RNA extended interventional nucleic acid longitudinal study: Clinical performance of Aptima messenger RNA HPV testing in cervical cancer screening with a 9-year follow-up.

BACKGROUND: There is a need for additional longitudinal studies with the Aptima messenger RNA human papillomavirus test (AHPV) to support the safety of extended screening intervals. RNA-based extended interventional nucleic acid (REINA) provides relevant information on the clinical performance of AHPV. METHODS: This is a longitudinal prospective analysis of 1538 participants after AHPV and liquid-based cytology (LBC) co-test complemented with REINA interventional protocol with a second co-test 4 years after negative screening on 2000 women. Diagnostic accuracy and cumulative risks for CIN2+ up to 9 years were calculated for all test combinations. RESULTS: Sensitivity and specificity for CIN2+ were 96.9% and 88.0% for AHPV and 72.3% and 92.0% for LBC. Negative predictive value (NPV) and positive predictive value (PPV) of AHPV were 99.9% and 23.6%. The 5- and 9-year risks of AHPV-negative women were 0.4% and 1.0% (CIN2+) and 0.3% and 0.7% (CIN3+), a 73% and 64% lower risk than with negative LBC (p ≤ .002). REINA participants with an AHPV-positive result at second co-test after a negative AHPV in first round had a significantly lower 5-year risk of CIN2+ (11.1%) than AHPV-positive women with unknown HPV history (29.5%). CONCLUSIONS: Currently, this constitutes the longest European longitudinal study with AHPV testing in screening population. It reveals 99.9% NPV and a significant protective effect of a previous negative test 5 years after a new HPV infection. These findings support the safety of Aptima for screening intervals beyond 5 years. The risk of disease is lower 9 years after a negative AHPV test than 3 years after a negative LBC. High specificity and PPV of Aptima may benefit controlling overtreatment and colposcopy referrals.

Factor XIII in major burns coagulation.

BACKGROUND: In the days following a burn injury, major burn patients (MBP) present a multifactorial coagulation disorder known as acute burn-induced coagulopathy. Several studies have investigated coagulation in MBPs; however, Factor XIII (FXIII), which converts fibrin monomers into a stable clot and promotes wound healing, has not yet been studied. OBJECTIVE: To determine the kinetics of FXIII and other coagulation factors and cofactors in MBPs in order to clarify coagulopathy in these patients and its potential relationship with surgical bleeding. METHODS: Prospective observational pilot study of the kinetics of FXIII and other coagulation factors and cofactors in MBPs during the first 30 days of burn injury. RESULTS: FXIII levels show a significant decline of 75.10% in the interval between the burn injury and surgery, and a decline of 87.70% in the 24 h following surgery. Patients undergo surgery with a median antigenic FXIII of 32%. Plasma levels of most factors decrease significantly 24 h after the burn injury. CONCLUSION: MBPs experience a significant decrease in plasma levels of FXIII from the time of admission up to 24 h after surgery. Abnormally low levels were observed at the time of surgery that could not be detected by other coagulation tests. The decrease in most factors at 24 h seems to be associated with dilution due to intensive fluid resuscitation.

DISE with CPAP: a useful procedure to evaluate upper airway collapsibility.

PURPOSE: Drug-induced sleep endoscopy (DISE) is commonly performed in patients suffering obstructive sleep apnea (OSA) with continuous positive airway pressure (CPAP) intolerance. We aimed to evaluate the effects of adding CPAP to DISE to provide understanding of the reason of its failure and better guidance in future therapeutic decisions. METHODS: A retrospective observational descriptive study was conducted on CPAP-intolerant patients with moderate-severe OSA. DISE was used to evaluate upper airway collapsibility, and CPAP was tested to better describe anatomical sites of obstruction and to measure the opening pharyngeal pressure. RESULTS: Sample size consisted of 38 patients with a mean age of 49 ± 9 years. Mean BMI was 28.4 ± 2.4 kg/m2, mean apnea-hypopnea index (AHI) was 35.4 events per hour ± 20.1, and mean saturation under 90% (TSat90) was 14.5%. In DISE we found a collapse at Velum in 92% of patients, at Oropharyngeal level in 89%, at tongue in 42%, and at epiglottis in 36%. In the subgroup of patients with clinical failure with CPAP, we observed 100% of epiglottic collapse and 50% of tongue obstruction. In this specific population, we recommended personalized surgery and myofunctional therapy. CONCLUSION: DISE-CPAP is a useful tool to select the treatment that better fits to each patient taking care all information available. It improves our ability to prescribe a multilevel treatment with an exhaustive topographic evaluation of upper airway collapsibility that complements CPAP classic titration, and it can be helpful to distinguish better candidates for surgery, myofunctional therapy or CPAP.

