobin, automated insulin delivery significantly reduced glycated hemoglobin compared with usual diabetes care, without resulting in severe hypoglycemia or diabetic ketoacidosis events. (Funded by Lions Clubs New Zealand District 202F and others; Australian New Zealand Clinical Trials Registry number, ACTRN12622001454763.)

Exacerbated Tree Growth Decline of an Old Platycladus orientalis Forest after Rapid Warming at the Northern Edge of the Taihang Mountain of China

Old trees are irreplaceable conservation resources with numerous ecological and socio-cultural values. While many forests have experienced significant declines under recent climate warming, the risk of growth declines in old trees remains unknown. Here, we tackle this problem by dendrochronological studies of 30 old trees in a Platycladus orientalis forest at the northern boundary of the Taihang Mountain of China. We examined annual growth trajectories of trees at individual level and discovered four severe growth decline events over the last 150 years, including the periods of 1894–1899, 1913–1919, 1964–1967 and 2004–2018. The most recent growth decline event lasted for 15-year and involced 50% to 75% of the old trees. This decline was unprecedented in both its extent and duration. Furthermore, the growth–climate relationship of these old trees has changed since 1990. Before 1990, tree growth was significantly correlated with minimum winter; after 1990, tree growth became significantly correlated with the self-calibrating Palmer Drought Index. These results suggest that warming-induced droughts after 1990 could be the primary driver of the recent growth decline. If climate warming continues and drought stresses intensify, the old trees may face an increased risk of growth decline and even mortality.

Modafinil Versus Amphetamine-Dextroamphetamine For Idiopathic Hypersomnia and Narcolepsy Type 2: A Randomized, Blinded, Non-inferiority Trial.

Although there are several treatments for narcolepsy type 2 and idiopathic hypersomnia, studies that assess amphetamines, symptoms beyond sleepiness, and comparative effectiveness are needed. We performed a randomized, fully blinded, noninferiority trial of modafinil versus amphetamine-dextroamphetamine in these disorders. Forty-four adults were randomized to modafinil or amphetamine-dextroamphetamine, individually titrated to a maximum of modafinil 200 mg twice daily or amphetamine-dextroamphetamine 20 mg twice daily, for 12 weeks. Primary outcome was change in Epworth from baseline to week 12, with a noninferiority threshold of 2 points. Secondary outcomes were (1) patient global impression of change measures of disease severity, sleepiness, sleep inertia, and cognition; (2) change from baseline in Hypersomnia Severity Index; and (3) change from baseline in Sleep Inertia Questionnaire. Adverse events were compared between groups. Epworth improved 5.0 [± standard deviation (SD) 2.7] points with modafinil and 4.4 (± SD 4.7) with amphetamine-dextroamphetamine; noninferiority of amphetamine-dextroamphetamine was not demonstrated (P = 0.11). Noninferiority of amphetamine-dextroamphetamine was demonstrated for change scores of severity, sleepiness, sleep inertia, Hypersomnia Severity Index, and Sleep Inertia Questionnaire. Dropouts due to adverse events were 31.8% for modafinil (including two severe events) and 9.1% for amphetamine-dextroamphetamine, P = 0.13. Anxiety was more common with modafinil and appetite suppression with amphetamine-dextroamphetamine. Noninferiority of amphetamine-dextroamphetamine to modafinil was not demonstrated for the primary outcome. However, amphetamine-dextroamphetamine was noninferior on multiple secondary measures of disease severity and symptomatology. These data may inform shared decision-making regarding treatment for idiopathic hypersomnia and narcolepsy type 2. Clinicaltrials.gov Registration (NCT03772314) 12/10/18. .

Add-on multidrug treatment based on quadruple therapy successfully treated worsening heart failure caused by anthracycline-induced cardiomyopathy in a survivor of cancer as a young adult: a case report

