Trends in Volumes and Survival After Hematopoietic Cell Transplantation in Racial/Ethnic Minorities.

There has been an increase in volume as well as improvement in overall survival (OS) after hematopoietic cell transplantation (HCT) for hematologic disorders. It is unknown if these changes have impacted racial/ethnic minorities equally. In this observational study from Center for International Blood and Marrow Transplant Research of 79,904 autologous (auto) and 65,662 allogeneic (allo) HCTs, we examined the volume and rates of change of auto HCT and allo HCT over time and trends in OS in 4 racial/ethnic groups: Non-Hispanic Whites (NHWs), Non-Hispanic African Americans (NHAAs), Hispanics across five 2-year cohorts from 2009 to 2018. Rates of change were compared using Poisson model. Adjusted and unadjusted Cox proportional hazards models examined trends in mortality in the 4 racial/ethnic groups over 5 study time periods. The rates of increase in volume were significantly higher for Hispanics and NHAAs vs. NHW for both autoHCT and alloHCT. Adjusted overall mortality after autoHCT was comparable across all racial/ethnic groups. NHAA adults (HR 1.13; 95% CI 1.04-1.22; p=0.004) and pediatric patients (HR 1.62; 95% CI 1.3-2.03; p<0.001 had a higher risk of mortality after alloHCT compared to NHWs. Improvement in OS over time was seen in all 4 groups after both autoHCT and alloHCT.Our study shows the rate of change for the use of autoHCT and alloHCT is higher in NHAAs and Hispanics compared to NHWs. Survival after autoHCT and alloHCT improved over time, however NHAAs have worse OS after alloHCT which has persisted. Continued efforts are needed to mitigate disparities for patients requiring alloHCT.

Whip-Lock Stitch Is Biomechanically Superior to Whipstitch for Semitendinosus Tendons.

Purpose: To assess the biomechanical performance of different stitching methods using a suturing device by comparing the elongation, stiffness, failure load, and time to stitch completion in cadaveric semitendinosus tendons (STs) and quadriceps tendons (QTs). Methods: A total of 24 STs and 16 QTs were harvested from cadaveric knee specimens (N = 40). Samples were randomly divided into 2 groups: whipstitch (WS) and whip-lock (WL) stitch. Both tendon ends were clamped to a graft preparation stand, and a 2-part needle was used to place 5 stitches, each 0.5 cm apart. Stitching time was recorded. Samples were preconditioned and then underwent cyclic loading from 50 to 200 N at 1 Hz for 500 cycles, followed by load-to-failure testing at 20 mm/min. Stiffness (in newtons per millimeter), ultimate failure load (in newtons), peak-to-peak displacement (in millimeters), elongation (in millimeters), and failure displacement (in millimeters) were recorded. Results: Completion of the WS was significantly faster than the WL stitch in the ST (P < .001) and QT (P = .004). For the ST, the WL stitch exhibited higher ultimate failure loads and construct stiffness than the WS. Regarding the QT, the WL stitch showed higher stiffness and displacement than the WS; however, the ultimate failure load was higher for the WS in the QT. The ultimate failure load in the QT was higher than that in the ST for both stitches. In the ST, only 25% of WSs and 100% of WL stitches failed due to suture breakage. In the QT, suture breakage led to the failure of 100% of both the WL stitches and WSs. Conclusions: In the ST, the WL stitch resulted in improved biomechanical performance through higher ultimate load and fewer failures from tissue damage compared with the WS. In the QT, both the WS and the WL stitch showed similar biomechanical performance with ultimate failure loads above established clinical failure thresholds. Clinical Relevance: Various types of ligament and tendon injuries require suturing to enable repair or reconstruction. The success of ligament or tendon surgery often relies on soft-tissue quality. It is important to investigate the biomechanical properties of stitching techniques that help preserve soft-tissue quality as a step to determining their clinical suitability.

Latin American consensus on diagnosis of gastroesophageal reflux disease.

BACKGROUND: Diagnosing gastroesophageal reflux disease (GERD) can be challenging given varying symptom presentations, and complex multifactorial pathophysiology. The gold standard for GERD diagnosis is esophageal acid exposure time (AET) measured by pH-metry. A variety of additional diagnostic tools are available. The goal of this consensus was to assess the individual merits of GERD diagnostic tools based on current evidence, and provide consensus recommendations following discussion and voting by experts. METHODS: This consensus was developed by 15 experts from nine countries, based on a systematic search of the literature, using GRADE (grading of recommendations, assessment, development and evaluation) methodology to assess the quality and strength of the evidence, and provide recommendations regarding the diagnostic utility of different GERD diagnosis tools, using AET as the reference standard. KEY RESULTS: A proton pump inhibitor (PPI) trial is appropriate for patients with heartburn and no alarm symptoms, but nor for patients with regurgitation, chest pain, or extraesophageal presentations. Severe erosive esophagitis and abnormal reflux monitoring off PPI are clearly indicative of GERD. Esophagram, esophageal biopsies, laryngoscopy, and pharyngeal pH monitoring are not recommended to diagnose GERD. Patients with PPI-refractory symptoms and normal endoscopy require reflux monitoring by pH or pH-impedance to confirm or exclude GERD, and identify treatment failure mechanisms. GERD confounders need to be considered in some patients, pH-impedance can identify supragrastric belching, impedance-manometry can diagnose rumination. CONCLUSIONS: Erosive esophagitis on endoscopy and abnormal pH or pH-impedance monitoring are the most appropriate methods to establish a diagnosis of GERD. Other tools may add useful complementary information.

