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Although continuous positive airway pressure is the gold standard for obstructive sleep apnea (OSA), it does not improve obesity. By contrast, bariatric surgery significantly improves obesity but with sustained OSA in the majority of patients. This study proposes a comprehensive techniquecombined airway and bariatric surgery (CABS)to improve both obesity and OSA. The aims of the study are to evaluate the feasibility, safety and efficacy of CABS in morbidly obese OSA patients. The retrospective study enrolled 20 morbidly obese OSA patients (13 males; median age, 44 years; median apnea−hypopnea index (AHI), 63.2 event/h; median body mass index (BMI), 41.4 kg/m2). The study population was divided into two groups based on patients' volition after shared decision making. The bariatric surgery (BS) group included laparoscopic sleeve gastrectomy (LSG, n = 8) and laparoscopic Roux-en-Y gastric bypass (LRYGB, n = 2). CABS involved bariatric surgeryLSG (n = 8) and LRYGB (n = 2) in conjunction with airway surgery (concurrent nasal/palatal/lingual surgery [n = 8], concurrent palatal/lingual surgery [n = 2]). Patients received a home sleep apnea test at baseline and one year after surgery. The two patient groups were not different in age, sex, preoperative AHI or preoperative BMI. There was no airway compromise, wound bleeding or infection throughout the postoperative period. One year after surgery, patients in both groups achieved significant improvement in AHI and BMI. Furthermore, the improvement in AHI was significantly higher (p = 0.04) in the CABS group than in the BS group despite the insignificant change in BMI reduction (p = 0.63) between the two groups. In the CABS group, the BMI dropped from 40.4 to 28.4 kg/m2 (p < 0.0001) and the AHI decreased from 75.1 to 4.5 event/h (p = 0.0004). The classic success rate for OSA was 90% and the cure rate was 60% in the CABS group. A perioperative assessment of CABS group patients also revealed a significant improvement in the Epworth sleepiness scale, minimal O2 saturation, snoring index and heart rate. CABS is feasible and safe in treating OSA with morbid obesity. CABS achieves more reduction in AHI than BS alone with high success and cure rates for OSA. CABS can also significantly improve quality of life and general health and offers a comprehensive alternative for morbidly obese OSA patients.
RESUMO
Objectives: To evaluate the safety and efficacy of a novel technique for transoral tongue suspension (TOTS) in obstructive sleep apnea (OSA) patients. Material and Methods: The retrospective study enrolled 24 consecutive OSA patients (21 males; average age, 43 years; average apnea−hypopnea index (AHI), 42.2 event/h; average body mass index (BMI), 25.7 kg/m2) with tongue obstruction confirmed by drug-induced sleep endoscopy. All patients received TOTS as the main procedure in conjunction with uvulopalatopharyngoplasty (UPPP). Key procedures of TOTS included a transoral sublabial approach, drilling two holes on the mandible, passing the polypropylene through the hole to the tongue base using a suture passer and returning the polypropylene through loop traction, and tying the polypropylene to the mandible. Lingual tonsil ablation (n = 8) was also implemented in hypertrophic lingual tonsils (grades III and IV). Results: The operation time for TOTS was around 30 min. No wound bleeding or airway compromise occurred throughout the postoperative period. Minor complications were temporary and included swelling of the tongue, numbness of the lower incisor, and sublabial wound dehiscence (n = 2). The quality of life improved significantly in the patients' subjective daytime sleepiness according to the Epworth Sleepiness Scale (11.4 ± 3.2 vs. 5.7 ± 1.6, p < 0.001). The objective parameters of OSA also improved significantly in the apnea/hypopnea index (42.2 ± 21.8 vs. 19.5 ± 16.2, p < 0.001), minimal oxygen saturation (77.1 ± 12.2 vs. 81.7 ± 8.1, p = 0.026), and snoring index (207 ± 141 vs. 101 ± 91, p = 0.03). Conclusions: The demonstrated TOTS showed its advantage in low morbidity with a scarless exterior and easy performance with free availability in treating adult OSA patients with tongue obstruction. TOTS combined with UPPP significantly improved AHI and daytime sleepiness. TOTS can be implemented with lingual tonsillectomy to achieve both stabilization of the tongue and widening of hypopharyngeal airway.
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BACKGROUND: Obstruction of the tongue is commonly seen in patients with obstructive sleep apnea (OSA). This study proposed whole tongue treatment using coblation ablation tongue (CAT) and aimed to explore the potential association between the dimensions of a tongue and the severity of OSA, to inspect volumetric changes of the tongue after CAT, and to search for factors that influence outcome of tongue volume change. METHODS: The prospective study enrolled 12 OSA patients (all male, average age: 35 years, average apnea/hypopnea index (AHI): 45.5 event/h, average body mass index (BMI): 27.0 kg/m2). All patients received multi-level sleep surgery including septomeatoplasty, uvulopalatopharyngoplasty, and CAT. The CAT used a coblation wand to perform uniform multiple ablations (15 points, body -6, base -9) on dorsal tongue. Three dimensions of the tongue (length, height, and width) and tongue volume were measured from head and neck computed tomography. The perioperative changes in the tongue dimension/volume and AHI were assessed at baseline and 3 months after surgery. RESULT: The baseline tongue length and AHI had a significant correlation (r = 0.60, p = 0.02). The multi-level surgery significantly improved AHI (43.8 vs. 23.7, p = 0.008). The CAT significantly decreased tongue volume from 91.3 to 85.6 cm3 (p = 0.02), with an average tongue volume reduction of 5.7 cm3 per person and 0.38 cm3 per ablation. Further outcome analysis showed surgical success was significantly higher in patients with non-hypertrophic lingual tonsils (grade I/II) than in those with hypertrophic lingual tonsils (grade III/IV) (p = 0.02). CONCLUSION: Length of the tongue is associated with the severity of OSA. The CAT significantly decreased the tongue volume in OSA patients. A volumetric reduction of 0.38 cm3 per ablation could be useful in the optimal reduction of tongue for OSA. The CAT significantly enlarged the retroglossal airway volume, which is related to the non-hypertrophic lingual tonsil.
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Wild-type p53 is known as "the guardian of the genome" because of its function of inducing DNA repair, cell-cycle arrest, and apoptosis, preventing the accumulation of gene mutations. TP53 is highly mutated in cancer cells and most TP53 hotspot mutations are missense mutations. Mutant p53 proteins, encoded by these hotspot mutations, lose canonical wild-type p53 functions and gain functions that promote cancer development, including promoting cancer cell proliferation, migration, invasion, initiation, metabolic reprogramming, angiogenesis, and conferring drug resistance to cancer cells. Among these hotspot mutations, p53-R175H has the highest occurrence. Although losing the transactivating function of the wild-type p53 and prone to aggregation, p53-R175H gains oncogenic functions by interacting with many proteins. In this review, we summarize the gain of functions of p53-R175H in different cancer types, the interacting proteins of p53-R175H, and the downstream signaling pathways affected by p53-R175H to depict a comprehensive role of p53-R175H in cancer development. We also summarize treatments that target p53-R175H, including reactivating p53-R175H with small molecules that can bind to p53-R175H and alter it into a wild-type-like structure, promoting the degradation of p53-R175H by targeting heat-shock proteins that maintain the stability of p53-R175H, and developing immunotherapies that target the p53-R175H-HLA complex presented by tumor cells.
