Quantitative comparison of spontaneous and paced 12-lead electrocardiogram during right ventricular outflow tract ventricular tachycardia

OBJECTIVES: The purpose of this study was to objectively quantify the similarity of 12-lead electrocardiogram (ECG) waveforms using two quantitative metrics, the correlation coefficient (CORR) and the mean absolute deviation (MAD). BACKGROUND: Comparison of the 12-lead ECG morphology between ventricular tachycardia (VT) and a pace-map is frequently performed; however, there are no objective criteria for quantifying the similarity between two waveform morphologies. METHODS: During ablation of right ventricular outflow tract (RVOT) VT, 12-lead ECG pace-maps were acquired from three superior septal sites, three superior free wall sites, and before each ablation attempt in 15 patients. The 12-lead ECG waveforms of the clinical tachycardia and pace-maps were compared using both MAD and CORR at each site. RESULTS: The MAD scores were lower (i.e., more closely matched) for septal compared with free wall sites (15.9 +/- 5.3% vs. 25.3 +/- 10.2%; p < 0.001). Successful ablation sites had a significantly lower MAD score compared with unsuccessful sites (9.5 +/- 2.8% vs. 13.3 +/- 5.6%; p = 0.01), whereas there was only a trend toward a higher CORR for successful ablation sites (98.2 +/- 1.2% vs. 96 +/- 4.7%; p = 0.07). A MAD score < or =12% was 93% sensitive and 75% specific for identifying a successful ablation site. There was an inverse correlation between MAD score and distance from the site of VT origin (r = 0.63, p < 0.001). CONCLUSIONS: A MAD score >12% between RVOT VT and a pace-map at any site suggests sufficient dissimilarity to dissuade ablation at that site. The MAD score can be used to standardize 12-lead ECG waveform morphology comparisons among different laboratories, and may be useful for guiding ablation of VT.     

Clinical, haematological and histomorphological profile of adult myelodysplastic syndrome. Study of 96 cases in a single institute

Myelodysplastic syndromes (MDS) are clonal haematopoietic stem cell disorders characterised by ineffective and dyspoietic haematopoiesis. The natural history of these disorders is variable and ranges from a chronic to a rapid course towards leukaemic progression. Certain shortcomings have been encountered in the French-American-British (FAB) classification over the years, and therefore there is a need for an alternative method of classification. In 1999, the WHO published a revised classification of MDS. In the present study, we have analysed the clinical, haematological and histomorphological features in 96 cases of primary MDS seen in the department of haematology at the All India Institute of Medical Sciences (AIIMS) over a 6-yr period (1996-2001). Both FAB and WHO classifications have been incorporated and the Bournemouth scoring system applied in each case at presentation. The Bournemouth scoring system, in the absence of a cytogenetic study, offers a good prognostication and long-term survival estimate.     

A NOD2-NALP1 complex mediates caspase-1-dependent IL-1beta secretion in response to Bacillus anthracis infection and muramyl dipeptide

NOD2, a NOD-like receptor (NLR), is an intracellular sensor of bacterial muramyl dipeptide (MDP) that was suggested to promote secretion of the proinflammatory cytokine IL-1beta. Yet, the molecular mechanism by which NOD2 can stimulate IL-1beta secretion, and its biological significance were heretofore unknown. We found that NOD2 through its N-terminal caspase recruitment domain directly binds and activates caspase-1 to trigger IL-1beta processing and secretion in MDP-stimulated macrophages, whereas the C-terminal leucine-rich repeats of NOD2 prevent caspase-1 activation in nonstimulated cells. MDP challenge induces the association of NOD2 with another NLR protein, NALP1, and gel filtration analysis revealed the formation of a complex consisting of NOD2, NALP1, and caspase-1. Importantly, Bacillus anthracis infection induces IL-1beta secretion in a manner that depended on caspase-1 and NOD2. In vitro, Anthrax lethal toxin strongly potentiated IL-1beta secretion, and that response was NOD2 and caspase-1-dependent. Thus, NOD2 plays a key role in the B. anthracis-induced inflammatory response by being a critical mediator of IL-1beta secretion.     

A study on pattern of resistance to second line anti tubercular drugs among multi drug resistant tuberculosis patients

Aims and objectives

To determine the prevalence and pattern of resistance to second line drugs among multi drug resistant (MDR) tuberculosis patients being treated on category IV regimen.

