Preclinical study of a novel ingestible bleeding sensor for upper gastrointestinal bleeding

Background/Aims@#Upper gastrointestinal bleeding (UGIB) is a life-threatening condition that necessitates early identification and intervention and is associated with substantial morbidity, mortality, and socioeconomic burden. However, several diagnostic challenges remain regarding risk stratification and the optimal timing of endoscopy. The PillSense System is a noninvasive device developed to detect blood in patients with UGIB in real time. This study aimed to assess the safety and performance characteristics of PillSense using a simulated bleeding model. @*Methods@#A preclinical study was performed using an in vivo porcine model (14 animals). Fourteen PillSense capsules were endoscopically placed in the stomach and blood was injected into the stomach to simulate bleeding. The safety and sensitivity of blood detection and pill excretion were also investigated. @*Results@#All the sensors successfully detected the presence or absence of blood. The minimum threshold was 9% blood concentration, with additional detection of increasing concentrations of up to 22.5% blood. All the sensors passed naturally through the gastrointestinal tract. @*Conclusions@#This study demonstrated the ability of the PillSense System sensor to detect UGIB across a wide range of blood concentrations. This ingestible device detects UGIB in real time and has the potential to be an effective tool to supplement the current standard of care. These favorable results will be further investigated in future clinical studies.

Novel upper gastrointestinal bleeding sensor capsule: a first human feasibility and safety trial

Background/Aims@#Upper gastrointestinal bleeding (UGIB) is the most common GI condition requiring hospitalization, and can be diagnosed by direct visualization. The present study aimed to evaluate the safety and feasibility of using the PillSense system (EnteraSense Ltd.), a novel diagnostic tool designed for the rapid in vivo detection of UGIB, in human volunteers. @*Methods@#In the present study, 10 volunteers swallowed a PillSense capsule, followed by 2 servings of an autologous blood preparation. Participants were monitored for capsule passage, overall tolerability of the procedure, and adverse events. @*Results@#The procedure was completed per the protocol established in the present study in 9/10 cases. In 9 of the subjects, after capsule ingestion, the device indicated the absence of blood with sensor output values of 1. After the ingestion of the first blood mixture, the sensor outputs of all devices increased from 2.8 to 4, indicating that each camera detected blood. The sensor output remained within that range after the ingestion of the second mixture; however, in one case, the baseline capsule signal was positive, because of a preexisting condition. The passage of the capsule was verified in all patients, and no adverse events were reported. @*Conclusions@#The first trial of the PillSense system in human subjects demonstrated the feasibility, safety, and tolerability of utilizing this product as a novel, noninvasive, and easy-to-use triage tool for the diagnosis of patients suspected of having UGIB.

Outcomes of Injection Laryngoplasty for Deep Interarytenoid Groove

Abstract Introduction Deep interarytenoid groove (DIG) may cause swallowing dysfunction in children; however, the management of DIG has not been established. Objective We evaluated the subjective and objective outcomes of interarytenoid augmentation with injection in children with DIG. Methods Consecutive children under 18 years of age who underwent injection laryngoplasty for DIG were reviewed. Data pertaining to demographics, past medical history, past surgical history, and results of pre and postoperative video fluoroscopic swallow study (VFSS) were obtained. The primary outcome measure was the presence of thin liquid aspiration or penetration on postoperative VFSS. The secondary outcome measure was caregiver-reported improvement of symptoms. Results Twenty-seven patients had VFSS before and after interarytenoid augmentation with injection (IA). Twenty (70%) had thin liquid penetration and 12 (44%) had thin liquid aspiration before the IA. Thin liquid aspiration resolved in 9 children (45%) and persisted in 11 (55%). Of the 12 children who had thin liquid aspiration prior to IA, 6 (50%) had resolution of thin liquid aspiration after IA. Conclusions Injection laryngoplasty is a safe tool to improve swallowing function in children with DIG. Further studies are needed to assess the long-term outcomes of IA and identify predictors of successful IA in children with DIG.