BackgroundThe overall mortality and morbidity benefit in patients with heart failure with a reduced ejection fraction is greatest with a treatment combination of sacubitril/valsartan, beta-blockers, mineralocorticoid-receptor antagonists, and sodium-glucose transporter-2 inhibitors, termed the “fantastic four” or “quadruple therapy.” The addition of vericiguat (an oral soluble guanylate cyclase stimulator) is believed to aid in managing worsening heart failure after quadruple therapy. Among childhood and young adult cancer survivors, cardiovascular complications that develop more than 10 years after anthracycline-based chemotherapy have a poor prognosis. Therefore, this study reports the efficacy of multidrug regimen based on quadruple therapy for worsening heart failure in cancer survivors with anthracycline-induced cardiomyopathy.Case presentationA survivor of cancer as a young adult who received high-dose anthracycline chemotherapy presented with acute decompensated heart failure 20 years post-chemotherapy and worsening heart failure 1.5 years after discharge. The patient showed signs of improvement after a step-wise introduction of carvedilol, empagliflozin, sacubitril/valsartan, ivabradine, and spironolactone for worsening heart failure. Vericiguat was accelerated owing to the risk of more severe cardiovascular events associated with ongoing aortic stenosis and the poor prognosis of anthracycline-induced cardiomyopathy. Heart failure symptoms continued to improve, with significant cardiac reverse remodeling, and the patient successfully underwent aortic valve replacement for severe aortic stenosis.ConclusionsOur case highlighted that multidrug treatment with add-on vericiguat and ivabradine based on quadruple therapy can potentially treat worsening heart failure in young adult cancer survivors with severe anthracycline-induced cardiomyopathy.

Evaluation of hemoglobin S percent threshold to prevent severe pain events: a secondary analysis of the SIT trial

Evaluation of hemoglobin S percent threshold to prevent severe pain events: a secondary analysis of the SIT trial

Fat storage and drought tolerance in a seasonally‐adapted primate: Implications for modeling the effects of animal responses to global climate change

AbstractGlobal warming is changing habitats and affecting biodiversity, and is expected to exacerbate aridification in many regions. Animals and plants in seasonally dry tropical forests often exhibit adaptations to cope with seasonal resource limitation. However, whether these adaptations will facilitate drought tolerance or increase drought vulnerability is unclear. Here, we combine long‐term individual‐based data on phenology, morphometrics, and demographics to investigate how drought impacts the food resources, health, reproduction, and behavior of a population of Verreaux's sifaka (Propithecus verreauxi), a critically endangered lemur inhabiting dry deciduous forests in Madagascar. Between December 2010 and May 2023, the population experienced 3 years of severe drought (2016, 2017, 2022). During green periods in severe drought, the availability of high‐quality sifaka foods (young leaves, fruit) was significantly reduced and fruit tree mortality increased. This reduced availability of fruit persisted in the year after a drought, despite typical rainfall. Yet surprisingly, we found no negative effects on body condition or commonly‐used metrics for reproductive success during drought years or years following a drought. Instead, sifaka exhibited significantly higher levels of subcutaneous body fat during severe droughts. We observed little change in sifaka behavior between drought and non‐drought periods. However, they were more likely to lick dew during severe drought, and spent significantly less time feeding on young and mature leaves. They also significantly increased their time feeding on flowers and fruits, despite the reduced abundance of fruit in the habitat. Together, our results suggest that increased consumption of water‐rich fruit and flowers during severe droughts could facilitate physiological mechanisms that help sifaka cope with water scarcity, including fructose‐mediated fat storage, metabolic water production, and water conservation. These results provide new insights into how critically endangered animals may respond to climate change, suggesting that behavioral and physiological adaptations to seasonal resource limitation may buffer some mammals from the effects of severe drought or other extreme weather events.

Nutraceuticals and pharmacological to balance the transitional microbiome to extend immunity during COVID-19 and other viral infections

Abstract Scope The underlying medical conditions and gut dysbiosis is known to influence COVID-19 severity in high-risk patients. The current review proposed the optimal usage of nutraceuticals &amp; pharmacological interventions can help regulate the protective immune response and balance the regulatory functionality of gut microbiota. Summary Many studies have revealed that the probiotic interventions viz., Lactobacillus rhamnosus, L. plantarum &amp; other bacterial spp. reduce IFNγ &amp; TNF-α and increase IL-4 &amp; IL-10 secretions to control the immunostimulatory effects in upper respiratory tract infection. Dietary fibres utilized by beneficial microbiota and microbial metabolites can control the NF-kB regulation. Vitamin C halts the propagation of pathogens and vitamin D and A modulate the GM. Selenium and Flavonoids also control the redox regulations. Interferon therapy can antagonize the viral replications, while corticosteroids may reduce the death rates. BCG vaccine reprograms the monocytes to build trained immunity. Bifidobacterium and related microbes were found to increase the vaccine efficacy. Vaccines against COVID-19 and season flu also boost the immunity profile for robust protection. Over all, the collective effects of these therapeutics could help increase the opportunities for faster recovery from infectious diseases. Conclusion The nutraceutical supplements and pharmacological medicines mediate the modulatory functionalities among beneficial microbes of gut, which in turn eliminate pathogens, harmonize the activity of immune cells to secrete essential regulatory molecular receptors and adaptor proteins establishing the homeostasis in the body organs through essential microbiome. Therefore, the implementation of this methodology could control the severity events during clinical sickness and reduce the mortalities.

