Surgery for ulcerative colitis in the era of the pouch: the St Mark's Hospital experience.

The choice of operation for ulcerative colitis among 422 patients having all their surgery at one hospital between 1976 (the year of the first restorative proctocolectomy) and 1990, was reviewed. The 15 year period was divided into three quinquennia (1976-80, 1981-85, 1986-90). Elective surgery was performed in 316 patients with one operative death. The proportions of conventional proctocolectomy, colectomy with ileorectal anastomosis, and restorative proctocolectomy for the three quinquennia were 36/60, 17/60, 4/60; 29/111, 30/111, 35/111; 30/145, 17/145, 75/145. Of 106 urgent operations with three postoperative deaths, 12 had a conventional proctocolectomy and 86 a colectomy with ileostomy and preservation of the rectum. Of 85 survivors of the latter there were two late deaths and in 13 no further surgery had been done at the time of this assessment. In the remaining 70 having subsequent surgery the proportion of conventional proctocolectomy, colectomy with ileorectal anastomosis, and restorative proctocolectomy for the three quinquennia respectively were 19/27, 4/27, 14/27; 11/21, 2/21, 8/21; 5/22, 4/22, 13/22. Of the 76 patients having colectomy with ileorectal anastomosis 12 (16%) no longer had a functioning rectum at the end of 1990. Of the 153 patients having an ileoanal pouch procedure, 11 (7%) no longer had, a functioning anus. The study showed an increase in the numbers of patients having elective surgery for ulcerative colitis during the three quinquennia. It also showed a rise of restorative over conventional proctocolectomy with diminution in elective colectomy with ileorectal anastomosis in the last five year period.     

The future is here: Integrating genetics into the pediatric pulmonary clinic

Recognition of underlying genetic etiologies of disease is increasing at an exponential rate, likely due to greater access to and lower cost of genetic testing. Monogenic causes of disease, or conditions resulting from a mutation or mutations in a single gene, are now well recognized in every subspecialty, including pediatric pulmonary medicine; thus, it is important to consider genetic conditions when evaluating children with respiratory disease. In the pediatric pulmonary clinic, genetic testing should be considered when multiple family members present with similar or related clinical features and when individuals have unusual clinical presentations, such as early‐onset disease or complex, syndromic features. This review provides a practical guide for genetic diagnosis in the pediatric pulmonary setting, including a review of genetic concepts, considerations for test selection and results in interpretation, as well as an overview of genetic differential diagnoses for common pediatric pulmonary phenotypes. Genetic conditions that commonly present to the pediatric pulmonary clinic are reviewed in a companion article by Yonker et al.     

Macrophage p38 mitogen-activated protein kinase activity regulates invariant natural killer T-cell responses during Borrelia burgdorferi infection

The interaction of macrophages with infectious agents leads to the activation of several signaling cascades, including mitogen-activated protein (MAP) kinases, such as p38. We now demonstrate that p38 MAP kinase-mediated responses are critical components to the immune response to Borrelia burgdorferi. The pharmacological and genetic inhibition of p38 MAP kinase activity during infection with the spirochete results in increased carditis. In transgenic mice that express a dominant negative form of p38 MAP kinase specifically in macrophages, production of the invariant natural killer T (iNKT) cell-attracting chemokine MCP-1 and of the antigen-presenting molecule CD1d are significantly reduced. The expression of the transgene therefore results in the deficient infiltration of iNKT cells, their decreased activation, and a diminished production of interferon γ (IFN-γ), leading to increased bacterial burdens and inflammation. These results show that p38 MAP kinase provides critical checkpoints for the protective immune response to the spirochete during infection of the heart.     

Epidemiology of paediatric minor head injury: Comparison of injury characteristics with Indices of Multiple Deprivation

Background

Head injury (HI) is a common presentation to Child Emergency Departments (CEDs), but the actual number of children attending with minor HI is unclear. Most research has focussed on admitted patients, often relying on hospital-coded admission data. We studied the incidence of minor HI presenting to the CED of a major teaching hospital in Coventry and Warwickshire. HI attendances were compared with population data to identify injury patterns relating to deprivation.

Methods

All CED admissions were screened by the research team, and data on minor head injuries (GCS 13–15) collected prospectively from 1st January until 31st August 2011. Information was collected on demographics, ethnicity, cause and severity of injury, injury location (in or outside the home), other injuries and mode of arrival. Deprivation data were obtained by cross-referencing postcodes with English Indices of Multiple Deprivation (IMD 2010). For comparison, the hospital audit department provided figures for coded head injuries during the same period.