In vitro antibacterial and antibiofilm activities of Piper betle L. ethanolic leaf extract on staphylococcus aureus ATCC 29213

Background and Objective@#Staphylococcus aureus is the leading cause of skin and soft tissue infections such as abscesses, furuncles, and cellulitis. Biofilm forming strains of S. aureus have higher incidence of antimicrobial resistance to at least three or more antibiotics and are considered as multidrug resistant. Since S. aureus biofilm-producing strains have higher rates of multidrug and methicillin resistance compared to non-biofilm-producing strains, the need for alternative therapeutic option is important. Furthermore, rates of methicillin-resistant Staphylococcus aureus (MRSA) in Asia remain high. Results of the study may provide support for the clinical uses of P. betle as a topical antibacterial and antiseptic in the treatment and prevention of infections involving the skin, mouth, throat, and indwelling medical devices. Thus, this study aimed to evaluate the in vitro antibacterial and antibiofilm activities of Piper betle L. ethanolic leaf extract (PBE) against a biofilm-forming methicillin-sensitive Staphylococcus aureus ATCC 29213 (MSSA).@*Methods@#The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of PBE against MSSA were determined using the agar dilution assay. The biofilm inhibition and eradication assays using crystal violet were done to quantify the antibiofilm activities of PBE on MSSA biofilm.@*Results@#PBE showed activity against MSSA in agar dilution assay with MIC and MBC values of 2500 μg/mL and 5000 μg/mL, respectively. At subinhibitory concentrations, PBE showed biofilm inhibition activity at 1250 μg/mL but a lower percent eradication of biofilms as compared to oxacillin was noted.@*Conclusion@#PBE showed antibacterial activities including biofilm inhibition against methicillin-sensitive Staphylococcus aureus ATCC 29213 (MSSA).

Mathematical modelling approach of the study of Ebola virus disease transmission dynamics in a developing country

Background: Ebola Virus causes disease both in human and non-human primatesespecially in developing countries. In 2014 during its outbreak, it led to majority of deaths especially in some impoverished area of West Africa and its effect is still witnessed up till date. Materials and Methods:We studied the spread of Ebola virus and obtained a system of equations comprising of eighteen equations which completely described the transmission of Ebola Virus ina population where control measures were incorporated and a major source of contacting the disease which is the traditional washing of dead bodies was also incorporated. We investigated the local stability of the disease-free equilibrium using the Jacobian Matrix approach and the disease-endemic stability using the center manifold theorem. We also investigated the global stability of the equilibrium points using the LaSalle's Invariant principle.Results: The result showed that the disease-free and endemic equilibrium where both local and globally stable and that the system exhibits a forward bifurcation.Conclusions: Numerical simulations were carried out and our graphs show that vaccine and condom use is best for susceptible population, quarantine is best for exposed population, isolation is best for infectious population and proper burial of the diseased dead is the best to avoid further disease spread in the population and have quicker and better recovery.

Kindlin-2 loss in condylar chondrocytes causes spontaneous osteoarthritic lesions in the temporomandibular joint in mice / 国际口腔科学杂志·英文版

The progressive destruction of condylar cartilage is a hallmark of the temporomandibular joint (TMJ) osteoarthritis (OA); however, its mechanism is incompletely understood. Here, we show that Kindlin-2, a key focal adhesion protein, is strongly detected in cells of mandibular condylar cartilage in mice. We find that genetic ablation of Kindlin-2 in aggrecan-expressing condylar chondrocytes induces multiple spontaneous osteoarthritic lesions, including progressive cartilage loss and deformation, surface fissures, and ectopic cartilage and bone formation in TMJ. Kindlin-2 loss significantly downregulates the expression of aggrecan, Col2a1 and Proteoglycan 4 (Prg4), all anabolic extracellular matrix proteins, and promotes catabolic metabolism in TMJ cartilage by inducing expression of Runx2 and Mmp13 in condylar chondrocytes. Kindlin-2 loss decreases TMJ chondrocyte proliferation in condylar cartilages. Furthermore, Kindlin-2 loss promotes the release of cytochrome c as well as caspase 3 activation, and accelerates chondrocyte apoptosis in vitro and TMJ. Collectively, these findings reveal a crucial role of Kindlin-2 in condylar chondrocytes to maintain TMJ homeostasis.

