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Study Design Systematic review.Objectives Intraoperative neuromonitoring (IOMN) has become a standard practice in the detection and prevention of nerve damage and postoperative deficit. While multicenter studies have addressed this inquiry, there have been no systematic reviews to date. This systematic review identifies the leading causes of IONM alerts during adult spinal deformity (ASD) surgeries.Methods Following PRISMA guidelines, a literature search was performed in PubMed and Embase. IONM alert causes were grouped by equivalent terms used across different studies and binned into larger categories, including surgical maneuver, Changes in blood pressure/temperature, Oxygenation, Anesthesia, Patient position, and Unknown.Results Inclusion criteria were studies on adult patients receiving ASD correction surgery using IONM with documented alert causes. 1544 references were included in abstract review, 128 in full text review, and 16 studies qualified for data extraction. From those studies, there was a total of 3945 adult patients with 299 IONM alerts. Surgical maneuver led the alert causes (258 alerts/86.3%), with signal loss most commonly occurring at correction or osteotomy (101/33.8% and 95/31.8% respectively). Pedicle screw placement caused 35 alerts (11.7%). Changes in temperature and blood pressure were the third largest category (34/11.4%).Conclusions The most frequent causes of IONM alerts in ASD surgery were surgical maneuvers such as correction, osteotomy, and pedicle screw placement. This information provides spine surgeons with a quantitative perspective on the causes of IONM changes and show that most occur at predictable times during ASD surgery.

Men of African descent have the highest prostate cancer incidence and mortality rates, yet the genetic basis of prostate cancer in African men has been understudied. We used genomic data from 3,963 cases and 3,509 controls from Ghana, Nigeria, Senegal, South Africa and Uganda to infer ancestry-specific genetic architectures and fine-map disease associations. Fifteen independent associations at 8q24.21, 6q22.1 and 11q13.3 reached genome-wide significance, including four new associations. Intriguingly, multiple lead associations are private alleles, a pattern arising from recent mutations and the out-of-Africa bottleneck. These African-specific alleles contribute to haplotypes with odds ratios above 2.4. We found that the genetic architecture of prostate cancer differs across Africa, with effect size differences contributing more to this heterogeneity than allele frequency differences. Population genetic analyses reveal that African prostate cancer associations are largely governed by neutral evolution. Collectively, our findings emphasize the utility of conducting genetic studies that use diverse populations.

Study Design Retrospective Study.Objective At the North American Spine Society (NASS) conference, participants may influence spine surgery practices and patient care through their contributions. Therefore, their financial conflicts of interest are of notable interest. This study aims to compare the demographics and payments made to participating surgeons.Methods A list of 151 spine surgeons was created based on those who participated in the 2022 NASS conference. Demographic information was obtained from public physician profiles. General payments, research payments, associated research funding, and ownership interest were collected for each physician. Descriptive statistics and two-tailed t-tests were used.Results In 2021, 151 spine surgeon participants received industry payments, totaling USD 48 294 115. The top 10% of orthopedic surgeons receiving payments accounted for 58.7% of total orthopedic general value, while the top 10% of neurosurgeons accounted for 70.1%. There was no significant difference between these groups’ general payment amounts. Surgeons with 21-30 years of experience received the most general funding. There was no difference in funding between surgeons in academic or private settings. For all surgeons, royalties accounted for the largest percentage of the general value exchanged, while food/beverage accounted for the largest percentage of transactions.Conclusion Our study found that only years of experience had a positive association with general payments, and most monetary value belonged to a small handful of surgeons. These participants receiving significant money may promote techniques requiring products of companies providing their compensation. Future conferences may require disclosure policy changes so attendees understand the degree of funding participants receive.

•Haploidentical HCT has similar survival as MUD-HCT in myelofibrosis.•Strategies to prevent graft failure in haploidentical HCT need to be investigated.

CD19 CAR T-cell (CAR-T) therapy is commonly administered to patients with relapsed or refractory large B-cell lymphomas (LBCL), but salvage or bridging therapy can sometimes lead to a complete response (CR) prior to infusion. Limited studies have assessed the outcomes of patients infused in CR. A total of 134 patients with LBCL in CR prior to CAR-T infusion were identified from the CIBMTR registry, with median prior lines of therapy of 3 (range 2–9). At two years post-infusion, the probability of progression-free survival was 43.5% (95% CI 34.4–52.8) and the probability of overall survival was 63.8% (95% CI 54.4–72.6). The cumulative incidence rates of non-relapse mortality and relapse/progression at two years were 9.2% (95% CI 4.5–15.4) and 47.3% (95% CI 38.2–56.6), respectively. The rate of grade 3 or higher cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) were 2.2% and 8.2%, respectively. In summary, CAR-T in heavily pretreated patients with LBCL who are in CR following two or more lines of prior therapy demonstrate that a subset of patients may remain free of progression at two years. Additionally, the toxicity profile was impressive with very low rates of grade 3 CRS and ICANS.

