Hyperdiluted Botulinum Toxin and Intense Pulsed Light Treatment: A Case Series to Illustrate a Novel Protocol for Hypertrophic Scar Reduction.

Hypertrophic scars can have significant and far-reaching effects on patients that range from itching to creating difficulty with mobility, all of which can negatively impact the individual's quality of life. A recent study showed that many patients with recent scars report pain, burning, pruritus, erythema, in combination with psychological difficulties that impact bodily movement, choice of clothing, and participation in leisure activities. Botulinum toxin Type A (BoNTA) and intense pulsed light (IPL) have shown promise in treating such scars. We propose a novel treatment protocol involving a 4-week intervention with hyperdiluted BoNTA injections and supplemental treatment with IPL for erythema, and a 6-month scar scale assessment and photographic documentation that occurs before and 6 months after treatment. We report four cases where using hyperdiluted BoNTA, either alone or in conjunction with IPL, substantially reduced scar size, improved overall scar appearance, and diminished erythema in areas on the face and the breasts. Although this report suggests that a schedule of alternating treatments with BoNTA and IPL may be beneficial in reducing scar size and enhancing appearance, further research is necessary to better understand the most effective dosages, the relationship between BoNTA and IPL, and the optimal management of scarring.

Long-term Outcomes of Vocal Fold Paralysis Following Patent Ductus Arteriosus Ligation in Neonates.

INTRODUCTION: In patients undergoing patent ductus arteriosus (PDA) ligation there is a significant risk of left vocal fold paralysis (LVFP) particularly in premature neonates who are small for gestational age. The objective of this study is to determine the incidence of LVFP in infants following PDA ligation and report on long-term outcomes in patients with LVFP. METHODS: We performed a prospective study of patients undergoing PDA ligation in the newborn intensive care unit (NICU) between April 2004 and May 2014. Following PDA ligation, flexible laryngoscopy was performed to assess vocal fold mobility. Patients were then followed longitudinally to determine long-term outcomes. RESULTS: A total of 163 infants underwent PDA ligation. Thirty-six patients (22%) developed LVFP following the procedure. Twenty-five percent of neonates <1500 g experienced LVFP versus 5% of patients >1500 g (p = 0.033). Patients with LVFP were more likely to require a feeding tube (64% vs. 19.6%; p < 0.05) and spent more time in the NICU (135 days vs. 106 days; p < 0.05). Twenty-four patients received long-term follow-up. Six (25%) had complete resolution of LVFP, 10 (42%) were compensated, and 8 (33%) demonstrated persistent LVFP with no improvement. CONCLUSIONS: The incidence of LVFP after PDA ligation is high especially in extremely low birth weight children. The majority of patients recovered well with time, but further surgical intervention was required in uncompensated cases. Long-term follow-up of these patients is needed to ensure improvement. Laryngoscope, 133:1257-1261, 2023.

Phalangeal Osteoid Osteoma of Thumb.

Osteoid osteomas are typically benign osteoblastic bone tumors. Patients often present in their twenties with progressively increasing pain that is worse at night and relieved with nonsteroidal anti-inflammatory drugs. These lesions rarely occur in the hand or wrist; however, when those are involved, the proximal phalanx is the most common location and the index finger is the most commonly affected digit. Lesions affecting the distal phalanges are least likely to occur and the thumb is least likely to be affected. Osteoid osteomas of the distal phalanges can cause great diagnostic challenges. They often present with atypical radiographic and physical examination findings. Although rare, osteoid osteomas of the distal phalanx can be a major cause of digit enlargement and pain. In a patient with a painful and/or swollen digit, the diagnosis should be considered.

Cerebrospinal Fluid Pressure Reduction Results in Dynamic Changes in Optic Nerve Angle on Magnetic Resonance Imaging.

BACKGROUND: Optic nerve sheath tortuosity is a previously reported, but incompletely characterized, finding in idiopathic intracranial hypertension (IIH). We hypothesized that optic nerve angle (ONA), as a quantitative measure of tortuosity, would change dynamically with cerebrospinal fluid (CSF) pressure status of patients with IIH immediately before and after lumbar puncture (LP). METHODS: Consecutive patients with suspected IIH referred for MRI and diagnostic LP were prospectively enrolled in this single institution, institutional review board-approved study. Each patient underwent a pre-LP MRI, diagnostic LP with opening pressure (OP) and closing pressure (CP), and then post-LP MRI all within 1 session. Sagittal and axial ONAs were measured on multiplanar T2 SPACE images by 2 neuroradiologists on pre- and post-LP MRI. Effects of measured pressure and CSF volume removal on changes in ONA were analyzed as was interrater reliability for ONA measurement. RESULTS: Ten patients with IIH were included {all female, median age 29 (interquartile range [IQR] 25-32)}. All patients had elevated OP (median 37, IQR 34-41 cm H2O), and significantly reduced CP (median 18, IQR 16-19 cm H2O, P < 0.001) after CSF removal (IQR 13-16 mL). Within patients, mean ONAs (sagittal and axial) were significantly lower before (162 ± 9°, 163 ± 10°) than after (168 ± 7°, 169 ± 5°) LP (P = 0.001, 0.008, respectively). Interrater reliability was higher with sagittal ONA measurements (0.89) than axial (0.72). CONCLUSIONS: ONA changes with short-term CSF pressure reduction in patients with IIH, establishing optic nerve tortuosity as a dynamic process related to CSF status.

