Evidence-Based Nursing Practice of Reducing Immune-Related Skin Toxicity of Tumor Patients Guided by Sensitive Indicators

Purpose research on nursing sensitive indicators in tumor Patients application effect in immune-related skin toxicity management. Method select our hospital April to June, 202360 cases patients with immune therapy settings as the control group. August-October, 2023 60 cases the patients treated with immune therapy were the experimental group. The control group adopted regular nursing methods, while the experimental group sensitive Indicators, evidence-based give preventive care. The social situation, psychological state, physical function, quality of life score, incidence of skin toxicity caused by immune checkpoint inhibitors, moderate and above of the two groups of patients were compared. Incidence of skin toxicity. Result: experience group SAS score, SDS score higher than the control group, the difference was statistically significant (P < 0.05);The incidence of skin toxic reactions caused by immune checkpoint inhibitors and the incidence of moderate and above skin toxic reactions in the experimental group are lower than those in the control group, and the difference is statistically significant (P < 0.05). Conclusion: sensitive indicator guidance evidence-based preventive care can reduce the degree of immune-related skin toxicity, improve the psychological state and quality of life of tumor patients treated with immune therapy and reduce the incidence of adverse reactions, improve nursing quality and patient satisfaction.

Effects of Yinzhihuang oral liquid and albumin on bilirubin, inflammatory factors, immune indexes and related factors in neonatal pathologic jaundice

Objective: To explore the effects of Yinzhihuang oral liquid and albumin on bilirubin, inflammatory factors, immune indexes and related factors in neonatal pathologic jaundice. Methods: A total of 134 neonates with pathologic jaundice admitted to our hospital from May 2017 to April 2018 were randomly selected as the control group (n=67) and the observation group (n=67), the control group was treated with albumin, the observation group was treated with Yinzhihuang Oral Liquid on the basis of the control group. The bilirubin, inflammatory factors, immune indicators, alpha-fetoprotein (AFP) and transferrin (TRF) were compared and analyzed before and after treatment. Results: After treatment, the levels of TBIL, DBIL and IBIL in both groups were significantly lower than those before treatment (P<0.05), and the levels of TBIL, DBIL and IBIL [(118.60±10.85) μmol/L, (6.95±1.52) μmol/L, (115.30±14.20)μmol/L] in observation group were significantly lower than those in control group;the levels of CRP and IL-6 in both groups were significantly lower than those before treatment (P<0.05), and the levels of CRP and IL-6 [(8.26±2.07) mg/L, (12.69±2.15) pg/mL] in observation group were significantly lower than those in control group (P<0.05);the levels of CD4+, CD4+/CD8+ in both groups were significantly higher than those before treatment (P<0.05), while the levels of CD8+ was significantly lower than that before treatment, the levels of CD4+, CD4+/CD8+ [(47.08±5.70)%, (2.08±0.41)] in observation group were significantly higher than those in control group (P<0.05), and the level of CD8+ [(22.90±2.05)%] was significantly lower than that in control group (P<0.05);the levels of AFP in significantly higher than before treatment (P<0.05), and the levels of AFP [(12.69±3.04)mg/L] in observation group were significantly lower than those in control group (P<0.05), the levels of TRF [(2.02±0.35) g/L] were significantly higher than those in control group (P<0.05). Conclusions: The combination of Yinzhihuang oral liquid and albumin can effectively reduce the bilirubin level in neonatal jaundice, inhibit its inflammatory reaction, enhance the cellular immune function and improve the expression of AFP and TRF, which is of clinical significance.

