International expert consensus statement: surgical failure in obstructive sleep apnea.

PURPOSE: Upper airway (UA) surgery is commonly employed in the treatment of patients with obstructive sleep apnea (OSA). The intricate pathophysiology of OSA, variability in sites and patterns of UA collapse, and the interaction between anatomical and non-anatomical factors in individual patients may contribute to possible surgical failures. This clinical consensus statement aims to identify areas of agreement among a development group comprising international experts in OSA surgery, regarding the appropriate definition, predictive factors in patients, and management of surgical failure in OSA treatment. METHODS: A clinical consensus statement (CCS) was developed using the Delphi method by a panel of 35 contributors from various countries. A systematic literature review adhering to PRISMA guidelines was conducted. A survey consisting of 60 statements was then formulated and presented to the experts. RESULTS: Following two rounds of the Delphi process, consensus or strong consensus was achieved on 36 items, while 24 items remained without consensus. Specifically, 5 out of 10 statements reached consensus regarding on the 'Definition of Surgical Success/Failure after OSA Surgery'. Regarding the 'Predictive Factors of Surgical Failure in OSA Surgery', consensus was reached on 10 out of 13 statements. In the context of the 'Diagnostic Workup in OSA Surgery', consensus was achieved on 9 out of 13 statements. Lastly, in 'Treatment in Surgical Failure Cases', consensus was reached on 12 out of 24 statements. CONCLUSION: The management of OSA after surgical failure presents a significant clinical challenge for sleep specialists. This CCS provides valuable guidance for defining, preventing, and addressing surgical failures in the treatment of OSA syndrome.

Comparison of the effects of calcium channel blockers plus iron chelation therapy versus chelation therapy only on iron overload in children and young adults with transfusion-dependent thalassemia: A randomized double-blind placebo-controlled trial.

BACKGROUND: Myocardial iron deposition is a significant cause of morbidity and mortality in patients with transfusion-dependent thalassemia (TDT). Amlodipine, L-type calcium channel blocker with regular chelation therapy may reduce myocardial iron overload. Lack of randomized trials prompted this study to assess the effect of calcium channel blocker (amlodipine) in combination with iron chelation therapy on iron overload in patients with TDT. METHODS: Sixty-four eligible patients were randomized to receive either amlodipine and chelation (group A) or chelation alone (group B) in double-blind placebo-controlled trial. Myocardial iron concentration (MIC) using T2* magnetic resonance imaging (MRI), liver iron concentration (LIC), left ventricular ejection fraction (LVEF), and serum ferritin were measured at baseline and 12 months. RESULTS: In the amlodipine group, mean cardiac T2* value significantly increased from 18.11 ± 8.47 to 22.15 ± 7.61 (p = .002) at 12 months, whereas in control group, there was a nonsignificant increase (p = .62) in cardiac T2* value from 19.50 ± 8.84 to 20.03 ± 9.07. There was a significant decrease in MRI-derived MIC in the amlodipine group compared to control group (1.93 ± 1.61 to 1.29 ± 0.90, p = .01). Changes in the LVEF (p = .45), MRI-derived LIC (p = .09), and serum ferritin (p = .81) were not significant between the two groups. CONCLUSION: Amlodipine is safe and when combined with chelation therapy appears to be more effective in reducing cardiac iron overload than chelation only in children and young adults with TDT.

Improving the Quality of Life in the Management of Allergic Rhinitis: New Perspective on Cetirizine.

