Effect of Long-term Peripheral Nerve Stimulation on Neuro-Muscular Complex Morphologic Recovery in Experiment / Efecto de la Estimulación del Nervio Periférico a Largo Plazo sobre la Recuperación Morfológica del Complejo Neuromuscular en Experimento

SUMMARY: Peripheral nerve injury is an extremely important medical and socio-economic problem. It is far from a solution, despite on rapid development of technologies. To study the effect of long-term electrical stimulation of peripheral nerves, we used a domestically produced electrical stimulation system, which is approved for clinical use. The study was performed on 28 rabbits. Control of regeneration was carried out after 3 month with morphologic techniques. The use of long-term electrostimulation technology leads to an improvement in the results of the recovery of the nerve trunk after an injury, both directly at the site of damage, when stimulation begins in the early period, and indirectly, after the nerve fibers reach the effector muscle.

La lesión de los nervios periféricos es un problema médico y socioeconómico extremadamente importante. Sin embargo, y a pesar del rápido desarrollo de las tecnologías, aún no tiene solución. Para estudiar el efecto de la estimulación eléctrica a largo plazo de los nervios periféricos, utilizamos un sistema de estimulación eléctrica de producción nacional, que está aprobado para uso clínico. El estudio se realizó en 28 conejos. El control de la regeneración se realizó a los 3 meses con técnicas morfológicas. El uso de tecnología de electro estimulación a largo plazo conduce a una mejora en los resultados de la recuperación del tronco nervioso después de una lesión, tanto directamente en el lugar del daño, cuando la estimulación comienza en el período temprano, como indirectamente, después de que las fibras nerviosas alcanzan el músculo efector.

Síndrome de Eisenmenger secundario a comunicación interatrial tipo ostium secundum en mujer adulta / Eisenmenger Syndrome Associated with an ostium secundum Atrial Septal Defect in an Adult Woman

El síndrome de Eisenmenger es la forma más severa de presentación de hipertensión arterial pulmonar secundaria a defectos cardíacos congénitos no reparados, aunque su prevalencia es baja, continúa siendo un reto para los sistemas de salud de los países en vías de desarrollo por su complejidad en el manejo. Presentación del caso. Paciente femenina sin antecedentes médicos conocidos quien consulta por disnea relacionada a los esfuerzos y policitemia. Intervención terapéutica. Se realiza ecocardiograma transesofágico que arroja la presencia de defecto interatrial tipo ostium secundum e hipertensión arterial pulmonar severa, con cortocircuito de derecha a izquierda, se inicia oxigenoterapia y terapia farmacológica. Evolución clínica. Paciente permaneció ingresada presentando notable mejora a la disnea, se le dio de alta con referencia a la clínica de cardiopatías congénitas del adulto en Hospital Nacional Rosales.

Eisenmenger syndrome is the most severe form of pulmonary arterial hypertension secondary to an unrepaired congenital heart disease. Despite the low prevalence, it remains a challenge for the public health service of developing countries due to the complexity of the treatment. Case presentation. A female patient without known medical history, who consults with dyspnea on exertion and polycythemia. Treatment. A transesophageal echocardiogram was performed, showing an ostium secundum atrial septal defect and severe pulmonary arterial hypertension with a right-left shunt. Supplemental oxygen was administrated and pharmacological treatment was started. Outcome. The patient presented remarkable clinical improvement to dyspnea, she was discharged with medical reference to the Adult Congenital Heart Disease clinic at Rosales National Hospital.

Novel antibacterial drug target against Gram-negative bacteria: lipopolysaccharide transport protein LptDE and its inhibitors / 药学学报

The outer membrane composed predominantly of lipopolysaccharide (LPS) is an essential biological barrier for most Gram-negative (G-) bacteria. Lipopolysaccharide transport protein (Lpt) complex LptDE is responsible for the critical final stage of LPS transport and outer membrane assembly. The structure and function of LptDE are highly conserved in most G- bacteria but absent in mammalian cells, and thus LptDE complex is regarded as an attractive antibacterial target. In recent 10 years, the deciphering of the three-dimensional structure of LptDE protein facilities the drug discovery based on such "non-enzyme" proteins. Murepavadin, a peptidomimetic compound, was reported to be the first compound able to target LptD, enlightening a new class of antibacterial molecules with novel mechanisms of action. This article is devoted to summarize the molecular characteristics, structure-function of LptDE protein complex and review the development of murepavadin and related peptidomimetic compounds, in order to provide references for relevant researches.

In Vitro and in Vivo Evaluation of Scutellarin-phospholipid Complex Nanoemulsion and Analysis of Its Activity in Ameliorating LPS-induced Vascular Endothelial Injury / 中国实验方剂学杂志

