Habitual Patella Dislocation in a patient with Osteogenesis Imperfecta.

Fahr's disease is characterized by idiopathic bilateral deposition of calcium in the striopallidodentate area. We are presenting 83-year-old female, who failed responding while having lunch around 10 AM soon after she lost consciousness for an hour. It was associated with difficulty in walking, mood disturbances, fatigability, blurring of vision and occasional dizziness since past 4 months. Her neurological examination revealed Parkinsonian features. Her computed tomography of head report showed bilateral, symmetrical, large area of calcification over the basal ganglia, the thalamus and the cerebellum. To rule out the seizure disorder we have done an electroencephalogram and some laboratory test including calcium, Phosphorus, Parathyroid hormone and magnesium, vitamin D which were suggestive of Fahr's disease.

Angiostatic Peptide, Endostatin, Predicts Severity in Pediatric Congenital Heart Disease-Associated Pulmonary Hypertension.

Background Endostatin, an angiogenic inhibitor, is associated with worse pulmonary arterial hypertension (PAH) outcomes in adults and poor lung growth in children. This study sought to assess whether endostatin is associated with disease severity and outcomes in pediatric PAH. Methods and Results Serum endostatin was measured in cross-sectional (N=160) and longitudinal cohorts (N=64) of pediatric subjects with PAH, healthy pediatric controls and pediatric controls with congenital heart disease (CHD) (N=54, N=15), and adults with CHD associated PAH (APAH-CHD, N=185). Outcomes, assessed by regression and Kaplan-Meier analysis, included hemodynamics, change in endostatin over time, and transplant-free survival. Endostatin secretion was evaluated in pulmonary artery endothelial and smooth muscle cells. Endostatin was higher in those with PAH compared with healthy controls and controls with CHD and was highest in those with APAH-CHD. In APAH-CHD, endostatin was associated with a shorter 6-minute walk distance and increased mean right atrial pressure. Over time, endostatin was associated with higher pulmonary artery pressure and pulmonary vascular resistance index, right ventricular dilation, and dysfunction. Endostatin decreased with improved hemodynamics over time. Endostatin was associated with worse transplant-free survival. Addition of endostatin to an NT-proBNP (N-terminal pro-B-type natriuretic peptide) based survival analysis improved risk stratification, reclassifying subjects with adverse outcomes. Endostatin was secreted primarily by pulmonary artery endothelial cells. Conclusions Endostatin is associated with disease severity, disease improvement, and worse survival in APAH-CHD. Endostatin with NT-proBNP improves risk stratification, better predicting adverse outcomes. The association of elevated endostatin with shunt lesions suggests that endostatin could be driven by both pulmonary artery flow and pressure. Endostatin could be studied as a noninvasive prognostic marker, particularly in APAH-CHD.

The angiostatic peptide endostatin enhances mortality risk prediction in pulmonary arterial hypertension.

Currently available noninvasive markers for assessing disease severity and mortality risk in pulmonary arterial hypertension (PAH) are unrelated to fundamental disease biology. Endostatin, an angiostatic peptide known to inhibit pulmonary artery endothelial cell migration, proliferation and survival in vitro, has been linked to adverse haemodynamics and shortened survival in small PAH cohorts. This observational cohort study sought to assess: 1) the prognostic performance of circulating endostatin levels in a large, multicentre PAH cohort; and 2) the added value gained by incorporating endostatin into existing PAH risk prediction models. Endostatin ELISAs were performed on enrolment samples collected from 2017 PAH subjects with detailed clinical data, including survival times. Endostatin associations with clinical variables, including survival, were examined using multivariable regression and Cox proportional hazards models. Extended survival models including endostatin were compared to null models based on the REVEAL risk prediction tool and European Society of Cardiology/European Respiratory Society (ESC/ERS) low-risk criteria using likelihood ratio tests, Akaike and Bayesian information criteria and C-statistics. Higher endostatin was associated with higher right atrial pressure, mean pulmonary arterial pressure and pulmonary vascular resistance, and with shorter 6-min walk distance (p<0.01). Mortality risk doubled for each log higher endostatin (hazard ratio 2.3, 95% CI 1.6-3.4, p<0.001). Endostatin remained an independent predictor of survival when incorporated into existing risk prediction models. Adding endostatin to REVEAL-based and ESC/ERS criteria-based risk assessment strategies improved mortality risk prediction. Endostatin is a robust, independent predictor of mortality in PAH. Adding endostatin to existing PAH risk prediction strategies improves PAH risk assessment.

