Temporal Relationship Between Serum Neurofilament Light Chain and Radiologic Disease Activity in Patients With Multiple Sclerosis.

BACKGROUND AND OBJECTIVES: Serum neurofilament light chain (sNfL) levels correlate with multiple sclerosis (MS) disease activity, but the dynamics of this correlation are unknown. We evaluated the relationship between sNfL levels and radiologic MS disease activity through monthly assessments during the 24-week natalizumab treatment interruption period in RESTORE (NCT01071083). METHODS: In the RESTORE trial, participants with relapsing forms of MS who had received natalizumab for ≥12 months were randomized to either continue or stop natalizumab and followed with MRI and blood draws every 4 weeks to week 28 and again at week 52 The sNfL was measured, and its dynamics were correlated with the development of gadolinium-enhancing (Gd+) lesions. Log-linear trend in sNfL levels were modeled longitudinally using generalized estimating equations with robust variance estimator from baseline to week 28. RESULTS: Of 175 patients enrolled in RESTORE, 166 had serum samples for analysis. Participants with Gd+ lesions were younger (37.7 vs 43.1, p = 0.001) and had lower Expanded Disability Status Scale scores at baseline (2.7 vs 3.4, p = 0.017) than participants without Gd+ lesions. sNfL levels increased in participants with Gd+ lesions (n = 65) compared with those without (n = 101, mean change from baseline to maximum sNfL value, 12.1 vs 3.2 pg/mL, respectively; p = 0.003). As the number of Gd+ lesions increased, peak median sNfL change also increased by 1.4, 3.0, 4.3, and 19.6 pg/mL in the Gd+ lesion groups of 1 (n = 12), 2-3 (n = 18), 4-9 (n = 21), and ≥10 (n = 14) lesions, respectively. However, 46 of 65 (71%) participants with Gd+ lesions did not increase above the 95th percentile threshold of the group without Gd+ lesions. The initial increase of sNfL typically trailed the first observation of Gd+ lesions, and the peak increase in sNfL was a median [interquartile range] of 8 [0, 12] weeks after the first appearance of the Gd+ lesion. DISCUSSION: Although sNfL correlated with the presence of Gd+ lesions, most participants with Gd+ lesions did not have elevations in sNfL levels. These observations have implications for the use and interpretation of sNfL as a biomarker for monitoring MS disease activity in controlled trials and clinical practice.

Measuring the probability of a financial crisis.

When financial firms are undercapitalized, they are vulnerable to external shocks. The natural response to such vulnerability is to reduce leverage, and this can endogenously start a financial crisis. Excessive credit growth, the main cause of financial crises, is reflected in the undercapitalization of the financial sector. Market-based measures of systemic risk such as SRISK, which stands for systemic risk, enable monitoring how such weakness emerges and progresses in real time. In this paper, we develop quantitative estimates of the level of systemic risk in the financial sector that precipitates a financial crisis. Common approaches to reduce leverage correspond to specific scaling of systemic risk measures. In an econometric framework that recognizes financial crises represent left tail events for the economy, we estimate the relationship between SRISK and the financial crisis severity for 23 developed countries. We develop a probability of crisis measure and an SRISK capacity measure based on our estimates. Our analysis highlights the important global externality whereby the risk of a crisis in one country is strongly influenced by the undercapitalization of the rest of the world.

Feasibility Study for Transnasal Endoscopic Repair of Orbital Floor Fracture With Alloplastic Implant.

OBJECTIVE: Fractures of the orbital floor are common yet repaired by various techniques, including open periorbital, transantral endoscopic, and endoscopic endonasal approaches. To date, endoscopic endonasal repair of an orbital floor fracture using an alloplastic implant has not been described. We aim to determine the technique and limitations of completely endoscopic endonasal orbital floor repair using an alloplastic implant. STUDY DESIGN: Cadaveric anatomic study and retrospective case series. METHODS: Cadaveric study of 12 sides with endoscopic sinonasal dissection followed by the creation and repair of an isolated orbital floor fracture using an alloplastic implant. Four representative patient cases are presented in which the techniques developed in the cadaveric study were employed. Patients were selected for this technique based on the results of the cadaveric study. RESULTS: Cadaveric study demonstrated feasibility of access and repair for fractures that did not extend lateral to the infraorbital canal or anterior to the nasolacrimal duct. In all cadaveric sides and in all 4 patient cases, successful alloplastic orbital floor reconstruction was achieved. CONCLUSION: This method of repair is feasible for selected patients and may be considered in cases of favorable fracture anatomy with or without concomitant indication for an ipsilateral sinus procedure.

Transnasal endoscopic medial maxillary sinus wall transposition with preservation of structures.

