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1.
West Afr J Med ; 41(4): 436-451, 2024 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-39003518

RESUMO

INTRODUCTION: Community-based prevalence studies are known to be more accurate than hospital-based records. However, such community-based prevalence studies are uncommon in low- and middle-income countries including Nigeria. Allocation of resources and prioritization of health care needs by policy makers require data from such community-based studies to be meaningful and sustainable. This study aims to assess the prevalence of common surgical conditions amongst adults in Nigeria. METHODS: A descriptive cross-sectional community-based study to determine the prevalence of congenital and acquired surgical conditions in adults in a mixed rural-urban area of Lagos was conducted. The study population comprised resident members in the Ikorodu Local Government Area (LGA) of Lagos State. Data was collected using a modified version of the interviewer-administered questionnaire, the Surgeons OverSeas Assessment of Surgical Need (SOSAS) survey tool. Data was analysed using the REDCap analytic tool. RESULTS: Eight hundred and fifty-six households were surveyed with a yield of 1,992 adults. There were 95 adults who complained of surgical conditions giving a prevalence rate of 5%. Vast majority of reported conditions were acquired deformities (n=94) while only 1 congenital deformity was reported. Others included breast lumps, anterior neck swelling, and groin swellings. CONCLUSION: The most common surgical complaints in our setting among adults were acquired conditions of the extremities and open wounds/sores. With an estimated population of 90 million adults and approximately 1,200 orthopaedic and general surgeons respectively, the surgeon-to-affected population ratio is 1:10,000. There is a large gap to be filled in terms of surgical manpower development.


INTRODUCTION: Les études de prévalence communautaires sont connues pour être plus précises que les dossiers hospitaliers. Cependant, de telles études de prévalence communautaires sont rares dans les pays à revenu faible et intermédiaire, y compris le Nigeria. L'allocation des ressources et la priorisation des besoins de santé par les décideurs nécessitent des données issues de telles études communautaires pour être significatives et durables. Cette étude vise à évaluer la prévalence des affections chirurgicales courantes chez les adultes au Nigeria. MÉTHODES: Une étude descriptive transversale basée sur la communauté pour déterminer la prévalence des conditions chirurgicales congénitales et acquises chez les adultes dans une zone rurale-urbaine mixte de Lagos a été menée. La population étudiée comprenait des membres résidents de la zone de gouvernement local (LGA) d'Ikorodu, dans l'État de Lagos. Les données ont été collectées à l'aide d'une version modifiée du questionnaire administré par un enquêteur, l'outil d'enquête Surgeons OverSeas Assessment of Surgical Need (SOSAS). Les données ont été analysées à l'aide de l'outil analytique REDCap. RÉSULTATS: Huit cent cinquante-six ménages ont été enquêtés, ce qui a donné 1 992 adultes. Quatre-vingt-quinze adultes se sont plaints de conditions chirurgicales, donnant un taux de prévalence de 5 %. La grande majorité des conditions rapportées étaient des déformations acquises (n=94) tandis qu'une seule déformation congénitale a été signalée. Les autres incluaient des nodules mammaires, des gonflements antérieurs du cou et des gonflements inguinaux. CONCLUSION: Les plaintes chirurgicales les plus courantes dans notre cadre parmi les adultes étaient des conditions acquises des extrémités et des plaies ouvertes/ulcères. Avec une population estimée à 90 millions d'adultes et environ 1 200 chirurgiens orthopédiques et généralistes respectivement, le ratio chirurgien-population affectée est de 1:10,000. Il y a un grand écart à combler en termes de développement de la main-d'œuvre chirurgicale. MOTS CLÉS: Prévalence, Charge de morbidité, Chirurgie, Plaies.


