Prediction of clinically actionable genetic alterations from colorectal cancer histopathology images using deep learning

BACKGROUND Identifying genetic mutations in cancer patients have been increasingly important because distinctive mutational patterns can be very informative to determine the optimal therapeutic strategy. Recent studies have shown that deep learning-based molecular cancer subtyping can be performed directly from the standard hematoxylin and eosin(H&E) sections in diverse tumors including colorectal cancers(CRCs). Since H&E-stained tissue slides are ubiquitously available, mutation prediction with the pathology images from cancers can be a time-and cost-effective complementary method for personalized treatment.AIM To predict the frequently occurring actionable mutations from the H&E-stained CRC whole-slide images(WSIs) with deep learning-based classifiers.METHODS A total of 629 CRC patients from The Cancer Genome Atlas(TCGA-COAD and TCGA-READ) and 142 CRC patients from Seoul St. Mary Hospital(SMH) were included. Based on the mutation frequency in TCGA and SMH datasets, we chose APC, KRAS, PIK3CA, SMAD4, and TP53 genes for the study. The classifiers were trained with 360 × 360 pixel patches of tissue images. The receiver operating characteristic(ROC) curves and area under the curves(AUCs) for all the classifiers were presented.RESULTS The AUCs for ROC curves ranged from 0.693 to 0.809 for the TCGA frozen WSIs and from 0.645 to 0.783 for the TCGA formalin-fixed paraffin-embedded WSIs.The prediction performance can be enhanced with the expansion of datasets. When the classifiers were trained with both TCGA and SMH data, the prediction performance was improved.CONCLUSION APC, KRAS, PIK3CA, SMAD4, and TP53 mutations can be predicted from H&E pathology images using deep learning-based classifiers, demonstrating the potential for deep learning-based mutation prediction in the CRC tissue slides.

The Comparison of the Manifestation of the Clinical Imageology and Pathology between the Brucellar Spondylitis and the Spine Turberculosis

Objective: To improve the clinical differential diagnosis level, the clinical manifestation of the brucellar spondylitis and the spine turberculosis were discussed in this paper. Method: The study was completed in the No. 1 Affiliated Hospital of Hebei North University in Zhangjiakou City, Hebei Province, China, from January 2001 to December 2013 by Analyzing the X-ray, CT scanning and MRI of 257 cases of the brucellar spondylitis retrospectively and comparing with the clinical imageology and pathology 332 cases of turberculosis of the spine diagnosed finally. Results: The brucellar spondylitis: The focuses usually locate in the lumbar vertebra and L4, 5 has the highest occurrence rate. The focuses are often small but multiple, and limited to the edge of the vertebra. Hyperostosis and osteoscterosis are usually found in the tissuses around the focuses. There are often new focuses in the newborn bones, and the destruction of intervertebral discs is usually slight. Hyperostosis and osteoscterosis might be found in the surfaces of the joints. The densites of the bones close to the focuses become high. There were less or no paravertebral abscesses but inflammational granuloma can be found frequently. Turberculosis of the spine: The focuses are usually located in the thoracic and lumbar vertebra, and are characterized by the destruction of the vertebra and the intervertebral discs, accompanied by the appearance of dead bones. In most cases, paravertebral abscesses and osteoporosis might be found. Conclusions: The specific manifestation of the clinical imageology can help to differentiate the brucelar spondylitis from the turberculosis of the spine.

