Treat to target in Crohn’s disease:A practical guide for clinicians

A treat-to-target(T2T)approach applies the principles of early intervention and tight disease control to optimise long-term outcomes in Crohn's disease.The Selecting Therapeutic Targets in Inflammatory Bowel Disease(STRIDE)-II guidelines specify short,intermediate,and long-term treatment goals,documenting specific treatment targets to be achieved at each of these timepoints.Scheduled appraisal of Crohn’s disease activity against pre-defined treatment targets at these timepoints remains central to determining whether current therapy should be continued or modified.Consensus treatment targets in Crohn’s disease comprise combination clinical and patient-reported outcome remission,in conjunction with biomarker normalisation and endoscopic healing.Although the STRIDE-II guidelines endorse the pursuit of endoscopic healing,clinicians must consider that this may not always be appropriate,acceptable,or achievable in all patients.This underscores the need to engage patients at the outset in an effort to personalise care and individualise treatment targets.The use of non-invasive biomarkers such as faecal calprotectin in conjunction with cross-sectional imaging techniques,particularly intestinal ultrasound,holds great promise;as do emerging treatment targets such as transmural healing.Two randomised clinical trials,namely,CALM and STARDUST,have evaluated the efficacy of a T2T approach in achieving endoscopic endpoints in patients with Crohn’s disease.Findings from these studies reflect that patient subgroups and Crohn’s disease characteristics likely to benefit most from a T2T approach,remain to be clarified.Moreover,outside of clinical trials,data pertaining to the real-world effectiveness of a T2T approach remains scare,highlighting the need for pragmatic real-world studies.Despite the obvious promise of a T2T approach,a lack of guidance to support its integration into real-world clinical practice has the potential to limit its uptake.This highlights the need to describe strategies,processes,and models of care capable of supporting the integration and execution of a T2T approach in real-world clinical practice.Hence,this review seeks to examine the current and emerging literature to provide clinicians with practical guidance on how to incorporate the principles of T2T into routine clinical practice for the management of Crohn’s disease.

Treating inflammatory bowel disease by adsorptive leucocytapheresis:A desire to treat without drugs

Ulcerative colitis and Crohn’s disease are the major phenotypes of the idiopathic inflammatory bowel disease (IBD), which afflicts millions of individuals throughout the world with debilitating symptoms, impairing function and quality of life. Current medications are aimed at reducing the symptoms or suppressing exacerbations. However, patients require life-long medications, and this can lead to drug dependency, loss of response together with adverse side effects. Indeed, drug side effects become additional morbidity factor in many patients on long-term medications. Nonetheless, the efficacy of anti-tumour necrosis factors (TNF)-α biologics has validated the role of inflammatory cytokines notably TNF-α in the exacerbation of IBD. However, inflammatory cytokines are released by patients’ own cellular elements including myeloid lineage leucocytes, which in patients with IBD are elevated with activation behaviour and prolonged survival. Accordingly, these leucocytes appear logical targets of therapy and can be depleted by adsorptive granulocyte/monocyte apheresis (GMA) with an Adacolumn. Based on this background, recently GMA has been applied to treat patients with IBD in Japan and in the European Union countries. Efficacy rates have been impressive as well as disappointing. In fact the clinical response to GMA seems to define the patients’ disease course, response to medications, duration of active disease, and severity at entry. The best responders have been first episode cases (up to 100%) followed by steroid naïve and patients with a short duration of active disease prior to GMA. Patients with deep ulcers together with extensive loss of the mucosal tissue and cases with a long duration of IBD refractory to existing medications are not likely to benefit from GMA. It is clinically interesting that patients who respond to GMA have a good long-term disease course by avoiding drugs including corticosteroids in the early stage of their IBD. Additionally, GMA is very much favoured by patients for its good safety profile. GMA in 21st century reminds us of phlebotomy as a major medical practice at the time of Hippocrates. However, in patients with IBD, there is a scope for removing from the body the sources of pro-inflammatory cytokines and achieve disease remission. The bottom line is that by introducing GMA at an early stage following the onset of IBD or before patients develop extensive mucosal damage and become refractory to medications, many patients should respond to GMA and avoid pharmacologics. This should fulfill the desire to treat without drugs.