OBJECTIVES/HYPOTHESIS: To evaluate the increase in access to the maxillary sinus (MS) with transnasal endoscopic medial maxillary sinus wall transposition (TEMMT), while preserving major structures of the nasal cavity. STUDY DESIGN: The study was divided into three parts: anatomical, radiographic, and case series. METHODS: Three cadaveric dissections (total of six sides) confirmed the feasibility of the TEMMT approach. Radiographic measurements using maxillofacial computed tomography scans were taken to assess the maximal antrostomy. The TEMMT approach was performed on six consecutive patients with benign MS disease. RESULTS: The cadaveric measurements were consistent with the radiographic measurements, which confirmed the maximum access to the MS. The radiographic measurements ranged from 14.4 to 39.1 mm in the anteroposterior dimension, 8.2 to 23.7 mm in the superior-inferior dimension, and 36° to 98° in the angle between the medial and anterior wall of the MS. In the patient series, five patients presented with an odontogenic cyst, and one patient had an antrochoanal polyp in the MS. The TEMMT approach provided excellent access and adequate resection, as well as preservation of the nasolacrimal duct and inferior turbinate. Finally, the mucosal flap was sufficient to cover the inferior meatal antrostomy. CONCLUSIONS: TEMMT provides excellent access into the MS, especially the floor and anterior wall, without the morbidities of the Caldwell-Luc or medial maxillectomy approach. In addition, the transposition of the inferior turbinate and the mucosal flap provides coverage of the medial wall with preservation of the inferior meatus, inferior turbinate, and nasolacrimal duct for patients with benign MS disease. LEVEL OF EVIDENCE: NA Laryngoscope, 126:1504-1509, 2016.

Endoscopic midfacial rejuvenation.

Early facial rejuvenation focused largely on the upper and lower thirds of the face. More recently, improvements in understanding of midfacial aging and anatomy have paralleled the development of endoscopic and minimally invasive surgical techniques. The midface is now understood to include both the lower lid subunit and the cheek down to the nasolabial fold. Many surgical techniques for midface rejuvenation have been used, including skin tightening with direct excision, skin-muscle flaps, isolated fat pad transposition, and subperiosteal lifting. The methods of endoscopic subperiosteal midface lifting and endoscopic malar fat pad lifting are discussed.

Split-calvarial osteopericranial flap for reconstruction following endoscopic anterior resection of cranial base.

OBJECTIVES/HYPOTHESIS: To conceive and critically evaluate an adaptation of the split calvarial osteopericranial flap for reconstruction following endoscopic endonasal resection of the anterior skull base. STUDY DESIGN: Cadaveric anatomic study. METHODS: Five cadavers were embalmed with methanol, and vasculature was injected with latex. Endoscopic endonasal resection of the anterior skull base was performed, followed by reconstruction with a unilateral osteopericranial flap and a contralateral conventional pericranial flap. RESULTS: Rigid reconstruction was achieved in all specimens. Osteoplastic flap harvest was made more reliable by drilling the diploe below the graft with a curved bur. Dimensions of the bony flap were ideally shorter and wider than the defect, allowing for flap inset and rigid support by the orbits without compromise of the flap vascular supply. Endoscopic inset of the flap is feasible via nasion-frontal osteotomy and inlay technique. CONCLUSION: Rigid anterior skull base reconstruction via split calvarial osteopericranial flap is adaptable to current endoscopic techniques. This provides more anatomic reconstruction than current methods and may lead to decreased complication rates following anterior skull base resection.

Impact of 13-valent pneumococcal conjugate vaccine on otitis media bacteriology.

OBJECTIVES: To determine the microbiology of otitis media (OM) since the introduction of the 13-valent pneumococcal conjugate vaccine (PCV13) in February 2010. METHODS: Middle ear effusion from a pediatric Otolaryngology population undergoing pressure equalization tube (PET) placement was obtained and sent for aerobic culture and antibiotic susceptibility testing between August 2012 and April 2013. Vaccination records were obtained and statistical analysis was completed. RESULTS: During the 8-month period, 236 ears were evaluated, and of those 39 ears were found to have positive cultures. The single nonvaccine Streptococcus pneumoniae (serotype 16) isolate was obtained from a PCV7-only vaccinated patient and was penicillin susceptible. The three most common isolates were Staphylococcus coagulase negative (57%), Haemophilus influenzae (17%), and Moraxella catarrhalis (7%). CONCLUSIONS: This study is the first to assess the bacteriology of OM in a pediatric population undergoing PET placement in the immediate post-PCV13 era. Our study is limited by sample size; however, the lack of S. pneumoniae cultures indicates that PCV13 has had a significant impact on pneumococcal infections during these initial years following licensure.

The safety of bendamustine in patients with chronic lymphocytic leukemia or non-Hodgkin lymphoma and concomitant renal impairment: a retrospective electronic medical record database analysis.

Abstract This retrospective study compared adverse-event rates in patients with chronic lymphocytic leukemia (CLL) or non-Hodgkin lymphoma (NHL), with and without renal impairment, receiving bendamustine alone or with rituximab. Patients (n = 940) were stratified into a renally impaired group (creatinine clearance [CrCL] < 40 mL/min) and two comparator groups (CrCL ≥ 40 mL/min and CrCL ≥ 60 mL/min). Renally impaired patients with NHL had a significantly greater incidence of grade 3-4 thrombocytopenia compared with the CrCL ≥ 60 mL/min group (hazard ratio [HR], 2.57; p = 0.025). For CLL and NHL together, grade 3-4 increased blood urea nitrogen was significantly higher in the renally impaired group than in the CrCL ≥ 40 mL/min (HR, 2.36; p = 0.02) and CrCL ≥ 60 mL/min (HR, 4.46; p = 0.001) groups. Based on these results, monitoring blood counts (including platelets) and renal function would be prudent in the management of patients with renal dysfunction and NHL or CLL who receive bendamustine-based regimens.