Post-transplant eosinophilic gastrointestinal disorders and lymphoproliferative disorder in pediatric liver transplant recipients on tacrolimus

AimTo examine and characterize post-transplant eosinophilic gastrointestinal disorders (PTEGID) and post-transplant lymphoproliferative disorder (PTLD) in pediatric liver transplant recipients.MethodsThis is a single center retrospective study of all liver transplant recipients aged 0–18 years from 1999 to 2019 who received tacrolimus as their primary immunosuppressant. Demographic data and clinical/laboratory data including PTEGID, PTLD, liver transplant types, Epstein-Barr virus status, and blood eosinophil count were reviewed. Analysis was done with logistic regression and Mann-Whitney U test.ResultsNinety-eight pediatric liver transplant recipients were included with median age at transplantation of 3.3 years (IQR: 1.1–9.3). The major indication for transplantation was biliary atresia, 51 (52%) cases. Eight (8%) children had PTLD and 14 (14%) had PTEGID. Receiving liver transplantation at an age of ≤1 year was associated with developing PTEGID (OR = 11.9, 95% CI = 3.5–45.6, p < 0.001). Additionally, eosinophilic count of ≥500/μL was associated with having PTLD (OR = 10.7, 95% CI = 1.8–206.0, p = 0.030) as well as having at least one liver rejection (OR = 2.8, 95% CI = 1.2–7.0, p = 0.024). The frequency of food-induced anaphylaxis significantly increased post-transplantation (p = 0.023).ConclusionsPTEGID and PTLD are common in this cohort and are associated with certain risk factors that help screen children to improve recipient survival. Further studies are needed to evaluate the clinical benefits of these findings.     

Risk factors associated with Hepatitis E virus infection in kidney transplant recipients in a single tertiary Center in the United States

BackgroundHepatitis E virus (HEV), the causative agent of hepatitis E, is a common but self-limiting disease. However, in immunosuppressed kidney transplant 47 recipients (KTRs), HEV infection can become chronic. We investigated risk factors associated with HEV infection among 271 KTRs at the Johns Hopkins Hospital transplanted between 1988 and 2012.MethodsHEV infection was defined as having positive anti-HEV IgM, anti-HEV IgG, or HEV RNA. The risk factors included: age at transplant, sex, hemodialysis/peritoneal dialysis, plasmapheresis, transfusions, community urbanization, and other socioeconomic factors. Logistic regression was used to determine independent risk factors associated with HEV infection.ResultsOut of 271 KTRs, 43 (16%) had HEV infection though not active disease. HEV infection in KTRs was associated with older age (≥45 years; OR = 4.04; 95% CI = 1.81–57 10.03; p = 0.001) and living in communities with low proportions of minorities (OR = 0.22; 95% 58 CI = 0.04–0.90; p = 0.046).ConclusionKTRs who had HEV infection may be at an increased risk of developing chronic HEV.     

Basiliximab is associated with a lower incidence of De novo donor-specific HLA antibodies in kidney transplant recipients: A single-center experience

PurposeInduction immunosuppression has improved the long-term outcomes after kidney transplant. This study explores the association of different induction immunosuppression medications (Basiliximab vs. Alemtuzumab vs. rabbit Antithymocyte Globulin) used at the time of kidney transplant with the development of de novo donor-specific HLA antibodies (DSA) in the first 12 months post-transplant period.MethodsA total of 390 consecutive kidney transplant recipients (KTR), between 2016 and 2018, were included in the analysis. A 104 (26.6%) received Basiliximab, 186 (47.6%) received Alemtuzumab, and 100 (25.6%) received rabbit Antithymocyte Globulin (rATG) for induction. All recipients had a negative flow cytometry crossmatch before transplant. Serum samples at 4- and 12-months post-transplant were assessed for the presence of de novo HLA DSA. kidney allograft function was compared among the three groups with calculated Creatinine Clearance on 24 h urine collection.ResultsDe novo HLA DSA were detected in total of 81 (20.8%) patients within 12 months post-transplant. De novo HLA DSA were detected in 12/104 (11.5%), 43/186 (23.11%), and 26/100 (26%) KTR that received Basiliximab, Alemtuzumab, and rATG respectively (p = 0.006). KTR that received Basiliximab were significantly older, and the last follow-up creatinine clearance was significantly lower at 42 ml/min compared to KTR that received Alemtuzumab or rATG (p = 0.006).ConclusionInduction immunosuppression utilizing Basiliximab is associated with significant reduction in development of de novo DSA within the first 12-months post kidney transplant but had lower creatinine clearance with long-term follow up.     

