Endothelial-Derived miR-17∼92 Promotes Angiogenesis to Protect against Renal Ischemia-Reperfusion Injury

BackgroundDamage to the renal microvasculature is a hallmark of renal ischemia-reperfusion injury (IRI)–mediated AKI. The miR-17∼92 miRNA cluster (encoding miR-17, -18a, -19a, -20a, -19b-1, and -92a-1) regulates angiogenesis in multiple settings, but no definitive role in renal endothelium during AKI pathogenesis has been established.MethodsAntibodies bound to magnetic beads were utilized to selectively enrich for renal endothelial cells from mice. Endothelial-specific miR-17∼92 knockout (miR-17∼92^endo−/−) mice were generated and given renal IRI. Mice were monitored for the development of AKI using serum chemistries and histology and for renal blood flow using magnetic resonance imaging (MRI) and laser Doppler imaging. Mice were treated with miRNA mimics during renal IRI, and therapeutic efficacies were evaluated.ResultsmiR-17, -18a, -20a, -19b, and pri–miR-17∼92 are dynamically regulated in renal endothelial cells after renal IRI. miR-17∼92^endo−/− exacerbates renal IRI in male and female mice. Specifically, miR-17∼92^endo−/− promotes renal tubular injury, reduces renal blood flow, promotes microvascular rarefaction, increases renal oxidative stress, and promotes macrophage infiltration to injured kidneys. The potent antiangiogenic factor thrombospondin 1 (TSP1) is highly expressed in renal endothelium in miR-17∼92^endo−/− after renal IRI and is a target of miR-18a and miR-19a/b. miR-17∼92 is critical in the angiogenic response after renal IRI, which treatment with miR-18a and miR-19b mimics can mitigate.ConclusionsThese data suggest that endothelial-derived miR-17∼92 stimulates a reparative response in damaged renal vasculature during renal IRI by regulating angiogenic pathways.     

ASO Author Reflections: Do Shorter Tumor-to-Nipple Distances Compromise the Local Oncologic Safety of Nipple-Sparing Mastectomy?

Annals of Surgical Oncology -     

A novel predictive model for pelvic lymph node metastasis in patients with penile cancer: A multi-institutional study

PurposeWe determined whether a clinicopathological nomogram is able to predict the risk of pelvic lymph node metastasis (LNM) in penile cancer patients after inguinal lymph node dissection (ILND).MethodsNinety-eight patients with bilateral ILND who underwent pelvic lymphadenectomy at 10 centers were retrospectively analyzed. The most predictive features in the nomogram were selected by the stepwise logistic regression method and then tested and verified by multivariate logistic regression analyses. The nomogram was assessed using concordance indices and calibration curves.ResultsOf the 181 pelvic basins, pelvic LNM was observed in 52 packages (43 patients). Bilateral pelvic LNM was present in 9 patients (9/43, 20.9%). There was no crossover metastatic spread from one inguinal side to the other pelvic side. Age, previous resection, the biopsy procedure for inguinal lymph nodes, vascular invasion, and ipsilateral inguinal lymph node status were all independent risk factors for pelvic LNM (all P < 0.05) in the multivariate logistic regression analysis. The nomogram exhibited a good probability for survival agreement, with a concordance index of 0.868 (95% CI: 0.813–0.922).ConclusionsA novel nomogram suggests that the risk of pelvic LNM can be effectively predicted in penile carcinoma patients and may provide a useful guide for clinicians. Further external validation is needed.     

Short- and Long-Term Outcome after Emergent Cardiac Surgery during Transcatheter Aortic Valve Implantation

Objective: Our study aimed to evaluate short- and long-term outcomes of patients who required emergent conversion from transcatheter aortic valve implantation (TAVI) to open surgery. Besides, the reasons and procedural settings of emergent cardiac surgery (ECS) were also reported.Methods: We retrospectively reviewed the patients who underwent TAVI in our institution between 2012 and 2019 and collected the clinical data of cases who converted from TAVI to bail-out surgery. Telephone and outpatient follow-ups were performed.Results: Of 516 TAVI patients, 20 required ECS, and the bail-out surgery occurred less frequently with the increase in TAVI volume. The most common reason for conversion was left ventricular perforation (7/20, 35.0%). Thirty-day mortality was 35.0% in ECS patients. Kaplan–Meier survival curves showed that the cumulative survival rate was 65.0% at 1 year, 50.1% at 5 years in all ECS patients, and 77.1% at 5 years in patients who survived over 30 days after conversion.Conclusion: Although the bail-out operation was performed immediately after TAVI abortion, ECS still associated with high 30-day mortality. The long-term survival benefit was seen in patients surviving from bail-out surgery. An experienced TAVI team is of crucial importance in avoiding ECS-related life-threatening complications and providing effective salvage surgery.     

