Neurodynamics Is an Effective Intervention for Carpal Tunnel Syndrome.

Clinical Scenario: Carpal tunnel syndrome (CTS) is the most common entrapment neuropathy of the upper-extremity. Due to the involvement of the median nerve, long-term compression of this nerve can lead to hand dysfunction and disability that can impact work and daily life. As such, early treatment is warranted to prevent any long-term damage to the median nerve. Conservative management is utilized in those with mild to moderate CTS. Neural mobilizations can aid in the reduction of neural edema, neural mobility, and neural adhesion while improving nerve conduction. Clinical Question: Is neurodynamics effective in reducing pain and reported symptoms in those with CTS? Summary of Key Findings: Four studies were included, with 2 studies utilizing passive neural mobilizations, one study using active techniques, and one study using active neural mobilizations with splinting. All studies showed large effect size for pain, symptom severity, and physical function. Clinical Bottom Line: Neurodynamics is an effective treatment for CTS. Splinting is only effective when combined with neurodynamics. Strength of Recommendation: Level B evidence to support the use of neurodynamics for the treatment of CTS.

Double bubble with the big-bubble technique during deep anterior lamellar keratoplasty.

PURPOSE: To report a case of intraoperative double bubble that formed during big-bubble DALK surgery in a patient with corneal scarring secondary to herpetic stromal keratitis. METHODS: Case report. RESULTS: A 22 year old woman presented with a large corneal scar, likely secondary to previous herpetic stromal keratitis. She underwent big-bubble DALK surgery for visual rehabilitation. Intraoperatively, a mixed bubble with persistent type 2 bubble postoperatively was noted. The second bubble resorbed with clearance of the graft and good visual outcome after 6 weeks. CONCLUSIONS: This case report describes the unusual development of a mixed bubble during big-bubble DALK surgery. This graft cleared with resolution of the second bubble postoperatively without further surgical intervention.

Corneal Cross-Linking in Pediatric Patients With Progressive Keratoconus.

PURPOSE: To evaluate corneal cross-linking (CXL) in the treatment of keratoconus in pediatric patients. Specifically, this study investigates the impact of CXL on uncorrected distance visual acuity (UDVA), best-corrected distance visual acuity (BDVA), manifest refraction, keratometry (K) measurements, and higher order aberrations. METHODS: This is a retrospective, observational case series of patients 18 years old or younger with progressive keratoconus who underwent CXL from January 2009 to August 2013. Preoperative and 1-year postoperative data including BDVA, manifest refraction, mean K readings, and corneal aberration measurements were extracted from clinical charts and topographical imaging. Visual acuity was converted to logarithm of the minimum angle of resolution (logMAR) scale, and mean refractive spherical equivalent (MRSE) was calculated from manifest refraction. RESULTS: The group consisted of 39 eyes from 28 patients, including 21 males and 7 females (mean age = 16.3 years, range: 11-18, standard deviation [SD] = 1.81). UDVA did not change significantly (preoperative UDVA = 1.20 logMAR, SD = 0.57, and postoperative UDVA = 0.90 logMAR, SD = 0.67, P = 0.19). BDVA did not change significantly (preoperative BDVA = 0.34 logMAR, SD = 0.27, and postoperative BDVA = 0.34 logMAR, SD = 0.23, P = 0.50). There was no significant change in mean K (preoperative K = 48.49, SD = 5.44, and postoperative K = 48.25, SD = 4.74, P = 0.34). Mean MRSE did not change significantly (preoperative MRSE = -3.29 D, SD = 4.04, and postoperative MRSE = -3.53 D, SD = 4.07, P = 0.31). Corneal aberration measurements were available for 10 eyes, and stability of measurements was demonstrated. There were no complications noted. CONCLUSIONS: This study suggests that CXL is a safe and effective procedure that halts the progression of keratoconus in pediatric patients at 1-year follow-up. To validate these findings, longer follow-up is required.

Surgical salvage of recurrent vestibular schwannoma following prior stereotactic radiosurgery.

