Surgical Experience in Prevention of Postoperative CSF Leaks Using Abdominal Fat Grafts in Endoscopic Endonasal Transsphenoidal Surgery for Pituitary Adenomas.

Objective Cerebrospinal fluid (CSF) leaks are the most common complication during endonasal endoscopic transsphenoidal approach (EETSA) and prevention of postoperative CSF leaks is critical. In this study, we report a single surgeon's experience of sellar floor reconstruction using abdominal fat grafts for prevention of postoperative CSF leaks in EETSA for pituitary adenomas. Study Design This study is presented as case series with retrospective chart review. Setting Present study was conducted at tertiary referral center. Participants A total of 216 patients who underwent surgery via EETSA for pituitary adenomas between 2008 and 2018 at our institution were evaluated. When an intraoperative CSF leak occurred, sellar floor reconstruction was performed using a fat graft harvested from the abdomen via a 2-cm skin incision. Main Outcome Measures Primary outcome and measures of this study was postoperative CSF leaks. Results A total of 53 patients showed intraoperative CSF leaks (24.5%) and 2 patients showed postoperative CSF leaks (0.93%). There were no postoperative CSF leaks in any patients who showed intraoperative CSF leaks and received sellar floor reconstruction using fat grafts. There were also no postoperative CSF leaks in 12 patients who received preventative sellar floor reconstruction using fat grafts due to extensive arachnoid herniation without intraoperative CSF leaks. However, there were two postoperative CSF leaks in patients who did not show intraoperative CSF leaks and did not receive sellar floor reconstruction. Conclusion The effectiveness of sellar floor reconstruction using abdominal fat grafts in patients receiving EETSA for pituitary adenoma was reported. We suggest that identification of intraoperative CSF leaks is important and preventive sellar floor reconstruction without evidence of intraoperative CSF leaks can also be beneficial.

Dose-response and functional role of whey permeate as a source of lactose and milk oligosaccharides on intestinal health and growth of nursery pigs.

Two experiments were conducted to evaluate dose-response and supplemental effects of whey permeate on growth performance and intestinal health of nursery pigs. In experiment (exp.) 1, 1,080 pigs weaned at 6.24 kg body weight (BW) were allotted to five treatments (eight pens/treatment) with increasing levels of whey permeate in three phases (from 10% to 30%, 3% to 23%, and 0% to 9% for phase 1, 2, and 3, respectively) fed until 11 kg BW and then fed a common phase 4 diet (0% whey permeate) until 25 kg BW in a 48-d feeding trial. Feed intake and BW were measured at the end of each phase. In exp. 2, 1,200 nursery pigs at 7.50 kg BW were allotted to six treatments (10 pens/treatment) with increasing levels of whey permeate from 0% to 18.75% fed until 11 kg BW. Feed intake and BW were measured during 11 d. Six pigs per treatment (1 per pens) were euthanized to collect the jejunum to evaluate tumor necrosis factor-alpha, interleukin-8 (IL-8), transforming growth factor-beta 1, mucin 2, histomorphology, digestive enzyme activity, crypt cell proliferation rate, and jejunal mucosa-associated microbiota. Data were analyzed using contrasts in the MIXED procedure and a broken-line analysis using the NLIN procedure of SAS. In exp. 1, increasing whey permeate had a quadratic effect (P < 0.05) on feed efficiency (G:F; maximum: 1.35 at 18.3%) in phase 1. Increasing whey permeate linearly increased (P < 0.05) average daily gain (ADG; 292 to 327 g/d) and G:F (0.96 to 1.04) of pigs in phase 2. In exp. 2, increasing whey permeate linearly increased (P < 0.05) ADG (349 to 414 g/d) and G:F (0.78 to 0.85) and linearly increased (P < 0.05) crypt cell proliferation rate (27.8% to 37.0%). The breakpoint from a broken-line analysis was obtained at 13.6% whey permeate for maximal G:F. Increasing whey permeate tended to change IL-8 (quadratic, P = 0.052; maximum: 223 pg/mg at 10.9%), to decrease Firmicutes:Bacteroidetes (P = 0.073, 1.59 to 1.13), to increase (P = 0.089) Bifidobacteriaceae (0.73% to 1.11%), and to decrease Enterobacteriaceae (P = 0.091, 1.04% to 0.52%) and Streptococcaceae (P = 0.094, 1.50% to 0.71%) in the jejunal mucosa. In conclusion, dietary inclusion of whey permeate increased the growth of nursery pigs from 7 to 11 kg BW. Pigs grew most efficiently with 13.6% whey permeate. Improvement in growth performance is partly attributed to stimulating intestinal immune response and enterocyte proliferation with positive changes in jejunal mucosa-associated microbiota in nursery pigs.

