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1.
Artigo em Inglês | MEDLINE | ID: mdl-32218019

RESUMO

BACKGROUND: Early single-dose treatment with human mesenchymal stem cell (MSC)-derived exosomes promotes neuroprotection and promotes blood-brain barrier (BBB) integrity in models of traumatic brain injury (TBI) and hemorrhagic shock (HS) in swine. The impact of an early single dose of exosomes on late survival (7-day), however, remains unknown. We sought to evaluate the impact of early single-dose exosome treatment on neurologic outcomes, brain lesion size, inflammatory cytokines, apoptotic markers, and mediators of neural plasticity in a 7-day survival model. METHODS: Yorkshire swine were subjected to a severe TBI (8-mm cortical impact) and HS (40% estimated total blood volume). After one hour of shock, animals were randomized (n=4/cohort) to receive either lactated Ringer's (LR; 5mL) or LR + exosomes (LR+EXO; 1 × 10 exosome particles). After an additional hour of shock, animals were resuscitated with normal saline. Daily neurologic severity scores (NSS) were compared. At 7 days following injury, lesion size, inflammatory markers, and mediators of inflammation (NF-κB), apoptosis (BAX), and neural plasticity (BDNF) in brain tissue were compared between groups. RESULTS: Exosome-treated animals had significantly lower NSS (first 4 days; p < 0.05) and faster neurologic recovery. At 7-days, exosome-treated animals had significantly smaller (p < 0.05) brain lesion sizes. Exosome-treated animals also had significantly lower levels of inflammatory markers (IL-1, IL-6, IL-8, and IL-18) and higher granulocyte-macrophage colony stimulating factor (GM-CSF) levels compared to the control animals, indicating specific impacts on various cytokines. BAX and NF-κB levels were significantly lower (p < 0.05) in exosome-treated animals, while BDNF levels were significantly higher (p < 0.05) in the exosome-treated animals. CONCLUSIONS: In a large animal model of TBI and HS, early single-dose exosome treatment attenuates neurologic injury, decreases brain lesion size, inhibits inflammation and apoptosis, and promotes neural plasticity over a seven-day period. LEVEL OF EVIDENCE: Not applicable (pre-clinical study).

2.
Artigo em Inglês | MEDLINE | ID: mdl-32195993

RESUMO

BACKGROUND: Trauma is the leading cause of death for young Americans. Nonspecific histone deacetylase (HDAC) inhibitors, such as valproic acid (VPA), have been shown to improve survival in preclinical models of lethal trauma, hemorrhage and sepsis. The doses needed to achieve a survival benefit are higher than FDA-approved doses, and the nonspecificity raises concerns about unintended adverse effects. The isoform specific HDAC-6 inhibitor, ACY-1083, has been found to be as efficacious as VPA in a rodent model of hemorrhagic shock. We hypothesized that ACY-1083 treatment would improve survival in a swine model of lethal hemorrhage, polytrauma and bacteremia. METHODS: Swine were subjected to 45% blood volume hemorrhage, brain injury, femur fracture, rectus crush, splenic and liver lacerations, and colon injury. After 1 hour of shock (mean arterial pressure 30-35 mmHg), animals were randomized to normal saline resuscitation (control) or normal saline+ACY-1083 30mg/kg treatment (n=5/group). After 3 hours (simulating delayed evacuation), packed red blood cells and antibiotics were administered, the colon injury was repaired, and the abdomen was closed. Animals were then monitored for another 4 hours. Survival was assessed using Kaplan-Meier and log-rank test. RESULTS: This combination of injuries was lethal. All animals became bacteremic, in addition to the severe hemorrhagic shock. Survival in the control group was 0% and ACY-1083 treatment increased survival to 80% (p=0.019). There was no difference in the brain lesion size between the groups. CONCLUSION: A single dose of ACY-1083 markedly improves survival in an otherwise lethal model of polytrauma, hemorrhagic shock and bacteremia. LEVEL OF EVIDENCE: Basic science.