Assuntos
População Rural , População Urbana , Humanos , Nigéria/epidemiologia , Estudos Transversais , Adulto , Feminino , Masculino , População Rural/estatística & dados numéricos , Pessoa de Meia-Idade , População Urbana/estatística & dados numéricos , Adulto Jovem , Prevalência , Inquéritos e Questionários , Adolescente , Procedimentos Cirúrgicos Operatórios/estatística & dados numéricos , Necessidades e Demandas de Serviços de Saúde , Idoso , Avaliação das Necessidades
2.
J Nucl Med ; 65(7): 1043-1050, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38782457

RESUMO

The incidence of androgen receptor (AR)-negative (AR-) prostate cancer, including aggressive neuroendocrine prostate cancer (NEPC), has more than doubled in the last decade, but its timely diagnosis is difficult as it lacks typical prostate cancer hallmarks. The carcinoembryonic antigen-related cell adhesion molecule 5 (CEACAM5) has recently been identified as an upregulated surface antigen in NEPC. We developed an immuno-PET agent targeting CEACAM5 and evaluated its ability to delineate AR- prostate cancer in vivo. Methods: CEACAM5 expression was evaluated in a panel of prostate cancer cell lines by immunohistochemistry and Western blotting. The CEACAM5-targeting antibody labetuzumab was conjugated with the chelator desferrioxamine (DFO) and radiolabeled with 89Zr. The in vivo distribution of the radiolabeled antibody was evaluated in xenograft prostate cancer models by PET imaging and ex vivo organ distribution. Results: The NEPC cell line H660 exhibited strong CEACAM5 expression, whereas expression was limited in the AR- cell lines PC3 and DU145 and absent in the AR-positive cell line LNCaP. [89Zr]Zr-DFO-labetuzumab imaging was able to clearly delineate both neuroendocrine H660 xenografts and AR- DU145 in vivo but could not detect the AR-positive xenograft LNCaP. Conclusion: Immuno-PET imaging with [89Zr]Zr-DFO-labetuzumab is a promising diagnostic tool for AR- prostate cancer.


Assuntos
Proteínas Ligadas por GPI , Tomografia por Emissão de Pósitrons , Neoplasias da Próstata , Receptores Androgênicos , Masculino , Humanos , Neoplasias da Próstata/diagnóstico por imagem , Neoplasias da Próstata/metabolismo , Neoplasias da Próstata/patologia , Linhagem Celular Tumoral , Animais , Camundongos , Receptores Androgênicos/metabolismo , Proteínas Ligadas por GPI/metabolismo , Antígenos CD/metabolismo , Zircônio , Distribuição Tecidual , Moléculas de Adesão Celular/metabolismo , Radioisótopos , Antígeno Carcinoembrionário
3.
ESMO Open ; 9(2): 102193, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38271786

RESUMO

BACKGROUND: Checkpoint inhibitors have shown improvement in recurrence-free survival in the post-operative setting for node-positive melanoma and were first approved in late 2015. However, single-agent checkpoint therapies have yet to show benefit to overall survival (OS) for lower-risk stage III cancers. We evaluated the OS benefit of post-operative immunotherapy in the National Cancer Database (NCDB). PATIENTS AND METHODS: Patient cases were selected from the NCDB 2020 Participant Use File. Patients diagnosed with stage III cutaneous melanoma between 2016 and 2019 who underwent definitive resection for their melanoma were included. OS between those who received post-operative immunotherapy within 84 days of surgery and those who did not was analyzed by the Kaplan-Meier method. Demographic and clinical characteristics between the two groups were compared via Cox proportional hazard models. RESULTS: 14 978 patients with stage III melanoma were included. Of those, 34.9% (n = 5234) received post-operative immunotherapy and 65.1% (n = 9744) did not. Using the American Joint Committee on Cancer version 8 (AJCCv8) staging, 36-month survival was significantly higher in patients who received post-operative immunotherapy compared to no post-operative systemic therapy in those diagnosed with stage IIIB (88.0% versus 84.7%, P = 0.011), IIIC (75.6% versus 68.1%, P < 0.001), or IIID (59.2% versus 48.4%, P = 0.002). No significant improvement in 36-month survival was seen in patients who received post-operative immunotherapy in patients with stage IIIA disease (93.0% versus 92.2%, P = 0.218). CONCLUSIONS: Post-operative immunotherapy had an OS benefit in patients with AJCCv8 stage IIIB, IIIC, and IIID disease, but had no significant survival benefit for patients with stage IIIA melanomas.