ObjectiveTo evaluate some properties of scutellarin-phospholipid complex nanoemulsion（SCU-PC-NE）， such as release， cell uptake and tissue distribution， and to investigate its effect on ameliorating lipopolysaccharide（LPS）-induced vascular endothelial injury. MethodSCU-PC-NE was prepared by weighting SCU-PC， ethyl oleate， Kolliphor HS15， 1，2-propylene glycol（50， 400， 514.3， 85.7 mg）， respectively. And the appearance of SCU-PC-NE was observed by transmission electron microscope， the average paticle size and Zeta potential were measured by nanopotential particle size analyzer. The cumulative release of SCU-PC-NE in vitro was measured by dynamic dialysis， thiazolyl blue（MTT） colorimetric assay was used to investigate the effect of SCU-PC-NE on the viability of human umbilical vein endothelial cells（HUVECs）， the inverted fluorescence microscope and flow cytometry were used to investigate cell uptake of HUVECs by SCU-PC-NE in vitro using coumarin 6 as a fluorescent probe， the tissue distribution of DiR/SCU-PC-NE labeled by near infrared fluorescent dyes was obeserved by small animal in vivo imaging system. The inflammation injury model was established by co-incubation with LPS（1 mg·L-1） and HUVECs， the effect of SCU-PC-NE on the levels of interleukin（IL）-1β and IL-6 were determined by enzyme-linked immunosorbent assay（ELISA）， 18 Kunming male mice were randomly divided into blank group， model group， blank preparation group（equivalent to high dose group）， SCU group and SCU-PC-NE low and high dose groups（5， 10 mg·kg-1）， 3 mice in each group， and the drug administration groups were administered once in the tail vein at the corresponding dose every 48 h， equal volume of normal saline was given to the blank group and the model group， and the drug was administered for 4 consecutive times. Except for the blank group， the endothelial inflammatory injury was induced by intraperitoneal injection of LPS（10 mg·kg-1） at 12 h before the last administration in each group. Hematoxylin-eosin（HE） staining was used to investigate the effect of SCU-PC-NE on the histopathological changes in the thoracic aorta of mice. ResultThe appearance of SCU-PC-NE displayed pale yellow milky light， mostly spherical with rounded appearance and relatively uniform particle size distribution， with the average particle size of 35.31 nm， Zeta potential of 7.23 mV， and the encapsulation efficiency of 75.24%. The cumulative release in vitro showed that SCU-PC-NE exhibited sustained release properties compared with SCU. The cell viability of SCU-PC-NE was >90% at a concentration range of 1.05-8.4 mg·L-1. The results of cellular uptake experiments showed that the cellular uptake ability of SCU-PC-NE was significantly enhanced when compared with the SCU group（P<0.01）. Compared with normal mice， the results of tissue distribution showed that the fluorescence intensity of DiR/SCU-PC-NE was significantly enhanced in the spleen， kidney， brain and thoracic aorta of mice at different time points after intraperitoneal injection of LPS（P<0.05， P<0.01）， especially in thoracic aorta. ELISA results showed that the levels of IL-1β and IL-6 in the model group were significantly increased when compared with the blank group（P<0.05， P<0.01）， and compare with the model group， all administration groups significantly down-regulated IL-1β level， with the strongest effect in the SCU-PC-NE high-dose group（P<0.01）， and all administration groups significantly down-regulated IL-6 level， with the strongest effect in the SCU-PC-NE low-dose group（P<0.05）. Compare with the blank group， the results of HE staining showed that the endothelial cells were damaged， the elastic fibers were broken and arranged loosely in the model group， although similar vascular injury could be observed in the blank preparation group， SCU group and SCU-PC-NE low-dose group， the vascular endothelial damage was significantly reduced in the high-dose group of SCU-PC-NE， which had a better effect than that in the SCU group. ConclusionSCU-PC-NE can promote the uptake of drugs by endothelial cells and effectively enriched in the site of vascular endothelial injury caused by LPS， suggesting that it has a protective effect on vascular endothelial injury and is a good carrier of SCU.

Effect of Xuanfei Zhisou Prescription on IL-17 Signaling Pathway in COPD Model Rats / 中国实验方剂学杂志

ObjectiveTo investigate the effect of Xuanfei Zhisou prescription on the interleukin-17 （IL-17） signaling pathway in model rats with chronic obstructive pulmonary disease （COPD）. MethodA total of 60 Wistar rats were randomly divided into a blank group （10 rats） and a model group （50 rats）， and COPD model rats were established by tracheal infusion of lipopolysaccharide combined with passive fumigation. After modeling， the rats were divided into the model group， dexamethasone group， and high， medium， and low-dose Xuanfei Zhisou prescription groups （3.6， 1.8， 0.9 g·kg-1·d-1） according to the random number table. Rats in the blank group and model group were given normal saline of 10 mL·kg-1·d-1 by gavage administration， and the intervention groups of Xuanfei Zhisou prescription were given corresponding drugs. Rats in the dexamethasone group were given dexamethasone of 2.57×10-4 g·kg-1·d-1 for 28 days. The level of pulmonary function indexes in rats was measured by a pulmonary function detector. The contents of interleukin-6 （IL-6）， interleukin-8 （IL-8）， IL-17， interleukin-1β （IL-1β）， and tumor necrosis factor-α （TNF-α） were detected by enzyme-linked immunosorbent assay （ELISA）. The positive expressions of IL-17A， IL-17RA， nuclear factor-κB activator 1 （Act1）， tumor necrosis factor-associated factor 6 （TRAF6）， p-p38 mitogen-activated protein kinase （p-p38 MAPK）， nuclear factor-κB p65 （NF-κB p65）， and phosphorylation were detected by immunohistochemistry （IHC）. The protein expression levels of IL-17A， IL-17RA， Act1， and TRAF6 in the lung tissue were detected by Western blot. The mRNA expressions of IL-17A， IL-17RA， Act1， and TRAF6 in the lung tissue were detected by Real-time polymerase chain reaction （Real-time PCR）. ResultCompared with the blank group， the serum contents of IL-6， IL-8， IL-17， IL-1β， and TNF-α in the model group were significantly increased （P<0.05）， and the flow rate and volume indexes of pulmonary function in the model group were significantly decreased （P<0.05）， while the time indexes and other indexes were significantly increased （P<0.05）. The mRNA and protein expression levels of IL-17A， IL-17RA， Act1， and TRAF6 in pulmonary tissue and the positive expressions of downstream NF-κB p65， p-NF-κB p65， and p-p38 MAPK were increased （P<0.05）. Compared with the model group， the levels of IL-6， IL-8， IL-17， IL-1β， and TNF-α in the serum of all treatment groups were decreased to varying degrees （P<0.05）， and the indexes of pulmonary function were improved to different degrees （P<0.05）. The mRNA and protein levels of IL-17A， IL-17RA， Act1， and TRAF6 and the positive expression of downstream NF-κB p65， p-NF-κB p65， and p-p38 MAPK in high and medium-dose Xuanfei Zhisou prescription groups were significantly decreased （P<0.05）. ConclusionXuanfei Zhisou prescription can effectively resist inflammation of COPD rats. The mechanism may be related to down-regulating the protein expression of IL-17A， IL-17RA， Act1， and TRAF6， inhibiting downstream NF-κB and p38 MAPK signaling pathways， and reducing the release of IL-6， IL-8， TNF-α， IL-17， and IL-1β， thus reducing the airway inflammation response.