BACKGROUND: Allergic rhinitis (AR) is associated with disturbed sleep and subsequent functioning, and an impaired quality of life (QoL). The symptoms of AR exhibit prominent circadian variations, with symptoms being more common at the night-time or early morning. Addressing these allergy-related sleep issues, impaired QoL, and circadian variation in symptoms is important from the patient perspective and should be considered in the management of AR. OBJECTIVE: To review the efficacy of cetirizine, a second-generation antihistamine and selective H1-receptor antagonist, in relation to improvement in the QoL of the patients, addressing the sleep disturbances and circadian variations in the symptoms of AR in clinical practice, and establishing its role as a contemporary antihistamine for the management of AR compared to newer antihistamines. METHODS: Systematic literature review of the databases such as PubMed/MEDLINE, Google Scholar, and the Cochrane Central Register of Controlled Trials from 1990 to 2020. RESULTS: The symptoms of AR exhibited a circadian variation, with symptoms being worse during the night and early morning. The patients with AR encountered several sleep-related symptoms, including poor sleep quality, daytime somnolence, fatigue, and impaired productivity and QoL. Impaired QoL in AR was related to the disease severity. Administration of cetirizine at bedtime provides effective control of sleep impairment and symptoms of AR, besides improving the QoL. The efficacy of cetirizine has been demonstrated to be superior or comparable to the newer second-generation antihistamines. Cetirizine exhibits a tolerability profile comparable to the newer antihistamines. CONCLUSION: With long years of clinical experience and a good tolerability profile, cetirizine represents a valuable therapeutic option for the management of AR, even 30 years after its introduction. Cetirizine is included in the National List of Essential Medicines of India for the management of allergic disorders in view of its established efficacy and safety profile as well as being a cost-effective option.

Role of ACE inhibitors in anthracycline-induced cardiotoxicity: A randomized, double-blind, placebo-controlled trial.

BACKGROUND: Several measures including drugs have been tried to reduce anthracycline cardiotoxicity. The lack of randomized trials prompted this study to assess the role of an angiotensin converting enzyme (ACE) inhibitor (enalapril) in anthracycline-induced cardiotoxicity in children with hematological malignancies. METHODS: A randomized, double-blind, placebo-controlled trial was conducted on 84 patients with leukemia (41) and lymphoma (43) who received anthracyclines (doxorubicin and/or daunorubicin) at cumulative dose ≥200 mg/m2 . The patients were randomized to receive either enalapril [group A (n = 44)] or placebo [group B (n = 40)] for 6 months. Left ventricular ejection fraction (LVEF) and cardiac biomarkers (cardiac troponin I [cTnI], probrain natriuretic peptide [proBNP], and creatine kinase MB [CK-MB]) were assessed at baseline and 6 months. The primary outcome was a measured decrease in LVEF (≥20%). Secondary outcome measures were changes in cardiac biomarkers and the development of heart failure or arrhythmias. RESULTS: LVEF decreased in both groups at 6 months, more so in group B (62.25 ± 5.49 vs 56.15 ± 4.79, P < 0.001). A ≥20% decrease was seen in 3 patients in group B but none in group A (P = 0.21). Cardiac biomarkers increased more in group B at 6 months, and the increase was significant for proBNP (49.60 ± 35.97 vs 98.60 ± 54.24, P < 0.001) and cTnI (0.01 ± 0.00 vs 0.011 ± 0.003, P = 0.035) but not significant for CK-MB (1.08 ± 0.18 vs 1.21 ± 0.44, P = 0.079). In group A, 9.1% of the patients showed an increase in proBNP level ≥100 compared with 37.5% in group B (P < 0.001). No patient developed heart failure or arrhythmia. CONCLUSION: Enalapril has a role in reducing cardiac toxicity after anthracycline administration.

Urinary Kidney injury molecule-1 can predict delayed graft function in living donor renal allograft recipients.

AIM: Delayed graft function is an early complication leading to impaired creatinine clearance, urine formation and determinant of long term graft outcome. The aim of the present study was to determine the earliest predictive cut-off value of uKIM-1 level in patients with delayed graft function and acute tubular necrosis. METHODS: We have determined the serial urinary KIM-1 normalized to urinary creatinine (uKIM-1, pg/mg) level at 0, 6, 12, 18, 24 and 48 h of post-transplant by ELISA methods. RESULT: The normalized uKIM-1 and AUC-ROC, of uKIM-1 were progressively increased up to 48 h in both delayed graft function (DGF) and immediate graft function (IGF). The u KIM-1 values were significantly high at 6, 12, 18, 24 and 48 h in patients with DGF as compared to that of IGF except at half an hour post-transplant values. Although, progressive increase in uKIM-1 values were observed in both groups of patients; there was an overlap of values between two groups up to 12 h. The earliest non-overlapping values of uKIM-1 between the groups were observed at 18 h onwards and minimum difference of 923.43 pg/mg. The earliest predictive AUC-ROC of uKIM-1 in patients with DGF without overlap with IGF was also observed at 18 h post-transplant with specificity of 100% and sensitivity of 89.9%. CONCLUSION: Serial uKIM-1 measurement can be used as non-invasive diagnostic biomarkers to predict the incident of DGF in living donor renal transplant recipients. At 18(th) post-transplant hour uKIM-1 can predict DGF with 100% specificity and 89.9% sensitivity with a cut-off value of normalized KIM-1 of 923.43 pg/mg.

