The molecular and cellular processes that lead to renal damage and to the heterogeneity of lupus nephritis (LN) are not well understood. We applied single-cell RNA sequencing (scRNA-seq) to renal ...biopsies from patients with LN and evaluated skin biopsies as a potential source of diagnostic and prognostic markers of renal disease. Type I interferon (IFN)-response signatures in tubular cells and keratinocytes distinguished patients with LN from healthy control subjects. Moreover, a high IFN-response signature and fibrotic signature in tubular cells were each associated with failure to respond to treatment. Analysis of tubular cells from patients with proliferative, membranous and mixed LN indicated pathways relevant to inflammation and fibrosis, which offer insight into their histologic differences. In summary, we applied scRNA-seq to LN to deconstruct its heterogeneity and identify novel targets for personalized approaches to therapy.
The high rate of immunosuppressive medication non-adherence in transplant recipients demands the search for a solution that targets modifiable risk factors and incorporates mobile health technology ...to better engage and educate patients. Kidney transplant recipients (kidneys alone or multi-organ) were randomized to receive a mobile app known as Transplant Hero, both the app and a smart watch, or neither. The coefficient of variability (CV) of tacrolimus levels was measured at one and three months. No statistically significant differences in CV levels were observed between the three groups at either one or three months. Although mobile health apps are a promising strategy for increasing medication adherence, further research is required to determine how to best use this technology.
•Mobile apps and smart watches may improve medication adherence in transplantation.•It is unclear if mobile apps and smart watches can significantly improve adherence.•Further research is necessary to assess patient utilization of mobile apps and smart watches.
Abstract Background Medication non-adherence in transplant patients is a grave problem that results in increased rejection episodes, graft loss and significant morbidity. Methods The efficacy of ...users and non-users of a mobile phone application (mobile app) in promoting medication adherence was investigated. The Beliefs about Medicine Questionnaire (BMQ) and Morisky Medication Adherence Scale (MMAS-8) were used in these cohorts to assess the predilection for poor adherence. Serum tacrolimus, creatinine levels, and rejection episodes were also recorded. Lastly, the patients were tested on their recall of their immunosuppression. Results Overall, patients had extremely negative beliefs about medication reflected in their tendency toward higher predicted rates of non-adherence. Interestingly, though not significant, app users had higher rates of medication recollection. Conclusions The high-risk nature of this population demands efforts to abrogate non-adherence. Caregivers are charged with the responsibility to offer patients a feasible option to safeguard treatment compliance. Mobile apps are a potentially powerful tool, which can be used to decrease non-adherence.
Abstract
In patients with locally advanced cancer without distant metastases, the neoadjuvant setting presents a platform to evaluate new drugs. For mismatch repair proficient/microsatellite stable ...(pMMR/MSS) colon and rectal cancer, immunotherapy has shown limited efficacy. Herein, we report exceptional responses observed with neoadjuvant botensilimab (BOT), an Fc-enhanced next-generation anti–CTLA-4 antibody, alongside balstilimab (BAL; an anti-PD-1 antibody) in two patients with pMMR/MSS colon and rectal cancer. The histological pattern of rapid immune response observed (“
inside-out
” (serosa-to-mucosa) tumor regression) has not been described previously in this setting. Spatial biology analyses (RareCyte Inc.) reveal mechanisms of actions of BOT, a novel innate-adaptive immune activator. These observations have downstream implications for clinical trial designs using neoadjuvant immunotherapy and potentially sparing patients chemotherapy.
In liver transplantation, cold preservation induces ischemia, resulting in significant reperfusion injury. Hypothermic oxygenated machine perfusion (HMP-O 2 ) has shown benefits compared to static ...cold storage (SCS) by limiting ischemia-reperfusion injury. This study reports outcomes using a novel portable HMP-O 2 device in the first US randomized control trial.
The PILOT trial (NCT03484455) was a multicenter, randomized, open-label, noninferiority trial, with participants randomized to HMP-O 2 or SCS. HMP-O 2 livers were preserved using the Lifeport Liver Transporter and Vasosol perfusion solution. The primary outcome was early allograft dysfunction. Noninferiority margin was 7.5%. From April 3, 2019, to July 12, 2022, 179 patients were randomized to HMP-O 2 (n=90) or SCS (n=89). The per-protocol cohort included 63 HMP-O 2 and 73 SCS. Early allograft dysfunction occurred in 11.1% HMP-O 2 (N=7) and 16.4% SCS (N=12). The risk difference between HMP-O 2 and SCS was -5.33% (one-sided 95% upper confidence limit of 5.81%), establishing noninferiority. The risk of graft failure as predicted by Liver Graft Assessment Following Transplant score at seven days (L-GrAFT 7 ) was lower with HMP-O 2 median (IQR) 3.4% (2.4-6.5) vs. 4.5% (2.9-9.4), p =0.024. Primary nonfunction occurred in 2.2% of all SCS (n=3, p =0.10). Biliary strictures occurred in 16.4% SCS (n=12) and 6.3% (n=4) HMP-O 2 ( p =0.18). Nonanastomotic biliary strictures occurred only in SCS (n=4).
HMP-O 2 demonstrates safety and noninferior efficacy for liver graft preservation in comparison to SCS. Early allograft failure by L-GrAFT 7 was lower in HMP-O 2 , suggesting improved early clinical function. Recipients of HMP-O 2 livers also demonstrated a lower incidence of primary nonfunction and biliary strictures, although this difference did not reach significance.
