Effectiveness of Yoga in Modulating Markers of Immunity and Inflammation: A Systematic Review and Meta-Analysis.

Chronic inflammation is central to the pathogenesis of many chronic inflammatory conditions. This review aims to analyze whether the practice of yoga, or yogic meditation and breathing, has any effect on the levels of inflammatory cytokines and other inflammatory markers in patients with various chronic inflammatory diseases such as rheumatoid arthritis, neoplastic disorders, and asthma, as well as in healthy subjects, compared to usual care or sham interventions. A comprehensive search of databases (PubMed, CENTRAL, Embase, and CINAHL) was performed. Randomized controlled trials (RCTs) that evaluated the effects of yoga as an intervention on inflammatory markers were analyzed. A total of 26 studies were included. Only two studies had a low risk of bias (RoB); 24 other studies had a high RoB. Most studies (n=24) reported a favorable outcome with yoga, irrespective of the type of yoga used, the condition studied, and the duration of the intervention. The commonly reported inflammatory markers included IL-6 (n=17), tumor necrosis factor-alpha (TNF-a) (n=13), and C-reactive protein (CRP) (n=10). Most studies showed a significant reduction in inflammatory markers in the yoga group (YG) compared to the control group (CG). Few studies also showed significant improvement in markers of cellular immunity (interferon gamma (IFN-g), IL-10, and transforming growth factor-beta (TGF-b); n=2 each) and improved mucosal defense (IgA, IL-6, and IL-2; n=2 each). A meta-analysis of IL-6, TNF-a, and CRP showed yoga had a favorable effect on the levels of these markers, but it was not statistically significant. Current evidence suggests that yoga can be a complementary intervention for various chronic inflammatory conditions. However, the quality of the evidence is poor, along with considerable heterogeneity. In the future, investigators should describe the intervention better, with a uniform assortment of outcome measures and treatment conditions, to generate high-quality evidence.

Dosimetric comparison of magnetic resonance-guided radiation therapy, intensity-modulated proton therapy and volumetric-modulated arc therapy for distal esophageal cancer.

Advances in radiotherapy (RT) technologies permit significant decreases in the dose delivered to organs at risk (OARs) for patients with esophageal cancer (EC). Novel RT modalities such as proton beam therapy (PBT) and magnetic resonance-guided radiotherapy (MRgRT), as well as motion management techniques including breath hold (BH) are expected to further improve the therapeutic ratio. However, to our knowledge, the dosimetric benefits of PBT vs MRgRT vs volumetric-modulated arc therapy (VMAT) have not been directly compared for EC. We performed a retrospective in silico evaluation using the images and datasets of nine distal EC patients who were treated at our institution with a 0.35-Tesla MR linac to 50.4 Gy in 28 fractions in mid-inspiration BH (BH-MRgRT). Comparison free-breathing (FB) intensity-modulated PBT (FB-IMPT) and FB-VMAT plans were retrospectively created using the same prescription dose, target volume coverage goals, and OAR constraints. A 5 mm setup margin was used for all plans. BH-IMPT and BH-VMAT plans were not evaluated as they would not reflect our institutional practice. Planners were blinded to the results of the treatment plans created using different radiation modalities. The primary objective was to compare plan quality, target volume coverage, and OAR doses. All treatment plans met pre-defined target volume coverage and OAR constraints. The median conformity and homogeneity indices between FB-IMPT, BH-MRgRT and FB-VMAT were 1.13, 1.25, and 1.43 (PITV) and 1.04, 1.15, 1.04 (HI), respectively. For FB-IMPT, BH-MRgRT and FB-VMAT the median heart dose metrics were 52.8, 79.3, 146.8 (V30Gy, cc), 35.5, 43.8, 77.5 (V40Gy, cc), 16.9, 16.9, 32.5 (V50Gy, cc) and 6.5, 14.9, 17.3 (mean, Gy), respectively. Lung dose metrics were 8.6, 7.9, 18.5 (V20Gy, %), and 4.3, 6.3, 11.2 (mean, Gy), respectively. The mean liver dose (Gy) was 6.5, 19.6, 22.2 respectively. Both FB-IMPT and BH-MRgRT achieve substantial reductions in heart, lung, and liver dose compared to FB-VMAT. We plan to evaluate dosimetric outcomes across these RT modalities assuming consistent use of BH.

Diabetic Ketoacidosis Unmasking a Diagnosis of Glucose-6-Phosphate Dehydrogenase Deficiency: A Case Report and Literature Review.

