Hyperfractionated Cyclophosphamide and Dexamethasone Alone or in Combination with Daratumumab and/or Carfilzomib for the Treatment of Relapsed or Refractory Multiple Myeloma: A Single-Center Retrospective Analysis.

BACKGROUND: Hyperfractionated cyclophosphamide and dexamethasone (HyperCd) alone, or with carfilzomib(K) and/or daratumumab(D), represents a potential treatment option when rapid disease control is needed for patients with aggressive presentations of relapsed/refractory multiple myeloma (RRMM). PATIENTS AND METHODS: This is a single-center, retrospective analysis of adult patients with RRMM who received HyperCd with or without K and/or D between May 1, 2016 and August 1, 2019 at the University of Texas MD Anderson Cancer Center. We here report treatment response and safety outcomes. RESULTS: Data from 97 patients, 12 with plasma cell leukemia (PCL), were reviewed in this analysis. Patients had had a median of 5 prior lines of therapy and received a median of 1 consecutive cycle of hyperCd-based therapy. The overall response rate (ORR) of all patients was 71.8% (HyperCd 75%, HyperCdK 64.3%, D-HyperCd 73.3%, and D-HyperCdK 76.9%). Median progression-free survival and overall survival among all patients was 4.3 months (HyperCd 3.1 months, HyperCdK 4.5 months, D-HyperCd 3.3 months, and D-HyperCdK 6 months) and 9.0 months (HyperCd 7.4 months, HyperCdK 9.0 months, D-HyperCd 7.5 months, and D-HyperCdK 15.2 months), respectively. Grade 3/4 hematologic toxicities were common, thrombocytopenia being the most frequent at 76%. Notably, 29-41% of patients per treatment group had existing grade 3/4 cytopenias at initiation of hyperCd-based therapy. CONCLUSION: HyperCd-based regimens provided rapid disease control among MM patients, even when heavily pre-treated and with few remaining treatment options. Grade 3/4 hematologic toxicities were frequent, but manageable with aggressive supportive care.

Siltuximab (CNTO 328) with lenalidomide, bortezomib and dexamethasone in newly-diagnosed, previously untreated multiple myeloma: an open-label phase I trial.

The safety and efficacy of siltuximab (CNTO 328) was tested in combination with lenalidomide, bortezomib and dexamethasone (RVD) in patients with newly-diagnosed, previously untreated symptomatic multiple myeloma. Fourteen patients were enrolled in the study, eleven of whom qualified to receive therapy. A majority of patients (81.8%) completed the minimal number or more of the four required cycles, while two patients completed only three cycles. The maximum tolerated dose (MTD) of siltuximab with RVD was dose level -1 (siltuximab: 8.3 mg/kg; bortezomib: 1.3 mg/m(2); lenalidomide: 25 mg; dexamethasone: 20 mg). Serious adverse events were grade 3 pneumonia and grade 4 thrombocytopenia, and no deaths occurred during the study or with follow-up (median follow-up 28.1 months). An overall response rate, after 3-4 cycles of therapy, of 90.9% (95% confidence interval (CI): 58.7%, 99.8%) (9.1% complete response (95% CI: 0.2%, 41.3%), 45.5% very good partial response (95% CI: 16.7%, 76.6%) and 36.4% partial response (95% CI: 10.9%, 69.2%)) was seen. Two patients withdrew consent, and nine patients (81.8%) opted for autologous stem cell transplantation.

Evidence of a role for CD44 and cell adhesion in mediating resistance to lenalidomide in multiple myeloma: therapeutic implications.

