Management of Intraoperative Contamination of the Custom Total Temporomandibular Joint Prosthesis.

Management of intraoperative contamination of a custom total temporomandibular joint prosthesis has not been reported in the literature. As this complication is rare, it can be unsettling for the surgeon. Improper management may lead to a complicated treatment course and financial consequences. Prevention is the primary strategy for avoidance and appropriate management is dependent on many variables. The purpose of this report is to identify a unique complication associated with placement of a custom temporomandibular joint prosthesis and offer an algorithm for management.

Impact of botulinum toxin injection into the masticatory muscles on mandibular bone: A systematic review.

BACKGROUND: Botulinum toxin type A (BoNTA) injection into the masticatory muscles has been widely used to treat a number of painful and nonpainful conditions; however, no systematic reviews have been performed on the long-term effect to the mandibular bone. OBJECTIVE: Our systematic review aimed to evaluate the impact of botulinum toxin injection into the masticatory muscles on mandibular bone based. METHODS: PubMed, Embase, Ovid, CINAHL and Web of Science were searched for human studies assessing mandibular bone after injection of BoNTA using computed tomography (CT) and cone beam CT (CBCT). RESULTS: Seven studies were eligible for review; five reported significant bony changes to one or more areas of the mandible. Most frequently affected were the condylar head, coronoid process and ramus. The most frequent changes were decreased bone volume, cortical thickness and cortical and trabecular density. CONCLUSIONS: This is the first systematic review to examine an association between BoNTA injection into the masticatory muscles and mandibular bone quality. Data were analysed from a limited number of studies with a small sample size, and the quality of the included studies was very low. While the majority of available evidence suggests BoNTA injection results in bony change, further study is required to confirm a dose-dependence effect and the impact of gender and age. High-quality trials should utilise a combination of software analysis and radiologist review, with longer-term follow-up to monitor for persistence of bony effect and clinical significance.

Treatment of Temporomandibular Joint Heterotopic Ossification: A Novel Protocol With Multimodal Therapy Based on Literature Review and Presentation of a Unique Case Report.

PURPOSE: The purpose of this study was to create a treatment protocol for cases of heterotopic ossification (HO) of the temporomandibular joint (TMJ), particularly those refractory to current TMJ HO protocols. In addition, we demonstrate the success of this protocol on a unique case of recurrent HO that failed multiple TMJ HO protocols in the setting of an improvised explosive device (IED) blast in a wounded warrior. METHODS: An electronic literature review was conducted via PubMed and Web of Science. Twenty-five studies were identified to provide supporting evidence for a proposed, up-to-date protocol for the treatment of refractory TMJ HO. The authors present a case report of a wounded warrior with HO ankylosis of bilateral TMJs in the setting of IED blast and demonstrate successful use of our surgical and pharmacotherapeutic protocol. RESULTS: Based on the literature review, our proposed protocol consists of pharmacotherapy with celecoxib and etidronate, with weekly forced dilation (brisement) and home physical therapy with the TheraBite Jaw Motion Rehab System. Surgically, the TMJ should be treated with two-stage reconstruction using initial polymethyl methacrylate spacers and subsequent total joint replacement with custom prostheses, fat grafting, and 3-dimensional-navigated total resection of HO. This protocol was successfully utilized in our patient's refractory HO ankylosed TMJ secondary to IED blast, and the patient's maximal incisal opening was regained and has remained stable 2 years after surgery without recurrent HO. CONCLUSIONS: Our method for treatment in this case deviated from the standard TMJ Concepts HO protocol in that it included multimodal pharmacotherapy with celecoxib and etidronate. Based on our literature review and experience, we advise that clinicians utilize our protocol for the management of all craniofacial HO cases, particularly in cases of recurrent HO that fail conventional therapies and/or involving high-order blast trauma.

