Cell free circulating tumor DNA in cerebrospinal fluid detects and monitors central nervous system involvement of B-cell lymphomas.

The levels of cell free circulating tumor DNA (ctDNA) in plasma correlated with treatment response and outcome in systemic lymphomas. Notably, in brain tumors, the levels of ctDNA in the cerebrospinal fluid (CSF) are higher than in plasma. Nevertheless, their role in central nervous system (CNS) lymphomas remains elusive. We evaluated the CSF and plasma from 19 patients: 6 restricted CNS lymphomas, 1 systemic and CNS lymphoma, and 12 systemic lymphomas. We performed whole exome sequencing or targeted sequencing to identify somatic mutations of the primary tumor, then variant-specific droplet digital PCR was designed for each mutation. At time of enrolment, we found ctDNA in the CSF of all patients with restricted CNS lymphoma but not in patients with systemic lymphoma without CNS involvement. Conversely, plasma ctDNA was detected in only 2/6 patients with restricted CNS lymphoma with lower variant allele frequencies than CSF ctDNA. Moreover, we detected CSF ctDNA in 1 patient with CNS lymphoma in complete remission and in 1 patient with systemic lymphoma, 3 and 8 months before CNS relapse was confirmed; indicating CSF ctDNA might detect CNS relapse earlier than conventional methods. Finally, in 2 cases with CNS lymphoma, CSF ctDNA was still detected after treatment even though a complete decrease in CSF tumor cells was observed by flow cytometry (FC), indicating CSF ctDNA better detected residual disease than FC. In conclusion, CSF ctDNA can better detect CNS lesions than plasma ctDNA and FC. In addition, CSF ctDNA predicted CNS relapse in CNS and systemic lymphomas.

Serum CXCL13, BAFF, IL-21 and IL-22 levels are related to disease activity and lymphocyte profile in primary Sjögren's syndrome.

OBJECTIVES: To investigate the utility of serum BAFF, IL-17, IL-18, IL-21, IL-22, CXCL13, TNF-R2 and PD-L2 as biomarkers of disease activity in primary Sjögren's syndrome (pSS), their relationship with lymphocyte subpopulations and their accuracy to discriminate pSS from Sicca syndrome. METHODS: We conducted an observational study on 66 pSS patients and 48 controls (25 with Sicca syndrome and 23 healthy volunteers). Serum levels of BAFF, IL-17 A/F, IL-18, IL-21, IL-22, CXCL13, TNF-R2 and PD-L2 were measured using a multiplex immunoassay. Lymphocyte subpopulations were analysed by flow cytometry. Disease activity of pSS was assessed with ESSDAI at study inclusion. RESULTS: Patients with pSS presented higher serum CXCL13 (364.7 vs. 205.2 pg/mL), IL-21 (43.2 vs. 0 pg/mL) and BAFF (1646 vs. 1369 pg/mL), and lower PD-L2 levels (1950.8 vs. 2792.3 pg/mL) than controls. ESSDAI was associated with BAFF, IL-18 and IL-22. Patients with ESSDAI >0 exhibited higher CXCL13, IL-21, IL-22 and TNFR2 concentrations. IL-21 levels correlated with lower memory B-cell and higher naïve B-cell percentages and IL-22 levels correlated with increased circulating activated CD4+ T-cells. The combination of serum CXCL13, BAFF and PDL2 levels using the formula [ln(CXCL13)+ln(BAFF)]/ln(PDL2) exhibit an AUC of 0.854 (95% CI: 0.750-0.919) to discriminate between pSS and Sicca syndrome (sensitivity 77.2% and specificity 86.4% using a cut-off of 1.7). CONCLUSIONS: CXCL13, BAFF, IL-21, and IL-22 are potential biomarkers of pSS activity and IL-21 and IL-22 are associated with disturbances of lymphocyte subpopulations in pSS. The combination of serum CXCL13, BAFF, and PD-L2 levels allows discrimination between pSS and Sicca syndrome.

