A rare case report on complications in pregnancy with systemic lupus erythematosus in a post-renal transplant patient

To preview the feto-maternal outcome in post-renal transplant pregnant women with systemic lupus erythematosus (SLE). To distinguish preeclampsia from hypertension in renal transplant recipients as diagnosis is not always straightforward and all differentials need a thorough evaluation. Hypertension is a prevalent issue among kidney transplant recipients, with reported incidence rates ranging from 52% to 69%. Additionally, the occurrence of pre-eclampsia in renal transplant recipients falls within the range of 24% to 38%, demonstrating a significantly elevated risk compared to the 4-5% incidence rate seen in the general population. A 29-year-old female para 1 IUFD 1 abortion 1, in a known case of SLE with hypothyroidism with lupus nephritis with post renal transplant status with thrombocytopenia with preeclampsia with day 7 of emergency LSCS done in view of non-progress of labor with intrauterine fetal demise with abruptio placenta referred in view of query SLE flare or severe preeclamptic features with rectus sheath hematoma. Renal transplant restores fertility; thus, pregnancy requires careful planning and affected women should be managed in tertiary care obstetrics centers working in tight multidisciplinary cooperation with transplant physicians.

Clinical management strategies for recipients with renal graft loss / 器官移植

With the maturity of kidney transplantation, introduction of new immunosuppressive drugs and improvement of immunosuppressive regimen, the short-term survival rate of kidney transplant recipients has been significantly improved, whereas the long-term survival rate has not been significantly elevated. Kidney transplant recipients may have the risk of renal graft loss. Clinical management after renal graft loss is complicated, including the adjustment of immunosuppressive drugs, management of renal graft and selection of subsequent renal replacement therapy. These management procedures directly affect clinical prognosis of patients with renal graft loss. Nevertheless, relevant guidelines or consensuses are still lacking. Clinical management of patients after renal graft loss highly depend upon clinicians’ experience. In this article, the adjustment of immunosuppressive drugs, management of renal graft and selection of subsequent renal replacement therapy were reviewed, aiming to provide reference for prolonging the survival and improving the quality of life of these patients.

Research progress of drugs for cancer immunotherapy based on CCL2/CCR2 signaling axis1 / 中国药科大学学报

@#C-C motif chemokine ligand 2 (CCL2) and its receptor CCR2 are closely related to tumorigenesis and tumor progression. The CCL2/CCR2 signaling axis promotes tumor progression through multiple mechanisms: CCL2 binds to CCR2 on the surface of tumor cells, and thus promotes tumor growth/survival and metastasis; more importantly, CCL2 recruits a variety of immunosuppressive cells to aggregate in the tumor microenvironment, and inhibits the function and activity of immune cells, promoting tumor progression. The article reviews the CCL2/CCR2 signaling axis and its role in tumors and tumor microenvironment, with particular focus on the advances in clinical research on drugs targeting CCL2/CCR2 signaling axis, in order to gain an in-depth and overall understanding of the mechanism of action of CCL2/CCR2 axis in tumor progression and develop more effective anti-tumor immunotherapeutic agents.

Research progress on immune checkpoint inhibitors for the treatment of adverse reactions related to gastric cancer / 国际外科学杂志

Traditional chemotherapy is the cornerstone of comprehensive treatment for gastric cancer, but its recurrence and metastasis rates are high, and the overall prognosis is not ideal. The rise of immune checkpoint inhibitors (ICI) has brought new hope to gastric cancer patients and changed the current pattern of comprehensive treatment for gastric cancer. With the increasing use of ICI, immune related adverse reactions (irAEs) such as skin toxicity and gastrointestinal toxicity are becoming increasingly common. Scientific understanding, early diagnosis, and graded management are currently the main strategies for handling irAEs. This article aims to review the mechanisms, clinical manifestations, and prediction, treatment, and management of irAEs after ICI treatment of gastric cancer, in order to enhance the understanding of irAEs among clinical physicians, better manage immunotherapy related adverse reactions, and improve the prognosis and quality of life of patients.