LUPUS NEPHRITIS COMPLICATED WITH MALIGNANT HYPERTENSION:FROM RENAL VASCULAR PATHOLOGY TO CLINICAL RELEVANCE

Objective To investigate the clinical and pathological characteristics of lupus nephritis patients complicated with malignant hypertension.Methods We retrospectively studied 19 patients with lupus nephritis complicated with malignant hypertension who underwent renal biopsy between January 2002 and December 2006.Results Of 19 patients,3 were men and 16 were women,with a mean age of 24.4±7.7 years old.All had positive antinuclear antibodies and low serum complement was found in 13 patients.All were anemic and 12 of them were thrombocytopenic.Impaired renal function was found in 17 patients with an average serum creatinine of 184.5±88.9 μmol/L.Severe intrarenal arteriolar lesion was found in all patients.Six patients had lupus vasculopathy,11 patients had renal thrombotic microangiopathy lesion,2 had severe arteriosclerosis.All patients received steroids and immunosuppressive drugs,15 received angiotensin-converting enzyme inhibitor(ACEI)/angiotensin receptor blocker(ARB)with resultant well-controlled blood pressure.Thrombocytopenia and hemolytic anemia resolved remarkably.The renal function improved or recovered in 14 of 17 patients,and 3 developed end-stage renal disease on maintenance dialysis.Conclusions Severe intrarenal vascular lesion complicated with renal nephritis parallels clinical manifestation of malignant hypertension.Renal pathology is the key of treatment strategy emphasizing on the significance of renal vascular involvement and type.On the basis of immunosuppressive drugs and steroids to control systemic lupus activity,timely initiation of ACEI/ARB could be of benefit to blood pressure control and long term renal survival.

How would preclinical Alzheimer’s disease (AD pathology) occur? An insight from a genomic instability mouse model

More than 95%of Alzheimer’s disease(AD)is late-onset,in which patients show clinical cognition/behavior symptoms after age 65.Unlike early-onset AD that comes with mutations in genes directly involved in amyloid metabolism(APP,PSEN),genetic predispositions associated with late-onset AD are harder to pinpoint,and their mechanistic links to AD development need further investigation.Although the development mechanism of late-onset AD remains controversial,amyloid-beta accumulation,initiated in middle age,is widely accepted as the triggering event for early AD pathology(Du Bois et al.,2010;Sterling et al.,2011).

Developing a better mouse model of Alzheimer disease with clinically relevant phenotypes in tau pathology

OBJECTIVE Transgenic mouse model has been widely used in pathogenesis study and preclinical drug evaluation in Alzheimer disease(AD).However,key differences are found between current animal models and clinical AD patients regarding phenotypes.Lack of complete models that recapitulate broad spectrum of human AD neuropathology restricts efficacy of research projects and leads to frequent failure in AD drug development at clinical trial stages.This study aims to develop better mouse models of AD through modifying key phenotype insufficiency.METHODS By crossing different single and double transgenic mice with different mutations of APP/PS1 or tau and under prion,Thy1 or PDGF-β promoter,as well as selected knockout mice,I produced a dozen of bigenic models for neuropathology screening.Further neurochemical,behavioral and pharmacological validations were conducted in the optimized mouse model.RESULTS Neuropathology phenotyping found remarkable differences in tau pathology and neurodegeneration among individual APP/PS1/tau transgenic models.I had identified a triple mouse model named FADT that showed(1) huge mature tau pathology in hippocampus and cortex;(2) abundant tau truncation,as seen in human AD brain;(3)progressive neurodegeneration;(4)selective brain atrophy in hippocampus and entorhinal cortex;(5) reproducible and late onset spatial memory defects,etc.Importantly,remarkable tau pathology in this FADT model is mainly driven by beta-amyloid pathology,which differs from high expression of tau in rTg4510 model.CONCLUSION I had developed a new triple transgenic mouse model that recapitulates broad spectrum of human AD neuropathology features.This study will not only establish a solid model basis for AD pathophysiology investigation and drug development,but also reveal important clues on the interaction of beta-amyloid and tau pathologies in the brain.

Undiscovered pathology of transient scaffolding remains a driver of failures in clinical trials

