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OBJECTIVE: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs), initially for type 2 diabetes mellitus, show promise in promoting weight loss and improving heart health in obese individuals without diabetes. Our goal was to examine existing research for conclusive evidence on various types of GLP-1 RAs for weight loss and cardiometabolic benefits in obesity without diabetes. METHODS: We conducted an electronic search on PubMed, Scopus, and Cochrane Central using keywords, such as "GLP-1 RA," "obesity," and "weight loss." We considered all available global GLP-1 RAs for inclusion. Our analysis focused on weight loss, blood pressure (BP) changes (systolic and diastolic BPs), and lipid profile effects (high-density lipoprotein, low-density lipoprotein, total cholesterol, and triacylglycerol). We used a random-effects meta-analysis with the standardized mean difference (SMD), mean difference (MD), odds ratio, and relative risk to present the results. RESULTS: Our search yielded a total of 7535 articles. We included 15 trials in our study. GLP-1 RAs led to significant weight loss (MD, -8.77 kg; P <.01) in obese individuals. GLP-1 RAs also improved the systolic BP (MD, -4.13 mm Hg; P <.01), diastolic BP (MD, -1.39 mm Hg; P <.01), and lipid profiles, including improved levels of triacylglycerol (SMD, -0.99 mg/dL; P <.01), total cholesterol (SMD, -0.73 mg/dL; P <.01), very low-density lipoprotein (SMD, -1.11 mg/dL; P <.01), and low-density lipoprotein (SMD, -0.27 mg/dL; P <.01), and significantly increased high-density lipoprotein levels (SMD, 0.11 mg/dL; P <.01). However, GLP-1 RAs were associated with an increased risk of gastrointestinal adverse events. CONCLUSION: GLP-1 RAs were found to be beneficial for not only weight loss but also reduction in risk factors for cardiovascular disease such as BP and lipid profile. Consistent beneficial results were observed across the various subtypes of GLP-1 RAs.
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Enfermedades Cardiovasculares , Diabetes Mellitus Tipo 2 , Humanos , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/complicaciones , Hipoglucemiantes/efectos adversos , Agonistas Receptor de Péptidos Similares al Glucagón , Péptido 1 Similar al Glucagón/efectos adversos , Obesidad/tratamiento farmacológico , Obesidad/complicaciones , Enfermedades Cardiovasculares/epidemiología , Enfermedades Cardiovasculares/prevención & control , Pérdida de Peso , Lípidos , Triglicéridos , Lipoproteínas HDL , Lipoproteínas LDL , Colesterol , Receptor del Péptido 1 Similar al Glucagón/agonistasRESUMEN
Cardiac arrhythmias pose a significant danger to human life; therefore, it is of utmost importance to be able to efficiently diagnose these arrhythmias promptly. There exist many techniques for the detection of arrhythmias; however, the most widely adopted method is the use of an Electrocardiogram (ECG). The manual analysis of ECGs by medical experts is often inefficient. Therefore, the detection and recognition of ECG characteristics via machine-learning techniques have become prevalent. There are two major drawbacks of existing machine-learning approaches: (a) they require extensive training time; and (b) they require manual feature selection. To address these issues, this paper presents a novel deep-learning framework that integrates various networks by stacking similar layers in each network to produce a single robust model. The proposed framework has been tested on two publicly available datasets for the recognition of five micro-classes of arrhythmias. The overall classification sensitivity, specificity, positive predictive value, and accuracy of the proposed approach are 98.37%, 99.59%, 98.41%, and 99.35%, respectively. The results are compared with state-of-the-art approaches. The proposed approach outperformed the existing approaches in terms of sensitivity, specificity, positive predictive value, accuracy and computational cost.
