A Sequencing Overview of Malignant Peripheral Nerve Sheath Tumors: Findings and Implications for Treatment.

Malignant peripheral nerve sheath tumors (MPNSTs) are rare but aggressive malignancies with a low 5-year survival rate despite current treatments. MPNSTs frequently harbor mutations in key genes such as , , , and PRC2 components ( or ) across different disease stages. With the rapid advancement of high-throughput sequencing technologies, the molecular characteristics driving MPNST development are becoming clearer.

A correctable immune niche for epithelial stem cell reprogramming and post-viral lung diseases.

Epithelial barriers are programmed for defense and repair but are also the site of long-term structural remodeling and disease. In general, this paradigm features epithelial stem cells (ESCs) that are called on to regenerate damaged tissues but can also be reprogrammed for detrimental remodeling. Here we identified a Wfdc21-dependent monocyte-derived dendritic cell (moDC) population that functioned as an early sentinel niche for basal ESC reprogramming in mouse models of epithelial injury after respiratory viral infection.

Ex vivo to in vivo model of malignant peripheral nerve sheath tumors for precision oncology.

Background: Malignant peripheral nerve sheath tumors (MPNST) are aggressive soft tissue sarcomas that often develop in patients with neurofibromatosis type 1 (NF1). To address the critical need for novel therapeutics in MPNST, we aimed to establish an ex vivo 3D platform that accurately captured the genomic diversity of MPNST and could be utilized in a medium-throughput manner for drug screening studies to be validated in vivo using patient-derived xenografts (PDX).

Methods: Genomic analysis was performed on all PDX-tumor pairs.

Mutations involving TGFB and MAPK may be associated with malignancy in granular cell tumors.

Granular cell tumors (GrCTs) are mesenchymal neoplasms of presumed schwannian differentiation that may present as solitary or multifocal lesions with excision usually being curative. A minority of cases, however, show histological features associated with an increased risk for metastasis and are highly aggressive leading to death in about a third of cases. While benign and malignant cases have been shown to harbor mutations in the H + ATPase genes, there is only limited data examining molecular aberrations associated with malignancy.

Computational Genomics in the Era of Precision Medicine: Applications to Variant Analysis and Gene Therapy.

Rapid methodological advances in statistical and computational genomics have enabled researchers to better identify and interpret both rare and common variants responsible for complex human diseases. As we continue to see an expansion of these advances in the field, it is now imperative for researchers to understand the resources and methodologies available for various data types and study designs. In this review, we provide an overview of recent methods for identifying rare and common variants and understanding their roles in disease etiology.

Basal epithelial stem cells cross an alarmin checkpoint for postviral lung disease.

Epithelial cells are charged with protection at barrier sites, but whether this normally beneficial response might sometimes become dysfunctional still needs definition. Here, we recognized a pattern of imbalance marked by basal epithelial cell growth and differentiation that replaced normal airspaces in a mouse model of progressive postviral lung disease due to the Sendai virus. Single-cell and lineage-tracing technologies identified a distinct subset of basal epithelial stem cells (basal ESCs) that extended into gas-exchange tissue to form long-term bronchiolar-alveolar remodeling regions.

Chromosome 8 gain is associated with high-grade transformation in MPNST.

One of the most common malignancies affecting adults with Neurofibromatosis type 1 (NF1) is the malignant peripheral nerve sheath tumor (MPNST), an aggressive and often fatal sarcoma that commonly arises from benign plexiform neurofibromas. Despite advances in our understanding of MPNST pathobiology, there are few effective therapeutic options, and no investigational agents have proven successful in clinical trials. To further understand the genomic heterogeneity of MPNST, and to generate a preclinical platform that encompasses this heterogeneity, we developed a collection of NF1-MPNST patient-derived xenografts (PDX).

Comparison of the responsiveness of the SF-36, the Oxford Knee Score, and the Knee Society Clinical Rating System in patients undergoing total knee replacement.

Objectives: To compare the responsiveness of the Knee Society (KS) Clinical Rating System, the general health status measure Short Form 36 (SF-36), and both the raw and Rasch-based scores of the condition-specific Oxford Knee Score (OKS) in patients undergoing total knee replacement (TKR) METHODS: Data were prospectively collected as part of routine care from adult patients who underwent TKR between 2001 and 2006. OKS data fit the Rasch partial credit model after removing items regarding limping and kneeling. Responsiveness was assessed using effect size (ES), standardised response mean (SRM), and relative validity (RV).

