Intraoperative Surgeon Assessment of Bone: Correlation to Bone Mineral Density, CT Hounsfield units and Vertebral Bone Quality.

STUDY DESIGN: Retrospective observational study of consecutive patients. OBJECTIVE: The purpose of the study is to determine if a surgeon's qualitative assessment of bone intraoperatively correlates with radiologic parameters of bone strength. SUMMARY OF BACKGROUND DATA: Preoperative radiologic assessment of bone can include modalities such as CT Hounsfield Units (HUs), dual-energy x-ray absorptiometry bone mineral density (DXA BMD) with trabecular bone score (TBS) and MRI vertebral bone quality (VBQ). Quantitative analysis of bone with screw insertional torque and pull-out strength measurement has been performed in cadaveric models and has been correlated to these radiologic parameters. However, these quantitative measurements are not routinely available for use in surgery. Surgeons anecdotally judge bone strength, but the fidelity of the intraoperative judgement has not been investigated. METHODS: All adult patients undergoing instrumented posterior thoracolumbar spine fusion by one of seven surgeons at a single center over a 3-month period were included. Surgeons evaluated the strength of bone based on intraoperative feedback and graded each patient's bone on a 5-point Likert scale. Two independent reviewers measured preoperative CT HUs and MRI VBQ. BMD, lowest T-score and TBS were extracted from DXA within 2 years of surgery. RESULTS: Eighty-nine patients were enrolled and 16, 28, 31, 13 and 1 patients had Likert grade 1 (strongest bone), 2, 3, 4, and 5 (weakest bone), respectively. The surgeon assessment of bone correlated with VBQ (τ=0.15, P=0.07), CT HU (τ=-0.31, P<0.01), lowest DXA T-score (τ=-0.47, P<0.01), and TBS (τ=-0.23, P=0.06). CONCLUSION: Spine surgeons' qualitative intraoperative assessment of bone correlates with preoperative radiologic parameters, particularly in posterior thoracolumbar surgeries. This information is valuable to surgeons as this supports the idea that decisions based on feel in surgery have statistical foundation.

Case report: Neonatal autoimmune lymphoproliferative syndrome with a novel pathogenic homozygous FAS variant effectively treated with sirolimus.

Background: Autoimmune lymphoproliferative syndrome (ALPS) is a rare disease characterized by defective FAS signaling, which results in chronic, nonmalignant lymphoproliferation and autoimmunity accompanied by increased numbers of "double-negative" T-cells (DNTs) (T-cell receptor αß+ CD4-CD8-) and an increased risk of developing malignancies later in life. Case presentation: We herein report a case of a newborn boy with a novel germline homozygous variant identified in the FAS gene, exon 9, c.775del, which was considered pathogenic. The consequence of this sequence change was the creation of a premature translational stop signal p.(lle259*), associated with a severe clinical phenotype of ALPS-FAS. The elder brother of the proband was also affected by ALPS and has been found to have the same FAS homozygous variant associated with a severe clinical phenotype of ALPS-FAS, whereas the unaffected parents are heterozygous carriers of this variant. This new variant has not previously been described in population databases (gnomAD and ExAC) or in patients with FAS-related conditions. Treatment with sirolimus effectively improved the patient clinical manifestations with obvious reduction in the percentage of DNTs. Conclusion: We described a new ALPS-FAS clinical phenotype-associated germline FAS homozygous pathogenic variant, exon 9, c.775del, that produces a premature translational stop signal p.(lle259*). Sirolimus significantly reduced DNTs and substantially relieved the patient's clinical symptoms.

Pragmatic, Prospective Comparative Effectiveness Trial of Carbon Ion Therapy, Surgery, and Proton Therapy for the Management of Pelvic Sarcomas (Soft Tissue/Bone) Involving the Bone: The PROSPER Study Rationale and Design.

Surgical treatment of pelvic sarcoma involving the bone is the standard of care but is associated with several sequelae and reduced functional quality of life (QOL). Treatment with photon and proton radiotherapy is associated with relapse. Carbon ion radiotherapy (CIRT) may reduce both relapse rates and treatment sequelae. The PROSPER study is a tricontinental, nonrandomized, prospective, three-arm, pragmatic trial evaluating treatments of pelvic sarcoma involving the bone. Patients aged at least 15 years are eligible for inclusion. Participants must have an Eastern Cooperative Oncology Group Performance Status score of two or less, newly diagnosed disease, and histopathologic confirmation of pelvic chordoma, chondrosarcoma, osteosarcoma, Ewing sarcoma with bone involvement, rhabdomyosarcoma (RMS) with bone involvement, or non-RMS soft tissue sarcoma with bone involvement. Treatment arms include (1) CIRT (n = 30) delivered in Europe and Asia, (2) surgical treatment with or without adjuvant radiotherapy (n = 30), and (3) proton therapy (n = 30). Arms two and three will be conducted at Mayo Clinic campuses in Arizona, Florida, and Minnesota. The primary end point is to compare the 1-year change in functional QOL between CIRT and surgical treatment. Additional comparisons among the three arms will be made between treatment sequelae, local control, and other QOL measures.

