Diagnostic utility of DNA methylation analysis in genetically unsolved pediatric epilepsies and CHD2 episignature refinement.

Sequence-based genetic testing identifies causative variants in ~ 50% of individuals with developmental and epileptic encephalopathies (DEEs). Aberrant changes in DNA methylation are implicated in various neurodevelopmental disorders but remain unstudied in DEEs. We interrogate the diagnostic utility of genome-wide DNA methylation array analysis on peripheral blood samples from 582 individuals with genetically unsolved DEEs. We identify rare differentially methylated regions (DMRs) and explanatory episignatures to uncover causative and candidate genetic etiologies in 12 individuals. Using long-read sequencing, we identify DNA variants underlying rare DMRs, including one balanced translocation, three CG-rich repeat expansions, and four copy number variants. We also identify pathogenic variants associated with episignatures. Finally, we refine the CHD2 episignature using an 850 K methylation array and bisulfite sequencing to investigate potential insights into CHD2 pathophysiology. Our study demonstrates the diagnostic yield of genome-wide DNA methylation analysis to identify causal and candidate variants as 2% (12/582) for unsolved DEE cases.

Instrumentation Failure in Adult Spinal Deformity Patients.

In recent years, advances in the surgical treatment of adult spinal deformity (ASD) have led to improved outcomes. Although these advances have helped drive the development of deformity surgery to meet the rising volume of patients seeking surgical treatment, many challenges have yet to be solved. Instrumentation failure remains one of the most common major complications following deformity surgery, associated with significant morbidity due to elevated re-operation rates among those experiencing mechanical complications. The two most frequently encountered subtypes of instrumentation failure are rod fracture (RF) and proximal junctional kyphosis/proximal junctional failure (PJK/PJF). While RF and PJK/PJF are both modes of instrumentation failure, they are two distinct entities with different clinical implications and treatment strategies. Considering that RF and PJK/PJF continue to represent a major challenge for patients with ASD and deformity surgeons alike, this review aims to discuss the incidence, risk factors, clinical impact, treatment strategies, preventive measures, and future research directions for each of these substantial complications.

Health care resource use and costs in patients with food allergies: a United States insurance claims database analysis.

AIMS: Food allergies impose a large clinical and financial burden on patients and the health care system. However, little is known about the factors associated with health care resource use and costs. The aim of this study was to investigate health care resource use and costs in individuals with food allergies utilizing health care in the United States. METHODS: We conducted a retrospective analysis of insurance claims data from the Merative MarketScan Research Databases (indexed from 1 January 2015 to 30 June 2022). All-cause and food allergy-related health care resource use, direct medical, and out-of-pocket costs for medical services were estimated for 12 months post-index using International Classification of Diseases [ICD] codes. RESULTS: Of 355,520 individuals with food allergies continuously enrolled in a health insurance plan for ≥12 months pre- and post-index, 17% had a food allergy-related emergency department visit and 0.9% were hospitalized. The top patient characteristic associated with all-cause and food allergy-related hospitalizations, all-cause costs, and food allergy-related outpatient visit costs was a Charlson Comorbidity Index score of ≥2. Food allergy-related direct medical and out-of-pocket costs were high among patients with a food allergy-related visit. Out-of-pocket cost per patient per year for outpatient visits, emergency department visits, and hospitalizations had an estimated mean of $1631 for patients with food allergy-related visits, which is ∼11% of the total costs for these services ($14,395 per patient per year). LIMITATIONS: Study limitations are primarily related to the nature of claims databases, including generalizability and reliance on ICD codes. Nevertheless, MarketScan databases provide robust patient-level insights into health care resource use and costs from a large, commercially insured patient population. CONCLUSION: The health care resource use of patients with food allergies imposes a burden on both the health care system and on patients and their families, especially if patients had comorbidities.

