Combination treatment of inflammatory bowel disease:Present status and future perspectives

The treatment of patients with inflammatory bowel disease(IBD),especially those with severe or refractory disease,represents an important challenge for the clinical gastroenterologist.It seems to be no exaggeration to say that in these patients,not only the scientific background of the gastroenterologist is tested,but also the abundance of“gifts”that he should possess(insight,intuition,determ-ination,ability to take initiative,etc.)for the successful outcome of the treatment.In daily clinical practice,depending on the severity of the attack,IBD is treated with one or a combination of two or more pharmaceutical agents.These combin-ations include not only the first-line drugs(e.g.,mesalazine,corticosteroids,antibiotics,etc)but also second-and third-line drugs(immunosuppressants and biologic agents).It is a fact that despite the significant therapeutic advances there is still a significant percentage of patients who do not satisfactorily respond to the treatment applied.Therefore,a part of these patients are going to surgery.In recent years,several small-size clinical studies,reviews,and case reports have been published combining not only biological agents with other drugs(e.g.,immunosuppressants or corticosteroids)but also the combination of two biologi-cal agents simultaneously,especially in severe cases.In our opinion,it is at least a strange(and largely unexplained)fact that we often use combinations of drugs in a given patient although studies comparing the simultaneous administration of two or more drugs with monotherapy are very few.As mentioned above,there is a timid tendency in the literature to combine two biological agents in severe cases unresponsive to the applied treatment or patients with severe extraintestinal manifestations.The appropriate dosage,the duration of the administration,the suitable timing for checking the clinical and laboratory outcome,as well as the treatment side-effects,should be the subject of intense clinical research shortly.In this editorial,we attempt to summarize the existing data regarding the already applied combination therapies and to humbly formulate thoughts and suggestions for the future application of the combination treatment of biological agents in a well-defined category of patients.We suggest that the application of biomarkers and artificial intelligence could help in establishing new forms of treatment using the available modern drugs in patients with IBD resistant to treatment.

Successful treatment of eyebrow intradermal nevi by shearing combined with electrocautery and curettage:Two case reports

BACKGROUND An intradermal nevus is a common skin tumour,and the classical method of removal has a risk of recurrence and scarring.It is a challenge for dermatologists to treat eyebrow intradermal nevi quickly and efficiently.This study focused on investigating the efficacy and safety of shearing combined with electrocautery and curettage in the treatment of eyebrow intradermal nevi.CASE SUMMARY We describe two adult patients with eyebrow intradermal nevi treated by shearing combined with electrocautery and curettage.Both patients were followed up regularly after surgery.At follow-up,no recurrence of eyebrow intradermal nevus and no obvious scars or hypopigmentation were found in either patient.The results indicated that shearing combined with electrocautery and curettage could remove eyebrow intradermal nevus without side effects and confirmed the efficacy and safety of this modality for treating these skin lesions.CONCLUSION Shearing combined with electrocautery and curettage has superior merits,including simple operation,good cosmetic effects,and high patient satisfaction,presenting great application potential for treating intracutaneous nevus.

Dual-targeted treatment for inflammatory bowel disease:Whether fecal microbiota transplantation can be an important part of it

Inflammatory bowel disease(IBD)is a chronic gastrointestinal inflammatory disease.With the emergence of biologics and other therapeutic methods,two biologics or one biologic combined with a novel small-molecule drug has been proposed in recent years to treat IBD.Although treatment strategies for IBD are being optimized,their efficacy and risks still warrant further consideration.This editorial explores the current risks associated with dual-targeted treatment for IBD and the great potential that fecal microbiota transplantation(FMT)may have for use in combination therapy for IBD.We are focused on addressing refractory IBD or biologically resistant IBD based on currently available dual-targeted treatment by incorporating FMT as part of this dual-targeted treatment.In this new therapy regimen,FMT represents a promising combination therapy.