Bacterial bloodstream infections (BSI) can be a substantial contributor to complications of GVHD treatment. The aim of this study was to determine the risk for BSI from neutrophil engraftment through day 100 post transplant in patients with acute GVHD (AGVHD) based on organ involvement and severity. Patients (n= 4064) who underwent an allogeneic hematopoietic stem cell transplant (HCT) reported to the CIBMTR registry were analyzed. Grade II-IV AGVHD occurred in 1607 (39.5%) patients and was associated with a greater day-100 incidence of post engraftment BSI than with grade 0/I (24.9 vs. 15.3%). Patients with grade III/IV AGVHD had the highest BSI risk (HR 2.45; 95% CI 1.99–3.0; p< 0.0001). Lower GI involvement increased BSI risk (HR 1.54; 95% CI 1.17–2.02; p= 0.0019). BSI post-engraftment through day 100 was associated with worse survival (HR 1.64, 95% CI 1.43–1.87; p< 0.001) and higher non-relapse mortality (NRM), (HR 2.22; 95% CI 1.91–2.59; p< 0.001). Those with stage III/IV GI involvement are at highest risk for BSI. Future studies evaluating novel methods for preventing BSI in these high risk populations are needed to reduce mortality associated with AGVHD.

•Age of >60 years and remission status at time of allo-HCT (CR2/primary induction failure/relapse vs CR1) was predictive of inferior OS.•Use of myeloablative conditioning with total body irradiation was predictive for improved DFS and reduced risk of relapse.

Repeating l- and d-chiral configurations determine polylactide (PLA) stereochemistry, which affects its thermal and physicochemical properties, including degradation profiles. Clinically, degradation of implanted PLA biomaterials promotes prolonged inflammation and excessive fibrosis, but the role of PLA stereochemistry is unclear. Additionally, although PLA of varied stereochemistries causes differential immune responses in vivo, this observation has yet to be effectively modeled in vitro. A bioenergetic model was applied to study immune cellular responses to PLA containing >99% l-lactide (PLLA), >99% d-lactide (PDLA), and a 50/50 melt-blend of PLLA and PDLA (stereocomplex PLA). Stereocomplex PLA breakdown products increased IL-1β, TNF-α, and IL-6 protein levels but not MCP-1. Expression of these proinflammatory cytokines is mechanistically driven by increases in glycolysis in primary macrophages. In contrast, PLLA and PDLA degradation products selectively increase MCP-1 protein expression. Although both oxidative phosphorylation and glycolysis are increased with PDLA, only oxidative phosphorylation is increased with PLLA. For each biomaterial, glycolytic inhibition reduces proinflammatory cytokines and markedly increases anti-inflammatory (IL-10) protein levels; differential metabolic changes in fibroblasts were observed. These findings provide mechanistic explanations for the diverse immune responses to PLA of different stereochemistries and underscore the pivotal role of immunometabolism in the biocompatibility of biomaterials applied in medicine.

Allogeneic hematopoietic cell transplantation (HCT) can cure many nonmalignant conditions, but concern for morbidity and mortality remains. To help physicians estimate patient-specific transplant mortality risk, the HCT comorbidity index (HCT-CI) is used. However, pediatric physicians use the HCT-CI less frequently than adult counterparts. We used the Center for International Blood and Marrow Transplant Research database to expand the HCT-CI comorbidity definitions to be more inclusive of children and adolescent and young adult (AYA) patients, adding history of mechanical ventilation, history of invasive fungal infection, assessment of chronic kidney disease (CKD) by estimated glomerular filtration rate, expanding the definition of obesity, and adding an underweight category. A total of 2815 children and AYAs (<40 years old) who received first allogeneic HCT for nonmalignant diseases from 2008 to 2017 were included to create an expanded youth nonmalignant HCT-CI (expanded ynHCT-CI) and a simplified non-malignant (simplified ynHCT-CI) HCT-CI. The expanded comorbidities occurred frequently—history of mechanical ventilation (9.6%), history of invasive fungal infection (5.9%), mild CKD (12.2%), moderate/severe CKD (2.1%), obesity (10.9%), and underweight (14.5%). Thirty-nine percent of patients had an increase in their comorbidity score using the expanded ynHCT-CI, leading to a redistribution of scores: ynHCT-CI score 0 (35%), 1-2 (36.4%), and ≥3 (28.6%). Patients with an increase in their comorbidity score had an increased hazard of mortality compared to those whose score remained the same (hazard ratio = 1.41; 95% confidence interval, 1.01-1.98). Modifications to the HCT-CI can benefit children and AYA patients with nonmalignant diseases, creating a risk assessment tool that is clinically relevant and better captures comorbidity in this younger population.

