Lymph node yield in treatment naïve cases of head and neck squamous cell carcinoma: en bloc lymphadenectomy versus level-by-level dissection.

BACKGROUND: Lymph node yield is an important prognostic factor in head and neck squamous cell carcinoma. Variability in neck dissection sampling techniques has not been studied as a determinant of lymph node yield. METHODS: This retrospective study used lymph node yield and average nodes per level to compare level-by-level and en bloc neck dissection sampling methods, in primary head and neck squamous cell carcinoma cases operated between March 2017 and February 2020. RESULTS: From 123 patients, 182 neck dissections were analysed, of which 133 were selective and the rest were comprehensive: 55 had level-by-level sampling and 127 had undergone en bloc dissection. The level-by-level method yielded more nodes in all neck dissections combined (20 vs 17; p = 0.097), but the difference was significant only for the subcohort of selective neck dissection (18.5 vs 15; p = 0.011). However, the gain in average nodes per level achieved by level-by-level sampling was significant in both groups (4.2 vs 3.33 and 4.4 vs 3, respectively; both p < 0.001). CONCLUSION: Sampling of cervical lymph nodes level-by-level yields more nodes than the en bloc technique. Further studies could verify whether neck dissection sampling technique has any impact on survival rates.

Frequency conversion of microwave signal without direct bias current using nanoscale magnetic tunnel junctions.

Frequency conversion forms an integral block of the electronic circuits used in various applications including energy harvesting, communications and signal processing. These frequency conversion units however require external power sources and occupy a large device footprint making it difficult to be integrated in micro-circuits. Here we demonstrate that nanoscale magnetic tunnel junctions can act as frequency converters without an external power supply or DC bias source. The device directly mixes an external microwave signal with the internal spin precession oscillations to create new frequencies tunable by an external magnetic field in a single device with a small device footprint. We observe up-conversion and down-conversion of the input signal for excitation frequencies between 2 GHz and 6 GHz. We also show that the device acts as a zero-bias rectifier that can generate voltages exceeding 12 mV when the excitation frequency matches the natural oscillations mode of the device.

Toxicology study for magnetic injection of prednisolone into the rat cochlea.

This paper investigates the safety of a novel 'magnetic injection' method of delivering therapy to the cochlea, in a rodent model. In this method of administration, a magnetic field is employed to actively transport drug-eluting superparamagnetic iron-oxide core nanoparticles into the cochlea, where they then release their drug payload (we delivered the steroid prednisolone). Our study design and selection of control groups was based on published regulatory guidance for safety studies that involve local drug delivery. We tested for both single and multiple delivery doses to the cochlea, and found that magnetic delivery did not harm hearing. There was no statistical difference in hearing between magnetically treated ears versus ears that received intra-tympanic steroid (a mimic of a standard-of-care for sudden sensorineural hearing loss), both 2 and 30 days after treatment. Since our treatment is local to the ear, the levels of steroid and iron circulating systemically after our treatment were low, below mass-spectrometry detection limits for the steroid and no different from normal for iron. No adverse findings were observed in ear tissue histopathology or in animal gross behavior. At 2 and 30 days after treatment, inflammatory changes examined in the ear were limited to the middle ear, were very mild in severity, and by day 90 there was ongoing and almost complete reversibility of these changes. There were no ear tissue scarring or hemorrhage trends associated with magnetic delivery. In summary, after conducting a pre-clinical safety study, no adverse safety issues were observed.

A hedgehog pathway-dependent gene signature is associated with poor clinical outcomes in Luminal A breast cancer.

