Postoperative Immunosuppression Research Articles

Combined Whole Eye and Face Transplant: Microsurgical Strategy and 1-Year Clinical Course.

Catastrophic facial injury with globe loss remains a formidable clinical problem with no previous reports of reconstruction by whole eye or combined whole eye and facial transplant. To develop a microsurgical strategy for combined whole eye and facial transplant and describe the clinical findings during the first year following transplant. A 46-year-old man who sustained a high-voltage electrical injury with catastrophic tissue loss to his face and left globe underwent combined whole eye and face transplant using personalized surgical devices and a novel microsurgical strategy at a specialized center for vascularized composite allotransplantation. Reperfusion and viability of the whole eye and facial allografts, retinal function, and incidence of acute rejection. The patient underwent a combined whole eye and face transplant from an immunologically compatible donor with primary optic nerve coaptation and conventional postoperative immunosuppression. Globe and retinal perfusion were maintained throughout the immediate postoperative period, evidenced by fluorescein angiography. Optical coherence tomography demonstrated atrophy of inner retinal layers and attenuation and disruption of the ellipsoid zone. Serial electroretinography confirmed retinal responses to light in the transplanted eye. Using structural and functional magnetic resonance imaging, the integrity of the transplanted visual pathways and potential occipital cortical response to light stimulation of the transplanted eye was demonstrated. At 1 year post transplant (postoperative day 366), there was no perception of light in the transplanted eye. This is the first report of whole eye transplant combined with facial transplant, demonstrating allograft survival including rejection-free graft survival and electroretinographic measurements indicating retinal response to light stimuli. These data highlight the potential for clinical allotransplantation for globe loss.

Impact of Surgery-Induced Myeloid-derived Suppressor Cells and the NOX2/ROS Axis on Postoperative Survival in Human Pancreatic Cancer.

Pancreatic cancer surgery triggered pronounced accumulation of NOX2+ myeloid-derived suppressor cells that inhibited NK cell function and negatively prognosticated postoperative patient survival. We propose the targeting of M-MDSC as a conceivable strategy to reduce postoperative immunosuppression in pancreatic cancer.

Overcoming neutrophil-induced immunosuppression in postoperative cancer therapy: Combined sialic acid-modified liposomes with scaffold-based vaccines

Immunotherapy is a promising approach for preventing postoperative tumor recurrence and metastasis. However, inflammatory neutrophils, recruited to the postoperative tumor site, have been shown to exacerbate tumor regeneration and limit the efficacy of cancer vaccines. Consequently, addressing postoperative immunosuppression caused by neutrophils is crucial for improving treatment outcomes. This study presents a combined chemoimmunotherapeutic strategy that employs a biocompatible macroporous scaffold-based cancer vaccine (S-CV) and a sialic acid (SA)-modified, doxorubicin (DOX)-loaded liposomal platform (DOX@SAL). The S-CV contains whole tumor lysates as antigens and imiquimod (R837, Toll-like receptor 7 activator)-loaded PLGA nanoparticles as immune adjuvants for cancer, which enhance dendritic cell activation and cytotoxic T cell proliferation upon localized implantation. When administered intravenously, DOX@SAL specifically targets and delivers drugs to activated neutrophils in vivo, mitigating neutrophil infiltration and suppressing postoperative inflammatory responses. In vivo and vitro experiments have demonstrated that S-CV plus DOX@SAL, a combined chemo-immunotherapeutic strategy, has a remarkable potential to inhibit postoperative local tumor recurrence and distant tumor progression, with minimal systemic toxicity, providing a new concept for postoperative treatment of tumors.

The role of surgical tissue injury and intraoperative sympathetic activation in postoperative immunosuppression after breast-conserving surgery versus mastectomy: a prospective observational study