Clinical features and initial outcomes in elderly patients with idiopathic membranous nephropathy / 中华老年医学杂志

Objective:The purpose of this study was to examine the clinical features and initial treatment outcomes of elderly individuals with idiopathic membranous nephropathy.Methods:This study retrospectively analyzed the clinical characteristics and therapeutic effect of hospitalized patients aged 60 years or older with renal-biopsy-proven idiopathic membranous nephropathy for at least one year.Results:This study enrolled a total of 91 elderly patients with IMN, consisting of 51 males(56.0%)and 40 females(44.0%). The median age of the patients was 67 years.The urinary protein creatinine ratio(uPCR)and urinary albumin creatinine ratio(uACR)of the patients were 4 454.3 mg/g and 2 258.5 mg/g, respectively.The median 24-hour urinary protein and urinary albumin levels were 5 098.2 mg/24 h and 2 800.6 mg/24 h, respectively.The average estimated glomerular filtration rate(eGFR)was(60.5±20.4)ml·min -1·1.73 m -2.Out of the total of 61 patients, 67.0% achieved remission, including complete and partial remission, within a year of renal biopsy.The levels of uPCR and uACR were significantly higher in the non-remission group compared to the remission group(5 462.5 vs.2 271.1 mg/g, P<0.001; 2 774.4 vs.1 320.0 mg/g, P=0.001). Additionally, the levels of 24h urinary protein and urinary albumin were significantly higher in the non-remission group compared to the remission group(6 526.4 vs.3 210.4 mg/g, P=0.002; 3 067.7 vs.2 102.4 mg/g, P=0.007). The remission group had a higher proportion of patients receiving immunosuppressive therapy(85.2% vs.33.3%, P<0.001). The remission rates were higher in patients treated with glucocorticoid combined with cyclophosphamide, glucocorticoid combined with calcineurin inhibitors, or glucocorticoid combined with mycophenolate mofetil compared to those receiving conservative treatment(88.2% vs.31.0%, P=0.001; 80.0% vs.31.0%, P<0.001; 100.0% vs.31.0%, P=0.007). There was no significant difference in remission rate between the three immunosuppressive therapy groups( P>0.05). However, upon further analysis, it was found that the levels of uPCR, uACR, and serum cystatin C(CysC)were higher in the immunosuppressive therapy groups compared to conservative treatment.Additionally, serum total protein and albumin were lower in the immunosuppressive therapy groups, and these differences were statistically significant( P<0.05). Conclusions:The majority of elderly patients diagnosed with IMN have multiple comorbidities.For those at high risk with elevated urinary protein levels, early initiation of immunosuppressive therapy may lead to a higher initial urinary protein remission rate.Therefore, it is advisable to develop individualized treatment plans for elderly patients with IMN based on their clinical characteristics, as well as the risks and benefits associated with immunosuppressive therapy.

Research progress of drugs for cancer immunotherapy based on CCL2/CCR2 signaling axis / 中国药科大学学报

C-C motif chemokine ligand 2(CCL2)and its receptor CCR2 are closely related to tumorigenesis and tumor progression.The CCL2/CCR2 signaling axis promotes tumor progression through multiple mechanisms:CCL2 binds to CCR2 on the surface of tumor cells,and thus promotes tumor growth/survival and metastasis;more importantly,CCL2 recruits a variety of immunosuppressive cells to aggregate in the tumor microenvironment,and inhibits the function and activity of immune cells,promoting tumor progression.The article reviews the CCL2/CCR2 signaling axis and its role in tumors and tumor microenvironment,with particular focus on the advances in clinical research on drugs targeting CCL2/CCR2 signaling axis,in order to gain an in-depth and overall understanding of the mechanism of action of CCL2/CCR2 axis in tumor progression and develop more effective anti-tumor immunotherapeutic agents.