Clinical significance of determining the level of biliary calprotectin in patients with cholangiocarcinoma or choledocholithiasis / 临床肝胆病杂志

ObjectiveTo investigate the difference in the level of biliary calprotectin between patients with cholangiocarcinoma and those with choledocholithiasis. MethodsClinical data and bile samples were collected from 34 patients with cholangiocarcinoma and 78 patients with choledocholithiasis who were diagnosed and treated with endoscopic retrograde cholangiopancreatography in The First Affiliated Hospital of Anhui Medical University from May 2021 to September 2022. Fluorescence lateral flow immunoassay was used to measure the levels of calprotectin， hemoglobin， and lactoferrin in bile. The Mann-Whitney U test was used for comparison of continuous data between two groups， and the chi-square test was used for comparison of categorical data between two groups； the Spearman correlation test was used for correlation analysis； the DeLong test was used for comparison of the area under the ROC curve （AUC）. ResultsCompared with the choledocholithiasis group， the cholangiocarcinoma group had significant increases in the levels of calprotectin ［4 795.50 （2 286.79‍ ‍—‍ ‍20 179.73） ng/mL vs 411.16 （67.03‍ ‍—‍ ‍1 991.88） ng/mL， Z=5.572， P<0.001］ and fluoride ［115.70 （109.10‍ — ‍125.50） mmol/L vs 106.60 （98.60‍ ‍—‍ ‍114.40） mmol/L， Z=2.702， P=0.007］. The patients with cholangiocarcinoma were further divided into high cholangiocarcinoma group and low cholangiocarcinoma group， and there was no significant difference between the two groups in the level of calprotectin ［3 867.71 （2 235.66‍ — ‍26 407.40） ng/mL vs 4 795.50 （2 361.15‍ — ‍13 070.53） ng/mL， Z=0.129， P>0.05］. Biliary calprotectin level was correlated with white blood cell count， hemoglobin concentration， and lactoferrin concentration in bile （r=0.316， 0.353， and 0.464， all P<0.05）. The ROC curve analysis showed that biliary calprotectin （with a sensitivity of 79.4% and a specificity of 75.6%）， blood CA19-9 （with a sensitivity of 82.4% and a specificity of 78.2%）， and their combination （with a sensitivity of 88.2% and a specificity of 73.1%） had good sensitivity and specificity in the diagnosis of cholangiocarcinoma. ConclusionThere is an increase in the level of biliary calprotectin in patients with cholangiocarcinoma， and therefore， it might become a biomarker for the diagnosis of cholangiocarcinoma.

Preparation and in vitro dissolution behaviors evaluation of silymarin phospholipid complex / 药学实践杂志

Objective To prepare silymarin phospholipids complex（SM-PC） and investigate its physicochemical properties. Methods On the basis of single-factor tests, the drug-lipid ratio, drug concentration and reaction temperature were selected as the factors of the central composite design and response surface methodology in the preparation of SM-PC by solvent volatilization, and the best process was optimized with the compound rate as the index. And its in vitro dissolution was measured. Results The optimum preparation technology of SM-PC was as follows: acetone was used as compound solvent, the concentration of SM was 8.0 mg/ml, the mass ratio of SM to phospholipid was 1∶1.8, the reaction temperature was 56 ℃ and the recombination rate was（95.15±1.55）% with deviation of less than 3%. The in vitro dissolution test showed that the dissolution of SM-PC was close to 90% in 60 min. The dissolution behavior of main component of silybin was similar to that of silymarin capsules（Legalon ®）, which was higher than SM-API. Conclusion SM-PC was successfully prepared by central composite design response surface method, which significantly improved the dissolution and laid a foundation for the study of subsequent preparations.