AIM To statistically examine the released clinical trials and meta-analyses of polymeric bioresorbable scaffolds resuming the main accomplishments in the field with a translation to the routine clinical practice. METHODS The statistical power in clinical trials such as ABSORB Japan, ABSORB China, EVERBIO II, AIDA, and few meta-analyses by the post hoc odds ratio-based sample size calculation, and the patterns of artery remodeling published in papers from ABSORB A and B trials were evaluated. RESULTS The phenomenal admiration from the first ABSORB studies in 2006-2013 was replaced by the tremendous disappointment in 2014-2017 due to reported relatively higher rates of target lesion failure(a mean prevalence of 9.16%) and device thrombosis(2.38%) in randomized controlled trials. Otherwise, bioresorbable vascular scaffold(BVS) performs as well as the metallic drugeluting stent(DES) with a trend toward some benefits for cardiac mortality [risk ratio(RR), 0.58-0.94, P > 0.05]. The underpowered design was confirmed for some studies such as ABSORB Japan, ABSORB China, EVERBIO Ⅱ, AIDA trials, and meta-analyses of Polimeni, Collet, and Mahmoud with some unintentional bias(judged by the asymmetrical Funnel plot). Scaffold thrombosis rates with Absorb BRS were comparable with DES performed with a so-called strategy of the BVS implantation with optimized pre-dilation(P), sizing(S) and post-dilation(P)(PSP) implantation(RR, PSP vs no PSP 0.37) achieving 0.35 per 100 patient-years, which is comparable to the RR 0.49 with bare-metal stents and the RR 1.06 with everolimus DES. Both ABSORB Ⅱ and ABSORB Ⅲ trials were powered enough for a five-year follow-up, but the results were not entirely conclusive due to the mostly non-significant fashion of data. The powered metaanalyses were built mostly on statistically poor findings. CONCLUSION The misunderstanding of the pathology of transient scaffolding drives the failures of the clinical trials. More bench studies of the vascular response are required. Several next-generation BVS including multifunctional electronic scaffold grant cardiology with a huge promise to make BVS technology great again.

Clinical pathology analysis of esophageal sarcomatoid carcinoma

Objective： The purpose of this study was to study the clinical, imaging characters and pathological characteristics of esophageal sarcomatoid carcinoma. Methods： We reviewed 23 cases of esophageal sarcomatoid carcinoma from Janu ary 2006 to December 2013 in four hospitals. The data of patients who were esophageal sarcomatoid carcinoma operated were retrospectively analyzed. All cases had completed upper gastrointestinal barium images materials and 14 of these cases had completed CT images materials. Upper gastrointestinal barium images and CT imaging features include tumor location, size, shape, and strengthen, etc. The biological parameters of lesions including the express of cytokeratin AE1/AE3, 34E12,, Vimentin, desmin, Actin, S100 and Ki67 detected by immunhistochemical UltraSensitiveTM SP method （n = 23）, and the patients＇ data of contrastographic picture （n = 23）, imaging characters of CT scan （n = 14）, and their relationship were studied. Results： Upper gastrointestinal barium images, CT imaging and gastrointestinal fiberscopy revealed Iobulated intraluminal filling defect 0.4 cm to 5.7 cm x 3.5 cmx 1.3 cm （mean = 3. 7 cm） in the mid （n = 14）, lower （n = 7） and upper （n = 2） intrathoracic esophagus. Among 23 cases of esophageal sarcomatoid carcinoma, 19 patients were of mushroom type, 2 patients was of ulcer type, and 2 patients were of medulla type; 19 patients were pedunculated, and 4 patients were no pedunculated （2 patients was of ulcer type）. The tumor surface was relatively smooth and esophageal compliance was maintained. The pathological changes of esophagus such as lightly locked, rigid wall nomanifest partly, esophageal lumens expand partly, major filling sublobe defect could be shown through contrast medium. Normal esophagus was no unpack obviously over pathological changes. Enhanced computed tomography showed tumors in the intrathoracic esophagus and 8 lymph nodes metastases in 3 cases. Histologically, carcinomatous and sarcomatous components coexist. Microscopically, the tumor comprised poorly differentiated squamous cell carcinoma and spindleshaped cells resembling leiomyosarcoma. Immu nohistochemically, spindleshaped sarcomatous cells displayed weekly positive reaction to cytokeratin AE1/AE3. Transitional zone was seen between sarcomatous and carcinomatous elements in 5 cases. The 17 lymph nodes metastases in 5 cases （53 lymph nodes） among 23 cases esophageal sarcomatoid carcinoma （187 lymph nodes） were observed. Conclusion： The clinical and radiologic features of esophageal sarcomatoid carcinoma overlap with those of other esophageal neoplasms. There are the radiologic imaging changes such as a large, intraluminal, polypoid mass, major filling sublobe defect and pedicle skin flap tumor in esophageal lumen, esophageal lumen extension partly, dissepiment rigidity wall no obviously, etc. Histologically, carcinomatous and sarcomatous components coexist and the biphasic pattern is the key diagnostic feature. However, esophageal sarcomatoid carcinoma has a more favorable prognosis than other malignant esophageal neoplasms. Immunohistochemical staining seems necessary to distinguish these lesions from other esophageal neoplasms.