Characterization of hippocampal histomorphology following R. vomitoria root extract treatment / Caracterización de la histomorfología del hipocampo después del tratamiento con extracto de la raíz de R. vomitoria

Rauwolfia vomitoria Afzel. is an antipsychotic plant used by several African communities in the management of psychiatric conditions with good outcomes. Concerns about its dosages on brain activity lead to this investigation of its action on the hippocampal microstructure.Twenty-four adult male Wistar rats of average weight 200 g, were assigned into four groups (n = 6): control; 200, 300 and 400 mg/kg body weight of RVroot bark extract, respectively. The administration was once daily, and orally for seven days. Daily observation of the animals was done till on day eight when they were sacrificed after deep anaesthesia. Each brain was processed for histology and immunohistochemical studies. Animals in the 200, 300 and 400 mg/kg RV groups appeared generally dull and drowsy, and barely fed. Their hippocampal histology showed neuronal atrophy and karyorrhexis, with no difference in cell count, although the pyramidal cell numbers decreased in the 300 and 400 mg/kg RV groups. Neuron-specific enolase decreased in the 400 mg/kg RV group, while neurofilament decreased in all test groups. Glial fibrillary acidic protein expression and density increased in the 200 and 300 mg/kg RV groups, but not the 400 mg/kg RV group, all compared with the control group.The given doses of RV root bark extractin adult Wistar rats showed sedative activities with hippocampal histopathological changes, which may not be reversible, thereby leading to the hippocampal functional deficit.

Introducción: Rauwolfia vomitoria (RV) Afzel es una planta antipsicótica utilizada por varias comunidades africanas en el tratamiento de enfermedades psiquiátricas con buenos resultados. Las preocupaciones sobre sus efecto sobre la actividad cerebral conducen a esta investigación de su acción sobre la microestructura del hipocampo.Materiales y métodos: Se asignaron veinticuatro ratas Wistar macho adultas de un peso medio de 200 g, en cuatro grupos (n = 6): control; 200, 300 y 400 mg / kg de peso corporal de extracto de corteza de raíz de RV, respectivamente. La administración fue una vez al día y por vía oral durante siete días. Se realizó una observación diaria de los animales hasta el día ocho, cuando fueron sacrificados después de una anestesia profunda. Cada cerebro fue procesado para estudios histológicos e inmunohistoquímicos.Resultados: Los animales en los grupos de RV de 200, 300 y 400 mg / kg parecían generalmente apagados y somnolientos, y apenas alimentados. Su histología hipocampal mostró atrofia neuronal y cariorrexis, sin diferencia en el recuento celular, aunque el número de células piramidales disminuyó en los grupos de RV de 300 y 400 mg / kg. La enolasa específica de neuronas disminuyó en el grupo de RV de 400 mg / kg, mientras que el neurofilamento disminuyó en todos los grupos de prueba. La expresión y densidad de la proteína fibrilar ácida glial aumentó en los grupos de RV de 200 y 300 mg / kg, pero no en el grupo de RV de 400 mg / kg, todos en comparación con el grupo de control.Conclusión: Las dosis administradas de extracto de corteza de raíz de RV en ratas Wistar adultas mostraron actividades sedantes, con cambios histopatológicos del hipocampo, que pueden no ser reversibles, lo que conduce al déficit funcional del hipocampo.

In Vitro Antibacterial and Antibiofilm activities of Piper betle L. Ethanolic Leaf Extract on Staphylococcus aureus ATCC 29213

