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1.
Med J Malaysia ; 79(5): 547-555, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39352156

RESUMEN

INTRODUCTION: Epithelial ovarian cancer (EOC) is the fourth most common malignancy among Malaysian women. This study aims to evaluate the outcomes of EOC, fallopian tube cancer and primary peritoneal serous carcinoma (PPSC) between a centre managed by both clinical oncologists and gynaecologic oncologists, Institut Kanser Negara (IKN) and a centre managed solely by gynaecologic oncologists, Hospital Ampang (HA). MATERIALS AND METHODS: This retrospective cohort study involved data review of all the newly diagnosed patients with EOC, fallopian tube cancer and PPSC who received treatment in IKN and HA from January 2015 to December 2019, with follow-up continuing until December 2022. The primary outcome is overall survival (OS) and the secondary outcome is progression free survival (PFS) rates; estimated using the Kaplan-Meier method and compared using the logrank test. Another secondary outcome is to determine the prognostic factors affecting the OS of patients from these two cohorts using Cox regression analysis. RESULTS: A total of 256 patients from both centres were recruited (106 and 150 patients from IKN and HA respectively) and at the time of diagnosis, more than half of the patients were diagnosed with advanced stage disease (67.5% and 62% from IKN and HA respectively). The median OS for patients with EOC was significantly longer for HA compared to IKN (69 months vs 39 months, p < 0.042). There was no significant difference in the median PFS for both centres. Furthermore, when the comparison was made based on the disease staging, there was no difference in the median OS and median PFS. Multivariate analysis identified that patients aged between 41 and 60 years (Hazard ratio [HR]: 2.83; 95% CI: 1.11, 7.25, p = 0.030), patients with medical illness (HR 1.51; 95% CI: 1.04, 2.21, p = 0.033), patients with advanced-stage disease (HR: 3.63; 95% CI: 2.20, 6.00, p < 0.001) and patients with ECOG ≥ 1 (HR: 2.00; 95%CI: 1.38, 2.91, p < 0.001) as independent risk factors for adverse outcome. Meanwhile, optimal surgery is found to be a protective factor (HR 0.60; 95% CI: 0.41, 0.89, p = 0.011). Patients with optimal surgery had reduced the risk of adverse outcome. CONCLUSION: Our findings confirmed that the median OS was significantly longer for patients with EOC in HA compared to IKN. However, there was no significant difference in the median OS based on the disease staging; therefore, we could not establish the non-inferiority outcome between the two centres. Furthermore, there was no significant difference in median PFS for both centres. This could be due to small sample size to be able to detect any difference. In addition, it could also be contributed by the different treatment options available and unequal volume of patients treated in both centres. Thus, further study with larger sample size and longer time period is needed to provide better guidance and treatments for the patients.


Asunto(s)
Carcinoma Epitelial de Ovario , Neoplasias de las Trompas Uterinas , Neoplasias Peritoneales , Humanos , Femenino , Neoplasias de las Trompas Uterinas/mortalidad , Neoplasias de las Trompas Uterinas/terapia , Neoplasias de las Trompas Uterinas/patología , Persona de Mediana Edad , Estudios Retrospectivos , Neoplasias Peritoneales/terapia , Neoplasias Peritoneales/mortalidad , Carcinoma Epitelial de Ovario/mortalidad , Carcinoma Epitelial de Ovario/terapia , Carcinoma Epitelial de Ovario/patología , Anciano , Adulto , Malasia , Neoplasias Ováricas/mortalidad , Neoplasias Ováricas/terapia , Neoplasias Ováricas/patología , Neoplasias Ováricas/diagnóstico , Cistadenocarcinoma Seroso/terapia , Cistadenocarcinoma Seroso/mortalidad , Cistadenocarcinoma Seroso/patología
2.
CJEM ; 26(3): 198-203, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38219263