Riesgo estimado de padecer diabetes mellitus tipo 2 en pacientes hipertensos con tratamiento farmacológico / Estimate Risk of Presenting Type 2 Diabetes Mellitus in Hypertensive Patients under Pharmacological Treatment

Introducción: La diabetes mellitus es un reto para los sistemas de salud pública de todas las naciones. Objetivo: Identificar el riesgo de padecer diabetes mellitus tipo 2 en pacientes que debutaron con hipertensión arterial que tienen tratamiento farmacológico. Métodos: Se realizó un estudio observacional, descriptivo de tipo serie de casos. El universo estuvo constituido por los 74 pacientes pertenecientes al área de salud del Policlínico Docente Universitario Alex Urquiola Marrero que debutaron con hipertensión arterial, en el año 2019; se estudió todo el universo. Las variables estudiadas fueron: edad, sexo, factores de riesgo asociados a la diabetes mellitus, antecedentes familiares de diabetes mellitus y riesgo de padecer diabetes mellitus. Luego de recolectar la información, esta fue digitalizada para su posterior procesamiento. La base de datos y su procesamiento se realizó utilizando el paquete de programas estadísticos SPSS. Se utilizó la escala Finnish Diabetes Risk Score para calcular el riesgo de padecer diabetes mellitus tipo 2. Resultados: 40 pacientes pertenecían al sexo masculino; 29,7 por ciento estaban entre 55 y 64 años; obesidad, sedentarismo y hábitos alimentarios inadecuados estuvieron presentes en más del 50 por ciento de los pacientes; 59,5 por ciento tenían antecedentes familiares de diabetes mellitus de 2do grado; 52,7 por ciento presentaron riesgo de padecer diabetes mellitus tipo 2 alto o muy alto. Conclusiones: En pacientes con hipertensión arterial de debut el riesgo de padecer diabetes mellitus tipo 2 es predominantemente alto y muy alto(AU)

Introduction: Diabetes mellitus is a challenge for the public health systems of all nations. Objective: To identify the risk of suffering type 2 diabetes mellitus in patients who debuted with arterial hypertension under pharmacological treatment. Methods: An observational, descriptive study pf case series was carried out. The universe was made up of the 74 patients belonging to the health area of Alex Urquiola Marrero University Teaching Polyclinic who debuted with arterial hypertension in 2019. The entire universe was studied. The variables studied were age, sex, risk factors associated with diabetes mellitus, family history of diabetes mellitus, and risk of suffering from diabetes mellitus. After collecting the information, it was entered into computer software for further processing. The database was processed using the SPSS statistical software package. The Finnish Diabetes Risk Score was used to calculate the risk of suffering from type 2 diabetes mellitus. Results: Of the total of patients, 40 belonged to the male sex. 29.7 percent were aged 55-64 years. Obesity, sedentary lifestyle and inadequate eating habits were present in more than 50 percent of the patients. 59.5 percent had a family history of diabetes mellitus, through a second-degree relative. 52.7 percent had a high or very high risk of suffering from type 2 diabetes mellitus. Conclusions: In patients who debuted with hypertension, the risk of suffering from type 2 diabetes mellitus is predominantly high or very high(AU)

Estimating Reference Shape Model for Personalized Surgical Reconstruction of Craniomaxillofacial Defects.

OBJECTIVE: To estimate a patient-specific reference bone shape model for a patient with craniomaxillofacial (CMF) defects due to facial trauma. METHODS: We proposed an automatic facial bone shape estimation framework using pre-traumatic conventional portrait photos and post-traumatic head computed tomography (CT) scans via a 3D face reconstruction and a deformable shape model. Specifically, a three-dimensional (3D) face was first reconstructed from the patient's pre-traumatic portrait photos. Second, a correlation model between the skin and bone surfaces was constructed using a sparse representation based on the CT images of training normal subjects. Third, by feeding the reconstructed 3D face into the correlation model, an initial reference shape model was generated. In addition, we refined the initial estimation by applying non-rigid surface matching between the initially estimated shape and the patient's post-traumatic bone based on the adaptive-focus deformable shape model (AFDSM). Furthermore, a statistical shape model, built from the training normal subjects, was utilized to constrain the deformation process to avoid overfitting. RESULTS AND CONCLUSION: The proposed method was evaluated using both synthetic and real patient data. Experimental results show that the patient's abnormal facial bony structure can be recovered using our method, and the estimated reference shape model is considered clinically acceptable by an experienced CMF surgeon. SIGNIFICANCE: The proposed method is more suitable to the complex CMF defects for CMF reconstructive surgical planning.

Retrieval of Displaced Third Molar Into the Sublingual Space Using 3-Dimensional Navigation Assistance.

Surgical removal of third molars is a common procedure undertaken by both general dentists and oral and maxillofacial surgeons. Although rare, iatrogenic displacement of the tooth or root fragments into adjacent fascial spaces is a known complication. This case report details the retrieval of displaced root tips from a mandibular third molar into the sublingual space using intraoperative navigation to minimize surgical exploration. Oral-maxillofacial surgeons should consider using 3-dimensional navigation during scheduled retrieval of displaced teeth, fragments, or foreign objects to minimize the risk of surgical complications.