Background and Objective@#Staphylococcus aureus is the leading cause of skin and soft tissue infections such as abscesses, furuncles, and cellulitis. Biofilm forming strains of S. aureus have higher incidence of antimicrobial resistance to at least three or more antibiotics and are considered as multidrug resistant. Since S. aureus biofilm-producing strains have higher rates of multidrug and methicillin resistance compared to non-biofilm-producing strains, the need for alternative therapeutic option is important. Furthermore, rates of methicillin-resistant Staphylococcus aureus (MRSA) in Asia remain high. Results of the study may provide support for the clinical uses of P. betle as a topical antibacterial and antiseptic in the treatment and prevention of infections involving the skin, mouth, throat, and indwelling medical devices. Thus, this study aimed to evaluate the in vitro antibacterial and antibiofilm activities of Piper betle L. ethanolic leaf extract (PBE) against a biofilm-forming methicillin-sensitive Staphylococcus aureus ATCC 29213 (MSSA).@*Methods@#The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of PBE against MSSA were determined using the agar dilution assay. The biofilm inhibition and eradication assays using crystal violet were done to quantify the antibiofilm activities of PBE on MSSA biofilm. @*Results@#PBE showed activity against MSSA in agar dilution assay with MIC and MBC values of 2500 μg/mL and 5000 μg/mL, respectively. At subinhibitory concentrations, PBE showed biofilm inhibition activity at 1250 μg/mL but a lower percent eradication of biofilms as compared to oxacillin was noted. @*Conclusion@#PBE showed antibacterial activities including biofilm inhibition against methicillin-sensitive Staphylococcus aureus ATCC 29213 (MSSA).

Effect of Aspiration Therapy on Obesity-Related Comorbidities: Systematic Review and Meta-Analysis

Background/Aims@#Aspiration therapy (AT) involves endoscopic placement of a gastrostomy tube with an external device that allows patients to drain 30% of ingested calories after meals. Its efficacy for inducing weight loss has been shown. This study aimed to assess the effect of AT on obesity-related comorbidities. @*Methods@#A meta-analysis of studies that assessed AT outcomes was conducted through December 2018. Primary outcomes were changes in comorbidities at 1 year following AT. Secondary outcomes were the amount of weight loss at up to 4 years and pooled serious adverse events (SAEs). @*Results@#Five studies with 590 patients were included. At 1 year, there were improvements in metabolic conditions: mean difference (MD) in systolic blood pressure: -7.8 (-10.7 – -4.9) mm Hg; MD in diastolic blood pressure: -5.1 (-7.0 – 3.2) mm Hg; MD in triglycerides: -15.8 (-24.0 – -7.6) mg/dL; MD in high-density lipoprotein: 3.6 (0.7–6.6) mg/dL; MD in hemoglobin A1c (HbA1c): -1.3 (-1.8 – -0.8) %; MD in aspartate transaminase: -2.7 (-4.1 – -1.3) U/L; MD in alanine transaminase: -7.5 (-9.8 – -5.2) U/L. At 1 (n=218), 2 (n=125), 3 (n=46), and 4 (n=27) years, the patients experienced 17.8%, 18.3%, 19.1%, and 18.6% total weight loss (TWL), corresponding to 46.3%, 46.2%, 48.0%, and 48.7% excess weight loss (EWL) (p<0.0001 for all). Subgroup analysis of 2 randomized controlled trials (n=225) showed that AT patients lost more weight than did controls by 11.6 (6.5–16.7) %TWL and 25.6 (16.0–35.3) %EWL and experienced greater improvement in HbA1c and alanine transaminase by 1.3 (0.8–1.8) % and 9.0 (3.9–14.0) U/L. The pooled SAE rate was 4.1%. @*Conclusions@#Obesity-related comorbidities significantly improved at 1 year following AT. Additionally, a subgroup of patients who continued to use AT appeared to experience significant weight loss that persisted up to at least 4 years.

Computed tomography-guided 3D printed patient-specific regional anesthesia

Classic anesthetic techniques for the inferior alveolar nerve, lingual nerve, and long buccal nerve blockade are achieved by estimating the intended location for anesthetic deposition based on palpation, inspection, and subsequent correlation for oral anatomical structures. The present article utilizes computed tomography (CT) data to 3D print a guide for repeatable and accurate deposition of a local anesthetic at the ideal location.This technical report aims to anatomically define the ideal location for local anesthetic deposition. This process has the potential to reduce patient discomfort, risk of nerve damage, and failed mandibular anesthesia, as well as to reduce the total anesthetic dose. Lastly, as robotic-based interventions improve, this provides the initial framework for robot-guided regional anesthesia administration in the oral cavity.