How to avoid baseplate failure: the effect of compression and reverse shoulder arthroplasty baseplate design on implant stability.

BACKGROUND: Failure to achieve fixation of the glenoid baseplate will lead to clinical failure. The fixation of the baseplate to the scapula must be able to withstand sufficient shear forces to allow bony ingrowth. The importance of compression to neutralize the forces at the baseplate-bone interface has been assumed to be critical in limiting excessive micromotion. The purpose of this study is to determine the effect of compression on implant stability with different baseplate designs. METHODS: Various baseplate designs (1-piece monolithic central screw [1P], 2-piece locking central screw [2PL], and 2-piece nonlocking center screw [2PNL]) were investigated at 3 different compressive forces (high [810 N], medium [640 N], and low [530 N]). Synthetic bone cylinders were instrumented, and peripheral screws were used in all models. The combination of 1 locking and 3 nonlocking peripheral screw fixation was selected as worst-case scenario. Dynamic testing protocol followed the ASTM F2028-17 standard. The baseplate micromotion at high compression was compared to low compression. Additionally, the baseplate micromotion for each design was compared at baseline (first 50 cycles) and at 10,000 cycles for the 3 different compressive forces where motion above 150 µm was defined as failure. RESULTS: Baseplate micromotion was found to negatively correlate with compression (rpb = -0.83, P < .0001). At baseline, all baseplate designs were considered stable, regardless of compression. With high compression, average micromotion at the glenoid baseplate-bone interface remained below the 150-µm threshold for all baseplate designs at 10,000 cycles (1P: 50 ± 10 µm; 2PL: 78 ± 32 µm; 2PNL: 79 ± 8 µm; P = .060). With medium compression, average micromotion at 10,000 cycles for all 3 designs remained below the 150-µm threshold (1P: 88 ± 22 µm; 2PL: 132 ± 26 µm; 2PNL: 107 ± 39 µm). The 2PL design had the highest amount of micromotion (P = .013). With low compression, both 2-piece designs had an average micromotion above the 150-µm threshold whereas the 1-piece design did not (1P: 133 ± 35 µm; 2PL: 183 ± 21 µm; 2PNL: 166 ± 39 µm). The 2PL design had significantly higher micromotion when compared to 1P design (P = .041). DISCUSSION: The stability of a central screw baseplate correlates with the amount of compression obtained and is affected by implant design. For the same amount of compression, more micromotion is observed in a 2-piece design than a 1-piece design.

Severity of Chronic Graft-versus-Host Disease and Late Effects Following Allogeneic Hematopoietic Cell Transplantation for Adults with Hematologic Malignancy.

The study aimed to determine the association of chronic graft-versus-host disease (cGVHD) diagnosis and severity with the development of subsequent neoplasms (SN) and nonmalignant late effects (NM-LE) in 2-year disease-free adult survivors following hematopoietic cell transplantation (HCT) for a hematologic malignancy. To do so, we conducted a retrospective analysis of 3884 survivors of HCT for hematologic malignancy in the Center of International Blood and Marrow Transplant Research database. We conducted a landmark analysis at the 2-year post-transplantation date, comparing first SN and NM-LE in survivors with and without cGVHD. The cumulative incidence (CuI) of SN and NM-LE were estimated through 10 years post-HCT in both groups, with death or disease relapse as a competing risk. Cox proportional hazards models were used to evaluate the associations of cGVHD and its related characteristics with the development of SN and NM-LE. The estimated 10-year CuI of SN in patients with GVHD (n = 2669) and patients without cGVHD (n = 1215) was 15% (95% confidence interval [CI], 14% to 17%) versus 9% (7.2% to 11%) (P < .001). cGVHD by 2 years post-HCT was independently associated with SN (hazard ratio [HR], 1.94; 95% CI, 1.53 to 2.46; P < .0001) with a standardized incidence ratio of 3.2 (95% CI, 2.9 to 3.5; P < .0001). Increasing severity of cGVHD was associated with an increased risk of SN. The estimated 10-year CuI of first NM-LE in patients with and without cGVHD was 28 (95% CI, 26% to 30%) versus 13% (95% CI, 11% to 15%) (P < .001). cGVHD by 2 years post-HCT was independently associated with NM-LE (HR, 2.23; 95% CI, 1.81 to 2.76; P < .0001). Multivariate analysis of cGVHD-related factors showed that increasing severity of cGVHD, extensive grade, having both mucocutaneous and visceral involvement, and receiving cGVHD treatment for >12 months were associated with the greatest magnitude of risk for NM-LE. cGVHD was closely associated with both SN and NM-LE in adult survivors of HCT for hematologic malignancy. Patients identified as having more severe involvement and both mucocutaneous and visceral organ involvement may warrant enhanced monitoring and screening for SNs and NM-LEs. However, caution is warranted when interpreting these results, as patients with cGVHD may have more vigilant post-transplantation health care and surveillance for late effects.

