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1.
Ann R Coll Surg Engl ; 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38746984

RESUMO

INTRODUCTION: Therapeutic mammaplasty (TM) facilitates large tumour resection while maintaining optimal aesthetic outcome. It carries higher wound complication risks, which may delay adjuvant therapy initiation. Whether this delay affects oncological outcome requires evaluation. METHODS: Data were collected for consecutive patients receiving TM at the Leeds breast unit (2009-2017). A prospectively maintained database was used to determine tumour characteristics, wound complication rates, receipt of adjuvant therapy and breast cancer recurrence or death. RESULTS: In total 112 patients (median age of 54 years) underwent 114 TM procedures. The most common histological subtypes were invasive ductal carcinoma (61.4%), invasive lobular carcinoma (13.2%) and ductal carcinoma in situ (13.2%). Of the patients, 88.2% had oestrogen receptor-positive cancer and 14% had human epidermal growth factor receptor-positive cancer; 26.3% had multifocal cancer. The median tumour size was 30mm. The median Nottingham Prognostic Index was 4.2. The local recurrence rate was 3.5% (median follow-up of 8.6 years). The 5- and 10-year disease-free survival (DFS) was 88.5% and 83.5%, and the equivalent overall survival (OS) rates were 94% and 83.5%. Wound complication rate was 23.6% (n=27), the commonest being wound infection (11.4%; n=13) and T-junction wound breakdown (10.5%; n=12). The median time to adjuvant therapy was 72 days (interquartile range [IQR] 56-90) for patients with wound complications, and 51 days (IQR 42-58) for those without. However, this delay did not affect DFS or OS (log-rank test; p=0.58 and p=0.94, respectively). This was confirmed on Cox regression analysis. CONCLUSION: Our study finding demonstrates that although wound complications after TM leads to a modest delay to adjuvant therapy, the long-term oncological outcomes were comparable with those in patients without wound complications.

2.
Obes Surg ; 34(5): 1975-1982, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38530551

RESUMO

BACKGROUND: Gender-specific post-surgical goals for 12-month percent body fat (%BF) based on World Health Organization (WHO) obesity thresholds and for lean mass-sparing were published as preliminary body composition (BC) guidelines to address a knowledge gap in metabolic-bariatric surgery (MBS). Other studies' %BF outcomes inconsistently fell below obesity thresholds; none described nutrition practices. To help practitioners positively influence patients' BC and weight changes, this study describes the team-supported process of conducting serial body composition analysis (sBCA) concomitantly with the evidence-based nutrition practices applied to generate the preliminary guidelines. METHODS: Guidelines were generated using the cumulative outcomes of separate, original research board-approved Roux-en-Y Gastric Bypass and Sleeve Gastrectomy studies. One dietitian assessed BC using the same bioimpedance machine, educated patients, and collected data from patients aged 18 and older in a 532-bed nonprofit acute-care institution in Northeast Ohio, USA, from May, 2007, through November, 2016. Essential to pre- and postoperative education was the "Nutrition Goal Checklist," an evidence-based synopsis of imperative practices. Body composition was assessed on initial visit, presurgically, and postoperative months 3, 6, and 12, generating individual patient handouts of progressive weight and BC changes with coordinating %BF graphs. Serial assessment enabled intervention toward meeting BC goals. RESULTS: For genders in both surgeries, the described process influenced highly significant fat mass reduction, transitioning %BF below obesity thresholds. Lean mass-sparing outcomes supported the suggested preliminary guidelines. CONCLUSIONS: Utilizing sBCA with evidence-based nutrition practices consistently generated outcomes to formulate preliminary BC guidelines following MBS. Further research is needed to solidify formal guidelines.


Assuntos
Cirurgia Bariátrica , Derivação Gástrica , Laparoscopia , Obesidade Mórbida , Humanos , Masculino , Feminino , Obesidade Mórbida/cirurgia , Índice de Massa Corporal , Redução de Peso , Obesidade/cirurgia , Gastrectomia
4.
Biotechnol Prog ; 40(3): e3429, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38334218

