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2.
PLoS One ; 19(7): e0290939, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39083479

RESUMO

INTRODUCTION: Molecular profiling of NSCLC is essential for optimising treatment decisions, but often incomplete. We assessed the efficacy of protocolised molecular profiling in the current standard-of-care (SoC) in a prospective observational study in the Netherlands and measured the effect of providing standardised diagnostic procedures. We also explored the potential of plasma-based molecular profiling in the primary diagnostic setting. METHODS: This multi-centre prospective study was designed to explore the performance of current clinical practice during the run-in phase using local SoC tissue profiling procedures. The subsequent phase was designed to investigate the extent to which comprehensive molecular profiling (CMP) can be maximized by protocolising tumour profiling. Successful molecular profiling was defined as completion of at least EGFR and ALK testing. Additionally, PD-L1 tumour proportions scores were explored. Lastly, the additional value of centralised plasma-based testing for EGFR and KRAS mutations using droplet digital PCR was evaluated. RESULTS: Total accrual was 878 patients, 22.0% had squamous cell carcinoma and 78.0% had non-squamous NSCLC. Stage I-III was seen in 54.0%, stage IV in 46.0%. Profiling of EGFR and ALK was performed in 69.9% of 136 patients included in the run-in phase, significantly more than real-world data estimates of 55% (p<0.001). Protocolised molecular profiling increased the rate to 77.0% (p = 0.049). EGFR and ALK profiling rates increased from 77.9% to 82.1% in non-squamous NSCLC and from 43.8% to 57.5% in squamous NSCLC. Plasma-based testing was feasible in 98.4% and identified oncogenic driver mutations in 7.1% of patients for whom tissue profiling was unfeasible. CONCLUSION: This study shows a high success rate of tissue-based molecular profiling that was significantly improved by a protocolised approach. Tissue-based profiling remains unfeasible for a substantial proportion of patients. Combined analysis of tumour tissue and circulating tumour DNA is a promising approach to allow adequate molecular profiling of more patients.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/diagnóstico , Feminino , Masculino , Idoso , Pessoa de Meia-Idade , Estudos Prospectivos , Receptores ErbB/genética , Mutação , Quinase do Linfoma Anaplásico/genética , Países Baixos , Proteínas Proto-Oncogênicas p21(ras)/genética , Biomarcadores Tumorais/genética , Adulto , Idoso de 80 Anos ou mais , Antígeno B7-H1/genética , Antígeno B7-H1/metabolismo , Perfilação da Expressão Gênica/métodos
3.
Clin Radiol ; 79(8): e1040-e1048, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38797610

RESUMO

AIM: Early diagnosis of scapholunate ligament (SLL) injuries is crucial to prevent progression to debilitating osteoarthritis. Four-Dimensional Computed Tomography (4DCT) is a promising dynamic imaging modality for assessing such injuries. Capitalizing on the known correlation between SLL injuries and an increased scapholunate distance (SLD), this study aims to develop a fully automatic approach to evaluate the SLD continuously during wrist motion and to apply it to a dataset of healthy wrists to establish reference values. MATERIALS AND METHODS: 50 healthy wrists were analysed in this study. All subjects performed radioulnar deviation (RUD), flexion-extension (FE), and clenching fist (CF) movements during 4DCT acquisition. A novel, automatic method was developed to continuously compute the SLD at five distinct locations within the scapholunate joint, encompassing a centre, volar, dorsal, proximal, and distal measurement. RESULTS: The developed algorithm successfully processed datasets from all subjects. Our results showed that the SLD remained below 2 mm and exhibited minimal changes (median ranges between 0.3 mm and 0.65 mm) during RUD and CF at all measured locations. During FE, the volar and dorsal SLD changed significantly, with median ranges of 0.90 and 1.27 mm, respectively. CONCLUSION: This study establishes a unique database of normal SLD values in healthy wrists during wrist motion. Our results indicate that, aside from RUD and CF, FE may also be important in assessing wrist kinematics. Given the labour-intensive and time-consuming nature of manual analysis of 4DCT images, the introduction of this automated algorithm enhances the clinical utility of 4DCT in diagnosing dynamic wrist injuries.