Adult hematopoietic stem cell transplantation (HSCT) recipients are at a high risk of adverse outcomes after COVID-19. Although children have had better outcomes after COVID-19 compared to adults, data on risk factors and outcomes of COVID-19 among pediatric HSCT recipients are lacking. We describe outcomes of HSCT recipients who were ≤21 years of age at COVID-19 diagnosis and were reported to the Center for International Blood and Marrow Transplant Research between March 27, 2020, and May 7, 2021. The primary outcome was overall survival after COVID-19 diagnosis. We determined risk factors of COVID-19 as a secondary outcome in a subset of allogeneic HSCT recipients. A total of 167 pediatric HSCT recipients (135 allogeneic; 32 autologous HSCT recipients) were included. Median time from HSCT to COVID-19 was 15 months (interquartile range [IQR] 7-45) for allogeneic HSCT recipients and 16 months (IQR 6-59) for autologous HSCT recipients. Median follow-up from COVID-19 diagnosis was 53 days (range 1-270) and 37 days (1-179) for allogeneic and autologous HSCT recipients, respectively. Although COVID-19 was mild in 87% (n = 146/167), 10% (n = 16/167) of patients required supplemental oxygen or mechanical ventilation. The 45-day overall survival was 95% (95% confidence interval [CI], 90-99) and 90% (74-99) for allogeneic and autologous HSCT recipients, respectively. Cox regression analysis showed that patients with a hematopoietic cell transplant comorbidity index (HCT-CI) score of 1-2 were more likely to be diagnosed with COVID-19 (hazard ratio 1.95; 95% CI, 1.03-3.69, P = .042) compared to those with an HCT-CI of 0. Pediatric and early adolescent and young adult HSCT recipients with pre-HSCT comorbidities were more likely to be diagnosed with COVID-19. Overall mortality, albeit higher than the reported general population estimates, was lower when compared with previously published data focusing on adult HSCT recipients.

•Allogeneic hematopoietic cell transplantation is effective in yielding durable remissions in patients with T cell prolymphocytic leukemia.•Myeloablative conditioning, age >60 years, and Karnofsky Performance Status <90 were associated with reduced overall survival (OS).•Reduced-intensity conditioning and avoidance of in vivo T cell depletion correlated with better disease-free survival (DFS) and lower treatment-related mortality (TRM).•Total body irradiation was found to have no significant effect on OS, DFS. or TRM.

The Urbach energy indicating the width of the exponentially decaying sub-bandgap absorption tail is commonly used as the indicator of electronic quality of thin-film materials used as absorbers in solar cells. Urbach energies of hybrid inorganic–organic metal halide perovskites with various anion–cation compositions are measured by photothermal deflection spectroscopy. The variation in anion–cation composition has a substantial effect on the measured Urbach energy and hence the electronic quality of the perovskite. Depending upon the compositions, the Urbach energy varies from 18 to 65 meV for perovskite films with similar bandgap energies. For most of the perovskite compositions studied here including methylammonium (MA) + formamidinium (FA)-based Pb iodides, mixed Sn + Pb narrow-bandgap perovskites with low or intermediate Sn contents, and wide-bandgap FA + Cs- and I + Br-based perovskites, the correlation between the Urbach energy of the perovskite thin film and open-circuit voltage (VOC) deficit for corresponding solar cells shows a direct relationship with reduction of the Urbach energy occurring with a beneficial decrease in the VOCdeficit. However, due to issues related to material quality, impurity phases and stability in laboratory ambient air, and unoptimized film processing techniques, the solar cells incorporating Cs-based inorganic and mixed Sn + Pb perovskites with a higher than optimum Sn content show a higher VOCdeficit even though the corresponding films show a lower Urbach energy.

The role of haploidentical hematopoietic cell transplantation (HCT) using posttransplant cyclophosphamide (PTCy) for acute lymphoblastic leukemia (ALL) is being defined. We performed a retrospective, multivariable analysis comparing outcomes of HCT approaches by donor for adults with ALL in remission. The primary objective was to compare overall survival (OS) among haploidentical HCTs using PTCy and HLA-matched sibling donor (MSD), 8/8 HLA-matched unrelated donor (MUD), 7 /8 HLA-MUD, or umbilical cord blood (UCB) HCT. Comparing haploidentical HCT to MSD HCT, we found that OS, leukemia-free survival (LFS), nonrelapse mortality (NRM), relapse, and acute graft-versus-host disease (aGVHD) were not different but chronic GVHD (cGVHD) was higher in MSD HCT. Compared with MUD HCT, OS, LFS, and relapse were not different, but MUD HCT had increased NRM (hazard ratio [HR], 1.42; P = .02), grade 3 to 4 aGVHD (HR, 1.59; P = .005), and cGVHD. Compared with 7/8 UD HCT, LFS and relapse were not different, but 7/8 UD HCT had worse OS (HR, 1.38; P = .01) and increased NRM (HR, 2.13; P ≤ .001), grade 3 to 4 aGVHD (HR, 1.86; P = .003), and cGVHD (HR, 1.72; P ≤ .001). Compared with UCB HCT, late OS, late LFS, relapse, and cGVHD were not different but UCB HCT had worse early OS (≤18 months; HR, 1.93; P < .001), worse early LFS (HR, 1.40; P = .007) and increased incidences of NRM (HR, 2.08; P < .001) and grade 3 to 4 aGVHD (HR, 1.97; P < .001). Haploidentical HCT using PTCy showed no difference in survival but less GVHD compared with traditional MSD and MUD HCT and is the preferred alternative donor HCT option for adults with ALL in complete remission.

