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.

Hypoxia-induced sympathetic inhibition of the fetal plasma insulin response to hyperglycemia.

Large-for-delivery date babies, considered characteristic of diabetic pregnancy, are believed to result from fetal hyperinsulinemia. Paradoxically, infant birth weights tend to be low-for-delivery date in mothers with more severe diabetes. We tested the hypothesis that hypoxemia in such fetuses leads to sympathoadrenal stimulation and inhibition of insulin secretion; and, thus, produces a net reduction in the growth-promoting effects. Fetal sheep were prepared with chronic peripheral and adrenal cannulas. Fetal blood gases, lactate, norepinephrine, and epinephrine secretion rates; and plasma norepinephrine, glucose, and immunoreactive insulin concentrations were determined at 30-min intervals during a 2-h baseline period and a 4-h period of hyperglycemia divided into 2-h segments of hypoxemia (with and without alpha-blockade) and hyperoxia. Hypoxemia-hyperoxia sequences were varied randomly. Well-oxygenated fetuses responded to a threefold increase in glucose with a sixfold increase in plasma immunoreactive insulin. With hypoxemia, norepinephrine and epinephrine secretion were elevated and the insulin response was blocked. With hypoxemia and phentolamine blockade, the insulin response was enhanced with a 10-fold increase above baseline. In severe maternal diabetes with vascular disease or with poor control and very high glucose levels, the fetus is likely to be relatively hypoxemic. Our experiments suggest that in this situation, the fetal insulin response to hyperglycemia will be attenuated; this effect is mediated, at least partly, through sympathoadrenal stimulation.

Adrenal secretion of glucocorticoids during hypoxemia in fetal sheep.

This work was undertaken to investigate the fetal adrenal corticoid secretory response to hypoxic stress in late gestation. Experiments were performed in two groups of fetal sheep of different gestational ages, group I, 129-132 (mean, 130) days and group II, 135-139 (mean, 136) days. Fetuses were prepared with chronic adrenal cannulas as well as peripheral arterial and venous catheters. With the fetus at rest and after 7, 9, 11 and, in some instances, 30 and 60 min of hypoxia (maternal FIO2 10%), precisely timed (2 min) samples of adrenal effluent were collected for determination of cortisol (F) and corticosterone (B) secretion rates. Peripheral samples were obtained intermittently for blood gas and lactate determinations. Resting corticoid secretory rates were highly variable, suggesting an episodic secretory pattern. Corticoid secretory responses to hypoxemia were significantly elevated at 7-11 min, peaked at 30 min, and remained stable at 60 min. Specifically, in group I, F secretion increased from a baseline value of 37 +/- 19 ng/min to a peak hypoxemic response of 376 +/- 80 ng/min; B secretion increased from 6 +/- 4 to 170 +/- 32 ng/min. In group II, F secretion increased from 99 +/- 20 to 653 +/- 107 ng/min; B secretion increased from 12 +/- 5 to 200 +/- 28 ng/min. When related to adrenal gland weight, there was no difference between F secretory responses in groups I and II, whereas relative B secretory responses were lower in group II than in group I at 9 and 11 min of hypoxemia. We conclude that the 129-139 day sheep fetal adrenal cortex is highly sensitive to hypoxic stress with the effect presumably mediated by elevated levels of endogenous ACTH. The B stress response decreases as gestational age advances from the 129-132 day range to 135-139 days.

Adrenal secretion of catecholamines during hypoxemia in fetal lambs.

