Prospective validation of the L-index reflecting both the intensity and duration of lymphopenia and its detailed evaluation using a lymphocyte subset analysis after allogeneic hematopoietic stem cell transplantation

We prospectively validated the previously reported L-index, which reflects both the intensity and duration of lymphopenia, and further evaluated it using a lymphocyte subset analysis after allogeneic hematopoietic stem cell transplantation (HSCT) (n = 30). The L-index was defined as the area over the lymphocyte curve during lymphopenia (<700/μl), and calculated from the start of conditioning to day30 (L-index(30)) and day100 (L-index(100)). The lymphocyte subset including CD3, CD4, CD8, CD19 and CD56 was analyzed before and at 14, 21, 28, 42, 56, 70, and 84 days after HSCT. Cytomegalovirus (CMV) antigenemia was detected as >3 cells/2 slides by the C10/11 method in 21 cases (CMV-AG ≥3 group) at a median of 34 days. L-index(30) was significantly higher in the CMV-AG ≥3 group than in the CMV-AG <3 group (median 20,358 vs 17,235, P = .028). Recovery of the CD4+ and CD56+ cell counts between days 14 and 28 after HSCT was impaired in the CMV-AG ≥3 group. Regarding graft-versus-host disease (GVHD), grade II-IV acute GVHD was identified in 14 patients (GVHD group) at a median of 31 days. L-index(30) was significantly lower in the GVHD group (median 19,048 vs 22,256, P = .043). Recovery of CD3+ cells including both CD4+ and CD8+ cells between days 14 and 28 tended to be better in the GVHD group. In conclusion, L-index(30) was significantly associated with CMV reactivation and grade II-IV acute GVHD, but its clinical significance seemed to differ according to the results of a lymphocyte subset analysis.     

A retrospective study of treatment and outcomes of patients with lymphoma undergoing hematopoietic stem cell transplantation: A single-center experience

BackgroundEarly evaluation of symptoms and taking appropriate preventive measures can improve outcomes for patients with lymphoma undergoing hematopoietic stem cell transplantation (HSCT). This study aimed to examine the treatment and outcomes of patients with lymphoma undergoing HSCT.MethodsPatients with lymphoma undergoing SCT at a university hospital between 15.06.2018 and 15.06.2020, were selected for a retrospective study. The medical treatments of patients were obtained from the records on the Hospital Information Management System (HIMS) database. The study was reported following the STROBE checklist.ResultsSixty-four patients were analyzed. The mean age of the patients was 48.25 ± 16.93 (p = 0.76). Although relapse developed in 26 (40.6%) patients with lymphoma, remission was achieved in 38 (59.4%) patients. The incidence of skin graft-versus-host disease (GVHD) symptoms in patients with relapse [14(53.8%)] was found to be significantly higher than in patients in remission [4(10.5%)] (p < 0.001). The most common symptoms seen in patients undergoing HSCT were oral mucositis (78.1%), febrile neutropenia (68.8%), and anemia (56.3%). In the treatments applied after SCT, the administration of antifungal (p = 0.033), analgesic (p = 0.001), and anticoagulant (p = 0.008) treatments to the patients who were in remission compared with the relapsed patients was significant. Less courses (OR: 0.446; 95% CI: 0.22–0.907; p = 0.026), analgesic therapy (OR:6.22; 95% CI: 1.61–24.027; p = 0.008), and anticoagulant treatment (OR:7.13; %) 95 CI: 1.374–37.1; p = 0.019) were found to increase the risk of relapse. Because of the increase in the number of cures in SCT, the incidence of diarrhea (p = 0.016) and GIS GVHD (p = 0.022) was high. It was determined that the hospitalization period was shorter in patients with febrile neutropenia (p = 0.021), thrombocytopenia/bleeding (p = 0.031), and secretion (p = 0.036) symptoms.ConclusionsPatients experienced severe symptoms such as oral mucositis, febrile neutropenia, and anemia due to HSCT, and necessary treatment was applied for the symptoms. Further clinical studies must determine the symptoms and patient outcomes associated with SCT. It is predicted that patients will benefit from regular follow-up of their symptoms and planning of appropriate evidence-based nursing interventions and that this will improve the quality of care to be offered to them and increase their life span.     

Comparison of del Nido Cardioplegia vs. blood cardioplegia in adult aortic surgery: Is the single-dose cardioplegia technique really advantageous?

