Association between a prolonged corrected QT interval and outcomes in patients in a medical Intensive Care Unit

Introduction:

Patients admitted into a medical Intensive Care Unit (ICU) have varying illnesses and risk factors. An electrocardiogram (ECG) is a useful tool to assess the cardiac status. The aim of the study was to determine the prevalence of QT prolongation of the ECG in patients admitted to a medical ICU in a tertiary hospital, to assess outcomes in terms of mortality, cardiovascular events, and duration of ICU stay.

Materials and Methods:

Prospective observational study, 6 months duration, assessing the prevalence of prolonged corrected QT interval (QTc) at admission into a medical ICU. A QTc calculated by Bazett''s formula, of >440 ms for males and >460 ms for females was considered prolonged. Details of illness, clinical and lab parameters were monitored.

Results:

The total number of patients screened was 182. There was a high prevalence of prolonged QTc (30%) on admission to the ICU. This reduced to 19% on day 3 (P = 0.011). In patients with a prolonged QTc the odds ratio of adverse outcome from ICU was 3.17 (confidence interval [CI]: 1.52–6.63) (P = 0.001) and of adverse outcome for hospital stay was 2.27 (CI: 1.11–4.66) (P = 0.014). In the study, 35% of all patients received drugs with QT prolonging action. Of patients with a prolonged QTc at admission 18 (35%) received a QT prolonging drug.

Conclusions:

We found that prolonged QTc is common (30%) in our medical ICU at admission and a large proportion (35%) received drugs capable of prolonging QT interval. These patients with QTc prolongation have a higher odds ratio for adverse outcomes.     

Autotransplantation of Teeth Associated with Dentigerous Cyst: A Case Report

This paper discusses the treatment of impacted permanent incisors and unerupted ectopic canine associated with a dentigerous cyst in mixed dentition that was successfully managed by the combined approach of decompression followed by enucleation, primary closure, autotransplantation and endodontic therapy which enabled the utilization of teeth which were hitherto nonfunctional, transferred to an optimal functional and esthetic position. Decompression is a less invasive technique which reduces the cystic pressure, avoids a more stressful surgical procedure and necessity for general anesthesia. It gives more pleasing results as the body’s own mechanism heals the defect gradually. Autotransplantation of teeth induces bone formation around the root with the help of viable periodontal ligament on their root surface. In this case, bone lost by cyst was regenerated and lamina dura was appreciable in the follow up radiographs and transplanted teeth are functioning well.     

Small Bowel Adenocarcinoma – Report of Two Cases and Review of Literature

Although accounting for 90 % of the intestinal surface area, small bowel adenocarcinomas are not common. The majority of these lesions are incidentally detected during laparotomy for intestinal obstruction or perforation. The symptoms associated with these lesions are not very specific and preoperative diagnosis is rare. We report two cases of jejunal adenocarcinomas detected in patients undergoing laparotomy for acute abdomen and review the literature for small bowel adenocarcinomas.     

Monocyte chemoattractant protein 3 as a mediator of fibrosis: Overexpression in systemic sclerosis and the type 1 tight-skin mouse

OBJECTIVE: To determine the gene-expression profile in dermal fibroblasts from type 1 tight-skin (Tsk1) mice, and to examine the expression and potential fibrotic activity of monocyte chemoattractant protein 3 (MCP-3) in Tsk1 mouse and human systemic sclerosis (SSc) skin. METHODS: Complementary DNA microarrays (Atlas 1.2) were used to compare Tsk1 fibroblasts with non-Tsk1 littermate cells at 10 days, 6 weeks, and 12 weeks of age. Expression of MCP-3 protein was assessed by Western blotting of fibroblast culture supernatants, and localized in the mouse and human skin biopsy samples by immunohistochemistry. Activation of collagen reporter genes by MCP-3 was explored in transgenic mouse fibroblasts and by transient transfection assays. RESULTS: MCP-3 was highly overexpressed by neonatal Tsk1 fibroblasts and by fibroblasts cultured from the lesional skin of patients with early-stage diffuse cutaneous SSc. Immunolocalization confirmed increased expression of MCP-3 in the dermis of 4 of 5 Tsk1 skin samples and 14 of 28 lesional SSc skin samples, compared with that in matched healthy mice (n = 5) and human controls (n = 11). Proalpha2(I) collagen promoter-reporter gene constructs were activated by MCP-3 in transgenic mice and by transient transfection assays. This response was maximal between 16 and 24 hours of culture and mediated via sequences within the proximal promoter. The effects of MCP-3 could be diminished by a neutralizing antibody to transforming growth factor beta. CONCLUSION: We demonstrate, for the first time, overexpression of MCP-3 in early-stage SSc and in Tsk1 skin, and suggest a novel role for this protein as a fibrotic mediator activating extracellular matrix gene expression in addition to promoting leukocyte trafficking. This chemokine may be an important early member of the cytokine cascade driving the pathogenesis of SSc.     