Inflammatory Cytokine Secretion Status of Bone Marrow Cells and Clinical Significance in Immune-related Hematocytopenia

Objective To observe the expression of inlfammatory molecules in bone marrow immune cells of patients with immune-related hematocytopenia (IRH), and to investigate the immune mechanism and clinical signiifcance of the disease. Methods Total of 36 IRH patients were selected as observation group and 30 healthy people were taken as control group. Serum cytokines levels, activity of immunocytes and expression of HLA-DR were detected. Immune lfuorescence was applied to observe the expression state of immunologic molecules and cytokines in IRH patients. Results Serum cytokines were elevated in various degrees in observation group. Compared with the control group, the cytokines levels were significantly higher (P < 0.05). After treatement with immunosuppressive drugs, the serum levels of cytokines in observation group reduced to a level close to the control group. HLA-DR were upregulated in activated tissue basophils, eosinophils, dendritic cells (DC) and macrophages of bone marrow in IRH patients, and POX activity in these immunocytes of IRH was higher than that of the control group. Immune molecules were highly expressed in eosinophils, DC and macrophages. Conclusions It is demonstrated that antibodies or self-reactive lymphocytes were produced in IRH marrow, which would cause lesions of hemocytes, and lead to pathological process ifnally. Structure of hematopoietic cells mutated and these cells might be acted as target cells of immunocytes in the pathological process. Immunocytes could secrete inlfammatory factors and lead to immunologic injury of hemocyte.

Pericardial Effusion with Tamponade, an Immune-Related Adverse Event Associated with Nivolumab Therapy: A Case Report and Review of the Literature

Immune checkpoint inhibitors have shown to be very effective when treating lung cancer. Nivolumab, a programmed death-1 (PD-1) inhibitor has been approved for the treatment of metastatic non-squamous and squamous NSCLC. Immunotherapy with checkpoint inhibitors are associated with toxicities defined as immune-related adverse events (irAEs). The most common irAEs are rash, colitis, hepatitis, pneumonitis, and endocrinopathies. Although any organ system can be affected, other rare irAEs can occur and affect the bone marrow, pancreas, and the neurologic and cardiac systems. Pericardial effusion induced by immunotherapy is uncommon and has been described only in a few case reports. Immune-related adverse events usually develop within the first weeks to months after treatment initiation. This is a case report of a 52-year-old male patient with metastatic squamous-cell lung cancer who had a massive pericardial effusion secondary to treatment with nivolumab as second line treatment. During his hospital stay, the patient underwent pericardiocentesis and treatment with corticosteroids. A CT scan after these treatments revealed complete tumor response and minimal pericardial effusion. Nivolumab was definitively ceased. The patient continues to show complete response for 16 months. In general, Nivolumab is well-tolerated and has an excellent safety profile. However, it is important to be aware of life-threatening immune-related adverse events, particularly cardiac toxicity. Consensus guidelines regarding the treatment of the most common irAEs have been established. The optimal management of irAEs is based on clinical experience. It’s crucial to report new or rare irAEs to conduct prospective trials to evaluate the best treatment strategy.

Effects of flexible ureteroscopy combined with percutaneous nephrolithotomy on inflammatory immune indexes and related factors in patients with renal calculi

Objective:To explore the effects of flexible ureteroscopy combined with percutaneous nephrolithotomy on inflammatory immune indexes and related factors in patients with renal calculi.Methods: From December 2016 to November 2017, 97 patients with renal calculi were selected and divided into control group (48 cases) and observation group (49 cases), the control group was treated with percutaneous nephrolithotomy. On the basis of the treatment of the control group, the observation group was treated with ureteroscopic lithotripsy. The changes of inflammatory mediators, immune index, thyroxine (TH), urokinase (UK) and renal function were compared between the two groups before and after treatment.Results: After treatment, the levels of prostaglandin E2 (PGE2), substance P (SP), nitric oxide (NO) and lipid peroxide (LPO) in the two groups were significantly higher than those before treatment, and the levels of PGE2, SP, NO and LPO in the control group were significantly higher than those in the observation group;the levels of CD4+, CD4+/CD8+ in the two groups were significantly lower than those before treatment, but the levels of CD8+ were significantly higher than those before treatment, and the levels of CD4+, CD4+/CD8+in the control group were significantly lower than those in the observation group, and the levels of CD8+ were significantly higher than those in the observation group;the levels of TH in the two groups were significantly lower than those before treatment, but the levels of UK were significantly higher than those before treatment, and the levels of TH in the observation group were significantly lower than those in the control group, and the levels of UK were significantly higher than those in the control group;the levels of urea nitrogen (BUN), serum creatinine (Scr), cystatin C (CysC) in the two groups were significantly higher than those before treatment, and the levels of BUN, Scr, CysC in the control group were significantly higher than those in the observation group. Conclusions:The combination of ureteroscope and percutaneous nephroscope can relieve inflammation stress, alleviate immunosuppression, enhance stone clearance and reduce the damage to renal function. It is of clinical significance.