Resistance of myeloma to lenalidomide is an emerging clinical problem, and though it has been associated in part with activation of Wnt/ß-catenin signaling, the mediators of this phenotype remained undefined. Lenalidomide-resistant models were found to overexpress the hyaluronan (HA)-binding protein CD44, a downstream Wnt/ß-catenin transcriptional target. Consistent with a role of CD44 in cell adhesion-mediated drug resistance (CAM-DR), lenalidomide-resistant myeloma cells were more adhesive to bone marrow stroma and HA-coated plates. Blockade of CD44 with monoclonal antibodies, free HA or CD44 knockdown reduced adhesion and sensitized to lenalidomide. Wnt/ß-catenin suppression by FH535 enhanced the activity of lenalidomide, as did interleukin-6 neutralization with siltuximab. Notably, all-trans retinoic acid (ATRA) downregulated total ß-catenin, cell-surface and total CD44, reduced adhesion of lenalidomide-resistant myeloma cells and enhanced the activity of lenalidomide in a lenalidomide-resistant in vivo murine xenograft model. Finally, ATRA sensitized primary myeloma samples from patients that had relapsed and/or refractory disease after lenalidomide therapy to this immunomodulatory agent ex vivo. Taken together, our findings support the hypotheses that CD44 and CAM-DR contribute to lenalidomide resistance in multiple myeloma, that CD44 should be evaluated as a putative biomarker of sensitivity to lenalidomide, and that ATRA or other approaches that target CD44 may overcome clinical lenalidomide resistance.

Health-related quality of life in men with corrected hypospadias: an explorative study.

OBJECTIVE: The aim of the study was to evaluate health-related quality of life (HRQoL) of men with a corrected hypospadias in comparison to circumcised controls. Furthermore, determinants of HRQoL were examined. PATIENTS AND METHODS: In a cross-sectional study, HRQoL of 45 men with corrected hypospadias (mean age: 26.2 years +/- 5.1) was compared with a control group of 46 circumcised men (mean age: 25.5 years +/- 4.9). Participants answered three questionnaires: The Medical Outcomes Study Short Form-36 item questionnaire (SF-36), the International Index of Erectile Function (IIEF), and the Penile Perception Score (PPS). RESULTS: Physical and mental dimensions of HRQoL were not impaired among men with corrected hypospadias if compared to circumcised men. Neither socio-demographic and medical variables nor erectile function (EF) predicted HRQoL. However, a negative genital self-perception (PPS) and a lower orgasmic function (OF) were risk factors for an impaired mental HRQoL. CONCLUSIONS: Our data suggest that the HRQoL of adult hypospadias patients is comparable to that of circumcised men. However, patients should be supported in developing a positive genital self-perception, because poor genital self-perception correlated with an impaired mental HRQoL. Since studies with non-operated men suggest that some adapt well to their penile condition, further studies should also include non-operated hypospadias.

[Scaphoid fractures in childhood]. / Skaphoidfrakturen im Kindesalter.

This article reviews current knowledge about scaphoid fractures in children and adolescents, including the development of the scaphoid, its injuries and age-specific treatment for acute and late presenting fractures. The following recommendations are based on the literature, although scientific evidence to support treatment strategies is scarce. The diagnosis of scaphoid fractures is often missed on initial X-rays. Therefore all suspected fractures should be treated with a thumb spica cast for 2 weeks, followed by clinical examination and repeat X-ray if symptoms persist. In cases of negative X-ray findings an MRI or alternatively a CT scan are indicated. None or minimally displaced paediatric scaphoid fractures should be treated in a spica cast for at least 7 weeks until union is documented. Unlike in adults, evidence has not been provided for a benefit of routine surgical therapy. Late presenting non-unions that have not yet been treated adequately warrant a trial of conservative therapy, because healing can be expected under prolonged immobilisation. Surgical treatment should be reserved for dislocated fractures, established pseudarthroses that have not united under adequate conservative treatment or for patients to whom prolonged immobilisation does not appear to be acceptable.

Pitfalls of lateral external fixation for supracondylar humeral fractures in children.

