Development of a simplified new method of bone age estimation using three bones of the hand and wrist.

Though the Greulich and Pyle (GP) method is easy, inter-observer variability, differential maturation of hand bones influences ratings. The Tanner-Whitehouse (TW) method is more accurate, but cumbersome. A simpler method combining the above, such that it utilizes fewer bones without affecting accuracy, would be widely used and more applicable in clinical practice. OBJECTIVES: 1. Devising a simplified method utilizing three bones of the hand and wrist for bone age (BA) assessment. 2. Testing whether the 3 bone method gives comparable results to standard methods (GP,TW2,TW3) in Indian children. METHODS: Developmental stages and corresponding BA for radius, hamate, terminal phalanx (left middle finger) epiphyses combining stages from GP,TW3 atlases were described; BA were rated by two blinded observers. 3 bone method ratings were compared with the same dataset analyzed earlier using GP,TW2,TW3 (4 raters). RESULTS: Radiographs analysed:493 (Girls=226). Mean chronological age:9.4 ± 4.6 yrs, mean BA 3 bone:9.8 ± 4.8 yrs, GP:9.6 ± 4.8 yrs, TW3:9.3 ± 4.5 yrs, TW2:9.9 ± 5.0 yrs. The 3 bone method demonstrated no significant inter-observer variability (p = 0.3, mean difference = 0.02 ± 0.6 yrs); a strong positive correlation (p < 0.0001) with GP (r = 0.985), TW3 (r = 0.983) and TW2 (r = 0.982) was noted. Bland-Altman plots demonstrated good agreement; the root mean square errors between 3 bone and GP,TW3,TW2 ratings were 0.6,0.7,0.6 years; mean differences were 0.19,0.49,-0.14 years respectively. Greatest proportion of outliers (beyond ±1.96 SD of mean difference) was between 6 and 8 years age for difference in 3 bone and GP, and between 4-6 years for difference in 3 bone and TW3,TW2. CONCLUSION: The 3 bone method has multiple advantages; it is easier, tackles differential maturation of wrist and hand bones, has good reproducibility, without compromising on accuracy rendering it suitable for office practice.

Is it worth the risk? Frailty transition and complications following robotic total knee arthroplasty: A retrospective observational study.

BACKGROUND: Frailty is an underutilized prognostic parameter in the geriatric population. Our study aimed to analyse the frailty incidence, its transition over 1 year and its influence on complication rate in patients undergoing elective robotic-assisted total knee arthroplasty (TKA). METHODS: This was a retrospective study wherein an accumulation of deficits model was used to evaluate frailty of 435 consecutive patients undergoing primary unilateral Mako-assisted cemented TKA between January 2020 and July 2021. Based upon the preoperative values, participants were divided into three groups; non-frail (FI < 0.11), vulnerable (0.11-0.20) and frail (FI > 0.20) states and were followed up for 1 year for change in frailty class, complications, re-admissions and mortality. RESULTS: A total of 435 patients were divided into three groups, non-frail (178), vulnerable (208) and frail (49). Improvement in mean frailty scores was seen in all three groups (P < 0.0001); 21.63% of the vulnerable and 48.97% of the frail participants improved by one frailty class. Multivariate analysis showed the co-relation of change in frailty index (ΔFI) with preoperative FI (r = 0.083) and Knee Society Score (KSS) (r = 0.742). The frail group had a significantly higher re-admission rate over 1 year. When compared with the vulnerable group, the frail group had a higher hazard ratio for readmission (3.12 vs. 0.96) and complications (1.62 vs. 1.26). CONCLUSION: Although frail individuals are at a higher risk for readmissions and perioperative complications, TKA significantly improves the mobility and frailty status of elderly individuals. With explained higher risk of complications, surgeons should not refrain from offering TKA to elderly frail individuals disabled with knee pain.

Intraoperative Periprosthetic Fractures during primary Total knee arthroplasty: Experience from an Asian high-volume arthroplasty centre.