Identification of an immune-related signature for the prognosis of uveal melanoma

AIM:To construct an immune-related prognostic signature(IPS)that can distinguish and predict prognosis in uveal melanoma(UM).METHODS:The transcriptomic data and clinicopathological information of 80 UM patients were extracted from the TCGA database.These patients were randomly assigned to a training and a testing set.RESULTS:Lasso Cox analysis was performed for the prognostic immune-related genes to develop an IPS for UM in the training set.The signature was validated in both the testing set and entire cohort.We confirmed the prognostic value of our IPS in distinct subgroups and found its association with the T stage and basal diameter of the tumor.Tumor Immune Estimation Resource database analysis revealed that the IPS was negatively correlated with the infiltration of neutrophils and dendritic cells,but positively correlated with the infiltration level of CD8+T cells.In addition,we demonstrated that immune checkpoints containing PD-1,CTLA-4,IDO,and TIGIT were moderately associated with the IPS.CONCLUSION:This is the first study to develop and validate an immune-related signature with the ability of predicting prognosis for UM patients.Further studies are needed to validate its prediction accuracy.

Immune Checkpoint Inhibitor Related Neuropathic Adverse Effects on Cancer Patients

With the recent development and clinical application, immune checkpoint inhibitors (ICIs) intervention is being increasingly common for multiple malignancies. With these, prospect on focus creates an increasing necessity for an early recognition with proper documentation of upcoming treatment-related toxicities. These treatment-related toxicities are generally termed as immune-related adverse effects (irAEs) [1]. It is a known fact that the upregulation of T-cell initiates autoimmunity resulting in these irAEs. The review focuses on increasing events of neuropathy associated with immunecheckpoint inhibitors, which is one of the rare neurological irAEs, therefore, the least reviewed. The severity and distribution of neurologic toxicities are important deciding factors for its management (CNS vs. PNS), although there is no strong evidence for patients treated with ICIs are specifically affected by the use of immune-modulating interventions. Furthermore, the review discusses on pathophysiology, incidence, clinical presentation, diagnosis, and management of neuropathies as a result of ICIs. Early administration of high-dose corticosteroids is the main management of neuropathies especially for grade 3 or 4 irAEs initial cessation of ICI therapy with continued steroids which are necessary. However, the optimal duration of ICI therapy to minimize the risk of toxicity should be kept under consideration.

Construction and Analysis of an Immune-Related Gene Prognostic Index for Bladder Cancer

Objective: To construct an Immune-Related Gene Prognostic Index (IRGPI) for bladder cancer using a bioanalytical approach to analyze its molecular and immunological characteristics, as well as to assess the benefit of Immune Checkpoint Inhibitor (ICI) therapy in the IRGPI-defined bladder cancer subgroup. Methods: Twenty-nine immune-related pivotal genes were identified by Weighted Gene Co-expression Network Analysis (WGCNA) based on The Cancer Genome Atlas (TCGA) bladder cancer immune dataset (n = 433). Six genes were identified using a multifactorial Cox regression approach to construct the IRGPI and validated against the Gene Expression Omnibus (GEO) dataset (n = 256). Then, molecular and immunological features in the subgroups defined by IRGPI were synthesized by GSEA, Kaplan-Meier survival curves, and other methods, and the benefit of ICI treatment was assessed. Results: IRGPI was constructed based on six genes including AHNAK, ILK, OGN, PDGFD, PPARGC1B, and JAM3. Patients with low IRGPI had better Overall Survival (OS) than those with high IRGPI, which was confirmed in the validation cohort of GEO. Pooled analysis showed that the low IRGPI subgroup was associated with higher infiltration of CD8 T cells, activated memory CD4 T cells, and could benefit from ICI treatment. Meanwhile, high IRGPI subgroups were associated with higher resting memory CD4T cells, M0 macrophages, and M2 macrophage content, immunosuppression, and benefited less from ICI treatment. Conclusion: IRGPI is a novel biomarker with better efficacy in differentiating the prognosis of bladder cancer, molecular and immune features, and evaluation of ICI therapy for individualized treatment of bladder cancer.