The Combined Effect of Botulinum Toxin Type A with a Biorevitalizing Treatment on Forehead Rejuvenation: A Case Series

Background: The forehead is particularly prone to repetitive facial expressions and hyperdynamic activity, resulting in deep wrinkles and a loss of elasticity and hydration. Although botulinum toxin type A (BoNTA) has been shown to reduce the appearance of wrinkles and allow patients to have a smoother and hence younger upper face, it cannot help to improve the other aspects that determine overall skin quality. Objective: This case series aims to evaluate the clinical efficacy of combining BoNTA injections with a biorevitalizing treatment (NCTF®135HA) on skin aging signs and quality using a split face approach. Patients and Methods: A total of eight patients from 30 to 55 years old were treated with botulinum toxin type A combined with NCTF®-135HA or alone. Results: At D60, clinical skin quality scoring showed that NCTF®135HA injection significantly reduced wrinkles and enhanced skin homogeneity, hydration, firmness, and radiance. The Global Aesthetic Improvement Scale (GAIS) by the evaluator at D60 reported mean scores of 2375 (much improved) on the side of the face treated with BoNTA + NCTF®-135HA compared to the side of the face without NCTF®135HA. According to patients, the NCTF®135HA injections resulted in a significantly better aesthetic improvement score on D60 (mean score of 2.5 compared to 0.125 without NCTF®135HA, p 0.001). Conclusions: Our findings show that combining a biorevitalizing treatment with a BoNTA injection can significantly improve the skin’s overall appearance and decrease the wrinkle score when compared to the BoNTA injections alone. The results suggest that the combinatory strategy is effective, safe, and associated with a high level of patient satisfaction.

Optimization and Characterization of Combined Degumming Process of Typha angustata L. Stem Fibers

Plant derived natural fibers have been widely investigated as alternatives to synthetic fibers in reinforcing polymers.Researchers over the years have explored many plant fibers using different extraction processes to study their physical,chemical,and mechanical properties.In this context,the present study relates to the extraction,characterization,and optimization of Typha angustata L.stem fibers.For this purpose,desirability functions and response surface methodology were applied to simultaneously optimize the diameter(D),linear density(LD);yield(Y),lignin fraction(L),and tenacity(T)of Typha stem fibers.Typha stems have been subjected to both alkali(NaOH)and enzymatic(pectinex ultra-SPL)treatments.Three levels of process variables including enzyme concentration(10,15,and 20 ml/L)and treatment duration(10,15,and 20 days)were used to design the experiments according to the factorial design.Experimental results were examined by analysis of variance and fitted to second order polynomial model using multiple regression analysis.The Derringer’s desirability function released that the values of process variables generating optimized diameter,linear density,yield,lignin ratio and tenacity are 20 ml/L and 20 days for concentration of pectinex ultra-SPL enzyme and treatment duration,respectively.Confirmation was performed and high degree of correlation was found between the experimental and statistical values.Moreover,the morphological structure has been investigated by the scanning electron microscope,showing a crenelated structure of ultimate fiber bundles of cellulose composing the Typha fiber.Compared to Typha stem non-treated fibers(TSNTF),Typha stem combined treated fibers(TSCTF),brings to improve mechanical properties.This change in mechanical properties is affected by modifying the fiber structure showing alpha cellulose of(66.86%)and lignin ratio of(10.83%)with a crystallinity index of(58.47%).

Anlotinib in combination with Envolizumab plus Etoposide for the treatment of EX-SCLC:a case report

Background:Small cell lung cancer(SCLC)is an aggressive malignant tumor with strong immunosuppressive effects,characterized by rapid doubling time and poor prognosis.Currently,effective therapeutic options are urgently needed for Extensive-stage small-cell lung Cancer.Case description:In the present case,a combination therapy of anlotinib,envolizumab,and etoposide was administered to treat an 80-year-old female patient with extensive-stage SCLC accompanied by mediastinal lymph node and bone metastasis.After two cycles of treatment,the tumor lesions in the right lungs decreased from 5.04*3.44 cm to 1.65*1.42 cm.As of now,no significant mass is seen there and no serious adverse reactions in this patient.Until September 2023,she has survived for 18 months with no disease progression.Conclusions:Research shows that Alectinib,in combination with evolocumab plus etoposide,could be an original,viable therapeutic option for the treatment option of patients with extensive-stage SCLC.