Assuntos
Melanoma , Neoplasias Cutâneas , Humanos , Melanoma/tratamento farmacológico , Neoplasias Cutâneas/tratamento farmacológico , Estadiamento de Neoplasias , Imunoterapia/métodos , Modelos de Riscos Proporcionais
5.
J Fr Ophtalmol ; 47(3): 104017, 2024 Mar.
Artigo em Francês | MEDLINE | ID: mdl-37945430

RESUMO

PURPOSE: The demand for eye care is growing continuously. We created a triage survey system, based on categories of severity, to optimize first line patient care in an ophthalmology emergency department. METHODS: This cross-sectional study was carried out from July 7th, 2021 to October 10th, 2021. During this period, a survey was taken by patients upon arrival to the emergency department. Patients completed the survey by ticking boxes that best fitted their situation. The survey classified patients into three categories of severity: GREEN, ORANGE and RED. A chart review was performed to record the final diagnoses. The severity of each diagnosis was rated according to the Base Score. This score was then compared to the level of severity as determined by our survey to calculate the agreement between the two methods. RESULTS: We collected 767 survey forms, with an 80% response rate. We noted 78 different diagnoses. We scored 564 patients as GREEN, 107 as ORANGE and 96 as RED. The sensitivity rates for the green, orange and red categories were 90%, 70% and 96% respectively. The specificity rates were 90% for the green category, 95% for orange and 94% for red, with good agreement (kappa coefficient=0.70). CONCLUSION: Our results suggest that a self-administered survey could be useful as a triage tool for common ocular emergencies. This survey could be performed better if complete by the patients with the assistance of emergency staff. Potentially helpful for high flow structures such as university-based hospitals, this triage survey might also help in comprehensive clinics or emergency departments.


Assuntos
Oftalmologia , Triagem , Humanos , Triagem/métodos , Emergências , Estudos Transversais , Serviço Hospitalar de Emergência
6.
Compr Psychiatry ; 127: 152412, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37717343

RESUMO

BACKGROUND: To explore the preferences of pediatricians for key factors around the implementation of universal routine screening guidelines for major depressive disorder in adolescent patients in a primary care setting. METHOD: Semi-structured qualitative interviews were conducted with U.S. pediatricians. Participants were recruited by convenience sampling and snowball sampling. Qualitive data were summarized using thematic analysis to identify themes relevant to preferences around implementing screening strategies for adolescent patients. Recruitment ended upon reaching thematic saturation when no new themes were revealed. RESULTS: Of the 14 participants, 11 identified as female, 3 male, 10 white, and 4 Asian. Top themes among pediatrician participants were around the screening modality (14/14 participants), screening validity (14/14), time barriers (14/14), and confidentiality barriers (12/14). Less frequently mentioned themes by pediatricians were workplace coordination and logistics (7/14), alternative starting ages for screening (7/14), more frequent screenings than annual screenings (3/14), and additional clinical training regarding depression diagnosis and treatment (2/14). LIMITATIONS: Pool of interviewed participants was limited by diversity in terms of geography, race/ethnicity, or practice settings. CONCLUSIONS: To promote the uptake of universal routine screening of adolescent major depression, pediatricians expressed it was important to address key implementation factors regarding the screening modality, screening validity, time constraints, and confidential care concerns in a primary care delivery context. Findings could be used to inform the development of implementation strategies to facilitate depression screening in primary care. Future research is needed to quantitively assess decisions and tradeoffs that pediatricians make when implementing universal screening to support adolescent mental health.


Assuntos
Transtorno Depressivo Maior , Humanos , Masculino , Feminino , Adolescente , Transtorno Depressivo Maior/diagnóstico , Pesquisa Qualitativa , Saúde Mental , Programas de Rastreamento , Pediatras
7.
Eur Rev Med Pharmacol Sci ; 27(16): 7720-7727, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37667950

RESUMO

OBJECTIVE: This study aimed to determine the rate of salvage chemotherapy and review associated factors in invasive mole patients treated by primary or delayed hysterectomy. PATIENTS AND METHODS: This study was carried out at the Tu Du Hospital, where a total of 189 patients were diagnosed with invasive mole based on histologic examination by hysterectomy between 01/2016 to 12/2020. We used the life table method to estimate the cumulative rate. We applied the Cox proportional hazard model to determine the factors associated with the need for salvage chemotherapy. RESULTS: At 12-month follow-up, 47 patients had required salvage chemotherapy. The incidence was 24.87% (95% CI: 18.88-31.66). Applying the multivariate model, prophylactic chemotherapy (HR = 2.75, 95% Cl: 1.20-6.30) and two weeks postoperative hCG value greater than 1,900 mIU/mL (HR = 4.30, 95% Cl: 2.08-8.87) increased the risk of requiring salvage chemotherapy. Postoperative chemotherapy decreased the risk of requiring salvage chemotherapy (HR = 0.43, 95% Cl: 0.22-0.83). CONCLUSIONS: Hysterectomy can be considered safe and effective in treating invasive mole patients. Although patients were treated by hysterectomy, 24.87% of patients needed salvage chemotherapy to achieve remission. This study affirms the malignant nature of invasive mole, a subtype of gestational trophoblastic neoplasia (GTN). It is not purely a local invasion of molar villi. Postoperative chemotherapy plays an essential role in reducing the risk of requiring salvage chemotherapy.