PURPOSE: High expression of glioma-associated oncogene homolog-1 (GLI1) is associated with poor prognosis in estrogen receptor (ER) positive breast cancers. We sought to define a GLI1-dependent gene signature in ER-positive tumors that could further stratify patients at higher risk for disease recurrence and potentially lead to novel combination therapies. METHODS: We identified an inverse correlation between GLI1 expression and distant disease-free survival (DFS) using a dataset developed at MD Anderson Cancer Center (Hatzis dataset) containing clinical data from 508 breast cancer patients. Using a qPCR-based microarray platform, we identified genes differentially regulated by GLI1 in MCF7 cells and then determined if expression of these genes correlated with GLI1 expression in patient tumor samples. Statistical comparison between the groups was performed by ANOVA. Direct comparison of two groups was done by a two-tailed t test. Correlations between variables were done by Pearson's method. RESULTS: Expression of GLI1 and its target genes correlated significantly with worse distant DFS in breast cancer patients with Luminal A molecular subtype. Particularly, co-expression of GLI1 with EGFR and/or SNAI1, two of the identified GLI1 targets, was predictive of worse distant DFS in this subtype. Furthermore, patients with Luminal A tumors with a high GLI1 signature had a shorter distant DFS compared to the Luminal B subtype and the outcome for this group was comparable to patients with HER2-positive or basal-like tumors. CONCLUSION: We have identified a novel GLI1 gene signature that is associated with worse clinical outcomes among the patients with Luminal A subtype of breast cancer.

A Short Term Subjective and Objective Analysis of Modified Endoscopic Lothrop's Procedure and Its Functional Outcome: Our Experience.

To study the short-term functional outcomes of the endoscopic modified Lothrop procedure with well defined subjective and objective criteria. It's a retrospective cohort study with chart review carried out at a tertiary referral center. 31 patients with chronic frontal sinusitis who underwent endoscopic modified Lothrop's procedure with uncinate preservation during the period Jan 2011-2014 were followed up for a period of minimum 6 months. Assessment was done post-operatively based on subjective severity score and Kennedy's 5 point endoscopic criteria. Subjective improvement was seen in all symptoms whereas statistically significant improvement was found for the three parameters headache (p < 0.025), nose block (p < 0.03) and rhinorrhea (p < 0.05). Post operative nasal endoscopy revealed crusting and polypoidal mucosa in few patients which were managed conservatively. Asymptomatic narrowing of ostium seen in two patients. No complications were identified. The study illustrates the benefit obtained from endoscopic modified Lothrop's surgery in chronic frontal sinusitis refractory to medical treatment and standard endoscopic sinus surgery.

Changing scenario of cataract blindness in Kolar District, Karnataka, South India. The utility of rapid assessment of avoidable blindness in reviewing programs.

PURPOSE: To estimate the prevalence and causes of blindness in persons aged 50 years and over in Kolar district, India, using rapid assessment of avoidable blindness (RAAB) methodology and compare results with a similar study done in 1995. METHODOLOGY: A total of 61 clusters of 50 people aged 50 years and over were selected by probability proportional to size sampling. Households were selected by compact segment sampling. Participants were evaluated using standard RAAB methodology. RESULTS: Of 3050 people visited, 2907 were examined (95.3%). Prevalence of bilateral blindness (visual acuity, VA, <3/60 in the better eye with available correction) was 3.9%, and severe visual impairment (SVI; VA <6/60 - 3/60 in the better eye with available correction) was 3.5%. Untreated cataract was the leading cause of blindness (74.6%) and SVI (73.3%). Compared with the previous study, results showed a significant drop in prevalence of blindness from all causes from 8.0% to 3.9% (p < 0.001). Prevalence of cataract blindness (VA <3/60) had also decreased. Cataract surgical coverage (CSC) showed a significant increase from the previous survey (46.2% to 81.7%). CONCLUSION: Rapid assessments conducted once in 8-10 years at a district level, give reliable estimates on the prevalence of blindness and help monitor planning and implementation of eye care programs. Despite a turnaround in Kolar district seen over the last 16 years, with a decrease in the prevalence of blindness and increased CSC, untreated cataract continues to be the leading cause of blindness, warranting sustained service delivery efforts and careful planning.

Phase I-II study of vorinostat plus paclitaxel and bevacizumab in metastatic breast cancer: evidence for vorinostat-induced tubulin acetylation and Hsp90 inhibition in vivo.

