The impact of spinal cord injury(SCI)on the immune system is increasingly recognized in a field traditionally focused on motor impairments.SCI can seriously affect the immune system by progressively disrupting the reg...The impact of spinal cord injury(SCI)on the immune system is increasingly recognized in a field traditionally focused on motor impairments.SCI can seriously affect the immune system by progressively disrupting the regulatory mechanisms that control immune responses.This dysregulation varies widely among patients and can evolve over time,ranging from systemic inflammatory responses to immunosuppression,greatly contributing to the morbidity and mortality of individuals with SCI(Bao et al.,2011;Brennan et al.,2024).展开更多
Spinal cord injuries have profound detrimental effects on individuals, regardless of whether they are caused by trauma or non-traumatic events. The compromised regeneration of the spinal cord is primarily attributed t...Spinal cord injuries have profound detrimental effects on individuals, regardless of whether they are caused by trauma or non-traumatic events. The compromised regeneration of the spinal cord is primarily attributed to damaged neurons, inhibitory molecules, dysfunctional immune response, and glial scarring. Unfortunately, currently, there are no effective treatments available that can fully repair the spinal cord and improve functional outcomes. Nevertheless, numerous pre-clinical approaches have been studied for spinal cord injury recovery, including using biomaterials, cells, drugs, or technological-based strategies. Combinatorial treatments, which target various aspects of spinal cord injury pathophysiology, have been extensively tested in the last decade. These approaches aim to synergistically enhance repair processes by addressing various obstacles faced during spinal cord regeneration. Thus, this review intends to provide scientists and clinicians with an overview of pre-clinical combinatorial approaches that have been developed toward the solution of spinal cord regeneration as well as update the current knowledge about spinal cord injury pathophysiology with an emphasis on the current clinical management.展开更多
BACKGROUND Adenomatous polyposis confers an increased risk of developing colorectal cancer.APC and MUTYH are the major genes investigated in patients suspected of having polyposis.In addition to APC and MUTYH genes,ot...BACKGROUND Adenomatous polyposis confers an increased risk of developing colorectal cancer.APC and MUTYH are the major genes investigated in patients suspected of having polyposis.In addition to APC and MUTYH genes,other genes,such as POLE,POLD1,NTHL1,MBD4,MSH3 and MLH3,have recently been associated with polyposis phenotypes,conferring heterogeneity in terms of the clinical,etiological and heritable aspects of patients with polyposis.AIM To investigate the underlying variant landscape in patients with suspected polyposis who lack variants in the APC and MUTYH genes using whole-exome sequencing.METHODS Twenty-seven participants were included in the study and subjected to germline whole-exome sequencing.In addition,their clinical-pathological,personal,and family history data were collected.RESULTS The mean age at diagnosis was 51 years,and most participants had attenuated forms of polyposis(88.9%),with 63.0%diagnosed with a primary tumor,mostly colorectal cancer(76.5%).Among the variants identified,17 were classified as pathogenic or likely pathogenic(in 12 participants),including variants in genes involved in the Wnt/β-catenin signaling pathway,such as ST7 L,A1CF,and DKK4,and variants in DNA-repair genes,such as NTHL1,PNKP,and PMS2,as well as a variant found at the FRK gene identified in a patient with classic polyposis at age 19 and with a family history of polyps.CONCLUSION This study identified novel genes potentially associated with polyposis in patients lacking germline pathogenic variants in the APC and MUTYH genes.These findings support the use of next-generation sequencing for screening,expanding the scope of polyposis-related variants beyond these two genes.展开更多
Spinal cord injury(SCI)involves an initial traumatic phase,followed by secondary events such as ischemia,increased blood-spinal cord barrier permeability,ionic disruption,glutamate excitotoxicity,and metabolic alterat...Spinal cord injury(SCI)involves an initial traumatic phase,followed by secondary events such as ischemia,increased blood-spinal cord barrier permeability,ionic disruption,glutamate excitotoxicity,and metabolic alterations.A pe rsistent and exagge rated inflammato ry response within the spinal cord accompanies these events(Lima et al.,2022).The complexity and interplay of these mechanisms exacerbate the initial injury,leading to a degenerative process at the injury site.While the initial trauma is unavoidable,the secondary injury begins within minutes and can last for months,creating an optimal window for therapeutic intervention.展开更多
Background:Constitutional mismatch repair deficiency(CMMRD)is a rare disorder resulting from biallelic germline pathogenic variants in mismatch repair genes.This study described the molecular profile of two metachrono...Background:Constitutional mismatch repair deficiency(CMMRD)is a rare disorder resulting from biallelic germline pathogenic variants in mismatch repair genes.This study described the molecular profile of two metachronous brain tumors and a patient-derived xenograft(PDX)from a Brazilian child with CMMRD.Methods:After PDX development,methylation array,whole exome sequencing,and Nano String techniques were applied to describe the genetic landscape of CMMRD.Results:A 6½-year-old girl was diagnosed with Sonic Hedgehog(SHH)-activated medulloblastoma and somatic TP53-mutant.After surgery and radiochemotherapy,she remained free of disease progression.At 10 years and 3 months,she developed a diffuse pediatric-type high-grade glioma(dp HGG).The child had a family history of cancer,and subsequent investigation revealed a biallelic germline variant on MSH6(c.3556+1G>A)with the absence of protein expression in both normal and tumor tissue.A PDX model of the dp HGG was developed.The methylation profile confirmed the diagnosis of both brain tumors and PDX,refining the classification of dp HGG,Rtk1 subtype,subclass A,with an actionable alteration on Platelet-derived growth factor receptor A(PDGFRA).Exome analysis showed high tumor mutational burden,with 3019,540,and 1049 pathogenic variants in the medulloblastoma,dp HGG,and PDX,respectively.Only the medulloblastoma exhibited microsatellite instability.The CD24,CD47,and CD276 immune checkpoints had elevated messenger RNA levels,yet no programmed death ligand 1 expression was observed in CMMRD-derived tumors.Conclusion:We report an extensive molecular profile of a CMMRD patient,and the developed PDX model can be applied to explore new therapeutic approaches for CMMRD-associated brain tumors.展开更多
Spinal cord injury(SCI)is a condition without treatment,mainly characterized by the loss of motor and sensory function below the level of injury.This is accompanied by several complications such as cardiac and respira...Spinal cord injury(SCI)is a condition without treatment,mainly characterized by the loss of motor and sensory function below the level of injury.This is accompanied by several complications such as cardiac and respiratory compromise,and often patients present psychological ailments associated with the drastic alteration of their normal lifestyle.SCI pathophysiology derives from a massive damage to the spinal cord tissue,which is propagated展开更多
