Cytokine release syndrome triggered by programmed death 1 blockade(sintilimab)therapy in a psoriasis patient:A case report

BACKGROUND In recent years,immune checkpoint inhibitors(ICIs)have demonstrated remarkable efficacy across diverse malignancies.Notably,in patients with advanced gastric cancer,the use of programmed death 1(PD-1)blockade has significantly prolonged overall survival,marking a pivotal advancement comparable to the impact of Herceptin over the past two decades.While the therapeutic benefits of ICIs are evident,the increasing use of immunotherapy has led to an increase in immune-related adverse events.CASE SUMMARY This article presents the case of a patient with advanced gastric cancer and chronic plaque psoriasis.Following sintilimab therapy,the patient developed severe rashes accompanied by cytokine release syndrome(CRS).Fortunately,effective management was achieved through the administration of glucocorticoid,tocilizumab,and acitretin,which resulted in favorable outcomes.CONCLUSION Glucocorticoid and tocilizumab therapy was effective in managing CRS after PD-1 blockade therapy for gastric cancer in a patient with chronic plaque psoriasis.

Metastatic pancreatic and lung cancer patient in complete remission following immunotherapy: A case report and review of literature

BACKGROUND Metastatic pancreatic ductal adenocarcinoma(PDAC)is a lethal malignancy with dispiriting survival data.Immunotherapy is a promising approach to many cancer types,but achieves poor outcomes in advanced PDAC due to its immunosuppressive tumor microenvironment.We describe a case of metastatic PDAC effectively treated with pembrolizumab.CASE SUMMARY We report the case of a 67-year-old woman with unresectable locally advanced PDAC,treated with gemcitabine plus nab-paclitaxel followed by radiotherapy plus capecitabine.At nine months,pancreatic tumor progression was observed at the level of the hepatic hilum with the appearance of a new pulmonary nodule suggestive of a second primary,confirmed by left lung biopsy.Systemic immunotherapy was then initiated with pembrolizumab,an immune checkpoint inhibitor targeting programmed cell death protein-1 that covers the two tumor types.The patient showed a complete metabolic response that was maintained throughout the treatment.The patient continues to be disease-free at 5.6 years since the start of immunotherapy.CONCLUSION These results suggest that the administration of pembrolizumab after chemoradiotherapy has a beneficial effect in patients with metastatic PDAC.To our knowledge,this is the first reported case of a patient with metastatic PDAC and metastatic lung cancer showing such a long-lasting complete response after pembrolizumab treatment without curative surgery.Further studies are required to determine biomarkers that identify PDAC patients most likely to benefit from this immunotherapy.

Advanced cervix cancer patient with chemotherapy-induced grade IV myelosuppression achieved complete remission with cadonilimab:A case report

BACKGROUND The prognosis for patients with advanced metastatic cervix cancer(MCC)is poor,and this disease continues to pose a considerable therapeutic challenge.Despite the administration of first-line regimens consisting of cisplatin,paclitaxel,and bevacizumab,survival rates for patients with metastasis remain poor.The emergence of bispecific antibodies(BsAbs)offers a novel treatment option for patients diagnosed with MCC.CASE SUMMARY In this report,we present a patient with MCC who was treated with cadonilimab monotherapy at a dose of 6 mg/kg every two weeks after chemotherapy was proven to be intolerable.The patient exhibited a sustained complete response for a duration of 6 months,demonstrating an optimistic outlook.CONCLUSION This case illustrates the considerable efficacy of cadonilimab for treating advanced MCC.Therefore,BsAb therapy is a promising strategy for effectively treating patients with advanced MCC and should be considered as an option when patients are intolerant to standard chemotherapy.