Some people with food allergies might need extra visits to the doctor or hospital to manage allergic reactions to food, and these visits add to the cost of medical services for both families and for health care providers. Using records of health insurance claims, we looked into the factors affecting medical visits and costs in people with food allergies in the United States. For people with food allergies, having additional medical conditions (measured using the Charleson Comorbidity Index) were linked with extra medical visits and costs. Out-of-pocket costs were high for people who visited a doctor or hospital for their food allergies (costing each person more than $1,600 per year). The total medical cost of food allergy-related care was $14,395 per person per year, paid for by families and health care providers. Our findings might help to better manage and treat people with food allergies and reduce medical costs.

Straightforward synthesis of complex polymeric architectures with ultra-high chain density.

Synthesis of complex polymeric architectures (CPAs) via reversible-deactivation radical polymerization (RDRP) currently relies on the rather inefficient attachment of monofunctional initiation/transfer sites onto CPA precursors. This drawback seriously limits the overall functionality of the resulting (macro)initiators and, consequently, also the total number of installable polymeric chains, which represents a significant bottleneck in the design of new polymeric materials. Here, we show that the (macro)initiator functionality can be substantially amplified by using trichloroacetyl isocyanate as a highly efficient vehicle for the rapid and clean introduction of trichloroacetyl groups (TAGs) into diverse precursors. Through extensive screening of polymerization conditions and comprehensive NMR and triple-detection SEC studies, we demonstrate that TAGs function as universal trifunctional initiators of copper-mediated RDRP of different monomer classes, affording low-dispersity polymers in a wide molecular weight range. We thus unlock access to a whole new group of ultra-high chain density CPAs previously inaccessible via simple RDRP protocols. We highlight new opportunities in CPA synthesis through numerous examples, including the de novo one-pot synthesis of a novel "star-on-star" CPA, the preparation of ß-cyclodextrin-based 45-arm star polymers, and facile grafting from otherwise problematic cellulose substrates both in solution and from surface, obtaining effortlessly ultra-dense, ultra-high-molecular weight bottle-brush copolymers and thick spatially-controlled polymeric coatings, respectively.

Am I Sedated or in Pain? Please Monitor by Brain.

How to cite this article: Gupta A, Tomar DS. Am I Sedated or in Pain? Please Monitor by Brain. Indian J Crit Care Med 2024;28(6):531-532.

Blended Tele-mentoring Support for Strengthening Antenatal Care by Private Health care Facilities: FOGSI VISTRIT INITIATIVE.

Introduction: The objective of the present initiative was to build capacity of health care providers in private sector along with standardisation of care during antenatal period for common antenatal problems of GDM and iron deficiency anaemia in private sector. Methods: A pilot project for all levels of health care providers including doctors, nurses, counsellors and laboratory technicians of 34 private facilities in six districts of Jharkhand was planned. Training modules for GDM and anaemia based on government of India guidelines were developed. End line evaluation included data collection and descriptive analysis of quantitative data quality scores from assessment standards on GDM and anaemia in pregnancy. Results: Knowledge assessment of health care providers and doctors through baseline and end line knowledge assessment survey questionnaire showed that 100% health care providers who were trained scored 85% or more in knowledge assessment questionnaires as seen by baseline and end line questionnaire results. All project hospitals (n = 34) in Jharkhand achieved quality standards of care in intervention period for gestational diabetes mellitus and anaemia in pregnancy. They achieved total score more than 80% and exceeded target of 80% of the quality standards. Conclusion: A systematic strengthening of private health care facilities through a blended tele-mentoring and onsite support is possible. Supplementary Information: The online version contains supplementary material available at 10.1007/s13224-023-01866-5.

The Impact of Autoantibodies on Outcomes in Patients with Idiopathic Pulmonary Fibrosis: Post-Hoc Analyses of the Phase III ASCEND Trial.

