BACKGROUND Stenting as a bridge to curative surgery(SBTS)for obstructing colon cancer(OCC)has been associated with possibly worse oncological outcomes.AIM To evaluate the recurrence patterns,survival outcomes,and colo...BACKGROUND Stenting as a bridge to curative surgery(SBTS)for obstructing colon cancer(OCC)has been associated with possibly worse oncological outcomes.AIM To evaluate the recurrence patterns,survival outcomes,and colorectal cancer(CRC)-specific death in patients undergoing SBTS for OCC.METHODS Data from 62 patients undergoing SBTS at a single tertiary centre over ten years between 2007 and 2016 were retrospectively examined.Primary outcomes were recurrence patterns,overall survival(OS),cancer-specific survival(CSS),and CRC-specific death.OS and CSS were estimated using the Kaplan-Meier curves.Competing risk analysis with cumulative incidence function(CIF)was used to estimate CRC-specific mortality with other cause-specific death as a competing event.Fine-Gray regressions were performed to determine prognostic factors of CRC-specific death.Univariate and multivariate subdistribution hazard ratios and their corresponding Wald test P values were calculated.RESULTS 28 patients(45.2%)developed metastases after a median period of 16 mo.Among the 18 patients with single-site metastases:Four had lung-only metastases(14.3%),four had liver-only metastases(14.3%),and 10 had peritoneum-only metastases(35.7%),while 10 patients had two or more sites of metastatic disease(35.7%).The peritoneum was the most prevalent(60.7%)site of metastatic involvement(17/28).The median follow-up duration was 46 mo.26(41.9%)of the 62 patients died,of which 16(61.5%)were CRC-specific deaths and 10(38.5%)were deaths owing to other causes. The 1-, 3-, and 5-year OS probabilities were 88%, 74%, and 59%;1-, 3-, and5-year CSS probabilities were 97%, 83%, and 67%. The highest CIF for CRC-specific death at 60 mowas liver-only recurrence (0.69). Liver-only recurrence, peritoneum-only recurrence, and two ormore recurrence sites were predictive of CRC-specific death.CONCLUSIONThe peritoneum was the most common metastatic site among patients undergoing SBTS. Liveronlyrecurrence, peritoneum-only recurrence, and two or more recurrence sites were predictors ofCRC-specific death.展开更多
BACKGROUND The incidence of intestinal malrotation in adults has been reported to only be about 0.2%.Duodenal web as a cause of intestinal obstruction is rare,with an incidence of about 1:20000-1:40000.Furthermore,whe...BACKGROUND The incidence of intestinal malrotation in adults has been reported to only be about 0.2%.Duodenal web as a cause of intestinal obstruction is rare,with an incidence of about 1:20000-1:40000.Furthermore,when described,these conditions are usually seen in early life and very infrequently in adulthood.CASE SUMMARY We report a case of a middle-aged woman with intestinal malrotation who presented with a three-month history of right-sided abdominal pain,early satiety,and a 22-pound weight loss.Patient underwent an esophagogastroduodenoscopy,which demonstrated numerous retained pills in a deformed first portion of the duodenum,concerning for a partial gastric outlet obstruction.An upper gastrointestinal series showed marked distention of the proximal duodenum with retained debris and the presence of a windsock sign,increasing the suspicion of a duodenal web.The patient subsequently underwent surgical intervention where a duodenal web with two lumens was noted and resected,opening the duodenum.There were over 150 pill capsules that were removed.The patient is doing well after this intervention.CONCLUSION Both intestinal malrotation and duodenal webs are infrequently encountered in the adult population.These pathologies can also present with nonspecific abdominal symptoms such as chronic abdominal pain and nausea.Hence,providers might not consider these pathologies in the differential for patients who present with vague symptoms which can lead to delay in management and increased mortality and morbidity.展开更多
Biliary obstructions can lead to infections of the biliary system, particularly in patients with occluded biliary stents. Fungal organisms are frequently found in bili-ary aspirates of patients who have been on antibi...Biliary obstructions can lead to infections of the biliary system, particularly in patients with occluded biliary stents. Fungal organisms are frequently found in bili-ary aspirates of patients who have been on antibiotics and have stents; however, fungal masses, or "balls", that fully obstruct the biliary system are uncommon and exceedingly diff icult to eradicate. We present 4 cases of obstructing fungal cholangitis in patients who had metal biliary stents placed for pancreatic malignancies, and subsequently required aggressive antifungal administration along with endoscopic and radiologic interventions. This report also reviews approaches previously undertaken to manage severe obstructing fungal cholangitis.展开更多
Objective:To observe the clinical efficacy and safety of oral administration of the traditional Chinese herb rhubarb to treat acute exacerbation of chronic obstructive pulmonary disease(AECOPD).Method:This was a multi...Objective:To observe the clinical efficacy and safety of oral administration of the traditional Chinese herb rhubarb to treat acute exacerbation of chronic obstructive pulmonary disease(AECOPD).Method:This was a multicenter randomized double-blinded placebo controlled study that took place in 7 provinces of China that enrolled 244 patients(aged 18e80 years)who had acute exacerbation of COPD with the traditional Chinese syndrome pattern of phlegm-heat obstructing lung.Participants were divided into experimental and control groups.The experimental group received 4.5 g of rhubarb granules twice daily and the control group received placebo granules.Both groups also received conventional Western therapy consisting of oxygen therapy,an antibiotic,expectorant,and a bronchodilator.Treatment lasted 10 days.Symptom scores for cough,sputum volume and color,wheezing and chest tightness before treatment and on days 3,5,7,and 10 during the treatment were recorded.Lung function,arterial blood gas and levels of serum inflammatory factors,interleukin-4(IL-4),interleukin-8(IL-8),and interleukin-10(IL-10)and tumor necrosis factor-alpha(TNF-a),before and after treatment were measured.Results:The sample size of the full analysis set(FAS)was 244 participants,and the sample size of per protocol set(PPS)was 235.Following 10 days’treatment,symptom scores of the experimental group were markedly lower than those of the placebo group(FAS:mean difference1.67,95%CI:e2.66 to0.69,P Z 0.001;PPS:mean difference1.55,95%CI:2.56 to0.54,P Z 0.003).Lung function in the experimental group was significantly higher than in the placebo group(FEV1,FAS:mean difference 0.12,95%CI:0.06 to 0.18;P<0.001;PPS:mean difference 0.12,95%CI 0.05 to 0.18;P<0.001.FVC:FAS:mean difference 0.16,95%CI:0.06 to 0.26;P Z 0.002;PPS:mean difference 0.16,95%CI 0.05 to 0.26;P Z 0.003.FEV1%,FAS:mean difference 5.95,95%CI:3.36 to 8.53;P<0.001;PPS:mean difference 5.92,95%CI 3.28 to 8.56;P<0.001.).PaO2,PaCO2,as well as serum inflammatory factors were also improved when compared to the placebo group.There were no significant differences in the incidence rate of adverse reaction between the two groups.Conclusions:Compared with placebo,rhubarb granules significantly reduced symptom scores,improved blood oxygen level,controlled systemic inflammatory response,without significant adverse effects.Thus,rhubarb may be a beneficial adjuvant method for treating the phlegm-heat obstructing the lung syndrome pattern of AECOPD.展开更多