RESUMEN

BACKGROUND AND AIM: Emergency Department (ED) renal point-of-care ultrasound (PoCUS) in renal colic by accredited specialists has good prognostic value. This may not be generalizable to under-resourced EDs. We investigated PoCUS in renal colic in our ED with lesser training. METHODS: We performed a single-centre health records review of adult ED patients with renal colic and PoCUS. Patients were managed by a non-ED specialist/resident doctor with no POCUS accreditation in consultation with an attending. These doctors attended a 3.5-h training session conducted by accredited attendings to examine hydronephrosis. They needed to verify their PoCUS findings with an attending during the first two weeks of their six-month posting before performing it independently. The primary outcome was 30-day urological procedures in hydronephrotic vs. non-hydronephrotic groups. Secondary outcomes were the distribution of primary outcome with grades of hydronephrosis, 30-day ED nephrolithiasis-related reattendances in hydronephrotic vs. non-hydronephrotic groups and its distribution with grades of hydronephrosis. We compared outcomes using Fisher's exact test. We also reported crude odds ratio (COR) and 95% CI of primary outcome between hydronephrotic vs. non-hydronephrotic groups. p values ≤ 0.05 were significant. RESULTS: We recruited 651 patients; 160 (24.6%) without and 491 (75.4%) with hydronephrosis. Rates of grades of hydronephrosis were: mild (76.6%), moderate (13.8%), severe (1.2%) and undifferentiated (8.4%). There was a difference in 30-day urological procedures (rates [95% CI]) in hydronephrotic vs. non-hydronephrotic groups, 11.2 [8.7-14.0]% vs. 2.5 [1.0-6.3]%; p < 0.001; COR (95% CI) 4.9 (1.8-13.8); p = 0.002. Increasing 30-day urological procedural rates were associated with increasing grade of hydronephrosis [no: 2.5%, mild: 7.7%, moderate: 23.5%, severe: 67.0% and undifferentiated: 14.6%; p < 0.001]. No differences occurred in other secondary outcomes. CONCLUSIONS: Renal PoCUS could be performed by non-ED specialist/resident doctors to identify patients without hydronephrosis who rarely required urological intervention. Hydronephrotic patients could benefit from further risk stratification.


ABSTRAIT: CONTEXTE ET OBJECTIF: L'échographie rénale au point de soin (PoCUS) dans les coliques rénales par des spécialistes agréés a une bonne valeur pronostique. Cela peut ne pas être généralisable aux SU sous-financés. Nous avons étudié PoCUS dans les coliques rénales dans notre DE avec une formation moindre. MéTHODES: Nous avons effectué un examen des dossiers médicaux d'un seul centre des patients adultes atteints de coliques rénales et de PoCUS. Les patients étaient pris en charge par un médecin résident/spécialiste non-membre de la DG sans accréditation POCUS en consultation avec un médecin traitant. Ces médecins ont assisté à une séance de formation de 3,5 heures menée par des titulaires accrédités pour examiner l'hydronéphrose. Ils devaient vérifier leurs résultats PoCUS auprès d'un assistant pendant les deux premières semaines de leur affectation de six mois avant de l'effectuer de manière indépendante. Le critère de jugement principal était des procédures urologiques de 30 jours dans les groupes hydronéphrotiques vs non-hydronephrotiques. Les critères de jugement secondaires étaient la distribution du critère de jugement primaire avec les grades d'hydronéphrose, les reattendances liées à la néphrose ED de 30 jours dans les groupes hydronéphrotiques vs non hydronéphrotiques et sa distribution avec les grades d'hydronéphrose. Nous avons comparé les résultats en utilisant le test exact de Fisher. Nous avons également signalé un rapport de cotes brut (RC) et un IC à 95 % du critère de jugement principal entre les groupes hydronéphrotiques et non hydronéphrotiques. Les valeurs de P 0,05 étaient significatives. RéSULTATS: Nous avons recruté 651 patients; 160 (24,6%) sans et 491 (75,4%) avec hydronéphrose. Les taux d'hydronéphrose étaient les suivants : légère (76,6 %), modérée (13,8 %), sévère (1,2 %) et indifférenciée (8,4 %). Il y avait une différence dans les interventions urologiques de 30 jours (taux [IC à 95 %]) dans les groupes hydronéphrotiques par rapport aux groupes non-hydronephrotiques, 11,2 [8,7-14,0] % contre 2,5 [1,0-6,3]%; p < 0,001; RCC (IC à 95 %) 4,9 (1,8-13,8); p = 0,002. L'augmentation des taux de procédures urologiques de 30 jours était associée à l'augmentation du grade d'hydronéphrose [non : 2,5%, léger : 7,7%, modéré : 23,5%, sévère : 67,0% et indifférencié : 14,6%; p < 0,001]. Aucune différence n'est survenue dans les autres critères de jugement secondaires. CONCLUSIONS: La PoCUS rénale pourrait être réalisée par des médecins non spécialistes/résidents de la D pour identifier les patients sans hydronéphrose qui ont rarement nécessité une intervention urologique. Les patients hydronéphrotiques pourraient bénéficier d'une meilleure stratification des risques.


