Renal allograft biopsies in the era of C4d staining: the need for change in the Banff classification system.

C4d immunostaining in the peritubular capillaries (PTC) is a marker of antibody-mediated rejection (AMR). We evaluated the histopathologic diagnoses of 388 renal transplant biopsies since the implementation of routine C4d immunostaining at our center. Of these, 155 (40%) biopsies had evidence of acute cellular rejection (ACR), out of which 119 (77%) had pure ACR, 31 (20%) had ACR with concomitant features of AMR, and five (3%) had ACR with focal C4d staining. Sixty-four (16%) biopsies exhibited features of AMR [33 (52%) pure AMR, and 31(48%) concomitant AMR and ACR]. One hundred and fifty-five (40%) biopsies had features of interstitial fibrosis and tubular atrophy (IFTA). Of these, 20 (13%) had concomitant AMR [13 (8.5%) had pure AMR and seven (4.5%) had concomitant ACR and AMR]. Creatinine at the time of biopsy was higher in patients with mixed ACR and AMR and the clinical behavior of mixed lesions is more aggressive over time. Despite having a lower serum creatinine at the time of biopsy, patients with IFTA experienced gradual decline in graft function over time. The pathologic findings in renal allograft biopsies are often mixed and mixed lesions appear to have more aggressive clinical behavior. These findings suggest the need for change in the Banff classification system to better capture the complexity of renal allograft pathologies.     

Circulating mitochondrial genes detect acute cardiac allograft rejection: Role of the mitochondrial calcium uniporter complex

Acute rejection after heart transplantation increases the risk of chronic dysfunction. Disturbances in mitochondrial function may play a contributory role, however, the relationship between histological signs of rejection in the human transplanted heart and expression levels of circulating mitochondrial genes, such as the mitochondrial Ca²⁺ uniporter (MCU) complex, remains unexplored. We conducted an RNA-sequencing analysis to identify altered mitochondrial genes in serum and to evaluate their diagnostic accuracy for rejection episodes. We included 40 consecutive samples from transplant recipients undergoing routine endomyocardial biopsies. In total, 112 mitochondrial genes were identified in the serum of posttransplant patients, of which 28 were differentially expressed in patients with acute rejection (p < .05). Considering the receiver operating characteristic analysis with an area under the curve (AUC) >0.900 to discriminate patients with moderate or severe degrees of rejection, we found that the MCU system showed a strong capability for detection: MCU (AUC = 0.944, p < .0001), MCU/MCUR1 ratio (AUC = 0.972, p < .0001), MCU/MCUB ratio (AUC = 0.970, p < .0001), and MCU/MICU1 ratio (AUC = 0.970, p < .0001). Mitochondrial alterations are reflected in peripheral blood and are capable of discriminating between patients with allograft rejection and those not experiencing rejection with excellent accuracy. The dysregulation of the MCU complex was found to be the most relevant finding.     

Primary seminal vesicle adenocarcinoma: A case report of rare entity and discussion of its differential diagnosis using immunohistochemical approach for the core biopsy specimen

Primary seminal vesicle adenocarcinoma is a rare malignancy of the male genito-urinary system with only a few confirmed reported cases. Initial tissue diagnostic modality is often a core biopsy specimen. Here, we report this rare entity in a 50-year-old male, highlighting the histomorphological and immunohistochemical approach to the core biopsy specimen of the seminal vesicle mass. The patient presented with a history of haematospermia and gross haematuria for one year, and radiological workup was found to have a right seminal vesicle mass. A trans-rectal ultrasound guided core biopsy revealed a tumourous lesion with a predominant papillary architecture and cytological features of neoplasia. Based on positivity for CK7, PAX-8 and CA-125, and Ki-67 index of 30%–40% and negativity for PSA, AMACR, CK20, CDX-2, p63, GATA3, WT1 and calretinin, a diagnosis of primary seminal vesicle adenocarcinoma was offered. The diagnosis was also confirmed on the surgically resected specimen. This case depicts the approach of a pathologist to diagnose this rare entity on the core biopsy specimen and the possible differential diagnoses one must consider.     

Validation of donor fraction cell-free DNA with biopsy-proven cardiac allograft rejection in children and adults

ObjectivesDonor-specific cell-free DNA shows promise as a noninvasive marker for allograft rejection, but as yet has not been validated in both adult and pediatric recipients. The study objective was to validate donor fraction cell-free DNA as a noninvasive test to assess for risk of acute cellular rejection and antibody-mediated rejection after heart transplantation in pediatric and adult recipients.MethodsPediatric and adult heart transplant recipients were enrolled from 7 participating sites and followed for 12 months or more with plasma samples collected immediately before all endomyocardial biopsies. Donor fraction cell-free DNA was extracted, and quantitative genotyping was performed. Blinded donor fraction cell-free DNA and clinical data were analyzed and compared with a previously determined threshold of 0.14%. Sensitivity, specificity, negative predictive value, positive predictive value, and receiver operating characteristic curves were calculated.ResultsA total of 987 samples from 144 subjects were collected. After applying predefined clinical and technical exclusions, 745 samples from 130 subjects produced 54 rejection samples associated with the composite outcome of acute cellular rejection grade 2R or greater and pathologic antibody-mediated rejection 2 or greater and 323 healthy samples. For all participants, donor fraction cell-free DNA at a threshold of 0.14% had a sensitivity of 67%, a specificity of 79%, a positive predictive value of 34%, and a negative predictive value of 94% with an area under the curve of 0.78 for detecting rejection. When analyzed independently, these results held true for both pediatric and adult cohorts at the same threshold of 0.14% (negative predictive value 92% and 95%, respectively).ConclusionsDonor fraction cell-free DNA at a threshold of 0.14% can be used to assess for risk of rejection after heart transplantation in both pediatric and adult patients with excellent negative predictive value.     

The outcome of intracapsular hip fracture fixation using the Targon Femoral Neck (TFN) locking plate system or cannulated cancellous screws: A comparative study involving 2004 patients

AimThis study compares the outcome of intracapsular hip fracture fixation using the Targon Femoral Neck (TFN) locking plate system with the standard fixation using cannulated cancellous screws (CCS).Patients and methodAnalyses of a prospectively collected data of all patients treated for intracapsular hip fractures using the TFN system and CCS at our department over a period of 28 years. Baseline characteristics and specific outcome measures where compared. The primary outcome measure was fracture revision during the 1st year. Secondary outcome measures were fracture complications, any revision surgery, mortality and mobility status at one year after surgery.ResultsA total of 2004 fractures were included, a third (n = 725, 36.2%) were treated using the TFN system. There were higher rates of non-union (19.5% vs 9.5%) and revision surgery (19% vs 9%) during the first year in the CCS cohort. Revision surgery was also higher in the same group during the whole of the follow-up period (22.2% vs 14.9%). The first year’s mortality rate was higher in the CCS cohort (21.1% vs 17.5%) but the reduction in mobility and mobility scores was the same in both cohorts.ConclusionThis study includes the largest cohort of cases treated for intracapsular hip fractures using the TFN system. It demonstrated that the TFN system was associated with lower rates of non-union, revisions and re-operations for any cause.