OBJECTIVES/HYPOTHESIS: To evaluate outcomes of salvage surgery for vestibular schwannoma (VS) that failed primary stereotactic radiosurgery (SRS). METHODS: Case-control study of 37 patients who underwent surgical resection of sporadic VS following prior SRS at two tertiary academic referral centers between 2003 and 2015. A cohort of nonirradiated control subjects, matched according to tumor size, age, and treatment center, were used as comparison. RESULTS: Thirty-seven patients were included. The median time from radiation to surgical salvage was 36 months (range 9.6-153 months). Following tumor progression after SRS, 18 (49%) patients underwent gross total resection, 10 (27%) underwent near-total resection, and nine (24%) underwent subtotal resection. Postoperative complications following salvage surgery included one (3%) case of stroke, four (11%) cases of cerebrospinal fluid leak, and two (5%) cases of meningitis. Twenty-seven (73%) patients had good postoperative facial nerve outcome (House-Brackmann Score I-II) at long-term follow-up. There were no cases of tumor recurrence or regrowth after a median length of 26 months following microsurgical salvage (range 3-114 months). The rate of satisfactory postoperative facial nerve function was not different between study and control subjects (73% vs. 76%; P = 0.8); however, less-than-complete resection was utilized more frequently among previously radiated patients (P = 0.01). CONCLUSION: Microsurgical salvage of VS following primary radiation therapy is challenging. Less-than-complete resection is required in a greater percentage of patients to preserve facial nerve integrity and prevent neurological complications. Long-term follow-up is needed to determine the risk of delayed progression following incomplete tumor removal. LEVEL OF EVIDENCE: 3b. Laryngoscope, 126:2580-2586, 2016.

Statin use and risk for cataract: a nested case-control study of 2 populations in Canada and the United States.

BACKGROUND: In current literature the association between statin use and cataracts is inconsistent and controversial. We sought to further examine the effect of statin use on the risk of cataract and need for surgical intervention in 2 North American populations. METHODS: This retrospective nested case-control study derived data from the British Columbia (BC) Ministry of Health databases from 2000-2007 and the IMS LifeLink database from 2001-2011 to form 2 patient cohorts. The BC cohort was comprised of female and male patients; 162,501 patients were matched with 650,004 control subjects. The IMS LifeLink cohort was comprised of male patients aged 40-85 years; 45,065 patients were matched with 450,650 control subjects. Patients with statin use for > 1 year before the initial ophthalmology visit were identified. Diagnosis and surgical management of cataract were followed. Conditional logistic regression models were used to analyze data. RESULTS: For the BC cohort, the crude rate ratio (RR) for use of any statin was 1.30, and the adjusted RR was 1.27 (95% confidence interval, 1.24-1.30). The adjusted RRs for each individual statin were all statistically significant. For the IMS LifeLink cohort, the crude RR for use of any statin was 1.13, and the adjusted RR was 1.07 (95% confidence interval, 1.04-1.10). CONCLUSIONS: This study demonstrates that statin use is significantly associated with cataract requiring surgical intervention. This relationship was consistent in both North American cohorts. Further assessment of this relationship is recommended, especially because of increased statin use and the importance of acceptable vision in old age when cardiovascular disease is common.

HSP90 Inhibitor SNX5422/2112 Targets the Dysregulated Signal and Transcription Factor Network and Malignant Phenotype of Head and Neck Squamous Cell Carcinoma.