Autosomal recessive otofaciocervical syndrome type 2 with novel homozygous small insertion in PAX1 gene

Otofaciocervical syndrome (OTFCS) is described as a single gene disorder of both autosomal dominant and autosomal recessive inheritance. The major clinical features of OTFCS include ear malformations (external/middle/inner ear), facial dysmorphism, shoulder girdle abnormalities, vertebral anomalies, and mild intellectual disability. The autosomal recessive form of OTFCS syndrome (OTFCS2) has been recently reported to be caused due to homozygous mutations in PAX1 gene. Here we report a third family of OTFCS2 phenotype wherein whole exome sequencing identified a novel homozygous small insertion in PAX1 as the underlying genetic cause.     

Pleiotropic consequences of Bruton tyrosine kinase deficiency in myeloid lineages lead to poor inflammatory responses

Bruton tyrosine kinase (Btk), a non-receptor-associated tyrosine kinase of the Tec family, appears to participate in many myeloid cell functions. We show that macrophages from X-linked immunodeficient (XID) mice lacking functional Btk cannot generate efficient bursts of reactive oxygen intermediates (ROIs). The induction of apoptotic cell death by inflammatory stimuli is also enhanced in XID macrophages. Phagocytosis of bacterial particles is only marginally affected in them. In vivo, XID mice show reduced severity of inflammatory diseases in models of experimental autoimmune encephalomyelitis (EAE), dextran sulfate sodium (DSS)-induced colitis, and carrageenan-induced acute edema. Also, polymorphonuclear neutrophil granulocytes (PMNs) in XID mice show poor ROI and nitric oxide (NO) induction, along with a reduction in PMN recruitment to peritoneal inflammation. XID mice show reduction in PMN numbers in peripheral blood, and their bone marrow shows a reduction in the numbers of both monocytic and granulocytic lineages, extending to the earliest progenitor populations. Thus, Btk is likely to play a significant role at multiple points during the development and functioning of the myeloid lineages, affecting the outcome of many infectious as well as noninfectious inflammatory events in vivo.     

Acute changes in liver tumour perfusion measured non-invasively with arterial spin labelling

Background:

Non-invasive measures of tumour vascular perfusion are desirable, in order to assess response to vascular targeting (or modifying) therapies. In this study, hepatic arterial spin labelling (ASL) magnetic resonance imaging (MRI) was investigated to measure acute changes in perfusion of colorectal cancer in the liver, in response to vascular disruption therapy with OXi4503.

Methods:

SW1222 and LS174T tumours were established in the liver of MF1 nu/nu mice via intrasplenic injection. Perfusion and R₂^* MRI measurements were acquired with an Agilent 9.4T horizontal bore scanner, before and at 90 min after 40 mg kg⁻¹ OXi4503.

Results:

A significant decrease in SW1222 tumour perfusion was observed (−43±33%, P<0.005). LS174T tumours had a significantly lower baseline level of perfusion. Intrinsic susceptibility MRI showed a significant increase in R₂^* in LS174T tumours (28±25%, P<0.05). An association was found between the change in tumour perfusion and the proximity to large vessels, with pre-treatment blood flow predictive of subsequent response. Histological evaluation confirmed the onset of necrosis and evidence of heterogeneous response between tumour deposits.

Conclusions:

Hepatic ASL-MRI can detect acute response to targeted tumour vascular disruption entirely non-invasively. Hepatic ASL of liver tumours has potential for use in a clinical setting.