Serrated adenocarcinoma is a recently described subset of colorectal cancer(CRC),which account for about10%of all CRCs and follows an alternative pathway in which serrated polyps replace the traditional adenoma as the...Serrated adenocarcinoma is a recently described subset of colorectal cancer(CRC),which account for about10%of all CRCs and follows an alternative pathway in which serrated polyps replace the traditional adenoma as the precursor lesion to CRC.Serrated polyps form a heterogeneous group of colorectal lesions that includes hyperplastic polyps(HPs),sessile serrated adenoma(SSA),traditional serrated adenoma(TSA)and mixed polyps.HPs are the most common serrated polyp followed by SSA and TSA.This distinct histogenesis is believed to have a major influence in prevention strategies,patient prognosis and therapeutic impact.Genetically,serrated polyps exhibited also a distinct pattern,with KRAS and BRAF having an important contribution to its development.Two other molecular changes that have been implicated in the serrated pathway include microsatellite instability and the CpG island methylator phenotype.In the present review we will address the current knowledge of serrated polyps,clinical pathological features and will update the most recent findings of its molecular pathways.The understanding of their biology and malignancy potential is imperative to implement a surveillance approach in order to prevent colorectal cancer development.展开更多
AIM: To study the practical applicability of the American Society for Gastrointestinal Endoscopy guidelines in suspected cases of choledocholithiasis.METHODS: This was a retrospective single center study, covering a 4...AIM: To study the practical applicability of the American Society for Gastrointestinal Endoscopy guidelines in suspected cases of choledocholithiasis.METHODS: This was a retrospective single center study, covering a 4-year period, from January 2010 to December 2013. All patients who underwent endoscopic retrograde cholangiopancreatography(ERCP) for suspected choledocholithiasis were included. Based on the presence or absence of predictors of choledocholithiasis(clinical ascending cholangitis, common bile duct(CBD) stones on ultrasonography(US), total bilirubin > 4 mg/d L, dilated CBD on US, total bilirubin 1.8-4 mg/d L, abnormal liver function test, age > 55 years and gallstone pancreatitis), patients were stratified in low, intermediate or high risk for choledocholithiasis. For each predictor and risk group we used the χ2 to evaluate the statistical associations with the presence of choledocolithiasis at ERCP. Statistical analysis was performed using SPSS version 21.0. A P value of less than 0.05 was considered statistically significant. RESULTS: A total of 268 ERCPs were performed for suspected choledocholithiasis. Except for gallstone pancreatitis(P = 0.063), all other predictors of cho-ledocholitiasis(clinical ascending cholangitis, P = 0.001; CBD stones on US, P ≤ 0.001; total bilirubin > 4 mg/dL, P = 0.035; total bilirubin 1.8-4 mg/dL, P = 0.001; dilated CBD on US, P ≤ 0.001; abnormal liver function test, P = 0.012; age > 55 years, P = 0.002) showed a statistically significant association with the presence of choledocholithiasis at ERCP. Approximately four fifths of patients in the high risk group(79.8%, 154/193 patients) had confirmed choledocholithiasis on ERCP, vs 34.2%(25/73 patients) and 0(0/2 patients) in the intermediate and low risk groups, respectively. The definition of "high risk group" had a sensitivity of 86%, positive predictive value 79.8% and specificity 56.2% for the presence of choledocholithiasis at ERCP. CONCLUSION: The guidelines should be considered to optimize patients' selection for ERCP. For high risk patients specificity is still low, meaning that some patients perform ERCP unnecessarily.展开更多
Minimally invasive surgery started spreading worldwide in 1987,when the first laparoscopic cholecystectomy was performed.Meanwhile,improvement of endoscopic equipment and instruments allowed gastroenterologists to att...Minimally invasive surgery started spreading worldwide in 1987,when the first laparoscopic cholecystectomy was performed.Meanwhile,improvement of endoscopic equipment and instruments allowed gastroenterologists to attempt more aggressive endoluminal interventions,even beyond the wall barrier.The first transgastric peri-toneoscopy,in 2004,brought to light the concept of natural orifice transluminal endoscopic surgery(NOTES).The idea of incisionless surgery is attractive and has become a new goal for both surgeons and other people interested in this field of investigation.The authors present a review of all developments concerning NOTES,including animal studies and human experience.展开更多
Upper gastrointestinal bleeding(UGIB) remains a significant cause of hospital admission. In order to stratify patients according to the risk of the compli-cations, such as rebleeding or death, and to predict the need ...Upper gastrointestinal bleeding(UGIB) remains a significant cause of hospital admission. In order to stratify patients according to the risk of the compli-cations, such as rebleeding or death, and to predict the need of clinical intervention, several risk scores have been proposed and their use consistently recommended by international guidelines. The use of risk scoring systems in early assessment of patients suffering from UGIB may be useful to distinguish high-risks patients, who may need clinical intervention and hospitalization, from low risk patients with a lower chance of developing complications, in which management as outpatients can be considered. Although several scores have been published and validated for predicting different outcomes, the most frequently cited ones are the Rockall score and the Glasgow Blatchford score(GBS). While Rockall score, which incorporates clinical and endoscopic variables, has been validated to predict mortality, the GBS, which is based on clinical and laboratorial parameters, has been studied to predict the need of clinical intervention. Despite the advantages previously reported, their use in clinical decisions is still limited. This review describes the different risk scores used in the UGIB setting, highlights the most important research, explains why and when their use may be helpful, reflects on the problems that remain unresolved and guides future research with practical impact.展开更多
Mesenchymal stem cells(MSCs)secretome:a good candidate for medical biotechnology?Medical biotechnology is currently defined as the application of biotechnological tools for producing multiple technologies and products...Mesenchymal stem cells(MSCs)secretome:a good candidate for medical biotechnology?Medical biotechnology is currently defined as the application of biotechnological tools for producing multiple technologies and products to health care,becoming an important bridge between different fields,namely neuroscience,regenerative medicine,pharmacology and bio-engineering(Pham,2018).The use and manipulation of stem cells can potentially represent a medical biotechnology breakthrough that brings regenerative medicine to a new era.Actually,over the last decade,the use of stem cells has remarkably been proposed as a regenerative tool,and within it,MSCs have emerged as a promising therapeutic option.展开更多
