Serum IgG Profiling of Toddlers Reveals a Subgroup with Elevated Seropositive Antibodies to Viruses Correlating with Increased Vaccine and Autoantigen Responses

Purpose

The human antibody repertoire forms in response to infections, the microbiome, vaccinations, and environmental exposures. The specificity of such antibody responses was compared among a cohort of toddlers to identify differences between seropositive versus seronegative responses.

Methods

An assessment of the serum IgM and IgG antibody reactivities in 197 toddlers of 1- and 2-years of age was performed with a microfluidic array containing 110 distinct antigens. Longitudinal profiling was done from years 1 to 2. Seropositivity to RNA and DNA viruses; bacteria; live attenuated, inactive, and subunit vaccines; and autoantigens was compared. A stratification was developed based on quantitative variations in the IgG responses. Clinical presentations and previously known genetic risk alleles for various immune system conditions were investigated in relation to IgG responses.

Results

IgG reactivities stratified toddlers into low, moderate, and high responder groups. The high group (17%) had elevated IgG responses to multiple RNA and DNA viruses (e.g., respiratory syncytial virus, Epstein-Barr virus, adenovirus, Coxsackievirus) and this correlated with increased responses to live attenuated viral vaccines and certain autoantigens. This high group was more likely to be associated with gestational diabetes and an older age. Genetic analyses identified polymorphisms in the IL2RB, TNFSF4, and INS genes in two high responder individuals that were associated with their elevated cytokine levels and clinical history of eczema and asthma.

Conclusion

Serum IgG profiling of toddlers reveals correlations between the magnitude of the antibody responses towards viruses, live attenuated vaccines, and certain autoantigens. A low responder group had much weaker responses overall, including against vaccines. The serum antibody screen also identifies individuals with IgG responses to less common infections (West Nile virus, parvovirus, tuberculosis). The characterization of the antibody responses in combination with the identification of genetic risk alleles provides an opportunity to identify children with increased risk of clinical disease.

     

Setting up a pediatric robotic urology program: A USA institution experience

Implementing a robotic urological surgery program requires institutional support, and necessitates a comprehensive, detail‐oriented plan that accounts for training, oversight, cost and case volume. Given the prevalence of robotic surgery in adult urology, in many instances it might be feasible to implement a pediatric robotic urology program within the greater context of adult urology. This involves, from an institutional standpoint, proportional distribution of equipment cost and operating room time. However, the pediatric urology team primarily determines goals for volume expansion, operative case selection, resident training and surgical innovation within the specialty. In addition to the clinical model, a robust economic model that includes marketing must be present. This review specifically highlights these factors in relationship to establishing and maintaining a pediatric robotic urology program. In addition, we share our data involving robot use over the program's first nine years (December 2007–December 2016).     

A retrospective analysis of complex proximal humerus fractures managed with reverse shoulder arthroplasty in a level 1 trauma center

BackgroundThe treatment of complex 3- and 4-part proximal humerus fractures (PHFs) in the elderly poses significant challenges because of osteoporosis and fracture comminution. The wide range of surgical options available is evidence of the complex nature of the injury. At present, reverse shoulder replacement is gaining popularity among shoulder surgeons for treating these difficult fractures, and the literature has shown equivalent or superior outcomes with reverse shoulder arthroplasty (RSA). We aimed to analyze the long-term results of these complex PHF treated with reverse shoulder replacement.MethodsFor this study, fractures from 39 patients with a mean age of 63.18 years who were treated with RSA for acute complex fractures of the proximal humerus in our institution between 2013 and 2019 were analyzed (n = 31, acute 4-part fractures; n = 4, acute fracture–dislocation; n = 3, fracture with irreparable cuff tear; n = 1, osteoporotic 2-part fracture). All patients had a standard reverse shoulder replacement (cemented humeral stem n = 37 and uncemented stem n = 2) surgery in a level 1 trauma center. The mean follow-up duration was 60 months (24-111 months). The clinical outcomes (Oxford Shoulder Score and Constant Shoulder Score) and the complications at 6 months, 12 months, and 24 months were analyzed.ResultsOur study found a relatively younger population, with 21 patients (53.84%) aged <66 years. Spearman's correlation showed that younger patients had better signs of improvement in Oxford Shoulder Scores at 2 years (P = .008). The average Oxford Shoulder Score was 39.12 ± 4.327, and the average Constant Shoulder Score was 67.67 on the operated side. The mean active forward elevation was 142.56 ± 22.29º, abduction was 136.538 ± 24.31º, external rotation was 27 ± 9.011º, and internal rotation was 33 ± 20.41º. The overall complication rate of 17.94% (periprosthetic infection n = 2, periprosthetic humerus fracture n = 1, and hematoma evacuation n = 4) in our study was similar to those of recent studies in the literature.ConclusionRSA provides a reliable option for PHFs and offers good results in the form of pain relief and good functional outcomes at 2 years even in a younger age group. Thus, it is fast becoming an important option in treating complex PHF, but we must be wary of the steep learning curve and the complications pertinent to this procedure.     

