Four year experience of sarcoma of soft tissues and bones in a tertiary care hospital and review of literature

<p>Abstract</p> <p>Background</p> <p>Sarcoma encompasses an uncommon group of cancer and the data is insufficient from Pakistan. We report our four years experience of Sarcoma of soft tissues and bones.</p> <p>Methods</p> <p>This cross sectional study was carried out at Aga Khan University Hospital from 2004 to 2008. The patients were divided into two groups from the outset i.e. initially diagnosed and relapsed group and separate sub group analysis was conducted.</p> <p>Results</p> <p>Out of 93 newly diagnosed patients, 58 belonged to bone sarcoma and 35 to soft tissue sarcoma group. While for relapsed patients, 5 had soft tissue sarcoma and 9 had bone sarcoma. Mean age was 32.5 years. At presentation, approximately two third patients had localised disease while remaining one third had metastatic disease. The Kaplan Meier estimate of median recurrence free survival was 25 months, 35 months, and 44 months for Osteogenic sarcoma, Ewing's sarcoma and Chondrosarcoma respectively. For Leiomyosarcoma and Synovial sarcoma, it was 20 and 19 months respectively. The grade of the tumour (p = 0.02) and surgical margin status (p = 0.001) were statistically significant for determination of relapse of disease.</p> <p>Conclusion</p> <p>The median recurrence free survival of patients in our study was comparable to the reported literature but with significant lost to follow rate. Further large-scale, multi centre studies are needed to have a more comprehensive understanding of this heterogeneous disease in our population.</p

Operator inequalities and characterization with applications in probability theory

EThOS - Electronic Theses Online ServiceGBUnited Kingdo

IPT uptake among child contacts of TB patients: Experience from the Indus Hospital TB program, Karachi, Pakistan

Background: Infants and young children are particularly susceptible to developing tuberculosis (TB) following exposure and infection, and isoniazid preventive therapy can substantially reduce this risk. This evidence-base provides the rationale for the policy and guidelines to screen and manage children that are household contacts of TB cases, prioritizing those with sputum smear-positive TB. The guidelines have been in place for decades, but are rarely implemented. IPT programs in high-TB burden countries are rare and fraught with low uptake and low rates of therapy completion. Methods: This study describes the demographics and outcomes of contact management and the IPT program for <5 years old at the Indus Hospital in Karachi, Pakistan from 2011 to 2014. Children <5 years old in contact with newly diagnosed sputum smear-positive pulmonary TB patients were referred by the counselor for contact evaluation. All children underwent a history, physical, CXR and TST. All contacts were started on IPT based on WHO recommendations after confirming that they had no TB disease. Outcomes were defined as children who were enrolled, started on IPT but never returned for follow-up (primary default), children who had one or more follow-up visits but did not complete treatment (default) and children who completed IPT (treatment completed). Results: A total of 240 children were enrolled in the Indus IPT program from 2011 to 2014. Of these, data from 184 contacts was analyzed in detail as the remainder were still on IPT. All children enrolled were less than 5 years of age (mean age 3 years) and 96 (52%) were males. Of all the enrolled children, 76/240 (31.6%) were <5% weight for their age (underweight), of these 52% were female children. A symptom of either cough or fever was reported by 29/184 (15.7%) children; however, all responded to routine antibiotics and did not have CXR findings suggestive of TB disease. Of the enrolled who had a TST done, 12/209 (5.8%) had a positive result. Analysis of outcomes revealed that only 60/184 (32.6%) completed 6 months of IPT (with no gender predisposition). Among those who completed therapy, none developed TB disease during follow-up. Outcome trends revealed an increase in completion rate (40% in 2013 compared with 26% in 2012), which may reflect improvement in counseling services in 2013. Children who had an initial symptom or were underweight at the start of IPT were more likely to complete treatment (p<0.01). Conclusion: Despite a large cohort of TB patients in the Indus TB program-5487 SS+ patients registered during the study period – this IPT program enrollment has been low. A high rate of patient default after the first visit indicates a lack of understanding about the benefit and safety of preventive therapy in young children among families of TB patients, and awareness enhancing efforts by community field teams will help improve outcomes. It is vital that the National TB Program strengthens and expands contact management with a community-based approach and incentives

Alterations of p53, BCL-2, and hMSH2 protein expression in the normal brain tissues, gliosis, and gliomas