AIM:To evaluate whether the use of real time viewer(RTV)and administration of domperidone to patients with delayed gastric passage of the capsule could reduce the rate of incomplete examinations(IE)and improve the dia...AIM:To evaluate whether the use of real time viewer(RTV)and administration of domperidone to patients with delayed gastric passage of the capsule could reduce the rate of incomplete examinations(IE)and improve the diagnostic yield of small bowel capsule endoscopy(SBCE).METHODS:Prospective single center interventional study,from June 2012 to February 2013.Capsule location was systematically checked one hour after ingestion using RTV.If it remained in the stomach,the patient received 10 mg domperidone per os and the location of the capsule was rechecked after 30 min.If the capsule remained in the stomach a second dose of10 mg of domperidone was administered orally.After another 30 min the position was rechecked and if the capsule remained in the stomach,it was passed into the duodenum by upper gastrointestinal(GI)endoscopy.The rate of IE and diagnostic yield of SBCE were compared with those of examinations performed before the use of RTV or domperidone in our Department(control group,January 2009-May 2012).RESULTS:Both groups were similar regarding age,sex,indication,inpatient status and surgical history.The control group included 307 patients,with 48(15.6%)IE.The RTV group included 82 patients,with3(3.7%)IE,P=0.003.In the control group,average gastric time was significantly longer in patients with IE than in patients with complete examination of the small bowel(77 min vs 26 min,P=0.003).In the RTV group,the capsule remained in the stomach one hour after ingestion in 14/82 patients(17.0%)vs 48/307(15.6%)in the control group,P=0.736.Domperidone did not significantly affect small bowel transit time(260min vs 297 min,P=0.229).The capsule detected positive findings in 39%of patients in the control group and 49%in the RTV group(P=0.081).CONCLUSION:The use of RTV and selective administration of domperidone to patients with delayed gastric passage of the capsule significantly reduces incomplete examinations,with no effect on small bowel transit time or diagnostic yield.展开更多
Parkinson's disease is the second most prevalent neurodegenerative disorder worldwide.Clinically,it is characterized by severe motor complications caused by progressive degeneration of dopaminergic neurons.Current...Parkinson's disease is the second most prevalent neurodegenerative disorder worldwide.Clinically,it is characterized by severe motor complications caused by progressive degeneration of dopaminergic neurons.Current treatment is focused on mitigating the symptoms through the administration of levodopa,rather than on preventing dopaminergic neuronal damage.Therefore,the use and development of neuroprotective/disease-modifying strategies is an absolute need that can lead to promising gains on translational research of Parkinson's disease.For instance,N-acetylcysteine,a natural compound with strong antioxidant effects,has been shown to modulate oxidative stress,preventing dopamine-induced cell death.Despite the evidence of neuroprotective and modulatory effects of this drug,as far as we know,it does not induce per se any regenerative process.Therefore,it would be of interest to combine the latter with innovative therapies that induce dopaminergic neurons repair or even differentiation,as stem cell-based strategies.Stem cells secretome has been proposed as a promising therapeutic approach for Parkinson's disease,given its ability to modulate cell viability/preservation of dopaminergic neurons.Such approach represents a shift in the paradigm,showing that cell-transplantation free therapies based on the use of stem cells secretome may represent a potential alternative for regenerative medicine of Parkinson's disease.Thus,in this review,we address the current understanding of the potential combination of stem cell free-based strategies and neuroprotective/disease-modifying strategies as a new paradigm for the treatment of central nervous system neurodegenerative diseases,like Parkinson's disease.展开更多
AIM To examine the effect of Fusobacterium nucleatum(F. nucleatum) on the microenvironment of colonic neoplasms and the expression of inflammatory mediators and microRNAs(miRNAs).METHODS Levels of F. nucleatum DNA, cy...AIM To examine the effect of Fusobacterium nucleatum(F. nucleatum) on the microenvironment of colonic neoplasms and the expression of inflammatory mediators and microRNAs(miRNAs).METHODS Levels of F. nucleatum DNA, cytokine gene mRNA(TLR2, TLR4, NFKB1, TNF, IL1 B, IL6 and IL8), and potentially interacting miRNAs(miR-21-3p, miR-22-3p, mi R-28-5p, miR-34a-5p, miR-135b-5p) were measured by quantitative polymerase chain reaction(qPCR) TaqMan? assays in DNA and/or RNA extracted from the disease and adjacent normal fresh tissues of 27 colorectal adenoma(CRA) and 43 colorectal cancer(CRC) patients. KRAS mutations were detected by direct sequencing and microsatellite instability(MSI) status by multiplex PCR. Cytoscape v3.1.1 was used to construct the postulated miRNA:mRNA interaction network.RESULTS Overabundance of F. nucleatum in neoplastic tissue compared to matched normal tissue was detected in CRA(51.8%) and more markedly in CRC(72.1%). We observed significantly greater expression of TLR4, IL1 B, IL8, and miR-135 b in CRA lesions and TLR2, IL1 B, IL6, IL8, mi R-34 a and miR-135 b in CRC tumours compared to their respective normal tissues. Only two transcripts for miR-22 and miR-28 were exclusively downregulated in CRC tumour samples. The mRNA expression of IL1 B, IL6, IL8 and miR-22 was positively correlated with F. nucleatum quantification in CRC tumours. The mRNA expression of miR-135 b and TNF was inversely correlated. The miRNA:mRNA interaction network suggested that the upregulation of miR-34 a in CRC proceeds via a TLR2/TLR4-dependent response to F. nucleatum. Finally, KRAS mutations were more frequently observed in CRC samples infected with F. nucleatum and were associated with greater expression of miR-21 in CRA, while IL8 was upregulated in MSI-high CRC.CONCLUSION Our findings indicate that F. nucleatum is a risk factor for CRC by increasing the expression of inflammatory mediators through a possible mi RNA-mediated activation of TLR2/TLR4.展开更多
Spinocerebellar ataxias are heritable neurodegenerative diseases caused by a cytosine-adenine-guanine expansion,which encodes a long glutamine tract(polyglutamine)in the respective wild-type protein causing misfolding...Spinocerebellar ataxias are heritable neurodegenerative diseases caused by a cytosine-adenine-guanine expansion,which encodes a long glutamine tract(polyglutamine)in the respective wild-type protein causing misfolding and protein aggregation.Clinical features of polyglutamine spinocerebellar ataxias include neuronal aggregation,mitochondrial dysfunction,decreased proteasomal activity,and autophagy impairment.Mutant polyglutamine protein aggregates accumulate within neurons and cause neural dysfunction and death in specific regions of the central nervous system.Spinocerebellar ataxias are mostly characterized by progressive ataxia,speech and swallowing problems,loss of coordination and gait deficits.Over the past decade,efforts have been made to ameliorate disease symptoms in patients,yet no cure is available.Previous studies have been proposing the use of stem cells as promising tools for central nervous system tissue regeneration.So far,pre-clinical trials have shown improvement in various models of neurodegenerative diseases following stem cell transplantation,including animal models of spinocerebellar ataxia types 1,2,and 3.However,contrasting results can be found in the literature,depending on the animal model,cell type,and route of administration used.Nonetheless,clinical trials using cellular implants into degenerated brain regions have already been applied,with the expectation that these cells would be able to differentiate into the specific neuronal subtypes and re-populate these regions,reconstructing the affected neural network.Meanwhile,the question of how feasible it is to continue such treatments remains unanswered,with long-lasting effects being still unknown.To establish the value of these advanced therapeutic tools,it is important to predict the actions of the transplanted cells as well as to understand which cell type can induce the best outcomes for each disease.Further studies are needed to determine the best route of administration,without neglecting the possible risks of repetitive transplantation that these approaches so far appear to demand.Despite the challenges ahead of us,cell-transplantation therapies are reported to have transient but beneficial outcomes in spinocerebellar ataxias,which encourages efforts towards their improvement in the future.展开更多
