Does closed treatment of paediatric mandibular condyle fractures result in restitutional remodelling?

The treatment of paediatric mandibular condylar fracture (PMCF) is typically non-operative. The purpose of this study was to determine if non-operative management of PMCF results in a new condylar process of normal morphology to regenerate after closed treatment (restitutional remodelling). The specific aim of the study was to observe restitutional remodelling (RM) in PMCF and review the literature. The investigators designed and implemented a retrospective study on paediatric patients (age<12) with unilateral or bilateral condyle fractures treated with non-operative treatment between January 2005 and July 2015. Patients with complete records and at least 1-year follow-up were included in the study. Primary outcome variable was RM and secondary outcome variables were occlusion, maximal incisal opening (MIO), displacement, infection, facial asymmetry, and signs of temporomandibular joint ankylosis (TMJA). The study evaluated 41 patients {n=57 PMCF, (m:f-35:6)} of unilateral (n=25) and bilateral (n=16) PMCF. Fractured condyles remodelled to normal morphology in all the cases at follow-up. The Wilcoxon test revealed a statistically significant difference in MIO from the preoperative value to postoperative (p=0.001). Occlusion (except 1) was satisfactory in all cases, at follow-up with no gross facial asymmetry. There was no sign of infection at the surgical site (anterior mandible). None of the patients showed signs of TMJA at follow-up. The result of the present study demonstrates that RM of condylar fracture occurs with non-operative management. Non-operative management should be the point of care in PMCF, owing to the rapid RM, bone regeneration, and satisfactory outcome. Review of the literature also supports closed treatment.

Cadaverless anatomy: Darkness in the times of pandemic Covid-19.

The pandemic Covid-19 is responsible for a major education crisis globally and has a drastic impact on medical training as well. The objective of the present study was to envision the present and future impact of Covid-19 on anatomy learning and research. The virtual education is the only mode of teaching in current scenario. Every anatomist is unlocking technology to deliver best education however understanding of the subject without dissections or other practical teaching aids like bones, specimens, embryology models, microscopic slides etc. is challenging. This approach misses the feel and human visual impacts. Potential educational disruption is felt currently and will be experienced even after the pandemic is over due to scarcity of cadavers. As the body donor may be carrier or died of Covid-19 and there is no proven screening to rule out this infection in donor, so the acceptance of body donations is not advisable for the safety of medical students and health care workers. To conclude, anatomy education is cadaverless currently due to Covid-19 lockdown and it is prophesied that after the pandemic, real cadavers will be replaced by virtual cadavers because of paucity of cadavers. Research in the field of anatomy will also be adversely affected.

Extent of Surgical Resection in Lower-Grade Gliomas: Differential Impact Based on Molecular Subtype.

BACKGROUND AND PURPOSE: Diffuse lower-grade gliomas are classified into prognostically meaningful molecular subtypes. We aimed to determine the impact of surgical resection on overall survival in lower-grade glioma molecular subtypes. MATERIALS AND METHODS: For 172 patients with lower-grade gliomas (World Health Organization grade II or III), pre- and postsurgical glioma volumes were determined using a semiautomated segmentation software based on FLAIR or T2-weighted MR imaging sequences. The association of pre- and postsurgical glioma volume and the percentage of glioma resection with overall survival was determined for the entire cohort and separately for lower-grade glioma molecular subtypes based on isocitrate dehydrogenase (IDH) and 1p/19q status, after adjustment for age, sex, World Health Organization grade, chemotherapy administration, and radiation therapy administration. RESULTS: For the entire cohort, postsurgical glioma volume (hazard ratio, 1.80; 95% CI, 1.18-2.75; P = .006) and the percentage of resection (hazard ratio, 3.22; 95% CI, 1.79-5.82; P < .001) were associated with overall survival. For IDH-mutant 1p/19q-codeleted oligodendrogliomas, the percentage of resection (hazard ratio, 6.69; 95% CI, 1.57-28.46; P = .01) was associated with overall survival. For IDH-mutant 1p/19q-noncodeleted astrocytomas, presurgical glioma volume (hazard ratio, 3.20; 95% CI, 1.22-8.39; P = .018), postsurgical glioma volume (hazard ratio, 2.33; 95% CI, 1.32-4.12; P = .004), and percentage of resection (hazard ratio, 4.34; 95% CI, 1.74-10.81; P = .002) were associated with overall survival. For IDH-wild-type lower-grade gliomas, pre-/postsurgical glioma volume and percentage of resection were not associated with overall survival. CONCLUSIONS: The extent of surgical resection has a differential survival impact in patients with lower-grade gliomas based on their molecular subtype. IDH-mutant lower-grade gliomas benefit from a greater extent of surgical resection, with the strongest impact observed for IDH-mutant 1p/19q-noncodeleted astrocytomas.

