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A 15-y-old captive-born female bottlenose dolphin (Tursiops truncatus) had slowly progressive lethargy, inappetence, and pallor of the oral mucosa. Serial hemograms and serum biochemistry analysis revealed hemolyzed plasma, gradually severe anemia with reticulocytosis, spherocytosis, pronounced neutrophilia with left shift and toxic change, and indirect hyperbilirubinemia. Urinalysis identified both hemoglobinuria and bilirubinuria. Hyperglobulinemia with polyclonal gammopathy was evident by protein electrophoresis, and the saline agglutination test was positive. Splenomegaly and hyperechogenic liver were also observed on ultrasound. These findings meet the diagnostic criteria established for immune-mediated hemolytic anemia (IMHA) in small animals, which is extremely rare in cetacean species, and, to our knowledge, has not been fully documented. Several potential triggers of a secondary IMHA were ruled out, including the most common cetacean virus, exposure to new drugs, and recent vaccination events. Following recommendations from companion animal medicine, immunosuppressive therapy was implemented and proved effective in this bottlenose dolphin; the CBC returned to normal after 3 mo of treatment. [ABSTRACT FROM AUTHOR]

Background: Pulmonary pseudoaneurysm (PAP) is a fatal complication of severe acute respiratory syndrome caused by coronavirus 2 infections in the lungs. Other causative agent such as fungal and tubercular also responsible for this entity. Early detection and treatment can save a patient's life. Case presentation: Here we describe a case of a left pulmonary artery pseudo aneurysm in a 54-year-old patient with COVID-19 pneumonia who presented with massive hemoptysis and which was treated with endovascular embolization. Conclusion: It is caused by vasculopathy due to immunosuppression /immune dysregulation in COVID-19. Minimally invasive endovascular embolization of pseudoaneurysm carries less mortality and morbidity. [ABSTRACT FROM AUTHOR]

Objective: To describe the evolution of pancreas transplantation, including improved outcomes and factors associated with improved outcomes over the past 5 decades. Background: The world's first successful pancreas transplant was performed in December 1966 at the University of Minnesota. As new modalities for diabetes treatment mature, we must carefully assess the current state of pancreas transplantation to determine its ongoing role in patient care. Methods: A single-center retrospective review of 2500 pancreas transplants was performed over >50 years in bivariate and multivariable models. Transplants were divided into 6 eras; outcomes are presented for the entire cohort and by era. Results: All measures of patient and graft survival improved progressively through the 6 transplant eras. The overall death-censored pancreas graft half-lives were > 35 years for simultaneous pancreas and kidney (SPK), 7.1 years for pancreas after kidney (PAK), and 3.3 years for pancreas transplants alone (PTA). The 10-year deathcensored pancreas graft survival rate in the most recent era was 86.9% for SPK recipients, 58.2% for PAK recipients, and 47.6% for PTA. Overall, graft loss was most influenced by patient survival in SPK transplants, whereas graft loss in PAK and PTA recipients was more often due to graft failures. Predictors of improved pancreas graft survival were primary transplants, bladder drainage of exocrine secretions, younger donor age, and shorter preservation time. Conclusions: Pancreas outcomes have significantly improved over time through sequential, but overlapping, advances in surgical technique, immunosuppressive protocols, reduced preservation time, and the more recent reduction of immune-mediated graft loss. [ABSTRACT FROM AUTHOR]

Obesity is associated with chronic low-grade inflammation, and adipose tissue inflammation is required for fatty tissue remodeling. Interestingly, immunosuppressed patients, as liver transplant recipients, often experience excessive weight gain. We investigated how liver recipients' inflammatory response affects body weight loss induced by dietary treatment. Overweight liver recipients were paired with non-transplanted subjects to compare their peripheral immune profiles. Transplanted patients had similar profiles of peripheral blood mononuclear cells compared to controls but lower CD8lowCD56+CD16+NK cells and higher B lymphocytes. Patients showed lower serum concentrations of IFN-γ, TNF, IL-4, IL-2, and IL-10 and lower inflammatory responsiveness of peripheral blood mononuclear cells under inflammatory stimuli. Liver recipients paired with non-transplanted subjects followed a weight loss dietary plan for 6 months to verify body composition changes. After 3 and 6 months of nutritional follow-up, the control group lost more body weight than the liver recipient group. The control group decreased fat mass and waist circumference, which was not observed in transplanted patients. Therefore, liver recipients under immunosuppressant treatment responded less to different inflammatory stimuli. This impaired inflammatory milieu might be implicated in the lack of response to weight loss dietary intervention. Inflammation may be essential to trigger the weight loss induced by dietary prescription. ClinicalTrials.gov identification number: NCT03103984. [ABSTRACT FROM AUTHOR]

The use of medication to alter the normal function of the immune system treads the fine balance between the body's ability to fend off foreign or aberrant antigens and increased susceptibility to opportunistic infections as well as decreased cancer immunosurveillance. The expanding array of immunosuppressive drugs, targeting specific mediators or pathways in the immune system, has improved patient outcome both for transplantation and autoimmune disease, but opportunistic infections remain a serious risk. Whilst many of these infections are successfully treated without any histopathological input, pathology plays a significant role by excluding mimics of infection, identifying viral, bacterial, fungal and parasitic infection even before their clinical suspicion, and in the diagnosis of malignancy. In a field which spans all pathogens and every organ system, this paper addresses the more commonly encountered organisms at their usual site of infection with emphasis on establishing a diagnosis and highlighting potential diagnostic traps. Malignancy is also discussed, including recently described lymphoproliferative processes. In recent years immune therapy for the treatment of a range of cancers is becoming routine practice. This too is associated with an increased risk of infection which needs to be differentiated from the spectrum of changes seen in immune therapy related disease. [ABSTRACT FROM AUTHOR]

Connective tissue, rheumatological and dermatological conditions affect a large proportion of the pregnant population and have important implications for women and their babies. Some conditions are chronic but may occur de novo in pregnancy whereas some are seen only during pregnancy. Multidisciplinary care is essential to maximise fetal and maternal outcomes, since many of these women require immunosuppressive treatment and close monitoring of their pregnancies. The development of biological therapies has revolutionised treatment of many connective tissue and arthritic diseases, allowing both more targeted treatments and an increase in treatment options. Their impact on fertility is minimal compared to older treatments and hence more women are able to conceive. With new treatments there will always be concerns about safety in pregnancy but concerns around neonatal immunosuppression have largely been unfounded and the benefits of continuing medication are significant. This article uses four cases to illustrate the challenges of management. [ABSTRACT FROM AUTHOR]

Intracerebral hemorrhage (ICH) is a major health problem. It is one of the most common types of stroke and results in mortality in approximately half of patients. More than half of the fatalities occur in the first 2 days. In addition to the mass effect after ICH hemorrhage, complex pathophysiological mechanisms such as intracranial vessel vasospasm, microthrombosis, and inflammatory immune reaction also increase brain damage. Both resident (including microglia and astrocytes) and circulating immune cells (including neutrophils, macrophages, and lymphocytes) involved in the inflammatory process. The inflammatory response is especially harmful in the acute phase due to harmful substances secreted by infiltrating immune cells. The inflammatory response also has beneficial effects, especially in the later stages. Their role in pathophysiology makes immune cells important therapeutic targets. General immunosuppressive approaches and depleting cell groups such as neutrophils or keeping them away from the lesion site may not be sufficient to prevent poor outcomes after ICH. This is most likely because they suppress anti-inflammatory activities and pro-inflammatory effects. Instead, directing immune cells to the beneficial subpopulation seems like a more rational solution. The pro-inflammatory N1 subpopulation of neutrophils damages the tissue surrounding ICH. In contrast, the N2 subpopulation is associated with anti-inflammatory reactions and tissue repair. Studies show that when neutrophils are polarized toward the N2 subpopulation, clinical outcomes improve and the volume of the infarct decreases. However, more research is still needed. This study aims to evaluate the role of neutrophils as immunotherapeutic targets in ICH in light of current knowledge. [ABSTRACT FROM AUTHOR]