BACKGROUND: Intraoperative periprosthetic fracture (IF) is an under-reported complication in primary total knee arthroplasty (TKA). This study aimed to audit the outcomes and complication rates in patients encountering IF during primary TKA and propose a new classification for its management. METHODS: A nested case-control study was performed at a tertiary referral hospital where 50 patients encountering IF during primary TKA operated by a single surgeon team between January 2016 to May 2021, were compared with 150 (3:1) age-, gender- and implant-matched patients not encountering IF. Demographic data, risk factors, outcomes and complications of both groups were compared at a minimum follow up of 1 year. RESULTS: The incidence of IF was 0.45%, with 44 fractures in the femur (88%), six (12%) in the tibia and none in the patella. Medial collateral ligament avulsion fracture (54.54%) in the femur and medial plateau fracture (66.66%) in the tibia were the most common fracture types. At final follow up, the fracture group had higher rates of 90-day re-admissions (8% vs. 2.66%, P = 0.095), deep infection (4% vs. 0.66%, P = 0.15) and revisions (6% vs. 1.33%, P = 0.06). The mean Knee Society Score was not significantly different between the two groups (152.22 ± 9.25 vs. 161.68 ± 11.22, P = 0.642) with union being achieved in all but one patient at a mean duration of 9.6 weeks. CONCLUSIONS: Patients with severe and fixed deformities have a higher risk for IF. The occurrence of fracture and the complexity of surgery equally contribute to the higher complication rates. Appropriately managed fractures have comparable functional outcomes.

Measurement of LAG-3 Expression Across Multiple Staining Platforms With the 17B4 Antibody Clone.

CONTEXT.­: An immunohistochemistry (IHC) assay developed to detect lymphocyte-activation gene 3 (LAG-3), a novel immune checkpoint inhibitor target, has demonstrated high analytic precision and interlaboratory reproducibility using a Leica staining platform, but it has not been investigated on other IHC staining platforms. OBJECTIVE.­: To evaluate the performance of LAG-3 IHC assays using the 17B4 antibody clone across widely used IHC staining platforms: Agilent/Dako Autostainer Link 48 and VENTANA BenchMark ULTRA compared to Leica BOND-RX (BOND-RX). DESIGN.­: Eighty formalin-fixed, paraffin-embedded melanoma tissue blocks were cut into consecutive sections and evaluated using staining platform-specific IHC assays with the 17B4 antibody clone. Duplicate testing was performed on the BOND-RX platform to assess intraplatform agreement. LAG-3 expression using a numeric score was evaluated by a pathologist and with a digital scoring algorithm. LAG-3 positivity was determined from manual scores using a 1% or greater cutoff. RESULTS.­: LAG-3 IHC staining patterns and intensities were visually similar across all 3 staining platforms. Spearman and Pearson correlations were 0.75 or greater for interplatform and BOND-RX intraplatform concordance when LAG-3 expression was evaluated with a numeric score determined by a pathologist. Correlation increased with a numeric score determined with a digital scoring algorithm (Spearman and Pearson correlations ≥0.88 for all comparisons). Overall percentage agreement was 77.5% or greater for interplatform and BOND-RX intraplatform comparisons when LAG-3 positivity was determined using a 1% or greater cutoff. CONCLUSIONS.­: Data presented here demonstrate that LAG-3 expression can be robustly and reproducibly assessed across 3 major commercial IHC staining platforms using the 17B4 antibody clone.

Adoption of robotics in arthroplasty- a survey of perceptions, utilization and challenges with technology amongst Indian surgeons.

Introduction: Total joint replacement surgeries are standard procedures for managing end-stage hip or knee arthritis. Despite advances in technology, some patients experience dissatisfaction after total knee arthroplasty (TKA). Robotic technology has evolved significantly and has shown promise in improving component positioning, alignment, and surgical outcomes. However, the widespread adoption of robotics in arthroplasty faces challenges such as high costs, a steep learning curve, and limited evidence on long-term outcomes. Methods: This cross-sectional observational study used a structured self-administered online survey to assess the perceptions of Indian arthroplasty surgeons regarding robotic technology. The survey included questions about the surgeon's background, experience, perceptions of robotic joint replacement, and limiting factors for robotic usage. A total of 417 responses were collected from practising arthroplasty surgeons. Results: Most participants(78.1 %) expressed a willingness to adopt robotics in their arthroplasty practice if the cost of installation was reduced. Robotic users were more convinced about the benefits of robotics, including improved alignment, reduced pain, faster rehabilitation, and better outcomes. High-volume robotic surgeons demonstrated a greater belief in the broader potential of robotics beyond implant positioning and alignment. The major barriers to adoption were the high cost of installation and limited insurance coverage for robotic-assisted procedures. Lack of formal robotic training opportunities, resistance from corporate management, patient acceptance issues, and limited published literature supporting robotic advantages were also cited as limiting factors. Conclusion: Robotic technology is increasingly being adopted in India for TKA. The main obstacle to widespread adoption is the high cost of installation. As technology costs decrease, we can expect a rise in the number of installations across the country. Advocacy from national orthopaedic organizations may be needed to address insurance reimbursement challenges. Overall, this study provides valuable insights into the perceptions and challenges associated with the adoption of robotic technology in arthroplasty in India.