THE ROLE OF PSYCHOSOCIAL STRESSORS,PERSONALITY AND COPING IN THE MULTIFACTORIAL ORIGIN,INITIATION AND CLINICAL COURSE OF NEOPLASTIC DISEASE AND IN HOST-DEFENSE

Summary: Retrospective and prospective bio-behavioral cancer studies have revealed that psycho social stressors may play a pivotal role in the initiation and progression of malignant neoplasia. In recent research, a pattern has emerged, which in analogy to the coronary prone pattern (type A) has been labelled type C, encompassing suppression of emotional responses, such as anger and hostility, rationality and antiemotionality, as well as high social conformity and a lack of self-assertiveness. There is growing evidence in both infrahuman and human research that specific coping styles (repressive coping) with stress may be associated with specific biologic responses, including neuroendocrine, immunologic and other bodily functions. The application of this model appears to be of importance for further research, as well as for the detection of high risk individuals, but also in regard to therapy, rehabilitation, early detection and possibly also prevention of malignant disease. This concept suggests also new directions and modifications of stress research, as stressors are to be viewed not necessarily as pathological, but in some instances as quite possibly salutary, depending on the nature of the stres-sor, the psychophysiologic state of the individual and his or her ability to cope with adverse life situations. Quite naturally, the development of this concept is still in its initial stages, there remain anumber of open questions, and it needs hardly to be pointed out in this connection that further and painstaking clinical and laboratory work is warranted in order to clarify the role of stressors, life and coping styles and its biological concomitants in neo-plastic disease.

Loss of efficacy and safety of the switch from infliximab original to infliximab biosimilar(CT-P13)in patients with inflammatory bowel disease

BACKGROUND Infliximab original has changed the natural history of inflammatory bowel diseases(IBD) over the past two decades. However, the recent expiration of its patent has allowed the entry of the first Infliximab biosimilar into the European and Spanish markets. Currently switching drugs data in IBD are limited. AIM To compare the efficacy of infliximab biosimilar, CT-P13, against infliximab original, analyzing the loss of response of both at the 12 mo follow-up in patients with IBD.METHODS An observational study of two cohorts has been conducted. One retrospective cohort that included patients with IBD treated with Infliximab original, and a prospective cohort of patients who were switching from infliximab original to infliximab biosimilar(CT-P13). We had analyzed the overall efficacy and loss of efficacy in patients in remission at the end of one year after treatment with the original drug compared to the results of the year of treatment with the biosimilar.RESULTS98 patients(CD 67, CU 31) were included in both cohorts. The overall efficacy for infliximab original per year of treatment was 71% vs 68.2% for infliximab biosimilar(P = 0.80). The loss of overall efficacy at 12 mo for infliximab original was 6.6% vs 14.5% for infliximab biosimilar(P = 0.806). The loss of efficacy in patients who were in basal remission was 16.3% for infliximab original vs 27.1% for infliximab biosimilar. Adverse events were 9.2% for infliximab original vs 11.2% for infliximab biosimilar. CONCLUSION The overall efficacy and loss of treatment response with infliximab biosimilar(CT-P13) is similar to that observed with infliximab original in patients who were switching at the 12 mo follow-up. There is no difference in the rate of adverse events.

The Substance and Cultural Connotations of Treating Prior to Disease

The substance of treating prior to disease in Traditional Chinese Medicine expects to dissipate symptoms before the disease occurs and maintain health until centenarian.This concept is a collective reflection of the intrinsic awareness of suffering by Chinese people.Moreover,its cultural connotations involve emphasis on preparation for adversity in times of safety and taking anticipative measures.