PD-1 antibody in combination with chemotherapy for the treatment of SMARCA4-deficient advanced undifferentiated carcinoma of the duodenum:Two case reports

BACKGROUND SMARCA4 is a component of chromatin remodeling of SWItch/sucrose-nonfermenting(SWI/SNF)complexes and plays an essential role in oncogenesis.SMARCA4-deficient malignancies arising from the gastrointestinal tract are rare and have a poor prognosis.There is no standard treatment for advanced and undifferentiated SMARCA4-deficient duodenal malignancies.Programmed death 1(PD-1)antibodies,known as immune checkpoint inhibitor antibodies,potentially play a role in treating gastrointestinal tract malignancies.CASE SUMMARY We present two patients with SMARCA4 deficiency and TP53 gene mutation in advanced undifferentiated carcinomas of the duodenum.For both patients,SMARCA4 deficiency was confirmed by immunohistochemical staining for the BRG1 protein,while TP53 gene mutations were observed via next-generation sequencing.Both patients were administered chemotherapy in combination with an anti-PD-1 antibody.The two patients exhibited completely different responses to treatment and had different prognoses.Case 1 experienced rapid progression after PD-1 infusion and chemotherapy,case 2 experienced a remarkable response after treatment,and the progression-free survival was more than 6 months.CONCLUSION This study described our clinical and pathological observations of SMARCA4-deficient advanced undifferentiated carcinoma of the duodenum.PD-1 combined with chemotherapy showed a certain efficacy in select patients,providing options for treating these highly malignant tumors.Patients with liver metastases had a worse prognosis than did those with only lymph node metastasis.

Analysis of 176 cases of death from kidney transplantation

Objective To review the cadaveric kidney transplantations at our center in the past 22 years and to analyze the causes and the influencing factors on death in 176 patients who died after renal transplantation. Methods A total of 1 039 patients received cadaveric kidney graftings between October 1977 and June 1999. Patient’ s mortality was calculated by the Kaplan-Meier method. The factors which might lead to patients’ death,including age and sex of the donors and recipients, frequency of transplantation, dialysis time and transfusion volume before transplantation, cold ischemic time(CIT),delayed graft function(DGF),rejection, immunosuppressive regimen, and post-transplant complications, were analyzed by log-rank and Cox model. Results Total mortalities of the patient at 1 - ,5 - , 10 - , and 15-year were 6.9%, 19.7%, 32.1% and 34.7%, respectively. The leading causes of patients’ death were infection, cardiocerebral vascular diseases, and hepatic failure. The factors of transplant times, dialysis time

Adult-onset Still's disease evolving with multiple organ failure and death:A case report and review of the literature

BACKGROUND Adult-onset Still’s disease(AOSD)is a rare systemic inflammatory disease,which is characterized by daily fever and arthritis,with an evanescent rash and neutrophilic leukocytosis.To date,there has been no definite laboratory or imaging test available for diagnosing AOSD;the diagnosis is one of exclusion,which can be very challenging.In particular,AOSD patients may experience different complications affecting their clinical picture,management,and prognosis.The treatment of AOSD remains largely empirical and involves therapeutic agents.CASE SUMMARY We report the case of a 36-year-old woman who presented with fever,red rash,arthralgia,and sore throat.Her serum ferritin level and white blood cell count were markedly elevated,and the first diagnosis 22 years prior was"juvenile rheumatoid arthritis of systemic type".The patient was treated with prednisone,sulfasalazine,methotrexate,and leflunomide.After remission of her symptoms,the patient stopped taking the medications,and the disease recurred.Ultimately,the patient was diagnosed with adult-onset Still's disease.Relapse occurred several times due to self-medication withdrawal,and an interleukin-6 antagonist(tocilizumab/Actemra)was administered to control the disease.Recently,she was hospitalized because an incision did not heal,and the patient suddenly developed high fever and diarrhea during hospitalization.The patient's disease progressed violently and quickly developed into macrophage activation syndrome,disseminated intravascular coagulation,shock,and multiple organ failure.The patient had sudden cardiac arrest,and she died despite emergency rescue efforts.CONCLUSION AOSD patients need regular follow-up in the long-term treatment process,and must press formulary standard medication,and do not voluntarily withdraw or reduce the dose.Otherwise it may cause disease back-and-forth or serious lifethreatening complications.Meanwhile,strict management of trauma,infections,tumors,and other diseases may contribute to improved outcomes in patients with complications.