RESUMO

The need for advanced therapy medicinal products (ATMPs) has gained increased attention in recent years. In this respect, a well-designed cell expansion process is needed to efficiently manufacture the required number of cells with the desired product quality. This step is challenging due to the biological complexity of the respective primary cell (e.g., mesenchymal stem cells (MSC)) and the usage of microcarrier-based expansion systems. One accelerating approach for process design is model-assisted Design of Experiments (mDoE) combining mathematical process models and statistical tools. In this study, the mDoE workflow was used for the development of an expansion processes with human immortalized mesenchymal stem cells (hMSC-TERT) and the aim of maximizing cell yield assuming only a limited amount of prior knowledge at a very early stage of development. First, suitable microcarriers for expansion in shake flasks were screened and the differentiation of the cells was proven. Second, initial experiments were performed to generate prior knowledge, which was then used to set up the mathematical model and to estimate the model parameters. Finally, the mDoE was used to determine and evaluate the design space to be performed experimentally. Overall, a cell expansion process using microcarriers in a shake flask culture was successfully implemented and a significant increase in cell yield (up to 6,2-fold) was achieved compared to literature.


Assuntos
Técnicas de Cultura de Células , Diferenciação Celular , Células-Tronco Mesenquimais , Células-Tronco Mesenquimais/citologia , Humanos , Técnicas de Cultura de Células/métodos , Proliferação de Células , Células Cultivadas , Modelos Teóricos
5.
Neurosurg Rev ; 47(1): 30, 2024 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-38172487

RESUMO

Pneumocephalus is the pathologic collection of air in the intracranial cavity. In sufficient volumes, it can contribute to symptoms ranging from headaches to death. For conservative treatment, oxygen use is commonplace. Although this is an accepted tenet of clinical practice, it is not necessarily founded on robust trials. An electronic search of databases EMBASE and MEDLINE and the Cochrane Library was undertaken as per the 2020 Preferred Reporting Items of Systematic Reviews and Meta-Analyses (PRISMA) statement. Three articles were included. Although the modes of oxygen delivery were heterogenous (non-rebreather versus endotracheal versus hyperbaric chamber), all studies concluded favorably on the use of oxygen therapy for increased reabsorption of pneumocephalus.


Assuntos
Pneumocefalia , Humanos , Pneumocefalia/terapia , Cefaleia , Oxigênio
6.
Tech Coloproctol ; 28(1): 25, 2024 01 17.
Artigo em Inglês | MEDLINE | ID: mdl-38231341

RESUMO

BACKGROUND: Total mesorectal excision using conventional straight fixed devices may be technically difficult because of the narrow and concave pelvis. Several laparoscopic articulating tools have been introduced as an alternative to robotic systems. The aim of this study was to compare perioperative outcomes between laparoscopic low anterior resection using ArtiSential® and robot-assisted surgery for rectal cancer. METHODS: This retrospective study included 682 patients who underwent laparoscopic or robotic low anterior resection  for rectal cancer from September 2018 to December 2021. Among them, 82 underwent laparoscopic surgery using ArtiSential® (group A) and 201 underwent robotic surgery (group B). A total of 73 [group A; 66.37 ± 11.62; group B 65.79 ± 11.34] patients were selected for each group using a propensity score matching analysis. RESULTS: There was no significant difference in the baseline characteristics between group A and B. Mean operative time was longer in group B than A (163.5 ± 61.9 vs 250.1 ± 77.6 min, p < 0.001). Mean length of hospital stay was not significantly different between the two groups (6.2 ± 4.7 vs 6.7 ± 6.1 days, p = 0.617). Postoperative complications, reoperation, and readmission within 30 days after surgery were similar between the two groups. Pathological findings revealed that the circumferential resection margins were above 10 mm in both groups (11.00 ± 7.47 vs 10.17 ± 6.25 mm, p = 0.960). At least 12 lymph nodes were sufficiently harvested, with no significant difference in the number harvested between the groups (20.5 ± 9.9 vs 19.7 ± 7.3, p = 0.753). CONCLUSIONS: Laparoscopic low anterior resection using ArtiSential® can achieve acceptable clinical and oncologic outcomes. ArtiSential®, a multi-joint and articulating device, may serve a feasible alternative approach to robotic surgery in rectal cancer.