A distinctive release profile of vancomycin and tobramycin from a new and injectable polymeric dicalcium phosphate dehydrate cement (P-DCPD).

A novel injectable polymeric dicalcium phosphate dehydrate (P-DCPD) cement was developed with superior mechanical strength and excellent cohesion. The purpose of this study was to assess the in vitro performance of P-DCPD loaded with vancomycin (VAN-P), tobramycin (TOB-P) and combination of both (VAN/TOB-P) (10%, w/w). There is a distinctive release profile between VAN and TOB. VAN-P showed decreased initial burst (<30% within 3 d) and sustained VAN release (76% in 28 d). In the presence of TOB (VAN/TOB-P), >90% of VAN was released within 3 d (p < 0.05). Slow and limited TOB release was observed both in TOB-P (<5%) and in TOB/VAN-P (<1%) over 28 d. Zone of inhibition (ZOI) of Staphylococcus aureus growth showed that eluents collected from VAN-P had stronger and longer ZOI (28 d) than that from TOB-P (14 d, p < 0.05). Direct contact of VAN-P, TOB-P and VAN/TOB-P cements displayed persistent and strong ZOI for >3 weeks. Interestingly, the cement residues (28 d after drug release) still maintained strong ZOI ability. P-DCPD with or without antibiotics loading were nontoxic and had no inferior impacts on the growth of osteoblastic MC3T3 cells. VAN-P and TOB-P were injectable. No significant influence on setting time was observed in both VAN-P (11.7 ± 1.9 min) and VAN/TOB-P (10.8 ± 1.5 min) as compared to control (12.2 ± 2.6 min). We propose that a distinctive release profile of VAN and TOB observed is mainly due to different distribution pattern of VAN and TOB within P-DCPD matrix. A limited release of TOB might be due to the incorporation of TOB inside the crystalline lattice of P-DCPD crystals. Our data supported that the bactericidal efficacy of antibiotics-loaded P-DCPD is not only depend on the amount and velocity of antibiotics released, but also probably more on the direct contact of attached bacteria on the degrading cement surface.

Elevated Interleukin-6 Levels Predict Clinical Worsening in Pediatric Pulmonary Arterial Hypertension.

OBJECTIVE: To assess whether circulating interleukin-6 (IL-6) is associated with measures of disease severity and clinical worsening in pediatric pulmonary arterial hypertension (PAH). STUDY DESIGN: IL-6 was measured by enzyme-linked immunosorbent assay in serum samples from a cross-sectional cohort from the National Heart, Lung, and Blood Institute Pulmonary Arterial Hypertension Biobank (n = 175) and a longitudinal cohort from Children's Hospital Colorado (CHC) (n = 61). Associations between IL-6, disease severity, and outcomes were studied with regression and Kaplan-Meier analysis. RESULTS: In analyses adjusted for age and sex, each log-unit greater IL-6 was significantly associated in the Pulmonary Arterial Hypertension Biobank cohort with greater pulmonary vascular resistance indices, lower odds of having idiopathic PAH or treatment with prostacyclin, and greater odds of having PAH associated with a repaired congenital shunt. In the CHC cohort, each log-unit greater IL-6 was significantly associated with greater mean pulmonary arterial pressure over time. Kaplan-Meier analysis in the CHC cohort revealed that IL-6 was significantly associated with clinical worsening (a composite score of mortality, transplant, or palliative surgery) (P = .037). CONCLUSIONS: IL-6 was significantly associated with worse hemodynamics at baseline and over time and may be associated with clinical worsening. IL-6 may provide a less-invasive method for disease monitoring and prognosis in pediatric PAH as well as a potential therapeutic target.

Cellular sources of interleukin-6 and associations with clinical phenotypes and outcomes in pulmonary arterial hypertension.