Endovascular approach to a complex thrombus in-transit through a patent foramen ovale.

Large atrial thrombi can be managed percutaneously. We present a case of a 76-year-old female patient who presented to our emergency room with an acute stroke and was managed with mechanical thrombectomy. Further work-up revealed a large complex thrombus in-transit trapped in a patent foramen ovale with a large mobile portion in the left atrium. Due to contraindications for thrombolysis and poor surgical candidacy, an endovascular approach was favored. The procedure was performed successfully, and the patient recovered uneventfully. Learning objective: Endovascular approach with mechanical thrombectomy can be a treatment option for patients that present with large thrombus in-transit when other therapies are contraindicated.

Study of the Reaction Mechanism of Triazines and Associated Species for H2S Scavenging.

Natural gas produced worldwide contains, among other compounds, H2S and CO2. Both gases in the presence of free water can generate problems of corrosion in pipes and subtract calorific value to this gaseous hydrocarbon. Natural gas containing H2S and CO2 above the permissible limits should be treated to remove these components. Particularly, H2S is removed mainly using hexahydro-1,3,5-tris-(-2-hydroxyethyl)-s-triazine (TZ), which is the liquid scavenger of H2S leading on the market. By means of computational methods, we have studied the reaction of H2S with TZ, oxazolidine, and oxazinane to elucidate, explain, or confirm different aspects related to their proposed reaction mechanisms. Our results validate thermodynamically the production of TZ from MEA and formaldehyde, justify the presence of mixtures of TZ and oxazolidine in some commercial products, and explain why in the complexity of the H2S scavenging mechanism with TZ, tritiane is not formed and dithiazine will prefer to react by polymerization to form amorphous dithiazine and that the scavenging capacity for H2S should follow the TZ ≫ oxazinane > oxazolidine sequence.

An Injectable Calcium Phosphate Bone Graft Substitute Improves the Pullout Strength of Various Suture Anchor Designs in an Osteoporotic Bone Model.

Purpose: To compare various suture anchor designs with and without calcium phosphate (CaP) augmentation in an osteoporotic foam block model and decorticated proximal humerus cadaveric model. Methods: This was a controlled biomechanical study, consisting of 2 parts: (1) an osteoporotic foam block model (0.12 g/cc; n = 42) and (2) a matched pair cadaveric humeral model (n = 24). Suture anchors selected were an all-suture anchor, PEEK (polyether ether ketone)-threaded anchor, and a biocomposite-threaded anchor. For each study arm, one half the samples were first filled with injectable CaP and the other half were not augmented with CaP. For the cadaveric portion, the PEEK- and biocomposite-threaded anchors were assessed. Biomechanical testing consisted of a stepwise, increasing load protocol for a total of 40 cycles, followed by ramp to failure. Results: For the foam block model, the average load to failure for anchors with CaP was significantly greater when compared with anchor fixation augmented without CaP; the all-suture anchor was 135.2 ± 20.2 N versus 83.3 ± 10.3 N (P = .0006); PEEK was 131 ± 34.3 N versus 58.5 ± 16.8 N (P = .001); and biocomposite was 182.2 ± 64.2 N versus 80.8 ± 17.4 N (P = .004). For the cadaveric model, the average load to failure for anchors augmented with CaP was again greater than anchor fixation without CaP; PEEK anchors went from 41.1 ± 21.1 N to 193.6 ± 63.9 N (P = .0034) and biocomposite anchors went from 70.9 ± 26.6 N to 143.2 ± 28.9 N (P = .004). Conclusions: Augmenting various suture anchors with CaP has shown to significantly increase pull-out strength and stiffness in an osteoporotic foam block and time zero cadaveric bone model. Clinical Relevance: Rotator cuff tears are common in the elderly patients, in whom poor bone quality jeopardizes treatment success. Exploring methods that increase the strength of fixation in osteoporotic bone to improve outcomes in this patient population is important.

HLA Class I Genotype Is Associated with Relapse Risk after Allogeneic Stem Cell Transplantation for NPM1-Mutated Acute Myeloid Leukemia.

