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4.
Respir Med Res ; 84: 101057, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37918184

RESUMO

BACKGROUD: Management of severe COVID-19 patients admitted to ICU considerably evolved during the first months of the pandemic. It is unclear, however, whether these changes improved long-term survival of these critically ill patients. METHODS: We conducted a retrospective cohort study in adults with COVID-19 pneumonia admitted to a French ICU between February 2020 and January 2021, a timeframe that covered the first two waves of the pandemic. Primary outcome was to compare long-term survival between the first and second waves. Survival predictor were identified using a Cox proportional-hazards model. RESULTS: We included 265 patients in the cohort: 140 (52.8 %) and 125 (47.2 %) belonging to the first and second waves, respectively. Baseline characteristics of the patients were similar between the two waves. During W2, use of early corticotherapy increased (86.4% vs. 17.8 %; p <0.001), as well as high-flow oxygen therapy use (68.5% vs. 37.4 %; p<0.001). Need for invasive mechanical ventilation decreased (49.6% vs. 72.9 %; p <0.001) and ICU length of stay was shorter (11 [6-22] vs 19 [8-32]days; p = 0.008). ICU mortality was 32.8 % without significant difference between waves. Survival analysis revealed that 3 variables were independently associated with a worse long-term prognosis: a higher SAPS II score (1.05 [1.04-1.06]; p<0.001), a higher age (1.05 [1.01-1.08]; p = 0.005) and admission during W2 (2.22 [1.15-4.28]; p = 0.017). DISCUSSION: Despite substantial changes on management of severe COVID-19 patients, we observed a decreased long-term survival among patients admitted during the second wave. We also noted a shorter ICU length of stay.


Assuntos
COVID-19 , Adulto , Humanos , COVID-19/epidemiologia , COVID-19/terapia , Estudos Retrospectivos , Unidades de Terapia Intensiva , Hospitalização , Respiração Artificial
5.
AACN Adv Crit Care ; 34(4): 350-358, 2023 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-38033213

RESUMO

The COVID-19 pandemic exacerbated staffing challenges in intensive care units, with increased burnout and moral distress cited as major problems. A healthy work environment is critical to nurses' success and wellbeing. During the pandemic, a survey by the American Association of Critical-Care Nurses revealed decreased composite scores in each of the 6 critical elements of a healthy work environment. Hospital units that improved even 1 critical element reported higher job satisfaction. The use of telehealth tools by expert nurses expanded care delivery during the pandemic by improving response to acutely and critically ill patients while supporting hospital-based nurses. All of the critical elements of a healthy work environment are relevant to the tele-critical care nurse's role and challenges. This article describes how tele-critical care nurses were affected by the pandemic and how healthy work environment strategies promoted successful nurse and patient outcomes.


Assuntos
Esgotamento Profissional , Enfermagem de Cuidados Críticos , Recursos Humanos de Enfermagem Hospitalar , Humanos , Condições de Trabalho , Pandemias , Unidades de Terapia Intensiva , Satisfação no Emprego
6.
BJA Open ; 7: 100221, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37638079

RESUMO

Background: The Obstetric Quality of Recovery-10 (ObsQoR-10) is a validated tool for assessing the quality of postpartum recovery. This study aimed to validate the French version of the ObsQoR-10 scale (ObsQoR-10-French). Methods: After translating the ObsQoR-10 into French, we conducted a psychometric validation involving internal consistency, convergent validity, construct validity, reliability, responsiveness, scaling properties, acceptability, and feasibility. French women who underwent either a vaginal delivery (spontaneous or induced labour), or an emergency or elective Caesarean section (C-section) were prospectively included. They completed the ObsQoR-10-French before delivery and at 24 h (H24) and 48 h (H48) after delivery. Results: Of the 500 women included, 431 (86%) completed the questionnaire at all three timepoints. A total of 352 women (82%) underwent vaginal delivery (with 228 [53%] experiencing spontaneous labour and 124 [29%] had labour induced), whereas 53 (12%) women underwent an emergency C-section and 26 (6%) an elective C-section. The ObsQoR-10-French demonstrated excellent internal consistency with a Cronbach's coefficient of 0.81, 95% confidence interval 0.78-0.84 at H24. The tool was correlated with an 11-item global health score (P<0.001). Of the list of hypotheses for evaluating the construct validity, 81% were confirmed (negative associations between ObsQoR-10-French and length of labour, hospital stay, the need for a C-section, and the emergency level of the C-section). The Cohen effect size at H24 was 0.58. The intra-class coefficient was 0.90, 95% confidence interval 0.86-0.93 at H24. Conclusion: The ObsQoR-10-French is a valid and reliable psychometric questionnaire, capable of assessing the quality of postpartum recovery in French-speaking populations. Clinical trial registration: NCT04489602.