Asunto(s)
Hidronefrosis , Cólico Renal , Adulto , Humanos , Cólico Renal/diagnóstico por imagen , Sistemas de Atención de Punto , Tomografía Computarizada por Rayos X , Hidronefrosis/diagnóstico por imagen , Ultrasonografía/métodos , Servicio de Urgencia en Hospital
3.
Oper Dent ; 49(1): 98-109, 2024 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-38058011

RESUMEN

PURPOSE: This study aimed to evaluate the substitutive and additive efficacy of multi-peak light-emitting diode (LED) curing units for post-curing of a three-dimensional- (3D-) printed crown and bridge resin. METHODS: A total of 792 disc- and 180 bar-shaped specimens were printed with a crown and bridge resin (NextDent C&B MFH) and post-cured using two LED curing units (VALO Cordless and Bluephase N G4) in fast and standard modes. Conventional post-curing (LC-3D Print Box, Group PC) was compared with LED-only curing (Groups V1, V2, B1, and B2) and LED-combined curing (Groups PV1, PV2, PB1, and PB2) in terms of microhardness, flexural strength, degree of conversion (DC), and CIE L*a*b* color and translucency parameters. Cytotoxicity of the resin eluates was evaluated using the WST-1 assay. Temperature increases on the resin surface were measured with infrared thermography. Data were statistically analyzed using ANOVA and Kruskal-Wallis tests (α=0.05). RESULTS: The microhardness and flexural strength in Groups V1, V2, B1, and DC in all LED-only groups were lower than in other groups (p<0.05). Larger color disparities existed between Group PC and all LED-only groups than between Group PC and the others (p<0.05). There was no significant difference in cytotoxicity among the groups. The temperature increase was lowest in Groups V1 and PV1 during light curing (p<0.05). CONCLUSIONS: Post-curing by multi-peak LED curing units was not as effective as the conventional post-curing device. Additional post-curing by LED curing units did not improve the material properties.


Asunto(s)
Coronas , Luces de Curación Dental , Polimerizacion , Impresión Tridimensional , Ensayo de Materiales , Resinas Compuestas/uso terapéutico , Propiedades de Superficie , Dureza
4.
Med J Malaysia ; 78(3): 364-371, 2023 05.
Artículo en Inglés | MEDLINE | ID: mdl-37271847

RESUMEN

INTRODUCTION: Dermatomycoses are common superficial cutaneous fungal infections which affect the skin, nails and human hairs. It affects 20 to 25% of the world population. The causative fungus varies geographically across the globe. Study on dermatomycoses is crucial to identify the aetiological fungus involved locally. The study aimed to determine the causative fungus of superficial fungal infections of the skin, nail and hair in patients presented to Hospital Melaka. METHODS: This was a prospective study conducted from 15th January 2022 till 15th October 2022 at Dermatology Clinic, Hospital Melaka. Subjects with clinical dermatomycoses were included in this study. The samples were collected from skin, nails and hairs clinically affected by tinea corporis/cruris/pedis, onychomycosis and tinea capitis respectively. A potassium hydroxide (KOH) study was performed on the sample in which the fungal hyphae/yeast positive subjects were sent for fungal culture and fungal PCR test. RESULT: A total of 222 clinical samples from skin, nails and hairs with a clinical suspicion of dermatomycoses yielded fungal hyphae/yeast in KOH. Majority of the samples were collected from skin (138, 62.2%), followed by nails (65, 29.3%) and hairs (19, 8.6%). Male to female ratio was 1.18: 1. The age ranged from 2 to 87 with the median of 55.5-yearsold. Out of 222 samples, 150 (67.6%) were fungal culture positive. From fungal culture positive samples, 87 samples were from tinea corporis, 50 samples were from onychomycoses and 13 samples were from tinea capitis. Trichophyton rubrum (39, 44.8%) was the commonest dermatophyte isolated in tinea corporis/cruris/pedis. Nondermatophyte moulds (NDM, 35, 70%) were the main fungi isolated in onychomycosis. Microsporum canis (7/53.8%) was the principal causative fungus among patients with tinea capitis. Among 150 fungal culture positive samples, 76 were fungal PCR positive. Only 38 samples consistently isolated same fungal species in both fungal culture and PCR test. CONCLUSION: Majority of tinea corporis and tinea capitis fungal culture isolated dermatophytes, especially Trichophyton rubrum and Microsporum canis, respectively. Non-dermatophyte moulds were mainly isolated in onychomycosis.