Background/objective: The aim of the present study was to compare the operative and early postoperative results of the use of del Nido Cardioplegia solution (dNCS) with traditional blood cardioplegia (BC) in adult aortic surgery.MethodsA retrospective single-center study was performed on 118 patients who underwent aortic surgery with cardiopulmonary bypass (CPB) between January 2016 and June 2020. Patients were divided in to two groups according to the type of cardioplegia solution used. Cardiac arrest was achieved in Group 1 (n = 65) with traditional BC and in Group 2 (n = 53) with dNCS. Operative and postoperative outcomes of the patients were compared between the two groups.ResultsPatient demographic characteristics were similar between the two groups. dNCS group showed significantly lower aortic cross-clamp (ACC) time (73.3 vs. 87.5 min, P = 0.001), cardioplegia volume (1323.9 ± 368.5 vs. 2773.8 ± 453.8 ml, P< 0.001), defibrillation rate (44.4%vs. 69.2%, P = 0.006), drainage amount (412 ± 73.2 vs. 446.9 ± 95.1 ml, P = 0.026) and inotropic support need (37% vs. 55.3%, P = 0.046). Also dNCS group had significantly lower high sensitive troponin I (hsTnI) levels at 6th (203.5 ± 68.6 vs. 275.7 ± 76.2 ng/L, P< 0.001) and 24th (253.1 ± 101 vs. 293.4 ± 80.1 ng/L, P = 0.017) postoperative hours. And dNCS group showed significantly higher hematocrit levels at 6th (25.1 ± 3.2 vs. 22.5 ± 2.5%, P< 0.001) and 24th (25.8 ± 2.7 vs. 24.6 ± 2.8%, P = 0.024) postoperative hours. Times of intensive care unit stay, durations of intuabation and hospital stay times were similar in both groups. There was no significant difference in terms of postoperative ejection fraction values (P = 0.714).ConclusionCompared with conventional BC, dNCS provided significantly shorter ACC times, reduced the need for intraoperative defibrillation, lowered postoperative hsTnI levels with comparable early clinical outcomes for adult patients undergoing aortic surgery. dNCS is a safe and efficient alternative to the traditional BC solution in adult aortic cardiac surgery.     

Gut microbiota intervention by pre and probiotics can induce regulatory T cells and reduce the risk of severe acute GVHD following allogeneic hematopoietic stem cell transplantation

BackgroundAcute graft-versus-host disease (aGVHD) is one of the leading causes of limitation and mortality after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Numerous studies have shown that changes in the gut microbiome diversity increased post-transplant problems, including the occurrence of aGVHD. Probiotics and prebiotics can reconstitute the gut microbiota and thus increase bacterial metabolites such as short-chain fatty acids (SCFAs) that have immunomodulatory effects preventing aGVHD in recipients of allo-HSCTs.Methods/Study DesignWe conducted a pilot randomized clinical trial to investigate whether oral synbiotics are associated with the prevention or reduction in occurrence/severity and mitigate complications of aGVHD following allo-HSCT. A commercially available synbiotic mixture containing high levels of 7 safe bacterial strains plus fructo-oligosaccharides as a prebiotic was administered to allo-HSCT recipients. Out of 40 allo-HSCT patients, 20 received daily a synbiotic 21 days prior to transplantation (days −21 to day 0). In contrast, in the control group 20 recipients of allo-HSCT did not receive a symbiotic therapy.ResultsWithin first 100 days of observation, the incidence of severe (grade III/IV) aGVHD in the a synbiotic-therapy group was 0% (0 out of 20 patients), whereas it was 25% (5 out of 20 patients) in the control group (P = 0.047). The median percentage of CD4 + CD25 + Foxp3+ regulatory T cells (Tregs) among CD4+ lymphocytes on day 28 after HSCT in the synbiotic group was higher (2.54%) than in control group (1.73%; P = 0.01). There was no difference in Treg cells on day 7 after HSCT between two groups. However, the median percentage and the absolute count of Tregs in patients who experience aGVHD was significantly lower on days 7 and 28 after HSCT (both P < 0.05). The overall 12-month survival (OS) rate was higher (90%) in the symbiotic-treated patients than in the control group (75%), but the difference was not statistically significant (P = 0.234).ConclusionOur preliminary findings suggest that synbiotic intake before and during the conditioning regimen of allo-HSCT patients may lead to a reduction in the incidence and severity of aGVHD through the induction of CD4 + CD25 + Foxp3+ regulatory T cells, thus contributing to the improvement of transplant outcomes. Much larger studies are needed to confirm our observations.     

