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1.
Vet Med Int ; 2023: 2493618, 2023.
Article in English | MEDLINE | ID: mdl-37649553

ABSTRACT

Bone marrow (BM) evaluation is highly important for the diagnosis of numerous hematological alterations in animals, especially cats, given their greater propensity for hematopoietic changes associated with retrovirus infections. This study aims to describe the main aspects of the BM of cats with different hematological conditions, comparing with reference intervals established from animals without hematological alterations and also with a previously established reference interval. To do so, we evaluated full blood and BM samples from 120 cats with no abnormalities on physical examination, negative for FeLV and FIV. Hemograms were performed from automated total cell and platelet and leukocyte differential counts in blood smears. BM samples were placed in Petri dishes; medullary spicules were selected to make up to eight cytological slides stained by the May-Grunwald-Giemsa technique, which were subjected to quantitative and cellular morphology evaluations. The cats were predominantly young, 64.2% female and 35.8% male. The average number of medullary spicules in samples was 13.7%, and density was 44%. In the BM quantitative analysis, prorubricytes and rubriblasts had higher quantities than the recommended one for all cats with or without hematological alterations. In all groups, lymphocytes were decreased, and cats with lymphocytosis were closest to the reference range, showing flame cells and Mott cells. The reference interval for the bone marrow cell count obtained from the samples in this work differs from previously established data, leading to different interpretations of the patient's BM condition, according to the cell population observed and the reference interval used. This divergence strongly emphasizes the need to correlate clinical, epidemiological, hematological, and bone marrow data of each patient for a better understanding of the patient's condition. The popularization of BM assessment is essential so that more reliable reference intervals can be established according to the population served by each pathologist and clinical laboratory.

2.
Hum Brain Mapp ; 44(15): 4986-5001, 2023 10 15.
Article in English | MEDLINE | ID: mdl-37466309

ABSTRACT

Magnetic resonance electrical properties tomography (MR-EPT) is a non-invasive measurement technique that derives the electrical properties (EPs, e.g., conductivity or permittivity) of tissues in the radiofrequency range (64 MHz for 1.5 T and 128 MHz for 3 T MR systems). Clinical studies have shown the potential of tissue conductivity as a biomarker. To date, model-based conductivity reconstructions rely on numerical assumptions and approximations, leading to inaccuracies in the reconstructed maps. To address such limitations, we propose an artificial neural network (ANN)-based non-linear conductivity estimator trained on simulated data for conductivity brain imaging. Network training was performed on 201 synthesized T2-weighted spin-echo (SE) data obtained from the finite-difference time-domain (FDTD) electromagnetic (EM) simulation. The dataset was composed of an approximated T2-w SE magnitude and transceive phase information. The proposed method was tested three in-silico and in-vivo on two volunteers and three patients' data. For comparison purposes, various conventional phase-based EPT reconstruction methods were used that ignore B 1 + magnitude information, such as Savitzky-Golay kernel combined with Gaussian filter (S-G Kernel), phase-based convection-reaction EPT (cr-EPT), magnitude-weighted polynomial-fitting phase-based EPT (Poly-Fit), and integral-based phase-based EPT (Integral-based). From the in-silico experiments, quantitative analysis showed that the proposed method provides more accurate and improved quality (e.g., high structural preservation) conductivity maps compared to conventional reconstruction methods. Representatively, in the healthy brain in-silico phantom experiment, the proposed method yielded mean conductivity values of 1.97 ± 0.20 S/m for CSF, 0.33 ± 0.04 S/m for WM, and 0.52 ± 0.08 S/m for GM, which were closer to the ground-truth conductivity (2.00, 0.30, 0.50 S/m) than the integral-based method (2.56 ± 2.31, 0.39 ± 0.12, 0.68 ± 0.33 S/m). In-vivo ANN-based conductivity reconstructions were also of improved quality compared to conventional reconstructions and demonstrated network generalizability and robustness to in-vivo data and pathologies. The reported in-vivo brain conductivity values were in agreement with literatures. In addition, the proposed method was observed for various SNR levels (SNR levels = 10, 20, 40, and 58) and repeatability conditions (the eight acquisitions with the number of signal averages = 1). The preliminary investigations on brain tumor patient datasets suggest that the network trained on simulated dataset can generalize to unforeseen in-vivo pathologies, thus demonstrating its potential for clinical applications.


Subject(s)
Image Processing, Computer-Assisted , Magnetic Resonance Imaging , Humans , Image Processing, Computer-Assisted/methods , Magnetic Resonance Imaging/methods , Brain/diagnostic imaging , Electric Conductivity , Phantoms, Imaging , Neuroimaging , Algorithms
3.
Arch Bone Jt Surg ; 11(2): 94-101, 2023.
Article in English | MEDLINE | ID: mdl-37168821

ABSTRACT

In orthopedic surgery, there is an increasing number of papers about online studies on the reliability of classification systems. Useful classification systems need to be reliable and valid. Measurement of validity can be variable and is prone to observer bias. These online collaboratives derive adequate power to study reliability by having a large group of trained surgeons review a small number of cases instead of the "classic" reliability studies in which a small number of observers evaluate many cases. Large online interobserver studies have advantages (i.e., less than 15 minutes to complete the survey, the ability to randomize, and the ability to study factors associated with reliability, accuracy, or decision-making). This 'handbook' paper gives an overview of current methods for online reliability studies. We discuss the study design, sample size calculation, statistical analyses of results, pitfalls, and limitations of the study design.

4.
Infect Dis (Lond) ; 54(11): 784-793, 2022 11.
Article in English | MEDLINE | ID: mdl-35794793

ABSTRACT

BACKGROUND: Bacterial infections are associated with acute exacerbations of chronic obstructive pulmonary disease (AECOPD), but the mechanism is incompletely understood. METHOD: In a COPD observational study (NCT01360398), sputum samples were collected monthly at the stable state and exacerbation. Post-hoc analyses of 1307 non-typeable Haemophilus influenzae (NTHi) isolates from 20 patients and 756 Moraxella catarrhalis isolates from 38 patients in one year of follow-up were conducted by multilocus sequence typing (MLST). All isolates came from cultured sputum samples that were analyzed for bacterial species presence, apparition (infection not detected at the preceding visit), or acquisition (first-time infection), with the first study visit as a baseline. Strain apparition or new strain acquisition was analyzed by MLST. The odds ratio (OR) of experiencing an exacerbation vs. stable state was estimated by conditional logistic regression modelling, stratified by patient. RESULTS: The culture results confirmed a significant association with exacerbation only for NTHi species presence (OR 2.28; 95% confidence interval [CI]: 1.12-4.64) and strain apparition (OR 2.38; 95% CI: 1.08-5.27). For M. catarrhalis, although confidence intervals overlapped, the association with exacerbation for first-time species acquisition (OR 5.99; 2.75-13.02) appeared stronger than species presence (OR 3.67; 2.10-6.40), new strain acquisition (OR 2.94; 1.43-6.04), species apparition (OR 4.18; 2.29-7.63), and strain apparition (OR 2.78; 1.42-5.42). This may suggest that previous M. catarrhalis colonization may modify the risk of exacerbation associated with M. catarrhalis infection. CONCLUSIONS: The results confirm that NTHi and M. catarrhalis infections are associated with AECOPD but suggest different dynamic mechanisms in triggering exacerbations.