SARS-CoV-2 Viral Load Is Correlated With the Disease Severity and Mortality in Patients With Cancer.

The correlation between severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) viral load and risk of disease severity in cancer patients is poorly understood. Given the fact that cancer patients are at increased risk of severe coronavirus disease 2019 (COVID-19), analysis of viral load and disease outcome in COVID-19-infected cancer patients is needed. Here, we measured the SARS-CoV-2 viral load using qPCR cycle threshold (Ct) values collected from 120 noncancer and 64 cancer patients' nasopharyngeal swab samples who are admitted to hospitals. Our results showed that the in-hospital mortality for high viral load cancer patients was 41.38%, 23.81% for medium viral load and 14.29% for low viral load patients (p < -0.01). On the other hand, the mortality rate for noncancer patients was lower: 22.22% among patients with high viral load, 5.13% among patients with medium viral load, and 1.85% among patients with low viral load (p < 0.05). In addition, patients with lung and hematologic cancer showed higher possibilities of severe events in proportion to high viral load. Higher attributable mortality and severity were directly proportional to high viral load particularly in patients who are receiving anticancer treatment. Importantly, we found that the incubation period and serial interval time is shorter in cancer patients compared with noncancer cases. Our report suggests that high SARS-CoV-2 viral loads may play a significant role in the overall mortality and severity of COVID-19-positive cancer patients, and this warrants further study to explore the disease pathogenesis and their use as prognostic tools.

Unusual accumulation of a wide array of antimicrobial resistance mechanisms in a patient with cytomegalovirus-associated hemophagocytic lymphohistiocytosis: a case report.

BACKGROUND: Infections with multidrug-resistant organisms (MDRO) pose a serious threat to patients with dysregulated immunity such as in hemophagocytic lymphohistiocytosis (HLH), but such infections have rarely been comprehensively characterized. Here, we present a fatal case of HLH secondary to cytomegalovirus (CMV) infection complicated by both anti-viral drug resistance and sepsis from multiple MDROs including pandrug-resistant superbug bacteria. CASE PRESENTATION: A previously healthy, six-year-old boy presented with a 45-day history of fever prior to a diagnosis of hemophagocytic lymphohistiocytosis and hemorrhagic colitis, both associated with CMV. On hospital admission, the patient was found to be colonized with multiple, multidrug-resistant (MDR) bacteria including vancomycin-resistant enterococci (VRE) and carbapenamase-producing organisms (CPO). He eventually developed respiratory, urine and bloodstream infections with highly drug-resistant, including pandrug-resistant bacteria, which could not be controlled by antibiotic treatment. Antiviral therapy also failed to contain his CMV infection and the patient succumbed to overwhelming bacterial and viral infection. Whole genome sequencing (WGS) of the MDR bacteria and metagenomic analysis of his blood sample revealed an unusual accumulation of a wide range of antimicrobial resistance mechanisms in a single patient, including antiviral resistance to ganciclovir, and resistance mechanisms to all currently available antibiotics. CONCLUSIONS: The case highlights both the risk of acquiring MDR superbugs and the severity of these infections in HLH patients.

Drinking Water Salinity, Urinary Macro-Mineral Excretions, and Blood Pressure in the Southwest Coastal Population of Bangladesh.

Background Sodium (Na+) in saline water may increase blood pressure ( BP ), but potassium (K+), calcium (Ca2+), and magnesium (Mg2+) may lower BP . We assessed the association between drinking water salinity and population BP . Methods and Results We pooled 6487 BP measurements from 2 cohorts in coastal Bangladesh. We used multilevel linear models to estimate BP differences across water salinity categories: fresh water (electrical conductivity, <0.7 mS/cm), mild salinity (electrical conductivity ≥0.7 and <2 mS/cm), and moderate salinity (electrical conductivity ≥2 and <10 mS/cm). We assessed whether salinity categories were associated with hypertension using multilevel multinomial logistic models. Models included participant-, household-, and community-level random intercepts. Models were adjusted for age, sex, body mass index ( BMI ), physical activity, smoking, household wealth, alcohol consumption, sleep hours, religion, and salt consumption. We evaluated the 24-hour urinary minerals across salinity categories, and the associations between urinary minerals and BP using multilevel linear models. Compared with fresh water drinkers, mild-salinity water drinkers had lower mean systolic BP (-1.55 [95% CI : -3.22-0.12] mm Hg) and lower mean diastolic BP (-1.26 [95% CI : -2.21--0.32] mm Hg) adjusted models. The adjusted odds ratio among mild-salinity water drinkers for stage 1 hypertension was 0.60 (95% CI : 0.43-0.84) and for stage 2 hypertension was 0.56 (95% CI : 0.46-0.89). Mild-salinity water drinkers had high urinary Ca2+, and Mg2+, and both urinary Ca2+ and Mg2+ were associated with lower BP. Conclusions Drinking mild-salinity water was associated with lower BP , which can be explained by higher intake of Ca2+ and Mg2+ through saline water.