Intraoperative Neuromonitoring Using a Single Transcartilage Needle Electrode During Thyroidectomy.

OBJECTIVES: Application of transcartilage needle electrode for intraoperative neuromonitoring (IONM) during thyroidectomy has been considered an alternative method of electromyography (EMG) tube recording. However, needle electrodes must be inserted into both sides of the thyroid cartilage with exposure of the cartilage lamina. We sought to evaluate the feasibility of applying a single ipsilateral transcartilage needle electrode for IONM during unilateral hemithyroidectomy. METHODS: Thirty-four patients underwent IONM during unilateral thyroidectomy. A dual disposable needle electrode was inserted obliquely into the inferior lower third of the ipsilateral lamina of the thyroid cartilage. Patients were classified as deep (≥ 5 mm) or superficial (< 5 mm) by the depth of the needle electrode inserted into the thyroid cartilage. Without using an EMG tube, IONM was done according to the standardized procedure using a single needle electrode only. RESULTS: IONM was successful in all nerves at risk. Amplitude of the EMG signal was stable during the surgery, with no cases presenting loss of signal. Amplitude of the signal from vagal and recurrent laryngeal nerve stimulation was significantly lower when needle insertion was superficial (< 5 mm). None of the patients showed postoperative vocal cord paralysis, and complications related to needle electrode were not identified. CONCLUSION: IONM using a single ipsilateral transcartilage needle electrode during unilateral hemithyroidectomy was feasible with no significant complications. It may serve as an alternative method of IONM with the advantage of minimal exposure of the thyroid cartilage lamina. LEVEL OF EVIDENCE: 4 Laryngoscope, 131:448-452, 2021.

Risperidone and Levothyroxine for Managing "Myxedema Madness".

Hypothyroidism is one of the common comorbidities seen in patients with psychiatric conditions. Sometimes few patients may present with neuropsychiatric symptoms such as cognitive slowing, depression, or psychosis ("myxedema madness"). These patients are managed with antipsychotic medications while admitting laboratory works are processed. It has been found that antipsychotic use is associated with lower free thyroxine levels, so untreated hypothyroid patients may experience worsening of symptoms with antipsychotic use. It is recommended that hypothyroid patients with psychosis be treated for the underlying hypothyroidism with thyroid hormone replacement. In this article, we are presenting a case of a hypothyroid patient presenting to a psychiatric facility for worsening psychosis and persecutory delusions, and medication non-compliance to levothyroxine. We also discuss the management of psychosis in a patient with worsening hypothyroidism with a combination regimen: levothyroxine and risperidone.

Association Between Reduced Brain Glucose Metabolism and Cortical Thickness in Alcoholics: Evidence of Neurotoxicity.

BACKGROUND: Excessive alcohol consumption is associated with reduced cortical thickness (CT) and lower cerebral metabolic rate of glucose (CMRGlu), but the correlation between these 2 measures has not been investigated. METHODS: We tested the association between CT and cerebral CMRGlu in 19 participants with alcohol use disorder (AUD) and 20 healthy controls. Participants underwent 2-Deoxy-2-[18F]fluoroglucose positron emission tomography to map CMRGlu and magnetic resonance imaging to assess CT. RESULTS: Although performance accuracy on a broad range of cognitive domains did not differ significantly between AUD and HC, AUD had widespread decreases in CT and CMRGlu. CMRGlu, normalized to cerebellum (rCMRGlu), showed significant correlation with CT across participants. Although there were large group differences in CMRGlu (>17%) and CT (>6%) in medial orbitofrontal and BA 47, the superior parietal cortex showed large reductions in CMRGlu (~17%) and minimal CT differences (~2.2%). Though total lifetime alcohol (TLA) was associated with CT and rCMRGlu, the causal mediation analysis revealed significant direct effects of TLA on rCMRGlu but not on CT, and there were no significant mediation effects of TLA, CT, and rCMRGlu. CONCLUSIONS: The significant correlation between decrements in CT and CMRGlu across AUD participants is suggestive of alcohol-induced neurotoxicity, whereas the findings that the most metabolically affected regions in AUD had minimal atrophy and vice versa indicates that changes in CT and CMRGlu reflect distinct responses to alcohol across brain regions.

Combination of fenretinide and ABT-263 induces apoptosis through NOXA for head and neck squamous cell carcinoma treatment.