Assuntos
Tomografia Computadorizada Quadridimensional , Osso Semilunar , Osso Escafoide , Articulação do Punho , Humanos , Tomografia Computadorizada Quadridimensional/métodos , Masculino , Feminino , Adulto , Articulação do Punho/diagnóstico por imagem , Valores de Referência , Osso Escafoide/diagnóstico por imagem , Osso Semilunar/diagnóstico por imagem , Amplitude de Movimento Articular/fisiologia , Ligamentos Articulares/diagnóstico por imagem , Pessoa de Meia-Idade , Voluntários Saudáveis , Algoritmos , Adulto Jovem
4.
Pain ; 165(3): 550-564, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-37851396

RESUMO

ABSTRACT: Neuromas are a substantial cause of morbidity and reduction in quality of life. This is not only caused by a disruption in motor and sensory function from the underlying nerve injury but also by the debilitating effects of neuropathic pain resulting from symptomatic neuromas. A wide range of surgical and therapeutic modalities have been introduced to mitigate this pain. Nevertheless, no single treatment option has been successful in completely resolving the associated constellation of symptoms. While certain novel surgical techniques have shown promising results in reducing neuroma-derived and phantom limb pain, their effectiveness and the exact mechanism behind their pain-relieving capacities have not yet been defined. Furthermore, surgery has inherent risks, may not be suitable for many patients, and may yet still fail to relieve pain. Therefore, there remains a great clinical need for additional therapeutic modalities to further improve treatment for patients with devastating injuries that lead to symptomatic neuromas. However, the molecular mechanisms and genetic contributions behind the regulatory programs that drive neuroma formation-as well as the resulting neuropathic pain-remain incompletely understood. Here, we review the histopathological features of symptomatic neuromas, our current understanding of the mechanisms that favor neuroma formation, and the putative contributory signals and regulatory programs that facilitate somatic pain, including neurotrophic factors, neuroinflammatory peptides, cytokines, along with transient receptor potential, and ionotropic channels that suggest possible approaches and innovations to identify novel clinical therapeutics.


Assuntos
Neuralgia , Neuroma , Membro Fantasma , Humanos , Qualidade de Vida , Neuroma/etiologia , Neuralgia/etiologia , Biologia
5.
J Hand Surg Eur Vol ; 49(4): 507-509, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37882645

RESUMO

This study developed a deep learning model for fully automatic segmentation and labelling of wrist bones from four-dimensional computed tomography (4DCT) scans. This is a crucial step towards implementing 4DCT for diagnosing wrist ligament lesions, reducing time-consuming analysis of extensive data.


Assuntos
Ossos do Carpo , Aprendizado Profundo , Humanos , Tomografia Computadorizada Quadridimensional/métodos , Punho , Ligamentos Articulares , Processamento de Imagem Assistida por Computador/métodos
6.
Ned Tijdschr Geneeskd ; 1672023 11 15.
Artigo em Holandês | MEDLINE | ID: mdl-37994718

RESUMO

BACKGROUND: Animal bite wounds are common and can cause serious hand infections. Risk factors not only include the oral flora of the animal and the anatomy of the teeth, but also the comorbidities of the bitten patient. CASE DESCRIPTION: In this case report we describe a 46-years old female patient with comorbidities, including diabetes mellitus type 2 and peripheral artery disease, suffering a fulminant hand infection after a domestic rat bite with the newly described bacterium Rodentibacterratti. Despite extensive antibiotic therapy and surgical debridement, a ray amputation was inevitable to maintain adequate hand function. CONCLUSION: Infections after animal bites may be caused by a variety of pathogens. The pathogen Rodentibacterratti has not previously been associated with infections in humans and future research is indicated to assess therapeutic strategies. Patients should be referred to a (plastic) surgeon if there is no clinical improvement within 48 hours of initiating antibiotic treatment.


