Elevated intracellular level of basic fibroblast growth factor correlates with stage of chronic lymphocytic leukemia and is associated with resistance to fludarabine

Chronic lymphocytic leukemia (CLL) is characterized by delayed senescence and slow accumulation of monoclonal, small lymphocytes. Basic fibroblast growth factor (bFGF) is a pleiotropic cytokine that plays a role in hematopoiesis and apoptosis. Elevated bFGF levels have been detected in urine from patients with a variety of neoplastic diseases including various leukemias; however, the cellular source of the bFGF has not been determined. In this study, the intracellular bFGF level in lymphocytes of 36 patients with B-CLL and 15 normal donors was determined using an enzyme-linked immunoassay. In cells derived from patients with high-risk disease, the median level of intracellular bFGF was 381.5 pg/2 x 10(5) cells, compared with a median of 90.5 pg/2 x 10(5) cells in patients with intermediate disease. In patients with low- risk disease, the median bFGF level was 4.9 pg/2 x 10(5) cells, and in normal controls, it was 6.0 pg/2 x 10(5) cells. The difference in the bFGF levels was significant for the comparison between low- and intermediate-risk (P = .00119), low- and high-risk (P < .0001), and intermediate- and high-risk disease (P = .0001). Immunofluorescent stains of peripheral blood mononuclear cells confirmed CLL lymphocytes as a cellular source of bFGF. To evaluate the potential contribution of elevated intracellular bFGF levels to the phenotype of CLL cells, leukemic cells were cultured in vitro with an apoptotic stimulus (fludarabine). CLL cells with high intracellular levels of bFGF appeared to be more resistant to fludarabine treatment. The addition of bFGF to fludarabine-treated CLL cells resulted in a delay of apoptosis and prolonged survival. These data suggest that bFGF may contribute to the resistance of CLL cells to an apoptotic stimulus.     

Impact of cardiac catheterization-percutaneous coronary intervention timing on inhospital mortality

Background It is more convenient and less costly to perform percutaneous coronary interventions (PCIs) in the catheterization laboratory after catheterization, but there is some doubt as to whether it is harmful to patients. Other studies on this topic have been hampered by small sample sizes and an inability to separate patients who underwent PCI after catheterization in the same admission from patients who underwent PCI in a subsequent admission. Methods Data from New York's PCI registry were used to develop a statistical model that predicted inhospital mortality based on preprocedural patient characteristics and the timing of the PCI (at same time as catheterization [combined procedure] or in the same admission as catheterization, but not at the same time [staged procedure]). The difference in mortality for the timing options was compared after adjusting for patient risk factors. Results Patients undergoing combined catheterization and PCI were more likely to have undergone a previous PCI and less likely to have had chronic obstructive pulmonary disease, renal failure, a history of congestive heart failure, carotid disease, or diabetes than patients who underwent a staged procedure. After adjustment for patient risk, there were no significant differences in mortality for the 2 timing options (OR 1.14, P = .38 for combined vs staged procedures). However, patients who underwent combined procedures who had congestive heart failure in the same admission or who had Canadian Cardiovascular Society class IV had odds ratios significantly higher than congestive heart failure patients who underwent staged procedures (OR = 1.59, P = .04 and OR = 1.64, P = .04, respectively). Conclusions Combined procedures appear to have mortality as low as staged procedures on average, but are less effective for some groups of high-risk patients. (Am Heart J 2002;144:561-7.)     

Comparison of 4.5‐Year Outcomes of Bare‐Metal and Zotarolimus‐Eluting Stents in New York

Background

Both bare‐metal stents (BMS; the first‐generation coronary stent) and zotarolimus‐eluting stents (ZES; a second‐generation drug‐eluting stent [DES]) have been widely utilized to treat coronary heart disease. However, the long‐term comparative effectiveness of BMS and ZES remains unclear. The purpose of this study was to evaluate long‐term comparative effectiveness of BMS versus ZES.

