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1.
Ann Oncol ; 35(3): 267-275, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38145866

RESUMEN

Current evaluation of treatment response in solid tumors depends on dynamic changes in tumor diameters as measured by imaging. However, these changes can only be detected when there are enough macroscopic changes in tumor volume, which limits the usability of radiological response criteria in evaluating earlier stages of disease response and necessitates much time to lapse for gross changes to be notable. One promising approach is to incorporate dynamic changes in circulating tumor DNA (ctDNA), which occur early in the course of therapy and can predict tumor responses weeks before gross size changes manifest. However, several issues need to be addressed before recommending the implementation of ctDNA response criteria in daily clinical practice such as clinical, biological, and regulatory challenges and, most importantly, the need to standardize/harmonize detection methods and ways to define ctDNA response and/or progression for precision oncology. Herein, we review the use of liquid biopsy (LB) to evaluate response in solid tumors and propose a plan toward standardization of LB-RECIST.


Asunto(s)
ADN Tumoral Circulante , Neoplasias , Humanos , Neoplasias/diagnóstico por imagen , Neoplasias/genética , Criterios de Evaluación de Respuesta en Tumores Sólidos , Medicina de Precisión , Biopsia Líquida , ADN Tumoral Circulante/genética , Biomarcadores de Tumor/genética
2.
Surg Endosc ; 35(11): 6150-6157, 2021 11.
Artículo en Inglés | MEDLINE | ID: mdl-33237461

RESUMEN

BACKGROUND: Operating room planning is a complex task as pre-operative estimations of procedure duration have a limited accuracy. This is due to large variations in the course of procedures. Therefore, information about the progress of procedures is essential to adapt the daily operating room schedule accordingly. This information should ideally be objective, automatically retrievable and in real-time. Recordings made during endoscopic surgeries are a potential source of progress information. A trained observer is able to recognize the ongoing surgical phase from watching these videos. The introduction of deep learning techniques brought up opportunities to automatically retrieve information from surgical videos. The aim of this study was to apply state-of-the art deep learning techniques on a new set of endoscopic videos to automatically recognize the progress of a procedure, and to assess the feasibility of the approach in terms of performance, scalability and practical considerations. METHODS: A dataset of 33 laparoscopic cholecystectomies (LC) and 35 total laparoscopic hysterectomies (TLH) was used. The surgical tools that were used and the ongoing surgical phases were annotated in the recordings. Neural networks were trained on a subset of annotated videos. The automatic recognition of surgical tools and phases was then assessed on another subset. The scalability of the networks was tested and practical considerations were kept up. RESULTS: The performance of the surgical tools and phase recognition reached an average precision and recall between 0.77 and 0.89. The scalability tests showed diverging results. Legal considerations had to be taken into account and a considerable amount of time was needed to annotate the datasets. CONCLUSION: This study shows the potential of deep learning to automatically recognize information contained in surgical videos. This study also provides insights in the applicability of such a technique to support operating room planning.


Asunto(s)
Colecistectomía Laparoscópica , Aprendizaje Profundo , Laparoscopía , Humanos , Redes Neurales de la Computación
3.
Malays J Pathol ; 42(1): 143-150, 2020 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-32342945

RESUMEN

INTRODUCTION: Plasma cell leukaemia (PCL) is a rare variant of multiple myeloma. We report a case of PCL to demonstrate the clonal evolution, resulting in disease relapse after achieving complete remission, and its aggressive nature of the disease, leading to poor clinical outcome. CASE REPORT: A 69-year-old man presented with a three-day-history of worsening generalized body weakness, poor oral intake, nausea, significant loss of weight and lower back pain. He was diagnosed as primary PCL, based on hypercalcaemia, renal insufficiency, anaemia, thrombocytopenia, lytic bone lesions, 24% abnormal plasma cells in peripheral blood, immunophenotype of clonal plasma cells which were positive for CD38, CD138 and CD56 markers with kappa light chain restriction, 49% abnormal plasma cells in bone marrow, monoclonal paraprotein (IgG kappa) in serum and urine, and positive IGH rearrangement (Fluorescence in-situ hybridisation, FISH). He achieved complete remission after four cycles of Bortezomib-based therapy. There was a plan for high-dose therapy plus autologous haematopoietic cell transplantation. A month later, the disease relapsed, as evidenced by 94% abnormal plasma cells in his bone marrow aspirate, complex karyotype and abnormal FISH results. He passed away a few days later, from severe septicaemia. Time-to-progression of disease was 1 month and overall survival was 5 months. DISCUSSION: This case report illustrates the clonal evolution and aggressive nature of primary PCL with older age at presentation, leading to a shorter duration of remission and overall survival.