Pre-transplant and post-transplant soluble CD30 for prediction and diagnosis of acute kidney allograft rejection

Background  Serum levels of soluble CD30 (sCD30) have been considered as a predictor of acute kidney allograft rejection. We have evaluated the pre-transplant and post-transplant levels of sCD30 with the aim of determining its value in predicting and diagnosing kidney rejection. Methods  We measured sCD30 serum levels before kidney transplantation, 5 days post-operatively, and at creatinine elevation episodes. The predictive value of sCD30 for diagnosing acute rejection (AR) within the first 6 post-operative months was assessed in 203 kidney recipients from living donors. Results  Pre-transplant and post-operative levels of serum sCD30 were 58.10 ± 52.55 and 51.55 ± 49.65 U/ml, respectively (P = 0.12). Twenty-three patients experienced biopsy-proven acute rejection, and 28 had acute allograft dysfunction due to non-immunologic diseases. The pre-transplant sCD30 level was not different between patients with and without AR. However, post-transplant sCD30 was higher in the AR group. The median serum level of post-transplant sCD30 was 52 U/ml in the AR group and 26.3 U/ml in a control group (P < 0.001). The relative changes of sCD30 on day 5 were higher in patients with AR (P = 0.003). Based on post-transplant sCD30 levels, we were able to differentiate between kidney recipients who experienced an AR within 6 months post-surgery and those without an AR (cutoff value 41 U/ml; sensitivity 70%; specificity 71.7%). The level of sCD30 during periods of elevated serum creatinine was not independently associated with the diagnosis of AR. Conclusion  Post-transplant sCD30 levels and their relative changes are higher in patients experiencing AR. We propose further studies on the post-transplant trend of this marker for the prediction of AR.     

Pre-emptive immunosuppression using tacrolimus monotherapy does not reduce the rate of early acute rejection in renal transplantation from live donors: a comparative cohort study

The planned nature of live donor kidney transplantation allows for immunosuppression to be initiated in the pretransplant period. The aim of this study was to determine the effect of pre-emptive immunosuppression on acute rejection rates after live donor kidney transplantation. In two consecutive cohorts of live donor kidneys transplants, 99 patients received pre-emptive immunosuppression with tacrolimus monotherapy for 2 weeks prior to transplantation (PET group – first era) and 100 patients received tacrolimus-based immunosuppression commencing on the day of transplantation (control group – second era). The main outcome measure was the incidence of biopsy-proven acute rejection (BPAR) in the first 3 months post-transplantation. Tacrolimus levels were significantly higher in the PET group at day 4 post-transplant (PET 9.08 ± 4.57 vs. control 5.92 ± 3.64 ng/ml; P < 0.0001), but there were no significant differences in tacrolimus levels at day 7 (PET 8.22 ± 3.58 vs. control 7.63 ± 3.56 ng/ml; P = 0.2452). BPAR was numerically higher in the PET group, but this difference did not reach statistical significance (PET 13/99 vs. control 6/100; P = 0.097). There were no differences in allograft function measured by serum creatinine at 1 year (PET 130 ± 36 vs. control 142 ± 69 μmol/l; P = 0.6829). Graft survival at 1 year was equivalent in both groups (PET 96.9 vs. control 97.0%; P = 0.9915). This study suggests that there is little role for the use of pre-emptive tacrolimus monotherapy in ABO blood group and HLA-compatible live donor kidney transplantation in patients on triple maintenance immunosuppression.     

Effects of recombinant thrombomodulin therapy and soluble human leukocyte antigen-G levels during hematopoietic stem cell transplantation

BackgroundConditioning chemotherapies for hematopoietic stem cell transplantation (HSCT), especially those that include total body irradiation, can result in serious complications such as graft-versus-host disease (GVHD). Human leukocyte antigen G (HLA-G) is a non-classical class I molecule with multiple immunoregulatory functions.MethodsWe measured interleukin (IL)-10, transforming growth factor (TGF)β₁, and soluble HLA-G (sHLA-G) in HSCT patients and examined the relationship between sHLA-G levels and acute GVHD (aGVHD). Additionally, we investigated the effect of recombinant soluble thrombomodulin (rTM) therapy on sHLA-G levels. Our study cohort included 135 patients who underwent allogeneic HSCT at several institutions in Japan.ResultsSerum levels of IL-10 and TGFβ₁ exhibited no significant changes following HSCT. In contrast, levels of sHLA-G were significantly increased at days 21 and 28 post-HSCT. For patients with confirmed complications, the frequency of aGVHD was significantly lower in those with a > 2.8-fold increase in sHLA-G levels at day 28 relative to day 7 post-HSCT. sHLA-G levels in patients who received rTM therapy were significantly higher at days 21 and 28 post-HSCT compared with those in patients who did not receive rTM therapy.ConclusionThese data suggest that HLA-G/sHLA-G participate in prevention of GVHD, and that rTM may prevent aGVHD following HSCT by promoting elevation of sHLA-G.     