8.
Int J Gen Med ; 15: 6645-6651, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36003084

RESUMO

Persistent COVID-19 symptoms may be related to residual inflammation, but no preventive treatment has been evaluated. This study aimed to analyze, in a prospective cohort, whether corticosteroid use in the acute phase of COVID-19 in hospitalized patients may reduce the risk of persistent COVID-19 symptoms. A total of 306 discharged patients, including 112 (36.6%) from the ICU, completed a structured face-to-face assessment 4 months after admission. Of these, 193 patients (63.1%) had at least one persistent symptom, mostly dyspnea (38.9%) and asthenia (37.6%). One-hundred and four patients have received corticosteroids. In multivariable adjusted regression analysis, corticosteroid use was not associated with the presence of at least one symptom (OR=1.00, 95% CI: 0.58-1.71, p=0.99) or with the number of persistent symptoms (p=0.74). Corticosteroid use remained ineffective when analyzing the ICU subpopulation separately. Our study suggests that corticosteroid use had no impact on persistent symptoms after COVID-19 in discharged patients.

9.
Int J Infect Dis ; 118: 220-223, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35257903

RESUMO

OBJECTIVES: Post-COVID-19 symptoms experienced by many survivors have a further devastating effect. This study aimed to analyze the risk factors associated with long COVID-19 in a prospective cohort of hospitalized patients including those requiring intensive care unit (ICU) transfer, taking into account objective measures of COVID-19 severity. METHODS: Hospitalized patients with confirmed COVID-19 were enrolled. A structured follow-up visit was performed 4 months after hospital admission. Multivariable adjusted regression models were used to analyse the association between parameters at the acute phase and persistent symptoms. RESULTS: A follow-up visit was performed in 316 patients including 115 (36.4%) discharged from the ICU. Mean age was 64.1 years, and 201 patients (58.3%) were men. Female sex (odds ratio [OR], 1.94; 95% confidence interval [CI], 1.17-3.22; P =.01), hypertension (OR, 2.01; 95% CI, 1.22-3.31; P <.01), and the number of initial symptoms (NIS) (OR, 1.35; 95% CI, 1.17-1.54; P <.001) were significantly associated with long COVID-19. Number of persistent symptoms was significantly associated with NIS (adjusted incidence rate ratio [aIRR], 1.16; 95% CI, 1.11-1.22; P <.001), female sex (aIRR, 1.56; 95% CI 1.29-1.87; P <.001), hypertension (aIRR, 1.23; 95% CI, 1.02-1.50; P =.03), and length of stay in hospital (aIRR, 1.01; 95% CI, 1.005-1.017; P <.001). CONCLUSION: Our study suggested that female sex, hypertension, and NIS had a significant impact on persistent symptoms in hospitalized patients in contrast to severity of acute COVID-19 infection.


Assuntos
COVID-19 , Hipertensão , COVID-19/complicações , Feminino , Hospitalização , Humanos , Hipertensão/epidemiologia , Unidades de Terapia Intensiva , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de Risco , SARS-CoV-2 , Síndrome de COVID-19 Pós-Aguda
10.
Clin Microbiol Infect ; 28(1): 124-129, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34537361