BackgroundBreast cancer is the second most common cause of death from cancer in women worldwide. Counterintuitively, large population-based retrospective trials report better survival after breast-conserving surgery (BCS) compared to mastectomy, corrected for tumour- and patient variables. More extensive surgical tissue injury and activation of the sympathetic nervous system by nociceptive stimuli are associated with immune suppression. We hypothesized that mastectomy causes a higher expression of plasma damage associated molecular patterns (DAMPs) and more intraoperative sympathetic activation which induce postoperative immune dysregulation. Immune suppression can lead to postoperative complications and affect tumour-free survival.MethodsIn this prospective observational study, plasma DAMPs (HMGB1, HSP70, S100A8/A9 and S100A12), intraoperative sympathetic activation (Nociception Level (NOL) index from 0 to 100), and postoperative immune function (plasma cytokine concentrations and ex vivo cytokine production capacity) were compared in patients undergoing elective BCS (n = 20) versus mastectomy (n = 20).ResultsEx vivo cytokine production capacity of TNF, IL-6 and IL-1β was nearly absent in both groups one hour after surgery. Levels appeared recovered on postoperative day 3 (POD3), with significantly higher ex vivo production capacity of IL-1β after BCS (p = .041) compared to mastectomy. Plasma concentration of IL-6 was higher one hour after mastectomy (p = .045). Concentrations of plasma alarmins S100A8/A9 and S100A12 were significantly higher on POD3 after mastectomy (p = .003 and p = .041, respectively). Regression analysis showed a significantly lower percentage of NOL measurements ≤ 8 (absence of nociception) during mastectomy when corrected for norepinephrine equivalents (36% versus 45% respectively, p = .038). Percentage of NOL measurements ≤ 8 of all patients correlated with ex vivo cytokine production capacity of IL-1β and TNF on POD3 (r = .408; p = .011 and r = .500; p = .001, respectively).ConclusionsThis pilot study revealed substantial early postoperative immune suppression after BCS and mastectomy that appears to recover in the following days. Differences between BCS and mastectomy in release of DAMPs and intraoperative sympathetic activation could affect postoperative immune homeostasis and thereby contribute to the better survival reported after BCS in previous large population-based retrospective trials. These results endorse further exploration of (1) S100 alarmins as potential therapeutic targets in breast cancer surgery and (2) suppression of intraoperative sympathetic activation to substantiate the observed association with postoperative immune dysregulation.

Basiliximab Induction and Postoperative Steroid-free Immunosuppression With Tacrolimus in Pediatric Liver Transplantation: A Randomized Clinical Trial.

Optimizing the immunosuppressive regimen is essential to improve the long-term outcomes of pediatric liver transplant recipients. We conducted a prospective, randomized, open-label study to compare the safety and efficacy of 2 treatment approaches during pediatric liver transplantation: tacrolimus monotherapy following basiliximab induction (the study group) and a dual regimen of tacrolimus plus steroids (the control group). A total of 150 patients were enrolled, with 75 patients allocated to each group. In both groups, recipients achieved graft and recipient overall survival rates exceeding 93%, with no statistically significant differences between them. However, the study group exhibited a significantly lower incidence of acute cellular rejection (ACR), delayed occurrence of ACR, and an improved ACR-free survival rate at 2 y compared with the control group. Notably, the study group also showed a significant reduction in the incidence of de novo donor-specific antibodies at 3-mo and 2-y posttransplant. Furthermore, 6 mo after the transplant, the study group demonstrated significant improvements in weight-for-age Z score and height-for-age Z score. No notable differences were observed in postoperative complications or the incidence of liver fibrosis between the 2 groups. Basiliximab induction combine with tacrolimus (TAC) monotherapy is a safe and effective immunosuppressive regimen to reduce the episodes of ACR without influencing the development of liver fibrosis and graft and recipient survival rate after pediatric liver transplantation.

Liver Transplantation for Unresectable Colorectal Liver Metastasis: Perspective and Review of Current Literature.

The treatment of unresectable colorectal liver metastasis (CRLM) has previously been limited to palliative chemotherapy. Traditionally, the role of liver transplant has not been associated with sufficient survival to justify a patient undergoing a major operation with the associated requirement for postoperative immunosuppression. With improvements in chemotherapy options, a certain subset of patients can experience stable disease for years, which has prompted investigation into the role of liver transplant in these patients. Several recent studies have shown promising results in well-selected patients, with posttransplant survival approaching that of liver transplant recipients for other diseases. Here, we present a review of the data and current protocols for liver transplant for unresectable CRLM.