New progress in the treatment of immunoglobulin A nephropathy / 中国医师杂志

Immunoglobulin A nephropathy (IgAN) is the most common primary glomerulonephritis worldwide, characterized by the deposition of IgA in the mesangial area of the glomerulus. At present, the pathogenesis of IgAN is not yet clear, and there has been a lack of specific and recognized treatment plans. In recent years, many domestic and foreign researchers have conducted research on important pathways and key molecules in its pathogenesis, aiming to explore new therapeutic drugs. This review mainly summarizes the latest progress in the treatment of IgAN, including drugs that have been proven effective against IgAN and drugs that are currently being evaluated in clinical studies.

Targeting FAPα-positive lymph node metastatic tumor cells suppresses colorectal cancer metastasis

Lymphatic metastasis is the main metastatic route for colorectal cancer, which increases the risk of cancer recurrence and distant metastasis. The properties of the lymph node metastatic colorectal cancer (LNM-CRC) cells are poorly understood, and effective therapies are still lacking. Here, we found that hypoxia-induced fibroblast activation protein alpha (FAPα) expression in LNM-CRC cells. Gain- or loss-function experiments demonstrated that FAPα enhanced tumor cell migration, invasion, epithelial-mesenchymal transition, stemness, and lymphangiogenesis via activation of the STAT3 pathway. In addition, FAPα in tumor cells induced extracellular matrix remodeling and established an immunosuppressive environment via recruiting regulatory T cells, to promote colorectal cancer lymph node metastasis (CRCLNM). Z-GP-DAVLBH, a FAPα-activated prodrug, inhibited CRCLNM by targeting FAPα-positive LNM-CRC cells. Our study highlights the role of FAPα in tumor cells in CRCLNM and provides a potential therapeutic target and promising strategy for CRCLNM.

Dual-responsive supramolecular photodynamic nanomedicine with activatable immunomodulation for enhanced antitumor therapy

A major challenge facing photodynamic therapy (PDT) is that the activity of the immune-induced infiltrating CD8+ T cells is subject to the regulatory T lymphocytes (Tregs), leaving the tumor at risk of recurrence and metastasis after the initial ablation. To augment the antitumor response and reprogram the immunosuppressive tumor microenvironment (TME), a supramolecular photodynamic nanoparticle (DACss) is constructed by the host-guest interaction between demethylcantharidin-conjugated β-cyclodextrin (DMC-CD) and amantadine-terminated disulfide-conjugated FFVLGGGC peptide with chlorin e6 decoration (Ad-ss-pep-Ce6) to achieve intelligent delivery of photosensitizer and immunomodulator for breast cancer treatment. The acid-labile β-carboxamide bond of DMC-CD is hydrolyzed in response to the acidic TME, resulting in the localized release of DMC and subsequent inhibition of Tregs. The guest molecule Ad-ss-pep-Ce6 can be cleaved by a high level of intracellular GSH, reducing photosensitizer toxicity and increasing photosensitizer retention in the tumor. With a significant increase in the CTL/Treg ratio, the combination of Ce6-based PDT and DMC-mediated immunomodulation adequately achieved spatiotemporal regulation and remodeling of the TME, as well as improved primary tumor and in situ lung metastasis suppression with the aid of PD-1 antibody.

Algoritmo de manejo hospitalario para la intoxicación aguda por Paraquat® en población pediátrica, serie de casos / A hospital management algorithm for acute poisoning by Paraquat® in a pediatric population, a series of cases