Simultaneous pancreas and kidney transplantation (SPK) in the setting of end-stage renal disease offers unmatched outcomes in insulin dependent diabetic patients. Donor pool expansion through the ...transplantation of kidneys with acute kidney injury (AKI) is controversial.
59 SPK transplants were classified by presence of donor AKI, defined as donor terminal creatinine ≥ 1.5x the initial creatinine or donor terminal creatinine > 4.0 mg/dL. Endpoints included graft and patient survival, delayed graft function (DGF), serum creatinine, glomerular filtration rate (GFR), Hemoglobin A1c (HbA1c) and acute rejection.
The donor AKI group (n = 35) had significantly higher rates of DGF (38 v. 9%, p = 0.01). There was no difference in creatinine or GFR at 1, 3, 6 and 12 months. HbA1c was comparable at 3, 6 and 12 months. There was no significant difference in the percentage of patients that required anti-diabetic agents after transplant (14 v. 4%, p = 0.56).
We observed increased rates of DGF in SPK recipients with donor AKI. However, equivalent outcomes of pancreas and kidney function in both groups were observed.
•SPK transplantation from donor’s with AKI can aid in expanding the donor pool.•AKI donors result in increased rates of DGF in SPK recipients.•However, no difference in eGFR at 1,3,6 and 12 month follow up was observed.•No difference in hemoglobin A1c at 3,6 and 12 month follow up was observed.
Extended release LCP-tacrolimus (LCPT) allows once-daily dosing in transplant recipients. The improved bioavailability may be beneficial for simultaneous pancreas-kidney recipients (SPK).
This is a ...study of 39 SPK recipients on standard immediate-release tacrolimus (IR-TAC, n = 21) or LCPT (n = 18). Coefficient of variability (CV = 100∗standard deviation/mean) was calculated to assess drug levels. Hemoglobin A1c (HbA1c), tacrolimus and creatinine levels were measured postoperatively.
There was no difference in tacrolimus CV in the IR-TAC and LCPT groups at 1 month or 3 months postoperatively; however, a greater difference was observed at 1 year (41.0 vs. 33.1%; p = 0.19). There were six episodes of acute rejection in the IR-TAC group compared to zero episodes in the LCPT group (p = 0.01). HbA1c was significantly higher in the IR-TAC group compared to LCPT at 3 (5.5 vs. 4.9%, p = 0.01), 6 (5.6 vs. 4.9%, p = 0.01) and 12 months (5.8 vs. 5.1%, p = 0.07).
Significantly lower rates of rejection were observed in patients receiving LCPT. The once daily dosing may facilitate medication adherence and result in improved long-term outcomes.
•Extended release LCP-tacrolimus (LCPT) is an appealing option for pancreas transplant recipients.•Significantly lower rates of biopsy proven acute rejection were observed in patients receiving LCPT.•Once daily dosing of tacrolimus may facilitate medication adherence and result in improved long-term outcomes.
This study assessed our experience transplanting kidneys from young donors with severe acute kidney injury.
We performed a single center retrospective analysis of 315 kidney transplants between ...1/1/2014-12/31/2016. Donor kidneys were classified according to the Acute Kidney Injury Network (AKIN) criteria. A case-matched cohort was created using recipient age, history of diabetes, donor specific antibody, donor age and donor after cardiac death. Primary endpoints were graft function measured by eGFR at 90 days and at 1-year.
Stage 3 AKIN recipients had significantly greater eGFR at one year (63.9 ml/min v. 51.2 ml/min, p < 0.001) compared to those with Stage 0 AKIN. This difference was abrogated when compared to a case matched cohort (eGFR at 90 days or 1 year; p > 0.05). Donor and recipient characteristics on eGFR at 1 year were analyzed using linear and logistic regression. Only donor age had a significant impact on recipient eGFR.
Donor kidneys with severe acute injury can achieve optimal 1-year outcomes. Donor age is the most significant predictor of eGFR >45 ml/min after transplant.
•Stage 3 AKIN recipients had significantly greater eGFR at 1-year.•A case matched cohort between cohorts abrogate any eGFR difference.•Donor age is the most significant predictor of eGFR >45 ml/min post-transplant across all cohorts.
Transplant surgical workforce concerns have arisen in the last 5 years as reflected in challenges securing job opportunities for new fellows. The present survey was designed by the ASTS Membership ...and Workforce Committee to describe the current practice characteristics of transplant centers in order to estimate changes in the workforce. The survey questionnaire requested information about the transplant programs, the transplant surgeons involved in the program, and the estimated changes in the staffing of the program over the next 3 years. Seventy‐one transplant centers responded from a total of 235 identified and queried (30.2% response rate), with median responding centers per UNOS region of 7 (IQR 4.5‐8.5). The recruitment outlook for the next 3 years forecasts a positive inflow of surgeons at a 2:1 rate (incoming:leaving). The new female transplant workforce within the responding cohort has increased from 3.7% in 1980 to 18.4% in 2010. Currently, 13.1% of practicing US transplant surgeons in this survey are female which is higher than many other surgical specialties. This report represents the most up‐to‐date view into the abdominal transplant surgical workforce. The positive job recruitment outlook for transplant surgeons and the narrowing gender gap are new findings from this study.
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