Cytogenetic and molecular abnormalities are known to influence post-transplant outcomes in acute myeloid leukemia (AML) but data assessing the prognostic value of combined genetic models in the HCT setting are limited. We developed an adapted European LeukemiaNet (aELN) risk classification based on available genetic data reported to the Center for International Blood and Marrow Transplant Research, to predict post-transplant outcomes in 2289 adult AML patients transplanted in first remission, between 2013 and 2017. Patients were stratified according to aELN into three groups: favorable (Fav, N= 181), intermediate (IM, N= 1185), and adverse (Adv, N= 923). Univariate analysis demonstrated significant differences in 2-year overall survival (OS) (Fav: 67.7%, IM: 64.9% and Adv: 53.9%; p< 0.001); disease-free survival (DFS) (Fav: 57.8%, IM: 55.5% and Adv: 45.3; p< 0.001) and relapse (Fav: 28%, IM: 27.5% and Adv: 37.5%; p< 0.001). Multivariate analysis (MVA) revealed no differences in outcomes between the Fav and IM groups, thus they were combined. On MVA, patients in the Adv risk group had the highest risk of relapse (HR 1.47 p≤ 0.001) and inferior DFS (HR 1.35 p < 0.001) and OS (HR 1.39 p< 0.001), even using myeloablative conditioning or in those without the pre-HCT measurable-residual disease. Novel approaches to mitigate relapse in this high-risk group are urgently needed.

Objective--To compare quality of care between 1990 and 1992 in patients with self diagnosed joint pain. Design--Questionnaire and record based study. Subjects--Patients identified at consecutive consultations during two weeks in [...]

Abstract Objective--To compare prescribing patterns between a group of fundholding practices and a group of non-fundholding practices in north east Scotland using a method which provides more accurate statements about […]

Background: The role of perioperative antibiotics in cleft palate remains a topic of debate. Advocates stress their importance in preventing local and systemic infections and decreasing the incidence of oronasal fistula formation. However, few studies to date have directly evaluated the role of antibiotics and other antimicrobial measures in cleft palate surgery.Objective: The aim of this review is to evaluate the evidence surrounding the use of perioperative antibiotics and other antimicrobial interventions in cleft palate surgery. Additionally, we review the literature on the oral flora unique to the cleft palate patient population.Methods: This was accomplished utilizing PubMed, Medline, and the Cochrane Library with MeSH and generic terms. Articles were selected based on predefined inclusion and exclusion criteria.Results: This review highlights the lack of higher level evidence on perioperative antibiotic use and other antimicrobial interventions in cleft palatoplasty and calls for further research on the matter.Conclusions: The literature appears to support the use of preoperative antibiotics for cleft palatoplasty, but the benefits of prolonged postoperative antibiotic use remain questionable.

•Nearly 40% of young adult hematopoietic cell transplantation (HCT) survivors were out of work at 3 years post-HCT.•Of those in full-time work pre-HCT, 50% were not working at 1 year post-HCT.•Myeloablative conditioning with total body irradiation was associated with a greater likelihood of unemployment at 1 year post-HCT.

Graphical Abstract

IMPORTANCE: Primary central nervous system lymphoma (PCNSL) requires induction and consolidation to achieve potential cure. High-dose therapy and autologous hematopoietic cell transplant (AHCT) is an accepted and effective consolidation strategy for PCNSL, but no consensus exists on the optimal conditioning regimens. OBJECTIVE: To assess the outcomes in patients with PCNSL undergoing AHCT with the 3 most commonly used conditioning regimens: thiotepa/busulfan/cyclophosphamide (TBC), thiotepa/carmustine (TT-BCNU), and carmustine/etoposide/cytarabine/melphalan (BEAM). DESIGN, SETTING, AND PARTICIPANTS: This observational cohort study used registry data from the Center for International Blood and Marrow Transplant Research registry. The Center is a working group of more than 380 transplantation centers worldwide that contributed detailed data on HCT to a statistical center at the Medical College of Wisconsin, Milwaukee. The participant data were from 603 adult patients with PCNSL who underwent AHCT as initial, or subsequent, consolidation between January 2010 and December 2018. Patients were excluded if they had a non-Hodgkin lymphoma subtype other than diffuse large B-cell lymphoma, systemic non-Hodgkin lymphoma, or HIV; received an uncommon conditioning regimen; or were not in partial remission or complete remission prior to AHCT. Statistical analysis was performed from July 5, 2020, to March 1, 2021. INTERVENTIONS: Patients received 1 of 3 conditioning regimens: TBC (n = 263), TT-BCNU (n = 275), and BEAM (n = 65). MAIN OUTCOMES AND MEASURES: The primary outcome was progression-free survival. Secondary outcomes included hematopoietic recovery, incidence of relapse, nonrelapse mortality, and overall survival. RESULTS: Of 603 patients, the mean age was 57 (range, 19-77) years and 318 (53%) were male. The 3-year adjusted progression-free survival rates were higher in the TBC cohort (75%) and TT-BCNU cohort (76%) compared with the BEAM cohort (58%) (P = .03) owing to a higher relapse risk in the BEAM cohort (hazard ratio [HR], 4.34; 95% CI, 2.45-7.70; P &lt; .001). In a multivariable regression analysis, compared with the TBC cohort, patients who received TT-BCNU had a higher relapse risk (HR, 1.79; 95% CI, 1.07-2.98; P = .03), lower risk of nonrelapse mortality (NRM) (HR, 0.50; 95% CI, 0.29-0.87; P = .01), and similar risk of all-cause mortality more than 6 months after HCT (HR, 1.54; 95% CI, 0.93-2.55; P = .10). Age of 60 years or older, Karnofsky performance status less than 90, and an HCT-comorbidity index greater than or equal to 3 were associated with lower rates of survival across all 3 cohorts. Subgroup analyses demonstrated that patients aged 60 years and older had considerably higher NRM with TBC. CONCLUSIONS AND RELEVANCE: In this cohort study, thiotepa-based conditioning regimen was associated with higher rates of survival compared with BEAM, despite higher rates of early toxic effects and NRM; these findings may assist clinicians in choosing between TBC or TT-BCNU based on patient and disease characteristics.