3.
Tuberculosis (Edinb) ; 120: 101902, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32090863

RESUMO

Despite the availability of potent antitubercular drugs, tuberculosis (TB) still remains one of the world's leading causes of death. The current antitubercular therapy (ATT) suffers from a drawback of longer duration that imposes a major challenge of patient non compliance and resistance development. The current scenario necessitates alternative strategies with potential to shorten treatment duration that could pave the way for improved clinical outcomes. In recent years, host directed adjunctive therapies have raised considerable attention and emerged as a promising intervention which targets clinically relevant biological pathways in hosts to modulate pathological immune responses. Few of the approved drugs namely statins, metformin, ibuprofen, aspirin, valproic acid, adalimumab, bevacizumab, zileuton and vitamin D3 have shown promising results in clinical outcomes during their preliminary screening in TB patients and can be potentially repurposed as antitubercular drugs. This review highlights clinical and non clinical evidences of some already existing drug and their targets in hosts that could help in shortening treatment duration and reducing bacterial burden at minimal doses.

4.
J Pediatr ; 218: 192-197.e1, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31955882

RESUMO

OBJECTIVE: To evaluate rates and characteristics of slipped capital femoral epiphysis (SCFE) in children who are not obese to prevent missed diagnoses and subsequent complications. STUDY DESIGN: A multicenter, retrospective review identified all patients with SCFE from January 1, 2003 to December 31, 2012. Patients were excluded if they received previous surgery at an outside institution, had no recorded height and weight, or had medical co-morbidity associated with increased risk of SCFE. Body mass index (BMI) percentile for age was calculated and categorized for each patient (patients without obesity vs with obesity). RESULTS: In total, 275 patients met inclusion criteria. Average BMI was 91.2 percentile (range: 8.4-99.7). Thirteen percent (34 patients) were considered "normal weight" (BMI 5%-85%), 17% (48 patients) were considered "overweight" (BMI 85%- 95%), and 70% (193 patients) were considered "obese" (BMI >95%). Average BMI percentile was higher in male than female patients (93.2 ± 12.7 vs 88.5 ± 21.4, P = .034). Patients without obesity were older compared with patients with obesity (12.2 ± 1.7 vs 11.7 ± 1.6 years, P = .015). Fewer patients without obesity were seen at the hospital in the southwest. The southwest had fewer patients without obesity than the northeast (18.3% vs 36.1%, P = .002). Patients without obesity were more likely to present with a severe slip as graded by Wilson percent displacement (27.2% vs 11.4%, P = .007) and an unstable slip (32.9% vs 14.7%, P = .001). CONCLUSION: Rates of nonobese SCFE in this study are higher than reported in the previous literature. Normal weight patients with SCFE are more likely to be older, female, and present with a severe and unstable SCFE.

5.
J Trauma Acute Care Surg ; 88(2): 207-218, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31804413

RESUMO

BACKGROUND: Administration of human mesenchymal stem cell (MSC)-derived exosomes can enhance neurorestoration in models of traumatic brain injury (TBI) and hemorrhagic shock (HS). The impact of early treatment with MSC-derived exosomes on brain injury in a large animal model remains unknown. We sought to evaluate the impact of early single-dose exosome treatment on brain swelling and lesion size, blood-based cerebral biomarkers, and blood-brain barrier (BBB) integrity. METHODS: Female Yorkshire swine were subjected to a severe TBI (12-mm cortical impact) and HS (40% estimated total blood volume). One hour into shock, animals were randomized (n = 5/cohort) to receive either lactated Ringer's (LR; 5 mL) or LR + exosomes (1 × 10 exosome particles in 5 mL LR). Animals then underwent additional shock (1 hour) followed by normal saline resuscitation. After 6 hours of observation, brain swelling (% increase compared with the uninjured side) and lesion size (mm) were assessed. Cerebral hemodynamics and blood-based biomarkers of brain injury were compared. Immunofluorescence and RNA sequencing with differential gene expression and pathway analysis were used to assess the integrity of the perilesion BBB. RESULTS: Exosome-treated animals had significantly less (p < 0.05) brain swelling and smaller lesion size. They also had significantly decreased (p < 0.05) intracranial pressures and increased cerebral perfusion pressures. Exosome-treated animals had significantly decreased (p < 0.05) albumin extravasation and significantly higher (p < 0.05) laminin, claudin-5, and zonula occludens 1 levels. Differential gene expression and pathway analysis confirmed these findings. Serum glial fibrillary acidic protein levels were also significantly lower (p < 0.05) in the exosome-treated cohort at the end of the experiment. CONCLUSION: In a large animal model of TBI and HS, early treatment with a single dose of MSC-derived exosomes significantly attenuates brain swelling and lesion size, decreases levels of blood-based cerebral biomarkers, and improves BBB integrity.


