In the realm of medical rarity,the convergence of infective endocarditis with the development of an aortic root abscess stands as a formidable challenge,often bearing a grim prognosis.Recognizing this perilous conditi...In the realm of medical rarity,the convergence of infective endocarditis with the development of an aortic root abscess stands as a formidable challenge,often bearing a grim prognosis.Recognizing this perilous condition requires a vigilant eye.Embolic events stemming from infective endocarditis can precipitate acute coronary syndrome,adding another layer of complexity to diagnosis and treatment.展开更多
A bicuspid aortic valve,from autologous tissue,with growth potential can be constructed using the simple,and reproducible telescoping arterial trunk technique.
BACKGROUND The persistent burden of cardiovascular(CV)disease in the United States requires innovative and cost-effective prognostic markers that can be relied upon.AIM To provide insights into how adiponectin can pre...BACKGROUND The persistent burden of cardiovascular(CV)disease in the United States requires innovative and cost-effective prognostic markers that can be relied upon.AIM To provide insights into how adiponectin can predict all-cause mortality and major adverse CV events(MACE)in patients with coronary artery disease(CAD)and to determine the prognostic value of adiponectin in predicting all-cause mortality and MACE in patients with stable CAD.METHODS We conducted a systematic search on PubMed,Scopus,and Google Scholar to find relevant studies published through June 2023 evaluating the long-term prognostic role of adiponectin in patients with stable CAD.Using a random effects model with 95%CI,we estimated the odds ratio(OR)while assessing heterogeneity through I^(2)statistics.To ensure robustness,we performed a sensitivity analysis using the leave-one-out approach.RESULTS After screening,we included five prospective studies involving 3225 patients who were followed up for a median duration of 3.8 years.Within the study population,prevalent risk factors included hypertension,diabetes,hyperlipidemia,and smoking.The commonly prescribed medications were angiotensin-converting enzyme inhibitors,beta blockers,and statins.The combined adjusted OR for all-cause mortality was found to be 2.51(95%CI:1.36–4.62),showing heterogeneity(I^(2)=65.51%,P=0.03).On the other hand,the combined adjusted OR for MACE was determined to be 1.04(95%CI:1.02–1.06)with no significant heterogeneity observed(I^(2)=0%,P=0.68).Through a sensitivity analysis,it was discovered that none of the studies significantly impacted the overall results of the meta-analysis,thus indicating their robustness.CONCLUSION Higher levels of adiponectin were found to be associated with an increased risk of long-term mortality and MACE in patients with CAD,which highlights its potential as a cost-effective marker for risk assessment and guiding treatment strategies.Further research on the role of adiponectin could greatly influence decision-making and resource allocation in CV care.展开更多
Rotavirus diarrhea is a major worldwide cause of infantile gastroenteritis; however, the mechanism responsible for intestinal fluid loss remains unclear. Water transfer across the intestinal epithelial membrane seems ...Rotavirus diarrhea is a major worldwide cause of infantile gastroenteritis; however, the mechanism responsible for intestinal fluid loss remains unclear. Water transfer across the intestinal epithelial membrane seems to occur because of aquaporins(AQPs). Accumulating evidence indicates that alterations in AQPs may play an important role in pathogenesis. Here, we focus on changes in AQPs in a mouse model of rotavirus diarrhea. In the present study, 32 of 35 mice developed diarrhea and mild dehydration within 24 hours after infection with rotavirus strain SA11. Intestinal epithelial cells demonstrated cytoplasmic vacuolation, malaligned villi, and atrophy. AQP1 expression was significantly attenuated in the ileum and colon in comparison with controls; likewise, AQP4 and-8 protein expression were significantly decreased in the colon of rotavirus diarrhea-infected mice. In contrast, AQP3 protein expression was significantly increased in the colon of rotavirus-infected mice in comparison with controls. These results indicate that rotavirus diarrhea is associated with the downregulation of AQP1,-4, and-8 expression. Therefore, AQPs play an important role in rotavirus diarrhea.展开更多
To determine the clinical characteristics of children with gastrointestinal bleeding (GIB) who died during the course of their admission.METHODSWe interrogated the Pediatric Hospital Information System database, inclu...To determine the clinical characteristics of children with gastrointestinal bleeding (GIB) who died during the course of their admission.METHODSWe interrogated the Pediatric Hospital Information System database, including International Classification of Diseases, Current Procedural Terminology and Clinical Transaction Classification coding from 47 pediatric tertiary centers extracting the population of patients (1-21 years of age) admitted (inpatient or observation) with acute, upper or indeterminate GIB (1/2007-9/2015). Descriptive statistics, unadjusted univariate and adjusted multivariate analysis of the associations between patient characteristics and treatment course with mortality was performed with mortality as primary and endoscopy a secondary outcome of interest. All analyses were performed using the R statistical package, v.3.2.3.RESULTSThe population with GIB was 19528; 54.6% were male, overall mortality was 2.07%; (0.37% in patients with the principal diagnosis of GIB). When considering only the mortalities in which GIB was the principal diagnosis, 48% (12 of 25 principal diagnosis GIB mortalities) died within the first 3 d of admission, whereas 19.8% of secondary diagnosis GIB patients died with 3 d of admission. Patients who died were more likely to have received octreotide (19.8% c.f. 4.04%) but tended to have not received proton pump inhibitor therapy in the first 48 h, and far less likely to have undergone endoscopy during their admission (OR = 0.489, P < 0.0001). Chronic liver disease associated with a greater likelihood of endoscopy. Mortalities were significantly more likely to have multiple complex chronic conditions.CONCLUSIONGIB associated mortality in children is highest within 7 d of admission. Multiple comorbidities are a risk factor whereas early endoscopy during the admission is protective.展开更多
AIM: To compare the hemostatic efficacy and safety of two mechanical endoscopic methods: endoscopic band ligation (EBL) and endoscopic hemoclip placement (EHP) in patients with actively bleeding Mallory-Weiss syndrome...AIM: To compare the hemostatic efficacy and safety of two mechanical endoscopic methods: endoscopic band ligation (EBL) and endoscopic hemoclip placement (EHP) in patients with actively bleeding Mallory-Weiss syndrome (MWS). METHODS: A prospective randomized study to compare the efficacy and safety of EHP with EBL was performed from January 2002 to August 2005. Forty-one patients with active bleeding from MWS were treated with EHP (n = 21) or EBL (n = 20). RESULTS: There were no significant differences between groups with respect to clinical and endoscopic characteristics. The mean number of hemoclips applied was 3.2 ± 1.5 and the mean number of bands applied was 1.2 ± 0.4. Primary hemostasis was achieved in all patients. Recurrent bleeding was observed in one patient from the EHP group and two from the EBL group. Patients with recurrent bleeding were treated by the same modality as at randomization and secondary hemostasis was achieved in all. There were no significant differences between the two groups in total transfusion amount or duration of hospital stay. No complications or bleeding-related death resulted. CONCLUSION: EHP and EBL are equally effective and safe for the management of active bleeding in patients with Mallory-Weiss syndrome, even in those with shock or comorbid diseases.展开更多