Idiopathic renal replacement lipomatosis.

Renal replacement lipomatosis (RRL) is a rare disorder which exhibits extensive proliferation of fatty tissue within the renal sinus, hilum, and perirenal region. The pathogenesis of this entity is unknown, though association with aging, renal atrophy, longstanding chronic urinary infections has been noted. Although imaging modalities may suggest the diagnosis of this entity, it is histopathology that clinches the diagnosis most accurately. We report a case of a 52 year old male who presented with nonfunctioning kidney and was histopathologically confirmed to be a case of renal replacement lipomatosis.

Quantitation of spatial and temporal variability of biomarkers for Barrett's Esophagus.

Chemoprevention and risk-stratification studies in Barrett's esophagus (BE) rely on biomarkers but the variability in their temporal and spatial expression is unknown. If such variability exists, it will impact sampling techniques and sample size calculations. Specimens from three levels of biopsies over two serial endoscopies in nondysplastic BE patients were analyzed for aneuploidy, proliferation markers (Ki67, Mcm2), and cell cycle markers (cyclin A and cyclin D1). A modification of the image cytometry technique, where cytokeratin staining automatically distinguished epithelial and stromal cells, measured aneuploidy on whole tissue sections. Other biomarkers were studied by immunohistochemistry. Coefficient of variability (SD/mean) was calculated; a value <10% indicated low variability. A total of 120 specimens (20 subjects each with three biopsy levels at two time points) from nondysplastic BE patients (71 ± 8.8 years, all Caucasian, 90% males, C5.1M7.5 ± 3.4 cm) were analyzed. The mean interval between endoscopies was 32.8 ± 8.4 months. Aneuploidy had a spatial variability of 6.8% at visit 1 (mean diploid index: 1.1 ± 0.09) and 7.9% at visit 2 (mean diploid index: 1.1 ± 0.06) and a temporal variability of 7.0-8.1% for the three levels. For other biomarkers, the spatial variability ranged from ∼5 to 30% at visit 1 and 11-92% at visit 2 and the temporal variability ranged from 0 to 77%. To conclude, of all the biomarkers, only aneuploidy had both spatial and temporal variability of <10%. Spatial and temporal variability were biomarker dependent and could be as high as 90% even without progression. These data will be useful to design chemoprevention and risk-stratification studies in BE.

Transport of Liposome Encapsulated Drugs in Voxelized Computational Model of Human Brain Tumors.

There are many obstacles in the transport of chemotherapeutic drugs to tumor cells that lead to irregular and non-uniform uptake of drugs inside tumors. The study of these transport problems will help with accurate prediction of drug transport and optimizing treatment strategy. To this end, liposome mediated drug delivery has emerged as an excellent anticancer therapy due to its ability to deliver drugs at site of action and reducing the chances of side effects to the healthy tissues. In this paper, a computational fluid dynamics (CFD) model based on realistic vasculature of human brain tumor is presented. This model utilizes dynamic contrast enhanced-magnetic resonance imaging (DCE-MRI) data to account for heterogeneity in tumor vasculature. Porosity of the interstitial space inside the tumor and normal tissue is determined voxel-wise by processing the DCE-MRI images by general tracer kinetic model (GTKM). The CFD model is applied to predict transport of two different types of liposomes (stealth and conventional) in tumors. The amount of accumulated liposomes is compared with accumulated free drug (doxorubicin) in the interstitial space. Simulation results indicate that stealth liposomes accumulate more and remain for longer periods of time in tumors as compared with conventional liposomes and free drug. The present model provides us a qualitative and quantitative examination on the transport and deposition of liposomes as well as free drugs in actual human brain tumors.

