Electric Field-Enhanced Ion Rejection Rate in Freeze Desalination.

Freeze desalination is an appealing method for seawater desalination through freezing seawater. The percentage of ions in the liquid phase, which is termed ion rejection rate, is a critical factor affecting the performance of freeze desalination. Improving the ion rejection rate is an important topic for freeze desalination. In this work, we investigate the effects of electric fields on the ion rejection rate during the freezing of seawater through molecular dynamics simulations.  It is found that the ion rejection rate increases with increasing electric field strength.  The enhanced ion rejection rate is due to the reduction of the energy barrier at the ice-water interface caused by the electric field, which affects the orientation of water molecules and ion-water interactions. However, the electric field hinders the ice growth rate, which affects the productivity of freeze desalination. Nevertheless, the finding in this work offers a new idea to improve the ion rejection rate. Practically, a trade-off needs to be found to optimize the overall performance of freeze desalination.

Recurrent rejections after liver transplantation for hepatocellular carcinoma with stem cell features in an adult patient.

Patients with hepatoblastoma featuring carcinoma characteristics have better outcomes after liver transplantation, than after chemotherapy and resection. Possibly this should be extrapolated to aggressive subtypes of hepatocellular carcinomas in non-cirrhotic livers, where early liver transplantation might also be indicated. However, the risks associated with liver transplantation and immunosuppressive treatment after liver transplantation are once again demonstrated by this case of a 32-year-old women with a negative personal and familial history of liver diseases. She underwent transplantation (DBD) for a hepatocellular carcinoma with stem cell features (HCC-HS; an aggressive 'hepatoblast subtype' of hepatocellular carcinoma) after chemotherapeutical downstaging techniques failed to sufficiently downstage the tumor. Despite being on conventional immunosuppressive regimens (tacrolimus and mycophenolate mofetil with initial corticosteroids tapered), this patient still developed two severe rejection episodes, one of which necessitated retransplantation (DCD). Both episodes were preceded by alterations in tacrolimus trough levels, either intentionally, when tacrolimus was reduced within a nephroprotective regimen, or unintentionally, when rifampicin, a CYP3A4 inducer, significantly lowered the trough levels. Together, these episodes stress the importance of therapeutic drug monitoring of tacrolimus. Furthermore, the patient experienced an everolimus-linked drug-induced thrombotic microangiopathy, underwent multiple ERCPs for an anastomotic stricture and only one and a half year after the first liver transplantation she already suffers from long-term immunosuppressive-related side effects such as impaired glucose tolerance, hypertension and a potential cardiomyopathy. At present, she is still alive and experienced no recurrence of her primary tumor. Her case underscores the significant challenges in post-liver transplantation care.

Elimination of GGTA1, CMAH, ß4GalNT2 and CIITA genes in pigs compromises human versus pig xenogeneic immune reactions.

BACKGROUND: Pig organ xenotransplantation is a potential solution for the severe organ shortage in clinic, while immunogenic genes need to be eliminated to improve the immune compatibility between humans and pigs. Current knockout strategies are mainly aimed at the genes causing hyperacute immune rejection (HAR) that occurs in the first few hours while adaptive immune reactions orchestrated by CD4 T cell thereafter also cause graft failure, in which process the MHC II molecule plays critical roles. METHODS: Thus, we generate a 4-gene (GGTA1, CMAH, ß4GalNT2, and CIITA) knockout pig by CRISPR/Cas9 and somatic cell nuclear transfer to compromise HAR and CD4 T cell reactions simultaneously. RESULTS: We successfully obtained 4KO piglets with deficiency in all alleles of genes, and at cellular and tissue levels. Additionally, the safety of our animals after gene editing was verified by using whole-genome sequencing and karyotyping. Piglets have survived for more than one year in the barrier, and also survived for more than 3 months in the conventional environment, suggesting that the piglets without MHC II can be raised in the barrier and then gradually mated in the conventional environment. CONCLUSIONS: 4KO piglets have lower immunogenicity, are safe in genomic level, and are easier to breed than the model with both MHC I and II deletion.

The bidirectional relationship between peer relationships and bullying: Evidence from cross-lagged analyses among Chinese children.