Evaluation of interleukin 12 and CD56 + lymphocyte cells in pediatric hematopoietic stem cell transplantation for early diagnosis of acute graft versus host disease

The present study tried to explain CD56 + lymphocyte cells activities and possible prognostic role of these cells in Graft-Versus-Host-Disease (GVHD). The role of IL-12 activation and function is of interest in this study. Peripheral blood samples of 51 Hematopoietic Stem Cell Transplantation (HSCT) recipients collected at before (day − 8) and after (days 7 and 14). PBMC were collected by Ficoll separation and analyzed by Flow Cytometry using triple antibody (CD45-PerCP, CD56-FITC, and CD69-PE staining and control antibody. Levels of the cytokine IL-12 in the patient's serum were evaluated by ELISA. Percentage of CD56 + lymphocytes (CD56 +^bright) cells was significantly increased at day 14 in patients with acute GVHD and percentage of lymphocytes expressing CD69 was significantly increased at days 7 and 14 posts HSCT in patients with acute GVHD in comparison to those in non-GVHD patients. Baseline serum IL-12 levels (pre-HSCT, day − 8) were significantly higher in those HSCT recipients who did not develop GVHD. This study showed that post-transplant CD56 + lymphocytes and pre-transplant serum levels of IL-12 play significant roles in the induction of and protection against GVHD, respectively. The increase in the percentage of CD69 + cells indicates the activation of lymphocyte in acute GVHD group.     

Serum angiopoietin-1 level is increased in patients with Behçet's disease

ObjectiveAngiogenesis may be involved in the pathogenesis of Behçet's disease (BD). Some angiogenic factors such as vascular endothelial growth factor, monocyte chemoattractant protein-1, and endothelin-1 are significantly associated with BD. Here, we investigate whether Angiopoietin contributes to disease activity and clinical manifestations of BD.MethodsWe recruited 59 consecutive patients with BD and sex- and age-matched 65 healthy control subjects for this study. We reviewed data regarding clinical features, erythrocyte sediment rate (ESR), and C-reactive protein (CRP) at the time of enrollment. Serum angiopoietin-1 and angiopoietin-2 were estimated by enzyme-linked immunosorbent assay. Statistical analyses were performed using the Student t test and Pearson's correlation coefficient analysis.ResultsLevels of serum angiopoietin-1 are significantly increased in BD patients compared to controls (284.5 ± 101.2 ng/ml of BD vs 237.1 ± 76.4 ng/ml of controls, p = 0.012). However, serum angiopoietin-2 levels are similar in both groups (974.2 ± 679.3 pg/ml of BD vs 858.3 ± 535.3 pg/ml of controls, p = 0.562). Serum angiopoietin-1 expression is significantly elevated in patients with skin lesions (p = 0.025) and positively correlated with disease duration (r = 0.320, p = 0.015). ESR levels are closely associated with serum angiopoietin-2 (r = 0.306, p = 0.018).ConclusionAngiopoiein-1 expression is enhanced in BD patients compared to controls. This preliminary study identifies that angiopoietin-1 may play an important role in the pathogenesis of BD.     

Early conversion to belatacept-based immunosuppression regimen promotes improved long-term renal graft function in kidney transplant recipients