BACKGROUND: More women of childbearing age are surviving after heart transplantation (HT), many of whom have a desire to become pregnant. Limited data exist evaluating patients' perspectives, receipt of counseling, and knowledge surrounding contraception, pregnancy, breastfeeding, and medication safety after HT. METHODS: We conducted a voluntary, confidential, web-based cross-sectional survey of women who were childbearing age (defined as 18-45 years) at the time of HT. Transplants occurred between January 2005 and January 2020. Surveys were conducted across 6 high-volume HT centers in the United States. RESULTS: There were 64 responses from women who were of childbearing age at the time of HT. Twenty-five women (39.1%) were pregnant before HT, and 6 (9.4%) women reported at least 1 pregnancy post-transplant. Fifty-three percent (n=34) reported they did not receive enough information on post-HT pregnancy before listing for HT, and 26% (n=16) did not discuss their ability to become pregnant with their care team before proceeding with HT. Following HT, 44% (n=28) still felt that they had not received enough information regarding pregnancy. The majority of women (n=49, 77%) had discussed contraception to prevent unplanned pregnancy with their transplant team. Twenty percent (n=13) reported that pregnancy was never safe after transplantation based on the information they had received from their transplant providers. CONCLUSIONS: Many women feel they are not receiving adequate counseling with regard to posttransplant reproductive health. This survey highlights an opportunity to improve both provider education and patient communication to better support women with HT desiring posttransplant pregnancy. [ABSTRACT FROM AUTHOR]

Infection of piglets with Glaesserella parasuis (G. parasuis) induces host immunosuppression. However, the mechanism underlying the immunosuppression of piglets remains unclear. Activation of the PD-1/PD-L1 axis has been shown to trigger host immunosuppression. Baicalin possesses anti-inflammatory and immunomodulatory functions. However, whether baicalin inhibits PD-1/PD-L1 activation and thus alleviates host immunosuppression has not been investigated. In this study, the effect of baicalin on the attenuation of piglet immunosuppression induced by G. parasuis was evaluated. Seventy piglets were randomly divided into the control group, infection group, levamisole group, BMS-1 group, 25 mg/kg baicalin group, 50 mg/kg baicalin group and 100 mg/kg baicalin group. Following pretreatment with levamisole, BMS-1 or baicalin, the piglets were challenged with 1 × 108 CFU of G. parasuis. Our results showed that baicalin, levamisole and BMS-1 modified routine blood indicators and biochemical parameters; downregulated IL-1β, IL-10, IL-18, TNF-α and IFN-γ mRNA expression; and upregulated IL-2 and IL-8 mRNA expression in blood. Baicalin, levamisole and BMS-1 increased the proportions of CD3+ T cells, CD3+CD4+ T cells, CD3+CD8+ T cells and CD3–CD21+ B cells in the splenocyte population, increased the proportions of CD3+ T cells, CD3+CD4+ T cells and CD3+CD8+ T cells in the blood, and inhibited PD-1/PD-L1 and TIM-3 activation. Baicalin, levamisole and BMS-1 reduced p-PI3K, p-Akt, and p-mTOR expression, the p-MEK1/2/MEK1/2 and p-ERK1/2/ERK1/2 ratios and increased RAS expression. Baicalin, levamisole and BMS-1 provided substantial protection against G. parasuis challenge and relieved tissue histopathological damage. Our findings might provide new strategies for controlling G. parasuis infection and other immunosuppressive diseases. [ABSTRACT FROM AUTHOR]

Clostridioides difficile infection (CDI) is a significant cause of morbidity and mortality among hospitalized patients, particularly those who are immunosuppressed. We aim to assess the outcomes of CDI among kidney transplant (KT) recipients. Nationwide Inpatient Sample from 2016 to 2020 was used to identify patients with KT and stratify based on the presence of CDI. Data were collected regarding demographics and comorbidities. Outcomes included in-hospital mortality, acute kidney injury, intensive care unit admission, transplant rejection, transplant failure, length of stay, and total hospitalization charges. The relationships between variables of interest and outcomes were analyzed using multivariate regression. A total of 557,635 KT recipients were included. CDI prevalence was 2.4%. The majority of patients in the CDI group were age >65 (43.6%), female (51%), White (55.3%), and had Medicare insurance (74.9%). On multivariate regression analysis, CDI was associated with increased odds of acute kidney injury (aOR 2.06, p < 0.001), intensive care unit admission (aOR 2.47, p < 0.001), and mortality (aOR 1.90, p < 0.001). CDI was also associated with longer length of stay (9.35 days vs 5.42 days, p < 0.001) and higher total hospitalization charges ($110,063 vs $100,006, p < 0.001). There was no difference in transplant rejection, complication, failure, or infection among KT recipients with CDI and those without. We found that CDI was associated with worse outcomes and higher costs. KT patients should be monitored closely for signs of CDI in order to initiate appropriate management. • Prevalence of CDI among hospitalized patients with a history of kidney transplant in the US is 2.4%. • CDI was associated with worse outcomes among kidney transplant recipients. • CDI was associated with higher resource utilization among kidney transplant recipients. • CDI did not confer an increased risk of kidney transplant rejection or failure. [ABSTRACT FROM AUTHOR]

Purpose: To report primary vitreoretinal lymphoma after surgical 0.59 mg fluocinolone acetonide implant (FAi) exchange in a patient treated with adalimumab for idiopathic bilateral panuveitis. Methods: Retrospective case review. Results: A 37-year-old woman with bilateral idiopathic panuveitis, who had favorable responses to previous FAi surgical implants, presented with right eye recurrent intraocular inflammation and cystoid macular edema that partially responded to systemic adalimumab. Her FAi was replaced, given her previous favorable response. She developed postoperative ocular inflammation transiently responsive to two serial vitreous taps and injections of intravitreal antimicrobials and then worsening inflammation and new layered flocculant material. Diagnostic vitrectomy showed a few atypical lymphocytes and cultures were negative. At postdiagnostic vitrectomy Month 1, flocculant material recurred. Aqueous cytology and flow cytometry revealed large CD45-positive B cells suspicious for lymphoma. Postoperatively, she revealed that she was pregnant. She was treated with eight monthly intravitreal methotrexate injections and postpartum consolidation radiotherapy. Subsequent repeat cytology, flow cytometry, and corneal pathologic examination revealed large B cells that were CD20 positive, and next-generation sequencing detected a dominant monoclonal B-cell population, diagnostic of PVRL. Nineteen months after FAi exchange, she developed an area of enhancement in the lateral aspect of the right frontal lobe on brain MRI, consistent with central nervous system involvement. Conclusion: The authors present a unique case of PVRL masquerading as postoperative endophthalmitis after FAi exchange in an eye with chronic panuveitis treated with adalimumab immunosuppressive therapy. The authors hypothesize that there may be a causal relationship between adalimumab and PVRL. [ABSTRACT FROM AUTHOR]