Resumen El dicloruro de 1,1'-dimetil-4,4'-bipiridilo (Paraquat®) es un compuesto químico de la familia de las piridinas, utilizado como herbicida no selectivo y desecante. Este compuesto puede causar intoxicación aguda por todas las vías de exposición. En el momento, no hay un antídoto conocido y los tratamientos disponibles, incluidos los pediátricos, se basan en contrarrestar su absorción y propiciar su remoción oportuna. Se describe una serie de casos de 14 pacientes pediátricos, procedentes en su mayoría del departamento del Cauca, con intoxicación aguda por ingestión de paraquat. Los pacientes fueron remitidos y atendidos en un hospital de mediana a alta complejidad en el suroccidente colombiano, con un protocolo institucional para el manejo de la intoxicación aguda por el herbicida. La intoxicación aguda con paraquat por vía oral se asocia con una alta tasa de mortalidad, aún con atención médica oportuna, pues fácilmente se alcanzan concentraciones sistémicas para ser fulminante. Basado en la literatura disponible, el Hospital Universitario San José ha propuesto un protocolo clínico -adecuado para la intoxicación aguda por paraquat en población pediátrica- que incluye manejo estándar temprano, tratamiento inmunosupresor y antioxidante, y técnicas para su remoción sistémica

Abstract Paraquat®, or N,N'-dimethyl-4,4'-bipyridinium dichloride, is a bipyridyl compound used as a non-selective herbicide and desiccant that can cause acute poisoning through all routes of exposure. There is no known antidote, and the available treatments are based on avoiding its absorption and timely removing it, in adults and children. We describe a case series of 14 pediatric patients from the department of Cauca, Colombia, with acute intoxication after oral intake of paraquat. Patients were referred to a medium-high complexity hospital in southwestern Colombia and treated according to an institutional protocol for acute paraquat poisoning. Acute paraquat poisoning after oral ingestion is associated with a high mortality rate, even with timely medical attention, as the compound has no known antidote and quickly reaches systemic concentrations for fulminant poisoning. Based on the available literature, our center has proposed a clinical protocol including early standard management, immunosuppressive and antioxidant treatments, and systemic removal techniques. This protocol suggests an adequate approach to acute paraquat poisoning in the pediatric population.

Cutting-edge issues in sympathetic ophthalmia approach and six case reports: a T cell-mediated autoimmune response / As questões de ponta na abordagem da oftalmia simpática e 6 relatos de caso: uma resposta autoimune mediada por células T

ABSTRACT Sympathetic ophthalmia is a rare and potentially devastating bilateral diffuse granulomatous panuveitis. It is caused by surgical or non-surgical eye injuries and is an uncommon and serious complication of trauma. It is diagnosed clinically and supported by imaging examinations such as ocular ultrasonography and optical coherence tomography. Its treatment consists of immunosuppressive therapy with steroids and sometimes steroid-sparing drugs, such as cyclosporine, azathioprine, cyclophosphamide, and mycophenolate mofetil. Fast and effective management with systemic immunosuppressive agents allows for disease control and achievement of good visual acuity in the sympathizing eye. By contrast, enucleation should be considered only in situations where the injured eye has no light perception or in the presence of severe trauma. In addition to a bibliographic review of this topic, we report six cases involving different immunosuppressive and surgical treatment modalities.

RESUMO A oftalmia simpática consiste em uma panuveíte granulomatosa bilateral rara e potencialmente devastadora, ocorrendo geralmente após trauma ocular cirúrgico ou não cirúrgico. O diagnóstico é baseado em aspectos clínicos e apoiado por exames de imagem, como ultrassonografia ocular e tomografia de coerência óptica. O tratamento consiste em terapia imunossupressora com esteróides e, eventualmente, drogas poupadoras de esteróides, como ciclosporina, azatioprina, ciclofosfamida e micofonato de mofetila. O manejo rápido e eficaz com agentes imunossupressores sistêmicos permite o controle da doença e a obtenção de boa acuidade visual no olho simpatizante. A enucleação, por outro lado, poderia ser considerada apenas em situações em que o olho lesado não tem percepção luminosa ou há trauma grave. Além de uma revisão bibliográfica sobre o tema, foi relatada uma série de 6 casos com diferentes modalidades de tratamento imunossupressor e cirúrgico.

