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CONTEXT: Antenatal complications such as hypertensive disorders of pregnancy (HDP), fetal growth restriction (FGR), gestational diabetes (GDM), and preterm birth (PTB) are associated with placental dysfunction. Kisspeptin has emerged as a putative marker of placental function, but limited data exist describing circulating kisspeptin levels across all 3 trimesters in women with antenatal complications. OBJECTIVE: We aimed to assess whether kisspeptin levels are altered in women with antenatal complications. METHODS: Women with antenatal complications (nâ =â 105) and those with uncomplicated pregnancies (nâ =â 265) underwent serial ultrasound scans and blood sampling at the Early Pregnancy Assessment Unit at Hammersmith Hospital, UK, at least once during each trimester (March 2014 to March 2017). The women with antenatal complications (HDP [nâ =â 32], FGR [nâ =â 17], GDM [nâ =â 35], PTB [nâ =â 11], and multiple complications [n=10]) provided 373 blood samples and the controls provided 930 samples. Differences in circulating kisspeptin levels were assessed. RESULTS: Third-trimester kisspeptin levels were higher than controls in HDP but lower in FGR. The odds of HDP adjusted for gestational age, maternal age, ethnicity, BMI, smoking, and parity were increased by 30% (95% CI, 16%-47%; Pâ <â 0.0001), and of FGR were reduced by 28% (95% CI, 4-46%; Pâ =â 0.025), for every 1 nmol/L increase in plasma kisspeptin. Multiple of gestation-specific median values of kisspeptin were higher in pregnancies affected by PTB (Pâ =â 0.014) and lower in those with GDM (Pâ =â 0.020), but not significantly on multivariable analysis. CONCLUSION: We delineate changes in circulating kisspeptin levels at different trimesters and evaluate the potential of kisspeptin as a biomarker for antenatal complications.
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Diabetes Gestacional/fisiopatología , Retardo del Crecimiento Fetal/epidemiología , Hipertensión Inducida en el Embarazo/epidemiología , Kisspeptinas/sangre , Enfermedades Placentarias/epidemiología , Preeclampsia/fisiopatología , Nacimiento Prematuro/epidemiología , Adulto , Biomarcadores/sangre , Estudios de Casos y Controles , Femenino , Retardo del Crecimiento Fetal/patología , Estudios de Seguimiento , Edad Gestacional , Humanos , Hipertensión Inducida en el Embarazo/patología , Recién Nacido , Londres/epidemiología , Masculino , Enfermedades Placentarias/patología , Embarazo , Trimestres del Embarazo , Nacimiento Prematuro/patología , PronósticoRESUMEN
OBJECTIVE: To compare the performance of kisspeptin and beta human chorionic gonadotropin (ßhCG), both alone and in combination, as biomarkers for miscarriage throughout the first trimester. DESIGN: Prospective, nested case-control study. SETTING: Tertiary Centre, Queen Charlotte Hospital, London, United Kingdom. PATIENT(S): Adult women who had miscarriages (n = 95, 173 samples) and women with healthy pregnancies (n = 265, 557 samples). INTERVENTION(S): The participants underwent serial ultrasound scans and blood sampling for measurement of plasma kisspeptin and ßhCG levels during the first trimester. MAIN OUTCOME MEASURE(S): The ability of plasma kisspeptin and ßhCG levels to distinguish pregnancies complicated by miscarriage from healthy pregnancies unaffected by miscarriage. RESULT(S): Gestation-adjusted levels of circulating kisspeptin and ßhCG were lower in samples from women with miscarriages than in women with healthy pregnancies by 79% and 70%, respectively. The area under the receiver-operating characteristic curve for identifying miscarriage during the first trimester was 0.874 (95% confidence interval [CI] 0.844-0.904) for kisspeptin, 0.859 (95% CI 0.820-0.899) for ßhCG, and 0.916 (95% CI 0.886-0.946) for the sum of the two markers. The performance of kisspeptin in identifying miscarriage improved with increasing length of gestation, whereas that of ßhCG worsened. A decision matrix incorporating kisspeptin, ßhCG, and gestational age had 83% to 87% accuracy for the prediction of miscarriage. CONCLUSION(S): Plasma kisspeptin is a promising biomarker for miscarriage and provides additional value to ßhCG alone, especially during later gestational weeks of the first trimester.