Assuntos
Laparoscopia , Neoplasias Retais , Procedimentos Cirúrgicos Robóticos , Humanos , Pontuação de Propensão , Estudos Retrospectivos , Neoplasias Retais/cirurgia
7.
Food Chem ; 439: 138111, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38104442

RESUMO

Despite bitterness being a common flavor attribute of aged cheese linked to casein-derived peptides, excessive bitterness is a sensory flaw that can lead to consumer rejection and economic loss for creameries. Our research employs a unique approach to identify bitter peptides in cheese samples using crossflow filtration-based fractionation, mass spectrometry-based peptidomics, statistics and sensory analysis. Applying peptidomics and statistical screening tools, rather than traditional chemical separation techniques, to identify bitter peptides allows for screening the whole peptide profile. Five peptides-YPFPGP (ß-casein [60-65]), YPFPGPIPN (ßA2-casein [60-68]), LSQSKVLPVPQKAVPYPQRDMPIQA (ß-casein [165-189]), YPFPGPIHNS (ßA1-casein [60-69]) and its serine phosphorylated version YPFPGPIHN[S] (ßA1-casein [60-69])- demonstrated high levels of bitterness with mean bitterness intensity values above 7 on a 15-point scale. In the future, this data can be combined with the microbial and protease profile of the Cheddar samples to help understand how these factors contribute to bitter taste development.


Assuntos
Queijo , Paladar , Caseínas/análise , Queijo/análise , Peptídeos/análise , Proteômica
8.
PLoS One ; 18(12): e0293046, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38039314

RESUMO

Human adenovirus (HAdV), particularly the HAdV type 5 (HAdV-5), has been extensively utilized in the development of vector vaccines due to its high immunogenicity, good safety profile, and ease of propagation. However, one of the main challenges in its use is the presence of pre-existing immunity among vaccine recipients. Pre-existing neutralizing antibodies (NAbs) can prevent the uptake of HAdV-5 vectors and reduce vaccine efficacy. Hence, this study investigated the seroprevalence of NAbs against HAdV-5 in urban and rural regions of the Philippines. Luciferase-based neutralization assay was performed on 391 plasma/serum samples. Out of these samples, 346 or 88.5% were positive for HAdV-5 NAbs, and the majority of them (56.8%) had high titers against the virus. Among the regions included in this study, Bicol (Region V) had the highest seroprevalence rate (94.1%). Our findings show that a significant number of adults in the Philippines have pre-existing immunity against HAdV-5. This supports the recommendation that vaccination programs in the country should consider implementing vaccination techniques, such as a prime-boost regimen or addition of booster doses, to address the potential negative effects of pre-existing HAdV-5 immunity in the efficacy of adenoviral vector-based vaccines.


Assuntos
Vacinas contra Adenovirus , Adenovírus Humanos , Adulto , Humanos , Anticorpos Neutralizantes , Anticorpos Antivirais , Estudos Soroepidemiológicos , Filipinas/epidemiologia
9.
Gut Microbes ; 15(2): 2281012, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37992398

RESUMO

The intestinal epithelium is constantly exposed to microbes residing in the lumen. Traditionally, the response to microbial interactions has been studied in cell lines derived from cancerous tissues, e.g. Caco-2. It is, however, unclear how the responses in these cancer cell lines reflect the responses of a normal epithelium and whether there might be microbial strain-specific effects. To address these questions, we derived organoids from the small intestine from a cohort of healthy individuals. Culturing intestinal epithelium on a flat laminin matrix induced their differentiation, facilitating analysis of microbial responses via the apical membrane normally exposed to the luminal content. Here, it was evident that the healthy epithelium across multiple individuals (n = 9) demonstrates robust acute both common and strain-specific responses to a range of probiotic bacterial strains (BB-12Ⓡ, LGGⓇ, DSM33361, and Bif195). Importantly, parallel experiments using the Caco-2 cell line provide no acute response. Collectively, we demonstrate that primary epithelial cells maintained as organoids represent a valuable resource for assessing interactions between the epithelium and luminal microbes across individuals, and that these models are likely to contribute to a better understanding of host microbe interactions.


Assuntos
Microbioma Gastrointestinal , Humanos , Células CACO-2 , Células Epiteliais/metabolismo , Organoides , Epitélio , Mucosa Intestinal/microbiologia
10.
Parkinsonism Relat Disord ; 115: 105810, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37660542