Subject(s)
Pulmonary Disease, Chronic Obstructive , Sputum , Bacteria , Haemophilus influenzae/genetics , Humans , Lung , Moraxella catarrhalis , Multilocus Sequence Typing , Prospective Studies , Pulmonary Disease, Chronic Obstructive/complications , Sputum/microbiology
5.
BMC Med Inform Decis Mak ; 22(1): 137, 2022 05 18.
Article in English | MEDLINE | ID: mdl-35585624

ABSTRACT

BACKGROUND: Acute kidney injury (AKI) is a serious complication after cardiac surgery. We derived and internally validated a Machine Learning preoperative model to predict cardiac surgery-associated AKI of any severity and compared its performance with parametric statistical models. METHODS: We conducted a retrospective study of adult patients who underwent major cardiac surgery requiring cardiopulmonary bypass between November 1st, 2009 and March 31st, 2015. AKI was defined according to the KDIGO criteria as stage 1 or greater, within 7 days of surgery. We randomly split the cohort into derivation and validation datasets. We developed three AKI risk models: (1) a hybrid machine learning (ML) algorithm, using Random Forests for variable selection, followed by high performance logistic regression; (2) a traditional logistic regression model and (3) an enhanced logistic regression model with 500 bootstraps, with backward variable selection. For each model, we assigned risk scores to each of the retained covariate and assessed model discrimination (C statistic) and calibration (Hosmer-Lemeshow goodness-of-fit test) in the validation datasets. RESULTS: Of 6522 included patients, 1760 (27.0%) developed AKI. The best performance was achieved by the hybrid ML algorithm to predict AKI of any severity. The ML and enhanced statistical models remained robust after internal validation (C statistic = 0.75; Hosmer-Lemeshow p = 0.804, and AUC = 0.74, Hosmer-Lemeshow p = 0.347, respectively). CONCLUSIONS: We demonstrated that a hybrid ML model provides higher accuracy without sacrificing parsimony, computational efficiency, or interpretability, when compared with parametric statistical models. This score-based model can easily be used at the bedside to identify high-risk patients who may benefit from intensive perioperative monitoring and personalized management strategies.


Subject(s)
Acute Kidney Injury , Cardiac Surgical Procedures , Acute Kidney Injury/diagnosis , Acute Kidney Injury/epidemiology , Acute Kidney Injury/etiology , Adult , Algorithms , Cardiac Surgical Procedures/adverse effects , Humans , Machine Learning , Retrospective Studies , Risk Assessment , Risk Factors
6.
CMAJ Open ; 10(1): E173-E182, 2022.
Article in English | MEDLINE | ID: mdl-35260467

ABSTRACT

BACKGROUND: Surgical delay may result in unintended harm to patients needing cardiac surgery, who are at risk for death if their condition is left untreated. Our objective was to derive and internally validate a clinical risk score to predict death among patients awaiting major cardiac surgery. METHODS: We used the CorHealth Ontario Registry and linked ICES health administrative databases with information on all Ontario residents to identify patients aged 18 years or more who were referred for isolated coronary artery bypass grafting (CABG), valvular procedures, combined CABG-valvular procedures or thoracic aorta procedures between Oct. 1, 2008, and Sept. 30, 2019. We used a hybrid modelling approach with the random forest method for initial variable selection, followed by backward stepwise logistic regression modelling for clinical interpretability and parsimony. We internally validated the logistic regression model, termed the CardiOttawa Waitlist Mortality Score, using 200 bootstraps. RESULTS: Of the 112 266 patients referred for cardiac surgery, 269 (0.2%) died while awaiting surgery (118/72 366 [0.2%] isolated CABG, 81/24 461 [0.3%] valvular procedures, 63/12 046 [0.5%] combined CABG-valvular procedures and 7/3393 [0.2%] thoracic aorta procedures). Age, sex, surgery type, left main stenosis, Canadian Cardiovascular Society classification, left ventricular ejection fraction, heart failure, atrial fibrillation, dialysis, psychosis and operative priority were predictors of waitlist mortality. The model discriminated (C-statistic 0.76 [optimism-corrected 0.73]). It calibrated well in the overall cohort (Hosmer-Lemeshow p = 0.2) and across surgery types. INTERPRETATION: The CardiOttawa Waitlist Mortality Score is a simple clinical risk model that predicts the likelihood of death while awaiting cardiac surgery. It has the potential to provide data-driven decision support for managing access to cardiac care and preserve system capacity during the COVID-19 pandemic, the recovery period and beyond.


Subject(s)
COVID-19 , Cardiac Surgical Procedures , Adolescent , Cardiac Surgical Procedures/adverse effects , Humans , Ontario/epidemiology , Pandemics , Risk Factors , SARS-CoV-2 , Stroke Volume , Ventricular Function, Left
7.
Hand (N Y) ; 17(1): 60-67, 2022 01.
Article in English | MEDLINE | ID: mdl-31971012

ABSTRACT

Background: Treatment decisions regarding volar base fractures of the middle phalanx depend on whether the proximal interphalangeal (PIP) joint is reduced. Our aim was to study the agreement among hand surgeons in determining whether the PIP joint fractures are subluxated and to study the factors associated with subluxation of these fractures. Methods: In this retrospective chart review, 413 volar base fractures of the middle phalanx were included. Demographic and injury-related factors were gathered from medical records and radiographs. Using a Web-based survey, interobserver agreement was determined among 105 hand surgeons on the assessment of PIP joint subluxation of a series of 26 cases. Using the cohort of 413 fractures, a threshold for percent articular involvement and relative fracture displacement that corresponds with subluxation of the PIP joint was analyzed. Results: We found moderate to substantial agreement between hand surgeons on subluxation (κ = 0.59, P < .0001) and an overall percent agreement of 85%. Percent articular involvement and relative fracture displacement were independently associated with subluxation of the PIP joint (P < .001). Percent articular involvement of 35% had a specificity of 90% and a negative predicting value (NPV) of 92% for joint subluxation. Relative fracture displacement of 35% had a specificity of 92% and an NPV of 94% for joint subluxation. Conclusions: Surgeons generally agree on whether a PIP joint is subluxated. Percent articular involvement and relative fragment displacement are objective measurements that can help characterize joint stability and assist with decision-making.


