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1.
Int J Gynecol Pathol ; 43(2): 158-170, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-37668363

RESUMO

Currently, there are limited and conflicting reports on the prognostic utility of PIK3CA and associated pathway markers for cervical cancers treated with primary surgical management. Moreover, current studies are lacking complete characterization of adjuvant treatment with RT and/or chemotherapy. We aimed to document the prevalence, clinicopathologic, adjuvant treatment details, and prognostic value of PI3K/AKT pathway mutations and copy number variation and phosphorylated AKT status in patients with cervical cancers treated with primary surgery. A clinicopathologic review was performed on a retrospective cohort of 185 patients with cervical cancer, treated with primary surgery at a single tertiary institution. Next-generation sequencing and digital PCR was used to determine PI3K/AKT pathway mutational status and PIK3CA copy number variation, respectively, and fluorescent immunohistochemistry measured phosphorylated AKT expression. In all, 179 of 185 (96.8%) of tumors were successfully sequenced; 48 (26.8%) were positive for PI3K/AKT pathway mutations-the majority (n=37, 77.1%) PIK3CA mutations. PIK3CA mutation was associated with pathologically positive lymph nodes [12 (32%) vs. 22 (16%); P =0.022] and indication for postoperative chemoradiotherapy [17 (45.9%) vs. 32 (22.5%); P =0.004]. On multivariable analysis, PIK3CA status was not associated with overall survival ( P =0.103) or progression-free survival ( P =0.240) at 5 yrs, nor was PIK3CA copy number variation status. phosphorylated AKT ≤ median significantly predicted for progression-free survival [multivariable hazard ratio 0.39 (0.17-0.89; P =0.025)] but not overall survival ( P =0.087). The correlation of PIK3CA with pathologic positive lymph node status yet lack of association with survival outcomes may be due to the use of adjuvant postoperative therapy. PIK3CA assessment before radical hysterectomy may help identify patients with a higher risk of node-positive disease.


Assuntos
Proteínas Proto-Oncogênicas c-akt , Neoplasias do Colo do Útero , Feminino , Humanos , Prognóstico , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Neoplasias do Colo do Útero/genética , Neoplasias do Colo do Útero/cirurgia , Fosfatidilinositol 3-Quinases/genética , Fosfatidilinositol 3-Quinases/metabolismo , Estudos Retrospectivos , Variações do Número de Cópias de DNA , Prevalência , Mutação , Classe I de Fosfatidilinositol 3-Quinases/genética
2.
J Oncol Pharm Pract ; : 10781552231179190, 2023 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-37259570

RESUMO

BACKGROUND: The introduction of CDK 4/6 inhibitors for breast cancer patients has contributed to increased ambulatory patient visits for oncologists. The Medication Assessment by Pharmacist program aims to evaluate the impact of oncology pharmacists performing medication assessment follow-up visits. METHODS: Breast cancer patients on a CDK 4/6 inhibitor deemed suitable by their oncologist for pharmacist assessment could be booked for a pharmacist medication assessment appointment at alternate treatment cycles. RESULTS: Between February 2019 to November 2021, 29 of 128 patients (22.7%) were selected for 46 total Medication Assessment by Pharmacist visits resulting in 920 min of clinic time savings for physicians. There were similar rates of adhering to provincial protocols for scheduling visits (99% vs. 96%, p = 0.12) and monitoring investigations (98% vs. 98%, p = 0.96) between those enrolled in Medication Assessment by Pharmacist or not. Surveys completed by medical oncologists and pharmacists demonstrated that nine of nine oncologists felt Medication Assessment by Pharmacist reduced workload and wanted Medication Assessment by Pharmacist expanded to additional oncology drugs. Pharmacist-completed surveys revealed that nine of nine pharmacists felt Medication Assessment by Pharmacist increased job satisfaction, and allowed further application of clinical skills. All agreed that patients were receptive to meeting with pharmacists. According to survey results, 33% of oncologists versus 100% of pharmacists routinely asked about medication adherence, new medications or supplements. CONCLUSION: Integrating pharmacists into a shared care model reduces ambulatory patient visits for oncologists without deviating from provincial protocol guidelines for monitoring and visits for patients on CDK 4/6 inhibitors. Leveraging the medication expertise of pharmacists also increases the frequency of addressing medication adherence and concurrent therapies. Medication Assessment by Pharmacist may be an effective strategy in alleviating projected shortages of oncology providers.