Physiological and therapeutic relevance of T cell receptor-mediated antigen trogocytosis.

Trogocytosis is an active process whereby fragments of plasma membrane proteins and cytoplasm are transferred from one cell to another in a cell-cell contact-dependent manner. T cells trogocytose pieces of the cells presenting antigen to them at the site of the immunological synapse. Fragments of the antigen-presenting cell membrane rich in antigen/major histocompatibility (MHC) complexes are internalized by the T cell. Those complexes are redirected to the plasma membrane of the T cell, which becomes an antigen-presenting cell to other T cells. Removing antigen/MHC complexes from professional and tumoral cells has consequences for the intensity and duration of the immune response. However, the acquired capacity of T cells to present the acquired cognate antigen/MHC complexes also affects the properties of the antigen-presenting trogocytotic T cells. Acting as antigen-presenting cells, trogocytotic CD4 T cells influence the differentiation of cytotoxic T cells and the differentiation of other CD4 T cells into pro-inflammatory effector T cells. Furthermore, trogocytosis of antigen/MHC complexes promotes the differentiation of the trogocytotic CD4 T cells towards regulatory T cells and Th2 effector cells. Trogoctyosis is, therefore, a parallel mechanism to signal transduction by membrane receptors, including the T cell antigen receptor, at the plane of the plasma membrane.

Growth hormone remodels the 3D-structure of the mitochondria of inflammatory macrophages and promotes metabolic reprogramming.

Introduction: Macrophages are a heterogeneous population of innate immune cells that support tissue homeostasis through their involvement in tissue development and repair, and pathogen defense. Emerging data reveal that metabolism may control macrophage polarization and function and, conversely, phenotypic polarization may drive metabolic reprogramming. Methods: Here we use biochemical analysis, correlative cryogenic fluorescence microscopy and cryo-focused ion-beam scanning electron microscopy. Results: We demonstrate that growth hormone (GH) reprograms inflammatory GM-CSF-primed monocyte-derived macrophages (GM-MØ) by functioning as a metabolic modulator. We found that exogenous treatment of GM-MØ with recombinant human GH reduced glycolysis and lactate production to levels similar to those found in anti-inflammatory M-MØ. Moreover, GH treatment of GM-MØ augmented mitochondrial volume and altered mitochondrial dynamics, including the remodeling of the inner membrane to increase the density of cristae. Conclusions: Our data demonstrate that GH likely serves a modulatory role in the metabolism of inflammatory macrophages and suggest that metabolic reprogramming of macrophages should be considered as a new target to intervene in inflammatory diseases.

Bacteria-instructed B cells cross-prime naïve CD8+ T cells triggering effective cytotoxic responses.

In addition to triggering humoral responses, conventional B cells have been described in vitro to cross-present exogenous antigens activating naïve CD8+ T cells. Nevertheless, the way B cells capture these exogenous antigens and the physiological roles of B cell-mediated cross-presentation remain poorly explored. Here, we show that B cells capture bacteria by trans-phagocytosis from previously infected dendritic cells (DC) when they are in close contact. Bacterial encounter "instructs" the B cells to acquire antigen cross-presentation abilities, in a process that involves autophagy. Bacteria-instructed B cells, henceforth referred to as BacB cells, rapidly degrade phagocytosed bacteria, process bacterial antigens and cross-prime naïve CD8+ T cells which differentiate into specific cytotoxic cells that efficiently control bacterial infections. Moreover, a proof-of-concept experiment shows that BacB cells that have captured bacteria expressing tumor antigens could be useful as novel cellular immunotherapies against cancer.

Quantification of Intracellular ATP Content in Ex Vivo GC B Cells.

The study of immunometabolism is an important and emerging field in immunology. B-cell activation upon antigen recognition induces profound metabolic changes in the cell, leading to an increase in ATP production to sustain cell proliferation and differentiation. Current methods available to determine the amount of ATP are time-consuming, require extensive sample processing, and need a large amount of starting material. We set up an easy follow-up protocol to determine the relative amount of ATP in living cells, combining cell surface staining with quinacrine. This acridine dye emits a green fluorescent signal in the presence of intracellular ATP. This protocol allows us to determine ATP in small populations of cells using flow cytometry, such as the germinal center.