Evaluation of pubertal onset and characteristics in Egyptian boys: A cross-sectional study.

The objective of this study was to evaluate pubertal onset and characteristics in Egyptian boys. Examination of schoolboys (9-18 years) included height (cm), penile length (cm) and testicular volume (ml). Pubertal onset was considered at gonadal (G) stage 2 (G2 indicated testicular volume from 4-8 ml). Out of 1,078 boys, 270 (25%) were residents in urban areas, 414 (38.4%) in suburban areas and 394 (36.5%) in rural areas. The mean (±SD) age of G2 was 11.1 ± 1.2 years (5th and 95th percentiles were 10 and 13 years respectively). The age of 10.5 years was predictive of G2 with 89.9% sensitivity and 86.2% specificity (95% confidence interval; p < 0.001). The changes in testicular volumes and penile lengths, at the age interval from 16 to 18 years, were not significant. Pubertal onset was earlier among Egyptian boys in urban areas, with smaller family size, less crowding conditions, adequate illumination and good ventilation, although the difference was not statistically significant (p > 0.05). In conclusion, the mean age of pubertal onset among Egyptian boys was 11.1 years. A tendency towards earlier pubertal onset was observed in Egyptian boys who lived in urban areas and had better socio-demographic conditions.

Mortality risk prediction models for coronary artery bypass graft surgery: current scenario and future direction.

INTRODUCTION: Many risk prediction models are currently in use for predicting short-term mortality following coronary artery bypass graft (CABG) surgery. This review critically appraised the methods that were used for developing these models to assess their applicability in current practice setting as well as for the necessity of up-gradation. EVIDENCE ACQUISITION: Medline via Ovid was searched for articles published between 1946 and 2016 and EMBASE via Ovid between 1974 and 2016 to identify risk prediction models for CABG. Article selection and data extraction was conducted using the CHARMS checklist for review of prediction model studies. Association between model development methods and model's discrimination was assessed using Kruskal-Wallis one-way analysis of variance and Mann-Whitney U-test. EVIDENCE SYNTHESIS: A total of 53 risk prediction models for short-term mortality following CABG were identified. The review found a wide variation in development methodology of risk prediction models in the field. Ambiguous predictor and outcome definition, sub-optimum sample size, inappropriate handling of missing data and inefficient predictor selection technique are major issues identified in the review. Quantitative synthesis in the review showed "missing value imputation" and "adopting machine learning algorithms" may result in better discrimination power of the models. CONCLUSIONS: There are aspects in current risk modeling, where there is room for improvement to reflect current clinical practice. Future risk modelling needs to adopt a standardized approach to defining both outcome and predictor variables, rational treatment of missing data and robust statistical techniques to enhance performance of the mortality risk prediction.

The role of cytokines as biomarkers in systemic lupus erythematosus and lupus nephritis.

Cytokines play an important role in the pathogenesis of systemic lupus erythematosus (SLE) and lupus nephritis. This is currently a very active area of research. Of particular interest is the use of cytokines as biomarkers of disease activity in SLE and lupus nephritis. Can cytokine measurements assist in early detection of renal flare in known lupus nephritis? Can such measurements be used to distinguish between flare and chronic damage? Or help to confirm renal remission? Could they be used to help assess the required duration of immunosuppression and reduce the need for invasive renal biopsy? This review discusses limitations of current laboratory methods in monitoring SLE, how measurements of cytokines may contribute in relation to following disease activity and summarizes what is known about cytokines as biomarkers in SLE and lupus nephritis.

Surfactant protein A stimulates release of neutrophil chemotactic factors by alveolar type II pneumocytes.

Mucosal immunity is an important mechanism in the response to injury. Our hypothesis is that surfactant protein A (SP-A) is an autocrine factor that stimulates alveolar type II epithelial cell release of neutrophil chemotactic factors by binding to the SP-A receptor expressed by these cells. We examined (1) the effect of SP-A (20 µg/ml) or IL-1ß (10 ng/ml) on release of neutrophil chemotactic factors by primary cultures of type II cells or alveolar macrophages, and (2) the effect of intratracheal instillation of the blocking antibody to the SP-A receptor on the response to oleic acid-induced lung injury in vivo. All media and cell culture supernates were assayed for neutrophil chemotactic activity, and bronchoalveolar lavage fluid from the in vivo experiments was analyzed for inflammatory cell counts. While SP-A and media used for the cell cultures has no intrinsic neutrophil chemotactic activity, supernates from primary cultures of type II cells incubated in either SP-A or IL-1ß had twofold higher neutrophil chemotactic factor activity compared to supernates from controls. SP-A had no effect on release of neutrophil chemotactic factor by alveolar macrophages. Oleic acid-induced lung injury resulted in a marked influx of neutrophils into BAL, and this influx was reduced by 70% by pretreatment with the antibody to SP-A receptor. We conclude that SP-A stimulates the release of neutrophil chemotactic factor by alveolar type II cells, and this effect is mediated by the receptor for SP-A specifically expressed by these cells.