Prevalence and Factors Associated with Shoulder Complex Function (SCF) Among the Elderly in Private Physiotherapy Clinic in Klang Valley, Malaysia

@#Introduction: Shoulder problems have been a challenge among the aging population. Although reports surfaced on factors affecting shoulder dysfunction, however, such studies in relation to other factors like neck pain (NP) factor are limited especially among the elderly in the urban population. This study investigated the prevalence and factors associated with shoulder complex dysfunction among the outpatient elderly attending private physiotherapy clinics. Methods: A total of 75 elderly aged ≥ 60 years old from four private physiotherapy clinics were recruited by simple random sampling method. The elderly were evaluated using the QuickDASH questionnaire to assess shoulder complex dysfunctions and NP scale. Results: A total of 92% of participants have shoulder complex dysfunction. A positive correlation of NP to shoulder complex dysfunction ( r (75) = 0.83, p<.001) with significant associations of sex ( z= -2.549, p=0.011), smoking ( z= -2.388, p=0.017), lifestyle ( z= -5.780, p=0.000), hypertension ( z= -2.808, p=0.005), osteoarthritis ( z= -2.966, p=0.003), and NP scale ( z= -2.173, p=0.031). The predicting factor of shoulder complex dysfunction is sex (β = 0.156, t (74) = 2.240, p= 0.028) and NP scale (β = 0.704, t (74) = 7.853, p= 0.000). Conclusion: There is a high prevalence of shoulder complex dysfunction among the outpatient elderly attending private physiotherapy clinics with a predicting associating factor of sex and NP.

A Case Report of Multidisciplinary Diagnosis and Treatment of a Patient with Tuberous Sclerosis Complex and Multi-Organ Involvement / 罕见病研究

Tuberous sclerosis complex(TSC)is a rare genetic disease that can lead to benign dysplasia in multiple organs such as the skin, brain, eyes, oral cavity, heart, lungs, kidneys, liver, and bones. Its main symptoms include epilepsy, intellectual disabilities, skin depigmentation, and facial angiofibromas, whilst incidence is approximately 1 in 10 000 to 1 in 6000 newborns. This case presents a middle-aged woman who initially manifested with epilepsy and nodular depigmentation. Later, she developed a lower abdominal mass, elevated creatinine, and severe anemia. Based on clinical features and whole exome sequencing, the primary diagnosis was confirmed as TSC. Laboratory and imaging examinations revealed that the lower abdominal mass originated from the uterus. CT-guided biopsy pathology and surgical pathology suggested a combination of leiomyoma and abscess. With the involvement of multiple organs and various complications beyond the main diagnosis, the diagnostic and therapeutic process for this patient highlights the importance of rigorous clinical thinking and multidisciplinary collaboration in the diagnosis and treatment of rare and challenging diseases.

The Analysis of Clinical Features of 186 Cases of Tuberous Sclerosis Complex-Associated Renal Angiomyolipoma / 罕见病研究

ObjectiveTuberous sclerosis complex (TSC) is a rare autosomal dominant genetic disease involving multiple organ system. Renal angiomyolipoma (RAML) is a leading cause of death for adult TSC patients. Our study aims at investigating the clinical manifestations of TSC-RAML to enable clinicians to have a better understanding of the disease in Chinese patients.MethodsWe reviewed retrospectively the data collected from patients with TSC-RAML in Peking Union Medical College Hospital from January 2014 to January 2023. We also collected information about the age, gender, imageological examination, RAML stage, and comorbidities.ResultsA total of 186 TSC-RAML patients were registered, 65 of whom were males and 121 were females(male-to-female ratio 1∶1.86). The median age of all patients was 31 years old. Totally, 117 cases (62.9%)of RAML were rated stage 6. Twenty-two cases (11.8%) had a history of tumor rupture and bleeding. Research shows statistical differences between high and low grade on RAML rupture bleeding(P=0.0475). Angiofibromas/fibrous cephalic plaque (155/186, 83.3%), subependymal nodules(103/146, 70.5%), lymphangioleiomyomatosis (102/157, 65.0%), hypomelanotic macules (114/186, 61.3%), and shagreen patch (83/186, 44.6%)were the most common clinical manifestations. All patients with lymphangioleiomyomatosis(LAM) were female(P < 0.0001).ConclusionsFemale patients predominated TSC-RAML patients. Most RAML were in stage 6. About 11.8% cases had a history of tumor rupture and hemorrhage. The higher grade meant the higher proportion of tumor rupture and hemorrhage. Dermatological and nervous lesions were the most common comorbidities. All patients with LAM in this study were female.

The Development and Current Status in the Diagnosis and Management of Tuberous Sclerosis Complex Associated with Renal Angiomyolipoma in China / 罕见病研究

Tuberous sclerosis complex(TSC) is a rare autosomal dominant genetic disorder caused by mutations in the TSC1 or TSC2 genes. The disease can cause multiple organ lesions. The most common renal lesions are renal angiomyolipoma(RAML). In recent years, China has made progresss in the understanding of TSC-RAML, so that the standardization of the diagnosis and management of TSC-RAML have improved. Efforts have been taken in the studies of the pathogenesis and treatment of TSC-RAML. This article reviews the diagnosis, therapy, and research development of TSC-RAML in China.

A Case Report of Surgical Resection of Tuberous Sclerosis Complex Related Renal Giant Angiomyolipoma / 罕见病研究

Tuberous sclerosis complex (TSC) is an autosomal dominant hereditary disease that affects multiple organs and systems throughout the body. TSC-associated kidney disease is the leading cause of death in adult TSC patients. This article retrospectively analyzed the characteristics of one TSC-related renal giant angiomyolipoma(RAML)treated with surgery. The patient, 25 years old, was diagnosed with tuberous sclerosis complex in 2000 due to multiple maculopapular rashes on both cheeks. At a regular follow-up in July 2019, imaging examinations revealed a tumor in the left lower quadrant with a maximum cross-sectional area of 16 cm×7 cm. Genetic testing showed a loss of heterozygosity in the EX18_ 41 of TSC2. After the diagnosis was confirmed, open left partial nephrectomy was performed, during which multiple tumors were found on the kidney surface and the largest one was located on the ventral side with a diameter of approximately 20 cm. After the renal artery was occluded, kidney tumors were completely enucleate. Postoperative pathological confirmed the diagnosis of angiomyolipoma. This case provides a reference for the treatment of TSC-related renal giant hamartoma.