RESUMO

OBJECTIVES: To evaluate a testing algorithm for the rapid identification of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants that includes the use of PCR-based targeted single nucleotide polymorphism (SNP) detection assays preceded by a multiplex PCR sensitive to S-Gene Target Failure (SGTF). METHODS: PCR SNP assays targeting SARS-CoV-2 S-gene mutations ΔH69-V70, L452R, E484K, N501Y, H655Y and P681R using melting curve analysis were performed on 567 samples in which SARS-CoV-2 viral RNA was detected by a multiplex PCR. Viral whole-genome sequencing (WGS) was performed to confirm the presence of SNPs and to identify the Pangolin lineage. Additionally, 1133 SARS-CoV-2 positive samples with SGTF were further assessed by WGS to determine the presence of ΔH69-V70. RESULTS: The N501Y-specific assay (n = 567) had an overall percentage agreement (OPA) of 98.5%. The ΔH69-V70-specific (n = 178) and E484K-specific (n = 401) assays had OPA of 96.6% and 99.7%, respectively. Assessment of H655Y (n = 139) yielded a 100.0% concordance when applied in the proposed algorithm. The L452R-specific (n = 67) and P681R-specific (n = 62) assays had an OPA of 98.2% and 98.1%, respectively. The proposed algorithm identified six variants of concern/interest (VOC/VOI)-Alpha (n = 149), Beta (n = 65), Gamma (n = 86), Delta (n = 49), Eta (n = 6), Kappa (n = 6)-and 205 non-VOC/VOI strains-including the variants under monitoring B.1.214.2 (n = 43) and B.1.1.318 (n = 18) and Epsilon (n = 1). An excellent concordance was observed for the identification of all SARS-CoV-2 lineages evaluated. CONCLUSIONS: We present a flexible testing algorithm for the rapid detection of current and emerging SARS-CoV-2 VOC/VOIs, which can be easily adapted based on the local endemicity of specific variants.


Assuntos
COVID-19/diagnóstico , Polimorfismo de Nucleotídeo Único , SARS-CoV-2/genética , Algoritmos , Humanos , Reação em Cadeia da Polimerase Multiplex , Mutação , Pandemias , Reação em Cadeia da Polimerase , Glicoproteína da Espícula de Coronavírus/genética
11.
Neuropharmacology ; 205: 108909, 2022 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-34875284

RESUMO

Neuropathic pain arises as a consequence of a lesion or disease affecting the somatosensory nervous system. It is accompanied by neuronal and non-neuronal alterations, including alterations in intracellular second messenger pathways. Cellular levels of 3',5'-cyclic adenosine monophosphate (cAMP) and 3',5'-cyclic guanosine monophosphate (cGMP) are regulated by phosphodiesterase (PDE) enzymes. Here, we studied the impact of PDE inhibitors (PDEi) in a mouse model of peripheral nerve injury induced by placing a cuff around the main branch of the sciatic nerve. Mechanical hypersensitivity, evaluated using von Frey filaments, was relieved by sustained treatment with the non-selective PDEi theophylline and ibudilast (AV-411), with PDE4i rolipram, etazolate and YM-976, and with PDE5i sildenafil, zaprinast and MY-5445, but not by treatments with PDE1i vinpocetine, PDE2i EHNA or PDE3i milrinone. Using pharmacological and knock-out approaches, we show a preferential implication of delta opioid receptors in the action of the PDE4i rolipram and of both mu and delta opioid receptors in the action of the PDE5i sildenafil. Calcium imaging highlighted a preferential action of rolipram on dorsal root ganglia non-neuronal cells, through PDE4B and PDE4D inhibition. Rolipram had anti-neuroimmune action, as shown by its impact on levels of the pro-inflammatory cytokine tumor necrosis factor-α (TNFα) in the dorsal root ganglia of mice with peripheral nerve injury, as well as in human peripheral blood mononuclear cells (PBMCs) stimulated with lipopolysaccharides. This study suggests that PDEs, especially PDE4 and 5, may be targets of interest in the treatment of neuropathic pain.


Assuntos
Hiperalgesia/tratamento farmacológico , Neuralgia/tratamento farmacológico , Traumatismos dos Nervos Periféricos/complicações , Inibidores da Fosfodiesterase 4/farmacologia , Inibidores da Fosfodiesterase 5/farmacologia , Fator de Necrose Tumoral alfa/efeitos dos fármacos , Animais , Modelos Animais de Doenças , Hiperalgesia/etiologia , Camundongos , Neuralgia/etiologia , Rolipram/farmacologia
12.
Biol Aujourdhui ; 216(3-4): 113-123, 2022.
Artigo em Francês | MEDLINE | ID: mdl-36744977

RESUMO

Oxytocin is a pleiotropic molecule which, in addition to its facilitating action during parturition and milk ejection, is involved in social and prosocial behaviors such as attachment. This article presents, after a brief historical review, the action of oxytocin during the milk ejection reflex. Oxytocin is indeed essential for this vital function in mammals. It is both a neurohormone released into the bloodstream by the axon terminals of the posterior pituitary and a neuromodulator released in the hypothalamus by the soma and dendrites of oxytocinergic magnocellular neurons. In addition, oxytocin is also released by the axon terminals of parvocellular neurons and axon collaterals of magnocellular neurons in the brain. Both maternal attachment in rats and ewes and attachment between sexual partners in the prairie vole, one of the few monogamous rodent species, are mediated by central oxytocin. However, neither administering oxytocin into the brain nor increasing expression of the oxytocin receptor in the nucleus accumbens using a gene transfer technique converts polygamous voles to monogamous ones. Unfortunately, translation of animal data to human remains problematic due to still unsolved difficulties in modifying the level of oxytocin in the brain.