Assuntos
Mordeduras e Picadas , Diabetes Mellitus Tipo 2 , Animais , Ratos , Humanos , Feminino , Pessoa de Meia-Idade , Mordeduras e Picadas/complicações , Antibacterianos/uso terapêutico , Fatores de Risco , Desbridamento , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/tratamento farmacológico
7.
Epilepsy Behav Rep ; 21: 100574, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36545476

RESUMO

We retrospectively studied the efficacy and tolerability of lacosamide (LCM) in children with drug-resistant epilepsy in a tertiary care centre in the Netherlands, from 2013 till 2019, with a follow-up of two years. 79 children, aged < 18 years, were included. Retention rate, effectiveness, reason for termination, and side-effects were analysed. Furthermore, prognostic variables for discontinuation as well as the incidence of side-effects were determined. The LCM retention rate and effectiveness of response were analysed at three, twelve and twenty-four months. The retention rate of LCM was respectively 89.9 %, 68.4 % and 54.4 %. LCM gave an effective response in 60.5 %, 67.9 % and 71.4 % of the participants who were still using LCM at the three follow-up periods. Lack of efficacy was most frequently reported as a reason for discontinuation (58.3 %). Side-effects occurred in 50.6 % of the patients, somnolence (18.2 %) being the most common, followed by behavioural changes (15.6 %), headache (9.1 %) and dizziness (9.1 %). Use of ≥ 1 sodium channel blocker (SCB) was associated with an increased risk (OR = 4.038) of side-effects. An increasing number of anti-seizure medications (ASM) was associated with a reduced risk (OR = 0.524) of stopping LCM. To conclude, LCM is an effective ASM with acceptable side-effects in children with drug-resistant epilepsy.

8.
J Plast Reconstr Aesthet Surg ; 75(9): 3628-3651, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35933286

RESUMO

Trigger finger is a common condition affecting the hand. Therapeutic variability surrounds the management of trigger finger, especially in the mild cases. The aim of this study was to survey secondary care surgeons to describe the current management of trigger fingers. The steering group developed a survey for hand surgeons. Following piloting, the survey was distributed to hand surgeons in the United Kingdom and The Netherlands. A total of 713 plastic surgeons and orthopaedic surgeons were invited to participate in the online survey and 440 (62%) surgeons completed the survey. In both mild and moderate cases of trigger finger, steroid injection was the preferred treatment option. Open surgery was the treatment of choice for severe cases. However, there was variation in delivery of care, including type and dosage of steroid, site of injection, interval between injections, maximum number of injections, type of incision and treatment of patients with diabetes or rheumatoid arthritis. This highlights the need for a better evidence base for the treatment of trigger fingers.


Assuntos
Ortopedia , Cirurgiões , Dedo em Gatilho , Humanos , Injeções , Esteroides/uso terapêutico , Dedo em Gatilho/cirurgia
9.
Cartilage ; 13(2): 19476035221098167, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35549461

RESUMO

OBJECTIVE: A fusion protein of interleukin-4 and interleukin-10 (IL4-10 FP) was developed as a disease-modifying osteoarthritis drug (DMOAD), and chondroprotection, anti-inflammation, and analgesia have been suggested. To better understand the mechanisms behind its potential as DMOAD, this systematic narrative review aims to assess the potential of IL-4, IL-10 and the combination of IL-4 and IL-10 for the treatment of osteoarthritis. It describes the chondroprotective, anti-inflammatory, and analgesic effects of IL-4, IL-10, and IL4-10 FP. DESIGN: PubMed and Embase were searched for publications that were published from 1990 until May 21, 2021 (moment of search). Key search terms were: Osteoarthritis, Interleukin-4, and Interleukin-10. This yielded 2,479 hits, of which 43 were included in this review. RESULTS: IL-4 and IL-10 showed mainly protective effects on osteoarthritic cartilage in vitro and in vivo, as did IL4-10 FP. Both cytokines showed anti-inflammatory effects, but also proinflammatory effects. Only in vitro IL4-10 FP showed purely anti-inflammatory effects, indicating that proinflammatory effects of one cytokine can be counteracted by the other when given as a combination. Only a few studies investigated the analgesic effects of IL-4, IL-10 or IL4-10 FP. In vitro, IL-4 and IL4-10 FP were able to decrease pain mediators. In vivo, IL-4, IL-10, and IL4-10 FP were able to reduce pain. CONCLUSIONS: In conclusion, this review describes overlapping, but also different modes of action for the DMOAD effects of IL-4 and IL-10, giving an explanation for the synergistic effects found when applied as combination, as is the case for IL4-10 FP.


