Reinjury Following Return to Play.

Radiologists are frequently called on for guidance regarding return to play (RTP) for athletes and active individuals after sustaining a musculoskeletal injury. Avoidance of reinjury is of particular importance throughout the rehabilitative process and following resumption of competitive activity. Understanding reinjury risk estimation, imaging patterns, and correlation of clinical and surgical findings will help prepare the radiologist to identify reinjuries correctly on diagnostic imaging studies and optimize management for a safe RTP.

Hydroxyapatite deposition disease, an overlooked differential diagnosis in the emergency department: a case series and review of literature.

Hydroxyapatite crystal deposition disease (HADD) poses diagnostic challenges in the emergency department (ED) as it may clinically present similarly to infection and other musculoskeletal conditions. Misdiagnosis often leads to unnecessary treatments and resource over-utilization. This review article provides an overview of HADD in seven patients who presented to the ED secondary to an acute presentation of this disease process. HADD is a prevalent pathology, which commonly involves the shoulder, followed by the hip, elbow, wrist, and knee. Predisposing risk factors, such as diabetes and certain genetic factors, have also been identified. Clinical history and imaging, particularly radiographs, play a vital role in diagnosing HADD, with characteristic calcification patterns observed in different stages of the disease. Conservative nonsurgical therapy is the mainstay of treatment, providing effective symptom relief in over 90% of cases. By recognizing HADD as a crucial differential diagnosis for patients with acute or chronic pain, healthcare resource utilization can be optimized, leading to improved patient care in the ED.

Multifocal emphysematous osteomyelitis, a do not miss diagnosis for the emergency radiologist: a case report with literature review.

Emphysematous osteomyelitis (EO) is an uncommon fatal condition with high morbidity and mortality. Simultaneous involvement of the axial and appendicular skeleton with multifocal disease is even rarer, with only a few cases being reported in the literature. We present a case of multifocal emphysematous osteomyelitis in a 56-year-old woman with concurrent emphysematous pyelonephritis complicated by psoas and epidural abscesses. The causative organism in our patient was Escherichia coli. Emergency radiologists should be aware of this condition and differentiate it from other benign entities that can present with intraosseous gas. Prompt diagnosis is important given the high morbidity and mortality with this condition. This case report emphasizes the specific pattern of intraosseous gas seen with EO, which can help diagnose EO with confidence.

Phosphaturic mesenchymal tumor: two cases highlighting differences in clinical and radiologic presentation.

Phosphaturic mesenchymal tumors are rare, usually benign neoplasms that occur in the soft tissue or bone and are the cause of nearly all cases of tumor-induced osteomalacia. Tumor-induced osteomalacia due to phosphaturic mesenchymal tumor is a challenging diagnosis to make-patients present with variable clinical and radiologic findings and the culprit neoplasm is often small and can occur anywhere head to toe. We present two cases of phosphaturic mesenchymal tumor in the scapular body and plantar foot. In both cases, the patient endured years of debilitating symptoms before a tissue diagnosis was eventually reached. Descriptions of clinical presentation, laboratory workup, surgical resection, and imaging characteristics, with a focus on CT, MRI, and functional imaging, are provided to assist with the diagnosis and management of this rare entity. A brief review of current literature and discussion of the differential diagnoses of phosphaturic mesenchymal tumor is also provided.

Vascular leiomyoma of the thigh: Classic presentation of a rare tumor with imaging and pathology correlation.

We report a case of a vascular leiomyoma arising from the superficial femoral artery presenting as a non-painful thigh mass in a 55-year-old woman. Leiomyomas typically arise from the uterus and gastrointestinal tract, and rarely arise from vessels. We present this case to emphasize that although extremity leiomyomas are rare, they should be considered if there is a soft tissue mass abutting a vessel. Radiologists should be familiar with the imaging features associated with vascular leiomyomas.

Atypical Chondroid Syringoma of the Toe.

Although chondroid syringoma rarely occurs outside the head and neck, the majority of malignant chondroid syringomas are identified in the extremities. Here, we present a case of atypical chondroid syringoma in the fifth toe. Diagnosis of chondroid syringoma with atypical cells was made following initial excisional biopsy and histology, necessitating repeated surgery for positive margins. In this case report, we examine the radiopathologic correlation of this diagnosis, detail the imaging findings of benign and malignant chondroid syringomas, and highlight how magnetic resonance imaging can be used to guide surgical planning and treatment course of this potentially malignant tumor.

The Use of Artificial Intelligence in the Evaluation of Knee Pathology.

Artificial intelligence (AI) holds the potential to revolutionize the field of radiology by increasing the efficiency and accuracy of both interpretive and noninterpretive tasks. We have only just begun to explore AI applications in the diagnostic evaluation of knee pathology. Experimental algorithms have already been developed that can assess the severity of knee osteoarthritis from radiographs, detect and classify cartilage lesions, meniscal tears, and ligament tears on magnetic resonance imaging, provide automatic quantitative assessment of tendon healing, detect fractures on radiographs, and predict those at highest risk for recurrent bone tumors. This article reviews and summarizes the most current literature.