INTRODUCTION: Clinical practice guidelines recommend autoimmune serological testing in patients newly diagnosed with interstitial lung disease of apparently unknown cause who may have idiopathic pulmonary fibrosis (IPF), in order to exclude connective tissue disease (CTD). Autoantibody positivity has been associated with unique patient profiles and prognosis in patients with IPF who otherwise lack a CTD diagnosis. METHODS: This post-hoc analysis of patients with IPF from the Phase III ASCEND trial (NCT01366209) evaluated the association of antinuclear antibodies (ANA), rheumatoid factor (RF) and anti-cyclic citrullinated peptide (anti-CCP) status with baseline disease characteristics, disease progression [percent predicted forced vital capacity (%FVC), forced vital capacity (FVC) volume and progression-free survival (PFS)], and treatment outcomes with pirfenidone and placebo (%FVC, FVC and PFS). RESULTS: Of 555 participants, 244/514 (47.5%) were ANA positive (ANA+), 83/514 (16.1%) had high ANA+ (ANA titre ≥ 1:160 or positive nucleolar- or centromere-staining patterns), 60/555 (10.8%) were RF positive (RF+) and/or anti-CCP positive (anti-CCP+) and 270/514 (52.5%) were autoantibody negative (AAb-). Baseline demographics and characteristics were generally comparable between autoantibody subgroups. Although not statistically significant, more placebo-treated participants with ANA+ or high ANA+ had a decline from baseline to Week 52 of ≥ 10% in %FVC or death (48.7% and 55.9%, respectively) or in FVC volume or death (48.7% and 47.1%, respectively) compared with the AAb- group (%FVC or death: 42.0%; FVC volume or death: 42.0%). The RF+ and/or anti-CCP+ group was similar to AAb-. No differences were observed in PFS. A treatment benefit for pirfenidone versus placebo was observed regardless of autoantibody status [PFS: ANA+ HR (95% CI): 0.56 (0.37 to 0.86), P = 0.007; AAb- HR (95% CI): 0.50 (0.32 to 0.78), P = 0.002]. CONCLUSION: IPF disease course did not differ by autoantibody status in ASCEND. Pirfenidone had a treatment benefit regardless of the presence of ANA. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT01366209.

People with idiopathic pulmonary fibrosis sometimes have abnormal antibodies, called autoantibodies, in their blood. Uncommonly, autoantibodies may mistakenly target the person's own tissues, including the lungs. It is unknown whether these autoantibodies cause idiopathic pulmonary fibrosis or make it worse. This analysis looked at data from the ASCEND clinical trial in people with idiopathic pulmonary fibrosis, who were split randomly into two groups to receive tablets of either a medicine called pirfenidone or a placebo for 52 weeks. One goal was to see whether people with certain autoantibodies called antinuclear antibodies ('ANA' for short), rheumatoid factor ('RF') and anti-cyclic citrullinated peptide ('anti-CCP') had different traits from people without autoantibodies, such as age, race or smoking history. Other goals were to see if autoantibodies affected (1) how well people's lungs worked during the trial, (2) how quickly people's idiopathic pulmonary fibrosis got worse or they died and (3) how well pirfenidone worked. The analysis showed that most traits were similar in people with and without autoantibodies. In people who received placebo, the change in lung function during the trial was not different for people with ANA, RF or anti-CCP compared with people with no autoantibodies. People who received pirfenidone were less likely to have worsening lung function, or die, than people who received placebo, regardless of whether or not they had autoantibodies. Doctors evaluating patients with idiopathic pulmonary fibrosis should consider the impact of autoantibodies and feel confident that pirfenidone is effective regardless of whether or not autoantibodies are present.

PermDroid a framework developed using proposed feature selection approach and machine learning techniques for Android malware detection.