Health-related quality of life after total knee replacement or unicompartmental knee arthroplasty in an urban asian population.

Objective: To examine health-related quality of life (HRQoL) after total knee replacement (TKR) or unicompartmental knee arthroplasty (UKA).

Methods: Asian adult patients undergoing either TKR or UKA in a hospital in Singapore between 2001 and 2006 were interviewed before surgery and 6 and 24 months postoperatively to obtain demographic information and HRQoL scores using the Short Form-36 Health Survey (SF-36) and the Oxford Knee Score (OKS).

Results: Data were collected from 2243, 1715, and 1113 patients at baseline and at 6 and 24 months, respectively.

Validation of Chinese Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) in patients scheduled for total knee replacement.

Objective: Our aim was to cross-culturally validate Chinese Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) in patients with knee osteoarthritis (OA) scheduled for total knee replacement in Singapore.

Methods: Chinese WOMAC was translated from the original English version following standard guidelines. Patients were asked to complete a questionnaire containing the WOMAC (twice within 6 days), the Short Form 36 (SF-36), and the EuroQoL EQ-5D.

A study on indirect and intangible costs for patients with knee osteoarthritis in Singapore.

Objectives: To estimate indirect costs through human capital approach and intangible costs through willingness-to-pay (WTP), and identify factors potentially affecting these costs in multiethnic Asian patients with knee osteoarthritis (OA).

Methods: Data were collected through face-to-face interviews among knee OA patients. Human capital approach was used to estimate indirect costs by multiplying: 1) days of absence from work because of OA, with average earnings per capita per day for working patients; or 2) productivity loss with the market price of housekeeping for retirees/homemakers.

Computer-assisted minimally invasive total knee arthroplasty compared with standard total knee arthroplasty. A prospective, randomized study.

Background: There is little information on the feasibility of computer navigation when using a minimally invasive approach for total knee arthroplasty, during which the anatomic landmarks for registration may be obscured. The purpose of the present study was to determine the radiographic accuracy of this technique and to compare the rate of functional recovery between patients who underwent computer-assisted minimally invasive arthroplasty and those who underwent conventional total knee arthroplasty.

Methods: One hundred and eight consecutive patients were randomized to undergo computer-assisted minimally invasive total knee arthroplasty or conventional total knee arthroplasty.

Comparison of the EuroQol and short form 6D in Singapore multiethnic Asian knee osteoarthritis patients scheduled for total knee replacement.

Objective: To compare the EuroQol (EQ-5D) and Short Form 6D (SF-6D) among multiethnic Asian patients with knee osteoarthritis (OA) scheduled for total knee replacement in Singapore.

Methods: Patients were asked to complete questionnaires including the EQ-5D, Short Form 36, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), and Lequesne knee index. EQ-5D and SF-6D utility scores were calculated using the scoring algorithms developed from the UK general population.

Direct and indirect costs of osteoarthritis in Singapore: a comparative study among multiethnic Asian patients with osteoarthritis.

Objective: To estimate and compare the direct and indirect costs of osteoarthritis (OA) in multiethnic Asian patients with OA in Singapore.

Methods: The study was a retrospective and cross-sectional design. Patients were stratified according to ethnicity and presence or absence of joint surgery.

Stress fracture of the medial tibial plateau after minimally invasive unicompartmental knee arthroplasty: a report of 2 cases.

Minimally invasive unicompartmental knee arthroplasty has been increasingly popular for the past few years. Several short- and medium-term published reports have shown it to be as efficacious as open unicompartmental knee arthroplasty, with reduced morbidity. However, complications specifically related to the minimally invasive techniques are not well documented.

Isolated congenital pseudoarthrosis of the fibula.

Congenital pseudarthrosis of the limb most commonly involves the tibia, although various combinations of bones including fibula, radius, ulna, clavicle and humerus have all been described. Isolated congenital pseudarthrosis of the fibula is a very rare entity with only 12 cases reported in the English literature. We report three cases of this condition treated in our institution.