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Performance‐based measures of frailty are associated with healthcare utilization after kidney transplantation (KT) but require in‐person assessment. A promising alternative is self‐reported frailty. The goal of this study was to examine the ability of performance‐based and self‐reported frailty measures to predict 30‐day rehospitalizations after KT. We conducted a prospective, observational cohort study involving 272 adults undergoing KT at Mayo Clinic in Minnesota, Florida, or Arizona. We simultaneously measured frailty before KT using the physical frailty phenotype (PFP), the short physical performance battery (SPPB), and self‐report (the Patient‐Reported Outcomes Measurement Information System [PROMIS] 4‐item physical function short form v2.0). Both the PFP and self‐reported frailty were independently associated with more than a 2‐fold greater odds of 30‐day rehospitalizations, while the SPPB was not. To our knowledge, this is the first study to assess the prognostic value of all three of the above frailty measures in patients undergoing KT. The PFP is more prognostic than the SPPB when assessing the risk of 30‐day rehospitalizations; self‐reported frailty can complement the PFP but not replace it. However, the 4‐item survey assessing self‐reported frailty represents a simple way to identify patients undergoing KT surgery who would benefit from interventions to lower the risk of rehospitalizations. [ABSTRACT FROM AUTHOR]

Aims: Graft dysfunction (GD) after heart transplantation (HTx) can develop without evidence of cell‐ or antibody‐mediated rejection. Cardiac magnetic resonance imaging (CMR) has an evolving role in detecting rejection; however, its role in biopsy‐negative GD has not been described. This study examines CMR findings, evaluates outcomes based on CMR results, and seeks to identify the possibility of rejection missed through endomyocardial biopsy by using CMR in HTx recipients with biopsy‐negative GD. Methods and results: HTx recipients with GD [defined as a decrease in left ventricular ejection fraction (LVEF) by >5% and LVEF < 50%] in the absence of rejection by biopsy or allograft vasculopathy and who underwent CMR were included in the study. The primary outcome was a composite of all‐cause mortality, re‐transplantation, or persistent LVEF < 50%. Overall, 34 HTx recipients developed biopsy‐negative GD and underwent CMR. Left ventricular late gadolinium enhancement (LGE) on CMR was observed in 16 patients with two distinct patterns: diffuse epicardial (n = 13) and patchy (n = 3) patterns. Patients with LGE developed GD later after HTx [4 (1.4–6.8) vs. 0.8 (0.3–1.2) years, P < 0.001], were more often symptomatic (88% vs. 56%, P = 0.06), and had greater haemodynamic derangement (pulmonary capillary wedge pressure: 19 ± 7 vs. 13 ± 3 mmHg, P = 0.002) as compared with those without LGE. No significant difference was observed in the primary composite outcome between patients with LGE and those without LGE (50% vs. 38% of patients with events, P = 0.515). During a median follow‐up of 3.8 years, mean LVEF improved similarly in the LGE‐negative (37–55%) and LGE‐positive groups (32–55%) (P = 0.16). Conclusions: Biopsy‐negative GD occurs with and without LGE when assessed by CMR, indicative of possible rejection/inflammation occurring only in a subset of patients. Irrespective of LGE, LVEF improvement occurs in most GD patients, suggesting that other neurohormonal or immunomodulatory mechanisms may also contribute to GD development. [ABSTRACT FROM AUTHOR]

Background: Pneumocystis jirovecii pneumonia (PJP) is a potentially fatal infection afflicting the immunocompromised population, including solid organ transplant (SOT) recipients. Several risk factors have been described; however, little is known regarding the risk of PJP in SOT recipients with posttransplant lymphoproliferative disorder (PTLD). Methods: We performed a nested case‐control study of SOT recipients diagnosed with PJP from 2000 to 2020. PJP was defined as positive microscopy or polymerase chain reaction testing with compatible symptoms and radiographic findings. Control patients were matched 2:1 by year of first transplant, first transplanted organ, transplant center, and sex. Multivariable conditional logistic regression was performed to test associations with PJP and Cox regression analyzed post‐PJP outcomes. Results: Sixty‐seven PJP cases were matched to 134 controls. The most common transplant was kidney (55.2%). Fourteen patients had a history of PTLD, 12 of whom developed PJP. After adjusting for age, acute rejection, cytomegalovirus infection, PJP prophylaxis, and lymphopenia (lymphocyte count <.5 × 109/L), PTLD was independently associated with PJP (OR 14.0, 95% CI 1.7–114.5; p =.014). Lymphopenia was also a significant association (OR 8.2, 95% CI 3.2–20.7; p <.001). PJP was associated with mortality within 90 days of diagnosis (p <.001), but not after 90 days (p =.317). PJP was also associated with 90‐day death‐censored renal allograft loss (p =.026). Conclusions: PTLD is independently associated with PJP after adjustment for recognized risk factors. This is likely influenced by PTLD‐directed chemotherapy, particularly rituximab‐containing regimens. PJP is associated with early mortality, but this effect is not persistent after 90 days. PJP prophylaxis should be considered in SOT recipients with PTLD. [ABSTRACT FROM AUTHOR]