Quilty in biopsy is associated with poor prognosis after heart transplantation

We tested if Quilty (endocardial infiltration of lymphocytes) in routinely processed endomyocardial biopsy is associated with poor outcome after heart transplantation (HTx).Biopsies (n = 9829) harvested within the first post-transplant year from 938 patients (778 men, mean age 49 years) were evaluated for Quilty and acute cellular rejection (according to the International Society for Heart and Lung Transplantation, ISHLT, classification). Transplant vasculopathy was evaluated by coronary angiography, and severe stenosis was found in 19% of patients. Survival was tested by Kaplan–Meier and Cox regression analyses for all-cause mortality and major cardiac events (lethal acute cellular rejection, graft loss or myocardial infarction).We found 1840 (19%) Quilty-positive biopsies in 487 Quilty-positive patients (52%). Quilty was more prevalent in women (p = 0.038) and younger men (p = 0.001), and was correlated with ISHLT grade 1R (OR 1.45, 95% CI 1.36–1.55; p < 0.001) and ISHLT grade 2R (OR 2.48, 95% CI 2.21–3.41; p < 0.001). Quilty in any biopsy was associated with a higher all-cause mortality (log rank p = 0.045) due to a higher risk for major cardiac event (p = 0.0001). Multivariate regression analysis showed Quilty (RR 1.69, 95%CI 1.05–2.73) and transplant vasculopathy (RR 2.78, 95%CI 1.68–4.61) as risk factors for major cardiac events and treated hyperlipidemia as lowering the risk for major cardiac events (RR 0.47, 95%CI 0.28–0.77).Quilty is associated with graft loss and poor outcome post HTx. Index biopsy during the first post-transplant year is a useful tool to identify patients at risk and is recommended during routine post-transplant management.     

Breast ultrasound in 22,131 asymptomatic women with negative mammography

PurposeTo evaluate increment cancer detection rate generated by ultrasound (US).Materials and methodsUS only detected cancers were assessed for 22,131 self-referring asymptomatic women with negative mammography and subgroups by age, previous cancer, breast density. Invasive assessment and surgical biopsy rate were evaluated.ResultsThe overall US detection was 1.85 per thousand (41/22,131). In the subgroups it was: 1.95 per thousand (22/11,274) in women <50 years vs 1.75 per thousand (19/10,857) in women ≥50 years (p = 0.42), 5.49 per thousand (12/2183) in women with previous cancer vs 1.45 per thousand (29/19,948) in women without cancer history (p = 0.0004), 2.21 per thousand (22/9960) in dense breasts (p = 0.17) vs 1.56 per thousand (19/12,171) in fatty breasts. The US generated invasive assessment was 1.9% (422/22,131). The benign to malignant open surgical biopsy ratio was 0.17 (7/41).ConclusionAdding US to negative mammography allowed for substantial incremental cancer detection rate (1.85 per thousand), particularly at age <50years, in women with previous breast cancer and in dense breasts.     

Antifungal Prophylaxis and Treatment Among Lung Transplant Recipients in Early Postoperative Stage: A Single-Center Study