Blood and Histopathological Biomarkers of Immune-related Adverse Effects of Treatment with Immune Checkpoint Inhibitors

Immune checkpoint inhibitors have been a recent major breakthrough in the management of tumors.They have broadened the scope of management in medical oncology,which has been heavily dependent on chemotherapy.Immune checkpoint inhibitors have renewed the hope of many patients for a more effective treatment.However,Immune checkpoint inhibitors are also associated with a variety of adverse effects,most commonly immunerelated adverse events,and these are often different from the known chemotherapy-induced toxicities.Hence,there is a need to identify specific biomarkers which are able to predict or diagnose these immune-related adverse events.

Study on the Changes and Correlation of Related Immune Factors before and after Chemotherapy in Non-Small Cell Lung Cancer

Objective: To investigate the changes of related immune cytokines (Dendritic Cells (DC) cells, CD4+, CD8+, Th17, IgG, IgM, IgA) in patients with non-small cell lung cancer (NSCLC) before and after chemotherapy. Methods: Eighty-five NSCLC patients who were treated in the Oncology Department of the Affiliated Hospital of Chengde Medical College from December 2018 to February 2021 were selected as the research objects, and the patients were analyzed at different time points (before chemotherapy, after the first chemotherapy, and after the second chemotherapy) Changes in the expression levels of DC cells, CD4+, CD8+, Th17, IgG, IgM, IgA in peripheral blood, and explore their correlation. Results: Before chemotherapy, after the first chemotherapy, and after the second chemotherapy, the peripheral blood CD4+ and CD8+ were significantly increased, and the Th17, IgG, IgM, and IgA levels gradually decreased. The difference was statistically significant. But there was no obvious change in DC cells. Conclusion: There is no significant change in DC cells in peripheral blood of NSCLC patients before and after chemotherapy. CD4+ and CD8+ are significantly increased, Th17, IgG, IgM, and IgA levels are all decreased, which is a manifestation of impaired immune function of patients after chemotherapy.

Effect of Astragalus Injection on Levels of Blood Selenium and Immunity Function in Children with Viral Myocarditis

Objective: To observe the effect of Astragalus Injection (AD on levels of blood selenium (Se) and cytokines, and T cellular immune function with viral myocarditis (VM) in children. Methods: Eighty children with VM were randomly divided into 2 groups. The control group consisted of 38 patients, to whom conventional therapy, including energy mixture, vitamin C and coenzyme Q10, etc. were given. The treated group (n = 42), to whom combination therapy of conventional therapy and Al were given. The levels of blood Se and cytokine, including interleukin-1 (IL-1), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and also evaluation of T lymphocyte subsets and cardiac function were observed. Results: The results showed that after treatment, the levels of blood Se were significantly higher (P<0.01), while IL-1,IL-6 and TNF-a were significantly lower (P<0.01) than those before treatment in the control group. The left ventricular end diameter (LVED) were significantly decreased (P<0.01), left ventricular ejection fraction (LVEF) and left ventricular fractional shortening (LVFS) were significantly increased than those before treatment in the treated group(P<0.01, P<0.05). T lymphocyte subsets got normalized (P<0.01), and compared with the control group, the difference was significant (P<0.01). Conclusion: Astragalus membranaceus possesses anti-viral effect, adjusts the balance of cytokine and T cellular immunity, and improves the clinical manifestation and cardiac function. It is an effective approach in treating viral myocarditis.

