Prediction of fracture risk in men: a cohort study

FRAX is a tool that identifies individuals with high fracture risk who will benefit from pharmacological treatment of osteoporosis. However, a majority of fractures among elderly occur in people without osteoporosis and most occur after a fall. Our aim was to accurately identify men with a high future risk of fracture, independent of cause. In the population‐based Uppsala Longitudinal Study of Adult Men (ULSAM) and using survival analysis we studied different models' prognostic values (R²) for any fracture and hip fracture within 10 years from age 50 (n = 2322), 60 (n = 1852), 71 (n = 1221), and 82 (n = 526) years. During the total follow‐up period from age 50 years, 897 fractures occurred in 585 individuals. Of these, 281 were hip fractures occurring in 189 individuals. The rates of any fracture were 5.7/1000 person‐years at risk from age 50 years and 25.9/1000 person‐years at risk from age 82 years. Corresponding hip fractures rates were 2.9 and 11.7/1000 person‐years at risk. The FRAX model included all variables in FRAX except bone mineral density. The full model combining FRAX variables, comorbidity, medications, and behavioral factors explained 25% to 45% of all fractures and 80% to 92% of hip fractures, depending on age. The corresponding prognostic values of the FRAX model were 7% to 17% for all fractures and 41% to 60% for hip fractures. Net reclassification improvement (NRI) comparing the full model with the FRAX model ranged between 40% and 53% for any fracture and between 40% and 87% for hip fracture. Within the highest quintile of predicted fracture risk with the full model, one‐third of the men will have a fracture within 10 years after age 71 years and two‐thirds after age 82 years. We conclude that the addition of comorbidity, medication, and behavioral factors to the clinical components of FRAX can substantially improve the ability to identify men at high risk of fracture, especially hip fracture. © 2012 American Society for Bone and Mineral Research.     

Reduced levels of active GLP-1 in patients with cystic fibrosis with and without diabetes mellitus

Glucagon like peptide 1 (GLP-1) is an incretin hormone released as a bioactive peptide from intestinal L-cells in response to eating. It acts on target cells and exerts several functions as stimulating insulin and inhibiting glucagon. It is quickly deactivated by the serine protease dipeptidyl peptidase IV (DPP-IV) as an important regulatory mechanism. GLP-1 analogues are used as antidiabetic drugs in patients with type 2 diabetes. We served patients with cystic fibrosis (CF, n=29), cystic fibrosis related diabetes (CFRD, n=19) and healthy controls (n=18) a standardized breakfast (23 g protein, 25 g fat and 76 g carbohydrates) after an overnight fasting. Blood samples were collected before meal as well as 15, 30, 45 and 60 min after the meal in tubes prefilled with a DPP-IV inhibitor. The aim of the study was to compare levels of GLP-1 in patients with CF, CFRD and in healthy controls. We found that active GLP-1 was significantly decreased in patients with CF and CFRD compared to in healthy controls (p<0.01). However, levels in patients with CFRD tended to be lower but were not significantly lower than in patients with CF without diabetes (p=0.06). Total GLP-1 did not differ between the groups, which points to that the inactive form of GLP-1 is more pronounced in CF patients. The endogenous insulin production (measured by C-peptide) was significantly lower in patients with CFRD as expected. However, levels in non-diabetic CF patients did not differ from the controls. We suggest that the decreased levels of GLP-1 could affect the progression toward CFRD and that more studies need to be performed in order to evaluate a possible treatment with GLP-1 analogues in CF-patients.     

A Swedish consensus on the surgical treatment of concomitant atrial fibrillation

Atrial fibrillation (AF) is a common arrhythmia among patients scheduled for open heart surgery and is associated with increased morbidity and mortality. According to international guidelines, symptomatic and selected asymptomatic patients should be offered concomitant surgical AF ablation in conjunction with valvular or coronary surgery. The gold standard in AF surgery is the Cox Maze III ("cut-and-sew") procedure, with surgical incisions in both atria according to a specified pattern, in order to prevent AF reentry circuits from developing. Over 90% of patients treated with the Cox Maze III procedure are free of AF after 1 year. Recent developments in ablation technology have introduced several energy sources capable of creating nonconducting atrial wall lesions. In addition, simplified lesion patterns have been suggested, but results with these techniques have been unsatisfactory. There is a clear need for standardization in AF surgery. The Swedish Arrhythmia Surgery Group, represented by surgeons from all Swedish units for cardiothoracic surgery, has therefore reached a consensus on surgical treatment of concomitant AF. This consensus emphasizes adherence to the lesion pattern in the Cox Maze III procedure and the use of biatrial lesions in nonparoxysmal AF.     