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Aborto Espontáneo/sangre , Kisspeptinas/sangre , Primer Trimestre del Embarazo/sangre , Aborto Espontáneo/diagnóstico por imagen , Aborto Espontáneo/etiología , Biomarcadores/sangre , Estudios de Casos y Controles , Gonadotropina Coriónica Humana de Subunidad beta/sangre , Regulación hacia Abajo , Femenino , Edad Gestacional , Humanos , Valor Predictivo de las Pruebas , Embarazo , Estudios Prospectivos , Ultrasonografía PrenatalRESUMEN
Trachoma is a neglected tropical disease that causes an eye infection which can lead to blindness if left untreated. In 1998, the World Health Organisation (WHO) launched a new goal to eradicate trachoma by 2020. Over the years, in partnership with the WHO, an effective strategy plan was devised to help tackle and control the disease. This involved surgery for trichiasis, antibiotic treatment, facial cleanliness, and environmental improvement (SAFE). Consequently, the number of people affected by trachoma has significantly decreased in recent times. Despite this, trachoma remains a major public health concern in 44 countries worldwide, including Nigeria. Although improvements have been seen throughout Nigeria, the disjointed application of the SAFE strategy has delayed progress compared to other countries. Providing quality treatment to those with trachoma, in addition to improving preventative measures are challenges faced throughout the country. However, a multi-pronged approach emulating the methods of other countries is recommended to achieve trachoma elimination. This review aims to evaluate the progress and challenges faced in Nigeria with regards to eliminating trachoma.
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CONTEXT: Alemtuzumab is an anti-CD52 monoclonal antibody used in the treatment of relapsing-remitting multiple sclerosis (MS). Between 20% and 40% of alemtuzumab-treated MS patients develop autoimmune thyroid disease (AITD) as a side effect. OBJECTIVE: The objective of this work is to determine whether MS disease progression following alemtuzumab treatment differs in patients who develop AITD compared to those who do not. DESIGN, SETTING, AND PATIENTS: A retrospective analysis of 126 patients with relapsing-remitting MS receiving alemtuzumab from 2012 to 2017 was conducted at a tertiary referral center. MAIN OUTCOME MEASURES: Thyroid status, new relapses, Expanded Disability Status Scale (EDSS) score change, and disability progression following alemtuzumab were evaluated. RESULTS: Twenty-six percent (33 out of 126, 25 female, 8 male) of alemtuzumab-treated patients developed AITD, 55% of which was Graves disease. EDSS score following alemtuzumab was reduced in patients who developed AITD compared to those who did not (median [interquartile range]; AITD: -0.25 [-1 to 0.5] vs non-AITD: 0 [1-0]. P = .007]. Multivariable regression analysis confirmed that the development of AITD was independently associated with EDSS score improvement (P = .011). Moreover, AITD patients had higher relapse-free survival following alemtuzumab (P = .023). There was no difference in the number of new focal T2 lesions and contrast-enhancing magnetic resonance imaging lesions developed following alemtuzumab between the 2 groups. CONCLUSION: Graves disease was the most common form of AITD developed by MS patients following alemtuzumab. This study suggests that MS patients who develop AITD may have an improved response to alemtuzumab, as measured by reduced disability and lower relapse rate.
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Alemtuzumab/efectos adversos , Esclerosis Múltiple Recurrente-Remitente/diagnóstico , Esclerosis Múltiple Recurrente-Remitente/tratamiento farmacológico , Tiroiditis Autoinmune/inducido químicamente , Adulto , Alemtuzumab/uso terapéutico , Progresión de la Enfermedad , Femenino , Estudios de Seguimiento , Humanos , Masculino , Esclerosis Múltiple Recurrente-Remitente/epidemiología , Esclerosis Múltiple Recurrente-Remitente/patología , Pronóstico , Recurrencia , Estudios Retrospectivos , Tiroiditis Autoinmune/epidemiología , Factores de Tiempo , Resultado del TratamientoRESUMEN
Ghrelin is a peptide hormone that is primarily released from the stomach. It is best known for its role in appetite initiation. However, evidence also suggests that ghrelin may play a much wider role in energy homeostasis and glucose metabolism. It is known that exogenous ghrelin exerts an orexigenic signal via growth hormone secretagogue receptors in the arcuate nucleus of the hypothalamus. However, blocking ghrelin signalling in the arcuate nucleus does not decrease feeding. Evidence now proposes that an alternative pathway for ghrelin's action is via the vagus nerve. Furthermore, it has been suggested that ghrelin signalling is an important physiological regulator of body adiposity and energy storage. Ghrelin also seems to be important in controlling glucose metabolism through action in the pancreatic islets of Langerhans, representing a promising novel therapeutic target in diabetes treatment. Despite these findings, further research in humans is required before ghrelin can be indicated as a therapeutic target in obesity or diabetes. This review summarises the current literature concerning ghrelin's physiological roles in energy and glucose homeostasis.