Noninvasive detection of tumor-infiltrating T cells by PET reporter imaging

Adoptive transfer of tumor-reactive T cells can successfully reduce tumor burden; however, in rare cases, lethal on-target/off-tumor effects have been reported. A noninvasive method to track engineered cells with high sensitivity and resolution would allow observation of correct cell homing and/or identification of dangerous off-target locations in preclinical and clinical applications. Human deoxycytidine kinase triple mutant (hdCK3mut) is a nonimmunogenic PET reporter that was previously shown to be an effective tool to monitor whole-body hematopoiesis. Here, we engineered a construct in which hdCK3mut is coexpressed with the anti-melanoma T cell receptor F5, introduced this construct into human CD34 cells or PBMCs, and evaluated this approach in multiple immunotherapy models. Expression of hdCK3mut allowed engrafted cells to be visualized within recipient bone marrow, while accumulation of [¹⁸F]-L-FMAU in hdCK3mut-expressing T cells permitted detection of intratumoral homing. Animals that received T cells coexpressing hdCK3mut and the anti-melanoma T cell receptor had demonstrably higher signals in HLA-matched tumors compared with those in animals that received cells solely expressing hdCK3mut. Engineered T cells caused cytotoxicity in HLA/antigen-matched tumors and induced IFN-γ production and activation. Moreover, hdCK3mut permitted simultaneous monitoring of engraftment and tumor infiltration, without affecting T cell function. Our findings suggest that hdCK3mut reporter imaging can be applied in clinical immunotherapies for whole-body detection of engineered cell locations.     

Meta‐analysis of observational studies: hepatitis C and survival after renal transplant

Recent evidence has shown that anti‐HCV‐positive serologic status is significantly linked to lower patient and graft survival after renal transplant, but conflicting results have been given on this point. The aim of this study was to conduct a systematic review of the published medical literature concerning the impact of HCV infection on all‐cause mortality and graft loss after RT. The relative risk of all‐cause mortality and graft loss was regarded as the most reliable outcome end‐point. Study‐specific relative risks were weighted by the inverse of their variance to obtain fixed‐ and random‐effect pooled estimates for mortality and graft loss with HCV across the published studies. We identified eighteen observational studies involving 133 530 unique renal transplant recipients. The summary estimate for adjusted relative risk (aRR) of all‐cause mortality was 1.85 with a 95% confidence interval (CI) of 1.49; 2.31 (P < 0.0001); heterogeneity statistics, Ri = 0.87 (P‐value by Q‐test = 0.001). The overall estimate for adjusted RR of all‐cause graft loss was 1.76 (95% CI, 1.46; 2.11) (P < 0.0001), heterogeneity statistics, Ri = 0.65 (P‐value by Q‐test = 0.001). Stratified analysis did not change meaningfully these results. Meta‐regression showed that living donor rate had a favourable influence on patient (P = 0.031) and graft survival (P = 0.01), whilst diabetes mellitus having a detrimental role on patient survival (P = 0.001). This meta‐analysis of observational studies supports the notion that HCV‐positive patients after RT have an increased risk of mortality and graft loss. Further studies are in progress to understand better the mechanisms underlying the relationship between HCV and mortality or graft dysfunction after renal transplant.     

Tissue expansion: Concepts,techniques and unfavourable results

The phenomenon of tissue expansion is observed in nature all the time. The same properties of the human skin to stretch and expand and yield extra skin if placed under continuous stress over a prolonged period of time has been utilised for reconstructive purposes with the help of a silicon balloon inserted under the skin and progressively filled with saline. The technique of tissue expansion is now more than three decades old and has been a value addition to our armamentarium in reconstructive surgery in all parts of the body. However, it still requires careful patient selection, meticulous planning and faultless execution to successfully carry out the process, which usually lasts for more than 8-12 weeks and involves two sittings of surgery. Any compromise in this process can lead to unfavourable results and complications, some minor, which allow continuance of the process to attain the expected goal and others major, which force abandonment of the process without reaching the expected goal. This article seeks to highlight the intricacies of the concept of tissue expansion, the technique related to flawless execution of the process and likely complications with emphasis on their management. We also present our results from a personal series of 138 patients operated over a period of 18 years between 1994 and 2012.KEY WORDS: Complications, tissue expansion, unfavourable results