Combined treatments in hepatocellular carcinoma:Time to put them in the guidelines?

The time for battling cancer has never been more suitable than nowadays and fortunately against hepatocellular carcinoma(HCC)we do have a far-reaching arsenal.Moreover,because liver cancer comprises a plethora of stages-from very early to advanced disease and with many treatment options–from surgery to immunotherapy trials–it leaves the clinician a wide range of options.The scope of our review is to throw light on combination treatments that seem to be beyond guidelines and to highlight these using evidence-based analysis of the most frequently used combination therapies,discussing their advantages and flaws in comparison to the current standard of care.One particular combination therapy seems to be in the forefront:Transarterial chemoembolization plus ablation for medium-size non-resectable HCC(3-5 cm),which is currently at the frontier between Barcelona Clinic Liver Cancer classification A and B.Not only does it improve the outcome in contrast to each individual therapy,but it also seems to have similar results to surgery.Also,the abundance of immune checkpoint inhibitors that have appeared lately in clinical trials are bringing promising results against HCC.Although the path of combination therapies in HCC is still filled with uncertainty and caveats,in the following years the hepatology and oncology fields could witness an HCC guideline revolution.

Hemiplegia Patients Treatment Should Combine Acupuncture with Rehabilitation Treatment

The acupuncturetherapy for hemiplegiapatients is popular insome Asian countries,and it has been graduallyaccepted in the rehabili-tative medical field ofsome developed countries.Although numer-ous clinical and experimental studies have beendone,many doctors usu-

A Biochemical Study on Combined Treatment of Experimental Silicosis with Tetradrine-PVNO and Tetradrine-QOHP in Rats

A better understanding is needed to explain the mechanism of therapeutic effect of combined use of tetradrine-PVNO and tetradrine-QOHP which play very important roles in treatment of silicosis. Blood prolidase (PLD), monoamine oxidase (MAO) and plasminogen (PLG) in silicotic rats after treatment with tetradrine-PVNO or tetradrine-QOHP were measured. The values obtained were compared with the untreated silicotic rats. It was found that the silicotic rats that received tetradrine-PVNO showed significant increase in PLD and decrease in PLG, but no significant change in MAO. The PLD in plasma of silicotic rats that received tetradrine-QOHP were elevated significantly, but PLG and MAO did not change appreciably. These findings suggest that the combined use of tetradrine-PVNO and tetradrine-QOHP can accelerate the degradation of collagen in silicotic rats

meta-analysis of randomized controlled trials of combined treatment with DGSN and western medicine on diabetic peripheral neuropathy

Objective:To systematically study the clinical effects of combined treatment with Dang gui si ni tang(DGSN)and western medicine(WM)on diabetic peripheral neuropathy.Methods:Seven databases,including Chinese National Knowledge Infrastructure(CNKI),Chinese Biomedical Database(CBM),Wanfang full-text database,VIP Database for Chinese Technical Periodicals,MEDLINE,PubMed,Embase,were retrieved.Related references about randomized controlled trials on the combination of DGSN and WM on diabetic peripheral neuropathy published during January 2012 up to now(recent 5 years)were reviewed.Related grey literatures were also reviewed according to the selected articles.RevMan5.3 software was used to analyze the publish bias,and to compare the total clinical effects of the combination of DGSN and WM with WM alone.Results:Ultimately,19 randomized controlled trials with 1690 patients were incorporated.The results of meta-analysis showed that combined treatment of diabetic peripheral neuropathy with DGSN and WM showed better general efficacy compared with control group,with a statistically significant difference(P<0.05).The results of study showed homogeneity(P=0.94>0.05).The general efficacy of combined treatment with DGSN and WM was significantly higher than that of control group(P<0.00001,OR=3.98,95%CI:3.01~5.27).Conclusion:Compared with treatment with WM alone,combined treatment of diabetic peripheral neuropathy with DGSN and WM is more effective.Meanwhile,due to the limited literature samples and low quality of literatures,large samples and high quality of multi-center randomized controlled double-blind trials are needed to verify these results.