The challenge of developing an Android malware detection framework that can identify malware in real-world apps is difficult for academicians and researchers. The vulnerability lies in the permission model of Android. Therefore, it has attracted the attention of various researchers to develop an Android malware detection model using permission or a set of permissions. Academicians and researchers have used all extracted features in previous studies, resulting in overburdening while creating malware detection models. But, the effectiveness of the machine learning model depends on the relevant features, which help in reducing the value of misclassification errors and have excellent discriminative power. A feature selection framework is proposed in this research paper that helps in selecting the relevant features. In the first stage of the proposed framework, t-test, and univariate logistic regression are implemented on our collected feature data set to classify their capacity for detecting malware. Multivariate linear regression stepwise forward selection and correlation analysis are implemented in the second stage to evaluate the correctness of the features selected in the first stage. Furthermore, the resulting features are used as input in the development of malware detection models using three ensemble methods and a neural network with six different machine-learning algorithms. The developed models' performance is compared using two performance parameters: F-measure and Accuracy. The experiment is performed by using half a million different Android apps. The empirical findings reveal that malware detection model developed using features selected by implementing proposed feature selection framework achieved higher detection rate as compared to the model developed using all extracted features data set. Further, when compared to previously developed frameworks or methodologies, the experimental results indicates that model developed in this study achieved an accuracy of 98.8%.

Pursuing Clinical Predictors and Biomarkers for Progression in ILD: Analysis of the Pulmonary Fibrosis Foundation (PFF) Registry.

INTRODUCTION: Pulmonary fibrosis is a characteristic of various interstitial lung diseases (ILDs) with differing etiologies. Clinical trials in progressive pulmonary fibrosis (PPF) enroll patients based on previously described clinical criteria for past progression, which include a clinical practice guideline for PPF classification and inclusion criteria from the INBUILD trial. In this study, we compared the ability of past FVC (forced vital capacity) progression and baseline biomarker levels to predict future progression in a cohort of patients from the PFF Patient Registry. METHODS: Biomarkers previously associated with pathobiology and/or progression in pulmonary fibrosis were selected to reflect cellular senescence (telomere length), pulmonary epithelium (SP-D, RAGE), myeloid activation (CXCL13, YKL40, CCL18, OPN) and fibroblast activation (POSTN, COMP, PROC3). RESULTS: PFF or INBUILD-like clinical criteria was used to separate patients into past progressor and non-past progressor groups, and neither clinical criterion appeared to enrich for patients with greater future lung function decline. All baseline biomarkers measured were differentially expressed in patient groups compared to healthy controls. Baseline levels of SP-D and POSTN showed the highest correlations with FVC slope over one year, though correlations were low. CONCLUSIONS: Our findings provide further evidence that prior decline in lung function may not predict future disease progression for ILD patients, and elevate the need for molecular definitions of a progressive phenotype. Across ILD subtypes, certain shared pathobiologies may be present based on the molecular profile of certain biomarker groups observed. In particular, SP-D may be a common marker of pulmonary injury and future lung function decline across ILDs.

Genome sequencing enables diagnosis and treatment of SLC5A6 neuropathy.

The sodium-dependent multivitamin transporter encoded by SLC5A6 is responsible for uptake of biotin, pantothenic acid, and α-lipoic acid. Thirteen individuals from eight families are reported with pathogenic biallelic SLC5A6 variants. Phenotype ranges from multisystem metabolic disorder to childhood-onset peripheral motor neuropathy. We report three additional affected individuals with biallelic SLC5A6 variants. In Family A, a male proband (AII:1) presenting in early childhood with gross motor regression, motor axonal neuropathy, recurrent cytopenia and infections, and failure to thrive was diagnosed at 12 years of age via genome sequencing (GS) with a paternal NM_021095.4:c.393+2T>C variant and a maternal c.1285A>G p.(Ser429Gly) variant. An uncle with recurrent cytopenia and peripheral neuropathy was subsequently found to have the same genotype. We also report an unrelated female with peripheral neuropathy homozygous for the c.1285A>G p.(Ser429Gly) recurrent variant identified in seven reported cases, including this study. RT-PCR studies on blood mRNA from AII:1 showed c.393+2T>C caused mis-splicing with all canonically spliced transcripts in AII:1 containing the c.1285A>G variant. SLC5A6 mRNA expression in AII:1 fibroblasts was ~50% of control levels, indicative of nonsense-mediated decay of mis-spliced transcripts. Biotin uptake studies on AII:1 fibroblasts, expressing the p.(Ser429Gly) variant, showed an ~90% reduction in uptake compared to controls. Targeted treatment of AII:1 with biotin, pantothenic acid, and lipoic acid resulted in clinical improvement. Health Economic analyses showed implementation of GS as an early investigation could have saved $ AUD 105,988 and shortened diagnostic odyssey and initiation of treatment by up to 7 years.