Barbed Suspension Bridge Pharyngoplasty: Introducing a Novel Technique for Barbed Pharyngoplasty.

Surgical management of Obstructive Sleep Apnea (OSA) and Snoring has undergone many major and minor changes over a period of last decade. The most common surgical approach for OSA is uvulopalatopharyngoplasty (Stuck et al. in Sleep Med 50:152-165, 2018). The main goals of treatment of OSA are to decrease the risk of deleterious health effects and improve quality of sleep (Evans et al. in Otolaryngol Clin North Am 53: 319-328, 2020). Since bimanual surgical techniques in the depth of oral cavity have been tricky, search for a less demanding & easy to learn technique is always on. The surgical technique should also provide long term results with manageable complications. Barbed suture has been in sporadic use for the last decade amongst sleep apnea surgeons for its advantage of knotless application and distributed suture tension. However, the barbed suture which has been used is absorbable and is used only to close the surgical wound on the soft palate. In this paper we are describing our technique of using the 3-0 Polybutester non absorbable barbed suture to perform a novel technique of palatal surgery, in which we suspend the lower part of the soft palate permanently as a suspension bridge between the right and left Pterygomandibular raphae, so that the lower part of the soft palate cannot move posteriorly to touch the posterior pharyngeal wall preventing airway obstruction whereas it can still move superiorly freely while swallowing or during phonation. This technique can prove to be a technically less demanding one which provides excellent long-term results in snoring and OSA with manageable complications.

Pulmonary Artery Hypertension in Transfusion-Dependent Thalassemia.

OBJECTIVE: Patients with transfusion-dependent thalassemia (TDT) are at risk of developing pulmonary artery hypertension (PAH) due to chronic hemolysis, iron overload, hypercoagulability and splenectomy. The objective of the study was to assess the prevalence and predictors of PAH in patients with TDT. METHODS: Patients aged 6-18 years with TDT were included. 2D-echocardiography was done to measure the pulmonary artery systolic pressure (PASP) and left ventricular ejection fraction (LVEF). T2* MRI was done to evaluate cardiac iron overload. N-terminal-pro brain natriuretic peptide (NT-pro BNP) level was also assessed. RESULTS: Out of 61 participants, PAH was noted in 19 (31.6%). Mean (SD) age of the patients with PAH and without PAH was 12.2 (3.8) and 9.6 (3.5) years, respectively (P = 0.016). Five of 19 patients with PAH (26.3%) had undergone splenectomy as against 5 of 41 patients without PAH (12.2%) (P = 0.17). Years since splenectomy was higher in the PAH group. Mean (SD) NT-Pro BNP levels were also higher in patients with PAH [63.80 (25.89) vs 41.97 (23.95), P = 0.01]. Significantly higher number of patients with PAH had cardiac T2* value of < 10 ms (P = 0.04). Age (OR 4.11; 95% CI 1.46-8.77), years since splenectomy (OR 3.24; 95% CI 1.30-7.86), NT-Pro BNP levels (OR 4.43; 95% CI 2.14-9.61) and cardiac T2* MRI (OR 2.46; 95% CI 2.18-6.90) values were predictors of PAH in patients with TDT. CONCLUSION: PAH was observed in 31.6% of patients, with older age and years since splenectomy being important risk factors. NT-Pro BNP can be used as screening test for detecting PAH.

Exploring factors influencing sustainable human capital development: Insights from Saudi Arabia.

