Immunotherapy for esophageal cancer:Where are we now and where can we go

Immune checkpoint inhibitor therapy has dramatically improved patient prognosis,and thereby transformed the treatment in various cancer types including esophageal squamous cell carcinoma(ESCC)in the past decade.Monoclonal antibodies that selectively inhibit programmed cell death-1(PD-1)activity has now become standard of care in the treatment of ESCC in metastatic settings,and has a high expectation to provide clinical benefit during perioperative period.Further,anti-cytotoxic T-lymphocyte–associated protein 4(CTLA-4)monoclonal antibody has also been approved in the treatment of recurrent/metastatic ESCC in combination with anti-PD-1 antibody.Well understanding of the existing evidence of immune-based treatments for ESCC,as well as recent clinical trials on various combinations with chemotherapy for different clinical settings including neoadjuvant,adjuvant,and metastatic diseases,may provide future prospects of ESCC treatment for better patient outcomes.

Re-evaluating the role of pelvic radiation in the age of modern precision medicine and systemic therapy

The efficacy of pelvic radiation in the management of locally advanced stage rectal cancer has come under scrutiny in the context of modern precision medicine and systemic therapy as evidenced by recent clinical trials such as FOWARC(J Clin Oncol 2019;37:3223-3233),NCT04165772(N Engl J Med 2022;386:2363-2376),and PROSPECT(N Engl J Med 2023;389:322-334).In this review,we comprehensively assess these pivotal trials and offer additional insights into the evolving role of pelvic radiation in contemporary oncology.

2022 Chinese expert consensus and guidelines on clinical management of toxicity in anti-CD19 chimeric antigen receptor T-cell therapy for B-cell non-Hodgkin lymphoma

Adoptive cellular immunotherapy with chimeric antigen receptor(CAR)T cells has emerged as a novel modality for treating relapsed and/or refractory B-cell non-Hodgkin lymphoma(B-NHL).With increasing approval of CAR T-cell products and advances in CAR T cell therapy,CAR T cells are expected to be used in a growing number of cases.However,CAR T-cell-associated toxicities can be severe or even fatal,thus compromising the survival benefit from this therapy.Standardizing and studying the clinical management of these toxicities are imperative.In contrast to other hematological malignancies,such as acute lymphoblastic leukemia and multiple myeloma,anti-CD19 CAR T-cell-associated toxicities in B-NHL have several distinctive features,most notably local cytokine-release syndrome(CRS).However,previously published guidelines have provided few specific recommendations for the grading and management of toxicities associated with CAR T-cell treatment for B-NHL.Consequently,we developed this consensus for the prevention,recognition,and management of these toxicities,on the basis of published literature regarding the management of anti-CD19 CAR T-cell-associated toxicities and the clinical experience of multiple Chinese institutions.This consensus refines a grading system and classification of CRS in B-NHL and corresponding measures for CRS management,and delineates comprehensive principles and exploratory recommendations for managing anti-CD19 CAR T-cell-associated toxicities in addition to CRS.

Observation on the Effect of Non-Invasive Ventilator Combined with Conventional Therapy in the Treatment of Chronic Obstructive Pulmonary Disease Complicated with Respiratory Failure