Assuntos
Mola Hidatiforme Invasiva , Neoplasias Uterinas , Feminino , Gravidez , Humanos , Vietnã , Duodeno , Histerectomia , Neoplasias Uterinas/cirurgia
8.
J Public Health (Oxf) ; 45(4): e702-e713, 2023 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-37541834

RESUMO

BACKGROUND: The aim of this scoping review was to identify key research gaps and priorities in order to advance policy and practice for people living with cancer in the UK. METHODS: The review adhered to PRISMA guidelines for scoping review. We searched MEDLINE, EMBASE, Scopus, Web of Science and Google Scholar on 16 July 2022. There were no restrictions in terms of study design and publication time; gray literature was included. The key words, 'financial' or 'economic', were combined with each of the following words 'hardship/stress/burden/distress/strain/toxicity/catastrophe/consequence/impact.' RESULTS: 29/629 studies/reports published during 1982-2022 were eligible to be included in the review. No study conducted a comprehensive inquiry and reported all aspects of financial toxicity (FT) or used a validated measure of FT. The most three commonly reported outcomes related to financial hardship were financial well-being (24/29), benefit/welfare (17/29) and mental health status (16/29). CONCLUSIONS: It is evident that FT is experienced by UK cancer patients/survivors and that the issue is under-researched. There is an urgent need for further research including rigorous studies which contribute to a comprehensive understanding about the nature and extent of FT, disparities in experience, the impacts of FT on outcomes and potential solutions to alleviate FT and related problems.


Assuntos
Sobreviventes de Câncer , Neoplasias , Humanos , Estresse Financeiro , Sobreviventes , Neoplasias/psicologia , Efeitos Psicossociais da Doença
9.
Int J Comput Assist Radiol Surg ; 18(7): 1311-1322, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37266886

RESUMO

PURPOSE: Validation metrics are a key prerequisite for the reliable tracking of scientific progress and for deciding on the potential clinical translation of methods. While recent initiatives aim to develop comprehensive theoretical frameworks for understanding metric-related pitfalls in image analysis problems, there is a lack of experimental evidence on the concrete effects of common and rare pitfalls on specific applications. We address this gap in the literature in the context of colon cancer screening. METHODS: Our contribution is twofold. Firstly, we present the winning solution of the Endoscopy Computer Vision Challenge on colon cancer detection, conducted in conjunction with the IEEE International Symposium on Biomedical Imaging 2022. Secondly, we demonstrate the sensitivity of commonly used metrics to a range of hyperparameters as well as the consequences of poor metric choices. RESULTS: Based on comprehensive validation studies performed with patient data from six clinical centers, we found all commonly applied object detection metrics to be subject to high inter-center variability. Furthermore, our results clearly demonstrate that the adaptation of standard hyperparameters used in the computer vision community does not generally lead to the clinically most plausible results. Finally, we present localization criteria that correspond well to clinical relevance. CONCLUSION: We conclude from our study that (1) performance results in polyp detection are highly sensitive to various design choices, (2) common metric configurations do not reflect the clinical need and rely on suboptimal hyperparameters and (3) comparison of performance across datasets can be largely misleading. Our work could be a first step towards reconsidering common validation strategies in deep learning-based colonoscopy and beyond.


