Integrating Radiomics With Clinicoradiological Scoring Can Predict High-Risk Patients Who Need Surgery in Crohn's Disease: A Pilot Study.

BACKGROUND: Early identification of Crohn's disease (CD) patients at risk for complications could enable targeted surgical referral, but routine magnetic resonance enterography (MRE) has not been definitively correlated with need for surgery. Our objective was to identify computer-extracted image (radiomic) features from MRE associated with risk of surgery in CD and combine them with clinical and radiological assessments to predict time to intervention. METHODS: This was a retrospective single-center pilot study of CD patients who had an MRE within 3 months prior to initiating medical therapy. Radiomic features were extracted from annotated terminal ileum regions on MRE and combined with clinical variables and radiological assessment (via Simplified Magnetic Resonance Index of Activity scoring for wall thickening, edema, fat stranding, ulcers) in a random forest classifier. The primary endpoint was high- and low-risk groups based on need for surgery within 1 year of MRE. The secondary endpoint was time to surgery after treatment. RESULTS: Eight radiomic features capturing localized texture heterogeneity within the terminal ileum were significantly associated with risk of surgery within 1 year of treatment (P < .05); yielding a discovery cohort area under the receiver-operating characteristic curve of 0.67 (n = 50) and validation cohort area under the receiver-operating characteristic curve of 0.74 (n = 23). Kaplan-Meier analysis of radiomic features together with clinical variables and Simplified Magnetic Resonance Index of Activity scores yielded the best hazard ratio of 4.13 (P = (7.6 × 10-6) and concordance index of 0.71 in predicting time to surgery after MRE. CONCLUSIONS: Radiomic features on MRE may be associated with risk of surgery in CD, and in combination with clinicoradiological scoring can yield an accurate prognostic model for time to surgery.

Understanding the Cautions and Contraindications of Immunomodulator and Biologic Therapies for Use in Inflammatory Bowel Disease.

Ulcerative colitis and Crohn's disease are chronic inflammatory bowel diseases for which there are no cures. These diseases are immunopathogenic, and medical treatment is centered on the temperance of a dysregulated immune response to allow mucosal healing and prevent the sequelae of fistulation and stenosis. Accordingly, the armamentarium of medications, which has expanded immensely in recent history, is not without significant infectious and neoplastic risks. Many of these untoward effects can be mitigated by screening and avoidance of contraindicated medications. This review seeks to highlight the cautions for use of immunomodulators, anticytokine, and α4-integrin antagonists. The potential adverse events are further complicated by substantial heterogeneity in disease phenotype in the inflammatory bowel disease population. Large patient registries and databases provide considerable experience and knowledge to calculate the incidence of safety outcomes. To identify rarer outcomes after prolonged therapy, more prospective studies and continued adverse event reporting will aid safe application and minimize potential harms.

[Efficacy and complications of a mini-trabeculectomy technique]. / Efficacité et complications d'une technique de mini-trabéculectomie ajustable.

OBJECTIVE: To assess the outcome and the complication rate of an adjustable mini-trabeculectomy in medically uncontrolled glaucoma. PATIENTS AND METHODS: This study retrospectively evaluated the medical records of 40 patients undergoing primary mini-trabeculectomy. All patients were followed at least 24 months, with a mean follow-up of 60.85 +/- 37.7 months. Visual acuity, intraocular pressure (IOP), visual field (MD, Humphrey), number of antiglaucoma medications, intra- and postoperative complications, postoperative procedures (laser suture lysis, 5-fluorouracil subconjunctival injections, or a new trabeculectomy) were analyzed. RESULTS: Preoperative IOP was 23.2 +/- 6.48 mmHg (range, 13-53 mmHg) with 2.42 +/- 0.74 (range, 1-4) antiglaucoma medications. At last examination, after 60.85 +/- 37.7 months (mean +/- standard deviation; minimum 24 months) of postoperative follow-up, IOP was 12.55 +/- 2.12 mmHg with 0.42 +/- 0.78 antiglaucoma medications (p<0.001 compared to preoperative IOP and p<0.001 compared to the number of medications); 85% and 92.5% of patients had IOP reduced by 30% or more and a final IOP less than 16 mmHg with or without antiglaucoma medications, respectively, and 52.5% had one or more scleral flap sutures released by laser. Postoperative complications were infrequent: flat anterior chamber with choroidal detachment (2.5%) and iris incarceration in the trabeculectomy site (2.5%). Seven patients had an encapsulation of the filtering bleb (17.5%) after a mean follow-up of 34.33 +/- 33 days after surgery. Four patients (10%) had cataract surgery during the 2 years following trabeculectomy. A significant decrease in visual acuity was observed after surgery (p=0.018); nevertheless, there was no statistically significant difference between preoperative and postoperative MD (-10.46+/-9.37 dB and -10.65+/-4.36 dB, respectively; p=0.971, for 23 patients). CONCLUSION: Adjustable mini-trabeculectomy controlled postoperative filtration. Easy to perform, this surgical technique seemed to be safe and effective, and it reduced the rate of early postoperative complications in the surgical management of patients with glaucoma.