Perfusion kinetics in human brain tumor with DCE-MRI derived model and CFD analysis.

Cancer is one of the leading causes of death all over the world. Among the strategies that are used for cancer treatment, the effectiveness of chemotherapy is often hindered by factors such as irregular and non-uniform uptake of drugs inside tumor. Thus, accurate prediction of drug transport and deposition inside tumor is crucial for increasing the effectiveness of chemotherapeutic treatment. In this study, a computational model of human brain tumor is developed that incorporates dynamic contrast enhanced-magnetic resonance imaging (DCE-MRI) data into a voxelized porous media model. The model takes into account realistic transport and perfusion kinetics parameters together with realistic heterogeneous tumor vasculature and accurate arterial input function (AIF), which makes it patient specific. The computational results for interstitial fluid pressure (IFP), interstitial fluid velocity (IFV) and tracer concentration show good agreement with the experimental results. The computational model can be extended further for predicting the deposition of chemotherapeutic drugs in tumor environment as well as selection of the best chemotherapeutic drug for a specific patient.

Change in Driving Performance following Arthroscopic Shoulder Surgery.

The current study aimed to measure perioperative changes in driving performance following arthroscopic shoulder surgery using a validated driving simulator.21 patients who underwent arthroscopic surgery for rotator cuff or labral pathology were tested on a driving simulator preoperatively, and 6 and 12 weeks postoperatively. An additional 21 subjects were tested to establish driving data in a control cohort. The number of collisions, centerline crossings, and off-road excursions were recorded for each trial. VAS and SPADI scores were obtained at each visit.The mean number of collisions in the study group significantly increased from 2.05 preoperatively to 3.75 at 6 weeks (p<0.001), and significantly decreased to 1.95 at 12 weeks (p<0.001). Centerline crossings and off-road excursions did not significantly change from preoperative through 12 weeks, although centerline crossings were statistically different from the controls at each time point (p<0.001). Surgery on the dominant driving arm resulted in greater collisions at 6 weeks than surgery on the non-dominant driving arm (p<0.001).Preliminary data shows that driving performance is impaired for at least 6 weeks postoperatively, with a return to normal driving by 12 weeks. Driving is more profoundly affected in conditions that require avoiding a collision and when the dominant driving arm is involved.

Multimodality imaging of fibromuscular dysplasia.

OBJECTIVE: Fibromuscular dysplasia (FMD) is an uncommon non-inflammatory and non-atherosclerotic cause of arterial disease that may result in stenosis, tortuosity, aneurysm, or dissection. The clinical presentation depends on the vascular bed involved and ranges from asymptomatic to multisystem disease and end organ ischemia. The purpose of this article is to review the role of imaging in patients with FMD with an emphasis on renal FMD. The relevant epidemiology, histopathology, imaging techniques, and interpretation of images will be discussed. CONCLUSION: Renal artery FMD requires a high index of suspicion for accurate and prompt diagnosis and implementation of appropriate therapy. The treatment will vary based on clinical presentation and distribution of involvement. Noninvasive imaging with duplex ultrasound (US), computed tomography (CT), and magnetic resonance imaging (MRI) are reasonable alternatives for the depiction of FMD in comparison to catheter-directed angiography (CA). Patients with FMD are often treated by multispecialty practice including the interventional radiologist.

Extended B cell phenotype in patients with myalgic encephalomyelitis/chronic fatigue syndrome: a cross-sectional study.