Results

During the 8 month period, hand-searching identified 1747 children with minor HI, aged between 0 and 16 years. Of these 99% had minimal HI (GCS 15 or ‘alert’). In the same period, hospital-coded minor HIs numbered only 1081. HIs formed 9% of all CED attendances. Thirteen children returned to the CED with worrying symptoms after discharge home. Approximately 3.4% of the local paediatric population attend the CED with HI per year (3419/100,000 population). Falls accounted for 62% of HIs overall, rising to 77% in children aged 0–5. Most in-home head injuries (81%) were the result of falls (p < 0.0001). Significantly more injuries took place inside the home for 0–5 year olds (58%) than for older children (20%) (p < 0.0001). Children living in the most deprived areas were more likely to attend the CED with HI (RR: 1.19; CI: 1.06–1.35, p = 0.004), and arrive using emergency services (OR: 1.77; CI: 1.30–2.40, p < 0.001). There were no significant differences between the deprived and non-deprived groups for location or cause of injury.

Conclusions

Young children are particularly at risk of HI and parents should be offered information on injury prevention. More children from deprived areas attended with HI and these families may benefit most from targeted interventions.     

A Randomized Trial of Dietary Sodium Restriction in CKD

There is a paucity of quality evidence regarding the effects of sodium restriction in patients with CKD, particularly in patients with pre-end stage CKD, where controlling modifiable risk factors may be especially important for delaying CKD progression and cardiovascular events. We conducted a double-blind placebo-controlled randomized crossover trial assessing the effects of high versus low sodium intake on ambulatory BP, 24-hour protein and albumin excretion, fluid status (body composition monitor), renin and aldosterone levels, and arterial stiffness (pulse wave velocity and augmentation index) in 20 adult patients with hypertensive stage 3–4 CKD as phase 1 of the LowSALT CKD study. Overall, salt restriction resulted in statistically significant and clinically important reductions in BP (mean reduction of systolic/diastolic BP, 10/4 mm Hg; 95% confidence interval, 5 to 15 /1 to 6 mm Hg), extracellular fluid volume, albuminuria, and proteinuria in patients with moderate-to-severe CKD. The magnitude of change was more pronounced than the magnitude reported in patients without CKD, suggesting that patients with CKD are particularly salt sensitive. Although studies with longer intervention times and larger sample sizes are needed to confirm these benefits, this study indicates that sodium restriction should be emphasized in the management of patients with CKD as a means to reduce cardiovascular risk and risk for CKD progression.Cardiovascular disease (CVD) is the leading cause of premature mortality in the CKD population.^1,2 CVD risk increases with only mild kidney impairment (estimated GFR [eGFR] <60 ml/min per 1.73 m²) and further escalates as CKD progresses,³ making early intervention to reduce CVD risk of utmost importance.⁴Dietary sodium intake shows great promise as a modifiable risk factor for reducing the risks of cardiovascular disease and CKD progression.^5,6 Extensive research has demonstrated the effect of sodium intake on fluid overload and hypertension,^7,8 which are predictors of cardiac and vascular remodeling.⁹ Trials in sodium restriction recently showed significant reductions in proteinuria and albuminuria,^7,10,11 which are strong predictors of CKD progression and CVD events.¹² In addition, excessive sodium intake is thought to have direct toxic effects on blood vessels through mediating factors such as oxidative stress, inflammation, endothelial cell dysfunction, and vascular stiffness.^13–15The available evidence detailing the effects of sodium restriction in CKD patients is of poor quality, lacks randomization,^16–18 a control group,¹⁷ or blinding,^10,11 or does not use gold-standard measurement techniques (e.g., using clinic instead of ambulatory BP).^10,11 Furthermore, several studies failed to either evaluate or adjust for the influence of key confounding factors, such as potassium intake or body weight,^{10,11,19–22} thereby making it difficult to assess whether the observed results can be solely attributed to dietary sodium.The aim of this double-blind placebo-controlled randomized crossover study was to evaluate the effects of dietary sodium intake on BP, proteinuria, extracellular fluid volume, and arterial stiffness as markers of risks of cardiovascular and CKD progression. We hypothesized that a low sodium intake would decrease 24-hour BP, fluid volume, and 24-hour urinary protein and albumin compared with high sodium intake in patients with moderate-to-severe CKD.