BackgroundLung transplantation remains the only feasible option for certain patients with end-stage lung disease. Lifelong immunosuppression increases the risk of infection, including fungal infections. The aim of this study was to assess the effect of antifungal prophylaxis and treatment among lung transplant recipients in the early postoperative stage.MethodsThis retrospective analysis included 127 patients who underwent lung transplantation between 2014 and 2021 in the lung transplant ward, 65.35% of whom were males. The most common indication for lung transplantation was cystic fibrosis (n = 59; 46.46%). All of the patients were receiving inhaled amphotericin B. Within this group there were patients who also were treated with intravenous caspofungin, intravenous/oral voriconazole, or both.ResultsThe difference in the efficacy against Candida spp. between caspofungin and voriconazole in the early post-transplant period was not statistically significant (χ₂ = 0.5, P = .477). Moreover, the difference in the efficacy against Candida spp. between itraconazole and voriconazole during the first post-transplant year was not statistically significant (χ₂ = 0.46, P = .496).ConclusionCaspofungin and voriconazole are proper and relatively efficient antifungal prophylaxis and treatment options after lung transplantation. There was no significant difference between voriconazole and caspofungin as antifungal agents used in the early post-transplant stage. There was no significant difference between voriconazole and itraconazole as antifungal agents used during the first post-transplant year. Further research on this issue is required.     

Serum follistatin level as a prognostic marker in Haploidentical stem cell transplantation

BackgroundThe treatment of hematological diseases with Haploidentical transplantation has made significant progress. Follistatin is an angiogenic factor that is elevated in the circulation after allogeneic Hematopoietic Cell Transplantation (HCT). Elevated follistatin levels have been linked to poor survival after graft versus host disease (GVHD).ObjectivePre- and post-transplant Follistatin levels were measured in patients subjected to Haploidentical HSCT and correlated with transplant outcomes.Patients and methodsThis study included 45 patients who underwent allogeneic stem cell transplants from Haploidentical donors.ResultsThe mean Follistatin level before stem cells infusion (88.81 ± 49.11 ng/ml) and at day 28 post-transplant (78.61 ± 45.50 ng/ml). The mean follistatin level was higher among the patients who had acute severe GVHD grade 3–4 pre-transplant at day zero and day 28 without statistical significance.The incidence of veno-occlusive disease was higher in patients with elevated serum follistatin levels on day 0 (108.58 ± 64.12 Vs 82.16 ± 46.05 ng/ml. p value = 0.134) and day 28 (112 ± 49.36 vs 66.06 ± 38.96 ng/ml) with statistically significance at day 28 post-transplant (p value = 0.011).After 180 days of follow-up, patients with high serum follistatin (i.e. >60 ng/ml) on day 28 post-transplant had lower OS, (P = 0.381).ConclusionIn the setting of Haploidentical HSCT, higher follistatin levels post-transplant are associated with severe acute GVHD and inferior overall survival.     

Factors Influencing Short-Term Patient Survival in Elderly Kidney Transplant Recipients

BackgroundFor the average patient with end-stage renal disease, kidney transplantation improves quality of life and prolongs survival compared with patients on the transplant waiting list who remain on dialysis. Patients ≥65 years of age represent an increasing proportion of adults with end-stage renal disease, and kidney transplantation outcomes remain controversial in this population. The aim of this study was to evaluate factors that may increase 1-year mortality after renal transplantation in older recipients.MethodsA retrospective study that included 147 patients (75.5% men) ≥65 years old (mean age 67.5 ± 2 years) who were transplanted between January 2011 and December 2020. The mean follow-up was 52.6 ± 27.2 months.ResultsRehospitalization (<1 year) occurred in 39.5% of patients. Infectious complications were present in 18.4% of patients. The overall mortality rate was 23.1%, and 1-year mortality was 6.8%. As 1-year mortality predictors, we found a positive correlation with factors related to kidney transplant, such as cold ischemia time (P = .003), increasing donor age (P = .001); and factors related to the receptor such as pretransplantation dialysis modality as peritoneal dialysis (P = .04), cardiovascular disease (P = .004), delayed graft function (P = .002), early cardiovascular complications after kidney transplant (P < .001), and early rehospitalizations (P < .001). No correlation was found between 1-year mortality and age, sex, race, body mass index, and type of kidney transplant.ConclusionA more rigorous pretransplant evaluation, focusing on cardiovascular disease and strict exclusion criteria, is recommended for patients ≥65 years old.     