The mental health burden of food allergies: Insights from patients and their caregivers from the Food Allergy Research & Education (FARE) Patient Registry.

Background: Food allergies impose a large psychosocial burden, including mental, emotional, and social aspects, on both patients and their caregivers. Patients, caregivers, and their families often experience anxiety, isolation, and fear around food allergies. Objective: To assess the real-world mental health burden of food allergies, using the Food Allergy Research & Education (FARE) Patient Registry (NCT04653324). Methods: Self-reported data from patients with food allergies, and their caregivers, were analyzed from the FARE Food Allergy History and Mental Health Concerns surveys. Odds ratios were also calculated as a measure of association between patient food allergy characteristics and the likelihood of having mental health concerns or a formal mental health diagnosis. Results: The FARE Patient Registry included 1680 patients/caregivers. Anxiety (54%) and panic (32%) were the most common emotions that patients reported as a result of eating the food that produced an allergic reaction. About two-thirds of patients reported mental health concerns related to food allergies (62%), including anxiety after an allergic reaction, anxiety about living with food allergies, and concerns about food avoidance. Caregivers also experienced fear for the safety of their children, and often sought mental health care to cope with worry related to caring for patients with food allergies. The likelihood of having food allergy-related mental health concerns was increased for patients experiencing more than 1 reaction per year (OR 1.68-1.90) and was lowered for patients having a formal mental health diagnosis (OR 0.43). Caregivers filling out the FARE survey for pediatric patients (OR 4.03) and experiencing food allergy-related mental health concerns (OR 2.36) were both significant predictors for having a formal mental health diagnosis. Conclusion: Our study highlights a continuing unmet need for mental health screening and support as part of the management of patients with food allergies.

Systematic review with expert consensus on use of extracorporeal hemoadsorption in septic shock: An Indian perspective.

BACKGROUND: Septic shock is a severe form of sepsis characterised by deterioration in circulatory and cellular-metabolic parameters. Despite standard therapy, the outcomes are poor. Newer adjuvant therapy, such as CytoSorb® extracorporeal haemoadsorption device, has been investigated and shown promising outcome. However, there is a lack of some guidance to make clinical decisions on the use of CytoSorb® haemoadsorption as an adjuvant therapy in septic shock in Indian Setting. Therefore, this expert consensus was formulated. AIM: To formulate/establish specific consensus statements on the use of CytoSorb® haemoadsorption treatment based on the best available evidence and contextualised to the Indian scenario. METHODS: We performed a comprehensive literature on CytoSorb® haemoadsorption in sepsis, septic shock in PubMed selecting papers published between January 2011 and March 2023 2021 in English language. The statements for a consensus document were developed based on the summarised literature analysis and identification of knowledge gaps. Using a modified Delphi approach combining evidence appraisal and expert opinion, the following topics related to CytoSorb® in septic shock were addressed: need for adjuvant therapy, initiation timeline, need for Interleukin -6 levels, duration of therapy, change of adsorbers, safety, prerequisite condition, efficacy endpoints and management flowchart. Eleven expert members from critical care, emergency medicine, and the intensive care participated and voted on nine statements and one open-ended question. RESULTS: Eleven expert members from critical care, emergency medicine, and the intensive care participated and voted on nine statements and one open-ended question. All 11 experts in the consensus group (100%) participated in the first, second and third round of voting. After three iterative voting rounds and adapting two statements, consensus was achieved on nine statements out of nine statements. The consensus expert panel also recognised the necessity to form an association or society that can keep a registry regarding the use of CytoSorb® for all indications in the open-ended question (Q10) focusing on "future recommendations for CytoSorb® therapy". CONCLUSION: This Indian perspective consensus statement supports and provides guidance on the use of CytoSorb® haemoadsorption as an adjuvant treatment in patients with septic shock to achieve optimal outcomes.