Role of adrenalectomy in treating recurrent Cushing's disease:A report of 43 cases

Objective To evaluate the efficacy of laparoscopic adrenalectomy and open adrenalectomy in treating recurrent Cushing ’s disease. Methods Forty-three patients ( 29 females and 14 males) with recurrent Cushing’s disease treated with laparoscopic adrenalectomy ( LA,n = 32) or open ( OA,n = 11) adrenalectomy from 2000

The origin, transmission and clinical therapies on coronavirus disease 2019(COVID-19) outbreak——an update on the status

An acute respiratory disease,caused by a novel coronavirus(SARS-CoV-2,previously known as 2019-nCoV),the coronavirus disease 2019(COVID-19)has spread throughout China and received worldwide attention.On 30 January 2020,World Health Organization(WHO)officially declared the COVID-19 epidemic as a public health emergency of international concern.The emergence of SARS-CoV-2,since the severe acute respiratory syndrome coronavirus(SARSCoV)in 2002 and Middle East respiratory syndrome coronavirus(MERS-CoV)in 2012,marked the third introduction of a highly pathogenic and large-scale epidemic coronavirus into the human population in the twenty-first century.As of 1 March 2020,a total of 87,137 confirmed cases globally,79,968 confirmed in China and 7169 outside of China,with 2977 deaths(3.4%)had been reported by WHO.Meanwhile,several independent research groups have identified that SARS-CoV-2 belongs toβ-coronavirus,with highly identical genome to bat coronavirus,pointing to bat as the natural host.The novel coronavirus uses the same receptor,angiotensin-converting enzyme 2(ACE2)as that for SARS-CoV,and mainly spreads through the respiratory tract.Importantly,increasingly evidence showed sustained human-tohuman transmission,along with many exported cases across the globe.The clinical symptoms of COVID-19 patients include fever,cough,fatigue and a small population of patients appeared gastrointestinal infection symptoms.The elderly and people with underlying diseases are susceptible to infection and prone to serious outcomes,which may be associated with acute respiratory distress syndrome(ARDS)and cytokine storm.Currently,there are few specific antiviral strategies,but several potent candidates of antivirals and repurposed drugs are under urgent investigation.In this review,we summarized the latest research progress of the epidemiology,pathogenesis,and clinical characteristics of COVID-19,and discussed the current treatment and scientific advancements to combat the epidemic novel coronavirus.

Dental pulp stem cells for treating neurodegenerative diseases

The hippocampal formation, important for spatial learn- ing and memory function, exhibits high level of plas- ticity in response to behavioral changes as well as injury. Dysfunction of the hippocampus is one of the hallmark features of neurodegenerative diseases like temporal lobe epilepsy （TLE） and Alzheimer＇s disease （AD） （Dhanush- kodi and Shetty 2008）. Excitotoxicity is one of the known mechanisms by which neurons undergo degeneration in neurodegenerative condition （Haglid et al., 1994; Doble et al., 1995）. Brain regions such as hippocampus are more susceptible to excitotoxic damage. During excitotoxicity.

Treat-to-target in Crohn's disease:Will transmural healing become a therapeutic endpoint?

Crohn's disease(CD) represents a chronic transmural inflammatory condition of the gastrointestinal tract, which usually leads to structural damage and signific-ant disability. Deep remission--defined by both clinical and endoscopic remission, signifying mucosal healing-represents the current endpoint in the treat--to--target strategy, significantly improving patients' long--term outcomes. Transmural healing(TH) could be a more effe-ctive target, but this possibility remains unclear. This narrative review aims to critically review and summarize the available literature relating TH to long--term outcomes, being the first of its kind and to the best of the author's knowledge. A systematic literature search(from incep-tion to March 31 2018) was performed, using multiple databases, and identifying seven full--text manuscripts. In those studies, long--term favorable outcomes(≥ 52 wk) included sustained clinical remission, as well as fewer therapeutic changes, CD--related hospitalizations, and surgeries. Despite heterogeneous design and me-thodological limitations, six of the studies demonstrated that TH or intestinal healing(TH plus mucosal healing) were predictive for the aforementioned favorable out-comes. Therefore, TH may become a reasonable the-rapeutic target and be included in the concept of deep remission. Further prospective, well-designed, multicenter trials aiming to better define the role of TH in personalized therapy for CD and to determine the long-term influence of TH on bowel damage and disability are warranted.