Prior studies suggest increased cytomegalovirus (CMV) infection after haploidentical donor transplantation with posttransplant cyclophosphamide (HaploCy). The role of allograft source and posttransplant cyclophosphamide (PTCy) in CMV infection is unclear. We analyzed the effect of graft source and PTCy on incidence of CMV infection, and effects of serostatus and CMV infection on transplant outcomes. We examined patients reported to the Center for International Blood and Marrow Transplantation Research between 2012 and 2017 who had received HaploCy (n = 757), matched related (Sib) with PTCy (SibCy, n = 403), or Sib with calcineurin inhibitor-based prophylaxis (SibCNI, n = 1605). Cumulative incidences of CMV infection by day 180 were 42%, 37%, and 23%, respectively (P < .001). CMV disease was statistically comparable. CMV infection risk was highest for CMV-seropositive recipients (R+), but significantly higher in PTCy recipients regardless of donor (HaploCy [n = 545]: hazard ratio [HR], 50.3; SibCy [n = 279]: HR, 47.7; SibCNI [n = 1065]: HR, 24.4; P < .001). D+/R− patients also had increased risk for CMV infection. Among R+ or those developing CMV infection, HaploCy had worse overall survival and nonrelapse mortality. Relapse was unaffected by CMV infection or serostatus. PTCy was associated with lower chronic graft-versus-host disease (GVHD) overall, but CMV infection in PTCy recipients was associated with higher chronic GVHD (P = .006). PTCy, regardless of donor, is associated with higher incidence of CMV infection, augmenting the risk of seropositivity. Additionally, CMV infection may negate the chronic GVHD protection of PTCy. This study supports aggressive prevention strategies in all receiving PTCy.

Renal dysfunction is a recognized risk factor for mortality after allogeneic hematopoietic cell transplantation (alloHCT), yet our understanding of the effect of different levels of renal dysfunction at time of transplantation on outcomes remains limited. This study explores the impact of different degrees of renal dysfunction on HCT outcomes and examines whether the utilization of incremental degrees of renal dysfunction based on estimated glomerular filtration rate (eGFR) improve the predictability of the hematopoietic cell transplantation comorbidity index (HCT-CI). The study population included 2 cohorts: cohort 1, comprising patients age ≥40 years who underwent alloHCT for treatment of hematologic malignancies between 2008 and 2016 (n = 13,505; cohort selected given a very low incidence of renal dysfunction in individuals age <40 years), and cohort 2, comprising patients on dialysis at the time of HCT (n = 46). eGFR was measured using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) method. The patients in cohort 1 were assigned into 4 categories—eGFR ≥90 mL/min (n = 7062), eGFR 60 to 89 mL/min (n = 5264), eGFR 45 to 59 mL/min (n = 897), and eGFR <45 mL/min (n=282)—to assess the impact of degree of renal dysfunction on transplantation outcomes. Transplantation outcomes in patients on dialysis at the time of alloHCT were analyzed separately. eGFR <60 mL/min was associated with an increased risk for nonrelapse mortality (NRM) and requirement for dialysis post-HCT. Compared with the eGFR ≥90 group, the hazard ratio (HR) for NRM was 1.46 (P = .0001) for the eGFR 45 to 59 mL/min group and 1.74 (P = .004) for the eGFR <45 mL/min group. Compared with the eGFR ≥90 mL/min group, the eGFR 45 to 59 mL/min group (HR, 2.45; P< .0001) and the eGFR <45 mL/min group (HR, 3.09; P< .0001) had a higher risk of renal failure necessitating dialysis after alloHCT. In addition, eGFR <45 mL/min was associated with an increased overall mortality (HR, 1.63; P< .0001). An eGFR-based revised HCT-CI was also developed and shown to be predictive of overall survival (OS) and NRM, with predictive performance similar to the original HCT-CI. Among 46 patients on dialysis at alloHCT, the 1-year probability of OS was 20%, and that of NRM was 67%. The degree of pretransplantation renal dysfunction is an independent predictor of OS, NRM, and probability of needing dialysis after alloHCT. An eGFR-based HCT-CI is a validated index for predicting outcomes in adults with hematologic malignancies undergoing alloHCT. The outcomes of alloHCT recipients on dialysis are dismal; therefore, one should strongly weigh the significant risks of being on hemodialysis as a factor in determining alloHCT candidacy.