Atherosclerotic Disease and its Relationship to Lumbar Degenerative Disk Disease, Facet Arthritis, and Stenosis With Computed Tomography Angiography.

BACKGROUND: The intervertebral disk is the largest avascular structure in the body. It relies on passive diffusion from arteries at the periphery of the disk for nutrition. Previous studies have suggested a correlation between vascular disease and lumbar degenerative disk disease (DDD), but the association with facet arthritis and stenosis has not been evaluated. OBJECTIVE: To evaluate the degree of lumbar artery stenosis, aortic atherosclerosis on computed tomography angiography, and its relationship to lumbar DDD, facet arthritis, and spinal canal stenosis. DESIGN: Retrospective case review. SETTING: Academic tertiary care hospital. PARTICIPANTS: Not applicable. METHODS: A total of 300 lumbar arteries (150 lumbar artery pairs of the first to fifth lumbar arteries) were evaluated on consecutive computed tomography angiography scans. Severity of vascular disease of lumbar arteries was documented as normal, mild, moderate, severe, or occluded. Aortic vascular disease was documented along the posterior wall where the lumbar arteries originate. MAIN OUTCOME MEASUREMENTS: The relationship between vascular disease with DDD, facet arthritis, and spinal canal stenosis was examined and further evaluated controlling for age. RESULTS: Lumbar artery and aortic atherosclerosis had a positive relationship with DDD, facet arthritis, and spinal stenosis that was statistically significant (P < .05) even after controlling for age. The correlation coefficient was greatest in the younger age group when looking at lumbar artery vascular disease with DDD (0.73, confidence interval 0.50-0.96, P < .0001) and aortic vascular disease with DDD (0.72, confidence interval 0.49-0.94, P < .0001). The correlation of vascular disease with facet arthritis and stenosis was not strong in the older age group. CONCLUSION: Atherosclerotic disease of the lumbar arteries and aorta correlated with lumbar DDD, facet arthritis, and spinal canal stenosis after we adjusted for age, although the correlation with facet arthritis and spinal canal stenosis was not as strong in the older age group. LEVEL OF EVIDENCE: IV.

Frequency of equivocation in surgical meta-evidence: a review of systematic reviews within IBD literature.

OBJECTIVE: To assess the level of equivocation among level 1 evidence in ulcerative colitis and Crohn's disease and determine whether any predisposing factors are present. METHOD: MEDLINE, Embase, CINHAL and Cochrane were searched from 2006 to 2017. Papers were scored using AMSTAR and categorised into surgical (S), medical (M) or medical and surgical (MS) groups. The ability of each paper to make a recommendation and conclusiveness in doing so was recorded. RESULTS: 278 papers were assessed. 82% (n=227) could make a recommendation, 18% (n=51) could not. There was a significant difference in ability to provide a recommendation between S and M (P=0.003) but not MS and M (P=0.022) nor S and MS (P=0.79). Where a recommendation was made, S papers were more likely to be tempered than M papers (P=0.014) but not MS papers (P=0.987). CONCLUSIONS: Surgical meta-evidence within the inflammatory bowel disease domain is more than twice as likely as medical meta-evidence to be unable to provide a recommendation for clinical practice. Where a recommendation was made, surgical reviews were twice as likely to temper their conclusion.

Assessing Foraminal Stenosis in the Cervical Spine: A Comparison of Three-Dimensional Computed Tomographic Surface Reconstruction to Two-Dimensional Modalities.