Effects of different anesthesia methods on perioperative immune function and long-term regression of patients undergoing thoracoscopic radical esophagectomy for esophageal cancer

ObjectiveThis study investigated the effects of different anesthetic methods on perioperative immune function and long-term regression of patients undergoing thoracoscopic radical surgery for esophageal cancer. MethodsData from 147 patients undergoing thoracoscopic radical surgery for esophageal cancer in our hospital from January 2017 to June 2019 were selected for retrospective analysis. Patients were divided into control (intravenous anesthesia combined with an epidural block, n = 83) and observation (intravenous anesthesia combined with a thoracic paravertebral nerve block, n = 64) groups. The use of relevant drugs during the surgery, indexes of the peripheral blood T-lymphocyte subpopulation at different time points (before induction of anesthesia, at the completion of surgery, 24 h postoperatively, and 48 h postoperatively), and 3-year postoperative survival were compared between the two groups. ResultsData on propofol and remifentanil use during surgery were not significantly different (P > 0.05) between the two groups. The proportion of vasoactive drug use was lower in the observation group than in the control group (P < 0.05). Differences in data for CD3+, CD4+, and CD4+/CD8+ cells between time points were significant (F = 13.256, 20.307, 18.035, P < 0.05), while those between the two groups were not (F = 1.005, 1.135, 1.204, P > 0.05). There was no interaction between data processing factors and time between the control and observation groups in CD3+, CD4+, and CD4+/CD8+ cells (F = 0.358, 0.778, 1.107, P > 0.05). The median overall survival time was 21.988 (95 % confidence interval: 18.436–25.541) and 26.978 (95 % confidence interval: 20.124–33.833) months in the control and observation groups, respectively, with a significant difference between the two groups (Log-rank χ2 = 3.925, P < 0.05). ConclusionsBoth anesthetic methods achieve satisfactory anesthetic results and reduce postoperative stress and immunosuppression. However intravenous anesthesia combined with an epidural block can increase the incidence of intraoperative hypotension in the patients, thoracic paravertebral nerve block combined with general anesthesia is more favorable for maintaining intraoperative blood pressure and heart rate stability, as well as for postoperative survival.

Abdominal surgery induces long-lasting changes in expression and binding of CTCF with impact on Major Histocompatibility Complex II transcription in circulating human monocytes.

Postoperative immunosuppression has been recognized as an important driver of surgery-related morbidity and mortality. It is characterized by lymphocyte depression and impaired monocyte capability to present foreign antigens to T-cells via Major Histocompatibility Complex, Class II (MHC-II) molecules. In patients with postoperative abdominal sepsis, we previously detected a persisting differential binding of the CCCTC-Binding Factor (CTCF), a superordinate regulator of transcription, inside the MHC-II region with specific impact on human leucocyte antigen (HLA) gene expression. In this prospective exploratory study, we investigated to which extent major surgery affects the MHC-II region of circulating CD14+-monocytes. In non-immunocompromised patients undergoing elective major abdominal surgery, a postoperative loss of monocyte HLA-DR surface receptor density was accompanied by a decline in the transcription levels of the classical MHC-II genes HLA-DRA, HLA-DRB1, HLA-DPA1 and HLA-DPB1. The surgical event decreased the expression of the transcriptional MHC-II regulators CIITA and CTCF and led to a lower CTCF enrichment at an intergenic sequence within the HLA-DR subregion. During the observation period, we found a slow and only incomplete restoration of monocyte HLA-DR surface receptor density as well as a partial recovery of CIITA, HLA-DRA and HLA-DRB1 expression. In contrast, transcription of HLA-DPA1, HLA-DPB1, CTCF and binding of CTCF within the MHC-II remained altered. In circulating monocytes, major surgery does not globally affect MHC-II transcription but rather induces specific changes in the expression of selected HLA genes, followed by differential recovery patterns and accompanied by a prolonged reduction of CTCF expression and binding within the MHC-II region. Our results hint toward a long-lasting impact of a major surgical intervention on monocyte functionality, possibly mediated by epigenetic changes that endure the life span of the individual cell.

One Year Experience of the Hand Allotransplantation First Performed after Korea Organ Transplantation Act (KOTA) Amendment.