Assuntos
Barreira Hematoencefálica/patologia , Lesões Encefálicas Traumáticas/terapia , Exossomos/transplante , Células-Tronco Mesenquimais/citologia , Choque Hemorrágico/terapia , Animais , Lesões Encefálicas Traumáticas/etiologia , Lesões Encefálicas Traumáticas/patologia , Modelos Animais de Doenças , Feminino , Humanos , Ressuscitação/métodos , Choque Hemorrágico/etiologia , Choque Hemorrágico/patologia , Sus scrofa , Fatores de Tempo , Resultado do Tratamento
7.
Endosc Int Open ; 7(11): E1419-E1423, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31673613

RESUMO

Background and study aims Fully covered self-expanding metal stents (FCSEMS) have been used to treat refractory pancreatic duct strictures. We aimed to evaluate the feasibility, safety, and efficacy of FCSEMS in chronic pancreatitis with refractory pancreatic duct strictures. Patients and methods This was a retrospective multicenter cases series of patients who underwent endoscopic retrograde cholangiopancreatography (ERCP) with FCSEMS placement in the main pancreatic duct (MPD) at five tertiary care centers between February 2010 and June 2016. Primary endpoints were technical success, clinical success, and procedure-related morbidity. Secondary endpoints were pain relief at the end of follow-up and resolution of the pancreatic stricture on ERCP. Results Thirty-three patients with previously drained stents, 76 % of whom were male, underwent ERCP with FCSEMS placement. Mean duration of follow-up was 14 months. All of the patients had prior therapy. The technical success rate for FCSEMS placement was 100 % (n = 33) and the clinical success rate was 93 % (was n = 31). Stents were removed after a median duration of 14.4 weeks. After stent removal, the diameter of the narrowest MPD stricture had increased significantly from 1 mm to 4.5 mm ( P  < 0.001). There was a statistically significant improvement on the Visual Analogue Scale (VAS) from a median of 8.5 to 2.5. At the end of the study, (n = 27) 87.1 % of patients reported significant pain reduction with reduced narcotic use. Conclusion FCSEMS appeared to be a feasible, safe, and potentially effective Intervention in patients who had not responded to endoscopic therapy with plastic stents.

8.
J Pediatr Orthop ; 2019 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-31770170

RESUMO

BACKGROUND: Controversy exists regarding the treatment of length unstable pediatric femoral shaft fractures. The purpose of this study was to investigate the outcomes of skeletally immature children with length unstable femur fractures treated with titanium elastic nails (TENs). METHODS: A retrospective review was conducted on all patients with femoral shaft fractures at a tertiary care pediatric hospital from April 2006 to January 2018. Patients with femoral shaft fractures treated with TEN and minimum 6 months follow-up were included. Exclusion criteria were age 11 years or above, weight >50 kg, pathologic fracture, and neuromuscular disorders. Femur fractures were categorized into 2 groups: length unstable (spiral, comminuted, or long oblique fractures) versus length stable (transverse and short oblique). Complications and reoperations were compared between the groups. RESULTS: A total of 57 patients with 58 femoral shaft fractures were included. The mean age was 5±2 (1 to 11) years and mean follow-up was 20.4±18.1 (6.0 to 81.2) months. The mean weight was 22.9±7.7 (11.0 to 40.5) kg. There was no difference in age (P=0.32), weight (P=0.28) or follow-up length (P=0.57) between patients with length unstable fractures and those with length stable fractures. A total of 32/58 (55%) fractures were length unstable and 26/58 (45%) were length stable. Mean time to union was 4.6 months, and there was no significant difference in mean time to union between the 2 groups (P=0.71). Thirty-one complications occurred in 27 patients. There was no difference between groups in the incidence of major complications requiring revision surgery (P=0.68) and minor complications that did not require revision surgery (P>0.99). CONCLUSIONS: In children with femoral shaft fractures treated with TEN, there was no difference in the incidence of complications or reoperations between those with length unstable fractures and those with length stable fractures. TEN are a safe and effective choice for operative fixation of length unstable femoral shaft fractures in children. LEVEL OF EVIDENCE: Level III-retrospective comparative study.