Assuntos
Interleucina-4 , Osteoartrite , Analgésicos/uso terapêutico , Animais , Anti-Inflamatórios/farmacologia , Citocinas/metabolismo , Modelos Animais de Doenças , Interleucina-10/farmacologia , Interleucina-10/uso terapêutico , Interleucina-4/farmacologia , Interleucina-4/uso terapêutico , Osteoartrite/tratamento farmacológico , Dor/tratamento farmacológico
10.
BMC Musculoskelet Disord ; 23(1): 109, 2022 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-35105316

RESUMO

AIMS: Ulnar-sided wrist pain has historically been equated to lower-back pain of wrist surgery. Little is known about the relationship between psychosocial profile and the manifestation of ulnar-sided wrist pathology and their treatment outcomes. This study aimed to determine the impact of pain catastrophising, psychological distress, illness perception, and patients' outcome expectations on patient-reported pain and hand function before and one year after surgery for ulnar-sided wrist pathology. PATIENTS AND METHODS: We included patients who underwent surgical treatment for ulnar-sided wrist pathology. Before surgery, patients completed the Pain Catastrophising Scale (PCS), Patient Health Questionnaire (PHQ), Brief-Illness Perception Questionnaire (B-IPQ), and Credibility/Expectancy Questionnaire (CEQ). Pain and dysfunction were assessed before (n = 423) and one year after surgery (n = 253) using the Patient Rated Wrist/Hand Evaluation (PRWHE). Hierarchical linear regression was used to assess the relationship between psychosocial factors and the preoperative PRWHE score, postoperative PRWHE score, and change in PRWHE. RESULTS: Psychosocial variables explained an additional 35% of the variance in preoperative PRWHE scores and 18% on postoperative scores. A more negative psychosocial profile was associated with higher (worse) preoperative PRWHE scores (PCS: B = 0.19, CI = [0.02-0.36]; B-IPQ Consequences: B = 3.26, CI = 2.36-4.15; and B-IPQ Identity, B = 1.88 [1.09-2.67]) and postoperative PRWHE scores (PCS: B = 0.44, CI = [0.08-0.81]) but not with the change in PRWHE after surgery. Higher treatment expectations were associated with a lower (better) postoperative PRWHE score (CEQ expectancy: B = -1.63, CI = [-2.43;-0.83]) and a larger change in PRWHE scores (B =|1.62|, CI = [|0.77; 2.47|]). CONCLUSION: A more negative psychosocial profile was associated with higher pain levels and dysfunction preoperatively and postoperatively. However, these patients showed similar improvement as patients with a more feasible psychosocial profile. Therefore, patients should not be withheld from surgical treatment based on their preoperative psychosocial profile alone. Boosting treatment expectations might further improve treatment outcomes. LEVEL OF EVIDENCE: III (Cohort study).


Assuntos
Articulação do Punho , Punho , Estudos de Coortes , Seguimentos , Humanos , Inquéritos e Questionários , Articulação do Punho/cirurgia
11.
J Orthop Traumatol ; 23(1): 1, 2022 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-34985595