A Hidden "Suspender" in Irreducible Isolated Anteromedial Radial Head Dislocations - A Case Report and Review.

Introduction: Isolated anteromedial radial head dislocations are rare and are infrequently associated with hidden musculotendinous sling of superficial brachialis or biceps tendon impeding closed reduction. Failure to identify this impeding tendon can lead an unsuccessful and unstable open reduction surgery. This is the first case of its kind where the delayed presenting patient was treated without resection of the tendon. Case Report: We describe a case of an irreducible neglected isolated anteromedial radial head dislocation in a 7-year-old male child presenting 2 months following injury with features of active heterotrophic ossification (HO). Open surgical exploration 4 months following the injury through the Boyd's approach revealed a hidden musculotendinous sling of superficial brachialis suspending the radial head anteromedially. Releasing the adhesions and relocation of the tendon allowed spontaneous radiocapitellar joint reduction. The joint congruency was maintained at 18 months and the functional outcome was excellent with a mild flexion-pronation deficit. Conclusion: Awareness of the rare impeding biceps/brachialis tendinous sling in cases of isolated anteromedial radial head dislocation can guide the surgeon to order an indicated preoperative magnetic resonance imaging and plan an early open reduction. HO may occur frequently with such an injury considering the severity of the associated soft-tissue injury.

Influence of vitamin D levels on outcomes and nosocomial COVID-19 infection in patients undergoing total knee arthroplasty- a cohort study.

Purpose: This study aimed to audit the effects of vitamin D3 on the early functional outcomes, the incidence of nosocomial COVID-19 infection and complications in patients undergoing elective Total Knee Arthroplasty (TKA). Methods: This was a retrospective study involving patients undergoing primary unilateral TKA between January 2020 to May 2021 operated by a single surgeon using a single implant. Participants were divided into two cohorts, Deficient-vitamin D3 level <20 ng/ml and Sufficient-vitamin D3 level ≥20 ng/ml. Assessment for Knee Society Score and Oxford Knee Score (OKS) was done preoperatively and one year after TKA. Nosocomial COVID-19 infection rate, 30-day re-admissions and complications were noted during the study. Results: 235 patients were divided into 2 cohorts matched by age, gender and ASA grades. 74 patients belonged to the deficient group and 161 belonged to the sufficient group. The mean preoperative scores in the sufficient group were higher than the deficient group (OKS = 15.74 vs 12.95; KSS = 88.91vs 85.62). Similarly, the one-year postoperative scores in the sufficient group were significantly higher (OKS = 36.54 vs 35.16; KSS = 164.01 vs 161.22). A linear correlation was present between preoperative score (r = 0.273) & post-operative scores (r = 0.141) with serum vitamin D3 levels. Vitamin D3 deficient individuals had higher nosocomial COVID-19 infection rate (10.81% vs 4.96%,p = 0.16). The incidence of complications like DVT, embolism, stroke, infection and fracture were not statistically different in the two groups. Conclusion: Vitamin D positively influences the outcomes of TKA and protects against nosocomial COVID-19 infection in patients undergoing elective TKA.

Radiological Evaluation of the Phenotype of Indian Osteoarthritic Knees based on the Coronal Plane Alignment of the Knee Classification (CPAK).