Seroprevalencia de anticuerpos contra Leptospira spp. en cerdos criados en Portoviejo, Ecuador / Seroprevalence of antibodies against Leptospira spp. in pigs raised in Portoviejo, Ecuador

Introducción: La leptospirosis es una enfermedad infecciosa bacteriana causada por leptospiras patógenas, que afectan a una amplia variedad de mamíferos incluido el hombre. Es considerada como una de las enfermedades zoonóticas de mayor distribución a nivel mundial. Objetivo: Determinar la seroprevalencia de anticuerpos contra Leptospira spp. y factores de riesgo asociados a la leptospirosis en algunas poblaciones de cerdos de Portoviejo. Métodos: Estudio descriptivo, realizado entre octubre de 2018 a marzo de 2019. Se estudiaron cerdos criados en parroquias del cantón Portoviejo, Manabí, Ecuador. Se colectaron un total de 280 muestras de sangre (115 de cerdos en crianza tecnificada y 165 en crianza de traspatio), 140 en el periodo lluvioso (enero-marzo) y 140 en el periodo seco (octubre-diciembre), de forma tal que fueran representativos los animales para ambas épocas. El diagnóstico serológico se realizó mediante la prueba de aglutinación microscópica. Resultados: En la crianza tecnificada, la seroprevalencia fue de 16,52 por ciento (19/115) y en la crianza de traspatio, 20,61 por ciento (34/165). Se presentó con mayor frecuencia en serovares Australis e Icterohaemorrhagiae en 14,28 por ciento (40/280), respectivamente, y Bataviae en 13,21 por ciento (37/280). El riesgo asociado a la infección por leptospiras fue mayor en los cerdos del sexo femenino, en las poblaciones de cerdos que consumieron agua de ríos y en los predios donde no se realizó un control de roedores silvestres. Conclusiones: La seroprevalencia a anticuerpos contra Leptospira spp. en la población de cerdos en crianza tecnificada y traspatio fue moderada, pero constituye un peligro potencial para la población humana expuesta. En ambos sistemas de crianza, los serovares más frecuentes fueron Australis, Icterohaemorrhagiae y Bataviae(AU)

Introduction: Leptospirosis is an infectious disease caused by pathogenic Leptospira sp. bacteria. It affects a large number of mammals, including humans, and is considered to be one of the most widely distributed zoonotic diseases worldwide. Objective: Determine the seroprevalence of antibodies against Leptospira spp. and the risk factors associated to leptospirosis in some pig populations from Portoviejo. Methods: A descriptive study was conducted from October 2018 to March 2019 of pigs raised in parishes from Portoviejo Canton in Manabí, Ecuador. A total 280 blood samples were collected (115 from pigs raised technically and 165 from pigs raised in backyards), 140 in the rainy season (January-March) and 140 in the dry season (October-December), so that the samples were representative of the two seasons. Serological diagnosis was performed with the microscopic agglutination test. Results: In technical breeding, seroprevalence was 16.52 percent (19/115), whereas in backyard breeding it was 20.61 percent (34/165). It was most common in serovars Australis and Icterohaemorrhagiae, with 14.28 percent (40/280), respectively, and Bataviae with 13.21 percent (37/280). Risk associated to Leptospira infection was greater in sows, in pig populations which drank river water, and in areas where wild rodent control was not present. Conclusions: Seroprevalence of antibodies against Leptospira spp. was moderate in technical and backyard pig raising populations, but it is a potential hazard for the human population exposed. In both breeding systems, the most common serovars were Australis, Icterohaemorrhagiae and Bataviae(AU)

Estimating Reference Bony Shape Model for Personalized Surgical Reconstruction of Posttraumatic Facial Defects.

In this paper, we introduce a method for estimating patient-specific reference bony shape models for planning of reconstructive surgery for patients with acquired craniomaxillofacial (CMF) trauma. We propose an automatic bony shape estimation framework using pre-traumatic portrait photographs and post-traumatic head computed tomography (CT) scans. A 3D facial surface is first reconstructed from the patient's pre-traumatic photographs. An initial estimation of the patient's normal bony shape is then obtained with the reconstructed facial surface via sparse representation using a dictionary of paired facial and bony surfaces of normal subjects. We further refine the bony shape model by deforming the initial bony shape model to the post-traumatic 3D CT bony model, regularized by a statistical shape model built from a database of normal subjects. Experimental results show that our method is capable of effectively recovering the patient's normal facial bony shape in regions with defects, allowing CMF surgical planning to be performed precisely for a wider range of defects caused by trauma.

