Clinical Significance of De Novo Malignancy After Liver Transplant: A Single-Center Study

BackgroundSeveral studies have reported that solid organ transplant recipients have a high risk for malignant tumors because the suppressed immune system fails in preventing malignant transformations. De novo malignancy after transplantation is the most common cause of death in the late period after liver transplant (LT). This study investigated the clinical significance of de novo malignancy after LT, and it is the largest study based in Korea to report long-term follow-up results associated with de novo malignancy after LT.MethodsData of 1793 adults who underwent LT in Seoul National University Hospital were retrospectively collected, and medical charts and data from the Ministry of Public Administration and Security were reviewed to examine the causes of death and de novo malignancy status. The Fisher exact test and Kaplan-Meier survival analysis were used to analyze the data.ResultsOf the 1793 recipients, 27 died of de novo malignancies. Of 875 hepatocellular carcinoma (HCC) patients, 12 died, and of 918 non-HCC patients, 15 died. De novo malignancy was the main cause of death at 5 years after LT but was not in the initial 5 years. In Korea the most common cancers that developed after LT were gastric cancer (21.4%) and lymphoma (14.3%). De novo HCC in non-HCC cases was found in 2 patients.ConclusionDe novo malignancy is a key factor affecting long-term survival after LT. Therefore, regular screening and education are important for improving long-term survival and quality of life in these patients after LT.     

Clinical Characteristics and Risk Factors of Early-Onset Tuberculosis After Liver Transplantation

BackgroundWe encountered some cases of early-onset tuberculosis (TB) after liver transplant (LT), leading to further transmission to other immunocompromised patients. Therefore, we investigated the clinical characteristics and risk factors of early-onset TB after LT.MethodsAll adult patients with TB after LT from 1996 to 2019 were retrospectively enrolled. Our hospital did not screen for latent TB infection (LTBI) in LT recipients because of concerns regarding the potential hepatotoxicity of anti-TB medication. Patients were categorized into 2 groups based on the TB onset time after LT: early-onset TB (≤2 months) and late-onset TB (>2 months).ResultsOf 4301 LT recipients, 91 patients developed TB after LT (2.1%). The median time from LT to TB development was 9.4 months. Of these 91 patients, 11 were classified as having early-onset TB (12.1%). Patients with early-onset TB had a greater pretransplant TB history than patients with late-onset TB (36.4% vs 11.3%, P = .048).ConclusionThis unusual early-onset TB was more common in patients with a pretransplant TB history, suggesting the possibility of missed TB or full manifestation of the indolent course of TB after LT. Therefore, LT recipients with a pretransplant TB history should undergo thorough screening for active TB and consider prophylaxis.     

Wound outcomes and factors associated with wound healing after first-time femoropopliteal artery intervention in patients with ischemic tissue loss

Background/objectiveThis study’s goal is to describe wound outcomes at 2 years following intervention for atherosclerotic femoropopliteal lesions in patients with ischemic tissue loss.MethodsA retrospective review of 135 first-time endovascular procedures for chronic femoropopliteal atherosclerotic lesions related to ischemic tissue loss was performed. The final wound outcomes were categorized according to the initial wound healing, recurrence and the need of major/minor amputation.ResultsAt 2-years of follow up, 76 limbs (56.3%) showed complete wound healing without recurrence, however, wound development occurred at other sites on the same foot following complete primary healing in 11 limbs (8.1%). Tolerable wounds persisted or wounds recurred at the same site in 30 limbs (22.2%), and 18 limbs (13.3%) needed major amputations. Independent factors that prevented wound healing without recurrence at 2 years were renal insufficiency (HR = 0.225, 95% C.I. = 0.091–0.556, p = 0.001), ankle pressure < 50 mmHg or flat forefoot PVR (HR = 0.328, 95% C.I. = 0.124–0.867, p = 0.025) and functional performance < 4 metabolic equivalents (MET) (HR = 0.150, 95% C.I. = 0.063–0.360, p < 0.001).ConclusionWound outcome classifications showed detailed information regarding clinical outcomes in patients with ischemic tissue loss. Renal insufficiency, ischemia grade 3 and poor functional performance were independent risk factors that prevented wound healing.     