Mutation-bearing peptide ligands from mutated nucleophosmin-1 (NPM1) protein have been empirically found to be presented by HLA class I in acute myeloid leukemia (AML). We hypothesized that HLA genotype may impact allogeneic hematopoietic stem cell transplantation (allo-HCT) outcomes in NPM1-mutated AML owing to differences in antigen presentation. We evaluated the effect of the variable of predicted strong binding to mutated NPM1 peptides using HLA class I genotypes from matched donor-recipient pairs on transplant recipients' overall survival (OS) and disease-free survival (DFS) as part of the primary objectives and cumulative incidence of relapse and nonrelapse mortality (NRM) as part of secondary objectives. Baseline and outcome data reported to the Center for International Blood and Marrow Transplant Research from a study cohort of adult patients (n = 1020) with NPM1-mutated de novo AML in first (71%) or second (29%) complete remission undergoing 8/8 matched related (18%) or matched unrelated (82%) allo-HCT were analyzed retrospectively. Class I alleles from donor-recipient pairs were analyzed for predicted strong HLA binding to mutated NPM1 using netMHCpan 4.0. A total of 429 (42%) donor-recipient pairs were classified as having predicted strong-binding HLA alleles (SBHAs) to mutated NPM1. In multivariable analyses adjusting for clinical covariates, the presence of predicted SBHAs was associated with a lower risk of relapse (hazard ratio [HR], .72; 95% confidence interval [CI], .55 to .94; P = .015). OS (HR, .81; 95% CI, .67 to .98; P = .028) and DFS (HR, .84; 95% CI, .69 to 1.01; P = .070) showed a suggestion of better outcomes if predicted SBHAs were present but did not meet the prespecified P value of <.025. NRM did not differ (HR, 1.04; P = .740). These hypothesis-generating data support further exploration of HLA genotype-neoantigen interactions in the allo-HCT context.

Clinical characteristics, treatment, and blood pressure control in patients with hypertension seen by primary care physicians in Spain: the IBERICAN study.

Objectives: To determine the clinical profile, according to the history of hypertension, the risk of developing hypertension, current antihypertensive treatment and BP control rates in patients with hypertension from the IBERICAN cohort. Methods: IBERICAN is an ongoing prospective cohort study, whose primary objective is to determine the frequency, incidence, and distribution of CVRF in the adult Spanish population seen in primary care settings. This analysis shows the baseline clinical characteristics of patients with hypertension. Adequate BP control was defined as BP <140/90 mmHg according to 2013 ESH/ESC guidelines. Results: A total of 8,066 patients were consecutively included, of whom 3,860 (48.0%) had hypertension. These patients were older (65.8 ± 10.9 vs. 51.6 ± 14.7 years; p < 0.001), had more cardiovascular risk factors, target organ damage and cardiovascular disease (CVD) in comparison with those without hypertension. The risk of hypertension increased with the presence of associated CV risk factors and comorbidities, particularly diabetes, obesity and the metabolic syndrome, and decreased with the intensity of physical activity. Regarding antihypertensive treatments, 6.1% of patients did not take any medication, 38.8% were taking one antihypertensive drug, 35.5% two drugs, and 19.6% three or more antihypertensive drugs. Overall, 58.3% achieved BP goals <140/90 mmHg. A greater probability of BP control was observed with increasing age of patients and the greater number of antihypertensive drugs. Blood pressure control was lower in hypertensive patients with diabetes, obesity, the metabolic syndrome, increased urinary albumin excretion, higher pulse pressure, and lack of antihypertensive treatment. Conclusions: About half of patients attended in primary care settings have hypertension in Spain. Patients with hypertension have a worse CV clinical profile than non-hypertensive patients, with greater association of CVRF and CVD. Around four out of ten patients do not achieve the recommended BP goals, and higher use of combination therapies is associated with a better BP control.

Conserved signalling components coordinate epidermal patterning and cuticle deposition in barley.

Faced with terrestrial threats, land plants seal their aerial surfaces with a lipid-rich cuticle. To breathe, plants interrupt their cuticles with adjustable epidermal pores, called stomata, that regulate gas exchange, and develop other specialised epidermal cells such as defensive hairs. Mechanisms coordinating epidermal features remain poorly understood. Addressing this, we studied two loci whose allelic variation causes both cuticular wax-deficiency and misarranged stomata in barley, identifying the underlying genes, Cer-g/ HvYDA1, encoding a YODA-like (YDA) MAPKKK, and Cer-s/ HvBRX-Solo, encoding a single BREVIS-RADIX (BRX) domain protein. Both genes control cuticular integrity, the spacing and identity of epidermal cells, and barley's distinctive epicuticular wax blooms, as well as stomatal patterning in elevated CO2 conditions. Genetic analyses revealed epistatic and modifying relationships between HvYDA1 and HvBRX-Solo, intimating that their products participate in interacting pathway(s) linking epidermal patterning with cuticular properties in barley. This may represent a mechanism for coordinating multiple adaptive features of the land plant epidermis in a cultivated cereal.