INTRODUCTION: Closed reduction and percutaneous pinning is a standard treatment for dislocated supracondylar humeral fractures in children. However, the management of these fractures remains challenging. The aim of this study was to evaluate lateral external fixation as a treatment alternative for these fractures. MATERIALS AND METHODS: All supracondylar fractures treated with lateral external fixation between 2005 and 2007 were evaluated retrospectively. Long-term outcome was assessed with regards to carrying angle, malalignment, and motion. RESULTS: Twenty-eight patients with Gartland type III fractures and one with a Y-type fracture were included in the study (mean age 6.5 years). Cosmetic results were excellent in 88%, good in 8%, and fair in one patient. Functional results were excellent in 83%, good in 10%, and fair in 7%. However, 3 patients (10%) showed complete radial palsy postoperatively. In all of these patients, high insertion of the proximal pin (2.9-3.6 cm above the fracture) was noted. On revision, one superficial lesion and one total transection of the nerve at the level of the proximal pin was detected. One patient showed no macroscopic damage. The transected nerve was reconstructed using an autograft, and all patients completely recovered within 2-6 months. CONCLUSION: Lateral external fixation is an alternative method for the treatment of displaced or unstable supracondylar fractures in children, facilitating reduction and improving fracture stability. However, iatrogenic radial nerve injury is a risk, and we therefore strongly recommend inserting the proximal pin under direct vision within 2 cm from the fracture line using a drill sleeve.

Evidence of a role for the novel zinc-finger transcription factor ZKSCAN3 in modulating Cyclin D2 expression in multiple myeloma.

Dysregulation of cyclin D2 contributes to the pathogenesis of multiple myeloma, and can occur through translocations that activate MAF/MAFB or MMSET/FGFR3. However, cyclin D2 induction can also be seen in the absence of such translocations, such as in patients with hyperdiploid disease, through unknown mechanisms. In UniGene cluster data-mining and ECgene analysis, we found that zinc-finger with KRAB and SCAN domains 3 (ZKSCAN3), a novel transcription factor, is overrepresented in this malignancy, and three consensus ZKSCAN3 binding sites were found in the cyclin D2 promoter. Analysis of a panel of myeloma cell lines, primary patient samples and datasets from Oncomine and the Multiple Myeloma Genomics Portal (MMGP) revealed expression of ZKSCAN3 messenger RNA (mRNA) in a majority of samples. Studies of cell lines by western blotting, and of primary tissue microarrays by immunohistochemistry, showed ZKSCAN3 protein expression in a majority, and in a manner that paralleled messenger levels in cell lines. ZKSCAN3 overexpression was associated with increased gene copy number or genomic DNA gain/amplification in a subset based on analysis of data from the MMGP, and from fluorescence in situ hybridization studies of cell lines and primary samples. Overexpression of ZKSCAN3 induced cyclin D2 promoter activity in a MAF/MAFB-independent manner, and to an extent that was influenced by the number of consensus ZKSCAN3 binding sites. Moreover, ZKSCAN3 protein expression correlated with cyclin D2 levels in cell lines and primary samples, and its overexpression induced cyclin D2. Conversely, ZKSCAN3 suppression using small hairpin RNAs (shRNAs) reduced cyclin D2 levels, and, importantly, inhibited myeloma cell line proliferation. Finally, ZKSCAN3 was noted to specifically bind to oligonucleotides representing sequences from the cyclin D2 promoter, and to the endogenous promoter itself in myeloma cells. Taken together, the data support the conclusion that ZKSCAN3 induction represents a mechanism by which myeloma cells can induce cyclin D2 dysregulation, and contribute to disease pathogenesis.

Conservative treatment of scaphoid nonunion in children and adolescents.

This is a retrospective study of six children with ununited scaphoid fractures treated conservatively. Their mean age was 12.8 years (9.7 to 16.3). Five had no early treatment. Radiological signs of nonunion were found at a mean of 4.6 months (3 to 7) after injury. Treatment consisted of cast immobilisation until clinical and radiological union. The mean clinical and radiological follow-up was for 67 months (17 to 90). We assessed the symptoms, the range of movement of the wrist and the grip strength to calculate the Modified Mayo Wrist score. The fracture united in all patients after a mean period of immobilisation of 5.3 months (3 to 7). Five patients were pain free; one had mild pain. All returned to regular activities, and had a range of movement and grip strength within 25% of normal, resulting in an excellent Modified Mayo Wrist score. Prolonged treatment with cast immobilisation resulted in union of the fracture and an excellent Modified Wrist Score in all patients.