Objective:To explore the clinical effect of a non-invasive ventilator combined with conventional therapy in the treatment of patients with chronic obstructive pulmonary disease(COPD)combined with respiratory failure.Methods:68 patients with COPD combined with respiratory failure treated in our hospital from September 2021 to October 2023 were selected as the research subjects.Using the random number table method,they were divided into a control group and an experimental group of 34 cases each.The control group received conventional symptomatic treatment,and the experimental group received non-invasive ventilator treatment based on the control group.The clinical effects,blood gas indicators(partial pressure of carbon dioxide(PaCO_(2)),partial pressure of oxygen(PaO_(2)),arterial oxygen saturation(SaO_(2))),lung function(forced expiratory volume in 1 second(FEV1),forced vital capacity(FVC),6 min walking distance),complications,and inflammatory factor levels(c-reactive protein(CRP),interleukin-6(IL-6),neutrophil-to-lymphocyte ratio(NLR))of the two groups of patients were observed.Results:(1)The clinical efficacy of the patients in the experimental group(33/97.06%)was more significant as compared with the control group(25/73.53%)(P<0.05);(2)After treatment,the clinical efficacy of the two groups of patients in terms of FEV1,FEV1/FVC,6-minute walking distance,PaO_(2)and SaO_(2)all increased in the experimental group as compared to that of the control group(P<0.05);(3)After treatment,the PaCO_(2),CRP,IL-6,and NLR of the two groups of patients decreased,and the decrease in the experimental group was higher than that of the control group(P<0.05);(4)The patients’complication rate in the experimental group(2/5.88%)was lower as compared to that of the control group(9/26.46%)(P<0.05).Conclusion:Non-invasive ventilators combined with conventional therapy achieved good clinical results in treating patients with COPD and respiratory failure.

Indications of external radiotherapy for hepatocellular carcinoma from updated clinical guidelines: Diverse global viewpoints

significantly vary among regions.Modern standard treatments commonly require multidisciplinary approaches,including applications of up-to date medicine and advanced procedures,and necessitate the support of socioeconomic systems.For these reasons,a number of clinical guidelines for HCC from different associations and regions have been presented.External beam radiation therapy was contraindicated for HCC until a few decades ago,but with the development of new technologies,its application has rapidly increased as selective irradiation for tumorous lesions became possible.Most of the guidelines had been opposed or indifferent to radiotherapy in the past,but several guidelines have introduced indications and recommendations for radiotherapy in their updated versions.This review will discuss the characteristics of important guidelines and their contents regarding radiotherapy and will also provide guidance to physicians who are considering applications of locoregional modalities that include radiotherapy.

A review on re-emerging bacteriophage therapy in the era of XDR

In the present medicine world antibiotic resistance is one of the key threats to universal health coverage.Researchers continue to work hard to combat this global health concern.Phage therapy,an age-old practice during the early twentieth century,was outshined by the discovery of antibiotics.With the advent of widespread antibiotic resistance,phage therapy has again redeemed itself as a potential alternative owing to its adeptness to target bacteria precisely.Limited side effects,the ability to migrate to different body organs,a distinct mode of action,and proliferation at the infection site,make phages a profitable candidate to replace conventional antibiotics.The progressive outcome of numerous in vitro studies and case reports has validated the clinical efficacy of phage therapy.The bright perspective of using phages to treat bacterial infections has fueled enormous medical research to exploit their potential as therapeutics.The gaps in the information about phages and the lack of consent for clinical trials is major hurdle for consideration of phage therapy.Crafting phage therapy as a reality in medicine requires a coordinated effort from different fraternities.With this review,we aim to emphasize the importance of phage therapy in modern medicine.This review explains their historical journey,basic phage biology,cross-talk with the host immunity,obstacles with phage therapy,and their possible remedies.Comprehensive data on the various significant clinical trials of phage therapy has been presented.We evaluated the efficacy of antibiotics and phage therapy in part and in combination,along with recent progress and future perspectives of phage therapy.

The Physical and Clinical Aspects of Radiation Therapy in Skin Cancer and Subcutaneous Tissue Neoplasm