BackgroundBelatacept has been demonstrated as an effective alternative immunosuppressant in kidney transplant recipients. This study focuses on outcomes of early and late conversion to Belatacept-based immunosuppression after kidney transplant.Materials and methodsThis retrospective analysis of a prospectively collected database included all adult kidney transplants patients at SUNY Upstate Medical Hospital from 1 January 2014 to 30 December 2022. Early conversion was defined as all conversions done at <6 months after kidney transplantation, and late conversion to belatacept was defined as conversion at >6 months after kidney transplantation.ResultsOut of 61 patients included in this study, 33 patients (54%) were in the early conversion group, and 28 patients (46%) were in the late conversion group. The mean eGFR in the early conversion group was 26.73 ± 16.26 ml/min/1.73 m2 before conversion to belatacept, which improved to 45.3 ± 21.01 ml/min/1.73 m2 at one-year post-conversion (p = 0.0006). Furthermore, eGFR changes in the late conversion group were insignificant, with 46.30 ± 15.65 ml/min/1.73 m2 before conversion to belatacept, and 44.76 ± 22.91 ml/min/1.73 m2 after one year of follow-up (p = 0.72). All four biopsy-proven allograft rejections in the early conversion group were acute T-cell-mediated rejections (ATMR). In the late conversion group, out of three biopsy-proven rejections, one was chronic antibody-mediated rejection (CAMR), one was ATMR, and one was mixed ATMR/CAMR. All four patients with ATMR rejection received mycophenolic acid (MPA) as part of their immunosuppressive regimen, and none received tacrolimus. The one-year post-conversion allograft survival rate in early and late conversion groups was 100%. However, the one-year post-conversion patient survival rate was 90.9% in the early conversion group and 100% in the late conversion group (P = 0.11).ConclusionsEarly post-transplant conversion to belatacept can improve the eGFR more meaningful when compared to late conversion. Patients who receive belatacept and MPA rather than tacrolimus may have increased rates of T-cell-mediated rejection.     

Total Cell-Free DNA as a Noninvasive Biomarker of a Delayed Graft Function After Kidney Transplantation From Donors After Cardiac Death

BackgroundBecause of the organ shortage, donation after cardiac death (DCD) kidney transplantation (KTx) is an alternative way of achieving KTx using brain-dead donors (BDs). Although the prognosis of DCD-KTx is improving, the graft suffers from delayed graft function (DGF), the management of which is essential. With progress in understanding the characteristics of cell-free DNA (CF-DNA), we consider plasma total CF-DNA (tCF-DNA) to be a useful biomarker for predicting DGF in DCD-KTx.Study Design and MethodConsecutive patients from living donors (LDs; n = 9), BDs (n = 8), or DCD donors (n = 13) were enrolled. Plasma samples were collected after KTx and on postoperative days 3 and 5. CF-DNA was isolated, and tCF-DNA was quantified using the TapeStation 2200 software program.ResultsThe tCF-DNA levels after BD-KTx and DCD-KTx were higher than those after LD-KTx (LD, 78 ± 27 (ng/mL); BD, 99 ± 20; DCD, 150 ± 23); the difference between DCD-KTx and LD-KTx was statistically significant (P < .05). The tCF-DNA levels declined at postoperative day 5 (LD, 45 ± 10; BD, 51 ± 11; DCD, 66 ± 13). tCF-DNA levels were significantly increased in patients with DGF after KTx (DGF, 139 ± 22; immediate function, 91 ± 18; P < .05). The tCF-DNA level was correlated with the duration of DGF (r = 0.5825, P < .05).ConclusionAlthough the mechanism underlying DNA release from transplanted grafts into the recipient circulation remains unclear, cell death by apoptosis or necrosis and the active secretion of the immune system may play important roles in DGF. These data suggest that monitoring tCF-DNA may help predict graft recovery after DCD-KTx.     

High plasma IL-6 levels following haploidentical allogeneic hematopoietic stem cell transplantation post-transplant cyclophosphamide as predictor of early death and worse outcome

IntroductionHaploidentical hematopoietic stem cell transplantation (haplo-HSCT) can be used as an alternative procedure in the absence of HLA-compatible donors. The use of high doses of cyclophosphamide after infusion improves the prognosis and eliminates the need for T cell depletion in vivo. Among the main complications of haplo-HSCT are acute graft-versus-host disease (a-GVHD) and cytokine release syndrome (CRS). This is a systemic inflammatory response that leads to the release of inflammatory proteins, including IL-6. This syndrome has several clinical features, with mild to severe symptoms. This study aimed to compare plasma IL-6 levels in patients submitted to different HSCT types and to associate them with the presence of acute graft versus host disease (a-GVHD), CRS and survival.MethodsA total of 84 patients (22 haploidentical and 62 non-haploidentical) were evaluated at different times. The IL-6 levels in haplo and non-haplo-HSCT recipients were measured before transplantation and on days D7, D14, D28, D60, and D100.ResultsIL-6 levels were higher in haplo-HSCT recipients than in non-haplo-HSCT recipients, remaining elevated from D14 until D100 (P = 0.006) and a cut-off ≥11 pg/mL on D7, which is related to worse overall survival. In our study, we found no association with a-GVHD (P = 0.239), a common complication of this type of transplant, but we found a relationship between the increase in IL-6 and CRS (P = 0.021).ConclusionIL6 can be used as a biomarker for patients submitted to haplo-HSCT, allowing clinical interference in patients having levels of IL-6 times larger than normality values, avoiding early death in this group of patients.     