RESUMO

BACKGROUND: Ulna shortening osteotomy (USO) for ulnar impaction syndrome (UIS) aims to improve pain and function by unloading the ulnar carpus. Previous studies often lack validated patient-reported outcomes or have small sample sizes. The primary objective of this study was to investigate patient-reported pain and hand function at 12 months after USO for UIS. Secondary objectives were to investigate the active range of motion, grip strength, complications, and whether outcomes differed based on etiology. MATERIALS AND METHODS: We report on 106 patients with UIS who received USO between 2012 and 2019. In 44 of these patients, USO was performed secondary to distal radius fracture. Pain and function were measured with the Patient Rated Wrist/Hand Evaluation (PRWHE) before surgery and at 3 and 12 months after surgery. Active range of motion and grip strength were measured before surgery and at 3 and 12 months after surgery. Complications were scored using the International Consortium for Health Outcome Measurement Complications in Hand and Wrist conditions (ICHAW) tool. RESULTS: The PRWHE total score improved from a mean of 64 (SD = 18) before surgery to 40 (22) at 3 months and 32 (23) at 12 months after surgery (P < 0.001; effect size Cohen's d = -1.4). There was no difference in the improvement in PRWHE total score (P = 0.99) based on etiology. Also, no clinically relevant changes in the active range of motion were measured. Independent of etiology, mean grip strength improved from 24 (11) before surgery to 30 (12) at 12 months (P = 0.001). Sixty-four percent of patients experienced at least one complication, ranging from minor to severe. Of the 80 complications in total, 50 patients (47%) had complaints of hardware irritation, of which 34 (32%) had their hardware removed. Six patients (6%) needed refixation because of nonunion. CONCLUSION: We found beneficial outcomes in patients with UIS that underwent USO, although there was a large variance in the outcome and a relatively high number of complications (which includes plate removals). Results of this study may be used in preoperative counseling and shared decision-making when considering USO. LEVEL OF EVIDENCE: Therapeutic III.


Assuntos
Ulna , Articulação do Punho , Humanos , Osteotomia , Amplitude de Movimento Articular , Estudos Retrospectivos , Resultado do Tratamento , Ulna/cirurgia , Articulação do Punho/cirurgia
12.
Eur J Surg Oncol ; 47(12): 2989-2994, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34039475

RESUMO

OBJECTIVES: This study assessed whether endobronchial therapy (EBT) for bronchial carcinoid, if not curative, reduces the extent of the surgical resection and whether EBT is associated with increased surgical morbidity. MATERIAL AND METHODS: Analysis was performed in a cohort of patients with bronchial carcinoid who have undergone surgical resection. A group that underwent EBT before the surgery (S + EBT) was compared with a group where no EBT was performed (S-EBT). Postoperative complications were also compared between both groups. RESULTS: A total of 254 patients treated for a bronchial carcinoid tumor between 2003 and 2019 were screened for inclusion. A total of 65 surgically treated patients were included, of whom 41 (63%) underwent EBT prior to surgery. In 5 out of 41 patients (12%) from the S + EBT group, less parenchyma was resected versus 2 out of 24 (8%) from the S-EBT group (OR 1.528, 95% CI 0.273-8.562, p = 1.000). Two patients from the S + EBT group (5%) underwent lobectomy instead of sleeve lobectomy versus 0 from the S-EBT group (OR 1.051, 95% CI 0.981-1.127, p = 0.527). Comparing complications between the S + EBT and S-EBT group did not result in increased postoperative surgical morbidity (15% S + EBT, 24% S-EBT). CONCLUSION: EBT, if not curative, does not reduce the extent of the subsequent surgical resection. Therefore, if curative EBT is not anticipated, patients should directly be referred for surgery. If curative EBT seems feasible, it should be attempted not only because surgical resection can be prevented, but also because failure of EBT is not associated with excess surgical morbidity.


Assuntos
Neoplasias Brônquicas/cirurgia , Tumor Carcinoide/cirurgia , Adulto , Neoplasias Brônquicas/diagnóstico por imagem , Neoplasias Brônquicas/patologia , Tumor Carcinoide/diagnóstico por imagem , Tumor Carcinoide/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pneumonectomia , Complicações Pós-Operatórias
13.
Hand Surg Rehabil ; 40(4): 405-412, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-33823294

RESUMO

The aim of this study was to assess return to work (RTW) after open Triangular Fibrocartilage Complex (TFCC) reinsertion. RTW after open surgery for TFCC injury was assessed by questionnaires at 6 weeks, 3 months, 6 months, and 12 months post-operatively. Median RTW time was assessed on inverted Kaplan-Meier curves and hazard ratios were calculated with Cox regression models. 310 patients with a mean age of 38 years were included. By 1 year, 91% of the patients had returned to work, at a median 12 weeks (25%-75%: 6-20 weeks). Light physical labor (HR 3.74) was associated with RTW within the first 15 weeks; this association altered from 23 weeks onward: light (HR 0.59) or moderate physical labor (HR 0.25) was associated with lower RTW rates. Patients with poorer preoperative Patient-Rated Wrist Evaluation (PRWE) total score returned to work later (HR 0.91 per 10 points). Overall cost of loss of productivity per patient was €13,588. In the first year after open TFCC reinsertion, 91% of the patients returned to work, including 50% within 12 weeks. Factors associated with RTW were age, gender, work intensity, and PRWE score at baseline.