AIM: To evaluate mucosal healing in patients with small bowel plus colonic Crohn's disease(CD) with a single non-invasive examination, by using PillCam COLON 2.(PCC2).METHODS: Patients with non-stricturing nonpene...AIM: To evaluate mucosal healing in patients with small bowel plus colonic Crohn's disease(CD) with a single non-invasive examination, by using PillCam COLON 2.(PCC2).METHODS: Patients with non-stricturing nonpenetrating small bowel plus colonic CD in sustained corticosteroid-free remission were included. At diagnosis,patients had undergone ileocolonoscopy to identify active CD lesions, such as ulcers and erosions, and small bowel capsule endoscopy to assess the Lewis Score(LS). After ≥ 1 year of follow-up, patients underwent entire gastrointestinal tract evaluation with PCC2. The primary endpoint was assessment of CD mucosal healing, defined as no active colonic CD lesions and LS < 135.RESULTS: Twelve patients were included(7 male;mean age: 32 years), and mean follow-up was 38 mo.The majority of patients(83.3%) received immunosuppressive therapy. Three patients(25%) achieved mucosal healing in both the small bowel and the colon,while disease activity was limited to either the small bowel or the colon in 5 patients(42%). It was possible to observe the entire gastrointestinal tract in 10 of the12 patients(83%) who underwent PCC2.CONCLUSION: Only three patients in sustainedcorticosteroid-free clinical remission achieved mucosal healing in both the small bowel and the colon, highlighting the limitations of clinical assessment when stratifying disease activity, and the need for pan-enteric endoscopy to guide therapeutic modification.展开更多
Since its emergence in 2000, small bowel capsule endoscopy(SBCE) has assumed a pivotal role as an investigation method for small bowel diseases. The PillCam SB2-ex offers 12 h of battery time, 4 more than the previous...Since its emergence in 2000, small bowel capsule endoscopy(SBCE) has assumed a pivotal role as an investigation method for small bowel diseases. The PillCam SB2-ex offers 12 h of battery time, 4 more than the previous version(SB2). Rahman et al recently found that the PillCam SB2-ex has a significantly increased completion rate, although without higher diagnostic yield, compared with the SB2. We would like to discuss these somewhat surprising results and the new potentialities of the PillCam SB3 regarding the diagnostic yield of small bowel studies. PillCam SB3 offers improved image resolution and faster adaptable frame rate over previous versions of SBCE. We recently compared the major duodenal papilla detection rate obtained with PillCam SB3 and SB2 as a surrogate indicator of diagnostic yield in the proximal small bowel. The PillCam SB3 had a significantly higher major duodenal papilla detection rate than the PillCam SB2(42.7% vs 24%, P = 0.015). Thus, the most recent version of the PillCam capsule, SB3, may increase diagnostic yield, particularly in the proximal segments of the small bowel.展开更多
BACKGROUND Anemia is considered a public health issue and is often caused by iron deficiency.Iron-deficiency anemia(IDA)often originates from blood loss from lesions in the gastrointestinal tract in men and postmenopa...BACKGROUND Anemia is considered a public health issue and is often caused by iron deficiency.Iron-deficiency anemia(IDA)often originates from blood loss from lesions in the gastrointestinal tract in men and postmenopausal women,and its prevalence among patients with gastrointestinal bleeding has been estimated to be 61%.However,few guidelines regarding the appropriate investigation of patients with IDA due to gastrointestinal bleeding have been published.AIM To review current evidence and guidelines concerning IDA management in gastrointestinal bleeding patients to develop recommendations for its diagnosis and therapy.METHODS Five gastroenterology experts formed the Digestive Bleeding and Anemia Workgroup and conducted a systematic literature search in PubMed and professional association websites.MEDLINE(via PubMed)searches combined medical subject headings(MeSH)terms and the keywords“gastrointestinal bleeding”with“iron-deficiency anemia”and“diagnosis”or“treatment”or“management”or“prognosis”or“prevalence”or“safety”or“iron”or“transfusion”or“quality of life”,or other terms to identify relevant articles reporting the management of IDA in patients over the age of 18 years with gastrointestinal bleeding;retrieved studies were published in English between January 2003 and April 2019.Worldwide professional association websites were searched for clinical practice guidelines.Reference lists from guidelines were reviewed to identify additional relevant articles.The recommendations were developed by consensus during two meetings and were supported by the published literature identified during the systematic search.RESULTS From 494 Literature citations found during the initial literature search,17 original articles,one meta-analysis,and 13 clinical practice guidelines were analyzed.Based on the published evidence and clinical experience,the workgroup developed the following ten recommendations for the management of IDA in patients with gastrointestinal bleeding:(1)Evaluation of hemoglobin and iron status;(2)Laboratory testing;(3)Target treatment population identification;(4)Indications for erythrocyte transfusion;(5)Treatment targets for erythrocyte transfusion;(6)Indications for intravenous iron;(7)Dosages;(8)Monitoring;(9)Indications for intravenous ferric carboxymaltose treatment;and(10)Treatment targets and monitoring of patients.The workgroup also proposed a summary algorithm for the diagnosis and treatment of IDA in patients with acute or chronic gastrointestinal bleeding,which should be implemented during the hospital stay and follow-up visits after patient discharge.CONCLUSION These recommendations may serve as a starting point for clinicians to better diagnose and treat IDA in patients with gastrointestinal bleeding,which ultimately may improve health outcomes in these patients.展开更多
The initial trauma to the spinal cord is just the starting point for a cascade of endogenous events that will collectively determine the injury extension. These secondary events include, but are not limited to: glutam...The initial trauma to the spinal cord is just the starting point for a cascade of endogenous events that will collectively determine the injury extension. These secondary events include, but are not limited to: glutamate excitoxicity, induction of apoptotic pathways, ionic imbalances and the development of a strong and dysfunctional inflammatory response. The secondary injury is associated to an aggravation of neuronal damage increasing the extent of neurological deficits (Ek et al., 2010).展开更多
基金funded by the Santa Casa Neuroscience Awards—Prize Melo e Castro for Spinal Cord Injury Research(MC-18-2021)(to AJS and NAS)by the Wings for Life Spinal Cord Research Foundation(WFL-PT-14/23)(to NAS)+2 种基金funded by national funds through the Foundation for Science and Technology(FCT)—projects UIDB/50026/2020,UIDP/50026/2020,and EXPL/MED-PAT/0931/2021-http://doi.org/10.54499/EXPL/MED PAT/0931/2021supported by the Norte Portugal Regional Operational Programme(NORTE 2020)under the PORTUGAL 2020 Partnership Agreement through the European Regional Development Fund(ERDF)(to SM)the support given by the Portuguese Foundation of Science and Technology to SM(CEECIND/01902/2017-Doi:10.54499/CEECIND/01902/2017/CP1458/CT0024),and NAS(CEECIND/04794/2007)。
文摘The impact of spinal cord injury(SCI)on the immune system is increasingly recognized in a field traditionally focused on motor impairments.SCI can seriously affect the immune system by progressively disrupting the regulatory mechanisms that control immune responses.This dysregulation varies widely among patients and can evolve over time,ranging from systemic inflammatory responses to immunosuppression,greatly contributing to the morbidity and mortality of individuals with SCI(Bao et al.,2011;Brennan et al.,2024).
