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BACKGROUND: Heart transplant recipients are at a high-risk of complications from the coronavirus-2019 (COVID-19) infection. Heart transplant recipients are a special group of persistently immunosuppressed people, and COVID-19 may cause them to experience an unpredictable course of infection, with a risk of hospitalization occurring well beyond their initial infection period. The seriousness of COVID-19 disease in heart transplant recipients emphasizes how vital it is to refer patients promptly and early to specialized heart transplant centers. METHODS: We retrospectively reviewed all heart transplant recipients at a single center between March 2019 and October 2021. All recipients with positive nasopharyngeal reverse transcriptase-polymerase chain reaction tests for COVID-19 were included in this study. After IRB approval, we obtained medical records and patient data from electronic medical records. RESULTS: This study followed 126 heart transplant patients from March 2019 to October 2021 of which only 49 had COVID-19 infections. The median age at infection was 58 years (49-65), with 41% female. Race distribution was as follows: 59% Caucasian and 39% African American. The median time from transplant to infection was 384 days (237-677). All infected patients had a 50% dose reduction in mycophenolate mofetil per institutional protocol. The majority of symptoms were cough, fatigue, shortness of breath, and fever. Among all patients with COVID-19, 45 (92%) were vaccinated. Of those vaccinated, 27 (60%) patients received Pfizer initial and booster doses, whereas 18 (40%) received Moderna initial and booster doses. Twelve patients (24%) were hospitalized within 90 days of infection, with only two requiring ICU level of care. The median duration of hospitalization was 5 days (4-9). Of the hospitalized patients, 11 (92%) were discharged, and 1 (8%) died in the hospital. Three of the four unvaccinated patients were hospitalized, and one died while hospitalized. The remaining 37 patients were managed as outpatients. CONCLUSION: Heart transplant recipients have an increased risk of contracting COVID-19 and developing severe symptoms due to multiple healthcare contacts, preexisting health conditions, and weakened immune systems. Our data highlight that most vaccinated patients do not require hospitalization within 90 days of infection, and those hospitalized have a high likelihood of survival without needing ICU care.
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Genetically modified maize MON 95275 was developed to confer protection to certain coleopteran species. These properties were achieved by introducing the mpp75Aa1.1, vpb4Da2 and DvSnf7 expression cassettes. The molecular characterisation data and bioinformatic analyses reveal similarity to known toxins, which was further assessed. None of the identified differences in the agronomic/phenotypic and compositional characteristics tested between maize MON 95275 and its conventional counterpart needs further assessment. The GMO Panel does not identify safety concerns regarding the toxicity and allergenicity of the Mpp75Aa1.1 and Vpb4Da2 proteins and the DvSnf7 dsRNA and derived siRNAs as expressed in maize MON 95275 and finds no evidence that the genetic modification would change the overall allergenicity of maize MON 95275. In the context of this application, the consumption of food and feed from maize MON 95275 does not represent a nutritional concern in humans and animals. The GMO Panel concludes that maize MON 95275 is as safe as the conventional counterpart and non-GM maize varieties tested, and no post-market monitoring of food/feed is considered necessary. In the case of accidental release of maize MON 95275 material into the environment, this would not raise environmental safety concerns. The post-market environmental monitoring plan and reporting intervals are in line with the intended uses of maize MON 95275. The GMO Panel concludes that maize MON 95275 is as safe as its conventional counterpart and the tested non-GM maize varieties with respect to potential effects on human and animal health and the environment.