Perovskite solar cell device performance is affected by optical and electronic losses. To minimize these losses in solar cells, it is important to identify their sources. Here, we report the optical and electronic losses arising from physically mixed interfacial layers between the adjacent component materials in highly efficient two terminal (2T) all-perovskite tandem, single-junction wide-bandgap, and single-junction narrow-bandgap perovskite-based solar cells. Physically mixed interfacial layers as the sources of optical and electronic losses are identified from spectroscopic ellipsometry measurements and data analysis followed by comparisons of simulated and measured external quantum efficiency spectra. Parasitic absorbance in the physically mixed regions between silver metal electrical contacts and electron transport layers (ETLs) near the back contact and a physical mixture of commercial indium tin oxide and hole transport layers (HTL) near the front electrical contact lead to substantial optical loss. A lower-density void + perovskite nucleation layer formed during perovskite deposition at the interface between the perovskite absorber layer and the HTL causes electronic losses because of incomplete collection of photogenerated carriers likely originating from poor coverage and passivation of the initially nucleating grains.

Individuals with gender dysphoria often seek medical interventions, such as hormone treatment and surgery, to live as their identified gender. Cross-sex hormone therapy typically consists of various estrogen formulations which confer varying risks of venous thromboembolism (VTE). Currently, there is no standard practice by surgeons regarding the preoperative gender-affirming surgery (GAS) hormone regimen of male-to-female (MTF) patients to minimize thromboembolic postoperative complications. The aim of this review is to examine the current literature on VTE occurring in MTF transgender patients on cross-sex hormone therapy (CSHT) when undergoing various gender-affirming surgeries—facial feminization surgery (FFS), top surgery (TS), and bottom surgery (BS)—to understand how evidence-based recommendations regarding perioperative hormone regimens can be established to improve clinical outcomes. Within the past 25 years, 7 published studies have examined the incidence of VTE in MTF patients undergoing GAS procedures. Two of these articles examined MTF patients undergoing FFS, 1 article reported a patient who had undergone BS and FFS during the same hospitalization, and the remaining 4 articles investigated VTE risk in BS. Our review supports that plastic surgeons who perform GAS are divided on their preferred CSHT protocols, with some requiring patients to suspend their CSHT weeks before surgery and others allowing patients to continue CSHT through the day of surgery. Three of the 7 studies detailed a CSHT perioperative regimen which instructed patients to suspend CSHT sometime before surgery; 1 study tapered CSHT to lower levels before surgery; the remaining 3 studies did not specify a CSHT perioperative regimen. This review highlights the paucity of data failing to support that continuing CSHT through GAS elevates VTE risk. We conclude that in the absence of definitive VTE risk factors (e.g., smoking, clotting disorders, or malignancy), surgeons may engage MTF patients in joint decision-making process to determine the most optimal perioperative CSHT management plan on a case-by-case basis. Future studies are warranted to evaluate VTE risk based on patient age, type of surgery, operating time, prophylactic measures, follow-up time, and CSHT perioperative regimens.

Among patients undergoing allogeneic hematopoietic cell transplant, continuous intravenous (IV) tacrolimus infusion is frequently used for graft-versus-host disease (GvHD) prophylaxis. Twice-daily intermittent IV tacrolimus dosing may confer safety and convenience benefits.