Glucose-6-phosphate dehydrogenase deficiency (G6PD) is the most common enzyme deficiency. Mode of inheritance is X-linked recessive with a high prevalence in endogamous marriages, such as Jehovah's Witness. Oxidative triggers such as infection, ingestion of certain medications, certain types of food, and in rare instances diabetic ketoacidosis (DKA) may unmask the diagnosis by triggering a hemolytic event. We describe the case of a 43-year-old male with type 2 diabetes who presented with DKA and subsequently became anemic four days after his admission, with the hemoglobin continuing to fall. After extensive workup, it was found that the patient had G6PD confirmed by a low glucose-6-phosphate dehydrogenase assay. We hypothesized that the oxidative stress from the DKA unmasked G6PD induced hemolysis in our patient. During our literature search, we also noticed that hemolysis was delayed on average by four to seven days in these patients after the initiation of insulin therapy similar to our patient. It is postulated that the delayed onset of hemolysis may be due to high levels of glucose in the blood. Hyperglycemia may offset the effects of G6PD deficiency by increasing the production of G6PD. When the levels of glucose start falling, hemolysis becomes apparent.

Disseminated Cysticercosis-Should we treat?

Disseminated cysticercosis is defined by the presence of multiple vesicular cystic lesions in the brain with cysts demonstrable in at least two other body parts. The exact course of disseminated cysticercosis is not known and the individual cysts either become inflamed or calcify. A patient's quality of life is often poor and disseminated cysticercosis treatment is far from satisfactory. Anecdotal reports have suggested dual antiparasitic therapy to be beneficial for treating diffuse parenchymal neurocysticerci and might be worth trying in patients with massively infiltrating disseminated cysticercosis with concomitant corticosteroids.

Investigating the utilization of beam-specific apertures for the intensity-modulated proton therapy (IMPT) head and neck cancer plans.

Intensity-modulated proton therapy (IMPT) planning for the head and neck (HN) cancer often requires the use of the range shifter, which can increase the lateral penumbrae of the pencil proton beam in the patient, thus leading to an increase in unnecessary dose to the organs at risks (OARs) in proximity to the target volumes. The primary goal of the current study was to investigate the dosimetric benefits of utilizing beam-specific apertures for the IMPT HN cancer plans. The current retrospective study included computed tomography datasets of 10 unilateral HN cancer patients. The clinical target volume (CTV) was divided into low-risk CTV1 and high-risk CTV2. Total dose prescriptions to the CTV1 and CTV2 were 54 Gy(RBE) and 70 Gy(RBE), respectively, with a fractional dose of 2 Gy(RBE). All treatment plans were robustly optimized (patient setup uncertainty = 3 mm; range uncertainty = 3.5%) on the CTVs. For each patient, 2 sets of plans were generated: (1) without beam-specific aperture (WOBSA), and (2) with beam-specific aperture (WBSA). Specifically, both the WOBSA and WBSA of the given patient used identical beam angles, air gap, optimization structures, optimization constraints, and optimization settings. Target coverage and homogeneity index were comparable in both the WOBSA and WBSA plans with no statistical significance (p > 0.05). On average, the mean dose in WBSA plans was reduced by 12.1%, 2.9%, 3.0%, 3.8%, and 5.2% for the larynx, oral cavity, parotids, superior pharyngeal constrictor muscle, and inferior pharyngeal constrictor muscle, respectively. The dosimetric results of the OARs were found to be statistically significant (p < 0.05). The use of the beam-specific apertures did not deteriorate the coverage and homogeneity in the target volume and allowed for a reduction in mean dose to the OARs with an average difference up to 12.1%.

Of dots and levels: a case of partial subacute combined degeneration.

Subacute combined degeneration of the spinal cord is a typical clinical syndrome due to vitamin B12 deficiency, characterised by the involvement of the posterior column and corticospinal tracts. Occasionally, it may present with atypical features such as a sensory level and Lhermitte's sign, both traditionally considered to be a feature of compressive myelopathy. Spinal magnetic resonance imaging strongly augments the diagnosis by exhibiting changes in the posterior column in the form of a 'dot'. We describe such a patient who responded to therapy.

Case Report: Neuroleptic malignant syndrome in a HIV-positive patient.