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Genetically modified (GM) maize DP910521 was developed to confer resistance against certain lepidopteran insect pests as well as tolerance to glufosinate herbicide; these properties were achieved by introducing the mo-pat, pmi and cry1B.34 expression cassettes. The molecular characterisation data and bioinformatic analyses did not identify issues requiring food/feed safety assessment. None of the identified differences in the agronomic/phenotypic and compositional characteristics tested between maize DP910521 and its conventional counterpart needs further assessment except for the levels of iron in grain, which do not raise safety and nutritional concerns. The GMO Panel does not identify safety concerns regarding the toxicity and allergenicity of the Cry1B.34, PAT and PMI proteins as expressed in maize DP910521. The GMO panel finds no evidence that the genetic modification impacts the overall safety of maize DP910521. In the context of this application, the consumption of food and feed from maize DP910521 does not represent a nutritional concern in humans and animals. The GMO Panel concludes that maize DP910521 is as safe as its conventional counterpart and non-GM maize varieties tested, and no post-market monitoring of food/feed is considered necessary. In the case of accidental release of maize DP910521 material into the environment, this would not raise environmental safety concerns. The post-market environmental monitoring plan and reporting intervals are in line with the intended uses of maize DP910521. The GMO Panel concludes that maize DP910521 is as safe as its conventional counterpart and the tested non-GM maize varieties with respect to potential effects on human and animal health and the environment.
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Background: Necrotizing fasciitis (NF) can affect any soft tissue and skin of the body. Its progression is rapid and it is associated with a high mortality rate. Therefore, the search for easily accessible and low-cost biomarkers that could predict the prognosis of patients with NF is necessary. Objective: To evaluate the role of neutrophil-lymphocyte ratio (NLR) as a predictor of mortality in patients with NF. Material and methods: Observational, cross-sectional, retrospective and analytical study of patients admitted between April and October 2020 in a tertiary-care hospital. The statistical tests used for the comparison of variables between the study groups were chi-square, Fisher's exact, Student's t and Mann-Whitney U. A receiver operating characteristic (ROC) curve was performed to determine the accuracy of NLR in predicting mortality in patients with NF. Results: A total of 25 patients were included and stratified into non-survivors and survivors. The non-survivor group had an elevated NLR value compared to survivors (15.57 [13.75] vs. 7.91 [4.13]; p = 0.065). The NLR had an area under the curve (AUC) of 0.729 (95% confidence interval [95% CI] 0.516-0.886; p = 0.044), sensitivity of 77.78% (40-97.2), and specificity of 75% (47.6-92.7). The optimal cut-off point obtained for NLR was > 9.21. Conclusions: An NLR value > 9.21 could be a predictor of mortality in patients with NF.
Introducción: la fascitis necrotizante (FN) puede afectar cualquier tejido blando y piel del cuerpo. Su progresión es rápida y está relacionada con un índice de mortalidad alto. Por lo tanto, la búsqueda de biomarcadores de fácil acceso y bajo costo que puedan predecir el pronóstico de los pacientes con FN es necesaria. Objetivo: evaluar el papel del índice neutrofilo-linfocito (INL) como un predictor de mortalidad en los pacientes con FN. Material y métodos: estudio observacional, transversal, retrospectivo y analítico de pacientes admitidos entre abril y octubre del 2020 en un hospital de tercer nivel. Las pruebas estadísticas utilizadas para la comparación de las variables entre los grupos de estudio fueron chi cuadrado, exacta de Fisher, t de Student y U de Mann-Whitney. Una curva característica operativa del receptor (ROC) fue realizada para determinar la precisión del INL en la predicción de mortalidad en pacientes con FN. Resultados: un total de 25 pacientes fueron incluidos y estratificados en no sobrevivientes y sobrevivientes. El grupo no sobreviviente tuvo un valor elevado del INL en comparación con los sobrevivientes (15.57 [13.75] frente a 7.91 [4.13]; p = 0.065). El INL tuvo un área bajo la curva (AUC) de 0.729 (intervalo de confianza del 95% [IC 95%] 0.516-0.886; p = 0.044), sensibilidad de 77.78% (40-97.2) y especificidad de 75% (47.6-92.7). El punto de corte óptimo obtenido para el INL fue > 9.21. Conclusiones: un valor de INL > 9.21 podría ser un predictor de mortalidad en los pacientes con FN.