Effect of Aspiration Therapy on Obesity-Related Comorbidities: Systematic Review and Meta-Analysis

Background/Aims@#Aspiration therapy (AT) involves endoscopic placement of a gastrostomy tube with an external device that allows patients to drain 30% of ingested calories after meals. Its efficacy for inducing weight loss has been shown. This study aimed to assess the effect of AT on obesity-related comorbidities. @*Methods@#A meta-analysis of studies that assessed AT outcomes was conducted through December 2018. Primary outcomes were changes in comorbidities at 1 year following AT. Secondary outcomes were the amount of weight loss at up to 4 years and pooled serious adverse events (SAEs). @*Results@#Five studies with 590 patients were included. At 1 year, there were improvements in metabolic conditions: mean difference (MD) in systolic blood pressure: -7.8 (-10.7 – -4.9) mm Hg; MD in diastolic blood pressure: -5.1 (-7.0 – 3.2) mm Hg; MD in triglycerides: -15.8 (-24.0 – -7.6) mg/dL; MD in high-density lipoprotein: 3.6 (0.7–6.6) mg/dL; MD in hemoglobin A1c (HbA1c): -1.3 (-1.8 – -0.8) %; MD in aspartate transaminase: -2.7 (-4.1 – -1.3) U/L; MD in alanine transaminase: -7.5 (-9.8 – -5.2) U/L. At 1 (n=218), 2 (n=125), 3 (n=46), and 4 (n=27) years, the patients experienced 17.8%, 18.3%, 19.1%, and 18.6% total weight loss (TWL), corresponding to 46.3%, 46.2%, 48.0%, and 48.7% excess weight loss (EWL) (p<0.0001 for all). Subgroup analysis of 2 randomized controlled trials (n=225) showed that AT patients lost more weight than did controls by 11.6 (6.5–16.7) %TWL and 25.6 (16.0–35.3) %EWL and experienced greater improvement in HbA1c and alanine transaminase by 1.3 (0.8–1.8) % and 9.0 (3.9–14.0) U/L. The pooled SAE rate was 4.1%. @*Conclusions@#Obesity-related comorbidities significantly improved at 1 year following AT. Additionally, a subgroup of patients who continued to use AT appeared to experience significant weight loss that persisted up to at least 4 years.

Determining the Safety and Effectiveness of Electrocautery Enhanced Scissors for Peroral Endoscopic Myotomy (with Video)

Background/Aims@#Peroral endoscopic myotomy (POEM) has recently come to the forefront in the management of achalasia. We aimed to analyze the efficacy and safety of the use of electrocautery enhanced scissors (EES) for POEM. @*Methods@#This retrospective cohort study prospectively collected the data of all adult patients (aged ≥18 years) with normal foregut anatomy who underwent POEM using EES. The patients’ baseline characteristics and procedure details (time, tunnel length, myotomy length, depth, and location) were recorded. The primary outcome was clinical success (3-month post-procedure Eckardt score of ≤3). The secondary outcomes were technical success and adverse events. A paired Student’s t-test was performed. @*Results@#Fifteen patients were included in this study. The technical success rate of myotomy using EES was 100%. Fellows participated in the myotomy in all cases. The clinical success rate was 93.3% (14/15). The mean pre-Eckardt score was 5.4±2.5, while the mean post-Eckardt score was 1.3±1.3, which indicated a significant improvement (p≤0.0001). The most common treatment-related adverse events were post-procedure pain (4, 26.7%) and symptomatic reflux disease (4, 26.7%). @*Conclusions@#In the largest series to date on the use of EES in POEM, we demonstrated that this technique has both technical and clinical efficacy as well as an excellent safety profile.