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Aprendizaje Profundo , Procesamiento de Señales Asistido por Computador , Algoritmos , Arritmias Cardíacas/diagnóstico , Electrocardiografía/métodos , Frecuencia Cardíaca , HumanosRESUMEN
PURPOSE: Sepsis and bacterial infections are common in patients with end-stage renal disease (ESRD). We aimed to compare patients with ESRD on hemodialysis presenting to hospital with severe sepsis or septic shock who received <20 ml/kg of intravenous fluid to those who received ≥20 ml/kg during initial resuscitation. MATERIALS AND METHODS: We conducted a retrospective chart review of adult patients with ICD codes for discharge diagnosis of sepsis, severe sepsis, septic shock, ESRD, and hemodialysis admitted to our institution between 2015 and 2018. RESULTS: We present outcomes for a total of 104 patients - 51 patients in conservative group and 53 in aggressive group. The mean age was 69.5 ± 11.2 years and 71 ± 11.5 years in the conservative group and aggressive group, respectively. There was no significant difference in the rate of ICU admission, and ICU or hospital length of stay between the two groups. Complications such as volume overload, rate of intubation, and urgent dialysis were not found to be significantly different. CONCLUSION: We found that aggressive fluid resuscitation with ≥20 ml/kg may not be detrimental in the initial resuscitation of ESRD patients with SeS or SS. However, a clinical decision of volume responsiveness should be made on a case-by-case basis rather than a universal approach for fluid resuscitation in ESRD patients.
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Fluidoterapia/métodos , Fallo Renal Crónico/complicaciones , Fallo Renal Crónico/terapia , Diálisis Renal , Choque Séptico/terapia , Anciano , Servicio de Urgencia en Hospital , Femenino , Hospitalización/estadística & datos numéricos , Humanos , Masculino , Estudios RetrospectivosRESUMEN
Shammah is a traditional form of smokeless tobacco (ST) that is manufactured and used locally by people of Middle East with highest usage in Saudi Arabia, Yemen and Sudan. In Saudi Arabia, shammah comes in three variants: white, brown and yellow. In the present study, we investigated the genotoxicity of yellow shammah (YS) on bone marrow (BM) cells in vivo using mice. Bone marrow (BM) chromosomal aberration (CA) and micronucleus (MN) assay were performed and hepatic markers of oxidative stress were determined. Swiss albino mice were divided into five groups (n = 6) including negative control (NC) and positive control (PC) groups. The three treated groups included YS-100, 200 and 300 mg/kg, doses freshly prepared in 0.5% carboxymethyl cellulose (CMC) and administered orally once a day for 2 weeks. PC animals were administered cyclophosphamide (CP) at a dose of 40 mg/kg body weight, 24 h before termination. Two weeks continuous treatment of YS induced a dose dependent and significant increase in aberrant metaphases (AM), CA per cell and depression in mitotic activity. In micronucleus assay, YS treatment increased the percentage of micronucleated polychromatic erythrocytes (MNPCE) frequency and showed statistically significant reduction in polychromatic erythrocyte/normochromatic erythrocyte ratio at all doses, as compared to NC. YS also markedly inhibited the activities of superoxide dismutase, reduced glutathione and increased malondialdehyde content. CP was used as clastogen (positive control) and yielded the expected positive results. Therefore, it may be concluded that YS has genotoxic and cytotoxic effects for BM cells of mice in vivo.