Myasthenia gravis (MG) is the most frequent transmission disease in the neuromuscular junction. Juvenile myasthenia gravis (JMG) is an autoimmune antibody-mediated disease of postsynaptic endplate defined as MG presentation in patients before the age of 18 years old. While many clinical features of JMG are identical to the adults, there are some significant differences between them regarding presentation, clinical course, antibody level, and thymus histopathology. In JMG, ocular symptoms are more frequent, the clinical course is comparably benign, and the outcome is better than adult MG. Antibodies attack the muscle endplate proteins in the postsynaptic membrane and interfere with transmission. These antibodies in most patients are against the acetylcholine receptors, but they may also be directed toward muscle-specific kinase, lipoprotein-related protein 4, and agrin. Findings show racial influences and genetic effects on the occurrence of JMG. The essential clinical symptom is fatigable weakness of muscles that can be in the form of isolated ocular type or more disseminated weakness. The diagnosis of JMG is essentially clinical, with fluctuating patterns of weakness and easy fatigability, but a series of diagnostic evaluations can confirm the diagnosis. Precise diagnostic evaluation and distinction from congenital myasthenic syndromes is critical. The treatment plan is conducted according to the clinical course (ocular or generalized), antibody type, and disease severity. The mainstay of treatment includes symptomatic therapy, long-lasting immunosuppressive treatment and treatment of myasthenic crisis. Novel medications are introduced and conducted to the specific pathophysiologic mechanisms of the disease, and they are used primarily in the refractory MG. [ABSTRACT FROM AUTHOR]

Total shoulder arthroplasty (TSA) is increasingly recognized as a therapeutic solution for various shoulder disorders. However, the correlation between preoperative determinants of health and postoperative TSA revisions remains underexplored. These correlations are scientifically important as they may be used to design higher-level clinical studies to confirm if they are in-fact predictive of revision. As such, this investigation aims to identify possible health and demographic disparities between primary TSA and revision TSA cohorts. Data for this research was sourced from the American College of Surgeons National Surgical Quality Improvement Program database from 2013 to 2021. Patients were classified based on Current Procedural Terminology (CPT) codes into 2 groups: primary TSA (CPT: 23472) and revision TSA (CPT: 23473 or 23474). Nineteen demographic and preoperative variables were compared between the cohorts using multivariate logistic regression. Odds ratios (ORs) along with their 95% confidence intervals (CIs) were calculated and graphically displayed. To account for multiple exploratory comparisons, Bonferroni correction was utilized with an adjusted significance threshold of 0.0026. TSA revision patients were more likely to arrive from a nursing home (OR 1.87, 95% CI [1.50, 2.32], P <.001), have diabetes (OR 1.09, 95% CI [1.05, 1.14], P <.001), be diagnosed with Systemic inflammatory response syndrome prior to surgery (1.38, 95% CI [1.13, 1.69], P =.002) and less likely to have independent functional status prior to surgery (OR 0.69, 95% CI [0.63, 0.76], P <.001). Moreover, those in the revision group were predominantly younger, male, receiving immunosuppressive therapy, exhibited baseline dyspnea, and had elevated American Society of Anesthesiologists class. Notably, factors such as smoking, racial background, and hypertension showed no significant differences (P >.0026). Contrary to contemporary literature, our findings suggest that, when demographic factors are controlled for, smoking is not correlated with revisions in TSA when compared to primary TSA. Furthermore, patients undergoing primary TSA are more likely to be functionally independent than patients undergoing revision TSA. While at the same time, a patient's arrival at surgery from a nursing home gave the greatest likelihood of a revision. [ABSTRACT FROM AUTHOR]

Solid organ transplant recipients (SOTRs) are believed to have an increased risk of metastatic cutaneous squamous cell carcinoma (cSCC), but reliable data are lacking regarding the precise incidence and associated risk factors. In a prospective cohort study, including 19 specialist dermatology outpatient clinics in 15 countries, patient and tumor characteristics were collected using standardized questionnaires when SOTRs presented with a new cSCC. After a minimum of 2 years of follow-up, relevant data for all SOTRs were collected. Cumulative incidence of metastases was calculated by the Aalen-Johansen estimator. Fine and Gray models were used to assess multiple risk factors for metastases. Of 514 SOTRs who presented with 623 primary cSCCs, metastases developed in 37 with a 2-year patient-based cumulative incidence of 6.2%. Risk factors for metastases included location in the head and neck area, local recurrence, size > 2 cm, clinical ulceration, poor differentiation grade, perineural invasion, and deep invasion. A high-stage tumor that is also ulcerated showed the highest risk of metastasis, with a 2-year cumulative incidence of 46.2% (31.9%-68.4%). SOTRs have a high risk of cSCC metastases and well-established clinical and histologic risk factors have been confirmed. High-stage, ulcerated cSCCs have the highest risk of metastasis. [ABSTRACT FROM AUTHOR]

Solid organ transplant is increasing globally. According to Kidney Research UK, around 5000 people in the UK are on the waiting list for a kidney and this is only increasing. Improved immunosuppression therapy and general management of transplanted patients mean their survival has improved. It will get more common for these patients to require input from a non-transplant centres. There are nuances of transplant patients which non-transplant anaesthetists and intensivists may not be aware of. A good understanding of some of these complexities are crucial to optimizing perioperative care and outcome. [ABSTRACT FROM AUTHOR]

Solid organ transplantation has progressed dramatically over the last 50 years; however, rejection still remains one of the barriers to successful transplantation. Immunological processes underlying the mechanisms of rejection are well described and numerous pharmacological agents exist to help suppress a recipient's immune system in order to prolong graft survival. Furthermore, clinician decisions and actions during both the work-up of a potential transplant recipient and in the perioperative phase can impact upon the immunological status of an individual and the likelihood of successful solid organ transplantation. In this article we aim to describe the key processes involved in solid organ immunology and their relevance in anaesthetic practice. [ABSTRACT FROM AUTHOR]

Haematogenous pyogenic bone and joint infection is rarely seen in developed countries, but in the developing world it is still a major and common problem. New forms of acute fulminating osteomyelitis are likely to appear due to immunosuppression in the wake of the worldwide spread of HIV infection, AIDS, and the increased use of steroids, antibiotics, and immune activators. Osteomyelitis due to candida and cryptococcus infection in certain regions, are occasionally observed, whilst osteomyelitis that is resistant to treatment is associated with diabetes mellitus. Bone and joint infections are difficult to cure. This difficulty is related to the presence of bacteria adherent to dead bone and foreign material in many cases, and also to the drug resistance and limited penetration of antibiotics into infected bone. This presentation summarizes present knowledge of bone and joint infection and its management. [ABSTRACT FROM AUTHOR]

The use of posttransplant cyclophosphamide has revolutionized the field of haploidentical hematopoietic stem cell transplant. The impact has been especially enhanced in low‑ and middle‑income countries. Unrelated donor pool in developing nations is often limited due to the lack of large unrelated donor registries. Donor‑specific antibodies (DSAs) are preformed immunoglobulin G anti‑human leukocyte antigen (HLA) antibodies against HLA antigens that are not shared with the donor. We present successful desensitization in a 13‑year‑old patient with classIII β‑thalassemia with very high MFI DSAs with flow crossmatch positivity, persisting after pretransplant immunosuppression. [ABSTRACT FROM AUTHOR]