Implementation of an Alcohol Screening, Brief Intervention, and a Referral Program at a Community Level II Trauma Center.

BACKGROUND: Trauma is the leading cause of years of potential life lost in the United States. Alcohol and drug use is a significant contributing factor. In 2017, a Level II community trauma center was achieving less than 80% screening rate compliance utilizing blood alcohol level as a screening method for trauma patients. The purpose of this article is to evaluate the implementation of a screening, brief intervention, and a referral-to-treatment service program. METHODS: In 2018, the trauma program adopted structured interviews as a screening method for trauma patients. The injury prevention coordinator conducted structured interviews as a screening method for trauma patients who met inclusion criteria. High-risk patients were referred to the social worker, who conducted a brief evaluation with subsequent referral to treatment. RESULTS: One year after the implementation of a structured interview approach, 1,021 trauma patients met inclusion criteria for this retrospective evaluation. From 2017 to 2018, the program observed an 86% statistically significant increase in screening using the structured interview SBIRT program (p < .0001) compared with the prior alcohol-level screening approach. CONCLUSIONS: On the basis of these data, a structured interview screening method demonstrated a significant improvement in screening compliance rates.

Robotic port-site hernias after general surgical procedures.

BACKGROUND: With the increasing use of the robotic platform in general surgery, whether 8-mm ports should be closed comes into question. We sought to characterize the incidence of port-site hernias (PSHs) among patients undergoing robotic-assisted general surgery. METHODS: A retrospective chart review of a single institutional database identified patients who underwent robotic-assisted general surgery from July 2010 to December 2016. For each patient, the number, type, location, and size of all ports were collected. Twelve-millimeter port sites were routinely closed, whereas 5-mm and 8-mm port sites were not. PSH was detected on review of documented physical examination and of postoperative cross-sectional imaging, when available, in which case it was defined as a disruption of the fascia with or without eventration of tissue at a site of prior port placement. RESULTS: One hundred and seventy-eight patients underwent robotic-assisted general surgery, with 725 total ports: 433 8-mm working ports, 72 12-mm working ports, 178 12-mm camera ports, and 42 5-mm assistant ports. Ninety-four percent of the patients were men, the mean age was 63 ± 12, body mass index was 29 ± 7 kg/m2, and the median American Society of Anesthesiologists score was 3. Types of cases included 68 rectal (38.2%), 36 colon (20.2%), 25 hepatopancreatobiliary (14.0%), 21 inguinal hernia (11.8%), and 28 "other" (15.7%) operations. At a median follow-up of 193 d, there were three PSHs through 8-mm port sites (0.7%), two PSHs through 12-mm port sites (0.8%), and no PSH through 5-mm port sites. Two of the three 8-mm PSHs occurred in the early postoperative period and required emergent repair due to small bowel incarceration. CONCLUSIONS: PSHs through 8-mm robotic port sites occur infrequently but can cause significant morbidity. Further investigation with longer follow-up is warranted to better understand the true incidence of robotic PSH.

Underlying Physics of Conductive Polymer Composites and Force Sensing Resistors (FSRs) under Static Loading Conditions.

Conductive polymer composites are manufactured by randomly dispersing conductive particles along an insulating polymer matrix. Several authors have attempted to model the piezoresistive response of conductive polymer composites. However, all the proposed models rely upon experimental measurements of the electrical resistance at rest state. Similarly, the models available in literature assume a voltage-independent resistance and a stress-independent area for tunneling conduction. With the aim of developing and validating a more comprehensive model, a test bench capable of exerting controlled forces has been developed. Commercially available sensors-which are manufactured from conductive polymer composites-have been tested at different voltages and stresses, and a model has been derived on the basis of equations for the quantum tunneling conduction through thin insulating film layers. The resistance contribution from the contact resistance has been included in the model together with the resistance contribution from the conductive particles. The proposed model embraces a voltage-dependent behavior for the composite resistance, and a stress-dependent behavior for the tunneling conduction area. The proposed model is capable of predicting sensor current based upon information from the sourcing voltage and the applied stress. This study uses a physical (non-phenomenological) approach for all the phenomena discussed here.