[Surgical key points. Trabeculectomy]. / Les points-clés de la chirurgie. La trabéculectomie.

Trabeculectomy is the filtering surgery of choice in the surgical treatment of glaucoma. Nevertheless, the technique is evolving rapidly. The use of a limbus-based or fornix-based conjunctival flap, the size and architecture of the scleral flap, the size of the sclerostomy, as well as the use of antimetabolites are currently being debated. There is a general tendancy to use smaller sclerostomy openings, 0.5-1 mm in diameter, with more liberal, but cautious, use of antimetabolites. The goal is to make glaucoma surgery as safe and successful as possible.

[What should be done when surgery fails? Managing the flat bleb after filtering surgery]. / Que faire quand la chirurgie marche mal? La bulle est plate le lendemain d'une chirurgie filtrante.

Approaches to treatment of the flat bleb after filtering surgery depends on the IOP, bleb appearance and absence or presence of a leak, anterior chamber depth, and the time since surgery. Treatment modalities include simple watching and waiting, reinstituting medical therapy, digital massage, laser suture lysis, YAG goniopuncture, or reoperation.

[Surgical controversy. Combined cataract and glaucoma surgery]. / Controverse chirurgicale. Combinée phaco-trabéculectomie.

A two-phase surgical approach may be chosen with the glaucoma intervention done first when there is advanced glaucomatous involvement and only moderate lens opacity; and cataract surgery is the first priority when there has been substantial vision loss due to the lens with a moderate case of glaucoma stabilized medically. In the case of closed-angle glaucoma, it may be preferable to operate on the lens alone rather than perform filtration or combined surgery. Our personal experience with 31 patients undergoing phacotrabeculectomy at two sites without adjunctive antimetabolites has shown that this technique is effective in controlling intraocular pressure in glaucoma patients (mean decrease in pressure, 29%), with few complications.

Isolated left-sided scimitar vein connecting all left pulmonary veins to the right inferior vena cava.

When the common pulmonary vein fails to develop, the embryonic connections of the pulmonary veins to one or more of the systemic veins almost always persist. Anomalous pulmonary venous connections to the inferior vena cava (IVC) are typically characterized by hypoplasia of the involved pulmonary veins and pulmonary artery, as well as abnormal parenchyma of the involved lung. Such cases have been described as "scimitar syndrome." We report the case of a young female patient in whom all the left pulmonary veins converged into a common vessel that drained into the IVC but who had a normal left pulmonary artery and left lung. Surgical intervention was successful, and our patient is still alive.

Direct measurements of Ab and Ac using vertex and kaon charge tags at the SLAC detector.

Exploiting the manipulation of the SLAC Linear Collider electron-beam polarization, we present precise direct measurements of the parity-violation parameters A(c) and A(b) in the Z-boson-c-quark and Z-boson-b-quark coupling. Quark-antiquark discrimination is accomplished via a unique algorithm that takes advantage of the precise SLAC Large Detector charge coupled device vertex detector, employing the net charge of displaced vertices as well as the charge of kaons that emanate from those vertices. From the 1996-1998 sample of 400 000 Z decays, produced with an average beam polarization of 73.4%, we find A(c)=0.673+/-0.029(stat)+/-0.023(syst) and A(b)=0.919+/-0.018(stat)+/-0.017(syst).

Improved direct measurement of the parity-violation parameter Ab using a mass tag and momentum-weighted track charge.

We present an improved direct measurement of the parity-violation parameter A(b) in the Z boson-b-quark coupling using a self-calibrating track-charge technique applied to a sample enriched in Z-->bb events via the topological reconstruction of the B hadron mass. Manipulation of the Stanford Linear Collider electron-beam polarization permits the measurement of A(b) to be made independently of other Z-pole coupling parameters. From the 1996-1998 sample of 400,000 hadronic Z decays, produced with an average beam polarization of 73.4%, we find A(b)=0.906+/-0.022(stat)+/-0.023(syst).

Improved direct measurement of A(b) and A(c) at the Z(0) pole using a lepton tag.

The parity violation parameters A(b) and A(c) of the Zb(b) and Zc(c) couplings have been measured directly, using the polar angle dependence of the polarized cross sections at the Z(0) pole. Bottom and charmed hadrons were tagged via their semileptonic decays. Both the electron and muon analyses take advantage of new multivariate techniques to increase the analyzing power. Based on the 1993-1998 SLD sample of 550,000 Z(0) decays produced with highly polarized electron beams, we measure A(b) = 0.919+/-0.030(stat)+/-0.024(syst), and A(c) = 0.583+/-0.055(stat)+/-0.055(syst).