Regional oxygenation and systemic inflammatory response during cardiopulmonary bypass: influence of temperature and blood flow variations

OBJECTIVE: To evaluate the role of target temperature (28 degrees or 34 degrees C) in cardiac surgery on regional oxygenation during hypothermia and rewarming and systemic inflammatory response. DESIGN: Prospective, controlled, and randomized clinical study. SETTING: University hospital. PARTICIPANTS: Elderly patients (mean age 70 +/- 2 years) with acquired heart disease with an anticipated bypass time exceeding 120 minutes (n = 30). INTERVENTIONS: The patients were cooled to either 28 degrees C (n = 15) or 34 degrees C (n = 15). At hypothermia, bypass blood flow was reduced twice from full flow (2.4 L/min/m(2) body surface area [BSA]) to 2.0 L/min/m(2). MEASUREMENTS AND MAIN RESULTS: Hepatic and jugular venous oxygen tension and saturation were higher at 28 degrees C than at 34 degrees C. In comparison with the preoperative values, at 28 degrees C hepatic venous values were higher; whereas at 34 degrees C, they were lower. The reduction of pump blood flow during hypothermia, from 2.4 to 2.0 L/min/m(2)was accompanied by reductions of central, jugular, and hepatic oxygenation at both target temperatures. During rewarming, central and regional venous oxygenation decreased irrespective of the preceding temperature. The decrease was most pronounced in hepatic venous blood, with the lowest individual values <10%. Serum concentrations of C3a and IL-6 increased during hypothermia and increased further during rewarming irrespective of the preceding temperature. CONCLUSION: During cardiopulmonary bypass, hypothermia at 28 degrees C increases regional and central venous oxygenation better than at 34 degrees C. In contrast, venous oxygenation decreases during rewarming irrespective of the preceding temperature. No significant difference in the systemic inflammatory response associated with target temperature was detected.     

Inhibitory smads and tgf-Beta signaling in glomerular cells

Smad6 and Smad7 are inhibitory SMADs with putative functional roles at the intersection of major intracellular signaling networks, including TGF-beta, receptor tyrosine kinase (RTK), JAK/STAT, and NF-kappaB pathways. This study reports differential functional roles and regulation of Smad6 and Smad7 in TGF-beta signaling in renal cells, in murine models of renal disease and in human glomerular diseases. Smad7 is upregulated in podocytes in all examined glomerular diseases (focal segmental glomerulosclerosis [FSGS], minimal-change disease [MCD], membranous nephropathy [MNP], lupus nephritis [LN], and diabetic nephropathy [DN]) with a statistically significant upregulation in "classical" podocyte-diseases such as FSGS and MCD. TGF-beta induces Smad7 synthesis in cultured podocytes and Smad6 synthesis in cultured mesangial cells. Although Smad7 expression inhibited both Smad2- and Smad3-mediated TGF-beta signaling in podocytes, it inhibited only Smad3 but not Smad2 signaling in mesangial cells. In contrast, Smad6 had no effect on TGF-beta/Smad signaling in podocytes and enhanced Smad3 signaling in mesangial cells. These data suggest that Smad7 is activated in injured podocytes in vitro and in human glomerular disease and participates in negative control of TGF-beta/Smad signaling in addition to its pro-apoptotic activity, whereas Smad6 has no role in TGF-beta response and injury in podocytes. In contrast, Smad6 is upregulated in the mesangium in human glomerular diseases and may be involved in functions independent of TGF-beta/Smad signaling. These data indicate an important role for Smad6 and Smad7 in glomerular cells in vivo that could be important for the cell homeostasis in physiologic and pathologic conditions.     