RESUMO

BACKGROUND: Weight loss in Parkinson's disease (PD) is common and associated with increased mortality. The clinical significance of weight changes following deep brain stimulation (DBS) of the subthalamic nucleus (STN) and globus pallidus internus (GPi) is unclear. OBJECTIVES: To address (1) whether PD patients exhibit progressive weight loss, (2) whether staged DBS surgery is associated with weight changes, and (3) whether survival after DBS correlates with post-DBS weight. METHODS: This is a single-center, longitudinal, retrospective cohort study of 1625 PD patients. We examined trends in weight over time and the relationship between weight and years survival after DBS using regression and mixed model analyses. RESULTS: There was a decline in body weight predating motor symptom onset (n = 756, 0.70 ± 0.03% decrease per year, p < 0.001). Weight decline accelerated in the decade preceding death (n = 456, 2.18 ± 0.31% decrease per year, p < 0.001). DBS patients showed a weight increase of 2.0 ± 0.33% at 1 year following the first DBS lead implant (n = 455) and 2.68 ± 1.1% at 3 years if a contralateral DBS lead was placed (n = 249). The bilateral STN DBS group gained the most weight after surgery during 6 years of follow up (vs bilateral GPi, 3.03 ± 0.45% vs 1.89 ± 0.31%, p < 0.01). An analysis of the DBS cohort with date of death available (n = 72) revealed that post-DBS weight (0-12 months after the first or 0-36 months after the second surgery) was positively associated with survival (R2 = 0.14, p < 0.001). DISCUSSION: Though PD is associated with significant weight loss, DBS patients gained weight following surgery. Higher post-operative weight was associated with increased survival. These results should be replicated in other cohorts.


Assuntos
Estimulação Encefálica Profunda , Doença de Parkinson , Humanos , Doença de Parkinson/terapia , Estudos Retrospectivos , Estimulação Encefálica Profunda/métodos , Globo Pálido/fisiologia , Redução de Peso , Resultado do Tratamento
11.
Exp Mol Med ; 55(9): 2039-2050, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37653040

RESUMO

Thus far, attempts to develop drugs that target corticotropin-releasing hormone receptor 1 (CRF1R), a drug target in stress-related therapy, have been unsuccessful. Studies have focused on using high-resolution G protein-coupled receptor (GPCR) structures to develop drugs. X-ray free-electron lasers (XFELs), which prevent radiation damage and provide access to high-resolution compositions, have helped accelerate GPCR structural studies. We elucidated the crystal structure of CRF1R complexed with a BMK-I-152 antagonist at 2.75 Å using fixed-target serial femtosecond crystallography. The results revealed that two unique hydrogen bonds are present in the hydrogen bond network, the stalk region forms an alpha helix and the hydrophobic network contains an antagonist binding site. We then developed two antagonists-BMK-C203 and BMK-C205-and determined the CRF1R/BMK-C203 and CRF1R/BMK-C205 complex structures at 2.6 and 2.2 Å, respectively. BMK-C205 exerted significant antidepressant effects in mice and, thus, may be utilized to effectively identify structure-based drugs against CRF1R.


Assuntos
Hormônio Liberador da Corticotropina , Elétrons , Camundongos , Animais , Sítios de Ligação , Descoberta de Drogas , Lasers , Cristalografia por Raios X
12.
Breast ; 71: 82-88, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37544090

RESUMO

BACKGROUND: Partial breast reconstruction with a pedicled chest wall perforator flap (CWPF) enables breast conservation in a higher tumour: breast volume ratio scenario. Since there is limited evidence, this retrospective cohort study aimed to ascertain immediate (30-days) and medium-term (follow-up duration) surgical outcomes. METHODS: STROBE-compliant protocol ascertained CWPF outcomes between March 2011-March 2021. UK centres known to perform CWPF were invited to participate if they performed at least 10 cases. Data were retrospectively collected, including patient demographics, tumour and treatment characteristics, and surgical and oncological outcomes. Statistical analysis (R™) included multivariable logistic regression and sensitivity analysis. RESULTS: Across 15 centres, 507 patients with median age (54 years, IQR; 48-62), body mass index (25.4 kg/m2, IQR; 22.5-29), tumour size (26 mm, IQR; 18-35), and specimen weight (62 g, IQR; 40-92) had following flap types: LiCAP (54.1%, n = 273), MiCAP/AiCAP (19.6%, n = 99), LiCAP + LTAP (19.8%, n = 100) and TDAP (2.2%, n = 11). 30-days complication rates were in 12%: haematoma (4.3%, n = 22), wound infection (4.3%, n = 22), delayed wound healing (2.8%, n = 14) and flap loss (0.6%, n = 3; 1 full) leading to readmissions (2.6%, n = 13) and re-operations (2.6%, n = 13). Positive margins (n = 88, 17.7%) led to 15.9% (n = 79) re-excisions, including 7.5% (n = 37) at the planned 2nd of 2-stage surgery and 1.8% (n = 9) mastectomy. At median 23 months (IQR; 11-39) follow-up, there were 1.2% (n = 6) symmetrisations; recurrences: local (1%), regional/nodal (0.6%) and distant (3.2%). CONCLUSIONS: This large multicentre cohort study demonstrates acceptable complication and margin re-excision rates. CWPF extends the range of breast conservation techniques. Further studies are required for long-term oncological outcomes.