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Células de la Médula Ósea/efectos de los fármacos , Aberraciones Cromosómicas/efectos de los fármacos , Tabaco sin Humo/toxicidad , Animales , Ciclofosfamida/toxicidad , Relación Dosis-Respuesta a Droga , Glutatión/metabolismo , Malondialdehído/metabolismo , Ratones , Pruebas de Micronúcleos/métodos , Medio Oriente , Pruebas de Mutagenicidad , Estrés Oxidativo/efectos de los fármacos , Superóxido Dismutasa/metabolismoRESUMEN
The management of ovarian immature teratoma (IT) presents several challenges. It occurs both in children and adults and therefore is managed by pediatric oncologists as well as adult and gynecologic oncologists. Treatment approach; however, varies significantly. Unlike pediatric patients in whom surgery is considered the mainstay of treatment, adult providers routinely prescribe postoperative chemotherapy. Management of recurrent IT can be challenging. Growing teratoma syndrome may occur after treatment of recurrent IT. We report the development and management of this phenomenon in a pediatric patient who had several recurrences of her IT.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Recurrencia Local de Neoplasia/tratamiento farmacológico , Recurrencia Local de Neoplasia/patología , Neoplasias Ováricas/tratamiento farmacológico , Neoplasias Ováricas/patología , Teratoma/tratamiento farmacológico , Teratoma/patología , Adolescente , Femenino , Humanos , Recurrencia Local de Neoplasia/cirugía , Neoplasias Ováricas/cirugía , Síndrome , Teratoma/cirugíaRESUMEN
This study was aimed to assess the genotoxicity of brown shammah (BS), a local form of smokeless tobacco, popular in Middle East countries including Yemen, Saudi Arabia and Sudan. The genotoxicity was explored using in vivo chromosomal aberration (CA), micronucleus (MN) and sperm abnormality (SA) assays. In addition, oxidative stress was also determined using various hepatic markers. Swiss albino mice were selected for the study, which were divided in to 5 groups of six animals each. They include, negative control (NC, received only vehicle) as well as positive control group (PC, received vehicle for 2 weeks followed by administration of cyclophosphamide, CP). Depending upon their dose, three BS treated animal groups were BS-100, 300 and 900 mg/kg. Doses of BS were obtained by suspending BS in 0.5% CMC (carboxy methyl cellulose) and orally administered once a day for 2 weeks. Significant augmentation of the average percentage of aberrant metaphase (AM), CA per cells and suppressed mitotic activity was observed on post administration of BS. In addition, BS increased the occurrence of MNPCEs (micronucleated polychromatic erythrocytes) formation, induced cytotoxicity and increased percentage of abnormal sperms as compared to NC. Moreover, BS also induced oxidative stress as the activities of hepatic superoxide dismutase (SOD) and glutathione (GSH) were reduced and malondialdehyde (MDA) content were increased by BS. Cyclophosphamide was utilized as clastogen, showed anticipated positive results and confirmed the sensitivity of test system. Therefore, it may be deduced from the study that the BS possesses genotoxic effects on mice bone marrow and germ cells in vivo.
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Colorectal carcinoma is one of the most common and significant causes of cancer-related death. Metastasis to mediastinal lymph nodes and/or pleura without liver or lung involvement is an atypical pattern of colon cancer metastasis. A 70-year-old male underwent curative right side hemicolectomy and omentectomy for ascending colon cancer followed by adjuvant chemotherapy. Around nine months after surgery, the patient was noted to have bilateral large pleural effusions on the restaging computed tomography scan of the chest/abdomen/pelvis. No intraabdominal or intrathoracic mass/metastasis was seen on the imaging. Multiple thoracentesis performed over the course of next few months revealed exudative effusion but failed to demonstrate malignant cells. A few months later, new mediastinal and right hilar lymphadenopathy was noted on the repeat computed tomography scan. A subsequent positron-emission tomography scan revealed multiple sites of fluorodeoxyglucose (FDG)-avid mediastinal lymphadenopathy. The sites of pleural effusion were not fluorodeoxyglucose-avid. Endobronchial ultrasound and biopsy of mediastinal nodes showed adenocarcinoma with signet-ring features. Immunohistochemistry confirmed the diagnosis of metastatic colon cancer. Systemic treatment with chemotherapy was initiated. Our case highlights the importance of mediastinal evaluation by imaging during the follow-up of patients with colorectal carcinoma. The ideal management strategy for mediastinal metastasis of colorectal carcinoma remains a question, two major options being local metastasectomy or systemic chemotherapy.
