Prospective analysis of clinical outcomes after percutaneous vertebroplasty for painful osteoporotic vertebral body fractures

BACKGROUND AND PURPOSE: Previous studies have retrospectively reported the positive effects of percutaneous vertebroplasty. The purpose of our study was to evaluate prospectively the effects of vertebroplasty on mobility, analgesic use, pain, and SF-36 (short-form 36-item) scales for patients with painful vertebral compression fractures that are refractory to medical therapy. METHODS: We prospectively followed 167 patients who received 207 vertebroplasty treatment sessions for stabilization of 264 symptomatic vertebral compression fractures between August 1999 and January 2003. The average age of patients was 74.6 years (SD = 12.2 years), and 76% were women. Pre- and postprocedural measurements of pain, mobility, analgesic use, and SF-36 scales were compared at 1 month after the procedure and between 6 months and 3 years after the procedure with the SF-36 scales. RESULTS: Respective pre- and post-treatment pain scores were 8.71 (SE = 0.1) and 2.77 (SE = 0.18; P < .00001). Respective pre- and post-treatment analgesic use scores were 2.93 (SE = 0.9) and 1.64 (SE = 0.09; P < .00001). Respective pre- and post-treatment activity levels were 2.66 (SE = 0.1) and 1.64 (SE = 0.11; P < .00001). There was a statistically significant improvement on nine of 10 SF-36 scales (P < .001) after 1 month and on eight of 10 SF-36 scales (P < .02) at long-term follow-up. CONCLUSION: Percutaneous vertebroplasty offers statistically significant benefits in decreasing pain, decreasing use of analgesics, and increasing mobility in appropriately selected patients. Percutaneous vertebroplasty also offers a statistically significant benefit in most SF-36 scales at both short- and long-term follow-up.     

Synthesis and positron emission tomography studies of carbon-11-labeled imatinib (Gleevec)

INTRODUCTION: Imatinib mesylate (Gleevec) is a well known drug for treating chronic myeloid leukemia and gastrointestinal stromal tumors. Its active ingredient, imatinib ([4-[(4-methyl-1-piperazinyl)methyl]-N-[4-methyl-3-[[4-(3-pyridyl)-2-pyrimidinyl]amino]phenyl]benzamide), blocks the activity of several tyrosine kinases. Here we labeled imatinib with carbon-11 as a tool for determining the drug distribution and pharmacokinetics of imatinib, and we carried out positron emission tomography (PET) studies in baboons. METHODS: [N-(11)C-methyl]imatinib was synthesized from [(11)C]methyl iodide and norimatinib was synthesized by the demethylation of imatinib (isolated from Gleevec tablets) according to a patent procedure [Collins JM, Klecker RW Jr, Anderson LW. Imaging of drug accumulation as a guide to antitumor therapy. US Patent 20030198594A1, 2003]. Norimatinib was also synthesized from the corresponding amine and acid. PET studies were carried out in three baboons to measure pharmacokinetics in the brain and peripheral organs and to determine the effect of a therapeutic dose of imatinib. Log D and plasma protein binding were also measured. RESULTS: [N-(11)C-methyl]imatinib uptake in the brain is negligible (consistent with P-glycoprotein-mediated efflux); it peaks and clears rapidly from the heart, lungs and spleen. Peak uptake and clearance occur more slowly in the liver and kidneys, followed by accumulation in the gallbladder and urinary bladder. Pretreatment with imatinib did not change uptake in the heart, lungs, kidneys and spleen, and increased uptake in the liver and gallbladder. CONCLUSIONS: [N-(11)C-methyl]imatinib has potential for assessing the regional distribution and kinetics of imatinib in the human body to determine whether the drug targets tumors and to identify other organs to which the drug or its labeled metabolites distribute. Paired with tracers such as 2'deoxy-2'-[(18)F]fluoro-D-glucose ((18)FDG) and 3'deoxy-3'-[(18)F]fluorothymidine ((18)FLT), [N-(11)C-methyl]imatinib may be a useful radiotracer for planning chemotherapy, for monitoring response to treatment and for assessing the role of drug pharmacokinetics in drug resistance.     

Preliminary results with accelerated partial breast irradiation in high-risk breast cancer patients

PurposeTo analyze prognostic factors in adequately staged breast cancer patients who were treated with accelerated partial breast irradiation (APBI).Methods and MaterialsAxillary staging was required for invasive carcinomas. Between February 2003 and June 2009, 204 women with early stage breast carcinomas were treated with APBI using multicatheter, MammoSite, or Contura brachytherapy to 34 Gy in 10 fractions 2 times per day. Six patient characteristics were examined for prognostic significance: (1) N stage, (2) estrogen receptor (ER) status, (3) histologic subtype, (4) margin status, (5) age, and (6) tumor size. The median followup was 22 months.ResultsThere were three failures in the ipsilateral breast (all were elsewhere failures), one relapse in the axilla, and seven relapses at any site. The presence of positive axillary node(s) had a significant adverse effect on ipsilateral breast tumor control (p = 0.045) and locoregional control (p = 0.001). The presence of an ER (?) tumor had a significant adverse effect on relapse-free survival (p = 0.04).ConclusionsThe patients with positive axillary node(s) were at increased risk for failure elsewhere in the ipsilateral breast or axilla, and the patients with ER (?) tumors were at increased risk for relapse at any site. However, it is unclear whether the pN1 and ER (?) patients would have faired any better if they had received whole breast irradiation rather than APBI. We believe that the patients with positive axillary node(s) or ER (?) tumors should be treated on clinical trials to better define the role of APBI.     

