Neurosarcoidosis: An under-diagnosed cause of myelopathy.

Sarcoidosis is a granulomatous disorder with multi-organ involvement, and etiology still remains unknown. Neurosarcoidosis is the involvement of the nervous system in sarcoidosis. Spinal cord involvement is usually intra-dural, but extra-dural involvement can also occur. Here, we report a case of 30 years old lady presenting with subacute onset paraparesis with bladder and bowel involvement, which was finally diagnosed as sarcoidosis-associated myelopathy with the longitudinally extensive transverse myelitis (LETM) phenotype.

Safety considerations for dietary supplement manufacturers in the United States.

Due to significant dietary supplement use in the US, product manufacturers must understand the importance of implementing a robust approach to establishing safety for all ingredients, including dietary ingredients, components, and finished dietary supplement products. Different regulatory pathways exist by which the safety of dietary ingredients can be established, and thus allowed to be marketed in a dietary supplement. For individual dietary ingredients, safety information may come from a variety of sources including history of safe use, presence of the ingredient in foods, and/or non-clinical and clinical data. On occasion safety data gaps are identified for a specific ingredient, particularly those of botanical origin. Modern toxicological methods and models can prove helpful in satisfying data gaps and are presented in this review. For finished dietary supplement products, issues potentially impacting safety to consider include claims, product labeling, overages, contaminants, residual solvents, heavy metals, packaging, and product stability. In addition, a safety assessment does not end once a product is marketed. It is important that manufacturers actively monitor and record the occurrence of adverse events reported in association with the use of their products, in accordance with the law. Herein, we provide a comprehensive overview of considerations for assessing dietary supplement safety.

High-resolution double vision of the allosteric phosphatase PTP1B.

Protein tyrosine phosphatase 1B (PTP1B) plays important roles in cellular homeostasis and is a highly validated therapeutic target for multiple human ailments, including diabetes, obesity and breast cancer. However, much remains to be learned about how conformational changes may convey information through the structure of PTP1B to enable allosteric regulation by ligands or functional responses to mutations. High-resolution X-ray crystallography can offer unique windows into protein conformational ensembles, but comparison of even high-resolution structures is often complicated by differences between data sets, including non-isomorphism. Here, the highest resolution crystal structure of apo wild-type (WT) PTP1B to date is presented out of a total of ∼350 PTP1B structures in the PDB. This structure is in a crystal form that is rare for PTP1B, with two unique copies of the protein that exhibit distinct patterns of conformational heterogeneity, allowing a controlled comparison of local disorder across the two chains within the same asymmetric unit. The conformational differences between these chains are interrogated in the apo structure and between several recently reported high-resolution ligand-bound structures. Electron-density maps in a high-resolution structure of a recently reported activating double mutant are also examined, and unmodeled alternate conformations in the mutant structure are discovered that coincide with regions of enhanced conformational heterogeneity in the new WT structure. These results validate the notion that these mutations operate by enhancing local dynamics, and suggest a latent susceptibility to such changes in the WT enzyme. Together, these new data and analysis provide a detailed view of the conformational ensemble of PTP1B and highlight the utility of high-resolution crystallography for elucidating conformational heterogeneity with potential relevance for function.

Screening for cryptococcal antigen in asymptomatic people with HIV: urgent need in Eastern India.

OBJECTIVE: Cryptococcal meningitis (CM) is a leading cause of mortality in people with HIV (PWH). Despite recommendation by the National programme, cryptococcal antigen (CrAg) screening in PWH with CD4 + <200/µl has not been implemented in practice. Therefore, we conducted a prospective study in government funded Antiretroviral treatment centre to determine the prevalence of asymptomatic cryptococcal antigenemia in PWH with CD4 + cell count <200 cells/µl, subclinical cryptococcal meningitis in serum CrAg positive subjects and their outcome. METHOD: Serum CrAg (BIOSYNEX CryptoPS) screening was conducted in newly diagnosed asymptomatic retro-positive adults with CD4 + <200/µl between January 2021 and March 2022. We also conducted cerebrospinal fluid (CSF) CrAg testing in all PWH who were serum CrAg positive and appropriate therapy was instituted. All the enrolled participants were followed up till February 2023. RESULT: Among enrolled 142 PWH patients, 22 (15.49%) were positive for serum CrAg. Among these 22, seven (31.8%) patients had CD4 + cell count between 100 and 199 cells/µl. CSF CrAg was positive in 11 (50%) serum CrAg positive cases. Serum CrAg positivity was significantly associated with low CD4 + cell count, poor clinical stage and concomitant Pneumocystis pneumonia. However, mortality was not significantly different in Serum CrAg positive and negative PWH. None of the deaths in CrAg positive PWH was due to cryptococcal disease. CONCLUSION: Higher prevalence of cryptococcal antigenemia and subclinical CM among PWH with CD4 + cell count <200 cells/µl with good treatment outcomes with therapy reiterates the need for CrAg screening among PWH in Eastern India.