Disease monitoring strategies in inflammatory bowel diseases: What do we mean by “tight control”?

In recent years,there has been a critical change in treatment paradigms in inflammatory bowel diseases(IBD)triggered by the arrival of new effective treatments aiming to prevent disease progression,bowel damage and disability.The insufficiency of symptomatic disease control and the well-known discordance between symptoms and objective measures of disease activity lead to the need of reviewing conventional treatment algorithms and developing new concepts of optimal therapeutic strategy.The treat-to-target strategies,defined by the selecting therapeutic targets in inflammatory bowel disease consensus recommendation,move away from only symptomatic disease control and support targeting composite therapeutic endpoints(clinical and endoscopical remission)and timely assessment.Emerging data suggest that early therapy using a treat-to-target approach and an algorithmic therapy escalation using regular disease monitoring by clinical and biochemical markers(fecal calprotectin and C-reactive protein)leads to improved outcomes.This review aims to present the emerging strategies and supporting evidence in the current therapeutic paradigm of IBD including the concepts of“early intervention”,“treat-to-target”and“tight control”strategies.We also discuss the real-word experience and applicability of these new strategies and give an overview on the future perspectives and areas in need of further research and potential improvement regarding treatment targets and(“tight”)disease monitoring strategies.

Quality of care in inflammatory bowel diseases: What is the best way to better outcomes?

Inflammatory bowel disease(IBD) is a lifelong, progres-sive disease that has disabling impacts on patient's lives. Given the complex nature of the diagnosis of IBD and its management there is consequently a large economic burden seen across all health care systems. Quality in-dicators(QI) have been created to assess the different fa?ades of disease management including structure, process and outcome components. Their development serves to provide a means to target and measure quality of care(Qo C). Multiple different QI sets have been published in IBD, but all serve the same purpose of trying to achieve a standard of care that can be attained on a national and international level, since there is still a major variation in clinical practice. There have been many recent innovative developments that aim to improve Qo C in IBD including telemedicine, home biomarker assessment and rapid access clinics. These are some of the novel advancements that have been shown to have great potential at improving Qo C, while offloading some of the burden that IBD can have vis-a-vis emergency room visits and hospital admissions. The aim of the current review is to summarize and discuss available QI sets and recent developments in IBD care including telemedicine, and to give insight into how the utilization of these tools could benefit the Qo C of IBD patients. Additionally, a treating-to-target structure as well as evidence surrounding aggressive management directed at tighter disease control will be presented.

Sixty-one Cases of Angina Pectoris due to Coronary Heart Disease Treated by External Use of the Paste of Nitrum and Realgar Powder on Zhiyang(GV 9)

In order to inquire into the therapeutic effects of Xiao Shi Xiong Huang San (硝石雄黄散the Nitrum and Realgar Powder), one of the Dunhuang Prescription, on angina pectoris due to coronary heart disease (APCHD), the authors have treated 61 cases of APCHD by externally applying paste of the powder on Zhiyang (GV 9), with another 30 cases of APCHD treated with the nitroglycerin paste on Zhiyang as the controls. The results showed that the total effective rate was 82% and markedly effective rate 31.2% in the treatment group (the Paste of Nitrum and Realgar Powder), and the total effective rate was 46.6% and markedly effective rate 23.2% in the control group (the nitroglycerin paste). The difference in therapeutic effects between the two groups was very significant (P<0.01), indicating that the therapeutic effect of the former was significantly superior to that of the latter.