Avoiding Glenoid Baseplate Fixation Failure by Altering Surgical Technique for Varying Bone Densities.

Glenoid baseplate failure is one of the causes of revision and poor outcomes in reverse shoulder arthroplasty (RSA). The objective of this study was to determine whether alterations in surgical technique can improve time-zero fixation of the baseplate in varying bone densities. A secondary objective was to identify whether preoperative radiographic glenoid sclerosis width was associated with the implementation of these techniques. Methods: This study included a biomechanical analysis and a retrospective radiographic review. The biomechanical portion describes 2 alterations to the standard surgical technique (under-preparation [A1] or over-preparation [A2] of the central screw pilot hole) and determined their torque-compression relationship via bone-substitute blocks with varying densities. Patients who underwent the described technical alterations were identified from a registry database of primary RSAs performed between 2007 and 2020. These patients were matched to patients who underwent the standard surgical technique, and preoperative radiographs were compared. Interrater reliability testing was performed to determine reproducibility. Results: With respect to the biomechanical arm, the average compressive force of the baseplate in the low-density block model when using the standard technique was 112 N compared with 300 N for the A1 technique (p = 0.01). In the high-density bone model, the standard technique resulted in failure to seat the baseplate, or screw breakage. Performing the A2 technique, the baseplate was seated without failure, with an average compressive force of 450 N. In the clinical arm, retrospective intraoperative video review for use of the alternative techniques found 20 shoulders in the "low-density" cohort and 21 in the "high-density" cohort. There was a significant difference in the glenoid sclerosis thickness between the experimental and matched control groups in our "high-density" cohort (p = 0.0014). The interrater reliability coefficient was found to be 0.69 for the "low-density" glenoid sclerosis thickness measurement and 0.92 for the "high-density" measurement. Conclusions: In low- and high-density bone models, alterations in surgical technique significantly improved compression and improved the ability to successfully seat the glenoid baseplate. Preoperative radiographs can assist in indicating the alternative technique in the sclerotic glenoid. Clinical Relevance: Utilization of these techniques intraoperatively will improve time-zero fixation of the glenoid baseplate and potentially avoid failure of fixation.

Long-term transplant outcomes after allogeneic hematopoietic transplant in pediatric patients with hematological malignancies are influenced by severe chronic graft vs. host disease and immune reconstitution.

Long-term follow-up studies are crucial to ensure surveillance and intervention for late complications after allogeneic stem cell transplantation, but they are scarce on the pediatric population. This study aims to analyze risk factors for long-term transplant outcomes. We report a landmark analysis of 162 pediatric patients who underwent allogeneic transplantation between 1991 and 2016, and survived for at least 12 months after the transplant. With a median follow-up time of 10 years for the survivors, the probability of disease-free survival (DFS) and overall survival (OS) is 81 ± 3 and 88 ± 2%, respectively. Variables that influenced DFS in the univariate analysis were: disease phase (early phase 87 ± 3% vs. advanced phase 74 ± 5%; p = 0.04), acute graft vs. host disease (aGvHD; yes 73 ± 5% vs. no 87 ± 3%; p = 0.038), severe chronic GvHD (cGvHD; yes 41 ± 13% vs. no 85 ± 3%; p = 0.0001), and CD4+ lymphocytes 2 years after the transplant (above the median of 837/µl 98 ± 2% vs. below the median 82 ± 6%, p = 0.026). However, in the multivariate analysis, the only variable that influenced DFS was presence of severe chronic GvHD (yes vs. no, HR 6.25; 95% CI, 1.35-34.48; p = 0.02). Transplant strategies should aim to reduce the risk of severe cGvHD. Immune reconstitution surveillance may help clinicians to better deal with late transplant complications.

T-Cell Depleted Haploidentical Transplantation in Children With Hematological Malignancies: A Comparison Between CD3+/CD19+ and TCRαß+/CD19+ Depletion Platforms.