Background: Nocardia is an opportunistic pathogen that primarily affects immunocompromised individuals, including solid organ transplant (SOT) recipients. Up to 2.65% of SOT recipients develop nocardiosis; however, few studies have examined risk factors and prophylaxis for nocardiosis. Methods: We performed a multicenter, matched nested case‐control study of adult SOT recipients with culture‐confirmed nocardiosis from 2000 through 2020. Controls were matched up to 2:1 by sex, first transplanted organ, year of transplant, transplant center, and adequate post‐transplant follow‐up. Multivariable conditional logistic regression was performed to analyze associations with nocardiosis. Cox proportional hazards regression compared 12‐month mortality between infection and uninfected patients. Results: One hundred and twenty‐three SOT recipients were matched to 245 uninfected controls. Elevated calcineurin inhibitor level, acute rejection, cytomegalovirus infection, lymphopenia, higher prednisone dose, and older age were significantly associated with nocardiosis while trimethoprim‐sulfamethoxazole prophylaxis was protective (odds ratio [OR].34; 95% confidence interval [CI].13‐.84). The effect of prophylaxis was similar, though not always statistically significant, in sensitivity analyses that only included prophylaxis dosed more than twice‐per‐week (OR.30; 95% CI.11‐.80) or restricted to years 2015‐2020 (OR.33, 95% CI.09‐1.21). Nocardiosis was associated with increased 12‐month mortality (hazard ratio 5.47; 95% confidence interval 2.42‐12.35). Conclusions: Multiple measures of immunosuppression and lack of trimethoprim‐sulfamethoxazole prophylaxis were associated with nocardiosis in SOT recipients. Effectiveness of prophylaxis may be related to trimethoprim‐sulfamethoxazole dose or frequency. Trimethoprim‐sulfamethoxazole should be preferentially utilized over alternative agents in SOT recipients with augmented immunosuppression or signs of heightened immunocompromise. [ABSTRACT FROM AUTHOR]

Objective: To identify social determinants of health care that are associated with poorer pediatric well-differentiated thyroid cancer (WDTC) outcomes and increased stage at presentation. Study Design: Using the SEER database (Surveillance, Epidemiology, and End Results), we retrospectively gathered data on pediatric WDTC across the United States between 1973 and 2015. Setting: All patients between 0 and 19 years old with a diagnosis of WDTC were included. Methods: Patient variables were analyzed for relationships to AJCC stage at presentation (American Joint Committee on Cancer), overall survival, and disease-specific survival. Results: Among 3913 patients with pediatric thyroid cancer, 3185 were female (81.4%), 3366 had papillary thyroid cancer (85.3%), and 367 had follicular thyroid cancer (9.4%). Two- and 5-year overall and disease-specific survival approached 100%. However, when outcomes were analyzed by specific populations, male sex, non-Caucasian race, poverty, and language isolation were linked to worse overall survival. Male sex and poverty were associated with poorer disease-specific survival. Regarding overall AJCC stage at presentation, male sex and Black race were related to higher overall presenting AJCC stage. Later AJCC T stage at presentation was seen in male, Hispanic, Asian, and Black patients. There were no variables significantly related to following through with recommended surgery. Conclusion: Pediatric WDTC continues to carry an excellent prognosis in the United States. However, when we consider specific populations, the social determinants of health care affect survival and disease burden at presentation: male sex, poverty, language isolation, and race affected survival and/or AJCC stage at presentation in pediatric WDTC. [ABSTRACT FROM AUTHOR]

Histologic findings on 1‐year biopsies such as inflammation with fibrosis and transplant glomerulopathy predict renal allograft loss by 5 years. However, almost half of the patients with graft loss have a 1‐year biopsy that is either normal or has only interstitial fibrosis. The goal of this study was to determine if there was a gene expression profile in these relatively normal 1‐year biopsies that predicted subsequent decline in renal function. Using transcriptome microarrays we measured intragraft mRNA levels in a retrospective Discovery cohort (170 patients with a normal/minimal fibrosis 1‐year biopsy, 54 with progressive decline in function/graft loss and 116 with stable function) and developed a nested 10‐fold cross‐validated gene classifier that predicted progressive decline in renal function (positive predictive value = 38 ± 34%%; negative predictive value = 73 ± 30%, c‐statistic =.59). In a prospective, multicenter Validation cohort (270 patients with Normal/Interstitial Fibrosis [IF]), the classifier had a 20% positive predictive value, 85% negative predictive value and.58 c‐statistic. Importantly, the majority of patients with graft loss in the prospective study had 1‐year biopsies scored as Normal or IF. We conclude predicting graft loss in many renal allograft recipients (i.e., those with a relatively normal 1‐year biopsy and eGFR > 40) remains difficult. [ABSTRACT FROM AUTHOR]

Kidney paired donation (KPD) and the new kidney allocation system (KAS) in the United States have led to improved transplantation rates for highly sensitized candidates. We aimed to assess the potential need for other approaches to improve the transplantation rate of highly sensitized candidates such as desensitization. Using the UNOS STAR file, we analyzed transplant rates in a prevalent active waiting‐list cohort as of June 1, 2016, followed for 1 year. The overall transplantation rate was 18.9% (11 129/58769). However, only 9.7% (213/2204) of candidates with a calculated panel reactive antibody ≥99.9% received a transplant, and highly sensitized candidates were less likely to receive a living donor transplant. Among candidates with a CPRA ≥ 99.5% (ie. 100%), only 2.5% of transplants were from living donors (13 total, 7 from KPD). Nearly 4 years after KAS (6/30/2018), 1791 actively wait‐listed candidates had a CPRA of ≥99.9% and 34.6% (620/1791) of these had ≥5 years of waiting time. Thus, despite KPD and KAS, many sensitized candidates have not been transplanted even with prolonged waiting time. We conclude that candidates with a CPRA ≥ 99.9% and sensitized candidates with an incompatible living donor and prolonged waiting time may benefit from desensitization to improve their ability to receive a transplant. [ABSTRACT FROM AUTHOR]