Effects of Temperature on Haemocyte and Granulocyte Counts and Expressions of Immunity-Related Genes in Haemocytes of Scallop Chlamys farreri After Vibrio anguillarum Infection

Bivalve live in aquatic environment and the water temperature can affect their immunity directly.In this research,the scallop Chlamys farreri was injected with 10^4 or 10^7 CFU mL^-1 Vibrio anguillarum and cultured at 11℃,17℃,23℃,and 28℃,respectively.For the control scallop,only phosphate-buffered saline(PBS)was injected.Then total haemocytes and granulocytes were measured by ELISA using monoclonal antibodies.In the meantime,expressions of six immunity-related genes,including lipopolysaccharide andβ-1,3-glucan binding protein(CfLGBP),C-type lectin(CfLec-2),Toll-like receptor(Cf TLR),Lysozyme(CfLYZ),superoxide dismutase(SOD),and phenoloxidase(CfPO)in haemocytes were measured using quantitative real-time PCR.The results showed that total haemocytes counts in 10^4 CFU mL^-1 injection groups showed no differences compared to the control group at all temperatures.However,they varied significantly in 10^7 CFU mL^-1 injection groups at 3 h at 11℃,6–12 h at 17℃,3–48 h at 23℃,and 12–48 h at 28℃.Granulocytes counts in 10^4 CFU mL^-1 injection groups showed no variance compared to the control group at all temperatures,except for 12 h at 23℃,and 24–36 h at 28℃.They were significantly decreased in 10^7 CFU mL^-1 injection groups during 6–48 h at 11℃,12–48 h at 17℃,3–48 h at 23℃,and 3–72 h at 28℃.The expression levels of six immunity-related genes in haemocytes of 10^7 CFU mL^-1 injection groups were significantly higher than those of control group and 10^4 CFU mL^-1 injection groups at all temperatures.The results indicated that infected with high concentration of vibrios,haemocyte counts,granulocyte counts and the expressions of immunity-related genes in scallop C.farreri were significantly affected by environmental temperature.

Significance of tumor-infiltrating immunocytes for predicting prognosis of hepatitis B virus-related hepatocellular carcinoma

BACKGROUND Hepatitis B virus (HBV) has been recognized as a leading cause of hepatocellular carcinoma (HCC). Numerous reports suggest that immune infiltration can predict the prognosis of HCC. Nonetheless, no creditable markers for prognosis of HBV-related HCC have been established by systematically assessing the immune-related markers based on tumor transcriptomes. AIM To establish an immune-related marker based on the cell compositions of immune infiltrate obtained based on tumor transcriptomes, so as to enhance the prediction accuracy of HBV-related HCC prognosis. METHODS RNA expression patterns as well as the relevant clinical data of HCC patients were obtained from The Cancer Genome Atlas. Twenty-two immunocyte fraction types were estimated by cell type identification by estimating relative subsets of RNA transcripts. Subsequently, the least absolute shrinkage and selection operator (LASSO) Cox regression model was employed to construct an immunoscore based on the immunocyte fraction types. Afterwards, the receiver operating characteristic (ROC) curve, Kaplan-Meier, and multivariate Cox analyses were performed. Additionally, a nomogram for prognosis that integrated the immunoscore as well as the clinical features was established. Meanwhile, the correlation of immunoscore with immune genes was also detected, and gene set enrichment analysis (GSEA) of the immunoscore was conducted. RESULTS A total of 22 immunocyte fraction types were predicted and compared among the tumor as well as non-tumor samples. An immunoscore was constructed through adopting the LASSO model, which contained eight immunocyte fraction types. Meanwhile, the areas under the ROC curves for the immunoscore biomarker prognostic model were 0.971, 0.912, and 0.975 for 1-, 3-, and 5-year overall survival (OS), respectively. Difference in OS between the high-immunoscore group and the low-immunoscore group was statistically significant [hazard ratio (HR)= 66.007, 95% confidence interval (CI): 8.361-521.105;P < 0.0001]. Moreover, multivariable analysis showed that the immunoscore was an independent factor for predicting the prognosis (HR = 2.997, 95%CI: 1.737-5.170). A nomogram was established, and the C-index was 0.757 (95%CI: 0.648-0.866). The immunoscore showed a significant negative correlation with the expression of PD-1 (P = 0.024), PD-L1 (P = 0.026), PD-L2 (P = 0.029), and CD27 (P = 0.033). Eight pathways were confirmed by GSEA. CONCLUSION The established immunoscore can potentially serve as a candidate marker to estimate the OS for HBV-related HCC cases.