Effect of electrochemically dealloying Ti6Al4V abutments on human gingival fibroblasts / 口腔疾病防治

Objective@#To investigate the effects of electrochemically dealloying of Ti6Al4V abutments on human gingival fibroblasts (HGFs) and to provide experimental evidence for surface modification of implant abutments.@*Methods@#The samples were divided into an NC group (negative control, no other treatment on a smooth surface), an NM-1 group (nanomesh-1, electrochemical dealloying treatment in 1 mol/L NaOH 1 h on 2 V voltage), and an NM-2 group (nanomesh-2, electrochemical dealloying treatment in 5 mol/L NaOH 1 h on 2 V voltage). The surface morphologies of the samples and the adhesion of HGFs on the sample surfaces were observed with scanning electron microscopy (SEM). The surface hydrophilicities of the samples were measured with a contact angle measuring instrument. The proliferation of HGFs on the different samples were evaluated with CCK-8, and the expression of adhesion-related genes, including collagen Ⅰ (COL1A1), collagen Ⅲ (COL3A1), fibronectin 1 (FN1), focal adhesion kinase (FAK), vinculin (VCL), integrin α2 (ITGA2), and integrin β1 (ITGB1), on the different samples was measured with qRT-PCR. The expression of vinculin on the surfaces of HGFs was observed via confocal laser scanning microscopy (CLSM) after immunofluorescent staining. Collagen fiber secretion and syntheses of HGFs from different samples were evaluated via Sirius red staining.@*Results@#SEM revealed the formation of ordered and uniform three-dimensional mesh structures on the surfaces of the NM-1 and NM-2 groups, with grid diameters of approximately 30 nm for the NM-1 group and approximately 150 nm for the NM-2 group. Compared with that of the NC group, the water contact angles of the NM-1 group and NM-2 groups were significantly lower (P<0.000 1). Cell proliferation in the NM-1 group was significantly greater than that in the NC group (P<0.01). Moreover, there was no significant difference in the water contact angles or cell proliferation between the NM-1 group and the NM-2 group. SEM revealed that HGFs were adhered well to the surfaces of all samples, while the HGFs in the NM-1 and NM-2 groups showed more extended areas, longer morphologies, and more developed pseudopodia than did those in the NC group after 24 h. qRT-PCR revealed that the expression levels of the adhesion-related genes COL1A1, COL3A1, FN1, FAK and VCL in the NM-1 group were significantly greater than those in the NC and NM-2 groups (P<0.01). The expression of vinculin protein in the NM-1 group was the highest, and the number of focal adhesions was greatest in the NM-1 group (P<0.01). The results of Sirius red staining showed that the NM-1 group had the highest secretion and syntheses of collagen fibers (P<0.000 1).@*Conclusion@#The three-dimensional nanomechanical structure of Ti6Al4V modified by electrochemical dealloying promoted the adhesion, proliferation, collagen fiber secretion and syntheses of HGFs, and electrochemical dealloying of Ti6Al4V with a grid diameter of approximately 30 nm obviously promoted HGF formation.

Hemostasis Using Prothrombin Complex Concentrate in Patients Undergoing Cardiac Surgery: Systematic Review with Meta-Analysis

ABSTRACT Objective: The purpose of present study was to comprehensively explore the efficacy and safety of prothrombin complex concentrate (PCC) to treat massive bleeding in patients undergoing cardiac surgery. Methods: PubMed®, Embase, and Cochrane Library databases were searched for studies investigating PCC administration during cardiac surgery published before September 10, 2022. Mean difference (MD) with 95% confidence interval (CI) was applied to analyze continuous data, and dichotomous data were analyzed as risk ratio (RR) with 95% CI. Results: Twelve studies were included in the meta-analysis. Compared with other non-PCC treatment regimens, PCC was not associated with elevated mortality (RR=1.18, 95% CI=0.86-1.60, P=0.30, I2=0%), shorter hospital stay (MD=-2.17 days; 95% CI=-5.62-1.28, P=0.22, I2=91%), reduced total thoracic drainage (MD=-67.94 ml, 95% CI=-239.52-103.65, P=0.44, I2=91%), thromboembolic events (RR=1.10, 95% CI=0.74-1.65, P=0.63, I2=39%), increase in atrial fibrillation events (RR=0.73, 95% CI=0.52-1.05, P=0.24, I2=29%), and myocardial infarction (RR=1.10, 95% CI=0.80-1.51, P=0.57, I2=81%). However, PCC use was associated with reduced intensive care unit length of stay (MD=-0.81 days, 95% CI=-1.48- -0.13, P=0.02, I2=0%), bleeding (MD=-248.67 ml, 95% CI=-465.36- -31.97, P=0.02, I2=84%), and intra-aortic balloon pump/extracorporeal membrane oxygenation (RR=0.65, 95% CI=0.42-0.996, P=0.05, I2=0%) when compared with non-PCC treatment regimens. Conclusion: The use of PCC in cardiac surgery did not correlate with mortality, length of hospital stay, thoracic drainage, atrial fibrillation, myocardial infarction, and thromboembolic events. However, PCC significantly improved postoperative intensive care unit length of stay, bleeding, and intra-aortic balloon pump/ extracorporeal membrane oxygenation outcomes in patients undergoing cardiac surgery.