This study investigates the critical factors influencing Saudi Arabia's sustainable human capital development. It primarily aims to explore the correlations among the postulated variables and how each variable influences the development of a skilled, adaptable, and socially conscious workforce, in alignment with the objectives of the Saudi Vision 2030. This study utilizes a quantitative approach, employing partial least squares structural equation modeling to analyze the data collected from 203 public personnel in Saudi Arabia through an online questionnaire. The findings reveal that training, community engagement, institutional support, and technology integration are essential in sustainable human capital development. However, learning, education, and access to resources were not statistically significant and did not improve sustainable human capital development in Saudi Arabia. The findings underscore the significance of an educational framework that transcends traditional perspectives, focusing on not only academic preparation but also the holistic development of individuals. This study contributes to understanding how training, community engagement, institutional support, and technology integration are transformative in shaping the future of Saudi Arabia by nurturing a skilled, adaptable, and socially responsible citizenry.

Real-World Evaluation of the Safety and Effectiveness of 2.3% Hypertonic Saline Soft Mist Spray for Sino-Nasal Symptoms.

Introduction and aims Mildly hypertonic saline is more effective in relieving symptoms of nasal congestion compared to placebo or isotonic saline. Recently, a unique device, delivering a soft mist of 2.3% hypertonic sea-salt saline (Nasoclear PureHaleTM; Zydus Healthcare Ltd., India) has been introduced in India. The device uses a power-less manual technique to release the saline as a soft mist at 1 ml/min. Methods This is a retrospective, multi-centric, single-arm study to evaluate the safety and effectiveness of 2.3% hypertonic sea-salt saline nasal irrigation delivered through a soft mist device in patients with sino-nasal symptoms. This is an analysis of data of 130 patients collected from the medical records of 11 practicing pediatricians across India. Results The mean age of the patients was 5.23 ± 4.24 years; 63 % were boys and 37% were girls (n = 130). The mean reduction in total nasal symptom score (TNSS) at follow-up from baseline was 6.28 ± 0.18 (median days = 7) (95% CI = 5.92 to 6.64; p<0.0001; mean TNSS at baseline = 7.75 ± 2.01, mean TNSS at follow-up = 1.47± 1.30). Out of 130 patients, 33 patients (25.3%) showed complete improvement in TNSS, 93 patients (71.5%) had ≥ 50% improvement in TNSS while 4 patients (3.07%) showed <50% improvement in TNSS. The effectiveness of the device was rated as excellent (75%-100% improvement) and very good (50%-75% improvement) in 41 and 74 patients, respectively. It was rated as very easy to use and easy to use by 62 patients and 57 patients, respectively. One hundred nineteen patients (91.5%) were compliant with the prescribed frequency of the device and 110 patients (84.6%) were compliant with the prescribed duration of use of the device. No serious adverse events were reported; two patients reported mild side effects - stinging and irritation of the throat. Conclusions The 2.3% hypertonic sea-salt saline nasal irrigation delivered through the soft mist device was found to be well-tolerated and effective in patients with sino-nasal symptoms in real-world clinical settings. Clinical trial number The clinical trial number of this study is CTRI/2022/07/043751.

Tetralogy of Fallot with Holt-Oram syndrome.

Holt-Oram syndrome (HOS) is characterised by mild to severe congenital cardiac defects and skeletal abnormalities of the upper limb. This syndrome is also referred to as Hand-Heart syndrome. The most common cardiac disorder is an ostium secundum detected an atrial septal defect (ASD), followed by ventricular septal defect (VSD) and ostium primum ASD. We report a case of HOS with tetralogy of Fallot (TOF). This association is very rare and is hardly reported in the literature.

Noncanonical Sonic Hedgehog signaling amplifies platelet reactivity and thrombogenicity.