Effect of pulmonary rehabilitation on functional status dyspnea and quality of life among post COVID-19 patients.

OBJECTIVES: To determine the Effect of pulmonary rehabilitation on functional status dyspnea and quality of life among post-COVID-19 patients. METHODS: The study utilized an experimental study design with a total of 120 participants to examine the effects of pulmonary rehabilitation. The participants were divided into two groups: Group A (experimental group) and Group B (control group). Demographic variables such as age, weight, and height were collected. Health-related quality of life (HRQL), post-COVID-19 functional status, and perceived exertion were assessed before and after the intervention. RESULTS: Group A demonstrated a higher mean age than Group B, indicating a significant age difference between the two groups, with no significant difference observed in weight and height. Following the intervention, Group A exhibited significant improvement in HRQL, post-COVID-19 functional status, and perceived exertion compared to Group B. CONCLUSION: Pulmonary rehabilitation had positive effects on health-related quality of life, post-COVID-19 functional status, and perceived exertion. The experimental group benefited from improved HRQL, suggesting an overall enhancement in their well-being. The study provides preliminary evidence supporting the effectiveness of pulmonary rehabilitation as an intervention for improving outcomes in individuals post-COVID-19.

Acute Kidney Injury and ECMO: Two Sides of the Same Coin.

How to cite this article: Gupta S, Tomar DS. Acute Kidney Injury and ECMO: Two Sides of the Same Coin. Indian J Crit Care Med 2024;28(1):3-4.

The clinical burden of food allergies: Insights from the Food Allergy Research & Education (FARE) Patient Registry.

Background: Food allergies are serious and potentially life-threatening, and often place a large burden on patients and their caregivers, including impacts on quality of life. Objective: To assess the real-world patient burden of food allergies, using self-reported data available from the Food Allergy Research & Education (FARE) Patient Registry (NCT04653324). Methods: The FARE Patient Registry is voluntary and captures real-world experiences of adults and pediatric patients in the United States, and their caregivers, through a series of surveys assessing patient health and experiences with food allergies. Self-reported data were descriptively analyzed. Results: The FARE study cohort included 5587 patients with food allergies; 82% had multiple food allergies and 62% were aged <18 years. About half of the patients were first diagnosed by an allergist/immunologist (53%), most commonly with a skin prick test (71%) or a serum immunoglobulin E test (62%). This analysis found that food allergies (most commonly peanut [66%], tree nuts [61%], egg [43%], and milk [37%]) impart a large clinical burden on patients, many of whom experience food-related allergic reactions and comorbidities. Many patients experienced >1 food-related allergic reaction per year (42%), with 46% experiencing food-induced anaphylaxis. Half of all food-related allergic reactions occurred at home. Accidental exposures to food allergens were experienced by 77% of patients. The most common allergic comorbidities reported by patients with food allergies were atopic dermatitis (48%), asthma (46%), and allergic rhinitis (39%). The clinical burden of food allergies were found to be greater in patients with multiple food allergies, and different for adults versus pediatric patients. Conclusion: This is the first study to assess patient experience and disease burden information from patients contributing to the FARE Patient Registry, thus providing a unique insight into the lives of patients in the United States with food allergies. These insights may assist clinicians and other public health stakeholders in the management of patients with food allergies.