Methods

We created a longitudinal database by linking the New York State (NYS) cardiac registries, statewide hospital discharge data, the National Death Index (NDI), and the U.S. Census file (2010) for patients receiving either BMS or ZES during the 2008–2009 period. We examined the rates of all‐cause mortality, acute myocardial infarction (AMI), target‐lesion PCI (TLPCI), and target‐vessel coronary artery bypass graft (TVCABG) surgery for a follow‐up period of 4.5 years. A total of 10,443 propensity score matched pairs were compared using the Kaplan–Meier method and Cox proportional hazards regression adjusting for patient risk factors.

Results

We found that patients receiving ZES had a lower rate of 4.5‐year mortality (adjusted hazard ratio AHR: 0.68, 95% confidence interval CI: 0.63–0.73), AMI (AHR: 0.89, 95% CI: 0.80–0.98), and TVCABG (AHR: 0.84, 95% CI: 0.71–0.99) but a similar rate of TLPCI (AHR: 1.02, 95% CI: 0.93–1.12). For “off‐label” and “high‐risk” subgroups, ZES was associated with improved mortality and generally better or non‐inferior AMI, TLPCI, and TVCABG outcomes relative to BMS.

Conclusions

Compared with BMS, ZES was associated with lower long‐term mortality, AMI and TVCABG. (J Interven Cardiol 2016;29:265–274)

     

Reduced bone mineral density in bulimia as well as anorexia nervosa

We conducted a case controlled study to examine bone mineral density (BMD) in 47 women with bulimia nervosa, 51 with anorexia nervosa, 45 women recovered from past eating disorders, and 40 healthy controls. Lumbar spine and whole body BMD were measured by dual energy X‐ray absorptiometry. In contrast with previous studies, we found that subjects with active bulimia nervosa, even with no previous history of anorexia, had lower whole body and lumbar spine BMD than controls, although higher than in anorexia. Non‐traumatic spinal fractures were detected in two anorexic subjects and two bulimic subjects, but none of the controls. Assessment of BMD should be considered in patients with severe bulimia as well as anorexia nervosa. Copyright © 2004 John Wiley & Sons, Ltd and Eating Disorders Association.     

Application of the “Hybrid Approach” to Chronic Total Occlusion Interventions: A Detailed Procedural Analysis

Objective

To assess the outcomes of the “hybrid” approach to chronic total occlusion (CTO) percutaneous coronary interventions (PCIs).

Background

The “hybrid approach” to CTO PCI advocates appropriate and early change of crossing strategy to maximize success, safety, and efficiency.

Methods

We prospectively recorded and analyzed detailed step‐by‐step procedural data in 73 consecutive CTO PCI cases performed by a single operator between July 2011 and August 2012.

Results

Technical success was achieved in 66 of 73 cases (90.4%). Mean patient age was 65 ± 7 years, and 30% had prior coronary artery bypass surgery. Dual injection was used in 78%. The primary approach was retrograde in 9 cases (12.5%) and antegrade in 64 cases (87.5%), of whom 25 cases (39.1%) underwent retrograde attempt after failed antegrade approach. The initial crossing approach was successful in 40 cases (54.8%), but 32 cases (44%) required 3.6 ± 1.4 approach changes (range 2–7). Antegrade wire escalation, antegrade dissection/reentry, and retrograde crossing were utilized in 97.2%, 46.6%, and 46.6% of cases, respectively. Among successful cases, the final CTO crossing technique was antegrade wire escalation in 50.0%, antegrade dissection/reentry in 24.2%, and retrograde in 25.8%. The mean procedure time, fluoroscopy time, and air kerma radiation exposure until CTO crossing or stopping the procedure were 66 ± 55 minutes, 25 ± 23 minutes, and 2.3 ± 1.9 Gray, respectively. Three patients (4.1%) had a major complication.

Conclusion

In the “hybrid approach” to CTO PCI, changes in crossing strategy were needed in approximately half the cases, resulting in high success and low complication rates. (J Interven Cardiol 2014;27:36–43)

     

Malignant fibrous histiocytoma presenting with complete opacification of the hemithorax: A case report

BACKGROUND

Malignant fibrous histiocytoma, a subtype of primary lung sarcoma is a very rare disease. It usually presents as a lung nodules and the final diagnosis is made by immunohistochemical studies.