Background: Understanding constitutional alignment of the lower limb is essential to optimize alignment strategies during total knee arthroplasty. The coronal plane alignment of knee (CPAK) classification system was proposed as a comprehensive assessment tool based on coronal alignment and variations in joint line obliquity (JLO). This prospective observational cross-sectional study aimed to evaluate the phenotype of knees in the Indian population based on the CPAK system. Methods: Two cohorts of individuals (250 young healthy volunteers and 250 elderly patients with knee osteoarthritis) underwent radiological assessment with long-leg radiographs and were classified based on the CPAK system. Measurements included the mechanical and arithmetic hip-knee-ankle angles (mHKA, aHKA), joint line obliquity (JLO), lateral distal femoral angle (mLDFA) and medial proximal tibial angle (mMPTA). Knees were grouped into 9 CPAK phenotypes based on aHKA and JLO. Results: A total of 1000 knees were evaluated. In cohort-1 of healthy young adults, most knees were distributed in the CPAK class II phenotype (128 knees, 25.6%) followed by CPAK Type I (106 knees, 21.2%). In cohort-2 of elderly arthritic adults, most knees were distributed in Type I (294 knees, 58.8%) with constitutional varus and apex-distal joint line orientation. Conclusion: The majority of the study population was found to have constitutional varus alignment. In addition, a high proportion of patients in both categories, especially arthritic patients undergoing TKA, were found to have varus alignment with an apex-distal oblique joint line. This classification may help optimize component positioning to restore constitutional alignment and joint line orientation during TKA.

Dissecting inflammatory complications in critically injured patients by within-patient gene expression changes: a longitudinal clinical genomics study.

BACKGROUND: Trauma is the number one killer of individuals 1-44 y of age in the United States. The prognosis and treatment of inflammatory complications in critically injured patients continue to be challenging, with a history of failed clinical trials and poorly understood biology. New approaches are therefore needed to improve our ability to diagnose and treat this clinical condition. METHODS AND FINDINGS: We conducted a large-scale study on 168 blunt-force trauma patients over 28 d, measuring ∼400 clinical variables and longitudinally profiling leukocyte gene expression with ∼800 microarrays. Marshall MOF (multiple organ failure) clinical score trajectories were first utilized to organize the patients into five categories of increasingly poor outcomes. We then developed an analysis framework modeling early within-patient expression changes to produce a robust characterization of the genomic response to trauma. A quarter of the genome shows early expression changes associated with longer-term post-injury complications, captured by at least five dynamic co-expression modules of functionally related genes. In particular, early down-regulation of MHC-class II genes and up-regulation of p38 MAPK signaling pathway were found to strongly associate with longer-term post-injury complications, providing discrimination among patient outcomes from expression changes during the 40-80 h window post-injury. CONCLUSIONS: The genomic characterization provided here substantially expands the scope by which the molecular response to trauma may be characterized and understood. These results may be instrumental in furthering our understanding of the disease process and identifying potential targets for therapeutic intervention. Additionally, the quantitative approach we have introduced is potentially applicable to future genomics studies of rapidly progressing clinical conditions. TRIAL REGISTRATION: ClinicalTrials.gov NCT00257231

Decoding the behaviour of extracapsular proximal femur fracture- dislocation - A systematic review of a rare fracture pattern.

PURPOSE: Proximal femoral extracapsular fractures with associated ipsilateral hip dislocation is an extremely rare pattern of injury. These fractures may be associated with a spectrum of severity from isolated trochanteric fractures to comminuted intertrochanteric and subtrochanteric fractures with hip dislocation. To date, this pattern of injury is not described in any injury classification system and no clear cut guidelines for the same are available. The aim of this review is to provide an evidence based pooled analysis of the existing literature and develop guidelines that help surgeons tackle this rare injury pattern. METHODS: A comprehensive review of the literature was undertaken using the PRISMA. Case reports and series of Extracapsular proximal femoral fracture dislocations published in PubMed, EMBASE, Springer, OvidSP, ScienceDirect, Web of Science and Google scholar between inception of journals to May 2020 were included in the review. A pooled analysis comparing the demography, pattern of the fracture, mode and mechanism of injury with the clinical and radiological outcome and complications was performed. RESULTS: 52 cases from 46 case studies were included in the pooled analysis. There was a near significant association between avascular necrosis and mean time to reduction (p = 0.0865). Individuals with compound injury had 10.12 times higher risk of avascular necrosis (p = 0.009). No significant association between the pattern of proximal femur fracture and incidence of avascular necrosis (p = 0.116, chi-square). There was no significant association between polytrauma and poor clinical outcomes. (p = 0.231). CONCLUSIONS: Principles of damage control orthopaedics should be followed in unstable patients with this rare fracture dislocation. Percutaneous Schanz screw reduction manoeuvre can be attempted gently with a low threshold to perform an open reduction. Every attempt at salvaging the fractured hip must be performed in young individuals with an arthroplasty standby for comminuted and unreconstructable cases.