BACKGROUND Magnetic resonance enterography (MRE) and wireless capsule endoscopy (WCE) are equally accepted modalities for noninvasive screening of small bowel involvement (SBI) in children with Crohn’s disease (CD) a...BACKGROUND Magnetic resonance enterography (MRE) and wireless capsule endoscopy (WCE) are equally accepted modalities for noninvasive screening of small bowel involvement (SBI) in children with Crohn’s disease (CD) and indeterminate colitis (IC) albeit there is a paucity of data comparing the two and thereby guiding the clinician in selecting the ideal diagnostic approach. Therefore, the goal of this study is to provide additional evidence for capsule endoscopy role in the evaluation of established Crohn’s disease exacerbation compared to MRE in relation to Pediatric Crohn's Disease Activity Index (PCDAI), and histological indices. AIM To prospectively compare the findings of MRE and WCE and their agreement with PCDAI or histology in children with CD or IC. METHODS Consecutive patients diagnosed with CD and IC were screened for inclusion. After informed consent, patient’s demographic and clinical data was abstracted. The current pediatric disease activity index (PCDAI) and endoscopic findings were included. Patients underwent MRE and WCE including preprocedural patency capsule within a maximum of 7 d of each other. Pathological presence of active small bowel disease in ileal and duodenal biopsies were collected if the endoscopy was performed within 2 mo of the WCE study. Patients who failed to pass the PC were excluded from the study. WCE was read by two different experienced gastroenterologists (Attard TM and Colombo JM) blinded to each other's findings and to the findings on MRE (Mardis NJ). Agreement between WCE reviewers, WCE and MRE findings and concordance between positive PCDAI and SBI based on MRE compared with WCE was computed. RESULTS Forty-five patients were included in the study, 18 withdrew and 27 (20 males and 20 CD), mean age (standard deviation) 13.46 (2.4) years, completed the study protocol. There were no instances of capsule retention. Concordance between gastroenterologist reviewers was excellent for the diagnosis of small intestinal CD with good correlation between the two Lewis scores (r=0.875, P<0.001). Concordance between WCE and MRE was poor (69%). In CD patients, when both MRE and WCE were compared using PCDAI>10 as the standard reference reflecting active small intestinal CD, the sensitivity of MRE and WCE were 100% and 83% respectively and the specificity of MRE and WCE were 57.14% and 78.6%, respectively. If the histology in ileum or/and duodenum was used as the reference for active small bowel involvement, WCE had a higher specificity as compared to MRE (83.3% vs 50%). In patients with Crohn’s disease, those with a positive PCDAI (>10) were more likely to have a positive WCE as compared to those with a negative PCDAI (83% vs 21%;P=0.018). CONCLUSION We suggest that MRE and WCE have a complementary role in the assessment of SBI in CD. WCE detected SBI with a much higher specificity while MRE had a higher sensitivity.展开更多
AIM: To determine whether thalidomide prevents microvascular injury in acute radiation proctitis in white rats. METHODS: Fourteen female Wistar rats were used: six in the radiation group, six in the thalidomide group,...AIM: To determine whether thalidomide prevents microvascular injury in acute radiation proctitis in white rats. METHODS: Fourteen female Wistar rats were used: six in the radiation group, six in the thalidomide group, and two in normal controls. The radiation and thalidomide groups were irradiated at the pelvic area using a single 30 Gy exposure. The thalidomide (150 mg/kg) was injected into the peritoneum for 7 d from the day of irradiation. All animals were sacrificed and the rectums were removed on day 8 after irradiation. The microvessels of resected specimens were immunohistochemically stained with thrombomodulin (TM), von Willebrand Factor (vWF), and vascular endothelial growth factor (VEGF). RESULTS: The microscopic scores did not differ significantly between the radiation and thalidomide groups, but both were higher than in the control group. Expression of TM was significantly lower inthe endothelial cells (EC) of the radiation group than in the control and thalidomide groups (P < 0.001). The number of capillaries expressing vWF in the EC was higher in the radiation group (15.3 ± 6.8) than in the control group (3.7 ± 1.7), and the number of capillaries expressing vWF was attenuated by thalidomide (10.8 ± 3.5, P < 0.001). The intensity of VEGF expression in capillaries was greater in the radiation group than in the control group and was also attenuated by thalidomide (P = 0.003). CONCLUSION: The mechanisms of acute radiation- induced proctitis in the rats are related to endothelial cell injury of microvessel, which may be attenuated with thalidomide.展开更多
Juvenile polyps are relatively common findings in children,while juvenile polyposis syndrome(JPS) is a rare hereditary syndrome entailing an increased risk of colorectal cancer.Mutations in BMPR1A or SMAD4 are found i...Juvenile polyps are relatively common findings in children,while juvenile polyposis syndrome(JPS) is a rare hereditary syndrome entailing an increased risk of colorectal cancer.Mutations in BMPR1A or SMAD4 are found in roughly half of patients diagnosed with JPS.Mutations in PTEN gene are also found in patients with juvenile polyps and in Bannayan-Riley-Ruvalcaba syndrome and Cowden syndrome.Several previous reports have described microdeletions in chromosome 10q23 encompassing both PTEN and BMPR1A causing aggressive polyposis and malignancy in childhood.These reports have also described extra-intestinal findings in most cases including cardiac anomalies,developmental delay and macrocephaly.In this report we describe a boy with a 5.75 Mb deletion of chromosome 10q23 and a 1.03 Mb deletion within chromosome band 1p31.3who displayed aggressive juvenile polyposis and multiple extra-intestinal anomalies including macrocephaly,developmental delay,short stature,hypothyroidism,atrial septal defect,ventricular septal defect and hypospadias.He required colectomy at six years of age,and early colectomy was a common outcome in other children with similar deletions.Due to the aggressive polyposis and reports of dysplasia and even malignancy at a young age,we propose aggressive gastrointestinal surveillance in children with 10q23 microdeletions encompassing the BMPR1A and PTEN genes to include both the upper and lower gastrointestinal tracts,and also include a flowchart for an effective genetic testing strategy in children with juvenile polyposis.展开更多