Background: T-cell depleted (TCD) haploidentical transplantation using CD3+/CD19+ and TCRαß+/CD19+ depletion techniques has been increasingly used in children with hematological malignancies. We present a retrospective study aimed to compare transplant outcomes in children with leukemia receiving a TCD haploidentical transplant using either CD3+/CD19+ or TCRαß+/CD19+ platforms. Methods: A total of 159 children with leukemia (ALL=80) (AML=79) that received a TCD haploidentical transplantation using either CD3+/CD19+ (n=79) or TCRαß+/CD19+ (n=80) platforms between 2005 and 2020 were included. Median age was 9 years in both groups. There were no differences in patient, donor, and transplant characteristics between groups except for donor KIR B genotype more frequent in the TCRαß+/CD19+ group (91%) than in the CD3+/CD19+ group (76%) (p=0.009) and a high number of NK+ cells and lower CD19+ cells infused in the TCRαß+/CD19+ group (35.32x106/kg and 0.06 x106/Kg) than in the CD3+/CD19 group (24.6x106/Kg and 0.25 x106/Kg) (p=0.04 and p=0.0001), respectively. Conditioning was based on TBF. Median follow-up for survivors was 11 years (range; 8-16 y) in CD3+/CD19+ group and 5 years (range; 2-9 y) in the TCRαß+/CD19+ group. Results: Engraftment kinetics were similar in both groups (13 days for neutrophils and 10 days for platelets). There was no difference in the incidence of acute GvHD II-IV (29 ± 5% in the CD3+/CD19+ group vs 38 ± 5% in the TCRαß+/CD19+ group) and chronic GvHD (32 ± 5% vs 23 ± 4%, respectively). NRM was 23 ± 5% in the CD3+/CD19+group vs 21 ± 4% in the TCRαß+/CD19+group. Relapse incidence was also similar, 32 ± 5% vs 34 ± 6%, respectively. DFS and OS were not different (45 ± 5% vs 45 ± 6% and 53 ± 6% vs 58 ± 6% respectively). As there were no differences on transplant outcomes between groups, we further analyzed all patients together for risk factors associated with transplant outcomes. On multivariate analysis, we identified that early disease status at transplant (HR: 0.16; 95%CI (0.07-0.35) (p=0.0001), presence of cGvHD (HR: 0.38; 95%CI (0.20-0.70) (p= 0.002), and donor KIR-B genotype (HR: 0.50; 95%CI (0.32-0.90) (p=0.04) were associated with better DFS. Conclusions: Our data suggest that there are no advantages in transplant outcomes between TCD platforms. Risk factors for survival are dependent on disease characteristic, donor KIR genotype, and chronic GvHD rather than the TCD platform used.

Association of Chronic Graft-versus-Host Disease with Late Effects following Allogeneic Hematopoietic Cell Transplantation for Children with Hematologic Malignancy.

Chronic graft-versus-host disease (cGVHD) occurs in up to 25% of children following allogeneic hematopoietic cell transplantation (HCT) and continues to be a major cause of late morbidity and poor quality of life among long-term survivors of pediatric HCT. Late effects (LEs) of HCT are well documented in this population, and cGVHD has been identified as a risk factor for subsequent neoplasms (SNs) and several nonmalignant LEs (NM-LEs); however, the reported correlation between cGVHD and LEs varies among studies. We compared LEs occurring ≥2 years following childhood HCT for a hematologic malignancy in 2-year disease-free survivors with and without cGVHD and further evaluated the association of cGVHD features on the development of LEs. This systematic retrospective analysis used data from the Center of International Blood and Marrow Transplant Research (CIBMTR) on a large, representative cohort of 1260 survivors of pediatric HCT for hematologic malignancy to compare first malignant LEs and NM-LEs in those with a diagnosis of cGVHD and those who never developed cGVHD. The cumulative incidences of any first LE, SN, and NM-LE were estimated at 10 years after HCT, with death as a competing risk for patients with cGVHD versus no cGVHD. Cox proportional hazards models were used to evaluate the impact of cGVHD and its related characteristics on the development of first LEs. The estimated 10-year cumulative incidence of any LE in patients with and without cGVHD was 43% (95% CI, 38% to 48.2%) versus 32% (95% confidence interval [CI], 28.5% to 36.3%) (P < .001), respectively. The development of cGVHD by 2 years post-HCT was independently associated with any LE (hazard ratio [HR], 1.38; 95% CI, 1.13 to 1.68; P = .001) and NM-LE (HR, 1.37; 95% CI, 1.10 to 1.70; P = .006), but not SN (HR, 1.30; 95% CI, .73 to 2.31; P = .38). cGVHD-related factors linked with the development of an NM-LE included having extensive grade cGVHD (HR, 1.60; 95% CI, 1.23 to 2.08; P = .0005), severe cGVHD (HR, 2.25; 95% CI, 1.60 to 3.17; P < .0001), interrupted onset type (HR, 1.57; 95% CI, 1.21 to 2.05; P = .0008), and both mucocutaneous and visceral organ involvement (HR, 1.59; 95% CI, 1.24 to 2.03; P = .0002). No significant association between cGVHD-specific variables and SN was identified. Finally, the duration of cGVHD treatment of cGVHD with systemic immunosuppression was not significantly associated with SNs or NM-LEs. cGVHD was more closely associated with NM-LEs than with SNs among survivors of pediatric HCT for hematologic malignancy. In this analysis, the development of SNs was strongly associated with the use of myeloablative total body irradiation. cGVHD-related characteristics consistent with a state of greater immune dysregulation were more closely linked to NM-LEs.

The Impact of Pre-Apheresis Health Related Quality of Life on Peripheral Blood Progenitor Cell Yield and Donor's Health and Outcome: Secondary Analysis of Patient-Reported Outcome Data from the RDSafe and BMT CTN 0201 Clinical Trials.