Assuntos
Neoplasias do Colo , Aprendizado Profundo , Humanos , Colonoscopia , Neoplasias do Colo/diagnóstico , Processamento de Imagem Assistida por Computador/métodos
10.
Eur Rev Med Pharmacol Sci ; 27(8): 3670-3680, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-37140317

RESUMO

OBJECTIVE: Our study aimed to evaluate the effect of soft tissue regeneration in nude mice using grafts made from the combination of adipocytes from fat tissue mesenchymal stem cells and fibrin gel from peripheral blood. MATERIALS AND METHODS: Mesenchymal stem cells were isolated from adipose tissue and identified according to ISCT criteria. The scaffold used was fibrin obtained from peripheral blood. The grafts in this study were generated by transferring mesenchymal stem cells onto a fibrin scaffold. Two types of grafts, the research sample (fibrin scaffold containing adipocytes differentiated from mesenchymal stem cells) and the control sample (fibrin scaffold only), were grafted under the dorsal skin of the same mouse. After each research period, samples were collected and evaluated by histological methods to observe the existence and growth of cells inside the grafts. RESULTS: The results showed that the study group's graft integrated better within the tissue when compared with the control group. In addition, the grafts in the study group showed the presence of cells with characteristic morphology of adipocytes one week after transplantation. In contrast, control samples showed dimorphous shapes and features mainly composed of non-homogenous fragments. CONCLUSIONS: These initial conclusions might be considered a first step in generating safe bio-compatible engineered grafts specifically usable in post-traumatic tissue regeneration procedures.


Assuntos
Células-Tronco Mesenquimais , Camundongos , Animais , Camundongos Nus , Tecido Adiposo , Fibrina/farmacologia , Modelos Animais
11.
Ann Surg ; 278(5): e1048-e1054, 2023 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-36727842

RESUMO

OBJECTIVE: To assess the learning curve of pancreaticojejunostomy during robotic pancreatoduodenectomy (RPD) and to predict the risk of postoperative pancreatic fistula (POPF) by using the objective structured assessment of technical skills (OSATS), taking the fistula risk into account. BACKGROUND: RPD is a challenging procedure that requires extensive training and confirmation of adequate surgical performance. Video grading, modified for RPD, of the pancreatic anastomosis could assess the learning curve of RPD and predict the risk of POPF. METHODS: Post hoc assessment of patients prospectively included in 4 Dutch centers in a nationwide LAELAPS-3 training program for RPD. Video grading of the pancreaticojejunostomy was performed by 2 graders using OSATS (attainable score: 12-60). The main outcomes were the combined OSATS of the 2 graders and POPF (grade B/C). Cumulative sum analyzed a turning point in the learning curve for surgical skill. Logistic regression determined the cutoff for OSATS. Patients were categorized for POPF risk (ie, low, intermediate, and high) based on the updated alternative fistula risk scores. RESULTS: Videos from 153 pancreatic anastomoses were included. Median OSATS score was 48 (interquartile range: 41-52) points and with a turning point at 33 procedures. POPF occurred in 39 patients (25.5%). An OSATS score below 49, present in 77 patients (50.3%), was associated with an increased risk of POPF (odds ratio: 4.01, P =0.004). The POPF rate was 43.6% with OSATS < 49 versus 15.8% with OSATS ≥49. The updated alternative fistula risk scores category "soft pancreatic texture" was the second strongest prognostic factor of POPF (odds ratio: 3.37, P =0.040). Median cumulative surgical experience was 17 years (interquartile range: 8-21). CONCLUSIONS: Video grading of the pancreatic anastomosis in RPD using OSATS identified a learning curve and a reduced risk of POPF in case of better surgical performance. Video grading may provide a valid method to surgical training, quality control, and improvement.


Assuntos
Fístula Pancreática , Procedimentos Cirúrgicos Robóticos , Humanos , Fístula Pancreática/epidemiologia , Fístula Pancreática/etiologia , Fístula Pancreática/prevenção & controle , Pancreaticoduodenectomia/efeitos adversos , Pancreaticoduodenectomia/métodos , Procedimentos Cirúrgicos Robóticos/efeitos adversos , Curva de Aprendizado , Pâncreas , Fatores de Risco , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/prevenção & controle
13.
RSC Adv ; 13(3): 1711-1726, 2023 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-36712622