Collagenous gastritis (CG) is characterized by patchy subepithelial collagen bands. Effective treatment and the clinical and histological outcome of CG in children are poorly defined. The aim of this study is to summa...Collagenous gastritis (CG) is characterized by patchy subepithelial collagen bands. Effective treatment and the clinical and histological outcome of CG in children are poorly defined. The aim of this study is to summarize the published literature on the clinical outcome and response to therapy of pediatric CG including two new cases. We performed a search in Pubmed, OVID for related terms; articles including management and clinical and/or endo-histologic follow up information were included and abstracted. Reported findings were pooled in a dedicated database including the corresponding data extracted from chart review in our patients with CG. Twenty-four patients were included (17 females) with a mean age of 11.7 years. The clinical presentation included iron deficiency anemia and dyspepsia. The reported duration of follow up (in 18 patients) ranged between 0.2-14 years. Despite most subjects presenting with anemia including one requiring blood transfusion, oral iron therapy was only documented in 12 patients. Other treatment modalities were antisecretory measures in 13 patients; proton pump inhibitors (12), or histamine-2 blockers (3), sucralfate (5), prednisolone (6), oral budesonide in 3 patients where one received it in fish oil and triple therapy (3). Three (13%) patients showed no clinical improvement despite therapy; conversely 19 out of 22 were reported with improved symptoms including 8 with complete symptom resolution. Spontaneous clinical resolution without antisecretory, anti-inflammatory or gastroprotective agents was noted in 5 patients (4 received only supplemental iron). Follow up endohistopathologic data (17 patients) included persistent collagen band and stable Mononuclear cell infiltrate in 12 patients with histopathologic improvement in 5 patients. Neither collagen band thickness nor mononuclear cell infiltrate correlated with clinical course. Intestinal metaplasia and endocrine cell hyperplasia were reported (1) raising the concern of long term malignant transformation. In summary, CG in children is a chronic disease, typically with a variable clinical response and an indolent course that is distinct from the adult phenotype. Long term therapy usually inclused iron supplementation but cannot be standardized, given the chronicity of the disease, variability of response and potential for adverse events.展开更多
AIM： To examine the predictive factors of capsule en- doscopy （CE） completion rate （CECR） including the ef- fect of inpatient and outpatient status.METHODS： We identified 355 consecutive patients who completed C...AIM： To examine the predictive factors of capsule en- doscopy （CE） completion rate （CECR） including the ef- fect of inpatient and outpatient status.METHODS： We identified 355 consecutive patients who completed CE at Rush University Medical Center between March 2003 and October 2005. Subjects for CE had either nothing by mouth or clear liquids for the afternoon and evening of the day before the pro- cedure. CE exams were reviewed by two physicians who were unaware of the study hypotheses. After retrospective analysis, 21 cases were excluded due to capsule malfunction, prior gastric surgery, endoscopic capsule placement or insufficient data. Of the remain- ing 334 exams [264 out-patient （OP）, 70 in-patient （IP）], CE indications, findings, location of the patients [IP vs OP and intensive care unit （ICU） vs general medical floor （GMF）] and gastrointestinal transit times were analyzed. Statistical analysis was completed us- ing SPSS version 17 （Chicago, IL）. Chi-square, t test or fisher exact-tests were used as appropriate. Multivari- ate logistic regression analysis was used to identify variables associated with incomplete CE exams. RESULTS： The mean age for the entire study popula- tion was 54.7 years. Sixty-one percent of the study population was female, and gender was not different between IPs vs OPs （P = 0.07）. The overall incomplete CECR was 14% in our study. Overt obscure gastroin- testinal bleeding （OGB） was significantly more com- mon for the IP CE （P = 0.0001）, while abdominal pain and assessment of IBD were more frequent indications for the OP CE exams （P = 0.002 and P = 0.01, respec- tively）. Occult OGB was the most common indication and arteriovenous malformations were the most com- mon finding both in the IPs and OPs. The capsule did not enter the small bowel （SB） in 6/70 IPs and 8/264 OPs （P = 0.04）. The capsule never reached the cecum in 31.4% （22/70） of IP vs 9.5% （25/ 264） of OP ex- aminations （P 〈 0.001）. The mean gastric transit time （GTT） was delayed in IPs compared to OPs, 98.5 ± 139.5 min vs 60.4 ± 92.6 min （P = 0.008）. Minimal SB transit time was significantly prolonged in the IP com- pared to the OP setting [IP = 275.1±111.6 min vs OP = 244.0 ± 104.3 min （P = 0.037）]. CECR was also sig- nificantly higher in the subgroup of patients with OGB who had OP vs IP exams （95% vs 80% respectively, P = 0.001）. The proportion of patients with incomplete exams was higher in the ICU （n = 7/13, 54%） as com- pared to the GMF （n = 15/57, 26%） （P = 0.05）. There was only a single permanent SB retention case which was secondary to a previously unknown SB stricture, and the remaining incomplete SB exams were due to slow transit. Medications which affect gastrointesti- nal system motility were tested both individually and also in aggregate in univariate analysis in hospitalized patients （ICU and GMF） and were not predictive of incomplete capsule passage （P 〉 0.05）. Patient loca- tion （IP vs OP） and GTT were independent predictors of incomplete CE exams （P 〈 0.001 and P = 0.008, respectively）. CONCLUSION： Incomplete CE is a multifactorial prob- lem. Patient location and related factors such as sever- ity of illness and sedentary status may contribute to incomplete exams.展开更多
There is an increasing appreciation for the importance of inflammation as a pathophysiologic entity that contributes to functional gastrointestinal disorders including functional dyspepsia(FD).Importantly,inflammation...There is an increasing appreciation for the importance of inflammation as a pathophysiologic entity that contributes to functional gastrointestinal disorders including functional dyspepsia(FD).Importantly,inflammation may serve as a mediator between psychologic and physiologic functions.This manuscript reviews the literature implicating two inflammatory cell types,mast cells and eosinophils,in the generation of dyspeptic symptoms and explores their potential as targets for the treatment of FD.There are a number of inciting events which may initiate an inflammatory response,and the subsequent recruitment and activation of mast cells and eosinophils.These include internal triggers such as stress and anxiety,as well as external triggers such as microbes and allergens.Previous studies suggest that there may be efficacy in utilizing medications directed at mast cells and eosinophils.Evidence exists to suggest that combining "anti-inflammatory" medications with other treatments targeting stress can improve the rate of symptom resolution in pediatric FD.展开更多
Hepatocellular carcinoma(HCC)is the most frequent primary liver malignancy and the third cause of cancer-related death in the Western Countries.The well-established causes of HCC are chronic liver infections such as h...Hepatocellular carcinoma(HCC)is the most frequent primary liver malignancy and the third cause of cancer-related death in the Western Countries.The well-established causes of HCC are chronic liver infections such as hepatitis B virus or chronic hepatitis C virus,nonalcoholic fatty liver disease,consumption of aflatoxins and tobacco smocking.Clinical presentation varies widely;patients can be asymptomatic while symptomatology extends from right upper abdominal quadrant paint and weight loss to obstructive jaundice and lethargy.Imaging is the first key and one of the most important aspects at all stages of diagnosis,therapy and follow-up of patients with HCC.The Barcelona Clinic Liver Cancer Staging System remains the most widely classification system used for HCC management guidelines.Up until now,HCC remains a challenge to early diagnose,and treat effectively;treating management is focused on hepatic resection,orthotopic liver transplantation,ablative therapies,chemoembolization and systemic therapies with cytotocix drugs,and targeted agents.This review article describes the current evidence on epidemiology,symptomatology,diagnosis and treatment of hepatocellular carcinoma.展开更多