There is a lack of evidence about how health-related quality of life (HRQoL), including psychosocial factors, might affect donation-related experiences and clinical markers in the context of hematopoietic stem cell donation. The broader literature suggests that psychological factors, including anxiety and depression, are associated with higher levels of inflammatory burden leading to poorer postprocedural outcomes including longer hospital stays and increased pain perception. In this study, we aimed to evaluate whether predonation HRQoL markers predict toxicity profile and stem cell yield after peripheral blood stem cell (PBSC) donation in healthy donors. The study population comprised adult granulocyte colony-stimulating factor mobilized PBSC-related donors (RD) (n = 157) and unrelated donors (URD) (n = 179) enrolled in the related donor safety study (RDSafe) and Blood and Marrow Transplant Clinical Trials Network (BMT CTN) 0201 clinical trials. Pre-donation HRQoL was assessed using the Short-Form-12 (SF-12) in RDSafe and SF-8 questionnaire in BMT CTN 0201 (higher score is better). The aims of this study were to (a) determine the impact of pre-donation HRQoL on peri-collection pain and acute toxicities experienced and (b) to investigate the pre-procedural HRQoL indicators on stem cells yield. URDs were younger than RDs (median age 35 versus 63). A higher proportion of RDs were female (50% versus 40%) and obese (41% versus 35%). A higher proportion of RD PBSC donations required 2 days or more of apheresis (44% versus 21%). More RD collections were lower volume procedures (<18L, 16% versus 28%), and required a central line (28% versus 11%). RDs were more likely to report pre-donation grade 1-2 pain (27% versus 8%) and other toxicities (16% versus 6%). Among RDs, a lower pre-donation physical component summary (PCS) score was associated with significantly more grade 2-4 pain at 1 month (P = .004) and at 1-year after donation (P = .0099) in univariable analyses. In multivariable analysis, pre-donation PCS remained significantly associated with grade 2-4 pain 1 month after donation (P = .0098). More specifically, RDs with predonation PCS scores in the highest quartile were less likely to report pain compared with donors with PCS scores in the lowest quartile (odds ratio 0.1; 95% confidence interval 0.01-0.83; P = .005). There was also a trend toward higher grade 2-4 pain at 1-year post-donation among RDs with lower predonation PCS score (P = .018). Among URDs, neither PCS nor mental component summary (MCS) scores were associated with pain or toxicities at any time point after donation based on the univariable analysis. Because of low rates of postdonation grade 2-4 pain and toxicities, multivariable analysis was not performed in the URD setting. Moreover, there was no correlation between preapheresis HRQoL score (PCS or MCS) and PBSC collection yield in either the RD or URD setting. Our study demonstrates that pre-donation HRQoL scores are significantly associated with the toxicity profile after PBSC donation in the RD setting, with adult RDs with lower predonation physical HRQoL experiencing higher levels of pain at 1 month and persisting up to 12 months after a PBSC collection procedure. There were no such associations found in URD. Our findings can help clinicians identify donors at higher risk of pain with donation, and lead to personalized information and interventions for specific donors. Lack of correlation between predonation HRQoL and stem cell yield may be due to a small sample size and warrants further evaluation.

Improved mechanical fixation of an all-polyethylene glenoid reduces postoperative radiolucent lines.

BACKGROUND: The rationale for advances in implant design is to improve performance in comparison to their predecessors. The purpose of this study was to compare a newer, self-pressurizing peripheral peg glenoid to a traditional polyethylene pegged glenoid through biomechanical evaluation and a retrospective radiographic and clinical review. METHODS: Three testing conditions (uncemented, partially cemented, and fully cemented) were chosen to assess the 2 component designs in a foam block model. The number of hammer hits to seat the component, amount of time to seat the component, and resistance-to-seat were collected. The implants were then cyclically loaded following ASTM F2028-17 testing standard. Clinically, postoperative radiographs of patients with a self-pressurized glenoid component (n = 225 patients) and traditional glenoid component (n = 206 patients) were evaluated for radiolucent lines and glenoid seating at various timepoints. Clinical outcomes (American Shoulder and Elbow Surgeons Standardized Shoulder Assessment Form, Simple Shoulder Test, and visual analog scale pain scores) and complications were recorded. The presence of radiolucent lines at the bone-cement interface was evaluated using the Modified Franklin Grade and the Lazarus grade. RESULTS: The self-pressurizing glenoid design required significantly more hammer hits than traditional glenoid designs in all groups tested (P < .029). Moreover, the self-pressurizing design had significantly more resistance-to-seat than traditional components in both the uncemented and partially cemented group (P < .002). No difference in resistance-to-seat was found between designs in the fully cemented group. The uncemented and partially cemented groups did not survive the full 50,000 cycles; however the self-pressurizing design had significantly less motion than the traditional design (P < .001). No differences between component designs were found in the fully cemented group at 50,000 cycles. The self-pressurizing glenoid component had 0.005% radiographic radiolucent lines, and the traditional glenoid component had 45% radiographic radiolucent lines, with 38% of the radiolucencies in the traditional glenoid component group being defined as grade E. There were no progressive radiolucencies, differences in clinical outcomes, or complications at 2 years postoperatively. CONCLUSION: In the fully cemented condition, the 2 component designs had comparable performance; however, the differences in designs could be better observed in the uncemented group. The self-pressurizing all-polyethylene design studied has superior biomechanical stability. Clinically, the improved stability of the glenoid component correlated with a reduction of radiolucent lines and will likely lead to a reduction in glenoid component loosening.