Evaluation of modified hemodilution combined therapy in the treatment of acute ischemic stroke in the elderly

BACKGROUND： Thrombolysis therapy is not suitable for the elderly patients with acute ischemic stroke who delayed to be diagnosed for more than 3 hours, but traditional medicine is also not very ideal. OBJECTIVE： To observe the clinical therapeutic effect of modified hemodilution combined therapy applied in elderly patients with acute cerebral thrombosis and analyze the mechanism of this therapeutic method. DESIGN： 1：1 paired grouping according to gender and controlled observation SETTING： Department of Internal Medicine, Chengzhanyuan District, First Hospital Affiliated to Zhejiang University. PARTICIPANTS： Totally 90 elderly patients with acute ischemic stroke who received the treatment in the Cadre Ward and Mental Ward, Department of Internal Medicine, Chengzhanyuan District, First Hospital Affiliated to Zhejiang University from March 1996 to June 2004 were recruited. They all met the diagnosis criteria revised by the Fourth Academic Conference of National Cerebrovascular Diseases in 1995 and were diagnosed as acute ischemic stroke by skull CT. They were informed of therapeutic plan and detected items. According to 1：1 paired principle in gender, 90 enrolled patients were assigned into treated group （n=45） and control group （n=45）. There were 39 male and 6 female in the treatment group, and they were aged （76±6）years, ranging from 71 to 84 years, and hospitalized at the 14^th to 76^th hours after onset. There were 39 male and 6 female in the control group, and they were aged （76±6）years , ranging from 70 to 82 years, and hospitalized at the 16^th to 72^th hours after onset. METHODS： Therapeutic method： Patients of treated group received modified hemodilution combined therapy. 200 mL whole blood of patients was exchanged with 500 mL dextran-40 （including 20 mL danshen parenteral solution and 32 mg heparin） at the beginning of therapy; From the 2^nd day, compound huangqi tea bag （Huangqi mainly, including danshen, honghua, chuanxiong, shishao and a little acetyl salicylic acid） was made, twice a day, 1 bag once. At the same time, the above-mentioned dextran-40 liquid of 500 mL was intravenously injected, once a day, 14 days in total; On the 6^th day after therapy, the above-mentioned aseptic autoblood stored in refrigerator at 4℃ was transfused back into the patients following pre-treatment of high-concentration oxygenation and ultraviolet irradiation by light quantum instrument. Patients of control group were intravenously injected of 0.4 g venoruton（Traditional Chinese medicine compound parenteral solution for promoting blood circulation and removing blood stasis ） and 50 g/L glucose of 500 mL, 75 mg acetosal was taken orally, once a day, 14 days in total. ② Measurement and observation of index： Blood coagulation index, change of platelet aggregation rate and change of hemorrheology of patients in two groups were monitored before and after therapy. The level of blood lipid of patients in two groups was measured with American Beckman automatic biochemistry analyzer. Blood flow rate of middle cerebral artery of resting electrocardiogram were measured with American HP SONOS 2500 sonoscope. Neuro-dysfunction score revised in the national conference （1995） was used to evaluate the recovery of neurological function of the patients in two groups at the 3rd, 5^th, 7^th and 14^th days after therapy. ③Therapeutic effect and adverse effect were observed at the same time. MAIN OUTCOME MEASURES ： ① Changes of coagulation index, blood lipid level and hemorheology; ② Blood flow rate of middle cerebral artery and NDS of patients with acute ischemic stroke in two groups; ③Adverse effect of drug. RESULTS： Totally 90 patients were enrolled in the experiment. One patient from treated group died of hyperosmolar nonketotic diabetic coma of complicated diabetes mellitus. One patient from control group died of severe pulmonary infection. The rest 88 patients entered the stage of result analysis. ① Change of coagulation index and platelet aggregation rate： prothrombin time （PT）, activated partial thromboplastin time （APTT） and thrombin time （TT） of patients after therapy were significantly longer than those before therapy in the treated group and those after therapy in control group [After therapy in treated group： （18.4±1.9）, （41.8±2.1）, （19.7±1.7） s, Before therapy in treated group： （13.4±1.3）, （35.8±1.3）, （12.5±0.9） s, After therapy in control group： （16.9±1.5）, （39.1±1.1）, （11.9±2.1） s, P〈 0.05]：Concentration of fibrinogen （Fbg） after therapy was significantly lower than that before therapy in the treated group and that after therapy in control group[After therapy in treated group： （3.4±0.4） g/L; Before therapy in treated group： （4.3±0.7） g/L; After therapy in control group：（4.0±0.6） g/L; P 〈 0.05]. Platelet aggregation rate decreased from （37.92 ±0.85）% before therapy to （26.42±1.01）% after therapy （P 〈 0.01）. ②Change of blood lipid level： Levels of total cholesterol （TC）, triacylglycerol（TG） and low density lipoprotein cholesterol （LDL-C） of patients after therapy were significantly lower than those before therapy in treated group and those after therapy in control group [After therapy in treated group： （5.2±0.9）, （1.9±0.9）, （2.08±1.1） mmol/L, before therapy in treated group： （5.9±1.2）, （2.8±0.9）, （3.94±0.5） mmol/L, After therapy in control group： （6.0±1.1）, （2.6±0.8）, （3.84±0.9） mmol/L, P 〈 0.05]. ③Change of hemorheology index： Hematocrit of patients of treated group was significantly lower after therapy than before therapy [Before therapy： （43.84±4.55）% ;After therapy： （40.48±4.02）%;P 〈 0.05]. Blood flow rate of middle cerebral artery of patients of treated group was significantly lower before therapy than after therapy [（90±1.2）, （97±2.1） cm/s,P〈 0.01]. ⑤NDS of patients in treated group was significantly lower than of control group 14 days after therapy. The total effective rate after therapy was significantly higher in the treated group than in the control group （93%,78%, P 〈 0.05）. ⑥There was no obvious adverse effect. CONCLUSION： Modified hemodilution combined therapy can improve hemorheology, decrease hematocrit, increase blood flow rate of middle cerebral artery, so as to improve the impaired clinical neurological function of elderly patients with acute cerebral thrombosis through anticoagulation and antiplatelet aggregative activity as well as regulating blood lipid.