Objective: The presence of donor‑specific antigens (human leukocyte antigen [HLA] incompatibility) leads to positive T‑cell or B‑cell crossmatch. Kidney transplant after desensitization protocols not only poses a financial burden on the patients but also there is an increased rate of infections and graft rejection. Paired kidney exchange (PKE) is cost‑effective and offers better postoperative graft outcome. Methods: We included six pairs of kidney transplant donors and recipients for 6‑way simultaneous PKE transplantation. These patients were ABO incompatible or HLA incompatible or both. Results: All patients underwent transplant in a single day without any perioperative surgical and anesthesia complications except for the need of mechanical ventilation in one patient in the postoperative care unit. The graft function was excellent in all recipients. Conclusion: This is the first 6‑way simultaneous kidney exchange transplantation in the northwestern region of India. The inclusion of multiple donors and recipients for a paired exchange kidney transplant, although challenging, increases the donor pool and decreases the waiting time and financial constraints. [ABSTRACT FROM AUTHOR]

Background and Objective: Pediatric renal transplantation is a life‑saving procedure for children with end‑stage renal disease. This study aims to analyze the outcomes of pediatric renal transplants at our center, focusing on patient demographics, donor sources, surgical techniques, posttransplant complications, graft survival, and rejection rates. Methodology: A retrospective analysis was conducted on 43 pediatric kidney transplant recipients. Data on recipient age, gender, donor type, pretransplant dialysis, donor characteristics, surgical techniques, native kidney disease, induction therapy, maintenance immunosuppression, posttransplant infections, graft survival, and rejection episodes were collected and analyzed. Results: We performed 43 pediatric kidney transplants in total. The average age was 13.7 years (±3.81), with 8 (18.6%) being under the age of ten, 11 (25.6%) being between the ages of eleven and fourteen, and 24 (55.8%) being between the ages of fifteen and eighteen. There were 43 recipients: 27 males and 16 females. There were four (9.3%) deceased donor renal transplants and 39 (90.7%) live‑related kidney transplants. Right internal iliac artery and right external iliac vein anastomosis were found in 32 (74.4%) cases, right external iliac artery and right external iliac vein in 9 (20.9%), right common iliac artery and right common iliac vein in 1 (2.3%), and right common iliac and right internal iliac in 1 (2.3%). Induction was used in 27 recipients (62.8%). Graft survival was seen at 1 year in 42 (97.7%) patients and at 5 years in 34 (81%). Biopsy‑proven rejection occurred in 22 (51.2%) of the recipients, with antibody‑mediated rejection occurring in 8 (18.6%) and cellular rejection occurring in 22 (51.2%). Graft loss was caused by acute cellular rejection in three (23.1%) cases, graft pyelonephritis in 2 (15.4%), and an unknown cause in 2 (15.4%). There were no significant connections with antibody‑mediated rejection. Conclusion: Our study provides valuable insights into the outcomes of pediatric renal transplantation at our center. Despite the challenges of graft rejection and posttransplant infections, favorable graft survival rates were achieved. Cellular rejection emerged as a significant risk factor for graft survival, highlighting the importance of effective immunosuppressive management. Our findings emphasize the need for close follow‑up, infection control measures, and individualized immunosuppressive strategies to optimize long‑term outcomes in pediatric renal transplant recipients. Further research is warranted to refine protocols and address the specific needs of this vulnerable patient population. [ABSTRACT FROM AUTHOR]

Objective: The objective of the study is to evaluate the outcomes of live‑donor renal allografts with multiple and single renal arteries taking into consideration ischemia times, graft function, and other complications including vascular and urological. Materials and Methods: We conducted a retrospective study by analyzing a prospectively maintained database from January 2021 to December 2021 of all patients undergoing live‑related renal allograft transplants at a tertiary care center in North India. A total of 239 live donor kidney transplants were performed during this period. Patients were divided into two groups – Group 1: Single artery single anastomosis and Group 2: Multiple arteries with two or more anastomoses. Duplex imaging of the graft was done at 6 months. Recipients were followed up for possible graft dysfunction, arterial insufficiency, and major urological complications. Results: Mean ischemia times in the two groups were 20.62 ± 1.05 and 30.45 ± 1.77 min, respectively. Failure to normalize creatinine (<1.2 mg/dl) within 72 h was seen in 6/183 and 3/56 (P > 0.05). Slow graft function was encountered in 6 cases in Group 1 and 3 cases in Group 2. Delayed graft function occurred in two patients in both groups. One‑year graft survival among the groups was 5/183 and 2/56, respectively (P > 0.05). One patient from Group 1 developed transplant renal artery stenosis. Six patients from Group 1 developed ureteric complications. Conclusion: Donor grafts with multiple renal arteries may be accepted safely with careful surgical reconstruction and close surveillance posttransplant. [ABSTRACT FROM AUTHOR]

There is a global shortage of transplantable organs, especially in a resource‑limited country like India. Deceased pediatric donors provide an excellent opportunity to expand the donor pool. Herein, we report a rare case of multi‑organ harvesting from a 3‑year‑old brain‑dead donor, where both the kidneys were transplanted en bloc to an adult male recipient and the liver to a 4‑year‑old male child. This case report provides the surgical steps and our experience. [ABSTRACT FROM AUTHOR]

Immunosuppression is a known risk factor for the development of cutaneous squamous cell carcinoma (CSCC), especially in solid organ transplant recipients and chronic lymphocytic leukemia. However, this risk is less well defined in autoimmune and inflammatory conditions. Assess the impact that disease-type, duration of immunosuppression, and systemic medications have on CSCC accrual rates, defined as the number of CSCCs a patient develops per year, in autoimmune and inflammatory conditions. Retrospective review of 94 immunosuppressed (rheumatoid arthritis: 31[33.0%], inflammatory bowel disease: 17[18.1%], psoriasis: 11[11.7%], autoimmune other (AO): 24[25.5%], inflammatory other: 21[22.3%]) and 188 immunocompetent controls to identify all primary, invasive CSCCs diagnosed from 2010 to 2020. Immunosuppressed patients had higher CSCC accrual rates than immunocompetent controls (0.44 ± 0.36): total cohort (0.82 ± 0.95, P <.01), rheumatoid arthritis (0.88 ± 1.10, P <.01), inflammatory bowel disease (0.94 ± 0.88, P <.01), psoriasis (1.06 ± 1.58, P <.01), AO (0.72 ± 0.56, P <.01), and inflammatory other (0.72 ± 0.61, P <.01). There was an association between increased tumor accrual rates and exposure to systemic medications including, immunomodulators, tumor necrosis factor-alpha inhibitors, non-tumor necrosis factor inhibitor biologics, and corticosteroids, but not with number of systemic medication class exposures or duration of immunosuppression. Retrospective, singlecenter study. Patients with autoimmune and inflammatory conditions accrue CSCCs at higher rates than immunocompetent patients. [ABSTRACT FROM AUTHOR]

COVID-19 has had enormous impact on health and social systems, with stringent public health measures enacted across Australia. The virus itself disproportionately affects immunocompromised individuals including people without functioning spleens. We thus sought to characterise the psychological and physical impact of COVID-19 and such measures upon this oft-neglected patient group. Adults ≥ 18 years old identified from the Spleen Australia (SA) database were invited to participate in an online survey in November to December 2021 to assess the impact of the COVID-19 pandemic. Stata (v17, StataCorps, Texas, USA) was used to conduct descriptive and frequency analyses. 2864 respondents were surveyed. The majority were female (1473/2838, 51.9%), Australian-born (2257/2835, 79.6%), and living in Victoria (1755/2822, 62.2%). The largest age group was 61–70 years-old (841/2858, 29.4%). Trauma was the commonest reason for asplenia (826/2724, 30.3%). Respondents reported the pandemic reduced their ability to visit a GP (753/2864, 26.3%), access food (153/2864, 5.3%), medications (179/2864, 6.3%) or spleen-specific vaccines (120/2864, 4.2%), maintain relationships (503/2864, 17.6%), or care for children (127/2864, 4.4%). 84.8% of participants reported at least one impact of COVID, including negative physical health (1463/2864, 51.1%), mental health (733/2864, 25.6%) and financial repercussions (509/2864, 17.8%). 96.9% (2743/2831) had received at least one dose of COVID-19 vaccines. Overall, we found detailed evidence of the negative psychological and physical impacts of the pandemic upon this cohort. We recommend that providers consider people without functioning spleens as requiring extra social and psychological support in circumstances such as the COVID-19 pandemic. [ABSTRACT FROM AUTHOR]