Relative Merits of Low-Carbohydrate Versus Low-Fat Diet in Managing Obesity.

OBJECTIVES: Although low-fat diets (LFD) have been the cornerstone of dietary guidelines for weight reduction, low-carbohydrate diets (LCD) continue to gain attention and popularity. Which diet can achieve significant and sustainable weight loss in unclear, however. Our objective in this study was to compare LCDs with LFDs and their impact on weight loss. METHODS: We performed a MEDLINE/PubMed search for English-language articles of randomized controlled studies conducted with adults who were overweight or obese for at least 6 months for the time period of January 2001-October 2014. Two reviewers independently abstracted data, including participants' characteristics, diet composition and duration, and change in weight from baseline at 6 and 12 months. RESULTS: A total of 17 studies were analyzed. At 6 months, the mean weight loss for participants on an LCD was -1.439 kg (95% confidence interval -2.319 to -0.558) compared with participants on an LFD (P < 0.001). At 12 months, the difference was smaller, -0.769 kg (95% confidence interval -1.361 to -0.178) but remained statistically significant (P < 0.010). The mean difference in the weight loss between the two diets was attenuated over time. CONCLUSIONS: Reducing carbohydrate intake may help patients achieve weight loss. The mean difference in weight change between an LCD and an LFD was too small to have a meaningful impact on weight loss. More studies are needed to better elucidate the role of LCDs in weight loss efforts.

Neurocognitive subtypes of schizophrenia.

OBJECTIVE: To empirically identify schizophrenia neurocognitive subtypes and establish their association with clinical characteristics. METHODS: Sustained attention, executive function, facial emotion recognition, verbal learning, and working memory tests were applied to 253 subjects with schizophrenia. We identified neurocognitive subtypes by a latent class analysis of the tests results. After, we made a search for the association of these subtypes with clinic characteristics. RESULTS: We identified four neurocognitive subtypes: 1) “Global cognitive deficit”, 2) “Memory and executive function deficit”, 3) “Memory and facial emotion recognition deficit,” and 4) “Without cognitive deficit.” In comparison with the subtype “without cognitive deficit,” we found that the “memory and executive function deficit subtype” and the “global cognitive deficit subtype” had a higher frequency of male, unemployed, severe impairment, and adherence to treatment participants. However, in the “global cognitive deficit subtype” the differences were higher and there was also a lower frequency of past major depressive episodes (OR 0.39; 95%CI: 0.16 to 0.97). The “memory and facial recognition deficit subtype” had a higher probability of severe impairment (OR 5.52; 95%CI: 1.89 to 16.14) and unemployed (OR 2.43; 95%CI: 1.06 to 5.55) participants, but also a lower probability of past depressive episodes (OR 0.21; 95%CI: 0.07 to 0.66). CONCLUSION: Our results suggest the existence of four neurocognitive subtypes in schizophrenia with a spectrum of dysfunction and severity. We found higher dysfunction in those with worse cognitive dysfunction, and higher affective psychopathology and less treatment adherence in those with less cognitive dysfunction.

A comparison of congestive heart failure readmissions among teaching and nonteaching hospital services.

OBJECTIVES: Heart failure (HF) is a leading cause of hospitalization in the United States. With the population trend shifting to a higher volume of elderly adults, the efficient management of HF will become increasingly essential. The development and implementation of The Patient Protection and Affordable Care Act and subsequent changes in reimbursement practices have made 30-day readmission rates a topic of much interest and relevance. The aim of the study was to compare rates of readmission among teaching and nonteaching hospitals. METHODS: The authors gathered retrospective data on HF quality measures and readmission rates between August 2011 and July 2012, extracted from the institution's managerial accounting database. These data were compared among teaching and nonteaching hospitals. Patient demographics, readmission rates, readmission diagnoses, severity of illness, patient disposition, medications prescribed, cost of services, and mortality were reviewed. Analysis of variance was used for continuous variables; χ(2) analysis was used for evaluating categorical variables. RESULTS: A higher proportion of patients on the cardiology teaching service were men than on either the medicine teaching service or the medicine nonteaching service. Length of stay, case costs, and care costs were lowest for the cardiology teaching service; however, patient illness severity was lower on this service than on the other two services. Overall, readmissions and mortality were similar among all groups, but readmission for the same diagnosis was more likely on the cardiology service than on the medicine teaching and nonteaching services. CONCLUSIONS: Studies comparing teaching and nonteaching providers for an HF diagnosis are needed. Hospital readmission and mortality rates were similar across services and compared favorably with national data. Opportunities that target cost reduction and length of stay may be leveraged.