Cancers, malignant melanoma and sarcomas of the skin represent the most common group of malignancies in humans. The main treatment method of almost all skin cancers and subcutaneous tissue tumours is surgery, which consists of complete removal of a neoplastic lesion, with an adequate margin of healthy tissue. Radiotherapy plays an adjuvant role in this process, meaning complementing of the surgical procedure. This study compared four methods of irradiation treatment of cancer located in the skin or in subcutaneous tissues: contact brachytherapy, conventional orthovoltage therapy, electron beam conformal teleradiotherapy and IMRT dynamically shaped photonic beams conformal teleradiotherapy. In order to compare the methods and techniques of surface radiotherapy, following specific objectives were formulated. At the beginning in order to compare the scopes of the absorbed doses at different tissue depths, an analysis of parameters describing particular beams or radiation source has been performed—the curves for the absorbed-dose depth drop-offs. Doses distribution in tissue-like phantoms stimulating homogeneous cuboidal tissue block has been determined. A quality comparison of dose distribution in 2D and 3D treatment planning system for contact brachytherapy application has been made. The dose distribution for electron beam in the system has been determined. Conformal plannings for electron beam treatment, contact brachytherapy applicator treatment and 4 photon beams treatment optimized in IMRT technology have been performed. Dose distribution has been performed for the irradiated female patient within the well chest—the target included the recurrence area in the post-operative scar. The radiation therapy with X-rays has actually been completely eliminated from skin cancer and subcutaneous tissue radiotherapy by the electrons generated in linear accelerators, contact brachytherapy HDR and by high-energy photons used in conformal techniques, ex. IMRT. It is because the residual dose beyond the target is the highest for single X-ray beam. Although in brachytherapy HDR a rapid dose drop-off is observed, 5 cm from its normalization level for the target the residual radiation remains at the level of several percent. So, both X-rays beam radiation and brachytherapy in skin cancer treatment is connected with the administration of the dose with a high gradient in the health tissues. The dose distribution for photon conformal techniques IMRT or for electron radiation looks different. There with the dose normalization at the level of 90% or 85% we deal with the dose layer, the division does not exceed 15% of heterogeneity.

Clinical benefits of rational-emotive stress management therapy for job burnout and dysfunctional distress of special education teachers

It has been observed that managing job burnout and dysfunctional distress constitute part of the major challenges among special educators,and that empirical data on the management of burnout and dysfunctional distress associated with the job of special education teachers are lacking in the literature.The current article discusses the clinical benefits of a rational-emotive stressmanagement therapy program in reducing the level of job burnout symptoms and dysfunctional distress in special education teachers,using evidence from a 2018 clinical trial study that reported the efficacy of this intervention.Results show the clinical benefits and implications of conducting a rational-emotive stress management intervention,and recommendations are made for future research.

Immuno-Chemotherapy Using Repeated Vaccine Treatment Can Produce Successful Clinical Responses in Advanced Metastatic Melanoma

Advanced Stage IV and IIIc melanoma has a dismal survival, with or without, standard chemotherapy. New therapies are required to improve survival and reduce morbidity. Repeated vaccine dosing does not appear to have been explored, so Vaccinia Melanoma Cell Lysate (VMCL) vaccine repetitive therapy was tested, either alone, or combined with chemotherapy. 37 patients (31 Stage IV [M1a(6), b(7), c(18)] and 6 Stage IIIc) were studied using intra-dermal VMCL vaccine therapy. If disease progressed, vaccine was continued with standard chemotherapy (DTIC and/or Fotemustine). Overall survival was assessed and clinical responses were also recorded. From vaccine commencement, median overall follow-up was 10 months. Survivals ranged from 4 to 73 months. Median (mean) overall survival was 10 (23.5) months;overall survival at 1, 2 and 3 years was 40.5%, 21.6% and 10.8% respectively. CR and PR occurred in 18.9% (7) and 18.9% (7) of patients;these were durable for up to 6.1 years in 4 patients. Stable disease was noted in a further 17 patients (45.9%). In 6 patients (16.2%) no response to therapy was apparent. Repeated vaccinations with or without chemotherapy produced strong, durable clinical responses with overall survival > 23 months occurring in nearly 25% of advanced melanoma patients. The overall disease control rate (CR, PR and SD) was 83.7%, including CR in very advanced cases. These results, in a largely unselected population of advanced metastatic melanoma patients, compare very favourably with other regimens, and notably were associated with minimal, if any, toxicity. Further analysis of this approach appears warranted.