Background: Current imaging techniques try to quantify 3-dimensional displacement of syndesmotic ankle injuries using 2-dimensional measurements, which may obscure an exact diagnosis. Therefore, our aim was to determine 3-dimensional displacement of syndesmotic ankle injuries under load and torque using a weightbearing computed tomography (WBCT) and to assess the relation with previously established 2-dimensional measurements.Methods: Seven paired cadaver specimens were mounted into a radiolucent frame. WBCT scans were obtained to generate 3-dimensional models after different patterns of axial load (0 kg, 85 kg) combined with external torque (0, 10 Nm). Sequential imaging was repeated in ankles containing intact syndesmotic ligaments, sectioning of the anterior inferior tibiofibular ligament (AITFL; condition 1A), deltoid ligament (DL; condition 1B), combined AITFL+DL (condition 2), and AITFl+DL+interosseous membrane (condition 3). Reference anatomical landmarks were established relative to the intact position of the fibula to quantify displacement. A subsequent correlation analysis was performed between the obtained 2- and 3-dimensional measurements.Results: Axial load increased lateral translation (mean = −0.9 mm, 95% confidence interval [CI]: 1.3, –0.1) significantly in condition 2 relative to the intact ankle (P< .05) but did not demonstrate other significant displacements. External torque increased displacement significantly in all directions (P< .05), except for dorsal translation of the fibula (P> .05). The highest displacement could be detected when external torque was applied in condition 3 and consisted of posterior translation (mean = −3.1 mm; 95% CI: –4.8, –2.7) and external rotation (mean = −4.7 degrees; 95% CI: –5.6, –2.9). Pearson correlation coefficients between the 2-dimensional and 3-dimensional measurements were moderate and ranged from 0.31 to 0.56 (P< .05).Conclusion: External torque demonstrated superiority over axial load in detecting syndesmotic ankle instability. Axial load increased lateral translation; however, differences were submillimeter in magnitude until torque was applied. A moderate correlation was found with previously established 2-dimensional measurements.Clinical Relevance: In clinical practice these findings substantiate application of external torque in current imaging modalities to improve detection of syndesmotic ankle injuries.

Background Enhanced recovery protocols after esophagectomy aim to discharge patients by day 7. A small risk of delayed complications exists. We aimed to assess whether C-reactive protein (CRP) levels on day 7 could help predict delayed complications and assist safe discharge.Methods All consecutive esophagectomies over 3 years were retrospectively reviewed. Patients were categorized on day 7 into (1) those clinically unsafe for discharge; (2) those clinically safe for discharge; and (3) those considered safe for discharge but develop a delayed complication. CRP level on day 7 and the trend in CRP levels between days 3 and 7 were compared.Results A total of 140 patients underwent esophagectomy, of which 64 patients (46%) had at least one complication. On day 7, 62 (44%) patients were considered clinically unsafe for discharge; 74 (53%) were considered safe for discharge; and 4 (3%) were safe but developed a delayed complication. No patient with delayed complication had a day 7 CRP level < 84 mg/L. CRP trend did not help predict delayed complications.Conclusions The actual CRP level on day 7 after esophagectomy, rather than the trend, can predict delayed complications. Early discharge after esophagectomy should be desisted if the clinical picture is better than the actual blood results.

The archaeological record of the Late Pueblo III (C.E.1250–1300) period in the Tsegi Canyon drainage reveals Kayenta communities shifted from locales favoring access to water and arable land to canyon alcoves with difficult to access entries, as part of a larger regional shift to defensively situated settlements. This coincides with the creation of large depictions of shields on the right side of alcove villages. While prior research has considered shield designs as possible symbols of group identity, this article argues that the placement of shield imagery within Pueblo III alcove communities is an indicator of consolidated group practice. Through comparison of spatial placement of shield imagery on Pueblo III sites throughout the Northern Southwest, I make a case that the peoples of the Tsegi Canyon system shared a form of community identity, marked by the placement of these iconic, highly visible images on the right side of cliff dwellings.

Introduction: Nigeria has the largest burden of Sickle Cell Disease (SCD) with estimated 100,000 new born affected annually. SCD is a Hemoglobin (Hb) disorder with the major form resulting from the substitution of a polar glutamate (Glu) by non-polar Valine (Val) in an invariant region of Hbβ chain-subunit. Species of Hb found in the sickle cell trait are HbA and HbS in a 60:40 proportion, in SCD only HbS, in the HbC disease only HbC, and in the SC disease it's HbS and HbC in a 50:50 equal proportion. Objective: This paper reviews herbal medicines usage in sub-Saharan Africa (sSA) to ameliorate the crisis associated with SCD. The model Hb tetramer suggests a higher membrane affinity of HbS and HbC, promoting dehydration of RBCs, with concomitant in vivo crystallization. Some drawbacks using these herbal drugs include; poor bioavailability and the lack of proper pharmacovigilance monitoring procedures arising from weak governance structure combined with under reporting of herbal usage to physicians were discussed. Probable epigenetic loci that could be targeted using phytomedicines for effective SCD management were also discussed. Methods: Using search engines, several databases including Google scholar, PubMed, Academic Resource Index were utilized as a source for relevant publications/ literature. The protein coordinates for the Hb tetramer were obtained from the Protein Data Bank (PDB). Conclusion: Manipulation of epigenetics to achieve better SCD management involves careful thinking. Herein, we discuss some epigenetic interactions that could be putatively tweaked with a view of enhancing soluble bioactive small molecular components with the potential to reactivate γ -globin genes, thereby boosting immune response in patient with SCD.