3.
Pediatr Diabetes ; 23(5): 556-561, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-33978300

RESUMO

OBJECTIVE: With increasing prevalence of childhood obesity worldwide, the incidence of pediatric-onset type 2 diabetes (T2D) is also increasing in many countries. We aim to analyze the time trend and incidence of T2D in children in Hong Kong from 2008 to 2017, and to characterize clinical characteristics at diagnosis. METHODS: Data were retrieved from the Hong Kong Childhood Diabetes Registry. All children with T2D diagnosed at the age of less than 18 years from January 1, 2008 to December 31, 2017 and managed in the public health care system were included in this study. RESULTS: In the incident years of 2008-2017 period, 391 children were diagnosed with T2D. The crude incidence rate was 3.42 per 100,000 persons/year [95% confidence interval (CI) 3.08-3.76], which was much higher than that in last registry of 1.27 per 100,000 persons/year in 1997-2007 (P < 0.001).Most children (76%) were asymptomatic and were diagnosed by routine screening. At presentation, a significant proportion presented with co-morbidities including fatty liver (37.9%), dyslipidaemia (35.3%), hypertension (22.5%), and microalbuminuria (12.8%). CONCLUSIONS: The incidence of T2D in children has increased significantly in Hong Kong. Most of them were asymptomatic and picked up on routine health screening. Yet, comorbidities were commonly identified at diagnosis.


Assuntos
Diabetes Mellitus Tipo 2 , Obesidade Infantil , Adolescente , Criança , Diabetes Mellitus Tipo 2/epidemiologia , Hong Kong/epidemiologia , Humanos , Incidência , Sistema de Registros
4.
J Nurs Care Qual ; 37(3): 199-205, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35125453

RESUMO

BACKGROUND: Inpatient falls with harm have severe implications on patients and the health care system. PURPOSE: We implemented a zero harm approach to falls prevention, which aimed to reduce falls with injury by 25% within 1 year. METHODS: We implemented a multifaceted and multidisciplinary quality improvement falls prevention strategy that included facilitating organization-wide education, adopting the Morse Fall Risk Assessment tool, displaying real-time unit-specific falls rates, and implementing a transparent root-cause analysis process after falls. Our outcome measure was falls with injury per 1000 patient-days. RESULTS: We observed a decrease in the rate of patient falls with injury from 2.03 (baseline period) to 1.12 (1 year later) per 1000 patient-days. We also observed increases in awareness around falls prevention and patient safety incident reporting. CONCLUSIONS: Our zero harm approach reduced falls with injury while improving our patient safety culture.


Assuntos
Melhoria de Qualidade , Gestão da Segurança , Humanos , Pacientes Internados , Segurança do Paciente
5.
J Allergy Clin Immunol ; 146(5): 1027-1034.e4, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32771560