Assessment and pre-assessment of compound hot and drought events over Yangtze River Basin

Abstract The severe compound hot and drought event (CHDE) in 2022 had serious impacts on water resources, agriculture, power supply, and ecosystems in the Yangtze River Basin (YRB). Have similar spatiotemporally overlapping compound events, like the one observed in 2022, occurred historically in the basin? How can we pre-assess the impacts of such potential events on subseasonal timescales? To address these, regional CHDEs in the YRB since 1961 were systematically identified and comprehensively assessed using a modified Intensity-Area-Duration (IAD) technique and hazard assessment method. Additionally, the subseasonal pre-assessment capability for CHDEs in the YRB using the China Meteorological Administration's third-generation climate model prediction system (CPSv3-S2S) was demonstrated. A total of 140 CHDEs occurred during 1961 to 2022, with the 21st century showing a remarkably high risk of such events. Among these, 2022 was the most intense year, with the event from July 26th to August 30th being unprecedented in severity. CPSv3-S2S effectively forecast this event’s occurrence within a 1-25 lead days, particularly in pre-assessing its extensively impacted area and high-hazard centers in the upper and middle reaches of the main river course. This pre-assessment method serves as a valuable reference in decision-making to anticipate and mitigate risks of hydropower supply shortages and heightened electricity demand during extremely high temperatures in the upstream area.

The Necessity of Updating IDF Curves for the Sharjah Emirate, UAE: A Comparative Analysis of 2020 IDF Values in Light of Recent Urban Flooding (April 2024)

In the arid Arabian Peninsula, particularly within the United Arab Emirates (UAE), the perception of rainfall has shifted from a natural blessing to a significant challenge for infrastructure and community resilience. The unprecedented storm on 17 April 2024, exposed critical vulnerabilities in the UAE’s urban infrastructure and flood management practices, revealing substantial gaps in handling accumulated precipitation. This study addresses the necessity of updating the Intensity–Duration–Frequency (IDF) curves for the Sharjah Emirate by utilizing recent precipitation data from 2021 to April 2024, alongside previously published 2020 data. By recalibrating the IDF curves based on data from three meteorological stations, this study reveals a substantial increase in rainfall intensities across all durations and return periods. Rainfall intensities increased by an average of 36.76% in Sharjah, 26.52% in Al Dhaid, and 17.55% in Mleiha. These increases indicate a trend towards more severe and frequent rainfall events, emphasizing the urgent need to revise hydrological models and infrastructure designs to enhance flood resilience. This study contributes valuable insights for policymakers, urban planners, and disaster management authorities in the UAE and similar regions worldwide.

Contribution of land-atmosphere coupling in 2022 CONUS compound drought-heatwave events and implications for forecasting

Severe compound drought-heatwave events were observed over three regions of the Contiguous United States (CONUS), Northwest (NW), Great Plains (GP), and Northeast (NE) regions, during July and August 2022. In this study, we have found that the developments of these drought-heatwave events were shaped by different land-atmosphere coupling behaviors which are associated with water and energy limitation regimes in these regions. In the NW and GP regions, the surface soil moisture (SM) and evapotranspiration (ET) were coupled through water-limited processes. Heatwaves in these two regions were affected by the decrease of ET and the available SM due to the precipitation deficit. This type of land-atmosphere coupling was especially prominent in the GP. In the NE region, the heatwave governed ET through the increase of potential ET (PET) based on energy-limited coupling, which played a crucial role in the development of drought.The impacts of the different land-atmosphere coupling behaviors on the predictability of the 13-km Geophysical Fluid Dynamics Laboratory (GFDL) System for High-resolution prediction on Earth-to-Local Domains (SHiELD) were also investigated by checking its 10-day forecasts during the same period. The analysis was particularly focused on the GP and NE regions, where different land-atmosphere coupling behaviors were observed. The model's warm bias in the GP region was associated with the overestimated net radiation, and the bias was further amplified through the water-limited coupling. In the NE region, the PET-related variables, including surface air temperature, influenced the predictability of drought onset by limiting ET through the energy-limited coupling. Based on our findings, this study highlights the crucial role of land-atmosphere coupling behaviors and provides a scientific strategy for enhancing the model predictability of compound drought-heatwaves.