Biomechanical Evaluation of Fourth Generation Minimally Invasive Distal First Metatarsal Osteotomy-Akin Osteotomy Technique on First Ray Articular Contact Properties.

BACKGROUND: Hallux valgus is a common deformity encountered but remains a complex clinical entity. Fourth-generation minimally invasive surgery (MIS) techniques consisting of a percutaneous distal metatarsal transverse osteotomy combined with an Akin osteotomy have been used to address mild to severe hallux valgus deformities. The benefits of an MIS approach include improved cosmesis, faster recovery, lower opiate requirement, immediate weightbearing, and favorable outcomes relative to a traditional, open procedure. An understudied area with respect to hallux valgus correction is the effect that osteotomies can have on the articular contact properties of the first ray following correction. METHODS: Sixteen paired cadaveric specimens were dissected to include the first ray and tested in a customized apparatus. Specimens were randomized to receive a distal transverse osteotomy translated either 50% or 100% of the width of the first metatarsal shaft. The osteotomy was performed with either a 0° or 20° distal angulation of the burr relative to the shaft in the axial plane. Specimens were tested in the intact state and following the distal first metatarsal osteotomy for peak pressure, contact area, contact force and center of pressure at the first metatarsophalangeal (MTP) and first tarsometatarsal (TMT) joints. An Akin osteotomy was then performed on each specimen, and peak pressure, contact area, contact force, and center of pressure were recalculated. RESULTS: There was a notable decrease in peak pressure, contact area, and contact force across the TMT joint with greater shifts of the capital fragment. However, at 100% translation of the capital fragment, distal angulation of the osteotomy by 20° appears to improve loading across the TMT joint. Addition of the Akin osteotomy at 100% translation also aids in increasing the contact force across the TMT joint. The MTP joint is less sensitive to changes in shifts and angulation of the capital fragment. The Akin osteotomy also leads to increased contact force across the MTP joint when the capital fragment is translated 100%. CONCLUSION: While the clinical significance is unknown, larger shifts of the capital fragment lead to greater load alterations at the level of the TMT joint than the MTP joint. Distal angulation of the capital fragment and the addition of an Akin osteotomy can aid in reducing the size of those changes. The Akin can lead to increased contact forces at the MTP joint with 100% translation of the capital fragment. LEVEL OF EVIDENCE: Not applicable, Biomechanical study.

The Effect of Chilled vs Room-Temperature Irrigation on Thermal Energy Dissipation During Minimally Invasive Calcaneal Osteotomy of Cadaver Specimens.

Background: Minimally invasive (MIS) calcaneal osteotomy has grown in popularity in recent years to address hindfoot deformity. A potential complication is thermal bone necrosis secondary to heat generation from the burr that may lead to osteotomy nonunion. Irrigation is commonly employed to reduce this risk. The effect of irrigation on reducing heat accumulation remains an understudied area. The purpose of this study was to evaluate the effect of cooled vs room-temperature irrigation on thermal energy dissipation during calcaneal osteotomy using a Shannon burr. Methods: Fourteen cadaveric limbs at room temperature (68 °F) were randomized to receive either cooled saline (7 limbs) or room-temperature (7 limbs) irrigation during MIS calcaneal osteotomy. Two thermocouple probes were inserted 5 mm away from the plane of the osteotomy, on the proximal and distal sides, respectively. A 3 × 30-mm Shannon burr was used to perform the osteotomy. The burr was run continuously with continuous irrigation using either room-temperature (68 °F) or chilled (37 °F) irrigation, until the osteotomy was completed. Temperature was recorded at 0, 15, 30, 45, and 60 seconds for the 2 groups and used as a measure of thermal energy accumulation. Results: Both room-temperature and chilled irrigation were effective in minimizing temperature change. On the proximal side, an overall mean increase of 2.5 °F with room-temperature irrigation and a mean decrease of 1.0 °F with chilled irrigation were observed at the 60-second interval (P = .004). On the distal side, there was a mean increase of 1.3 °F with room-temperature irrigation and a mean increase of 0.5 °F with chilled irrigation (P = .05). Conclusion: For the duration of an MIS calcaneal osteotomy, both continuous room-temperature and chilled irrigation can minimize temperature increases and potentially reduce the risk of an osteotomy nonunion. Clinical Relevance: Both room-temperature and chilled irrigation can minimize bone temperature increases during MIS calcaneal osteotomy.

