Do Current Recommendations for Upper Instrumented Vertebra Predict Shoulder Imbalance? An Attempted Validation of Level Selection for Adolescent Idiopathic Scoliosis

Background

Shoulder balance for adolescent idiopathic scoliosis (AIS) patients is associated with patient satisfaction and self-image. However, few validated systems exist for selecting the upper instrumented vertebra (UIV) post-surgical shoulder balance.

Questions/Purposes

The purpose is to examine the existing UIV selection criteria and correlate with post-surgical shoulder balance in AIS patients.

Methods

Patients who underwent spinal fusion at age 10–18 years for AIS over a 6-year period were reviewed. All patients with a minimum of 1-year radiographic follow-up were included. Imbalance was determined to be radiographic shoulder height |RSH| ≥ 15 mm at latest follow-up. Three UIV selection methods were considered: Lenke, Ilharreborde, and Trobisch. A recommended UIV was determined using each method from pre-surgical radiographs. The recommended UIV for each method was compared to the actual UIV instrumented for all three methods; concordance between these levels was defined as “Correct” UIV selection, and discordance was defined as “Incorrect” selection.

Results

One hundred seventy-one patients were included with 2.3 ± 1.1 year follow-up. For all methods, “Correct” UIV selection resulted in more shoulder imbalance than “Incorrect” UIV selection. Overall shoulder imbalance incidence was improved from 31.0% (53/171) to 15.2% (26/171). New shoulder imbalance incidence for patients with previously level shoulders was 8.8%.

Conclusions

We could not identify a set of UIV selection criteria that accurately predicted post-surgical shoulder balance. Further validated measures are needed in this area. The complexity of proximal thoracic curve correction is underscored in a case example, where shoulder imbalance occurred despite “Correct” UIV selection by all methods.

Electronic supplementary material

The online version of this article (doi:10.1007/s11420-015-9451-y) contains supplementary material, which is available to authorized users.     

Molecular basis of Tank-binding kinase 1 activation by transautophosphorylation

Tank-binding kinase (TBK)1 plays a central role in innate immunity: it serves as an integrator of multiple signals induced by receptor-mediated pathogen detection and as a modulator of IFN levels. Efforts to better understand the biology of this key immunological factor have intensified recently as growing evidence implicates aberrant TBK1 activity in a variety of autoimmune diseases and cancers. Nevertheless, key molecular details of TBK1 regulation and substrate selection remain unanswered. Here, structures of phosphorylated and unphosphorylated human TBK1 kinase and ubiquitin-like domains, combined with biochemical studies, indicate a molecular mechanism of activation via transautophosphorylation. These TBK1 structures are consistent with the tripartite architecture observed recently for the related kinase IKKβ, but domain contributions toward target recognition appear to differ for the two enzymes. In particular, both TBK1 autoactivation and substrate specificity are likely driven by signal-dependent colocalization events.     

The association of pre‐operative STOP‐BANG scores with postoperative critical care admission

The STOP‐BANG questionnaire screens for obstructive sleep apnoea. We retrospectively analysed the independent association of pre‐operative variables with postoperative critical care admission using multivariable logistic regression for patients undergoing elective surgery from January to December 2011. Of 5432 patients, 338 (6.2%) were admitted postoperatively to the critical care unit. In multivariate analysis, the odds ratios (95% CI) for critical care admission were: 2.2 (1.1–4.6), p = 0.037; 3.2 (1.2–8.1), p = 0.017; and 5.1 (1.8–14.9), p = 0.002, for STOP‐BANG scores of 4, 5 and ≥ 6, respectively. The odds ratio was also independently increased for: each year of age, 1.015 (1.004–1.026), p = 0.019; asthma, 1.6 (1.1–2.4), p = 0.016; obstructive sleep apnoea, 3.2 (1.9–5.6), p < 0.001; and for ASA physical status 2, 3 and ≥ 4, 2.1 (1.4–3.3), 6.5 (3.9–11.0), 6.3 (2.9–13.8), respectively, p < 0.001 for all.     

Patterns and prognostic indicators of response to CML treatment in a multi-country medical record review study

We conducted a review of patient medical records to assess treatment response patterns and prognostic indicators of response among chronic myeloid leukemia (CML) patients in the United States, the United Kingdom, Germany, and Japan. All 1,063 patients selected met the following inclusion criteria: aged 18 or older and in chronic phase at the time of diagnosis, Philadelphia chromosome and/or BCR-ABL positive, received first-line treatment with imatinib, and not enrolled in a randomized clinical trial during the period of retrospective review. Multivariable logistic regression models were used to evaluate prognostic indicators of complete hematological response (CHR), complete cytogenetic response (CCyR), and complete or major molecular response (C/MMR). Among patients treated with first-line imatinib, CHR at three months, CCyR at 12 months, and C/MMR at 18 months were observed in 53, 53.1, and 57.8 % of patients, respectively. Among patients treated with second-line dasatinib or nilotinib, CHR was achieved at three months in 49 and 42 %, CCyR at 12 months in 32 and 23 %, and MMR at 18 months in 30.5 and 26.1 % of patients, respectively. Prognostic indicators of first-line response included age, race, and Sokal score. For second-line treatment, duration of first-line hematological response and choice of drug used were also significant.     