Predicting factors for extremity fracture among border-fall patients using machine learning computing.

Background: The factors causing the injuries sustained from falls at US-Mexican border include falls from border wall or fence, fleeing from border patrols, ejecting from vehicle, and others. This study aimed to determine the factors leading to anatomical injuries and to identify the importance of factors leading to limb fracture and internal organ injuries. Methods: A total of 178 patients who sustained musculoskeletal injuries or internal organ injuries and were admitted to our hospital were included in this retrospective study. Factors indexed for analysis included demographics, comorbidities, and falling mechanic factors. Correlations between anatomical injuries and mechanical injuries were analyzed. Multilayer perceptron neural network (MPNN) was used to identify predictive factors and to stratify the importance of these factors leading to injuries. The SPSS software was used for statistical analysis and predictive factor analysis. Results: The extremity fracture was associated with border wall/fence fall (p = 0.001) and fleeing (p = 0.002). The spine fracture was correlated with bridge jump/fall (p = 0.007), fence jump/fall (p = 0.026). The vehicle ejecting/MVA was correlated with head injury (P < 0.001), chest injury (P < 0.001), and abdominal injury p < 0.001). MNPP stratify the importance of factor causing injury with multiple factor considered. Conclusion: The various injury factors caused different anatomical injuries. Multifactorial assessment associated with these injuries can improve the accuracy of diagnosis and develop a predictive model for clinical applications.

Operative Management Improves Near-term Survival of Patients With Odontoid Type II Fractures: A Propensity-matched National Registry Analysis.

STUDY DESIGN: National Trauma Data Bank (NTDB) review and propensity-matched analysis. OBJECTIVE: To evaluate differences in clinical outcomes by operative management. SUMMARY OF BACKGROUND DATA: Odontoid type II fractures are the most prevalent cervical fracture. Operative intervention on these fractures is frequently debated; surgical risks are compounded by clinical severity, patient age, and comorbidities. METHODS: This registry review included index admissions for odontoid type II fractures [International Classification of Diseases (ICD)-10 codes beginning with S12.11] from 1/1/2017 to 1/1/2020; patients who died in the emergency department (ED) were excluded. Propensity score techniques were used to match patients 1:1 by surgical management, using a caliper distance of 0.05, after matching on the following covariates that differed significantly between surgical and nonsurgical patients: age, sex, race, cause of injury, transfer status, injury severity score, ED Glasgow coma score, ED systolic blood pressure, presence of transverse ligamentous injury, cervical dislocation, and 8 comorbidities. The following outcomes were analyzed with McNemar tests and Wilcoxon signed-rank tests: near-term survival (discharged from the hospital to locations other than morgue or hospice), intensive care unit (ICU) admission, hospital complications, median hospital length of stay (LOS), and median ICU LOS. RESULTS: There were 16,607 patients, 2916 (17.6%) were operatively managed and 13,691 were nonoperatively managed. Before matching, survival was greater for patients managed operatively compared with nonoperatively (95.0% vs. 88.2%). The matched population consisted of 5334 patients: 2667 patients in the operative group (91.5% of this population) and 2667 well-matched patients in the nonoperative group. After matching, there was a survival benefit for patients who were operatively managed compared with nonoperative management (94.8% vs. 91.4% P <0.001). However, operative management was associated with greater development of complications, ICU admission, and longer hospital and ICU LOS. CONCLUSION: Compared with nonoperative management, operative management demonstrated a significant near-term survival benefit for patients with odontoid type II fractures in select patients. LEVEL OF EVIDENCE: III.