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Adenocarcinoma/secundario , Neoplasias del Colon/cirugía , Neoplasias del Mediastino/secundario , Anciano , Humanos , Metástasis Linfática , Masculino , Derrame PleuralRESUMEN
OBJECTIVE: To evaluate the accuracy of biometry in the post-op phase of cataract surgery. METHODS: This study was conducted at Liaquat National Hospital, Karachi, from June 2015 to July 2016, and comprised the audit of patients who underwent cataract surgery during the period. Keratometry was done on Haag-Strait manual keratometer and A-scan was done by applanation contact method on SonoMed machine. Theoretic-T formula was used to calculate desired intraocular lens power for all kinds of axial lengths. A single surgeon operated upon the same Alcon Constellation phacoemulsification machine. Postoperative follow-up was done by monitoring auto refraction and visual acuity on days 1, 7, 30 and 90. SPSS 21 was used for data analysis.. RESULTS: Of 244 patients, 121(49.60%) were males and 123(50.40%) were females. There were 123(50.40%) right eyes and 121(49.60%) left eyes. Overall, 132(54.10%) achieved postoperative refraction within ±0.5 D of target and 193(79.10%) within ±1 D of target. Age, gender and laterality had no significant effect on outcomes (p>0.05 each). CONCLUSIONS: Postoperative refraction corresponded quite closely with global recommendations.
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Implantación de Lentes Intraoculares/normas , Lentes Intraoculares , Facoemulsificación/normas , Adulto , Anciano , Biometría , Femenino , Humanos , Lentes Intraoculares/normas , Lentes Intraoculares/estadística & datos numéricos , Masculino , Auditoría Médica , Persona de Mediana Edad , Pakistán , Centros de Atención Terciaria , Agudeza Visual/fisiologíaRESUMEN
OBJECTIVE: To analyse the frequency of different types of amblyopia and its association with gender. METHODS: The cross-sectional study was conducted from March 2014 to October 2014 at the Department of Ophthalmology of a tertiary care hospital inKarachi. The patients were classified into different types of amblyopia like anisometropic, strabismic, sensory deprivation and meridional amblyopia. Stratification was done according to age, gender and type of amblyopia by using SPSS version 21. RESULTS: Out of 130 patients, 71 were male and 59 were female. The amblyopia rate determined was anisometropic 69.23%, strabismic amblyopia 21.51% and others 9.23%. The mean age of subjects was 18.02±9 years. Type of amblyopia was independent of gender, and anisometropic amblyopia was the most common type of amblyopia found in both genders. CONCLUSIONS: This study found no significant association between gender and types of amblyopia and anisometropic amblyopia was the most common type of amblyopia in the data collected.
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Ambliopía/clasificación , Adolescente , Adulto , Ambliopía/epidemiología , Niño , Estudios Transversales , Femenino , Humanos , Masculino , Pakistán/epidemiología , Factores Sexuales , Centros de Atención Terciaria , Adulto JovenRESUMEN
The study assessed changes in cerebral blood flow and need for chronic blood transfusions in sickle cell disease children after splenectomy. A retrospective chart review of 40 children splenectomized between 1999 and 2014 was performed. The mean time-average maximum velocity before splenectomy was 129 cm/sec; which increased to 157 cm/sec and then decreased to 137 cm/sec, 2 and 5 years postsplenectomy, respectively. There was a persistent and statistically significant elevation in platelet count noted after splenectomy. The mean cerebral blood flow velocity seemed to increase transiently after splenectomy. Close monitoring and screening for stroke risk should be continued postsplenectomy.