Sonic Hedgehog (Shh) is a morphogen in vertebrate embryos that is also associated with organ homeostasis in adults. We report here that human platelets, though enucleate, synthesize Shh from preexisting mRNAs upon agonist stimulation, and mobilize it for surface expression and release on extracellular vesicles, thus alluding to its putative role in platelet activation. Shh, in turn, induced a wave of noncanonical signaling in platelets leading to activation of small GTPase Ras homolog family member A and phosphorylation of myosin light chain in activated protein kinase-dependent manner. Remarkably, agonist-induced thrombogenic responses in platelets, which include platelet aggregation, granule secretion, and spreading on immobilized fibrinogen, were significantly attenuated by inhibition of Hedgehog signaling, thus, implicating inputs from Shh in potentiation of agonist-mediated platelet activation. In consistence, inhibition of the Shh pathway significantly impaired arterial thrombosis in mice. Taken together, the above observations strongly support a feed-forward loop of platelet stimulation triggered locally by Shh, similar to ADP and thromboxane A2, that contributes significantly to the stability of occlusive arterial thrombus and that can be investigated as a potential therapeutic target in thrombotic disorders.

Understanding controls on the geochemistry of hydrocarbon produced waters from different basins across the US.

The most massive waste stream generated by conventional and unconventional hydrocarbon exploration is the produced water (PW). The costs and environmental issues associated with the management and disposal of PW, which contains high concentrations of inorganic and organic pollutants, is one of the most challenging problems faced by the oil and gas industry. Many of the current strategies for the reuse and recycling of PW are inefficient because of varying water demand and the spatial and temporal variations in the chemical composition of PW. The chemical composition of PW is controlled by a multitude of factors and can vary significantly over time. This study aims to understand different parameters and processes that control the quality of PW generated from hydrocarbon-bearing formations by analyzing relationships between their major ion concentrations, O, H, and Sr isotopic composition. We selected PW data sets from three conventional (Trenton, Edwards, and Wilcox Formations) and four unconventional (Lance, Marcellus, Bakken, and Mesaverde Formations) oil and gas formations with varying lithology and depositional environment. Using comparative geochemical data analysis, we determined that the geochemical signature of PW is controlled by a complex interplay of several factors, including the original source of water (connate marine vs. non-marine), migration of the basinal fluids, the nature and degree of water-mineral-hydrocarbon interactions, water recharge, processes such as evaporation and ultrafiltration, and production techniques (conventional vs. unconventional). The development of efficient PW recycle and reuse strategies requires a holistic understanding of the geological and hydrological history of each formation to account for the temporal and spatial heterogeneities.

Design and evaluation of microemulsion-based efinaconazole formulations for targeted treatment of onychomycosis through transungual route: Ex vivo and nail clipping studies.

The onychomycosis treatment remains a big challenge for onychologist due to the shorter nail residence time of topical formulations and the lack of availability of novel formulations in markets for new generation antifungal drugs. The objective of this work was to design, develop, optimize, and evaluate microemulsion formulations for effective delivery of efinaconazole through transungual route in onychomycosis treatment. Capmul® MCM (Glyceryl Caprylate/Caprate) as oil, Labrasol® (caprylocaproyl polyoxyl-8 glycerides) as a surfactant, and Transcutol® P (diethylene glycol monoethyl ether) as co-surfactant exhibited higher solubility of efinaconazole and surfactant-cosurfactant mixture (Smix) in a ratio of 1:1 rendered higher microemulsion region in the pseudo-ternary phase diagram. The optimized microemulsion formulation containing 6%w/w oil phase, 22.5%w/w surfactant, 22.5%w/w co-surfactant, and 49%w/w demineralized water was converted into gel formulation using 1.0%w/w Carbopol® 934 P gelling agent and evaluated for stability of 6 months. The optimized microemulsion formulation globule size was less than 100 nm. The ex vivo permeation confirmed improved permeation of efinaconazole from microemulsion formulations (346.36±12.90µgcm-2) in comparison to reference formulation without observing any lag in drug permeation through the nail plate. The in vitro antifungal study data indicated increased antifungal efficacy relative to efinaconazole topical solution against Trichophyton rubrum, Trichophyton mentagrophytes, and Candida albicans species. Further, an in vitro cell cytotoxicity study exhibited no toxic effect for any excipients used in the formulation while applied on nail cells. Hence, the efinaconazole loaded microemulsion formulations could be considered as an effective therapy in the treatment of onychomycosis.

Effect of ivabradine on heart rate, functional capacity and pulmonary artery pressure in patients of COPD with cor pulmonale.