Asunto(s)
Leucemia de Células Plasmáticas/patología , Recurrencia Local de Neoplasia/patología , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Bortezomib/administración & dosificación , Ciclofosfamida/administración & dosificación , Dexametasona/administración & dosificación , Progresión de la Enfermedad , Resultado Fatal , Humanos , Leucemia de Células Plasmáticas/tratamiento farmacológico , Masculino , Inducción de Remisión
4.
Int J Clin Pract ; 72(7): e13083, 2018 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-29665199

RESUMEN

BACKGROUND: A transparent and explicit reporting on authors' contributions to the development of clinical practice guidelines and on panelists' characteristics is essential for their credibility and trustworthiness. We did not find published studies on authorship or panel involvement in clinical practice guidelines. OBJECTIVE: To describe the approach to authorship in reports of clinical practice guidelines, and the characteristics of individual authors. METHODS: We conducted a cross-sectional survey of guidelines listed in the National Guideline Clearing House (NGC) in 2016. We abstracted data on the general characteristics of the guidelines, report approach to authorship, and individual authors characteristics. Data abstraction was in duplicate and independent manner using standardised form. Data analyses were both descriptive and regression analyses. RESULTS: Overall, 139 eligible guidelines with published papers were identified. Of these, 48 (35%) included a group authorship statement in the author byline. A third of these guidelines (n = 45; 32%) reported on authors' contributions, while about half of the guidelines (n = 74; 53%) reported who of the authors served as panel members. Around one-fifth of the guidelines (n = 30; 22%) reported group membership (eg, content expert, patient representative) for at least 1 author. Less than one-seventh of the eligible guidelines indicated who selected the panel members (n = 18; 13%), reported the types of panel members (n = 18; 13%) or the selection criteria (n = 12; 9%). Higher journal impact factor was associated with both "reporting of the author contributions" (OR = 1.07) and "the inclusion of a panel membership section in the guideline report" (OR = 1.21). CONCLUSION: Low percentages of clinical practice guidelines report information on important aspects of authorship and characteristics of individual authors. Better reporting of some of these criteria was associated with journal impact factor.


Asunto(s)
Autoria/normas , Guías como Asunto/normas , Factor de Impacto de la Revista , Escritura Médica/normas , Estudios Transversales , Humanos , Edición/normas , Sociedades Científicas/normas
5.
BMC Public Health ; 18(1): 533, 2018 04 23.
Artículo en Inglés | MEDLINE | ID: mdl-29688846

RESUMEN

BACKGROUND: Public health journals need to have clear policies for reporting the funding of studies and authors' personal financial and non-financial conflicts of interest (COI) disclosures. This study aims to assess the policies of public health journals on reporting of study funding and the disclosure of authors' COIs. METHODS: This is a cross-sectional study of "Public, Environmental & Occupational Health" journals. Teams of two researchers abstracted data in duplicate and independently using REDCap software. RESULTS: Of 173 public health journals, 155 (90%) had a policy for reporting study funding information. Out of these, a majority did not require reporting of the phase of the study for which funding was received (88%), nor the types of funding sources (87%). Of the 173 journals, 163 (94%) had a policy requiring disclosure of authors' COI. However, the majority of these journals did not require financial conflicts of interest disclosures relating to institutions (75%) nor to the author's family members (90%) while 56% required the disclosure of at least one form of non-financial COI. CONCLUSIONS: The policies of the majority of public health journals do not require the reporting of important details such as the role of the funder, and non-financial COI. Journals and publishers should consider revising their editorial policies to ensure complete and transparent reporting of funding and COI.