Ascites in an uncorrected tetralogy of Fallot with pulmonary valve absence in an adult patient.

This is a case of a 37-year-old woman with uncorrected tetralogy of Fallot with the absence of pulmonary valve and history of heart murmur in childhood who did not have a medical approach. At 29 years of age she started with dyspnoea that in the last 7 months progressed to be of small effort and also referred increase of the abdominal perimeter.

Mechanical deformation in adult patients with unrepaired aortic coarctation.

Aortic coarctation is a congenital heart disease that causes an increased left ventricular afterload, resulting in increased systolic parietal tension, compensatory hypertrophy, and left ventricular systolic and diastolic dysfunction. The speckle tracking is a new echocardiographic technique that allows the detection of subclinic left ventricular systolic dysfunction. The aim of this study was to detect early left ventricular dysfunction using mechanical deformation by echocardiography in adults with un-repaired aortic coarctation. A total of 41 subjects were studied, 20 patients with aortic coarctation and 21 control subjects, 21 women (51.2%), with an average age of 30 ± 10 years. All patients with aortic coarctation had systemic arterial hypertension (p < 0.001). Seventy percent (14/20) of the patients had bicuspid aortic valve. Statistically significance (p < 0.005) were found in left ventricular mass index, E/e ratio, pulmonary artery systolic pressure and peak velocity and maximum gradient of the aortic valve. The global longitudinal deformation of the left ventricle in patients with aortic coarctation was significative decreased, p < 0.001. The ejection fraction and the global longitudinal deformation of the left ventricle were significantly lower in patients with aortic coarctation compared to the control group, p < 0.003, p < 0.001, respectively. The subgroup of patients with coarctation and left ventricular ejection fraction < 55% had a marked decrease in global longitudinal strain (- 15.9 ± 4%). The radial deformation was increased in patients with aortic coarctation and showed a trend to be significant (r = 0.421; p < 0.06). A significant negative correlation was observed between the global longitudinal deformation and left ventricular mass index (r = 0.54; p = 0.01) in the aortic coarctation group. The patients with aortic coarctation and left ventricular hypertrophy had marked reduction of left ventricular global longitudinal deformation (- 16%, p < 0.05). In our study patients with normal left ventricular ejection fraction had abnormal global longitudinal deformation and also the increased left ventricular mass was related with a decreased left ventricular global longitudinal deformation as a sign of subclinical systolic dysfunction.

Subclinical ventricular dysfunction by Speckle Tracking in adult patients with coarctation of the aorta. / Disfunción ventricular subclínica por Speckle Tracking en pacientes adultos con coartación de aorta.

Objective: The aim of this study was to investigate the presence of early left ventricular (LV) systolic dysfunction in adult patients with aortic coarctation (AoCo) and systemic arterial hypertension (SAH) compared to systemic hypertensive patients without coarctation and healthy controls by speckle tracking. Methods: Sixty-one subjects were studied, who attended consecutively to external consultation. All were submitted to clinical history, resting electrocardiogram, conventional echocardiogram and with Speckle Tracking. Results: 15 patients with AoCo and SAH were in functional class NYHA I, and five in functional class NYHA II. A significant inverse correlation was observed between the global longitudinal deformation and the left ventricular mass index in the AoCo and SAH group and in the hypertensive patients (r = 0.53, p = 0.02; r = 0.52, p < 0.0001, respectively). Conclusions: In patients with AoCo and SAH, global longitudinal deformation and left ventricular mass index are significantly related to subclinical LV dysfunction. These parameters are important and should be taken into account to regulate timely therapeutic behavior.

Development of in-house serological methods for diagnosis and surveillance of chikungunya.