9.
Spine Deform ; 7(6): 985-991, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31732012

RESUMO

DESIGN: Multicenter retrospective review. OBJECTIVE: To evaluate radiographic outcomes and complication rates of patients treated with distraction based implants and pelvic fixation with either screws (sacral-alar-iliac [SAI] screws or iliac screws) or hooks (S hook iliac fixation). SUMMARY OF BACKGROUND DATA: Multiple options exist for pelvic fixation in distraction-based growing rod systems; however, limited comparative data are available. METHODS: Early-onset scoliosis (EOS) patients of all diagnoses with distraction-based implants that had pelvic fixation from 2000 to 2013 were reviewed from two EOS multicenter databases. Patients were divided into two groups by type of pelvic fixation: (1) screw group (SAI screws or iliac screws) or (2) S hooks. Exclusion criteria were as follows: index instrumentation ≥10 years old and follow up <2 years. A total of 153 patients met the inclusion criteria. Mean age at index surgery was 6.1 years (range 1.0-9.9 years) and mean follow-up was 4.9 years. RESULTS: Pelvic fixation in the 153 patients was as follows: screw group = 42 and S hook group = 111. When comparing patients with >20° of initial pelvic obliquity, the screw group had significantly more correction; mean 26° ± 13° for the screw group versus mean 17° ± 7° in the S hook group (p = .039). There was no significant difference in change in T1-S1 length (40 vs. 39 mm, p = .89) or correction of Cobb angle (30° vs. 24°, p = .24). The total complication rate for the screw group was 14% (6/42) versus 25% (28/111) in the S hook group, though this did not achieve significance (p = .25). The most common complications were device migration (13), implant failure (8), and implant prominence (4) for S hooks and implant failure (3), implant prominence (2), and device migration (1) for the screw group. CONCLUSION: In distraction-based growth-friendly constructs, pelvic fixation with screws achieved better correction of pelvic obliquity than S hooks. Complications were almost twice as common with S hooks than screws, though this did not reach statistical significance.

10.
Minerva Gastroenterol Dietol ; 65(3): 193-199, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31617695

RESUMO

BACKGROUND: There is currently limited long-term data regarding the clinical outcomes of endoscopic stents as an alternative for emergency surgery in the treatment of acute esophageal perforation. Our aim was to compare the long-term outcomes of endoscopic stenting with those of surgery for patients with acute esophageal perforation. METHODS: We performed a retrospective study of acute esophageal perforation patients who underwent insertion of esophageal stents (N.=80) or surgery (N.=85) for treatment. The primary endpoint was technical and clinical success to resolve esophageal perforation. Secondary endpoints include early (procedural) and long-term adverse event, acute mortality, and hospital stay duration. RESULTS: Technical success was achieved in 78% of patients treated with stent, and 90.6% of patients who underwent surgery. Clinical success to resolve perforation was 88.7% of patients with stent placement and 95.3% in the surgery group (P=0.15). Stent patients had significantly less procedural adverse events compared to the surgery group (3.8% vs. 15%, P=0.0001). The acute mortality for the stent group was 2.5% compared to 3.5% in surgery group (P=0.6). Patients in the stent group had shorter median hospital stay (22 days) as compared to the surgery group (32 days) (P<0.00001). Stent placement was associated with higher long-term complication rates as compared to surgery (31.2% vs. 10.6%, P=0.0001). Patients who underwent surgery had a significantly higher mortality (10.6%) compared to stent group (2.5%) (P=0.05). CONCLUSIONS: Technical and clinical success for acute esophageal perforation therapy were similar among patients who underwent placement of stents as compared to surgery. Surgery was associated with a higher mortality, longer hospital stay and a markedly higher rate of procedural adverse events. Esophageal stents may be considered as the initial mode of therapy of a patient with acute esophageal perforation.