The pro-inflammatory cytokine interleukin (IL)-6 has been associated with outcomes in small pulmonary arterial hypertension (PAH) cohorts composed largely of patients with severe idiopathic PAH (IPAH). It is unclear whether IL-6 is a marker of critical illness or a mechanistic biomarker of pulmonary vascular remodelling. We hypothesised that IL-6 is produced by pulmonary vascular cells and sought to explore IL-6 associations with phenotypes and outcomes across diverse subtypes in a large PAH cohort.IL-6 protein and gene expression levels were measured in cultured pulmonary artery smooth muscle cells (PASMCs) and endothelial cells (PAECs) from PAH patients and healthy controls. Serum IL-6 was measured in 2017 well-characterised PAH subjects representing each PAH subgroup. Relationships between IL-6 levels, clinical variables, and mortality were analysed using regression models.Significantly higher IL-6 protein and gene expression levels were produced by PASMCs than by PAECs in PAH (p<0.001), while there was no difference in IL-6 between cell types in controls. Serum IL-6 was highest in PAH related to portal hypertension and connective tissue diseases (CTD-PAH). In multivariable modelling, serum IL-6 was associated with survival in the overall cohort (hazard ratio 1.22, 95% CI 1.08-1.38; p<0.01) and in IPAH, but not in CTD-PAH. IL-6 remained associated with survival in low-risk subgroups of subjects with mild disease.IL-6 is released from PASMCs, and circulating IL-6 is associated with specific clinical phenotypes and outcomes in various PAH subgroups, including subjects with less severe disease. IL-6 is a mechanistic biomarker, and thus a potential therapeutic target, in certain PAH subgroups.

Noninvasive Prognostic Biomarkers for Left-Sided Heart Failure as Predictors of Survival in Pulmonary Arterial Hypertension.

BACKGROUND: Three biomarkers, soluble suppression of tumorigenicity 2 (ST2), galectin 3 (Gal3), and N-terminal brain natriuretic peptide prohormone (NT-proBNP), are approved for noninvasive risk assessment in left-sided heart failure, and small observational studies have shown their prognostic usefulness in heterogeneous pulmonary hypertension cohorts. We examined associations between these biomarkers and disease severity and survival in a large cohort of patients with pulmonary arterial hypertension (PAH) (ie, group 1 pulmonary hypertension). We hypothesized that additive use of biomarkers in combination would improve the prognostic value of survival models. METHODS: Biomarker measurements and clinical data were obtained from 2,017 adults with group 1 PAH. Associations among biomarker levels and clinical variables, including survival times, were examined with multivariable regression models. Likelihood ratio tests and the Akaike information criterion were used to compare survival models. RESULTS: Higher ST2 and NT-proBNP were associated with higher pulmonary pressures and vascular resistance and lower 6-min walk distance. Higher ST2 and NT-proBNP levels were associated with increased risk of death (hazard ratios: 2.79; 95% CI, 2.21-3.53; P < .001 and 1.84; 95% CI, 1.62-2.10; P < .001, respectively). The addition of ST2 to survival models composed of other predictors of survival, including NT-proBNP, significantly improved model fit and predictive capacity. CONCLUSIONS: ST2 and NT-proBNP are strong, noninvasive prognostic biomarkers in PAH. Despite its prognostic value in left-sided heart failure, Gal3 was not predictive in PAH. Adding ST2 to survival models significantly improves model predictive capacity. Future studies are needed to develop multimarker assays that improve noninvasive risk stratification in PAH.

Intra-Articular Synovial Fibroma of the Knee in a Young Boy.

Synovial fibroma, a benign fibro collagenous soft tissue tumour, arising in the knee joint is a rare entity. It is even rarer in the paediatric age group. The clinical symptoms, investigations, diagnosis, and treatment with the literature reviews are presented for this uncommon occurrence in an 11 year old boy.

In vitro macrophage activation: A technique for screening anti-inflammatory, immunomodulatory and anticancer activity of phytomolecules.