A new method for quantifying adrenal secretory function in chronically catheterized fetal lambs was developed. This preparation included insertion of a catheter distally into the fetal left renal vein and placement of a remotely operated, hydraulically controlled choker around the renal vein at its junction with the vena cava. With the choker open, adrenal venous blood flowed into the renal vein and then into the vena cava. With the choker closed, adrenal blood flowed into the catheter so that timed samples of adrenal venous effluent could be obtained. With this technique, left adrenal secretory rates of norepinephrine and epinephrine were determined across a spectrum of oxygen concentrations in five near-term fetal lambs. There was a rapid rise in norepinephrine secretion after induction of hypoxemia. Maximum secretory rates occurred at about 5 min, concomitantly with the lowest attained fetal arterial partial pressure of oxygen (PO2s). There was an inverse exponential relation between these catecholamine secretion rates and fetal arterial PO2 (P less than 0.001). Norepinephrine secretion appeared to increase in response to lesser degrees of hypoxemia than did epinephrine, although a longer time delay between stimulation and epinephrine response may have been a factor. Overall, norepinephrine secretion was greater than that of epinephrine. The ratios of norepinephrine to epinephrine in individual adrenal samples varied considerably and in some instances were less than one. These ratios did not correlate significantly with the degree of hypoxemia. During 25 min of a relatively steady state of hypoxemia, norepinephrine secretion declined markedly after about 5 min, although it remained above control levels throughout. Epinephrine secretion rose more gradually but then was relatively stable during the remaining period of hypoxemia.

Panel 2: phase II investigations.

At the end of Phase II, a decision must be made as to whether or not the drug should be developed as a therapeutic agent. Such a decision may be based on many criteria in addition to the scientific data derived from the Phase II study. At this point, expert judgment is needed. One should like to assume that if the decision is made to proceed with the increasingly expensive and laborious process of further development, the drug will, barring some completely unforeseen misadventure, ultimately find its way into clinical therapeutics. Phase II studies, therefore, are the most crucial stage in the course of drug development. Planning of these studies requires great care and investigators of the highest caliber should be used for their conduct. The escalating costs of new drug development are resulting in an undesirable imbalance of efforts in the direction of studies characterized more by easily defined end points than by therapeutic needs. Industry, academia, and the FDA must all be concerned with facilitationg studies in areas of most-needed therapeutic advances.

Analysis of cell type and radiographic presentation as predictors of the clinical course of patients with bronchioalveolar cell carcinoma.

STUDY OBJECTIVES: Bronchioloalveolar carcinoma is a primary lung neoplasm of variable histopathologic, radiologic, and clinical expression. There are three cell types described in bronchioloalveolar carcinoma: Clara cells, mucin-producing cells, and alveolar type II epithelial cells. It is unclear whether these three tumor cell types are associated with a specific radiologic presentation and clinical course. In this study, we investigated whether tumor cell type, identified by transmission electron microscopy, correlated with a specific radiologic pattern, and whether tumor cell type or radiologic presentation correlated with the patient's clinical course and outcome. DESIGN: Transmission electron microscopy was used to restudy tissue blocks from the original surgical histopathologic specimens in 54 patients with primary bronchioloalveolar carcinoma diagnosed over a 10-year period (1980 to 1990). The pretreatment radiographs were reviewed in each case, and the first chest radiograph obtained at the time of the discovery of the tumor in each patient was compared with the results of the ultrastructural study. The medical records of each patient were examined to obtain pertinent radiologic, clinical, and patient outcome information. MEASUREMENT AND RESULTS: There were 32 Clara cell tumors, 10 mucin-producing cell tumors, and 1 alveolar type II epithelial cell tumor in this series. Eleven additional tumors had mixtures of two or more cell types. No statistically significant relationship was detected between tumor cell type and radiologic presentation or patient mortality pattern. There was increased mortality among patients who presented radiologically with segmental, lobar, multifocal, or diffuse disease compared with those patients exhibiting a solitary pulmonary nodule at presentation. CONCLUSION: Radiologic presentation, rather than tumor cell type, provides prognostic information that aids in predicting patient outcome.

Retinal complications of gas myelography.

Bilateral retinal and preretinal hemorrhages with an acute and permanent partial loss of visual acuity developed in a 60-year-old man after an oxygen myelogram. In order to increase the contrast of the myelogram, a greater volume of oxygen was injected in the subarachnoid space than the volume of CSF that was removed. It is believed that the hemorrhages and visual loss were secondary to the sudden increase in CSF pressure caused by the excess volume of oxygen injected.