Cholesterol Chip for the Study of Cholesterol-Protein Interactions Using SPR.

Cholesterol, an important lipid in animal membranes, binds to hydrophobic pockets within many soluble proteins, transport proteins and membrane bound proteins. The study of cholesterol-protein interactions in aqueous solutions is complicated by cholesterol's low solubility and often requires organic co-solvents or surfactant additives. We report the synthesis of a biotinylated cholesterol and immobilization of this derivative on a streptavidin chip. Surface plasmon resonance (SPR) was then used to measure the kinetics of cholesterol interaction with cholesterol-binding proteins, hedgehog protein and tyrosine phosphatase 1B.

Early Catastrophic Failure of a Synthetic Cartilage Implant for Hallux Rigidus.

Hallux rigidus is a common arthritic disorder of the foot. Surgical treatments are varied, from isolated cheilectomy to arthrodesis. A synthetic cartilage implant has been embraced recently as a joint-sparing alternative to arthrodesis, with good early and midterm outcomes. However, early clinical failures have been described relating to implant subsidence. This case report focuses on another mode of failure consisting of early catastrophic wear resulting in conversion to a lengthening arthrodesis at short-term follow-up.Levels of Evidence: Level V.

Management of Hallux Valgus in Metatarsus Adductus.

Metatarsus adductus is common clinical entity with an estimated prevalence of approximately 30%. Multiple radiographic methods exist to evaluate the extent of the deformity, with the Sgarlato and Engel methods most commonly used. Surgical treatment varies, consisting of proximal versus distal metatarsal osteotomies, TMT arthrodesis, and realignment of the lesser rays. Particularly in severe cases, addressing all deformities is critical to obtaining a good outcome.

State of the Art in Lesser Metatarsophalangeal Instability.

Advancements in lesser metatarsophalangeal (MTP) instability have involved the use of minimally invasive surgery techniques, synthetic augmentation of existing transfers, and use of arthroscopy for both diagnosing and addressing MTP disorder. Advances in imaging modalities, particularly MRI, have aided in diagnosing subtle instability. Clinical outcomes seem to be similar to traditional approaches as the indications and applicability continue to evolve.

Biomechanical Comparison of the Influences of 2 Proximal Metatarsal Osteotomies on First Ray Articular Contact Characteristics.

BACKGROUND: An understudied area of proximal first metatarsal osteotomies is the effect on articular contact properties following the surgeries. Potential long-term risks include altered joint mechanics and possible arthritic progression. A biomechanical comparison of articular characteristics of the proximal opening wedge and Ludloff osteotomies was performed in this study. It was hypothesized that the proximal opening wedge osteotomy (POWO) would lead to greater alterations in articular contact properties along the first ray. METHODS: Seven paired fresh-frozen below-knee cadaveric limbs with hallux valgus were selected. Specimens in each pair were tested in the intact state and then randomized to receive either a Ludloff or POWO. A 4-mm opening wedge osteotomy was used in all cases. Loading of the flexor hallucis longus was to 100 N using an instrumented tensioner. A 28-N load was added at the distal phalanx to simulate the ground reaction force. First metatarsophalangeal (MTP) and tarsometatarsal (TMT) articular properties were recorded simultaneously using 2 pressure sensors. For each state, a pressure map was generated and contact area, peak pressure, and center of pressure were calculated. Wilcoxon signed-rank test was used to assess statistical significance. RESULTS: Average peak pressure was noted to be elevated at the MTP (4.6 vs 6.9 mPa, P = .04) and TMT (3.3 mPa vs 5.1 mPa, P = .30) joints when comparing the Ludloff and the POWO, respectively. Contact area was also noted to be lower in the POWO relative to the Ludloff for the MTP (86.6 vs 69.1 mm2, P = .30) but not the TMT joints (89.1 vs 88.5 mm2, P = .97). There was a slight plantar-lateral and dorsomedial shift in pressure at the MTP and TMT articulations, respectively, of the POWO relative to the Ludloff. A trend toward decreased contact force within the TMT joint was noted following opening wedge osteotomy relative to the intact state (103.8 vs 113.9 N, P = .31), while forces were elevated at the MTP joint (104.3 vs 96.0 N, P = .63), although not statistically significant. Smaller increases in TMT and MTP joint forces were noted following the Ludloff when compared to the intact state (95.6 vs 93.3 N at TMT and 109.2 vs 103.2 N at MTP). CONCLUSION: POWO can potentially change articular contact characteristics along the TMT and MTP articulations of the first ray. This could possibly lead to altered loading patterns and possible long-term damage vs other osteotomies. CLINICAL RELEVANCE: While it is unlikely that the changes observed with the sizes of the osteotomy commonly used would lead to long-term significant clinical consequences, further study with larger group sizes would be beneficial.