RESUMO

Environmental pollution, climate change, and fossil fuel extinction have aroused serious global interest in the search for alternative energy sources. The dry reforming of methane (DRM) could be a good technique to harness syngas, a starting material for the FT energy process from greenhouse gases. Noble metal DRM catalysts are effective for the syngas generation but costly. Therefore, they inevitably, must be replaced by their Ni-based contemporaries for economic reasons. However, coking remains a strong challenge that impedes the industrialization of the FT process. This article explains the secondary reactions that lead to the production of detrimental graphitic coke deposition on the surface of active nickel catalyst. The influence of nickel particle size, impact of extra surface oxygen species, interaction of Ni catalysts with metal oxide supports/promoters, and larger fraction of exposed nickel active sites were addressed in this review. Size of active metal determines the conversion, surface area, metal dispersion, surface reactions, interior diffusion effects, activity, and yield. The influence of oxygen vacancy and coke deposition on highly reported metal oxide supports/promoters (Al2O3, MgO and La2O3) was postulated after studying CIFs (crystallographic information files) obtained from the Crystallography open database (COD) on VESTA software. Thus, overcoming excessive coking by La2O3 promotion is strongly advised in light of the orientation of the crystal lattice characteristics and the metal-support interaction can be used to enhance activity and stability in hydrogen reforming systems.

14.
Breast Cancer ; 30(1): 68-76, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36028594

RESUMO

PURPOSE: For many low- and middle-income countries (LMICs), breast cancer (BC) screening based on mammography is not a viable option. Clinical breast examination (CBE) may represent a pragmatic and cost-effective alternative. This paper examines the cost-effectiveness of CBE screening programme among a patient group for whom its cost-effectiveness is likely to be least evident (HER2-positive patients) and discuss the wider implications for BC screening in LMICs. METHODS: A Markov model was used to examine clinical and economic outcomes over a life-time horizon from the patient, public payer, and healthcare sector perspective. HER2-positive patients entered the model at either disease-free survival or metastatic BC state. The downstaging effect of CBE determined the starting probabilities in the no-screening and screening scenarios. The model used a monthly cycle length, with half-cycle correction. Costs and outcomes were discounted at 1.5% annually. RESULTS: Compared with no-screening, the cost-effectiveness ratio (ICER) per quality-adjusted life-year gained for the CBE screening programme was $1801, $2381, and $4179 from three mentioned perspectives, respectively. The finding of cost-effectiveness remained robust to a range of sensitivity analyses. The parameters to which ICERs are most sensitive are average age of cohorts, reduction in proportion of metastatic patients at diagnosis, cost of CBE, and BC detection rate of the programme. CONCLUSION: For HER2-positive patients and compared with no-screening, CBE screening programme in Vietnam is cost-effective from all investigated perspectives. CBE is a 'good value' intervention and should be considered for implementation throughout Vietnam as well as in LMICs where mammography is not feasible.


Assuntos
Neoplasias da Mama , Humanos , Feminino , Neoplasias da Mama/patologia , Análise Custo-Benefício , Detecção Precoce de Câncer , Mamografia , Programas de Rastreamento
15.
BMJ Open ; 12(11): e066128, 2022 11 11.
Artigo em Inglês | MEDLINE | ID: mdl-36368749

RESUMO

INTRODUCTION: Donor-derived modified immune cells (MIC) induced long-term specific immunosuppression against the allogeneic donor in preclinical models of transplantation. In a phase I clinical trial (TOL-1 Study), MIC treatment resulted in a cellular phenotype that was directly and indirectly suppressive to the recipient's immune system allowing for reduction of conventional immunosuppressive therapy. Here, we describe a protocol for a randomised controlled, multicentre phase-IIb clinical trial of individualised immunosuppression with intravenously administered donor MIC compared with standard-of-care (SoC) in living donor kidney transplantation (TOL-2 Study). METHODS AND ANALYSIS: Sixty-three living donor kidney transplant recipients from six German transplant centres are randomised 2:1 to treatment with MIC (MIC group, N=42) or no treatment with MIC (control arm, N=21). MIC are manufactured from donor peripheral blood mononuclear cells under Good Manufacturing Practice conditions. The primary objective of this trial is to determine the efficacy of MIC treatment together with reduced conventional immunosuppressive therapy in terms of achieving an operational tolerance-like phenotype compared with SoC 12 months after MIC administration. Key secondary endpoints are the number of patient-relevant infections as well as a composite of biopsy-proven acute rejection, graft loss, graft dysfunction or death. Immunosuppressive therapy of MIC-treated patients is reduced during follow-up under an extended immunological monitoring including human leucocyte antigen-antibody testing, and determination of lymphocyte subsets, for example, regulatory B lymphocytes (Breg) and antidonor T cell response. A Data Safety Monitoring Board has been established to allow an independent assessment of safety and efficacy. ETHICS AND DISSEMINATION: Ethical approval has been provided by the Ethics Committee of the Medical Faculty of the University of Heidelberg, Heidelberg, Germany (AFmu-580/2021, 17 March 2022) and from the Federal Institute for Vaccines and Biomedicines, Paul-Ehrlich-Institute, Langen, Germany (Vorlage-Nr. 4586/02, 21 March 2022). Written informed consent will be obtained from all patients and respective donors prior to enrolment in the study. The results from the TOL-2 Study will be published in peer-reviewed medical journals and will be presented at symposia and scientific meetings. TRIAL REGISTRATION NUMBER: NCT05365672.