Asunto(s)
Políticas Editoriales , Publicaciones Periódicas como Asunto/normas , Salud Pública , Conflicto de Intereses , Estudios Transversales , Revelación , Apoyo Financiero , Humanos
6.
Women Health ; 58(10): 1124-1134, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-29240535

RESUMEN

Waterpipe tobacco smoking (WTS) has become a serious public health threat in the Middle East and beyond. To estimate the prevalence rates of cigarette and WTS among Lebanese women and describe characteristics associated with each behavior. Secondary analysis of women's health data obtained in a national survey in 2010. Of 2,255 selected women, 78 percent reported no or past long-term WTS. Among the 12 percent of regular waterpipe smokers, 40 percent were light users (mean three waterpipe heads weekly), while 60 percent were heavy users (mean of 11 heads per week). About 70 percent were never or past long-term cigarette smokers. Younger age, location within Greater Beirut (GB) and having professional employment were significantly associated with use of WTS. Older age, GB location, lower education, and ever-married were significantly associated with cigarette smoking. WTS is becoming a socially normative behavior among empowered professional women, who can spare the time and expense to engage in this behavior in easily accessible cafés, which prohibit cigarette smoking. Government, media, and NGO campaigns against smoking should target waterpipe use, not only in Lebanon but also across the Arab world and among Arab communities in the Diaspora with messages different from anti-cigarette campaigns.


Asunto(s)
Árabes , Fumar Cigarrillos/etnología , Fumar en Pipa de Agua/etnología , Adulto , Distribución por Edad , Fumar Cigarrillos/epidemiología , Estudios Transversales , Femenino , Conocimientos, Actitudes y Práctica en Salud , Humanos , Líbano/epidemiología , Masculino , Persona de Mediana Edad , Prevalencia , Tabaco para Pipas de Agua , Fumar en Pipa de Agua/epidemiología
7.
Bull Exp Biol Med ; 165(6): 772-776, 2018 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-30353337

RESUMEN

Implantation of ovarian tissue allografts in outbred Wistar rats and inbred August rats against the background of induction of donor-specific tolerance was accompanied by an increase in liver content of mononuclear cells expressing LMP2 immune of proteasome subunit by day 37 after transplantation in comparison with day 0. Graft rejection, on the contrary, was associated with a decrease in the number of LMP2+ cells in the liver of rats of both lines during this period. The difference in the content of these cells and the graft take rate were higher in Wistar rats. The number of mononuclear cells expressing LMP7 immune proteasome subunit in the liver did not change in rats of both lines by day 37 in comparison with day 0. Thus, the level of immune proteasomes with LMP2 subunit in mononuclear cells of the liver is related to fine mechanisms of regulation of immune responses and their shift toward graft take or rejection.


Asunto(s)
Leucocitos Mononucleares/citología , Hígado/citología , Hígado/inmunología , Ovario/trasplante , Complejo de la Endopetidasa Proteasomal/metabolismo , Animales , Línea Celular , Cisteína Endopeptidasas/metabolismo , Femenino , Citometría de Flujo , Tolerancia Inmunológica , Leucocitos Mononucleares/metabolismo , Ratas , Ratas Endogámicas , Ratas Wistar , Especificidad de la Especie , Bazo/inmunología , Trasplante Homólogo
8.
Bull Exp Biol Med ; 164(5): 641-644, 2018 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-29577193

RESUMEN

Induction of donor-specific tolerance in outbred Wistar rats (RT1u) and inbred August rats (RT1c) increased the expression of immune proteasome subunits in liver with a peak on day 7 after beginning of the induction. The increase in the level of immune subunits LMP2 and LMP7 was more pronounced in the liver of August rats in comparison with Wistar rats (by 2 and 6 times, respectively), which was associated with higher concentrations of monoamines in the CNS of August rats. After induction of donor-specific tolerance in August and Wistar rats, the immune subunits were in cells of sinusoidal lining and in cells located in sinusoid lumens. It can be suggested that immune proteasomes in these cells producing antigenic peptides for presentation to immunocompetent participate in the suppression of their activity and form the molecular basis for the development of donor-specific tolerance at very early stages of this process.