Assessing the Utilization of Total Ankle Replacement in the United States.

BACKGROUND: Total ankle arthroplasty (TAR) has been shown to be a cost-effective procedure relative to conservative management and ankle arthrodesis. Although its use has grown considerably over the last 2 decades, it is less common than arthrodesis. The purpose of this investigation was to analyze the cost and utilization of TAR across hospitals. METHODS: Our analytical sample consisted of Medicare claims data from 2011 and 2012 for Inpatient Prospective Payment System hospitals. Outcome variables of interest were the likelihood of a hospital performing TAR, the volume of TAR cases, TAR hospital costs, and hospital profit margins. Data from the 2010 Cost Report and Medicare inpatient claims were utilized to compute average margins for TAR cases and overall hospital margins. TAR cost was calculated based on the all payer cost-to-charge ratio for each hospital in the Cost Report. Nationwide Inpatient Sample data were used to generate descriptive statistics on all TAR patients across payers. RESULTS: Medicare participants accounted for 47.5% of the overall population of TAR patients. Average implant cost was $13 034, accounting for approximately 70% of the total all-payer cost. Approximately, one-third of hospitals were profitable with respect to primary TAR. Profitable hospitals had lower total costs and higher payments leading to a difference in profit of approximately $11 000 from TAR surgeries between profitable and nonprofitable hospitals. No difference was noted with respect to length of stay or number of cases performed between profitable and nonprofitable hospitals. TAR surgeries were more likely to take place in large and major teaching hospitals. Among hospitals performing at least 1 TAR, the margin on TAR cases was positively associated with the total number of TARs performed by a hospital. CONCLUSION: There is an overall significant financial burden associated with performing TAR with many health systems failing to demonstrate profitability despite its increased utilization. While additional factors such as improved patient outcomes may be driving utilization of TAR, financial barriers may exist that can affect utilization of TAR across health systems. LEVEL OF EVIDENCE: Level III, comparative study.

Plasma exchange for paediatric kidney disease-indications and outcomes: a single-centre experience.

BACKGROUND: Outcome data in paediatrics regarding the use of plasmapheresis for immunological kidney disease are scarce. OBJECTIVES: We aimed to evaluate the role of plasmapheresis in children presenting with severe renal impairment secondary to immunological kidney diseases. METHODS: A retrospective chart review of children admitted between January 2009 and August 2013 to the Paediatric Nephrology Unit, Christian Medical College, Vellore, India, and requiring plasma exchange was undertaken. Demographic and clinical data were studied and descriptive statistics applied for analysis. RESULTS: Sixteen children underwent plasmapheresis with a male:female ratio of 10:6 and a mean age of 10.2 years (range 5-15 years). Twelve children had atypical haemolytic uraemic syndrome, two had anti-glomerular basement disease and one each had lupus nephritis with neurological manifestation and anti-nuclear cytoplasmic antibody-associated vasculitis. The mean serum creatinine at presentation was 6.52 [interquartile range (IQR) 4.96-7.85] mg/dL with a mean eGFR of 43 (IQR 27.54-56.7) mL/min/1.73 m(2). Other presenting features included nephrotic range proteinuria (69%), gross haematuria (27%), hypertension (94%) and seizures (37.5%). All children received 1.5 times plasma volume plasmapheresis (mean 11 sessions, range 5-26), dialysis and immunosuppressive therapy. The mean duration of follow-up was 4 months (range 2-24 months) with a majority of the children (15/16, 93.75%) surviving acute illness. One child died of overwhelming sepsis and another was lost to follow-up. Of the survivors, eight had eGFR >60 mL/min/1.73 m(2), while eGFR was 15-60 mL/min/1.73 m(2) in the remaining six children. Eight children were still requiring antihypertensive medications and two were continuing peritoneal dialysis at the last follow-up. Thus early introduction of plasmapheresis along with other supportive therapy in immunological kidney disease may improve outcome.

Correction of moderate to severe coronal plane deformity with the STAR ankle prosthesis.