The revision of the Korea Organ Transplantation Act (KOTA) in 2018 included hand/arm among the organs that can be transplanted. The first hand transplantation since the revision of KOTA took place in January 2021. A 62-year-old male patient experienced hand amputation on July 13, 2018, by a catapult injury. The patient first visited our institute 3 months after the injury. After serial interviews and an overall evaluation, the patient was registered on the hand transplantation waiting list in January 2020. On January 9, 2021, the patient underwent hand transplantation at the right distal forearm level. The total operation time was 17 hours 15 minutes, and the cold ischemic time was 4 hours 9 minutes. Postoperative immunosuppression was administered based on the protocol used for kidney transplantation. Two acute rejection episodes occurred, on postoperative days 33 and 41. Both rejection episodes were reversible with rescue therapy of a higher tacrolimus trough level, steroid pulse therapy, and topical immunosuppressants. Controlled passive range of motion exercise was started on postoperative day 10. Dynamic splint was applied on postoperative day 18. At 1 year, graft maintenance and functional improvement were satisfactory, and the patient showed a Disabilities of Arm, Shoulder and Hand score of 25.8. We successfully performed the first hand transplantation surgery under the KOTA amendment. It came from the organic and effective cooperation of plastic, orthopaedic, and transplantation departments and we believe it will guarantee the future ongoing success.

Topical Tacrolimus Compared With Oral Tacrolimus for Postoperative Immunosuppression in Primary Keratolimbal Allograft.

The aim of this study was to compare outcomes between topical tacrolimus and oral tacrolimus as the primary calcineurin inhibitor for postoperative immunosuppression after primary keratolimbal allograft (KLAL) transplantation for limbal stem cell deficiency (LSCD). We performed a retrospective, comparative cohort study at a single tertiary referral center (University of MN) of all patients who underwent primary KLAL between 2014 and 2021. Eyes were grouped into those which received topical tacrolimus as the only calcineurin inhibitor (topical group) and eyes in which patients received oral tacrolimus with or without topical tacrolimus (oral group). Clinical and donor tissue data were obtained and compared between the 2 groups. In total, 27 eyes of 22 patients (median age 42 years, range 20-79 years) were included, of which 18 eyes were in the oral group and 9 eyes were in the topical group. The mean follow-up time was 33.2 ± 22.6 months. The most frequent etiology of LSCD was alkaline burn (33.3%). At 36 months, graft failure occurred in 6 eyes in the oral group (33.3%) and 2 eyes in the topical group (22.1%) ( P = 0.57). The failure rate in the oral group was 9.1 per 1000 person-months versus 8.4 per 1000 person-months in the topical group ( P = 0.96). The median improvement in BCVA was logMAR -0.975 and logMAR -0.45 for the oral and topical group, respectively ( P = 0.50). With careful patient selection, topical tacrolimus may be a viable alternative to oral tacrolimus in KLAL.

Perioperative oncolytic virotherapy to counteract surgery-induced immunosuppression and improve outcomes in pancreatic ductal adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDAC) is a high fatality cancer with one of the worst prognoses in solid tumors. Most patients present with late stage, metastatic disease and are not eligible for potentially curative surgery. Despite complete resection, the majority of surgical patients will recur within the first two years following surgery. Postoperative immunosuppression has been described in different digestive cancers. While the underlying mechanism is not fully understood, there is compelling evidence to link surgery with disease progression and cancer metastasis in the postoperative period. However, the idea of surgery-induced immunosuppression as a facilitator of recurrence and metastatic spread has not been explored in the context of pancreatic cancer. By surveying the existing literature on surgical stress in mostly digestive cancers, we propose a novel practice-changing paradigm: alleviate surgery-induced immunosuppression and improve oncological outcome in PDAC surgical patients by administering oncolytic virotherapy in the perioperative period.

Remifentanil combined with dexmedetomidine on the analgesic effect of breast cancer patients undergoing modified radical mastectomy and the influence of perioperative T lymphocyte subsets.

To study the analgesic effect of breast cancer patients undergoing modified radical mastectomy (MRM) and the influence of perioperative T lymphocyte subsets by remifentanil combined with dexmedetomidine. 80 breast patients were divided into control group and research group based on the anesthesia protocol. Patients in control group was given remifentanil for anesthesia induction and maintenance, and patients in research group was given remifentanil and dexmedetomidine for anesthesia induction and maintenance. We compared the anesthesia time, operation time, surgical blood loss, postoperative wake-up time, extubation time, incidence of adverse reactions, VAS score and T lymphocyte subsets in peripheral blood in the two groups of patients. The baseline data including age, height, weight and BMI, ASA classification, stage of breast cancer, frequency of neoadjuvant therapy, and surgical characteristics including anesthesia time, operation time and bleeding volume all have no significant difference between two groups (P > 0.05). Compared to control group, the time of wake up and extubation in patients of research group were all significantly decreased (P < 0.05), and significantly decreased MBP and HR after loading dose of dexmedetomidine in research group (P < 0.05). The VAS scores of patients at 4, 8, 12, 16, 20 and 24 h after surgery in the research group are all significantly lower than those in the control group (P < 0.05). Before induction of anesthesia, there was no significant difference in the ratio of CD4+, CD8+ and CD4+/CD8+ T lymphocytes in peripheral blood between the two groups (P > 0.05). At 1 h during operation and 24 h after operation, the ratio of CD4+ and CD4+/CD8+ cells in the research group was significantly higher than these of the control group (P < 0.05), while the ratio of CD8+ cells was lower than that of the control group (P < 0.05). For breast cancer patients undergoing MRM, the use of remifentanil combined with dexmedetomidine can enhance postoperative analgesia and reduce postoperative immunosuppression.