BACKGROUND: In the digital age, bullying manifests in two distinct forms: traditional bullying and cyberbullying. Children's peer relationships are important predictors of bullying, and bullying in turn predicts peer relationships. However, few researchers have noted the bidirectional relationship between peer relationships and bullying. METHODS: The present study used a two-wave cross-lagged longitudinal design to fill this gap. The potential sex differences were also examined in this relationship. The sample consisted of 527 Chinese children aged 8 to 12 years (M = 9.69, SD = .96; 53.5% female). Participants completed peer nominations for peer acceptance, peer rejection and social dominance, as well as self-reports of traditional bullying and cyberbullying. RESULTS: Results showed that peer rejection at the first time point (T1) significantly and positively predicted traditional bullying perpetration, cyberbullying perpetration and cyberbullying victimization at the second time point (T2). Traditional bullying victimization at T1 significantly and negatively predicted peer acceptance and social dominance at T2. The results also revealed significant male and female differences. For instance, among boys, peer acceptance at T1 significantly and negatively predicted cyberbullying victimization at T2. In contrast, this relationship was not observed among girls. The present findings have important implications for understanding the cyclical relationship between peer relationships and bullying and providing practical guidance for improving peer relationships and reducing bullying.

Prior to ABOi liver transplant with PD-1 inhibitor in patients with hepatocellular carcinoma: A case report.

BACKGROUND: Liver transplantation (LT) is a unique and effective method for treating end-stage liver diseases and acute liver failure, bringing hope to many patients with liver cancer. LT is currently widely used in the treatment of liver diseases. However, a few cases of patients with liver cancer who experience ABO-incompatible (ABOi) LT after using programmed cell death protein 1 (PD-1) inhibitor have been reported. CASE PRESENTATION: A patient with liver cancer who received sintilimab injection, an anti-PD1 therapy, before LT was admitted in the transplantation centre. This patient underwent ABOi LT. The perioperative treatment strategy of this patient was reported. A desensitisation protocol was conducted urgently for the patient before operation, and the immunosuppression programme of LT was adjusted. After operation, isoagglutinin titer and liver function indicators were strictly monitored. The patient recovered well after operation, and no sign of rejection reaction was observed. CONCLUSION: We reported a patient with hepatocellular carcinoma (HCC) who received PD-1 inhibitor treatment before operation and successfully underwent ABOi LT. The present case report provides novel insights into the perioperative management of utilizing PD-1 inhibitors prior to ABOi LT in patients diagnosed with hepatocellular carcinoma (HCC).

Harnessing Immunomodulatory Polymers for Treatment of Autoimmunity, Allergy, and Transplant Rejection.

Autoimmunity, allergy, and transplant rejection are a collection of chronic diseases that are currently incurable, drastically decrease patient quality of life, and consume considerable health care resources. Underlying each of these diseases is a dysregulated immune system that results in the mounting of an inflammatory response against self or an innocuous antigen. As a consequence, afflicted patients are required to adhere to lifelong regimens of multiple immunomodulatory drugs to control disease and reclaim agency. Unfortunately, current immunomodulatory drugs are associated with a myriad of side effects and adverse events, such as increased risk of cancer and increased risk of serious infection, which negatively impacts patient adherence rates and quality of life. The field of immunoengineering is a new discipline that aims to harness endogenous biological pathways to thwart disease and minimize side effects using novel biomaterial-based strategies. We highlight and discuss polymeric micro/nanoparticles with inherent immunomodulatory properties that are currently under investigation in biomaterial-based therapies for treatment of autoimmunity, allergy, and transplant rejection.

Effects of a dual functional filler, polyethersulfone-g-carboxymethyl chitosan@MWCNT, for enhanced antifouling and penetration performance of PES composite membranes.

Ultrafiltration technology, separating water from impurities by the core membrane, is an effective strategy for treating wastewater to meet the ever-growing requirement of clean and drinking water. However, the similar nature of hydrophobic organic pollutants and the membrane surface leads to severe adsorption and aggregation, resulting unavoidable membrane degradation of penetration and rejection. The present study presents a novel block amphiphilic polymer, polyethersulfone-g-carboxymethyl chitosan@MWCNT (PES-g-CMC@MWCNT), which is synthesized by grafting hydrophobic polyethersulfone to hydrophilic carboxymethyl chitosan in order to suspend CMC in organic solution. A mixture of hydrophilic carboxymethyl chitosan and hydrophobic polymers (polyethersulfone), in which hydrophilic segments are bonded to hydrophobic segments, could provide hydrophilic groups, as well as gather and remain stable on membrane surfaces by their hydrophobic interaction for improved compatibility and durability. The resultant ultrafiltration membranes exhibit high water flux (198.10 L m-2·h-1), suitable hydrophilicity (64.77°), enhanced antifouling property (82.96%), while still maintains excellent rejection of bovine serum albumin (91.75%). There has also been an improvement in membrane cross-sectional morphology, resulting in more regular pores size (47.64 nm) and higher porosity (84.60%). These results indicate that amphiphilic polymer may be able to significantly promote antifouling and permeability of ultrafiltration membranes.