11.
J Trauma Acute Care Surg ; 87(5): 1133-1139, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31389922

RESUMO

BACKGROUND: Trauma is a leading cause of death, and traumatic brain injury is one of the hallmark injuries of current military conflicts. Valproic acid (VPA) administration in high doses (300-400 mg/kg) improves survival in lethal trauma models, but effectiveness of lower doses on survival is unknown. This information is essential for properly designing the upcoming clinical trials. We, therefore, performed the current study to determine the lowest dose at which VPA administration improves survival in a model of lethal injuries. METHODS: Swine were subjected to traumatic brain injury (10-mm cortical impact), 40% blood volume hemorrhage, and multiple trauma (femur fracture, rectus crush, and Grade V liver laceration). After 1 hour of shock, animals were randomized (n = 6/group) to four groups: normal saline (NS) resuscitation; or NS with VPA doses of 150 mg/kg (VPA 150) or 100 mg/kg (VPA 100) administered over 3 hours or 100 mg/kg over 2 hours (VPA 100 over 2 hours). Three hours after shock, packed red blood cells were given, and animals were monitored for another 4 hours. Survival was assessed using Kaplan-Meier and log-rank test. RESULTS: Without resuscitation, all of the injured animals died within 5 hours. Similar survival rates were observed in the NS (17%) and VPA 100 (0%) resuscitation groups. Survival rates in the 100-mg/kg VPA groups were significantly (p < 0.05) better when it was given over 2 hours (67%) compared to 3 hours (0%). 83% of the animals in the VPA 150 group survived, which was significantly higher than the NS and VPA 100 over 3 hours groups (p < 0.05). CONCLUSION: A single dose of VPA (150 mg/kg) significantly improves survival in an otherwise lethal model of multiple injuries. This is a much lower dose than previously shown to have a survival benefit and matches the dose that is tolerated by healthy human subjects with minimal adverse effects. LEVEL OF EVIDENCE: Therapeutic, level V.

12.
Dig Liver Dis ; 51(11): 1557-1561, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31272934

RESUMO

INTRODUCTION: Lumen apposing metal stents (LAMS) have been used increasingly for drainage of pancreatic fluid collections (PFC). We present an international, multicenter study evaluating the safety and efficacy of LAMS in PFCs. METHODS: Consecutive patients undergoing LAMS placement for PFC at 12 international centers were included (ClinicalTrials.gov NCT01522573). Demographics, clinical history, and procedural details were recorded. Technical success was defined as successful LAMS deployment. Clinical success was defined as PFC resolution at three-month follow-up. RESULTS: 192 patients were included (140 males (72.9%), mean-age 53.8 years), with mean follow-up of 4.2 months ±â€¯3.8. Mean PFC size was 11.9 cm (range 2-25). The median number of endoscopic interventions was 2 (range 1-14). Etiologies for PFC were gallstone (n = 82, 42.7%), alcohol (n = 50, 26%), idiopathic (n = 26, 13.5%), and other (n = 34, 17.7%). Technical success was achieved in 189 patients (98.4%). Clinical success was observed in 125 of 135 patients (92.6%). Adverse events included bleeding (n = 11, 5.7), infection (n = 2, 1%), and perforation (n = 2, 1%). Three or more endoscopy sessions were a positive predictor for PFC resolution and the only significant predictor for AEs. CONCLUSION: LAMS has a high technical and clinical success rate with a low rate of AEs. PFC drainage via LAMS provides a minimally invasive, safe, and efficacious procedure for PFC resolution.