Macrophage activation plays a significant role in homeostasis of organisms. Various internal and external stress factors may affect their function, leading to adverse effects on the body. 'In vitro macrophage activation techniques provide us with a window to understand the mechanisms of inflammation and response of macrophages to the modulating interventions. Apart from infectious diseases, inflammation is also the major culprit in pathogenesis of many noncommunicable diseases such as arthritis, obesity, metabolic syndrome, diabetes, cancer, cardiovascular disease etc. In vitro macrophage activation allows us to study the role of polarized macrophages in the process of pathogenesis. This emerging technique leads to newer diagnostics, understanding pathophysiological mechanism/s, drug development and management of chronic inflammatory diseases. We, at MRC-KHS, use this technique for screening of medicinal plant-derived phytomolecules for their anti-inflammatory, immunomodulatory and anticancer activities. This review briefly outlines the different experimental models of in vitro macrophage activation and their applications for understanding the pathophysiological mechanisms of underlying chronic inflammation and screening of therapeutic activity of plant-based phytomolecules.

A simple model to predict the biodiesel blend density as simultaneous function of blend percent and temperature.

A simple method to estimate the density of biodiesel blend as simultaneous function of temperature and volume percent of biodiesel is proposed. Employing the Kay's mixing rule, we developed a model and investigated theoretically the density of different vegetable oil biodiesel blends as a simultaneous function of temperature and volume percent of biodiesel. Key advantage of the proposed model is that it requires only a single set of density values of components of biodiesel blends at any two different temperatures. We notice that the density of blend linearly decreases with increase in temperature and increases with increase in volume percent of the biodiesel. The lower values of standard estimate of error (SEE = 0.0003-0.0022) and absolute average deviation (AAD = 0.03-0.15 %) obtained using the proposed model indicate the predictive capability. The predicted values found good agreement with the recent available experimental data.

Prognostic factors for diffuse large B-cell lymphoma in the R(X)CHOP era.

BACKGROUND: The introduction of rituximab (R) to conventional CHOP chemotherapy for newly diagnosed diffuse large B-cell lymphoma (DLBCL) led to an unequivocal improvement in survival, establishing RCHOP as the standard of care. Still, nearly 40% of DLBCL patients will eventually die of relapsed disease. Efforts to improve outcomes by addition of new biologic agents (X) to the RCHOP backbone are underway. In this era of R(X)CHOP, it is imperative to develop prognostic and predictive markers, not only to identify patients who will suffer a particularly aggressive course, but also to accurately select patients for clinical trials from which they will most benefit. DESIGN: The following review was undertaken to describe prognostic factors in DLBCL, with emphasis on markers that are accurate, relatively available, and clinically applicable in 2014. RESULTS: The International Prognostic Index retains its validity in the era of RCHOP, although with limited ability to predict those with <50% chance of long-term survival. Gene expression profiling has provided novel insights into the biology of DLBCL and led to the development of immunohistochemistry (IHC) algorithms that are in routine practice. Identification of a 'double-hit' (DH) lymphoma by fluorescent in situ hybridization with aberrations involving MYC and/or BCL2 and BCL6 genes has important implications due to its extremely dismal prognosis with RCHOP. Other markers such as the absolute lymphocyte count (ALC), serum immunoglobulin free light chains, vitamin D levels, serum cytokines/chemokines, and imaging with positron emission tomography (PET) have all shown promise as future predictive/prognostic tests. CONCLUSIONS: The future for new treatment options in DLBCL is promising with current clinical trials testing novel targeted agents such as bortezomib, lenalidomide, and ibrutinib as the 'X' in R(X)CHOP. Predictive factors are required to select and randomize patients appropriately for these trials. We envision the day when 'X' will be chosen based on the biological characteristics of the tumor.

Survival and prognosis among 1545 patients with contemporary polycythemia vera: an international study.

Under the auspices of an International Working Group, seven centers submitted diagnostic and follow-up information on 1545 patients with World Health Organization-defined polycythemia vera (PV). At diagnosis, median age was 61 years (51% females); thrombocytosis and venous thrombosis were more frequent in women and arterial thrombosis and abnormal karyotype in men. Considering patients from the center with the most mature follow-up information (n=337 with 44% of patients followed to death), median survival (14.1 years) was significantly worse than that of the age- and sex-matched US population (P<0.001). In multivariable analysis, survival for the entire study cohort (n=1545) was adversely affected by older age, leukocytosis, venous thrombosis and abnormal karyotype; a prognostic model that included the first three parameters delineated risk groups with median survivals of 10.9-27.8 years (hazard ratio (HR), 10.7; 95% confidence interval (CI): 7.7-15.0). Pruritus was identified as a favorable risk factor for survival. Cumulative hazard of leukemic transformation, with death as a competing risk, was 2.3% at 10 years and 5.5% at 15 years; risk factors included older age, abnormal karyotype and leukocytes ≥15 × 10(9)/l. Leukemic transformation was associated with treatment exposure to pipobroman or P32/chlorambucil. We found no association between leukemic transformation and hydroxyurea or busulfan use.