Subject(s)
Fasciitis, Necrotizing , Lymphocytes , Neutrophils , Humans , Fasciitis, Necrotizing/mortality , Fasciitis, Necrotizing/blood , Fasciitis, Necrotizing/diagnosis , Male , Retrospective Studies , Female , Cross-Sectional Studies , Middle Aged , Prognosis , Adult , Aged , ROC Curve , Lymphocyte Count , Predictive Value of Tests , Biomarkers/bloodABSTRACT
This study aimed to evaluate pain assessment strategies and factors associated with outcomes after microvascular decompression for the treatment of primary trigeminal neuralgia in adults. We conducted a systematic review and meta-analysis of English, Spanish, and French literature. We searched three databases, PubMed, Ovid, and EBSCO, from 2010 to 2022 and selected studies including patients with primary trigeminal neuralgia, clear pain assessment, and pain outcomes. Population means and standard deviations were calculated. Studies that included factors associated with postoperative outcomes were included in the meta-analysis. A total of 995 studies involving 5673 patients with primary trigeminal neuralgia following microvascular decompression were included. Patients with arteries compressing the trigeminal nerve demonstrated optimal outcomes following microvascular decompression (odds ratio [OR]= 0.39; 95% confidence interval [CI] = 0.19-0.80; X2 = 46.31; Dof = 15; I2 = 68%; P = < 0.0001). Conversely, when comparing arterial vs venous compression of the trigeminal nerve (OR = 2.72; 95% CI = 1.16-6.38; X2 = 23.23; Dof = 10; I2 = 57%; P = 0.01), venous compression demonstrated poor outcomes after microvascular decompression. Additionally, when comparing single-vessel vs multiple-vessel compression (OR = 2.72; 95% CI = 1.18-6.25; X2 = 21.17; Dof = 9; I2 = 57%; P = 0.01), patients demonstrated unfavorable outcomes after microvascular decompression. This systematic review and meta-analysis evaluated factors associated with outcomes following microvascular decompression (MVD) for primary trigeminal neuralgia (PTN). Although MVD is an optimal treatment strategy for PTN, a gap exists in interpreting the results when considering the lack of evidence for most pain assessment strategies.
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Despite the potential of photodynamic therapy (PDT) in cancer treatment, the development of efficient and photostable photosensitizing molecules that operate at long wavelengths of light has become a major hurdle. Here, we report for the first time an Ir(III)-phthalocyanine conjugate (Ir-ZnPc) as a novel photosensitizer for high-efficiency synergistic PDT treatment that takes advantage of the long-wavelength excitation and near infrared (NIR) emission of the phthalocyanine scaffold and the known photostability and high phototoxicity of cyclometalated Ir(III) complexes. In order to increase water solubility and cell membrane permeability, the conjugate and parent zinc phthalocyanine (ZnPc) were encapsulated in amphoteric redox-responsive polyurethane-polyurea hybrid nanocapsules (Ir-ZnPc-NCs and ZnPc-NCs, respectively). Photobiological evaluations revealed that the encapsulated Ir-ZnPc conjugate achieved high photocytotoxicity in both normoxic and hypoxic conditions under 630 nm light irradiation, which can be attributed to dual Type I and Type II reactive oxygen species (ROS) photogeneration. Interestingly, PDT treatments with Ir-ZnPc-NCs and ZnPc-NCs significantly inhibited the growth of three-dimensional (3D) multicellular tumor spheroids. Overall, the nanoencapsulation of Zn phthalocyanines conjugated to cyclometalated Ir(III) complexes provides a new strategy for obtaining photostable and biocompatible red-light-activated nano-PDT agents with efficient performance under challenging hypoxic environments, thus offering new therapeutic opportunities for cancer treatment.