An 81-year-old man presented with epigastric pain and weight loss for one month. He had a past history of pulmonary tuberculosis, 10 years ago. We performed a gastroscopy, which showed a linear depressed whitish gastr...An 81-year-old man presented with epigastric pain and weight loss for one month. He had a past history of pulmonary tuberculosis, 10 years ago. We performed a gastroscopy, which showed a linear depressed whitish gastric ulcer scar (0.8 cm in length) in the posterior wall of the prepyloric antrum. The result of biopsy was reported as squamous epithelium. Immunohistochemical staining using an antibody to high molecular weight cytokeratin (HMC) revealed positive staining in the squamous epithelium. Two years later, the lesion was followed up. The lesion remained at same site endoscopically, but no squamous epithelium could be seen microscopically.展开更多
We report here how a heterotopic penetrating peptic ulcer progressed to cause small bowel obstruction in a pa- tient with multiple previous negative investigations. The clinical presentation, radiographic features and...We report here how a heterotopic penetrating peptic ulcer progressed to cause small bowel obstruction in a pa- tient with multiple previous negative investigations. The clinical presentation, radiographic features and patho- logical findings of this case are described, along with the salient lessons learnt. The added value of wireless cap- sule endoscopy （WCE） in such circumstances is debated.展开更多
We report a case of gastric penetration caused by accidental ingestion of a chicken bone in a 42-year old woman with a partially wearing denture. Three days ago, she accidentally swallowed several lumps of poorly-chew...We report a case of gastric penetration caused by accidental ingestion of a chicken bone in a 42-year old woman with a partially wearing denture. Three days ago, she accidentally swallowed several lumps of poorly-chewed chicken. Physical examination disclosed mild tenderness in the periumbilical area. Abdominal Computed tomography (CT) showed a suspicious penetration or perforation of the stomach wall measuring about 3 cm, by a linear radiopaque material at the lesser curvature of the antrum. The end of a chicken bone was very close to but did not penetrate the liver. Endoscopic examination revealed a chicken bone that penetrated into the prepyloric antrum. The penetrating chicken bone was removed with grasping forceps. Five endoscopic clips were applied immediately at the removal site and the periumbilical pain resolved promptly. After removal of the chicken bone, the patient was treated with conservative care for three days, after which she was completely asymptomatic and discharged without complication. To treat gastric penetration by a foreign body, endoclipping can be a useful method in patients with no signs or symptoms of peritoneal irritation.展开更多
AIM： To assess the occurrence of gastric acid reflux into the esophagus in endoscopically confirmed prolapse gastropathy syndrome （PGS）. METHODS： Using ambulatory esophageal pH measurement （BRAVOTM wireless esoph...AIM： To assess the occurrence of gastric acid reflux into the esophagus in endoscopically confirmed prolapse gastropathy syndrome （PGS）. METHODS： Using ambulatory esophageal pH measurement （BRAVOTM wireless esophageal pH monitoring system）, twenty-six patients with PGS were compared with twenty-one patients with erosive esophagitis （EE） as controls. We assessed several reflux parameters, including the percentage of total time at pH 〈 4, and the DeMeester score. RESULTS： There were no statistical differences between the PGS group and the EE group as to mean age, sex ratio and pH recording time. The EE group showed more severe reflux than the PGS group, as evaluated in terms of the longest duration of reflux, the number of reflux episodes, the number of reflux episodes lasting 〉 5 min, the total time with pH 〈 4 during acid reflux episodes, and the DeMeester score, but none of these parameters showed statistically significant difference. Although 53.8% （14/26） of the PGS group and 76.2% （16/22） of the EE group demonstrated pathologic acid reflux （DeMeester score 〉 14.72）, there was no statistically significant difference between the two groups in the incidence of pathologic acid reflux （P = 0.11）. CONCLUSION： There was no statistically significant difference in pathologic acid reflux between the PGS and EE group. These data suggest that endoscopically diagnosed PGS might be a predictor of pathologic acid reflux.展开更多
Introduction: Neuroblastoma is the most common extracranial solid tumor in childhood and survival rate has improved during the last few decades. Only a few studies, related to Neuroblastoma in Saudi Arabian children, ...Introduction: Neuroblastoma is the most common extracranial solid tumor in childhood and survival rate has improved during the last few decades. Only a few studies, related to Neuroblastoma in Saudi Arabian children, have been performed. We report epidemiologic data and our clinical experience from the department of Pediatric Hematology Oncology (PHO), King Fahad Medical City (KFMC), Riyadh, Saudi Arabia. Method: A retrospective observational study of all patients, with diagnosis of Neuroblastoma, who attended PHO-KFMC from July 2006 to June 2014 was performed. The survival periods (overall survival and disease-free survival) and the final outcomes for patients treated and followed at KFMC were recorded. The survival data were statistically correlated with the clinical, pathological and biological features of patients and tumors and compared to national and international cohorts. Results: Eight-year data were available for the 42 patients of which 22 (52.4%) were male and 20 (47.6%) were females. Age at diagnosis ranged 0 - 91 months with a mean and median of 26.3 and 18.5 months respectively. 16 (38.1%) patients were under one year and 26 (61.9%) above 1 year of age. The event-free survival (EFS) and overall survival (OS) rates were 66.5% and 71.5% respectively. EFS and OS among those who were <1 year age at presentation was 75% and 82%, whereas ≥1 yr age group had 59% and 62% survival rates respectively. Patients with tumors in the adrenal had considerably lower EFS (59%) and OS (63%);in comparison to patients with tumors sites other than the adrenal who had EFS and OS of 85% and 89% respectively. Both EFS and OS survival rates at the end of follow-up interval were 100.0%, in the low and intermediate risk groups. In contrast, patients in the high risk group had EFS and OS rates of 44% and 48% respectively. This difference was statistically significant (p < 0.05). Conclusion: Our results are very encouraging and comparable with known published international cohorts, and reveal an excellent outcome for stage 1, 2, 3 & 4 s. The prognosis for advanced (stage 4) disease remains rather poor. A collaborative Saudi-wide effort, with an emphasis on research in detecting clinical and biologic characteristics of aggressive disease and tailoring therapy, is needed.展开更多
文摘In the realm of medical rarity,the convergence of infective endocarditis with the development of an aortic root abscess stands as a formidable challenge,often bearing a grim prognosis.Recognizing this perilous condition requires a vigilant eye.Embolic events stemming from infective endocarditis can precipitate acute coronary syndrome,adding another layer of complexity to diagnosis and treatment.