What benefit can be obtained from magnetic resonance imaging diagnosis with artificial intelligence in prostate cancer compared with clinical assessments?

The present study aimed to explore the potential of artificial intelligence(AI)methodology based on magnetic resonance(MR)images to aid in the management of prostate cancer(PCa).To this end,we reviewed and summarized the studies comparing the diagnostic and predictive performance for PCa between AI and common clinical assessment methods based on MR images and/or clinical characteristics,thereby investigating whether AI methods are generally superior to common clinical assessment methods for the diagnosis and prediction fields of PCa.First,we found that,in the included studies of the present study,AI methods were generally equal to or better than the clinical assessment methods for the risk assessment of PCa,such as risk stratification of prostate lesions and the prediction of therapeutic outcomes or PCa progression.In particular,for the diagnosis of clinically significant PCa,the AI methods achieved a higher summary receiver operator characteristic curve(SROC-AUC)than that of the clinical assessment methods(0.87 vs.0.82).For the prediction of adverse pathology,the AI methods also achieved a higher SROC-AUC than that of the clinical assessment methods(0.86 vs.0.75).Second,as revealed by the radiomics quality score(RQS),the studies included in the present study presented a relatively high total average RQS of 15.2(11.0–20.0).Further,the scores of the individual RQS elements implied that the AI models in these studies were constructed with relatively perfect and standard radiomics processes,but the exact generalizability and clinical practicality of the AI models should be further validated using higher levels of evidence,such as prospective studies and open-testing datasets.

Assessment of Appropriateness of Diagnostic Lymph Node Tissue Collection from the Operating Theater and by Interventional Radiologist. A Clinical Audit

Background: Appropriate sample requesting, collecting and timely dispatch to the appropriate laboratory is essential in establishing diagnosis of pathologies with lesions. Much time and effort may be wasted if this is not done according to certain standards. We conducted this study to assess the route of lymph node samples from requests to reaching the laboratories. Methods: We conducted an audit over a period from 4th June until 10th Aug 2023. Data for all the procedures performed over this period on lymph node samples (was entered into and analysed using Excel. Results: A total of eighteen samples for sixteen patients were obtained during this period. Median age of the patients was 34 years (19 - 73) with a M:F ratio of 5:11. Among the IR samples, nine samples were from the neck, three from inguinal area and one from axilla. Seven samples (53.8%) were tru-cut biopsies, six samples (46.15%) were FNA. All samples were sent to the pathology laboratory fixed in formalin. Samples for TB were sent only for five cases (31.25%) and for only two cases (12.5%) were samples sent for bacterial culture. For the OR samples, none were sent for either bacterial culture or TB. Overall, eight patients (50%) were not investigated for any infectious etiologies like brucella, toxoplasmosis, CMV, EBV plus other possible causes. Repeat sampling was required for 25% of patients (within and out of the audit period). Conclusions: to avoid delays in making diagnoses, it is paramount to consider infectious etiologies as possible diagnosis for lymphadenopathy and request appropriate investigations. This requires liaising with infectious diseases/clinical microbiology experts to guide regarding types of samples, types of media and timely dispatch to the correct laboratory.

Virtual reality:The bridge between medical education and clinical practice

After perusing the paper by Kim et al,I discovered that this is an interesting manuscript and a successful study.Virtual reality(VR)is an emerging and promising technology employed in the domain of medical practice and medical education over the past decade.In the era of big data,VR is constantly progressing in the fields of medical education and clinical diagnosis and treatment.As a novel scientific and technological tool,VR not only overcomes multiple limitations of the traditional medical teaching mode but also reduces the reliance on personnel and equipment.VR can simulate the real clinical situation,stimulate the enthusiasm of young doctors and nurses for clinical study,and simultaneously safeguard and promote medical safety and doctor-patient harmony.Favorable outcomes have been attained in clinical teaching and diagnosis and treatment activities.While enhancing the training conditions of medical cosmetics and elevating the level of clinical practice and teaching,the risks resulting from improper clinical diagnosis and treatment have been circumvented.All of this is evident and comprehensible.