Exclusive Hormonal Therapy in Breast Cancer in Elderly Women:Clinical Response and Survival over 10 Years

Breast cancer is the first cancer of women in the world and in France.In very elderly patients,the treatment options are often very limited.Neoadjuvant hormone therapy has shown similar or even better results than chemotherapy.This is why we decided to evaluate the clinical response following exclusive hormonal therapy and the 5,then 10 years survival in these very elderly women.This was a retrospective,longitudinal cohort-type study with descriptive and analytical purposes.The study population consisted of 59 patients,with an average age of 85 years.Fifteen(15,25%)of our patients had a complete clinical response after two years of treatment,16(27%)a partial clinical response,23(39%)lesion stabilization and 5(9%)cancer progression.The presence of metastasis at diagnosis increased the risk of cancer progression by 2.84.Overall 5-year survival was 72.5%,and breast cancer mortality 5.88%.The 10-year survival was 27.5%and breast cancer mortality 15%.In the age group 85 and over increased the risk of death by 3.25 in the first 10 years of treatment.The clinical response after 2 years was marked by a low rate of cancer progression.Mortality over 5 and 10 years was mostly related to patient comorbidities.

Clinical application of multidisciplinary teams in tumor therapy

Multidisciplinary team （MDT） model is a diagnostic and treatment model characterized by interdisciplinarity, integration, centralism, individualization, and precision and is becoming more common in the management of complex malignancies. MDT emphasizes team spirit and a personalized treatment strategy according to the actual condition of each patient. A cooperative and effective multidisciplinary team is an important guarantee for delivering high-quality services to patients. Under the guidance of a medical humanistic concept, MDT provides reasonable, effective, convenient, and a full range of excellent quality medical service to patients. The MDT maximizes patient benefits, and it is the developmental direction for large-scale general hospitals. At the same time, the MDT is also an important measure to strengthen the core competitiveness of hospitals. Here, we introduce the clinical application of the model in tumor therapy as well as the current state and development in our hospital.

Mesenchymal stem cell therapy in retinal and optic nerve diseases: An update of clinical trials

Retinal and optic nerve diseases are degenerative ocular pathologies which lead to irreversible visual loss. Since the advanced therapies availability, cell-based therapies offer a new all-encompassing approach. Advances in the knowledge of neuroprotection, immunomodulation and regenerative properties of mesenchymal stem cells(MSCs) have been obtained by several preclinical studies of various neurodegenerative diseases. It has provided the opportunity to perform the translation of this knowledge to prospective treatment approaches for clinical practice. Since 2008, several first steps projecting new treatment approaches, have been taken regarding the use of cell therapy in patients with neurodegenerative pathologies of optic nerve and retina. Most of the clinical trials using MSCs are in Ⅰ/Ⅱ phase, recruiting patients or ongoing, and they have as main objective the safety assessment of MSCs using various routes of administration. However, it is important to recognize that, there is still a long way to go to reach clinical trials phase Ⅲ-Ⅳ. Hence, it is necessary to continue preclinical and clinical studies to improve this new therapeutic tool. This paper reviews the latest progress of MSCs in human clinical trials for retinal and optic nerve diseases.