The physiological range of the Böhler’s angle in the adult Croatian population

BackgroundTo examine the relationship of the Böhler’s angle with age, sex, and laterality, and to analyze the interrater agreement.MethodsAfter 248 digital lateral radiographs of the foot were submitted to exclusion criteria, three raters independently measured the Böhler’s angle on the remaining 130 X-rays in PACS. The variables were analyzed with correlation coefficients, and one-way ANOVA. The repeated measures of ANOVA were computed across age groups (30–39, 40–49, 50–59, and 60–69 years). The interrater agreement was calculated using intraclass correlation coefficient (ICC).ResultsThe mean value of the Böhler’s angle was 34 ± 5° (21–46°). It was not related to age (in general [p = 0.057], and across groups [p from 0.107 to 0.122]), sex (p = 0.344; p = 0.342), and laterality (p = 0.618; p = 0.617). The interrater reliability was almost perfect (ICC = 0.94).ConclusionsThe Böhler’s angle was not related to age, sex, and laterality, whereas the interrater agreement was almost perfect.     

Value of aortic volumes assessed by automated segmentation of 3D MRI data in patients with thoracic aortic dilatation: A case-control study

PurposeThe purpose of this study was to investigate the benefit of aortic volumes compared to diameters or cross-sectional areas on three-dimensional (3D) magnetic resonance imaging (MRI) in discriminating between patients with dilated aorta and matched controls.Materials and methodsSixty-two patients (47 men and 15 women; median age, 66 years; age range: 33–86 years) with tricuspid aortic valve and ascending thoracic aorta aneurysm (TAV-ATAA) and 43 patients (35 men and 8 women; median age, 51 years; age range: 17–76 years) with bicuspid aortic valve and dilated ascending aorta (BAV) were studied. One group of 54 controls matched for age and sex to patients with TAV-ATAA (39 men and 15 women; median age, 68 years; age range: 33–81 years) and one group of 42 controls matched for age and sex to patients with BAV (34 men and 8 women; median age, 50 years; age range: 17–77 years) were identified. All participants underwent 3D MRI, used for 3D-segmentation for measuring aortic length, maximal diameter, maximal cross-sectional area (CSA) and volume for the ascending aorta.ResultsAn increase in ascending aorta volume (TAV-ATAA: +107%; BAV: +171% vs. controls; P < 0.001) was found, which was three times greater than the increase in diameter (TAV-ATAA: +29%; BAV: +40% vs. controls; P < 0.001). In differentiating patients with TAV-ATAA from their controls, the indexed ascending aorta volume showed better performances (AUC, 0.935 [95% confidence interval (CI): 0.882–0.989]; accuracy, 88.7% [95% CI: 82.9–94.5]) than indexed ascending aorta length (P < 0.001), indexed ascending aorta maximal diameter (P = 0.003) and indexed ascending aorta maximal CSA (P = 0.03). In differentiating patients with BAV from matched controls, indexed ascending aorta volume showed significantly better performances performance (AUC, 0.908 [95% CI: 0.829–0.987]; accuracy, 88.0% [95% CI: 80.9–95.0]) than indexed ascending aorta length (P = 0.02) and not different from indexed ascending aorta maximal diameter (P = 0.07) or from indexed ascending aorta maximal CSA (P = 0.27)ConclusionAortic volume measured by 3D-MRI integrates both elongation and luminal dilatation, resulting in greater classification performance than maximal diameter and length in differentiating patients with dilated ascending aorta or aneurysm from controls.     

The effect of pre-conditioning immunoglobulin and absolute lymphocyte count on the outcomes of allogeneic hematopoietic cell transplantation