Objective:To explore the molecular mechanism of the prescription for the syndrome of cold-damp-ness obstructing the lung in the treatment of corona virus disease 2019(COVID-19).Methods:The medicinals for the treatment...Objective:To explore the molecular mechanism of the prescription for the syndrome of cold-damp-ness obstructing the lung in the treatment of corona virus disease 2019(COVID-19).Methods:The medicinals for the treatment of the syndrome of cold-dampness obstructing the lung,such as Cangzhu(Rhizoma Atractylo-dis),Chenpi(Pericarpium Gitri Reticulatae),Houpo(Cortex Magnoliae Officinalis),Huoxiang(Herba Agastachis),Caoguo(Fructus Tsaoko),Mahuang(Herba Ephedrae),Qianghuo(Rhizoma et Radix Notoptery-gi),Shengjiang(Rhizoma Zingiberis Recens),Binlang(Semen Arecae)in the Diagnosis and Treatment Pro-gram of COVID-19(Trial Version 6)were taken as research subjects,and the combination of these nine me-dicinals can be called Hanshi Zufei Fang(寒湿阻肺方,HSZFF).The active components and targets of each single Chinese materia medica was screened and obtained through the Traditional Chinese Medicine Systems Pharmacology(TCMSP)database.The target information related to COVID-19 was retrieved through the Gene-Cards disease-related target database.The medicinal prediction targets were mapped to the disease target to ob-tain the intersection targets.The DAVID database was applied to perform gene ontology(GO)enrichment anal-ysis and kyoto encyclopedia of genes and genomes(KEGG)pathway analysis on the targets;GraphPad Prism 5.0 software was applied to plot the biological process(BP)of GO enrichment analysis,cellular component(CC),molecular function(MF)histograms;OmicShare online software was applied to make KEGG advanced bubble chart;Cytoscape software was applied to visualize the interaction with the targets and Chinese materia medica-components-targets results.Results:Totally 56 key active components of 9 Chinese materia medica for cold-dampness obstructing lung syndrome were screened,and 55 targets were obtained.The results of GO and KEGG enrichment analysis showed that the compound prescription mainly regulated the body's immune re-sponse and reduced inflammation by regulating such signaling pathways of inflammatory response and immune regulation as TNF signaling pathway,HIF-1 signaling pathway,Toll-like receptor signaling pathway,infuenza A signaling pathway,T cell receptor signaling pathway.Conclusion:HSZFF can eliminate infl ammation and inhibit virus by regulating immune inflammatory factors closely related to the occurrence and development of diseases through multi-component and multi-target.展开更多
BACKGROUND Surgery 5-10 d after stent insertion was recommended by the European Society of Gastrointestinal Endoscopy for obstructing colonic cancer. For some obstructive patients, this may be not a good choice. Here,...BACKGROUND Surgery 5-10 d after stent insertion was recommended by the European Society of Gastrointestinal Endoscopy for obstructing colonic cancer. For some obstructive patients, this may be not a good choice. Here, we report the successful treatment of obstructing colonic cancer by combining self-expandable stent and neoadjuvant chemotherapy.CASE SUMMARY The patient was a 72-year-old man who was admitted with a chief complaint of abdominal pain for more than 1 mo. Computed tomography(CT) scanning revealed that there was a mass in the descending colon, which led to intestinal obstruction. On admission, a series of therapeutic measures, such as fasting and water deprivation, gastrointestinal decompression, total parenteral nutrition, and octreotide acetate, were taken to improve the obstructive symptoms. At the same time, a self-expandable metal stent was successfully placed across the stenosis,and a biopsy was obtained and diagnosed as adenocarcinoma. CT scanning 14 d after insertion of the stent revealed that the intestine was swollen significantly.Systemic chemotherapy with modified FOLFOX6(mFOLFOX6) was administered. After two courses of mFOLFOX6, CT scanning showed clearly that swelling of the intestine was improved. Subsequently, the patient underwent left hemi-colectomy without stoma placement. The postoperative course was uneventful, and he has been disease-free for 6 mo after surgery.CONCLUSION This modified treatment strategy may provide an alternative therapy for patients with obstructing colonic cancers.展开更多
From 1973 to 1989, 90 cases of obstructing carcinoma of the left colon were treated with five different operative procedures, the Incidence of anastomotic leakage was 6.7%, the operative mortality was 7. 8%. Among all...From 1973 to 1989, 90 cases of obstructing carcinoma of the left colon were treated with five different operative procedures, the Incidence of anastomotic leakage was 6.7%, the operative mortality was 7. 8%. Among all the patients, 14 cases were treated by primary resection with anastomosis. Anastomotic leakage occurred in 6 cases, and 5 of them were died. Of 25 cases with the traditional staged management, the tumors were resected only in 20 cases, and not resectable in the other 5 patients. 19 with modified Hartmann's procedure and 26 with extended right hemlcolectomy with ileorectal or low ileosigmoid anastomosis gave satisfactory results. In terms of this series, the five-year survival rate in primary resection group was significantly higher than that in staged resection group (P< 0. 05). It is suggested that extented right hemlcolectomy or modified Hartmann' s procedure in cases of acute cancerous obstruction of the left colon would be favord.展开更多