A direct comparison of the radial growth response to drought of European and Oriental beech

Climate change-related extreme drought events already have a significant impact on the productivity and mortality of Central European forests. European beech (Fagus sylvatica ssp. sylvatica), one of the most important European broadleaved species, has responded to such drought periods with increasing mortality and reduced volume increment. This has raised concerns about its suitability and adaptive capacity in relation to future climatic conditions and motivated the search for alternative tree species that are suitable for assisted migration into European beech forests. One of the candidates is the Oriental beech species complex (F. sylvatica ssp. orientalis), whose range extends from the Balkan to Iran and, at least in some parts of its range, grows under a warmer and drier climate. In order to evaluate whether Oriental beech is more drought tolerant, we compared the radial growth response to droughts between 1920 and 2018 of a total of 138 European and 122 Oriental beeches growing under identical site conditions in eight different locations in Germany and France. The species identity of all analysed trees was verified by microsatellite analyses, and the origin of the introduced Oriental beech was traced to the Greater Caucasus (7 stands) and the Black Sea coast (1 stand). The drought responses of radial growth were quantified using the indices resistance, resilience, and recovery as suggested by Lloret et al. (2011) and growth recovery time (GRT) (Thurm et al., 2016) and used as response variables in generalized linear mixed effect models.Considering only the average radial growth response to severe and extreme drought events, both the different Lloret indices and the GRT did not show prominent difference between Oriental and European beech. However, the mixed model analyses, which also included interaction terms, revealed interspecific differences in drought tolerance, depending on the intensity and timing of the drought. In extreme summer drought years, values of resistance predicted by the mixed-effect models were significantly higher in Oriental beech than in European beech, whereas its resilience was only slightly better than in European beech, regardless of drought intensities. In contrast, Oriental beech was much more susceptible to spring drought with significantly weaker growth recovery and distinctly longer growth recovery times.Based on these results, Oriental beech provenances from the Caucasus do not appear to be sufficiently more drought tolerant than European beech to justify an assisted migration approach to adapt Central European forests to climate change. To analyse the drought tolerance of Oriental beech more comprehensively, introduced trees representing other genetic clusters need to be analysed, as well as the effects of repeated drought events on growth and mortality.

Optimal duration of dual antiplatelet therapy for minor stroke within 72 hours of symptom onset: a prospective cohort study

ObjectivesDespite the potential spillover effect, the optimal duration of dual antiplatelet therapy for minor stroke within 72 hours of symptom onset is still uncertain.MethodsSafety and Efficacy of Aspirin-Clopidogrel in Acute...

Persistence, effectiveness, and tolerability of anti-calcitonin gene-related peptide monoclonal antibodies in patients with chronic migraine.