Assuntos
Fibrocartilagem Triangular , Adulto , Humanos , Modalidades de Fisioterapia , Retorno ao Trabalho , Inquéritos e Questionários , Fibrocartilagem Triangular/lesões , Fibrocartilagem Triangular/cirurgia , Articulação do Punho
14.
Int J Tuberc Lung Dis ; 23(2): 236-238, 2019 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-30808457

RESUMO

A paediatric case of multidrug-resistant tuberculosis in which endo-oesophageal ultrasound-guided fine-needle aspiration using an endobronchial ultrasound-guided bronchoscope was used to collect a sample for microbial analyses is presented. In our experience, ultrasound-guided sampling techniques, both endo-oesophageal and endobronchial, can be safely used for the diagnosis of paediatric intrathoracic tuberculous lymphadenopathy in children aged 3 years. Interventional pulmonologists with experience in using these techniques should be part of the multidisciplinary team treating these patients.


Assuntos
Aspiração por Agulha Fina Guiada por Ultrassom Endoscópico/métodos , Tuberculose Resistente a Múltiplos Medicamentos/diagnóstico , Broncoscópios , Criança , Aspiração por Agulha Fina Guiada por Ultrassom Endoscópico/instrumentação , Humanos , Masculino
16.
PLoS One ; 12(11): e0188448, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29155877

RESUMO

Conventional control and eradication strategies for bovine tuberculosis (BTB) face tremendous difficulties in developing countries; countries with wildlife reservoirs, a complex wildlife-livestock-human interface or a lack of veterinary and veterinary public health surveillance. Vaccination of cattle and other species might in some cases provide the only suitable control strategy for BTB, while in others it may supplement existing test-and-slaughter schemes. However, the use of live BCG has several limitations and the global rise of HIV/AIDS infections has furthermore warranted the exploration of inactivated vaccine preparations. The aim of this study was to compare the immune response profiles in response to parenteral vaccination with live BCG and two inactivated vaccine candidates in cattle. Twenty-four mixed breed calves (Bos taurus) aged 4-6 months, were allocated to one of four groups and vaccinated sub-cutaneously with live M. bovis BCG (Danish 1331), formalin-inactivated M. bovis BCG, heat-killed M. bovis or PBS/Montanide™ (control). Interferon-γ responsiveness and antibody production were measured prior to vaccination and at weekly intervals thereafter for twelve weeks. At nine weeks post-priming, animals were skin tested using tuberculins and MTBC specific protein cocktails and subsequently challenged through intranodular injection of live M. bovis BCG. The animals in the heat-killed M. bovis group demonstrated strong and sustained cell-mediated and humoral immune responses, significantly higher than the control group in response to vaccination, which may indicate a protective immune profile. Animals in this group showed reactivity to the skin test reagents, confirming good vaccine take. Lastly, although not statistically significant, recovery of BCG after challenge was lowest in the heat-killed M. bovis group. In conclusion, the parenteral heat-killed M. bovis vaccine proved to be clearly immunogenic in cattle in the present study, urging further evaluation of the vaccine in challenge studies using virulent M. bovis and assessment of vaccine efficacy in field conditions.