13.
Endosc Int Open ; 7(6): E751-E756, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31157292

RESUMO

Background and study aims Stent migration is a common complication of fully-covered self-expanding metal stents (FCSEMS), but the rate of clinically relevant migration as defined by stent migration followed by reintervention via endoscopy for stent replacement is unknown. The goal of this study is to gain insight into the total migration rate and clinically relevant migration rate of different types of FCSEMS placed within benign and malignant strictures with specific attention paid to stent manufacturer, diameter, and length. Patients and methods Multicenter retrospective analysis of endoscopic data from patients with FCSEMS placed within benign or malignant strictures. FCSEMS used included a variety of sizes and manufacturers. Results A total of 369 patients were included, 161 of whom had benign strictures and 208 of whom had malignant strictures. The total migration rate and clinically relevant migration rate in benign strictures were 30 % and 17 %, respectively. For benign strictures, Wallflex stents had a clinically relevant migration rate of 15 %, compared to Endomaxx stents with 19 %, and Evolution stents with 25 % ( P  = 0.52). The total migration rate and clinically relevant migration rates in malignant strictures were 23 % and 14 %, respectively. Evolution stents had a significantly higher clinically relevant migration rate (29 %) than the Wallflex stents (7 %) and the endomaxx stents (12 %), P  = 0.003. Conclusion This study is the largest to investigate migration rates for FCSEMS in benign and malignant strictures. Clinically relevant migration is a relatively common occurrence with all stent types studied and better anti-migration features are needed.

14.
Semin Cancer Biol ; 2019 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-31100322

RESUMO

Cancer and autoimmune diseases are the two devastating conditions that together constitute a leading health problem worldwide. The rising burden of these disorders in the developing world demands a multifaceted approach to address the challenges it poses. Understanding the root causes and specific molecular mechanisms by which the progression of the diseases takes place is need of the hour. A strong inflammatory background and common developmental pathways, such as activation of immune cells, proliferation, increased cell survival and migration which are controlled by growth factors and inflammatory cytokines have been considered as the critical culprits in the progression and complications of these disorders. Enzymes are the potential immune modulators which regulate various inflammatory events and can break the circulating immune complexes via macrophages production. In the current manuscript, we have uncovered the possible role of proteolytic enzymes in the pathogenesis and progression of cancer and autoimmune diseases. In the light of the available scientific literature, we advocate in-depth comprehensive studies which will shed light towards the role of proteolytic enzymes in the modulation of inflammatory responses in cancer and autoimmune diseases together.

16.
Endosc Ultrasound ; 8(3): 194-198, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30719997

RESUMO

Background and Objectives: Endoscopic drainage/debridement of symptomatic walled off necrosis (WON) using lumen-apposing metal stents (LAMS) is both safe and effective. While endoscopic management of WON is the standard approach to treatment, the ideal concomitant medical therapy remains unclear. The purpose of this study was to further elucidate the effect of proton pump inhibitor (PPIs) therapy on the technical and clinical success of endoscopic treatment of WON. Methods: Two hundred and seventy-two patients in 8 centers with WON managed by endoscopic drainage using LAMS were evaluated. Patients were followed for at least 6 months following treatment. The patients were divided into two groups: Those that used PPIs continuously during the therapy and those not on PPIs continuously during the interval of therapy. Outcomes included but were not limited to technical success, clinical success, number of procedures performed, and adverse events. Results: From 2013 to 2016, 272 patients underwent WON drainage with successful transmural LAMS placement. The two groups were split evenly into PPI users and non-PPI users, and matched in regards to demographics, etiology of pancreatitis, WON size, and location. There was no difference in the technical success between the two groups (100% vs. 98.8%, P = 1), or in clinical success rates (78.7% vs. 77.9%). There was a significant difference in the required number of direct endoscopic necrosectomies to achieve clinical success in the PPI vs. non-PPI group (3.2 vs. 4.6 respectively, P < 0.01). There were significantly more cases of stent occlusion in the non-PPI group vs. PPI group (9.5% vs. 20.1% P = 0.012), but all other documented adverse events were not significantly different. Conclusion: Discontinuing PPIs during endoscopic drainage and necrosectomy of symptomatic WON appears to reduce the number of endoscopic procedures required to achieve resolution. Continuous PPI results in higher rates of early stent occlusion.