Radiological presentation of active pulmonary tuberculosis in kidney transplant recipients: a retrospective study of four cases and a review of the literature / Apresentação radiológica da tuberculose pulmonar ativa em transplantados renais: um estudo retrospectivo de quatro casos e revisão da literatura

Abstract Although kidney transplantation is the best therapeutic option for patients with chronic kidney disease, the immunosuppression required greatly increases susceptibility to infections that are responsible for high post-transplant mortality. Pulmonary tuberculosis (TB) represents a major cause of such infections, and its early diagnosis is therefore quite important. In view of that, we researched the manifestations of active pulmonary TB in kidney transplant recipients, through chest X-ray and computed tomography (CT), as well as determining the number of cases of active pulmonary TB occurring over a 3.5-year period at our institution. We identified four cases of active pulmonary TB in kidney transplant recipients. The CT scans provided information complementary to the chest X-ray findings in all four of those cases. We compared our CT findings with those reported in the literature. We analyzed our experience in conjunction with an extensive review of the literature that was nevertheless limited because few studies have been carried out in lowand middle-income countries, where the incidence of TB is higher.

Resumo Apesar de o transplante renal ser a melhor opção terapêutica para pacientes com doença renal crônica, a imunodepressão decorrente desse tratamento eleva muito a suscetibilidade desses pacientes a infecções, responsáveis por altas taxas de mortalidade pós-operatórias. A tuberculose (TB) pulmonar é uma significativa causa dessas infecções, sendo muito importante o seu diagnóstico precoce. Assim, nós pesquisamos as manifestações da TB pulmonar ativa nessa população de transplantados renais por meio de radiografias simples e tomografia computadorizada (TC) do tórax, também para estabelecer o número de casos de TB pulmonar ativa em nossa instituição após levantamento de 3,5 anos. Encontramos quatro casos de TB pulmonar ativa em pacientes transplantados renais. A TC forneceu informações adicionais em relação às radiografias de tórax em 100% dos casos analisados. Comparamos os nossos achados de TC com os relatados na literatura. Somamos a experiência obtida com extensa revisão da literatura, ainda limitada nessa questão, com poucos estudos realizados em países em desenvolvimento onde a incidência de TB é maior.

Frequency of skin diseases in renal transplant recipients and patients with chronic kidney disease in a tertiary center: a cross-sectional study

ABSTRACT BACKGROUND: The prevalence of chronic kidney disease (CKD) has increased in the recent decades, along with the number of patients in the terminal stages of this disease, requiring transplantation. Some skin disorders are more frequent in patients with CKD and in renal transplant recipients (RTR). OBJECTIVES: To evaluate the frequency of skin diseases in RTR and patients with CKD receiving conservative treatment. DESIGN AND SETTING: This observational cross-sectional study recruited consecutive patients with CKD and RTR from a nephrology clinic at a teaching hospital in Brazil between 2015 and 2020. METHODS: Quantitative, descriptive, and analytical approaches were used. The sample was selected based on convenience sampling. Data were collected from dermatological visits and participants' medical records. RESULTS: Overall, 308 participants were included: 206 RTR (66.9%, median age: 48 years, interquartile range [IQR] 38.0-56.0, 63.6% men) and 102 patients with CKD (33.1%, median age: 61.0 years, IQR 50.0-71.2, 48% men). The frequency of infectious skin diseases (39.3% vs. 21.6% P = 0.002) were higher in RTR than in patients with CKD. Neoplastic skin lesions were present in nine (4.4%) RTR and in only one (1.0%) patient with CKD. Among the RTR, the ratio of basal cell carcinoma to squamous cell carcinoma was 2:1. CONCLUSIONS: This study revealed that an increased frequency of infectious skin diseases may be expected in patients who have undergone kidney transplantation. Among skin cancers, BCC is more frequently observed in RTR, especially in those using azathioprine.