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a heterogeneous condition of unknown aetiology characterized by multiple symptoms including fatigue, post-exertional malaise and cognitive impairment, lasting for at least 6 months. Recently, two clinical trials of B cell depletion therapy with rituximab (anti-CD20) reported convincing improvement in symptoms. A possible but undefined role for B cells has therefore been proposed. Studies of the relative percentages of B cell subsets in patients with ME/CFS have not revealed any reproducible differences from healthy controls (HC). In order to explore whether more subtle alterations in B cell subsets related to B cell differentiation exist in ME/CFS patients we used flow cytometry to immunophenotype CD19⁺ B cells. The panel utilized immunoglobulin (Ig)D, CD27 and CD38 (classical B cell subsets) together with additional markers. A total of 38 patients fulfilling Canadian, Centre for Disease Control and Fukuda ME/CFS criteria and 32 age- and sex-matched HC were included. We found no difference in percentages of classical subsets between ME/CFS patients and HC. However, we observed an increase in frequency (P < 0·01) and expression (MFI; P = 0·03) of CD24 on total B cells, confined to IgD⁺ subsets. Within memory subsets, a higher frequency of CD21⁺ CD38⁻ B cells (> 20%) was associated with the presence of ME/CFS [odds ratio: 3·47 (1·15-10·46); P = 0·03] compared with HC, and there was a negative correlation with disease duration. In conclusion, we identified possible changes in B cell phenotype in patients with ME/CFS. These may reflect altered B cell function and, if confirmed in other patient cohorts, could provide a platform for studies based on clinical course or responsiveness to rituximab therapy.

Hypofractionated stereotactic body radiotherapy in spinal metastasis - with or without epidural extension.

AIMS: To evaluate clinical outcome and the effect of malignant epidural compression (MEC) in the treatment of spine metastasis with stereotactic body radiotherapy (SBRT). MATERIALS AND METHODS: Seventy-six lesions in 52 patients with spinal metastasis received SBRT during the period July 2010 to December 2012. MEC was detected in 20 patients (38.4%) and was separately contoured. The median dose prescribed to involved vertebra (planning target volume) was 24 Gy (range 24-27 Gy) in a median of three fractions (range 1-3). Uninvolved elements were prescribed 21 Gy in three fractions. In 59 lesions (77.6%), the entire vertebra was treated and in 17 lesions (22.4%) only the anterior elements were treated. All patients were treated with volumetric modulated arc therapy with image guidance on a Novalis Tx linear accelerator with the ExacTrac system. Dosimetric and clinical outcomes were compared in patients with or without MEC. RESULTS: At a median follow-up of 8.48 months (range 3-40 months), 1 year local control and overall survival was 94 and 68%, respectively. In patients with or without epidural extension, the median dose to the gross tumour volume (GTV; 95%) was 23.48 Gy (range 13.70-25.75) and 22.99 Gy (range 13.55-26.84), the median spinal cord Dmax was 17.36 Gy (range 8.47-21.63) and 15.71 Gy (range 8.39-23.33). The median GTV epidural (D95%) was 21.16 Gy (range 15.43-23.92). Complete pain relief was seen in 90% of patients with MEC and 93.75% without MEC (P=NS) and neurological improvement was seen in 60% of patients in both groups of patients. CONCLUSION: It is feasible to deliver a high dose of radiation (∼90% of the prescription dose) to the epidural component with volumetric modulated arc therapy SBRT and image guidance. It yielded high rates of pain control and local control in patients with spine metastases with or without MEC.

Role of neo-adjuvant chemotherapy in locally advanced breast cancer.

BACKGROUND AND AIMS: Locally advanced breast cancer (LABC) is common in developing countries. The advancement of disease leads to decreased probability of radical cure and increase in treatment cost. The study evaluated neo adjuvant chemotherapy with MRM and MRM followed by adjuvant chemotherapy and also the effectiveness of neo-adjuvant chemotherapy in down staging advanced disease and offering radical cure. SETTINGS AND DESIGN: A rural hospital-based prospective comparative study. MATERIALS AND METHODS: All histologically proven and investigated LABC (T3 N0, T3N1, Any T4, Any N2/N3, M0) were selected as subjects and divided into two groups. One group received neo adjuvant chemotherapy (5 fluorouracil, adriamycin and cyclophosphamide) followed by modified radical mastectomy and other group received adjuvant chemotherapy after modified radical mastectomy. Both groups were compared for disease free survival, overall survival and post-operative complications. Tumor response to chemotherapy in neo adjuvant group was also studied. STATISTICAL ANALYSIS: All continuous variables were analyzed using student's' test and categorical variable by Fischer exact test. RESULTS: Thirty one patients were enrolled, of these 16 patients received neo adjuvant chemotherapy. Clinical complete response was observed in two patients (12.5%). Clinical partial response was found in 12 patients (75%) and no response was seen in two patients (12.5%). Disease free survival and overall survival was 82% in neo adjuvant group while in adjuvant group disease free survival was 75% and overall survival was 83%. Post operative complications were similar in both groups. CONCLUSION: Neo adjuvant chemotherapy helps in down staging LABC and offers opportunity in vivo to assess the effect of chemotherapy on individual basis. There was no significant difference in disease free survival, overall survival and post operative complication in between two groups.