Outcomes of patients with traumatic brain injury after stress ulcer prophylaxis: a retrospective multicenter study.

Background: Stress ulcers in patients with traumatic brain injury (TBI) and spinal cord injury (SCI) present significant morbidity and mortality risks. Despite the low reported stress ulcer rates, stress ulcer prophylaxis (SUP) is widely administered in neurocritical care. It was hypothesized that universal SUP administration may not be associated with reduced rates of complications across all neurocritical care patients. Methods: This retrospective study encompassed neurocritical care patients aged ≥18 with moderate or severe TBI or SCI, admitted to the intensive care unit (ICU) between October 2020 and September 2021, across six level I trauma centers. Exclusions included patients with an ICU stay <2 days, prior SUP medication use, and pre-existing SUP diagnoses. The primary exposure was SUP, with the primary outcome being clinically significant gastrointestinal bleeds (CSGIBs). Secondary outcomes included pneumonia and in-hospital mortality. Patients were stratified by admission Glasgow Coma Scale (GCS) groups. Results: Among 407 patients, 83% received SUP, primarily H2 receptor antagonists (88%) and proton pump inhibitors (12%). Patients on SUP were significantly younger, had lower admission GCS scores, higher Injury Severity Scores, longer ICU stays, and higher rates of mechanical ventilation than non-SUP patients. Overall, CSGIBs were rare (1%) and not significantly different between the SUP and non-SUP groups (p=0.06). However, CSGIBs exclusively occurred in patients with GCS scores of 3-8, and SUP was associated with a significantly lower rate of CSGIBs in this subgroup (p=0.03). SUP was also linked to significantly higher pneumonia rates in both GCS 3-8 and GCS 9-12 patients. Conclusions: This study highlights the low incidence of CSGIBs in neurocritical trauma patients and suggests potential benefits of SUP, particularly for those with severe neurological impairment. Nevertheless, the increased risk of pneumonia associated with SUP in these patients warrants caution. Further research is crucial to refine SUP guidelines for neurocritical care patients and inform optimal strategies. Level of evidence: Level III, retrospective.

African-Americans, Hispanic Americans, and non-Hispanic whites without GERD or reflux symptoms have equivalent 24-h pH esophageal acid exposure.

BACKGROUND: Ambulatory esophageal pH monitoring is, currently, the recommended diagnostic exam for gastroesophageal reflux disease. Data are currently available for African-American (AA) and non-Hispanic white (nHw) volunteers among United States ethnic groups. The purpose of this study was to obtain normal values of 24-h esophageal pH by monitoring healthy adult Hispanic American (HA) volunteers and to compare these with values obtained from healthy AA and nHw volunteers to determine if ethnic variation exists in 24-h esophageal pH. METHODS: 24-h Dual esophageal pH monitoring was performed for healthy AA, HA, and nHw. Values for total number of reflux episodes, episodes longer than 5 min, total reflux time, and longest reflux episode in the proximal and/or distal esophagus were obtained for all groups. Differences between groups were considered significant if p<0.05. RESULTS: One-hundred and thirty-six subjects volunteered and completed 24-h pH testing. Fifty-three were AA, 25 HA, and 58 nHw, with males accounting for 52, 47, and 47%, respectively, of each group. AA were older than nHw only and nHw had a lower body mass index than both AA and HA. Shorter study duration was observed for HA than for AA and nHw. No difference was observed between ethnic groups for any measured pH data in the proximal or distal esophagus. CONCLUSIONS: No difference exists in values obtained during esophageal pH monitoring among healthy AA, HA, and nHw. This indicates that currently accepted normal values of ambulatory esophageal pH monitoring can be used for all major United States ethnic groups without compromising diagnostic accuracy.

Verbal working memory in individuals with schizophrenia and their first degree relatives: relationship with negative and disorganized symptoms.