BACKGROUND Self-expandable metal stents(SEMSs) are frequently used in the setting of palliation for occluding, inoperable colorectal cancer(CRC). Among possible complications of SEMS positioning, re-obstruction is the...BACKGROUND Self-expandable metal stents(SEMSs) are frequently used in the setting of palliation for occluding, inoperable colorectal cancer(CRC). Among possible complications of SEMS positioning, re-obstruction is the most frequent. Its management is controversial, potentially involving secondary stent-in-stent placement, which has been poorly investigated. Moreover, the issue of secondary stent-in-stent re-obstruction and of more-than-two colonic stenting has never been assessed. We describe a case of tertiary SEMS-in-SEMS placement, and also discuss our practice based on available literature.CASE SUMMARY A 66-year-old male with occluding and metastatic CRC was initially treated by positioning of a SEMS, which had to be revised 6 mo later when a symptomatic intra-stent tumor ingrowth was treated by a SEMS-in-SEMS. We hereby describe an additional episode of intestinal occlusion due to recurrence of intra-stent tumor ingrowth. This patient, despite several negative prognostic factors(splenic flexure location of the tumor, carcinomatosis with ascites, subsequent chemotherapy that included bevacizumab and two previously positioned stents(1 SEMS and 1 SEMS-in-SEMS)) underwent successful management through the placement of a tertiary SEMS-in-SEMS, with immediate clinical benefit and no procedure-related adverse events after 150 d of post-procedural follow-up. This endoscopic management has permitted 27 mo of partial control of a metastatic disease without the need for chemotherapy discontinuation and, ultimately, a good quality of life until death.CONCLUSION Tertiary SEMS-in-SEMS is technically feasible, and appears to be a safe and effective option in the case of recurrent SEMS obstruction.展开更多
BACKGROUND Mycobacterium tuberculosis(TB)is the causative agent of TB,a chronic granulo-matous illness.This disease is prevalent in low-income countries,posing a significant global health challenge.Gastrointestinal TB...BACKGROUND Mycobacterium tuberculosis(TB)is the causative agent of TB,a chronic granulo-matous illness.This disease is prevalent in low-income countries,posing a significant global health challenge.Gastrointestinal TB is one of the three forms.The disease can mimic other intra-abdominal conditions,leading to delayed diagnosis owing to the absence of specific symptoms.While gastric outlet obs-truction(GOO)remains a frequent complication,its incidence has declined with the advent of proton pump inhibitors and Helicobacter pylori eradication therapy.Gastroduodenal TB can cause upper gastrointestinal hemorrhage,obstruction,and malignancy-like tumors.CASE SUMMARY A 23-year-old male presented with recurrent epigastric pain,distension,nausea,vomiting,and weight loss,prompting a referral to a gastroenterologist clinic.Endoscopic examination revealed distorted gastric mucosa and signs of chronic inflammation.However,treatment was interrupted,possibly owing to vomiting or comorbidities such as human immunodeficiency virus infection or diabetes.Subsequent surgical intervention revealed a dilated stomach and diffuse thickening of the duodenal wall.Resection revealed gastric wall effacement with TB.CONCLUSION Primary gastric TB is rare,frequently leading to GOO.Given its rarity,suspicions should be promptly raised when encountering relevant symptoms,often requiring surgical intervention for diagnosis and treatment.展开更多
BACKGROUND Endoscopic ultrasound-guided biliary drainage using electrocautery-enhanced(ECE)delivery of lumen-apposing metal stent(LAMS)is gradually being re-cognized as a viable palliative technique for malignant bili...BACKGROUND Endoscopic ultrasound-guided biliary drainage using electrocautery-enhanced(ECE)delivery of lumen-apposing metal stent(LAMS)is gradually being re-cognized as a viable palliative technique for malignant biliary obstruction after endoscopic retrograde cholangiopancreatography(ERCP)failure.However,most of the studies that have assessed its efficacy and safety were small and hetero-geneous.Prior meta-analyses of six or fewer studies that were published 2 years ago were therefore underpowered to yield convincing evidence.AIM To update the efficacy and safety of ECE-LAMS for treatment of biliary ob-struction after ERCP failure.METHODS We searched PubMed,EMBASE,and Scopus databases from the inception of the ECE technique to May 13,2022.Primary outcome measure was pooled technical success rate,and secondary outcomes were pooled rates of clinical success,re-intervention,and adverse events.Meta-analysis was performed using a random-effects model following Freeman-Tukey double-arcsine transformation in R soft-ware(version 4.1.3).RESULTS Fourteen eligible studies involving 620 participants were ultimately included.The pooled rate of technical success was 96.7%,and clinical success was 91.0%.Adverse events were reported in 17.5%of patients.Overall reinter-vention rate was 7.3%.Subgroup analyses showed results were generally consistent.CONCLUSION ECE-LAMS has favorable success with acceptable adverse events in relieving biliary obstruction when ERCP is impossible.The consistency of results across most subgroups suggested that this is a generalizable approach.展开更多
This narrative review provides an overview of the utilization of endoscopic ultrasound-guided gallbladder drainage(EUS-GBD)as a salvage approach in cases of unsuccessful conventional management.EUS-GBD is a minimally ...This narrative review provides an overview of the utilization of endoscopic ultrasound-guided gallbladder drainage(EUS-GBD)as a salvage approach in cases of unsuccessful conventional management.EUS-GBD is a minimally invasive and effective technique for drainage in patients with acute cholecystitis with high risk of surgery.The procedure has demonstrated impressive technical and clinical success rates with low rates of adverse events,making it a safe and effective option for appropriate candidates.Furthermore,EUS-GBD can also serve as a rescue option for patients who have failed endoscopic retrograde cholangiopancreatography or EUS biliary drainage for relief of jaundice in malignant biliary stricture.However,patient selection is critical for the success of EUS-GBD,and proper patient selection and risk assessment are important to ensure the safety and efficacy of the procedure.As the field continues to evolve and mature,ongoing research will further refine our understanding of the benefits and limitations of EUS-GBD,ultimately leading to improved outcomes for patients.展开更多