17.
J Gastroenterol Hepatol ; 34(6): 975-984, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30614083

RESUMO

BACKGROUND AND AIM: Atrial fibrillation is one of the most common comorbid conditions in hemodialysis patients, and warfarin is widely prescribed anticoagulant to prevent thromboembolic complications in such patients. In the last decade, several epidemiological studies pointed out the risk of bleeding with the use of warfarin. So, this meta-analysis is aimed to assess the bleeding risk associated with the use of warfarin. METHODS: This meta-analysis was conducted in accordance with the Preferred Reporting Items for Systematic Review and Meta-analysis guidelines. PubMed, Embase, Scopus, and Cochrane central databases were searched from inception to June 10, 2018. The primary outcome was to quantify the bleeding risk associated with warfarin use. The secondary outcome was to assess the bleeding risk based on different subgroups. Review Manager (RevMan) version 5.3 was used for performing statistical analysis. RESULTS: A total of 15 studies, constituting a pooled sample of 53 581 patients (37.14% female), were included. Of these, 17 469 were warfarin users. We found that warfarin use had a significant association with the bleeding risk. The pooled relative risk (RR) of bleeding was estimated to be 1.35 (95% CI: 1.18-1.53, P = < 0.00001), and the pooled RR of major bleeding (five studies) was estimated to be 1.32 (95% CI: 1.07-1.63, P = 0.009). Subgroup analysis revealed a significant association of warfarin use with the intracranial hemorrhage/hemorrhagic stroke (nine studies) (pooled RR: 1.43 [95% CI: 1.20-1.71, P = < 0.0001]). CONCLUSIONS: The results indicate that warfarin use increases the risk of bleeding in hemodialysis patients with atrial fibrillation.


Assuntos
Anticoagulantes/efeitos adversos , Fibrilação Atrial/complicações , Hemorragia Cerebral/induzido quimicamente , Hemorragia/induzido quimicamente , Diálise Renal/efeitos adversos , Varfarina/efeitos adversos , Estudos de Coortes , Bases de Dados Bibliográficas , Feminino , Humanos , Masculino , Risco , Tromboembolia/etiologia , Tromboembolia/prevenção & controle
18.
Endosc Ultrasound ; 8(1): 36-42, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-29770780

RESUMO

Backgrounds and Objectives: No study on the use of lumen-apposing fully covered self-expanding metal stent (LAMS) to drain pancreatic fluid collections (PFCs) has evaluated outcomes of patients in the outpatient setting. The objective of this multicenter study was to evaluate the clinical outcomes, success rate, and adverse events of the LAMS for endoscopic ultrasound (EUS)-guided transmural drainage of patients with symptomatic PFCs on an inpatient versus an outpatient basis. Methods: This was a multicenter, retrospective study conducted at 4 tertiary care centers. Results: We identified eighty patients with PFCs in whom EUS-guided transmural drainage using the LAMS was performed. The mean age of the patients was 53.1 years old. Mean size of the PFC was 11.8 ± 5.1 cm. A total of 33 patients had PFCs drained in an outpatient setting while 47 patients underwent PFC drainage as inpatients. The overall technical success (ability to access and drain a PFC by placement of transmural stents) was 98.7% (79 patients). There was no statistically significant difference in the technical success rate between the inpatient and outpatient groups (100% vs. 98%, respectively, P = 1). There was no significant difference in resolution of PFCs in the inpatient and outpatient groups (91% vs. 87% respectively; P = 1). The number of procedures required for PFC resolution was significantly lower in the inpatient group as compared to the outpatients (2.3 vs. 3.1 respectively, P = 0.025). Procedure-related adverse events were significantly lower in the inpatient group compared to the outpatient group (P < 0.01). There was no significant difference in the 2 groups in terms of development of adverse events requiring endoscopic reintervention within 30 days of initial stent placement (P = 0.69). Conclusion: This study shows that LAMS placement for PFCs can be performed safely on an outpatient basis with overall technical and clinical outcomes that are comparable to those seen in inpatients.