Expanding access to transplantation with hepatitis C‐positive donors: A new perspective on an old issue

With the need for organs far exceeding supply, donors previously exposed to hepatitis B (HBV) and hepatitis C (HCV) viral infections should be considered for transplantation. Although many centers have protocols for transplanting organs from HBV core antibody‐positive (HBcAb+) donors into select recipients, in the era of direct‐acting antivirals (DAAs), a new focus should be placed on HCV‐positive donors. The transmission rate from HCV antibody‐positive (HCVAb+) nucleic acid testing negative (HCV NAT‐) donors is expected to be very low, and we encourage use of such organs in HCV recipients provided a normal biopsy, appropriate counseling, and careful post‐transplant monitoring. While transmission of HCV from HCV NAT+ donors is universal, the success of DAA in obtaining a sustained viral response in post‐transplant recipients should make the use of these organs more appealing. We herein provide information to help guide the use of organs from HCV donors.     

Laparoscopically supervised PEG at time of Nissen fundoplication: a safe option

BACKGROUND/PURPOSE: Children with gastroesophageal reflux disease (GERD) often have associated feeding difficulties that warrant the insertion of a feeding gastrostomy at the time of the antireflux procedure. Options for gastrostomy tube insertion at the time of laparoscopic Nissen fundoplication (LNF) include laparoscopic gastrostomy, percutaneous endoscopic gastrostomy (PEG), and classic open gastrostomy. The complication rate of PEG may be decreased if it is placed under laparoscopic supervision. The purpose of this paper is to describe our experience with laparoscopically supervised PEG tube placement at the time of antireflux procedure. METHODS: A retrospective chart review was conducted on all children undergoing a PEG tube placement at the time of the LNF. Perioperative complications were recorded. RESULTS: Forty-four patients had attempted PEG tube placement at the time of the LNF. In 3 (7%) cases, laparoscopic supervision was crucial in the prevention of a complication. No major PEG-related complications were recorded. In 43% of patients, minor PEG tube problems arose in the postoperative period: all were transient and/or easily correctable. Management of all these problems was in an outpatient setting. Follow-up ranged from 11 to 41 months. CONCLUSIONS: PEG tube placement at the time of a LNF is safe and effective. A combined laparoscopic and endoscopic approach minimizes complications. This method also allows for an intra- and extraluminal evaluation of the fundoplication at its completion.     

Lactate and base deficit in trauma: does alcohol or drug use impair their predictive accuracy?

BACKGROUND: Abnormal blood lactate and base deficit (BD) reflect hypoperfusion and have been documented to predict outcome in trauma. Alcohol and drug use may also induce metabolic acidosis in trauma victims, potentially diminishing the predictive accuracy of lactate and BD. We, therefore, sought to examine the effect of alcohol and drug use on the predictive accuracy of admission blood lactate and BD in trauma. METHODS: Prospective data were collected on 15,179 patients admitted to the R Adams Cowley Shock Trauma Center over a 3-year period from 1998 to 2000. Patients were stratified by age, gender, race, injury severity score (ISS), Glasgow coma score (GCS), alcohol concentration and illicit drug use. Multiple regression analyses were used to assess admission blood lactate and BD as independent risk factors for mortality, intensive care unit (ICU) admission, and ICU and hospital length of stay (LOS) controlling for alcohol and drug use [cocaine, phencyclidine and methamphetamines] by measured serum concentrations. RESULTS: The mean age of the study cohort was 37 +/- 19 years, mean ISS was 9 +/- 10, mean GCS 14.1 +/- 2.7, 71% were male and 77% sustained blunt trauma. Alcohol testing was completed in 13,102 of 15,179 (86.3%) of patients. Alcohol screen was positive in 27% (n = 3536) of the total cohort tested (n = 13,102) with a mean blood alcohol concentration of 141 +/- 95 mg/dL; 7% (n = 992) had positive drug screens. Increasing injury severity was associated with significantly increased admission blood lactate and BD (p < 0.001). Patients with positive alcohol and drug screens had significantly increased admission blood lactate, BD and injury severity compared with patients with negative alcohol and drug screens (p < 0.01). Patients with positive alcohol and drug screens had a significant increase in admission to the ICU (p < 0.05), but no significant increase in mortality, ICU or hospital LOS compared with patients with negative screens. Multiple logistic and linear regression analyses confirmed admission lactate and BD as significant independent predictors of mortality, ICU and hospital LOS (p < 0.01). These results were unchanged after controlling for alcohol and drug use as covariates in the logistic and linear regression analyses. CONCLUSION: Alcohol and drug use are common in trauma, but do not impair the predictive accuracy of admission lactate and BD in trauma outcome. Admission lactate and BD are therefore confirmed as significant independent predictors of trauma outcome in patients with acute alcohol and drug use in this largest clinical study to date.