Hypophysitis induced by anti-programmed cell death protein 1 immunotherapy in non-small cell lung cancer:Three case reports

BACKGROUND Hypophysitis induced by programmed cell death 1 protein(PD-1)immune checkpoint inhibitors is rare and poorly described.We report three patients with non-small cell lung cancer who developed hypophysitis after anti-PD-1 immunotherapy.CASE SUMMARY Both case 1 and case 2 presented with common symptoms of fatigue,nausea,and vomiting.However,case 3 showed rare acute severe symptoms such as hoarse voice,bucking,and difficulty in breathing even when sitting.Following two cycles of immunotherapy in case 3,the above severe symptoms and pituitary gland enlargement were found on magnetic resonance imaging at the onset of hypophysitis.These symptoms were relieved after 10 d of steroid treatment.Case 3 was the first patient with these specific symptoms,which provided a new insight into the diagnosis of hypophysitis.In addition,we found that the clinical prognosis of patients with hypophysitis was related to the dose of steroid therapy.Case 3 was treated with high-dose hormone therapy and her pituitary-corticotropic axis dysfunction returned to normal after more than 6 mo of steroid treatment.Cases 1 and 2 were treated with the low-dose hormone,and dysfunction of the pituitary-corticotropic axis was still present after up to 7 mo of steroid treatment.CONCLUSION The clinical symptoms described in this study provide a valuable reference for the diagnosis and treatment of immune-related hypophysitis.

A Lazarus effect： A case report of Bupropion overdose mimicking brain death

Dear editor,We report a case of a 47-year-old female who presented with a toxic bupropion ingestion leading to cardiac arrest.She initially exhibited a loss of brainstem reflexes in conjunction with burst-suppression pattern on EEG.Burst suppression is an EEG waveform pattern of alternating isoelectric suppressions and high voltage bursts.^([1])

Tumor recurrence after pathological complete response in locally advanced gastric cancer after neoadjuvant therapy:Two case reports

BACKGROUND The pathological complete response(ypCR)rate following neoadjuvant chemotherapy for advanced gastric cancer remains low and lacks a universally accepted treatment protocol.Immunotherapy has achieved breakthrough progress.CASE SUMMARY We report two female patients with gastric cancer defined as clinical stage cT4N1-2M0.Detection of mismatch repair protein showed mismatch repair function defect,and perioperative treatment with programmed death protein 1 inhibitor combined with S-1+oxaliplatin achieved ypCR.Surprisingly,the patients underwent clinical observation after surgery but developed different degrees of metastasis at~6 mo after surgery.CONCLUSION PD-1 inhibitor combined with chemotherapy provides a more strategic choice for comprehensive perioperative treatment of gastric cancer.

Maternal death due to severe and critical COVID-19 in Qom,Iran:A case series

Objective:To report the maternal death due to COVID-19.Methods:A total of 14 maternal deaths due to severe and critical COVID-19 who were referred to the obstetric department of Nekouie-Forghani-Hedayati Hospital,Qom,Iran from December 2019 to May 2022 were collected.The clinical manifestations and maternal and perinatal outcomes were analyzed.Results:Dexamethasone was used in 7 cases,while remdesivir was used in 5 cases.Acute respiratory distress syndrome,multiple organ failure,and sepsis were the main cause of mother death.The pregnancy in 8 cases were terminated by caesarean and only one neonatal death was reported from a mother at 13th week of gestational age,while all other fetus delivered were healthy and alive.Conclusions:COVID-19 in pregnancy is an emergency.Critical appraisal is needed to detect the other comorbidities and positive PCR test by throat swap should be performed as soon as possible.