Understanding the interaction of Lipoarabinomannan with membrane mimetic architectures

Lipoarabinomannan (LAM) is a critical virulence factor in the pathogenesis of Mycobacterium tuberculosis, the causative agent of tuberculosis. LAM is secreted in urine and serum from infected patients and is being studied as a potential diagnostic indicator for the disease. Herein, we present a novel ultra-sensitive and specific detection strategy for monomeric LAM based on its amphiphilic nature and consequent interaction with supported lipid bilayers. Our strategy involves the capture of LAM on waveguides functionalized with membrane mimetic architectures, followed by detection with a fluorescently labeled polyclonal antibody. This approach offers ultra-sensitive detection of lipoarabinomannan (10?fM, within 15?min) and may be extended to other amphiphilic markers. We also show that chemical deacylation of LAM completely abrogates its association with the supported lipid bilayers. The loss of signal using the waveguide assay for deacylated LAM, as well as atomic force microscopy (AFM) images that show no change in height upon addition of deacylated LAM support this hypothesis. Mass spectrometry of chemically deacylated LAM indicates the presence of LAM-specific carbohydrate chains, which maintain antigenicity in immunoassays. Further, we have developed the first three-dimensional structural model of mannose-capped LAM that provides insights into the orientation of LAM on supported lipid bilayers.     

Circulating microparticle tissue factor,thromboembolism and survival in pancreaticobiliary cancers

Background

Tissue factor (TF), the physiologic initiator of coagulation, is over-expressed in pancreatic cancer, and is associated with a pro-coagulant and pro-angiogenic state. We hypothesized that in patients with pancreaticobiliary cancers (PBC), elevated circulating microparticle-associated TF (MP-TF) activity would be associated with thrombosis and worsened survival.

Patients and Methods

Clinical data and plasma were obtained for consecutive patients with PBC seen at Roswell Park Cancer Institute from 2005-08. MP-TF activity levels were measured using a TF-dependent FXa generation assay.

Results

The study population comprised 117 patients, including pancreatic (n = 80), biliary (n = 34) or unknown primary histologically consistent with PBC (n = 3). Of these, 52 patients (44.5%) experienced thromboembolism, including pulmonary embolism (n = 15), deep venous thrombosis (n = 21) and other arterial or venous events (n = 32). Mean TF was 2.15 (range 0.17- 31.01) pg/mL. Median survival was 98.5 days for MP-TF activity ≥ 2.5 pg/mL versus 231 days for MP-TF activity < 2.5 pg/mL (p < 0.0001). In multivariate analysis, elevated MP-TF activity was associated with both VTE (OR 1.4, 95% CI 1.1-1.6) and mortality (HR 2.5, 95% CI 1.4-4.5).

Conclusions

Elevated circulating MP-TF activity is associated with thrombosis and worsened survival in patients with PBC. MP-TF activity as a prognostic biomarker warrants further prospective evaluation.     

Clinico – diagnostic and therapeutic relevance of computed tomography scan of brain in children with partial seizures

Background:

Therapeutic relevance of computed tomography (CT) in children with partial seizures is reported to be remarkably low (1-2%). However, in the developing countries where infections involving the nervous system are common, routine CT scan of brain may help in finding treatable causes of seizures.

Objective:

Aim of this study was to evaluate the significance of CT scan of brain in the management of children with partial seizures.

Materials and Methods:

Children with partial epilepsy, whose predominant seizure type was focal motor seizures, were included in the study. CT scan of brain was done in all children aged between 1 month and 12 years with partial seizures of unknown etiology prospectively. The clinical findings of these children were noted along with the CT findings.

Results:

Between August 2001 and July 2002, of the 200 children with seizure disorder 50 children who satisfied the inclusion criteria were included in the study. CT scan of brain was normal in 16 children (32%) and was abnormal in 34 children (68%). Twenty children (~60% of abnormal scan) had potentially correctable lesions: Tuberculoma (n = 13), neurocysticercosis (n = 3), and brain abscess (n = 4). Five children had changes representing static pathology that did not influence patient management. The clinical features correlated with CT findings in 78% children.

Conclusion:

Children with partial motor seizures have high probability of having abnormal findings on CT scan of brain, especially, neuro-infections which are potentially treatable. Therefore, CT scan brain should be carried out in all children with partial motor seizures especially, in developing countries.     

Serum levels of interferon-gamma, tumour necrosis factor-alpha, soluble interleukin-6R and soluble cell activation markers for monitoring response to treatment of leprosy reactions

Identifying pathogen and host-related laboratory parameters are essential for the early diagnosis of leprosy reactions. The present study aimed to clarify the validity of measuring the profiles of serum cytokines [interleukin (IL)-4, IL-6, IL-10, interferon (IFN)-gamma and tumour necrosis factor (TNF)-alpha], the soluble IL-6 receptor (sIL-6R), soluble T cell (sCD27) and macrophage (neopterin) activation markers and Mycobacterium leprae-specific anti-PGL-I IgM antibodies in relation to the leprosy spectrum and reactions. Serum samples from 131 Indonesian leprosy patients (82 non-reactional leprosy patients and 49 reactional) and 112 healthy controls (HC) from the same endemic region were investigated. Forty-four (89.8%) of the reactional patients had erythema nodosum leprosum (ENL) while only five (10.2%) had reversal reaction (RR). Follow-up serum samples after corticosteroid treatment were also obtained from 17 of the patients with ENL and one with RR. A wide variability in cytokine levels was observed in the patient groups. However, IFN-gamma and sIL-6R were elevated significantly in ENL compared to non-ENL patients. Levels of IFN-gamma, TNF-alpha and sIL-6R declined significantly upon corticosteroid treatment of ENL. Thus, although the present study suggests limited applicability of serial measurement of IFN-gamma, TNF-alpha and sIL-6R in monitoring treatment efficacy of ENL, reactions it recommends a search for a wider panel of more disease-specific markers in future studies.