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.     

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.     

Locomotor Training and Muscle Function After Incomplete Spinal Cord Injury: Case Series

Abstract

Background/Objective: To determine whether 9 weeks of locomotor training (LT) results in changes in muscle strength and alterations in muscle size and activation after chronic incomplete spinal cord injury (SCI). Study Design: Longitudinal prospective case series.

Methods: Five individuals with chronic incomplete SCI completed 9 weeks of LT. Peak isometric torque, torque developed within the initial 200 milliseconds of contraction (Torque₂₀₀), average rate of torque development (ARTD), and voluntary activation deficits were determined using isokinetic dynamometry for the knee-extensor (KE) and plantar-flexor (PF) muscle groups before and after LT. Maximum muscle crosssectional area (CSA) was measured prior to and after LT.

Results: Locomotor training resulted in improved peak torque production in all participants, with the largest increases in the more-involved PF (43.9% ± 20.0%), followed by the more-involved KE (21.1% ± 12.3%). Even larger improvements were realized in Torque200 and ARTD (indices of explosive torque), after LT. In particular, the largest improvements were realized in the Torque200 measures of the PF muscle group. Improvements in torque production were associated with enhanced voluntary activation in both the KE and ankle PF muscles and an increase in the maximal CSA of the ankle PF muscles.

Conclusion: Nine weeks of LT resulted in positive alterations in the KE and PF muscle groups that included an increase in muscle size, improved voluntary activation, and an improved ability to generate both peak and explosive torque about the knee and ankle joints.     

Genetic polymorphisms of CCL2, CCL5, CCR2 and CCR5 genes in Sahariya tribe of North Central India: an association study with pulmonary tuberculosis

The association of genetic variants of chemokines, CCL2 [MCP-1 (monocyte chemoattractant protein-1)], CCL5 [RANTES (regulated on activation, normal T-cell expressed and secreted)] and their receptors CCR2 and CCR5, respectively, earlier reported to be associated with susceptibility to pulmonary tuberculosis (PTB) in certain ethnic populations, were explored in Sahariya tribe, a primitive tribe of North Central India having a high prevalence of TB. We genotyped 215 cases and 215 controls of Sahariya tribe for polymorphisms in CCL2 (-2518A/G, -362G/C) by PCR-RFLP method and in CCR2 (V64I), CCL5 (-403G/A, -28C/G) and CCR5 (-59029G/A) by ARMS-PCR method. The frequencies of 'AA' genotype and 'A' allele of -403G/A were found significantly higher in cases than in controls (OR, 2.616 [95%CI, 1.302-5.320] and OR, 1.348 [95%CI, 0.980-1.853], respectively). Conversely, the frequencies of 'AA' genotype and 'A' allele of V64I were significantly (p=0.05 and 0.04, respectively) higher in controls than in cases. Also, the "AA" genotype of V64I was found to provide significant (p=0.05) protection against high bacillary load (3+). Likewise, the comparison of frequencies of different combinations of these polymorphisms further strengthens the association of -403G/A with susceptibility and V64I with resistance to TB in Sahariya tribe. However, no significant association of other polymorphisms with either resistance or susceptibility to TB was found. Thus, our findings support the association of -403G/A and V64I polymorphisms with genetic susceptibility and resistance to TB, respectively , alone or in combination with other polymorphisms in Sahariya tribe.     

The untapped potential of Instagram to facilitate rheumatology academia

Clinical Rheumatology - Instagram allows for graphical and visual information exchange. This paper aims to explore the current landscape of rheumatology on Instagram and analyse the accounts...     

The Story of the Texas Pain Society: Formation and Function of a Regional Pain Society

Abstract: The idea of forming a Texas Pain Society came to the Founders in 1987 due to disparity and deficiencies in the practice of pain management in the United States and, in particular, the State of Texas. The Founders considered very carefully the implication of forming such a society. They diligently mapped out the mission and goals of the Texas Pain Society in those early formative years. This report is the history of Texas Pain Society as the activities unfolded from 1989 to 2011. The reader may question why there is a need to tell such a story. We believe strongly that, with disparities of standards of practice in pain medicine and poor recognition of advances in pain management, this scenario is quite common in many states and countries. The practitioners of pain management in these regions certainly must have considered getting together and forming a consensus on the standards of practice in their communities. This historical report of the Texas Pain Society provides the relevant information necessary and the efforts to be made for a society’s mission to achieve its goals and have an ongoing impact in its own region. We hope that we have shed some light on a process for the formation of a regional pain society such as ours. ?