Introduction: Patients being on immunosuppressive treatment of any reason, along with other risk factors such as smoking and obesity, are vulnerable to be infected from SARS-CoV2. Aim of this report is to describe a case of a female patient under Rituximab therapy who experienced episodes of lung infection due to Severe Acute Coronavirus 2 (SARS-CoV-2) invasion although fully vaccinated. Case report: A 50-year-old woman, with a past medical history of lupus nephritis on rituximab was diagnosed with lung infection due to SARS-CoV-2. Eight months later, following her last infusion of Rituximab (RTX), she developed moderate Coronavirus Disease 2019 (COVID-19). After a partial recovery, she exhibited exacerbation of respiratory symptoms leading to readmission and invasive oxygenation. She was eventually discharged home after 31 days. Her monthly neurological evaluation did not reveal evidence of disease activity. She later received intravenous immunoglobulin and a decision was made to restart rituximab. Conclusions: This case raises the possibility of persistent virus shedding and reactivation of severe acute respiratory syndrome coronavirus in a patient with SLE and Rituximab therapy. We emphasize a precise consideration of management of patients with autoimmune disorders during the COVID-19 pandemic. [ABSTRACT FROM AUTHOR]

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• Treatment includes TCM, hormone and immunosuppressive combination therapy. • Improvement of lower extremity skin ulcers in cutaneous polyarteritis nodosa. • Provided a therapeutic idea that TCM can effectively reduce the side effects of hormones in delaying wound healing. Cutaneous polyarteritis nodosa (cPAN) is a systemic disease that is limited to the skin. cPAN usually presents with cutaneous reticular cyanotic, erythematous and palpable nodules, and cutaneous ulcers.Research has indicated that the use of hormones and immunosuppressive drugs can delay ulcer healing and associated neuropathy, and also elevate the risk of disease recurrence upon their reduction or withdrawal. Therefore, it is a necessary to find a safe and effective approach that minimize hormone side effects in ulcer treatment. The patient, a 48-year-old female of Han Chinese ethnicity, has suffered from recurrent erythema nodosum on both lower limbs for 8 years. The condition was aggravated by skin breakdown over the last 3 months. Despite multiple treatments, the patient's condition did not improve significantly, leading to the exploration of a combined approach of traditional Chinese and Western medicine. Following six months of combined traditional Chinese and Western medicine treatment, t the patient's newborn erythema and ulcers on both lower limbs did not reappear, and the ulcers gradually decreased in size and the erythema disappeared. The patient took the TCM regularly until April 15, 2023, when the ulcers were completely healed. Three months after the patient stopped taking TCM, the ulcers had completely healed with no recurrence, as observed during the follow-up visit on July 14th, 2023. Traditional Chinese Medicine Combined with Low-Dose Hormones May Effectively Treat Bilateral Lower Extremity Skin Ulcers Caused by Cutaneous Polyarteritis Nodosa. [ABSTRACT FROM AUTHOR]

Zearalenone (ZEN) is a mycotoxin that extensively contaminates food and feed, posing a significant threat to public health. However, the mechanisms behind ZEN-induced intestinal immunotoxicity remain unclear. In this study, Sprague-Dawley (SD) rats were exposed to ZEN at a dosage of 5 mg/kg/day b.w. for a duration of 14 days. The results demonstrated that ZEN exposure led to notable pathological alterations and immunosuppression within the intestine. Furthermore, ZEN exposure caused a significant reduction in the levels of apolipoprotein E (ApoE) and liver X receptor (LXR) (P < 0.05). Conversely, it upregulated the levels of myeloid-derived suppressor cells (MDSCs) markers (P < 0.05) and decreased the presence of 27-hydroxycholesterol (27-HC) in the intestine (P < 0.05). It was observed that ApoE or LXR agonists were able to mitigate the immunosuppressive effects induced by ZEN. Additionally, a bioinformatics analysis highlighted that the downregulation of ApoE might elevate the susceptibility to colorectal, breast, and lung cancers. These findings underscore the crucial role of the 27-HC/LXR/ApoE axis disruption in ZEN-induced MDSCs proliferation and subsequent inhibition of T lymphocyte activation within the rat intestine. Notably, ApoE may emerge as a pivotal target linking ZEN exposure to cancer development. [Display omitted] • ZEN induces intestinal immunosuppression by inhibiting T lymphocyte activation. • ZEN inhibits LXR/ApoE activation and promotes MDSCs proliferation by downregulating 27-HC. • ZEN may promote the occurrence and progression of colorectal cancer by downregulating ApoE. [ABSTRACT FROM AUTHOR]

Objectives: To review the outcomes of immune checkpoint inhibitor (ICI) treatment of advanced cutaneous squamous cell carcinoma (CSCC) outside clinical trials. Study design: Retrospective observational study; review of patient records in fifteen Australian institutions. Setting, participants: All Australian adults with locally advanced or metastatic CSCC not amenable to curative surgery or radiotherapy treated with ICIs, 5 May 2017 – 23 May 2022, through a cemiplimab compassionate access scheme (Therapeutic Goods Administration Special Access Scheme) or who personally covered the cost of pembrolizumab prior to the start of the access scheme. Main outcome measures: Best overall response rate (ORR) according to standardised assessment criteria using the hierarchy: Response Evaluation Criteria in Solid Tumors (RECIST 1.1), the modified World Health Organization clinical response criteria, and the Positron Emission Tomography Response Criteria (PERCIST 1.0); overall and progression‐free survival. Results: A total of 286 people with advanced CSCC received ICI therapy during May 2017 – May 2022 (cemiplimab, 270; pembrolizumab, 16). Their median age was 75.2 years (range, 39.3–97.5 years) and 232 were men (81%); median follow‐up time was 12.2 months (interquartile range, 5.5–20.5 months). Eighty‐eight people (31%) were immunocompromised, 27 had autoimmune disease, and 59 of 277 (21%) had ECOG performance scores of 2 or 3. The ORR was 60% (166 of 278 evaluable patients): complete responses were recorded for 74 (27%) and partial responses for 92 patients (33%). Twelve‐month overall survival was 78% (95% confidence interval [CI], 72–83%); progression‐free survival was 65% (95% CI, 58–70%). Poorer ECOG performance status was associated with poorer overall survival (per unit: adjusted hazard ratio [aHR], 3.0; 95% CI, 2.0–4.3) and progression‐free survival (aHR, 2.4; 95% CI, 1.8–3.3), as was being immunocompromised (overall: aHR, 1.8; 95% CI, 1.1–3.0; progression‐free: aHR, 1.8; 95% CI, 1.2–2.7). Fifty‐five people (19%) reported immune‐related adverse events of grade 2 or higher; there were no treatment‐related deaths. Conclusion: In our retrospective study, the effectiveness and toxicity of ICI therapy were similar to those determined in clinical trials. Our findings suggest that ICIs could be effective and well tolerated by people with advanced CSCC who are ineligible for clinical trials. [ABSTRACT FROM AUTHOR]