O fim da extensão das patentes e as Parcerias para Desenvolvimento Produtivo: reflexos no acesso a medicamentos no Brasil / The end of patent extensions and the Productive Development Partnerships: effects on access to medicines in Brazil

Resumo A covid-19 jogou luz sobre o impacto negativo da propriedade intelectual na saúde e deu nova relevância à Ação Direta de Inconstitucionalidade 5529/DF, que, acatada pelo Supremo Tribunal Federal em 2021, culminou na extinção da extensão automática de patentes no Brasil. Este estudo busca analisar o efeito do julgamento histórico da ADI 5529/DF sobre pedidos de patente e as patentes de interesse das Parcerias para Desenvolvimento Produtivo (PDP). Trata-se de um estudo com base em uma pesquisa documental de análise do andamento, até 31 de dezembro de 2020, de 90 pedidos de patente relacionados a 15 medicamentos objetos de PDP. Nos sites do Instituto Nacional de Propriedade Industrial, do Ministério da Saúde, da Anvisa e da Câmara de Regulação do Mercado de Medicamentos, foram pesquisadas variáveis para comparar o cenário patentário dos medicamentos com o das PDP. De 88 pedidos válidos, 28 patentes foram concedidas, das quais dezessete foram estendidas para mais de vinte anos (média de 24 anos e nove meses). A decisão do STF resultou em mais de 68 anos de monopólio perdidos, potencialmente desanuviando alternativas para a produção de genéricos no país. Neste momento de retomada das PDP, estratégias para a superação de barreiras patentárias deveriam ser incorporadas à política.

Abstract The COVID-19 pandemic has shed light on the negative impact of intellectual property on health and has given new relevance to the Direct Action of Unconstitutionality 5529/DF, which was ruled by the Supreme Court in 2021, resulting in the extinction of automatic patent extensions in Brazil. This documentary case study analyzes the effects of the judicial decision on patent applications and patents of interest for Productive Development Partnerships (PDP), investigating the progress of 90 patent applications related to 15 PDPs drugs of interest until Decembre 31, 2020. Variables for comparing the drug patent scenario with that of the PDPs were researched on the websites of the National Institute of Industrial Property, the Ministry of Health, ANVISA, and the Brazilian Medicines Market Regulation Chamber. Of 88 valid applications, 28 patents were granted, 17 of which had been extended to more than 20 years (24 years and 09 months average). The court decision resulted in a loss of over 68 years of monopoly, potentially opening alternatives for generic production. This resumption of the PDP policy should incorporate strategies to overcome patent barriers.

Rehabilitation protocols in neuropathic pain: bibliometric review / Protocolos de reabilitação na dor neuropática: revisão bibliométrica

ABSTRACT BACKGROUND AND OBJECTIVES: Neuropathic pain (NP) affects the afferent somatosensory pathways, generating various symptoms, however, there is difficulty in terms of diagnosis and in the formation of treatment protocols. There is a need to search the current literature for effective resources for the treatment of peripheral neuropathy in rehabilitation. The objective of this study was to describe reproducible assessment and treatment approaches capable of reducing NP. CONTENTS: Full articles produced between 2018 and 2022, found in the Pubmed, Scielo, Medline, Embase and Cochrane databases were included. Fifteen Boolean descriptors were used, and data were cross-referenced with the words "AND" or "OR". The selected articles went through the Methodi Ordinatio of classification and organization of studies. Eleven articles were selected and used in this review, two from 2018, five from 2020, and three from 2021. Regarding the type of study, five review articles, one case study, and six intervention studies were obtained. Of these 11 studies, only three used quality of life (QoL) indicators. Most studies used combined interventions, and in more than half of the publications transcranial direct current stimulation (tDCS) was present. The somatosensory rehabilitation method was able to redeem neuropathy through specific techniques. CONCLUSION: The implications of the neuropathic pain treatment in terms of QoL were left in the background by the bibliometric survey carried out. It is suggested that new studies could associate analgesia techniques with rehabilitation methods, including and measuring the effects on the QoL of these patients.

RESUMO JUSTIFICATIVA E OBJETIVOS: A dor neuropática (DN) acomete as vias somatossensoriais aferentes, gerando diversos sintomas, entretanto há dificuldades em termos de diagnóstico e na formação de protocolos de tratamento. Há a necessidade de buscar, na literatura atual, recursos eficazes para o tratamento da neuropatia periférica na área da reabilitação. O objetivo deste estudo foi descrever abordagens reprodutíveis de avaliação e tratamento capazes de diminuir a DN. CONTEÚDO: Foram incluídos artigos completos produzidos entre os anos de 2018 e 2022, encontrados nos bancos de dados Pubmed, Scielo, Medline, Embase e Cochrane. Foram usados 15 descritores booleanos, e os dados foram cruzados com as palavras "AND" ou "OR". Os artigos passaram pelo Methodi Ordinatio de classificação e organização de estudos. Foram selecionados e utilizados 11 artigos, sendo dois de 2018, cinco de 2020 e três de 2021. Acerca do tipo de estudo, foram obtidos cinco artigos de revisão, um estudo de caso e seis estudos de intervenção. Desses 11 estudos, apenas três utilizaram indicadores de qualidade de vida (QV). A maioria dos estudos utilizou intervenções combinadas, e em mais da metade das publicações a estimulação transcraniana por corrente contínua (ETCC) estava presente. O método de reabilitação somatossensorial foi capaz de redimir a neuropatia por meio de técnicas específicas. CONCLUSÃO: As implicações do tratamento da dor neuropática no quesito QV ficaram em segundo plano pelo levantamento bibliométrico realizado. Sugere-se que novos estudos possam associar técnicas de analgesia a métodos de reabilitação, incluindo e mensurando os efeitos sobre a QV desses pacientes.