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Anemia de Células Falciformes/fisiopatología , Anemia de Células Falciformes/cirugía , Circulación Cerebrovascular , Esplenectomía , Adolescente , Velocidad del Flujo Sanguíneo , Niño , Preescolar , Femenino , Estudios de Seguimiento , Humanos , MasculinoRESUMEN
UNLABELLED: Hemostatic system is designed to maintain blood in a fluid state yet provide important defenses against bleeding when injury occurs to the vessel. During surgery, patients are exposed to hemostatic stress causing complications of either hypercoagulability or hemorrhage. The goal of the present study was to describe the clotting changes in patients who underwent major surgeries especially procoagulant mechanisms. METHODS: 30 patients belonging to both sexes who were undergoing surgery for various reasons were included in the study. Tests to assess the integrity of hemostatic system were conducted. Results: Analysed and expressed in mean and SD. There was a significant (p < 0.05) difference in the hemostatic parameters like bleeding time, clotting time, thrombin time, platelet count and fibrinogen concentration between the preoperative and postoperative periods.
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Trastornos de la Coagulación Sanguínea/etiología , Pérdida de Sangre Quirúrgica , Hemostasis , Hemorragia Posoperatoria/etiología , Adulto , Anciano , Biomarcadores/sangre , Trastornos de la Coagulación Sanguínea/sangre , Pruebas de Coagulación Sanguínea , Femenino , Fibrinógeno/metabolismo , Humanos , Masculino , Persona de Mediana Edad , Recuento de Plaquetas , Hemorragia Posoperatoria/sangre , Factores de Tiempo , Adulto JovenRESUMEN
Rumex vesicalius L. (Polygonaceae) is an annual, monoecious, glabrous, pale green herb cultivated as a leafy vegetable in south western Asia and northern Africa. Its seeds are prescribed as a refrigerant, laxa- tive, antidote for scorpion venom and to cure dysentery and liver diseases. Phytochemical investigation of a methanolic extract of the seeds of R. vesicarius resulted in the isolation of a new aliphatic ester n-heptacosanyl n-hexanoate (2), a steroidal diglucoside stigmasta-5-en-3-ol-3-O-ß-D-glucopyranosido-(4--->1")-O-ß-D-glu- copyranoside (3) and two bioflavonoids characterized as (2a,3a-trans)-3a(ß),5a,7a,3'a,4'a-pentahydroxyfla- vanolyl-(8a-2')-5,7,3'-trihydroxy-4'-methoxy-8-n-but-3"-enyl-flavanone (4) and 5,7,3',4',5'-pentahydroxy- 8-(cis-1" α,2"ß-dihydroxyhept-4"-enyl-7"-oic acid)-flavanoyl-(2'--8a)-5a,7a,3'a,5'a-tetrahydroxy-4'a- methoxyflavanone (5) together with stigmasterol (1). The structures of all the isolated phytoconstituents have been established on the basis of spectral data analysis and chemical reactions.
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Biflavonoides/análisis , Rumex/química , Sitoesteroles/análisis , Biflavonoides/química , Ésteres/análisis , Semillas/química , Sitoesteroles/químicaRESUMEN
Key Clinical Message: Timely diagnosis, multidisciplinary surgical intervention, and appropriate imaging are crucial in managing transorbital-penetrating intracranial injuries (TOPIs), minimizing morbidity, and optimizing patient outcomes. Abstract: Transorbital-penetrating intracranial injuries (TOPIs) are rare occurrences with potential for severe neurological complications and high mortality rates. Prompt diagnosis and management are essential to mitigate adverse outcomes. Understanding injury patterns and employing appropriate imaging modalities are crucial for effective surgical planning and patient care. We present a case of a 22-year-old male mechanic who sustained a TOPI involving bilateral frontal lobes with evisceration of the right eye following a workplace accident with a metal cutter. Upon arrival at the emergency department, the patient exhibited vision loss in the right eye, proptosis, and a dilated pupil. Imaging studies revealed the trajectory of a metal arrow through the right orbital roof, necessitating surgical intervention. A multidisciplinary team performed bifrontal craniectomy with duroplasty to remove the foreign body and address associated injuries. Postoperatively, the patient received broad-spectrum antibiotics and anticonvulsants, leading to full recovery and discharge on postoperative day 10. TOPIs present unique challenges due to their rarity and potential for devastating consequences. Our case highlights the importance of timely diagnosis, meticulous surgical planning, and multidisciplinary collaboration in achieving favorable outcomes. Radiological imaging plays a crucial role in guiding treatment decisions and optimizing patient care. This report underscores the significance of early surgical intervention, antimicrobial therapy, and prophylactic measures in reducing morbidity and mortality associated with TOPIs.