Subject(s)
Antineoplastic Agents , Indoles , Isoindoles , Photochemotherapy , Photosensitizing Agents , Humans , Indoles/chemistry , Indoles/pharmacology , Photosensitizing Agents/chemistry , Photosensitizing Agents/pharmacology , Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacology , Iridium/chemistry , Iridium/pharmacology , Organometallic Compounds/chemistry , Organometallic Compounds/pharmacology , Zinc Compounds/chemistry , Reactive Oxygen Species/metabolism , Nanocapsules/chemistry , Cell Line, Tumor , Cell Survival/drug effectsABSTRACT
The European Commission asked EFSA for a risk assessment on small organoarsenic species in food. For monomethylarsonic acid MMA(V), decreased body weight resulting from diarrhoea in rats was identified as the critical endpoint and a BMDL10 of 18.2 mg MMA(V)/kg body weight (bw) per day (equivalent to 9.7 mg As/kg bw per day) was calculated as a reference point (RP). For dimethylarsinic acid DMA(V), increased incidence in urinary bladder tumours in rats was identified as the critical endpoint. A BMDL10 of 1.1 mg DMA(V)/kg bw per day (equivalent to 0.6 mg As/kg bw per day) was calculated as an RP. For other small organoarsenic species, the toxicological data are insufficient to identify critical effects and RPs, and they could not be included in the risk assessment. For both MMA(V) and DMA(V), the toxicological database is incomplete and a margin of exposure (MOE) approach was applied for risk characterisation. The highest chronic dietary exposure to DMA(V) was estimated in 'Toddlers', with rice and fish meat as the main contributors across population groups. For MMA(V), the highest chronic dietary exposures were estimated for high consumers of fish meat and processed/preserved fish in 'Infants' and 'Elderly' age class, respectively. For MMA(V), an MOE of ≥ 500 was identified not to raise a health concern. For MMA(V), all MOEs were well above 500 for average and high consumers and thus do not raise a health concern. For DMA(V), an MOE of 10,000 was identified as of low health concern as it is genotoxic and carcinogenic, although the mechanisms of genotoxicity and its role in carcinogenicity of DMA(V) are not fully elucidated. For DMA(V), MOEs were below 10,000 in many cases across dietary surveys and age groups, in particular for some 95th percentile exposures. The Panel considers that this would raise a health concern.
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BACKGROUND: Bile duct injury (BDI) repair surgery is usually associated with morbidity/mortality. The neutrophil-to-lymphocyte ratio (NLR) easily assesses a patient's inflammatory status. The study aims to determine the possible relationship between preoperative NLR (pNLR) with postoperative outcomes in BDI repair surgery. METHODS: Approved Ethics/Research Committee retrospective study, in patients who had a Bismuth-Strasberg type E BDI repair (2008-2023). Data registered was: morbidity, mortality, and long-term outcomes (primary patency and loss of primary patency) (Kaplan-Meier). Group comparison (U Mann-Whitney), receiver operator characteristic (ROC): area under curve [AUC]; cut-off value, and Youden index [J], and logistic regression analysis were used for pNLR evaluation. RESULTS: Seventy-three patients were studied. Mean age was 44.4 years. E2 was the commonest BDI (38.4%). Perioperative morbidity/mortality was 31.5% and 1.4%. Primary patency was 95.9%. 8.2% have lost primary patency (3-year actuarial patency: 85.3%). Median pNLR was higher in patients who had any complication (4.84 vs. 2.89 p = 0.015), biliary complications (5.29 vs. 2.86 p = 0.01), and patients with loss of primary patency (5.22 vs. 3.1 p = 0.08). AUC's, cut-off values and (J) were: any complication (0.678, pNLR = 4.3, J = 0.38, p = 0.007), serious complication (0.667, pNLR = 4.3, J = 0.34, p = 0.04), biliary complications (0.712, pNLR = 3.64, J = 0.46, p = 0.001), and loss of primary patency (0.716, pNLR = 3.24, J = 0.52, p = 0.008). Logistic regression was significant in any complication (Exp [B]: 0.1, p = 0.002), serious complications (Exp [B]: 0.2, p = 0.03), and biliary complications (Exp [B]: 8.1, p = 0.003). CONCLUSIONS: pNLR is associated with complications in BDI repair with moderate to acceptable predictive capacity. pNLR could potentially predict patency of a BDI repair.