Oncolytic virus-based hepatocellular carcinoma treatment:Current status,intravenous delivery strategies,and emerging combination therapeutic solutions

Current treatments for advanced hepatocellular carcinoma(HCC)have limited success in improving patients’quality of life and prolonging life expectancy.The clinical need for more efficient and safe therapies has contributed to the exploration of emerging strategies.Recently,there has been increased interest in oncolytic viruses(OVs)as a therapeutic modality for HCC.OVs undergo selective replication in cancerous tissues and kill tumor cells.Strikingly,pexastimogene devacirepvec(Pexa-Vec)was granted an orphan drug status in HCC by the U.S.Food and Drug Administration(FDA)in 2013.Meanwhile,dozens of OVs are being tested in HCC-directed clinical and preclinical trials.In this review,the pathogenesis and current therapies of HCC are outlined.Next,we summarize multiple OVs as single therapeutic agents for the treatment of HCC,which have demonstrated certain efficacy and lowtoxicity.Emerging carrier cell-,bioengineered cell mimetic-or nonbiological vehicle-mediated OV intravenous delivery systems in HCC therapy are described.In addition,we highlight the combination treatments between oncolytic virotherapy and other modalities.Finally,the clinical challenges and prospects of OV-based biotherapy are discussed,with the aim of continuing to develop a fascinating approach in HCC patients.

Combined targeted therapy and immunotherapy for cancer treatment

Although targeted therapies and immunotherapies have been effective againstseveral malignancies, the respective monotherapies are limited by low and/orshort-term responses. Specific inhibitors of oncogenic signaling pathways andtumor-associated angiogenesis can activate the anti-tumor immune responses byincreasing tumor antigen presentation or intratumor T cell infiltration. Additionalinsights into the effects and mechanisms of targeted therapies on the induction ofanti-tumor immunity will facilitate development of rational and effective combinationstrategies that synergize rapid tumor regression and durable response. Inthis review, we have summarized the recent combinations of targeted therapiesand immunotherapies, along with the associated clinical challenges.