基金funded by internal grants from the Ward Family Heart Center.
文摘A bicuspid aortic valve,from autologous tissue,with growth potential can be constructed using the simple,and reproducible telescoping arterial trunk technique.
文摘BACKGROUND The persistent burden of cardiovascular(CV)disease in the United States requires innovative and cost-effective prognostic markers that can be relied upon.AIM To provide insights into how adiponectin can predict all-cause mortality and major adverse CV events(MACE)in patients with coronary artery disease(CAD)and to determine the prognostic value of adiponectin in predicting all-cause mortality and MACE in patients with stable CAD.METHODS We conducted a systematic search on PubMed,Scopus,and Google Scholar to find relevant studies published through June 2023 evaluating the long-term prognostic role of adiponectin in patients with stable CAD.Using a random effects model with 95%CI,we estimated the odds ratio(OR)while assessing heterogeneity through I^(2)statistics.To ensure robustness,we performed a sensitivity analysis using the leave-one-out approach.RESULTS After screening,we included five prospective studies involving 3225 patients who were followed up for a median duration of 3.8 years.Within the study population,prevalent risk factors included hypertension,diabetes,hyperlipidemia,and smoking.The commonly prescribed medications were angiotensin-converting enzyme inhibitors,beta blockers,and statins.The combined adjusted OR for all-cause mortality was found to be 2.51(95%CI:1.36–4.62),showing heterogeneity(I^(2)=65.51%,P=0.03).On the other hand,the combined adjusted OR for MACE was determined to be 1.04(95%CI:1.02–1.06)with no significant heterogeneity observed(I^(2)=0%,P=0.68).Through a sensitivity analysis,it was discovered that none of the studies significantly impacted the overall results of the meta-analysis,thus indicating their robustness.CONCLUSION Higher levels of adiponectin were found to be associated with an increased risk of long-term mortality and MACE in patients with CAD,which highlights its potential as a cost-effective marker for risk assessment and guiding treatment strategies.Further research on the role of adiponectin could greatly influence decision-making and resource allocation in CV care.
基金supported by funding from Guangdong Natural Science Foundation (grants:S2012010009211,S2012010009538)Key Specialty Projects of Guangzhou Board of Health (grant:20121A021014)
文摘Rotavirus diarrhea is a major worldwide cause of infantile gastroenteritis; however, the mechanism responsible for intestinal fluid loss remains unclear. Water transfer across the intestinal epithelial membrane seems to occur because of aquaporins(AQPs). Accumulating evidence indicates that alterations in AQPs may play an important role in pathogenesis. Here, we focus on changes in AQPs in a mouse model of rotavirus diarrhea. In the present study, 32 of 35 mice developed diarrhea and mild dehydration within 24 hours after infection with rotavirus strain SA11. Intestinal epithelial cells demonstrated cytoplasmic vacuolation, malaligned villi, and atrophy. AQP1 expression was significantly attenuated in the ileum and colon in comparison with controls; likewise, AQP4 and-8 protein expression were significantly decreased in the colon of rotavirus diarrhea-infected mice. In contrast, AQP3 protein expression was significantly increased in the colon of rotavirus-infected mice in comparison with controls. These results indicate that rotavirus diarrhea is associated with the downregulation of AQP1,-4, and-8 expression. Therefore, AQPs play an important role in rotavirus diarrhea.
文摘To determine the clinical characteristics of children with gastrointestinal bleeding (GIB) who died during the course of their admission.METHODSWe interrogated the Pediatric Hospital Information System database, including International Classification of Diseases, Current Procedural Terminology and Clinical Transaction Classification coding from 47 pediatric tertiary centers extracting the population of patients (1-21 years of age) admitted (inpatient or observation) with acute, upper or indeterminate GIB (1/2007-9/2015). Descriptive statistics, unadjusted univariate and adjusted multivariate analysis of the associations between patient characteristics and treatment course with mortality was performed with mortality as primary and endoscopy a secondary outcome of interest. All analyses were performed using the R statistical package, v.3.2.3.RESULTSThe population with GIB was 19528; 54.6% were male, overall mortality was 2.07%; (0.37% in patients with the principal diagnosis of GIB). When considering only the mortalities in which GIB was the principal diagnosis, 48% (12 of 25 principal diagnosis GIB mortalities) died within the first 3 d of admission, whereas 19.8% of secondary diagnosis GIB patients died with 3 d of admission. Patients who died were more likely to have received octreotide (19.8% c.f. 4.04%) but tended to have not received proton pump inhibitor therapy in the first 48 h, and far less likely to have undergone endoscopy during their admission (OR = 0.489, P < 0.0001). Chronic liver disease associated with a greater likelihood of endoscopy. Mortalities were significantly more likely to have multiple complex chronic conditions.CONCLUSIONGIB associated mortality in children is highest within 7 d of admission. Multiple comorbidities are a risk factor whereas early endoscopy during the admission is protective.