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INTRODUCTION: Mucocutaneous Behcet's disease is often a therapeutic challenge. Roflumilast has shown promise in other inflammatory dermatological conditions. The objective of this study is to evaluate the characteristics, effectiveness and safety of roflumilast in the treatment of Behçet's Disease-associated aphthosis in routine clinical practice. METHODS: Single cohort ambispective observational study. 11 patients with Behçet disease treated with roflumilast participated. Data collection included demographic, clinical and outcome variables. Statistical analysis compared 12 weeks of treatment with roflumilast with a previous period without treatment and with a period with the previous treatment. RESULTS: During treatment with roflumilast, a reduction in flare-ups and oral ulcers was observed compared to the untreated period and the previous treatment period. A reduction in genital ulcers, pain and ulcer duration was observed between the Whitout treatment period and the Roflumilast treatment period.Adverse effects occurred in 54% of patients, most of which were self-limiting or manageable with dose adjustment. No patient withdrew treatment. DISCUSSION: Roflumilast appears a promising option in the treatment of Behçet's disease with favourable effectiveness, safety and tolerability profiles. Although further research is needed, roflumilast offers a promising treatment option for Behçet's Disease-associated aphthosis, which could improve patients' quality of life and address unmet therapeutic needs.
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Biofilm-associated wound infections in diabetic and immunocompromised patients are an increasing threat due to rising antibiotic resistance. Various wound models have been used to screen for efficient antiinfection treatments. However, results from in vitro models do not always match in vivo results, and this represents a bottleneck for development of new infection treatments. In this study, a static 2-D microtiter plate-based biofilm model was tested for growing clinically relevant Staphylococcus aureus wound isolates in various operating conditions, seeking to identify an optimal setup that would yield physiologically relevant results. Specifically, the tested variables included wound-mimicking growth media, precoating of surface with different proteins, multiwell plates with various surface properties, and the effect of bacterial pre-attachment step. Our results indicated that protein precoating is a key factor for supporting biofilm growth. The same wound isolate responded with significant differences in biofilm formation to different wound-mimicking media. Biofilm dispersal, as a proxy for effectiveness of antibiofilm treatments, was also investigated in response to proteinase K. The dispersal effect of proteinase K showed that the biofilm dispersal is contingent upon the specific wound isolate, with isolates CCUG 35571 and ATCC 6538 showing considerable dispersal responses. In conclusion, this study observed a higher biofilm formation in isolates when a protein precoating of collagen type I was applied but being dependent on the growth media selected. That is why we recommend to use simulated wound fluid or a wound-mimicking growth media to perform similar studies. Furthermore, proteinase K is suggested as an important factor that could affect biofilm dispersal within such models, since biofilm dispersal was induced in isolates CCUG 35571 and ATCC 6538 in simulated wound fluid on precoated collagen type I plates.
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INTRODUCTION: Huntington's disease (HD) is a hereditary condition caused by the expansion of the CAG trinucleotide in the huntingtin gene on chromosome 4, resulting in motor, cognitive, and psychiatric disorders that significantly impact patients' quality of life. Despite the lack of effective treatments for the disease, various surgical strategies have been explored to alleviate symptoms and slow its progression. METHODOLOGY: A comprehensive systematic literature review was conducted, including MeSH terms, yielding only 38 articles that were categorized based on the surgical procedure. The study aimed to describe the types of surgeries performed and their efficacy in HD patients. RESULTS: Deep brain stimulation (DBS) involved 41 predominantly male patients with bilateral implantation in the globus pallidus, showing a preoperative Unified Huntington's Disease Rating Scale (UHDRS) score of 60.25 ± 16.13 and a marked postoperative value of 48.54 ± 13.93 with a p < 0.018 at one year and p < 0.040 at three years. Patients experienced improvement in hyperkinesia but worsening of bradykinesia. Additionally, cell transplantation in 119 patients resulted in a lower preoperative UHDRS score of 34.61 ± 14.61 and a significant postoperative difference of 32.93 ± 15.87 (p < 0.016), respectively, in the first to third years of following. Some now, less used procedures were crucial for understanding brain function, such as pallidotomies in 3 patients, showing only a 25 % difference from their baseline. CONCLUSION: Despite advancements in technology, there is still no curative treatment, only palliative options. Promising treatments like trophic factor implantation offer new prospects for the future.