Factores influyentes en la respuesta al rescate con radioterapia tras prostatectomía radical

ObjectiveTo analyze the influential factors in the response in prostatectomized patients with subsequent biochemical relapse (BCR) and treated with salvage radiotherapy (RTP).Material and methodsWe analyzed 313 patients with pT2/pT3 prostate cancer who were receiving salvage therapy due to biochemical relapse (from a series of 1,310 radical prostatectomies between 1989-2012). Of the 313 patients; 159 (50.8%) only received androgen deprivation (AD), 63 (20.1%) Radiotherapy (RTP) plus concomitant AD and 91 (29.1%) only RTP. Of these, 57 (62.6%) have maintained complete response and 34 (37.4%) had failure response with post-RTP BCR.ResultsStudy of the group treated exclusively with salvage RTP. Ninety-one patients were treated with salvage RTP. Median follow-up was 6.4 years and median to recurrence 11 months. Post-RTP biochemical relapse-free survival (PRBRFS) was 68 ± 7% and 30 ± 10% in 5 to 10 years. Median PRBRFS was 7.3 years (6.3-8.3). Initial PSA (HR: 1.08; 95% CI: 1.01-1.1 P = .02) with best PSA cut-off point PSA > 20 ng/ml (HR: 13.6; 95% CI: 2.1-86 P = .005) and PSA pre-RTP (HR: 1.9; 95% CI: 1.2-3.3; P = .009), best PSA cut-off point PSA preRTP 0.92 ng/ml (HR: 4.5; 95% CI: 1.3-15.6; P = .01) showed independent influence in the response in the multivariate study. PRBRFS at 5 years, 81 ± 9% versus 58 ± 9% with initial PSA < 20 or > 20 ng/ml (P = .03). PRBRFS at 5 years, 93 ± 5% versus 53 ± 10% according to PSA pre-RTP < 0.9 or > 0.9 ng/ml (P = .02).ConclusionsIn patients treated with salvage RTP after radical prostatectomy, the preoperative PSA > 20 ng/ml and PSA preRTP > 0.92 ng/ml shows an independent influence on the response.     

Interpectoral-pectoserratus plane (PECS II) block in patients undergoing trans-axillary thoracic outlet decompression surgery; A prospective double-blind,randomized, placebo-controlled clinical trial

Study objectiveTo investigate if an interpectoral-pectoserratus plane (PECS II) block decreases postoperative pain, postoperative nausea and vomiting and improves quality of recovery in patients with neurogenic thoracic outlet syndrome (NTOS) undergoing trans-axillary thoracic outlet decompression surgery.DesignA prospective single center double blinded randomized placebo-controlled trial.SettingPerioperative period; operating room, post anesthesia care unit (PACU) and hospital ward.PatientsSeventy patients with NTOS, undergoing trans-axillary thoracic outlet decompression surgery.InterventionsPatients were randomized to an interventional arm, receiving the block with 40 ml ropivacaine 0.5% (concentration was adjusted if the patient's weight was <66 kg), and a placebo group, receiving a sham block with 40 ml NaCl 0.9%. The interpectoral-pectoserratus plane block was performed ultrasound guided; the first injection below the pectoral minor muscle and the second below the pectoral major muscle. The hospitals' pharmacist prepared the study medication and was the only person able to see the randomization result. The study was blinded for patients, researchers and medical personnel.MeasurementsPrimary outcome parameters were postoperative pain, measured by numeric rating scale on the PACU (start and end) and on the ward on postoperative day (POD) 0 and 1, and postoperative morphine consumption, measured on the PACU and on the ward during the first 24 h. Secondary outcome parameters were postoperative nausea and vomiting, and quality of recovery.Main resultsThere was no statistically significant difference in NRS on the PACU at the start (ropivacaine 4.9 ± 3.2 vs placebo 6.2 ± 3.0, p = .07), at the end (ropivacaine 4.0 ± 1.7 vs placebo 3.9 ± 1.7, p = .77), on the ward on POD 0 (ropivacaine 4.6 ± 2.0 vs placebo 4.6 ± 2.0, p = 1.00) or POD 1 (ropivacaine 3.9 ± 1.8 vs placebo 3.6 ± 2.0, p = .53). There was no difference in postoperative morphine consumption at the PACU (ropivacaine 11.0 mg ± 6.5 vs placebo 10.8 mg ± 4.8, p = .91) or on the ward (ropivacaine 11.6 mg ± 8.5 vs placebo 9.6 mg ± 9.4, p = .39).ConclusionsThe interpectoral-pectoserratus plane block is not effective for postoperative analgesia in patients with NTOS undergoing trans-axillary thoracic outlet decompression surgery.     