Evaluation and model to achieve sex parity in cataract surgical coverage in Theni district, India.

BACKGROUND/AIMS: To propose an approach to determine the target ratio of cataract surgical rates (CSRs) of female to male subpopulations to increase sex parity in cataract surgical coverage (CSC), based on the sex gap in cataract burden and incidence, and demonstrate its application to Theni district, India. METHODS: A population-based longitudinal study between January 2016 and April 2018. We recruited 24 327 participants using random cluster sampling. We conducted detailed eye examinations of 7087 participants aged ≥40 years (4098 females, 2989 males). We fit exponential models to the age-specific and sex-specific cataract burden and estimated annual incidence rates. We developed a spreadsheet-based planning tool to compute the target CSR ratio of female to male subpopulations. RESULTS: Among those aged ≥40 years, cataract burden was 21.4% for females and 17.5% for males (p<0.05). CSC was 73.9% for females versus 78.6% for males (p<0.05), with an effective CSC of 52.6% for females versus 57.6% for males (p<0.05). Treating only incident cataracts each year requires a target CSR ratio of female to male subpopulations of 1.30, while addressing in addition 10% of the coverage backlog for females and 5% for males requires a target CSR ratio of 1.48. CONCLUSIONS: The female population in Theni district, as in many low-income and middle-income countries, bears a higher cataract burden and lower CSC. To enhance sex parity in coverage, both the higher number of annual incident cataracts and the larger backlog in females will need to be addressed.

Mechanical Thrombectomy for Pediatric Arterial Ischemic Stroke from Acute M2 Occlusion.

Pediatric large-vessel occlusion has a poor natural history. Recent retrospective studies have demonstrated the potential benefits, feasibility, and safety profile of mechanical thrombectomy in children. However, the role of thrombectomy in pediatric M2 occlusions remains uncertain. In this clinical report, we present a multicenter series of 6 pediatric patients with acute M2 occlusion (female = 1, male = 5; age range, 0.9-16.0 years, mean = 9.2). All 6 patients having undergone thrombectomy had excellent clinical outcomes (pediatric mRS = 0-1) at 3 months and final available follow-up (median, 12 months; range, 3-72 months). Factors relevant to treatment decision-making in pediatric M2 occlusions are discussed, including the important role of multidisciplinary team discussions during acute management.

Biomechanical analysis of complications following T10-Pelvis spinal fusion: A population based computational study.

Proximal junctional kyphosis (PJK) and proximal junctional failure (PJF) are challenging complications of long fusion constructs for the treatment of adult spinal deformity. The objective of this study is to understand the biomechanical stresses proximal to the upper instrumentation of a T10-pelvis fusion in a large patient cohort. The pre-fusion models were subject-specific thoracolumbar spine models that incorporate the height, weight, spine curvature, and muscle morphology of 250 individuals from the Framingham Heart Study Multidetector CT Study. To create post-fusion models, the subject-specific models were further modified to eliminate motion between the intervertebral joints from T10 to the pelvis. OpenSim analysis tools were used to calculate the medial lateral shear force, anterior posterior shear force, and compressive force on the T9 vertebra during the static postures. Differences between pre-fusion and post-fusion T9 biomechanics were consistent between increased segmental mobility and unchanged segmental mobility conditions. For all static postures, compression decreased (p < 0. 0005). Anterior-posterior shear force significantly increased (p < 0. 0005) during axial twist and significantly increased (p < 0. 0005) during trunk flexion. Medial lateral shear force significantly increased (p < 0. 0005) during axial twist. This computational study provided the first use of subject-specific models to investigate the biomechanics of long spinal fusions. Patients undergoing T10-Pelvis fusion were predicted to have increased shear forces and decreased compressive force at the T9 vertebra, independent of change in segmental mobility. The computational model shows potential for the investigation of spinal fusion biomechanics to reduce the risk of PJK or PJF.