Title: Comment, au fil du temps, l'ocytocine est devenue l'hormone de l'attachement. Abstract: L'ocytocine est une molécule pléiotrope qui, en plus de son action facilitatrice au cours de l'accouchement et de l'allaitement, est impliquée dans des comportements sociaux et prosociaux comme l'attachement. Cet article présente, après un bref rappel historique, l'action de l'ocytocine pendant le réflexe d'éjection de lait. L'ocytocine est en effet indispensable à cette fonction vitale chez les mammifères. Elle est à la fois une neurohormone, libérée dans la circulation sanguine par les terminaisons axonales de la post-hypophyse, et un neuromodulateur, libéré dans l'hypothalamus par le soma et les dendrites des neurones magnocellulaires ocytocinergiques. D'autre part, l'ocytocine est également libérée dans le cerveau par les terminaisons axonales des neurones parvocellulaires et des collatérales d'axones des neurones magnocellulaires. La libération centrale de l'ocytocine est à l'origine de ses effets dans l'attachement, qu'il s'agisse de l'attachement maternel comme chez la ratte et la brebis ou de l'attachement entre les partenaires sexuels chez le campagnol des prairies, une des rares espèces de rongeurs monogames. Toutefois, ni l'injection d'ocytocine dans le cerveau, ni l'augmentation de l'expression du récepteur de l'ocytocine dans le noyau accumbens grâce à une technique de transfert de gène, ne rendent monogames des campagnols polygames. La transposition à l'espèce humaine des données obtenues chez l'animal reste problématique en raison principalement de la difficulté à modifier le taux d'ocytocine dans le cerveau.


Assuntos
Ocitocina , Receptores de Ocitocina , Animais , Feminino , Humanos , Ratos , Encéfalo/metabolismo , Neurônios , Ocitocina/metabolismo , Receptores de Ocitocina/metabolismo , Ovinos
13.
J Foot Ankle Res ; 14(1): 30, 2021 Apr 13.
Artigo em Inglês | MEDLINE | ID: mdl-33849632

RESUMO

BACKGROUND: An intractable plantar keratoma (IPK) is a conical thickening of the epidermis' stratum corneum and a common cause of foot pain which can have a significant, detrimental impact on the mobility, quality of life and independence of individuals. Conservative treatments are currently offered to patients with IPK, but they are unsatisfactory since they do not offer a sufficient or permanent reduction of symptoms. The purpose of this study was the evaluation of the feasibility, safety and effectiveness of innovative treatments for intractable plantar keratoma (IPK). METHODS: A randomized single blind trial with 40 patients divided with block randomization in four parallel groups was conducted to compare treatment combinations: conservative sharp debridement only or sharp debridement with needle insertion, physiological water injection or lidocaine injection. All patients obtained the same treatment four times at a four-week interval. At each visit, visual analog scale (VAS), Foot Function Index (FFI) and IPK size were evaluated. VAS and FFI were also completed at a six and twelve-month follow-up. RESULTS: Our findings in regards to feasibility demonstrated recruitment challenges because of the anticipated pain that would be provoked by needle insertion may not be worth the potential pain relief compared to debridement alone from the patient's perspective. This was also the principal cause of drop out. Our preliminary results show no main effect of group for any of the clinical outcomes: pain felt on VAS, FFI score, IPK's size (p > 0.05). However, the analysis revealed a statistically significant effect of time on VAS (p < 0.001), FFI score (p < 0.001) and IPK's size (width and depth (p < 0.001); length (p = 0.001)), but no group x time interaction was found (p > 0.05). CONCLUSIONS: This study demonstrates that IPK treatment consisting of sharp debridement with needle insertion, physiological saline water injection or lidocaine injection is feasible and safe. There was a non-statistically significant trend toward diminishing pain intensity compared to scalpel debridement alone. The pain provoked by needle insertion and injection treatments must be addressed with a scientifically proven protocol to make it more comfortable for patients before these treatments could be considered in further studies. TRIAL REGISTRATION: ClinicalTrials.gov, NCT04777227 . 2 March, 2021 - Retrospectively registered (All participants were recruited prior to registration).