Treatment of metastatic melanoma with autologous, hapten-modified melanoma vaccine: regression of pulmonary metastases.

A human cancer vaccine composed of autologous tumor cells modified with the hapten dinitrofluorobenzene (DNP) induces cell-mediated immunity to the tumor cells and the development of inflammatory responses within metastatic sites. In this study we determined whether DNP vaccine could induce regression of established metastases. Ninety-seven patients (83 evaluable) with surgically incurable metastatic melanoma were treated with DNP vaccine preceded by low-dose cyclophosphamide. Tumor regression was assessed by standard criteria. The development of cell-mediated immunity to melanoma-associated antigens was measured by delayed-type hypersensitivity (DTH) testing before and after DNP vaccine treatment. Survival analysis was performed by the Kaplan-Meier method. There were 11 antitumor responses: 2 complete, 4 partial and 5 mixed. Both complete responses and 2 of the 4 partial responses occurred in patients with lung metastases. Response durations were as follows: partial responses-5, 6, 8 and 47+ months; and complete responses-12 and 29 months. Tumor regression required at least 4 months to become evident and in 2 cases maximum regression was not observed until 1 year after beginning treatment. Patients who exhibited tumor regression survived longer than those who did not (median survival times: responders, 21.4 months; non-responders, 8.7 months; p = 0.010). DTH to DNP-modified and unmodified autologous melanoma cells was induced in 87% and 42% of patients, respectively. The DTH response to unmodified cells was significantly associated with prolonged survival. Autologous DNP-modified melanoma vaccine can induce clinically meaningful regression of metastases and small lung metastases appear to be unusually sensitive. The development of DTH to unmodified, autologous tumor cells may be an important indicator of the vaccine's efficacy.

Bronchial atresia with relapsing pulmonary infection in a middle-aged man.

Congenital bronchial atresia (CBA) is a rare disorder, first reported in 1953. Less than 100 cases are reported in the literature, mostly in young, asymptomatic male patients with involvement of the apical-posterior segment of the left upper lobe. Patients may complain of fever, cough, or shortness of breath, symptoms that result from post-obstructive, sometimes recurrent, infections. Chest radiography and computed tomography reveal a tubular branching density representing mucus impaction or mucocele with surrounding focal hyperinflation. Surgical excision is reserved for symptomatic cases. We report an unusual case of CBA in a middle-aged man with a history of relapsing infections, who was found to have an atretic superior segment of the left lower lobe, with surrounding areas of organizing pneumonia.

[An observational, retrospective two-year cost study in primary open-angle glaucoma and ocular hypertension in newly diagnosed patients]. / Etude observationnelle rétrospective de coûts des deux premières années de traitement dans le glaucome primitif à angle ouvert et l'hypertension oculaire en France.

PURPOSE: To investigate the different treatment strategies in France and the direct costs for patients with newly diagnosed primary open-angle glaucoma or ocular hypertension who have started treatment with beta-blockers, and to estimate the total direct cost for two years of treat. MATERIAL: and methods: We analyzed 225 medical charts retrospective in eleven academically and office-based centers in France over the first two years after diagnosis. Standard costs for each resource in current medical practice were determined from the French Social Security perspective. RESULTS: The vast majority of patients (90%) had a diagnosis of primary, open-angle glaucoma or ocular hypertension in both eyes. In 60% of the patients we found a moderate or severe defect in their visual field or optic nerve. Intraocular pressure before treatment was 23.9+4.7mmHg and 17.5+4.2mmHg after two years of treatment. Over the first two years, 25% of visits led to a change in therapy (medical or surgical), involving 64% of the patients. Two-thirds of the changes occurred during the first year of treatment and in around 80% of cases for low intraocular pressure at check-up. Laser surgery or surgical intervention was performed in 25% of the patients. Total direct costs for two years were 5698F.F. The intraocular pressure before treatment was positively correlated (p<0.01) with treatment costs, while the initial intraocular pressure-lowering effects of treatment were negatively correlated with two-year costs. CONCLUSION: After two years of treatment, the mean intraocular pressure decreased from 24 to 17.5mmHg. The higher the basal intraocular pressures is, the more intensive the treatment and the higher the costs. The more efficient the treatment to decrease baseline intraocular pressure is, the earlier the costs will be reduced.

First symmetry tests in polarized Z0 decays to bbg.

We have made the first direct symmetry tests in the decays of polarized Z0 bosons into fully identified bbg states, collected in the SLD experiment at SLAC. We searched for evidence of parity violation at the bbg vertex by studying the asymmetries in the b-quark polar- and azimuthal-angle distributions, and for evidence of T-odd, CP-even or CP-odd, final-state interactions by measuring angular correlations between the three-jet plane and the Z0 polarization. We found results consistent with standard model expectations and set 95% C. limits on anomalous contributions.