基金funded by National funds,through the Foundation for Science and Technology (FCT)-project UIDB/50026/2020 (DOI 10.54499/UIDB/50026/2020),UIDP/50026/2020 (DOI 10.54499/UIDP/50026/2020) and LA/P/0050/2020 (DOI 10.54499/LA/P/0050/2020)(to NAS)Financial support was also provided by Prémios Santa Casa Neurociências–Prize Melo e Castro for Spinal Cord Injury Research (MC-18-2021)Wings for Life Spinal Cord Research Foundation (WFL-PT-14/23)(to NAS)。
文摘Spinal cord injuries have profound detrimental effects on individuals, regardless of whether they are caused by trauma or non-traumatic events. The compromised regeneration of the spinal cord is primarily attributed to damaged neurons, inhibitory molecules, dysfunctional immune response, and glial scarring. Unfortunately, currently, there are no effective treatments available that can fully repair the spinal cord and improve functional outcomes. Nevertheless, numerous pre-clinical approaches have been studied for spinal cord injury recovery, including using biomaterials, cells, drugs, or technological-based strategies. Combinatorial treatments, which target various aspects of spinal cord injury pathophysiology, have been extensively tested in the last decade. These approaches aim to synergistically enhance repair processes by addressing various obstacles faced during spinal cord regeneration. Thus, this review intends to provide scientists and clinicians with an overview of pre-clinical combinatorial approaches that have been developed toward the solution of spinal cord regeneration as well as update the current knowledge about spinal cord injury pathophysiology with an emphasis on the current clinical management.
基金Supported by the National Oncology Care Support Program,No.25000.056766/2015-64.
文摘BACKGROUND Adenomatous polyposis confers an increased risk of developing colorectal cancer.APC and MUTYH are the major genes investigated in patients suspected of having polyposis.In addition to APC and MUTYH genes,other genes,such as POLE,POLD1,NTHL1,MBD4,MSH3 and MLH3,have recently been associated with polyposis phenotypes,conferring heterogeneity in terms of the clinical,etiological and heritable aspects of patients with polyposis.AIM To investigate the underlying variant landscape in patients with suspected polyposis who lack variants in the APC and MUTYH genes using whole-exome sequencing.METHODS Twenty-seven participants were included in the study and subjected to germline whole-exome sequencing.In addition,their clinical-pathological,personal,and family history data were collected.RESULTS The mean age at diagnosis was 51 years,and most participants had attenuated forms of polyposis(88.9%),with 63.0%diagnosed with a primary tumor,mostly colorectal cancer(76.5%).Among the variants identified,17 were classified as pathogenic or likely pathogenic(in 12 participants),including variants in genes involved in the Wnt/β-catenin signaling pathway,such as ST7 L,A1CF,and DKK4,and variants in DNA-repair genes,such as NTHL1,PNKP,and PMS2,as well as a variant found at the FRK gene identified in a patient with classic polyposis at age 19 and with a family history of polyps.CONCLUSION This study identified novel genes potentially associated with polyposis in patients lacking germline pathogenic variants in the APC and MUTYH genes.These findings support the use of next-generation sequencing for screening,expanding the scope of polyposis-related variants beyond these two genes.
基金funded by national funds,through the Foundation for Science and Technology(FCT)-project UIDB/50026/2020,UIDP/50026/2020(to NAS),EXPL/MEDPAT/0931/2021(to SM)Financial support was provided by Prémios Santa Casa Neurociências-Prize Melo e Castro for Spinal Cord Injury Research(MC-18-2021)+2 种基金Wings For Life Spinal Cord Research Foundation(WFL-PT-14/23)"la Caixa"Foundation(HR23-00484)(to NAS)the FCT for the Scientific Employment Stimulus to NAS and SM(CEECIND/04794/2017 and CEECIND/01902/2017)。
文摘Spinal cord injury(SCI)involves an initial traumatic phase,followed by secondary events such as ischemia,increased blood-spinal cord barrier permeability,ionic disruption,glutamate excitotoxicity,and metabolic alterations.A pe rsistent and exagge rated inflammato ry response within the spinal cord accompanies these events(Lima et al.,2022).The complexity and interplay of these mechanisms exacerbate the initial injury,leading to a degenerative process at the injury site.While the initial trauma is unavoidable,the secondary injury begins within minutes and can last for months,creating an optimal window for therapeutic intervention.
基金Brazilian National Program of Genomics and Precision Health-Genomas Brasil,Grant/Award Number:MS-SECTICS-Decit/CNPq 16/2023São Paulo Research Foundation,Grant/Award Number:FAPESP-2021/07957-5+5 种基金Barretos Cancer Hospital,Grant/Award Number:13/2021National Oncology Care Support Program (PRONON),CNPq,Grant/Award Number:444217/2023-1Public Ministry of Labor Campinas (Research, Prevention, and Education of Occupational Cancer)Brazilian Ministry of Health (MoH)National Council for Scientific and Technological DevelopmentCNPq Productivity
文摘Background:Constitutional mismatch repair deficiency(CMMRD)is a rare disorder resulting from biallelic germline pathogenic variants in mismatch repair genes.This study described the molecular profile of two metachronous brain tumors and a patient-derived xenograft(PDX)from a Brazilian child with CMMRD.Methods:After PDX development,methylation array,whole exome sequencing,and Nano String techniques were applied to describe the genetic landscape of CMMRD.Results:A 6½-year-old girl was diagnosed with Sonic Hedgehog(SHH)-activated medulloblastoma and somatic TP53-mutant.After surgery and radiochemotherapy,she remained free of disease progression.At 10 years and 3 months,she developed a diffuse pediatric-type high-grade glioma(dp HGG).The child had a family history of cancer,and subsequent investigation revealed a biallelic germline variant on MSH6(c.3556+1G>A)with the absence of protein expression in both normal and tumor tissue.A PDX model of the dp HGG was developed.The methylation profile confirmed the diagnosis of both brain tumors and PDX,refining the classification of dp HGG,Rtk1 subtype,subclass A,with an actionable alteration on Platelet-derived growth factor receptor A(PDGFRA).Exome analysis showed high tumor mutational burden,with 3019,540,and 1049 pathogenic variants in the medulloblastoma,dp HGG,and PDX,respectively.Only the medulloblastoma exhibited microsatellite instability.The CD24,CD47,and CD276 immune checkpoints had elevated messenger RNA levels,yet no programmed death ligand 1 expression was observed in CMMRD-derived tumors.Conclusion:We report an extensive molecular profile of a CMMRD patient,and the developed PDX model can be applied to explore new therapeutic approaches for CMMRD-associated brain tumors.