Postoperative Plasmacytoid Dendritic Cells Secrete IFNα to Promote Recruitment of Myeloid-Derived Suppressor Cells and Drive Hepatocellular Carcinoma Recurrence.

IFNα secreted by plasmacytoid dendritic cells drives postoperative immunosuppression and early recurrence of hepatocellular carcinoma, providing new biomarkers and therapeutic targets to improve patient outcomes after surgical resection.

Robotic Kidney Transplantation Under Regional Hypothermia.

The technique of robotic kidney transplantation (RKT) under regional hypothermia is being described. It may be performed in all patients requiring kidney transplantation with some relative contraindications. Unlike open transplantation, RKT is a transperitoneal procedure. Patient lies supine with low lithotomy and 15° to 20° reverse Trendelenburg position. Port placement is like standard radical prostatectomy with a multiport device placed at the umbilicus. The graft after harvest needs special care on the bench to ligate all vascular communications and placed in a gauze jacket for easy handling. After transplant bed preparation, the graft is introduced in peritoneal cavity through the umbilical opening and placed over the bladder flap bed with ice slush for hypothermia. End-to-side vascular anastomoses of renal vein and artery are done with the graft lying in pelvic hollow and renal vessels facing laterally to external iliac vessels. After vascular anastomoses, the graft is rotated laterally to iliac fossa to be fixed with preformed peritoneal flap. A stented ureterovesicostomy to the recipient is done using extravesical technique. The external opening for introducing the graft and the robotic port openings is closed after leaving a drain. Postoperative (PO) care and PO immunosuppression are like the open counterpart, except the treatment of drain, which is removed on second PO day. Obese recipients and multiple graft vessels may be handled comfortably during RKT with described techniques. It is important to follow certain checkpoints to avoid bleeding. With graft and patient survival of 95.2% and 94.5%, respectively, RKT outcomes are noninferior to open technique in the published data. The RKT has less incidence of PO pain, wound infection, and symptomatic lymphoceles.

Visceral Surgery Profoundly Affects the Cellular and Humoral Components of the Anti-Tumour Immune Response in a Murine Pancreatic Adenocarcinoma Model.

Simple SummarySurgery is a fundamental part of the multimodal therapy concepts in oncological patients, especially in the early stage of pancreas tumour. There are numerous studies on the impact of primary tumour resection on the immune status, but to our knowledge, the impact of tumour-unrelated surgery on the anti-tumour immune response to the primary tumour it is not yet understood. Therefore, we used a murine model combining an orthotopically implanted adenocarcinoma of the pancreas and the model of surgically-induced immune dysfunction to assess the impact of postoperative immunosuppression on the growth of the primary tumour, on mortality and on the most important immune cell compartments in tumour defence. This knowledge might contribute to a basic understanding of the interaction of the primary tumour and the immune system and could guide new approaches to therapeutic strategies.(1) Background: Surgery is the most important element of multimodal treatment concepts in oncological patients, especially in the early stages of pancreatic tumours. While the influence of primary tumour resection on the immune status was analysed in several studies, the impact of tumour-unrelated visceral surgery on the tumour-bearing organism and on the primary tumour itself is not yet fully understood. (2) Methods: We combined a murine model of orthotopically implanted adenocarcinoma of the pancreas with the model of surgically-induced immune dysfunction (SID). Mortality and general condition including body weight were observed over a period of 28 days. Tumour growth was analysed by MRI scans on days 8 and 27 following tumour implantation. On day 28, the immune cell populations in the blood and spleen as well as the serum cytokines were quantified. (3) Results: SID results in a significant deterioration of the general condition and a reduced increase in the body weight of tumour-bearing mice compared to the control groups, while mortality and tumour growth rate were not influenced. The numbers of spleen macrophages and neutrophils were increased in tumour-bearing animals following SID. Furthermore, both macrophage and neutrophil levels were increased in the peripheral blood. (4) Conclusions: The presented results might contribute to the basic understanding of the interaction of tumour and immune system and could contribute to new approaches to immunotherapeutic strategies.