Long-term follow-up on overall survival from the MM-009 and MM-010 phase III trials of lenalidomide plus dexamethasone in patients with relapsed or refractory multiple myeloma.

We present a pooled update of two large, multicenter MM-009 and MM-010 placebo-controlled randomized phase III trials that included 704 patients and assessed lenalidomide plus dexamethasone versus dexamethasone plus placebo in patients with relapsed/refractory multiple myeloma (MM). Patients in both studies were randomized to receive 25 mg daily oral lenalidomide or identical placebo, plus 40 mg oral dexamethasone. In this pooled analysis, using data up to unblinding (June 2005 for MM-009 and August 2005 for MM-010), treatment with lenalidomide plus dexamethasone significantly improved overall response (60.6 vs 21.9%, P<0.001), complete response rate (15.0 vs 2.0%, P<0.001), time to progression (median of 13.4 vs 4.6 months, P<0.001) and duration of response (median of 15.8 months vs 7 months, P<0.001) compared with dexamethasone-placebo. At a median follow-up of 48 months for surviving patients, using data up to July 2008, a significant benefit in overall survival (median of 38.0 vs 31.6 months, P=0.045) was retained despite 47.6% of patients who were randomized to dexamethasone-placebo receiving lenalidomide-based treatment after disease progression or study unblinding. Low beta(2)-microglobulin and low bone marrow plasmacytosis were associated with longer survival. In conclusion, these data confirm the significant response and survival benefit with lenalidomide and dexamethasone.

Early mobilization after flexor tendon repair in children.

PURPOSE: Aim of the study was to provide an age-adapted rehabilitation protocol for flexor tendon repairs of children and to evaluate a patient series accordingly. METHODS: A modified Kessler's technique was used to repair 49 flexor tendon injuries in 39 children. All children had immediate postoperative mobilization according to the protocol that provides specific guidelines for preschoolers, children and teenagers. Range of motion was monitored and the final results were evaluated retrospectively. RESULTS: All children could be treated successfully according to the protocol with no occurrence of secondary tendon ruptures. Forty finger injuries were evaluated according to the Strickland classification, resulting in a median total active motion of 92.6 % with 29 (72.5 %) excellent results, 8 (20 %) good results, 3 (7.5 %) fair results and no poor result. All 7 thumbs had an excellent result according to the Buck-Gramcko score. There was no significant difference in outcomes between the three age groups. CONCLUSIONS: The rehabilitation protocol provided in this study allows an age-adapted early mobilization of children's hands after flexor tendon injuries. It respects age-specific limitations in rehabilitation and takes a child's superior healing capacity compared to adults into account. The good results and the very low complication rate observed in the present series suggest that the extra effort of early mobilization may be justified.

Is there an ideal age for hypospadias repair? A pilot study.

OBJECTIVE: To assess whether repairing hypospadias before or after 18 months affects psychological adjustment, health-related quality of life (HRQoL) and surgical outcome. PATIENTS AND METHODS: Seventy-seven boys aged 6-17 years were assigned to one of two groups, according to whether they had a hypospadias repair before or after the age of 18 months. The surgical outcome was assessed using the pediatric penile perception score by non-involved urologists. A psychologist interviewed the patients to assess HRQoL and gender-role behavior. The child's psychological adjustment was assessed with a questionnaire for parents. RESULTS: The surgical outcome and complication rate were not significantly different between groups. A covariance analysis of HRQoL, gender-role behavior and psychological adjustment as a function of age at the last operation with current age as covariant was performed, but differences did not reach significance. CONCLUSION: This study does not provide evidence to support recommendations concerning the ideal age for hypospadias repair. In the absence of evidence of a benefit of early surgery, anesthesia-related risk factors must be considered when operating in very early infancy. Large, prospective studies, measuring surgical and psychological outcome with similar instruments to those presented may reveal whether there is a true ideal age for hypospadias surgery.