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PURPOSE: Bintrafusp alfa, a first-in-class bifunctional fusion protein composed of the extracellular domain of TGFß receptor II (a TGFß "trap") fused to a human IgG1 mAb blocking programmed death-ligand 1 (PD-L1), was evaluated as treatment in patients with locally advanced or persistent, recurrent, or metastatic (P/R/M) cervical cancer. PATIENTS AND METHODS: In this multicenter, open-label, phase Ib trial (NCT04551950), patients with P/R/M cervical cancer received bintrafusp alfa 2,400 mg once every 3 weeks plus cisplatin or carboplatin plus paclitaxel with (Cohort 1A; n = 8) or without (Cohort 1B; n = 9) bevacizumab; patients with locally advanced cervical cancer received bintrafusp alfa 2,400 mg every 3 weeks plus cisplatin plus radiation, followed by bintrafusp alfa monotherapy maintenance (Cohort 2; n = 8). The primary endpoint was safety; secondary endpoints included efficacy (including objective response rate) and pharmacokinetics. RESULTS: At the data cutoff of April 27, 2022, patients in Cohorts 1A, 1B, and 2 had received bintrafusp alfa for a median duration of 37.9, 31.1, and 16.7 weeks, respectively. Two dose-limiting toxicities (grade 4 amylase elevation and grade 3 menorrhagia) unrelated to bintrafusp alfa were observed in Cohort 1B and none in other cohorts. Most treatment-emergent adverse events of special interest were grades 1-2 in severity, most commonly anemia (62.5%-77.8%) and bleeding events (62.5%-77.8%). Objective response rate was 75.0% [95% confidence interval (CI), 34.9-96.8], 44.4% (95% CI, 13.7-78.8), and 62.5% (95% CI, 24.5-91.5) in Cohorts 1A, 1B, and 2, respectively. CONCLUSIONS: Bintrafusp alfa had manageable safety and demonstrated clinical activity, further supporting the investigation of TGFß/PD-L1 inhibition in human papillomavirus-associated cancers, including cervical cancer.
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Neoplasias del Cuello Uterino , Femenino , Humanos , Neoplasias del Cuello Uterino/tratamiento farmacológico , Antígeno B7-H1 , Cisplatino/efectos adversos , Recurrencia Local de Neoplasia/tratamiento farmacológico , Factores Inmunológicos , Paclitaxel/efectos adversos , Factor de Crecimiento Transformador betaRESUMEN
Mucormycosis is a rare, but invasive infection caused by ubiquitous molds. Amphotericin B and surgery have been known to help improve the outcome. Sporadic case reports support the use of posaconazole in adults. We report a toddler with acute lymphoblastic leukemia who acquired rhino-orbital mucormycosis caused by Rhizopus species at the end of induction chemotherapy. She was successfully treated with multiple surgical debridements, amphotericin B, posaconazole and hyperbaric oxygen therapy. In conclusion, mucormycosis is a serious infection that requires aggressive surgical and medical therapy. To the best of our knowledge the use of posaconazole combined with hyperbaric oxygen therapy has not been reported in a toddler with leukemia and invasive Rhizopus sp. infection. This approach was found to be safe and effective in our patient.