Subject(s)
Finger Injuries , Fractures, Bone , Joint Dislocations , Finger Injuries/diagnostic imaging , Finger Injuries/surgery , Finger Joint/diagnostic imaging , Finger Joint/surgery , Fractures, Bone/diagnostic imaging , Fractures, Bone/surgery , Humans , Joint Dislocations/diagnostic imaging , Joint Dislocations/etiology , Joint Dislocations/surgery , Retrospective Studies
8.
Ann Thorac Surg ; 113(5): 1469-1475, 2022 05.
Article in English | MEDLINE | ID: mdl-34228974

ABSTRACT

BACKGROUND: Aortic valve repair (AVr) has emerged as a feasible and effective alternative to AV replacement (AVR) in patients with aortic insufficiency (AI); however, little data exist comparing outcomes. Thus, the objective of this study was to compare early and long-term valve-related complications between AVr and AVR in the treatment of AI. METHODS: This was a single-center, retrospective study of all patients (n = 417) undergoing AVr (n = 264) or AVR (n = 153) for primary AI. Propensity matching using a 1:1 greedy matching algorithm identified 140 patients using 6 covariates (age, sex, left ventricular function, size, presence of aortopathy, and urgency of operation) for comparison. The primary outcome was a composite of all valve-related events (VREs), including endocarditis, myocardial infarction stroke, transient ischemic attack, thromboembolisms, bleeding, and AV reoperation. VREs were defined as per published guidelines. Survival and freedom from VREs were reported using the Kaplan-Meier method. RESULTS: Propensity matching identified 70 well-matched pairs with no major differences in baseline demographics, comorbidities, or AI severity (P = .57). Perioperative outcomes showed no significant differences in VREs (AVR 8 vs AVr 7; P = .78) or mortality (AVR 3 vs AVr 1; P = .62). Event-free survival from the primary outcome at 10 years was significantly better after AVr than after AVR (82% vs 68%; P = .024), with no significant differences in 10-year overall survival between groups (82% vs 72%; P = .29). No significant differences in AI severity (P = .07) or reoperation rate (P = .44) were detected between groups. CONCLUSIONS: This study demonstrated a lower long-term risk of VREs with repair compared with replacement, with low mortality and comparable durability. Further prospective randomized control trials are necessary to formally compare outcomes and determine superiority.


Subject(s)
Aortic Valve Insufficiency , Aortic Valve Stenosis , Heart Valve Prosthesis Implantation , Aortic Valve/surgery , Aortic Valve Stenosis/surgery , Artificial Intelligence , Heart Valve Prosthesis Implantation/methods , Humans , Propensity Score , Retrospective Studies , Risk Factors , Treatment Outcome
9.
Pesqui. vet. bras ; 42: e06961, 2022. ilus
Article in English | LILACS, VETINDEX | ID: biblio-1356551

ABSTRACT

Baccharis vulneraria Backer is a sub-shrub frequently found in southern Brazil, which leads to gastrointestinal tract intoxication. The objective of this study is to describe epidemiological, clinical and anatomopathological aspects of two cases of B. vulneraria poisoning in cattle. Two bovines from two different municipalities in the Itajaí Valley, Santa Catarina, Brazil were necropsied and performed the histopathological evaluation and botanical classification of the plant found in the pasture. Bovine 1 had dehydration, ruminal atony, diarrhea, congested mucous membranes and hypothermia for 20 hours, and died during clinical care. At necropsy, there was moderate multifocal detachment and reddening of the forestomachs mucosa. Bovine 2 presented anorexia, dry feces, ruminal atony, vocalization and muscle tremors for ten days, unresponsive to treatments, evolving to death. At necropsy were seen loosening of the mucosa with marked diffuse reddening and transmural edema. The microscopic exam revealed degeneration, necrosis, vesiculation, and detachment of the forestomachs' mucosa, associated with moderate multifocal neutrophilic infiltrate (Bovine 1); marked diffuse transmural necrosis, edema, hemorrhage, and marked fibrinous exudation (Bovine 2). A large amount of B. vulneraria was found in the pastures, with signs of consumption. In this report, a case of subacute evolution of B. vulneraria poisoning was observed, since the poisoning by this plant is usually acute. More knowledge about poisoning by this plant is necessary for the prevention and control, avoiding new mortality cases.(AU)


Baccharis vulneraria Backer é um subarbusto frequentemente encontrado no sul do Brasil, que leva a um quadro de intoxicação nocivo ao trato gastrointestinal. O objetivo deste trabalho é descrever aspectos epidemiológicos, clínicos e anatomopatológicos de dois casos de intoxicação por B. vulneraria em bovinos. Foram necropsiados dois bovinos de dois municípios do Vale do Itajaí, Santa Catarina, Brasil, com avaliação histopatológica dos órgãos e classificação botânica dos exemplares da planta localizada nos piquetes. No exame clínico do Bovino 1 foram constatados desidratação, atonia ruminal, diarreia, mucosas congestas e hipotermia durante 20 horas, com morte durante atendimento clínico. Na necropsia, havia desprendimento e avermelhamento multifocais moderados na mucosa dos proventrículos. Já o Bovino 2 teve manifestações clínicas de anorexia, fezes secas, atonia ruminal, vocalização e tremores musculares por 10 dias, não responsivas a tratamento, evoluindo para óbito. Na necropsia, havia desprendimento da mucosa dos proventrículos, com avermelhamento e edema transmural difusos acentuados. No exame histológico havia degeneração e necrose da mucosa proventricular, vacuolização e desprendimento do epitélio, infiltrado neutrofílico multifocal moderado (Bovino 1), e necrose transmural difusa acentuada, edema, hemorragia e exsudação fibrinosa acentuados (Bovino 2). Grande quantidade de B. vulneraria foi encontrada nas pastagens dos bovinos, com sinais de consumo. É relatado um caso de evolução subaguda de intoxicação por B. vulneraria, visto que a intoxicação por essa planta geralmente tem curso agudo. Conhecimentos acerca desta planta são necessários para prevenção e controle da intoxicação, evitando novos casos de mortalidade.(AU)


Subject(s)
Animals , Cattle , Plant Poisoning/pathology , Plant Poisoning/veterinary , Cattle Diseases/pathology , Baccharis/poisoning , Gastrointestinal Tract/pathology , Plants, Toxic , Fatal Outcome
10.
Pesqui. vet. bras ; 42: e06968, 2022. tab, ilus
Article in English | LILACS, VETINDEX | ID: biblio-1356557