Twenty years’ experience of laparoscopic 1-anastomosis gastric bypass: surgical risk and long-term results

BackgroundLaparoscopic 1- (single-) anastomosis gastric bypass (OAGB) was developed as a simplified technique of Roux-en-Y gastric bypass (RYGB), but super long-term data are lacking.ObjectivesTo evaluate the risks and long-term results of OAGB over a period of 20 years.SettingTertiary teaching hospital.MethodsA total of 2223 patients underwent OAGB from 2001 to 2020; the mean age was 35.3 ± 11.4 years (range, 14–71 yr), 70.2% were female, and the mean body mass index was 40.2 ± 11.9 kg/m². All data were kept in a prospective bariatric database. Patients were divided into 4 groups, based on the 5-year period in which their surgery was performed, and a retrospective analysis was conducted.ResultsThe means for operating time, intraoperative blood loss, and length of hospital stay after OAGB were 131.9 ± 40.1 minutes, 38.5 ± 30.7 mL, and 4.5 ± 4.0 days, respectively. There were 27 patients (1.2%) with 30-day postoperative major complications overall, but the group rate decreased to .4% in the last 5-year period. At postoperative years 5, 10, and 15, the percentages of total weight loss were 31.9%, 29.6%, and 29.5%, respectively, and the percentages of excess weight loss were 77.2%, 68.4%, and 65.5%, respectively. Among 739 patients (33.2%) with type 2 diabetes (T2D), the rates of complete remission (glycated hemoglobin < 60%) at 5, 10, and 15 years were 67.3%, 73.8%, and 66.7%, respectively. The weight loss and antimetabolic effects were similar in each 5-year period, but a significant malnutrition effect was observed. A total of 113 (5.1%) patients needed revision surgery at follow-up, due to malnutrition (n = 51), weight regain (n = 24), acid or bile reflux (n = 22), marginal ulcer (n = 8), ileus (n = 3), and other causes (n = 5). At 15 years, the overall revision rate was 11.9% (27/226), and 80% of the patients were very satisfied with their procedures.ConclusionOur results showed that OAGB is a safe and durable primary bariatric procedure, with sustained weight loss and a high resolution of T2D up to 20 years post surgery in Taiwan, although malnutrition is a major side effect.     

Congenital Thumb-Index Web Space Deficiency

Background: There are several congenital hand differences that cause thumb-index (TI) web space deficiency. There is a knowledge gap in the literature about the hand differences that are associated with TI web space deficiency. We aimed to identify these congenital differences and the various specific reconstructive surgical procedures that are used for these conditions. Methods: We conducted a retrospective chart review of children treated operatively over a period of 30 years for congenital TI web space deficiency by the senior author (G.M.R.). We gathered data on demographics and associated congenital hand differences and compiled a list of all surgical procedures performed for the web space and the ipsilateral upper extremity. Results: We included 71 patients (77 hands) with 12 congenital hand differences (62 developmental and 9 spastic). The total number of upper extremity operations, (ie), anesthetics performed for these patients was 186, averaging 2.6 settings and 7.5 procedures for each patient. Cutaneous reconstructive procedures included first dorsal metacarpal artery pedicle flaps (49 patients), 4-flap Z-plasties (15), and transposition flaps (13). In addition, 16 different thumb reconstructive procedures were necessary. Ten patients required revision of their TI web space procedures for recurrence. Conclusions: The prevalence of TI web space deficiency is underappreciated. These patients often have multiple musculoskeletal anomalies of the hand and upper extremity that should be ruled out and require surgical treatment to optimize hand function. Consideration should be given to performing more than one procedure in one setting when possible.     

Targeting NF-κB c-Rel in regulatory T cells to treat corneal transplantation rejection

The relevance of Tregs in the induction of tolerance against corneal allografts has been well established. Although it is well known that the conversion of Tregs into effector-like cells contributes to the loss of corneal immune privilege, the underlying mechanism is still not fully understood. Using heterologous penetrating keratoplasty model, we found that Tregs from corneal allograft rejected mice (inflam-Tregs) exhibit impaired function and characteristics of effector T cells. Further study showed that the expression of NF-κB c-Rel, a key mediator of effector T cell function, was significantly increased in inflam-Tregs. Mechanistic study revealed that elevated NF-κB c-Rel level in inflam-Tregs impaired Treg function through the promotion of inflammatory cytokine production and glycolysis. More importantly, we demonstrated that targeting NF-κB c-Rel was able to improve the immune suppressive function of inflam-Tregs in vitro and enhance the potential of them to suppress corneal transplantation rejection. Therefore, our current study identified NF-κB c-Rel as a key mediator of the conversion of Tregs into effector-like cells when under inflammatory environment.