Asunto(s)
Arthrodermataceae , Dermatomicosis , Onicomicosis , Tiña del Cuero Cabelludo , Tiña , Humanos , Masculino , Femenino , Preescolar , Niño , Adolescente , Adulto Joven , Adulto , Persona de Mediana Edad , Anciano , Anciano de 80 o más Años , Onicomicosis/epidemiología , Estudios Prospectivos , Saccharomyces cerevisiae , Dermatomicosis/epidemiología , Tiña/epidemiología , Tiña/microbiología , Tiña del Cuero Cabelludo/epidemiología , Tiña del Cuero Cabelludo/microbiología , Hospitales
5.
Ultramicroscopy ; 243: 113640, 2023 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-36356407

RESUMEN

Poles and zone lines observed within atom probe field evaporation images are useful for a range of atom probe crystallography studies, including calibration of the reconstruction and crystallographic characterisation of microstructural features such as grain boundaries. However, this information is not always readily apparent. Techniques for plotting crystallographically correlated metrics contained within atom probe data to enhance pole and zone line contrast across the detector space are developed. This includes consideration of the electric field, molecular ions, lattice structure retained within the reconstruction, specific elemental species, the number of pulses between detection events, and the lateral distance between sequential detection events. These approaches are then applied to experimental atom probe tomography datasets on technically pure Al, nanocrystalline Al, highly doped Si, and additively manufactured Inconel 738, Haynes 282, and Ti-6Al-4V. The results facilitate the extension of atom probe crystallography studies to a broader range of crystalline datasets where crystallographic information is not readily apparent from existing methods, as well as a deeper understanding of field evaporation behaviour during an atom probe experiment.

6.
Trop Biomed ; 40(4): 430-438, 2023 Dec 01.
Artículo en Inglés | MEDLINE | ID: mdl-38308830

RESUMEN

Entamoeba histolytica is the parasite responsible for amoebiasis, which can result in amoebic colitis or amoebic liver abscess. Metronidazole has been the conventional treatment for intestinal amoebiasis, but concerns regarding resistance have emerged due to the identification of resistance pathways in E. histolytica. This study investigates a novel anti-amoebic approach targeting the CDP-choline pathway. Inhibition studies were conducted using potential choline kinase (CK) inhibitors to inhibit the EhCK enzyme, and RNA interference was employed to knock down the EhCK gene. Km and Vmax of purified EhCK and hCKa2 proteins were determined by pyruvate kinase-lactate dehydrogenase (PK-LDH) coupled assay. The IC50 values for EhCK and hCKa2 were determined with several commercial CK inhibitors. Selected inhibitors were incubated with E. histolytica trophozoites for 48 hours to determine the EC50 for each inhibitor. Silencing of gene encoding EhCK was carried out using duplex siRNA and the gene expression level was measured by real-time qPCR. Based on the IC50 values, three of the inhibitors, namely CK37, flavopiridol and H-89 were more potent against EhCK than hCKa2. Trophozoites growth inhibition showed that only HDTAB, H-89 and control drug metronidazole could penetrate and induce cell death after 48-hour incubation. siRNA concentration of 10 µg/mL was used for the transfection of positive control GAPDH, EhCK, and non-targeting GFP siRNAs. RNAi experiment concluded with positive control GAPDH downregulated by 99% while the level of EhCK mRNA was downregulated by 47%. In this study, potential inhibitors of EhCK and siRNA have been identified, paving the way for further refinement and testing to enhance their potency against EhCK while sparing hCK. The utilization of these specific inhibitors and siRNA targeting EhCK represents a novel approach to impede the growth of E. histolytica by disrupting its phospholipid synthesis pathway.


Asunto(s)
Amebiasis , Entamoeba histolytica , Entamebiasis , Isoquinolinas , Sulfonamidas , Humanos , Entamebiasis/tratamiento farmacológico , Metronidazol/farmacología , Colina Quinasa/metabolismo , Entamoeba histolytica/genética , Entamoeba histolytica/metabolismo , ARN Interferente Pequeño/metabolismo
7.
Poult Sci ; 101(12): 102167, 2022 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-36257074