Endodontic treatment as a Reduction in the Risk of infective Endocarditis in a Male Patient with Eisenmenger Syndrome

This case report aimed to describe the importance of endodontic treatment in reducing infectious foci in patients with Eisenmenger syndrome (ES) and describe the characteristics of ES, so that the endodontist can safely treat these patients. A 57-year-old male with ES sought dental care complaining of dental pain. Irreversible pulpitis was diagnosed in tooth 37 and pulp necrosis in teeth 36, 34 and 31. Tests of prothrombin time (PT), activated partial thromboblastin time (APTT) and international normalized ratio (INR) were prescribed to evaluate the profile of coagulation using Marevan and antibiotic prophylaxis with amoxicillin. The endodontic treatments were performed. At the end, the patient reported no pain or discomfort in the teeth and improved masticatory function. The removal of oral infectious foci in patients with ES is important to reduce the risk of IE, which could seriously compromise the health and overall prognosis of the patient.

Este reporte de caso tuvo como objetivo describir la importancia del tratamiento endodóntico en la reducción de focos infecciosos en pacientes con síndrome de Eisenmenger (SE) y describir las características del SE, para que el endodoncista pueda tratar con seguridad a estos pacientes. Un hombre de 57 años con ES buscó atención dental quejándose de dolor dental. Se diagnosticó pulpitis irreversible en el diente 37 y necrosis pulpar en los dientes 36, 34 y 31. Se solicitaron pruebas de tiempo de protrombina (PT), tiempo de tromboblastina parcial activada (TTPA) y índice internacional normalizado (INR) para evaluar el perfil de coagulación utilizando Marevan y profilaxis antibiótica con amoxicilina. Se realizaron los tratamientos de endodoncia. Al final, el paciente no refirió dolor ni molestias en los dientes y mejoró la función masticatoria. La eliminación de focos infecciosos orales en pacientes con ES es importante para reducir el riesgo de EI, que podría comprometer gravemente la salud y el pronóstico general del paciente.

Feridas complexas: abordagem por equipa multidisciplinar. Uma scoping review. / Complex wounds: approach by a multidisciplinary team. A scoping review

Objetivos: - reconhecer a importância da equipa multidisciplinar na abordagem à pessoa com ferida complexa na cicatrização de feridas; - mapear a evidência/conhecimento sobre a temática em estudo. Método: Scoping review realizada entre 04 de janeiro e 01 de fevereiro de 2020, nas bases de dados Repositório Científico de Acesso Aberto de Portugal (RCAAP), EBSCO host (CINAHL e Medline) e Web of Science, utilizando estratégias de pesquisa adaptadas a cada base de dados. Resultados e discussão: A evidência científica demonstra a importância das equipas multidisciplinares na abordagem à pessoa com ferida complexa. Conclusão: Tratando-se de um processo complexo, é fundamental ter em consideração todos os elementos que influenciam e atrasam a cicatrização, para se conseguir melhorar os resultados no tratamento e nos custos associados.(AU)

Objectives: - to recognize the importance of the multidisciplinary team in the approach to the person with a complex wound in wound healing; - to map the evidence/knowledge on the subject under study. Method: Scoping review carried out between January 4 and February 1, 2020, in the databases Repositório Científico de Acesso Aberto de Portugal (RCAAP), EBSCO host (CINAHL and Medline) and Web of Science, using search strategies adapted to each database. Results and discussion: The scientific evidence demonstrates the importance of multidisciplinary teams in dealing with people with complex wounds. Conclusion: As this is a complex process, it is essential to take into account all the elements that influence and delay healing, in order to improve treatment results and associated costs. (AU)

Objetivos: - reconocer la importancia del equipo multidisciplinar en el abordaje de la persona con herida compleja en la cicatrización de heridas; - mapear la evidencia/conocimiento sobre el tema objeto de estudio. Método: Revisión de alcance realizada entre el 04 de enero y el 01 de febrero de 2020, en las bases de datos Repositório Científico de Acesso Aberto de Portugal (RCAAP), EBSCO host (CINAHL y Medline) y Web of Science, utilizando estrategias de búsqueda adaptadas a cada base de datos. Resultados y discusión: La evidencia científica demuestra la importancia de los equipos multidisciplinares en el abordaje de las personas con heridas complejas. Conclusión: Al tratarse de un proceso complejo, es fundamental tener en cuenta todos los elementos que influyen y retrasan la cicatrización para mejorar los resultados del tratamiento y los costes asociados.(AU)

Currículo para el Desarrollo del Pensamiento Bioético en Profesionales de la Fisioterapia / Curriculum for the Development of Bioethical Thinking in Physiotherapy Professionals