19.
J Clin Gastroenterol ; 53(1): 71-75, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-29517713

RESUMO

INTRODUCTION: In patients with pancreaticobiliary lesions anticipating surgical resection, digital pancreaticocholangioscopy can be used to identify the extent of disease. This presurgical"mapping" could change the surgical plan and optimize patient care. MATERIALS AND METHODS: Patients with pancreaticobiliary lesions anticipating surgery who underwent endoscopic retrograde cholangiopancreatography with digital pancreaticocholangioscopy from 9 international centers were included. Primary outcome was whether pancreaticocholangioscopy altered the surgical plan. Secondary outcome was correlation between surgical and endoscopic histology and adverse events. RESULTS: A total of 118 patients were included (64% male, mean age 69 y): cholangioscopy in 105 patients (89%), pancreatoscopy in 13 patients (11%). Pancreaticocholangioscopy changed the surgical plan in 39 (34%) of patients: 8 of 13 in the pancreatic duct, 32 of 105 in the bile duct. In the bile duct, 6 patients (5%) had less extensive surgery, 26 patients (25%) avoided surgery. In the pancreatic duct, 4 patients (31%) had more extensive surgery and 4 patients (31%) had less extensive surgery. Four patients with downstaged surgery had positive margins on surgical resection; 1 required additional surgical intervention. Overall correlation between endoscopy and surgical histology was 88%. Adverse events included post endoscopic retrograde cholangiopancreatography pancreatitis in 3 patients (2.5%). CONCLUSION: Digital pancreaticocholangioscopy can be effectively used as a mapping tool to delineate the degree of involvement of biliary lesions before surgical resection, in some cases altering the surgical plan. Prospective studies are needed, especially when downstaging surgery.

20.
Endosc Ultrasound ; 8(3): 172-179, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-29882517

RESUMO

Background and Objectives: EUS-guided drainage, and direct endoscopic necrosectomy (DEN) of walled-off necrosis (WON) using a lumen-apposing metal stent (LAMS) is safe and effective. Early debridement of WON may improve overall clinical outcomes. The aim of this study is to perform a multicenter retrospective study to compare the clinical outcomes and predictors of success for endoscopic drainage of WON with LAMS followed by immediate or delayed DEN performed at standard intervals. Methods: Patients with WON managed by EUS-guided drainage with LAMS were divided into 2 groups: (1) those that underwent immediate DEN at the time of stent placement and (2) those that underwent delayed DEN 1 week after stent placement. DEN was subsequently performed every 1-2 week (s). Technical success (successful placement of LAMS), adverse events (AEs), and clinical success (complete resolution of the WON) were evaluated. Results: Totally, 271 patients underwent WON drainage with LAMS: 69 who underwent immediate DEN and 202 who underwent delayed DEN. The technical success for LAMS placement was 100% in both groups. There was no significant difference in the overall procedural AEs between the immediate and delayed DEN groups (P = 7.2% vs. 9.4%; P = 0.81). Stent dislodgement during index endoscopy occurred in three patients in the immediate DEN group compared to zero in the delayed DEN group (P = 0.016); all three dislodgements occurred during necrosectomy. Clinical success for WON resolution in the immediate DEN group was 91.3% compared to 86.1% in the delayed DEN group (P = 0.3). The mean number of necrosectomy sessions for WON resolution was significantly lower in the immediate DEN group compared to the delayed DEN group (3.1 vs. 3.9, P < 0.001). Performing DEN at the time of stent placement was an independent predictor for resolution of WON with lesser number of DEN sessions (odds ratio 2.3; P = 0.004). Conclusions: DEN at the time of initial stent placement reduces the number of necrosectomy sessions required for successful clinical resolution of WON.

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