Impact of COVID-19 on liver transplant recipients: A nationwide cohort study evaluating hospitalization, transplant rejection, and inpatient mortality.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has posed a major public health concern worldwide. Patients with comorbid conditions are at risk of adverse outcomes following COVID-19. Solid organ transplant recipients with concurrent immunosuppression and comorbidities are more susceptible to a severe COVID-19 infection. It could lead to higher rates of inpatient complications and mortality in this patient population. However, studies on COVID-19 outcomes in liver transplant (LT) recipients have yielded inconsistent findings. AIM: To evaluate the impact of the COVID-19 pandemic on hospital-related outcomes among LT recipients in the United States. METHODS: We conducted a retrospective cohort study using the 2019-2020 National Inpatient Sample database. Patients with primary LT hospitalizations and a secondary COVID-19 diagnosis were identified using the International Classification of Diseases, Tenth Revision coding system. The primary outcomes included trends in LT hospitalizations before and during the COVID-19 pandemic. Secondary outcomes included comparative trends in inpatient mortality and transplant rejection in LT recipients. RESULTS: A total of 15720 hospitalized LT recipients were included. Approximately 0.8% of patients had a secondary diagnosis of COVID-19 infection. In both cohorts, the median admission age was 57 years. The linear trends for LT hospitalizations did not differ significantly before and during the pandemic (P = 0.84). The frequency of in-hospital mortality for LT recipients increased from 1.7% to 4.4% between January 2019 and December 2020. Compared to the pre-pandemic period, a higher association was noted between LT recipients and in-hospital mortality during the pandemic, with an odds ratio (OR) of 1.69 [95% confidence interval (CI): 1.55-1.84), P < 0.001]. The frequency of transplant rejections among hospitalized LT recipients increased from 0.2% to 3.6% between January 2019 and December 2020. LT hospitalizations during the COVID-19 pandemic had a higher association with transplant rejection than before the pandemic [OR: 1.53 (95%CI: 1.26-1.85), P < 0.001]. CONCLUSION: The hospitalization rates for LT recipients were comparable before and during the pandemic. Inpatient mortality and transplant rejection rates for hospitalized LT recipients were increased during the COVID-19 pandemic.

Comparison of Cardiac Allograft Vasculopathy Incidence Between Simultaneous Multi-Organ and Isolated Heart Transplant Recipients in the United States.

BACKGROUND: Prior studies have shown reduced development of cardiac allograft vasculopathy (CAV) in multi-organ transplant recipients. The aim of this study was to compare the incidence of CAV between isolated heart transplants and simultaneous multi-organ heart transplants in the contemporary era. METHODS: We utilized the Scientific Registry of Transplant Recipients to perform a retrospective analysis of first-time adult heart transplant recipients between January 1, 2010 and December 31, 2019 in the United States. The primary endpoint was the development of angiographic CAV within 5 years of follow-up. RESULTS: Among 20,591 patients included in the analysis, 1,279 (6%) underwent multi-organ heart transplantation (70% heart-kidney, 16% heart-liver, 13% heart-lung, and 1% triple-organ) and 19,312 (94%) were isolated heart transplant recipients. The average age was 53 years and 74% were male. There were no significant between-group differences in cold ischemic time between the groups. The incidence of acute rejection during the first year after transplant was significantly lower in the multi-organ group (18% vs. 33%, p<0.01). The 5-year incidence of CAV was 33% in the isolated heart group and 27% in the multi-organ group (p<0.0001); differences in CAV incidence were seen as early as 1 year after transplant and persisted over time. In multivariable analysis, multi-organ heart transplant recipients had a significantly lower likelihood of CAV at 5 years (hazard ratio=0.76, 95% confidence interval: 0.66-0.88, p<0.01). CONCLUSIONS: Simultaneous multi-organ heart transplantation is associated with significantly lower long-term risk of angiographic CAV compared with isolated heart transplantation in the contemporary era.