Do preoperative factors and implant design features influence humeral stem extraction efforts?

BACKGROUND: Variations in humeral component designs in hemiarthroplasty and anatomic total shoulder arthroplasty cases can impact the degree of difficulty during a revision surgery that necessitates the removal of the humeral stem. However, no metric exists to define stem extraction effort nor to identify associated factors that contribute to extraction difficulty. The purpose of this study is to describe a method to quantify stem extraction difficulty and to define features that will impact the effort during stem removal. METHODS: This was a retrospective review of 58 patients undergoing revision of hemiarthroplasty or anatomic total shoulder arthroplasty requiring stem extraction. Each included patient had existing preoperative radiographic examination, an intraoperative video of the stem removal process, and explants available for analysis by 3 surgeons. The following factors were assessed for the impact on extraction difficulty: (1) preoperative features such as cement use, fill of proximal humerus, and stem design features; (2) intraoperative data on extraction time and bone removal; and (3) postoperative findings related to extraction artifacts (EAs). A scoring system was established to distinguish easy (Easy group) and difficult (Difficult group) stem removal cases and further used to identify the features that may affect intraoperative difficulty of stem removal. RESULTS: The Difficult group accounted for 26% (15/58) of the study population with an 18-minute average stem extraction time, average EA count of 69, and 35 mm of bone removed. The Easy group accounted for 74% (43/58) of patients, with a 4-minute average extraction time, average EA count of 23, and 10 mm of bone removed. Logistic regression model was able to correctly classify 82% of the cases, explaining 26.7% of the variance in humeral stem removal with cement and proximal coating variables. The likelihood of cemented stem removal being difficult is 5 times greater compared to an uncemented stem, and having proximal coating doubles the likelihood of a difficult stem removal compared to cases with no coating. CONCLUSIONS: Quantifying stem extraction difficulty is possible with intraoperative video as well as explant analysis. Preoperative features of the fixation type and specific features of stem design such as proximal coating will impact difficulty of stem extraction.

A systematic review and meta-analysis of delayed coronary artery access for coronary angiography with or without percutaneous coronary intervention (PCI) in patients who underwent transcatheter aortic valve replacement (TAVR).

Coronary artery disease (CAD) and severe aortic valve stenosis frequently coexist. Given the progressive nature of CAD, silent or non-significant CAD may become symptomatic or functionally relevant years after TAVR. However, there is a paucity of data documenting the feasibility of either coronary angiography and/or PCI after TAVR. We systematically searched Medline, Pubmed, Embase, Cochrane database, Google Scholar, Science Direct, Web of Science, and conference abstracts from conception to March 2020 using OvidSP in TAVR patients undergoing coronary angiography with or without PCI at least 6 months after TAVR. Patients and procedural characteristics were summarized. The primary outcome of interest was successful coronary angiography for either the left main coronary artery (LMCA) or right coronary artery (RCA) with or without PCI. Pooled estimates were calculated using a random-effects meta-analysis. The study protocol was registered in PROSPERO. Eleven reports for a total of 696 coronary angiograms and 287 PCI were included in the analysis. Patients were slightly predominantly male, older and had a mean left ventricular ejection fraction of more than 50% with an intermediate STS. The summary estimate rates of successful LMCA and RCA angiography with a Medtronic self-expandable valve (SEV) were 84% (95% CI 73-90%, I2 = 79, p = 0.015) and 69% (95% CI 37-89%, I2 = 86, p = 0.23), respectively, while with the Edwards Lifesciences balloon expandable valve (BEV), the summary estimate rates for successful LMCA and RCA angiography were 94% (95% CI 72-99%, I2 = 66, p = 0.003) and 95% (95% CI 48-99%, I2 = 83, p = 0.05), respectively. The summary estimate rate of successful PCI post TAVR with either a Medtronic SEV or Edwards Lifesciences BEV was 93% (95% CI 86-96%, I2 = 33, p = 0.0001). The overall achievement of a successful coronary angiography with or without PCI in post-TAVR patients is high, with a lower success rate for RCA angiography in patients with the Medtronic SEV Mortality and bleeding did not differ in our analysis.