OBJECTIVE: To develop and evaluate serological methods for chikungunya diagnosis and research in Nicaragua. METHODS: Two IgM ELISA capture systems (MAC-ELISA) for diagnosis of acute chikungunya virus (CHIKV) infections, and two Inhibition ELISA Methods (IEM) to measure total antibodies against CHIKV were developed using monoclonal antibodies (mAbs) and hyperimmune serum at the National Virology Laboratory of Nicaragua in 2014-2015. The sensitivity, specificity, predictive values, and agreement of the MAC-ELISAs were obtained by comparing the results of 198 samples (116 positive; 82 negative) with the Centers for Disease Control and Prevention's IgM ELISA (Atlanta, Georgia, United States; CDC-MAC-ELISA). For clinical evaluation of the four serological techniques, 260 paired acute and convalescent phase serum samples of suspected chikungunya cases were used. RESULTS: All four assays were standardized by determining the optimal concentrations of the different reagents. Processing times were substantially reduced compared to the CDC-MAC-ELISA. For the MAC-ELISA systems, a sensitivity of 96.6% and 97.4%, and a specificity of 98.8% and 91.5% were obtained using mAb and hyperimmune serum, respectively, compared with the CDC method. Clinical evaluation of the four serological techniques versus the CDC real-time RT-PCR assay resulted in a sensitivity of 95.7% and a specificity of 88.8%-95.9%. CONCLUSION: Two MAC-ELISA and two IEM systems were standardized, demonstrating very good quality for chikungunya diagnosis and research demands. This will achieve more efficient epidemiological surveillance in Nicaragua, the first country in Central America to produce its own reagents for serological diagnosis of CHIKV. The methods evaluated here can be applied in other countries and will contribute to sustainable diagnostic systems to combat the disease.

Melanoma Metastasis to the Mandible-Case Report and Comprehensive Literature Review.

With the incidence of melanoma increasing yearly, there is a need for heightened awareness of its metastatic potential and for screening with appropriate referral for identification of pre-metastatic lesions. Melanoma has a 16- to 25-month period to metastasize from a localized disease to one with a median survival no longer than 12 months once metastasis occurs. Nearly one third of oral metastases are found to be the first indication of occult malignancy from a distant site. This report describes the case of a 54-year-old woman with a longstanding undiagnosed acral lentiginous melanoma with metastasis to the maxillofacial region. She underwent resection and died 7 months later. The authors analyzed case reports and the current literature for biological mechanisms of metastasis, risk factors, clinical presentation, classifications, staging, treatment modalities, prognosis, and current therapy modalities.

Development of in-house serological methods for diagnosis and surveillance of chikungunya / Desarrollo de métodos serológicos propios para el diagnóstico y la vigilancia del chikungunya

Objective. To develop and evaluate serological methods for chikungunya diagnosis and research in Nicaragua. Methods. Two IgM ELISA capture systems (MAC-ELISA) for diagnosis of acute chikungunya virus (CHIKV) infections, and two Inhibition ELISA Methods (IEM) to measure total antibodies against CHIKV were developed using monoclonal antibodies (mAbs) and hyperimmune serum at the National Virology Laboratory of Nicaragua in 2014–2015. The sensitivity, specificity, predictive values, and agreement of the MAC-ELISAs were obtained by comparing the results of 198 samples (116 positive; 82 negative) with the Centers for Disease Control and Prevention’s IgM ELISA (Atlanta, Georgia, United States; CDC-MAC-ELISA). For clinical evaluation of the four serological techniques, 260 paired acute and convalescent phase serum samples of suspected chikungunya cases were used. Results. All four assays were standardized by determining the optimal concentrations of the different reagents. Processing times were substantially reduced compared to the CDC-MACELISA. For the MAC-ELISA systems, a sensitivity of 96.6% and 97.4%, and a specificity of 98.8% and 91.5% were obtained using mAb and hyperimmune serum, respectively, compared with the CDC method. Clinical evaluation of the four serological techniques versus the CDC real-time RT-PCR assay resulted in a sensitivity of 95.7% and a specificity of 88.8%–95.9%. Conclusion. Two MAC-ELISA and two IEM systems were standardized, demonstrating very good quality for chikungunya diagnosis and research demands. This will achieve more efficient epidemiological surveillance in Nicaragua, the first country in Central America to produce its own reagents for serological diagnosis of CHIKV. The methods evaluated here can be applied in other countries and will contribute to sustainable diagnostic systems to combat the disease.