Comparative analysis of breast and lung cancer survival rates and clinical trial enrollments among rural and urban patients in Georgia

Objectives:Rural patients have poor cancer outcomes and clinical trial(CT)enrollment compared to urban patients due to attitudinal,awareness,and healthcare access differential.Knowledge of cancer survival disparities and CT enrollment is important for designing interventions and innovative approaches to address the stated barriers.The study explores the potential disparities in cancer survival rates and clinical trial enrollments in rural and urban breast and lung cancer patients.Our hypotheses are that for both cancer types,urban cancer patients will have longer 5-year survival rates and higher enrollment rates in clinical trials than those in rural counties.Methods:We compared breast and lung cancer patients’survival rates and enrollment ratios in clinical trials between rural(RUCC 4-9)and urban counties in Georgia at a Comprehensive Cancer Center(CCC).To assess these differences,we carried out a series of independent samples t-tests and Chi-Square tests.Results:The outcomes indicate comparable 5-year survival rates across rural and urban counties for breast and lung cancer patients,failing to substantiate our hypothesis.While clinical trial enrollment rates demonstrated a significant difference between breast and lung cancer patients at CCC,no significant variation was observed based on rural or urban classification.Conclusion:These findings underscore the need for further research into the representation of rural patients with diverse cancer types at CCC and other cancer centers.Further,the findings have considerable implications for the initiation of positive social change to improve CT participation and reduce cancer survival disparities.

Assessing the Levels of Clinical Reasoning Skills Using Self-Assessment of Clinical Reflection and Reasoning in Undergraduate Nursing Students: A Descriptive Comparative Study

Background: Clinical reasoning is a critical cognitive skill that enables undergraduate nursing students to make clinically sound decisions. A lapse in clinical reasoning can result in unintended harm to patients. The aim of the study was to assess and compare the levels of clinical reasoning skills between third year and fourth year undergraduate nursing students. Methods: The study utilized a descriptive comparative research design, based on the positivism paradigm. 410 undergraduate nursing students were systematically sampled and recruited into the study. The researchers used the Self-Assessment of Clinical Reflection and Reasoning questionnaire to collect data on clinical reasoning skills from third- and fourth-year nursing students while adhering to ethical principles of human dignity. Descriptive statistics were done to analyse the level of clinical reasoning and an independent sample t-test was performed to compare the clinical reasoning skills of the student. A p value of 0.05 was accepted. Results: The results of the study revealed that the mean clinical reasoning scores of the undergraduate nursing students were knowledge/theory application (M = 3.84;SD = 1.04);decision-making based on experience and evidence (M = 4.09;SD = 1.01);dealing with uncertainty (M = 3.93;SD = 0.87);reflection and reasoning (M = 3.77;SD = 3.88). The mean difference in clinical reasoning skills between third- and fourth-year undergraduate nursing students was not significantly different from an independent sample t-test scores (t = −1.08;p = 0.28);(t = −0.29;p = 0.73);(t = 1.19;p = 0.24);(t = −0.57;p = 0.57). Since the p-value is >0.05, the null hypothesis (H0) “there is no significantno significant difference in clinical reasoning between third year and fourth year undergraduate nursing students”, was accepted. Conclusion: This study has shown that the level of clinical reasoning skills of the undergraduate nursing students was moderate to low. This meant that the teaching methods have not been effective to improve the students clinical reasoning skills. Therefore, the training institutions should revise their curriculum by incorporating new teaching methods like simulation to enhance students’ clinical reasoning skills. In conclusion, evaluating clinical reasoning skills is crucial for addressing healthcare issues, validating teaching methods, and fostering continuous improvement in nursing education.