Prevalence of hypoglycemia during oral glucose tolerance testing in adults with cystic fibrosis and risk of developing cystic fibrosis-related diabetes

Background

Hypoglycemia in cystic fibrosis (CF) patients during the oral glucose tolerance test (OGTT) has been reported; however, these patients have not been well-characterized. Few studies have examined whether hypoglycemia during the OGTT increases the risk of developing CF-related diabetes (CFRD). Objectives of this study were to describe the characteristics of CF patients with hypoglycemia during the OGTT and to determine the incidence and time to development of CFRD in those with hypoglycemia.

A short-duration restrictive diet reduces visceral adiposity in the morbidly obese surgical patient

Background

This study aims to determine if visceral obesity can be reduced after a brief preoperative diet in obese patients.

Methods

Forty morbidly obese patients were placed on a 1,000 kCal per day diet for 14 days before bariatric surgery. Patients had weight measurements and an abdominal ultrasound performed on days 1 and 14. The ultrasound measured visceral obesity using the distance between the abdominal muscle and the aorta, the fat thickness of the perinephric space, and the distance between the abdominal muscle and splenic vein. Mesenteric fat burden was calculated and compared.

Results

Thirty-eight patients (95%) lost weight on the diet, with a mean loss of 5.2 lbs. Twenty-five patients (63%) had a reduction in mesenteric fat. The average visceral obesity lost was 7.76 cm³ or 3% of the visceral adiposity of the average obese patient (250 cm³).

Conclusions

A short preoperative calorie restricting diet is well tolerated and results in a reduction in visceral obesity.     

IL-18 promoter polymorphisms correlate with the development of post-injury sepsis

BACKGROUND: Interleukin (IL)-18 is a proinflammatory cytokine involved in the regulation of cell-mediated and innate immune responses to infection, trauma, and inflammation. Elevated levels of IL-18 have been noted to correlate with organ dysfunction after injury. This study evaluates the relationship between IL-18 promoter polymorphisms and the development of sepsis after injury. METHODS: DNA was extracted from peripheral leukocytes of trauma patients with an injury severity score of 16 or greater. Patient clinical course was followed for the development of sepsis as an endpoint. Two SNPs (-607bp and -137bp) were amplified using polymerase chain reaction. Alleles were identified via agarose gel separation. Genotypes were then determined and correlated with patient data. Postinjury IL-18 levels were determined by enzyme-linked immunoassay. RESULTS: Sixty-six patients were evaluated; 36 (52%) developed sepsis. Each SNP had 2 alleles and 3 genotypes. The SNP at -607bp had an allelic frequency of 59% for C and 41% for A; whereas -137bp was a G 79% of the time and a C 21% of the time. Individually, each SNP had no direct correlation between the patient's genotype and development of infection. However, when the -607bp CA genotype was combined with the -137bp GC genotype (CA/GC), only 4 patients (27%) developed sepsis (P =.02). CONCLUSIONS: This study supports the conclusion that IL-18 genetic promoter polymorphisms correlate with the development of postinjury sepsis. Further investigation is needed to identify the impact of variation in genotype across a range of genes involved in connected regulatory pathways.     

Subtotal Pancreatectomy for Chronic Pancreatitis

Chronic pancreatitis results when pancreatic structure or function is irreversibly damaged by repeated or ongoing inflammation, regardless of the underlying etiology. Most patients present with medically intractable pain and radiological evidence of diffuse gland involvement. Surgical therapy is directed mainly toward palliation of symptoms, and cure is unusual except when the inflammatory process is limited to a specific segment of the pancreas. Surgical strategy should be individualized on the basis of alterations in pancreatic morphology and duct anatomy. In properly selected patients, duct drainage procedures effectively relieve pain and preserve pancreatic function with low perioperative morbidity and mortality. Extensive distal pancreatectomy is effective in relieving pain, but it can be technically challenging and in general should be limited to patients with small-duct disease because of severe metabolic consequences. Intraportal islet cell autotransplantation or segmental pancreatic autotransplantation may ameliorate the long-term effects of insulin-dependent diabetes, but it will have limited applicability until methods for optimizing and purifying islets are developed and the optimal route and site of islet cell implantation have been identified.     

Prevalence of Liver Steatosis and Fibrosis and the Diagnostic Accuracy of Ultrasound in Bariatric Surgery Patients

Background  

Liver steatosis can progress to fibrosis, cirrhosis, and eventually to end-stage liver disease and hepatocellular carcinoma. We thus determined the prevalence of liver steatosis and fibrosis in patients undergoing bariatric surgery using liver biopsy. We also determined the suitability of ultrasound for diagnosis of liver steatosis with and without simultaneously considering patient characteristics.