Improved direct measurement of leptonic coupling asymmetries with polarized Z bosons.

We present final measurements of the Z boson-lepton coupling asymmetry parameters A(e), A(mu), and A(tau) with the complete sample of polarized Z bosons collected by the SLD detector at the SLAC Linear Collider. From the left-right production and decay polar angle asymmetries in leptonic Z decays we measure A(e) = 0.1544+/-0.0060, A(mu) = 0.142+/-0.015, and A(tau) = 0.136+/-0.015. Combined with our left-right asymmetry measured from hadronic decays, we find A(e) = 0.1516+/-0.0021. Assuming lepton universality, we obtain a combined effective weak mixing angle of sin (2)theta(eff)(W) = 0.230 98+/-0.000 26.

Control of fetal insulin secretion.

In this study, we investigated the way in which fetal insulin secretion is influenced by interrelated changes in blood glucose and sympathoadrenal activity. Experiments were conducted in late gestation sheep fetuses prepared with chronic peripheral and adrenal catheters. The fetus mounted a brisk insulin response to hyperglycemia but with only a minimal change in the glucose-to-insulin ratio, indicating a tight coupling between insulin secretion and plasma glucose. In well-oxygenated fetuses, alpha(2)-adrenergic blockade by idazoxan effected no change in fetal insulin concentration, indicating the absence of a resting sympathetic inhibitory tone for insulin secretion. With hypoxia, fetal norepinephrine (NE) and epinephrine secretion and plasma NE increased markedly; fetal insulin secretion decreased strikingly with the degree of change related to extant plasma glucose concentration. Idazoxan blocked this effect showing the hypoxic inhibition of insulin secretion to be mediated by a specific alpha(2)-adrenergic mechanism. alpha(2)-Blockade in the presence of sympathetic activation secondary to hypoxic stress also revealed the presence of a potent beta-adrenergic stimulatory effect for insulin secretion. However, based on an analysis of data at the completion of the study, this beta-stimulatory mechanism was seen to be absent in all six fetuses that had been subjected to a prior experimentally induced hypoxic stress but in only one of nine fetuses not subjected to this perturbation. We speculate that severe hypoxic stress in the fetus may, at least in the short term, have a residual effect in suppressing the beta-adrenergic stimulatory mechanism for insulin secretion.

High-precision measurement of the left-right Z Boson cross-section asymmetry.

We present a measurement of the left-right cross-section asymmetry ( A(LR)) for Z boson production by e(+)e(-) collisions. The measurement includes the final data taken with the SLD detector at the SLAC Linear Collider during the period 1996-1998. Using a sample of 383 487 Z decays collected during the 1996-1998 runs we measure the pole value of the asymmetry, A(0)(LR), to be 0.150 56+/-0.002 39 which is equivalent to an effective weak mixing angle of sin (2)straight theta(eff)(W) = 0.231 07+/-0.000 30. Our result for the complete 1992-1998 data set comprising approximately 537 000 Z decays is sin (2)straight theta(eff)(W) = 0.230 97+/-0.000 27.

The utility of sestamibi scanning in the operative management of patients with primary hyperparathyroidism.

BACKGROUND: The role of imaging studies before parathyroidectomy has been extensively debated and recent advances in unilateral parathyroidectomy intensify this controversy. The purpose of this study was to review the parathyroidectomy experience of a single surgeon, looking at the role of sestamibi scans and a standard postoperative care regimen. STUDY DESIGN: Retrospective review of office and hospital charts was completed on 90 patients with primary hyperparathyroidism who underwent parathyroidectomy from 1991 to 1998. Patient workup and outcomes were noted, as were results of preoperative imaging. True-positive scans visualized an abnormality ipsilateral to the adenoma found at operation. Statistics were performed using nonparametric testing and Student's t-test. RESULTS: There were 21 male and 69 female patients, with an average age of 54 years (range 29 to 81). There were zero mortalities, three morbidities (3.3%), and three patients who had persistent hypercalcemia, yielding a 96.7% success rate. Sixty-seven patients underwent preoperative sestamibi scanning, with a sensitivity of 74% and positive predictive value of 89%. Operative time in imaged patients averaged 103 +/- 49.9 minutes versus 121.5 +/- 85.9 minutes for patients without sestamibi scans. Operating time differences were not statistically significant and a preoperative sestamibi scan did not affect the success of parathyroidectomy. Discharge on postoperative day 1 was accomplished in 80% of patients and 13% were discharged the next day. There was no morbidity from hypocalcemia. CONCLUSIONS: A preoperative sestamibi scan does not improve efficacy or decrease operating time for primary hyperparathyroidism when bilateral neck exploration is performed. A postoperative care protocol including oral calcium and vitamin D supplementation allows the majority of patients to be discharged on postoperative day 1 with excellent results.