IntroductionThe prevention of mortality and morbidity related to the increasingly used allogeneic hematopoietic cell transplantation (allo-HCT), along with the effects of pre- and post-transplant immune status on transplant outcomes, have become the focus of the studies conducted on this subject in recent years. In parallel, this study was designed to investigate the effects of pre-conditioning immunoglobulin (pre-conditioning-Ig) and pre-conditioning absolute lymphocyte count (pre-conditioning-ALC) levels on transplant outcomes.MethodsThis study was designed as a retrospective, observational and cross-sectional study. The objective of the study is to investigate the effects of pre-conditioning-Ig and ALC levels primarily on the rate of patients with febrile neutropenia (FEN) and the duration of FEN and length of hospital stay (LoS), and secondarily on acute graft-versus-host disease (aGVHD), cytomegalovirus (CMV) viremia, and mortality in the acute leukemia patients who underwent allo-HCT.ResultsA total of 104 acute leukemia patients, of whom 55 had acute lymphoblastic leukemia (ALL) and 49 had acute myeloid leukemia (AML), were included in the study. Compared to the AML group, the median pre-conditioning-IgG, IgA, and IgM levels were found to be significantly lower in the ALL group (11.3 vs. 6.6, p < 0.001; 1.8 vs. 0.9, p < 0.001; and 0.7 vs. 0.4, p < 0.001; respectively). But, there was no significant difference between the groups in pre-conditioning-Ig and ALC levels and transplant outcomes. However, subgroup analysis revealed that high pre-conditioning-ALC levels were significantly correlated with aGVHD levels (Odds Ratio: 1.02; p = 0.034) and low pre-conditioning-IgM levels were significantly correlated with increased mortality rate (Hazard Ratio: 0.08; p = 0.042) in AML patients.ConclusionThe significant difference determined between the ALL and AML groups in pre-conditioning-Ig levels was not reflected on the effects of pre-conditioning-Ig and ALC levels on transplant outcomes. However, we observed that pre-conditioning-IgM and ALC levels have an impact on transplant outcomes in AML patients.     

Hepatitis E virus infection and rejection in kidney transplant recipients

BackgroundHepatitis E virus (HEV) infection has been associated with immune-mediated kidney diseases in developing countries. However, its relationship with kidney transplant outcomes has never been studied. We investigated the association between HEV infection and kidney graft rejection among kidney transplant recipients (KTRs).MethodsWe conducted a matched cohort and longitudinal study utilizing banked sera following kidney transplantation during 1988–2012. Studies with evidence of post-transplantation HEV infection were identified by positive ELISA tests (anti-HEV IgM or anti-HEV IgG seroconversion) or positive HEV PCR and matched to KTR controls with negative HEV ELISA and PCR tests in a 1:5 ratio by age, sex, crossmatch status, immunosuppression era, and time of HEV testing. Outcome data collected included time to first kidney graft rejection, transaminases, and glomerular filtration rates. Log-ranked test was used to analyze survival.ResultsOf 271 KTRs, 9 (3%) had evidence of post-transplantation HEV infection and were compared to 45 negative, matched controls. Median age at transplantation was 46 years. Kidney graft rejection was reported in 8 (89%) of cases and 21 (47%) of controls. Median time to first episode of kidney graft rejection was 17.4 months in cases and 30.8 months in controls (p = 0.029), with a higher hazard of developing kidney graft rejection in cases (HR = 3.23, 95% CI: 1.19–8.79). Lower mean glomerular filtration rates over time were observed in cases (35 mL/min/1.73m²) versus controls (42.4 mL/min/1.73m²) but did not reach significance (p = 0.24).ConclusionSubjects with evidence of post-transplantation HEV infection demonstrated earlier kidney graft rejection compared to controls.     

Differences among sexes in presentation and outcomes in acute type A aortic dissection repair

ObjectiveFemale sex is a known risk factor in most cardiac surgery, including coronary and valve surgery, but unknown in acute type A aortic dissection repair.MethodsFrom 1996 to 2018, 650 patients underwent acute type A aortic dissection repair; 206 (32%) were female, and 444 (68%) were male. Data were collected through the Cardiac Surgery Data Warehouse, medical record review, and National Death Index database.ResultsCompared with men, women were significantly older (65 vs 57 years, P < .0001). The proportion of women and men inverted with increasing age, with 23% of patients aged less than 50 years and 65% of patients aged 80 years or older being female. Women had significantly less chronic renal failure (2.0% vs 5.4%, P = .04), acute myocardial infarction (1.0% vs 3.8%, P = .04), and severe aortic insufficiency. Women underwent significantly fewer aortic root replacements with similar aortic arch procedures, shorter cardiopulmonary bypass times (211 vs 229 minutes, P = .0001), and aortic crossclamp times (132 vs 164 minutes, P < .0001), but required more intraoperative blood transfusion (4 vs 3 units) compared with men. Women had significantly lower operative mortality (4.9% vs 9.5%, P = .04), especially in those aged more than 70 years (4.4% vs 16%, P = .02). The significant risk factors for operative mortality were male sex (odds ratio, 2.2), chronic renal failure (odds ratio, 3.4), and cardiogenic shock (odds ratio, 6.8). The 10-year survival was similar between sexes.ConclusionsPhysicians and women should be cognizant of the risk of acute type A aortic dissection later in life in women. Surgeons should strongly consider operations for acute type A aortic dissection in women, especially in patients aged 70 years or more.     