Objetivo. Elaborar y evaluar métodos serológicos para el diagnóstico y la investigación del chikungunya. Métodos. Se elaboraron dos sistemas de ELISA de captura de IgM (MAC-ELISA por sus siglas en inglés) para el diagnóstico de la infección aguda por el virus de (CHIKV) y dos métodos de ELISA de inhibición (MEI) para determinar el valor cuantitativo de los anticuerpos totales contra el CHIKV, en el Laboratorio Nacional de Virología de Nicaragua en 2014–2015, para lo cual se utilizaron anticuerpos monoclonales (AcMo) y sueros hiperinmunes. Se determinó la sensibilidad, la especificidad y los valores predictivos, así como la concordancia de los MAC-ELISA, comparando los resultados de 198 muestras (116 positivas y 82 negativas) con el ELISA de los Centros para el Control y la Prevención de Enfermedades de los Estados Unidos (Atlanta; MACELISA- CDC). Para la evaluación clínica de las cuatro técnicas serológicas, se emplearon 260 muestras de suero obtenidas en la fase aguda y en la fase de convalecencia de presuntos casos de chikungunya. Resultados. Se estandarizaron los cuatro métodos analíticos determinando las concentraciones óptimas de los diferentes reactivos. La duración del procesamiento se redujo sustancialmente en comparación con el MAC-ELISA-CDC. Con los sistemas de MAC-ELISA, se obtuvo una sensibilidad del 96,6% y del 97,4% y una especificidad del 98,8% y del 91,5% al utilizar AcMo y suero hiperinmune, respectivamente, en comparación con el método de los CDC. La evaluación clínica de las cuatro técnicas serológicas, en comparación con la PCR en tiempo real de los CDC, arrojó una sensibilidad del 95,7% y una especificidad del 88,8%–95,9%. Conclusiones. Se estandarizaron dos sistemas de ELISA-MAC y dos de MEI y se comprobó que poseen la calidad adecuada para el diagnóstico y las investigaciones del chikungunya, con lo cual mejorará la eficiencia de la vigilancia epidemiológica en Nicaragua, el primer país centroamericano que produce sus propios reactivos para el diagnóstico serológico del CHIKV. Los métodos estudiados en este trabajo pueden aplicarse en otros países y contribuyen al desarrollo de sistemas de diagnóstico sostenibles para combatir la enfermedad.

Development of in-house serological methods for diagnosis and surveillance of chikungunya / Desarrollo de métodos serológicos propios para el diagnóstico y la vigilancia del chikungunya

ABSTRACT Objective To develop and evaluate serological methods for chikungunya diagnosis and research in Nicaragua. Methods Two IgM ELISA capture systems (MAC-ELISA) for diagnosis of acute chikungunya virus (CHIKV) infections, and two Inhibition ELISA Methods (IEM) to measure total antibodies against CHIKV were developed using monoclonal antibodies (mAbs) and hyperimmune serum at the National Virology Laboratory of Nicaragua in 2014-2015. The sensitivity, specificity, predictive values, and agreement of the MAC-ELISAs were obtained by comparing the results of 198 samples (116 positive; 82 negative) with the Centers for Disease Control and Prevention's IgM ELISA (Atlanta, Georgia, United States; CDC-MAC-ELISA). For clinical evaluation of the four serological techniques, 260 paired acute and convalescent phase serum samples of suspected chikungunya cases were used. Results All four assays were standardized by determining the optimal concentrations of the different reagents. Processing times were substantially reduced compared to the CDC-MAC-ELISA. For the MAC-ELISA systems, a sensitivity of 96.6% and 97.4%, and a specificity of 98.8% and 91.5% were obtained using mAb and hyperimmune serum, respectively, compared with the CDC method. Clinical evaluation of the four serological techniques versus the CDC real-time RT-PCR assay resulted in a sensitivity of 95.7% and a specificity of 88.8%-95.9%. Conclusion Two MAC-ELISA and two IEM systems were standardized, demonstrating very good quality for chikungunya diagnosis and research demands. This will achieve more efficient epidemiological surveillance in Nicaragua, the first country in Central America to produce its own reagents for serological diagnosis of CHIKV. The methods evaluated here can be applied in other countries and will contribute to sustainable diagnostic systems to combat the disease.

