Branch-first Continuous Perfusion Aortic Arch Replacement: Midterm Results.

BACKGROUND: Aortic arch surgery necessitates interruption of perfusion, thus conferring higher morbidity and mortality compared with other aortic surgery. This report describes a branch-first continuous perfusion aortic arch replacement (BF-CPAR) technique that overcomes these shortcomings and describes midterm results with this technique. METHODS: This report represents the corresponding author's 15-year experience with BF-CPAR, which involves preliminary mobilization and branch reconstruction before circulatory arrest by using a modified trifurcation graft. Demographic, procedural, and outcome (mortality, reintervention, morbidity, and stroke) were analyzed with Kaplan-Meier and Cox regression. RESULTS: Over 15 years (July 2005-February 2021), 155 patients underwent BF-CPAR, at a median age of 66.8 years, 106 (68.3%) on an elective basis and 49 (31.6%) on an emergency basis. There were no aortic deaths after the first postoperative year, thereby resulting in a 1- and 10-year freedom from aortic death constant at 95.6% in patients undergoing elective BF-CPAR and 93.3% in patients undergoing emergency BF-CPAR patients, respectively. Freedom from reintervention on the operated segment at 5 and 9 years was 93.2% and 93.2% in patients undergoing elective cases and 97.1% and 91.4% in emergency cases, respectively. The 10-year freedom from any aortic reintervention was 72.8% in elective patients and 29.2% in emergency patients; there were 38 reinterventions, 76.3% (n = 29/38) done for progression of aneurysmal or dissection disease, of which 79.3% (n = 23/29) were completed endovascularly. Freedom from cerebrovascular-related events at 5 and 10 years was 90.3% and 82.6% in patients undergoing elective BF-CPAR and 75.4% for both time points in patients undergoing emergency BF-CPAR, respectively. CONCLUSIONS: BF-CPAR has excellent 10-year results for elective and emergency cases of arch replacement.

A systematic review on the outcomes of local anaesthetic transperineal prostate biopsy.

OBJECTIVE: To conduct a systematic review of the literature to assess the diagnostic ability, complication rate, patient tolerability, and cost of local anaesthetic (LA) transperineal prostate biopsy. METHODS: Two reviewers searched Medline, the Cochrane Library, and Embase for publications on LA transperineal prostate biopsy up to March 2021. Outcomes of interest included cancer detection rates, complication rates, pain assessments and cost. RESULTS: A total of 35 publications with 113 944 men were included in this review. The cancer detection rate for LA transperineal prostate biopsy in patients undergoing primary biopsy was 52% (95% confidence interval [CI] 0.45-0.60; I2 = 97) and the clinically significant cancer detection rate (Gleason≥3 + 4) was 37% (95% CI 0.24-0.52; I2 = 99%). The rate of infection-related complications in the included studies was 0.15% (95% CI 0.0000-0.0043; I2 = 86). The LA transperineal procedures had a low rate of procedural abandonment (26/6954, 0.37%), with the greatest pain scores measured during LA administration. No formal cost analyses on LA transperineal prostate biopsies were identified in the literature. The overall risk of bias in the included studies was high, with considerable study heterogeneity and publication bias. CONCLUSION: Transperineal prostate biopsy performed under LA is a viable option for centres interested in avoiding the risk of infection associated with transrectal biopsy, and the logistical burden of general anaesthesia. Further investigation into LA transperineal prostate biopsy with comparative studies is warranted for its consideration as the standard in prostate biopsy technique.

Natural killer cell receptors regulate responses of HLA-E-restricted T cells.

Human cytomegalovirus (CMV) infection can stimulate robust human leukocyte antigen (HLA)-E-restricted CD8+ T cell responses. These T cells recognize a peptide from UL40, which differs by as little as a single methyl group from self-peptides that also bind HLA-E, challenging their capacity to avoid self-reactivity. Unexpectedly, we showed that the UL40/HLA-E T cell receptor (TCR) repertoire included TCRs that had high affinities for HLA-E/self-peptide. However, paradoxically, lower cytokine responses were observed from UL40/HLA-E T cells bearing TCRs with high affinity for HLA-E. RNA sequencing and flow cytometric analysis revealed that these T cells were marked by the expression of inhibitory natural killer cell receptors (NKRs) KIR2DL1 and KIR2DL2/L3. On the other hand, UL40/HLA-E T cells bearing lower-affinity TCRs expressed the activating receptor NKG2C. Activation of T cells bearing higher-affinity TCRs was regulated by the interaction between KIR2D receptors and HLA-C. These findings identify a role for NKR signaling in regulating self/non-self discrimination by HLA-E-restricted T cells, allowing for antiviral responses while avoiding contemporaneous self-reactivity.

Local versus general anesthesia transperineal prostate biopsy: Tolerability, cancer detection, and complications.