Subject(s)
Deep Brain Stimulation , Huntington Disease , Huntington Disease/surgery , Huntington Disease/therapy , Humans , Neurosurgical Procedures/methodsABSTRACT
Mosquitoes, as insect vectors, play a crucial role in transmitting viruses and parasites, leading to millions of human deaths in tropical and subtropical regions worldwide. This study aimed to evaluate the effects of ethanolic extracts of three species within the genus Myrothecium (M. roridum, M. dimerum, and M. nivale) on Aedes aegypti mosquito larvae to assess the inhibitory effect on growth and development, as well as to determine mortality. We quantify the average lethal concentrations and provide a qualitative characterization of the chemical groups responsible for their potential. Phytochemical screening revealed the presence of alkaloids, flavonoids, and terpenoids in the ethanolic extracts of the three fungal species. Tannins were found only in the extracts of M. dimerum and M. roridum. We observed a clear dependence of the effects of the crude extracts on mosquito larvae on the concentrations used and the duration of exposure. The toxic effect was observed after 48 h at a concentration of 800 ppm for both M. dimerum and M. nivale, while M. roridum showed effectiveness after 72 h. All three species within the genus Myrothecium exhibited 100% biological activity after 72 h of exposure at 600 ppm. At lower concentrations, there was moderate growth and development inhibitory activity in the insect life cycle. The study highlights the effectiveness of crude Myrothecium extracts in combating mosquito larvae, with effects becoming apparent between 48 and 72 h of exposure. This initial approach underscores the potential of the fungus's secondary metabolites for further in-depth analysis of their individual effects or synergies between them.
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Objective: The objective of the study was to analyze the diagnostic process and the time until the start of treatment of patients with idiopathic pulmonary fibrosis in relation to the publication of successive clinical practice guide. Material and methods: Multicenter, observational, ambispective study, in which patients includes in the idiopathic pulmonary fibrosis registry of the Spanish Society of Pulmonologist and Thoracic Surgery were analyzed. An electronic data collection notebook was enabled on the society's website. Sociodemographic and clinical variables were collected at diagnosis and follow-up of the patients. Results: From January 2012 to december 2019, 1064 patients were included in the registry, with 929 finally analyzed. The diagnosis process varied depending on the year in which it was performed, and the radiological pattern observed in the high-resolution computed tomography. Up to 26.3% of the cases (244) were diagnosed with chest high-resolution computed tomography and clinical evaluation. Surgical biopsy was used up to 50.2% of cases diagnosed before 2011, while it has been used in 14.2% since 2018. The median time from the onset of symptoms to diagnosis was 360 days (IQR 120-720), taking more than 2 years in the 21.0% of patients. A percentage of 79.4 of patients received antifibrotic treatment. The average time from diagnosis to the antifibrotic treatment has been 309 ± 596.5 days, with a median of 49 (IQR 0-307). Conclusions: The diagnostic process, including the time until diagnosis and the type of test used, has changed from 2011 to 2019, probably due to advances in clinical research and the publication of diagnostic-therapeutic consensus guidelines.
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BACKGROUND: Globally, fall-related injuries are a substantial problem, and 80% of fatal falls occur in low-income and middle-income countries. We aimed to measure time from injury to hip-fracture surgery in people aged 50 years or older living in low-income and middle-income regions, as well as to measure the proportion of patients with surgical stabilisation of their hip fracture within 72 h of admission to hospital and to identify risk factors associated with surgical delay. METHODS: For this secondary analysis, we analysed data collected from Africa, Latin America, China, India, and Asia (excluding China and India) for the International Orthopaedic Multicentre Study in Fracture Care (INORMUS) between March 29, 2014, and June 15, 2022. Patients from INORMUS were included in this analysis if they were aged 50 years or older and had an isolated, primary hip fracture sustained from a ground-level fall. Staff at participating hospitals identified patients