OBJECTIVE: To determine whether there are differences in verbal working memory amongst subjects with schizophrenia, their first degree relatives and controls, and to evaluate the influence of symptoms on these differences, as an initial step to assess whether this cognitive function is an endophenotype. METHODS: We examined 197 cases with schizophrenia, 197 first degree relatives and 200 controls through psychiatric interviews and the Letters and Numbers Sequencing test (LNS). Performance was compared among the three groups adjusting for age, sex and education level. Adjustment for "negative symptoms" and "disorganization" was performed afterwards. RESULTS: Subjects with schizophrenia showed lower performance in the LNS than their first degree relatives and the healthy controls; the effect sizes were 0.75 and 1.18 respectively. There was a small difference between relatives and controls (effect size =0.38). These differences were significant after adjustment for negative and disorganized symptoms, but the effect sizes became smaller: 0.26 for relatives vs. subjects with schizophrenia, 0.56 for controls vs. subjects with schizophrenia and 0.33 for relatives vs. controls. Among individuals with schizophrenia, performance in the LNS was not associated with disorder duration, disease onset age, antipsychotics, history of depressive episodes or substance use disorders. CONCLUSION: Results suggest verbal working memory may be considered as an endophenotype in schizophrenia.

Long COVID: Is there a kidney link?

Metabolic causes such as altered bioenergetics and amino acid metabolism may play a major role in Long COVID. Renal-metabolic regulation is an integral part of these pathways but has not been systematically or routinely investigated in Long COVID. Here we discuss the biochemistry of renal tubular injury as it may contribute to Long COVID symptoms. We propose three potential mechanisms that could be involved in Long COVID namely creatine phosphate metabolism, un-reclaimed glomerular filtrate and COVID specific proximal tubule cells (PTC) injury-a tryptophan paradigm. This approach is intended to allow for improved diagnostics and therapy for the long-haul sufferers.

Border-fence falls versus domestic falls at a South Texas trauma center.

Objectives: Falling from height may lead to significant injuries and time hospitalized; however, there are few studies comparing the specific mechanism of fall. The purpose of this study was to compare injuries from falls after attempting to cross the USA-Mexico border fence (intentional) with injuries from domestic falls (unintentional) of comparable height. Methods: This retrospective cohort study included all patients admitted after a fall from a height of 15-30 ft to a level II trauma center between April 2014 and November 2019. Patient characteristics were compared by falls from the border fence with those who fell domestically. Fisher's exact test, χ2 test and Wilcoxon Mann-Whitney U test were used as appropriate. A significance level of α<0.05 was used. Results: Of the 124 patients included, 64 (52%) were falls from the border fence while 60 (48%) were domestic falls. Patients sustaining injuries from border falls were on average younger than patients who had domestic falls (32.6 (10) vs 40.0 (16), p=0.002), more likely males (58% vs 41%, p<0.001), fell from a significantly higher distance (20 (20-25) vs 16.5 (15-25), p<0.001), and had a significantly lower median injury severity score (ISS) (5 (4-10) vs 9 (5-16.5), p=0.001). Additionally, compared with domestic falls, border falls had fewer injuries to the head (3% vs 25%, p=0.004) and chest (5% vs 27%, p=0.007), yet more extremity injuries (73% vs 42%, p=0.003), and less had an intensive care unit (ICU) stay (30% vs 63%, p=0.002). No significant differences in mortality were found. Conclusion: Patients sustaining injuries from border crossing falls were slightly younger, and although fell from higher, had a lower ISS, more extremity injuries, and fewer were admitted to the ICU compared with patients sustaining falls domestically. There was no difference in mortality between groups. Level of evidence: Level III, retrospective study.

How do we PI? Results of an EAST quality, patient safety, and outcomes survey.