RESUMO

BACKGROUND: Several underlying conditions have been associated with severe acute respiratory syndrome coronavirus 2 illness, but it remains unclear whether underlying asthma is associated with worse coronavirus disease 2019 (COVID-19) outcomes. OBJECTIVE: Given the high prevalence of asthma in the New York City area, our objective was to determine whether underlying asthma was associated with poor outcomes among hospitalized patients with severe COVID-19 compared with patients without asthma. METHODS: Electronic heath records were reviewed for 1298 sequential patients 65 years or younger without chronic obstructive pulmonary disease who were admitted to our hospital system with a confirmed positive severe acute respiratory syndrome coronavirus 2 test result. RESULTS: The overall prevalence of asthma among all hospitalized patients with COVID-19 was 12.6%, yet a higher prevalence (23.6%) was observed in the subset of 55 patients younger than 21 years. There was no significant difference in hospital length of stay, need for intubation, length of intubation, tracheostomy tube placement, hospital readmission, or mortality between patients with and without asthma. Observations between patients with and without asthma were similar when stratified by obesity, other comorbid conditions (ie, hypertension, hyperlipidemia, and diabetes), use of controller asthma medication, and absolute eosinophil count. CONCLUSIONS: Among hospitalized patients 65 years or younger with severe COVID-19, asthma diagnosis was not associated with worse outcomes, regardless of age, obesity, or other high-risk comorbidities. Future population-based studies are needed to investigate the risk of developing COVID-19 among patients with asthma once universal testing becomes readily available.


Assuntos
Asma/complicações , Asma/epidemiologia , Infecções por Coronavirus/complicações , Pneumonia Viral/complicações , Adulto , Asma/mortalidade , Betacoronavirus , COVID-19 , Infecções por Coronavirus/mortalidade , Feminino , Humanos , Tempo de Internação/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Cidade de Nova Iorque/epidemiologia , Pandemias , Readmissão do Paciente/estatística & dados numéricos , Pneumonia Viral/mortalidade , Prevalência , SARS-CoV-2
6.
Gynecol Oncol ; 158(3): 776-784, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32653099

RESUMO

PURPOSE: This study aimed to describe the prognostic value of PI3K/AKT pathway mutations in a large cohort of patients with cervical cancer. EXPERIMENTAL DESIGN: Patients with pre-treatment archival specimens, diagnosed with FIGO stages IB-IVA cervical cancer between 1998 and 2014 and treated with radical, curative intent chemoradiotherapy (CRT) at a single center were identified. Mutational status was determined by next generation sequencing and PIK3CA copy number (CNV) was assessed by digital PCR. RESULTS: 190 patients with available pre-treatment tumor specimens were identified. Median OS and PFS were 57.4 and 46.0 months, respectively. A total of 161 tumors were successfully sequenced; 60 (37.3%) had PI3K/AKT pathway mutations, with 50 (30.1%) having PIK3CA hotspot mutations. PIK3CA CNV gain was noted in 79 (59.2%) of the 154 successfully analyzed. On univariate analysis, PIK3CA mutation was associated with poor OS (HR 1.73; 95% CI: 1.03-2.92; p = .037) but not PFS (HR 1.38; 0.84-2.28; p = .204). Absence of any PI3K/AKT pathway mutation was associated with improved OS (HR 1.68; 1.01-2.81; p = .046) but not PFS (HR 1.50; 0.93-2.43; p = .202). Associations were not maintained when adjusting for clinical factors. On univariate analysis, PIK3CA mutation positive, CNV normal tumors were associated with poorer OS (HR 2.55; 1.18-5.50; p = .017) and trend to worse PFS (HR 1.87; 0.90-3.83; p = .094) when compared to those with CNV gain and wildtype PIK3CA. CONCLUSIONS: PI3K/AKT pathway mutations are common in cervical cancer. Consideration of PIK3CA mutational status with CNV status may be important in predicting outcome in cervical cancer patients.


Assuntos
Classe I de Fosfatidilinositol 3-Quinases/genética , Neoplasias do Colo do Útero/genética , Neoplasias do Colo do Útero/terapia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Quimiorradioterapia , Feminino , Dosagem de Genes , Células HeLa , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Imuno-Histoquímica , Pessoa de Meia-Idade , Mutação , Estadiamento de Neoplasias , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais , Taxa de Sobrevida , Análise Serial de Tecidos , Neoplasias do Colo do Útero/metabolismo , Neoplasias do Colo do Útero/patologia , Adulto Jovem
7.
Pediatr Diabetes ; 21(5): 713-719, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32267057