ABSTRACT

Coccidiosis is a disease of great importance in industrial poultry. The correct diagnosis directs the poultry industry to its best treatment and control. Thus, a survey of Eimeria spp. was carried out in intestines of 64 broiler flocks, with an average age of 29 days. Eight broilers from each flock were randomly removed from the slaughter line, in a total of 512 samples. Macroscopic and histopathological lesions in the intestine were classified into Scores 0 to 4. Polymerase chain reaction (PCR) was used to research the oocysts from the seven species of Eimeria spp. in the intestinal content. The macroscopic evaluations showed that 59.4% (38/64) of the flocks were positive for E. acervulina, 32.8% (21/64) for E. maxima, 29.7% (19/64) for E. tenella, and 34.4% (22/64) for E. brunetti. The histopathological evaluation showed that 87.5% (56/64) of the flocks had at least one broiler with parasitic structures compatible with Eimeria spp. in the duodenum, 70.3% (45/64) in the jejunum, 18.8% (12/64) in the ileum, 46.9% (30/64) in the cecum, and 4.7% (3/64) in the colon. In PCR, 21.9% (14/64) of the flocks were positive for E. acervulina, 12.5% (8/64) for E. maxima, 3.1% (2/64) for E. mitis, and 32.8% (21/64) for E. tenella. The Kappa Cohen test between macroscopy, histopathology, and PCR demonstrated concordance ranging from weak to moderate with the exception of histopathology and PCR of the cecum, which was strong. In the comparison between macroscopy and histopathology, there were significative differences between Scores 0 and 1 (apart from the cecum). For Score 3, there were significative differences in duodenum, jejunum and cecum (p<0.05). In conclusion, the macroscopic diagnosis and PCR can generate false-negative results, and the histopathological exam proved to be effective, making it essential to associate different techniques for the correct diagnosis of Eimeria spp. in broiler chickens.(AU)


A coccidiose é uma doença de grande importância na avicultura industrial. O diagnóstico correto direciona a indústria avícola ao seu melhor tratamento e controle. Desta forma, realizou-se a pesquisa de Eimeria spp. em intestinos de 64 lotes de frangos de corte, com idade média de 29 dias. Em cada lote foram retirados aleatoriamente oito frangos da linha de abate, totalizando 512. Os intestinos foram classificados na macroscopia e na histopatologia em Grau de 0 a 4. No conteúdo intestinal pesquisou-se por reação em cadeia da polimerase (PCR) oocistos das sete espécies de Eimeria. As avaliações macroscópicas demonstraram que 59,4% (38/64) dos lotes foram positivos para E. acervulina, 32,8% (21/64) para E. maxima, 29,7% (19/64) para E. tenella e 34,4% (22/64) para E. brunetti. Na avaliação histopatológica, 87,5% (56/64) dos lotes apresentaram pelo menos um frango com estruturas parasitárias compatíveis com Eimeria spp. no duodeno, 70,3% (45/64) no jejuno, 18,8% (12/64) no íleo, 46,9% (30/64) no ceco e 4,7% (3/64) no cólon. Na PCR 21,9% (14/64) dos lotes foram positivos para E. acervulina, 12,5% (8/64) para E. maxima, 3,1% (2/64) para E. mitis e 32,8% (21/64) para E. tenella. O teste de concordância de Kappa Cohen entre macroscopia, histopatologia e PCR demonstrou concordância variando de fraca a moderada com exceção da histopatologia e PCR do ceco que foi forte. Na comparação dos graus de macroscopia e histopatologia, foram encontradas diferenças significativas entre o Grau 0 e 1 (exceto no ceco) e no Grau 3 houve diferença para duodeno, jejuno e cecos (p<0,05). Conclui-se que o diagnóstico macroscópico e a PCR podem gerar resultados falsos negativos e que o exame histopatológico se demostrou eficaz, tornando fundamental a associação de diferentes técnicas para o correto diagnóstico de Eimeria spp. em frangos de corte.(AU)


Subject(s)
Animals , Female , Poultry Diseases/parasitology , Chickens/parasitology , Coccidiosis/diagnosis , Coccidiosis/pathology , Eimeria , Polymerase Chain Reaction
11.
Pesqui. vet. bras ; 42: e06961, 2022. ilus
Article in English | LILACS, VETINDEX | ID: biblio-1487683

ABSTRACT

Baccharis vulneraria Backer is a sub-shrub frequently found in southern Brazil, which leads to gastrointestinal tract intoxication. The objective of this study is to describe epidemiological, clinical and anatomopathological aspects of two cases of B. vulneraria poisoning in cattle. Two bovines from two different municipalities in the Itajaí Valley, Santa Catarina, Brazil were necropsied and performed the histopathological evaluation and botanical classification of the plant found in the pasture. Bovine 1 had dehydration, ruminal atony, diarrhea, congested mucous membranes and hypothermia for 20 hours, and died during clinical care. At necropsy, there was moderate multifocal detachment and reddening of the forestomachs mucosa. Bovine 2 presented anorexia, dry feces, ruminal atony, vocalization and muscle tremors for ten days, unresponsive to treatments, evolving to death. At necropsy were seen loosening of the mucosa with marked diffuse reddening and transmural edema. The microscopic exam revealed degeneration, necrosis, vesiculation, and detachment of the forestomachs' mucosa, associated with moderate multifocal neutrophilic infiltrate (Bovine 1); marked diffuse transmural necrosis, edema, hemorrhage, and marked fibrinous exudation (Bovine 2). A large amount of B. vulneraria was found in the pastures, with signs of consumption. In this report, a case of subacute evolution of B. vulneraria poisoning was observed, since the poisoning by this plant is usually acute. More knowledge about poisoning by this plant is necessary for the prevention and control, avoiding new mortality cases.


Baccharis vulneraria Backer é um subarbusto frequentemente encontrado no sul do Brasil, que leva a um quadro de intoxicação nocivo ao trato gastrointestinal. O objetivo deste trabalho é descrever aspectos epidemiológicos, clínicos e anatomopatológicos de dois casos de intoxicação por B. vulneraria em bovinos. Foram necropsiados dois bovinos de dois municípios do Vale do Itajaí, Santa Catarina, Brasil, com avaliação histopatológica dos órgãos e classificação botânica dos exemplares da planta localizada nos piquetes. No exame clínico do Bovino 1 foram constatados desidratação, atonia ruminal, diarreia, mucosas congestas e hipotermia durante 20 horas, com morte durante atendimento clínico. Na necropsia, havia desprendimento e avermelhamento multifocais moderados na mucosa dos proventrículos. Já o Bovino 2 teve manifestações clínicas de anorexia, fezes secas, atonia ruminal, vocalização e tremores musculares por 10 dias, não responsivas a tratamento, evoluindo para óbito. Na necropsia, havia desprendimento da mucosa dos proventrículos, com avermelhamento e edema transmural difusos acentuados. No exame histológico havia degeneração e necrose da mucosa proventricular, vacuolização e desprendimento do epitélio, infiltrado neutrofílico multifocal moderado (Bovino 1), e necrose transmural difusa acentuada, edema, hemorragia e exsudação fibrinosa acentuados (Bovino 2). Grande quantidade de B. vulneraria foi encontrada nas pastagens dos bovinos, com sinais de consumo. É relatado um caso de evolução subaguda de intoxicação por B. vulneraria, visto que a intoxicação por essa planta geralmente tem curso agudo. Conhecimentos acerca desta planta são necessários para prevenção e controle da intoxicação, evitando novos casos de mortalidade.