Background: Quality improvement is a cornerstone for any verified trauma center. Conducting effective quality and performance improvement, however, remains a challenge. In this study, we sought to better explore the landscape and challenges facing the members of the Eastern Association for the Surgery of Trauma (EAST) through a survey. Methods: A survey was designed by the EAST Quality Patient Safety and Outcomes Committee. It was reviewed by the EAST Research and Scholarship Committee and then distributed to 2511 EAST members. The questions were designed to understand the frequency, content, and perceptions surrounding quality improvement processes. Results: There were 151 respondents of the 2511 surveys sent (6.0%). The majority were trauma faculty (55%) or trauma medical directors (TMDs) (37%) at American College of Surgeons level I (62%) or II (17%) trauma centers. We found a wide variety of resources being used across hospitals with the majority of cases being identified by a TMD or attending (81%) for a multidisciplinary peer review (70.2%). There was a statistically significant difference in the perception of the effectiveness of the quality improvement process with TMDs being more likely to describe their process as moderately or very effective compared with their peers (77.5% vs. 57.7%, p=0.026). The 'Just Culture' model appeared to have a positive effect on the process improvement environment, with providers less likely to report a non-conducive environment (10.9% vs. 27.6%, p=0.012) and less feelings of assigning blame (3.1% vs. 13.8%, p=0.026). Conclusion: Case review remains an essential but challenging process. Our survey reveals a need to continue to advocate for appropriate time and resources to conduct strong quality improvement processes. Level of evidence: Epidemiological study, level III.

Epidemiology of C2 fractures and determinants of surgical management: analysis of a national registry.

Objective: Operative management of axis fractures (C2) usually depend on the stability and location of the break and individual patient characteristics. We sought to describe the epidemiology of C2 fractures and hypothesized that determinants for surgery would differ by fracture diagnosis. Methods: Patients with C2 fractures were identified from the US National Trauma Data Bank from January 1, 2017, to January 1, 2020. Patients were classified by C2 fracture diagnosis: odontoid type II, odontoid types I and III, and non-odontoid fracture (hangman's fracture or fractures through base of the axis). The primary comparison was C2 fracture surgery versus non-operative management. Multivariate logistic regression was used to identify independent associations with surgery. Decision tree-based models were developed to identify determinants for surgery. Results: There were 38 080 patients; 42.7% had an odontoid type II fracture; 16.5% had an odontoid type I/III fracture; and 40.8% had a non-odontoid fracture. All examined patient demographics, clinical characteristics, outcomes, and interventions differed by C2 fracture diagnosis. Overall, 5292 (13.9%) were surgically managed (17.5% odontoid type II, 11.0% odontoid type I/III, and 11.2% non-odontoid; p<0.001). The following covariates increased odds of surgery for all three fracture diagnoses: younger age, treatment at a level I trauma center, fracture displacement, cervical ligament sprain, and cervical subluxation. Determinants of surgery differed by fracture diagnosis: for odontoid type II, age ≤80 years, a displaced fracture, and cervical ligament sprain were determinants; for odontoid type I/III, age ≤85 years, a displaced fracture, and cervical subluxation were determinants; for non-odontoid fractures, cervical subluxation and cervical ligament sprain were the strongest determinants for surgery, by hierarchy. Conclusions: This is the largest published study of C2 fractures and current surgical management in the USA. Odontoid fractures, regardless of type, had age and fracture displacement as the strongest determinants for surgical management, whereas associated injuries were determinants of surgery for non-odontoid fractures. Level of evidence: III.

Hypoxia Dysregulates the Transcription of Myoendothelial Junction Proteins Involved with Nitric Oxide Production in Brain Endothelial Cells.