Endoscopic Ultrasound-Guided Fine Needle Aspiration and Endoscopic Retrograde Cholangiopancreatography-Based Tissue Sampling in Suspected Malignant Biliary Strictures: A Meta-Analysis of Same-Session Procedures

Background/Aims@#The diagnosis of biliary strictures can be challenging. There are no systematic reviews studying same-session endoscopic retrograde cholangiopancreatography (ERCP)-based tissue sampling and endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) for the diagnosis of biliary strictures. @*Methods@#A systematic review was conducted on studies analyzing same-session EUS and ERCP for tissue diagnosis of suspected malignant biliary strictures. The primary outcome was the accuracy of each method individually compared to the two methods combined. The secondary outcome was the accuracy of each method in pancreatic and biliary etiologies. In the meta-analysis, we used Forest plots, summary receiver operating characteristic curves, and estimates of the area under the curve for intention-to-treat analysis. @*Results@#Of the 12,132 articles identified, six were included, resulting in a total of 497 patients analyzed. The sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, and accuracy of the association between the two methods were: 86%, 98%, 12.50, 0.17, and 96.5%, respectively. For the individual analysis, the sensitivity, specificity and accuracy of EUS-FNA were 76%, 100%, and 94.5%, respectively; for ERCP-based tissue sampling, the sensitivity, specificity, and accuracy were 58%, 98%, and 78.1%, respectively. For pancreatic lesions, EUS-FNA was superior to ERCP-based tissue sampling. However, for biliary lesions, both methods had similar sensitivities. @*Conclusions@#Same-session EUS-FNA and ERCP-based tissue sampling is superior to either method alone in the diagnosis of suspected malignant biliary strictures. Considering these results, combination sampling should be performed when possible.

Validation of a Novel Endoscopic Retrograde Cholangiopancreatography Cannulation Simulator

Background/Aims@#Endoscopic retrograde cholangiopancreatography (ERCP) requires a unique skill set. Currently, there is no objective methodology to assess and train a professional to perform ERCP. This study aimed to develop and validate a novel ERCP simulator. @*Methods@#The simulator consists of papillae presenting different anatomy and positioned in varied locations. Deep cannulation of the pancreatic duct, followed by the bile duct, was performed. The time allotted was 5 minutes. The content validity indexes (CVIs) for realism, relevance, and representativeness were calculated. Correlation between ERCP experience and simulator score was determined. @*Results@#Twenty-three participants completed the simulation. The CVIs for realism were orientation of duodenoscope to papilla (1.00), angulation of papillotome to achieve cannulation (0.71), and haptic feedback during cannulation (0.80). The CVIs for relevance were use of elevator (1.00), wheels to achieve en face orientation (1.00), and papillotome for selective cannulation (1.00). Regarding CVI for representativeness, the results were as follows: basic cannulation (0.83), papilla locations (0.83), and papilla anatomies (0.80). The novice, intermediate, and experienced groups scored 6.7±8.7, 30.0±16.3, and 74.4±43.9, respectively (p<0.0001). There was a strong correlation between the ERCP experience level and the individual’s simulator score (Pearson value of 0.77, R2 of 0.60). @*Conclusions@#This simulator appears to be realistic, relevant, and representative of ERCP cannulation techniques. Additionally, it is effective at objectively assessing basic ERCP skills by differentiating scores based on clinical experience.

Endoscopic Ultrasound Fine-Needle Aspiration versus Fine-Needle Biopsy for Lymph Node Diagnosis: A Large Multicenter Comparative Analysis