Effects of Xiaocangping tablets combined with 5-fluorouracil and cisplatin on immunity, tumor markers, angiogenesis and related factors in patients with advanced esophageal cancer

Objective:To explore the effects of Xiaocangping tablets combined with 5-fluorouracil and cisplatin on immunity, tumor markers, angiogenesis and related factors in patients with advanced esophageal cancer.Methods:86 patients with advanced esophageal cancer admitted to our hospital from March 2014 to February 2017 were randomly divided into control group (43 cases) and observation group (43 cases). All the subjects were treated with 5-fluorouracil plus cisplatin, and the observation group was treated with Xiaocangping tablets on this basis. The changes of immune function, tumor markers, angiogenesis and related factors in the two groups were compared and analyzed.Results:After treatment, the levels of CD4+, CD4+/CD8 + in both groups were significantly higher than those before treatment (P<0.05), while the levels of CD8+ were significantly lower than those before treatment (P<0.05), the levels of CD4+ and CD4+/CD8+ in the observation group were significantly higher than those in the control group (P<0.05), while the levels of CD8+ in the observation group was significantly lower than that in the control group (P<0.05);the levels of CA125, CEA and CA19-9 in the two groups were significantly lower than those before treatment (P<0.05), and the levels of CA125, CEA and CA19-9 in the observation group were significantly lower than those in the control group (P<0.05);the levels of VEGF, TGF-β1, MMP-9, NGAL in the two groups were significantly lower than those before treatment (P<0.05), and the levels of VEGF, TGF-β1, MMP-9, NGAL in the observation group were significantly lower than the control group (P<0.05).Conclusions:Chemotherapy combined with fluorouracil + cisplatin chemotherapy for advanced esophageal cancer can effectively improve the immune function of patients, reduce the level of tumor markers, inhibit the proliferation of tumor blood vessels, and have significant anti-cancer effects, which is of positive significance for controlling the development of patients' conditions.

Immunological aspects of age-related diseases

The proportion of elderly people rises in the developed countries. The increased susceptibility of the elderly to infectious diseases is caused by immune dysfunction, especially T cell functional decline. Age-related hematopoietic stem cells deviate from lymphoid lineage to myeloid lineage. Thymus shrinks early in life, which is followed by the decline of na?ve T cells. T-cell receptor repertoire diversity declines by aging, which is caused by cytomegalovirus-driven T cell clonal expansion. Functional decline of B cell induces antibody affinity declines by aging. Many effector functions including phagocytosis of myeloid cells are down regulated by aging. The studies of aging of myeloid cells have some controversial results. Although M1 macrophages have been shown to be replaced by antiinflammatory(M2) macrophages by advanced age, many human studies showed that pro-inflammatory cytokines are elevated in older human. To solve this discrepancy here we divide age-related pathological changes into two categories. One is an aging of immune cell itself. Second is involvement of immune cells to age-related pathological changes. Cellular senescence and damaged cells in aged tissue recruit pro-inflammatory M1 macrophages, which produce pro-inflammatory cytokines and proceed to agerelated diseases. Underlying biochemical and metabolic studies will open nutritional treatment.