Multidisciplinary approach to suspected sudden unexpected infant death caused by milk-aspiration:A case report

BACKGROUND The term sudden unexpected infant death(SUID)is not always properly invoked.It refers to a broad range of conditions that sometimes defy classification.There is not only a strong emotional impact on the family,but such cases are also quite complex.Underlying causes may be multiple,not always readily apparent,and have potential repercussions,especially in terms of forensics.CASE SUMMARY A 5-month-old male baby was pronounced dead following acute lung failure and cardiopulmonary arrest.The parents had immediately rushed their child to the hospital,stating the baby was found prone and not breathing.Total-body postmortem computed tomography(PMCT)was performed,revealing a hypodense material of indeterminate nature within the main airways and areas of ground-glass parenchymal change.At autopsy,the respiratory tract mucosa appeared edematous and was coated with a whitish stringy material.There was widespread airspace reduction due to parenchymal collapse.Alveolar sacs and bronchial openings contained abundant amorphous material admixed with white blood cells.Immunohistochemical studies were performed,targeting CD15,CD68,and alpha-lactalbumin.Ultimately,the focus was on alpha-lactalbumin(milk protein),which showed marked immunopositivity within alveolar spaces.Cytoplasmic staining of macrophages was also particularly prominent.CONCLUSION Postmortem investigations are thus essential to identify causes of death and surrounding circumstances.PMCT is a useful tool in this setting,given the frequent dearth of autopsy findings and ambiguity as to cause of death in SUID cases.These findings,later confirmed by immunohistochemical investigations,were indicative of active pneumonia due to aspirated milk.The present account illustrates the importance a broad diagnostic approach to SUID in cases of forensic concern.PMCT is a very valuable aid in cases of forensic interest,as it can provide useful information in all those situations in which the cause of death is uncertain or there are no suggestive dynamics or lesions.

Anti-programmed cell death ligand 1-based immunotherapy in recurrent hepatocellular carcinoma with inferior vena cava tumor thrombus and metastasis:Three case reports

BACKGROUND Recurrent hepatocellular carcinoma(HCC)with inferior vena cava tumor thrombus is a great challenge for oncologists and has a poor prognosis.To date,the safety and efficacy of programmed cell death ligand 1(PD-L1)inhibitors are still unknown.CASE SUMMARY A 59-year-old male was identified as having a tumor thrombus in the inferior vena cava 3 years after surgery.The patient underwent a second surgery and adjuvant chemotherapy.However,the level of alpha-fetoprotein was elevated after 2 mo,and lung metastases and mediastinal lymph node metastases were identified.The expression of PD-L1 in HCC and inferior vena cava tumor thrombus tissues was analyzed by immunohistochemistry.Then,the patient received atezolizumab immunotherapy.The level of alpha-fetoprotein dropped to normal,the mediastinal lymph node metastases decreased in size and the lung metastases disappeared after 3 mo of immunotherapy.The patient had no signs of recurrence at 21 mo of follow-up.A 60-year-old male underwent left hepatic tumor resection,inferior vena cava incision and thrombus removal,followed by regular chemotherapy.The patient developed lung and splenic metastases after surgery.Pembrolizumab was used for six courses,and the splenic metastasis shrank,after which splenectomy was performed.The patient continued to receive pembrolizumab for thirteen courses,and the lung metastases showed no progression.A 34-year-old male was diagnosed with liver cancer with inferior vena cava tumor thrombus.The patient underwent right hepatectomy and received tislelizumab for three courses.He is still receiving immunotherapy and in good condition.CONCLUSION Anti-PD-L1 therapy in HCC patients with inferior vena cava tumor thrombus and metastasis is associated with relatively good patient outcomes.

Refractory lymphoma treated with chimeric antigen receptor T cells combined with programmed cell death-1 inhibitor:A case report

BACKGROUND Diffuse large B-cell lymphoma(DLBCL)is a common aggressive non-Hodgkin's lymphoma(NHL),accounting for 30%-40%of adult NHL.Primary testicular(PT)lymphoma is an uncommon extranodal disease representing approximately 1%-2%of lymphoma.Approximately 30%–40%of patients are refractory to frontline therapy or relapse after complete remission.Refractory DLBCL responds poorly to other lines of chemotherapy,and experiences short-term survival.CASE SUMMARY We present a 41-year-old male patient who was diagnosed with PT-DLBCL.Further disease progression was observed after multiline chemotherapy.Chimeric antigen receptor T cells(CAR-T)therapy salvaged the patient.Unfortunately,a new mass was observed in the right adrenal area after six months.The patient was administered programmed cell death protein-1(PD-1)inhibitor therapy and maintained progression-free survival at more than 17 mo of follow-up.CONCLUSION Our findings support the potential benefit of CAR-T combined with PD-1 inhibitor therapies in this type of relapsed and refractory PT-DLBCL.