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Oxigenoterapia Hiperbárica , Mucormicosis/microbiología , Enfermedades Orbitales/microbiología , Leucemia-Linfoma Linfoblástico de Células Precursoras/complicaciones , Rhizopus/efectos de los fármacos , Triazoles/uso terapéutico , Adulto , Anfotericina B/uso terapéutico , Antifúngicos/uso terapéutico , Preescolar , Terapia Combinada , Femenino , Humanos , Mucormicosis/diagnóstico , Mucormicosis/tratamiento farmacológico , Enfermedades Orbitales/tratamiento farmacológico , Enfermedades Orbitales/patología , Leucemia-Linfoma Linfoblástico de Células Precursoras/microbiología , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Pronóstico , Inducción de Remisión , Tomografía Computarizada por Rayos XRESUMEN
We performed a retrospective chart review of children with sickle cell disease hospitalized for fever at our local institution. We reviewed 456 hospitalizations in 133 patients between January 2006 and June 2012. The prevalence of true bacteremia was 4%. The mean C-reactive protein values and temperatures were nonsignificantly higher in patients with positive blood cultures. The mean time to detection was 22.5 hours in bacteremia compared to 32.6 hours in blood cultures that grew contaminants (p = .034). Only two (0.4%) cases of pneumococcal bacteremia were reported and both occurred before May 2010, which marks the introduction of 13-valent pneumococcal vaccine (PCV13). Both patients with pneumococcal bacteremia had discontinued penicillin prophylaxis after the age of 5 years. The first patient was immunized but contracted a nonvaccine serotype (23B). The second patient was partially vaccinated and acquired a vaccine-preventable serotype (23F). Both serotypes were sensitive to ceftriaxone and vancomycin; one was resistant to penicillin. This is the first study reporting the prevalence of pneumococcal bacteremia since the introduction of PCV13.
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Anemia de Células Falciformes/complicaciones , Neumonía Neumocócica/epidemiología , Streptococcus pneumoniae/aislamiento & purificación , Adolescente , Alabama/epidemiología , Anemia de Células Falciformes/microbiología , Niño , Preescolar , Femenino , Estudios de Seguimiento , Humanos , Lactante , Masculino , Vacunas Neumococicas/uso terapéutico , Neumonía Neumocócica/microbiología , Neumonía Neumocócica/prevención & control , Prevalencia , Pronóstico , Estudios RetrospectivosRESUMEN
Comorbidities such as diabetes worsen COVID-19 severity and recovery. Metformin, a first-line medication for type 2 diabetes, has antiviral properties and certain studies have also indicated its prognostic potential in COVID-19. Here, we report that metformin significantly inhibits SARS-CoV-2 growth in cell culture models. First, a steady increase in AMPK phosphorylation was detected as infection progressed, suggesting its important role during viral infection. Activation of AMPK in Calu3 and Caco2 cell lines using metformin revealed that metformin suppresses SARS-CoV-2 infectious titers up to 99%, in both naïve as well as infected cells. IC50 values from dose-variation studies in infected cells were found to be 0.4 and 1.43 mM in Calu3 and Caco2 cells, respectively. Role of AMPK in metformin's antiviral suppression was further confirmed using other pharmacological compounds, AICAR and Compound C. Collectively, our study demonstrates that metformin is effective in limiting the replication of SARS-CoV-2 in cell culture and thus possibly could offer double benefits as diabetic COVID-19 patients by lowering both blood glucose levels and viral load.
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Dubin-Johnson syndrome (DJS) is a rare autosomal recessive genetic disease caused by mutations in the bilirubin transporter MRP2. It is characterized by recurrent episodes of jaundice and conjugated hyperbilirubinemia. Numerous instances of hyperbilirubinemia disorders resembling Dubin-Johnson syndrome have been documented, but they differ in the clinical presentation, amount of conjugated bilirubin present, and their reaction to therapy. Most people with this syndrome do not have any symptoms, so their cases are often misdiagnosed and not properly taken care of. Here, we present a case of a teenage male patient who complained of recurring jaundice and abdominal pain. Further examination and testing revealed that the patient had been jaundiced since birth and had a family history of the condition. Conservative management was implemented, and follow-up demonstrated a positive prognosis. This case is a rare example of Dubin-Johnson syndrome, although patients with the condition generally have a normal life expectancy and only require conservative management.