Functional and Cost Audit of Primary Total Knee Arthroplasty in Public vs Private Hospitals: A Retrospective Cohort Study.

BACKGROUND: Government funded hospitals are believed to be stigmatised with 'substandard care' and constant fear of infection. The aim of this study is to compare the results and direct expenditure incurred for total knee arthroplasty (TKA) done at a government funded public teaching hospital with an economy packaged private hospital in India. MATERIALS AND METHODS: A review of electronic and physical records of the patients operated by the senior author for primary TKA at a government funded hospital and a private hospital spanning 2007 to 2019 was done. A retrospective cohort study was designed matching the implant design and the ASA grade of the patients. Knee injury and Osteoarthritis Outcome Score (KOOS), Hospital for Special Surgery score (HSS), Knee Society Score (KSS) at 2 years follow-up were the primary outcome parameters. The retrieved data describing the cost of surgery and perioperative complications were analyzed. The confounders were minimized by including only the surgeries performed by the author, using the same instruments and implants in similar operating theatre environments. RESULTS: This study involved two cohorts comprising 280 patients each, with no differences in gender, ASA grade and primary diagnosis. There was no significant difference in the 2-year HSS, KSS and KOOS score between the two groups. The 2-year cumulative incidence of major and minor complications in both the study cohorts showed no significant difference. The mean cost of an uncomplicated primary TKA (2019) in government hospital was INR. 85,927; 39.476% of that required in a private setup (INR. 2,17,667). CONCLUSION: Affordable TKA package in a government funded hospital can produce results comparable to that in a private hospital setup at a reasonably lower cost without increasing the complication rates.

Development and Performance of a CD8 Gene Signature for Characterizing Inflammation in the Tumor Microenvironment across Multiple Tumor Types.

Across multiple tumor types, immune checkpoint inhibitors (ICIs) have demonstrated clinical benefit to patients with cancer, yet there is a need to identify predictive biomarkers of response to these therapies. A multiparameter gene expression profiling-based tumor inflammation assay may offer robust characterization of the tumor microenvironment, thereby extending the utility of single-gene analysis or immunohistochemistry (IHC) in predicting response to ICIs. The authors interrogated 1778 commercially procured, formalin-fixed, paraffin-embedded samples using gene expression profiling and pathology-assisted digital CD8 IHC. A machine-learning approach was used to develop gene expression signatures that predicted CD8+ immune cell abundance as surrogates for tumor inflammation in melanoma and squamous cell carcinoma of the head and neck samples. An assay for a 16-gene CD8 signature was developed and analytically validated across 12 tumor types. CD8 signature scores correlated with CD8 IHC in a platform-independent manner, and inflammation prevalence was similar between assay methods for all tumor types except prostate cancer and small cell lung cancer. In retrospective analyses, CD8 signature scores were associated with progression-free survival and overall survival with nivolumab in patients with urothelial carcinoma from CheckMate 275. This study demonstrated that the CD8 signature assay can be used to accurately quantify CD8+ immune cell abundance in the tumor microenvironment and has potential clinical utility for determining patients with cancer likely to respond to ICIs.

Bilateral Traumatic Proximal Humeral Physeal Fracture in an Adolescent Child - A Rare Case Report and Review of Literature.

INTRODUCTION: Proximal humerus fractures in the pediatric population are relatively uncommon accounting for <3% of all the fractures. Being the growing end of the bone, these fractures have a high threshold for conservative management. Dilemma does exist when such a fracture occurs in a borderline adolescent age group. Occurrence of bilateral physeal fractures in the same anatomical location is exceedingly rare and such a case of bilateral traumatic physeal fracture of proximal humerus has not been reported in the literature. CASE PRESENTATION: A 14-year-old male child presented with post-traumatic pain and swelling of both the shoulders. Radiographs revealed displaced proximal humerus physeal fracture bilaterally. The displaced fracture was treated with closed reduction and percutaneous fixation using smooth Kirschner wires and cannulated screw. CONCLUSION: Considering the bilateral nature of the injury and a borderline age with limited remodeling potential, a lower threshold for conservative therapy must be adopted in young active individuals. High-velocity trauma does form a major cause of such bilateral injuries, however, nutritional deficiencies and metabolic causes should be kept in mind while treating such a rare pattern of injury.