Caracterización clínica de la Nefropatía por Poliomavirus BK en pacientes trasplantados renales / Clinical characterization of Polyomavirus BK nephropathy in kidney transplanted patients

INTRODUCCIÓN. La nefropatía por poliomavirus BK resulta un problema emergente en el trasplante renal, pues contribuye a la pérdida temprana de los injertos renales. OBJETIVO. Caracterizar clínicamente a los pacientes trasplantados renales con nefropatía por poliomavirus BK. MATERIALES Y MÉTODOS. Estudio observacional, descriptivo, realizado en el Hospital de Especialidades Carlos Andrade Marín en el período 2013-2022, se obtuvo una base de datos anonimizada, 479 pacientes trasplantados renales, de estos se identificaron 37 pacientes que corresponde a un 7,7% con nefropatía por poliomavirus BK, se realizó un análisis con el programa estadístico SPSS v26®. RESULTADOS. La población estuvo caracterizada por pacientes del sexo masculino (56,8%), con una edad media de 48,2 años, el donante cadavérico fue el más frecuente (94,5%), la mayor parte del tratamiento de la nefropatía por poliomavirus BK consistió en cambio de micofenolato sódico a everolimus y se mantuvo con 50% de Tacrolimus y Prednisona (40,5%); al valorar el cambio de los valores de creatinina, los niveles más elevados fueros a los 12 meses cuando la pérdida renal fue temprana (p: 0,042), y de la misma manera a los 12 meses, fueron más elevados los niveles de creatinina cuando el diagnóstico histopatológico fue Nefropatía por Poliomavirus Clase 3 (p: 0,01). DISCUSIÓN. La prevalencia de la nefropatía se mantuvo por debajo del 10% reportado a nivel global, la creatinina empeoró en pacientes con pérdida temprana del injerto renal y con una clase patológica avanzada, hecho reportado en la fisiopatología de la enfermedad. CONCLUSIÓN. La pérdida del injerto renal temprano presentó una creatinina más alta que la tardía. Es recomendable un tamizaje adecuado para la detección temprana del virus BK siendo crucial para prevenir el deterioro de la función renal y limitar la posterior pérdida del injerto.

INTRODUCTION: BK polyomavirus nephropathy is emerging as a significant concern in kidney transplantation, as it contributes to the early loss of renal grafts. OBJECTIVE: The aim of this study was to clinically characterize renal transplant recipients with BK polyomavirus nephropathy. MATERIALS AND METHODS: An observational and descriptive study was conducted at Carlos Andrade Marín Specialties Hospital during the period of 2013 to 2022. An anonymized database comprising 479 renal transplant patients was utilized. Among these, 37 patients, constituting 7.7%, were identified with BK polyomavirus nephropathy. Data analysis was performed using the statistical program SPSS v26®. RESULTS: The study population was predominantly composed of male patients (56.8%) with a mean age of 48.2 years. Deceased donors accounted for the majority (94.5%) of cases. The primary approach for managing BK polyomavirus nephropathy involved transitioning from mycophenolate sodium to everolimus, alongside maintaining a regimen of 50% tacrolimus and 40.5% prednisone. When assessing changes in creatinine values, the highest levels were observed at 12 months, coinciding with early renal loss (p: 0.042). Similarly, at the 12-month mark, elevated creatinine levels were associated with a histopathological diagnosis of Polyomavirus nephropathy Class 3 (p: 0.01). DISCUSSION: The prevalence of nephropathy remained below the globally reported threshold of 10%. Creatinine levels worsened in patients experiencing early graft loss and an advanced pathological classification, aligning with established disease pathophysiology. CONCLUSION: Early renal graft loss was associated with higher creatinine levels compared to delayed loss. Adequate screening for early detection of BK virus is recommended, as it plays a crucial role in preventing renal function deterioration and limiting subsequent graft loss.