Interpreting Dose-Response Relation for Exposure to Multiple Sound Impulses in the Framework of Immunity

Hearing loss is a common military health problem and it is closely related to exposures to impulse noises from blast explosions and weapon firings. In a study based on test data of chinchillas and scaled to humans (Military Medicine, 181: 59-69), an empirical injury model was constructed for exposure to multiple sound impulses of equal intensity. Building upon the empirical injury model, we conduct a mathematical study of the hearing loss injury caused by multiple impulses of non-uniform intensities. We adopt the theoretical framework of viewing individual sound exposures as separate injury causing events, and in that framework, we examine synergy for causing injury (fatigue) or negative synergy (immunity) or independence among a sequence of doses. Starting with the empirical logistic dose-response relation and the empirical dose combination rule, we show that for causing injury, a sequence of sound exposure events are not independent of each other. The phenomenological effect of a preceding event on the subsequent event is always immunity. We extend the empirical dose combination rule, which is applicable only in the case of homogeneous impulses of equal intensity, to accommodate the general case of multiple heterogeneous sound exposures with non-uniform intensities. In addition to studying and extending the empirical dose combination rule, we also explore the dose combination rule for the hypothetical case of independent events, and compare it with the empirical one. We measure the effect of immunity quantitatively using the immunity factor defined as the percentage of decrease in injury probability attributed to the sound exposure in the preceding event. Our main findings on the immunity factor are: 1) the immunity factor is primarily a function of the difference in SELA (A- weighted sound exposure level) between the two sound exposure events;it is virtually independent of the magnitude of the two SELA values as long as the difference is fixed;2) the immunity factor increases monotonically from 0 to 100% as the first dose is varied from being significantly below the second dose, to being moderately above the second dose. The extended dose-response formulation developed in this study provides a theoretical framework for assessing the injury risk in realistic situations.

Sintilimab-induced autoimmune diabetes:A case report and review of the literature

BACKGROUND With the widespread application of immune checkpoint inhibitor(ICI)therapy,the number of immune-related adverse effects(irAEs)has increased over the years.Autoimmune diabetes mellitus(DM)is a rare irAEs of ICIs and can be troublesome and life threatening.CASE SUMMARY We report a 78-year-old woman with no history of diabetes who presented with hyperglycemia up to 23.4 mmol/L(random blood glucose level)after 14 courses of sintilimab.Hemoglobin A1c was 8.2%,fasting insulin was 0.29 mIU/mL,and fasting C-peptide was decreased to a level with negative autoantibodies.Combing her medical history and laboratory examination,she was diagnosed with programmed cell death(PD)-1-inhibitor-induced,new-onset autoimmune DM.After controlling her blood glucose,she was treated with daily insulin by subcutaneous injection.She was allowed to continue anti-PD-1 therapy and she still obtained some therapeutic efficacy.We also reviewed some published cases(n=36)of PD-1/PD-ligand 1(PD-L1)inhibitor-induced DM.We also discuss potential pathogenic mechanisms,clinical features,prognostic markers(βcell antibodies,human leukocyte antigen type,PD-L1 Level)of this rare adverse effect.CONCLUSION It is important for all clinicians to be aware of DM as an irAEs of ICIs.

Immune checkpoint inhibitor-induced colitis:A comprehensive review

Immune checkpoint inhibitors(ICIs) are monoclonal antibodies that target downregulators of the anti-cancer immune response: Cytotoxic T-lymphocyte antigen-4, programmed cell death protein-1, and its ligand programmed death-ligand 1.ICIs have revolutionized the treatment of a variety of malignancies. However,many immune-related adverse events have also been described which mainly occurs as the immune system becomes less suppressed, affecting various organs including the gastrointestinal tract and causing diarrhea and colitis. The incidence of immune-mediated colitis(IMC) ranges from 1%-25% depending on the type of ICI and if used in combination. Endoscopically and histologically there is a significant overlap between IMC and inflammatory bowel disease,however more neutrophilic inflammation without chronic inflammation is usually present in IMC. Corticosteroids are recommended for grade 2 or more severe colitis while holding the immunotherapy. About one third to two thirds of patients are steroid refractory and benefit from infliximab. Recently vedolizumab has been found to be efficacious in steroid and infliximab refractory cases. While in grade 4 colitis, the immunotherapy is permanently discontinued, the decision is controversial in grade 3 colitis.