A case of posterior HIP dislocation with intertrochanteric fracture: Beware of the sharp calcar spike.

Posterior dislocation of hip is commonly associated with acetabular lip fractures. Involvement of neck, trochanter or intertrochanteric region is uncommon. Very few cases of posterior hip dislocation with ipsilateral intertrochanteric fracture in the absence of head or acetabular fracture have been reported in the literature. We report such a case in a 19yr male treated with open reduction and internal fixation with sliding hip screw with good functional and radiological outcome at 1 year. Being an extremely rare form of injury, such an injury pattern does not exist in present classification systems. There is a need to revise the existing classification systems and formulate a protocol for the management of the same. Such fractures may also be associated with a sharp calcar spike of the proximal fragment impinging femoral vessels and branches. Attempt at closed reduction without adequate anatomical orientation of the spike can lead to hazardous vascular consequences.

Reliable Gene Expression Profiling from Small and Hematoxylin and Eosin-Stained Clinical Formalin-Fixed, Paraffin-Embedded Specimens Using the HTG EdgeSeq Platform.

Clinical biomarker studies are often hindered by the scarcity or suboptimal quality of biological specimens. EdgeSeq, a transcriptomics analysis platform, combines quantitative nuclease protection assay technology with next-generation sequencing, using small amounts of starting material and delivering reproducible gene expression profiles from challenging material, such as formalin-fixed, paraffin-embedded (FFPE) tissue. To evaluate EdgeSeq for analysis of archives of stained FFPE tissue, EdgeSeq was performed on unstained, hematoxylin and eosin (H&E)-stained, and immunohistochemistry-stained slides from patients with small-cell and non-small-cell lung cancer. Pairwise comparisons of gene expression profiles from stained and unstained slides showed higher Pearson correlation coefficients with H&E staining (0.86 to 0.97) than with immunohistochemistry staining (0.21 to 0.56). A 25-gene interferon-γ signature score from unstained slides showed a Pearson correlation coefficient of 0.92 with H&E-stained slides and a significant Spearman correlation (P = 0.0025) with immune scores. To test gene expression profiling in small samples, FFPE sample equivalents were examined from 5.0 to 0.08 mm2 of a section (5 µm thick); sample equivalents ≥0.31 mm2 showed alignment rates >69% and pairwise Pearson correlation coefficients ≥0.87. EdgeSeq can, thus, be used to profile small and H&E-stained FFPE tumor specimens to obtain biomarker data from limited tissue in oncology clinical trials and enable research into tumor microenvironment and immune cell engagement with tumors at the locoregional level.

Understanding heterogeneous tumor microenvironment in metastatic melanoma.

A systemic analysis of the tumor-immune interactions within the heterogeneous tumor microenvironment is of particular importance for understanding the antitumor immune response. We used multiplexed immunofluorescence to elucidate cellular spatial interactions and T-cell infiltrations in metastatic melanoma tumor microenvironment. We developed two novel computational approaches that enable infiltration clustering and single cell analysis-cell aggregate algorithm and cell neighborhood analysis algorithm-to reveal and to compare the spatial distribution of various immune cells relative to tumor cell in sub-anatomic tumor microenvironment areas. We showed that the heterogeneous tumor human leukocyte antigen-1 expressions differently affect the magnitude of cytotoxic T-cell infiltration and the distributions of CD20+ B cells and CD4+FOXP3+ regulatory T cells within and outside of T-cell infiltrated tumor areas. In a cohort of 166 stage III melanoma samples, high tumor human leukocyte antigen-1 expression is required but not sufficient for high T-cell infiltration, with significantly improved overall survival. Our results demonstrate that tumor cells with heterogeneous properties are associated with differential but predictable distributions of immune cells within heterogeneous tumor microenvironment with various biological features and impacts on clinical outcomes. It establishes tools necessary for systematic analysis of the tumor microenvironment, allowing the elucidation of the "homogeneous patterns" within the heterogeneous tumor microenvironment.

Morphological and surface properties of electrospun chitosan nanofibers.