The efficacy of anti–TNF-? agents in the treatment of juvenile idiopathic arthritis-associated uveitis in a pediatric cohort

Purpose: Biologic therapy has shown promising control in children with often intractable juvenile idiopathic arthritis (JIA)?associated uveitis (JIA?U). Methods: This is a retrospective cohort study of 35 eyes of 35 children who received biologics for JIA?U. Pretreatment and posttreatment data (at 3, 6, 9, 12, 18, 24, and >24 months) were analyzed to determine functional success (stable/improved visual acuity), quiescence success (?0.5 cells in the anterior chamber), complete steroid success (termination of systemic, periocular therapy and decreased topical drops to ?2/day) or systemic steroid success (termination of systemic steroids only), and complete success (all of the above). Results: This study included 35 eyes up to 12 months and 21 eyes beyond 24 months. Steroid?sparing, functional, and quiescence success showed a rate of success of 52.43%, 77%, and 91%, respectively, at 12 months and 66.67%, 85.7%, and 76.2%, respectively, beyond 24 months. Complete success was 34.29% at 12 months, peaking at 18 months (65.62%) and reached 57.14% beyond 24 months. In their final follow?up, the best corrected visual acuity (BCVA) remained the same in 45.71%, improved in 37.14%, and worsened in 17.14% children. Conclusion: Biologic therapy is effective in JIA?U, especially in termination of systemic steroids, stabilization of vision, and maintaining quiescence

Immunosuppressive drugs in renal transplantation

A kidney transplant, sometimes known as a renal transplant, is the treatment of choice for kidney failure at end stage renal disease (ESRD). The renal transplant surgery is followed by a lifetime course of immunosuppressive agents, divided into initial induction phase and later maintenance phase. It is seen that the risk of acute rejection is maximum in the initial months after transplantation (induction phase) and then reduces later (maintenance phase). In induction phase there is use of high-intensity immunosuppression immediately after transplantation, when the risk of rejection is maximum and then the dose reduced for long- term therapy. The main challenge in the renal transplantation community is long- term transplant survival. Long-term graft loss is mainly due to acute and chronic graft rejection, and also due to complications of immunosuppressive therapy. Currently, there is triple therapy as conventional immunosuppressive protocol: a calcineurin inhibitor, an antimetabolite agent, and a corticosteroid. The main aim of development of new immunosuppressive agents is not only improvement of short- term outcomes but also to increase the long- term graft survival by less nephrotoxicity, and minimal side-effects.

Granulomatosis with Polyangiitis Presenting as a Renal Mass: A Scarce Case Report with a Review of the Literature

Wegener granulomatosis (WG) now known as granulomatosis with polyangiitis (GPA) is an uncommon autoimmune disorder of undivulged etiology affecting the respiratory tract including paranasal sinuses, nasal cavity, lungs, and kidneys predominantly. GPA presenting as a solitary renal mass is rarely seen. We present a case report of a 27-year-old female presenting with a right renal mass along with pain, low-grade fever, and arthralgia. Computed tomography scan of the abdomen revealed a hypodense low attenuated renal mass with indistinct margins. Ultrasound-guided biopsy revealed features typical of GPA. She was started on oral steroids (prednisolone 40?mg) and azathioprine. She developed pain, vomiting, and diarrhea after starting treatment with azathioprine. Azathioprine was stopped and rituximab 1?g weekly was started for 4 weeks followed by 500?mg 6 monthly injections. She got symptomatic relief at 4 weeks with a diminution of renal mass at 6 months follow-up. We report this rare entity of WG presenting as renal mass. Suspecting and diagnosing renal mass as a part of GPA prevented us from undertaking unnecessary surgical treatment in this patient. Medical treatment with steroids and rituximab is effective in inducing remission and maintenance.