Programmed cell death-1 inhibitor-related sclerosing cholangitis:A systematic review

BACKGROUND Programmed cell death-1(PD-1)inhibitor has been indicated for many types of malignancies.However,these inhibitors also cause immune-related adverse events.Hepatobiliary disorder is a phenotype of immune-related adverse event affecting 0%–4.5%of patients treated with PD-1 inhibitors.Recent studies have reported PD-1 inhibitor-related sclerosing cholangitis(SC);however,the associated clinical and pathological features are unclear.AIM To evaluate the clinical and pathological features of PD-1 inhibitor-related SC through a systematic review of the literature.METHODS The review,conducted using electronic databases in PubMed,was restricted to the period from January 2014 to September 2019 and focused on case reports/series on PD-1 inhibitor-related SC published in English.We scanned the references of the selected literature to identify any further relevant studies.Six cases previously studied by us,including three that have not yet been published,were included in this review.RESULTS Thirty-one PD-1 inhibitor-related SC cases were evaluated.Median age of patients was 67 years(range,43–89),with a male to female ratio of 21:10.The main disease requiring PD-1 inhibitor treatment was non-small cell lung cancer.Agents that caused PD-1 inhibitor-related SC were nivolumab(19 cases),pembrolizumab(10 cases),avelumab(1 case),and durvalumab(1 case).The median number of cycles until PD-1 inhibitor-related SC onset was 5.5(range,1–27).Abdominal pain or discomfort(35.5%,11/31)was the most frequent symptom.Blood serum tests identified liver dysfunction with a notable increase in biliary tract enzymes relative to hepatic enzymes,and a normal level of serum immunoglobulin G4.Biliary dilation without obstruction(76.9%,20/26),diffuse hypertrophy of the extrahepatic biliary tract(90.5%,19/21),and multiple strictures of the intrahepatic biliary tract(30.4%,7/23)were noted.In 11/23(47.8%)cases,pathological examination indicated that CD8+T cells were the dominant inflammatory cells in the bile duct or peribiliary tract.Although corticosteroids were mainly used for PD inhibitor-related SC treatment,the response rate was 11.5%(3/26).CONCLUSION Some clinical and pathological features of PD-1 inhibitor-related SC were revealed.To establish diagnostic criteria for PD-1 inhibitor-related SC,more cases need to be evaluated.

Endoscopic appearance of AIDS-related gastrointestinal lymphoma with c-MYC rearrangements: Case report and literature review

Acquired immune deficiency syndrome (AIDS)-related lymphoma (ARL) remains the main cause of AIDS-related deaths in the highly active anti-retroviral therapy (HAART) era. Recently, rearrangement of MYC is associated with poor prognosis in patients with diffuse large B-cell lymphoma. Here, we report a rare case of gastrointestinal (GI)-ARL with MYC rearrangements and coinfected with Epstein-Barr virus (EBV) infection presenting with various endoscopic findings. A 38-yearold homosexual man who presented with anemia and was diagnosed with an human immunodeficiency virus infection for the first time. GI endoscopy revealed multiple dish-like lesions, ulcerations, bloody spots, nodular masses with active bleeding in the stomach, erythematous flat lesions in the duodenum, and multiple nodular masses in the colon and rectum. Magnified endoscopy with narrow band imaging showed a honeycomb-like pattern without irregular microvessels in the dish-like lesions of the stomach. Biopsy specimens from the stomach, duodenum, colon, and rectum revealed diffuse large B-cell lymphoma concomitant with EBV infection that was detected by high tissue EBV-polymerase chain reaction levels and Epstein-Barr virus small RNAs in situ hybridization. Fluorescence in situ hybridization analysis revealed a fusion between the immunoglobulin heavy chain (IgH) and c-MYC genes, but not between the IgH and BCL2 loci. After 1-mo of treatment with HAART and R-CHOP, endoscopic appearance improved remarkably, and the histological features of the biopsy specimens revealed no evidence of lymphoma. However, he died from multiple organ failure on the 139 th day after diagnosis. The cause of his poor outcome may be related to MYC rearrangement. The GI tract involvement in ARL is rarely reported, and its endoscopic findings are various and may be different from those in non-AIDS GI lymphoma; thus, we also conducted a literature review of GI-ARL cases.