A Translational Randomized Trial of Perioperative Arginine Immunonutrition on Natural Killer Cell Function in Colorectal Cancer Surgery Patients.

Surgery results in severe impairment of natural killer (NK) cell cytotoxicity (NKC) and activity (NKA, cytokine secretion), and a dramatic drop in arginine levels. Postoperative immunosuppression is associated with increased complications and recurrence. Perioperative arginine is reported to reduce postoperative complications. Because arginine modulates NK cell function, this study aimed to determine whether perioperative consumption of arginine-enriched supplements (AES) can improve NK cell function in colorectal cancer (CRC) surgery patients. This study randomized 24 CRC patients to receive the AES or isocaloric/isonitrogenous control supplement three times a day for five days before and after surgery. The AES contained 4.2 g of arginine per dose (12.6 g/day). The primary objective was to determine whether AES improved NKC by 50 % compared with the control group after surgery. On surgery day (SD) 1, NKC was significantly reduced postoperatively in the control group by 50 % (interquartile range [IQR], 36-55 %; p = 0.02) but not in the AES group (25 % reduction; IQR, 28-75 %; p = 0.3). Furthermore, AES had no benefit in terms of NKA or NK cell number. Compliance was much greater preoperatively (>91 %) than postoperatively (<46 %). However, despite excellent preoperative compliance, arginine was rapidly cleared from the blood within 4 h after consumption and therefore, did not prevent the postoperative drop in arginine. Oral consumption of arginine immunonutrition resulted in a modest improvement in NKC after surgery but was unable to prevent postoperative arginine depletion or the suppression of NKA (ClinicalTrials.gov NCT02987296).

Percutaneous Endoscopic Interbody Debridement and Fusion (PEIDF) Decreases Risk of Sepsis and Mortality in Treating Infectious Spondylodiscitis for Patients with Poor Physical Status, a Retrospective Cohort Study.

Background: Postoperative immunosuppression is associated with blood loss and surgical trauma during surgery and subsequently predisposes patients to increased morbidity. Spine endoscopic surgery has been accepted as an effective surgical technique with less surgical trauma and less blood loss for the complication of infectious spondylodiscitis. Therefore, the aim of this study was to investigate whether PEIDF could reduce the morbidity rates for patients with infectious spondylodiscitis. Methods: We launched a retrospective cohort study on the comparison of the perioperative prognosis between PEIDF and conventional open surgery for single-level lumbar infectious spondylodiscitis in patients with poor physical health (ASA ≥ 4) from 2014 to 2019. Results: Forty-four patients were included in this study. Fifteen of them underwent PEIDF, and the rest of the 29 patients were treated with open surgery. Less surgical blood loss (p < 0.001) and intraoperative transfusions (p < 0.001) with a better decline of CRP (p = 0.017) were statistically significant in patients receiving PEIDF. Patients undergoing conventional open surgery encountered more postoperative sepsis (p = 0.030), a higher qSOFA score (p = 0.044), and prolonged-time for CRP normalization (p = 0.001). Conclusions: PEIDF minimizes a poor postoperative outcome due to less surgical trauma, intraoperative blood loss, and the need for a blood transfusion.

A bio-responsive, cargo-catchable gel for postsurgical tumor treatment via ICD-based immunotherapy.

Tumor recurrence and metastasis after surgery remain challenges for tumor treatment. Strategy that can promote the immunogenicity, activate adaptative immune response and eliminate post-operative immunosuppression would be a promising way to achieve a desired clinical benefit. In this study, immunogenic cell death (ICD) priming anti-tumor adaptive immune response was executed to potentiate immune checkpoint blockade (ICB) therapy through the PD1/PDL1 pathway for postsurgical treatment. Here, we present a bio-responsive and cargo-catchable gel depot composed of pullulan and chitosan cross-linking through matrix metalloproteinase (MMP) sensitive peptide for co-delivery of anti-programmed death-ligand 1 antibody (aPDL1) and doxorubicin -encapsulated liposomes (DOX-Lip). This drug carrier showed expected ability to respond to the highly expressed MMP in postsurgical tumor microenvironment (TME). In vivo studies on 4T1 breast tumor mouse model demonstrated that the gel depot could efficiently prolong the mouse survival after tumor resection by preventing tumor recurrence and metastasis. The results suggested that ICD combining with PD1/PDL1 blockade based on the bio-responsive and cargo-catchable gel depot could facilitate the maturation of DCs and reverse the immunosuppressive environment in tumor resection area, thus amplifying the systemic anti-tumor immune response.