Assuntos
Anticorpos Antibacterianos/biossíntese , Vacina BCG/administração & dosagem , Imunidade Celular/efeitos dos fármacos , Imunidade Humoral/efeitos dos fármacos , Interferon gama/biossíntese , Mycobacterium bovis/efeitos dos fármacos , Tuberculose Bovina/prevenção & controle , Animais , Bovinos , Formaldeído , Temperatura Alta , Esquemas de Imunização , Imunogenicidade da Vacina , Injeções Subcutâneas , Interferon gama/metabolismo , Masculino , Mycobacterium bovis/imunologia , Tuberculose Bovina/imunologia , Tuberculose Bovina/microbiologia , Vacinas Atenuadas , Vacinas Vivas não Atenuadas
17.
Clin Cancer Res ; 23(15): 4251-4258, 2017 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-28183714

RESUMO

Purpose: ALK rearrangement detection using FISH is the standard test to identify patients with non-small cell lung carcinoma (NSCLC) eligible for treatment with ALK inhibitors. Recently, ALK protein expression in resectable NSCLC showed predictive value. We evaluated tumor response rate and survival after crizotinib treatment of patients with advanced NSCLC with ALK activation using both dichotomous immunohistochemical (IHC) staining and FISH.Experimental Design: Patients with stage IV NSCLC treated with crizotinib were selected. Tumor response was assessed. ALK rearrangements were detected by FISH (Vysis ALK-break-apart FISH-Probe KIT) and IHC [Ventana ALK (D5F3) CDx assay]. Cohorts of patients with ALK-FISH-positive advanced NSCLC from four other hospitals were used for validation.Results: Twenty-nine consecutive patients with ALK-positive advanced NSCLC diagnosed by FISH and/or IHC on small biopsies or fine-needle aspirations (FNA) were treated with ALK inhibitors. All ALK-IHC-positive patients responded to crizotinib except three with primary resistance. No tumor response was observed in 13 ALK-FISH-positive but ALK-IHC-negative patients. This was confirmed in an external cohort of 16 patients. Receiver operator characteristic (ROC) curves for ALK-IHC and ALK-FISH compared with treatment outcome showed that dichotomous ALK-IHC outperforms ALK-FISH [tumor response area under the curve: (AUC), 0.86 vs. 0.64, P = 0.03; progression-free survival (PFS): AUC 0.86 vs. 0.36, P = 0.005; overall survival (OS): AUC, 0.78 vs. 0.41, P = 0.01, respectively].Conclusions: Dichotomous ALK-IHC is superior to ALK-FISH on small biopsies and FNA to predict tumor response and survival to crizotinib for patients with advanced NSCLC. Our data strongly suggest adapting the guidelines and using dichotomous ALK-IHC as standard companion diagnostic test to select patients with NSCLC who benefit from ALK-targeting therapy. Clin Cancer Res; 23(15); 4251-8. ©2017 AACR.


Assuntos
Biomarcadores Tumorais/genética , Carcinoma Pulmonar de Células não Pequenas/genética , Prognóstico , Receptores Proteína Tirosina Quinases/genética , Adulto , Idoso , Quinase do Linfoma Anaplásico , Biomarcadores Tumorais/antagonistas & inibidores , Biomarcadores Tumorais/isolamento & purificação , Biópsia por Agulha Fina , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/patologia , Crizotinibe , Intervalo Livre de Doença , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Rearranjo Gênico/genética , Humanos , Hibridização in Situ Fluorescente , Masculino , Pessoa de Meia-Idade , Pirazóis/administração & dosagem , Piridinas/administração & dosagem , Receptores Proteína Tirosina Quinases/administração & dosagem , Receptores Proteína Tirosina Quinases/antagonistas & inibidores , Receptores Proteína Tirosina Quinases/isolamento & purificação
18.
Ned Tijdschr Geneeskd ; 160: A9948, 2016.
Artigo em Holandês | MEDLINE | ID: mdl-27334082

RESUMO

BACKGROUND: The incidence of hereditary haemorrhagic telangiectasia (HHT - Osler-Weber-Rendu disease) in the Netherlands is 1:5000 but approximately 1:1300 in people from the Antilles. The disease is characterised by the development of telangiectasia and arteriovenous malformations (AVMs) that may result in serious morbidity and mortality. CASE DESCRIPTION: A 31-year-old primigravid patient consulted her general practitioner at 31 1/7 weeks gestational age with dyspnoea. She was referred for further diagnostics because of suspected pulmonary embolism. A CT scan showed haemothorax and a bleeding arteriovenous malformation (AVM) in the left lung. Family history suggested the possibility of HHT. After multidisciplinary consideration, a primary caesarean section was performed, followed by embolisation of the AVM during the same surgical session. The patient had a gene mutation consistent with HHT type 2. CONCLUSION: Pregnant patients with HHT are at risk of serious morbidity, especially if they are not screened for AVMs. A multidisciplinary approach for such patients, with consideration of various scenarios, is highly recommended.