with musculoskeletal injury and referred them for assessment of eligibility. We report time from injury to surgery as three distinct time periods: time from injury to hospital admission, time from admission to surgery, and a total time from injury to surgery. Date and time of injury were self-reported by patients at the time of study recruitment. If time to hospital admission after injury exceeded 24 h, patients reported the primary reason for delayed admission. Reasons for surgery, no surgery, and surgical delay were reported by the treating team. For patients undergoing surgery, multivariable regression analyses were used to identify risk factors for surgical delay. FINDINGS: 4486 adults aged 50 years or older with an isolated, primary hip fracture were enrolled in INORMUS from 55 hospitals in 24 countries. Countries were grouped into five regions: Africa (418 [9·3%] of 4486), Latin America (558 [12·4%]), China (1680 [37·4%]), India (1059 [23·6%]) and Asia (excluding China and India; 771 [17·2%]). Of 4486 patients, 3805 (84·8%) received surgery. The rate of surgery was similar in all regions except in Africa, where only 193 (46·3%) of 418 patients had surgery. Overall, 2791 (62·2%) of 4486 patients were admitted to hospital within 24 h of injury. However, 1019 (22·7%) of 4486 patients had delayed hospital admission of 72 h or more from injury. The two most common reasons for delayed admission of more than 24 h were transfer from another hospital (522 [36·2%] of 1441) and delayed care-seeking because patients thought the injury would heal on its own (480 [33·3%]). Once admitted to hospital, 1451 (38·1%) of 3805 patients who received surgery did so within 72 h (median 4·0 days [IQR 1·7-6·0]). Regional variation was seen in the proportion of patients receiving surgery within 72 h of hospital admission (92 [17·9%] of 514 in Latin America, 53 [27·5%] of 193 in Africa, 454 [30·9%] of 1471 in China, 318 [44·4%] of 716 in Asia [excluding China and India], and 534 [58·6%] of 911 in India). Of all 3805 patients who received operative treatment, 2353 (61·8%) waited 72 h or more from hospital admission. From time of injury, the proportion of patients who were surgically stabilised within 72 h was 889 (23·4%) of 3805 (50 [9·7%] of 517 in Latin America, 31 [16·1%] of 193 in Africa, 277 [18·8%] of 1471 in China, 189 [26·4%] of 716 in Asia [excluding China and India], and 342 [37·5%] of 911 in India). INTERPRETATION: Access to surgery within 72 h of hospital admission was poor, with factors that affected time to surgery varying by region. Data are necessary to understand existing pathways of hip-fracture care to inform the local development of quality-improvement initiatives. FUNDING: The National Health and Medical Research Council of Australia, the Canadian Institutes of Health Research, McMaster Surgical Associates, Hamilton Health Sciences, and the US National Institutes of Health.
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BACKGROUND: The optimal dose of rabbit anti-thymocyte globulin (r-ATG) in renal transplantation is still under debate. We previously reported that a low-dose r-ATG induction of 3 mg/kg can be used safely and effectively in low-risk kidney transplants with good results in the first year after transplantation compared to basiliximab induction. AIMS: The purpose of this study is to evaluate the long-term impact of this trial of low-dose r-ATG versus basiliximab on post-transplant outcomes (patient and graft survival, biopsy-proven acute rejection incidence [BPAR], infectious complications, and side effects). METHODS: Observational study (three-year follow-up) of a 12-month single-center, open-label RCT in de novo kidney allograft recipients assigned to receive either thymoglobulin or basiliximab before transplantation. RESULTS: Patients in the basiliximab group (BG) underwent more kidney transplant biopsies than patients in the low-dose r-ATG group (TG) (50 vs. 31.8%, p = 0.07). Although the 12-month cumulative incidence of BPAR was lower in BG, by the end of the three-year follow-up period this incidence was higher (22%) than in the low-dose TG (15%) (p = ns). Steroids were withdrawn more frequently in the TG group and sirolimus was most frequently indicated. Graft function and graft survival were higher in the low-dose TG than in the BG at three-year follow-up but not statistically significant. Patient survival was similar between groups (>90%). CONCLUSIONS: These three-year follow-up data confirm the efficacy and favorable safety aspects of the low-dose r-ATG (3 mg/kg) in low-risk kidney transplantation.