Subject(s)
Animals , Cattle , Baccharis/poisoning , Cattle Diseases/pathology , Plant Poisoning/pathology , Plant Poisoning/veterinary , Gastrointestinal Tract/pathology , Fatal Outcome , Plants, Toxic
12.
Pesqui. vet. bras ; 42: e06968, 2022. tab, ilus
Article in English | LILACS, VETINDEX | ID: biblio-1487689

ABSTRACT

Coccidiosis is a disease of great importance in industrial poultry. The correct diagnosis directs the poultry industry to its best treatment and control. Thus, a survey of Eimeria spp. was carried out in intestines of 64 broiler flocks, with an average age of 29 days. Eight broilers from each flock were randomly removed from the slaughter line, in a total of 512 samples. Macroscopic and histopathological lesions in the intestine were classified into Scores 0 to 4. Polymerase chain reaction (PCR) was used to research the oocysts from the seven species of Eimeria spp. in the intestinal content. The macroscopic evaluations showed that 59.4% (38/64) of the flocks were positive for E. acervulina, 32.8% (21/64) for E. maxima, 29.7% (19/64) for E. tenella, and 34.4% (22/64) for E. brunetti. The histopathological evaluation showed that 87.5% (56/64) of the flocks had at least one broiler with parasitic structures compatible with Eimeria spp. in the duodenum, 70.3% (45/64) in the jejunum, 18.8% (12/64) in the ileum, 46.9% (30/64) in the cecum, and 4.7% (3/64) in the colon. In PCR, 21.9% (14/64) of the flocks were positive for E. acervulina, 12.5% (8/64) for E. maxima, 3.1% (2/64) for E. mitis, and 32.8% (21/64) for E. tenella. The Kappa Cohen test between macroscopy, histopathology, and PCR demonstrated concordance ranging from weak to moderate with the exception of histopathology and PCR of the cecum, which was strong. In the comparison between macroscopy and histopathology, there were significative differences between Scores 0 and 1 (apart from the cecum). For Score 3, there were significative differences in duodenum, jejunum and cecum (p<0.05). In conclusion, the macroscopic diagnosis and PCR can generate false-negative results, and the histopathological exam proved to be effective, making it essential to associate different techniques for the correct diagnosis of Eimeria spp. in broiler chickens.


A coccidiose é uma doença de grande importância na avicultura industrial. O diagnóstico correto direciona a indústria avícola ao seu melhor tratamento e controle. Desta forma, realizou-se a pesquisa de Eimeria spp. em intestinos de 64 lotes de frangos de corte, com idade média de 29 dias. Em cada lote foram retirados aleatoriamente oito frangos da linha de abate, totalizando 512. Os intestinos foram classificados na macroscopia e na histopatologia em Grau de 0 a 4. No conteúdo intestinal pesquisou-se por reação em cadeia da polimerase (PCR) oocistos das sete espécies de Eimeria. As avaliações macroscópicas demonstraram que 59,4% (38/64) dos lotes foram positivos para E. acervulina, 32,8% (21/64) para E. maxima, 29,7% (19/64) para E. tenella e 34,4% (22/64) para E. brunetti. Na avaliação histopatológica, 87,5% (56/64) dos lotes apresentaram pelo menos um frango com estruturas parasitárias compatíveis com Eimeria spp. no duodeno, 70,3% (45/64) no jejuno, 18,8% (12/64) no íleo, 46,9% (30/64) no ceco e 4,7% (3/64) no cólon. Na PCR 21,9% (14/64) dos lotes foram positivos para E. acervulina, 12,5% (8/64) para E. maxima, 3,1% (2/64) para E. mitis e 32,8% (21/64) para E. tenella. O teste de concordância de Kappa Cohen entre macroscopia, histopatologia e PCR demonstrou concordância variando de fraca a moderada com exceção da histopatologia e PCR do ceco que foi forte. Na comparação dos graus de macroscopia e histopatologia, foram encontradas diferenças significativas entre o Grau 0 e 1 (exceto no ceco) e no Grau 3 houve diferença para duodeno, jejuno e cecos (p<0,05). Conclui-se que o diagnóstico macroscópico e a PCR podem gerar resultados falsos negativos e que o exame histopatológico se demostrou eficaz, tornando fundamental a associação de diferentes técnicas para o correto diagnóstico de Eimeria spp. em frangos de corte.


Subject(s)
Female , Animals , Coccidiosis/diagnosis , Coccidiosis/pathology , Poultry Diseases/parasitology , Eimeria , Chickens/parasitology , Polymerase Chain Reaction
13.
Article in English | LILACS-Express | LILACS, VETINDEX | ID: biblio-1487692

ABSTRACT

ABSTRACT: Baccharis vulneraria Backer is a sub-shrub frequently found in southern Brazil, which leads to gastrointestinal tract intoxication. The objective of this study is to describe epidemiological, clinical and anatomopathological aspects of two cases of B. vulneraria poisoning in cattle. Two bovines from two different municipalities in the Itajaí Valley, Santa Catarina, Brazil were necropsied and performed the histopathological evaluation and botanical classification of the plant found in the pasture. Bovine 1 had dehydration, ruminal atony, diarrhea, congested mucous membranes and hypothermia for 20 hours, and died during clinical care. At necropsy, there was moderate multifocal detachment and reddening of the forestomachs mucosa. Bovine 2 presented anorexia, dry feces, ruminal atony, vocalization and muscle tremors for ten days, unresponsive to treatments, evolving to death. At necropsy were seen loosening of the mucosa with marked diffuse reddening and transmural edema. The microscopic exam revealed degeneration, necrosis, vesiculation, and detachment of the forestomachs mucosa, associated with moderate multifocal neutrophilic infiltrate (Bovine 1); marked diffuse transmural necrosis, edema, hemorrhage, and marked fibrinous exudation (Bovine 2). A large amount of B. vulneraria was found in the pastures, with signs of consumption. In this report, a case of subacute evolution of B. vulneraria poisoning was observed, since the poisoning by this plant is usually acute. More knowledge about poisoning by this plant is necessary for the prevention and control, avoiding new mortality cases.