Rheological properties of antibody-coated red cells

In vivo and in vitro antibody-coated nonspherocytic red cells have normal deformability in iso-osmolar media, and their isolated membranes have normal mechanical stability as measured in the ektacytometer, a laser visco-diffractometer. The deformability of red cells from patients with hemolytic anemia was proportionately reduced with the degree of spherocytosis irrespective of whether the direct antiglobulin test was positive. However, when antibody-sensitized nonspherocytic cells were suspended in hyperosmolar media and exposed to constant shear stress in the ektacytometer, they showed reduction of their deformability index in the presence of polyvinylpyrrolidone (PVP; 360,000 Daltons) but not dextran. This reduction was not due to alterations in cell water or cation content. Also, when incubated at 37 degrees C, sensitized red cells reacted specifically with PVP, and underwent a decrease in cell deformability. This appears to be the result of changes either in red cell membrane rigidity or membrane viscosity. The PVP effect was reproducible, time- and temperature- dependent, and predicted reliably the Rh phenotype. These observations were used to develop a novel approach to the antiglobulin test in the blood bank.     

Spinal Cord Stimulation: A Comparison of Efficacy versus Other Novel Treatments for Refractory Angina Pectoris

Abstract: Recently much attention has been directed toward novel treatment alternatives for refractory angina pectoris. Refractory angina is persistent stable class III or IV angina despite maximally tolerated medical treatment in patients with end-stage coronary artery disease. Transmyocardial laser revascularization (TMLR), gene therapy, intermittent urokinase therapy, enhanced external balloon counterpulsation, and spinal cord stimulation have all been employed to treat refractory angina pectoris. TMLR and gene therapy are invasive open-chest procedures that have yielded controversial results. Intermittent urokinase and enhanced external balloon counterpulsation studies have limited follow-up times and require multiple clinic visits for treatment. Spinal cord stimulation has a proven short- and long-term efficacy and cost-effectiveness in the treatment of refractory angina. When compared to coronary artery bypass grafting (CABG), it has been shown to decrease the frequency of anginal attacks and consumption of short-acting nitrates to the same extent in refractory angina. Spinal cord stimulation's safety profile has also been well established and it can be used concurrently with cardiac pacemakers or MRI systems, provided the proper precautions are taken. Since spinal cord stimulation is a minimally invasive procedure with a favorable efficacy and safety profile, it should be considered as a valid treatment alternative after medical management has failed in refractory angina prior to implementing invasive modalities such as TMLR or gene therapy.     

Surgical management of symptomatic Chiari II malformation in infants and children

Purpose

Variation exists in the surgical methods employed for decompression of Chiari II malformation (CIIM), yet an evaluation of these techniques has not been performed. The purpose of this study was to assess the efficacy of bony decompression (cervical laminectomy alone versus suboccipital craniectomy with laminectomy) with or without dural augmentation for the treatment of symptomatic CIIM.

Methods

Clinical records of children 0–18 years of age who underwent surgical repair of myelomeningocele or CIIM decompression at St. Louis Children’s Hospital (SLCH) from 1990–2011 were reviewed. Signs/symptoms prompting decompression, surgical technique, operative parameters, and clinical outcomes were recorded for analysis.

Results

Thirty-three subjects were treated at SLCH for CIIM decompression. Twenty-six subjects underwent bony decompression only (21 cervical laminectomy alone, 5 suboccipital craniectomy?+?cervical laminectomy) while seven underwent bony decompression with upfront dural augmentation (three cervical laminectomy alone, four suboccipital craniectomy?+?cervical laminectomy). Median follow up was 5.0 years (range, 3 months–19 years). Symptomatic improvement was noted in 20/33 subjects (60.6 %). Sixty-two (61.5 %) percent of children who underwent bony decompression had symptomatic improvement, compared with 57.1 % of those with upfront dural augmentation (p?=?0.37). Estimated blood loss, operative time, and length of perioperative hospital stay appeared lower in the bony decompression group but were not statistically different in this limited cohort.

Conclusions

The results from this series suggest that bony CIIM decompression via tailored cervical laminectomies alone, without suboccipital craniectomy or upfront dural augmentation, is a reasonable initial management approach for decompression of symptomatic CIIM.     

Aspirin in coronary artery surgery: 1-year results of the Aspirin and Tranexamic Acid for Coronary Artery Surgery trial

Background

Aspirin may reduce the risk of vascular graft thrombosis after cardiovascular surgery. We previously reported the 30-day results of a trial evaluating aspirin use before coronary artery surgery. Here we report the 1-year outcomes evaluating late thrombotic events and disability-free survival.

Agminated segmental plaque‐type blue nevus associated with hypertrichosis and soft tissue hypertrophy: Report of a case and review of the literature

Blue nevi are common skin neoplasms that typically present as asymptomatic solitary papules, although they may rarely occur in an agminated configuration. We describe a case of agminated blue nevus in a segmental facial distribution associated with soft tissue hypertrophy and hypertrichosis in a 16‐year‐old boy and present a review of the literature. Although they are generally considered to be benign, concurrent soft tissue changes occurring within an agminated blue nevus should be investigated thoroughly to exclude alternate diagnoses.