In preclinical models, the histone deacetylase inhibitor vorinostat sensitizes breast cancer cells to tubulin-polymerizing agents and to anti-vascular endothelial growth factor-directed therapies. We sought to determine the safety and efficacy of vorinostat plus paclitaxel and bevacizumab as first-line therapy in metastatic breast cancer (MBC), and the biological effects of vorinostat in vivo. For this purpose of this study, 54 patients with measurable disease and no prior chemotherapy for MBC received vorinostat (200 or 300 mg PO BID) on days 1-3, 8-10, and 15-17, plus paclitaxel (90 mg/m(2)) on days 2, 9, 16, and bevacizumab (10 mg/kg) on days 2 and 16 every 28 days. The primary objective of the phase I study was to determine the recommended phase II dose (RPTD) of vorinostat, and for the phase II to detect an improvement of response rate from 40 to 60% (alpha = 0.10, beta = 0.10). No dose limiting toxicities were observed, and the RPTD of vorinostat was 300 mg BID. For the primary efficacy analysis in 44 patients at the RPTD, we observed 24 objective responses (55%, 95% confidence intervals (C.I) 39%, 70%). The adverse event profile was consistent with paclitaxel-bevacizumab, with the exception of increased diarrhea with the addition of vorinostat. Analysis of serial tumor biopsies in seven patients showed increased acetylation of Hsp90 and α-tubulin following vorinostat. Vorinostat induces histone and alpha tubulin acetylation and functional inhibition of Hsp90 in breast cancer in vivo and can be safely combined with paclitaxel and bevacizumab.

Epigenetic targeting in breast cancer: therapeutic impact and future direction.

Breast carcinogenesis is a multistep process involving both genetic and epigenetic changes. Epigenetics is defined as a reversible and heritable change in gene expression that is not accompanied by alteration in gene sequence. DNA methylation and histone modifications are the two major epigenetic changes that influence gene expression in cancer. The interaction between methylation and histone modification is intricately orchestrated by the formation of repressor complexes. Several genes involved in proliferation, antiapoptosis, invasion and metastasis have been shown to be methylated in various malignant and premalignant breast neoplasms. The histone deacetylase inhibitors (HDi) have emerged as an important class of drugs to be used synergistically with other systemic therapies in the treatment of breast cancer. Since epigenetic changes are potentially reversible processes, much effort has been directed toward understanding this mechanism with the goal of finding novel therapies as well as more refined diagnostic and prognostic tools in breast cancer.

LMA-Supreme--a new single-use LMA with gastric access: a report on its clinical efficacy.

BACKGROUND: LMA-Supreme (SLMA) is a new, single-use, latex-free, laryngeal mask airway with gastric access. The anatomically shaped airway tube permits easy insertion without placing fingers in the patient's mouth. The cuff is designed to provide higher seal pressures than the LMA-Classic or Unique. METHODS: A prospective, randomized, cross-over study of LMA-Proseal (PLMA) and SLMA in 36 fasted, adult, female patients with general anaesthesia, neuromuscular block (NMB) and positive pressure ventilation (PPV) is presented. RESULTS: First attempt insertion in 35/36 patients in each group (two attempts in one PLMA and three in one SLMA patient) with successful PPV in all. Median insertion time (15 s) and glottic seal pressure (28 cm H(2)O) were similar in both groups. Median volume of air for cuff inflation to 60 cm H(2)O was 22.4 ml (PLMA) and 21.9 ml (SLMA). Median age and BMI: 50 yr (range 25-74), 51 yr (23-72) and 29 kg m(-2) (range 21-46), 30 kg m(-2) (20-42) in PLMA and SLMA groups, respectively. Mallampati score mean arterial pressures after induction, and 1 min after induction and insertion of the first device were similar. A lubricated gastric tube (16Fr) was passed at the first attempt in both devices: median gastric content 15 ml (5-75), 17.5 (5-124) and a median pH of 3 (1-6), 1.5 (1-6) in the PLMA and SLMA groups, respectively. Fibreoptic laryngoscopic scores of 1-2 were recorded in 29/36 in both groups. CONCLUSIONS: Insertion success, glottic seal pressure and gastric access were similar in SLMA and PLMA.