High rate of clinically relevant improvement following anatomical total shoulder arthroplasty for glenohumeral osteoarthritis

BACKGROUND The minimal clinically important difference(MCID)is defined as the smallest meaningful change in a health domain that a patient would identify as important.Thus,an improvement that exceeds the MCID can be used to define a successful treatment for the individual patient.AIM To quantify the rate of clinical improvement following anatomical total shoulder arthroplasty for glenohumeral osteoarthritis.METHODS Patients were treated with the Global Unite total shoulder platform arthroplasty between March 2017 and February 2019 at Herlev and Gentofte Hospital,Denmark.The patients were evaluated preoperatively and 3 months,6 months,12 months,and 24 months postoperatively using the Western Ontario Osteoarthritis of the Shoulder index(WOOS),Oxford Shoulder Score(OSS)and Constant-Murley Score(CMS).The rate of clinically relevant improvement was defined as the proportion of patients who had an improvement 24 months postoperatively that exceeded the MCID.Based on previous literature,MCID for WOOS,OSS,and CMS were defined as 12.3,4.3,and 12.8 respectively.RESULTS Forty-nine patients with a Global Unite total shoulder platform arthroplasty were included for the final analysis.Mean age at the time of surgery was 66 years(range 49.0-79.0,SD:8.3)and 65%were women.One patient was revised within the two years follow-up.The mean improvement from the preoperative assessment to the two-year follow-up was 46.1 points[95%confidence interval(95%CI):39.7-53.3,P<0.005]for WOOS,18.2 points(95%CI:15.5-21.0,P<0.005)for OSS and 37.8 points(95%CI:31.5-44.0,P<0.005)for CMS.Two years postoperatively,41 patients(87%)had an improvement in WOOS that exceeded the MCID,45 patients(94%)had an improvement in OSS that exceeded the MCID,and 42 patients(88%)had an improvement in CMS that exceeded the MCID.CONCLUSION Based on three shoulder-specific outcome measures we find that approximately 90%of patients has a clinically relevant improvement.This is a clear message when informing patients about their prognosis.

Clinical,muscle pathology and molecular genetic analysis of myofibrillar myopathy 3 associated with MYOT gene mutation

Objective To analyze the clinical phenotypic characteristics,muscle pathology,genetic mutations and related proteins of myofibrillar myopathy 3 caused by mutation in MYOT gene,and to conduct a literature review and summary of this disease.Methods A retrospective analysis of the clinical phenotypic characteristics.

Methylation status of c-fms oncogene in HCC and its relationship with clinical pathology

INTRODUCTIONThe mechanism that DNA hypomethylation leads toactivation of oncogene and occurrence of malignantneoplasm is being increasingly recognized byresearchers. Normal DNA methylation playsimportant role in stabilizing the phenotype of cell.DNA methylation status reduction and/or patternalteration are related to activation and abnormallyhigh expression of some oncogenes and cellularmalignancy[1-6]. c-fms oncogene encodes for colonystimulating factor 1 receptor (CSF-1R)[7], c-fms/CSF-1R was highly expressed in hepatocellularcarcinoma (HCC) tissue, but the mechanismremained obscure[8,9].

Expanding role and scope of artificial intelligence in the field of gastrointestinal pathology

Digital pathology(DP)and its subsidiaries including artificial intelligence(AI)are rapidly making inroads into the area of diagnostic anatomic pathology(AP)including gastrointestinal(GI)pathology.It is poised to revolutionize the field of diagnostic AP.Historically,AP has been slow to adopt digital technology,but this is changing rapidly,with many centers worldwide transitioning to DP.Coupled with advanced techniques of AI such as deep learning and machine learning,DP is likely to transform histopathology from a subjective field to an objective,efficient,and transparent discipline.AI is increasingly integrated into GI pathology,offering numerous advancements and improvements in overall diagnostic accuracy,efficiency,and patient care.Specifically,AI in GI pathology enhances diagnostic accuracy,streamlines workflows,provides predictive insights,integrates multimodal data,supports research,and aids in education and training,ultimately improving patient care and outcomes.This review summarized the latest developments in the role and scope of AI in AP with a focus on GI pathology.The main aim was to provide updates and create awareness among the pathology community.

Clinical competency:perceptions of nursing interns and clinical mentors

Objective:To assess the clinical competency of nursing interns and the perception of clinical nurse mentors toward student nurses'clinical competency.Methods:A study was carried out among 104 nursing interns and 26 clinical nurse mentors using the purposive sampling technique.A self-repor ted perception scale was used to collect the data.Results:In general,most nursing interns perceived themselves as clinically competent during the internship.The clinical nurse mentors too repor ted that the current internship is helping the nursing interns in becoming competent.Conclusions:Frequent clinical evaluation,buddy system,provision of stipends,good leadership,and coordination between the academic institute and hospital are repor ted as the critical motivating factors for improving the clinical competency of student interns.