To evaluate, in patients with chronic migraine (CM) in real-world conditions, the persistence, effectiveness, and tolerability of erenumab, fremanezumab, and galcanezumab anti-calcitonin gene-related peptide (anti-CGRP) monoclonal antibodies (mAbs) and the persistence and effects of switching. Anti-CGRP mAbs represent a novel therapeutic approach to the management of CM; however, real-world data on persistence, effectiveness, and tolerability, especially after switching, are scarce. This was a retrospective observational cohort study including all patients with CM treated with erenumab, fremanezumab, and/or galcanezumab in a tertiary hospital between January 2019 and December 2022. Treatment persistence was measured as the number of days between treatment start and end dates or the end of follow-up and also as a percentage of persistent patients at 3, 6, and 12 months; effectiveness as a ≥50% reduction in monthly migraine days (MMD); and tolerability as the number and type of adverse events. Included were 281 patients (383 treatments) with CM (91.5% [257/281] female) receiving anti-CGRP mAbs. Median (interquartile range [IQR]) treatment persistence was 267 (103-550) days. At 12 months, persistence was greater for the first (66.7%) compared to the second (49.8%) and third (37.2%) anti-CGRP mAb treatments (hazard ratio [HR] = 1.93, 95% confidence interval [CI]: 1.35-2.74; HR = 2.75, 95% CI: 1.69-4.47, respectively). Persistence minimum observed median (IQR) was also greater for the first (291 [112-594] days) compared to both the second (188 [90-403] days; p < 0.001) and third (167 [89-352] days; p < 0.001) anti-CGRP mAb treatments. For the first anti-CGRP mAb treatment, there were no differences in persistence among the different drugs. In terms of effectiveness of the first, second, and third anti-CGRP mAb treatments, a ≥50% reduction in MMD was achieved by 57.6% (117/203), 25.0% (11/44), and 11.8% (2/17) of patients, respectively, at 3 months, and by 55.8% (87/156), 29.6% (8/27), and 12.5% (1/8) of patients, respectively, at 6 months. At 12 months, no significant effectiveness differences were observed among anti-CGRP mAb treatments. As for tolerability, 55 adverse events were reported by 43 (15.3%) patients, mostly mild and leading to treatment discontinuation in only 14 (5.0%) patients. The most common adverse events were constipation, injection site reaction, and pruritus. Erenumab patients (3%, 3/99) experienced a higher rate of discontinuation for constipation. Our findings showed a 12-month higher treatment persistence with the use of a first anti-CGRP mAb treatment when the switch to a second treatment was due to ineffectiveness or severe side events. This persistence was lower after a second or third anti-CGRP. Additionally, in terms of effectiveness, the first anti-CGRP treatment achieved a higher response in terms of ≥50% reduction in MMD; however, some patients may benefit from a switching strategy. Finally, the tolerability profile for anti-CGRP mAbs was favorable. Further studies are needed to identify predictors of response after switching from the first anti-CGRP mAb treatment.

Predictors of diagnostic delays and loss to follow-up in women with von Willebrand disease: a single-center retrospective cohort study

BackgroundWomen with von Willebrand disease (VWD) often face diagnostic delays, leading to increased bleeds, stress, and healthcare use. The factors influencing these delays and their effects on gynecologic outcomes are not well understood. ObjectivesThis study aimed to 1) identify the prevalence and predictors of diagnostic delays and loss to follow-up in women with VWD and 2) determine how these delays affect severe gynecologic bleeding, emergency visits, transfusions, and hysterectomies. MethodsWe conducted a single-center retrospective cohort study and included women aged ≥18 years diagnosed with VWD. Delayed diagnosis was defined as ≥3 bleeding events prior to VWD diagnosis, excluding easy bruising due to its subjectivity. Loss to follow-up was defined as ≥5 years since the last hematology visit. We used logistic regression for analysis. ResultsAmong 178 diagnosed women (median age, 27 years), 71 (40%) experienced ≥3 bleeding events before diagnosis. The median time from the first bleeding event to VWD diagnosis was 14.2 years. Severe bleeding events significantly predicted diagnostic delays (adjusted odds ratio, 3.1; 95% CI, 1.5-6.2). Fifty-four (30%) women were lost to follow-up, with remote era of initial bleed and VWD type identified as significant predictors. Delays were associated with increased risks of hysterectomies (odds ratio, 2.7; 95% CI, 1.2-6.3) and other gynecologic procedures. ConclusionDelayed diagnosis and loss to follow-up in VWD are common even in a specialized Hemophilia Treatment Centre. Such delays lead to more severe bleeding and increased gynecologic interventions. Prompt diagnosis is paramount for better patient outcomes and reduced healthcare utilization.

HIV-1-DNA/RNA and immunometabolism in monocytes: contribution to the chronic immune activation and inflammation in people with HIV-1