We studied the effects of heart rate reduction by ivabradine to the ongoing therapy in patients with chronic obstructive pulmonary disease (COPD) and cor pulmonale.100 patients of COPD with cor pulmonale with sinus heart rate ≥ 90 bpm were randomly assigned to either ivabradine 5 mg twice daily (50 patients) or placebo (50 patients) alongwith standard therapy. Assessment was done at baseline and after 6 months which included 6 min walk test (6MWT), dyspnea scoring by modified borg scale, Lung function test by forced expiratory volume in 1 s (FEV1) and pulmonary artery systolic pressure (PASP) by echocardiogram. The drug group showed a significant reduction in heart rate from 95.1 ± 8.2 bpm to 71.1 ± 6.2 bpm (p < 0.001). This group also showed significant improvement in 6-min walk distance and dyspnea on modified Borg scale (p < 0.001) at 6 months follow up. However no significant difference was found between both groups regarding PASP or FEV1 at 6 months.

Unilateral Basal Ganglia Hyperintensity Secondary to Venous Congestion in a Case of Indirect Carotico-cavernous Fistula.

Intraparenchymal venous congestive changes secondary to carotico-cavernous fistula are not common. Isolated basal ganglia venous congestive changes in carotico-cavernous fistula have been rarely described. We report MRI findings of the unilateral basal ganglia hyperintensity, angiographic features including cortical venous reflux into a variant basal vein of Rosenthal, in a postpartum woman presenting with the left eye proptosis and the right upper limb weakness. We also describe the reversal of imaging findings and resolution of patients' symptoms after definitive treatment of the carotico-cavernous fistula by endovascular embolization.

Geochemical controls on CO2 interactions with deep subsurface shales: implications for geologic carbon sequestration.

One of the primary drivers of global warming is the exponential increase in CO2 emissions. According to IPCC, if the CO2 emissions continue to increase at the current rate, global warming is likely to increase by 1.5 °C, above pre-industrial levels, between the years 2030 and 2052. Efficient and sustainable geologic CO2 sequestration (GCS) offers one plausible solution for reducing CO2 levels. The impermeable shale formations have traditionally served as good seals for reservoirs in which CO2 has been injected for GCS. The rapid development of subsurface organic-rich shales for hydrocarbon recovery has opened up the possibility of utilizing these hydraulically fractured shale reservoirs as potential target reservoirs for GCS. However, to evaluate the GCS potential of different types of shales, we need to better understand the geochemical reactions at CO2-fluid-shale interfaces and how they affect the flow and CO2 storage permanence. In this review, we discuss the current state of knowledge on the interactions of CO2 with shale fluids, minerals, and organic matter, and the impact of parameters such as pressure, temperature, and moisture content on these interactions. We also discuss the potential of using CO2 as an alternate fracturing fluid, its role in enhanced shale gas recovery, and different geochemical tracers to identify whether CO2 or brine migration occurred along a particular fluid transport pathway. Additionally, this review highlights the need for future studies to focus on determining (1) the contribution of CO2 solubility and the impact of formation water chemistry on GCS, (2) the rates of dissolution/precipitation and sorption reactions, (3) the role of mineralogical and structural heterogeneities in shale, (4) differences in reaction mechanisms/rates between gaseous CO2vs. brine mixed CO2vs. supercritical CO2, (5) the use of CO2 as a fracturing fluid and its proppant carrying capacity and (6) the role of CO2 in enhanced hydrocarbon recovery.

Intraoperative Transcranial Embolization following Decompressive Craniectomy for a Dural Arteriovenous Fistula Presenting with Acutely Raised Intracranial Pressure.

We report the clinical details, imaging findings, and management of a 58-year-old female who presented with rapidly deteriorating neurological function and acute raise in intracranial pressure secondary to posterior fossa dural arteriovenous fistula (DAVF). In this report, we present the emergency management of the DAVF with single-stage combined surgical decompressive craniotomy and direct transcranial embolization.

Long-term Complications of Palate Surgery: A Multicenter Study of 217 Patients.