Roles of M1 and M2 macrophage infiltration in post-renal transplant antibody-mediated rejection.

BACKGROUND: We aimed to analyze the roles of M1 and M2 macrophage infiltration in post-renal transplant antibody-mediated rejection (AMR). METHODS: A total of 102 recipients who underwent renal allotransplant from January 2020 to February 2023 were divided into an immune tolerance group (n = 56) and a rejection group (n = 46). The transplant renal biopsy specimens were harvested by ultrasound-guided puncture. The M1 and M2 macrophages in renal tissues were counted, and the M1/M2 ratio was calculated. The numbers of M1 and M2 macrophages and M1/M2 ratios in patients with different severities of interstitial fibrosis/tubular atrophy (IF/TA) and different degrees of tubulointerstitial inflammatory cell infiltration were compared. The predictive values of M1 and M2 macrophages and M1/M2 ratio for post-renal transplant AMR were clarified. RESULTS: The rejection group had significantly more M1 and M2 macrophages and higher M1/M2 ratio than those of the immune tolerance group (P < 0.05). In the rejection group, infiltrating macrophages were mainly distributed in the glomerular and interstitial capillaries, with M1 macrophages being the predominant type. With increasing severity of IF/TA, the numbers of M1 and M2 macrophages and M1/M2 ratio rose in patients with post-renal transplant AMR (P < 0.05). The numbers and ratio had significant positive correlations with the levels of blood urea nitrogen and serum creatinine (P < 0.05). The areas under the curves (AUCs) of numbers and M1 and M2 macrophages and M1/M2 ratio for predicting post-renal transplant AMR were 0.856, 0.839 and 0.887, respectively. The combined detection had AUC of 0.911 (95% CI: 0.802-0.986), sensitivity of 90.43% and specificity of 83.42%. CONCLUSIONS: Significant macrophage infiltration is present in the case of post-renal transplant AMR, and closely related to the severity of IF/TA and the degree of tubulointerstitial inflammatory cell infiltration.

European Society for Organ Transplantation (ESOT) Consensus Statement on the Use of Non-invasive Biomarkers for Cardiothoracic Transplant Rejection Surveillance.

While allograft rejection (AR) continues to threaten the success of cardiothoracic transplantation, lack of accurate and repeatable surveillance tools to diagnose AR is a major unmet need in the clinical management of cardiothoracic transplant recipients. Endomyocardial biopsy (EMB) and transbronchial biopsy (TBBx) have been the cornerstone of rejection monitoring since the field's incipience, but both suffer from significant limitations, including poor concordance of biopsy interpretation among pathologists. In recent years, novel molecular tools for AR monitoring have emerged and their performance characteristics have been evaluated in multiple studies. An international working group convened by ESOT has reviewed the existing literature and provides a series of recommendations to guide the use of these biomarkers in clinical practice. While acknowledging some caveats, the group recognized that Gene-expression profiling and donor-derived cell-free DNA (dd-cfDNA) may be used to rule out rejection in heart transplant recipients, but they are not recommended for cardiac allograft vasculopathy screening. Other traditional biomarkers (NT-proBNP, BNP or troponin) do not have sufficient evidence to support their use to diagnose AR. Regarding lung transplant, dd-cfDNA could be used to rule out clinical rejection and infection, but its use to monitor treatment response is not recommended.

Multiple Facets of Rejections in Online Dating: Exploring Types, Reasons, and Impact.

Romantic rejections are a hurtful yet common occurrence in online dating. While research in this area is growing, there is a need for a comprehensive and comparative overview to understand these rejection experiences better. This article presents the results of two cross-sectional survey studies that aimed to create a more comprehensive overview of multiple facets of rejections in online dating, particularly the types of rejections used, the (provided) reasons for rejecting, and the painfulness of being rejected. Results of Study 1 (n = 177) show that ghosting was the most often experienced rejection type, even when a considerable number of messages was exchanged before the rejection. Unmatching/blocking and rejections with an explanation occurred less but equally often. Moreover, individuals who experienced rejections with an explanation reported the highest painfulness rates, which raised important questions about the reasons behind such explicit rejections. Study 2 further unpacked the provided rejection reasons, from the rejecter and the rejectee perspective. Five categories were identified among the reasons, such as (lack of) attraction and reasons related to relationship investment. Several interesting discrepancies that emerged between reasons provided by rejecters versus rejectees are discussed. Our work underlines the multifaceted nature of rejection experiences in online dating and sets directions for future research that further explores the relationships between rejection types, reasons, and painfulness in detail.