An Overview of Quality Management of Therapeutic Vaccines in Clinical Trials in China

Objective To provide suggestions and a reference for improving the quality management system of clinical trials of therapeutic vaccines and promoting the development of therapeutic vaccines in China.Methods Literature research,case study and comparative study were used to analyze the quality management system of clinical trials of therapeutic vaccines.Results and Conclusion From the perspective of the sponsor,investigators and the thirdparty technical service company,the problems such as the low efficiency of clinical trial sample preparation and the lax implementation of the protocol by hospital departments in the quality management of clinical trials of therapeutic vaccines in China were found.Then,the optimization plan for the quality management of clinical trials of therapeutic vaccines is proposed,including optimizing the preparation process of therapeutic vaccines and strengthening the training of hospital department personnel.

Patient Recruitment in Clinical Trials: Areas of Challenges and Success, a Practical Aspect at the Private Research Site

Enrolling in clinical trials could be time-sensitive and time-demanding tasks for the research site, especially if it is a private research organization compared to the research conducted at an academic or medical center. Every study differs in various aspects, such as phases, study indication, eligibility criteria, etc. In terms of meeting the enrollment deadline, typically, the study indication and availability of the patient’s population at the geographical area of the research site would decide if the trial could be time-consuming. Patient recruitment and retention are critical for the success of every clinical trial;however, worldwide, this area is facing tremendous pressure and challenges. Globally 55% of clinical trials terminated due to low recruitment, with an average enrollment success rate of 40% for Phase III and IV trials. Over 80% of clinical trial attempts fail to enroll, extending the study and adding new study sites. In the United States, more than 80% of clinical trials fail to achieve targeted patient enrollment, and 30% of study participants discontinue participation. This article reviewed various factors hindering clinical trial recruitment and retention and suggested strategies to make the research site successful.

Clinical manifestations,diagnosis and long-term prognosis of adult autoimmune enteropathy:Experience from Peking Union Medical College Hospital

BACKGROUND Autoimmune enteropathy(AIE)is a rare disease whose diagnosis and long-term prognosis remain challenging,especially for adult AIE patients.AIM To improve overall understanding of this disease’s diagnosis and prognosis.METHODS We retrospectively analyzed the clinical,endoscopic and histopathological characteristics and prognoses of 16 adult AIE patients in our tertiary medical center between 2011 and 2023,whose diagnosis was based on the 2007 diagnostic criteria.RESULTS Diarrhea in AIE patients was characterized by secretory diarrhea.The common endoscopic manifestations were edema,villous blunting and mucosal hyperemia in the duodenum and ileum.Villous blunting(100%),deep crypt lymphocytic infiltration(67%),apoptotic bodies(50%),and mild intraepithelial lymphocytosis(69%)were observed in the duodenal biopsies.Moreover,there were other remarkable abnormalities,including reduced or absent goblet cells(duodenum 94%,ileum 62%),reduced or absent Paneth cells(duodenum 94%,ileum 69%)and neutrophil infiltration(duodenum 100%,ileum 69%).Our patients also fulfilled the 2018 diagnostic criteria but did not match the 2022 diagnostic criteria due to undetectable anti-enterocyte antibodies.All patients received glucocorticoid therapy as the initial medication,of which 14/16 patients achieved a clinical response in 5(IQR:3-20)days.Immunosuppressants were administered to 9 patients with indications of steroid dependence(6/9),steroid refractory status(2/9),or intensified maintenance medication(1/9).During the median of 20.5 months of followup,2 patients died from multiple organ failure,and 1 was diagnosed with non-Hodgkin’s lymphoma.The cumulative relapse-free survival rates were 62.5%,55.6%and 37.0%at 6 months,12 months and 48 months,respectively.CONCLUSION Certain histopathological findings,including a decrease or disappearance of goblet and Paneth cells in intestinal biopsies,might be potential diagnostic criteria for adult AIE.The long-term prognosis is still unsatisfactory despite corticosteroid and immunosuppressant medications,which highlights the need for early diagnosis and novel medications.