BACKGROUND Obstructive sleep apnea-hypopnea syndrome(OSAHS)is primarily caused by airway obstruction due to narrowing and blockage in the nasal and nasopha-ryngeal,oropharyngeal,soft palate,and tongue base areas.The m...BACKGROUND Obstructive sleep apnea-hypopnea syndrome(OSAHS)is primarily caused by airway obstruction due to narrowing and blockage in the nasal and nasopha-ryngeal,oropharyngeal,soft palate,and tongue base areas.The mid-frequency anti-snoring device is a new technology based on sublingual nerve stimulation.Its principle is to improve the degree of oropharyngeal airway stenosis in OSAHS patients under mid-frequency wave stimulation.Nevertheless,there is a lack of clinical application and imaging evidence.METHODS We selected 50 patients diagnosed with moderate OSAHS in our hospital between July 2022 and August 2023.They underwent a 4-wk treatment regimen involving the mid-frequency anti-snoring device during nighttime sleep.Following the treatment,we monitored and assessed the sleep apnea quality of life index and Epworth Sleepiness Scale scores.Additionally,we performed computed tomo-graphy scans of the oropharynx in the awake state,during snoring,and while using the mid-frequency anti-snoring device.Cross-sectional area measurements in different states were taken at the narrowest airway point in the soft palate posterior and retrolingual areas.RESULTS Compared to pretreatment measurements,patients exhibited a significant reduction in the apnea-hypopnea index,the percentage of time with oxygen saturation below 90%,snoring frequency,and the duration of the most prolonged apnea event.The lowest oxygen saturation showed a notable increase,and both sleep apnea quality of life index and Epworth Sleepiness Scale scores improved.Oropharyngeal computed tomography scans revealed that in OSAHS patients cross-sectional areas of the oropharyngeal airway in the soft palate posterior area and retrolingual area decreased during snoring compared to the awake state.Conversely,during mid-frequency anti-snoring device treatment,these areas increased compared to snoring.CONCLUSION The mid-frequency anti-snoring device demonstrates the potential to enhance various sleep parameters in patients with moderate OSAHS,thereby improving their quality of life and reducing daytime sleepiness.These therapeutic effects are attributed to the device’s ability to ameliorate the narrowing of the oropharynx in OSAHS patients.展开更多
Objective: To study the efficacy of modified Wuzhuyu Decoction Granule (加减吴茱萸汤颗粒剂, MWDG) in the treatment of migraine patients with cold and stasis obstructing meridian syndrome. Methods: This study was a...Objective: To study the efficacy of modified Wuzhuyu Decoction Granule (加减吴茱萸汤颗粒剂, MWDG) in the treatment of migraine patients with cold and stasis obstructing meridian syndrome. Methods: This study was a randomized, double-blind, placebo-controlled trial. A total of 78 migraine patients with cold and stasis obstructing meridian syndrome were recruited and randomly assigned by a ratio of 2:1 into a treatment group (51 cases) and a placebo group (27 cases). Patients in the treatment group were treated with MWDG while placebo granules were applied in the control group. The treatment course lasted for 12 weeks with a follow-up of 4 weeks. The primary outcome measures included frequency and days of migraine attacks and the secondary outcome measures were analgesics consumption and visual analogue scale (VAS) scores. All outcome assessments were conducted respectively at baseline, the 4th, 8th and 12th week, and the end of follow-up. Results: In the treatment group, significant decrease in frequency of migraine attacks were observed since the 4th week and that of analgesics consumption since the 8th week (both P〈0.05). While, in the placebo group, significant decrease in frequency of migraine attacks were observed since the 8th week and that of analgesics consumption since the 12th week (both P〈0.05). No significant decrease in days of migraine attacks and VAS scores of migraine pain were observed in both groups. Between the two groups, there were significant differences in VAS scores and intensity of pain appeared in the 8th week (P〈0.05). However, no significant differences were found in days and frequency of migraine attacks and analgesics consumption (P〉0.05). Conclusions: MWDG was probably effective in the treatment of migraine especially for alleviating pain intensity. Furthermore, MWDG could reduce the frequency of migraine attacks and analgesics consumption sooner than the placebo.展开更多
Radiological imaging findings may contribute to the differentiation of malignant biliary obstruction from choledocholithiasis in the etiology of acute cholangitis.
BACKGROUND Despite being one of the most prevalent sleep disorders,obstructive sleep apnea hypoventilation syndrome(OSAHS)has limited information on its immunologic foundation.The immunological underpinnings of certai...BACKGROUND Despite being one of the most prevalent sleep disorders,obstructive sleep apnea hypoventilation syndrome(OSAHS)has limited information on its immunologic foundation.The immunological underpinnings of certain major psychiatric diseases have been uncovered in recent years thanks to the extensive use of genome-wide association studies(GWAS)and genotyping techniques using highdensity genetic markers(e.g.,SNP or CNVs).But this tactic hasn't yet been applied to OSAHS.Using a Mendelian randomization analysis,we analyzed the causal link between immune cells and the illness in order to comprehend the immunological bases of OSAHS.AIM To investigate the immune cells'association with OSAHS via genetic methods,guiding future clinical research.METHODS A comprehensive two-sample mendelian randomization study was conducted to investigate the causal relationship between immune cell characteristics and OSAHS.Summary statistics for each immune cell feature were obtained from the GWAS catalog.Information on 731 immune cell properties,such as morphologic parameters,median fluorescence intensity,absolute cellular,and relative cellular,was compiled using publicly available genetic databases.The results'robustness,heterogeneity,and horizontal pleiotropy were confirmed using extensive sensitivity examination.RESULTS Following false discovery rate(FDR)correction,no statistically significant effect of OSAHS on immunophenotypes was observed.However,two lymphocyte subsets were found to have a significant association with the risk of OSAHS:Basophil%CD33dim HLA DR-CD66b-(OR=1.03,95%CI=1.01-1.03,P<0.001);CD38 on IgD+CD24-B cell(OR=1.04,95%CI=1.02-1.04,P=0.019).CONCLUSION This study shows a strong link between immune cells and OSAHS through a gene approach,thus offering direction for potential future medical research.展开更多