文摘AIM: To compare the hemostatic efficacy and safety of two mechanical endoscopic methods: endoscopic band ligation (EBL) and endoscopic hemoclip placement (EHP) in patients with actively bleeding Mallory-Weiss syndrome (MWS). METHODS: A prospective randomized study to compare the efficacy and safety of EHP with EBL was performed from January 2002 to August 2005. Forty-one patients with active bleeding from MWS were treated with EHP (n = 21) or EBL (n = 20). RESULTS: There were no significant differences between groups with respect to clinical and endoscopic characteristics. The mean number of hemoclips applied was 3.2 ± 1.5 and the mean number of bands applied was 1.2 ± 0.4. Primary hemostasis was achieved in all patients. Recurrent bleeding was observed in one patient from the EHP group and two from the EBL group. Patients with recurrent bleeding were treated by the same modality as at randomization and secondary hemostasis was achieved in all. There were no significant differences between the two groups in total transfusion amount or duration of hospital stay. No complications or bleeding-related death resulted. CONCLUSION: EHP and EBL are equally effective and safe for the management of active bleeding in patients with Mallory-Weiss syndrome, even in those with shock or comorbid diseases.
基金Supported by the donation of wireless Small bowel capsule and patency capsules from Giving imaging,Ltd Medtronic company with the funding agreement from Given investigator-initiated study No.13-12
文摘BACKGROUND Magnetic resonance enterography (MRE) and wireless capsule endoscopy (WCE) are equally accepted modalities for noninvasive screening of small bowel involvement (SBI) in children with Crohn’s disease (CD) and indeterminate colitis (IC) albeit there is a paucity of data comparing the two and thereby guiding the clinician in selecting the ideal diagnostic approach. Therefore, the goal of this study is to provide additional evidence for capsule endoscopy role in the evaluation of established Crohn’s disease exacerbation compared to MRE in relation to Pediatric Crohn's Disease Activity Index (PCDAI), and histological indices. AIM To prospectively compare the findings of MRE and WCE and their agreement with PCDAI or histology in children with CD or IC. METHODS Consecutive patients diagnosed with CD and IC were screened for inclusion. After informed consent, patient’s demographic and clinical data was abstracted. The current pediatric disease activity index (PCDAI) and endoscopic findings were included. Patients underwent MRE and WCE including preprocedural patency capsule within a maximum of 7 d of each other. Pathological presence of active small bowel disease in ileal and duodenal biopsies were collected if the endoscopy was performed within 2 mo of the WCE study. Patients who failed to pass the PC were excluded from the study. WCE was read by two different experienced gastroenterologists (Attard TM and Colombo JM) blinded to each other's findings and to the findings on MRE (Mardis NJ). Agreement between WCE reviewers, WCE and MRE findings and concordance between positive PCDAI and SBI based on MRE compared with WCE was computed. RESULTS Forty-five patients were included in the study, 18 withdrew and 27 (20 males and 20 CD), mean age (standard deviation) 13.46 (2.4) years, completed the study protocol. There were no instances of capsule retention. Concordance between gastroenterologist reviewers was excellent for the diagnosis of small intestinal CD with good correlation between the two Lewis scores (r=0.875, P<0.001). Concordance between WCE and MRE was poor (69%). In CD patients, when both MRE and WCE were compared using PCDAI>10 as the standard reference reflecting active small intestinal CD, the sensitivity of MRE and WCE were 100% and 83% respectively and the specificity of MRE and WCE were 57.14% and 78.6%, respectively. If the histology in ileum or/and duodenum was used as the reference for active small bowel involvement, WCE had a higher specificity as compared to MRE (83.3% vs 50%). In patients with Crohn’s disease, those with a positive PCDAI (>10) were more likely to have a positive WCE as compared to those with a negative PCDAI (83% vs 21%;P=0.018). CONCLUSION We suggest that MRE and WCE have a complementary role in the assessment of SBI in CD. WCE detected SBI with a much higher specificity while MRE had a higher sensitivity.
文摘AIM: To determine whether thalidomide prevents microvascular injury in acute radiation proctitis in white rats. METHODS: Fourteen female Wistar rats were used: six in the radiation group, six in the thalidomide group, and two in normal controls. The radiation and thalidomide groups were irradiated at the pelvic area using a single 30 Gy exposure. The thalidomide (150 mg/kg) was injected into the peritoneum for 7 d from the day of irradiation. All animals were sacrificed and the rectums were removed on day 8 after irradiation. The microvessels of resected specimens were immunohistochemically stained with thrombomodulin (TM), von Willebrand Factor (vWF), and vascular endothelial growth factor (VEGF). RESULTS: The microscopic scores did not differ significantly between the radiation and thalidomide groups, but both were higher than in the control group. Expression of TM was significantly lower inthe endothelial cells (EC) of the radiation group than in the control and thalidomide groups (P < 0.001). The number of capillaries expressing vWF in the EC was higher in the radiation group (15.3 ± 6.8) than in the control group (3.7 ± 1.7), and the number of capillaries expressing vWF was attenuated by thalidomide (10.8 ± 3.5, P < 0.001). The intensity of VEGF expression in capillaries was greater in the radiation group than in the control group and was also attenuated by thalidomide (P = 0.003). CONCLUSION: The mechanisms of acute radiation- induced proctitis in the rats are related to endothelial cell injury of microvessel, which may be attenuated with thalidomide.
文摘Juvenile polyps are relatively common findings in children,while juvenile polyposis syndrome(JPS) is a rare hereditary syndrome entailing an increased risk of colorectal cancer.Mutations in BMPR1A or SMAD4 are found in roughly half of patients diagnosed with JPS.Mutations in PTEN gene are also found in patients with juvenile polyps and in Bannayan-Riley-Ruvalcaba syndrome and Cowden syndrome.Several previous reports have described microdeletions in chromosome 10q23 encompassing both PTEN and BMPR1A causing aggressive polyposis and malignancy in childhood.These reports have also described extra-intestinal findings in most cases including cardiac anomalies,developmental delay and macrocephaly.In this report we describe a boy with a 5.75 Mb deletion of chromosome 10q23 and a 1.03 Mb deletion within chromosome band 1p31.3who displayed aggressive juvenile polyposis and multiple extra-intestinal anomalies including macrocephaly,developmental delay,short stature,hypothyroidism,atrial septal defect,ventricular septal defect and hypospadias.He required colectomy at six years of age,and early colectomy was a common outcome in other children with similar deletions.Due to the aggressive polyposis and reports of dysplasia and even malignancy at a young age,we propose aggressive gastrointestinal surveillance in children with 10q23 microdeletions encompassing the BMPR1A and PTEN genes to include both the upper and lower gastrointestinal tracts,and also include a flowchart for an effective genetic testing strategy in children with juvenile polyposis.