An overview of systematic reviews of clinical evidence for cupping therapy

Background:As a traditional treatment method,cupping therapy is widely used in Asian countries.This overview of systematic reviews (SRs) investigated the effectiveness and safety of cupping therapy through an evidence-based approach.Methods:SRs that assessed the effectiveness of cupping therapy for any type of disease were searched through 6 electronic databases.Target diseases,cupping methods,numbers and types of included studies,quality of included trials,main results (including meta-analysis re sults),and authors' conclusions of SRs were extracted.The Assessment of Multiple Systematic Reviews measurement was used to evaluate methodologic quality of the SRs.Results Eight SRs met the inclusion criteria and effectiveness and safety of cupping therapy for 11 diseases were assessed.All included SRs were of good methodologic quality.However,quality of trials included in the SRs was generally poor.Meta-analysis was performed in 4 studies.Results:showed cupping therapy (alone or combined with other interventions) was better than medications (or other interventions alone) for herpes zoster,acne,facial paralysis,low back pain,or cervical spondylosis.One review reported adverse events,including hematoma,increased pain and tingling following cupping treatment.Conclusions:Cupping therapy may be beneficial for pain-related conditions,acne,and facial paralysis.However,a firm conclusion could not be drawn due to the insufficient number of included reviews and the low quality of the original studies.

PHOTODYNAMIC THERAPY—AN UPDATE ON CLINICAL APPLICATIONS

Photodynamic therapy(PDT)has received increased attention since the regulatory approvals of several photosensitizers and light applicators in numerous countries and regions around the world.In recent years,much progress has been seen in basic research as well as clinical application.PDT clinical application has now extended from treating malignant diseases to nonmalignant diseases.This review article will present recent clinical data published in English journals.The data will be organized according to their clinical specialties.The new development and future direction in clinical applications of PDT for the management of both malignant and nonmalignant diseases will be discussed.

Eye-acupuncture as adjuvant therapy for stroke:A bibliometric analysis of clinical studies

Background:Eye-acupuncture(EA)is a fine-needle acupuncture therapy for systemic diseases.This bibliometric analysis aims to provide a comprehensive review of the characteristics of EA for ischemic or hemorrhagic apoplexy based on clinical studies.Methods:A total of 195 clinical studies from six databases such as CNKI,VIP,Wanfang Data,SinoMed,PubMed and the Cochrane Library from inception to December 31,2017 were included.Bibliometric information mainly including study type,participant characteristics,intervention and comparison details,and outcomes were extracted.Data was analyzed descriptively using SPSS
software to determine their distribution(range,interquartile range)and central tendency(median).Results:The studies covered 108 RCTs,36 controlled clinical trials,45 case series and 6 case reports on EA for treatment of ischemic or hemorrhagic apoplexy,involved 15466 stroke patients.EA was used at different stages of ischemic or hemorrhagic apoplexy:acute stage(n Z 38),recovery(n Z 32),sequela(n Z 13)and unclear(n Z 112).The most frequently used EA acupoints were in the upper-jiao and lower-jiao regions.The commonly used comparisons were EA alone versus traditional acupuncture,or EA plus traditional acupuncture versus traditional acupuncture.Neurological deficit scale,Modified Barthel Index,and activities of daily living were the most frequently used outcome measures.Conclusion:EA as an adjuvant therapy is effective and safe in treating stroke at acute and recovery stages,but high-quality RCTs are lacking.

Stem cell therapy for COVID-19 and other respiratory diseases:Global trends of clinical trials

Respiratory diseases,including coronavirus disease 2019 and chronic obstructive pulmonary disease(COPD),are leading causes of global fatality.There are no effective and curative treatments,but supportive care only.Cell therapy is a promising therapeutic strategy for refractory and unmanageable pulmonary illnesses,as proved by accumulating preclinical studies.Stem cells consist of totipotent,pluripotent,multipotent,and unipotent cells with the potential to differentiate into cell types requested for repair.Mesenchymal stromal cells,endothelial progenitor cells,peripheral blood stem cells,and lung progenitor cells have been applied to clinical trials.To date,the safety and feasibility of stem cell and extracellular vesicles administration have been confirmed by numerous phase I/II trials in patients with COPD,acute respiratory distress syndrome,bronchial dysplasia,idiopathic pulmonary fibrosis,pulmonary artery hypertension,and silicosis.Five routes and a series of doses have been tested for tolerance and advantages of different regimes.In this review,we systematically summarize the global trends for the cell therapy of common airway and lung diseases registered for clinical trials.The future directions for both new clinical trials and preclinical studies are discussed.