Combined treatment promotes the long-range axon regeneration to right brain targets

Axons in the peripheral nervous system(PNS)can regenerate after injury.However,the adult mammalian central nervous system(CNS)loses the intrinsic regrowth ability.No robust axon regeneration occurs spontaneously after nerve injury,which was clearly observed by Ramon y Cajal in the early 20^(th) century(1,2).Due to lack

Therapeutic response and safety of different treatments for cutaneous leishmaniasis in patients: A retrospective cross-sectional study

Objective:To analyze the therapeutic response and safety of different treatments for cutaneous leishmaniasis,received by patients in the Program for the Study and Control of Tropical Diseases-PECET-Medellín-Colombia.Methods:This is a retrospective cross-sectional study of patients attended at PECET Research Center during 2016-2021.Relevant information regarding sociodemographic characteristics,history of leishmaniasis,characterization of current infection,treatment received,follow-up of therapeutic response and safety was collected from the medical records.Data were analyzed with Pearson's Chi-square association tests and Mann-Whitney U test using statistical software.Results:A total of 486 clinical records of patients were analyzed,and 356 received treatment.Eight different therapeutic alternatives(systemic,local and in combination)were analyzed.The therapeutic response of the different alternatives used(except thermotherapy)was higher than 50%.Most frequent adverse events were myalgias,arthralgias and headache,and vesicles for systemic and local treatment,respectively.Conclusions:Safety profile and performance of local therapeutic alternatives and combined schemes for the treatment of uncomplicated cutaneous leishmaniasis are an interesting option for the management of the disease.

Treatment of Cervical Spondylopathy with a Combined Therapy

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Effect of Combined Chemical Treatment on Physical, Mechanical and Chemical Properties of Posidonia Fiber

The aim of this study is to investigate the effect of chemical treatment method on the properties of Posidonia fibers. The chemical treatment which is carried out is a combined hydrogen peroxide and sodium hydroxide treatment. First, an investigation of the treatment processes was undertaken. Secondly, the physical properties (linear density, diameter and ratio length per diameter), the mechanical properties (tenacity, elongation) and chemical properties (FT-IR spectra and X ray diffraction) of posidonia fibers were investigated. The optimum operating conditions were identified using a factorial design.

Combined Use of the Points Shenmai and Zhaohai for Treatment of Craniofacial Diseases

Shenmai (BL 62) and Zhaohai (KI 6), first recorded in A Classic of Acupuncture and Moxibustion (针灸甲乙经), are respectively the starting point of the YangqiaoChannel and the Yinqiao Channel, and they are two of the eight confluence points. Although records about the right-left compatible use of these two points can be found in documents, the same-side compatible use of them has never been heardabout. Inspired by the good therapeutic effects in the treatment of paralytic strabismus by means of the same-side compatible use of these two points1, the author has applied this compatible use of them in the treatment of craniofacial diseases and obtained obvious therapeutic effects. Some of the sample cases are reported in the following. ……

Treatment of Sepsis by Hemofiltration Combined with Plasma Exchange in One Case

Female patients,44 years old,due to'regular peritoneal dialysis5 years,stomach ache 1 week'admission.Previous had 2 times for'Peritoneal dialysis related peritonitis'in hospital,after anti-infection treatment patients symptoms improved and discharged.1 week ago in patients admitted to hospital because of abdominal pain again.Physical:abdominal tenderness,bowel sounds hyperthyroidism.Laboratory inspection index:CRP:172.22 mg/l,WBC:23.26×10~9/L,NEU%:89.23%,D dimer:3 800 ng/ml,PCT:14.86 ng/ml。

CLINICAL OBSERVATION ON COMBINED TREATMENT OF 360 CASES OF PROSTATITIS WITH ACUPUNCTURE OF SISHENCHONG POINT, ETC. AND SELF-DRAFTED PRESCRIPTION I, II AND III

In the present series of observations, 360 cases of prostatitis were treated with acupuncture of Sishenchong (EX HN 1), etc. and self drafted prescription I, II and III. After 4 courses (28 sessions) of treatment, 321 cases (89.17%) were cured, 35 cases (9.72%) had improvement and 4 cases (1.11%) failed. The total effective rate was 98.89%.