RESUMO: Baccharis vulneraria Backer é um subarbusto frequentemente encontrado no sul do Brasil, que leva a um quadro de intoxicação nocivo ao trato gastrointestinal. O objetivo deste trabalho é descrever aspectos epidemiológicos, clínicos e anatomopatológicos de dois casos de intoxicação por B. vulneraria em bovinos. Foram necropsiados dois bovinos de dois municípios do Vale do Itajaí, Santa Catarina, Brasil, com avaliação histopatológica dos órgãos e classificação botânica dos exemplares da planta localizada nos piquetes. No exame clínico do Bovino 1 foram constatados desidratação, atonia ruminal, diarreia, mucosas congestas e hipotermia durante 20 horas, com morte durante atendimento clínico. Na necropsia, havia desprendimento e avermelhamento multifocais moderados na mucosa dos proventrículos. Já o Bovino 2 teve manifestações clínicas de anorexia, fezes secas, atonia ruminal, vocalização e tremores musculares por 10 dias, não responsivas a tratamento, evoluindo para óbito. Na necropsia, havia desprendimento da mucosa dos proventrículos, com avermelhamento e edema transmural difusos acentuados. No exame histológico havia degeneração e necrose da mucosa proventricular, vacuolização e desprendimento do epitélio, infiltrado neutrofílico multifocal moderado (Bovino 1), e necrose transmural difusa acentuada, edema, hemorragia e exsudação fibrinosa acentuados (Bovino 2). Grande quantidade de B. vulneraria foi encontrada nas pastagens dos bovinos, com sinais de consumo. É relatado um caso de evolução subaguda de intoxicação por B. vulneraria, visto que a intoxicação por essa planta geralmente tem curso agudo. Conhecimentos acerca desta planta são necessários para prevenção e controle da intoxicação, evitando novos casos de mortalidade.

14.
Article in English | LILACS-Express | LILACS, VETINDEX | ID: biblio-1487693

ABSTRACT

ABSTRACT: Coccidiosis is a disease of great importance in industrial poultry. The correct diagnosis directs the poultry industry to its best treatment and control. Thus, a survey of Eimeria spp. was carried out in intestines of 64 broiler flocks, with an average age of 29 days. Eight broilers from each flock were randomly removed from the slaughter line, in a total of 512 samples. Macroscopic and histopathological lesions in the intestine were classified into Scores 0 to 4. Polymerase chain reaction (PCR) was used to research the oocysts from the seven species of Eimeria spp. in the intestinal content. The macroscopic evaluations showed that 59.4% (38/64) of the flocks were positive for E. acervulina, 32.8% (21/64) for E. maxima, 29.7% (19/64) for E. tenella, and 34.4% (22/64) for E. brunetti. The histopathological evaluation showed that 87.5% (56/64) of the flocks had at least one broiler with parasitic structures compatible with Eimeria spp. in the duodenum, 70.3% (45/64) in the jejunum, 18.8% (12/64) in the ileum, 46.9% (30/64) in the cecum, and 4.7% (3/64) in the colon. In PCR, 21.9% (14/64) of the flocks were positive for E. acervulina, 12.5% (8/64) for E. maxima, 3.1% (2/64) for E. mitis, and 32.8% (21/64) for E. tenella. The Kappa Cohen test between macroscopy, histopathology, and PCR demonstrated concordance ranging from weak to moderate with the exception of histopathology and PCR of the cecum, which was strong. In the comparison between macroscopy and histopathology, there were significative differences between Scores 0 and 1 (apart from the cecum). For Score 3, there were significative differences in duodenum, jejunum and cecum (p 0.05). In conclusion, the macroscopic diagnosis and PCR can generate false-negative results, and the histopathological exam proved to be effective, making it essential to associate different techniques for the correct diagnosis of Eimeria spp. in broiler chickens.


RESUMO: A coccidiose é uma doença de grande importância na avicultura industrial. O diagnóstico correto direciona a indústria avícola ao seu melhor tratamento e controle. Desta forma, realizou-se a pesquisa de Eimeria spp. em intestinos de 64 lotes de frangos de corte, com idade média de 29 dias. Em cada lote foram retirados aleatoriamente oito frangos da linha de abate, totalizando 512. Os intestinos foram classificados na macroscopia e na histopatologia em Grau de 0 a 4. No conteúdo intestinal pesquisou-se por reação em cadeia da polimerase (PCR) oocistos das sete espécies de Eimeria. As avaliações macroscópicas demonstraram que 59,4% (38/64) dos lotes foram positivos para E. acervulina, 32,8% (21/64) para E. maxima, 29,7% (19/64) para E. tenella e 34,4% (22/64) para E. brunetti. Na avaliação histopatológica, 87,5% (56/64) dos lotes apresentaram pelo menos um frango com estruturas parasitárias compatíveis com Eimeria spp. no duodeno, 70,3% (45/64) no jejuno, 18,8% (12/64) no íleo, 46,9% (30/64) no ceco e 4,7% (3/64) no cólon. Na PCR 21,9% (14/64) dos lotes foram positivos para E. acervulina, 12,5% (8/64) para E. maxima, 3,1% (2/64) para E. mitis e 32,8% (21/64) para E. tenella. O teste de concordância de Kappa Cohen entre macroscopia, histopatologia e PCR demonstrou concordância variando de fraca a moderada com exceção da histopatologia e PCR do ceco que foi forte. Na comparação dos graus de macroscopia e histopatologia, foram encontradas diferenças significativas entre o Grau 0 e 1 (exceto no ceco) e no Grau 3 houve diferença para duodeno, jejuno e cecos (p 0,05). Conclui-se que o diagnóstico macroscópico e a PCR podem gerar resultados falsos negativos e que o exame histopatológico se demostrou eficaz, tornando fundamental a associação de diferentes técnicas para o correto diagnóstico de Eimeria spp. em frangos de corte.

