Computed tomography in diagnosis and management of multiple myeloma and its variants

The use of computed tomography (CT) was evaluated in 25 patients with multiple myeloma, six with extramedullary plasmacytoma, and two with undiagnosed lesions. We found that CT was useful for (1) patients with multiple myeloma who had bone pain but normal roentgenograms, (2) patients with an M-protein, bone marrow plasmacytosis, and back pain from osteoporosis and compression fractures but an inconclusive diagnosis of multiple myeloma, (3) the determination of extent of tumor, and (4) guidance in needle biopsy.     

Unique white matter microstructural patterns in ADHD presentations—a diffusion tensor imaging study

Attention‐deficit/hyperactivity disorder predominantly inattentive (ADHD‐PI) and combined (ADHD‐C) presentations are likely distinct disorders that differ neuroanatomically, neurochemically, and neuropsychologically. However, to date, little is known about specific white matter (WM) regions differentiating ADHD presentations. This study examined differences in WM microstructure using diffusion tensor imaging (DTI) data from 20 ADHD‐PI, 18 ADHD‐C, and 27 typically developed children. Voxel‐wise analysis of DTI measurements in major fiber bundles was carried out using tract‐based spatial statistics (TBSS). Clusters showing diffusivity abnormalities were used as regions of interest for regression analysis between fractional anisotropy (FA) and neuropsychological outcomes. Compared to neurotypicals, ADHD‐PI children showed higher FA in the anterior thalamic radiations (ATR), bilateral inferior longitudinal fasciculus (ILF), and in the left corticospinal tract (CST). In contrast, the ADHD‐C group exhibited higher FA in the bilateral cingulum bundle (CB). In the ADHD‐PI group, differences in FA in the left ILF and ATR were accompanied by axial diffusivity (AD) abnormalities. In addition, the ADHD‐PI group exhibited atypical mean diffusivity in the forceps minor (FMi) and left ATR and AD differences in right CB compared to healthy subjects. Direct comparison between ADHD presentations demonstrated radial diffusivity differences in FMi. WM clusters with FA irregularities in ADHD were associated with neurobehavioral performance across groups. In conclusion, differences in WM microstructure in ADHD presentations strengthen the theory that ADHD‐PI and ADHD‐C are two distinct disorders. Regions with WM irregularity seen in both ADHD presentations might serve as predictors of executive and behavioral functioning across groups. Hum Brain Mapp 37:3323–3336, 2016. © 2016 Wiley Periodicals, Inc.     

Primary localized amyloidosis of the bladder: experience with dimethyl sulfoxide therapy

PURPOSE: We present our long-term experience with intravesical dimethyl sulfoxide (DMSO) for primary localized amyloidosis of the bladder. MATERIALS AND METHODS: The study included 4 males and 2 females 28 to 68 years old (mean age 54) at diagnosis of biopsy proven primary localized amyloidosis involving the bladder diffusely or extensively in 1 locale. All patients had normal upper urinary tracts. They continued to be symptomatic (hematuria in 3, irritative voiding symptoms in 1, and hematuria and irritative voiding symptoms in 2) despite conventional transurethral destructive therapy. Every 2 weeks they received 30-minute instillations of 50 ml. 50% DMSO intravesically for 3 months (patient 1), 6 months (1) and 1 year (4). RESULTS: Therapy failed at 3 and 6 months in 2 patients of whom 1 with a contracted bladder underwent cystectomy and another was stabilized for 1 year with laser therapy. In the remaining 4 patients who were followed for 6 years disease stabilized for 2 to 6 years (mean 3.5) but 3 later required additional therapy including repeat DMSO in 1 and laser therapy in 2. CONCLUSIONS: Diffuse or locally extensive bladder involvement by primary localized amyloidosis usually fails to respond to conventional transurethral destructive surgical procedures. Collectively, our experience and the literature suggest that intravesical DMSO can be a bladder saving measure and help resolve ureterovesical obstruction in some patients. High recurrence rate mandates lifelong cystoscopic surveillance.     