Measles Edmonston vaccine strain derivatives have potent oncolytic activity against osteosarcoma.

Osteosarcoma (OS) is the most common primary bone tumor affecting children and young adults, and development of metastatic disease is associated with poor prognosis. The purpose of this study was to evaluate the antitumor efficacy of virotherapy with engineered measles virus (MV) vaccine strains in the treatment of OS. Cell lines derived from pediatric patients with OS (HOS, MG63, 143B, KHOS-312H, U2-OS and SJSA1) were infected with MV expressing green fluorescent protein (MV-GFP) and MV-expressing sodium iodide symporter (MV-NIS) strains. Viral gene expression and cytotoxicity as defined by syncytial formation, cell death and eradication of cell monolayers were demonstrated. Findings were correlated with in vivo efficacy in subcutaneous, orthotopic (tibial bone) and lung metastatic OS xenografts treated with the MV derivative MV-NIS via the intratumoral or intravenous route. Following treatment, we observed decrease in tumor growth of subcutaneous xenografts (P=0.0374) and prolongation of survival in mice with orthotopic (P<0.0001) and pulmonary metastatic OS tumors (P=0.0207). Expression of the NIS transgene in MV-NIS infected tumors allowed for single photon emission computed tomography and positron emission tomography-computed tomography imaging of virus infected tumors in vivo. Our data support the translational potential of MV-based virotherapy approaches in the treatment of recurrent and metastatic OS.

Composite indicator: new tool for monitoring RNTCP performance in India.

India's Revised National Tuberculosis Control Programme (RNTCP) used the international benchmarks of 70% case detection rate and 85% treatment success rate among new smear-positive tuberculosis (TB) cases for assessing programme performance. This approach overemphasises outcomes and focuses on quantitative benchmarks without sufficient regard to developing systems to monitor appropriate programme practice to achieve a minimum standard of TB care services. The RNTCP has developed a novel composite indicator tool based on a logical framework pathway to move beyond narrow-focused outcome indicators such as case detection to encourage a broad-based analysis of programme implementation. The constituent indicators are from routinely monitored information, spanning input, process, output and outcome indicators across various thematic categories of the RNTCP.

Initial bone preparation followed by a 2-week delay before implant placement enhances the clinical and radiographic outcome: a randomized controlled trial.

Initial bone preparation followed by a 2-week delay before implant placement enhances the biological activity at the osteotomy site, which may improve the treatment outcome. The aim of this study was to compare the clinical and radiographic outcomes of initial bone preparation and a 2-week delay in implant placement with the conventional method. Subjects were outpatients selected from a department of periodontology and oral implantology. The implant sites were randomly allocated to a test group and a control group (n=7 each). Test sites were treated with initial bone preparation followed by implant placement after a 2-week delay; control sites were treated with the conventional protocol. All sites were assessed over 12 months for the keratinized mucosa index, probing depth, implant mobility, and radiographic peri-implant crestal bone levels. A total of 14 implants were placed in 12 subjects (five males and seven females, mean age 31.5 years, range 18-45 years). The results showed a statistically significant reduction in peri-implant probing depth and crestal bone levels in the test group (P<0.01). This randomized controlled trial demonstrated better clinical and radiographic outcomes for initial bone preparation followed by a 2-week delay in implant placement; this may be an alternative to the conventional protocol.

Evaluation of the updated confocal laser endomicroscopy criteria for Barrett's esophagus among gastrointestinal pathologists.