Assuntos
Anestésicos Locais/administração & dosagem , Calosidades/terapia , Desbridamento/métodos , Ceratose/terapia , Lidocaína/administração & dosagem , Águas Salinas/administração & dosagem , Idoso , Desbridamento/instrumentação , Estudos de Viabilidade , Feminino , Humanos , Injeções , Masculino , Pessoa de Meia-Idade , Medição da Dor , Dor Processual/etiologia , Dor Processual/prevenção & controle , Método Simples-Cego , Resultado do Tratamento
14.
Cancers (Basel) ; 13(8)2021 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-33918704

RESUMO

Glioblastoma (GBM), the most frequent and aggressive glial tumor, is currently treated as first line by the Stupp protocol, which combines, after surgery, radiotherapy and chemotherapy. For recurrent GBM, in absence of standard treatment or available clinical trials, various protocols including cytotoxic drugs and/or bevacizumab are currently applied. Despite these heavy treatments, the mean overall survival of patients is under 18 months. Many clinical studies are underway. Based on clinicaltrials.org and conducted up to 1 April 2020, this review lists, not only main, but all targeted therapies in phases II-IV of 257 clinical trials on adults with newly diagnosed or recurrent GBMs for the last twenty years. It does not involve targeted immunotherapies and therapies targeting tumor cell metabolism, that are well documented in other reviews. Without surprise, the most frequently reported drugs are those targeting (i) EGFR (40 clinical trials), and more generally tyrosine kinase receptors (85 clinical trials) and (ii) VEGF/VEGFR (75 clinical trials of which 53 involving bevacizumab). But many other targets and drugs are of interest. They are all listed and thoroughly described, on an one-on-one basis, in four sections related to targeting (i) GBM stem cells and stem cell pathways, (ii) the growth autonomy and migration, (iii) the cell cycle and the escape to cell death, (iv) and angiogenesis.

15.
Front Pain Res (Lausanne) ; 2: 755877, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-35295511

RESUMO

Background: Spinal manipulations (SMT) and mobilizations (MOB) are interventions commonly performed by many health care providers to manage musculoskeletal conditions. The clinical effects of these interventions are believed to be, at least in part, associated with their force-time characteristics. Numerous devices have been developed to measure the force-time characteristics of these modalities. The use of a device may be facilitated or limited by different factors such as its metrologic properties. Objectives: This mixed-method scoping review aimed to characterize the metrologic properties of devices used to measure SMT/MOB force-time characteristics and to determine which factors may facilitate or limit the use of such devices within the context of research, education and clinical practice. Methods: This study followed the Joanna Briggs Institute's framework. The literature search strategy included four concepts: (1) devices, (2) measurement of SMT or MOB force-time characteristics on humans, (3) factors facilitating or limiting the use of devices, and (4) metrologic properties. Two reviewers independently reviewed titles, abstracts and full articles to determine inclusion. To be included, studies had to report on a device metrologic property (e.g., reliability, accuracy) and/or discuss factors that may facilitate or limit the use of the device within the context of research, education or clinical practice. Metrologic properties were extracted per device. Limiting and facilitating factors were extracted and themes were identified. Results: From the 8,998 studies initially retrieved, 46 studies were finally included. Ten devices measuring SMT/MOB force-time characteristics at the clinician-patient interface and six measuring them at patient-table interfaces were identified. Between zero and eight metrologic properties were reported per device: measurement error (defined as validity, accuracy, fidelity, or calibration), reliability/repeatability, coupling/crosstalk effect, linearity/correlation, sensitivity, variability, drift, and calibration. From the results, five themes related to the facilitating and limiting factors were developed: user-friendliness and versatility, metrologic/intrinsic properties, cost and durability, technique application, and feedback. Conclusion: Various devices are available to measure SMT/MOB force-time characteristics. Metrologic properties were reported for most devices, but terminology standardization is lacking. The usefulness of a device in a particular context should be determined considering the metrologic properties as well as other potential facilitating and limiting factors.