RESUMEN

Climate change has numerous effects on poultry that result in welfare concerns and economic losses in agricultural industries. However, the mechanisms underlying the acclimation to heat stress in poultry have not been comprehensively defined. Therefore, identifying associated patterns of gene regulation and understanding the molecular mechanisms of acclimation to a warmer environment will provide insights into the acclimation system of broiler chickens. We profiled differentially expressed genes (DEGs) associated with differences in growth performance under heat stress conditions in the liver tissues of broilers based on RNA sequencing data. The DEGs were identified by comparison to the gene expression levels of broilers exhibiting average growth at 28 d of age (D28A) and D36A relative to those at D21A. In D36A, 507 and 312 DEGs were up- and downregulated, respectively, whereas 400 and 156 DEGs were up- and downregulated in D28A, respectively. Pathway enrichment analysis further revealed that "fatty acid degradation" and "heat shock protein expression" were upregulated in broilers exhibiting a higher growth and weight, whereas "cell cycle arrest" and "amino acid metabolism" were downregulated. Transcriptome profiling revealed that the acclimatized group supplied fat and energy from the liver to tissues through the breakdown of fatty acids. Furthermore, homeostasis was maintained via heat shock proteins and antioxidant enzymes. The characterized candidate genes and mechanisms associated with the response to heat stress might serve as a foundation for improving the ability of broilers to acclimatize under heat stress conditions.


Asunto(s)
Pollos , Trastornos de Estrés por Calor , Animales , Perfilación de la Expresión Génica/veterinaria , Respuesta al Choque Térmico/genética , Trastornos de Estrés por Calor/veterinaria , Hígado/metabolismo , Aclimatación , Transcriptoma
9.
Med J Malaysia ; 77(4): 454-461, 2022 07.
Artículo en Inglés | MEDLINE | ID: mdl-35902935

RESUMEN

INTRODUCTION: Coronavirus disease 2019 (COVID-19) variants pose unique challenges with inevitable premature death when cases of severe disease exponentially rise in a healthcare system. It is imperative that palliative care is provided with a proactive approach to symptom recognition, assessment, management and treatment escalation to ensure comfort throughout the course of this illness. OBJECTIVES: To evaluate the characteristics, symptom burden, palliative care management and outcomes of COVID-19 patients referred to a palliative care unit (PCU) in a single tertiary hospital. Clinical outcomes specifically observed the management of agitation in these patients based on their Richmond Agitation and Sedation Scale (RASS) scores. METHODS: A retrospective observational study was conducted in a tertiary hospital by reviewing electronic medical records and extracting data from 1st June 2021to 31st July 2021 of all COVID-19 patients referred to the PCU. RESULTS: A cohort of 154 (75 males, 79 females) COVID-19 patients was referred to the PCU with a mean age of 67 (20- 95) years. The median number of days of COVID-19 illness before referral was 7(4-11), with 79.3% of patients being in categories 4 and 5. The median duration of the PCU involvement was 4(1-24) days; 74% of families were engaged in virtual platform communication. The most prevalent symptoms were dyspnoea (73.4%) and agitation (41.6%). Common medications used were opioids, antipsychotics and benzodiazepines. Among agitated patients, none had RASS scores above +2 in the last encounter. Palliative care doctors in the team reported complete effectiveness in patient's symptom control in 74% of patients. CONCLUSIONS: A hallmark of severe COVID-19 is rapid deterioration, which calls for proactive assessment and urgent palliation. Breathlessness and agitation are priority symptoms to address. Among agitated patients, benzodiazepines and antipsychotics are highly effective in addressing agitation and reducing RASS scores. Communication with families using virtual platforms is effective in providing a supportive presence and closure when face-to-face communication is not possible.


Asunto(s)
COVID-19 , Cuidados Paliativos , Anciano , Benzodiazepinas , COVID-19/terapia , Femenino , Humanos , Masculino , Derivación y Consulta , Centros de Atención Terciaria
11.
Med J Malaysia ; 76(4): 534-540, 2021 07.
Artículo en Inglés | MEDLINE | ID: mdl-34305115