Assuntos
Transplante de Rim , Humanos , Transplante de Rim/efeitos adversos , Doadores Vivos , Padrão de Cuidado , Leucócitos Mononucleares , Terapia de Imunossupressão , Imunossupressores/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto , Estudos Multicêntricos como Assunto , Ensaios Clínicos Fase II como Assunto
16.
SAR QSAR Environ Res ; 33(10): 753-778, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36318662

RESUMO

Since interleukin-8 (IL-8/CXCL8) and its receptor, CXCR1 and CXCR2, were known in the early 1990s, biological pathways related to these proteins were proven to have high clinical value in cancer and inflammatory/autoimmune conditions treatment. Recently, IL-8 has been identified as biomarker for severe COVID-19 patients and COVID-19 prognosis. Boyles et al. (mAbs 12 (2020), pp. 1831880) have published a high-resolution X-ray crystal structure of the LY3041658 Fab in a complex human CXCL8. They described the ability to bind to IL-8 and the blocking of IL-8/its receptors interaction by the LY3041658 monoclonal antibody. Therefore, the study has been designed to identify potential small molecules inhibiting interleukin-8 by targeting LY3041658/IL-8 complex structure using an in silico approach. A structure­based pharmacophore and molecular docking models of the protein active site cavity were generated to identify possible candidates, followed by virtual screening with the ZINC database. ADME analysis of hit compounds was also conducted. Molecular dynamics simulations were then performed to survey the behaviour and stability of the ligand-protein complexes. Furthermore, the MM/PBSA technique has been utilized to evaluate the free binding energy. The final data confirmed that one newly obtained compound, ZINC21882765, may serve as the best potential inhibitor for IL-8.


Assuntos
Tratamento Farmacológico da COVID-19 , Interleucina-8 , Humanos , Simulação de Acoplamento Molecular , Relação Quantitativa Estrutura-Atividade , Simulação de Dinâmica Molecular , Ligantes
17.
Chemosphere ; 309(Pt 1): 136628, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36181849

RESUMO

Adsorption in the continuous mode plays a significant role in wastewater treatment. In this study, Mimosa pigra-derived biochar modified with 2 M AlCl3 salt was used to pack a lab-scale column to eliminate PO43- from aqueous solutions. The influence of the operational factors, such as inlet PO43- concentration (25-100 mg/L), flow rate (6-18 mL/min), and biochar bed height (1.5-4.5 cm), on the breakthrough curve was evaluated. The kinetic models of Adam-Bohart and Yoon-Nelson were utilized to analyze the experimental results. The best conditions were determined to be the influent PO43- strength of 50 mg/L, injection speed of 6 mL/min, and column height of 4.5 cm. These results can be applied in the design of large-scale columns for the sequestration of PO43- from wastewater.


Assuntos
Poluentes Químicos da Água , Purificação da Água , Adsorção , Águas Residuárias , Fosfatos , Carvão Vegetal , Purificação da Água/métodos , Poluentes Químicos da Água/análise , Água
18.
Acta Chir Plast ; 64(2): 62-68, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36068080