Assuntos
Neoplasias da Mama , Mamoplastia , Retalho Perfurante , Parede Torácica , Humanos , Feminino , Mastectomia/métodos , Estudos Retrospectivos , Estudos de Coortes , Parede Torácica/cirurgia , Neoplasias da Mama/cirurgia , Neoplasias da Mama/patologia , Mamoplastia/métodos , Reino Unido
13.
Eng Life Sci ; 23(5): e2200059, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-37153028

RESUMO

Adherent cells, mammalian or human, are ubiquitous for production of viral vaccines, in gene therapy and in immuno-oncology. The development of a cell-expansion process with adherent cells is challenging as scale-up requires the expansion of the cell culture surface. Microcarrier (MC)-based cultures are still predominate. However, the development of MC processes from scratch possesses particular challenges due to their complexity. A novel approach for the reduction of development times and costs of cell propagation processes is the combination of mathematical process models with statistical optimization methods, called model-assisted Design of Experiments (mDoE). In this study, an mDoE workflow was evaluated successfully for the design of a MC-based expansion process of adherent L929 cells at a very early stage of development with limited prior knowledge. At the start, the analytical methods and the screening of appropriate MCs were evaluated. Then, cause-effect relationships (e.g., cell growth related to medium conditions) were worked out, and a mathematical process model was set-up and adapted to experimental data for modeling purposes. The model was subsequently used in mDoE to identify optimized process conditions, which were proven experimentally. An eight-fold increase in cell yield was achieved basically by reducing the initial MC concentration.

14.
Cell Stem Cell ; 30(4): 348-361, 2023 04 06.
Artigo em Inglês | MEDLINE | ID: mdl-37028402

RESUMO

Tissues with a high turnover rate produce millions of cells daily and have abundant regenerative capacity. At the core of their maintenance are populations of stem cells that balance self-renewal and differentiation to produce the adequate numbers of specialized cells required for carrying out essential tissue functions. Here, we compare and contrast the intricate mechanisms and elements of homeostasis and injury-driven regeneration in the epidermis, hematopoietic system, and intestinal epithelium-the fastest renewing tissues in mammals. We highlight the functional relevance of the main mechanisms and identify open questions in the field of tissue maintenance.


Assuntos
Mucosa Intestinal , Células-Tronco , Animais , Epiderme , Diferenciação Celular , Homeostase , Mamíferos
15.
Malays J Pathol ; 45(1): 111-122, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37119251

RESUMO

INTRODUCTION: Desmoid fibromatosis is a multifactorial disorder classified as a category of intermediate, locally aggressive behaviour, which might be associated with CTNNB1 or APC mutations, trauma, surgery, or pregnancy. CASE REPORTS: We present two cases of postoperative intra-abdominal desmoid fibromatosis. The first case occurred 14 months after the resection of a retroperitoneal gastrointestinal stromal tumour. The second case was located in the mesentery, as evidenced on an 18-month followup after a laparoscopy-assisted anterior resection for adenocarcinoma at the rectosigmoid junction. Under the clinical diagnosis of recurrence, tissue excisions were conducted. Microscopically, the tissue was composed of bland spindle cells without cytological atypia, admixed with collagen bundles. Both tumours exhibited nuclear expression of ß-catenin on immunohistochemical staining, which is a desirable criterion for desmoid fibromatosis. DISCUSSION: Although positron emission tomography aids the diagnosis of recurrence, the radiological features of desmoid fibromatosis in computed tomography or magnetic resonance images are nonspecific and preoperative diagnosis of desmoid fibromatosis is difficult. The histological diagnosis of desmoid fibromatosis is difficult, especially when the specimen is small. The histological differential diagnosis of desmoid fibromatosis includes other myofibroblastic or fibroblastic tumours or lesions. Additional studies, such as ß-catenin immunohistochemistry or CTNNB1 mutation analysis, can enable accurate diagnosis of desmoid fibromatosis. A correct diagnosis is essential, because the current therapeutic strategy is a "waitand- watch" approach, which is significantly different from those of the other locally aggressive, intermediate soft tissue neoplasms. We have summarised the clinicopathological, histological and immunohistochemical features of the post-operative desmoid fibromatosis.