RESUMEN Objetivo Elaborar y evaluar métodos serológicos para el diagnóstico y la investigación del chikungunya. Métodos Se elaboraron dos sistemas de ELISA de captura de IgM (MAC-ELISA por sus siglas en inglés) para el diagnóstico de la infección aguda por el virus de (CHIKV) y dos métodos de ELISA de inhibición (MEI) para determinar el valor cuantitativo de los anticuerpos totales contra el CHIKV, en el Laboratorio Nacional de Virología de Nicaragua en 2014-2015, para lo cual se utilizaron anticuerpos monoclonales (AcMo) y sueros hiperinmunes. Se determinó la sensibilidad, la especificidad y los valores predictivos, así como la concordancia de los MAC-ELISA, comparando los resultados de 198 muestras (116 positivas y 82 negativas) con el ELISA de los Centros para el Control y la Prevención de Enfermedades de los Estados Unidos (Atlanta; MAC-ELISA-CDC). Para la evaluación clínica de las cuatro técnicas serológicas, se emplearon 260 muestras de suero obtenidas en la fase aguda y en la fase de convalecencia de presuntos casos de chikungunya. Resultados Se estandarizaron los cuatro métodos analíticos determinando las concentraciones óptimas de los diferentes reactivos. La duración del procesamiento se redujo sustancialmente en comparación con el MAC-ELISA-CDC. Con los sistemas de MAC-ELISA, se obtuvo una sensibilidad del 96,6% y del 97,4% y una especificidad del 98,8% y del 91,5% al utilizar AcMo y suero hiperinmune, respectivamente, en comparación con el método de los CDC. La evaluación clínica de las cuatro técnicas serológicas, en comparación con la PCR en tiempo real de los CDC, arrojó una sensibilidad del 95,7% y una especificidad del 88,8%-95,9%. Conclusiones Se estandarizaron dos sistemas de ELISA-MAC y dos de MEI y se comprobó que poseen la calidad adecuada para el diagnóstico y las investigaciones del chikungunya, con lo cual mejorará la eficiencia de la vigilancia epidemiológica en Nicaragua, el primer país centroamericano que produce sus propios reactivos para el diagnóstico serológico del CHIKV. Los métodos estudiados en este trabajo pueden aplicarse en otros países y contribuyen al desarrollo de sistemas de diagnóstico sostenibles para combatir la enfermedad.

Evaluation of immunological markers in serum, filter-paper blood spots, and saliva for dengue diagnosis and epidemiological studies.

BACKGROUND: Numerous immunological approaches exist to diagnose dengue or detect dengue virus (DENV) infections. OBJECTIVES: To determine the best immunological markers and specimen types for dengue diagnosis and for measuring incidence of DENV infection in community-based studies. STUDY DESIGN: In one study, acute- and convalescent-phase samples were collected from hospitalized suspected pediatric dengue cases in Managua, Nicaragua, from September 2003 to February 2004. A second study examined specimens collected in a community setting in Managua before and after the 2003-2004 dengue season to measure incidence of DENV infection. In both studies, detection of anti-DENV IgM, IgA, and IgG in serum, filter-paper blood spots, and saliva was compared to a gold standard performed on serum samples. RESULTS: For dengue diagnosis, the highest sensitivity and specificity was obtained by measuring IgM or IgA in serum or filter-paper blood spots; intermediate and poor results were obtained in saliva for IgM and IgA, respectively. Detection of IgG alone in serum, filter-paper blood spots, or saliva functioned best for measuring DENV infection. CONCLUSIONS: Detection of IgM and IgA in serum and filter-paper blood spots yielded optimal results for diagnosis of dengue cases, whereas IgG was the best marker for measuring incidence of DENV infection.

A phase II study of gemcitabine plus cisplatin in previously untreated advanced ovarian cancer.

BACKGROUND: The primary objective was the evaluation of the effects of gemcitabine plus cisplatin on the overall response rate (ORR) of patients with advanced ovarian cancer; the secondary assessments included toxicity, time to progressive disease (TtPD) and the duration of response. MATERIALS AND METHODS: Chemonaive patients with stage III/IV ovarian cancer received gemcitabine 1250 mg/m2 (d 1,8) and cisplatin 75 mg/m2 (d 1), every 21 days for a maximum of six cycles. RESULTS: Between March 1999 and June 2003, 28 patients (median age 52 years, range 23-72) had received chemotherapy. Of 26 assessable patients, the ORR was 57.7% (95% CI, 42.7%-83.6%) based on four complete responses and eleven partial responses, six patients experienced stable disease, while five had progressive disease. The median survival was 28.1 months (95% CI, 11.4-33.4 months), the median TtPD was 10.5 months (95% CI, 1.4-44.2 months) and the median duration of response was 24.3 months (95% CI, 12.3-33.4 months). The most common grade 3/4 toxicities were nausea/vomiting (15.2%) and neutropenia (10.7%). There was no grade 3 or 4 thrombocytopenia. CONCLUSION: Gemcitabine plus cisplatin exhibited activity in advanced ovarian cancer with an acceptable toxicity profile.