The neuroprotective effects of oxygen therapy in Alzheimer’s disease:a narrative review

Alzheimer’s disease(AD)is a degenerative neurological disease that primarily affects the elderly.Drug therapy is the main strategy for AD treatment,but current treatments suffer from poor efficacy and a number of side effects.Non-drug therapy is attracting more attention and may be a better strategy for treatment of AD.Hypoxia is one of the important factors that contribute to the pathogenesis of AD.Multiple cellular processes synergistically promote hypoxia,including aging,hypertension,diabetes,hypoxia/obstructive sleep apnea,obesity,and traumatic brain injury.Increasing evidence has shown that hypoxia may affect multiple pathological aspects of AD,such as amyloid-beta metabolism,tau phosphorylation,autophagy,neuroinflammation,oxidative stress,endoplasmic reticulum stress,and mitochondrial and synaptic dysfunction.Treatments targeting hypoxia may delay or mitigate the progression of AD.Numerous studies have shown that oxygen therapy could improve the risk factors and clinical symptoms of AD.Increasing evidence also suggests that oxygen therapy may improve many pathological aspects of AD including amyloid-beta metabolism,tau phosphorylation,neuroinflammation,neuronal apoptosis,oxidative stress,neurotrophic factors,mitochondrial function,cerebral blood volume,and protein synthesis.In this review,we summarized the effects of oxygen therapy on AD pathogenesis and the mechanisms underlying these alterations.We expect that this review can benefit future clinical applications and therapy strategies on oxygen therapy for AD.

Investigating the Effectiveness of Dialectical Behavior Therapy in Clinical Symptoms, Anger Control and Emotional Regulation of Bully Children

The present study aims to investigate the effectiveness of dialectical behavior therapy in clinical symptoms, anger control and emotional regulation of bully children. This research is a pretest-posttest quasi-experimental study design with a nonequivalent control group. The research sample comprises 24 bully children who were purposefully selected from among the students who had responded positively to the researcher’s call. The participants were randomly assigned into two experimental and control groups. Group therapy intervention was conducted on the experimental group during ten sessions. The tools applied in this study consisted of Cognitive Emotion Regulation Questionnaire by Garnefski et al., State-Trait Anger Expression Inventory by Spielberger and Bullying Scale by Illinois, Espelage and Holt and the subjects answered to their questions in the stage of pretest and posttest. In this research, the data was analyzed based on the analysis of covariance test and with the aid of SPSS software. The findings demonstrated that dialectical behavior therapy has a significant impact on clinical symptoms, anger control and its components and emotional regulation and its components (P < 0.01).

Impact of modern antiviral therapy of chronic hepatitis B and C on clinical outcomes of liver disease

Chronic infections with the hepatitis B and C viruses have significant worldwide health and economic impacts.Previous treatments for hepatitis C such as interferon and ribavirin therapy were ineffective and poorly tolerated by patients.The introduction of directly acting curative antiviral therapy for hepatitis C and the wider use of nucleos(t)ide analogues for suppression of chronic Hepatitis B infection have resulted in many positive developments.Decreasing the prevalence of hepatitis B and C have concurrently reduced transmission rates and hence,the number of new infections.Antiviral treatments have decreased the rates of liver decompensation and as a result,lowered hospitalisation and mortality rates for both chronic hepatitis B and C infection.The quality of life of chronically infected patients has also been improved significantly by modern treatment.Antiviral therapy has stopped the progression of liver disease to cirrhosis in certain patient cohorts and prevented ongoing hepatocellular damage in patients with existing cirrhosis.Longer term benefits of antiviral therapy include a reduced risk of developing hepatocellular carcinoma and decreased number of patients requiring liver transplantation.This review article assesses the literature and summarises the impact of modern antiviral therapy of chronic hepatitis B and C on clinical outcomes from liver disease.

Clinical Experience of Pricking Therapy

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