The overall survival for recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) remains low, with little progress made over decades. Cisplatin, most frequently used for HNSCC treatment, activates mitochondria-dependent apoptosis through the BCL-2 family proteins. We have previously demonstrated that the pro-apoptotic BH3-only protein, NOXA plays a critical role in this process. NOXA binds and inactivates anti-apoptotic MCL-1, while the BCL-2 inhibitor ABT-263 is capable of inactivating anti-apoptotic BCL-2 and BCL-XL. We hypothesized that combination of NOXA and ABT-263 treatment increases cell death by simultaneously inhibiting anti-apoptotic BCL-2 family proteins in HNSCC cells. Here, we demonstrated that combination of ectopic NOXA expression and ABT-263 enhanced apoptosis in p53-inactive, p53 wild-type, and human papillomavirus (HPV)-positive HNSCC cell lines. Furthermore, a retinoid derivative and an endoplasmic reticulum stress inducer, fenretinide, induced NOXA, and combination of fenretinide and ABT-263 strongly induced apoptosis in HNSCC cells regardless of the HPV or p53 statuses. We also found that MCL-1 and BCL-XL are the primary targets of apoptosis induced by the combinations. These results will develop novel and alternative therapeutic strategies to directly modify the cell death machinery in HNSCC.

Experimental demonstration of quenched transmission effect of an ultrathin metallic grating.

We report on the experimental study of an anomalous transmission effect in ultrathin metallic gratings, where the metal thickness is much thinner than the skin depth. In particular, incident transverse magnetic polarized waves are reflected while incident transverse electric polarized waves are transmitted. This anomalous effect is strongly dependent on the metal thickness and metal width. We systematically investigate and demonstrate the anomalous effect and find the optimized nanostrip thickness and width by introducing a shadow-mask fabrication approach. Our results demonstrate the possibility of developing ultrathin nanostrip based planar metasurfaces with low loss.

Composite dielectric metasurfaces for phase control of vector field.

We designed, fabricated, and characterized a dielectric metamaterial lens created by varying the density of subwavelength low refractive index nanoholes in a high refractive index substrate, resulting in a locally variable effective refraction index. It is shown that a constructed graded index lens can overcome diffraction effects even when the aperture/wavelength (D/λ) ratio is smaller than 40. In addition to the conventional design of a polarization insensitive lens, we also show that a polarization diversity lens (f(o)≠f(e)) can be realized by arranging nanoholes in patterns with variable density in different transverse directions. Such a anisotropic microlens demonstrates polarization dependent focal lengths of 32 and 22 µm for linearly x- and y-polarized light, respectively, operating at a wavelength of λ=1550 nm. We also show numerically and demonstrate experimentally achromatic performance of the devices operating in the wavelength range of 1500-1900 nm with full width at half-maximum (FWHM) of the focal spots of about 4 µm.

Effect of the Pillar implant on snoring and mild obstructive sleep apnea: A multicenter study in Korea.

OBJECTIVES/HYPOTHESIS: The effect of the Pillar implant on mild sleep-disordered breathing (SDB) has been assessed in various studies. However, most of these were conducted among a non-Asian population at a single institution. Therefore, the aim of this study was to prospectively evaluate the efficacy of the Pillar implant in Asian patients with simple snoring and mild obstructive sleep apnea (OSA) at multiple centers. STUDY DESIGN: Multicenter prospective clinical trials. METHODS: This study included consecutive subjects with simple snoring or mild OSA. We examined subjective symptoms (snoring intensity, frequency, witnessed apnea, and daytime sleepiness) and objective snoring and respiratory parameters (snoring duration [proportion of sleep while snoring louder than 50 dB], snoring loudness, apnea-hypopnea index, respiratory disturbance index, minimum arterial oxygen saturation, and oxygen desaturation index ≥ 4%) at 3 to 6 months after surgery. Adverse events were also investigated. RESULTS: Twenty-nine subjects with mild SDB completed the study. Whole group analysis found significant improvements in various subjective symptoms, but not in the objective snoring and respiratory parameters. A subgroup analysis of subjects with mild OSA (n = 11) found significant alleviation in various subjective symptoms, apnea-hypopnea index, respiratory disturbance index, and oxygen desaturation index ≥ 4%. No major complication related to surgery was observed, and most minor adverse effects were resolved without morbidity. CONCLUSIONS: In selected Korean patients, the Pillar implant significantly improved not only subjective symptoms of mild SDB but also respiratory disturbances in mild OSA. LEVEL OF EVIDENCE: 2b.

Olfactory changes after endoscopic endonasal transsphenoidal approach for skull base tumors.