Programmed cell death protein-1 inhibitor combined with chimeric antigen receptor T cells in the treatment of relapsed refractory non- Hodgkin lymphoma: A case report

BACKGROUND Chimeric antigen receptor T cell(CART)therapy has benefited many refractory lymphoma patients,but some patients experience poor effects.Previous studies have shown that programmed cell death protein-1(PD-1)inhibitors can improve and prolong the therapeutic effect of CAR-T cell treatment.CASE SUMMARY A 61-year-old male presented with 15-d history of diarrhea and lower-limb edema.A large mass was detected in the pelvis,and pathology indicated non-Hodgkin diffuse large B-cell lymphoma.After three cycles of the R-CHOP chemotherapeutic regimen,the patient showed three subcutaneous nodules under the left armpit and both sides of the cervical spine.Pathological examination of the nodules indicated DLBCL again.The patient was diagnosed with relapsed and refractory diffuse large B-cell lymphoma.We recommended CAR-T cell treatment.Before treatment,the patient’s T cell function and expression of immune detection points were tested.Expression of PD-1 was obviously increased(52.7%)on cluster of differentiation(CD)3+T cells.The PD-1 inhibitor(3 mg/kg)was infused prior to lymphodepleting chemotherapy with fludarabine and cyclophosphamide.CAR-CD19 T cells of 3×10^(6)/kg and CAR-CD22 T cells 1×10^(6)/kg were infused,respectively.The therapeutic effect was significant,and the deoxyribonucleic acid copy numbers of CAR-CD19 T cells and CAR-CD22 T cells were stable.Presently,the patient has been disease-free for more than 12 mo.CONCLUSION This case suggests that the combination of PD-1 inhibitors and CAR-T cellsimproved therapeutic efficacy in B-cell lymphoma.

Edaravone administration and its potential association with a new clinical syndrome in cerebral infarction patients:Three case reports

BACKGROUND Edaravone is a widely used treatment for patients with cerebral infarction and,in most cases,edaravone-induced side effects are mild.However,edaravone-related adverse reactions have been receiving increasing attention.CASE SUMMARY We treated three patients with acute cerebral infarction who died following treatment with edaravone.Edaravone is a widely used treatment for patients with cerebral infarction and,in most cases,edaravone-induced side effects are mild.However,edaravone-related adverse reactions have been receiving increasing attention.CONCLUSION Our cases highlight the importance of educating clinicians regarding the new edaravone-induced clinical syndromes of cerebral infarction as potentially fatal adverse drug reactions.Considering that no laboratory or confirmatory test exists to diagnose edaravone-induced death from cerebral infarction,clinicians’knowledge is the key element in recognizing this phenomenon.

Immunotherapy in combination with chemotherapy for Peutz-Jeghers syndrome with advanced cervical cancer:A case report

BACKGROUND Peutz-Jeghers syndrome(PJS)is a rare autosomal dominant disorder,and female patients may develop gynecologic tumours.The prognosis for such patients is poor and the specific pathogenesis remains uncertain.Therefore,there are currently no uniform treatment options.CASE SUMMARY Herein,we introduce the case of a 45-year-old female who was diagnosed with PJS for 45 years and cervical cancer for 3 years.Postoperative pathological examination showed metastases in the right external iliac lymph nodes.The patient was initially treated with a combination of doxorubicin and carboplatin chemotherapy and pelvic magnetic resonance showed that the metastases had grown.Subsequently,we performed whole exome sequencing in this patient and identified the relevant causative gene.In addition to the chemotherapy regimen,sindilizumab was administered and the patient was followed up.After 4 cycles of treatment,the metastases were substantially reduced and were not enlarged after six months of follow-up.This case report suggests that patients with PJS combined with cervical cancer may have a sustained response to immunecombination chemotherapy regimens.CONCLUSION Clinicians should be aware of the importance of immunotherapy in patients with PJS combined with advanced cervical cancer.