We report a 29-year-old, HIV-positive woman being treated with antipsychotic medication for psychosis (Clopixol 200mg intramuscularly monthly, Risperidone 2mg orally daily Haloperidol 2.5mg twice a day), who presented with neuroleptic malignant syndrome. She was also receiving lorazepam and sodium valproate. The patient was referred to our department as she had developed involuntary upper limb movements and simple permanent focal seizure on the lower part of the left hemiface. Clinically the patient had altered consciousness, autonomic dysfunction, and rigidity. Her blood tests showed elevated creatine kinase (1467U/L) but no leucocytosis. We did a thorough workup for other causes of such a presentation. A comprehensive history was taken from the family to exclude other medications used. Her cerebrospinal fluid results were average. Blood tests did not show evidence of infection or other abnormalities. Computed tomography brain was normal. The patient died a few days after the beginning of the attack, which we have also observed  in other HIV-female patients. As far as we know, it is the first report about this comorbidity reported in the medical literature.

Microbiological profile of septic arthritis in adults: Lessons learnt and treatment strategies.

Objective: The aim of this study is to characterise the clinical and microbiological profile of adult patients treated at our orthopaedic unit with septic arthritic between 2006 and 2017. Materials and Methods: A total of 70 patients who were admitted with a diagnosis of septic arthritis between 2006 and 2017 were included in the study. The patients' clinical and epidemiological characteristics were surveyed; microbiological profile and the complications relating to the patients' treatment were identified. Results: Septic arthritis was more common among males (83%). About 75% of the patients presented with a history of fever. The knee was the most commonly affected joint (71%), followed by the hip. While C-reactive protein was found to be consistently >75, total blood white blood cell (WBC) counts were found not to be reflective of the presence of infection with a mean WBC count of only 13,561/cu.mm, and Gram stain examination had a poor sensitivity of 47%. Among the co-morbidities, the most prevalent association was with diabetes mellitus. The infectious agent most frequently isolated was Staphylococcus aureus(42.85%). The antibiotic sensitivity pattern has evolved since the early years, with resistant strains becoming increasingly prevalent. Unusually, high incidence of streptococci was noted (30%), contrary to the published literature. One-third of the patients had multi-resistant organisms. Septic arthritis left 70% of the patients with a significant residual disability at 6 months follow-up and had 4.25% mortality. Conclusion: Changing sensitivity patterns of microbes in septic arthritis point to a need for reconsidering empirical antibiotic therapy. Joint damage following infection can lead to significant disability.

Microbiological profile and outcomes of two-stage revision hip arthroplasty.

Background: Prosthetic joint infection (PJI) is one of the most challenging cases that confront modern orthopaedics. Two-stage revision, which is the standard of care for PJI, is the preferred mode of treatment for these infections. Aims and Objectives: To study the microbiological profile of prosthetic joint infections (PJI) in the hip and to assess the efficacy of a two stage revision surgery for PJI. We also aimed to study the sensitivity and specificity of ESR and CRP in the diagnosis of PJI. Materials and Methods: The microbiological profile, clinical and radiological outcomes of 22 patients who had a two-stage revision for PJI of the hip between 2013 and 2017 were retrospectively analysed. PJI was defined using the criteria provided by the International Consensus Statement on PJI 2013. Results: Staphylococcus aureus was found to be the most common organism in PJI. Debridement was successful in removing the organism in 74% of PJI. At the time of re-implantation (second stage), six joints grew organisms that were different from that isolated at the index debridement - coagulase-negative staphylococci (3cases) and enterococci (3cases). Other infection parameters for these patients were negative. None of the patients who had two-stage revision surgery had clinical evidence of reinfection or radiological evidence of loosening at a mean of 2-year follow-up. An ESR cut off of >30mm/hr had a sensitivity of 75% and specificity of 88% in predicting PJI. A CRP >10mg/L had a sensitivity of 75% and specificity of 69%. The sensitivity and specificity of using both ESR and CRP cut-offs in the diagnosis of infection were 57% and 94%, respectively. The positive predictive value was 94% and negative predictive value was 56%. Conclusion: The outcomes of the study justify a two-stage revision arthroplasty for PJI of the hip. The use of ESR and CRP as screening tests for the success of debridement has value - but should be interpreted with caution.

Association of Delay in Appendectomy With Perforation in Children With Appendicitis.