Assuntos
Fibromatose Agressiva , Humanos , Fibromatose Agressiva/diagnóstico , Fibromatose Agressiva/cirurgia , Fibromatose Agressiva/genética , beta Catenina/genética , beta Catenina/análise , Recidiva Local de Neoplasia/diagnóstico , Recidiva Local de Neoplasia/patologia , Imuno-Histoquímica , Diagnóstico Diferencial
16.
Healthcare (Basel) ; 11(5)2023 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-36900663

RESUMO

HPV infection is one of the most studied risk factors in cervical cancer-the second most common cancer site and cause of death due to cancer in the Philippines. However, there is a lack of population-based epidemiological data on cervical HPV infection in the Philippines. Local reports on co-infections with other lower genital tract pathogens, commonly reported globally, are also lacking, which emphasizes the need to increase efforts in targeting HPV prevalence, genotype, and distribution. Hence, we aim to determine the molecular epidemiology and natural history of HPV infection among reproductive-age Filipino women using a community-based prospective cohort design. Women from rural and urban centers will be screened until the target sample size of 110 HPV-positive women (55 from rural sites and 55 from urban sites) is reached. Cervical and vaginal swabs will be collected from all screened participants. For HPV-positive patients, HPV genotypes will be determined. One hundred ten healthy controls will be selected from previously screened volunteers. The cases and controls will comprise the multi-omics subset of participants and will be followed up after 6 and 12 months for repeat HPV screening. Metagenomic and metabolomic analyses of the vaginal swabs will also be performed at baseline, after 6 months, and after 12 months. The results of this study will update the prevalence and genotypic distribution of cervical HPV infection among Filipino women, determine whether the current vaccines used for HPV vaccination programs capture the most prevalent high-risk HPV genotypes in the country, and identify vaginal community state types and bacterial taxa associated with the natural history of cervical HPV infection. The results of this study will be used as the basis for developing a biomarker that can help predict the risk of developing persistent cervical HPV infection in Filipino women.

17.
Retin Cases Brief Rep ; 17(2): 212-218, 2023 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-34009903

RESUMO

PURPOSE: To report a case of Noonan syndrome with multiple lentigines with unusual ocular features. METHODS: The authors describe a case of a 7-year-old girl with Noonan syndrome with multiple lentigines and anomalous optic disks. RESULTS: A 7-year-old girl with genetically proven Noonan syndrome with multiple lentigines ( PTPN11 gene mutation) and anomalous optic disks was referred for treatment of persistent macular detachment after 1 year of conservative follow-up. The right eye demonstrated an optic disk coloboma with the best-corrected visual acuity of 20/32, the left eye demonstrated an optic disk pit with serous macular detachment (best-corrected visual acuity 20/50-20/80). Optical coherence tomography demonstrated a neurosensory detachment. Twenty-five gauge pars plana vitrectomy was performed with posterior hyaloid detachment, drainage over disk pit area, and SF6 20% gas tamponade. Surgery resulted in subretinal fluid reduction and improvement of the visual acuity to 20/32. CONCLUSION: A case of Noonan syndrome with multiple lentigines with optic disk coloboma in the right eye and optic disk pit with related maculopathy in the left eye. To the best of the authors' knowledge, this is the first reported case describing the association of Noonan syndrome with multiple lentigines and congenital optic disk anomalies. Optic disk pit maculopathy was managed surgically because of its longstanding nature with the deteriorating visual acuity.


