Serum and cerebrospinal fluid magnesium in severe traumatic brain injury outcome

Serum magnesium concentration has a neuroprotective effect in experimental models of traumatic brain injury (TBI). This study was designed to assess the relationship between initial serum magnesium, cerebrospinal fluid (CSF) magnesium, neurological outcome and the efficacy of magnesium replacement therapy (MgSO4). A retrospective analysis was performed on a prospectively collected dataset from 216 patients admitted during 1996-2006 to the University of Pittsburgh Medical Center with severe TBI. Admission serum and CSF magnesium were dichotomized into low and normal magnesium concentration groups for serum and normal and high concentration groups for CSF. A logistic-regression analysis was performed with 6-month Glasgow Outcome Scale (GOS) scores as outcome variable. The outcome of a subset of 31 patients who presented with low serum magnesium and who were rapidly corrected within 24 h of admission was also analyzed. Low initial serum magnesium was measured in 56.67% of all patients. Patients with an initial serum magnesium of <1.3 mEq/L were 2.37 times more likely to have a poor outcome (CI: 1.18-4.78, p = 0.016). The prognostic significance of depressed serum magnesium remained, even in patients whose serum magnesium levels were corrected within 24 h (OR = 11.03, CI: 1.87-68.14, p = 0.008). Patients with an initial high CSF magnesium were 7.63 more likely to have a poor outcome (p = 0.05). Elevated CSF magnesium correlated with depressed serum magnesium only in patients with poor outcome (p = 0.013). Patients with low serum magnesium and high CSF magnesium are most likely to have poor outcome after severe TBI. Rapid correction of serum magnesium levels does not reverse the prognostic value of these markers.     

Smaller Hip Circumference is Associated with Dyslipidemia and the Metabolic Syndrome in Obese Women

BACKGROUND: There is great need for simple anthropometric measures that predict risk. The authors explored the relationship between body composition measures and features of the metabolic syndrome (MtS) in women aged between 20 and 50 years with class I obesity. METHODS:This is a cross-sectional study of 49 obese (BMI 30-35) women recruited into a weight management randomized trial. An analysis was conducted of the baseline weight, anthropometric measures, skin-fold thickness, bioelectrical impedance, whole body dual-energy x-ray absorptiometry (DEXA), and their relationships with the features of the MtS. RESULTS: All women but one (n=48) had a population risk waist circumference of >88 cm. 16 of the 49 (33%) fulfilled the criteria of the metabolic syndrome. Simple anthropometric measures provided the strongest correlations with the presence of the MtS. Cut-off values were selected using receiver operator characteristics. Waist circumference of >100 cm and hip circumference <115cm was associated with odds ratios of 5.2 (95% CI, 1.4-20) and 12.3 (95% CI, 3.0-51) respectively for the MtS. Regional DEXA analysis showed that lower leg fat mass rather than fat-free mass was associated with the MtS. The dyslipidemia of the MtS was associated with a lower leg fat mass, while higher HbAlc levels and HOMA, an indirect measure of insulin resistance, were seen with increased trunk fat. Percentage fat as measured by skin-fold thickness and bioelectrical impedance were not related to any features. Women with the metabolic syndrome were found to have lower bone mineral content as measured by DEXA. CONCLUSION: Weight distribution is highly predictive of metabolic risk. Smaller hip and larger waist circumference provided independent effect. BMI adjusted anthropometric measures may be of value.     

The epididymal fat pad as a transplant site for minimal islet mass

The epididymal fat pad was evaluated as a site of islet transplantation in a syngeneic murine model of diabetes by comparing the transplant outcomes to that of islets transplanted intraportal. Mouse islets engrafted on the intra-abdominal epididymal fat pad ameliorated streptozotocin-induced hyperglycemia with similar efficacy as grafts implanted intraportally. Mice that received as few as 50 islets, either intraportal or in the epididymal fat pad, displayed similar glucose tolerance curves. Bioluminescence imaging and glucose measurement showed stable luminescence signals and blood glucose levels for over 5 months in both transplant sites using transgenic luciferase-positive islets. Prompt recurrent hyperglycemia occurred in all mice after removal of the epididymal fat pad bearing the islet graft. Histological examination of the grafts showed well-granulated insulin containing cells surrounded by healthy adipocytes. This study indicates that the epididymal fat pad maybe a useful islet transplant site in the mouse model for effective glycemic control.     

Conversion from calcineurin inhibitor–based immunosuppression to mammalian target of rapamycin inhibitors or belatacept in renal transplant recipients

The calcineurin inhibitors (CNIs) remain the standard of care for maintenance immunosuppression following renal transplantation. CNIs have demonstrated their effectiveness in reducing acute cellular rejection; however, some evidence suggests that these compounds negatively affect native renal function and are associated with allograft injury in renal transplant recipients. CNIs have also been linked with hypertension, new‐onset diabetes after transplantation, tremor, and thrombotic microangiopathy, which have significant consequences for long‐term allograft function and patient health overall. Thus, converting patients to a non‐CNI‐based regimen may improve renal function and also provide extrarenal benefits. A number of studies have been conducted that explore CNI conversion strategies in renal transplant recipients in an effort to improve long‐term allograft function and survival. These include converting to alternative, non‐nephrotoxic, maintenance immunosuppressants, such as the mammalian target of rapamycin inhibitors (sirolimus and everolimus) and the costimulation blocker belatacept. In this review of literature, evidence for the potential renal and extrarenal benefits of conversion to these non‐CNI‐based regimens is evaluated. Clinical challenges, including the adverse event profiles of non‐CNI‐based regimens and the selection of candidates for conversion, are also examined.     