Management of esophageal injuries.

A multiinstitutional study of 39 esophageal injuries treated between 1982 and 1988 and a comprehensive review of the literature revealed an unacceptably high mortality rate of more than 20%. Results of the current study indicated that prompt diagnosis and aggressive surgical management of esophageal injuries could improve the outcome and lower the associated mortality. The clinical experience and literature review allowed us to elaborate caveats and principles that, if adhered to, should improve the outcome in esophageal injuries.

Bronchoalveolar cell carcinoma of the lung.

A multivariable analysis was performed of all patients registered and confirmed to have bronchoalveolar cell carcinoma of the lung in the Tumor Registry of Thomas Jefferson University Hospital between 1969 and 1983. These 122 patients were reviewed for age, sex, smoking history, occupational exposure, symptoms, radiographic findings, methods of diagnosis, clinical and pathologic staging, methods of treatment, survival, and complications of treatment. No correlation could be found in this series between a patient's age, sex, smoking history, or occupational exposure and the incidence or outcome of the disease. Seventy-one of the 122 patients in this series were asymptomatic, and the carcinoma was discovered in them by routine chest roentgenogram. Of these asymptomatic patients, 50 were seen with pathologic stage I disease. Of the 51 symptomatic patients, 32 (65%) were seen with stage IIIm0 or IIIm1 disease. Despite medical evaluations, 77% of the T1 and T2 lesions required thoracotomy for diagnosis. The overall five-year survival rate was 42.3%, ranging from 75% for those with stage I disease to 8.7% for those with stage IIIm1 disease.

Rounded atelectasis: a pulmonary pseudotumor.

Rounded atelectasis is a benign entity that is often misinterpreted as a pulmonary neoplasm. The roentgenologic appearance of a mass is due to an infolding of atelectatic tissue intermingled with pleura, blood vessels, and bronchi. Rounded atelectasis is usually asymptomatic and is commonly associated with chronic pleural disease or pleural effusions. The distinctive radiologic features include a rounded, pleural-based opacity associated with adjacent pleural thickening and volume loss of the affected lobe. The pathognomonic sign is the "comet tail" that results from the crowding of vessels and bronchi as they enter the atelectatic region. Many authors consider this constellation of findings diagnostic. Rounded atelectasis usually remains stable over time; however, slow growth, as well as diminution in size, has been described. A retrospective analysis revealed 7 cases of rounded atelectasis at our institution over a 9-year period. Three were operated on to exclude malignancy, one was confirmed at operation performed for other reasons, and 3 were followed up expectantly. We conclude that recognition of this entity and its radiologic features can be diagnostic and render further workup, including thoracotomy, unnecessary.

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.

Reopening blocked trabeculectomy sites with the YAG laser.

After unsuccessful attempts to reduce the intraocular pressure of a 70-year-old man with advanced open-angle glaucoma by drugs, trabeculoplasty, and trabeculectomy, we used a mode-locked, pulsed picosecond neodymium YAG laser to cut away an opaque nonpigmented membrane that had occluded the trabeculectomy site. The intraocular pressure decreased immediately from 18 mm Hg to 5 mm Hg and a diffuse conjunctival bleb formed. One month later, the intraocular pressure was 11 mm Hg and the bleb was still present.

YAG laser treatment in a series of failed trabeculectomies.

YAG laser treatment was used in 22 consecutive cases of failed or failing trabeculectomy. Seven treatments were considered to be successful with a mean decrease in intraocular pressure of 9.8 mm Hg (6 to 13 mm Hg) over a mean follow-up period of 10.7 months (two to 18 months). In the successful cases the trabeculectomy was the first intraocular surgery that the eye had undergone and the average time from trabeculectomy to YAG laser treatment was relatively short, 6.7 weeks, compared to 1.1 years for the failures. The major complication was an increase in intraocular pressure of 4 mm Hg or more in nine (60%) of the failed cases two hours after laser treatment.

Marginal corneal ulcers with acute beta streptococcal conjunctivitis and chronic dacryocystitis.