Zinc alloys have demonstrated considerable potentials as implant materials for biodegradable vascular and orthopedic applications. However, the high initial release of Zn2+ can trigger intense immune responses that impede tissue healing. To address this challenge and enhance the osteogenic capacity of zinc alloys, the surface of Zn1Mg was subjected to CO 2 plasma modification (Zn1Mg-PP) followed by grafting with choline phosphate chitosan (Zn1Mg-PP-PCCs). This study aims to investigate the in vitro and in vivo biocompatibility of the surface-modified Zn1Mg. The effect of the surface modification on the inflammatory response and osteogenic repair process was investigated. Compared with unmodified Zn1Mg, the degradation rate of Zn1Mg-PP-PCCs was significantly decreased, avoiding the cytotoxicity triggered by the release of large amounts of Zn2+. Moreover, PCCs significantly enhanced the cell-material adhesion, promoted the proliferation of osteoblasts (MC3T3-E1) and upregulated the expression of key osteogenic factors in vitro. Notably, the in vivo experiments revealed that the surface modification of Zn1Mg suppressed inhibited the expression of inflammatory cytokines, promoting the secretion of anti-inflammatory factors, thereby reducing inflammation and promoting bone tissue repair. Furthermore, histological analysis of tissue sections exhibited strong integration between the material and the bone, along with well-defined new bone formation and reduced osteoclast aggregation on the surface. This was attributed to the improved immune microenvironment by PCCs, which promoted osteogenic differentiation of osteoblasts. These findings highlight that the preparation of PCCs coatings on zinc alloy surfaces effectively inhibited ion release and modulated the immune environment to promote bone tissue repair. Surface modification of biodegradable Zn alloys facilitates the suppression of intense immune responses caused by excessive ion release concentrations from implants. We modified the surface of Zn1Mg with choline phosphate chitosan (PCCs) and investigated the effects of surface modification on the inflammatory response and osteogenic repair process. In vitro results showed that the PCCs coating effectively reduced the degradation rate of Zn1Mg to avoid cytotoxicity caused by high Zn2+ concentration, favoring the proliferation of osteoblasts. In addition, in vivo results indicated that Zn1Mg-PP-PCCs attenuated inflammation to promote bone repair by modulating the release of inflammation-related factors. The surface-modified Zn1Mg implants demonstrated strong osseointegration, indicating that the PCCs coating effectively modulated the immune microenvironment and promoted bone healing. [Display omitted] [ABSTRACT FROM AUTHOR]

Background: Tacrolimus metabolism is known to be determined by gene polymorphisms. Cyp3A5 genotype has most widely been seen to be associated with tacrolimus metabolism. Studies on other genes have produced mixed results. Objective: We studied the association of three polymorphisms CYP3A4*1B (-392 G>A), CYP3A5 (6986 A>G), and ABCB1 (3435 T>C) on tacrolimus levels and their association with either rejection or nephrotoxicity (infection or tacrolimus toxicity) in renal transplant recipients from India. Materials and Methods: In this prospective cohort study, patients who underwent kidney transplantation between July 2018 and July 2023 were studied. Inclusion criteria: Patients who underwent Kidney Transplantation and were (i) on tacrolimus-based immunosuppression and (ii) not on medications known to interact with calcineurin inhibitors, such as ketoconazole, phenytoin, and diltiazem, were studied. Tacrolimus levels, tacrolimus concentration/dose (C/D) and tacrolimus C/D per kg body weight, at monthly time points posttransplant for 6 months and biopsy-proven rejection, infection, tacrolimus toxicity, and acute tubular necrosis data were collected. Results: Three hundred and twenty-seven patients were included in the study. Two hundred and fifty-seven were male and 70 were female. A total of 1402 tacrolimus samples were collected, with an average of 3.2 ± 2.1 samples per patient. Tacrolimus levels were significantly lower in the Cyp3A5 AG and AA GG genotypes versus GG (5.27 ± 2.95 and 6.22 ± 2.79 vs. 8.05 ± 4.83, P < 0.001) as were C/D (3.45 ± 2.29 and 3.37 ± 1.91 vs. 6.47 ± 4.44, P < 0.001) and C/D/W (52.45 ± 33.98 and 52.19 ± 32.61 vs. 98.09 ± 73.80, P < 0.001). Cyp3A5 AA and AG had higher rejection rates than GG (20% vs. 13 vs. 8%, P = 0.03). The relative risk of rejection with A versus G polymorphism was 1.9 (confidence interval: 1.03-3.58), P = 0.03. Cyp3A4 and ABCB1 polymorphism studies did not show any association with the parameters studied. Conclusion: Our study showed that Cyp3A5 gene polymorphisms were significantly associated with tacrolimus metabolism, rejection episodes, and rejection risk. Cyp3A4 and ABCB1 were not significantly associated with the parameters studied. [ABSTRACT FROM AUTHOR]

Introduction: Kidney allograft survival has increased significantly in the past few decades. However, the more potent immunosuppression has also resulted in a higher incidence of infections including BK virus nephropathy (BKVN). The profile of kidney transplant (KT) recipients including age, basic kidney disease, comorbidities, dialysis vintage, and type of kidney donor in India is different from that of high-income countries. There are very few studies on the incidence and outcomes of BKVN from India. We studied the incidence, clinical features, and the impact of a screening strategy on patients with BKVN at our center. Materials and Methods: This was a single-center retrospective record-based study. We screened the medical records of all KT recipients at our center from March 2012 to December 2020 for patients who were diagnosed with BKVN. We compared the incidence of BKVN before and after the implementation of a proactive screening strategy in 2017. Results: From March 2012 to December 2020, a total of 212 KTs were performed at our center. Twenty-eight patients were diagnosed to have BKVN at this time. The incidence of BKVN in our study was 13.2%. The incidence of BKVN before routine screening was initiated at our center was 11.3% whereas it was 13.6% after routine screening was initiated. Graft loss from BKVN was 7.14%. Conclusion: The incidence of BKVN at our center is higher than previously reported in India; however, the rate of graft loss is low. A proactive screening strategy using nucleic acid test may allow early detection of BKVN and may have a beneficial impact on graft outcomes. [ABSTRACT FROM AUTHOR]

Introduction: Kidney transplantation is the preferred treatment for end-stage kidney disease, offering improved outcomes compared to dialysis. However, factors such as immunological rejection, drug toxicity, and infections limit its success. Incorporating protocol biopsies (PBs) into standard care for kidney transplant recipients varies widely. This study aims to review the literature on the practice, histopathological findings, and benefits of performing PB on allograft function. Materials and Methods: A systematic review was conducted using PubMed, ScienceDirect, and other databases from 2000 to 2023. Studies describing findings of PBs within 2 years posttransplant were included. Data extraction covered study design, immunosuppression, biopsy timing, incidence of subclinical rejection (SCR), clinical rejection, and allograft function measures. Statistical analysis was performed using R and RevMan software. Results: Among 25 studies (3384 patients) included, 8 were randomized controlled studies. Protocol biopsy timing varied, with the highest number performed at 1 year (44.84%). The pooled incidence of SCR was 13%, with heterogeneity across estimates. Subgroup analysis did not reveal significant differences in SCR rates between high- and low-immunologic risk patients. Patients who underwent PBs had lower clinical rejection rates (12.64% vs. 20.17%) and better allograft function. Incidence of calcineurin inhibitor toxicity ranged from 1.2% to 63.4%, and BK virus nephropathy ranged from 0% to 5.9% in included studies. Conclusion: Performing PB at 6 months, 1 year, and 2 years posttransplant can reveal SCR and potentially improve long-term graft outcomes. Treatment of SCR may reduce clinical rejection episodes. However, further research, particularly comparing PB with noninvasive methods, is needed to better understand their efficacy and complications in the modern transplant landscape. [ABSTRACT FROM AUTHOR]