Bowel perforation in intestinal lymphoma: incidence and clinical features.

BACKGROUND: Perforation is a serious life-threatening complication of lymphomas involving the gastrointestinal (GI) tract. Although some perforations occur as the initial presentation of GI lymphoma, others occur after initiation of chemotherapy. To define the location and timing of perforation, a single-center study was carried out of all patients with GI lymphoma. PATIENTS AND METHODS: Between 1975 and 2012, 1062 patients were identified with biopsy-proven GI involvement with lymphoma. A retrospective chart review was undertaken to identify patients with gut perforation and to determine their clinicopathologic features. RESULTS: Nine percent (92 of 1062) of patients developed a perforation, of which 55% (51 of 92) occurred after chemotherapy. The median day of perforation after initiation of chemotherapy was 46 days (mean, 83 days; range, 2-298) and 44% of perforations occurred within the first 4 weeks of treatment. Diffuse large B-cell lymphoma (DLBCL) was the most common lymphoma associated with perforation (59%, 55 of 92). Compared with indolent B-cell lymphomas, the risk of perforation was higher with aggressive B-cell lymphomas (hazard ratio, HR = 6.31, P < 0.0001) or T-cell/other types (HR = 12.40, P < 0.0001). The small intestine was the most common site of perforation (59%). CONCLUSION: Perforation remains a significant complication of GI lymphomas and is more frequently associated with aggressive than indolent lymphomas. Supported in part by University of Iowa/Mayo Clinic SPORE CA97274 and the Predolin Foundation.

The bikini area and bikini line as a location for anterior subcutaneous pelvic fixation: an anatomic and clinical investigation.

Anterior external fixation for pelvic fractures has been the standard for acute stabilization but definitive treatment often leads to pin tract infection, is uncomfortable, and limits patient mobility. We recently developed a subcutaneous anterior pelvic fixator which addresses these issues (INFIX). The objective of this study is to introduce the Bikini Area and Bikini Line as the subcutaneous anatomical location where this apparatus is placed. A study was preformed on eight cadaveric specimens to define the location of the subcutaneous device with respect to anatomic structures. We examined 23 people of various body mass indexes to examine the anterior pelvic anatomy. This was followed by implantation on 42 individuals in whom we reviewed CT scans to assess the location of the implant. We asked these same 42 individuals whether they could sit, stand, and lie on their sides and if they had any discomfort. We measured the dimensions of 26 retrieved rods to approximate the curve of the Bikini Line. Finally in 14 individuals we performed vascular ultrasound to assess the flow in the iliac and femoral vessels with the implant in place in the sitting and standing position. Neurovascular structures are not affected by placing the INFIX device at the Bikini Line, patients are comfortable, mobile and complications are minimized by this procedure. A rod placed on the Bikini Line which connects screws inserted into the anterior inferior iliac spine on each side does not interfere with sitting, standing, or the neurovascular structures.

Refined cytogenetic-risk categorization for overall and leukemia-free survival in primary myelofibrosis: a single center study of 433 patients.

We have previously identified sole +9, 13q- or 20q-, as 'favorable' and sole +8 or complex karyotype as 'unfavorable' cytogenetic abnormalities in primary myelofibrosis (PMF). In this study of 433 PMF patients, we describe additional sole abnormalities with favorable (chromosome 1 translocations/duplications) or unfavorable (-7/7q-) prognosis and also show that other sole or two abnormalities that do not include i(17q), -5/5q-, 12p-, inv(3) or 11q23 rearrangement are prognostically aligned with normal karyotype, which is prognostically favorable. These findings were incorporated into a refined two-tired cytogenetic-risk stratification: unfavorable and favorable karyotype. The respective 5-year survival rates were 8 and 51% (hazard ratio (HR): 3.1, 95% confidence interval (CI): 2.2-4.3; P<0.0001). Multivariable analysis confirmed the International Prognostic Scoring System (IPSS)-independent prognostic value of cytogenetic-risk categorization and also identified thrombocytopenia (platelets <100 × 10(9)/l) as another independent predictor of inferior survival (P<0.0001). A similar multivariable analysis showed that karyotype (P=0.001) and platelet count (P=0.04), but not IPSS (P=0.27), predicted leukemia-free survival; the 5-year leukemic transformation rates for unfavorable versus favorable karyotype were 46 and 7% (HR: 5.5, 95% CI: 2.5-12.0; P<0.0001). This study provides the rationale and necessary details for incorporating cytogenetic findings and platelet count in future prognostic models for PMF.