Hyperglycemia is associated with poor outcomes in surgical critically ill patients receiving parenteral nutrition

Background and aimsHyperglycemia, a major side effect of patients receiving total parenteral nutrition (PN), is associated with higher mortality in critically ill patients. The aim of this study was to determine whether elevated blood glucose levels would be associated with worse outcomes in patients receiving PN.MethodsThis retrospective study included postoperative patients admitted to our surgical intensive care unit (SICU) from July 2008 to June 2009. Data collected included blood glucose levels, length of stay, and outcome measures. Correlations among daily average, maximum, and minimum blood glucose levels and outcome measures were calculated.ResultsSixty-nine patients were enrolled and divided into PN (n = 40) and non-PN (n = 29) groups. The initial mean blood glucose levels were 138.4 ± 63.1 mg/dL and 123.2 ± 41.8 mg/dL for the PN and non-PN groups, respectively. The mean blood glucose concentration was significantly increased (ΔBS = 44.8 ± 57.3 mg/dL; p < 0.001) in the PN group compared with the non-PN group (ΔBS = 39.4 ± 67.0 mg/dL; p = 0.004). The blood glucose concentration was significantly increased and consequently, consumption of insulin was increased on the 2^nd day of ICU admission. The risk of mortality increased by a factor of 1.3 (OR = 1.30, 95% CI = 1.07–1.59, p = 0.010) for each 10 mg/dL increase in blood glucose level, when the daily maximum blood glucose level was >250 mg/dL. There were no cases of mortality in the current study when the blood glucose levels were controlled below 180 mg/dL. The mean blood glucose level in patients receiving PN was higher in those with diabetes than in those without diabetes (215.5 ± 42.8 vs. 165.8 ± 42.0 mg/dL, respectively, p = 0.001).ConclusionThe blood glucose level was associated with patient outcome and should be intensively monitored in critically ill surgical patients. We suggest that blood glucose levels should be controlled below 180 mg/dL in postoperative critically ill patients.     

Immunoglobulin isotype switching of antibodies to vimentin is associated with development of transplant glomerulopathy following human renal transplantation

BackgroundImmune responses to tissue-restricted self-antigens are thought to play a role in chronic rejection after solid organ transplantation. De novo development of antibodies (Abs) to vimentin have been reported to be associated with interstitial fibrosis/tubular atrophy after kidney transplant, and it has been suggested that immunoglobulin isotype switching of Abs to vimentin may occur during this process. We aimed to determine the correlation between immunoglobulin isotype switching of Abs to vimentin and development of transplant glomerulopathy (TG) after kidney transplant, and to determine whether citrullinated modification of vimentin is required for de novo anti-vimentin development.MethodsSera were collected from 24 patients with TG (diagnosed on biopsy), 24 matched stable kidney transplant recipients (KTxRs) and 22 normal healthy subjects who did not undergo transplant. Serum vimentin Abs concentrations were measured using enzyme-linked immunosorbent assay (ELISA). Immunoglobulin isotypes of anti-vimentin were determined using isotype-specific Abs conjugated with horseradish peroxidase. Samples were considered positive to vimentin Abs if the values were above mean + 2 × standard deviations of the levels in the healthy control subjects. Specificities of anti-vimentin for mutated citrullinated vimentin and anti-mutated citrullinated vimentin were measured by ELISA.ResultsIn this retrospective analysis of 24 KTxRs with TG, 16/24 (67%) patients with biopsy-proven TG developed Abs to vimentin (645 ± 427 ng/ml). In contrast, only 4/24 (17%) stable KTxRs had detectable Abs to vimentin (275 ± 293 ng/ml; p = 0.001). Of the patients with TG, 15/24 (63%) developed Abs to vimentin of IgG isotype (572 ± 276 ng/ml), whereas only 6/24 (25%) stable KTxRs (310 ± 288 ng/ml) had anti-vimentin of IgG isotype (p = 0.002). However, no significant difference was noted in the concentration of IgM isotype anti-vimentin between KTxRs with TG (9/24 [38%], 407 ± 401 ng/ml) and stable KTxRs (5/24 [21%], 348 ± 439 ng/ml; p = 0.631). The serum concentration of Abs specific for the mutated form of citrullinated vimentin was not significantly different between KTxRs with TG and stable KTxRs.ConclusionsPatients with biopsy-proven TG demonstrated significantly increased levels of anti-vimentin Abs of the IgG isotype compared with stable KTxRs. Anti-vimentin in stable KTxRs was primarily of IgM isotype. Therefore, the observed isotype switching of anti-vimentin from IgM to IgG isotype strongly suggests ongoing immune responses to vimentin in KTxRs diagnosed with TG. Furthermore, as opposed to patients with rheumatoid arthritis (who develop immune responses primarily to citrullinated vimentin), KTxRs diagnosed with TG developed immune responses to non-citrullinated vimentin, suggesting that modification of vimentin protein via citrullination is not required for the de novo anti-vimentin response seen in patients with TG.     