BACKGROUND Percutaneous transhepatic cholangiodrainage(PTCD)and endoscopic retrograde cholangiopancreatography/endoscopic nasobiliary drainage are the most common clinical procedures for jaundice control in patients w...BACKGROUND Percutaneous transhepatic cholangiodrainage(PTCD)and endoscopic retrograde cholangiopancreatography/endoscopic nasobiliary drainage are the most common clinical procedures for jaundice control in patients with unresectable malignant obstructive jaundice,yet the safety and effect of endobiliary radiofrequency ablation(EB-RFA)combined PTCD is rarely reported,in this article,we report our experience of EB-RFA combined PTCD in such patients.AIM To retrospectively study the efficacy and safety of EB-RFA combined PTCD in patients with unresectable malignant obstructive jaundice.METHODS Patients with unresectable malignant obstructive jaundice treated with EB-RFA under PTCD were selected,the bile ducts of the right posterior lobe was selected as the target bile ducts in all cases.The general conditions of all patients,preoperative tumour markers,total bilirubin(TBIL),direct bilirubin(DBIL),albumin(ALB),alkaline phosphatase(ALP),and glutamyl transferase(GGT)before and on the 7th day after the procedure,as well as perioperative complications,stent patency time and patient survival were recorded.RESULTS All patients successfully completed the operation,TBIL and DBIL decreased significantly in all patients at the 7th postoperative day(P=0.009 and 0.006,respectively);the values of ALB,ALP and GGT also decreased compared with the preoperative period,but the difference was not statistically significant.Perioperative biliary bleeding occurred in 2 patients,which was improved after transfusion of blood and other conservative treatments,pancreatitis appeared in 1 patient after the operation,no serious complication and death happened after operation.Except for 3 patients with loss of visits,the stent patency rate of the remaining 14 patients was 100%71%and 29%at the 1^(st),3^(rd),and 6^(th)postoperative months respectively,with a median survival of 4 months.CONCLUSION EB-RFA under PTCD in patients with unresectable malignant obstructive jaundice has a satisfactory therapeutic effect and high safety,which is worthy of further clinical practice.展开更多
文摘BACKGROUND Stenting as a bridge to curative surgery(SBTS)for obstructing colon cancer(OCC)has been associated with possibly worse oncological outcomes.AIM To evaluate the recurrence patterns,survival outcomes,and colorectal cancer(CRC)-specific death in patients undergoing SBTS for OCC.METHODS Data from 62 patients undergoing SBTS at a single tertiary centre over ten years between 2007 and 2016 were retrospectively examined.Primary outcomes were recurrence patterns,overall survival(OS),cancer-specific survival(CSS),and CRC-specific death.OS and CSS were estimated using the Kaplan-Meier curves.Competing risk analysis with cumulative incidence function(CIF)was used to estimate CRC-specific mortality with other cause-specific death as a competing event.Fine-Gray regressions were performed to determine prognostic factors of CRC-specific death.Univariate and multivariate subdistribution hazard ratios and their corresponding Wald test P values were calculated.RESULTS 28 patients(45.2%)developed metastases after a median period of 16 mo.Among the 18 patients with single-site metastases:Four had lung-only metastases(14.3%),four had liver-only metastases(14.3%),and 10 had peritoneum-only metastases(35.7%),while 10 patients had two or more sites of metastatic disease(35.7%).The peritoneum was the most prevalent(60.7%)site of metastatic involvement(17/28).The median follow-up duration was 46 mo.26(41.9%)of the 62 patients died,of which 16(61.5%)were CRC-specific deaths and 10(38.5%)were deaths owing to other causes. The 1-, 3-, and 5-year OS probabilities were 88%, 74%, and 59%;1-, 3-, and5-year CSS probabilities were 97%, 83%, and 67%. The highest CIF for CRC-specific death at 60 mowas liver-only recurrence (0.69). Liver-only recurrence, peritoneum-only recurrence, and two ormore recurrence sites were predictive of CRC-specific death.CONCLUSIONThe peritoneum was the most common metastatic site among patients undergoing SBTS. Liveronlyrecurrence, peritoneum-only recurrence, and two or more recurrence sites were predictors ofCRC-specific death.
文摘BACKGROUND The incidence of intestinal malrotation in adults has been reported to only be about 0.2%.Duodenal web as a cause of intestinal obstruction is rare,with an incidence of about 1:20000-1:40000.Furthermore,when described,these conditions are usually seen in early life and very infrequently in adulthood.CASE SUMMARY We report a case of a middle-aged woman with intestinal malrotation who presented with a three-month history of right-sided abdominal pain,early satiety,and a 22-pound weight loss.Patient underwent an esophagogastroduodenoscopy,which demonstrated numerous retained pills in a deformed first portion of the duodenum,concerning for a partial gastric outlet obstruction.An upper gastrointestinal series showed marked distention of the proximal duodenum with retained debris and the presence of a windsock sign,increasing the suspicion of a duodenal web.The patient subsequently underwent surgical intervention where a duodenal web with two lumens was noted and resected,opening the duodenum.There were over 150 pill capsules that were removed.The patient is doing well after this intervention.CONCLUSION Both intestinal malrotation and duodenal webs are infrequently encountered in the adult population.These pathologies can also present with nonspecific abdominal symptoms such as chronic abdominal pain and nausea.Hence,providers might not consider these pathologies in the differential for patients who present with vague symptoms which can lead to delay in management and increased mortality and morbidity.
文摘Biliary obstructions can lead to infections of the biliary system, particularly in patients with occluded biliary stents. Fungal organisms are frequently found in bili-ary aspirates of patients who have been on antibiotics and have stents; however, fungal masses, or "balls", that fully obstruct the biliary system are uncommon and exceedingly diff icult to eradicate. We present 4 cases of obstructing fungal cholangitis in patients who had metal biliary stents placed for pancreatic malignancies, and subsequently required aggressive antifungal administration along with endoscopic and radiologic interventions. This report also reviews approaches previously undertaken to manage severe obstructing fungal cholangitis.
基金This study was funded by the China National Key Basic Research Project through The Ministry of Science and Technology(No.2009CB522704).