Gender differences in long‐term survival post‐transplant: A single‐institution analysis in the lung allocation score era

The purpose of this study was to clarify the significance of recipient gender status on lung transplant outcomes in a large single‐institution experience spanning three decades, we analyzed data from all lung transplants performed in our institution since 1986. Kaplan‐Meier curves and Cox proportional hazard models were used to evaluate the effect of recipient characteristics on survival and BOS score ≥1‐free survival. Logistic regression analysis was used to explore the association of gender with short‐term graft function. About 876 lung transplants were performed between 1986 and 2016. Kaplan‐Meier survival estimates at 5 years post‐transplant for females vs males in the LAS era were 71% vs 58%. In the LAS era, females showed greater unadjusted BOS≥1‐free survival than males (35% vs 25%, P=.02) over 5 years. Female gender was the only factor in the LAS era significantly associated with improved adjusted 5‐year survival [HR 0.56 (95% CI 0.33, 0.95) P=.03]. Conversely, in the pre‐LAS era female gender was not associated with improved survival. Female recipients showed significantly improved survival over 5 years compared to males in the LAS era. A prospective analysis of biologic and immunologic differences is warranted.     

Does noncontact low‐frequency ultrasound therapy contribute to wound healing at the molecular level?

Noncontact low‐frequency ultrasound (NLFU) is used to treat various types of chronic wounds including venous, diabetic, and pressure ulcers. The objective for this substudy of the IN BALANCE RCT VLU trial was to characterize and compare the NLFU treatment group and patients receiving standard of care (SOC) with respect to the effect of the assigned study treatment on content/quantity of inflammatory cytokines and fibrinogen as well as bacteria. Higher mean wound area reduction was observed in the NLFU treatment group (67.0%) compared to the SOC group (41.6%, p < 0.05). Hypertension, diabetes type II, coronary artery disease, and anemia were identified as the most common comorbidities of the Chronic venous leg ulcer (CVLU) patients included in the study. Pseudomonas, Corynebacterium, and unclassified Enterobacteriaceae were dominant in the highest number of samples. Anaerococcus, Peptoniphilus, and Finegoldia, had the highest median proportion in the samples overall. Peptoniphilus abundance decreased more in the NLFU treatment group relative to SOC; similar trends were observed for Anaerococcus and Finegoldia. Progression of mediators like TNF‐alpha, IL‐1beta, IL‐6, IL‐8, and IL‐10 as well as PF4, TGF‐beta, and fibrinogen was monitored and trends for several of the mediators were identified. Fibrinogen amounts were significantly reduced over time in the NLFU treatment group (p < 0.05). IL‐8 levels declined in wound fluid from NLFU responders as well as SOC responders. Bacterial load (total bacterial abundance) determined local parameters of ulcer inflammation. If a bioburden of ≥ 10E⁵ was found compared to < 10E⁵, levels of IL‐1beta, IL‐8, and TNF‐alpha were significantly higher. In conclusion, NLFU treatment is an effective adjuvant tool for CVLU therapy. This study demonstrates that it improves wound healing by equally inhibiting abundant levels of pro‐inflammatory cytokines as well as by reducing the overall bacterial burden.     

Effects of Denosumab and Teriparatide Transitions on Bone Microarchitecture and Estimated Strength: the DATA‐Switch HR‐pQCT study

In postmenopausal osteoporosis, switching from teriparatide to denosumab results in continued bone mineral density (BMD) gains whereas switching from denosumab to teriparatide results in BMD loss. To assess the effects of these transitions on bone microarchitecture and strength, we performed high‐resolution peripheral QCT (HR‐pQCT) at the distal tibia and radius in postmenopausal osteoporotic women who received 24 months of teriparatide 20 μg daily followed by 24 months of denosumab 60 mg every 6 months, 24 months of denosumab followed by 24 months of teriparatide, or 24 months of both medications followed by 24 months of denosumab. The 77 women who completed at least one post‐switch visit are included in this analysis. Tibial cortical volumetric BMD (vBMD) increased between months 24 and 48 in the teriparatide‐to‐denosumab (net 48‐month change –0.8% ± 2.4%) and combination‐to‐denosumab groups (net 48‐month changes +2.4% ± 4.1%) but decreased in the denosumab‐to‐teriparatide group (net 48‐month change –3.4% ± 3.2%, p < 0.001 for all between‐group comparisons). Changes in total vBMD, cortical thickness, and estimated stiffness (by micro–finite element analysis [µFEA]) followed a similar pattern, as did changes at the radius. Conversely, tibial cortical porosity remained stable between months 24 and 48 in the teriparatide‐to‐denosumab and combination‐to‐denosumab groups (net 48‐month changes +7.2% ± 14.8% and –3.4% ± 12.1%, respectively) but increased in the denosumab‐to‐teriparatide group (net 48‐month change +16.2% ± 11.5%, p < 0.05 versus other groups). Trabecular vBMD changes did not differ among groups. Together, these findings demonstrate that in women treated with denosumab, switching to teriparatide is associated with a reduction in total and cortical vBMD, cortical thickness, and estimated strength, whereas switching to denosumab from teriparatide or combination therapy results in improvements in these parameters with the greatest improvements observed in women treated with combined therapy followed by denosumab. These findings strongly suggest that the use of teriparatide after denosumab should be avoided and that the use of combined teriparatide/denosumab followed by denosumab alone may be a useful treatment strategy in those with severe osteoporosis. © 2017 American Society for Bone and Mineral Research.     