High seroprevalence of antibodies against dengue virus in a prospective study of schoolchildren in Managua, Nicaragua.

To investigate the incidence of dengue virus (DENV) infection in Nicaragua, a 2-year prospective study was conducted in schoolchildren 4-16 years old in the capital city of Managua. Blood samples were collected before the rainy season in 2001, 2002 and 2003, and were assayed for DENV-specific antibodies. Participants were monitored for dengue-like illness, and acute and convalescent blood samples were collected from suspected dengue cases. In 2001 and 2002, 602 and 397 students were recruited, respectively, and paired annual serum samples were available from 467 and 719 participants in 2001-2002 and 2002-2003, respectively. The overall seroprevalence of anti-DENV antibodies was 91%, increasing from 75% at age 4 to 100% at age 16. The incidence of DENV infection was 12% in Year 1 and 6% in Year 2 (P < 0.001). During Year 1, four laboratory-confirmed dengue cases were detected, with one DENV2 isolate; during Year 2, there were six confirmed dengue cases, with one DENV1 isolate. These and additional circulating serotypes were confirmed by plaque reduction neutralisation test. This study demonstrates surprisingly high transmission of DENV in urban Nicaragua.

Phase II study of gemcitabine plus cisplatin in metastatic breast cancer.

Our objectives were to assess the efficacy and toxicity of gemcitabine plus cisplatin as first-line therapy in metastatic breast cancer (MBC). Patients with stage IV MBC and no prior chemotherapy for metastatic disease were treated with gemcitabine 1200 mg/m on days 1 and 8, and cisplatin 75 mg/m on day 1 every 21 days. Up to 6 cycles were given. A total of 46 patients with a median age of 49 years (range 24-77) and Karnofsky performance status of 80 or above were enrolled. In total, 238 cycles were administered. Of the 42 patients evaluable for response, seven (17%) achieved a complete response and 27 (64%) a partial response, for an overall response rate of 81% [95% confidence interval (CI) 69-93%]. Median time to progression was 14.9 months (95% CI 0-30.2 months). Median duration of response was 24.2 months (95% CI 11.2-37.3 months). The median survival was 27.9 months (95% CI 23.1-32.7 months), and the 1- and 2-year survival probabilities were 71.4 and 61.4%, respectively. All patients were evaluable for toxicity, and grade 3/4 WHO toxicities included neutropenia (41.3%), anemia (8.7%), thrombocytopenia (8.7%), alopecia (26.1%) and nausea/vomiting (32.6%). We conclude that gemcitabine plus cisplatin is a highly effective and safe first-line treatment for patients with MBC. The time to progression of 14.9 months compares favorably with other standard treatments (anthracyclines, taxanes). A randomized study is required to further investigate the role of this combination as first-line treatment for MBC.

Serotype-specific differences in clinical manifestations of dengue.

Dengue, the most prevalent arthropod-borne viral disease of humans, is caused by four serotypes of dengue virus (DENV 1-4). Although all four DENV serotypes cause a range of illness, defining precisely which clinical characteristics are associated with the distinct serotypes has been elusive. A cross-sectional study was conducted on 984 and 313 hospitalized children with confirmed DENV infections during two time periods, respectively, in the same hospitals in Nicaragua: a 3-year period (1999-2001) when DENV-2 accounted for 96% of the viruses identified, and the 2003 dengue season when DENV-1 predominated (87% of identified serotypes). When the two periods were compared, more shock (OR 1.91, 95% CI 1.35-2.71) and internal hemorrhage (OR 2.05, CI 1.16-3.78) were observed in the period when DENV-2 predominated, whereas increased vascular permeability was associated to a greater degree with the DENV-1 period (OR 2.36, CI 1.80-3.09). Compared with the DENV-2 period, the DENV-1 season was associated with more hospitalized primary dengue cases (OR 3.86, CI 2.72-5.48) and more primary DENV infections with severe manifestations (OR 2.93, CI 2.00-4.28). These findings provide new data to characterize the pathogenic potential of distinct DENV serotypes in human populations.