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Hydraulic failure due to xylem embolism has been identified as one of the main mechanisms involved in drought-induced forest decline. Trees vulnerability to hydraulic failure depends on their hydraulic safety margin (HSM). While it has been shown that HSM globally converges between tree species and biomes, there is still limited knowledge regarding how HSM can adjust locally to varying drought conditions within species. In this study, we relied on three long-term partial rainfall exclusion experiments to investigate the plasticity of hydraulic traits and HSM for three Mediterranean tree species (Quercus ilex L., Quercus pubescens Willd., and Pinus halepensis Mill.). For all species, a homeostasis of HSM in response to rainfall reduction was found, achieved through different mechanisms. For Q. ilex, the convergence in HSM is attributed to the adjustment of both the turgor loss point (Ψtlp) and the water potential at which 50% of xylem conductivity is lost due to embolism (P50). In contrast, the maintenance of HSM for P. halepensis and Q. pubescens is related to its isohydric behavior for the first and leaf area adjustment for the latter. It remains to be seen whether this HSM homeostasis can be generalized and if it will be sufficient to withstand extreme droughts expected in the Mediterranean region.
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Endothelial dysfunction (ED) is associated with progressive changes contributing to clinical complications related to macro- and microvascular diseases. Garlic (Allium sativum L.) and its organosulfur components have been related to beneficial cardiovascular effects and could improve endothelial function. The ENDOTALLIUM Study aimed to evaluate the effect of the regular consumption of encapsulated purple garlic oil on microvascular function, endothelial-related biomarkers, and the components of metabolic syndrome (MetS) in untreated subjects with cardiometabolic alterations. Fifty-two individuals with at least one MetS component were randomized (1:1) in a single-center, single-blind, placebo-controlled, parallel-group study. The participants received encapsulated purple garlic oil (n = 27) or placebo (n = 25) for five weeks. Skin microvascular peak flow during post-occlusive reactive hyperemia significantly increased in the purple garlic oil group compared to the placebo group (between-group difference [95%CI]: 15.4 [1.5 to 29.4] PU; p = 0.031). Likewise, hs-CRP levels decreased in the purple garlic group compared to the control group (-1.3 [-2.5 to -0.0] mg/L; p = 0.049). Furthermore, we observed a significant reduction in the mean number of MetS components in the purple garlic group after five weeks (1.7 ± 0.9 vs. 1.3 ± 1.1, p = 0.021). In summary, regular consumption of encapsulated purple garlic oil significantly improved microvascular function, subclinical inflammatory status, and the overall MetS profile in a population with cardiometabolic alterations.
Subject(s)
Garlic , Metabolic Syndrome , Humans , Metabolic Syndrome/drug therapy , Male , Garlic/chemistry , Female , Middle Aged , Single-Blind Method , Adult , Sulfides/pharmacology , Sulfides/administration & dosage , Allyl Compounds/pharmacology , Allyl Compounds/administration & dosage , Biomarkers/blood , Plant Oils/pharmacology , Plant Oils/administration & dosage , Endothelium, Vascular/drug effects , Endothelium, Vascular/physiopathology , Skin/blood supply , Skin/drug effects , Microcirculation/drug effects , Microvessels/drug effects , Microvessels/physiopathologyABSTRACT
Introduction: Hypereosinophilic Syndrome (HES) is a rare disorder characterized by persistent elevation of eosinophils, leading to multi-organ infiltration and damage. Eosinophilic Myocarditis (EM) is one of its severe complications contributing significantly to morbidity and mortality. Herein, we describe the diagnostic and therapeutic challenges of EM, emphasizing the significance of early recognition and multidisciplinary management. Case presentation: A 51-year-old female with a history of EM, heart failure, and peripheral eosinophilia presented with NYHA class 3b symptoms. Laboratory findings revealed elevated peripheral eosinophil count, NT-Pro BNP, and characteristic electrocardiogram abnormalities. Imaging studies confirmed biventricular thrombi and myocardial abnormalities consistent with EM. Treatment involved Solu-Medrol for HES and heparin for ventricular thrombi, leading to initial clinical improvement. However, refractory heart failure necessitated urgent heart transplantation. Discussion: EM, an under-recognized complication of HES, poses diagnostic and management challenges. Management includes standard heart failure treatments, steroids, and emerging therapies like Mepolizumab. Early diagnosis and aggressive management are pivotal for improving outcomes in this rare and potentially fatal condition. Conclusion: Advancements in the detection of complications, surgical management, and therapeutic options have improved outcomes in HES. Ongoing research is essential to further understand and address the diagnostic and therapeutic challenges of HES and EM.