Routing kinetics of human immunoglobulin-G after transamniotic fetal immunotherapy (TRAFIT) in a rodent model

PurposeThe transamniotic route was recently discovered as a minimally invasive means of fetal immunoglobulin administration, however by unclear mechanisms. We sought to examine IgG routing after intra-amniotic delivery.MethodsSprague-Dawley fetuses (n = 78) received intra-amniotic injections of 15 mg/mL of human IgG on gestational-day 18 (E18; term=21 and 22 days). Amniotic fluid, amnion, chorion, placenta, fetal serum, liver, and stomach-aspirate samples were procured on E19, E20, and E21 for IgG quantification by ELISA. Statistical analysis was by median regression with Bonferroni-adjusted significance at p < 0.017.ResultsHuman IgG was detected at all sampled sites across all time points, though at significantly higher levels in the gestational membranes and fetal serum than in the stomach aspirate and liver (p < 0.001 for both). Gestational membranes showed a daily decrease after injection, stabilizing by E20 and E21 (p = 0.792 to < 0.001). Placental levels were significantly lower at E21 than E19 (p = 0.010). Fetal serum showed the highest human IgG levels at term.ConclusionsThe chronology of exogenous IgG kinetics after intra-amniotic injection is suggestive of direct placental transport leading to consistently high fetal serum levels, possibly combined with some fetal ingestion. Transamniotic fetal immunotherapy (TRAFIT) may become a practicable strategy for the prenatal treatment of select alloimmune disorders and infections.Level of evidenceN/A (Animal and Laboratory study).Type of studyAnimal and Laboratory Study.     

FRAX (Aus) and falls risk: Association in men and women

PurposeThe WHO fracture risk prediction tool (FRAX®) utilises clinical risk factors to estimate the probability of fracture over a 10-year period. Although falls increase fracture risk, they have not been incorporated into FRAX. It is currently unclear if FRAX captures falls risk and whether addition of falls would improve fracture prediction. We aimed to investigate the association of falls risk and Australian-specific FRAX.MethodsClinical risk factors were documented for 735 men and 602 women (age 40–90 yr) assessed at follow-up (2006–2010 and 2000–2003, respectively) of the Geelong Osteoporosis Study. FRAX scores with and without BMD were calculated. A falls risk score was determined at the time of BMD assessment and self-reported incident falls were documented from questionnaires returned one year later. Multivariable analyses were performed to determine: (i) cross-sectional association between FRAX scores and falls risk score (Elderly Falls Screening Test, EFST) and (ii) prospective relationship between FRAX and time to a fall.ResultsThere was an association between FRAX (hip with BMD) and EFST scores (β = 0.07, p < 0.001). After adjustment for sex and age, the relationship became non-significant (β = 0.00, p = 0.79). The risk of incident falls increased with increasing FRAX (hip with BMD) score (unadjusted HR 1.04, 95% CI 1.02, 1.07). After adjustment for age and sex, the relationship became non-significant (1.01, 95% CI 0.97, 1.05).ConclusionsThere is a weak positive correlation between FRAX and falls risk score, that is likely explained by the inclusion of age and sex in the FRAX model. These data suggest that FRAX score may not be a robust surrogate for falls risk and that inclusion of falls in fracture risk assessment should be further explored.     