Asunto(s)
Tolerancia Inmunológica/fisiología , Hígado/metabolismo , Complejo de la Endopetidasa Proteasomal/metabolismo , Animales , Monoaminas Biogénicas/metabolismo , Sistema Nervioso Central/metabolismo , Hígado/inmunología , Masculino , Ratas , Ratas Wistar
9.
Pituitary ; 18(4): 448-55, 2015 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-25134488

RESUMEN

PURPOSE: Radiation fields for nasopharyngeal cancer (NPC) include the base of skull, which places the hypothalamus and pituitary at risk of damage. We aimed to establish the prevalence, pattern and severity of hypothalamic pituitary (HP) dysfunction amongst NPC survivors. METHODS: We studied 50 patients (31 males) with mean age 57 ± 12.2 years who had treatment for NPC between 3 and 21 years (median 8 years) without pre-existing HP disorder from other causes. All patients had a baseline cortisol, fT4, TSH, LH, FSH, oestradiol/testosterone, prolactin and renal function. All patients underwent dynamic testing with insulin tolerance test to assess the somatotroph and corticotroph axes. Baseline blood measurements were used to assess thyrotroph, gonadotroph and lactotroph function. RESULTS: Hypopituitarism was present in 82% of patients, 30% single axis, 28% two axes, 18% three axes and 6% four axes deficiencies. Somatotroph deficiency was most common (78%) while corticotroph, gonadotroph and thyrotroph deficiencies were noted in 40% (4 complete/16 partial), 22 and 4% of the patients respectively. Hyperprolactinaemia was present in 30% of patients. The development of HP dysfunction was significantly associated with the time elapsed from irradiation, OR 2.5 (1.2, 5.3), p = 0.02, for every 2 years post treatment. The use of concurrent chemo-irradiation (CCRT) compared to those who had radiotherapy alone was also significantly associated with HP dysfunction, OR 14.5 (2.4, 87.7), p < 0.01. CONCLUSION: Despite low awareness and detection rates, HP dysfunction post-NPC irradiation is common. Use of CCRT may augment time related pituitary damage. As these endocrinopathies result in significant morbidity and mortality we recommend periodic assessment of pituitary function amongst NPC survivors.


Asunto(s)
Hormona de Crecimiento Humana/deficiencia , Hiperprolactinemia/epidemiología , Hipopituitarismo/epidemiología , Sistema Hipotálamo-Hipofisario , Neoplasias Nasofaríngeas/terapia , Sobrevivientes , Anciano , Quimioradioterapia , Estudios Transversales , Estradiol/sangre , Femenino , Hormona Folículo Estimulante/sangre , Humanos , Hidrocortisona/sangre , Hiperprolactinemia/sangre , Hipogonadismo/sangre , Hipogonadismo/epidemiología , Hipopituitarismo/sangre , Hipotiroidismo/sangre , Hipotiroidismo/epidemiología , Hormona Luteinizante/sangre , Masculino , Persona de Mediana Edad , Órganos en Riesgo , Prolactina/sangre , Radioterapia , Testosterona/sangre , Tirotropina/sangre , Tiroxina/sangre
10.
Clin Exp Dermatol ; 39(5): 596-9, 2014 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-24890685

RESUMEN

Trigeminal trophic syndrome (TTS) is a rare cause of facial ulceration, which is usually associated with damage to the trigeminal nerve pathway, either centrally or peripherally, the most common causes being cerebrovascular accidents and trigeminal nerve ablation procedures. We present three cases of TTS, emphasizing the histopathological features. All three patients presented with facial ulceration. Two patients had a single lesion, and the third had several ulcers. However, in all cases, there was involvement of the nasal ala, and the lesions were strictly unilateral. Histology consistently showed ulceration with signs of severe chronic trauma: scarring, lichenification and/or pseudoepitheliomatous hyperplasia. Diagnosis of TTS can be difficult, and requires close clinicopathological correlation. Histology is important in excluding the majority of possible conditions included in the differential diagnosis, mainly malignancy and infectious processes. Several treatments have been described, but TTS is frequently refractory to treatment.