METHODS

A 45-year-old patient presented with progressive dyspnea, dry cough and right shoulder pain. Chest X-ray revealed complete opacification of the right hemithorax. Chest computed tomography confirmed the presence of a heterogeneous lesion occupying the whole right hemithorax causing a mass effect on the trachea. Ultrasound guided biopsy was done and final pathology was suggestive of malignant fibrous histiocytoma.

CONCLUSION

Progressive dyspnea in young otherwise healthy patients should be investigated early on. In our case the presence of right shoulder pain indicates advance disease illustrated by the singular imaging findings.     

Is the tongue position influenced by the palatal vault dimensions?

Summary The influence of the palatal vault dimensions on tongue position is here studied through evaluation of the in‐mouth air cavity (IMAC) volume when the mandible is in maximal intercuspal position. A sample of 35 women (mean age 21·2 ± 1·0) and 15 men (mean age 22·1 ± 0·9) was selected. The sagittal cross‐section area of the IMAC, which is modulated by the tongue position, was measured on lateral cephalograms. Dental casts were used to measure the palatal vault volume, which was defined by the occlusal plane, the hard palate and the posterior face of the second molars. Palatal vault volume allowed deduction of the IMAC volume through a rule of three procedure relating volume to area ratios. No IMAC could be calculated from cephalograms of 10 subjects who had the tongue stuck to the palate. For the 40 other subjects, the IMAC volume was 8·9 ± 4·8 mL. It was 2 mL larger in men (n = 14) than in women (n = 26) and was the largest in skeletal Class III and the smallest in skeletal Class II (P > 0·05). IMAC volume was strongly correlated with palatal vault height but neither with palatal width nor length. It was thus assumed that the height of the palatal vault could influence the most observed position of the tongue but this does not exclude a possible growth influence of the tongue on its surrounding skeletal structures.     

PRIME: impact of previous mental health problems on health-related quality of life in women with childbirth trauma

We investigated the impact of pre-existing mental ill health on postpartum maternal outcomes. Women reporting childbirth trauma received counselling (Promoting Resilience in Mothers' Emotions; n?=?137) or parenting support (n?=?125) at birth and 6 weeks. The EuroQol Five dimensional (EQ-5D)-measured health-related quality of life at 6 weeks, 6 and 12 months. At 12 months, EQ-5D was better for women without mental health problems receiving PRIME (mean difference (MD) 0.06; 95 % confidence interval (CI) 0.02 to 0.10) or parenting support (MD 0.08; 95 % CI 0.01 to 0.14). Pre-existing mental health conditions influence quality of life in women with childbirth trauma.     

Increased activity of Diaphanous homolog 3 (DIAPH3)/diaphanous causes hearing defects in humans with auditory neuropathy and in Drosophila

Auditory neuropathy is a rare form of deafness characterized by an absent or abnormal auditory brainstem response with preservation of outer hair cell function. We have identified Diaphanous homolog 3 (DIAPH3) as the gene responsible for autosomal dominant nonsyndromic auditory neuropathy (AUNA1), which we previously mapped to chromosome 13q21-q24. Genotyping of additional family members narrowed the interval to an 11-Mb, 3.28-cM gene-poor region containing only four genes, including DIAPH3. DNA sequencing of DIAPH3 revealed a c.-172G > A, g. 48G > A mutation in a highly conserved region of the 5′ UTR. The c.-172G > A mutation occurs within a GC box sequence element and was not found in 379 controls. Using genome-wide expression arrays and quantitative RT-PCR, we demonstrate a 2- to 3-fold overexpression of DIAPH3 mRNA in lymphoblastoid cell lines from affected individuals. Likewise, a significant increase (≈1.5-fold) in DIAPH3 protein was found by quantitative immunoblotting of lysates from lymphoblastoid cell lines derived from affected individuals in comparison with controls. In addition, the c.-172G > A mutation is sufficient to drive overexpression of a luciferase reporter. Finally, the expression of a constitutively active form of diaphanous protein in the auditory organ of Drosophila melanogaster recapitulates the phenotype of impaired response to sound. To date, only two genes, the otoferlin gene OTOF and the pejvakin gene PJVK, are known to underlie nonsyndromic auditory neuropathy. Genetic testing for DIAPH3 may be useful for individuals with recessive as well as dominant inheritance of nonsyndromic auditory neuropathy.