Objectives: To compare data on transperineal template biopsy (TPTB) under general anesthesia (GA) compared with local anesthesia (LA) procedures using the PrecisionPoint™ Transperineal Access System (PPTAS) in relation to tolerability, cancer detection rate, complications, and cost. Methods: A prospective pilot cohort study of patients undergoing transperineal biopsy was performed. Patients were excluded if they had concurrent flexible cystoscopy or language barriers. Patients had a choice of GA or LA. A prospective questionnaire on Days 0, 1, 7, and 30 was applied. The primary outcome was patient tolerability. Secondary outcomes were cancer detection rate, complication rate, and theater utilization. Results: This study included 80 patients (40 GA TPTB and 40 LA PPTAS). Baseline characteristics including age, prostate-specific antigen (PSA), digital rectal examination (DRE), findings, and prostate volume were comparable between the groups (p = 0.3790, p = 0.9832, p = 0.444, p = 0.3939, respectively). Higher median prostate imaging-reporting and data system (PI-RADS) score of 4 (interquartile range [IQR] 2) versus 3 (IQR 1) was noted in the LA group (p = 0.0326). Pain was higher leaving recovery in the GA group however not significantly (p = 0.0555). Median pain score at LA infiltration was 5/10 (IQR 3), with no difference in pain at Days 1, 7, or 30 (p = 0.2722, 0.6465, and 0.8184, respectively). For GA versus LA, the overall cancer detection rate was 55% versus 55% (p = 1.000) with clinically significant cancer in 22.5% versus 35% (p = 0.217). Acute urinary retention (AUR) occurred in 5% of GA and 2.5% of LA patients (p = 1.000). The GA cohort spent longer in theater and in recovery with a median of 93.5 min versus 57 min for the LA group (p = <0.0001). Conclusion: This study demonstrates that transperineal biopsy is safely performed under LA with no difference between the cohorts in relation cancer detection or AUR. LA biopsy also consumed less theater and recovery resources. A further larger prospective randomized controlled trial is required to confirm the findings of this study.

Long-term oncological outcomes of the Agarwal loop-ligation technique for management of the distal ureter during laparoscopic radical nephroureterectomy.

OBJECTIVES: To describe the Agarwal loop-ligation technique for the management of the distal ureter during laparoscopic radical nephroureterectomy (LRNU) for upper tract urothelial carcinoma (UTUC) and report on long-term oncological outcomes. PATIENTS AND METHODS: In the Agarwal loop-ligation technique, the distal ureteric stump is controlled using endoscopic Endoloop® or PolyLoop® ligation to ensure en bloc excision of the bladder cuff and prevent spillage of upper tract urine into the perivesical space. A retrospective review of the medical records of 76 patients who underwent the Agarwal loop-ligation technique for UTUC at participating centres from July 2004 to December 2017 was performed. Data collected included demographics, perioperative, and long-term oncological outcomes. Survival was calculated using Kaplan-Meier survival analyses. RESULTS AND LIMITATIONS: A total of 76 patients were included. The median age was 71.5 years and median operative time was 4.3 h. The intramural ureter and bladder cuff were completely excised in all patients. Distal surgical margins were clear in all, with only two patients found to have tumour extending to the circumferential surgical margin. There were no cases of perivesical recurrence or port-site metastasis. The 5-year bladder, local, and contralateral recurrence-free survival was 59.6%, 89.0% and 93.5%, respectively. Metastasis-free survival at 5-years was 73.5%. The 5-year overall survival and cancer-specific survival rates were 70.3% and 84.7%, respectively. CONCLUSIONS: We have described the Agarwal loop-ligation technique for the management of the distal ureter in LRNU. This technique complies with oncological principles outlined in the European Association of Urology guidelines, which minimises tumour spillage. Long-term oncological outcomes are satisfactory, with no cases of perivesical recurrence detected in this series.

Enrichment of Cytomegalovirus-induced NKG2C+ Natural Killer Cells in the Lung Allograft.

BACKGROUND: In lung transplant recipients, immunosuppressive medications result in impaired antiviral immunity and a propensity for cytomegalovirus (CMV) reactivation within the lung allograft. Natural killer (NK) cells play a key role in immunity to CMV, with an increase in the proportion of NK cells expressing activating CD94-NKG2C receptors in the blood being a strong correlate of CMV infection. Whether a similar increase in NKG2C NK cells occurs in lung transplant recipients following CMV reactivation in the allograft and if such cells contribute to viral control remains unclear. METHODS: In this pilot study, we longitudinally assessed the frequency and phenotype of NKG2C NK cells in the blood and bronchoalveolar lavage (BAL) of lung transplant recipients and stratified recipients based on their risk of developing CMV disease. RESULTS: We observed an increase in the proportion of NKG2C NK cells in the blood and BAL of CMV high-risk patients, coincident with both the cessation of antiviral prophylaxis and subsequent detection of actively replicating CMV in the blood and lung allograft. Additionally, these NKG2C NK cells expressed killer-cell immunoglobulin-like receptors distinct from those of other NK subsets and BAL NKG2C NK cells possessed an activated phenotype. Finally, the frequency of NKG2C NK cells in the BAL may be inversely correlated with CMV blood titers. CONCLUSIONS: Monitoring the phenotype of NK cells postlung transplant may be a useful biomarker for monitoring patient levels of CMV immunity.