Asunto(s)
Dermatosis Facial/patología , Deformidades Adquiridas Nasales/patología , Enfermedades Raras/patología , Úlcera Cutánea/patología , Traumatismos del Nervio Trigémino , Diagnóstico Diferencial , Dermatosis Facial/etiología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Deformidades Adquiridas Nasales/etiología , Úlcera Cutánea/etiología , Síndrome
11.
Biol Trace Elem Res ; 202(10): 4823-4841, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-38196052

RESUMEN

Different types of infant foods categorized as formulas, cereals, and purees imported from seven different countries and available on the Kuwaiti retail market were collected to determine the elemental content, including essential trace elements namely chromium (Cr), manganese (Mn), iron (Fe), copper (Cu), zinc (Zn), selenium (Se), and molybdenum (Mo); potentially toxic trace elements such as aluminum (Al), nickel (Ni), tin (Sn), antimony (Sb), and uranium (U); and toxic trace elements including arsenic (As), lead (Pb), cadmium (Cd), and mercury (Hg). The samples were analyzed using ICP-MS. An extensive literature search illustrated the uniqueness of this study since seven different essential elements, five different potentially toxic elements, and four different toxic trace elements were measured in a variety of infant foods; in addition, the different trace etlemental levels measured in the investigated infant foods were compared to the ones associated with the different infant foods types reported in the literature. The essential trace element concentrations detected in this study were implemented to calculate their total daily intake, where the calculated daily intake values were compared to their recommended dietary allowance (RDA) to assess the percentage total daily intake for the essential trace elements. Further, the calculated potentially toxic and toxic trace elements daily intake values were used to assess the potential health risks to infants incurred by consuming different infant foods by calculating the hazard quotient (HQ), while the margin of exposure (MOE) was calculated for the toxic ones only. It was concluded that infant formulas and foods should be added to the infant diet in addition to breast milk to meet specific nutritional needs. This study confirms that infants are exposed to toxic trace elements via diet, warranting careful attention to diet choices both to limit this exposure and to avert potentially hazardous adverse health effects to the infants. However, based on the calculated hazard quotients (HQs) and margin of exposures (MOEs), consuming breast milk in addition to almost all different types of infant foods is considered safe and unlikely to contribute to infants' non-cancerous health hazards.


Asunto(s)
Alimentos Infantiles , Oligoelementos , Humanos , Oligoelementos/análisis , Kuwait , Lactante , Alimentos Infantiles/análisis , Dieta , Exposición Dietética/análisis
12.
Mymensingh Med J ; 22(3): 513-21, 2013 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-23982542

RESUMEN

Two hundred consecutive patients of acute coronary syndrome aged 30-80 years (inclusive) admitted to the coronary care unit of National institute of Cardiovascular Diseases, Dhaka, were prospectively recruited as cases. Two hundred controls were prospectively selected either from individuals attending in the Shaheed Suhrawardy Medical College Hospital, admitted for elective surgery or in medicine ward for conditions that were unlikely to confound a comparative analysis. The Cases had significantly lower yearly incomes than controls, and significantly higher number of cases is occupied as sedentary worker. Smoking was an important risk factor. About 70% of cases and 45% of controls smoked previously cigarettes. Consumption of non smoke tobacco is another risk factor. The high risk of IHD in developing countries attributed to low consumption of fruit and vegetables, and in our study regular consumption of fruits (taking fruit at least 4 days a week) shows 20.5% cases and 33% of controls (OR 0.524, 95%CI 0.333-0.823) and p value was 0.005. Around 23.5% of the cases were diabetic compared with 4.5% of controls. We found 5% cases and 1.5% controls having known dyslipidemia. Although the body-mass index of cases was 24.68±3.06 Kg/M² and controls 20.54±4.37 Kg/M². The WHR was also significantly greater in cases 0.98±0.05M vs. controls 0.93±0.102M (p<0.001). About 31% of cases and 2% of controls had past history of myocardial infarction. The most predictive independent variables were previous smoking (p<0.001), WHR (p<0.001), history of hypertension (p<0.001), and income (p<0.001). Smoking and WHR were associated with the highest risks. The variables revealed to be significantly associated with acute coronary syndrome by bivariate analyses were all entered into the model directly. Eleven variables entered into the model. Of them Age, occupation, family income (yearly), fruit consumption, known hypertension, known DM, known dyslipidemia, previous MI, previous smoking, BMI and Waist and hip ratio were found to be the independent predictors of acute coronary syndrome. The study found that smoking tobacco, diabetes mellitus, hypertension, visceral obesity and less fruit intake are the important factors of acute coronary syndrome in Bangladesh.