BACKGROUND: Prior studies have demonstrated a correlation between the degree of preoperative coronal plane deformity and failure following ankle replacement. We reviewed all of our patients who underwent ankle replacement utilizing the STAR prosthesis from 2000 to 2009 to evaluate the outcome of those with moderate (10 to 19 degrees) and severe (20 degrees or greater) coronal plane deformity. MATERIALS AND METHODS: Out of 130 consecutive patients, 43 patients had at least 10 degrees of preoperative coronal plane deformity. Twenty-five ankles had 10 to 19 degrees degrees of deformity and 18 ankles had 20 degrees or greater deformity. Average age was 66 years. Average length of followup was 41 (range, 12 to 98) months. RESULTS: Average talar preoperative deformity was 17.9 (range, 10 to 29) degrees, while average initial talar postoperative deformity was 3.5 (range, 0 to 12) degrees. Average final talar postoperative deformity was 4.7 (range, 0 to 14) degrees. Preoperative and final correction of deformity was statistically significant (p < 0.01), but there was no significant difference between initial and final postoperative correction. Overall, recurrence of the preoperative coronal plane deformity occurred in six of 43 patients (14%). All three patients who had deformities over 25 degrees developed recurrences. Correction of the coronal plane deformities was achieved by using intraoperative soft-tissue balancing, including deltoid ligament release in 12 patients and lateral ligament reconstruction in one patient. Deltoid ligament release was found to be necessary for all patients with greater than 18 degrees of varus plane deformity. CONCLUSION: Correction of moderate to severe coronal plane deformity with the STAR prosthesis was achievable with only soft-tissue balancing procedures with predictable results especially for deformities less than 25 degrees.

Repair of the posterior root of the medial meniscus.

Tears of the posterior root of the medial meniscus are becoming increasingly recognized. Early identification and treatment of these tears help halt the progression of cartilage degeneration and osteoarthritis of the knee. Repair of these tears is essential for recreating the hoop stress of the medial meniscus. In this note, we describe a successful arthroscopic technique to repair this lesion. A posteromedial portal is established by which two 2-0 PDS sutures are placed through the meniscus root and pulled down through a trans-tibial tunnel and fixed using an EndoButton distally along the anterolateral cortex of the tibia. This has been performed successfully in five patients with no complications.

The correction of pelvic obliquity in patients with cerebral palsy and neuromuscular scoliosis: is there a benefit of anterior release prior to posterior spinal arthrodesis?

STUDY DESIGN: A retrospective study of 61 patients with cerebral palsy (CP) and neuromuscular scoliosis treated by either a combined anterior-posterior spinal arthrodesis or a posterior-only arthrodesis with the unit rod. OBJECTIVES: Compare coronal and sagittal plane radiographic outcomes in patients undergoing either a combined anterior-posterior spinal fusion (PSF) or a posterior-only fusion with the unit rod for neuromuscular scoliosis in patients with CP. SUMMARY OF BACKGROUND DATA: Although an anterior release before posterior spinal arthrodesis is commonly done for larger and stiffer neuromuscular curves, it is unclear whether or not an all-posterior construct produces similar correction in pelvic obliquity as that seen with an anterior-posterior spinal fusion. METHODS: Sixty-one consecutive children with CP and scoliosis were treated at a single institution between 1991 and 2003 with PSF using the unit rod with an anterior release (group A: 19 patients; average = 14.4 years) or without an anterior release (group B: 42 patients; average = 13.7 years). Side-bending, AP, and lateral radiographs were used to assess various sagittal and coronal plane parameters at baseline, after surgery, and at 2 years. RESULTS.: Before surgery, group A had larger major curves (91 degrees A vs. 72 degrees B; P = 0.001), less flexible major curves (21% A vs. 40% B; P = 0.01), with greater pelvic obliquity (26 degrees A vs. 19 degrees B, P = 0.02) than group B. In the subset of patients with a more severe preoperative pelvic obliquity (>20 degrees ), percent correction in pelvic obliquity was equivalent between groups A (71%) and B (74%, P = 0.91). With respect to coronal and sagittal plane radiographic outcomes, there were no significant group differences in major curve correction (58% A vs. 60% B), but group A trended toward greater % correction from preop bending films. At most recent follow-up, there were no differences with respect to loss of curve correction (7.6 A vs. 8.1 degrees B, P = 0.80). The rate of major complications was 26% for both groups, but group A patients had significantly longer operative times. CONCLUSION: We demonstrate that excellent correction in severe pelvic obliquity can be achieved in smaller, more flexible curves using an all-posterior PSF, and in larger, less flexible curves using an anterior release with PSF.