Pre-operative predictors of poor reduction in acetabular fractures submitted to surgical treatment

IntroductionAcetabular fractures are among the most complex orthopedic injuries, and their treatment and understanding have evolved remarkably in the last 50 years. Several factors affect the reduction quality of the surgically treated displaced acetabular fractures. Thus, this study aimed to identify these factors by analyzing patients’ data.Patients and methodsRetrospective data from fractures operated in one center over 8 years were analyzed. Patients with a mature skeleton who underwent open reduction and internal fixation and had a minimum follow-up period of 6 weeks were included. Non-displaced fractures were excluded from the study. Radiographic assessment of the reduction was performed before surgery and at follow-up using the method described by Borelli et al. The effects of age (<40 or >40 years), sex, initial displacement (< 20 mm or > 20 mm), time to surgery (<14 days or>14 days), fracture pattern (elementary or associated), number of associated fractures (< 3 or > 3), and associated pelvic injury were analyzedResultsThe study included 115 (83.9%) men and 22 (16.1%) women, with a mean age of 34.1 years (range 16–74 years). In the sixth week of follow-up, reductions were satisfactory in 96 (70.7%) patients and unsatisfactory in 41 (29.3%). The most prevalent patterns were the posterior wall (23.1%) and both column (15.7%). Linear regression showed that residual displacement was directly correlated with initial displacement (p = 0.027) but without association with reduction quality. Age, sex, and initial displacement had no effect on reduction quality, which is in contrast with longer time to surgery (p = 0.004), associated fracture pattern (p = 0.002), three or more associated fractures (p = 0.001), and presence of associated pelvic injury (p = 0.021).ConclusionAttempting to shorten the time to operate the fractures can lead to better results for patients because the other factors associated with poor reduction are inherent the trauma and cannot be modified by the surgeon.     

Humoral Response After SARS-CoV-2 Vaccination in Kidney Transplant Recipients: Role of Immunosuppression Therapy

BackgroundMessenger RNA vaccination against COVID-19 has been shown to produce an immune response with sufficient efficacy to prevent natural infection in immunocompetent recipients. However, the response in kidney transplant recipients is low. We aimed to evaluate the specific humoral response to SARS-CoV-2 after vaccination in a population of kidney transplant recipients and assess the main factors associated with a lack of response.MethodsWe undertook a prospective study of 105 kidney transplant recipients and 11 recipients of a combined kidney-pancreas transplant. We analyzed immunoglobulin G and immunoglobulin M antibodies after the patients received their second and third doses of the messenger RNA 1273 (Moderna) or BNT162b1 (BionTECH-Pfizer) vaccinations between February and November 2021.ResultsMean (SD) age of the 116 patients was 50 (16) years, and 65% were men. They had their transplants for 40 months (IQR, 15-123 months), with 14% undergoing retransplant and 11% sensitized. The maintenance immunosuppression regimen was steroids + tacrolimus + mycophenolate (MMF) in 68% of the patients and any combination with mammalian target of rapamycin inhibitor (mTORi) in 28%. A humoral response developed in 40% of the patients 6 weeks (IQR, 4-10 weeks) after receiving the second dose of the vaccine. Of the 67 patients with no response to the second dose, 51 had an analysis of the humoral response after the third dose, which was positive in 16 (31%). A total of 80% received the Moderna vaccine and 20% the BionTECH-Pfizer. No patient experienced major adverse effects after the vaccination.Factors associated with a lack of humoral response to the vaccine were recipient age (odds ratio [OR], 1.02; 95% CI, 1.001-1.05; P = .04), diabetes (OR, 2.8; 95% CI, 1.2-6.9; P = .02), and treatment with MMF (OR, 2.6; 95% CI, 1.08-6.8; P = .03). Treatment with mTORi was associated with a better response to vaccination (OR, 0.3; 95% CI, 0.1-0.9; P = .04).ConclusionsThe humoral response to the COVID-19 vaccine in kidney transplant recipients is poor. Factors related with this lack of immunity are recipient age and diabetes, plus MMF therapy, whereas mTORi therapy was associated with a better response to vaccination.     