RESUMO

OBJECTIVE: The incidence of childhood-onset type 1 diabetes (T1D) has been reported to be rising but there is also evidence that it has been attenuated in recent years. We described the time trends and the incidence of T1D in children in Hong Kong from 2008 to 2017 and compared with the previous local registry in 1997 to 2007. METHODS: Data were extracted from the Hong Kong Childhood Diabetes Registry, which was established in 2016. It consists of a retrospective registry (including all childhood diabetes diagnosed in 2008 to 2015) and a prospective registry (including all T1D children diagnosed from 2016 onwards). All T1D children diagnosed at the age of less than 18 years from 1 January 2008 to 31 December 2017 and managed in the public system were included in this study. RESULTS: For the incident years in the 2008 to 2017 period, a total of 498 children with T1D was identified. The crude incidence rate was 4.3 per 100 000 person/year (95% confidence interval 3.96-4.72), which was much higher than the last registry of 2.2 per 100 000 persons/year. Using general linear model, the increment is statistically significant (P = .02). When compared to the last registry, the rate of increment had attenuated, with annual increment in crude incidence in the two periods for T1D <15 years changing from 4.3% to 3.5% (P = .02). CONCLUSIONS: The incidence of T1D children increased significantly in the past two decades in Hong Kong, but the rate of increase had attenuated in recent years.


Assuntos
Diabetes Mellitus Tipo 1/epidemiologia , Adolescente , Criança , Pré-Escolar , Diabetes Mellitus Tipo 1/história , Feminino , História do Século XXI , Hong Kong/epidemiologia , Humanos , Incidência , Lactente , Recém-Nascido , Masculino , Sistema de Registros/estatística & dados numéricos , Estudos Retrospectivos
8.
Sensors (Basel) ; 21(1)2020 Dec 29.
Artigo em Inglês | MEDLINE | ID: mdl-33383809

RESUMO

This article explores the affective impact of remote touch when used in conjunction with video telecon. Committed couples were recruited to engage in semi-structured discussions after they watched a video clip that contained emotionally charged moments. They used paired touch input and output devices to send upper-arm squeezes to each other in real-time. Users were not told how to use the devices and were free to define the purpose of their use. We examined how remote touch was used and its impact on skin conductance and affective response. We observed 65 different touch intents, which were classified into broader categories. We employed a series of analyses within a framework of behavioral and experiential timescales. Our findings revealed that remote touches created a change in the overall psychological affective experience and skin conductance response. Only remote touches that were judged to be affective elicited significant changes in EDA measurements. Our study demonstrates the affective power of remote touch in video telecommunication, and that off-the-shelf wearable EDA sensing devices can detect such affective impacts. Our findings pave the way for new species of technologies with real-time feedback support for a range of communicative and special needs such as isolation, stress, and anxiety.

9.
PLoS Genet ; 11(4): e1005186, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25906395

RESUMO

Telomerase, the enzyme that maintains telomeres, preferentially lengthens short telomeres. The S. cerevisiae Pif1 DNA helicase inhibits both telomerase-mediated telomere lengthening and de novo telomere addition at double strand breaks (DSB). Here, we report that the association of the telomerase subunits Est2 and Est1 at a DSB was increased in the absence of Pif1, as it is at telomeres, suggesting that Pif1 suppresses de novo telomere addition by removing telomerase from the break. To determine how the absence of Pif1 results in telomere lengthening, we used the single telomere extension assay (STEX), which monitors lengthening of individual telomeres in a single cell cycle. In the absence of Pif1, telomerase added significantly more telomeric DNA, an average of 72 nucleotides per telomere compared to the 45 nucleotides in wild type cells, and the fraction of telomeres lengthened increased almost four-fold. Using an inducible short telomere assay, Est2 and Est1 no longer bound preferentially to a short telomere in pif1 mutant cells while binding of Yku80, a telomere structural protein, was unaffected by the status of the PIF1 locus. Two experiments demonstrate that Pif1 binding is affected by telomere length: Pif1 (but not Yku80) -associated telomeres were 70 bps longer than bulk telomeres, and in the inducible short telomere assay, Pif1 bound better to wild type length telomeres than to short telomeres. Thus, preferential lengthening of short yeast telomeres is achieved in part by targeting the negative regulator Pif1 to long telomeres.