Immune checkpoint inhibitor therapy-induced autoimmune polyendocrine syndrome typeⅡand Crohn's disease:A case report

BACKGROUND The development of immune checkpoint inhibitors(ICIs)has heralded a new era in cancer treatment,enabling the possibility of long-term survival in patients with metastatic disease.Unfortunately,ICIs are increasingly implicated in the development of autoimmune diseases.CASE SUMMARY We present a man with squamous cell carcinoma of the oropharynx on a combination of teriprizumab,docetaxel,and cisplatin therapy who developed autoimmune polyendocrine syndrome typeⅡ(APS-2)including thyroiditis and type 1 diabetes mellitus and Crohn’s disease(CD).He developed thirst,abdominal pain,and fatigue after two-week treatment with the protein 1 ligand inhibitor teriprizumab.Biochemistry confirmed APS-2 and thyrotoxicosis.He was commenced on an insulin infusion.However,his abdominal pain persisted.Follow-up surgery confirmed CD and his abdominal pain was relieved by mesalazine.He was continued on insulin and mesalazine therapy.CONCLUSION Immunotherapy can affect all kinds of organs.When clinical symptoms cannot be explained by a single disease,clinicians should consider the possibility of multisystem damage.

玉林市第一人民医院2013-2021年住院死亡病例分析

目的分析影响人民生命安全的主要疾病及影响因素,为预防疾病和提高医院医疗质量提供科学依据。方法通过病案管理系统导出广西壮族自治区玉林市第一人民医院2013年1月1日至2021年12月31日的住院患者的信息,采用SPSS 26.0统计软件对住院死亡患者的病案进行回顾性统计分析。结果各年度病死率呈下降趋势,男性病死率高于女性(P<0.05)。死亡年龄平均(56.29±22.97)岁,60~<80岁死亡人数最多;各年龄段死亡患者性别比例:40~<60岁男女死亡比例最高,整体男女死亡比例为2.0∶1.0;随着年龄的增长,病死率不断升高(P<0.05)。前5位死因依次为循环系统疾病、肿瘤、损伤、中毒和外因的某些其他后果及呼吸系统、消化系统疾病;其中循环系统疾病的前3位死因依次为脑出血、心肌梗死、脑梗死,肿瘤的前3位死因依次为肝恶性肿瘤、肺恶性肿瘤、白血病。首要死因:0~<20岁是损伤、中毒和外因的某些其他后果;20~<60岁是肿瘤;≥60岁是循环系统疾病。结论广西壮族自治区玉林市第一人民医院住院患者的病死率逐年下降,病死率具有性别差异和年龄差异,依据死因分析,应加强循环系统疾病、肿瘤、损伤、中毒和外因的某些其他后果及呼吸系统、消化系统疾病的防治工作,提升医院管理,降低住院患者病死率。

考古遗存中难产死亡推判、成因及案例研究

难产是导致古代孕产妇和胎儿死亡的重要原因,但是相关案例的具体体质形态在文献中却鲜有记载,考古学证据也不多见。本文试图通过梳理考古遗存中发现的难产死亡案例,对难产死亡的考古学推判标准和难产成因作简要综述,同时对郑州洄沟等遗址的典型难产案例进行分析。难产研究的梳理,对相关的墓葬发掘、人骨收集、资料整理等都具有重要的启示意义。

急诊猝死相关疑难病诊治的新近认识

本文介绍11种急诊猝死相关的疑难疾病,有心脏震荡、胸腺淋巴体质、青壮年猝死综合征、小心脏综合征、浅水昏迷、小麦依赖运动诱发的严重过敏反应、Kounis综合征、双相过敏反应、血液净化过滤器过敏、McKittrick-Wheelock综合征和Mendelson综合征等。急诊临床医师应认识这些比较疑难、实际上并不少见的疾病,以提高急诊临床诊治水平,最大限度地避免误诊误治。