文摘Objective:To observe the clinical efficacy and safety of oral administration of the traditional Chinese herb rhubarb to treat acute exacerbation of chronic obstructive pulmonary disease(AECOPD).Method:This was a multicenter randomized double-blinded placebo controlled study that took place in 7 provinces of China that enrolled 244 patients(aged 18e80 years)who had acute exacerbation of COPD with the traditional Chinese syndrome pattern of phlegm-heat obstructing lung.Participants were divided into experimental and control groups.The experimental group received 4.5 g of rhubarb granules twice daily and the control group received placebo granules.Both groups also received conventional Western therapy consisting of oxygen therapy,an antibiotic,expectorant,and a bronchodilator.Treatment lasted 10 days.Symptom scores for cough,sputum volume and color,wheezing and chest tightness before treatment and on days 3,5,7,and 10 during the treatment were recorded.Lung function,arterial blood gas and levels of serum inflammatory factors,interleukin-4(IL-4),interleukin-8(IL-8),and interleukin-10(IL-10)and tumor necrosis factor-alpha(TNF-a),before and after treatment were measured.Results:The sample size of the full analysis set(FAS)was 244 participants,and the sample size of per protocol set(PPS)was 235.Following 10 days’treatment,symptom scores of the experimental group were markedly lower than those of the placebo group(FAS:mean difference1.67,95%CI:e2.66 to0.69,P Z 0.001;PPS:mean difference1.55,95%CI:2.56 to0.54,P Z 0.003).Lung function in the experimental group was significantly higher than in the placebo group(FEV1,FAS:mean difference 0.12,95%CI:0.06 to 0.18;P<0.001;PPS:mean difference 0.12,95%CI 0.05 to 0.18;P<0.001.FVC:FAS:mean difference 0.16,95%CI:0.06 to 0.26;P Z 0.002;PPS:mean difference 0.16,95%CI 0.05 to 0.26;P Z 0.003.FEV1%,FAS:mean difference 5.95,95%CI:3.36 to 8.53;P<0.001;PPS:mean difference 5.92,95%CI 3.28 to 8.56;P<0.001.).PaO2,PaCO2,as well as serum inflammatory factors were also improved when compared to the placebo group.There were no significant differences in the incidence rate of adverse reaction between the two groups.Conclusions:Compared with placebo,rhubarb granules significantly reduced symptom scores,improved blood oxygen level,controlled systemic inflammatory response,without significant adverse effects.Thus,rhubarb may be a beneficial adjuvant method for treating the phlegm-heat obstructing the lung syndrome pattern of AECOPD.
基金We thank for the funding support from the National Natural Science Foundation of China(81873285)。
文摘Objective:To explore the molecular mechanism of the prescription for the syndrome of cold-damp-ness obstructing the lung in the treatment of corona virus disease 2019(COVID-19).Methods:The medicinals for the treatment of the syndrome of cold-dampness obstructing the lung,such as Cangzhu(Rhizoma Atractylo-dis),Chenpi(Pericarpium Gitri Reticulatae),Houpo(Cortex Magnoliae Officinalis),Huoxiang(Herba Agastachis),Caoguo(Fructus Tsaoko),Mahuang(Herba Ephedrae),Qianghuo(Rhizoma et Radix Notoptery-gi),Shengjiang(Rhizoma Zingiberis Recens),Binlang(Semen Arecae)in the Diagnosis and Treatment Pro-gram of COVID-19(Trial Version 6)were taken as research subjects,and the combination of these nine me-dicinals can be called Hanshi Zufei Fang(寒湿阻肺方,HSZFF).The active components and targets of each single Chinese materia medica was screened and obtained through the Traditional Chinese Medicine Systems Pharmacology(TCMSP)database.The target information related to COVID-19 was retrieved through the Gene-Cards disease-related target database.The medicinal prediction targets were mapped to the disease target to ob-tain the intersection targets.The DAVID database was applied to perform gene ontology(GO)enrichment anal-ysis and kyoto encyclopedia of genes and genomes(KEGG)pathway analysis on the targets;GraphPad Prism 5.0 software was applied to plot the biological process(BP)of GO enrichment analysis,cellular component(CC),molecular function(MF)histograms;OmicShare online software was applied to make KEGG advanced bubble chart;Cytoscape software was applied to visualize the interaction with the targets and Chinese materia medica-components-targets results.Results:Totally 56 key active components of 9 Chinese materia medica for cold-dampness obstructing lung syndrome were screened,and 55 targets were obtained.The results of GO and KEGG enrichment analysis showed that the compound prescription mainly regulated the body's immune re-sponse and reduced inflammation by regulating such signaling pathways of inflammatory response and immune regulation as TNF signaling pathway,HIF-1 signaling pathway,Toll-like receptor signaling pathway,infuenza A signaling pathway,T cell receptor signaling pathway.Conclusion:HSZFF can eliminate infl ammation and inhibit virus by regulating immune inflammatory factors closely related to the occurrence and development of diseases through multi-component and multi-target.
基金Supported by National High-Tech R and D Program of China(863Program),No.2015AA033602Personnel Training Program of Beijing Chao-Yang Hospital Affiliated to Capital Medical University,No.CYXZ-2017-09
文摘BACKGROUND Surgery 5-10 d after stent insertion was recommended by the European Society of Gastrointestinal Endoscopy for obstructing colonic cancer. For some obstructive patients, this may be not a good choice. Here, we report the successful treatment of obstructing colonic cancer by combining self-expandable stent and neoadjuvant chemotherapy.CASE SUMMARY The patient was a 72-year-old man who was admitted with a chief complaint of abdominal pain for more than 1 mo. Computed tomography(CT) scanning revealed that there was a mass in the descending colon, which led to intestinal obstruction. On admission, a series of therapeutic measures, such as fasting and water deprivation, gastrointestinal decompression, total parenteral nutrition, and octreotide acetate, were taken to improve the obstructive symptoms. At the same time, a self-expandable metal stent was successfully placed across the stenosis,and a biopsy was obtained and diagnosed as adenocarcinoma. CT scanning 14 d after insertion of the stent revealed that the intestine was swollen significantly.Systemic chemotherapy with modified FOLFOX6(mFOLFOX6) was administered. After two courses of mFOLFOX6, CT scanning showed clearly that swelling of the intestine was improved. Subsequently, the patient underwent left hemi-colectomy without stoma placement. The postoperative course was uneventful, and he has been disease-free for 6 mo after surgery.CONCLUSION This modified treatment strategy may provide an alternative therapy for patients with obstructing colonic cancers.
文摘From 1973 to 1989, 90 cases of obstructing carcinoma of the left colon were treated with five different operative procedures, the Incidence of anastomotic leakage was 6.7%, the operative mortality was 7. 8%. Among all the patients, 14 cases were treated by primary resection with anastomosis. Anastomotic leakage occurred in 6 cases, and 5 of them were died. Of 25 cases with the traditional staged management, the tumors were resected only in 20 cases, and not resectable in the other 5 patients. 19 with modified Hartmann's procedure and 26 with extended right hemlcolectomy with ileorectal or low ileosigmoid anastomosis gave satisfactory results. In terms of this series, the five-year survival rate in primary resection group was significantly higher than that in staged resection group (P< 0. 05). It is suggested that extented right hemlcolectomy or modified Hartmann' s procedure in cases of acute cancerous obstruction of the left colon would be favord.