Rejection resistant CD30.CAR-modified Epstein-Barr virus-specific T cells as an off-the-shelf platform for CD30+ lymphoma.

Off-the-shelf (OTS) adoptive T cell therapies have many benefits such as immediate availability, improved access and reduced cost, but face the major challenges of graft-vs-host disease (GVHD) and graft rejection, mediated by alloreactive T cells present in the graft and host, respectively. We have developed a platform for OTS T cell therapies by using Epstein-Bar virus (EBV)-specific T cells (EBVSTs) expressing a chimeric antigen receptor (CAR) targeting CD30. Allogeneic EBVSTs have not caused GVHD in several clinical trials, while the CD30.CAR, that is effective for the treatment of lymphoma, can also target alloreactive T cells that upregulate CD30 on activation. Although EBVSTs express high levels of CD30, they were protected from fratricide in cis, by the CD30.CAR. Hence, they could proliferate extensively and maintained function both through their native EBV-specific T cell receptor and the CD30.CAR. The CD30.CAR enabled EBVSTs to persist in co-cultures with naive and primed alloreactive T cells and eliminate activated natural killer cells that can also be alloreactive. In conclusion, we show that CD30.CAR EBVSTs have the potential to be an effective OTS therapy against CD30+ tumors and, if successful, could then be used as a platform to target other tumor antigens.

Long-Term Outcomes After Lung Transplantation in Children With Intellectual Disabilities.

BACKGROUND: The United Network for Organ Sharing (UNOS) started recording data on intellectual disability status in 2008. This study aimed to characterize the long-term outcomes for children with intellectual disabilities (IDs) undergoing lung transplantation. METHODS: All pediatric patients (under 18 years old) undergoing bilateral lung transplantation were identified using the UNOS database. The patients were grouped into the following categories: no cognitive delay, possible cognitive delay, and definite cognitive delay. The primary endpoint was graft survival at 3-year posttransplantation. Multivariate Cox proportional hazards modeling was used to estimate the independent effect of cognitive disability on graft survival. RESULTS: Five hundred four pediatric patients who underwent lung transplantation between March 2008 and December 2022 were retrospectively analyzed. 59 had a definite cognitive delay (12%), 23 had a possible delay (5%), and 421 had no delay (83%). When comparing these three groups, there was no significant difference in 60-day graft survival (p = 0.4), 3-year graft survival (p = 0.6), 3-year graft survival for patients who survived at least 60-day posttransplantation (p = 0.9), distribution of causes of death (p = 0.24), nor distribution treatment of rejection within 1-year posttransplantation (p = 0.06). CONCLUSIONS: Intellectual disability does not impact long-term outcomes after bilateral lung transplantation. Intellectual disability should not be a contraindication to bilateral lung transplantation on the basis of inferior graft survival.

A personalised delisting strategy enables successful kidney transplantation in highly sensitised patients with preformed donor-specific anti HLA antibodies.

This study investigates kidney transplant outcomes in highly sensitised patients after implementing a delisting strategy aimed at enabling transplantation despite preformed donor-specific antibodies (preDSA), with the goal of reducing acute antibody-mediated rejection (aAMR) risk. Fifty-three sensitised recipients underwent kidney transplant after delisting prohibited HLA antigens, focusing initially in low MFI antibodies (<5000), except for anti-HLA-DQ. If insufficient, higher MFI antibodies were permitted, especially for those without an immunogenic eplet pattern assigned. Delisting of Complement-fixing antibodies (C1q+) was consistently avoided. Comparison cohorts included 53 sensitised recipients without DSA (SwoDSA) and 53 non-sensitised (NS). The average waiting time prior to delisting was 4.4 ± 1.8 years, with a reduction in cPRA from 99.7 ± 0.5 to 98.1 ± 0.7, followed by transplantation within 7.2 ± 8.0 months (analysed in 34 patients). Rejection rates were similar among preDSA, SwoDSA, and NS groups (16%, 8%, and 11%, respectively; p = 0.46). However, aAMR was higher in the preDSA group (12%, 4%, and 2%, respectively; p = 0.073), only presented in recipients with DSA of MFI >5000. The highest MFI DSA were against HLA-DP (Median: 10796 MFI), with 50% of preDSA aAMR cases due to anti-DP antibodies (n = 3). Graft survival rates at 1 and 5 years in preDSA group were 94%, and 67%, comparable to SwoDSA (94%, and 70%; p = 0.69), being significantly higher in the NS group (p = 0.002). The five-year recipient survival rate was 89%, comparable to SwoDSA and NS groups (p = 0.79). A delisting strategy enables safe kidney transplant in highly sensitised patients with preDSA, with a slight increase in aAMR and comparable graft and patient survivals to non-DSA cohorts.