Background/Aims@#Endoscopic ultrasound fine-needle aspiration (EUS-FNA) is preferred for sampling of lymph nodes (LNs) adjacent to the gastrointestinal wall; however, fine-needle biopsy (FNB) may provide improved diagnostic outcomes. This study aimed to evaluate the comparative efficacy and safety of FNA versus FNB for LN sampling. @*Methods@#This was a multicenter retrospective study of prospectively collected data to evaluate outcomes of EUS-FNA and EUS-FNB for LN sampling. Characteristics analyzed included sensitivity, specificity, accuracy, the number of needle passes, diagnostic adequacy of rapid on-site evaluation (ROSE), cell-block analysis, and adverse events. @*Results@#A total of 209 patients underwent EUS-guided LN sampling. The mean lesion size was 16.22±8.03 mm, with similar sensitivity and accuracy between FNA and FNB ([67.21% vs. 75.00%, respectively, p=0.216] and [78.80% vs. 83.17%, respectively, p=0.423]). The specificity of FNB was better than that of FNA (100.00% vs. 93.62%, p=0.01). The number of passes required for diagnosis was not different. Abdominal and peri-hepatic LN location demonstrated FNB to have a higher sensitivity (81.08% vs. 64.71%, p=0.031 and 80.95% vs. 58.33%, p=0.023) and accuracy (88.14% vs. 75.29%, p=0.053 and 88.89% vs. 70.49%, p=0.038), respectively. ROSE was a significant predictor for accuracy (odds ratio, 5.16; 95% confidence interval, 1.15–23.08; p=0.032). No adverse events were reported in either cohort. @*Conclusions@#Both EUS-FNA and EUS-FNB are safe for the diagnosis of LNs. EUS-FNB is preferred for abdominal LN sampling. EUSFNA+ ROSE was similar to EUS-FNB alone, showing better diagnosis for EUS-FNB than traditional FNA. While ROSE remained a significant predictor for accuracy, due to its poor availability in most centers, its use may be limited to cases with previous inconclusive diagnoses.

Synthesis and biological evaluation of a series of 2-(((5-akly/aryl-1-pyrazol-3-yl)methyl)thio)-5-alkyl-6-(cyclohexylmethyl)-pyrimidin-4(3)-ones as potential HIV-1 inhibitors

A series of 2-(((5-akly/aryl-1-pyrazol-3-yl)methyl)thio)-5-alkyl-6-(cyclohexylmethyl)-pyrimidin-4(3)-ones were synthesized and their anti-HIV-1 activities were evaluated. Most of these compounds were highly active against wild-type (WT) HIV-1 strain (IIIB) with EC values in the range of 0.0038-0.4759 μmol/L. Among those compounds, had an EC value of 3.8 nmol/L and SI (selectivity index) of up to 25,468 indicating excellent activity against WT HIV-1. anti-HIV-1 activity and resistance profile studies suggested that compounds and displayed potential anti-HIV-1 activity against laboratory adapted strains and primary isolated strains including different subtypes and tropism strains (ECs range from 4.3 to 63.6 nmol/L and 18.9-219.3 nmol/L, respectively). On the other hand, it was observed that those two compounds were less effective with EC values of 2.77 and 4.87 μmol/L for HIV-1A (K103N + Y181C). The activity against reverse transcriptase (RT) was also evaluated for those compounds. Both and obtained sub-micromolar IC values showing their potential in RT inhibition. The pharmacokinetics examination in rats indicated that compound has acceptable pharmacokinetic properties and bioavailability. Preliminary structure-activity relationships and molecular modeling studies were also discussed.

Gastrointestinal manifestations and associated health outcomes of COVID-19: a brazilian experience from the largest south american public hospital

OBJECTIVES: Brazil has rapidly developed the second-highest number of COVID-19 cases in the world. As such, proper symptom identification, including gastrointestinal manifestations, and relationship to health outcomes remains key. We aimed to assess the prevalence and impact of gastrointestinal symptoms associated with COVID-19 in a large quaternary referral center in South America. METHODS: This was a single-center cohort study in a COVID-19 specific hospital in São Paulo, Brazil. Consecutive adult patients with laboratory confirmed SARS-CoV-2 were included. Baseline patient history, presenting symptoms, laboratory results, and clinically relevant outcomes were recorded. Regression analyses were performed to determine significant predictors of the gastrointestinal manifestations of COVID-19 and hospitalization outcomes. RESULTS: Four-hundred patients with COVID-19 were included. Of these, 33.25% of patients reported ≥1 gastrointestinal symptom. Diarrhea was the most common gastrointestinal symptom (17.25%). Patients with gastrointestinal symptoms had higher rates of concomitant constitutional symptoms, notably fatigue and myalgia (p<0.05). Gastrointestinal symptoms were also more prevalent among patients on chronic immunosuppressants, ACE/ARB medications, and patient with chronic kidney disease (p<0.05). Laboratory results, length of hospitalization, ICU admission, ICU length of stay, need for mechanical ventilation, vasopressor support, and in-hospital mortality did not differ based upon gastrointestinal symptoms (p>0.05). Regression analyses showed older age [OR 1.04 (95% CI, 1.02-1.06)], male gender [OR 1.94 (95% CI, 1.12-3.36)], and immunosuppression [OR 2.60 (95% CI, 1.20-5.63)], were associated with increased mortality. CONCLUSION: Based upon this Brazilian study, gastrointestinal manifestations of COVID-19 are common but do not appear to impact clinically relevant hospitalization outcomes including the need for ICU admission, mechanical ventilation, or mortality.