OBJECTIVE: The aim of this study was to assess whether increased time from emergency department (ED) triage to appendectomy is associated with a greater risk of children developing appendiceal perforation. METHODS: We performed a multicenter retrospective cohort study of children younger than 18 years hospitalized with appendicitis. To avoid enrolling patients who had perforated prior to ED arrival, we included only children who had a computed tomography (CT) scan demonstrating nonperforated appendicitis. Time to appendectomy was measured as time from ED triage to incision. The main outcome was appendiceal perforation as documented in the surgical report. Variables associated with perforation in bivariate analysis (P < 0.05) were adjusted for using logistic regression. RESULTS: Overall, 857 patients had a CT scan that demonstrated nonperforated appendicitis. The median age was 12 years (interquartile range, 9-15 years), and 500 (58%) were male. The median time to appendectomy was 11 hours (interquartile range, 8-15 hours). In total, 111 patients (13%) had perforated appendicitis at operation. Children who developed perforation were more likely to require additional CT scans and return to the ED and had a significantly longer length of stay. After adjusting for potential confounders, every hour increase in the time from ED triage to incision was independently associated with a 2% increase in the odds of perforation (P = 0.03; adjusted odds ratio, 1.02; 95% confidence interval, 1.00-1.04). CONCLUSIONS: Delays in appendectomy were associated with an increase in the odds of perforation. These results suggest that prolonged delays to appendectomy might be harmful for children with appendicitis and should be minimized to prevent associated morbidity.

Prevalence of Dental Anxiety and Associated Factors among Indian Children

Objective: To determine the prevalence of dental anxiety and associated factors among 5 to10 years old Indian children. Material and Methods: In this cross-sectional study, the sample was composed by 462 children (240 male and 222 female). Questionnaires consisting of dental anxiety scales were distributed to mother-child pair participants. Children fear survey schedule-dental subscale was used to assess child dental anxiety and Corah's dental anxiety scale was used to measure maternal dental anxiety. Age, gender, religion were also recorded to check the correlation of these factors with the child dental anxiety. Data was analyzed using SPSS software. Fisher's exact test and Pearson correlation tests were applied. The level of significance was set at 5%. Results: The cut-off score for CFSS-DS was 36. The prevalence of dental anxiety was 24.5% among 5 to 10 year old children. Although a statistically significant association was found between maternal and child dental anxiety (p=0.000), no significant association existed between age, gender, culture (religion) and child dental anxiety (p>0.05). Conclusion: Prevalence of dental anxiety was high in the Indian child population. Maternal dental anxiety was found to significantly influence the child dental anxiety, as compared to age, gender or the religion.

Dabigatran overdose secondary to acute kidney injury and amiodarone use.

Oral direct thrombin inhibitors have improved treatment of non-valvular atrial fibrillation. Safety concerns have been raised since there is no antidote for treatment of secondary haemorrhages and the absence of widely validated test to monitor drug levels. We present a case of dabigatran overdose in an 82-year-old female who was treated with a seemingly appropriate dose.

Variations in the RBE for cell killing along the depth-dose profile of a modulated proton therapy beam.

Considerable evidence now exists to show that that the relative biological effectiveness (RBE) changes considerably along the proton depth-dose distribution, with progressively higher RBE values at the distal part of the modulated, or spread out Bragg peak (SOBP) and in the distal dose fall-off (DDF). However, the highly variable nature of the existing studies (with regards to cell lines, and to the physical properties and dosimetry of the various proton beams) precludes any consensus regarding the RBE weighting factor at any position in the depth-dose profile. We have thus conducted a systematic study on the variation in RBE for cell killing for two clinical modulated proton beams at Indiana University and have determined the relationship between the RBE and the dose-averaged linear energy transfer (LETd) of the protons at various positions along the depth-dose profiles. Clonogenic assays were performed on human Hep2 laryngeal cancer cells and V79 cells at various positions along the SOBPs of beams with incident energies of 87 and 200 MeV. There was a marked variation in the radiosensitivity of both cell lines along the SOBP depth-dose profile of the 87 MeV proton beam. Using Hep2 cells, the D(0.1) isoeffect dose RBE values (normalized against (60)Co) were 1.46 at the middle of SOBP, 2.1 at the distal end of the SOBP and 2.3 in the DDF. For V79 cells, the D(0.1) isoeffect RBE for the 87 MEV beam were 1.23 for the proximal end of the SOBP: 1.46 for the distal SOBP and 1.78 for the DDF. Similar D(0.1) isoeffect RBE values were found for Hep2 cells irradiated at various positions along the depth-dose profile of the 200 MeV beam. Our experimentally derived RBE values were significantly correlated (P = 0.001) with the mean LETd of the protons at the various depths, which confirmed that proton RBE is highly dependent on LETd. These in vitro data suggest that the RBE of the proton beam at certain depths is greater than 1.1, a value currently used in most treatment planning algorithms. Thus, the potential for increased cell killing and normal tissue damage in the distal regions of the proton SOBP may be greater than originally thought.