文摘BACKGROUND Self-expandable metal stents(SEMSs) are frequently used in the setting of palliation for occluding, inoperable colorectal cancer(CRC). Among possible complications of SEMS positioning, re-obstruction is the most frequent. Its management is controversial, potentially involving secondary stent-in-stent placement, which has been poorly investigated. Moreover, the issue of secondary stent-in-stent re-obstruction and of more-than-two colonic stenting has never been assessed. We describe a case of tertiary SEMS-in-SEMS placement, and also discuss our practice based on available literature.CASE SUMMARY A 66-year-old male with occluding and metastatic CRC was initially treated by positioning of a SEMS, which had to be revised 6 mo later when a symptomatic intra-stent tumor ingrowth was treated by a SEMS-in-SEMS. We hereby describe an additional episode of intestinal occlusion due to recurrence of intra-stent tumor ingrowth. This patient, despite several negative prognostic factors(splenic flexure location of the tumor, carcinomatosis with ascites, subsequent chemotherapy that included bevacizumab and two previously positioned stents(1 SEMS and 1 SEMS-in-SEMS)) underwent successful management through the placement of a tertiary SEMS-in-SEMS, with immediate clinical benefit and no procedure-related adverse events after 150 d of post-procedural follow-up. This endoscopic management has permitted 27 mo of partial control of a metastatic disease without the need for chemotherapy discontinuation and, ultimately, a good quality of life until death.CONCLUSION Tertiary SEMS-in-SEMS is technically feasible, and appears to be a safe and effective option in the case of recurrent SEMS obstruction.
文摘BACKGROUND Mycobacterium tuberculosis(TB)is the causative agent of TB,a chronic granulo-matous illness.This disease is prevalent in low-income countries,posing a significant global health challenge.Gastrointestinal TB is one of the three forms.The disease can mimic other intra-abdominal conditions,leading to delayed diagnosis owing to the absence of specific symptoms.While gastric outlet obs-truction(GOO)remains a frequent complication,its incidence has declined with the advent of proton pump inhibitors and Helicobacter pylori eradication therapy.Gastroduodenal TB can cause upper gastrointestinal hemorrhage,obstruction,and malignancy-like tumors.CASE SUMMARY A 23-year-old male presented with recurrent epigastric pain,distension,nausea,vomiting,and weight loss,prompting a referral to a gastroenterologist clinic.Endoscopic examination revealed distorted gastric mucosa and signs of chronic inflammation.However,treatment was interrupted,possibly owing to vomiting or comorbidities such as human immunodeficiency virus infection or diabetes.Subsequent surgical intervention revealed a dilated stomach and diffuse thickening of the duodenal wall.Resection revealed gastric wall effacement with TB.CONCLUSION Primary gastric TB is rare,frequently leading to GOO.Given its rarity,suspicions should be promptly raised when encountering relevant symptoms,often requiring surgical intervention for diagnosis and treatment.
基金The authors have read the PRISMA 2009 Checklist,and the manuscript was prepared and revised according to the PRISMA 2009 Checklist.
文摘BACKGROUND Endoscopic ultrasound-guided biliary drainage using electrocautery-enhanced(ECE)delivery of lumen-apposing metal stent(LAMS)is gradually being re-cognized as a viable palliative technique for malignant biliary obstruction after endoscopic retrograde cholangiopancreatography(ERCP)failure.However,most of the studies that have assessed its efficacy and safety were small and hetero-geneous.Prior meta-analyses of six or fewer studies that were published 2 years ago were therefore underpowered to yield convincing evidence.AIM To update the efficacy and safety of ECE-LAMS for treatment of biliary ob-struction after ERCP failure.METHODS We searched PubMed,EMBASE,and Scopus databases from the inception of the ECE technique to May 13,2022.Primary outcome measure was pooled technical success rate,and secondary outcomes were pooled rates of clinical success,re-intervention,and adverse events.Meta-analysis was performed using a random-effects model following Freeman-Tukey double-arcsine transformation in R soft-ware(version 4.1.3).RESULTS Fourteen eligible studies involving 620 participants were ultimately included.The pooled rate of technical success was 96.7%,and clinical success was 91.0%.Adverse events were reported in 17.5%of patients.Overall reinter-vention rate was 7.3%.Subgroup analyses showed results were generally consistent.CONCLUSION ECE-LAMS has favorable success with acceptable adverse events in relieving biliary obstruction when ERCP is impossible.The consistency of results across most subgroups suggested that this is a generalizable approach.
文摘This narrative review provides an overview of the utilization of endoscopic ultrasound-guided gallbladder drainage(EUS-GBD)as a salvage approach in cases of unsuccessful conventional management.EUS-GBD is a minimally invasive and effective technique for drainage in patients with acute cholecystitis with high risk of surgery.The procedure has demonstrated impressive technical and clinical success rates with low rates of adverse events,making it a safe and effective option for appropriate candidates.Furthermore,EUS-GBD can also serve as a rescue option for patients who have failed endoscopic retrograde cholangiopancreatography or EUS biliary drainage for relief of jaundice in malignant biliary stricture.However,patient selection is critical for the success of EUS-GBD,and proper patient selection and risk assessment are important to ensure the safety and efficacy of the procedure.As the field continues to evolve and mature,ongoing research will further refine our understanding of the benefits and limitations of EUS-GBD,ultimately leading to improved outcomes for patients.
文摘BACKGROUND Obstructive sleep apnea-hypopnea syndrome(OSAHS)is primarily caused by airway obstruction due to narrowing and blockage in the nasal and nasopha-ryngeal,oropharyngeal,soft palate,and tongue base areas.The mid-frequency anti-snoring device is a new technology based on sublingual nerve stimulation.Its principle is to improve the degree of oropharyngeal airway stenosis in OSAHS patients under mid-frequency wave stimulation.Nevertheless,there is a lack of clinical application and imaging evidence.METHODS We selected 50 patients diagnosed with moderate OSAHS in our hospital between July 2022 and August 2023.They underwent a 4-wk treatment regimen involving the mid-frequency anti-snoring device during nighttime sleep.Following the treatment,we monitored and assessed the sleep apnea quality of life index and Epworth Sleepiness Scale scores.Additionally,we performed computed tomo-graphy scans of the oropharynx in the awake state,during snoring,and while using the mid-frequency anti-snoring device.Cross-sectional area measurements in different states were taken at the narrowest airway point in the soft palate posterior and retrolingual areas.RESULTS Compared to pretreatment measurements,patients exhibited a significant reduction in the apnea-hypopnea index,the percentage of time with oxygen saturation below 90%,snoring frequency,and the duration of the most prolonged apnea event.The lowest oxygen saturation showed a notable increase,and both sleep apnea quality of life index and Epworth Sleepiness Scale scores improved.Oropharyngeal computed tomography scans revealed that in OSAHS patients cross-sectional areas of the oropharyngeal airway in the soft palate posterior area and retrolingual area decreased during snoring compared to the awake state.Conversely,during mid-frequency anti-snoring device treatment,these areas increased compared to snoring.CONCLUSION The mid-frequency anti-snoring device demonstrates the potential to enhance various sleep parameters in patients with moderate OSAHS,thereby improving their quality of life and reducing daytime sleepiness.These therapeutic effects are attributed to the device’s ability to ameliorate the narrowing of the oropharynx in OSAHS patients.