Paediatric surgery carried out by general surgeons: a rural New Zealand experience

Background: There are increasing moves towards centralization in paediatric surgery. With only four paediatric tertiary centres in New Zealand, many general surgeons still routinely carry out paediatric surgery. We present an audit of paediatric surgical patients admitted to our general surgical unit. Methods: Data were prospectively recorded using a standardized pro forma on all children aged 15 years and below, who presented to general surgery between 11 December 2005 and 11 December 2006. Results: There were 209 admissions (194 children); the median age was 8 years (range 6 weeks to 15 years) with 153 (73%) acutes. Male : female ratio was 3:2 and 37 children (18%) were less than 2 years of age. Procedures (n = 119) comprised appendicectomy (35), inguinal herniotomy (30), skin procedures (29), endoscopy (10), testicular (10) and others (5). The commonest acute and elective operations were appendicectomy and inguinal herniotomy, respectively, with 51% of all operations carried out acutely. There were 10 tertiary hospital transfers (5%) for burns (4), pyloric stenosis (3), intussusception (1), neonatal inguinal hernia (1) and pyoderma gangrenosum (1). Median age of transfers was 11 months (range 6 weeks to 14 years). Complications were wound infection (1), postoperative ileus (2) and infarcted ovary (1). Conclusion: A large number of children presented to our surgical department. Approximately half required surgery and half of the operations were acute. There is still a significant need for general paediatric surgery in the provinces and hence close collaboration with specialist paediatric surgeons.     

Reduction of hepatic and adipose tissue glucocorticoid receptor expression with antisense oligonucleotides improves hyperglycemia and hyperlipidemia in diabetic rodents without causing systemic glucocorticoid antagonism

Glucocorticoids (GCs) increase hepatic gluconeogenesis and play an important role in the regulation of hepatic glucose output. Whereas systemic GC inhibition can alleviate hyperglycemia in rodents and humans, it results in adrenal insufficiency and stimulation of the hypothalamic-pituitary-adrenal axis. In the present study, we used optimized antisense oligonucleotides (ASOs) to cause selective reduction of the glucocorticoid receptor (GCCR) in liver and white adipose tissue (WAT) and evaluated the resultant changes in glucose and lipid metabolism in several rodent models of diabetes. Treatment of ob/ob mice with GCCR ASOs for 4 weeks resulted in approximately 75 and approximately 40% reduction in GCCR mRNA expression in liver and WAT, respectively. This was accompanied by approximately 65% decrease in fed and approximately 30% decrease in fasted glucose levels, a 60% decrease in plasma insulin concentration, and approximately 20 and 35% decrease in plasma resistin and tumor necrosis factor-alpha levels, respectively. Furthermore, GCCR ASO reduced hepatic glucose production and inhibited hepatic gluconeogenesis in liver slices from basal and dexamethasone-treated animals. In db/db mice, a similar reduction in GCCR expression caused approximately 40% decrease in fed and fasted glucose levels and approximately 50% reduction in plasma triglycerides. In ZDF and high-fat diet-fed streptozotocin-treated (HFD-STZ) rats, GCCR ASO treatment caused approximately 60% reduction in GCCR expression in the liver and WAT, which was accompanied by a 40-70% decrease in fasted glucose levels and a robust reduction in plasma triglyceride, cholesterol, and free fatty acids. No change in circulating corticosterone levels was seen in any model after GCCR ASO treatment. To further demonstrate that GCCR ASO does not cause systemic GC antagonism, normal Sprague-Dawley rats were challenged with dexamethasone after treating with GCCR ASO. Dexamethasone increased the expression of GC-responsive genes such as PEPCK in the liver and decreased circulating lymphocytes. GCCR ASO treatment completely inhibited the increase in dexamethasone-induced PEPCK expression in the liver without causing any change in the dexamethasone-induced lymphopenia. These studies demonstrate that tissue-selective GCCR antagonism with ASOs may be a viable therapeutic strategy for the treatment of the metabolic syndrome.