Asunto(s)
Síndrome Coronario Agudo/epidemiología , Síndrome Coronario Agudo/etiología , Adulto , Anciano , Anciano de 80 o más Años , Bangladesh/epidemiología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Prevalencia , Estudios Prospectivos , Factores de Riesgo
13.
Epilepsy Behav Rep ; 23: 100605, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37332897

RESUMEN

We report a 60-year-old woman who presented to the emergency department after experiencing a witnessed unknown onset bilateral tonic clonic seizure (GTCS) that culminated in cardiac arrest. A neurology consultant uncovered a years-long history of frequent episodic staring followed by confusion and expressive aphasia, which strongly suggested that she suffered from epilepsy. Thus, her cardiac arrest and subsequent resuscitation met criteria for a near-sudden unexpected death in epilepsy (SUDEP) diagnosis. Serial bloodwork demonstrated transient troponin I elevations and leukocytoses, while a brain MRI revealed global cerebral anoxic injury and a small acute right cerebellar ischemic infarction. A review of her medical record uncovered a hospitalization sixteen months earlier for a likely GTCS whose workup showed similar troponin I elevations and leukocytoses, and surprisingly, a different small acute right cerebellar ischemic infarction in the same vascular territory. To our knowledge, this is the first report of subcortical ischemic infarctions occurring concurrently with GTCSs in a near-SUDEP patient. Aside from illustrating the key role of inpatient neurologists in the diagnosis of near-SUDEP, this manuscript discusses the potential significance of postictal ischemic infarctions, transient asymptomatic troponin elevations, and transient non-infectious leukocytoses in epilepsy patients with cardiovascular risk factors.

14.
Chronobiol Int ; 40(3): 272-283, 2023 03.
Artículo en Inglés | MEDLINE | ID: mdl-36803265

RESUMEN

Previously we had demonstrated the development and feasibility of an integrated chrono-nutrition weight reduction program among non-shift workers with morning and evening chronotypes. In this current paper, we described the association between the changes in chrono-nutrition practice and weight loss outcomes upon completing the weight reduction program. A total of 91 overweight/obese non-shift workers participated in the 12-week integrated chrono-nutrition weight reduction program (Age: 39.6 ± 6.3 y; 74.7% women; BMI: 31.2 ± 4.5 kg/m2). All the assessments including anthropometry, dietary, sleep habits, physical activity, and process of change were measured during pre- and post-intervention. Participants who had lost ≥3% of their body weight were categorized as satisfactory weight loss outcome, and those who did not achieve 3% weight loss were categorized as unsatisfactory weight loss. The satisfactory weight loss had greater daily percent energy intake during earlier in the day from protein (Mean difference (MD): +3.2%, 95% CI: 1.6, 4.9, p < .001) and smaller intake from fat during later in the day (MD: -2.6%, 95% CI: -5.1, -0.1, p = .045), earlier last mealtime (MD: -49.5 min, 95% CI: -86.5, -12.6, p = .009) and midpoint of eating (MD: -27.3 min, 95% CI: -46.3, -8.2, p = .006), shorter eating window (-0.8 h, 95% CI: -1.4, -0.1, p = .031) and greater reduction in night eating syndrome score (MD: -2.4, 95% CI: -4.3, -0.5, p = .015) compared to unsatisfactory weight loss outcome. After accounting for potential confounders, the temporal pattern of energy, protein, and fat intake were associated with greater odds of achieving a satisfactory weight loss. The findings suggest a promising role of chrono-nutrition as one of the strategies in weight reduction intervention.


Asunto(s)
Ritmo Circadiano , Conducta Alimentaria , Humanos , Femenino , Adulto , Persona de Mediana Edad , Masculino , Estudios de Factibilidad , Estado Nutricional , Ingestión de Energía , Pérdida de Peso , Índice de Masa Corporal
16.
Ophthalmol Sci ; 2(2): 100154, 2022 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-36249705