[The psychosocial/-sexual development of boys with hypospadias]. / Die psychosoziale/-sexuelle Entwicklung von Knaben mit einer Hypospadie.

Boys with hypospadias can suffer from specific psychological stress as a result of genital surgery and a cosmetically and/or functionally impaired penis. During recent decades intensive efforts have been made to improve the surgical techniques; yet the psychosocial and psychosexual development of children and adolescents after hypospadias surgery has only rarely been investigated. While the results of the few studies are altogether very contradictory, they also indicate that hypospadias patients suffer from specific problems like a negative perception of genital appearance. Therefore, they should be offered long-term follow-ups and psychosocial support until they reach young adulthood. For future research, it is necessary to systematically investigate the boys' quality of life and development in methodologically sound studies.

Autologous stem cell transplantation is safe and feasible in elderly patients with multiple myeloma.

Several clinical trials have shown the superiority of autologous stem cell transplantation over conventional dose therapy for patients with multiple myeloma. This treatment, however, is limited to younger patients (<65 years) owing to concerns about toxicity and treatment-related mortality (TRM) in older patients. We treated 26 elderly myeloma patients (>70 years), who received a preparative regimen of melphalan 200 mg/m2 (19 patients), melphalan 180 mg/m2 (six patients) or melphalan 140 mg/m2 (one patient). Twenty-two of the 26 patients were alive after a median follow-up of 25 months (range=8-74). Responses (complete+partial response) were seen in 20 patients (77%), five (19%) of which were complete responses. Median PFS was 24 months, whereas median OS has not been reached. Cumulative incidence of 100-day TRM was 0%. Three-year PFS and OS were 39% (range=16-61) and 65% (range=35-83), respectively. A low serum albumin (<3.5 g/dl) was associated with a shorter PFS (P=0.02). Patients with relapsed disease at transplant, and an interval of >12 months between diagnosis and autotransplant, had a shorter OS (P=0.0004 and 0.04). HDT and autologous transplant is safe and feasible in elderly myeloma patients.

Absorbable sutures help minimise patient discomfort and reduce cost in syndactyly release.

Many surgeons hesitate to use absorbable suture material to correct syndactylies because they fear that it may induce hypertrophic scarring and compromise the outcome functionally and aesthetically. In a series of 25 syndactylies all sutures were carried out using an absorbable, multifilament polyglactin suture material (Vicryl Rapid, Ethicon). A good result with no functional impairment and a natural looking commissure was achieved in 20 syndactylies. 4 syndactylies had a fair result with no functional impairment but with certain aesthetic deficits such as a slightly hypertrophic scar in 2 and a hyperpigmentation of the skin graft in 2. One patient had a poor result with hypertrophic scars that were responsible for temporary flexion contractures. No patient needed to be reoperated. This case series demonstrates that good results can be achieved using absorbable sutures for syndactyly release. Children and parents appreciated the fact that no stitches had to be removed. Secondary anaesthesia for suture removal with its inherent risks and cost was not necessary.

Laparoscopic cholecystectomy.

BACKGROUND: This study was undertaken to determine if patients undergoing laparoscopic cholecystectomy may be discharged home 4 h postoperatively with similar outcomes as patients admitted overnight. METHODS: Patients were randomized to an outpatient group (OP), consisting of patients who were discharged after a 4-h stay in the Post Anesthesia Care Unit (PACU), or to an inpatient group. Variables compared between the two groups included patient demographics; degree of postoperative pain, nausea, vomiting, and patient satisfaction; amount of pain and nausea medication taken; and number of phone calls, readmissions, or complications. Statistical analysis was performed with students t-test, Fisher's exact test, and Wilcoxon's signed rank and rank sums tests as appropriate. RESULTS: Eighty patients were initially enrolled. Two were converted and 4 required admission after being randomized to the OP group. Patients in the OP group received more oral pain medication prior to PACU discharge. Degree of pain, number of phone calls, readmission and complication rates, and patient satisfaction were similar between both groups. Of the 4 unexpected admissions, all were identified within the 4-h PACU stay. CONCLUSIONS: Patients undergoing laparoscopic cholecystectomy who are discharged home 4 h postoperatively will experience the same satisfaction with no increase in complications as patients admitted overnight.