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INTRODUCTION: According to American Heart Association standards, hypertension is classified into three stages based on blood pressure measurements: essential hypertension, stage 1 hypertension, and stage 2 hypertension. The global target is to reduce the prevalence of high blood pressure by 25% by the year 2025. Worldwide, the prevalence of high blood pressure among men and women aged 18 and above reported to be 24% and 20%, respectively. AIM: The aim of this study was to overall reduce high blood pressure of hypertensive patients to the recommended level of 140/90 mm of Hg through implementing a non-pharmacological and multi-component intervention based on Disease Control Priorities (3rd edition). METHODS: A randomized controlled trial in which a multi-component intervention for lowering high blood pressure was tested. This was pilot-tested for its acceptance, appropriateness, and relevance, explored through an earlier formative research and desk review conducted from the available evidence. A total of 240 study participants were enrolled after obtaining informed consent. Ethical approval was obtained from the Institutional Review Board of Health Services Academy and the trial was registered in clinicaltrials.gov number NCT04336631. SPSS software version 21 was used to enter and analyze the data. RESULTS: High blood pressure of hypertensive patients in a hospital setting during 03 months yielded -23.9 mm Hg of systolic blood pressure reduction (95% confidence interval, p ≤ 0.005). A significant reduction was observed in intervention group after delivering the intervention. Compared to patients in the usual care group, improved health outcomes were achieved for diet control, reducing salt intake and increased physical exercise. In the intervention group, the mean blood pressure among male hypertensive patients was 145/90 mm Hg and in female hypertensive patients, the mean blood pressure was recorded as 140/100 mm Hg. CONCLUSION: High blood pressure was significantly reduced in hypertensive patients who adhered to a low salt diet, weight loss measures, and increased physical activity.
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Hipertensión , Hipotensión , Humanos , Masculino , Femenino , Presión Sanguínea , Pakistán/epidemiología , Hipertensión/diagnóstico , Hipertensión/epidemiología , Hipertensión/terapia , Ejercicio FísicoRESUMEN
Background and objectives: The incidence of morbidity and mortality in patients with type 2 diabetes mellitus is substantially correlated with cardiovascular disease and chronic kidney disease. The current guidelines recommend the use of renin-angiotensin system blockers, but recent studies probed into the effects of finerenone to mitigate the risk of cardiorenal events. This meta-analysis was performed to demonstrate the effects of finerenone on cardiorenal events, comprising cardiovascular mortality, heart failure, change in estimated glomerular filtration rate, and serum potassium levels. Methods: After screening with our eligibility criteria, 350 articles were identified with an initial literature search on multiple databases, including PubMed, Science Direct, and Cochrane Central. Seven randomized controlled trials with a total of 15 462 patients (n=8487 in the finerenone group; n=6975 in the control group) were included. Results: Patients receiving finerenone were at a reduced risk for cardiovascular mortality [HR: 0.84 (0.74, 0.95)], heart failure [OR: 0.79 (0.68, 0.92)], decrease in estimated glomerular filtration rate by 40% [OR: 0.82 (0.74, 0.91)] and by 57% [OR: 0.70 (0.59, 0.82)]; and a higher incidence of moderate hyperkalemia [OR: 2.25 (1.78, 2.84)]. Conclusion: Finerenone, owing to its better mineralocorticoid affinity, and a much lower risk of adverse effects, promises to be a much better alternative than other renin-angiotensin system blockers available for the treatment of chronic kidney disease patients with type 2 diabetes. Further trials should be conducted to provide more definitive evidence to assess the safety and efficacy of finerenone compared to spironolactone and eplerenone.