RESUMEN

Purpose: To establish the safety, tolerability, pharmacokinetics, and pharmacodynamics of an intravitreal injection of recombinant human complement factor H (CFH), GEM103, in individuals with genetically defined age-related macular degeneration (AMD) and geographic atrophy (GA). Design: Phase I single ascending-dose, open-label clinical trial (ClinicalTrials.gov identifier, NCT04246866). Participants: Twelve individuals 50 years of age or older with a confirmed diagnosis of foveal GA in the study eye. Methods: Participants were assigned to the increasing dose cohorts and received 1 50-µl intravitreal injection of GEM103 at doses of 50 µg/eye, 100 µg/eye, 250 µg/eye, or 500 µg/eye; dose escalation was dependent on the occurrence of dose-limiting toxicities. Main Outcome Measures: Safety assessments included ocular and systemic adverse events (AEs), ocular examinations, clinical laboratory and vital signs, and serum antidrug antibody levels. Biomarkers, measured in the aqueous humor (AH), included CFH and complement activation biomarkers factor Ba and complement component 3a. Results: No dose-limiting toxicities were reported, enabling escalation to the maximum study dose. No anti-GEM103 antidrug antibodies were detected during the study. Four participants experienced AEs; these were nonserious, mild or moderate in severity, and unrelated to GEM103. The AEs in 2 of these participants were related to the intravitreal injection procedure. No clinically significant ophthalmic changes and no ocular inflammation were observed. Visual acuity was maintained and stable throughout the 8-week follow-up period. No choroidal neovascularization occurred. CFH levels increased in a dose-dependent manner after GEM103 administration with supraphysiological levels observed at week 1; levels were more than baseline for 8 weeks or more in all participants receiving single doses of 100 µg or more. Complement activation biomarkers were reduced 7 days after dose administration. Conclusions: A single intravitreal administration of GEM103 (up to 500 µg/eye) was well tolerated in individuals with GA. Of the few mild or moderate AEs reported, none were determined to be related to GEM103. No intraocular inflammation or choroidal neovascularization developed. CFH levels in AH were increased and stable for 8 weeks, with pharmacodynamic data suggesting that GEM103 restored complement regulation. These results support further development in a repeat-dose trial in patients with GA with AMD.

17.
J Adv Res ; 28: 63-75, 2021 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-33364046

RESUMEN

Platinum is the most commonly used catalyst in fuel cell application. However, platinum is very expensive, thus limits the commercialisation of fuel cell system due to the cost factor. This study introduces a biosynthesis platinum from plant extracts that can reduce the cost of platinum production compared to the conventional method and the hazardous during the production of the catalyst. The biogenic platinum was tested on a Direct Methanol Fuel Cell. Advanced biogenic of Pt nano-cluster was synthesized through a novel and facile of one-pot synthesis bio-reduction derived from natural source in the form of plant extracts as reducing agent. Several selected plant extracts drawn from agricultural waste such as banana peel, pineapple peels and sugarcane bagasse extracts were comparatively evaluated on the ability of phytochemical sources of polyphenols rich for the development of single-step synthesis for Pt NPs. Notably, the biogenic Pt NPs from sugar cane bagasse has superior electro-catalytic activity, the enhanced utilization efficiency of Pt and appreciable stability towards methanol oxidation reaction, whose ECSA value approximates 94.58 m2g-1, mass activity/specific activity (398.20 mAmg-1/0.8471 mA/cm2 Pt) which greater than commercial Pt black (158.12 mAmg-1/1.41 mA/cm2 Pt).

18.
Front Pediatr ; 9: 698577, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34422723

RESUMEN

Background: Hereditary tyrosinemia type 1 is a rare genetic disorder leading to liver cirrhosis and hepatocellular carcinoma. Few decades ago, dietary measures and ultimately liver transplant constituted the only treatment modalities. Nowadays, early diagnosis and therapy with nitisinone can reverse the clinical picture. In developing countries, diagnostic and therapeutic challenges may affect the outcome of this disease. The choice of the treatment modality may depend on the economic status of each country. Few reports on the long-term outcome of hereditary tyrosinemia type 1 are available from developing and Arab countries. Methods: A retrospective study of charts of Lebanese patients diagnosed with tyrosinemia type 1 and followed, at the American University of Beirut, during a 12-year period was performed. Clinical presentation and liver biochemical profile at diagnosis were analyzed, along with therapeutic modalities and long-term outcome. Results: Twenty-two children were diagnosed and followed during the study period. Median age at diagnosis was 7 months (range: one day to 35 months). Most of the patients presented with hepatomegaly and jaundice. Four patients were referred for atypical presentations with developmental delay and seizures, secondary to undiagnosed hypoglycemia episodes. Around half of the patients presented with failure to thrive. Transaminitis, cholestasis and increased α-fetoprotein level were variably present at diagnosis (36% to 50%). All patients had elevated plasma tyrosine and urinary succinylacetone levels. Genetic testing was performed in 9%. Only one third could be treated with nitisinone. Liver transplant was electively performed in 9% of cases, to overcome the long-term cost of nitisinone. One third of the patients died between the age of 1 month and 11 years. Surviving patients are still candidates for liver transplant. Conclusion: Our experience reflects the challenges of diagnosis and treatment of hereditary tyrosinemia type 1 in a developing country. In the absence of specific neonatal screening, early diagnosis relies mostly on the clinical awareness of the physician. Long-term nitisinone use may be deterred by its high cost and liver transplantation carries risks of surgical complications. New, effective, and less expensive treatments are needed, especially for developing countries.