OBJECTIVES/HYPOTHESIS: The increased number of endoscopic endonasal transsphenoidal approaches (EETSA) has been associated with sinonasal complications such as olfactory dysfunction. Current studies have compared preoperative and postoperative olfactory function according to surgical type and age. STUDY DESIGN: Retrospective review of medical records at a tertiary referral center. METHODS: Patients were divided into two groups according to surgical type and into four groups according to age. The two surgical groups were defined based on the bilateral nasoseptal flap technique (group A: right conventional nasoseptal flap and left modified nasoseptal rescure flap; group B: bilateral modified nasoseptal rescue flap). The four age groups were ≤ 30, 31-45, 46-60, and ≥ 61 years. Patients underwent preoperative olfactory function evaluation using a visual analogue scale (VAS), the Connecticut Chemosensory Clinical Research Center Test (CCCRC), and the Cross-Cultural Smell Identification Test (CCSIT). Repeat testing was performed 6-months postoperatively. RESULTS: A total of 226 patients who underwent binostril four-hand EETSA were included in this study. In both groups A and B, the olfactory function was significantly decreased according to CCCRC and CCSIT scores (P < 0.05). The VAS scores were significantly decreased in both groups (P < 0.05). The symptom scores and olfactory test results were significantly changed in >30-year-old patients who had undergone EETSA. CONCLUSION: EETSA might contribute to olfactory dysfunction independent of surgery type. In addition, age may affect the restoration of olfaction after EETSA. Patients who plan to undergo EETSA must be informed that their olfaction may be impaired. LEVEL OF EVIDENCE: 4.

Optical tuning of silicon photonic structures with nematic liquid crystal claddings.

An analysis of and experimental demonstration of active optical tuning of silicon strip waveguides with methyl red doped nematic liquid crystal claddings is presented. Under low-power irradiation by polarized light, the reorientation of the nematic, the resulting index change, and phase shift produce a tuning range of 5.6 nm for the microresonator resonances.

Primary cardiomyocyte-targeted bioreducible polymer for efficient gene delivery to the myocardium.

A cardiomyocyte-targeted Fas siRNA delivery system was developed using primary cardiomyocyte (PCM) specific peptide-modified polymers with high transfection efficiency and low cytotoxicity. Primary cardiomyocyte (PCM) specific peptide, selected by phage display, was conjugated to bioreducible poly(cystamine bisacrylamide-diaminohexane, CBA-DAH) (PCD). The specificity of the PCM-modified polymer to cardiomyocytes was confirmed by competition study with free PCM ligand and by delivery to non-cardiomyocyte NIH 3T3 fibroblasts. The cellular binding and uptake of the PCM-polymer/pDNA polyplex was inhibited by addition of free PCM peptide. The impact of PCM conjugation on cellular uptake and transfection efficiency was greater in H9C2 rat cardiomyocytes than in NIH 3T3 cells. Fas siRNA/PCM-polymer polyplexes exhibited significant Fas gene silencing in rat cardiomyocytes under hypoxic conditions, leading to inhibition of cardiomyocyte apoptosis. These findings demonstrate the utility of the addition of a primary cardiomyocyte (PCM) specific peptide modification to a bioreducible polymer for targeted delivery of Fas siRNA to inhibit cardiomyocyte apoptosis.

Functionalized injectable hydrogels for controlled insulin delivery.

The concept of this research is using poly(beta-amino ester) (PAE) as a duo-functional group for synthesis of the novel sensitive injectable hydrogel for controlled drug/protein delivery. Firstly, PAE made of 1,4-butanediol diacrylate and 4,4'-trimethylene dipiperidine is used as a pH-sensitive moiety to conjugate to the temperature-sensitive biodegradable triblock copolymer of poly(ethylene glycol)-poly(epsilon-caprolactone) (PCL-PEG-PCL) to manufacture pH/temperature-sensitive injectable hydrogel of pentablock copolymer PAE-PCL-PEG-PCL-PAE. Furthermore, the cationic nature of PAE is used as the second function to make the ionic complexes with anionic biomolecule loaded into the hydrogel such as insulin. As a result, the release of drug/protein from this hydrogel device can be controlled by the degradation of copolymer. Sol-gel phase transition behavior of PAE-PCL-PEG-PCL-PAE block copolymer was investigated; the results showed that the aqueous media of the pentablock copolymer changed from a sol to a gel phase with increasing temperature and pH. The effect of anionic biomolecule such as insulin on sol-gel phase transition, degradation of the complex gel of the material with insulin was studied in vitro. Then the schematic of the ionic complexes between positive charges in PAE and the negatively charges in protein was simulated. In addition, the mechanism of controlled release behavior of insulin from the complex gel was supposed, which includes the chemically-controlled and diffusion-controlled stages. To prove the simulations, the cumulative release of the protein from the complex gel was investigated in vitro with different methods. Furthermore, the pharmacokinetic release of insulin from the complex gel in vivo on male Sprague-Dawley (SD) rats was compared with that from triblock copolymer hydrogel of PCL-PEG-PCL.