Nonwoven fiber mats of chitosan with potential applications in air and water filtration were successfully made by electrospinning of chitosan and poly(ethyleneoxide) (PEO) blend solutions. Electrospinning of pure chitosan was hindered by its limited solubility in aqueous acids and high degree of inter- and intrachain hydrogen bonding. Nanometer-sized fibers with fiber diameter as low as 80 +/- 35 nm without bead defects were made by electrospinning high molecular weight chitosan/PEO (95:5) blends. Fiber formation was characterized by fiber shape and size and was found to be strongly governed by the polymer molecular weight, blend ratios, polymer concentration, choice of solvent, and degree of deacetylation of chitosan. Weight fractions of polymers in the electrospun nonwoven fibers mats were determined by thermal gravimetric analysis and were similar to ratio of polymers in the blend solution. Surface properties of fiber mats were determined by measuring the binding efficiency of toxic heavy metal ions like chromium, and they were found to be related with fiber composition and structure.

Plasma Protein Biomarkers for the Prediction of CSF Amyloid and Tau and [18F]-Flutemetamol PET Scan Result.

Background: Blood biomarkers may aid in recruitment to clinical trials of Alzheimer's disease (AD) modifying therapeutics by triaging potential trials participants for amyloid positron emission tomography (PET) or cerebrospinal fluid (CSF) Aß and tau tests. Objective: To discover a plasma proteomic signature associated with CSF and PET measures of AD pathology. Methods: Liquid chromatography-tandem mass spectrometry (LC-MS/MS) based proteomics were performed in plasma from participants with subjective cognitive decline (SCD), mild cognitive impairment (MCI), and AD, recruited to the Amsterdam Dementia Cohort, stratified by CSF Tau/Aß42 (n = 50). Technical replication and independent validation were performed by immunoassay in plasma from SCD, MCI, and AD participants recruited to the Amsterdam Dementia Cohort with CSF measures (n = 100), MCI participants enrolled in the GE067-005 study with [18F]-Flutemetamol PET amyloid measures (n = 173), and AD, MCI and cognitively healthy participants from the EMIF 500 study with CSF Aß42 measurements (n = 494). Results: 25 discovery proteins were nominally associated with CSF Tau/Aß42 (P < 0.05) with associations of ficolin-2 (FCN2), apolipoprotein C-IV and fibrinogen ß chain confirmed by immunoassay (P < 0.05). In the GE067-005 cohort, FCN2 was nominally associated with PET amyloid (P < 0.05) replicating the association with CSF Tau/Aß42. There were nominally significant associations of complement component 3 with PET amyloid, and apolipoprotein(a), apolipoprotein A-I, ceruloplasmin, and PPY with MCI conversion to AD (all P < 0.05). In the EMIF 500 cohort FCN2 was trending toward a significant relationship with CSF Aß42 (P ≈ 0.05), while both A1AT and clusterin were nominally significantly associated with CSF Aß42 (both P < 0.05). Conclusion: Associations of plasma proteins with multiple measures of AD pathology and progression are demonstrated. To our knowledge this is the first study to report an association of FCN2 with AD pathology. Further testing of the proteins in larger independent cohorts will be important.

Lemmel Syndrome Secondary to Duodenal Diverticulitis: A Case Report.

Lemmel syndrome occurs when a duodenal diverticulum causes obstructive jaundice due to a mechanical obstruction of the common bile duct. Additional pathophysiologic processes may also contribute to the development of Lemmel syndrome. These include duodenal diverticula causing dysfunction of the sphincter of Oddi as well as compression of the common bile duct by duodenal diverticula. It is uncommon for duodenal diverticulum to become inflamed. We report the case of a 25-year-old female presenting with unintentional weight loss and fatigue. Since her initial labs were concerning for possible infection with hepatobiliary abnormalities, a contrast-enhanced CT was obtained. This study revealed a large periampullary diverticulum with mucosal enhancement and fat stranding consistent with diverticulitis.

Extra-adrenal pheochromocytoma at the organ of Zuckerkandl: a case report and literature review.

Pheochromocytomas and paragangliomas are tumors that occur in characteristic locations and are commonly detected on imaging studies. A correct diagnosis is important because of differences in associated neoplasms, risk for malignancy, and need for genetic testing. In addition, associated complications, including death, can be avoided if appropriately recognized and treated. Here, we report a rare case of an extra-adrenal paraganglioma of the organ of Zuckerkandl.