Serum IL-6 and micrometry of pap smears in women with cervical low-grade intraepithelial lesions.

OBJECTIVE: To assess serum IL-6 in women with or without low-grade squamous intraepithelial lesions (LSILs) in Pap smears and correlate with the nucleo/cytoplasmic (N/C) ratio. METHODS: Manual micrometry was carried out on Pap smears for N/C ratios: Group A, negative findings (N=15); Group B, inflammation without abnormality (N=14); Group C, LSIL with inflammation (N=13). Serum IL-6 was measured in Groups B and C after treatment of nonviral genital infections. Women with pelvic inflammatory or systemic diseases were excluded. RESULTS: The N/C ratio was significantly higher in Group C vs Group B, both before and after treatment of nonviral infections and also vs group A (p<0.001, Students t test). After treatment for non-viral infections serum IL-6 levels were >50 pg/ml in 5/13 cases of Group C and significantly higher than levels in Group B (p<0.05), correlating positively with the N/C ratio in the 13 cases of LSIL (Pearson's coefficient r=0.659, p<0.05). CONCLUSIONS: High peripheral circulating level of IL-6, despite prior treatment of nonviral infections, was observed in more than one third of women with persistent LSIL in Pap smears, and may serve as an additional biomarker for early cervical neoplasia. Long term follow up is indicated.

Anthropometric Parameters of Armed Forces Personnel.

BACKGROUND: The prevalence of obesity has increased globally in the last few decades. Anthropometry is an accepted method of measuring obesity. Charts of weight for height and age as well as Anthropometric indices like Body Mass Index (BMI) are commonly used to define normal, overweight and obese individuals. Weight for height charts currently in use in the Army belong to pre-independence era. It is widely believed that these have been obtained from life insurance tables made for British / American civilian population. The World Health Organization (WHO) encourages its member countries to develop their own reference anthropometric indices. METHODS: Anthropometric measurements were recorded for 902 healthy Armed Forces personnel in the age range of 28 to 52 years selected by stratified random sampling. These measurements were used to obtain mean values, standard deviations, medians and percentiles for various anthropometric parameters. RESULT: BMI for the study subjects ranged from 14.67 to 27.90 kg/m(2) with a mean of 20.52 Kg/m(2). No individual was categorized as obese using the current international cut-off of BMI >30 kg/m(2). With the exception of height, all other anthropometric parameters like weight, BMI, waist circumference, and waist-hip ratio were found to increase with increasing age. Correlation of BMI with waist circumference and BMI with Waist Hip Ratio in the study subjects was found to be statistically significant. The weight for height and age chart developed by this study shows an increase in weight in all age and height categories as compared to the weight for height chart currently in vogue in the Indian Army. CONCLUSION: The weight for height and age chart calculated in our study, shows considerable variation when compared to weight for height and age chart currently being used in Indian Army. The average weight for majority of height and age categories was found to be higher than in the Indian Army chart. It is recommended that a large multi-centric study should be taken up to gather more evidence to replace the current chart.

Mad honey poisoning: a rare case report of seven cases.

The cause of mad honey poisoning is the toxin grayanotoxin, found in honey obtained from the nectar of Rhododendron species on the higher altitudes. This case report is about seven cases of grayanotoxin poisoning that occurred after consumption of wild honey that was brought from the Himalayan belt of Nepal. Most of them presented with symptoms of blurring of vision, diplopia, nasea and vomiting and two of them presented with symptoms of cardiac depression. All of the cases responded well to intravenous fluid and/or pressor agents while none proved to be fatal