Comparison of Open Anterior Syndesmotic Repair Augmented With Suture-Tape and Trans-syndesmotic Screw Fixation: A Biomechanical Study

The treatment of syndesmotic injuries with ankle fractures is controversial. The purpose of this study was to compare the biomechanical properties of open anterior syndesmotic repair with those of screw fixation. Ten matched pairs of human cadaver specimens were subjected to open syndesmotic repair or screw fixation. Each specimen underwent initial intact physiologic loading, consisting of 10 cycles of external torsional loading with a peak torque of 7.5 Nm at 0.05 Hz. Injuries of the anterior inferior tibiofibular ligament, tibiofibular interosseous membrane, and deltoid ligament were applied to each specimen. Postfixation cyclic loading consisted of 50 cycles of combined axial and external rotation loading with peak torques of 750 N and 7.5 Nm at a rate of 0.05 Hz. After postfixation loading, each specimen underwent failure loading by external rotation at 0.25 degrees/second. Failure torque and failure angle were measured. The paired t test and Wilcoxon signed-rank test were used to analyze the data. Mean failure torques were 95.63 Nm in the open anterior syndesmotic repair augmented with suture-tape group and 108.61 Nm in the screw group. Mean failure angles were 34.93 degrees in the open anterior syndesmotic repair augmented with suture-tape group and 43.55 degrees in the screw group. These data were not statistically significantly different between the groups (p= .7682 and .4133, respectively). Open anterior syndesmotic repair augmented with suture tape for ankle syndesmotic injury provides similar torsional strength to that of screw fixation. Therefore, this technique can be considered as an alternative treatment option for syndesmosis injury.     

A prognostic immune predictor,HLA-DRA,plays diverse roles in non-muscle invasive and muscle invasive bladder cancer

BackgroundThere is an increasing demand for prognostic immune biomarkers of cancer. The prognostic significance of immune markers has been shown for various cancers, but biomarkers of bladder cancer (BCa) have not been fully evaluated. To clarify the role of human leukocyte antigen DR alpha chain (HLA-DRA) in BCa development, we examined expression of HLA-DRA mRNA in tissue samples of non-muscle invasive bladder cancer (NMIBC) and muscle invasive bladder cancer (MIBC).Materials and MethodsTissues of 96 NMIBC, 43 MIBC and 59 controls comprising noncancerous BCa surrounding tissues were used to examine the expression of HLA-DRA gene by real-time polymerase chain reaction. The expression of up-stream genes regulating HLA-DRA were also measured to explain the role of HLA-DRA in BCa.ResultsPatients with high grade NMIBC showed higher expression of HLA-DRA than those with low grade NMIBC (P < 0.05). In addition, NMIBC patients who progressed to MIBC showed high expression of HLA-DRA mRNA. Kaplan-Meier analysis showed that NMIBC patients with low expression of HLA-DRA had better progression-free survival than those with high expression (P = 0.004). Moreover, the expression of genes regulating HLA-DRA varied in NMIBC and MIBC, indicating a different immunoregulation effect of HLA-DRA in both cancers.ConclusionsHigh expression of HLA-DRA in NMIBC patients has implications for patient stratification strategies, as well as for BCa tumor immunology.     