基金the financial support from Prémios Santa Casa Neurociências-Prize Melo e Castro for Spinal Cord Injury Research (MC-04/17)Portuguese Foundation for Science and Technology [Doctoral fellowship (SFRH/BD/103075/2014) to EDG+9 种基金Post- Doctoral fellowship (SFRH/BPD/97701/2013) to NASIF Development Grant to AJSfunded by national funds through FCT under the scope of grant reference TUBITAK/0007/20143599-PPCDT Project: PTDC/DTP-FTO/5109/2014developed under the scope of the projects NORTE-01-0145FEDER-000013supported by the Northern Portugal Regional Operational Programme (NORTE 2020)under the Portugal 2020 Partnership Agreement, through the European Regional Development Fund (FEDER)funded by FEDER funds, through the Competitiveness Factors Operational Programme (COMPETE)by National funds, through the Foundation for Science and Technology (FCT)under the scope of the project POCI-010145-FEDER-007038
文摘Spinal cord injury(SCI)is a condition without treatment,mainly characterized by the loss of motor and sensory function below the level of injury.This is accompanied by several complications such as cardiac and respiratory compromise,and often patients present psychological ailments associated with the drastic alteration of their normal lifestyle.SCI pathophysiology derives from a massive damage to the spinal cord tissue,which is propagated
文摘Serrated adenocarcinoma is a recently described subset of colorectal cancer(CRC),which account for about10%of all CRCs and follows an alternative pathway in which serrated polyps replace the traditional adenoma as the precursor lesion to CRC.Serrated polyps form a heterogeneous group of colorectal lesions that includes hyperplastic polyps(HPs),sessile serrated adenoma(SSA),traditional serrated adenoma(TSA)and mixed polyps.HPs are the most common serrated polyp followed by SSA and TSA.This distinct histogenesis is believed to have a major influence in prevention strategies,patient prognosis and therapeutic impact.Genetically,serrated polyps exhibited also a distinct pattern,with KRAS and BRAF having an important contribution to its development.Two other molecular changes that have been implicated in the serrated pathway include microsatellite instability and the CpG island methylator phenotype.In the present review we will address the current knowledge of serrated polyps,clinical pathological features and will update the most recent findings of its molecular pathways.The understanding of their biology and malignancy potential is imperative to implement a surveillance approach in order to prevent colorectal cancer development.
文摘AIM: To study the practical applicability of the American Society for Gastrointestinal Endoscopy guidelines in suspected cases of choledocholithiasis.METHODS: This was a retrospective single center study, covering a 4-year period, from January 2010 to December 2013. All patients who underwent endoscopic retrograde cholangiopancreatography(ERCP) for suspected choledocholithiasis were included. Based on the presence or absence of predictors of choledocholithiasis(clinical ascending cholangitis, common bile duct(CBD) stones on ultrasonography(US), total bilirubin > 4 mg/d L, dilated CBD on US, total bilirubin 1.8-4 mg/d L, abnormal liver function test, age > 55 years and gallstone pancreatitis), patients were stratified in low, intermediate or high risk for choledocholithiasis. For each predictor and risk group we used the χ2 to evaluate the statistical associations with the presence of choledocolithiasis at ERCP. Statistical analysis was performed using SPSS version 21.0. A P value of less than 0.05 was considered statistically significant. RESULTS: A total of 268 ERCPs were performed for suspected choledocholithiasis. Except for gallstone pancreatitis(P = 0.063), all other predictors of cho-ledocholitiasis(clinical ascending cholangitis, P = 0.001; CBD stones on US, P ≤ 0.001; total bilirubin > 4 mg/dL, P = 0.035; total bilirubin 1.8-4 mg/dL, P = 0.001; dilated CBD on US, P ≤ 0.001; abnormal liver function test, P = 0.012; age > 55 years, P = 0.002) showed a statistically significant association with the presence of choledocholithiasis at ERCP. Approximately four fifths of patients in the high risk group(79.8%, 154/193 patients) had confirmed choledocholithiasis on ERCP, vs 34.2%(25/73 patients) and 0(0/2 patients) in the intermediate and low risk groups, respectively. The definition of "high risk group" had a sensitivity of 86%, positive predictive value 79.8% and specificity 56.2% for the presence of choledocholithiasis at ERCP. CONCLUSION: The guidelines should be considered to optimize patients' selection for ERCP. For high risk patients specificity is still low, meaning that some patients perform ERCP unnecessarily.
文摘Minimally invasive surgery started spreading worldwide in 1987,when the first laparoscopic cholecystectomy was performed.Meanwhile,improvement of endoscopic equipment and instruments allowed gastroenterologists to attempt more aggressive endoluminal interventions,even beyond the wall barrier.The first transgastric peri-toneoscopy,in 2004,brought to light the concept of natural orifice transluminal endoscopic surgery(NOTES).The idea of incisionless surgery is attractive and has become a new goal for both surgeons and other people interested in this field of investigation.The authors present a review of all developments concerning NOTES,including animal studies and human experience.
文摘Upper gastrointestinal bleeding(UGIB) remains a significant cause of hospital admission. In order to stratify patients according to the risk of the compli-cations, such as rebleeding or death, and to predict the need of clinical intervention, several risk scores have been proposed and their use consistently recommended by international guidelines. The use of risk scoring systems in early assessment of patients suffering from UGIB may be useful to distinguish high-risks patients, who may need clinical intervention and hospitalization, from low risk patients with a lower chance of developing complications, in which management as outpatients can be considered. Although several scores have been published and validated for predicting different outcomes, the most frequently cited ones are the Rockall score and the Glasgow Blatchford score(GBS). While Rockall score, which incorporates clinical and endoscopic variables, has been validated to predict mortality, the GBS, which is based on clinical and laboratorial parameters, has been studied to predict the need of clinical intervention. Despite the advantages previously reported, their use in clinical decisions is still limited. This review describes the different risk scores used in the UGIB setting, highlights the most important research, explains why and when their use may be helpful, reflects on the problems that remain unresolved and guides future research with practical impact.
基金supported by Portuguese Foundation for Science and Technology(FCT):IF Development Grant(IF/00111/2013)to AJ Salgado and Post-Doctoral Fellowship to FGT(SFRH/BPD/118408/2016)funded by European Regional Development Fund(FEDER)+7 种基金through the Competitiveness Internationalization Operational Programme(POCI)National funds,through the Foundation for Science and Technology(FCT)under the scope of the project POCI-01-0145-FEDER-029751developed under the scope of the project NORTE-01-0145-FEDER-000023supported by the Northern Portugal Regional Operational Programme(NORTE 2020)under the Portugal 2020 Partnership Agreement,through the FEDERfunded by FEDER funds,through the Competitiveness Factors Operational Programme(COMPETE)National funds,through FCT,under the scope of the project POCI-01-0145-FEDER-007038
文摘Mesenchymal stem cells(MSCs)secretome:a good candidate for medical biotechnology?Medical biotechnology is currently defined as the application of biotechnological tools for producing multiple technologies and products to health care,becoming an important bridge between different fields,namely neuroscience,regenerative medicine,pharmacology and bio-engineering(Pham,2018).The use and manipulation of stem cells can potentially represent a medical biotechnology breakthrough that brings regenerative medicine to a new era.Actually,over the last decade,the use of stem cells has remarkably been proposed as a regenerative tool,and within it,MSCs have emerged as a promising therapeutic option.