There is a paucity of information regarding the health status of free-ranging eastern indigo snakes (EIS; Drymarchon couperi) in heavily modified and developing landscapes. As a component of regional Florida Everglades restoration efforts, several areas occupied by EIS are being converted from agricultural lands to reservoirs. From 2020 to 2022, 28 EIS were opportunistically captured at two of these sites and brought into captivity to join a captive breeding colony; however, 11 snakes died within 5 mo of capture. Health assessments were performed on 28 individuals and included hematology and plasma biochemistry analysis, as well as screening for pesticide contaminant levels, parasites, and other pathogens. Overall, the presence of pathogens was relatively high, suggesting immunosuppression secondary to stress: 25/28 (89.4%) Kalicephalus sp.; 12/28 (42.9%) Raillietiella orientalis; 11/28 (39.2%) Ochetosoma validum; 7/28 (25.0%) Cryptosporidium serpentis; 3/28 (10.7%) snake adenovirus 1; and 1/28 (3.6%) Ferlavirus genotype C. Stress may have been caused by physical displacement, habitat modification, and noise pollution. These potential stressors (including the presence of remnant harmful chemicals from previous land use and the impacts on this federally threatened species) should be considered further when making restoration or construction decisions. [ABSTRACT FROM AUTHOR]

Purpose: To describe cytomegalovirus retinitis in a patient with Good syndrome (hypogammaglobulinemia and thymoma), ocular progression despite treatment and fatal outcome. Methods: A 71-year-old woman with unilateral panuveitis of unknown cause and a history of thymoma resection was referred to the clinic. Visual acuity was 20/100 in her right eye and light perception in her left eye. In slit-lamp examination, the right eye had inferior, fine, pigmented keratic precipitates, 2+ anterior chamber cells, cataract, and 2+ vitreous cells, with no fundus detail and normal ocular ultrasound results. Left eye presented a white cataract, chronic hypotony, and increased choroidal thickness with calcifications. Laboratory evaluations showed normal or negative results for common causes of infection and inflammation. Prednisolone acetate eye drops were started, with improvement of AC inflammation. Cataract surgery was performed, reaching visual acuity of 20/30. Two years later, visual acuity had decreased and 2+ vitritis and retinitis were found. On clinical suspicion of masquerade syndrome, a vitrectomy biopsy was performed; pathologic assessments reported no data on ocular lymphoma. Leukopenia and lymphopenia were found: immunoglobulin levels, CD4 count, and viral load revealed systemic immunosuppression. The aqueous tap was positive for cytomegalovirus. Oral valganciclovir and intravitreal ganciclovir were initiated. Results: In a patient with previous resection of thymoma and hypogammaglobulinemia, final diagnosis was Good syndrome, with cytomegalovirus retinitis being secondary to immunosuppression. Despite treatment, cytomegalovirus retinitis progressed and systemic deterioration resulted in mortal outcome. Conclusion: Good syndrome is an extremely rare disease, and association with cytomegalovirus retinitis is uncommon. To the authors' knowledge, only 14 cases exist in the literature. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this study was to describe a case of endogenous endophthalmitis (EE) after severe COVID-19 disease, review patient outcomes with EE after COVID-19 infection, and review evidence regarding risk factors for developing EE. Methods: This is a review of health records, imaging, intravitreal injection, and pars plana vitrectomy for bilateral fungal EE after severe COVID-19 disease, and is a literature review on outcomes in EE after COVID-19 disease. Results: Sixty-three year-old man with diabetes and hypertension was admitted to hospital for severe COVID-19 disease for 3 months. His stay required intensive care unit admission, intubation, high-dose corticosteroids, tocilizumab, and was complicated by bacteremia, empyema, and fungal esophagitis. He developed floaters and bilateral vision loss (visual acuity 20/40 in the right eye, counting fingers in the left eye) with vitritis 2.5 months into his stay that did not respond to intravitreal voriconazole. Pars plana vitrectomy was performed for both eyes, resulting in visual acuity of 20/40 in the right eye, 20/30 in the left eye. Vitreous cultures were positive for Candida albicans. Endogenous endophthalmitis after COVID-19 disease has been reported in 22 patients to date, and outcomes are poor, with 40%+ of eyes legally blind (20/200 or worse). Although influenced by availability of imaging modalities and degree of training of the evaluating physician, misdiagnosis can affect 1/4 of cases, delaying treatment. Age, male sex, and diabetes increase the risk of severe COVID-19, which requires prolonged hospitalization, invasive catheterization, and immunosuppression, which in turn increases the risk of nosocomial infection. Conclusion: Low threshold for suspecting EE in patients presenting with floaters and decreased vision after severe COVID-19 disease is necessary to ensure prompt recognition and treatment. [ABSTRACT FROM AUTHOR]

This study examines inhibiting galectin 1 (Gal1) as a treatment option for hepatocellular carcinoma (HCC). Gal1 has immunosuppressive and cancer-promoting roles. Our data showed that Gal1 was highly expressed in human and mouse HCC. The levels of Gal1 positively correlated with the stages of human HCC and negatively with survival. The roles of Gal1 in HCC were studied using overexpression (OE) or silencing using Igals1 siRNA delivered by AAV9. Prior to HCC initiation induced by RAS and AKT mutations, lgals1- OE and silencing had opposite impacts on tumor load. The treatment effect of lgals1 siRNA was further demonstrated by intersecting HCC at different time points when the tumor load had already reached 9% or even 42% of the body weight. Comparing spatial transcriptomic profiles of Gal1 silenced and OE HCC, inhibiting matrix formation and recognition of foreign antigen in CD45+ cell-enriched areas located at tumor-margin likely contributed to the anti-HCC effects of Gal1 silencing. Within the tumors, silencing Gal1 inhibited translational initiation, elongation, and termination. Furthermore, Gal1 silencing increased immune cells as well as expanded cytotoxic T cells within the tumor, and the anti-HCC effect of lgals1 siRNA was CD8-dependent. Overall, Gal1 silencing has a promising potential for HCC treatment. Targeting Gal1 is effective in preventing as well as treatment of HCC and has translational potential. [Display omitted] [ABSTRACT FROM AUTHOR]