RESUMEN

BACKGROUND: The significance of pelvic and para-aortic lymph nodes (retroperitoneal lymph nodes) metastasis in the five-year survival of early stage cervical cancer (CC) patients is well established. The previous International Federation of Gynaecology and Obstetrics (FIGO) 2009 staging of CC was clinical and excluded advanced radiological assessment in assigning a stage. However, with the current FIGO 2018 staging, advanced radiological assessment and pathological findings were allowed to assign a stage which would alter the subsequent management. This pilot study aims to obtain local data on the correlation between radiological retroperitoneal lymph node positivity and histological lymph node positivity in early stage CC (stage 1A2 to 2A1) and seeks to correlate independent prognostic factors for recurrence to histological lymph node positivity. MATERIALS AND METHODS: In this retrospective cross-sectional analysis, clinical data, including clinical staging, Computed Tomography (CT) scan findings and histopathological results were collected and analysed in the Department of Obstetrics and Gynaecology, Hospital Ampang, Ministry of Health Malaysia. RESULTS: A total of 31 patients had surgery for CC from 1st August 2018 till 31st August 2020. Radical hysterectomy was done on 23 of them as primary treatment for early stage cervical cancer. Both pelvic and para-aortic lymph node dissection was done in 6 patients while 17 patients had only pelvic lymph node dissection. All patients had thoracoabdomino- pelvic CT scans done preoperatively. Among the 82.6% patients with no enlarged pelvic lymph nodes on CT scan, all were confirmed by histology to be negative of malignancy. In the remainder 17.4% of patients with enlarged pelvic nodes on CT scan, three quarters had histology positive pelvic nodes for malignancy (p=0.002). Among patients with no enlarged para-aortic lymph nodes on CT scan, 83.3% had histologically negative para-aortic nodes. Among patients with clinical tumour diameter 2- 3.9 cm, 14.3% had positive pelvic nodes while a quarter of patients with clinical tumour diameter ≥ 4cm had histological positive pelvic nodes. None of the patients with tumour diameter < 2cm had positive pelvic nodes (p=0.993). Positive pelvic lymph nodes involvement was present in 37.5% of those with positive lymphovascular space invasion (LVSI). All patients with negative LVSI had no histological positive pelvic nodes (p=0.103). Among patients with tumour invasion involving the inner third of the stroma, 16.7% had histological positive pelvic nodes while 18.2% with outer third stromal invasion had positive nodes (p=0.977). None of the patients had histologically positive para-aortic lymph nodes with negative pelvic lymph nodes. Among patients with clinical stage 1B2, 20% would have been upstaged to stage 3C based on radiological imaging and final histology confirmation. CONCLUSION: This study shows that in early stage CC, there is a statistically significant correlation between CT scan findings of enlarged pelvic lymph nodes and histological positive pelvic lymph nodes.


Asunto(s)
Neoplasias del Cuello Uterino , Estudios Transversales , Femenino , Humanos , Escisión del Ganglio Linfático , Ganglios Linfáticos/diagnóstico por imagen , Ganglios Linfáticos/patología , Metástasis Linfática , Recurrencia Local de Neoplasia , Estadificación de Neoplasias , Proyectos Piloto , Estudios Retrospectivos , Neoplasias del Cuello Uterino/diagnóstico por imagen , Neoplasias del Cuello Uterino/patología , Neoplasias del Cuello Uterino/cirugía
12.
Ann Oncol ; 32(5): 661-672, 2021 05.
Artículo en Inglés | MEDLINE | ID: mdl-33736924

RESUMEN

BACKGROUND: High tumor mutation burden (TMB-H) has been proposed as a predictive biomarker for response to immune checkpoint blockade (ICB), largely due to the potential for tumor mutations to generate immunogenic neoantigens. Despite recent pan-cancer approval of ICB treatment for any TMB-H tumor, as assessed by the targeted FoundationOne CDx assay in nine tumor types, the utility of this biomarker has not been fully demonstrated across all cancers. PATIENTS AND METHODS: Data from over 10 000 patient tumors included in The Cancer Genome Atlas were used to compare approaches to determine TMB and identify the correlation between predicted neoantigen load and CD8 T cells. Association of TMB with ICB treatment outcomes was analyzed by both objective response rates (ORRs, N = 1551) and overall survival (OS, N = 1936). RESULTS: In cancer types where CD8 T-cell levels positively correlated with neoantigen load, such as melanoma, lung, and bladder cancers, TMB-H tumors exhibited a 39.8% ORR to ICB [95% confidence interval (CI) 34.9-44.8], which was significantly higher than that observed in low TMB (TMB-L) tumors [odds ratio (OR) = 4.1, 95% CI 2.9-5.8, P < 2 × 10-16]. In cancer types that showed no relationship between CD8 T-cell levels and neoantigen load, such as breast cancer, prostate cancer, and glioma, TMB-H tumors failed to achieve a 20% ORR (ORR = 15.3%, 95% CI 9.2-23.4, P = 0.95), and exhibited a significantly lower ORR relative to TMB-L tumors (OR = 0.46, 95% CI 0.24-0.88, P = 0.02). Bulk ORRs were not significantly different between the two categories of tumors (P = 0.10) for patient cohorts assessed. Equivalent results were obtained by analyzing OS and by treating TMB as a continuous variable. CONCLUSIONS: Our analysis failed to support application of TMB-H as a biomarker for treatment with ICB in all solid cancer types. Further tumor type-specific studies are warranted.