Small bowel capsule endoscopy and treat-to-target in Crohn’s disease: A systematic review

BACKGROUND Crohn’s disease(CD)can affect the entire gastrointestinal tract.Proximal small bowel(SB)lesions are associated with a significant risk of stricturing disease and multiple abdominal surgeries.The assessment of SB in patients with CD is therefore necessary because it may have a significant impact on prognosis with potential therapeutic implications.Because of the weak correlation that exists between symptoms and endoscopic disease activity,the“treat-to-target”paradigm has been developed,and the associated treatment goal is to achieve and maintain deep remission,encompassing both clinical and endoscopic remission.Small bowel capsule endoscopy(SBCE)allows to visualize the mucosal surface of the entire SB.At that time,there is no recommendation regarding the use of SBCE during follow-up.AIM To investigate the impact of SBCE in a treat-to-target strategy in patients with CD.METHODS An electronic literature search was conducted in PubMed and Cochrane library using the following search terms:“capsule endoscopy”,in combination with“Crohn’s disease”and“treat-to-target”or synonyms.Two authors independently reviewed titles and abstracts identified by the search strategy after duplicates were removed.Following the initial screening of abstracts,all articles containing information about SBCE in the context of treat-to-target strategy in patients with CD were included.Full-text articles were retrieved,reference lists were screened manually to identify additional studies.RESULTS Forty-seven articles were included in this review.Two indexes are currently used to quantify disease activity using SBCE,and there is good correlation between them.SBCE was shown to be useful for disease reclassification in patients who are suspected of having or who are diagnosed with CD,with a significant incremental diagnostic yield compared to other diagnostic modalities.Nine studies also demonstrated that the mucosal healing can be evaluated by SBCE to monitor the effect of medical treatment in patients with CD.This review also demonstrated that SBCE can detect post-operative recurrence to a similar extent as ileocolonoscopy,and proximal SB lesions that are beyond the reach of the colonoscope in over half of the patients.CONCLUSION SBCE could be incorporated in the treat-to-target algorithm for patients with CD.Randomized controlled trials are required to confirm its usefulness and reliability in this indication.

Observation of Therapeutic Effect with Hand Treating the Spine Relative Disease

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Scientific connotation of “treating different diseases with the same method” from the perspective of metabolic-immune dysregulation in inflammation-mediated carcinogenesis of digestive organs

Inflammation-mediated carcinogenesis develops in the context of chronic inflammation and is a significant cause of cancer within the digestive system.In the chronic inflammation microenvironment,the metabolic activity of tissue cells undergoes extensive changes,which interfere with the normal function of immune cells.Dysregulation of cell metabolism and immune function has been identified as a key factor contributing to inflammation-mediated carcinogenesis within the major digestive organs,such as the stomach,liver,and colorectum.This metabolic-immune imbalance also corresponds to traditional Chinese medicine(TCM)theories of“yin-yang disharmony”and“disharmony between Ying-nutrients and Wei-defense.”The metabolic-immune imbalance has also been regarded as the key factor supporting“treatment of different diseases with the same method”,in which the same approach is adopted in the treatment of different conditions.In the TCM treatment process,it is necessary to first identify TCM patterns and then apply the corresponding TCM to correct the dysregulated metabolic and immune function,thereby blocking the progression from inflammation to malignancy.Our study findings deepen the TCM understanding of metabolic-immune dysregulation and the relationship between metabolic-immune dysregulation,pattern identification,and treatment method.They also provide new insights for the treatment of inflammation-mediated carcinogenesis in major digestive organs and help us further explore the scientific connotation of the TCM strategy of“treating different diseases with the same method”.

Consideration of the Necessity of Prophylactic Bypass Grafting for Anomalous Origin of the Right Coronary Artery—Based on a Case with Concomitant Left Main Trunk Disease Resuscitated from Cardiopulmonary Arrest

Anomalous origin of the right coronary artery is a rare congenital anomaly, but is associated with sudden death. Originating from the opposite sinus of Valsalva, an interarterial?course and an intramural course are especially considered as the risk factor for fatal cardiac events. Surgical indication remains controversial because many patients are asymptomatic. A 52-year-old man with anomalous origin of the right coronary artery with an interarterial?course concomitant with the left main trunk disease was resuscitated from cardiopulmonary arrest. It was likely to be attributed to the left main trunk disease, but anatomical structure of the right coronary artery suggests its possible involvement. Prophylactic bypass grafting for the right coronary artery was performed using saphenous vein graft without ligating native vessel to prevent future cardiac events, as well as revascularization of the left main trunk disease. All grafts were patent in one-year follow-up coronary angiography. Any cardiac event has not occurred.