文摘Collagenous gastritis (CG) is characterized by patchy subepithelial collagen bands. Effective treatment and the clinical and histological outcome of CG in children are poorly defined. The aim of this study is to summarize the published literature on the clinical outcome and response to therapy of pediatric CG including two new cases. We performed a search in Pubmed, OVID for related terms; articles including management and clinical and/or endo-histologic follow up information were included and abstracted. Reported findings were pooled in a dedicated database including the corresponding data extracted from chart review in our patients with CG. Twenty-four patients were included (17 females) with a mean age of 11.7 years. The clinical presentation included iron deficiency anemia and dyspepsia. The reported duration of follow up (in 18 patients) ranged between 0.2-14 years. Despite most subjects presenting with anemia including one requiring blood transfusion, oral iron therapy was only documented in 12 patients. Other treatment modalities were antisecretory measures in 13 patients; proton pump inhibitors (12), or histamine-2 blockers (3), sucralfate (5), prednisolone (6), oral budesonide in 3 patients where one received it in fish oil and triple therapy (3). Three (13%) patients showed no clinical improvement despite therapy; conversely 19 out of 22 were reported with improved symptoms including 8 with complete symptom resolution. Spontaneous clinical resolution without antisecretory, anti-inflammatory or gastroprotective agents was noted in 5 patients (4 received only supplemental iron). Follow up endohistopathologic data (17 patients) included persistent collagen band and stable Mononuclear cell infiltrate in 12 patients with histopathologic improvement in 5 patients. Neither collagen band thickness nor mononuclear cell infiltrate correlated with clinical course. Intestinal metaplasia and endocrine cell hyperplasia were reported (1) raising the concern of long term malignant transformation. In summary, CG in children is a chronic disease, typically with a variable clinical response and an indolent course that is distinct from the adult phenotype. Long term therapy usually inclused iron supplementation but cannot be standardized, given the chronicity of the disease, variability of response and potential for adverse events.
文摘AIM： To examine the predictive factors of capsule en- doscopy （CE） completion rate （CECR） including the ef- fect of inpatient and outpatient status.METHODS： We identified 355 consecutive patients who completed CE at Rush University Medical Center between March 2003 and October 2005. Subjects for CE had either nothing by mouth or clear liquids for the afternoon and evening of the day before the pro- cedure. CE exams were reviewed by two physicians who were unaware of the study hypotheses. After retrospective analysis, 21 cases were excluded due to capsule malfunction, prior gastric surgery, endoscopic capsule placement or insufficient data. Of the remain- ing 334 exams [264 out-patient （OP）, 70 in-patient （IP）], CE indications, findings, location of the patients [IP vs OP and intensive care unit （ICU） vs general medical floor （GMF）] and gastrointestinal transit times were analyzed. Statistical analysis was completed us- ing SPSS version 17 （Chicago, IL）. Chi-square, t test or fisher exact-tests were used as appropriate. Multivari- ate logistic regression analysis was used to identify variables associated with incomplete CE exams. RESULTS： The mean age for the entire study popula- tion was 54.7 years. Sixty-one percent of the study population was female, and gender was not different between IPs vs OPs （P = 0.07）. The overall incomplete CECR was 14% in our study. Overt obscure gastroin- testinal bleeding （OGB） was significantly more com- mon for the IP CE （P = 0.0001）, while abdominal pain and assessment of IBD were more frequent indications for the OP CE exams （P = 0.002 and P = 0.01, respec- tively）. Occult OGB was the most common indication and arteriovenous malformations were the most com- mon finding both in the IPs and OPs. The capsule did not enter the small bowel （SB） in 6/70 IPs and 8/264 OPs （P = 0.04）. The capsule never reached the cecum in 31.4% （22/70） of IP vs 9.5% （25/ 264） of OP ex- aminations （P 〈 0.001）. The mean gastric transit time （GTT） was delayed in IPs compared to OPs, 98.5 ± 139.5 min vs 60.4 ± 92.6 min （P = 0.008）. Minimal SB transit time was significantly prolonged in the IP com- pared to the OP setting [IP = 275.1±111.6 min vs OP = 244.0 ± 104.3 min （P = 0.037）]. CECR was also sig- nificantly higher in the subgroup of patients with OGB who had OP vs IP exams （95% vs 80% respectively, P = 0.001）. The proportion of patients with incomplete exams was higher in the ICU （n = 7/13, 54%） as com- pared to the GMF （n = 15/57, 26%） （P = 0.05）. There was only a single permanent SB retention case which was secondary to a previously unknown SB stricture, and the remaining incomplete SB exams were due to slow transit. Medications which affect gastrointesti- nal system motility were tested both individually and also in aggregate in univariate analysis in hospitalized patients （ICU and GMF） and were not predictive of incomplete capsule passage （P 〉 0.05）. Patient loca- tion （IP vs OP） and GTT were independent predictors of incomplete CE exams （P 〈 0.001 and P = 0.008, respectively）. CONCLUSION： Incomplete CE is a multifactorial prob- lem. Patient location and related factors such as sever- ity of illness and sedentary status may contribute to incomplete exams.
文摘There is an increasing appreciation for the importance of inflammation as a pathophysiologic entity that contributes to functional gastrointestinal disorders including functional dyspepsia(FD).Importantly,inflammation may serve as a mediator between psychologic and physiologic functions.This manuscript reviews the literature implicating two inflammatory cell types,mast cells and eosinophils,in the generation of dyspeptic symptoms and explores their potential as targets for the treatment of FD.There are a number of inciting events which may initiate an inflammatory response,and the subsequent recruitment and activation of mast cells and eosinophils.These include internal triggers such as stress and anxiety,as well as external triggers such as microbes and allergens.Previous studies suggest that there may be efficacy in utilizing medications directed at mast cells and eosinophils.Evidence exists to suggest that combining "anti-inflammatory" medications with other treatments targeting stress can improve the rate of symptom resolution in pediatric FD.