16.
Can J Diabetes ; 45(4): 327-333.e2, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33229195

RESUMO

OBJECTIVES: Diabetic foot ulcer (DFU), a serious complication of diabetes, is associated with increased morbidity and mortality and presents a substantial socioeconomic burden. However, DFU quality of care has been insufficiently studied. Therefore, the aim of this study was to evaluate the quality of DFU care at an interdisciplinary wound care clinic in Canada, based on an extended Donabedian model: structure, process and outcome quality indicators combined with patient characteristics. METHODS: This was a retrospective cohort study of 140 adult patients with diabetes who were treated between 2012 and 2018 at a wound care clinic in a university-affiliated hospital in the Québec City area of Canada. Twenty-two internationally recognized quality-of-care indicators were identified from the literature. Data were collected from medical files, and the results were used to document the selected quality-of-care indicators. RESULTS: The principal indicators regarding structure and process were met, and outcome indicators were influenced by study population characteristics, particularly peripheral artery disease and critical limb ischemia. Moreover, this study highlights that quality-of-care indicators are essential when evaluating DFU outcomes, as structure and process indicators can also affect wound healing outcomes. CONCLUSIONS: This study suggests that DFU care at a Canadian wound care clinic, with an interdisciplinary approach, meets most quality-of-care indicators. The socioeconomic burden of DFUs for patients, health-care organizations and policymakers, and the paucity of quality and performance evaluations, call for more studies evaluating DFU care.


Assuntos
Instituições de Assistência Ambulatorial , Pé Diabético/terapia , Qualidade da Assistência à Saúde , Adulto , Idoso , Feminino , Pesquisa sobre Serviços de Saúde/métodos , Humanos , Masculino , Pessoa de Meia-Idade , Avaliação de Processos e Resultados em Cuidados de Saúde , Quebeque , Estudos Retrospectivos
17.
Int Wound J ; 18(2): 134-146, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33236835

RESUMO

The aim of this study was to determine the wound healing outcomes of patients with a plantar diabetic foot ulcer (DFU) treated with an interdisciplinary team approach, and to identify associated variables. A retrospective observational cohort study of 140 adult patients, with a plantar DFU, treated between 2012 and 2018 at a wound care clinic of a University affiliated hospital was conducted. Predictive and explicative analyses were conducted with logistic multivariate methods and with a Receiver Operating Characteristics curve. The best predictor of wound healing at 3 months was a 41.8% wound size reduction at 4 weeks (AUC: 0.86; sensitivity: 83.1%; specificity: 67.2%, positive predictive value: 72.8%; negative predictive value: 78.9%; positive and negative likelihood ratios: 2.53 and 0.25, respectively). Main baseline variables independently associated with this predictor were: a monophasic Doppler waveform (OR 7.52, 95% CI [2.64-21.39]), cigarette smoking (OR 4.7, 95% CI [1.44-15.29]), and male gender (OR 3.58, 95% CI [1.30-9.87]). The health care provider should be cautious and intensify its management of DFUs particularly with patients of male gender; smoking, having a monophasic waveform with a hand-held Doppler, and not achieving a minimal 41.8% wound area reduction at 4 weeks of treatment.


Assuntos
Pé Diabético , Equipe de Assistência ao Paciente , Cicatrização , Adulto , Idoso , Canadá , Diabetes Mellitus , Pé Diabético/terapia , Feminino , Hospitais Universitários , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Resultado do Tratamento
18.
Cell Mol Life Sci ; 78(6): 2949-2962, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33151388

RESUMO

Overexpression of EGFR drives glioblastomas (GBM) cell invasion but these tumours remain resistant to EGFR-targeted therapies such as tyrosine kinase inhibitors (TKIs). Endocytosis, an important modulator of EGFR function, is often dysregulated in glioma cells and is associated with therapy resistance. However, the impact of TKIs on EGFR endocytosis has never been examined in GBM cells. In the present study, we showed that gefitinib and other tyrosine kinase inhibitors induced EGFR accumulation in early-endosomes as a result of an increased endocytosis. Moreover, TKIs trigger early-endosome re-localization of another membrane receptor, the fibronectin receptor alpha5beta1 integrin, a promising therapeutic target in GBM that regulates physiological EGFR endocytosis and recycling in cancer cells. Super-resolution dSTORM imaging showed a close-proximity between beta1 integrin and EGFR in intracellular membrane compartments of gefitinib-treated cells, suggesting their potential interaction. Interestingly, integrin depletion delayed gefitinib-mediated EGFR endocytosis. Co-endocytosis of EGFR and alpha5beta1 integrin may alter glioma cell response to gefitinib. Using an in vitro model of glioma cell dissemination from spheroid, we showed that alpha5 integrin-depleted cells were more sensitive to TKIs than alpha5-expressing cells. This work provides evidence for the first time that EGFR TKIs can trigger massive EGFR and alpha5beta1 integrin co-endocytosis, which may modulate glioma cell invasiveness under therapeutic treatment.