“It’s a tool,not a cure”: the preoperative teen perspective on bariatric surgery

BackgroundBariatric surgery is well established in adults as the most effective tool for sustained weight loss and reduction of obesity-related co-morbidities, and is an emerging option for adolescents in whom conservative approaches have failed. Narratives are vital in understanding the motivating reasons and psychosocial profiles of adolescents considering bariatric surgery during a developmental period of evolving self-concept, body image sensitivity, peer pressure, and increased opportunity for risky behaviors.ObjectivesTo explore preoperative adolescent patient perspectives on their decision to pursue bariatric surgery, anticipated physical and psychosocial effects, and preparation process.SettingsThe Hospital for Sick Children (SickKids) in Toronto, Ontario, Canada.MethodsWe conducted 14 semi-structured interviews with adolescents (16–18 yr old) 2–4 months before bariatric surgery. A theoretical thematic analysis was conducted with 3 independent reviewers (interrater reliability, Cronbach’s α= .81) and conflicts were resolved through discussion.ResultsPatients’ perspectives are captured in 4 themes: motivation for surgery, effects on health and habits, psychosocial changes, and support systems during preparation. Participants perceived surgery as a tool but not a solution for weight loss. Most were motivated for health and daily functional improvement rather than aesthetic reasons, and some anticipated improved social interactions while maintaining their self-identity. Participants were selective in sharing news of their surgery, and received varying levels of support from families, friends, and healthcare teams.ConclusionAdolescents seem generally prepared for and informed about surgery, with expectations for weight loss and psychosocial improvements, although uncertainty and contradictory thoughts were prevalent. Insights provided by these adolescent patients will help optimize bariatric surgery assessments and support from clinical teams and inform preoperative education for future patients and families.     

Short-term therapy with anti-ICAM-1 monoclonal antibody induced long-term liver allograft survival in nonhuman primates

Tolerance induction remains challenging following liver transplantation and the long-term use of immunosuppressants, especially calcineurin inhibitors, leads to serious complications. We aimed to test an alternative immunosuppressant, a chimeric anti-ICAM-1 monoclonal antibody, MD-3, for improving the outcomes of liver transplantation. We used a rhesus macaque liver transplantation model and monkeys were divided into three groups: no immunosuppression (n = 2), conventional immunosuppression (n = 4), and MD-3 (n = 5). Without immunosuppression, liver allografts failed within a week by acute rejection. Sixteen-week-long conventional immunosuppression that consisted of prednisolone, tacrolimus, and an mTOR inhibitor prolonged liver allograft survival; however, recipients died of acute T cell–mediated rejection (day 52), chronic rejection (days 62 and 66), or adverse effects of mTOR inhibitor (day 32). In contrast, 12-week-long MD-3 therapy with transient conventional immunosuppression in the MD-3 group significantly prolonged the survival of liver allograft recipients (5, 96, 216, 412, 730 days; p = .0483). MD-3 effectively suppressed intragraft inflammatory cell infiltration, anti-donor T cell responses, and donor-specific antibody with intact anti-cytomegalovirus antibody responses. However, this regimen ended in chronic rejection. In conclusion, short-term therapy with MD-3 markedly improved liver allograft survival to 2 years without maintenance of immunosuppressant. MD-3 is therefore a promising immune-modulating agent for liver transplantation.     

Leg-length discrepancy and associated risk factors after paediatric femur shaft fracture: a multicentre study

PurposeThis study was performed to investigate leg-length discrepancy (LLD) and associated risk factors after paediatric femur shaft fractures.MethodsA total of 72 consecutive patients under 13 years old (mean age 6.7 years; 48 boys, 24 girls) with unilateral femur shaft fracture, and a minimum follow-up of 18 months, were included. The amount of LLD was calculated by subtracting the length of the uninjured from that of the injured limb. Risk factors for an LLD ≥ 1 cm and ≥ 2 cm were analyzed using multivariable logistic regression analysis.ResultsHip spica casting, titanium elastic nailing and plating were performed on 22, 40 and ten patients, respectively. The mean LLD was 7.8 mm (sd 8.8) and 29 (40.3%) had a LLD of ≥ 1 cm, while nine (12.5%) had a LLD of ≥ 2 cm. There were significant differences in fracture stability (p = 0.005) and treatment methods (p = 0.011) between patients with LLD < 1 cm and ≥ 1 cm. There were significant differences in fracture site shortening (p < 0.001) and LLD (p < 0.001) between patients with length-stable and length-unstable fractures. Fracture stability was the only factor associated with LLD ≥ 1 cm (odds ratio of 4.0; p = 0.020) in the multivariable analysis.ConclusionThis study demonstrated that fracture stability was significantly associated with LLD after paediatric femur shaft fractures. Therefore, the surgeon should consider the possibility of LLD after length-stable femur shaft fracture in children.Level of EvidencePrognostic level III