A 73-year-old woman had right dacryocystitis, intense conjunctival hyperemia and chemosis, marginal corneal ulcers, and abscesses and conjunctival cultures that were positive for beta hemolytic streptococci. A distinct lucid interval separated the peripheral corneal ulcers and infiltrates from the corneoscleral limbus. Gram stain of corneal scrapings revealed polymorphonuclear leukocytes but no bacteria, and corneal cultures were negative for bacteria. The peripheral corneal ulcers and abscesses in our patient with the lacrimal conjunctivitis of Morax clinically resembled the catarrhal ulcers found with staphylococcal blepharitis. A hypersensitivity or toxic reaction to streptococci or their products may have played a role in the development of the marginal ulcers in this patient.

Sensitivity and specificity of optic disc variables and analysis of a new variable (MP/D) for glaucoma diagnosis with the Glaucoma-Scope.

AIM: In an attempt to use the quantitative optic disc measurements of the Glaucoma-Scope (OIS Sacramento, CA, USA) to distinguish glaucomatous from normal optic discs, a new variable was investigated, the mean disc corrected for the disc size by dividing by the disc area: MP/D. METHODS: Glaucoma-Scope disc evaluation was performed on 81 eyes of 51 patients split into the following groups based on Humphrey 24-2 visual field and clinical criteria of glaucoma: chronic glaucoma n = 27 (including only early, n = 17, and low tension glaucoma, n = 10), ocular hypertension n = 24, pseudoglaucomatous large discs, n = 12, and normal eyes, n = 18. Classic optic disc variables (the vertical and horizontal c/d ratios, and the c/d area) were compared with the new MP/D index calculating receiver operating characteristic curves. RESULTS: The MP/D ratio was able to identify the glaucomatous eyes more easily than other ratios. Areas under the curves were: 0.91 (MP/D); 0.87 (c/d area); 0.85 (c/d vertical); and 0.80 (c/d horizontal). The MP/D index was also correlated with the mean deviation (r = 0.466; p = 0.001). CONCLUSION: MP/D may prove useful in detecting glaucomatous optic nerve damage and could be an interesting screening tool for primary open angle glaucoma.

Sex differences in the left and right hemifields of normal subjects with computerised static perimetry.

Results of routine perimetric testing of the left and right hemifields in normal subjects have been assumed to be symmetric although asymmetry due to hemispheric dominance has been established for other psychophysical tests. These asymmetries have sometimes been related to sex. With the advent of computerised static perimetry, subtle differences between the left and the right hemifields might be found that were not obvious before. This study investigated differences in retinal sensitivity between the hemifields and the role of sex and eye dominance. Forty three unequivocally right handed and right eye dominant normal adult volunteers, 24 females and 19 males, underwent Humphrey 24-2 testing, half beginning with the left eye, the other half with the right eye. The Peridata program was used to calculate decibel totals per hemifield. Four subjects were excluded because of poor cooperation or test artefacts. In females, the total of the left hemifield was significantly less than the right (p < 0.01) by a mean 18.2 (SD 24) dB equivalent to a difference of 0.34 dB per tested point. No significant difference in hemifields was found for males, between the sexes for both eyes combined, or between the two eyes for either sex. It was concluded that asymmetries in retinal sensitivity with respect to the vertical axis may be physiological and found in females, but not in males.

One-movement insertion of the superior loop into the bag.

An efficient, simple technique for one-movement insertion of the superior intraocular lens loop into the capsular bag is described. This bimanual technique avoids undue stress on the capsular bag and zonules, may be used with all extracapsular techniques, and is suitable for almost all flexible loop intraocular lenses designed for in-the-bag implantation.

Intrathoracic chordoma presenting as a posterior superior mediastinal tumor.

A case of thoracic chordoma successfully treated with surgical excision is reported and described. Thoracic chordomata presenting as posterior superior mediastinal tumors occur infrequently and may be highly malignant lesions. Early radical surgery through thoracotomy provide the best hope of cure, and radiation offers only temporary regression of tumor.