A Method for Choosing the Smoothing Parameter in a Semi-parametric Model for Detecting Change-points in Blood Flow.

In a smoothing spline model with unknown change-points, the choice of the smoothing parameter strongly influences the estimation of the change-point locations, and the function at the change-points. In a tumor biology example, where change-points in blood flow in response to treatment were of interest, choosing the smoothing parameter based on minimizing generalized cross validation, GCV, gave unsatisfactory estimates of the change-points. We propose a new method, aGCV, that re-weights the residual sum of squares and generalized degrees of freedom terms from GCV. The weight is chosen to maximize the decrease in the generalized degrees of freedom as a function of the weight value, while simultaneously minimizing aGCV as a function of the smoothing parameter and the change-points. Compared to GCV, simulation studies suggest that the aGCV method yields improved estimates of the change-point and the value of the function at the change-point.

Diffuse optical characterization of an exercising patient group with peripheral artery disease.

Peripheral artery disease (PAD) is a common condition with high morbidity. While measurement of tissue oxygen saturation (S(t)O(2)) has been demonstrated, this is the first study to assess both S(t)O(2) and relative blood flow (rBF) in the extremities of PAD patients. Diffuse optics is employed to measure hemodynamic response to treadmill and pedal exercises in 31 healthy controls and 26 patients. For S(t)O(2), mild and moderate/severe PAD groups show pronounced differences compared with controls. Pre-exercise mean S(t)O(2) is lower in PAD groups by 9.3% to 10.6% compared with means of 63.5% to 66.2% in controls. For pedal, relative rate of return of S(t)O(2) to baseline is more rapid in controls (p < 0.05). Patterns of rBF also differ among groups. After both exercises, rBF tend to occur at depressed levels among severe PAD patients compared with healthy (p < 0.05); post-treadmill, rBF tend to occur at elevated levels among healthy compared with severe PAD patients (p < 0.05). Additionally, relative rate of return to baseline S(t)O(2) is more rapid among subjects with reduced levels of depression in rBF (p = 0.041), even after adjustment for ankle brachial index. This suggests a physiologic connection between rBF and oxygenation that can be measured using diffuse optics, and potentially employed as an evaluative tool in further studies.

Tumor blood flow differs between mouse strains: consequences for vasoresponse to photodynamic therapy.

Fluctuations in tumor blood flow are common and attributed to factors such as vasomotion or local vascular structure, yet, because vessel structure and physiology are host-derived, animal strain of tumor propagation may further determine blood flow characteristics. In the present report, baseline and stress-altered tumor hemodynamics as a function of murine strain were studied using radiation-induced fibrosacomas (RIF) grown in C3H or nude mice. Fluctuations in tumor blood flow during one hour of baseline monitoring or during vascular stress induced by photodynamic therapy (PDT) were measured by diffuse correlation spectroscopy. Baseline monitoring revealed fluctuating tumor blood flow highly correlated with heart rate and with similar median periods (i.e., ∼9 and 14 min in C3H and nudes, respectively). However, tumor blood flow in C3H animals was more sensitive to physiologic or stress-induced perturbations. Specifically, PDT-induced vascular insults produced greater decreases in blood flow in the tumors of C3H versus nude mice; similarly, during baseline monitoring, fluctuations in blood flow were more regular and more prevalent within the tumors of C3H mice versus nude mice; finally, the vasoconstrictor L-NNA reduced tumor blood flow in C3H mice but did not affect tumor blood flow in nudes. Underlying differences in vascular structure, such as smaller tumor blood vessels in C3H versus nude animals, may contribute to strain-dependent variation in vascular function. These data thus identify clear effects of mouse strain on tumor hemodynamics with consequences to PDT and potentially other vascular-mediated therapies.

Necrotizing fasciitis of the thigh secondary to radiation colitis in a rectal cancer patient.

Necrotizing fasciitis usually occurs after dermal injury or through hematogenous spread. To date, few cases have been reported as necrotizing fasciitis of the thigh secondary to rectal perforation in rectal cancer patients. A 66-year-old male complained of pelvic and thigh pain and subsequently developed necrotizing fasciitis in his right thigh. Four years earlier, he had undergone a low anterior resection and radiotherapy due to of rectal cancer. An ulcerative lesion had been observed around the anastomosis site during the colonoscopy that had been performed two months earlier. Pelvic computed tomography and sigmoidoscopy showed rectal perforation and presacral abscess extending to buttock and the right posterior thigh fascia. Thus, the necrotizing fasciitis was believed to have occurred because of ulcer perforation, one of the complications of chronic radiation colitis, at the anastomosis site. When a rectal-cancer patient complains of pelvic and thigh pain, the possibility of a rectal perforation should be considered.

Clinical significance of subjective foamy urine.

Foamy urine is widely regarded as a sign of proteinuria. However, there is no objective definition of foamy urine and there are no reports on the proportion of involved patients who have overt proteinuria or microalbuminuria. We performed this study to investigate this proportion and to identify possible risk factors for these two conditions. We reviewed all new outpatients from 1 November 2011 to 30 April 2012 and identified patients complaining of foamy urine. Their demographic data and medical records were examined. In particular, we tabulated the patients' spot urinary protein to creatinine ratio, spot urinary microalbumin to creatinine ratio (ACR), blood urea nitrogen (BUN), and serum levels of creatinine (Cr), uric acid, calcium, phosphate, and glucose. In addition, we calculated estimated glomerular filtration rates (eGFRs) by using the CKD-EPI equation. We also performed risk factor analysis with the Chi-squared test and by logistic regression. Seventy-two patients (6.3% of total new outpatients) complained of foamy urine; of these, there were 59 males with a median age of 65.5 years (range, 36-87 years). Of the 72 patients, 16 (22.2%) had overt proteinuria. We found that diabetes, poor renal function (high Cr, BUN, low eGFR), increased serum phosphate, and increased serum glucose were associated with overt proteinuria. Multiple logistic regression analysis showed that serum Cr and serum phosphate were associated with overt proteinuria. The ACR was available for 38 patients, and in this subgroup, 12 (31.6%) showed microalbuminuria or overt proteinuria. In this subgroup, a high serum Cr was the only statistically significant risk factor. Among patients who complained of foamy urine, approximately 20% had overt proteinuria, and increased serum Cr and phosphate were statistically significant risk factors.