Assuntos
Coloboma , Anormalidades do Olho , Síndrome LEOPARD , Degeneração Macular , Disco Óptico , Transtornos da Pigmentação , Descolamento Retiniano , Doenças Retinianas , Feminino , Humanos , Criança , Disco Óptico/anormalidades , Coloboma/complicações , Coloboma/diagnóstico , Coloboma/cirurgia , Vitrectomia/métodos , Síndrome LEOPARD/complicações , Síndrome LEOPARD/cirurgia , Doenças Retinianas/complicações , Descolamento Retiniano/cirurgia , Anormalidades do Olho/complicações , Anormalidades do Olho/diagnóstico , Anormalidades do Olho/cirurgia , Degeneração Macular/complicações , Tomografia de Coerência Óptica , Transtornos da Pigmentação/complicações
18.
Cancers (Basel) ; 14(21)2022 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-36358844

RESUMO

Introduction: Nivolumab (N), pembrolizumab (P), and dabrafenib plus trametinib (D + T) have been registered as adjuvant treatments for resected stage III and IV melanoma since 2018. Electronic health records (EHRs) are a real-world data source that can be used to review treatments in clinical practice. In this study, we applied EHR text-mining software to evaluate the real-world tolerability, safety, and efficacy of adjuvant melanoma treatments. Methods: Adult melanoma patients receiving adjuvant treatment between January 2019 and October 2021 at the Leiden University Medical Center, the Netherlands, were included. CTcue text-mining software (v3.1.0, CTcue B.V., Amsterdam, The Netherlands) was used to construct rule-based queries and perform context analysis for patient inclusion and data collection from structured and unstructured EHR data. Results: In total, 122 patients were included: 54 patients treated with nivolumab, 48 with pembrolizumab, and 20 with D + T. Significantly more patients discontinued treatment due to toxicity on D + T (N: 16%, P: 6%, D + T: 40%), and X2 (6, n = 122) = 14.6 and p = 0.024. Immune checkpoint inhibitors (ICIs) mainly showed immune-related treatment-limiting adverse events (AEs), and chronic thyroid-related AE occurred frequently (hyperthyroidism: N: 15%, P: 13%, hypothyroidism: N: 20%, P: 19%). Treatment-limiting toxicity from D + T was primarily a combination of reversible AEs, including pyrexia and fatigue. The 1-year recurrence-free survival was 70.3% after nivolumab, 72.4% after pembrolizumab, and 83.0% after D + T. Conclusions: Text-mining EHR is a valuable method to collect real-world data to evaluate adjuvant melanoma treatments. ICIs were better tolerated than D + T, in line with RCT results. For BRAF+ patients, physicians must weigh the higher risk of reversible treatment-limiting AEs of D + T against the risk of long-term immune-related AEs.

19.
Support Care Cancer ; 30(11): 9181-9189, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36044088

RESUMO

PURPOSE: Chemotherapy-induced febrile neutropenia (FN) is a life-threatening and chemotherapy dose-limiting adverse event. FN can be prevented with granulocyte-colony stimulating factors (G-CSFs). Guidelines recommend primary G-CSF use for patients receiving either high (> 20%) FN risk (HR) chemotherapy, or intermediate (10-20%) FN risk (IR) chemotherapy if the overall risk with additional patient-related risk factors exceeds 20%. In this study, we applied an EHR text-mining tool for real-world G-CSF treatment evaluation in breast cancer patients. METHODS: Breast cancer patients receiving IR or HR chemotherapy treatments between January 2015 and February 2021 at LUMC, the Netherlands, were included. We retrospectively collected data from EHR with a text-mining tool and assessed G-CSF use, risk factors, and the FN and neutropenia (grades 3-4) and incidence. RESULTS: A total of 190 female patients were included, who received 77 HR and 113 IR treatments. In 88.3% of the HR regimens, G-CSF was administered; 7.3% of these patients developed FN vs. 33.3% without G-CSF. Although most IR regimen patients had ≥ 2 risk factors, only 4% received G-CSF, of which none developed neutropenia. However, without G-CSF, 11.9% developed FN and 31.2% severe neutropenia. CONCLUSIONS: Our text-mining study shows high G-CSF use among HR regimen patients, and low use among IR regimen patients, although most had ≥ 2 risk factors. Therefore, current practice is not completely in accordance with the guidelines. This shows the need for increased awareness and clarity regarding risk factors. Also, text-mining can effectively be implemented for the evaluation of patient care.


Assuntos
Neoplasias da Mama , Neutropenia Febril Induzida por Quimioterapia , Neutropenia Febril , Humanos , Feminino , Fator Estimulador de Colônias de Granulócitos , Neoplasias da Mama/epidemiologia , Estudos Retrospectivos , Registros Eletrônicos de Saúde , Neutropenia Febril Induzida por Quimioterapia/prevenção & controle , Mineração de Dados , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neutropenia Febril/tratamento farmacológico
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