OBJECTIVES/HYPOTHESIS: To investigate long-term complications of newer reconstructive palate surgery techniques. STUDY DESIGN: Retrospective case-series analysis. METHODS: Retrospective six-country clinical study of OSA patients who had nose and palate surgery. RESULTS: There were 217 patients, mean age = 43.9 ± 12.5 years, mean body mass index = 25.9 ± 4.7, mean preoperative apnea-hypopnea index [AHI] = 30.5 ± 19.1, follow-up 41.3 months. A total of 217 palatal procedures were performed, including 50 expansion sphincter pharyngoplasties (ESP), 34 functional expansion pharyngoplasties (FEP), 40 barbed reposition pharyngoplasties (BRP), 64 modified uvulopalatopharyngoplasties (mUPPP), 11 uvulopalatal flap procedures (UPF), nine suspension pharyngoplasties (SP), eight relocation pharyngoplasties (RP), and one z-pharyngoplasty (ZPP). Complications included were constant and/or felt twice per week; dry throat (7.8%), throat lump feeling (11.5%), throat phlegm (10.1%), throat scar feeling (3.7%), and difficulty swallowing (0.5%). Of the 17 patients who had a dry throat complaint, two were constant (one SP, one RP), 15 were occasional (10 mUPPP, three SP, two BRP). Of the 25 patients with the throat lump feeling, four were constant (three RP, one ZPP), 21 were occasional (10 mUPPP, five SP, five UPF, one BRP). Of the 22 patients with the throat phlegm feeling, four were constant (two SP, two RP), 18 were occasional (10 mUPPP, four BRP, two FEP, two SP). Of the eight patients with throat scar feeling, eight were occasional (four SP, two mUPPP, one FEP, one RP), none were constant. One patient had difficulty swallowing (RP procedure). There was no velopharyngeal incompetence, taste disturbance, nor voice change. Highest symptom complaints were mUPPP, SP, and RP, whereas the lowest symptom complaint was ESP. CONCLUSIONS: Newer palatal techniques have shown to have less long-term complications compared to the older ablative techniques. LEVEL OF EVIDENCE: 4 Laryngoscope, 130:2281-2284, 2020.

C/EBPbeta regulates metastatic gene expression and confers TNF-alpha resistance to prostate cancer cells.

BACKGROUND: CCAAT/enhancer-binding protein beta (C/EBPbeta) is a transcription factor and consists of three isoforms, transcription-activating A/B (C/EBPbeta-AB) and transcription inhibitory C (C/EBPbeta-C). We previously reported that C/EBPbeta-C was predominantly expressed in hormone-dependent LNCaP cells, while C/EBPbeta-AB forms were predominant in hormone-independent prostate cancer (HI-PCa) cells. METHODS: Reporter gene analysis was performed to investigate transcriptional activity of C/EBPbeta on metastatic gene expression upon TNF-alpha treatment. NF-kappaB activation and C/EBPbeta protein upregulation were determined by immunoblotting. WST assay was used to determine the role of C/EBPbeta in TNF-alpha-induced cell death. RESULTS: We first determined that the C/EBPbeta-C overexpression or siRNA-mediated C/EBPbeta depletion decreased TNF-alpha-induced promoter activities of Bfl-1, IL-6, and IL-8 genes. IL-6 and IL-8 are autocrine growth factors of HI-PCa cells and Bfl-1 is an anti-apoptotic protein whose function in prostate cancer is yet to be determined. Secondly, we determined differential regulation of C/EBPbeta by TNF-alpha. In DU-145 cells, C/EBPbeta was upregulated by TNF-alpha, but downregulated in LNCaP cells, although NF-kappaB was activated in both cells. This result suggested cell-type specific activation of signaling pathways leading to C/EBPbeta upregulation, which was distinct from that leading to NF-kappaB activation. Most importantly, C/EBPbeta depletion decreased cell growth and sensitized DU-145 cells to TNF-alpha-induced cell death. Conversely, overexpression of C/EBPbeta-A in LNCaP cells increased resistance to TNF-induced cell death and TNF-induced promoter activities of IL-6 and Bfl-1. CONCLUSION: Our study, for the first time, demonstrated that C/EBPbeta regulated cell growth and conferred TNF-alpha resistance to PCa cells, in part, via regulation of metastatic gene expression. Prostate 69: 1435-1447, 2009. (c) 2009 Wiley-Liss, Inc.