STUDY DESIGN: Retrospective radiographic study. OBJECTIVE: The optimal radiographic modality for assessing cervical foraminal stenosis is unclear. Determination on conventional axial cuts is made difficult due in part to the complex, oblique orientation of the cervical neuroforamen. The utility of 3-dimensonal (3D) computed tomography (CT) reconstruction in improving neuroforaminal assessment is not well understood. The objective of this study is to determine inter-rater variability in grading cervical foraminal stenosis using 3 different CT imaging modalities: 3D CT surface reconstructions (3DSR), 2D sagittal oblique multiplanar reformations (2D-SOMPR), and conventional 2D axial CT imaging. METHODS: Pretreatment CT scans of 25 patients undergoing surgery for cervical spondylotic radiculopathy were analyzed at 2 levels: C5-C6 and C6-C7. Simple interrater agreement and kappa-Fleiss coefficients were calculated for each imaging modality and stenosis grade. Image reviewers (attending spine surgeon, attending neuroradiologist, spine fellow) interpreted each CT scan in 3 different formats: axial, 2D-SOMPR, and 3DSR. Four cervical foramina at 2 spinal levels were graded as normal (no stenosis), mild (≤25% stenosis), moderate (25%-50% stenosis), or severe (>50% stenosis). RESULTS: Across all imaging modalities, interrater reliability was fair when grading foraminal stenosis (κ < 0.4). Agreement was lowest for the axial images (κ = 0.119) and highest for the 3D CT reconstructions (κ = 0.334). 2D-SOMPR images also led to improved interrater reliability when compared with axial images (κ = 0.255). CONCLUSION: Grading cervical foraminal stenosis using conventional axial CT imaging is difficult with low interrater reliability. CT modalities that provide a circumferential view of the cervical foramen, such as 2D-SOMPR and 3D CT reconstruction, had higher rates of interobserver reliability in grading foraminal stenosis than conventional axial cuts, with 3D having the highest. As these 3D reconstructions can be obtained at no additional cost or radiation exposure over a conventional CT scan, and because they can provide useful information in determining levels being considered for surgical decompression, we recommend they be utilized when evaluating cervical foramina.

Epidural Lipomatosis and Associated Spinal Stenosis-The Impact of Weight Loss: A Case Report.

Lumbar stenosis is a common radiographic finding that sometimes can be symptomatic. It usually results from a degenerative process of hypertrophic facets, ligamentum flavum hypertrophy, and disc involvement. A prominence of fat in the epidural space, epidural lipomatosis, can also be a contributing factor. This case report presents a 55-year-old man with radiographic improvement of epidural lipomatosis and stenosis from dietary weight loss. Given the rising obesity epidemic, practitioners should be cognizant of epidural lipomatosis and consider weight loss as a possible treatment option.

Imaging of Intracranial Pressure Disorders.

Intracranial pressure (ICP) is the pressure inside the bony calvarium and can be affected by a variety of processes, such as intracranial masses and edema, obstruction or leakage of cerebrospinal fluid, and obstruction of venous outflow. This review focuses on the imaging of 2 important but less well understood ICP disorders: idiopathic intracranial hypertension and spontaneous intracranial hypotension. Both of these ICP disorders have salient imaging findings that are important to recognize to help prevent their misdiagnosis from other common neurological disorders.

Novel orbital findings of intracranial hypotension.

PURPOSE: To determine whether orbital findings on routine brain MRI can be used to differentiate patients with intracranial hypotension from controls. METHODS: The authors evaluated axial T2-weighted images for the amount of optic nerve sheath CSF and 3D-T1-weighted images for optic nerve angle of sixteen patients with intracranial hypotension and 60 controls. RESULTS: Patients with intracranial hypotension demonstrated significantly decreased CSF in the optic nerve sheath. Optic nerve angle was higher in the intracranial hypotension group compared to controls. CONCLUSIONS: Decreased optic nerve sheath CSF and straightened optic nerve angle are significantly more common in the setting of intracranial hypotension.

Repair of a traumatic subarachnoid-pleural fistula with the percutaneous injection of fibrin glue in a 2-year-old.

Subarachnoid-pleural fistulas (SPFs) are rare clinical entities that occur after severe thoracic trauma or iatrogenic injury during anterolateral approaches to the spine. Treatment of these fistulas often entails open repair of the dural defect. The authors present the case of an SPF in a 2-year-old female after a penetrating injury to the chest. The diagnosis of an SPF was suspected given the high chest tube output and was confirmed with a positive ß2-transferrin test of the chest tube fluid, as well as visualization of dural defects on MRI. The dural defects were successfully repaired with CT-guided percutaneous epidural injection of fibrin glue alone. This case represents the youngest pediatric patient with a traumatic SPF to be treated percutaneously. This technique can be safely used in pediatric patients, offers several advantages over open surgical repair, and could be considered as an alternative first-line therapy for the obliteration of SPFs.

Intracranial abscess as a complication of allergic fungal sinusitis.

BACKGROUND AND PURPOSE: This case involves a common disease, allergic fungal sinusitis (AFS), with the uncommon complication of intracranial abscess. Although AFS is known to result in bone erosion, invasive complications are rare. METHODS: The clinical and pathologic information were reviewed. A literature review was performed to clarify the clinical, radiologic, and pathologic features of AFS. RESULTS: The clinical and radiographic presentations were typical for AFS, including the relatively common complication of sinus wall erosion. Follow-up imaging demonstrated spread of fungal disease into the adjacent masticator space and intracranial spread by foramen ovale. CONCLUSION: This case illustrates the importance of identifying AFS and describing findings such as sinus erosion that may alter management. In this example, knowledge of the altered anatomy and potential for mucosal injury may facilitate surgical planning and decrease the likelihood of future complications.