Anti-PD-L1 antibody enhances curative effect of cryoablation via antibody-dependent cell-mediated cytotoxicity mediating PD-L1highCD11b+ cells elimination in hepatocellular carcinoma

Cryoablation (CRA) and microwave ablation (MWA) are two main local treatments for hepatocellular carcinoma (HCC). However, which one is more curative and suitable for combining with immunotherapy is still controversial. Herein, CRA induced higher tumoral PD-L1 expression and more T cells infiltration, but less PD-L1highCD11b+ myeloid cells infiltration than MWA in HCC. Furthermore, CRA had better curative effect than MWA for anti-PD-L1 combination therapy in mouse models. Mechanistically, anti-PD-L1 antibody facilitated infiltration of CD8+ T cells by enhancing the secretion of CXCL9 from cDC1 cells after CRA therapy. On the other hand, anti-PD-L1 antibody promoted the infiltration of NK cells to eliminate PD-L1highCD11b+ myeloid cells by antibody-dependent cell-mediated cytotoxicity (ADCC) effect after CRA therapy. Both aspects relieved the immunosuppressive microenvironment after CRA therapy. Notably, the wild-type PD-L1 Avelumab (Bavencio), compared to the mutant PD-L1 atezolizumab (Tecentriq), was better at inducing the ADCC effect to target PD-L1highCD11b+ myeloid cells. Collectively, our study uncovered the novel insights that CRA showed superior curative effect than MWA in combining with anti-PD-L1 antibody by strengthening CTL/NK cell immune responses, which provided a strong rationale for combining CRA and PD-L1 blockade in the clinical treatment for HCC.

Application of immune checkpoint inhibitors in liver transplantation for patients with hepatocellular carcinoma / 临床肝胆病杂志

Liver transplantation, as one of the radical treatment strategies for hepatocellular carcinoma, has a good clinical effect in patients meeting the Milan criteria; however, the high recurrence rate and metastasis rate after surgery bring great challenges to the long-term survival of such patients. Therefore, how to improve long-term survival rate and reduce postoperative tumor metastasis has become a key problem that needs to be solved urgently. In recent years, immune checkpoint inhibitors (ICIs), with their good safety and objective reactivity, have provided a new opportunity for the treatment of patients with advanced liver cancer and have become potential candidates for improving the therapeutic effect of liver transplantation. At present, early clinical studies have reported the unique advantages of ICIs used alone or in combination in downstaging or bridging therapy before liver transplantation for hepatocellular carcinoma and adjuvant therapy after liver transplantation. Therefore, this article reviews the clinical trials of ICIs in liver transplantation for hepatocellular carcinoma and the advances in the application of ICIs in recent years and discuss its safety and efficacy, in order to provide a certain reference for clinical medication.

Role of new potential immune blocking molecules in the development and progression of hepatocellular carcinoma / 临床肝胆病杂志

Hepatocellular carcinoma (HCC) is one of the most common malignant tumors around the world. The emergence of immune checkpoint inhibitors targeting programmed death-1/programmed death-ligand 1 and cytotoxic T lymphocyte-associated antigen-4 has brought great breakthroughs in the treatment of HCC. However, since HCC is a type of tumor with high heterogeneity, monotherapy is only effective for a small number of patients and may not be able to achieve long-lasting benefits due to drug resistance, and therefore, it is necessary to explore the potential of new immune checkpoint inhibitors in the prevention and treatment of HCC. This article analyzes and summarizes the biological characteristics of the new immune checkpoints T cell immunoglobulin and ITIM domain (TIGIT), V-domain immunoglobulin suppressor of T-cell activation (VISTA), B and T lymphocyte attenuator (BTLA), and B7 homologous protein-4 (B7-H4) and their expression and function in HCC. The analysis shows that TIGIT, VISTA, BTLA, and B7-H4 are highly expressed in HCC tissue and are associated with the prognosis of HCC patients, and targeted blocking of corresponding pathways can effectively inhibit the progression of HCC, suggesting that these molecules are potential targets for tumor treatment and that in-depth studies can provide new directions for HCC immunotherapy.