Cholic acid-modified polyethylenimine: in vitro and in vivo studies.

Low-molecular-weight polyethylenimine has lower cytotoxicity than high molecular weight polyethylenimine, but it is not an efficient transfection agent because of limitations of DNA delivery into the cytoplasm. Therefore, in the present study, the hydrophobic modification of low-molecular-weight polyethylenimine (PEI 2 kDa [PEI2]) by cholic acid (ChA) was performed to form PEI2-ChA, and in vitro and in vivo studies were performed. Results indicate that the nanoplexes of PEI2-ChA with gWIZ-GFP have greater transfection efficiency (27%) in NT8e cell lines as evaluated by flow cytometry and also observed by fluorescence imaging. The present study concluded that the transferrin-containing nanoplexes of PEI2-ChA conjugates with plasmid p53 warrant clinical trials in humans after exhaustive animal studies for use as a novel gene delivery system.

Hydrophobically modified polyethylenimine-based ternary complexes for targeting brain tumor: stability, in vitro and in vivo studies.

Hydrophobic modification of low molecular weight polyethylenimine (PEI 2 kDa) by cholic acid (ChA) was done to obtain PEI2-ChA. The nanoplexes of PEI2-ChA with gWIZ-GFP demonstrated increase transfection efficiency (∼27%) in NT8e cell lines. The cell-cycle analysis of NT8e cells (p53 mutant) treated with transferrin containing nanoplexes showed increased apoptosis of cells. In vitro protein expression revealed expression of exogenous p53 protein. In vivo imaging of mice showed localized signal for GFP protein in brain region. The tumors of mice treated with transferrin containing nanoplexes of PEI2-ChA were ∼5 times smaller in size than the tumor of untreated animals.

Imaging of ocular melanoma metastasis.

Ocular melanoma is the most common adult primary intraocular tumour. Although <1% of patients have metastatic disease at the time of initial diagnosis, most will develop metastasis at varying lengths of time. Metastasis surveillance is therefore critical in the follow-up of patients with ocular melanoma. Liver is the most common site of metastasis and prognosis is based on the treatment of liver metastasis. Hence, imaging of liver metastasis is vital. MRI is the most specific modality for imaging liver metastasis and is at least as sensitive as CT. Extrahepatic metastasis such as retroperitoneal nodules and bone metastases are also better evaluated on MRI. Gadolinium-based contrast agents are extremely helpful for detecting liver lesions. In particular, newer hepatobiliary contrast agents which offer an additional hepatobiliary phase of excretion help in the detection of even tiny liver metastases. Diffusion-weighted imaging is helpful when an i.v. contrast cannot be administered. Treated lesions are also better evaluated with MRI. CT is useful for evaluating lung nodules, large liver metastasis or in patients in whom MRI is medically contraindicated. The disadvantage lies in its inability to detect small liver metastasis and the radiation dose involved. The lesions treated with iodized oil as part of chemoembolization procedures can be followed on CT. Ultrasound can be used only for detecting hepatic metastases. However, it is heavily operator dependent, technically challenging and time consuming especially in patients who are large. Extrahepatic metastasis cannot be seen on ultrasound. Its utility is primarily for the biopsy of liver lesions. Positron emission tomography (PET)-CT can detect lung nodules and large liver lesions but is insensitive to small liver lesions. Moreover, the high radiation dose is a major disadvantage.

Study of menstrual patterns in adolescent girls with disabilities in a residential institution.

BACKGROUND: The gynecological health needs of girls with disabilities is an issue related to their rights as individuals. OBJECTIVE: The objective of this study is to describe the menstrual pattern of girls with disabilities. MATERIALS AND METHODS: A descriptive study was undertaken on thirty girls with different types of disabilities in a residential institution. The diagnosis, type of disability, secondary sexual characters, age at menarche, menstrual pattern and practice of menstrual hygiene was noted. RESULTS: The girls with intellectual disabilities had later age of menarche, irregular cycles and more behaviour problems. The girls with hearing impairment and locomotor disabilities had normal menstrual pattern. The girl with low vision had earlier menarche and regularized cycles. Girls with normal intelligence and mild intellectual disabilities were independent in maintaining menstrual hygiene. The menstrual disorders are managed conservatively in accordance with latest guidelines. CONCLUSION: Onset of menarche is towards the extremes of normal age range in girls with intellectual disabilities or visual impairment but not in girls with hearing impairments or locomotor disabilities. Girls with disabilities have potential for independent menstrual care. Menstrual disorders were managed conservatively.

Apoptosis induction and anti-cancer activity of LeciPlex formulations.