Assuntos
DNA Helicases/genética , Proteínas de Saccharomyces cerevisiae/genética , Telomerase/genética , Proteínas de Ligação a Telômeros/genética , Telômero/genética , Quebras de DNA de Cadeia Dupla , Saccharomyces cerevisiae/genética , Homeostase do Telômero/genética , Proteínas de Ligação a Telômeros/metabolismo
10.
Histopathology ; 70(3): 347-358, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-27575406

RESUMO

AIMS: The clinical courses of patients with low-grade serous carcinoma (LGSC) can be substantially different. The purpose of this study was to explore whether molecular or pathological features could identify patients who follow a more aggressive course. METHODS AND RESULTS: Twenty-six primary LGSCs (11 with an aggressive clinical course, and 15 with an indolent clinical course) and five paired recurrences were assessed for non-synonymous somatic mutations in 18 MAPK pathway genes and in 42 other classic cancer 'hotspot' genes by use of a custom-designed AmpliSeq panel based on the AmpliSeq Cancer hotspot panel v2. Copy number alterations for 94 target genes were assessed with the nCounter v2 Cancer CN assay. Immunohistochemistry for 12 proteins was performed. We detected 16 mutations in 13 of 26 cases (50%), affecting five genes that signal through the MAPK pathway, and one ESR1 mutation implicated in resistance to endocrine therapy in breast cancer. Recurrent samples were concordant with the primary tumour with respect to the mutational status, but all five cases showed additional alterations at the copy number or protein expression level. The absence of progesterone receptor (PR) expression and the presence of myometrial lymphovascular invasion were associated with an unfavourable outcome (log-rank P = 0.016 and P < 0.0001, respectively), but none of the other molecular features assessed showed an association. CONCLUSION: Despite limited case numbers, it appears that current molecular testing is inferior to a pathological parameter or protein expression in predicting the outcome of LGSCs. Prediction of outcome based on the primary tumour may be confounded by additional changes acquired over time.


Assuntos
Biomarcadores Tumorais/análise , Cistadenocarcinoma Seroso/genética , Cistadenocarcinoma Seroso/patologia , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/patologia , Adulto , Idoso , Cistadenocarcinoma Seroso/mortalidade , Intervalo Livre de Doença , Feminino , Perfilação da Expressão Gênica , Humanos , Imuno-Histoquímica , Estimativa de Kaplan-Meier , Pessoa de Meia-Idade , Neoplasias Ovarianas/mortalidade , Prognóstico , Análise Serial de Tecidos
11.
Br J Cancer ; 114(1): 59-62, 2016 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-26645240

RESUMO

BACKGROUND: Metabolomics has shown promise in gastric cancer (GC) detection. This research sought to identify whether GC has a unique urinary metabolomic profile compared with benign gastric disease (BN) and healthy (HE) patients. METHODS: Urine from 43 GC, 40 BN, and 40 matched HE patients was analysed using (1)H nuclear magnetic resonance ((1)H-NMR) spectroscopy, generating 77 reproducible metabolites (QC-RSD <25%). Univariate and multivariate (MVA) statistics were employed. A parsimonious biomarker profile of GC vs HE was investigated using LASSO regularised logistic regression (LASSO-LR). Model performance was assessed using Receiver Operating Characteristic (ROC) curves. RESULTS: GC displayed a clear discriminatory biomarker profile; the BN profile overlapped with GC and HE. LASSO-LR identified three discriminatory metabolites: 2-hydroxyisobutyrate, 3-indoxylsulfate, and alanine, which produced a discriminatory model with an area under the ROC of 0.95. CONCLUSIONS: GC patients have a distinct urinary metabolite profile. This study shows clinical potential for metabolic profiling for early GC diagnosis.