Tumorigenesis involves alterations in the tumor suppressor genes (p53), protooncogenes (BCL-2), and housekeeping genes (human MutS homologue-2 (hMSH2). We hypothesized that development of gliomas is associated with alterations of p53, BCL-2, and hMSH2 protein expression. To test our hypothesis and to examine these issues, we immunostained 60 specimens entailing normal brain tissues, gliosis, and gliomas (Grade I, II, III, IV) for p53, BCL-2, and hMSH2 protein expression. As compared with the normal brain and gliosis, examination of the average weighted scores in gliomas (Grade I, II, III, IV, respectively) showed significant up-regulation of: (i) p53 protein (0.0 ± 0.0; 0.0 ± 0.0; 0.9 ± 0.5; 1.6 ± 0.8; 1.7 ± 0.5; and 4.1 ± 0.8, P < 0.0001) (ii) hMSH2 (1.3 ± 0.3; 1.5 ± 0.7; 1.9 ± 1.1; 2.2 ± 0.5; 4.1 ± 1.5; and 4.7 ± 1.1, P < 0.0006), and (iii) BCL-2 (0.8 ± 0.5; 1.9 ± 0.5; 1.9 ± 0.6; 2.0 ± 0.6; 4.4 ± 1.2; and 4.6 ± 0.8, P < 0.001). The expression values (p53, BCL-2, and hMSH2) were statistically significantly higher (P < 0.05) in astrocytomas (Grade III) than in other gliomas. There was an insignificant negative correlation between p53 and BCL-2 (r = −0.07, P > 0.05) and between p53 and hMSH2 (r = −0.08, P > 0.05) protein expression. Alterations of the p53, BCL-2, and hMSH2 proteins occur during the development of these tumors

Global epidemiology of invasive meningococcal disease

Neisseria meningitidis is one of the leading causes of bacterial meningitis globally and can also cause sepsis, pneumonia, and other manifestations. In countries with high endemic rates, the disease burden places an immense strain on the public health system. The worldwide epidemiology of invasive meningococcal disease (IMD) varies markedly by region and over time. This review summarizes the burden of IMD in different countries and identifies the highest-incidence countries where routine preventive programs against Neisseria meningitidis would be most beneficial in providing protection. Available epidemiological data from the past 20 years in World Health Organization and European Centre for Disease Prevention and Control collections and published articles are included in this review, as well as direct communications with leading experts in the field. Countries were grouped into high-, moderate-, and low-incidence countries. The majority of countries in the high-incidence group are found in the African meningitis belt; many moderate-incidence countries are found in the European and African regions, and Australia, while low-incidence countries include many from Europe and the Americas. Priority countries for vaccine intervention are high- and moderate-incidence countries where vaccine-preventable serogroups predominate. Epidemiological data on burden of IMD are needed in countries where this is not known, particularly in South- East Asia and Eastern Mediterranean regions, so evidence-based decisions about the use of meningococcal vaccines can be made

Multicenter, Randomized Trial of a Bionic Pancreas in Type 1 Diabetes.

BACKGROUND: Currently available semiautomated insulin-delivery systems require individualized insulin regimens for the initialization of therapy and meal doses based on carbohydrate counting for routine operation. In contrast, the bionic pancreas is initialized only on the basis of body weight, makes all dose decisions and delivers insulin autonomously, and uses meal announcements without carbohydrate counting. METHODS: In this 13-week, multicenter, randomized trial, we randomly assigned in a 2:1 ratio persons at least 6 years of age with type 1 diabetes either to receive bionic pancreas treatment with insulin aspart or insulin lispro or to receive standard care (defined as any insulin-delivery method with unblinded, real-time continuous glucose monitoring). The primary outcome was the glycated hemoglobin level at 13 weeks. The key secondary outcome was the percentage of time that the glucose level as assessed by continuous glucose monitoring was below 54 mg per deciliter; the prespecified noninferiority limit for this outcome was 1 percentage point. Safety was also assessed. RESULTS: A total of 219 participants 6 to 79 years of age were assigned to the bionic-pancreas group, and 107 to the standard-care group. The glycated hemoglobin level decreased from 7.9% to 7.3% in the bionic-pancreas group and did not change (was at 7.7% at both time points) in the standard-care group (mean adjusted difference at 13 weeks, -0.5 percentage points; 95% confidence interval [CI], -0.6 to -0.3; P&lt;0.001). The percentage of time that the glucose level as assessed by continuous glucose monitoring was below 54 mg per deciliter did not differ significantly between the two groups (13-week adjusted difference, 0.0 percentage points; 95% CI, -0.1 to 0.04; P&lt;0.001 for noninferiority). The rate of severe hypoglycemia was 17.7 events per 100 participant-years in the bionic-pancreas group and 10.8 events per 100 participant-years in the standard-care group (P = 0.39). No episodes of diabetic ketoacidosis occurred in either group. CONCLUSIONS: In this 13-week, randomized trial involving adults and children with type 1 diabetes, use of a bionic pancreas was associated with a greater reduction than standard care in the glycated hemoglobin level. (Funded by the National Institute of Diabetes and Digestive and Kidney Diseases and others; ClinicalTrials.gov number, NCT04200313.)