Sex differences in Japanese patients with ruptured aortic aneurysms

ObjectiveThis study aimed to assess the sex differences in clinical presentation and outcomes of Japanese patients with ruptured aortic aneurysm (rAA) using a large nationwide claims-based database in Japan.MethodsWe identified patients hospitalized in certified teaching hospitals in Japan with rAA between April 1, 2012, and March 31, 2015. Patients' characteristics and in-hospital outcomes were compared between men and women. The Barthel index was used for evaluating functional status at discharge by examining the ability to perform basic daily activities.ResultsOf 7086 eligible patients, 32.3% (2291/7086) were women. Women were older than men (81.9 years vs 76.1 years; P < .001), had higher prevalence of coma at admission (33.2% vs 25.2%; P < .001), and were less likely to undergo emergency operation including endovascular aneurysm repair (35.7% vs 51.1%; P < .001). The unadjusted mortality rate (62.5% vs 52.0%; P < .001) and Barthel index at discharge (78.7 vs 86.1; P < .001) were significantly worse in women than in men. However, multilevel mixed-effect logistic regression analyses showed that female sex itself was not an independent predictor for in-hospital death (odds ratio [OR], 0.90; 95% confidence interval [CI], 0.78-1.04; P = .17). Older age, coma at admission, and vasopressor use were detected as independent predictors for in-hospital death. The same results were confirmed for each rupture site. Stratified analyses showed that older women (threshold, 80 years; OR, 0.81; 95% CI, 0.66-0.98; P = .028) and those who underwent emergency operation (OR, 0.75; 95% CI, 0.61-0.93; P = .009) showed significantly better outcomes than men.ConclusionsIn a univariate analysis, female patients with rAA showed worse mortality than men because of their older age, more severe clinical presentation, and low emergency operation rate. However, after adjustment for covariates, female sex itself was not associated with increased mortality.     

Circulating “Neutrophils extra-cellular traps” during the early post-renal transplant period and correlation with graft dysfunction and rejection

BackgroundNeutrophil extracellular traps (NETs) have a role in infection, autoimmunity, autoinflammation, thrombosis, ischemia-reperfusion injury (IRI), epithelial-mesenchymal transition, vasculitis, and metabolic diseases. However, its role in early graft injury and graft outcome has not been elucidated till now. We evaluated the circulating NETs during early post-transplant periods and their correlation with graft outcome and IRI.MethodsProspectively, thirty kidney transplants recipient (KTR) were recruited and grouped into non-dysfunction (Group-A) and dysfunction groups (Group-B). Serum levels of circulating NETs were estimated by measuring myeloperoxidase-DNA complex at three-time points: pre-transplant, 8 h post-transplant, and 18 h post-transplant; and correlated with early graft outcome. Malondialdehyde (MDA), a marker of oxidative stress or IRI, was also measured to assess its relation with NETs and early graft outcome.ResultsCirculating NETs were significantly increased in both non-dysfunctional [Median OD: 0.11 (0.01–0.19) to 0.51 (0.22–0.91); p = 0.001] and dysfunctional [Median OD: 0.16 (0.12–0.27) to 0.38 (0.19–0.68); p = 0.047] KTR during first 8 h of transplant followed by fall at 18 h post-transplant [0.25 (0.18–0.72) and 0.35 (0.26–0.36) respectively]; however, no significant difference were observed between two groups at any time points. Isolated biopsy-proven graft rejection KTR also had higher circulating NETs during the early post-transplant period [Median OD: 0.16 (0.13–0.31) to 0.38 (0.28–1.5); p > 0.05] but no significant difference compared to non-dysfunctional KTR. MDA also displayed similar trends with an early significant rise [9.30 (7.74–12.56) μM to 17.37 (9.11–22.25) μM; p = 0.03 in group-A, and 8.7 (6.04–10.30) μM to 14.66 (13.39–21.63) μM; p = 0.01in group-B] followed by fall at 18 h in both groups [10.21 (7.64–13.90) μM and 11.11 (9.15–17.54) μM respectively]. Despite similar trends of both NETs and MDA, there was no significant correlation between these; however, creatinine exhibits a significant inverse correlation with NETs and MDA both.ConclusionCirculating NETs are significantly increased during the early post-transplant period in KTR irrespective of early graft outcome. Similar dynamics of MDA indicate that the early rise of NETs might be a part of IRI. However, molecular studies with large sample sizes and longer follow up are required to reach more defined conclusions.