Assuntos
Espectroscopia de Ressonância Magnética/métodos , Metabolômica/métodos , Neoplasias Gástricas/diagnóstico , Idoso , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Neoplasias Gástricas/urina
14.
Adv Health Sci Educ Theory Pract ; 20(4): 1061-71, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-25638697

RESUMO

Central venous catheterization (CVC) is a complex but commonly performed procedure. How best to teach this complex skill has not been clearly delineated. We conducted a randomized trial of the effects of two types of teaching of CVC on skill acquisition and retention. We randomly assigned novice internal medicine residents to learning CVC in-part or in-whole. The part-group was taught the first part of the procedure, followed by practice, followed by being taught the second and final portion of the procedure, and followed by practice. The whole-group was taught the procedure in its entirety, followed by practice. Teaching and practice time for both groups was otherwise held constant. Performances were assessed at baseline, post-training, and at 1 month. The primary outcome was skill retention at 1-month, rated by using a global rating scale and a 22-item checklist, and defined as the score increase between 1-month and baseline. Skill acquisition is defined as the score increase post-training and baseline. Raters were blinded to the participants' identity, group assignment, and time point. Participants in the part-task group outperformed the whole-task group in skill acquisition (2.2 ± 0.8 vs 1.3 ± 1.0; g = 1.01; p = 0.04) and in skill retention (1.5 ± 0.7 vs 0.5 ± 0.8; g = 1.39; p = 0.006) using the global rating scale. Scores rated by the checklist were not significantly different (52.0 ± 25.3 vs 43.5 ± 23.4; g = 0.33; p = 0.47 for skill acquisition; and 48.5 ± 34.9 vs 41.1 ± 20.4; g = 0.35; p = 0.44 for skill retention). For teaching ultrasound-guided CVC to novice learners, teaching in part is preferable than teaching in whole.


Assuntos
Cateterismo Venoso Central/normas , Competência Clínica , Educação de Pós-Graduação em Medicina/métodos , Medicina Interna/educação , Avaliação Educacional , Humanos , Internato e Residência , Manequins , Reprodutibilidade dos Testes
15.
PLoS Genet ; 7(5): e1002060, 2011 May.
Artigo em Inglês | MEDLINE | ID: mdl-21573139

RESUMO

Telomerase is a telomere dedicated reverse transcriptase that replicates the very ends of eukaryotic chromosomes. Saccharomyces cerevisiae telomerase consists of TLC1 (the RNA template), Est2 (the catalytic subunit), and two accessory proteins, Est1 and Est3, that are essential in vivo for telomerase activity but are dispensable for catalysis in vitro. Est1 functions in both recruitment and activation of telomerase. The association of Est3 with telomeres occurred largely in late S/G2 phase, the time when telomerase acts and Est1 telomere binding occurs. Est3 telomere binding was Est1-dependent. This dependence is likely due to a direct interaction between the two proteins, as purified recombinant Est1 and Est3 interacted in vitro. Est3 abundance was neither cell cycle-regulated nor Est1-dependent. Est3 was the most abundant of the three Est proteins (84.3±13.3 molecules per cell versus 71.1±19.2 for Est1 and 37.2±6.5 for Est2), so its telomere association and/or activity is unlikely to be limited by its relative abundance. Est2 and Est1 telomere binding was unaffected by the absence of Est3. Taken together, these data indicate that Est3 acts downstream of both Est2 and Est1 and that the putative activation function of Est1 can be explained by its role in recruiting Est3 to telomeres.