Effects of helium pneumoperitoneum in pregnant ewes.

BACKGROUND: Previous animal studies have demonstrated that a carbon dioxide (CO(2)) pneumoperitoneum in pregnant ewes causes maternal and fetal acidosis, decreased uterine blood flow (UtBF), and fetal hypertension. This study was undertaken to determine whether helium (He) produces these same effects when used as an insufflating gas. METHODS: Six gravid ewes, at 116 to 120 days gestation, underwent catheterization of the maternal femoral artery and vein and the fetal hindlimb artery and vein, as well as insertion of a uterine artery flow probe. After a 6-day recovery period, the animals were anesthetized; a Hasson trocar was placed; and an He pneumoperitoneum was established (10 mmHg for 30 min followed by 15 mmHg for 30 min). The following parameters were recorded at baseline and at preset time points: maternal and fetal heart rate (HR), blood pressure (BP), arterial blood gasses, maternal end-tidal CO(2) (EtCO2), and UtBF. The percentage of change over time was determined for each variable. The results were compared with results previously obtained in control animals and in animals undergoing CO(2) pneumoperitoneum. Statistical significance was determined by repeated measures analysis of variance (ANOVA). RESULTS: The following statistically significant changes were found. CONCLUSIONS: Like CO(2), He used for pneumoperitoneum resulted in decreased UtBF and fetal hypertension because of increased intra-abdominal pressure. Unlike a CO(2), He used for pneumoperitoneum does not cause maternal or fetal acidosis, indicating that the metabolic effects seen with CO(2) are the result of the specific gas used. Therefore, He may be a safer gas than CO(2) to use for laparoscopic procedures in pregnant patients.

Cytogenetic findings in lymphoplasmacytic lymphoma/Waldenström macroglobulinemia. Chromosomal abnormalities are associated with the polymorphous subtype and an aggressive clinical course.

We correlated bone marrow cytogenetic findings with morphologic and immunophenotypic data in 37 patients with lymphoplasmacytic lymphoma (LPL)/Waldenström macroglobulinemia (WM). Each LPL/WM case was classified as lymphoplasmacytoid (n = 18), lymphoplasmacytic (n = 10), or polymorphous (n = 9) using the Kiel criteria. Of 12 cases with chromosomal abnormalities, a single numeric abnormality was present in 4 and a complex karyotype in 8. The most common numeric abnormalities were and -8 in 3 cases each; the most common structural abnormality was del(6q) in 6 cases. Cytogenetic abnormalities were significantly less common in the lymphoplasmacytic and lymphoplasmacytoid groups (5/28 [18%]) compared with the polymorphous group (7/9 [78%]). Clinical follow-up was available for 28 patients for a median of 36 months. Six (67%) of 9 patients with aneuploid tumors, including 4 with polymorphous subtype, subsequently had clinical progression or developed high-grade lymphoma. In contrast, 4 (21%) of 19 patients with diploid tumors, including 1 of polymorphous type, developed clinical progression or high-grade lymphoma. We conclude that abnormal cytogenetic findings in LPL/WM correlate with the polymorphous subtype and poor prognosis.

Periumbilical necrotizing fasciitis in the newborn.