Myoendothelial junctions (MEJs) are structures that allow chemical signals to be transmitted between endothelial cells (ECs) and vascular smooth muscle cells, which control vascular tone. MEJs contain hemoglobin alpha (Hbα) and endothelial nitric oxide synthase (eNOS) complexes that appear to control the production and scavenging of nitric oxide (NO) along with the activity of cytochrome b5 reductase 3 (CYB5R3). The aim of this study was to examine how hypoxia affected the regulation of proteins involved in the production of NO in brain ECs. In brief, human brain microvascular endothelial cells (HBMEC) were exposed to cobalt chloride (CoCl2), a hypoxia mimetic, and a transcriptional analysis was performed using primers for eNOS, CYB5R3, and Hbα2 with ΔΔCt relative gene expression normalized to GAPDH. NO production was also measured after treatment using 4,5-diaminofluorescein diacetate (DAF-DA), a fluorescent NO indicator. When HBMEC were exposed to CoCl2 for 48 h, eNOS and CYB5R3 messenger RNA significantly decreased (up to -17.8 ± 4.30-fold and -10.4 ± 2.8, respectively) while Hbα2 increased to detectable levels. Furthermore, CoCl2 treatment caused a redistribution of peripheral membrane-generated NO production to a perinuclear region. To the best of our knowledge, this is the first time this axis has been studied in brain ECs and these findings imply that hypoxia may cause dysregulation of proteins that regulate NO production in brain MEJs.

The relapsed acute lymphoblastic leukemia network (ReALLNet): a multidisciplinary project from the spanish society of pediatric hematology and oncology (SEHOP).

Acute lymphoblastic leukemia (ALL) is the most common pediatric cancer, with survival rates exceeding 85%. However, 15% of patients will relapse; consequently, their survival rates decrease to below 50%. Therefore, several research and innovation studies are focusing on pediatric relapsed or refractory ALL (R/R ALL). Driven by this context and following the European strategic plan to implement precision medicine equitably, the Relapsed ALL Network (ReALLNet) was launched under the umbrella of SEHOP in 2021, aiming to connect bedside patient care with expert groups in R/R ALL in an interdisciplinary and multicentric network. To achieve this objective, a board consisting of experts in diagnosis, management, preclinical research, and clinical trials has been established. The requirements of treatment centers have been evaluated, and the available oncogenomic and functional study resources have been assessed and organized. A shipping platform has been developed to process samples requiring study derivation, and an integrated diagnostic committee has been established to report results. These biological data, as well as patient outcomes, are collected in a national registry. Additionally, samples from all patients are stored in a biobank. This comprehensive repository of data and samples is expected to foster an environment where preclinical researchers and data scientists can seek to meet the complex needs of this challenging population. This proof of concept aims to demonstrate that a network-based organization, such as that embodied by ReALLNet, provides the ideal niche for the equitable and efficient implementation of "what's next" in the management of children with R/R ALL.

African Americans with Barrett's esophagus are less likely to have dysplasia at biopsy.

BACKGROUND: Barrett's Esophagus (BE) is a pre-malignant condition. Limited data on BE dysplasia prevalence exists among United States ethnic groups. AIM: The purpose of this study was to determine if the frequency of BE with dysplasia varies among the major ethnic groups presenting to our institution. METHODS: The University of Florida-Jacksonville endoscopy database was searched for all cases of endoscopic BE from September 2002 to August 2007. Histologic BE was diagnosed if salmon colored esophageal mucosa was endoscopically seen at least 1 cm above the top of the gastric folds and biopsy revealed intestinal metaplasia with Alcian blue-containing goblet cells. Demographic data collected for all included: age at diagnosis, ethnicity, sex, previous history of esophageal reflux, atypical manifestations (chronic cough, aspiration), endoscopic length of BE, presence or absence of hiatal hernia, esophageal stricture or ulcer, and presence or absence of dysplasia. RESULTS: Salmon colored esophageal mucosa was observed in 405 of 7,308 patients (5.5%) and histologically confirmed in 115 of 405 patients (28%) reflecting an overall prevalence of BE of 115/7308 (1.6%) in this cohort. Ethnic distribution of histologic BE patients was as follows: 95 (83%) non-Hispanic white (nHw), 16 (14%) African American (AA) and 4 (3%) other. Long segment BE (LSBE) and any form of dysplasia was observed less frequently in AA than nHw (LSBE: 12% vs. 26% and dysplasia: 0% vs. 7%). CONCLUSIONS: LSBE and dysplasia are less frequent in AA than nHw. Studies in AA with BE may illustrate factors limiting dysplasia and LSBE risk.