Assuntos
Malformações Arteriovenosas/genética , Hemotórax/genética , Complicações Cardiovasculares na Gravidez/genética , Telangiectasia Hemorrágica Hereditária/complicações , Adulto , Feminino , Idade Gestacional , Humanos , Pulmão/irrigação sanguínea , Gravidez , Telangiectasia Hemorrágica Hereditária/genética , Tomografia Computadorizada por Raios X
19.
Vet Immunol Immunopathol ; 169: 68-73, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26827841

RESUMO

The African buffalo (Syncerus caffer) is considered the most important maintenance host of bovine tuberculosis (BTB) in wildlife in Southern Africa. The diagnosis of Mycobacterium bovis infection in this species mostly relies on the single intradermal comparative tuberculin test (SICTT). As an alternative, the BOVIGAM® 1G, an interferon-gamma (IFN-γ) release assay, is frequently used. The test performance of cell-mediated immunity (CMI-) and humoral immunity (HI-) based assays for the detection of M. bovis infections in buffaloes was compared to identify the test or test combination that provided the highest sensitivity in the study. Buffaloes were sampled during the annual BTB SICTT testing in the Hluhluwe-iMfolozi-Park (KwaZulu-Natal, South Africa) during June 2013. A total of 35 animals were subjected to the SICTT, 13 of these tested positive and one showed an inconclusive reaction. CMI-based assays (BOVIGAM® 1G (B1G) and BOVIGAM® 2G (B2G)) as well as a serological assay (IDEXX TB ELISA) were used to further investigate and compare immune responsiveness. Thirteen SICTT positive buffaloes and one inconclusive reactor were slaughtered and a post-mortem (PM) examination was conducted to confirm BTB. Lesions characteristic of BTB were found in 8/14 animals (57.1%). Test results of individual assays were compared with serial and parallel test interpretation and the sensitivity was calculated as a percentage of test positives out of the number of SICTT positive animals with granulomatous lesions (relative sensitivity). The B1G assay showed the highest individual sensitivity (100%; 8/8) followed by the B2G assay (75%; 6/8) and the IDEXX TB ELISA (37.5%; 3/8). Therefore, using in parallel interpretation, any combination with the B1G showed a sensitivity of 100% (8/8), whereas combinations with the B2G showed a 75% sensitivity (6/8). Out of the 21 SICTT negative animals, 7 animals showed responsiveness in the B2G or IDEXX TB ELISA. In conclusion, this study has shown that the BOVIGAM® IFN-γ assay had the highest test performance.


Assuntos
Búfalos , Imunoensaio/veterinária , Tuberculose/veterinária , Animais , Animais Selvagens , Búfalos/imunologia , Testes Imunológicos/veterinária , Interferon gama/metabolismo , Sensibilidade e Especificidade , África do Sul , Teste Tuberculínico/veterinária , Tuberculose/diagnóstico
20.
Ned Tijdschr Geneeskd ; 159: A9075, 2015.
Artigo em Holandês | MEDLINE | ID: mdl-26230345

RESUMO

A 79-year-old woman consulted a plastic surgeon, because since 3 years she had a large wound at the base of her left index finger. Histology of a skin biopsy showed cutaneous squamous cell carcinoma. Because of the extension of the defect, amputation of the index finger with a split-skin-graft was performed.


Assuntos
Carcinoma de Células Escamosas/diagnóstico , Neoplasias Cutâneas/diagnóstico , Idoso , Amputação Cirúrgica , Biópsia , Carcinoma de Células Escamosas/cirurgia , Feminino , Dedos/patologia , Humanos , Neoplasias Cutâneas/cirurgia
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