文摘AIM:To evaluate whether the use of real time viewer(RTV)and administration of domperidone to patients with delayed gastric passage of the capsule could reduce the rate of incomplete examinations(IE)and improve the diagnostic yield of small bowel capsule endoscopy(SBCE).METHODS:Prospective single center interventional study,from June 2012 to February 2013.Capsule location was systematically checked one hour after ingestion using RTV.If it remained in the stomach,the patient received 10 mg domperidone per os and the location of the capsule was rechecked after 30 min.If the capsule remained in the stomach a second dose of10 mg of domperidone was administered orally.After another 30 min the position was rechecked and if the capsule remained in the stomach,it was passed into the duodenum by upper gastrointestinal(GI)endoscopy.The rate of IE and diagnostic yield of SBCE were compared with those of examinations performed before the use of RTV or domperidone in our Department(control group,January 2009-May 2012).RESULTS:Both groups were similar regarding age,sex,indication,inpatient status and surgical history.The control group included 307 patients,with 48(15.6%)IE.The RTV group included 82 patients,with3(3.7%)IE,P=0.003.In the control group,average gastric time was significantly longer in patients with IE than in patients with complete examination of the small bowel(77 min vs 26 min,P=0.003).In the RTV group,the capsule remained in the stomach one hour after ingestion in 14/82 patients(17.0%)vs 48/307(15.6%)in the control group,P=0.736.Domperidone did not significantly affect small bowel transit time(260min vs 297 min,P=0.229).The capsule detected positive findings in 39%of patients in the control group and 49%in the RTV group(P=0.081).CONCLUSION:The use of RTV and selective administration of domperidone to patients with delayed gastric passage of the capsule significantly reduces incomplete examinations,with no effect on small bowel transit time or diagnostic yield.
基金the financial support from Prémios Santa Casa Neurociências Prize Mantero Belard for Neurodegenerative Diseases Research(MB-28-2019)supported by the European Regional Development Fund(FEDER)+8 种基金through the Competitiveness Internationalization Operational Programme(POCI)by National fundsthrough the Foundation for Science and Technology(FCT)under the scope of projects UIDB/50026/2020UIDP/50026/2020 and POCI-01-0145-FEDER-029751developed under the scope of the project NORTE-01-0145-FEDER-000023supported by the Northern Portugal Regional Operational Programme(NORTE 2020)under the Portugal 2020 Partnership Agreement,through the European Regional Development Fund(FEDER)funded by ICVS Scientific Microscopy Platform,member of the national infrastructure PPBI-Portuguese Platform of Bioimaging(PPBI-POCI-01-0145-FEDER-022122)(to FGT)。
文摘Parkinson's disease is the second most prevalent neurodegenerative disorder worldwide.Clinically,it is characterized by severe motor complications caused by progressive degeneration of dopaminergic neurons.Current treatment is focused on mitigating the symptoms through the administration of levodopa,rather than on preventing dopaminergic neuronal damage.Therefore,the use and development of neuroprotective/disease-modifying strategies is an absolute need that can lead to promising gains on translational research of Parkinson's disease.For instance,N-acetylcysteine,a natural compound with strong antioxidant effects,has been shown to modulate oxidative stress,preventing dopamine-induced cell death.Despite the evidence of neuroprotective and modulatory effects of this drug,as far as we know,it does not induce per se any regenerative process.Therefore,it would be of interest to combine the latter with innovative therapies that induce dopaminergic neurons repair or even differentiation,as stem cell-based strategies.Stem cells secretome has been proposed as a promising therapeutic approach for Parkinson's disease,given its ability to modulate cell viability/preservation of dopaminergic neurons.Such approach represents a shift in the paradigm,showing that cell-transplantation free therapies based on the use of stem cells secretome may represent a potential alternative for regenerative medicine of Parkinson's disease.Thus,in this review,we address the current understanding of the potential combination of stem cell free-based strategies and neuroprotective/disease-modifying strategies as a new paradigm for the treatment of central nervous system neurodegenerative diseases,like Parkinson's disease.
基金Supported by Sao Paulo Research Foundation(FAPESP),No.2012/15036-8National Council for Scientific and Technological Development(CNPq),No.474.776/2013-1+2 种基金the Sao Paulo Research Foundation(FAPESP,NO.2015/21464-0)for the support for English revisionthe Coordination for the Improvement of Higher Education Personnel(CAPES)for the doctoral scholarshipthe National Council for Scientific and Technological Development(CNPq,NO.310120/2015-2)for the productivity research scholarship
文摘AIM To examine the effect of Fusobacterium nucleatum(F. nucleatum) on the microenvironment of colonic neoplasms and the expression of inflammatory mediators and microRNAs(miRNAs).METHODS Levels of F. nucleatum DNA, cytokine gene mRNA(TLR2, TLR4, NFKB1, TNF, IL1 B, IL6 and IL8), and potentially interacting miRNAs(miR-21-3p, miR-22-3p, mi R-28-5p, miR-34a-5p, miR-135b-5p) were measured by quantitative polymerase chain reaction(qPCR) TaqMan? assays in DNA and/or RNA extracted from the disease and adjacent normal fresh tissues of 27 colorectal adenoma(CRA) and 43 colorectal cancer(CRC) patients. KRAS mutations were detected by direct sequencing and microsatellite instability(MSI) status by multiplex PCR. Cytoscape v3.1.1 was used to construct the postulated miRNA:mRNA interaction network.RESULTS Overabundance of F. nucleatum in neoplastic tissue compared to matched normal tissue was detected in CRA(51.8%) and more markedly in CRC(72.1%). We observed significantly greater expression of TLR4, IL1 B, IL8, and miR-135 b in CRA lesions and TLR2, IL1 B, IL6, IL8, mi R-34 a and miR-135 b in CRC tumours compared to their respective normal tissues. Only two transcripts for miR-22 and miR-28 were exclusively downregulated in CRC tumour samples. The mRNA expression of IL1 B, IL6, IL8 and miR-22 was positively correlated with F. nucleatum quantification in CRC tumours. The mRNA expression of miR-135 b and TNF was inversely correlated. The miRNA:mRNA interaction network suggested that the upregulation of miR-34 a in CRC proceeds via a TLR2/TLR4-dependent response to F. nucleatum. Finally, KRAS mutations were more frequently observed in CRC samples infected with F. nucleatum and were associated with greater expression of miR-21 in CRA, while IL8 was upregulated in MSI-high CRC.CONCLUSION Our findings indicate that F. nucleatum is a risk factor for CRC by increasing the expression of inflammatory mediators through a possible mi RNA-mediated activation of TLR2/TLR4.