Diagnostic characteristics of serological-based COVID-19 testing: a systematic review and meta-analysis

Serologic testing for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) promises to assist in assessing exposure to and confirming the diagnosis of coronavirus disease 2019 (COVID-19), and to provide a roadmap for reopening countries worldwide. Considering this, a proper understanding of serologic-based diagnostic testing characteristics is critical. The aim of this study was to perform a structured systematic review and meta-analysis to evaluate the diagnostic characteristics of serological-based COVID-19 testing. Electronic searches were performed using Medline (PubMed), EMBASE, and Cochrane Library. Full-text observational studies that reported IgG or IgM diagnostic yield and used nucleic acid amplification tests (NAATs) of respiratory tract specimens, as a the reference standard in English language were included. A bivariate model was used to compute pooled sensitivity, specificity, positive/negative likelihood ratio (LR), diagnostic odds ratio (OR), and summary receiver operating characteristic curve (SROC) with corresponding 95% confidence intervals (CIs). Five studies (n=1,166 individual tests) met inclusion criteria. The pooled sensitivity, specificity, and diagnostic accuracy for IgG was 81% [(95% CI, 61-92);I2=95.28], 97% [(95% CI, 78-100);I2=97.80], and 93% (95% CI, 91-95), respectively. The sensitivity, specificity, and accuracy for IgM antibodies was 80% [(95% CI, 57-92);I2=94.63], 96% [(95% CI, 81-99);I2=92.96] and 95% (95% CI, 92-96). This meta-analysis demonstrates suboptimal sensitivity and specificity of serologic-based diagnostic testing for SARS-CoV-2 and suggests that antibody testing alone, in its current form, is unlikely to be an adequate solution to the difficulties posed by COVID-19 and in guiding future policy decisions regarding social distancing and reopening of the economy worldwide.

Approach to endoscopic procedures: a routine protocol from a quaternary university referral center exclusively for coronavirus disease 2019 patients

OBJECTIVES: The present coronavirus disease (COVID-19) pandemic has ushered in an unprecedented era of quality control that has necessitated advanced safety precautions and the need to ensure the adequate protection of healthcare professionals (HCPs). Endoscopy units, endoscopists, and other HCP may be at a significant risk for transmission of the virus. Given the immense burden on the healthcare system and surge in the number of patients with COVID-19, well-designed protocols and recommendations are needed. We aimed to systematically characterize our approach to endoscopic procedures in a quaternary university hospital setting and provide summary protocol recommendations. METHOD: This descriptive study details a COVID-19-specific protocol designed to minimize infection risks to patients and healthcare workers in the endoscopy unit. RESULTS: Our institution, located in São Paulo, Brazil, includes a 900-bed hospital, with a 200-bed-specific intensive care unit exclusively designed for patients with moderate and severe COVID-19. We highlighted recommendations for infection prevention and control during endoscopic procedures, including appropriate triage and screening, outpatient management and procedural recommendations, role and usage of personal protective equipment (PPE), and role and procedural logistics involving COVID-19-positive patients. We also detailed hospital protocols for reprocessing endoscopes and cleaning rooms and also provided recommendations to minimize severe acute respiratory syndrome coronavirus 2 transmission. CONCLUSION: This COVID-19-specific administrative and clinical protocol can be replicated or adapted in multiple institutions and endoscopy units worldwide. Furthermore, the recommendations and summary protocol may improve patient and HCP safety in these trying times.

Multicenter Implementation of a New Electronic Medical Record System Leads to Longer Procedure Times and Poor Staff Satisfaction

No abstract available.