A study on recovery of oil from sludge containing oil using froth flotation.

Induced air flotation was used to recover oil from synthetically prepared sludge containing oil. A commercial surfactant was used as the collector and frother. The effects of various parameters, namely flotation time, initial amount of oil in the feed and the amount of surfactant used on the recovery of oil were investigated. Within the range of operating conditions studied herein, the maximum oil recovery obtained was about 55%. A detailed study of flotation kinetics based on oil recovery was carried out. It showed that the process followed first-order kinetics.

Pharmacodynamics of orally administered sustained- release hydromorphone in humans.

BACKGROUND: The disposition kinetics of hydromorphone generally necessitates oral administration every 4 h of the conventional immediate-release tablet to provide sustained pain relief. This trial examined time course and magnitude of analgesia to experimental pain after administration of sustained-release hydromorphone as compared with that after immediate-release hydromorphone or placebo. METHODS: Using a 4 x 4 Latin square double-blind design, 12 subjects were randomized to receive a single dose of 8, 16, and 32 mg sustained-release hydromorphone and placebo. The same subjects had received 8 mg immediate-release hydromorphone before this study. Using an electrical experimental pain paradigm, analgesic effects were assessed for up to 30 h after administration, and venous hydromorphone plasma concentrations were measured at corresponding times. RESULTS: The hydromorphone plasma concentration peaked significantly later (12.0 h [12.0--18.0] vs. 0.8 h [0.8--1.0]; median and interquartile range) but was maintained significantly longer at greater than 50% of peak concentration (22.7 +/- 8.2 h vs. 1.1 +/- 0.7 h; mean +/- SD) after sustained-release than after immediate-release hydromorphone. Similarly, sustained-release hydromorphone produced analgesic effects that peaked significantly later (9.0 h [9.0--12.0] vs. 1.5 h [1.0--2.0]) but were maintained significantly longer at greater than 50% of peak analgesic effect (13.3 +/- 6.3 h vs. 3.6 +/- 1.7 h). A statistically significant linear relation between the hydromorphone plasma concentration and the analgesic effect on painful stimuli existed. CONCLUSION: A single oral dose of a new sustained-release formulation of hydromorphone provided analgesia to experimental pain beyond 24 h of its administration.

Lumbar epidural morphine in humans and supraspinal analgesia to experimental heat pain.

BACKGROUND: Epidural administration of morphine is a common analgesic technique to manage pain. Morphine spreads from the epidural space to the cerebrospinal fluid and then rostrally, causing side effects mediated by the brain stem. However, data on the rostral spread of morphine-mediated analgesia are sparse. This study examined the rostral spread of analgesic effects on heat and electrical pain after epidural administration of morphine. METHODS: In a randomized, double-blinded, placebo-controlled, crossover study, 5 mg morphine or saline placebo were injected into the lumbar epidural space in nine healthy volunteers. Correct needle placement was confirmed with fluoroscopy. Analgesia to experimental nociceptive heat and electrical stimuli was measured at lumbar (L4), thoracic (T10), cervical (C2), and trigeminal (V2) levels before and 2, 5, 10, and 24 h after epidural injection. Plasma samples for assaying morphine concentrations were drawn before and after each analgesic evaluation. RESULTS: Epidural morphine significantly attenuated experimental heat pain at all dermatomes tested compared with saline placebo. Analgesic effects were significant at L4 after 2, 5, and 10 h, at T10 after 5, 10, and 24 h, and at V2 after 10 h. Electrical pain was attenuated at the lumbar and thoracic but not at the cervical dermatome. Analgesic effects were significant at L4 after 2, 5, and 10 h and at T10 after 5 and 10 h. Morphine plasma concentrations were below the detection limit (1 ng/ml) in eight of the nine subjects 10 h after epidural injection. CONCLUSIONS: Lumbar epidural injection of morphine attenuated cutaneous heat pain up to the trigeminal dermatome during a 24-h observation period. In a clinical context, this implies that some types of pain may be attenuated up to the supraspinal level after lumbar epidural administration of morphine.