Report of renal allograft tuberculosis a decade after transplant: challenges in diagnosis and management.

Post-transplant infections constitute an important cause of morbidity and mortality in renal transplant recipients worldwide. Tuberculosis (TB) contributes significantly to this burden in endemic countries, such as India. We report a case of renal allograft TB, 10 years post-transplantation, diagnosed during a routine outpatient visit. An asymptomatic rise in serum creatinine level and a 6 month history of immunosuppressive drug non-compliance prompted evaluation of graft dysfunction. Biopsy of the renal allograft tissue suggested chronic active antibody mediated rejection with epithelioid granulomas in the interstitium. Guided by kidney biopsy, further testing with urine acid fast bacilli and urinary GeneXpert yielded positive results for TB. Treatment of TB was further complicated by the development of anti-tubercular therapy induced hepatitis and immune reconstitution inflammatory syndrome, which were managed with the reintroduction regimen and escalation of steroid dose, respectively. Our case highlights the atypical presentation and challenges in managing patients with TB in a post-renal transplant setting.

A Decade-Long Cohort Analysis of Human Cytomegalovirus (HCMV)-Induced Early and Late Renal Rejection in Post-Transplant Patients in the Eastern Indian Population.

Background: HCMV causes severe clinical complications in transplant recipients and may lead to graft rejection. Successful renal transplantation heavily relies on the early prevention and diagnosis of CMV infections, followed by prompt prophylactic treatment before transplantation. Despite the majority of renal rejection cases with acute HCMV infections being asymptomatic and occurring one to two years later, the objective of this research was to comprehend the effect of late HCMV infection on renal rejection by examining specific clinical parameters in the Eastern Indian cohort. Method: In this study, 240 patients were studied for five years following transplantation, and their data were collected from the local metropolitan hospital in Eastern India. Both HCMV-positive and -negative post-transplant patients were investigated using the clinical parameters and viral loads for latent infection. Results: Within the studied population, 79 post-transplant patients were found to be HCMV positive. Among them, 13 (16.45%) patients suffered from renal rejection within less than 2 yrs. of transplantation (early rejection) and 22 (27.84%) patients suffered from renal rejection after 2 yrs. from the operation date (late rejection). Assessment of clinical parameters with respect to HCMV infection revealed that in early rejection cases, fever (p-0.035) and urinary tract infection (p-0.017) were prominent, but in late rejection, hematuria (p-0.032), diabetes (p-0.005), and creatinine level changes (p < 0.001) were significant along with urinary tract infection (p-0.047). Conclusions: This study provides valuable insights into monitoring latent CMV infections and highlights the understanding of reducing renal rejection rates and the need for further research in this field.

Endobiogenic Biology of Function Indices in a Cohort of Kidney Transplant Recipients.