Mechanisms of Huanglian Jiedu Decoction in treating coronary heart disease and type 2 diabetes mellitus based on network pharmacology

Objective:To explore the common mechanism of Huanglian Jiedu Decoction in treating coronary heart disease and type 2 diabetes by network pharmacology.Methods:All chemical components and targets of the four drugs in Huanglian Jiedu Decoction were retrieved through TCMSP,and the genes were standardized through Uniprot database.Acquire disease targets related to coronary heart disease and diabetes in OMIM and GeneCards databases.The network diagram of"drug-component-target-disease"is constructed by using the software of cytopscape 3.7.2,the PPI network diagram of protein interaction is constructed by using STRING database,and the network diagram of"drug-disease"core target is constructed by using the software of cytopscape 3.7.2.DAVID's online database platform was used to analyze GO biological process and KEGG pathway enrichment of common targets of Huanglian Jiedu Decoction in treating coronary heart disease and type 2 diabetes.Results:103 active ingredients of Huanglian Jiedu Decoction were retrieved,including 140 acting targets,5342 coronary heart disease targets,114 diabetes targets,and 14 common intersection targets of drugs and diseases,involving AR,PPARG,TNF,IL6,CCL2,VEGFA,PON1,etc.The GO biological process analysis results in 98 biological processes,10 cell components and 10 molecular functions.Among them are positive regulation of gene expression,positive regulation of nitric oxide biosynthesis process,Extracellular space,cytokine activity,steroid hormone receptor activity and other biological processes;The enrichment analysis of KEGG pathway yielded 20 signal pathways(P≤0.05).It mainly involves Malaria,cancer in cancer,HIF-1 signaling pathway,TNF signaling pathway,NOD-like receptor signaling pathway,PI3K-Akt signaling pathway,etc.Conclusion:Huanglian Jiedu Decoction"treats different diseases at the same time"coronary heart disease and type 2 diabetes have the characteristics of multiple components,multiple targets and multiple pathways,which provide theoretical basis for Huanglian Jiedu Decoction to treat coronary heart disease and type 2 diabetes in clinic,but the key targets and pathways of Huanglian Jiedu Decoction to treat diseases still need further experimental verification.

Clinical Observation on 100 Cases of Postoperative Pain of Anal-Intestinal Diseases Treated with Vitamine K Blocking at Changqiang Point

Since the latter half of 1996, we have used vitamine K blocking at Changqiang (GV 1) for relieving the postoperative pain of anal fissure with satisfactory results. A report follows.……

WRIST-ANKLE ACUPUNCTURE FOR ANALGESIA IN TREATING SOME COMMON DISEASES IN ATHLETES

With gradual generalization of acupuncture-moxibustion therapy in developed countries, an increasing attention has been paid to its application in the athletic field. Wrist-ankle acupuncture is a kind of shallow acupuncture, by which 6 points in the wrist and ankle regions are selected and punctured for treating diseases related to individual parts of the body. It is a kind of information therapy concerning biological hologram regularities. The analgesic effects of the therapy in treating some common diseases in 64 athletes are reported as follows.

China Association of Chinese Medicine Paper notice for seminar on clinical application of new technology of integrated Chinese and western medicine in treating sequelae of cerebrovascular diseases

Hosted by ChinaAssociation of Chinese Medicine,and organized by World Journal of Integrated traditional and western Medicine,seminar on clinical application of new technology of integrated Chinese and western medicine in treating sequelae of cerebrovascular diseases is planned to be held in Nanning,Guangxi in August.