Assuntos
Endocitose/efeitos dos fármacos , Gefitinibe/farmacologia , Integrina alfa5beta1/metabolismo , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/patologia , Linhagem Celular Tumoral , Membrana Celular/efeitos dos fármacos , Membrana Celular/metabolismo , Movimento Celular/efeitos dos fármacos , Endossomos/metabolismo , Fator de Crescimento Epidérmico/metabolismo , Receptores ErbB/metabolismo , Glioblastoma/metabolismo , Glioblastoma/patologia , Humanos , Integrina alfa5beta1/antagonistas & inibidores , Integrina alfa5beta1/genética , Inibidores de Proteínas Quinases/farmacologia , Interferência de RNA , RNA Interferente Pequeno/metabolismo
19.
J Clin Med ; 9(10)2020 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-32992732

RESUMO

Acute myeloid leukemia (AML) is a hematologic malignancy characterized by the rapid and uncontrolled clonal growth of myeloid lineage cells in the bone marrow. The advent of oral, selective inhibitors of the B-cell leukemia/lymphoma-2 (BCL-2) apoptosis pathway, such as venetoclax, will likely induce a paradigm shift in the treatment of AML. However, the high cost of this treatment and the risk of additive toxicity when used in combination with standard chemotherapy represent limitations to its use and underscore the need to identify which patients are most-and least-likely to benefit from incorporation of venetoclax into the treatment regimen. Bone marrow specimens from 93 newly diagnosed AML patients were collected in this study and evaluated for BCL-2 protein expression by immunohistochemistry. Using this low-cost, easily, and readily applicable analysis method, we found that 1 in 5 AML patients can be considered as BCL-2-. In addition to a lower bone marrow blast percentage, this group exhibited a favorable molecular profile characterized by lower WT1 expression and underrepresentation of FLT3 mutations. As compared to their BCL-2+ counterparts, the absence of BCL-2 expression was associated with a favorable response to standard chemotherapy and overall survival, thus potentially precluding the necessity for venetoclax add-on.

20.
Crit Care Nurse ; 40(4): 25-31, 2020 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-32464662

RESUMO

BACKGROUND: The coronavirus disease 2019 pandemic has exacerbated staffing challenges already facing critical care nurses in intensive care units. Many intensive care units have been understaffed and the majority of nurses working in these units have little experience. OBJECTIVE: To describe how the skilled tele-intensive care unit nurses in our health system quickly changed from a patient-focused strategy to a clinician-focused approach during the coronavirus disease 2019 crisis. METHODS: We modified workflows, deployed home workstations, and changed staffing models with the goal of providing additional clinical support to bedside colleagues while reducing exposure time and conserving personal protective equipment for those caring for this highly contagious patient population. The unit changed focus and granted more than 300 clinicians access to technology that enabled them to care for patients remotely, added nearly 200 mobile carts, and allowed more than 20 tele-intensive care unit nurses to work from home. RESULTS: Tele-intensive care unit nursing provided clinical knowledge to the nurses covering current and expanded critical care units. Using technology, virtual rounding, and increased collaboration with nurses, tele-intensive care unit nursing minimized the risk to bedside nurses while maintaining a high level of care for patients. CONCLUSION: Tele-intensive care unit nurses provided a proactive, holistic approach to caring for critically ill patients via camera as part of their routine workflow. In addition, during the coronavirus disease 2019 pandemic, these nurses created a new strategy in virtual health care to be implemented during a crisis.


Assuntos
Infecções por Coronavirus/enfermagem , Unidades de Terapia Intensiva , Pandemias , Pneumonia Viral/enfermagem , Telemedicina , COVID-19 , Infecções por Coronavirus/epidemiologia , Humanos , Pesquisa em Avaliação de Enfermagem , Pneumonia Viral/epidemiologia
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