Assuntos
Ciclo Celular/fisiologia , Proteínas de Saccharomyces cerevisiae/metabolismo , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/metabolismo , Telomerase/metabolismo , Telômero/metabolismo , Glicina/química , Glicina/metabolismo , Fosforilação , Ligação Proteica , Proteínas Proto-Oncogênicas c-myc/química , Proteínas Proto-Oncogênicas c-myc/metabolismo , Saccharomyces cerevisiae/enzimologia
16.
Knee Surg Sports Traumatol Arthrosc ; 22(3): 590-8, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-23982758

RESUMO

PURPOSE: The aim of this work was to develop a computational biomechanical study to compare the performance of tibial trays with different offsets for a total knee arthroplasty. The goal was to investigate whether the offset tibial tray shifts the bone stress distribution, influencing the clinical outcome. METHODS: Three geometric models were developed for the intact tibia bone: one considering a standard tibia case and the other two reproducing tibias with a medial or a lateral offset of the metaphysis. Appropriate prosthetic components were assembled in the bone for the aforementioned cases. The finite element method was used to obtain the mechanical stress distribution for the models, and the stress shielding effect due to the prosthesis was analysed. RESULTS: The obtained results revealed that the offset cases are subjected to higher stresses than the standard case. These values can be two times superior to the ones verified in a standard case. The stress shielding effect was confirmed along all the analysed paths, except near the stem's end in some areas. CONCLUSION: The higher stresses registered can originate lower clinical outcomes in the offset cases. These findings can be an important beginning to understand whether better bone stress distribution could be achieved in deformity correction with associated osteotomies instead of offsetting.


Assuntos
Artroplastia do Joelho/instrumentação , Prótese do Joelho , Tíbia , Fenômenos Biomecânicos , Análise de Elementos Finitos , Humanos , Modelos Anatômicos , Estresse Mecânico
17.
Virchows Arch ; 484(1): 119-125, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38063896

RESUMO

DEK::AFF2 fusion-associated papillary squamous cell carcinoma is a novel entity characterized by its unique translocation and malignant clinical course. In this study, AFF immunohistochemistry (IHC) was performed in recurrent sinonasal papillomas for reviewing the prevalence of undiagnosed DEK::AFF2 carcinomas and to investigate the performance of AFF IHC in diagnosis of DEK::AFF2 carcinomas. Recurrent sinonasal papillomas after surgical excision in a two-decade period were retrieved. Histologic slides were reviewed for features of DEK::AFF2 carcinoma. AFF IHC was performed, and cases with any (> 1%) nuclear positivity were validated by DEK break apart fluorescence in situ hybridization. Totally 43 cases were included, comprising 28 inverted, 6 exophytic, one oncocytic, and 8 non-specified sinonasal papillomas. Five (11.6%) cases exhibited positivity to AFF IHC. Three cases exhibited patchy weak to moderate staining intensity predominantly in a granular cytoplasmic pattern. Two cases exhibited strong and diffuse (> 90%) nuclear staining. Cases showing weak staining were negative for DEK rearrangement, while those with strong staining were positive. Both cases of DEK::AFF2 carcinoma showed aggressive behavior with extensive local invasion and nodal metastasis. Background stromal plasma cells, when present, consistently showed strong and diffuse staining. AFF IHC was further performed in plasmacytoma samples as control and showed strong and diffuse immunoreactivity. A significant minority of recurrent sinonasal papillomas represent DEK::AFF2 carcinomas. Granular, cytoplasmic, or incomplete AFF staining should be considered as negative. In view of the rarity of DEK::AFF2 carcinomas, plasma cells and plasma cell neoplasms are potential for internal and surrogate external controls.


Assuntos
Carcinoma de Células Escamosas , Neoplasias de Cabeça e Pescoço , Papiloma , Humanos , Estudos Retrospectivos , Prevalência , Hibridização in Situ Fluorescente , Papiloma/patologia , Carcinoma de Células Escamosas/patologia , Proteínas Nucleares
18.
Antioxidants (Basel) ; 13(6)2024 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-38929190