Heat shock protein 90 (HSP90) is a chaperone protein that stabilizes proteins involved in oncogenic and therapeutic resistance pathways of epithelial cancers, including head and neck squamous cell carcinomas (HNSCCs). Here, we characterized the molecular, cellular, and preclinical activity of HSP90 inhibitor SNX5422/2112 in HNSCC overexpressing HSP90. SNX2112 inhibited proliferation, induced G2/M block, and enhanced cytotoxicity, chemosensitivity, and radiosensitivity between 25 and 250 nM in vitro. SNX2112 showed combinatorial activity with paclitaxel in wild-type (wt) TP53-deficient and cisplatin in mutant (mt) TP53 HNSCC lines. SNX2112 decreased expression or phosphorylation of epidermal growth factor receptor (EGFR), c-MET, v-akt murine thymoma viral oncogene homolog 1 (AKT), extracellular signal-regulated kinases (ERK) 1 and 2, inhibitor κB kinase, and signal transducer and transcription factor 3 (STAT3), corresponding downstream nuclear factor κB, activator protein-1, and STAT3 reporter genes, and target oncogenes and angiogenic cytokines. Furthermore, SNX2112 enhanced re-expression of TP53 and targets p21WAF1 and PUMA, while TP53 inhibitor Pifithrin or siRNA attenuated the antiproliferative activity of SNX2112 in wtTP53 HNSCC in vitro. Prodrug SNX5422 similarly down-modulated key signal targets, enhanced TP53 expression and apoptosis, and inhibited proliferation, angiogenesis, and tumorigenesis in a wtTP53-deficient HNSCC xenograft model. Thus, HSP90 inhibitor SNX5422/2112 broadly modulates multiple key nodes within the dysregulated signaling network, with corresponding effects upon the malignant phenotype. Our data support investigation of SNX5422/2112 in combination with paclitaxel, cisplatin, and radiotherapy in HNSCC with different TP53 status.

Apolipoprotein B levels in adults with type 1 diabetes not receiving lipid-lowering therapy.

OBJECTIVES: To investigate apolipoprotein B (apoB) levels in adult patients with type 1 diabetes with no history of cardiovascular disease and not receiving lipid-lowering therapy. DESIGN AND METHODS: Subjects (n=169) were divided into two groups based on gender. Primary analysis examined lipid parameters and glycosylated hemoglobin. Secondary analysis involved classifying patients according to the Canadian Diabetes Association's (CDA) LDL cholesterol and apoB targets. RESULTS: Mean apoB levels were 0.81+/-0.17 g/L in males and 0.78+/-0.18 g/L in females. We also found that among patients who failed to achieve the CDA LDL cholesterol target, 62% of males and 66% of females [corrected]met the apoB target. CONCLUSIONS: There is low prevalence of elevated apoB among patients with type 1 diabetes. In addition, there is discordance between the proportions of patients meeting either LDL cholesterol or apoB targets, thus a significant number of patients may be prescribed lipid-lowering medications unnecessarily.

Low Prevalence of Elevated ApoB Levels in Patients with Type 2 Diabetes Not Receiving Lipid-Lowering Therapy.

OBJECTIVE: Cardiovascular disease (CVD) is the leading cause of death in people with type 2 diabetes. Apolipoprotein B (apoB) is known to be a better marker of CVD risk than low-density lipoprotein cholesterol (LDL-C). This study investigated apoB levels in people with type 2 diabetes. METHODS: We obtained blood samples from 507 consenting people with type 2 diabetes who were not receiving lipid-lowering medication and who had no previous history of CVD. Subjects were divided into 3 groups: men (M), women <50 years old (W1) and women ≥50 years old (W2). Primary analysis examined lipid parameters, specifically apoB. Secondary analysis involved classifying patients according to the Canadian Diabetes Association's apoB, LDL-C and triglyceride (TG) targets. RESULTS: We found a total mean apoB level of 0.92 g/L. Among patients who failed to achieve the LDL-C target, 28% of M, 39% of W1 and 30% of W2 met the apoB target. The proportions of individuals categorized as being above the LDL-C and apoB targets were significantly different in all 3 groups (p<0.01). When LDL-C was below target and TG was <1.5 mmol/L, 100% of M and W1 and 93% of W2 met the apoB target. CONCLUSIONS: The discordance between the proportions of patients meeting LDL-C and apoB targets may lead to patients being erroneously classified. ApoB and LDL-C correlate very well when TG is <1.5 mmol/L, but not when ≥1.5 mmol/L. Approximately one-third of patients met both LDL-C and apoB goals. Thus, not all patients with type 2 diabetes should be considered to be at a high risk of CVD.