Mapping local matrix remodeling induced by a migrating tumor cell using three-dimensional multiple-particle tracking.

Mesenchymal cell migration through a three-dimensional (3D) matrix typically involves major matrix remodeling. The direction of matrix deformation occurs locally in all three dimensions, which cannot be measured by current techniques. To probe the local, 3D, real-time deformation of a collagen matrix during tumor cell migration, we developed an assay whereby matrix-embedded beads are tracked simultaneously in all three directions with high resolution. To establish a proof of principle, we investigated patterns of collagen I matrix deformation near fibrosarcoma cells in the absence and presence of inhibitors of matrix metalloproteinases and acto-myosin contractility. Our results indicate that migrating cells show patterns of local matrix deformation toward the cell that are symmetric in magnitude with respect to the axis of cell movement. In contrast, patterns of matrix release from the cell are asymmetric: the matrix is typically relaxed first at the back of the cell, allowing forward motion, and then at the cell's leading edge. Matrix deformation in regions of the matrix near the cell's leading edge is elastic and mostly reversible, but induces irreversible matrix rupture events near the trailing edge. Our results also indicate that matrix remodeling spatially correlates with protrusive activity. This correlation is mediated by myosin II and Rac1, and eliminated after inhibition of pericellular proteolysis or ROCK. We have developed an assay based on high-resolution 3D multiple-particle tracking that allows us to probe local matrix remodeling during mesenchymal cell migration through a 3D matrix and simultaneously monitor protrusion dynamics.

Fibronectin fibrillogenesis regulates three-dimensional neovessel formation.

During vasculogenesis and angiogenesis, endothelial cell responses to growth factors are modulated by the compositional and mechanical properties of a surrounding three-dimensional (3D) extracellular matrix (ECM) that is dominated by either cross-linked fibrin or type I collagen. While 3D-embedded endothelial cells establish adhesive interactions with surrounding ligands to optimally respond to soluble or matrix-bound agonists, the manner in which a randomly ordered ECM with diverse physico-mechanical properties is remodeled to support blood vessel formation has remained undefined. Herein, we demonstrate that endothelial cells initiate neovascularization by unfolding soluble fibronectin (Fn) and depositing a pericellular network of fibrils that serve to support cytoskeletal organization, actomyosin-dependent tension, and the viscoelastic properties of the embedded cells in a 3D-specific fashion. These results advance a new model wherein Fn polymerization serves as a structural scaffolding that displays adhesive ligands on a mechanically ideal substratum for promoting neovessel development.

Nuclear lamin A/C deficiency induces defects in cell mechanics, polarization, and migration.

Lamin A/C is a major constituent of the nuclear lamina, a thin filamentous protein layer that lies beneath the nuclear envelope. Here we show that lamin A/C deficiency in mouse embryonic fibroblasts (Lmna(-/-) MEFs) diminishes the ability of these cells to polarize at the edge of a wound and significantly reduces cell migration speed into the wound. Moreover, lamin A/C deficiency induces significant separation of the microtubule organizing center (MTOC) from the nuclear envelope. Investigations using ballistic intracellular nanorheology reveal that lamin A/C deficiency also dramatically affects the micromechanical properties of the cytoplasm. Both the elasticity (stretchiness) and the viscosity (propensity of a material to flow) of the cytoplasm in Lmna(-/-) MEFs are significantly reduced. Disassembly of either the actin filament or microtubule networks in Lmna(+/+) MEFs results in decrease of cytoplasmic elasticity and viscosity down to levels found in Lmna(-/-) MEFs. Together these results show that both the mechanical properties of the cytoskeleton and cytoskeleton-based processes, including cell motility, coupled MTOC and nucleus dynamics, and cell polarization, depend critically on the integrity of the nuclear lamina, which suggest the existence of a functional mechanical connection between the nucleus and the cytoskeleton. These results also suggest that cell polarization during cell migration requires tight mechanical coupling between MTOC and nucleus, which is mediated by lamin A/C.