RESUMO

Chronic kidney disease (CKD) presents a substantial global public health challenge, with high morbidity and mortality. CKD patients often experience dyslipidaemia and poor glycaemic control, further exacerbating inflammation and oxidative stress in the kidney. If left untreated, these metabolic symptoms can progress to end-stage renal disease, necessitating long-term dialysis or kidney transplantation. Alleviating inflammation responses has become the standard approach in CKD management. Medications such as statins, metformin, and GLP-1 agonists, initially developed for treating metabolic dysregulation, demonstrate promising renal therapeutic benefits. The rising popularity of herbal remedies and supplements, perceived as natural antioxidants, has spurred investigations into their potential efficacy. Notably, lactoferrin, Boerhaavia diffusa, Amauroderma rugosum, and Ganoderma lucidum are known for their anti-inflammatory and antioxidant properties and may support kidney function preservation. However, the mechanisms underlying the effectiveness of Western medications and herbal remedies in alleviating inflammation and oxidative stress occurring in renal dysfunction are not completely known. This review aims to provide a comprehensive overview of CKD treatment strategies and renal function preservation and critically discusses the existing literature's limitations whilst offering insight into the potential antioxidant effects of these interventions. This could provide a useful guide for future clinical trials and facilitate the development of effective treatment strategies for kidney functions.

19.
NPJ Breast Cancer ; 10(1): 3, 2024 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-38182588

RESUMO

Circulating tumour DNA (ctDNA) detection via liquid biopsy is an emerging alternative to tissue biopsy, but its potential in treatment response monitoring and prognosis in triple negative breast cancer (TNBC) is not yet well understood. Here we determined the prevalence of actionable mutations detectable in ctDNA using a clinically validated cancer gene panel assay in patients with TNBC, without recurrence at the time of study entry. Sequencing of plasma DNA and validation of variants from 130 TNBC patients collected within 7 months of primary treatment completion revealed that 7.7% had detectable residual disease with a hotspot panel. Among neoadjuvant treated patients, we observed a trend where patients with incomplete pathologic response and positive ctDNA within 7 months of treatment completion were at much higher risk of reduced progression free survival. We propose that a high risk subset of early TNBC patients treated in neoadjuvant therapy protocols may be identifiable by combining tissue response and sensitive ctDNA detection.

20.
J Pediatr Endocrinol Metab ; 37(2): 130-136, 2024 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-38282366

RESUMO

OBJECTIVES: Obesity and type 2 diabetes mellitus (T2DM) are growing health concerns. Since 2005, Student Health Service (SHS) and Hong Kong Paediatric Society formulated a protocol on urine glucose screening (UGS) for early diagnosis of T2DM in students with obesity in Hong Kong. This study reviews students with T2DM captured by this screening program and compare the data with the Hong Kong Children Diabetes Registry (HKCDR) database, to see if the UGS program facilitates early diagnosis of T2DM. METHODS: Students between the ages of 10-18 years old with age- and sex-specific body mass index (BMI) >97th percentile who attended SHS between the school years from 2005/06 to 2017/18 were recruited for UGS. Those tested positive for random urine glucose underwent diagnostic testing for T2DM according to ADA guidelines. Demographic data and investigatory results from UGS and HKCDR within the same time period were compared. RESULTS: A total of 216,526 students completed UGS in the said period; 415 (0.19 %) students were tested positive for urine glucose of which 121 students were diagnosed with T2DM. UGS picked up 23 % of the newly diagnosed T2DM cases. When compared to the HKCDR database, students diagnosed via UGS were significantly younger, less obese, and had fewer diabetic related complications. The negative predictive value of UGS is high and can effectively rule out T2DM. CONCLUSIONS: Urine glucose screening is an inexpensive and simple test that allows for early diagnosis of T2DM among obese school students. Other methods including POCT HbA1c can be explored to improve program effectiveness.


Assuntos
Complicações do Diabetes , Diabetes Mellitus Tipo 2 , Obesidade Infantil , Masculino , Feminino , Adolescente , Humanos , Criança , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/epidemiologia , Hong Kong/epidemiologia , Glucose , Diagnóstico Precoce
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