PURPOSE: Cationic agents have been reported to possess anti-neoplastic properties against various cancer cell types. However, their complexes with lipids appear to interact differently with different cancer cells. The purpose of this study was to (i) design and generate novel cationic lecithin nanoparticles, (ii) assess and understand the mechanism underlying their putative cytotoxicity and (iii) test their effect on cell cycle progression in various cancer-derived cell lines. In addition, we aimed to evaluate the in vivo potential of these newly developed nanoparticles in oral anti-cancer delivery. METHODS: Cationic lecithin nanoparticles were generated using a single step nanoprecipitation method and they were characterized for particle size, zeta potential, stability and in vitro release. Their cytotoxic potential was assessed using a sulforhodamine B assay, and their effect on cell cycle progression was evaluated using flow cytometry. The nanoparticle systems were also tested in vivo for their anti-tumorigenic potential. RESULTS: In contrast to cationic agents alone, the newly developed nanoformulations showed a specific toxicity against cancer cells. The mechanism of toxic cell death included apoptosis, S and G2/M cell cycle phase arrest, depending on the type of cationic agent and the cancer-derived cell line used. Both blank and drug-loaded systems exhibited significant anti-cancer activity, suggesting a synergistic anti-tumorigenic effect of the drug and its delivery system. CONCLUSIONS: Both in vitro and in vivo data indicate that cationic agents themselves exhibit broad anti-neoplastic activities. Complex formation of the cationic agents with phospholipids was found to provide specificity to the anti-cancer activity. These formulations thus possess potential for the design of effective anti-cancer delivery systems.

Mode of cell death associated with adenovirus-mediated suicide gene therapy in HNSCC tumor model.

BACKGROUND: Adenoviral mediated suicide gene therapy has been shown to have a tumoricidal effect against a variety of tumor models. Although the efficacy of this treatment regimen has been verified, the molecular mechanism of Herpes simplex virus thymidine kinase gene (HSVtk)- and ganciclovir (GCV)-induced cell death is still not well established. MATERIALS AND METHODS: The mode of cell death by adenoviral (Adv)-HSVtk/GCV was examined in the head and neck squamous cell carcinoma cell line, NT8e. RESULTS: The cell death was independent of apoptotic gene expression. Moreover apoptosis was not evident from cell cycle kinetic analysis. Adv-HSVtk/GCV treated cells showed time dependent accumulation of cells in the S-phase of the cell cycle although there was no increase in the "apoptotic peak" or sub-G1 population. Swelling of the cytoplasm without apparent nuclear condensation suggested a possible involvement of necrosis. CONCLUSION: The apoptotic mechanism may not play a central role in the Adv-HSVtk/GCV induced NT8e cell death and other mechanisms should be considered.

Effect of suicide gene therapy in combination with immunotherapy on antitumour immune response & tumour regression in a xenograft mouse model for head & neck squamous cell carcinoma.

BACKGROUND & OBJECTIVES: Prodrug activation strategy as well as immunotherapy have been widely used for cancer gene therapy. In the present study, using a head and neck squamous cell carcinoma (HNSCC) xenograft nude mouse model, we have investigated whether the two therapies in combination could improve tumour cell kill. We also investigated induction of immune effector cells viz., NK (DX5+) and DC (CD11c+) in vivo, post-combination gene therapy. METHODS: A retroviral vector producing cell line (PLTK47.1 VPC) carrying Herpes simplex virus thymidine kinase gene (HSVtk) was used for intratumoural injection into NT8e xenograft tumours followed by the prodrug ganciclovir (GCV). IL-2 plasmid DNA was injected intramuscularly. Immune cells were analyzed by flow-cytometry. Non parametric ANOVA was performed with Kruskal Wallis test. RESULTS: IL-2 could induce proliferation of both NK cells (DX5+) and dendritic cells (CD11c+) in vivo. Apoptosis was higher in combination therapy group as compared to HSVtk/GCV alone or IL-2 alone and was mediated through caspase-3 dependent pathway. Significant reduction in tumour volume was seen in all 3 treatment arms as compared to controls. INTERPRETATION & CONCLUSIONS: Combination of suicide gene therapy and immunotherapy leads to successful tumour regression in a HNSCC xenograft mouse model. Immunotherapy could help in a systemic long lived anti-tumour immune response which would prove powerful for the treatment of metastatic cancers, and also for minimal residual disease. The results of this study may form the basis for Phase 1 clinical trials.

HDAC inhibitor valproic acid enhances tumor cell kill in adenovirus-HSVtk mediated suicide gene therapy in HNSCC xenograft mouse model.

Safety, efficacy and enhanced transgene expression are the primary concerns while using any vector for gene therapy. One of the widely used vectors in clinical trials is adenovirus which provides a safe way to deliver the therapeutic gene. However, adenovirus has poor transduction efficiency in vivo since most tumor cells express low coxsackie and adenovirus receptors. Similarly transgene expression remains low, possibly because of the chromatization of adenoviral genome upon infection in eukaryotic cells, an effect mediated by histone deacetylases (HDACs). Using a recombinant adenovirus (Ad-HSVtk) carrying the herpes simplex thymidine kinase (HSVtk) and GFP genes we demonstrate that HDAC inhibitor valproic acid can bring about an increase in CAR expression on host cells and thereby enhanced Ad-HSVtk infectivity. It also resulted in an increase in transgene (HSVtk and GFP) expression. This, in turn, resulted in increased cell kill of HNSCC cells, following ganciclovir treatment in vitro as well as in vivo in a xenograft nude mouse model.