15.
CMAJ ; 193(34): E1333-E1340, 2021 08 30.
Article in English | MEDLINE | ID: mdl-34462293

ABSTRACT

BACKGROUND: Waitlist management is a global challenge. For patients with severe cardiovascular diseases awaiting cardiac surgery, prolonged wait times are associated with unplanned hospitalizations. To facilitate evidence-based resource allocation, we derived and validated a clinical risk model to predict the composite outcome of death and cardiac hospitalization of patients on the waitlist for cardiac surgery. METHODS: We used the CorHealth Ontario Registry and linked ICES health care administrative databases, which have information on all Ontario residents. We included patients 18 years or older who waited at home for coronary artery bypass grafting, valvular or thoracic aorta surgeries between 2008 and 2019. The primary outcome was death or an unplanned cardiac hospitalizaton, defined as nonelective admission for heart failure, myocardial infarction, unstable angina or endocarditis. We randomly divided two-thirds of these patients into derivation and one-third into validation data sets. We derived the model using a multivariable Cox proportional hazard model with backward stepwise variable selection. RESULTS: Among 62 375 patients, 41 729 patients were part of the derivation data set and 20 583 were part of the validation data set. Of the total, 3033 (4.9%) died or had an unplanned cardiac hospitalization while waiting for surgery. The area under the curve of our model at 15, 30, 60 and 89 days was 0.85, 0.82, 0.81 and 0.80, respectively, in the derivation cohort and 0.83, 0.80, 0.78 and 0.78, respctively, in the validation cohort. The model calibrated well at all time points. INTERPRETATION: We derived and validated a clinical risk model that provides accurate prediction of the risk of death and unplanned cardiac hospitalization for patients on the cardiac surgery waitlist. Our model could be used for quality benchmarking and data-driven decision support for managing access to cardiac surgery.


Subject(s)
Cardiac Surgical Procedures/methods , Cardiovascular Diseases/mortality , Cardiovascular Diseases/surgery , Hospitalization/statistics & numerical data , Waiting Lists , Aged , Angina, Unstable/mortality , Cardiac Surgical Procedures/mortality , Cohort Studies , Endocarditis/mortality , Female , Heart Failure/mortality , Humans , Male , Middle Aged , Models, Statistical , Myocardial Infarction/mortality , Ontario/epidemiology , Proportional Hazards Models , Retrospective Studies , Risk Assessment/standards
16.
BMJ Open ; 11(8): e051192, 2021 08 25.
Article in English | MEDLINE | ID: mdl-34433609

ABSTRACT

BACKGROUND: Effective teamwork between anaesthesiologists and surgeons is essential for optimising patient safety in the cardiac operating room. While many factors may influence the relationship between these two physicians, the role of sex and gender have yet to be investigated. OBJECTIVES: We sought to determine the association between cardiac physician team sex discordance and patient outcomes. DESIGN: We performed a population-based, retrospective cohort study. PARTICIPANTS AND SETTING: Adult patients who underwent coronary artery bypass grafting (CABG) and/or aortic, mitral or tricuspid valve surgery between 2008 and 2018 in Ontario, Canada. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcome was all-cause 30-day mortality. Secondary outcomes included major adverse cardiovascular events at 30 days and hospital and intensive care unit lengths of stay (LOS). Mixed effects logistic regression was used for categorical outcomes and Poisson regression for continuous outcomes. RESULTS: 79 862 patients underwent cardiac surgery by 98 surgeons (11.2% female) and 279 anaesthesiologists (23.3% female); 19 893 (24.9%) were treated by sex-discordant physician teams. Physician sex discordance was not associated with overall patient mortality or LOS; however, patients who underwent isolated CABG experienced longer hospital LOS when treated by an all-male physician team as compared with an all-female team (adjusted OR=1.07; p=0.049). When examining the impact of individual physician sex, the length of hospital stay was longer when isolated CABG procedures were attended by a male surgeon (OR=1.10; p=0.004) or anaesthesiologist (OR=1.02; p=0.01). CONCLUSIONS: Patient mortality and length of stay after cardiac surgery may vary by sex concordance of the attending surgeon-anaesthesiologist team. Further research is needed to examine the underlying mechanisms of these observed relationships.


Subject(s)
Cardiac Surgical Procedures , Surgeons , Thoracic Surgery , Adult , Female , Humans , Length of Stay , Male , Ontario/epidemiology , Retrospective Studies , Treatment Outcome
17.
Arch Bone Jt Surg ; 9(2): 158-166, 2021 Mar.
Article in English | MEDLINE | ID: mdl-34026932

ABSTRACT

BACKGROUND: Treatment recommendations for trapeziometacarpal (TMC) arthrosis are highly variable from surgeon to surgeon. This study addressed the influence of viewing radiographs on a decision to offer surgery for TMC arthrosis. METHODS: In an online survey, 92 hand surgeons viewed clinical scenarios and were asked if they would offer surgery to 30 patients with TMC arthrosis. Forty-two observers were randomly assigned to review clinical information alone and 50 to review clinical information as well as radiographs. The degree of limitation of daily activities, time since diagnosis, prior treatment, pain with grind, crepitation with grind, and metacarpal adduction with metacarpophalangeal hyperextension were randomized for each patient scenario to determine the influence of these factors on offers of surgery. A cross-classified binary logistic multilevel regression analysis identified factors associated with surgeon offer of surgery. RESULTS: Surgeons were more likely to offer surgery when they viewed radiographs (42% vs. 32%, P = 0.01). Other factors associated variation in offer of surgery included greater limitation of daily activities, symptoms for a year, prior splint or injection, deformity of the metacarpophalangeal joint. Factors not associated included limb dominance, prominence of the TMC joint, crepitation with the grind test, and pinch and grip strength. CONCLUSION: Surgeons that view radiographs are more likely to offer surgery to people with TMC arthrosis. urgeons are also more likely to offer surgery when people do not adapt with time and nonoperative treatment. Given the notable influence of surgeon bias, and the potential for surgeon and patient impatience with the adaptation process, methods for increasing patient participation in the decision-making process merit additional attention and study.

18.
PLoS Genet ; 17(5): e1009561, 2021 05.
Article in English | MEDLINE | ID: mdl-33999950

ABSTRACT

The DEFECTIVE EMBRYO AND MERISTEMS 1 (DEM1) gene encodes a protein of unknown biochemical function required for meristem formation and seedling development in tomato, but it was unclear whether DEM1's primary role was in cell division or alternatively, in defining the identity of meristematic cells. Genome sequence analysis indicates that flowering plants possess at least two DEM genes. Arabidopsis has two DEM genes, DEM1 and DEM2, which we show are expressed in developing embryos and meristems in a punctate pattern that is typical of genes involved in cell division. Homozygous dem1 dem2 double mutants were not recovered, and plants carrying a single functional DEM1 allele and no functional copies of DEM2, i.e. DEM1/dem1 dem2/dem2 plants, exhibit normal development through to the time of flowering but during male reproductive development, chromosomes fail to align on the metaphase plate at meiosis II and result in abnormal numbers of daughter cells following meiosis. Additionally, these plants show defects in both pollen and embryo sac development, and produce defective male and female gametes. In contrast, dem1/dem1 DEM2/dem2 plants showed normal levels of fertility, indicating that DEM2 plays a more important role than DEM1 in gamete viability. The increased importance of DEM2 in gamete viability correlated with higher mRNA levels of DEM2 compared to DEM1 in most tissues examined and particularly in the vegetative shoot apex, developing siliques, pollen and sperm. We also demonstrate that gamete viability depends not only on the number of functional DEM alleles inherited following meiosis, but also on the number of functional DEM alleles in the parent plant that undergoes meiosis. Furthermore, DEM1 interacts with RAS-RELATED NUCLEAR PROTEIN 1 (RAN1) in yeast two-hybrid and pull-down binding assays, and we show that fluorescent proteins fused to DEM1 and RAN1 co-localize transiently during male meiosis and pollen development. In eukaryotes, RAN is a highly conserved GTPase that plays key roles in cell cycle progression, spindle assembly during cell division, reformation of the nuclear envelope following cell division, and nucleocytoplasmic transport. Our results demonstrate that DEM proteins play an essential role in cell division in plants, most likely through an interaction with RAN1.