Background and Objectives: Endobiogeny is a global systems approach to human biology based on the concept that the endocrine system manages the metabolism. Biology of function (BoF) indices are diagnostic tools in endobiogenic medicine that reflect the action of the endocrine system on the cells and the metabolic activity of an organism. Kidney transplant recipients are a very specific patient population due to their constant use of immunosuppressive agents such as steroids and anamnesis of chronic kidney disease. The aim of this study was to assess the tendencies of endobiogenic BoF indices in a kidney transplant recipient population and to determine the relationship between BoF index values and histology-proven kidney transplant rejection. Materials and Methods: A total of 117 kidney transplant recipients undergoing surveillance or indication allograft biopsy were included in this study. Endobiogenic BoF indices were calculated from complete blood count tests taken before the kidney biopsy. Histology samples were evaluated by an experienced pathologist according to the Banff classification system. Clinical and follow-up data were collected from an electronic patient medical record system. Results: Overall, <35% of the patients had BoF index values assumed to be normal, according to the general population data. Additionally, >50% of the patients had lower-than-normal adaptation, leucocyte mobilization, genital, and adjusted genital ratio indices, while the Cata-Ana, genito-thyroid ratio, adrenal gland, and cortisol indices were increased in >50% of the transplant recipients. The adaptation index was significantly higher in patients with biopsy-proven transplant rejection and demonstrated an AUC value of 0.649 (95%CI 0.540-0.759) for discriminating rejectors from patients without transplant rejection. Conclusions: Most of the kidney transplant recipients had abnormal BoF index values, reflecting increased corticotropic effects on their cells. The adaptation index distinguished patients with biopsy-proven transplant rejection from those without it.

Granulomatous Tubulointerstitial Nephritis in a Kidney Allograft: Treatment with Interleukin-6 Receptor Antagonist Stabilises Kidney Function.

Granulomatous tubulointerstitial nephritis (GTIN) attributed to early onset sarcoidosis is an ultrarare finding in an allograft kidney biopsy. We present the case of a young man with allograft dysfunction who had GTIN upon biopsy. We performed a thorough case review based on recovered records from early childhood and reassessed genetic testing results. We revised his underlying diagnosis from cryopyrin-associated periodic syndrome to early-onset sarcoidosis with wild-type NOD2 and established a rationale to use the interleukin-6 (IL-6) receptor blocker tocilizumab (TCZ). This suppressed his inflammatory disease and stabilised kidney function. We performed a literature review related to the emerging role of IL-6 pathway blockade in kidney transplantation. We identified 18 reports with 417 unique patients treated with TCZ for indications including HLA-desensitisation, transplant immunosuppression induction, treatment of chronic antibody-mediated rejection, and treatment of subclinical rejection. Both TCZ and the direct IL-6 inhibitor clazakizumab are being studied in ongoing randomised control trials.

Rejection in romantic relationships: Does rejection sensitivity modulate emotional responses to perceptions of negative interactions?

BACKGROUND: Rejection is a highly stressful experience and individuals tend to avoid it whenever possible. In intimate relationships, experiences of rejection can shape the interaction dynamics between partners. Highly rejection sensitive people fear that their romantic partner will reject them and they overreact to any ambiguous cues that might indicate rejection. Furthermore, because they focus on the threat of rejection, they may have difficulty disengaging from rejection-related emotions, persevere in a rejection-focused state and have a reduced capacity to regulate their emotions. The prolonged experience of strong negative emotions, together with maladaptive attempts to respond to rejection, may undermine key relationship maintenance processes that contribute to relationship functioning and lead to negative reciprocity in interactions. The goal of the present study was to shed light on how individuals experience rejection-related emotions and determine whether, following perceptions of negative interactions, rejection sensitivity was associated with stronger negative responses and less efficient downregulation of negative emotions. In addition, we examined whether dyadic patterns of rejection sensitivity were associated with negative emotion dynamics following perceptions of negative interactions. METHODS: The participants (N = 298) were couples experiencing the transition to parenthood. A multilevel modelling approach was used to assess the associations between rejection sensitivity, perceptions of negative interactions and emotional states. The analyses included repeated daily reports for both rejection and emotions. RESULTS: The results suggest that rejection sensitive individuals do not report higher negative emotions when they perceive negative interactions. Moreover, rejection sensitive men and women did not remain longer in a negative emotional state after they perceived negative interactions with their partner. Finally, when both men and women partners reported higher levels of rejection sensitivity, neither reported having higher negative emotions after experiencing negative interaction perceptions. CONCLUSIONS: Our findings provide further insights into emotional dynamics and rejection sensitivity in romantic relationships. Our results do not provide evidence for a link between rejection sensitivity and higher negative emotions or slower recovery after reports of negative interactions. If individuals suppress their emotions, they may not benefit from regulation with their partner and instead may protect themselves over their relationships. However, in this context, rejection sensitivity might also not constitute a strong predictor of daily emotion fluctuations, but other variables- such as relationship satisfaction - might. Future research may investigate emotional responses in a sample with higher levels of rejection sensitivity and use more diverse measures of perceptions of negative interactions.