Outcomes after simultaneous kidney‐pancreas versus pancreas after kidney transplantation in the current era

Simultaneous pancreas and kidney (SPK) and pancreas after kidney (PAK) transplant are both potential options for diabetic ESRD patients. Historically, PAK pancreas graft outcomes were felt to be inferior to SPK pancreas graft outcomes. Little is known about outcomes in the modern era of transplantation. We analyzed our SPK and PAK recipients transplanted between 01/2000 and 12/2016. There were a total of 635 pancreas and kidney transplant recipients during the study period, 611 SPK and 24 PAK. Twelve of the PAK patients received a living donor kidney. There were no significant differences between the two groups in kidney or pancreas graft rejection at 1 year. Similarly, 1‐year graft survival for both organs was not different. At last follow‐up, uncensored and death‐censored graft survival was not statistically different for kidney or pancreas grafts. In addition, in Cox regression analysis SPK and PAK were associated with similar graft survival. Although the majority of pancreas transplants are in the form of SPK, PAK is an acceptable alternative. Simultaneous pancreas and kidney avoids donor risks associated with live donation, so may be preferable in regions with short wait times, but PAK with a living donor kidney may be the best alternative in regions with long SPK wait times.     

Diagnostic delay in breast cancer

BACKGROUND: Delay in the diagnosis of breast cancer has important clinical and medicolegal implications. This study assessed the frequency, causes and effects of delay in the diagnosis of breast cancer in a specialist breast unit. METHODS: Details of women who attended the breast clinic between 1988 and 1999 inclusive, and for whom the interval between first attendance and diagnosis of invasive breast cancer was greater than 2 months, were reviewed. Potential causes of delay were identified and the consequence of the delay assessed. The clinical features were compared with those of patients diagnosed with breast cancer during a 2-year period from 1999 and 2001. RESULTS: Breast cancer was diagnosed in 5283 women during the interval reviewed; delay in diagnosis was suggested in 72 women (1.4 per cent). Women with a delayed diagnosis were younger (P < 0.001) and had a smaller tumour at diagnosis (P = 0.011) compared with all women diagnosed with breast cancer between 1999 and 2001. There were no differences in the rate of axillary node positivity or the need for mastectomy. Women unsuitable for conservation therapy in the delayed group had a significantly longer interval to diagnosis (P = 0.006). CONCLUSION: The likelihood that conservation therapy will be appropriate is reduced when the hospital delay in the diagnosis of breast cancer is more than 240 days. All patients with a palpable mass require triple assessment to minimize delay in diagnosis of breast cancer.     

Test-retest reproducibility of quantitative CBF measurements using FAIR perfusion MRI and acetazolamide challenge.

The reproducibility of quantitative cerebral blood flow (CBF) measurements using MRI with arterial spin labeling and acetazolamide challenge was assessed in 12 normal subjects, each undergoing the identical experimental procedure on two separate days. CBF was measured on a 1.5T scanner using a flow-sensitive alternating inversion recovery (FAIR) pulse sequence, performed both at baseline and 12 min after intravenous administration of acetazolamide. T(1) was measured in conjunction with the FAIR scan in order to calculate quantitative CBF. The CBF maps were segmented to separate gray matter (GM) from white matter (WM) for region-of-interest (ROI) analyses. Post- acetazolamide CBF values (ml/100 g/min, mean +/- SD) of 87.5 +/- 12.5 (GM) and 46.1 +/- 10.8 (WM) represented percent increases of 37.7% +/- 24.4% (GM) and 40.1% +/- 24.4% (WM). Day-to-day differences in baseline CBF were -1.7 +/- 6.9 (GM) and -1.4 +/- 4.7 (WM) or, relative to the mean CBF over both days for each subject, -2.5% +/- 11.7% (GM) and -3.8% +/- 13.6% (WM) Day- to-day differences in absolute post-ACZ CBF increase were -2.5 +/- 6.8 (GM) and 2.7 +/- 9.4 (WM) or, relative to the mean CBF increase over both days for each subject, -4.7% +/- 13.3% (GM) and 9.1% +/- 26.2% (WM). Thus, FAIR- based CBF measurements show satisfactory reproducibility from day to day, but with sufficient variation to warrant caution in interpreting longitudinal data. The hemispheric asymmetry of baseline CBF and post-acetazolamide CBF increases varied within a narrower range and should be sensitive to small changes related to disease or treatment.     

Combination therapy with pulsed methylprednisolone in rheumatoid arthritis.

Pulsed methylprednisolone (PMP) has been shown to produce clinical improvement and reduction in the ESR and acute phase protein concentrations in patients with active rheumatoid arthritis and has been advocated for use either as an alternative to slow-acting antirheumatoid drugs (SAARDs) or in conjunction with SAARDs to accelerate the response to treatment. To test these potential roles for PMP 45 patients with active RA were randomly allocated to treatment with PMP alone, PMP + sulphasalazine (SAS - at a maintenance dose of 2.0 g/day), or PMP + D-penicillamine (DPA - at a maintenance dose of 500 mg/day). In each case three 1 g intravenous infusions were given on alternate days during the first week of the trial. Patients were monitored for 24 weeks by standard clinical and laboratory measurements. All three treatment groups showed significant clinical and laboratory improvements at two weeks. With PMP + DPA and PMP + SAS these improvements were sustained and were not significantly different in these two treatment groups. However, in the 'PMP only' group ESR and CRP rose to pretreatment values by eight weeks. Twelve patients withdrew from the study owing to a relapse of the RA. No serious adverse effects were seen in the 'PMP only' group. Both combination regimens were well tolerated; adverse effects seen were attributable to either DPA or SAS. We conclude that PMP alone is insufficient for treatment of RA but can be used successfully in combination with either DPA or SAS. A comparison between these results obtained from two previous groups of 15 patients treated with DPA alone and SAS alone (using the same study design) shows that PMP accelerated the response to therapy by at least six weeks.