Introducción. Todo ser humano necesita gozar de bienestar y ser reconocido como un sujeto activo en el desarrollo de la sociedad, por lo que la administración pública debe garantizar, respetar y proteger el derecho a la salud, el cual ha sido transgredido en las últimas décadas, vulnerando a la población a nivel mundial. Objetivo. Fundamentar teórica, metodológica y epistemológicamente la propuesta de un currículo, que desarrolle el pensamiento bioético en el profesional de la Fisioterapia. Métodos. Se sustenta en el paradigma sociocrítico y en la investigación acción educativa, desde la visión de Miguel Martínez-Miguélez, que busca reconceptualizar la indagación en el aula en términos participativos, relacionándolo con las actividades propias del quehacer educativo, como es la construcción y desarrollo del currículo. Resultados. Con el proceso investigativo se construyó ­en colectivo­ la definición del concepto de pensamiento bioético y se diseñó un currículo prácti-senti-pensante para los estudiantes de Fisioterapia, a partir de la pedagogía sentipensante y del paradigma del cerebro triádico (o triúnico) que interrelaciona las acciones, los sentimientos y los conocimientos en la formación humana de los futuros fisioterapeutas. Conclusiones. El currículo práctisentipensante trasciende a una estructura cognitiva trinitaria, resaltando la importancia de entrelazar las disciplinas por la supervivencia del ser humano y el equilibrio del planeta, destacando lo humanístico y la bioética, a través de un currículo que evoca a la reflexión de la comunidad educativa con el fin de articular lo desunido.

Background. Every human being needs to enjoy well-being and be recognized as an active subject in the development of society, so public administration must guarantee, respect and protect the right to health, which has been transgressed in recent decades, violating the population worldwide. Objective. To theoretically, methodologically and epistemologically base the proposal of a curriculum that develops bioethical thinking in the Physiotherapy professional. Methods. It is based on the socio-critical paradigm and educational action research, from the vision of Miguel Martínez-Miguélez, who seeks to reconceptualize inquiry in the classroom in participatory terms, relating it to the activities of educational work, such as construction and development of the curriculum. Results. With the research process, the definition of the concept of bioethical thinking was built ­collectively­ and a practical-senti-thinking curriculum was designed for Physiotherapy students, based on senti-thinking pedagogy and the paradigm of the triadic (or triune) brain that interrelates actions, feelings and knowledge in the human training of future physiotherapists. Conclusion. The practical thinking curriculum transcends a trinitarian cognitive structure, highlighting the importance of interweaving the disciplines for the survival of the human being and the balance of the planet, highlighting the humanistic and bioethics, through a curriculum that evokes the reflection of educational community to articulate the disunited.

Tratamiento endovascular de aneurismas con anatomía aórtica compleja / Endovascular treatment of aneurysms with complex aortic anatomy

RESUMEN Introducción: la anatomía arterial es la principal limitante para el abordaje aórtico endovascular estándar. Presentamos nuestra experiencia para la reparación endovascular de aneurismas aórticos complejos. Material y métodos: estudio observacional retrospectivo en pacientes con aneurismas complejos (yuxta/pararrenales y toracoabdominales) tratados en forma consecutiva mediante: endoprótesis fenestradas (FEVAR), ramificadas (BEVAR), con EndoAnchors (ESAR), o en chimenea (ChEVAR). La decisión de la técnica fue determinada con base en la anatomía arterial. Resultados: se evaluaron los últimos 50 procedimientos (6 mujeres; edad promedio 71,3 años; diámetro 69,6mm; 3 pacientes con aneurismas complicados), de los cuales 22 recibieron FEVAR (2,8 fenestraciones / paciente), 11 BEVAR, 11 ESAR y 6 ChEVAR (1,8 chimeneas /paciente). La tasa de éxito técnico fue del 100% (ausencia de endoleak I o III con permeabilidad adecuada de los vasos viscerales). A 30 días 3 pacientes fallecieron (6%). Durante el seguimiento, 5 pacientes presentaron oclusión de la arteria renal, repermeabilizada en 4. Cuatro pacientes desarrollaron un endoleak tipo IA (3 ESAR secundarios y un ChEVAR), un paciente un endoleak IC y un cuarto uno IIIB (22%, 3 de los 11 ESAR, ninguno de los FEVAR industriales). En el análisis de supervivencia, la supervivencia global fue del 88,6% al año, y libre de reoperación del 86,5%. Conclusiones: se trata de la primera publicación en nuestro medio que muestra un enfoque global del paciente con un aneurisma de aorta complejo, de acuerdo con sus características anatómicas. Estas tecnologías ya desempeñan un papel primario en el tratamiento de estos pacientes.

ABSTRACT Background: Arterial anatomy is the main limiting factor for standard endovascular aortic (EVAR) approach. We present our experience for endovascular repair of complex aortic aneurysms. Material and Methods: This is a retrospective observational study in patients with complex aneurysms (juxta/pararenal and thoracoabdominal) treated consecutively with: fenestrated (FEVAR), branched (BEVAR), EndoAnchors (ESAR), or chimney (ChEVAR) stents. The decision of the technique was determined based on the arterial anatomy. Results: The last 50 procedures were evaluated (6 women; mean age 71.3 years; diameter 69.6 mm; and 3 patients with complicated aneurysms), among whom 22 received FEVAR (2.8 fenestrated stents/patient), 11 BEVAR, 11 ESAR and 6 ChEVAR (1.8 chimney stents/patient). Technical success rate was 100% (absence of type I or III endoleak with adequate patency of the visceral vessels). Three patients died within the first 30 days (6%). During follow-up, 5 patients presented with renal artery occlusion, treated successfully in 4 cases. Four patients developed type IA endoleak (3 secondary ESAR and one ChEVAR), one patient IC endoleak and almost a quarter of cases type IIIB endoleak (22%, 3 out of 11 patients receiving ESAR, none of the industrial FEVAR group). In survival analysis, overall survival analysis was 88.6% at one year, and 86.5% of cases were free from reoperation. Conclusions: This is the first publication in our setting that shows a global approach to the patient with complex aortic aneurysm, according to the anatomical characteristics. These technologies already play a primary role in the treatment of these patients.