A Novel Biomarker for Post-Transplant Recurrent IgA Nephropathy

Background

The serum levels of galactose-deficient immunoglobulin (Ig)A1 (Gd-IgA1) represent the most promising candidate biomarker for IgA nephropathy (IgAN). The aim of this study was to evaluate the serum levels of Gd-IgA1 as a novel noninvasive biomarker for post-transplant IgAN recurrence.

Does obesity affect the plasma level of Plasminogen Activator Inhibitor-1? And does CO2 pneumoperitoneum affect it?

BackgroundThis prospective controlled study was designed to evaluate the effect of obesity on the plasma level of Plasminogen Activator Inhibitor-1 (PAI-1) and also to evaluate the effect of CO₂ pneumoperitoneum on the plasma level of PAI-1 in patients underwent laparoscopic surgery.MethodsThe study included two groups; first group (non obese) included 30 patients with normal average BMI underwent laparoscopic cholecystectomy while the second group included 30 obese patients with BMI > 30 kg/m² underwent laparoscopic band ligation or fundoplication surgery. Five ml of venous blood was collected from each patient in the non obese group once before induction of anesthesia while three venous blood samples (5 ml) were collected from each patient in the obese group as follows: first sample was taken before induction of anesthesia to compare it with the non obese group, second sample was taken after 1 h of CO₂ insufflations (to know the effect of CO₂ insufflations on PAI-1 level) and third sample was taken 1 week after surgery (to know the remaining effect in the postoperative period).ResultsThe level of PAI-1 was significantly high (5.423 ± 2.5 ng/ml) in the obese patients compared to non obese patients (1.4 ± 0.641 ng/ml) (P value = 0.001). The level of PAI-1 was significantly high after CO₂ insufflations compared to baseline level (6.396 ± 2.542 ng/ml vs. 5.423 ± 2.5 ng/ml) in obese group (P value = 0.001). And this level also showed significant increase up to 1 week (6.01 ± 2.492 ng/ml vs. 5.423 ± 2.5 ng/ml) (P value = 0.028) in the obese group.ConclusionThe PAI-1 level was higher in obese patients when compared to non obese patients. PAI-1 level was elevated after CO₂ insufflations and this elevation did not reach base line level up to 1 week after laparoscopic surgery.     

First‐line choice for severe aplastic anemia in children: Transplantation from a haploidentical donor vs immunosuppressive therapy

We retrospectively compared the outcomes of children with severe aplastic anemia (SAA) who received immunosuppressive therapy (IST) or who underwent hematopoietic stem cell transplantation (HSCT) from a haploidentical donor (HID), between 2007 and 2016. A total of 52 children with SAA under the age of 17 years were initially treated with IST (n = 24) or haploidentical HSCT (n = 28) as first‐line treatment. The estimated 10‐year overall survival was 73.4 ± 12.6% and 89.3 ± 5.8% in patients treated with IST or HID‐HSCT (P = .806). The failure‐free survival was significantly inferior in patients receiving IST than in those undergoing transplantation from an HID (52.6 ± 10.5% vs 89.3 ± 5.8, P = .008). In univariate and multivariate analysis, the choice of first‐line immunosuppressive therapy was the only adverse predictor for failure‐free survival. At the last follow‐up, completely normal blood count was observed in 11 of 20 (55.0%) and 24 of 25 (96.0%) live cases in IST and HID‐HSCT cohort (P = .003). These suggest that HSCT from a haploidentical donor could be considered as first‐line treatment in children who lack a matched related donor, especially in experienced transplantation centers.