Multimodality treatment of brain metastases: an institutional survival analysis of 275 patients.

BACKGROUND: Whole brain radiation therapy (WBRT), surgical resection, stereotactic radiosurgery (SRS), and combinations of the three modalities are used in the management of patients with metastatic brain tumors. We present the previously unreported survival outcomes of 275 patients treated for newly diagnosed brain metastases at Cancer Care Northwest and Gamma Knife of Spokane between 1998 and 2008. METHODS: The effects treatment regimen, age, Eastern Cooperative Oncology Group-Performance Status (ECOG-PS), primary tumor histology, number of brain metastases, and total volume of brain metastases have on patient overall survival were analyzed. Statistical analysis was performed using Kaplan-Meier survival curves, Andersen 95% confidence intervals, approximate confidence intervals for log hazard-ratios, and multivariate Cox proportional hazard models. RESULTS: The median clinical follow up time was 7.2 months. On multivariate analysis, survival statistically favored patients treated with SRS alone when compared to patients treated with WBRT alone (p<0.001), patients treated with resection with SRS when compared to patients treated with SRS alone (p=0.020), patients in ECOG-PS class 0 when compared to patients in ECOG-PS classes 2 (p=0.04), 3 (p<0.001), and 4 (p<0.001), patients in the non-small-cell lung cancer group when compared to patients in the combined melanoma and renal-cell carcinoma group (p<0.001), and patients with breast cancer when compared to patients with non-small-cell lung cancer (p<0.001). CONCLUSIONS: In our analysis, patients benefited from a combined modality treatment approach and physicians must consider patient age, performance status, and primary tumor histology when recommending specific treatments regimens.

Nonclinical dose formulation analysis method validation and sample analysis.

Nonclinical dose formulation analysis methods are used to confirm test article concentration and homogeneity in formulations and determine formulation stability in support of regulated nonclinical studies. There is currently no regulatory guidance for nonclinical dose formulation analysis method validation or sample analysis. Regulatory guidance for the validation of analytical procedures has been developed for drug product/formulation testing; however, verification of the formulation concentrations falls under the framework of GLP regulations (not GMP). The only current related regulatory guidance is the bioanalytical guidance for method validation. The fundamental parameters for bioanalysis and formulation analysis validations that overlap include: recovery, accuracy, precision, specificity, selectivity, carryover, sensitivity, and stability. Divergence in bioanalytical and drug product validations typically center around the acceptance criteria used. As the dose formulation samples are not true "unknowns", the concept of quality control samples that cover the entire range of the standard curve serving as the indication for the confidence in the data generated from the "unknown" study samples may not always be necessary. Also, the standard bioanalytical acceptance criteria may not be directly applicable, especially when the determined concentration does not match the target concentration. This paper attempts to reconcile the different practices being performed in the community and to provide recommendations of best practices and proposed acceptance criteria for nonclinical dose formulation method validation and sample analysis.

Comment on "Wetland sedimentation from hurricanes Katrina and Rita".

Turner et al. (Reports, 20 October 2006, p. 449) measured sedimentation from Hurricanes Katrina and Rita in coastal Louisiana and inferred that storm deposition overwhelms direct Mississippi River sediment input. However, their annualized hurricane deposition rate is overestimated, whereas riverine deposition is underestimated by at least an order of magnitude. Their numbers do not provide a credible basis for decisions about coastal restoration.

Aromatase inhibition for the treatment of idiopathic hypogonadotropic hypogonadism in men with premature ejaculation.

BACKGROUND: Idiopathic hypogonadotropic hypogonadism (IHH) has been observed to occur in men with premature ejaculation (PE). Common IHH therapies include testosterone replacement, which increases testosterone levels but suppresses gonadotropin release; and gonadotropin-releasing hormone supplementation, which restores gonadotropin levels but is impractical for chronic use. Hormonal imbalances associated with IHH/PE are thought to be related to hyperactivity of the cytochrome P-450 enzyme aromatase. METHODS: Ten male patients with a diagnosis of IHH/PE were treated with the aromatase inhibitor anastrazole (1 mg/d orally). Levels of free and total testosterone, luteinizing hormone, follicle-stimulating hormone, prolactin, and estradiol were determined at baseline and after 2 weeks of therapy. RESULTS: After 2 weeks of therapy with anastrazole, levels of testosterone, luteinizing hormone, and estradiol had returned to normal. No effect was noted on premature ejaculation. CONCLUSION: These results suggest that aromatase inhibition with anastrazole may provide a practical and efficacious alternative for the treatment of IHH but is not effective in preventing premature ejaculation.