Asunto(s)
Inhibidores de Puntos de Control Inmunológico , Neoplasias , Biomarcadores de Tumor , Humanos , Masculino , Mutación , Neoplasias/tratamiento farmacológico , Neoplasias/genética , Resultado del Tratamiento
13.
Sci Rep ; 10(1): 14506, 2020 Sep 02.
Artículo en Inglés | MEDLINE | ID: mdl-32879420

RESUMEN

We study the change in magnetisation with paramagnetic Al addition in the CoFeNi0.5Cr0.5-Alx (x: 0, 0.5, 1, and 1.5) complex concentrated alloy. The compositions were developed utilising the Mulliken electronegativity and d-electron/atom ratio. Spherical FeCr rich nanoprecipitates are observed for X: 1.0 and 1.5 in an AlCoNi-rich matrix. A ~ 5 × increase in magnetisation (from 22 to 96 Am2/kg) coincides with this nanoprecipitate formation-the main magnetic contribution is determined to be from FeCr nanoprecipitates. The magnetisation increase is strange as paramagnetic Al addition dilutes the ferromagnetic Fe/Co/Ni additions. In this paper we discuss the magnetic and structural characterisation of the CoFeNi0.5Cr0.5-Alx composition and attempt to relate it to the interfacial energy.

14.
MethodsX ; 7: 100892, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32373482

RESUMEN

• Herein we propose a framework for assembling and analyzing Genotype by Sequencing (GBS) data to better understand evolutionary relationships within a group of closely related species using the mastiff bats (Molossus) as our model system. Many species within this genus have low-levels of genetic variation within and between morphologically distinct species, and the relationships among them remain unresolved using traditional Sanger sequencing methods. Given that both de novo and reference genome pipelines can be used to assemble next generation sequences, and that several tree inference methodologies have been proposed for single nucleotide polymorphism (SNP) data, we test whether different alignments and phylogenetic approaches produce similar results. We also examined how the process of SNP identification and mapping can affect the consistency of the analyses. Different alignments and phylogenetic inferences produced consistent results, supporting the GBS approach for answering evolutionary questions on a macroevolutionary scale when the genetic distance among phenotypically identifiable clades is low. We highlight the importance of exploring the relationships among groups using different assembly assumptions and also distinct phylogenetic inference methods, particularly when addressing phylogenetic questions in genetic and morphologically conservative taxa. • The method uses the comparison of several filter settings, alignments, and tree inference approaches on Genotype by Sequencing data. • Consistent results were found among several approaches. • The methodology successfully recovered well supported species boundaries and phylogenetic relationships among species of mastiff bats not hypothesized by previous methods.

15.
BJOG ; 127(11): 1430-1437, 2020 10.
Artículo en Inglés | MEDLINE | ID: mdl-32356413

RESUMEN

OBJECTIVE: To evaluate fasting for 12 hours compared with expedited oral feeding in hospitalised women with hyperemesis gravidarum (HG). DESIGN: Randomised trial. SETTING: University Hospital, Malaysia: April 2016-April 2017. POPULATION: One hundred and sixty women hospitalised for HG. METHOD: Women were randomised upon admission to fasting for 12 hours or expedited oral feeding. Standard HG care was instituted. MAIN OUTCOME MEASURE: Primary outcome was satisfaction score with overall treatment at 24 hours (0-10 Visual Numerical Rating Scale VNRS), vomiting episodes within 24 hours and nausea VNRS score at enrolment, and at 8, 16 and 24 hours. RESULTS: Satisfaction score, median (interquartile range) 8 (5-9) versus 8 (7-9) (P = 0.08) and 24-hour vomiting episodes were 1 (0-4) versus 1 (0-5) (P = 0.24) for 12-hour fasting versus expedited feeding, respectively. Repeated measures analysis of variance of nausea scores over 24 hours showed no difference (P = 0.11) between trial arms. Participants randomised to 12-hour fasting compared with expedited feeding were less likely to prefer their feeding regimen in future hospitalisation (41% versus 65%, P = 0.001), to recommend to a friend (65% versus 84%, P = 0.01; RR 0.8, 95% CI 0.6-0.9) and to adhere to protocol (85% versus 95%, P = 0.04; RR 0.9, 95% CI 0.8-1.0). Symptoms profile, ketonuria status at 24 hours and length of hospital stay were not different. CONCLUSION: Advisory of 12-hour fasting compared with immediate oral feeding resulted in a non-significant difference in satisfaction score but adherence to protocol and fidelity to and recommendation of immediate oral feeding to a friend were lower. The 24-hour nausea scores and vomiting episodes were similar. TWEETABLE ABSTRACT: Women hospitalised for hyperemesis gravidarum could feed as soon, as much and as often as can be tolerated compared with initial fasting.