Previously developed novel probe-based confocal laser endomicroscopy (pCLE) criteria have been found to have high accuracy and substantial interobserver agreement (IOA) for diagnosing dysplasia in Barrett's esophagus (BE) when used by endoscopists. These updated criteria are: (i) epithelial surface: saw toothed, (ii) cells: enlarged, (iii) cells: pleomorphic, (iv) glands: not equidistant, (v) glands: unequal in size and shape, and (vi) goblet cells: not easily identified. The accuracy and IOA among pathologists in the diagnosis of dysplasia using the novel pCLE criteria is not known. The primary objective of the study was to evaluate the accuracy, overall IOA and learning curve among three gastrointestinal (GI) pathologists in diagnosing dysplasia in BE using the updated pCLE criteria. The secondary aim was to compare the accuracy and IOA between GI pathologists and gastroenterology endoscopists. Ninety pCLE videos and respective histology were retrieved from a previously conducted multicenter, prospective, randomized, controlled trial evaluating the utility of pCLE in BE patients. Videos were obtained from 101 BE patients previously enrolled for surveillance or endoscopic treatment of high-grade dysplasia or early esophageal adenocarcinoma. Three GI pathologists reviewed 90 pCLE video clips for dysplasia versus no dysplasia, confidence in their diagnosis, and image quality. The overall accuracy for the diagnosis of dysplasia (low-grade dysplasia/high-grade dysplasia/esophageal adenocarcinoma) was 77.8% (95% confidence interval [CI]: 72.4-82.3). The accuracy was higher when pathologists had 'high confidence' in their assessment of the videos (93.8% vs. 69.3%, P < 0.001). There was no significant difference in accuracy between the first set of 30 and second set of 60 videos (84% vs. 74%, P = 0.065). IOA among GI pathologists was substantial, k = 0.65 (95% CI: 0.53-0.73). The sensitivity for detecting dysplasia was 85% (95% CI: 78.1-90.7) and the specificity was 70% (95% CI: 61.91-77.92). These results were comparable with the evaluation of the same set of videos by endoscopists. GI pathologists have high accuracy and substantial IOA for diagnosing BE dysplasia with pCLE. Pathologists appear to have similar accuracy and IOA as endoscopists. These results provide further support of endoscopists accurately interpreting the in vivo optical histology provided by pCLE.

Solubility advantage from amorphous etoricoxib solid dispersions.

OBJECTIVE: This study aimed to evaluate kinetic solubility advantage of amorphous etoricoxib solid dispersions prepared with three water soluble polymers and correlate it with solid state and supersaturated drug solution stabilization potential of these polymers. METHODS: Amorphous solid dispersions (ASDs) of etoricoxib were prepared with polyvinyl alcohol (PVA), polyvinyl pyrrolidone (PVP) and hydroxyethyl cellulose (HEC) at 70:30w/w ratio and characterized for glass transition temperature (Tg), miscibility and intermolecular interactions. Kinetic solubility profiles of amorphous etoricoxib and its ASDs were determined in water at 37 °C. Solid-state stability was assessed by enthalpy relaxation studies at a common degree of undercooling of around 19.0 °C at 0% RH. Recrystallization behavior of supersaturated drug solution was evaluated in the absence and presence of pre-dissolved polymer at 37 °C. RESULTS: Amorphous etoricoxib exhibited rapid solid-to-solid transition to yield a solubility advantage of merely 1.5-fold in water. Among the ASDs, etoricoxib-PVP dispersion exhibited maximal "peak" (2-fold) and "plateau" (1.8-fold) solubility enhancement, while etoricoxib-PVA dispersion could only sustain the "peak" solubility achieved by amorphous etoricoxib. In contrast, etoricoxib-HEC dispersion displayed no solubility advantage. The rank order for solid state and supersaturated solution stabilization followed a similar trend of amorphous etoricoxib < HEC < PVA < PVP. CONCLUSION: Dissolution behavior of ASDs is influenced by concomitantly occurring solid phase changes, thus understanding these processes independently can enable assessment of the predominant route of drug crystallization and stabilization by the polymer.