文摘Hepatocellular carcinoma(HCC)is the most frequent primary liver malignancy and the third cause of cancer-related death in the Western Countries.The well-established causes of HCC are chronic liver infections such as hepatitis B virus or chronic hepatitis C virus,nonalcoholic fatty liver disease,consumption of aflatoxins and tobacco smocking.Clinical presentation varies widely;patients can be asymptomatic while symptomatology extends from right upper abdominal quadrant paint and weight loss to obstructive jaundice and lethargy.Imaging is the first key and one of the most important aspects at all stages of diagnosis,therapy and follow-up of patients with HCC.The Barcelona Clinic Liver Cancer Staging System remains the most widely classification system used for HCC management guidelines.Up until now,HCC remains a challenge to early diagnose,and treat effectively;treating management is focused on hepatic resection,orthotopic liver transplantation,ablative therapies,chemoembolization and systemic therapies with cytotocix drugs,and targeted agents.This review article describes the current evidence on epidemiology,symptomatology,diagnosis and treatment of hepatocellular carcinoma.
文摘An 81-year-old man presented with epigastric pain and weight loss for one month. He had a past history of pulmonary tuberculosis, 10 years ago. We performed a gastroscopy, which showed a linear depressed whitish gastric ulcer scar (0.8 cm in length) in the posterior wall of the prepyloric antrum. The result of biopsy was reported as squamous epithelium. Immunohistochemical staining using an antibody to high molecular weight cytokeratin (HMC) revealed positive staining in the squamous epithelium. Two years later, the lesion was followed up. The lesion remained at same site endoscopically, but no squamous epithelium could be seen microscopically.
文摘We report here how a heterotopic penetrating peptic ulcer progressed to cause small bowel obstruction in a pa- tient with multiple previous negative investigations. The clinical presentation, radiographic features and patho- logical findings of this case are described, along with the salient lessons learnt. The added value of wireless cap- sule endoscopy （WCE） in such circumstances is debated.
文摘We report a case of gastric penetration caused by accidental ingestion of a chicken bone in a 42-year old woman with a partially wearing denture. Three days ago, she accidentally swallowed several lumps of poorly-chewed chicken. Physical examination disclosed mild tenderness in the periumbilical area. Abdominal Computed tomography (CT) showed a suspicious penetration or perforation of the stomach wall measuring about 3 cm, by a linear radiopaque material at the lesser curvature of the antrum. The end of a chicken bone was very close to but did not penetrate the liver. Endoscopic examination revealed a chicken bone that penetrated into the prepyloric antrum. The penetrating chicken bone was removed with grasping forceps. Five endoscopic clips were applied immediately at the removal site and the periumbilical pain resolved promptly. After removal of the chicken bone, the patient was treated with conservative care for three days, after which she was completely asymptomatic and discharged without complication. To treat gastric penetration by a foreign body, endoclipping can be a useful method in patients with no signs or symptoms of peritoneal irritation.
文摘AIM： To assess the occurrence of gastric acid reflux into the esophagus in endoscopically confirmed prolapse gastropathy syndrome （PGS）. METHODS： Using ambulatory esophageal pH measurement （BRAVOTM wireless esophageal pH monitoring system）, twenty-six patients with PGS were compared with twenty-one patients with erosive esophagitis （EE） as controls. We assessed several reflux parameters, including the percentage of total time at pH 〈 4, and the DeMeester score. RESULTS： There were no statistical differences between the PGS group and the EE group as to mean age, sex ratio and pH recording time. The EE group showed more severe reflux than the PGS group, as evaluated in terms of the longest duration of reflux, the number of reflux episodes, the number of reflux episodes lasting 〉 5 min, the total time with pH 〈 4 during acid reflux episodes, and the DeMeester score, but none of these parameters showed statistically significant difference. Although 53.8% （14/26） of the PGS group and 76.2% （16/22） of the EE group demonstrated pathologic acid reflux （DeMeester score 〉 14.72）, there was no statistically significant difference between the two groups in the incidence of pathologic acid reflux （P = 0.11）. CONCLUSION： There was no statistically significant difference in pathologic acid reflux between the PGS and EE group. These data suggest that endoscopically diagnosed PGS might be a predictor of pathologic acid reflux.
文摘Introduction: Neuroblastoma is the most common extracranial solid tumor in childhood and survival rate has improved during the last few decades. Only a few studies, related to Neuroblastoma in Saudi Arabian children, have been performed. We report epidemiologic data and our clinical experience from the department of Pediatric Hematology Oncology (PHO), King Fahad Medical City (KFMC), Riyadh, Saudi Arabia. Method: A retrospective observational study of all patients, with diagnosis of Neuroblastoma, who attended PHO-KFMC from July 2006 to June 2014 was performed. The survival periods (overall survival and disease-free survival) and the final outcomes for patients treated and followed at KFMC were recorded. The survival data were statistically correlated with the clinical, pathological and biological features of patients and tumors and compared to national and international cohorts. Results: Eight-year data were available for the 42 patients of which 22 (52.4%) were male and 20 (47.6%) were females. Age at diagnosis ranged 0 - 91 months with a mean and median of 26.3 and 18.5 months respectively. 16 (38.1%) patients were under one year and 26 (61.9%) above 1 year of age. The event-free survival (EFS) and overall survival (OS) rates were 66.5% and 71.5% respectively. EFS and OS among those who were <1 year age at presentation was 75% and 82%, whereas ≥1 yr age group had 59% and 62% survival rates respectively. Patients with tumors in the adrenal had considerably lower EFS (59%) and OS (63%);in comparison to patients with tumors sites other than the adrenal who had EFS and OS of 85% and 89% respectively. Both EFS and OS survival rates at the end of follow-up interval were 100.0%, in the low and intermediate risk groups. In contrast, patients in the high risk group had EFS and OS rates of 44% and 48% respectively. This difference was statistically significant (p < 0.05). Conclusion: Our results are very encouraging and comparable with known published international cohorts, and reveal an excellent outcome for stage 1, 2, 3 & 4 s. The prognosis for advanced (stage 4) disease remains rather poor. A collaborative Saudi-wide effort, with an emphasis on research in detecting clinical and biologic characteristics of aggressive disease and tailoring therapy, is needed.