基金funded by national fundsthrough the Foundation for Science and Technology(FCT)-project UIDB/50026/2020 and UIDP/50026/2020by the National Ataxia Foundation(NAF)
文摘Spinocerebellar ataxias are heritable neurodegenerative diseases caused by a cytosine-adenine-guanine expansion,which encodes a long glutamine tract(polyglutamine)in the respective wild-type protein causing misfolding and protein aggregation.Clinical features of polyglutamine spinocerebellar ataxias include neuronal aggregation,mitochondrial dysfunction,decreased proteasomal activity,and autophagy impairment.Mutant polyglutamine protein aggregates accumulate within neurons and cause neural dysfunction and death in specific regions of the central nervous system.Spinocerebellar ataxias are mostly characterized by progressive ataxia,speech and swallowing problems,loss of coordination and gait deficits.Over the past decade,efforts have been made to ameliorate disease symptoms in patients,yet no cure is available.Previous studies have been proposing the use of stem cells as promising tools for central nervous system tissue regeneration.So far,pre-clinical trials have shown improvement in various models of neurodegenerative diseases following stem cell transplantation,including animal models of spinocerebellar ataxia types 1,2,and 3.However,contrasting results can be found in the literature,depending on the animal model,cell type,and route of administration used.Nonetheless,clinical trials using cellular implants into degenerated brain regions have already been applied,with the expectation that these cells would be able to differentiate into the specific neuronal subtypes and re-populate these regions,reconstructing the affected neural network.Meanwhile,the question of how feasible it is to continue such treatments remains unanswered,with long-lasting effects being still unknown.To establish the value of these advanced therapeutic tools,it is important to predict the actions of the transplanted cells as well as to understand which cell type can induce the best outcomes for each disease.Further studies are needed to determine the best route of administration,without neglecting the possible risks of repetitive transplantation that these approaches so far appear to demand.Despite the challenges ahead of us,cell-transplantation therapies are reported to have transient but beneficial outcomes in spinocerebellar ataxias,which encourages efforts towards their improvement in the future.
文摘AIM: To evaluate mucosal healing in patients with small bowel plus colonic Crohn's disease(CD) with a single non-invasive examination, by using PillCam COLON 2.(PCC2).METHODS: Patients with non-stricturing nonpenetrating small bowel plus colonic CD in sustained corticosteroid-free remission were included. At diagnosis,patients had undergone ileocolonoscopy to identify active CD lesions, such as ulcers and erosions, and small bowel capsule endoscopy to assess the Lewis Score(LS). After ≥ 1 year of follow-up, patients underwent entire gastrointestinal tract evaluation with PCC2. The primary endpoint was assessment of CD mucosal healing, defined as no active colonic CD lesions and LS < 135.RESULTS: Twelve patients were included(7 male;mean age: 32 years), and mean follow-up was 38 mo.The majority of patients(83.3%) received immunosuppressive therapy. Three patients(25%) achieved mucosal healing in both the small bowel and the colon,while disease activity was limited to either the small bowel or the colon in 5 patients(42%). It was possible to observe the entire gastrointestinal tract in 10 of the12 patients(83%) who underwent PCC2.CONCLUSION: Only three patients in sustainedcorticosteroid-free clinical remission achieved mucosal healing in both the small bowel and the colon, highlighting the limitations of clinical assessment when stratifying disease activity, and the need for pan-enteric endoscopy to guide therapeutic modification.
文摘Since its emergence in 2000, small bowel capsule endoscopy(SBCE) has assumed a pivotal role as an investigation method for small bowel diseases. The PillCam SB2-ex offers 12 h of battery time, 4 more than the previous version(SB2). Rahman et al recently found that the PillCam SB2-ex has a significantly increased completion rate, although without higher diagnostic yield, compared with the SB2. We would like to discuss these somewhat surprising results and the new potentialities of the PillCam SB3 regarding the diagnostic yield of small bowel studies. PillCam SB3 offers improved image resolution and faster adaptable frame rate over previous versions of SBCE. We recently compared the major duodenal papilla detection rate obtained with PillCam SB3 and SB2 as a surrogate indicator of diagnostic yield in the proximal small bowel. The PillCam SB3 had a significantly higher major duodenal papilla detection rate than the PillCam SB2(42.7% vs 24%, P = 0.015). Thus, the most recent version of the PillCam capsule, SB3, may increase diagnostic yield, particularly in the proximal segments of the small bowel.
基金Supported by OM Pharma(Amadora,Portugal)for payment for medical writing support.
文摘BACKGROUND Anemia is considered a public health issue and is often caused by iron deficiency.Iron-deficiency anemia(IDA)often originates from blood loss from lesions in the gastrointestinal tract in men and postmenopausal women,and its prevalence among patients with gastrointestinal bleeding has been estimated to be 61%.However,few guidelines regarding the appropriate investigation of patients with IDA due to gastrointestinal bleeding have been published.AIM To review current evidence and guidelines concerning IDA management in gastrointestinal bleeding patients to develop recommendations for its diagnosis and therapy.METHODS Five gastroenterology experts formed the Digestive Bleeding and Anemia Workgroup and conducted a systematic literature search in PubMed and professional association websites.MEDLINE(via PubMed)searches combined medical subject headings(MeSH)terms and the keywords“gastrointestinal bleeding”with“iron-deficiency anemia”and“diagnosis”or“treatment”or“management”or“prognosis”or“prevalence”or“safety”or“iron”or“transfusion”or“quality of life”,or other terms to identify relevant articles reporting the management of IDA in patients over the age of 18 years with gastrointestinal bleeding;retrieved studies were published in English between January 2003 and April 2019.Worldwide professional association websites were searched for clinical practice guidelines.Reference lists from guidelines were reviewed to identify additional relevant articles.The recommendations were developed by consensus during two meetings and were supported by the published literature identified during the systematic search.RESULTS From 494 Literature citations found during the initial literature search,17 original articles,one meta-analysis,and 13 clinical practice guidelines were analyzed.Based on the published evidence and clinical experience,the workgroup developed the following ten recommendations for the management of IDA in patients with gastrointestinal bleeding:(1)Evaluation of hemoglobin and iron status;(2)Laboratory testing;(3)Target treatment population identification;(4)Indications for erythrocyte transfusion;(5)Treatment targets for erythrocyte transfusion;(6)Indications for intravenous iron;(7)Dosages;(8)Monitoring;(9)Indications for intravenous ferric carboxymaltose treatment;and(10)Treatment targets and monitoring of patients.The workgroup also proposed a summary algorithm for the diagnosis and treatment of IDA in patients with acute or chronic gastrointestinal bleeding,which should be implemented during the hospital stay and follow-up visits after patient discharge.CONCLUSION These recommendations may serve as a starting point for clinicians to better diagnose and treat IDA in patients with gastrointestinal bleeding,which ultimately may improve health outcomes in these patients.
基金supported by Prémios Santa Casa Neurociências-Prize Meloe Castro for Spinal Cord Injury ResearchPortuguese Foundation for Science and Technology(Financiado noambito do Projecto 3599-Promover a Producao Científica e Desenvolvimento Tecnológico e a Constituicao de Redes Temáticas(3599-PPCDT)+2 种基金project:PTDC/DTP-FTO/5109/2014Post-Doctoral fellowship-SFRH/BPD/97701/2013-to N.A.SilvaIF Development Grant to A.J.Salgado
文摘The initial trauma to the spinal cord is just the starting point for a cascade of endogenous events that will collectively determine the injury extension. These secondary events include, but are not limited to: glutamate excitoxicity, induction of apoptotic pathways, ionic imbalances and the development of a strong and dysfunctional inflammatory response. The secondary injury is associated to an aggravation of neuronal damage increasing the extent of neurological deficits (Ek et al., 2010).