19.
BMJ Case Rep ; 14(6)2021 Jun 29.
Artículo en Inglés | MEDLINE | ID: mdl-34187796

RESUMEN

We report on an 8-year-old boy, who presented to the emergency department at our institution with fever, generalised oedema and hypotension. Investigations revealed anaemia, thrombocytopenia in addition to elevated serum inflammatory markers, a negative COVID-19 PCR test and a positive COVID-19 IgG. His echocardiography was consistent with carditis in otherwise morphologically normal heart with depressed cardiac function, moderate-to-severe mitral valve regurgitation, moderate tricuspid regurgitation with an estimated right ventricular systolic pressure half systemic, trace aortic regurgitation, bilateral small pleural effusions, distended inferior vena cava and normal coronaries. He was started on inotropic support, intravenous immunoglobulin and methylprednisolone, and was transferred to the paediatric intensive care unit. To the best of our knowledge, this was the first case of multisystem inflammatory syndrome in children encountered in Lebanon. The presentation and management were thoroughly described in this article aiming to share our experience and to contribute to the rapidly emerging literature on this syndrome.


Asunto(s)
COVID-19 , Insuficiencia de la Válvula Mitral , Insuficiencia de la Válvula Tricúspide , Niño , Humanos , Líbano , Masculino , Insuficiencia de la Válvula Mitral/diagnóstico por imagen , Insuficiencia de la Válvula Mitral/etiología , SARS-CoV-2 , Síndrome de Respuesta Inflamatoria Sistémica
20.
Front Pediatr ; 9: 637463, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34381742

RESUMEN

Introduction: The incidence of acute kidney injury (AKI) in pediatric patients following cardiac surgery varies between 15 and 64%, with a mortality rate of 10-89% among those requiring dialysis. This variation in the incidence and mortality of AKI across studies is probably due to the inconsistent definitions used for AKI. The purpose of this study is to present our experience with AKI post-cardiac surgery with emphasis on predisposing or aggravating factors. Patients and Methods: We evaluated the incidence of AKI using the KDIGO criteria in 150 infants and children undergoing cardiac surgeries between 2015 and 2017. Post-operatively, all patients were admitted to the pediatric intensive care unit (PICU) at a tertiary care center in a developing country. This is a retrospective chart review in which data collected included age, gender, type of heart disease, prior cardiac surgeries, RACHS-1 category, and pre- and post-operative creatinine levels. Neonates were not included in this study. Results: Six percent of the studied patients were below 1 year of age, 84% 1-10 years, and 10% 10-18 years. Fourteen patients (9.3%) developed AKI. Patients with cyanotic heart disease were more prone to develop AKI (78%) compared to those with non-cyanotic heart disease (44%). Children with AKI had a higher length of stay in PICU, 2.56 ± 1.44 vs. 4 ± 2.66 (p- 0.02). Serum lactic acid was higher in patients who developed AKI with a mean value of 6.8 ± 6.9 vs. 2.85 ± 1.55 mmol/l in the non-AKI group (p- 0.03). Lower hemoglobin levels and hyperlactic acidemia were significantly more prevalent in the AKI group. There were five deaths in this series (3.3%), and four of those (80%) were in the AKI group. Conclusion: Using the KDIGO criteria, the incidence of AKI in infants and children following cardiac surgery was 9.3%. This is slightly lower than in previously published studies where the range was between 15 and 64%. Children with cyanotic cardiac disease, hyperlactic acidemia, and anemia were more prone to developing AKI. Identifying patients at risk might help decrease the risk of post-operative AKI.

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