基金Supported by the "Eleventh Five-Year Plan" of China State Science&Technology Ministry(No.2007BAI20B053)National Natural Science Foundation of China(No.81273688)
文摘Objective: To study the efficacy of modified Wuzhuyu Decoction Granule (加减吴茱萸汤颗粒剂, MWDG) in the treatment of migraine patients with cold and stasis obstructing meridian syndrome. Methods: This study was a randomized, double-blind, placebo-controlled trial. A total of 78 migraine patients with cold and stasis obstructing meridian syndrome were recruited and randomly assigned by a ratio of 2:1 into a treatment group (51 cases) and a placebo group (27 cases). Patients in the treatment group were treated with MWDG while placebo granules were applied in the control group. The treatment course lasted for 12 weeks with a follow-up of 4 weeks. The primary outcome measures included frequency and days of migraine attacks and the secondary outcome measures were analgesics consumption and visual analogue scale (VAS) scores. All outcome assessments were conducted respectively at baseline, the 4th, 8th and 12th week, and the end of follow-up. Results: In the treatment group, significant decrease in frequency of migraine attacks were observed since the 4th week and that of analgesics consumption since the 8th week (both P〈0.05). While, in the placebo group, significant decrease in frequency of migraine attacks were observed since the 8th week and that of analgesics consumption since the 12th week (both P〈0.05). No significant decrease in days of migraine attacks and VAS scores of migraine pain were observed in both groups. Between the two groups, there were significant differences in VAS scores and intensity of pain appeared in the 8th week (P〈0.05). However, no significant differences were found in days and frequency of migraine attacks and analgesics consumption (P〉0.05). Conclusions: MWDG was probably effective in the treatment of migraine especially for alleviating pain intensity. Furthermore, MWDG could reduce the frequency of migraine attacks and analgesics consumption sooner than the placebo.
文摘Radiological imaging findings may contribute to the differentiation of malignant biliary obstruction from choledocholithiasis in the etiology of acute cholangitis.
基金Supported by Doctoral Research Fund Project of Henan Provincial Hospital of Traditional Chinese Medicine,No.2022BSJJ10.
文摘BACKGROUND Despite being one of the most prevalent sleep disorders,obstructive sleep apnea hypoventilation syndrome(OSAHS)has limited information on its immunologic foundation.The immunological underpinnings of certain major psychiatric diseases have been uncovered in recent years thanks to the extensive use of genome-wide association studies(GWAS)and genotyping techniques using highdensity genetic markers(e.g.,SNP or CNVs).But this tactic hasn't yet been applied to OSAHS.Using a Mendelian randomization analysis,we analyzed the causal link between immune cells and the illness in order to comprehend the immunological bases of OSAHS.AIM To investigate the immune cells'association with OSAHS via genetic methods,guiding future clinical research.METHODS A comprehensive two-sample mendelian randomization study was conducted to investigate the causal relationship between immune cell characteristics and OSAHS.Summary statistics for each immune cell feature were obtained from the GWAS catalog.Information on 731 immune cell properties,such as morphologic parameters,median fluorescence intensity,absolute cellular,and relative cellular,was compiled using publicly available genetic databases.The results'robustness,heterogeneity,and horizontal pleiotropy were confirmed using extensive sensitivity examination.RESULTS Following false discovery rate(FDR)correction,no statistically significant effect of OSAHS on immunophenotypes was observed.However,two lymphocyte subsets were found to have a significant association with the risk of OSAHS:Basophil%CD33dim HLA DR-CD66b-(OR=1.03,95%CI=1.01-1.03,P<0.001);CD38 on IgD+CD24-B cell(OR=1.04,95%CI=1.02-1.04,P=0.019).CONCLUSION This study shows a strong link between immune cells and OSAHS through a gene approach,thus offering direction for potential future medical research.
文摘BACKGROUND Percutaneous transhepatic cholangiodrainage(PTCD)and endoscopic retrograde cholangiopancreatography/endoscopic nasobiliary drainage are the most common clinical procedures for jaundice control in patients with unresectable malignant obstructive jaundice,yet the safety and effect of endobiliary radiofrequency ablation(EB-RFA)combined PTCD is rarely reported,in this article,we report our experience of EB-RFA combined PTCD in such patients.AIM To retrospectively study the efficacy and safety of EB-RFA combined PTCD in patients with unresectable malignant obstructive jaundice.METHODS Patients with unresectable malignant obstructive jaundice treated with EB-RFA under PTCD were selected,the bile ducts of the right posterior lobe was selected as the target bile ducts in all cases.The general conditions of all patients,preoperative tumour markers,total bilirubin(TBIL),direct bilirubin(DBIL),albumin(ALB),alkaline phosphatase(ALP),and glutamyl transferase(GGT)before and on the 7th day after the procedure,as well as perioperative complications,stent patency time and patient survival were recorded.RESULTS All patients successfully completed the operation,TBIL and DBIL decreased significantly in all patients at the 7th postoperative day(P=0.009 and 0.006,respectively);the values of ALB,ALP and GGT also decreased compared with the preoperative period,but the difference was not statistically significant.Perioperative biliary bleeding occurred in 2 patients,which was improved after transfusion of blood and other conservative treatments,pancreatitis appeared in 1 patient after the operation,no serious complication and death happened after operation.Except for 3 patients with loss of visits,the stent patency rate of the remaining 14 patients was 100%71%and 29%at the 1^(st),3^(rd),and 6^(th)postoperative months respectively,with a median survival of 4 months.CONCLUSION EB-RFA under PTCD in patients with unresectable malignant obstructive jaundice has a satisfactory therapeutic effect and high safety,which is worthy of further clinical practice.