Periumbilical necrotizing fasciitis (PNF) in the newborn is an invasive bacterial infection of the abdominal wall with a fulminant course and a high mortality rate. Little is known about the etiology, risk factors and microbiology of the disease. 18 patients with periumbilical necrotizing fasciitis were included in this retrospective study and were compared with 50 patients with omphalitis over a 6-year period, between 1992 and 1998. This represents the largest reported study. The children with periumbilical necrotizing fasciitis presented at a younger age compared to the omphalitis group (8.4 days vs. 9.1 days) and had a shorter clinical history (1.9 days vs. 2.8 days), suggesting that PNF is not a mere sequela of omphalitis but has distinctive underlying causes. None of our patients in the omphalitis group had a progression of the disease towards necrotizing fasciitis. The microbial spectrum of cultures obtained in patients with PNF consisted of mixed anaerobes and aerobes in 55%, and mixed aerobes in 36% of cases. Early aggressive therapy, including elective endotracheal intubation, immediate surgical debridement of the abdominal wall, antibiotics and supportive measurements resulted in a survival rate of 56%. Far from being satisfactory, this is nevertheless higher than the 12.5% to 45% survival rate quoted in previous publications.

Quantitative nuclear morphometry by image analysis for prediction of recurrence of ductal carcinoma in situ of the breast.

Clinical management of ductal carcinoma in situ (DCIS) remains a challenge because significant proportions of patients experience recurrence after conservative surgical treatment. Unfortunately, it is difficult to prospectively identify, using objective criteria, patients who are at high risk of recurrence and might benefit from additional treatment. We conducted a multi-institutional, collaborative case-control study to identify nuclear morphometric features that would be useful for identifying women with DCIS at the highest risk of recurrence. Tissue sections of archival breast tissue of 29 women with recurrent and 73 matched women with nonrecurrent DCIS were stained for DNA, and nuclei in the DCIS lesions were evaluated by image analysis. A clear correlation between mean fractal2_area (FA2) and nuclear grade was observed (P < 0.001), allowing an objective determination of nuclear grade. Several nuclear morphometric features, including mean and variance of variation of radius, mean area, mean and variance of frequency of high boundary harmonics (FQH), and variance in sphericity, were found to be useful in discriminating recurrent from nonrecurrent DCIS subjects. However, the nuclear features associated with recurrence differed between high- and low-grade lesions. For lesions with high FA2 (nuclear grade 3), mean variation of radius, mean FQH, and mean area alone yielded recurrence odds ratios of 4.55 [95% confidence interval (CI) 0.45-45.96], 3.86 (95% CI, 0.88-16.98), 2.90 (95% CI, 0.31-27.2), respectively. Using a summed feature model, high-FA2 lesions showing three poor prognostic features had an odds ratio of 15.63 (95% CI, 1.22-200), compared with those with zero or one poor prognostic feature. Lesions with low mean FA2 (nuclear grade 1 or 2) showing high variances in sphericity and FQH had an odds ratio of 7.71 (95% CI, 1.77-33.60). Addition of other features did not enhance the odds ratio or its significance. These results suggest that nuclear image analysis of DCIS lesions may provide an adjunctive tool to conventional pathological analysis, both for the objective assessment of nuclear grade and for the identification of features that predict patient outcome.

Quadratic Gabor filters for object detection.

We present a new class of quadratic filters that are capable of creating spherical, elliptical, hyperbolic and linear decision surfaces which result in better detection and classification capabilities than the linear decision surfaces obtained from correlation filters. Each filter comprises of a number of separately designed linear basis filters. These filters are linearly combined into several macro filters; the output from these macro filters are passed through a magnitude square operation and are then linearly combined using real weights to achieve the quadratic decision surface. For detection, the creation of macro filters (linear combinations of multiple single filters) allows for a substantial computational saving by reducing the number of correlation operations required. In this work, we consider the use of Gabor basis filters; the Gabor filter parameters are separately optimized. The fusion parameters to combine the Gabor filter outputs are optimized using an extended piecewise quadratic neural network (E-PQNN). We demonstrate methods for selecting the number of macro Gabor filters, the filter parameters and the linear and nonlinear combination coefficients. We present preliminary results obtained for an infrared (IR) vehicle detection problem.