Asunto(s)
Ingestión de Alimentos , Ayuno , Hiperemesis Gravídica/terapia , Adulto , Femenino , Hospitalización , Humanos , Análisis de Intención de Tratar , Malasia , Satisfacción del Paciente , Embarazo , Resultado del Tratamiento
18.
Malays Orthop J ; 13(3): 45-52, 2019 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-31890110

RESUMEN

Introduction: Diabetic foot infection, a complication which can lead to lower limb amputation, is a major source of morbidity and mortality in Malaysia. The objective of this study was to determine the predictive factors of major lower limb amputation among patients with diabetes mellitus in a cluster of three district hospitals in Pahang, Malaysia. Materials and Methods: This cross-sectional study involved 170 patients who had undergone surgical interventions for diabetic foot infections at three district hospitals from 1st of September 2014 to 31st December 2015. The predictors for major amputation of lower limb were determined using simple logistic regression (LR) and forward LR multiple logistic regression. Results: A total of 21 patients had undergone major amputations of lower limb (15 transtibial and 6 transfemoral). The following factors were associated with major amputation of lower limb; longer duration of disease, age ≥ 60 years, patients from Bentong Hospital, presence of hypertension, presence of fever, history of multiple limb-salvaging surgeries, monomicrobial culture, necrotising fasciitis, anemia and leukocytosis. Upon forward LR multiple logistic regression, only duration of disease, history of more than three previous limb-salvaging surgeries and total white blood cell count ≥15X109/L were found to be significant as predictive factors of major amputation of lower limb. Conclusion: Among the factors analysed in this study, a longer duration of disease, raised total white blood cell count and history of more than three limb-salvaging surgeries were identified as predictors for major amputation of lower limb in diabetic foot infections using stepwise logistic regression analysis.

19.
Heliyon ; 4(10): e00845, 2018 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-30338304

RESUMEN

The flow distribution of a proton exchange membrane fuel cell within a manifold plays an important role on its performance. This study presents a numerical analysis of the flow distribution behavior within different manifold configurations. A two-dimensional model with 75 cells was employed to study the flow behavior. The variation in the stoichiometry and number of cells was also studied. Three different flow configurations were considered with different numbers of flow inlets and outlets. The flow characteristics, such as the pressure and velocity variations in the manifold and cells, were measured to determine the effects of the different flow configurations. The results indicated that the double inlet/outlet configuration had the best flow distribution when using 75 cells. Moreover, increasing the stoichiometry resulted in a better flow distribution to the cells in a stack.

20.
Transplant Proc ; 50(4): 1005-1008, 2018 May.
Artículo en Inglés | MEDLINE | ID: mdl-29731056

RESUMEN

BACKGROUND: The significance of proinflammatory M1 (classically activated) and profibrotic M2 (alternatively activated) macrophages in antibody-mediated rejection (ABMR) after kidney transplantation has not been investigated. METHODS: Fifty-five biopsy-confirmed ABMR samples were stained with MRP 8/14 (a marker of M1 macrophages) and CD163 (a marker of M2 macrophages), and positive cells were counted in glomeruli and the tubulointerstitium, respectively. Patients were classified into M1 and M2 polarization groups according to the glomerular and tubulointerstitial M1:M2 ratio, and the results were compared with Banff scores, serum creatinine level, estimated glomerular filtration rate (eGFR), and graft survival. RESULTS: The glomerular M2 polarization group showed significantly higher chronic glomerulopathy scores, serum creatinine levels, and lower eGFR at the time of biopsy (P = .019 and P = .015, respectively) and 3-month postbiopsy (P = .016 and P = .032, respectively) than the M1 polarization group. The tubulointerstitial M2 polarization group had significantly lower glomerulitis, arteritis, peritubular capillaritis, and glomerulitis + peritubular capillaritis scores than the M1 polarization group, but there was no significant difference in renal function. Long-term graft survival was not associated with macrophage polarization. CONCLUSION: Glomerular M2 polarization in ABMR biopsy samples is associated with chronic glomerular injury and poorer graft function, but without graft survival.


Asunto(s)
Rechazo de Injerto/inmunología , Supervivencia de Injerto/inmunología , Trasplante de Riñón/efectos adversos , Macrófagos/inmunología , Adulto , Femenino , Rechazo de Injerto/patología , Humanos , Estimación de Kaplan-Meier , Trasplante de Riñón/métodos , Trasplante de Riñón/mortalidad , Macrófagos/patología , Masculino , Persona de Mediana Edad , Modelos de Riesgos Proporcionales , Estudios Retrospectivos , Trasplante Homólogo
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