Study Design Retrospective Cohort Analysis.Objectives Extended hospital length of stay (LOS) poses a significant cost burden to patients undergoing adult spinal deformity (ASD) surgery. The purpose of this study is to investigate the relationship between late-week surgery and LOS in patients undergoing ASD surgery.Methods 256 patients who underwent ASD surgery between January 2018 and December 2021 by a single fellowship-trained orthopedic spine surgeon comprised the patient sample. Demographics, intraoperative, and perioperative data were collected for the 256 patients who underwent ASD surgery. Patients were divided into two groups based on surgical day of the week: (1) Early-week (Monday/Tuesday) n = 126 and (2) Late-week (Thursday/Friday) n = 130. Descriptive statistics, T-tests, and linear and logistic regression models were used to analyze the data.Results Surgical details and sociodemographic characteristics did not differ between the groups. When controlling for TLIF/DLIF status and PSO status there was no difference in mean length of stay between the groups. The late-week group was associated with a greater risk of 30-day readmission, but there was no difference in complications, infections, or intraoperative complications.Conclusions We found no difference in mean length of stay between surgeries performed early in the week vs late in the week. Although late-week surgeries had higher 30-day readmission risk, all other outcomes, including complication rates, showed no significant differences. When adequate weekend post-operative care is available, we do not advise restricting ASD surgeries to specific weekdays.

Composite biomaterials comprising polylactide (PLA) and hydroxyapatite (HA) are applied in bone, cartilage and dental regenerative medicine, where HA confers osteoconductive properties. However, after surgical implantation, adverse immune responses to these composites can occur, which have been attributed to size and morphology of HA particles. Approaches to effectively modulate these adverse immune responses have not been described. PLA degradation products have been shown to alter immune cell metabolism (immunometabolism), which drives the inflammatory response. Accordingly, to modulate the inflammatory response to composite biomaterials, inhibitors were incorporated into composites comprised of amorphous PLA (aPLA) and HA (aPLA+HA) to regulate glycolytic flux. Inhibition at specific steps in glycolysis reduced proinflammatory (CD86+CD206-) and increased pro-regenerative (CD206+) immune cell populations around implanted aPLA+HA. Notably, neutrophil and dendritic cell (DC) numbers along with proinflammatory monocyte and macrophage populations were decreased, and Arginase 1 expression among DCs was increased. Targeting immunometabolism to control the proinflammatory response to biomaterial composites, thereby creating a pro-regenerative microenvironment, is a significant advance in tissue engineering where immunomodulation enhances osseointegration and angiogenesis, which could lead to improved bone regeneration.

The date of the Moon-forming impact places an important constraint on Earth’s origin. Lunar age estimates range from about 30 Myr to 200 Myr after Solar System formation. Central to this age debate is the greater abundance of 182W inferred for the silicate Moon than for the bulk silicate Earth. This compositional difference has been explained as a vestige of less late accretion to the Moon than to the Earth after core formation. Here we present high-precision trace element composition data from inductively coupled plasma mass spectrometry for a wide range of lunar samples. Our measurements show that the Hf/W ratio of the silicate Moon is higher than that of the bulk silicate Earth. By combining these data with experimentally derived partition coefficients, we found that the 182W excess in lunar samples can be explained by the decay of the now extinct 182Hf to 182W. 182Hf was only extant for the first 60 Myr after the Solar System formation. We conclude that the Moon formed early, approximately 50 Myr after the Solar System, and that the excess 182W of the silicate Moon is unrelated to late accretion.

To review systematically the published literature regarding the impact of treatment for OSA on monetized health economic outcomes.

A critical part of the development of CXCR4 modulators is to have a simple and sensitive assay system to complement the search by screening and evaluating the binding affinity. Herein, a NanoBRET assay system was developed, and its feasibility as a high-throughput screening tool for potent CXCR4 ligands was ascertained. TAMRA-Ac-TZ14011, a fluorescent-labeled CXCR4 antagonist, was adopted as a fluorescent acceptor of bioluminescent energy from N-terminally fused NanoLuc-CXCR4 stably expressed in CHO cells. The ratio of fluorescence at 620 nm to the luminescence at 460 nm represents the interaction between test compounds and CXCR4. We have demonstrated in the present study that the NanoBRET assay system is applicable for the evaluation of CXCR4 ligands using the combination of TAMRA-Ac-TZ14011 as an acceptor and NanoLuc tagged to CXCR4 as a bioluminescent donor expressed in living cells. IC50values of known CXCR4 ligands were determined and found to be compatible with the values obtained by other existing and sensitive methods, such as SDF-1:3.2 nM, Ac-TZ14011:15.3 nM, and FC131:4.5 nM, which confirmed the feasibility of our system (Z′ values ≥0.5). The introduction of an IL-6 secretory signaling peptide (secNluc-CXCR4) further enhanced the expression and trafficking of the tagged receptor, which, in turn, increased the dynamic range of the NanoBRET assay system. Thus, we have successfully developed a NanoBRET system in living cells, which is simple, homogeneous, and useful in multiwell plate screening of potent CXCR4 ligands.

Time may not lead to quality EDITOR--Howie et al claim from their study that the outcome of a consultation in general practice is better if more time is given and [...]