Subject(s)
Arabidopsis/cytology , Arabidopsis/genetics , Genes, Essential , Genes, Plant/genetics , Germ Cells/metabolism , Alleles , Arabidopsis Proteins/metabolism , Cell Division , Cell Survival/genetics , Evolution, Molecular , Gene Dosage , Gene Expression Regulation, Plant , Genetic Complementation Test , Germ Cells/cytology , Meiosis , Multigene Family , Organ Specificity , Pollen/growth & development , RNA, Messenger/genetics , RNA-Binding Proteins/metabolism , Seeds , Transgenes , ran GTP-Binding Protein/metabolism
19.
CMAJ Open ; 9(2): E384-E393, 2021.
Article in English | MEDLINE | ID: mdl-33863796

ABSTRACT

BACKGROUND: Cardiovascular research has traditionally been dedicated to "tombstone" outcomes, with little attention dedicated to the patient's perspective. We evaluated disability-free survival as a patient-defined outcome after cardiac surgery. METHODS: We conducted a retrospective cohort study of patients aged 40 years and older who underwent coronary artery bypass grafting (CABG) or single or multiple valve (aortic, mitral, tricuspid) surgery in Ontario between Oct. 1, 2008, and Dec. 31, 2016. The primary outcome was disability (a composite of stroke, 3 or more nonelective hospital admissions and admission to a long-term care facility) within 1 year after surgery. We assessed the procedure-specific risk of disability using cumulative incidence functions, and the relative effect of covariates on the subdistribution hazard using Fine and Gray models. RESULTS: The study included 72 824 patients. The 1-year incidence of disability and death was 2431 (4.6%) and 1839 (3.5%) for CABG, 677 (6.5%) and 539 (5.2%) for single valve, 118 (9.0%) and 140 (10.7%) for multiple valve, 718 (9.0%) and 730 (9.2%) for CABG and single valve, and 87 (13.1%) and 94 (14.1%) for CABG and multiple valve surgery, respectively. With CABG as the reference group, the adjusted hazard ratios for disability were 1.34 (95% confidence interval [CI] 1.21-1.48) after single valve, 1.43 (95% CI 1.18-1.75) after multiple valve, 1.38 (95% CI 1.26-1.51) after CABG and single valve, and 1.78 (95% CI 1.43-2.23) after CABG and multiple valve surgery. Combined CABG and multiple valve surgery, heart failure, creatinine 180 µmol/L or greater, alcohol use disorder, dementia and depression were independent risk factors for disability. INTERPRETATION: The cumulative incidence of disability was lowest after CABG and highest after combined CABG and multiple valve surgery. Our findings point to a need for models that predict personalized disability risk to enable better patient-centred care.


Subject(s)
Coronary Artery Bypass , Disability Evaluation , Heart Valve Prosthesis Implantation , Postoperative Complications , Risk Assessment/methods , Adult , Coronary Artery Bypass/adverse effects , Coronary Artery Bypass/methods , Coronary Artery Bypass/statistics & numerical data , Coronary Disease/epidemiology , Coronary Disease/surgery , Female , Heart Valve Diseases/epidemiology , Heart Valve Diseases/surgery , Heart Valve Prosthesis Implantation/adverse effects , Heart Valve Prosthesis Implantation/methods , Heart Valve Prosthesis Implantation/statistics & numerical data , Hospitalization/statistics & numerical data , Humans , Incidence , Long-Term Care/statistics & numerical data , Male , Needs Assessment , Ontario/epidemiology , Outcome Assessment, Health Care/methods , Postoperative Complications/epidemiology , Postoperative Complications/etiology , Postoperative Complications/therapy , Prognosis , Risk Factors , Stroke/epidemiology , Stroke/etiology
20.
Toxicol Pathol ; 49(2): 235-260, 2021 02.
Article in English | MEDLINE | ID: mdl-33455525

ABSTRACT

The inhalation route is a relatively novel drug delivery route for biotherapeutics and, as a result, there is a paucity of published data and experience within the toxicology/pathology community. In recent years, findings arising in toxicology studies with inhaled biologics have provoked concern and regulatory challenges due, in part, to the lack of understanding of the expected pathology, mechanisms, and adversity induced by this mode of delivery. In this manuscript, the authors describe 12 case studies, comprising 18 toxicology studies, using a range of inhaled biotherapeutics (monoclonal antibodies, fragment antigen-binding antibodies, domain antibodies, therapeutic proteins/peptides, and an oligonucleotide) in rodents, nonhuman primates (NHPs), and the rabbit in subacute (1 week) to chronic (26 weeks) toxicology studies. Analysis of the data revealed that many of these molecules were associated with a characteristic pattern of toxicity with high levels of immunogenicity. Microscopic changes in the airways consisted of a predominantly lymphoid perivascular/peribronchiolar (PV/PB) mononuclear inflammatory cell (MIC) infiltrate, whereas changes in the terminal airways/alveoli were characterized by simple ("uncomplicated") increases in macrophages or inflammatory cell infiltrates ranging from mixed inflammatory cell infiltration to inflammation. The PV/PB MIC changes were considered most likely secondary to immunogenicity, whereas simple increases in alveolar macrophages were most likely secondary to clearance mechanisms. Alveolar inflammatory cell infiltrates and inflammation were likely induced by immune modulation or stimulation through pharmacologic effects on target biology or type III hypersensitivity (immune complex disease). Finally, a group of experts provide introductory thoughts regarding the adversity of inhaled biotherapeutics and the basis for reasonable differences of opinion that might arise between toxicologists, pathologists, and regulators.


Subject(s)
Biological Products , Hypersensitivity , Administration, Inhalation , Animals , Biological Products/adverse effects , Bronchoalveolar Lavage Fluid , Inflammation , Lung , Macrophages, Alveolar , Rabbits
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