Among people living with HIV-1 (PHIV), immunological non-responders (INR) experience incomplete immune recovery despite suppressive antiretroviral treatment (ART), facing more severe non-AIDS events than immunological responders (IR) due to higher chronic immune activation and inflammation (cIA/I). We analyzed the HIV-1 reservoir and immunometabolism in monocytes as a source of cIA/I. Cross-sectional study in which 110 participants were enrolled: 25 treatment-naïve; 35 INR; 40 IR; and 10 healthy controls. Cell-associated HIV-1-DNA (HIV-DNA) and -RNA (HIV-RNA) were measured in FACS-isolated monocytes using digital droplet PCR. Intact, 5' deleted, and 3' deleted proviruses were quantified by the intact proviral DNA assay. Systemic inflammation, monocyte immunophenotype, and immunometabolism were characterized by immunoassays, flow cytometry, and real-time cellular bioenergetics measurements, respectively. Monocytes from INR harbor higher HIV-RNA and HIV-DNA levels than IR. HIV-RNA was found in 14/21 treatment-naïve [2512 copies/106 TBP (331-4666)], 17/33 INR [240 (148-589)], and 15/28 IR [144 (15-309)], correlating directly with sCD163, IP-10, GLUT1high cells and glucose uptake, and inversely with the CD4+/CD8+ ratio. HIV-DNA was identified in all participants with detectable HIV-RNA, with intact provirus in 9/12 treatment-naïve [13 copies/106 monocytes (7-44)], 8/14 INR [46 (18-67)], and 9/13 IR [9 (7-24)]. INR presented glucose metabolism alterations and mitochondrial impairment; decreased coupling efficiency and BHI, and increased mitochondrial dysfunction inversely correlating with the CD4+/CD8+ ratio. HIV-RNA, more than HIV-DNA, in monocytes and their altered metabolism are factors associated with the higher cIA/I that characterize INR. This work was supported by the European Regional Development Fund, ISCIII, grant PI20/01646. Other funding sources:Instituto de Salud Carlos III through the Subprogram Miguel Servet (CP19/00159) to AGV, PFIS contracts (FI19/00304) to EMM, (FI21/00165) to ASA, and (FI19/00083) to CGC, and a mobility grant (MV21/00103) to EMM, from the Ministerio de Ciencia e Innovación, Spain. AJM was granted by a CSL Centenary Award.

Don't wait, vaccinate: evaluation of routine vaccination administration and reactogenicity in preterm infants.

To evaluate the incidence of cardiorespiratory events in preterm infants when administering the 2-month vaccine series all at once compared to spreading vaccines over multiple days. This single-center, retrospective cohort study from 2019-2022 included preterm neonates receiving 2-month vaccinations. The primary outcome was incidence of cardiorespiratory events from time of initial vaccine administration up to 48 h after final administration. Univariate analysis was performed to identify predictors of primary outcome. There were 127 patients (pre-practice change n1 = 52, post-practice change n2 = 75) included with no difference in the number of cardiorespiratory events between groups. Predictors of severe event included younger gestational age, smaller birth weight, shorter birth length, and greater cardiorespiratory events at baseline. Vaccine schedule interruptions occur more often when administration is spread over multiple days. Administration of 2-month vaccinations all at once was not associated with increased cardiorespiratory events and prevents interruptions to vaccine schedule.

Thinning followed by slash burning enhances growth and reduces vulnerability to drought for Pinus nigra.

Increasingly frequent severe drought events are pushing Mediterranean forests to unprecedented responses. Lack of management leads to dense forests that are highly susceptible to drought stress, potentially resulting in extensive dieback and increased vulnerability to other disturbances. Forest treatments like thinning and slash burning reduce competition for resources and have the potential to enhance tree growth and vigor and minimize tree vulnerability to drought. Here, we used tree rings to study the growth and physiological response of black pine (Pinus nigra) to drought in northeastern Spain under different treatments, including two thinning intensities (light and heavy, with 10% and 40% basal area reduction, respectively) followed by two understory treatments (clearing alone and in combination with slash burning), resulting in a research design of four treatments plus an untreated control with three replicates. Specifically, we studied basal area increment (BAI), resilience indices, and intrinsic water use efficiency (iWUE) using carbon and oxygen isotope composition (δ13C and δ18O in tree-ring cellulose) before and after treatments. Our results showed that BAI and resistance to drought increased in the heavy-thin (burned and unburned) and light-thin burned units. Resilience increased in the burned units regardless of the thinning intensity, while recovery was not affected by treatment. Slash burning additionally increased BAI in the light-thin and resistance and resilience in the heavy-thin units compared with clearing alone. The stable isotope analysis revealed a minor effect of treatments on δ13C and δ18O. No change in iWUE among treatments was presumably linked to a proportional increase in both net CO2 assimilation and stomatal conductance, which particularly increased in the heavy-thin (burned and unburned) and light-thin burned units, indicating that these trees were the least affected by drought. This study shows that management approaches aimed at reducing wildfire hazard can also increase the vigor of dominant trees under drought stress. By reducing competition both from the overstory and the understory, thinning followed by clearing alone or in combination with slash burning promotes tree growth and vigor and increases its resistance and resilience to drought.