Patients considering total elbow arthroplasty (TEA) may be receiving immunosuppressive therapy; however, the relationship between immunosuppressive medications and postoperative complications is not well defined. Our purpose was to assess the relationship between preoperative immunosuppression and short-term complications following TEA. The American College of Surgeons National Surgical Quality Improvement Program database was reviewed from 2005 to 2020 to identify patients undergoing TEA. Procedures indicated for malignancy or infection were excluded. Patients were grouped according to preoperative chronic immunosuppressive status. Demographic and operative characteristics were compared between groups. The 30-day incidence of complications and reoperations were compared between groups. Multiple logistic regression models, inverse-weighted by propensity scores, were used to calculate odds ratio (OR) of experiencing any complication or return to the operating room based on immunosuppression status and other demographic characteristics. A total of 769 patients undergoing TEA were included, of whom 142 (18.5%) received chronic immunosuppression. Distribution of age, sex, race, body mass index, diabetes, and American Society of Anesthesiologists classification differed significantly between groups. Most procedures were performed on an inpatient basis, and the median operative duration was 148 minutes. Most procedures were indicated for fracture in the nonimmunosuppressed group and rheumatoid arthritis in the immunosuppressed group. Overall complication rates were 7.0% for immunosuppressed patients and 10.2% for nonimmunosuppressed patients. The incidence of complications and reoperations did not significantly differ between groups. After controlling for confounding and adjusting for patient characteristics, immunosuppressed patients were 0.52 times less likely to experience a complication. Additionally, there was no association between immunosuppression status and odds of return to the operating room. Similar rates of complications were observed following TEA, regardless of preoperative immunosuppression status. Chronic immunosuppression does not appear to increase the rates of postoperative complications for patients undergoing TEA. Prognostic II. [ABSTRACT FROM AUTHOR]

Recurrent focal segmental glomerulosclerosis (FSGS) after kidney transplantation is a serious concern with poor allograft outcomes. Possible circulating permeability factors are postulated as pathogenetic factors leading to recurrence. Genetic FSGS is said to have a negligible risk of posttransplant recurrence. Here, we describe an unfortunate patient of genetic FSGS (pathogenic genetic variant) who had a recurrence within hours after transplant and presented with a sudden onset of anuria. The patient did not respond to plasma exchange and subsequently underwent allograft nephrectomy. [ABSTRACT FROM AUTHOR]

Solid organ transplant patients are at an increased risk of developing various types of malignancies. Herein, we have reported the case of a 32‑year‑old male patient, who presented with a nodular mass in the left shoulder 4 months after undergoing deceased donor renal transplantation. Local excision and biopsy were performed which revealed a malignant spindle cell tumor. Immunohistochemistry revealed S100 faint nuclear positivity in a few cells, CD34 positive, Ki67 1% low, and SMA negative suggestive of low‑grade fibroblastic origin spindle cell tumor. This is a rare low‑grade sarcoma with a high rate of local recurrence, rarely leading to amputation. Metastasis to the lungs and liver has been seldom reported. Our patient had local recurrence twice posttransplant for which he underwent wide local excision. [ABSTRACT FROM AUTHOR]

To evaluate the cost-effectiveness of pharmacological treatment in maintenance therapy for adult heart transplant recipients from the Colombian health system perspective. We constructed a decision tree model with a 1-year time horizon. A review of the clinical literature was performed to extract probabilities of health events and acute rejections avoided were used as the health outcome. Costs were calculated from the base-case approximation and were obtained from administrative databases in Colombia (Sistema de Información de Precios de Medicamentos 2020 and Suficiencia 2012-2019), and the prices were adjusted to US dollar 2021. Two evaluation results were presented. The first evaluates the tacrolimus + azathioprine + corticosteroid (TAC) scheme compared with cyclosporine + azathioprine + corticosteroid (CAC), in which the incremental cost-effectiveness ratio indicates that 1 additional rejection avoided has a cost of US dollar $5461.09 which, compared with the cost-effectiveness threshold in the base case, indicates that the TAC scheme is not a cost-effective (CE) strategy with respect to the CAC scheme. The second result shows the comparison of tacrolimus + mycophenolate mofetil + corticosteroid (TMC) with cyclosporine + mycophenolate mofetil + corticosteroid (CMC) in which TMC was found to be a dominant alternative to CMC. The tacrolimus-based immunosuppression scheme is not CE in its TAC scheme, versus CAC, and is dominant in its TMC scheme, versus CMC, sensitivity analyses show that tacrolimus could become a CE alternative in any scheme used against higher cost-effectiveness threshold. • Tacrolimus and cyclosporine are the most used options in clinical practice for maintenance therapy. • In this study, we performed a cost-effectiveness analysis of tacrolimus versus cyclosporine, evaluating the cost-effective therapeutic scheme in the Colombian context, considering organ rejection avoided as a clinical outcome. • The result of this research shows the economic and clinical benefits of the use of both therapeutic schemes, tacrolimus only achieves cost-effectiveness in 1 treatment regimen, being above the cost-effectiveness threshold in the remaining regimen. [ABSTRACT FROM AUTHOR]

Photodynamic therapy, consisting of aminolevulinic acid and blue light in combination, is a treatment option for diffuse actinic keratosis in patients with cutaneous manifestations of graft-versus-host disease resulting from an allogenic stem cell transplantation for lymphoma. Different treatment options, such as imiquimod and 5-fluorouracil, are effective treatment options in the general population, but risk flaring graft-versus-host disease in patients with this condition.We present a case where photodynamic therapy was successfully used in the treatment of actinic keratosis for a patient with chronic graft-versus-host disease without flaring the cutaneous manifestations of graft-versus-host disease. [ABSTRACT FROM AUTHOR]

Mortality rates for autoimmune hepatitis (AIH) vary. Data are lacking beyond 20 years follow-up. Analysis of a consecutively recruited large AIH cohort from a single non-transplant tertiary centre in England and an overlapping cohort, already followed for ≥ 20 years. We assessed 330 patients presenting 1987–2016 and 65 patients presenting 1971–96 already followed for 20 years. Death/liver transplant rate was 51±4% (all-cause) and 21±4% (liver-related) over 20 years and was independently associated with: decompensation and lower serum ALT at diagnosis; and failure of serum ALT normalisation and higher relapse rate. There was excess mortality over the first year. Patients (n = 65) already followed for twenty years had similar subsequent rates of relapse, disease progression and mortality, to those followed from diagnosis. Azathioprine-intolerant patients (n = 23) switching to Mycophenolate did not have higher mortality over 4(1–17) years, than patients continuing Azathioprine. Following immunosuppression withdrawal (n = 26), six (23% patients) relapsed with no liver-related deaths over 2.3(0–23.1) years. In this consecutive autoimmune hepatitis cohort, mortality was similar to that in national registry studies, disease progression continued after 20 years, and immunosuppression withdrawal did not compromise survival. [ABSTRACT FROM AUTHOR]

Parvovirus B19 is an uncommon cause of anaemia in kidney transplant recipients (KTRs). The study aims to determine the incidence, clinical presentation, laboratory findings and outcome of parvovirus B19-related anaemia in KTR. We conducted a 12-year retrospective, single-centre study describing the clinical profile of KTRs with parvovirus B19-related anaemia. Amongst the 714 patients who underwent kidney transplantation between January 2011 and January 2023, (cumulative follow-up: 1287 patient-years), six females and one male, developed parvovirus B19-related anaemia. The incidence proportion (risk) is 0.98% with an incidence rate of 5.43 cases per 1000 patient-year. The median duration from transplant to development of anaemia was 6 weeks (range: 4–40 weeks). The mean fall in haemoglobin was 2.88 ± 1.55 gm/dl; concomitant leukopenia and thrombocytopenia were observed in 57.1 and 28.6% of patients. Three patients responded to a reduction in immunosuppression, the four non-responders required the administration of low-dose intravenous immunoglobulin. The mean duration from initiation of therapy to a sustained rise in haemoglobin was 7.71 ± 2.62 weeks. None of the patients had a relapse of the infection. Parvovirus B19 infection is an uncommon cause of post-transplant refractory anaemia. The key to successfully managing such patients includes a high index of suspicion, early diagnosis and reduction of immunosuppression with or without administration of intravenous immunoglobulin. [ABSTRACT FROM AUTHOR]