Long-Term Clinical Outcomes of Keratolimbal Allograft Alone or in Combination With Keratoplasty in Chronic and Delayed-Onset Mustard Gas Keratopathy.

The purpose of this study was to investigate the long-term clinical outcome of keratolimbal allograft (KLAL) alone or in combination with keratoplasty, in the management of patients with chronic and delayed-onset mustard gas keratopathy (MGK). Patients who had KLAL for MGK with or without corneal transplantation between 2002 and 2016 were recalled to be enrolled in this retrospective interventional case series. The primary outcome was the success rate of the KLAL demonstrated by Kaplan-Meier cumulative survival analysis. The secondary outcomes were postoperative BCVA and the need for further surgery. A total of 108 eyes of 68 patients with MGK underwent KLAL. All patients were male with an average age of 54 ± 6 years with an average follow-up duration of 81.9 ± 38.4 months. Sectoral KLAL alone was performed in 62 eyes (57.4%), combined with lamellar keratoplasty (LKP) in 40 eyes (37%) and combined with penetrating keratoplasty in 6 eyes (5.6%). The cumulative probability of success was 75% within the follow-up duration. The mean duration of successful KLAL survival was 80.6 ± 38 months. 88.1% of these eyes needed only 1 operation to stabilize the ocular surface. Average BCVA did not improve significantly after KLAL alone, except in those accompanied by keratoplasty. KLAL combined with LKP achieved the superior clinical outcome compared with KLAL alone. Infectious keratitis occurred in 6 eyes (5.5%). No adverse event due to postoperative systemic immunosuppression was observed. KLAL alone or combined with LKP is effective, durable, and visually acceptable in the reconstruction of ocular surface in patients with limbal stem cell deficiency secondary to MGK.

Clinical Manifestations and Outcomes of Renal Transplantation Patients With Pneumocystis jirovecii Pneumonia and Cytomegalovirus Co-infection.

BackgroundPneumocystis jirovecii pneumonia (PJP) and cytomegalovirus (CMV) infection are common opportunistic infections among renal transplantation (RT) recipients, and both can increase the risk of graft loss and patient mortality after RT. However, few studies had evaluated PJP and CMV co-infection, especially among RT patients. Therefore, this study was performed to evaluate the impact of CMV co-infection with PJP among RT recipients.MethodsWe retrospectively analyzed the clinical data of patients with confirmed diagnosis of PJP between 2015 and 2021 in our hospital. We divided patients into PJP and PJP+CMV groups according to their CMV infection status, and the clinical severity and outcomes of the two groups were evaluated.ResultsA total of 80 patients after RT were diagnosed with PJP. Of these, 37 (46.2%) patients had co-existing CMV viremia. There were no statistically significant intergroup differences in age, sex, diabetes, onset time of PJP after RT and postoperative immunosuppressant. Compared to serum creatinine (Cr) at admission, the serum Cr at discharge in both the PJP and PJP+CMV groups were decreased. The PJP+CMV group had a higher C-reactive protein level, higher procalcitonin level, and lower albumin level than the PJP group. The PJP+CMV group showed a higher PSI score than the PJP group. Moreover, the initial absorption time of the lesion was longer in the PJP+CMV group. However, the duration of hospitalization showed no significant differences between the two groups. The mortality rate was 9.4-times higher in the PJP+CMV group than in the PJP group. The rate of admittance to the intensive care unit was 3.2-times higher in the PJP+CMV group than in the PJP group.ConclusionCMV co-infection may result in more serious inflammatory response. RT patients with PJP+CMV infection had more severe clinical symptoms, slower recovery from pneumonia, and higher mortality than those with PJP alone. Therefore, when RT patients present with severe PJP, the possibility of CMV co-infection should be considered. Short-term withdrawal of immunosuppressants in case of severe infection is safe for the renal function of RT patients.