RESUMO

INTRODUCTION: The temporoparietal fascia flaps (TPFF) have been widely used to cover the framework in auricular reconstructions. However, flap harvesting is mostly done by open surgery which may be easier but often results in bad scarring and hair loss. We would like to present a series of cases using endoscopic-assisted flap harvesting techniques with only one single cosmetic auricular incision. PATIENTS AND METHODS: Prospective studies from June 2018 to September 2021 on patients who underwent single-stage total auricular reconstruction using autologous costal cartilage and porous polyethylene (PPE) framework. Variables include age, gender, flap survivability as well as visual results and complications. RESULTS: A total of 61 TPFFs were harvested to cover 15 autologous costal cartilages and 46 PPE frameworks in 60 patients (one patient had operation on both sides). TPFF harvests are performed by endoscopic techniques with one single auricular incision. There was no flap necrosis, no bleeding and no cases required framework removal. Only 7/61 (11.5%) ears had small framework exposure which resolved on their own or only required local skin flap coverage and 1 ear had frontal nerve injury. CONCLUSION: Single-stage auricular reconstruction is a difficult surgery, yet greatly beneficial to young children. Through a single-incision endoscopic technique, we can obtain sufficiently large high-survivability TPFFs ensuring full coverage of the autologous costal cartilage or PPE framework. This method is reliable, and reproducible with advanced training. After reviewing the literature, we can state that our report probably includes the largest endoscopic-assisted TPFF harvesting series and the first to implement single-incision endoscopic technique in auricular reconstructions.


Assuntos
Procedimentos de Cirurgia Plástica , Ferida Cirúrgica , Criança , Pré-Escolar , Fáscia , Humanos , Polietileno , Estudos Prospectivos , Procedimentos de Cirurgia Plástica/métodos , Retalhos Cirúrgicos
19.
Breast Cancer Res Treat ; 196(1): 1-15, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36085533

RESUMO

PURPOSE: Circulating microRNAs (miRNAs) are potential diagnostic biomarkers for breast cancer (BC). The application of miRNA panels could improve the performance of screening tests. Here, we integrated bioinformatic tools and meta-analyses to select circulating miRNAs with high diagnostic accuracy and combined these markers to develop diagnostic panels for BC. METHODS: Analyses across databases were performed to identify potential BC-related circulating miRNAs. Next, a comprehensive meta-analysis was conducted for each miRNA following the PRISMA guidelines. An electronic and manual search for relevant literature was carried out by two reviewers through PubMed, ScienceDirect, Biomed Central, and Google Scholar. The quality of the included studies was assessed using the QUADAS-2, and the statistical analyses were performed using R software 4.1.1. Finally, the accurate biomarkers confirmed through meta-analyses were combined into diagnostic models for BC. RESULTS: Twenty-seven circulating miRNAs were identified as BC-related by bioinformatic tools. After screening, only 10 miRNAs presented in 45 studies were eligible for meta-analyses. By assessing pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratio, 8 miRNAs (miR-21, miR-30b, miR-125b, miR-145, miR221 miR-222, and miR-335) were revealed as promising BC diagnostic biomarkers. Two panels constructed from these miRNAs showed excellent diagnostic accuracy for BC, with areas under the SROC curve of 0.917 and 0.944. CONCLUSION: We identified 8 potential circulating miRNAs and 2 diagnostic models that are useful for diagnosing BC. However, the established miRNA panels have not been tested in any experimental studies and thus should be validated in large case-control studies for clinical use.


Assuntos
Neoplasias da Mama , MicroRNA Circulante , MicroRNAs , Biomarcadores , Biomarcadores Tumorais/genética , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/genética , Feminino , Humanos , MicroRNAs/genética , Razão de Chances
20.
Surg J (N Y) ; 8(2): e123-e126, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35712051

RESUMO

Primary breast tuberculosis (TB) is a rare extrapulmonary TB mainly affecting young women of childbearing age from endemic countries. Its incidence is increasing in immunocompromised and HIV-infected people and with the emergence of drug-resistant strains of Mycobacterium tuberculosis (MTB). There are no specific clinical signs suggestive of this disease, it often presents as a hard mass or breast abscess. There is an overlap of features with other inflammatory, infectious, benign lesions, fat necrosis and malignant neoplasms of the breast. The detection of MTB remains the gold standard for diagnosis. Several other diagnostic modalities are used, with varying lack of sensitivity and specificity, and with a range of false negatives. A quarter of cases were treated solely on the basis of clinical, imaging or histological suspicion, without confirmation of the diagnosis. Therefore, we report the case of a young Vietnamese woman, presented for a nonhealing breast abscess, and diagnosed with breast TB based on the patient's ethnicity, histological findings, lack of clinical response to conventional antibiotic therapy, and a good clinical response to anti-TB treatment.

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