Recovery of hypothalamic-pituitary-gonadal function with low dose testosterone treatment in a male with congenital hypogonadotropic hypogonadism.

Congenital hypogonadotropic hypogonadism (CHH) is a rare disease caused by deficiency or action of gonadotropin-releasing hormone. While generally considered a long-life condition, CHH can be reversible in about 5%-20% of cases, but mechanisms of reversibility are unknown. We report the case of a male with CHH who began treatment with low dose (20 mg/day) transdermal testosterone to induce pubertal development at age 17. Following the start of treatment, he experienced testicular growth and his serum testosterone concentrations increased beyond the expectations in relation to the dose. Treatment was withdrawn, but this led to the reappearance of symptoms of hypogonadism and a drop in testosterone levels. Testosterone was again prescribed at the same dose and, for the subsequent years, he completed full puberty, including attainment of 20 cc testicular volume, mature secondary sexual characteristics, normal levels of testosterone and only partially arrested germinal function, as demonstrated by inhibin B levels and spermogram. Testosterone treatment was withdrawn three more times, but hypogonadism resumed on each occasion. This case suggests that low-dose testosterone treatment can induce reversal of CHH through the activation, albeit non-permanent, of the hypothalamic-pituitary-gonadal axis, indicating that testosterone administration might be a reliable therapeutic option for reverting GnRH deficiency.

[Consequences of the COVID-19 lockdown in patients with chronic diseases in Andalusia]. / Repercusiones del confinamiento por COVID-19 en pacientes crónicos de Andalucía.

OBJECTIVE: To understand the consequences of the COVID-19 pandemic lockdown on the self-care of people living with chronic diseases and on their self-perceived health, and to identify factors that may influence the management of their disease in emergency situations. METHOD: A qualitative study conducted in 2020 (March and April) in Andalusia (Spain) during the COVID-19 pandemic lockdown, through virtual focus groups, using the Zoom telematics tool. Three virtual focus groups were conducted, including 34 patients from Andalusia with different chronic conditions such as arthritis, diabetes, cardiovascular disease, inflammatory bowel disease, breast cancer and fibromyalgia. RESULTS: People with chronic diseases reported effects of the lockdown in relation to their emotional experience, their coping resources, the information they received, the difficulties to manage self-care, and the contact or access to health services. They also suggested some lessons learned for the future. The need for more and better information, patient training, involving patient associations, and improving telematics access to health services are the main areas for improvement to minimize the impact of future quarantines on the self-care and the health of people with chronic diseases. CONCLUSIONS: Besides the risk of contracting COVID-19, the difficulties encountered by people with chronic diseases during the lockdown include interferences in the self-care and the health care received. Health crisis situations demand more information, training for patients and improvements in the health services accessibility for patients with chronic conditions.

Drug Induced Sleep Endoscopy Versus Awake Endoscopy in Retrolingual Obstruction Assessment in Obstructive Sleep Apnea Patients: A Comparative Study.

ABSTRACT: The aim of this study is to evaluate the correlation of retrolingual obstruction determined by drug induced sleep endoscopy (DISE) and awake endoscopy evaluation of Muller maneuver (MM) and lingual tonsil hypertrophy (LTH) in patients with obstructive sleep apnea.A prospective cohort of 100 patients with obstructive sleep apnea who underwent DISE was assessed. The inclusion criteria were age between 18 and 70 years, and apnea-hypopnea index higher than 5. Friedman staging, LTH and MM were determined by awake endoscopy, as other physical findings. The authors evaluated the correlation of retrolingual obstruction determined by DISE using velum oropharynx tongue, epiglottis (VOTE) and nose, oropharynx, hypopharynx, larynx (NOHL) classification.When retrolingual MM was assessed, significant changes between awake and DISE were observed ( P = 0.000). Conversely, Friedman stage had no significant changes to DISE retrolingual findings ( P = 0.868). Analyzing LTH and DISE retrolingual findings according to NOHL and VOTE, if a cutoff value was established at 50%, DISE findings differ from awake: NOHL ( P <0.001) and VOTE ( P = 0.004). Nevertheless, if a restrictive cutoff at 75% was attached, DISE findings were similar to awake: NOHL ( P = 0.124) and VOTE ( P = 0.123).This study demonstrates that awake endoscopy determining LTH and Friedman stage is a mild predictor of collapse at retrolingual level, showing significant correlation to DISE only when severe retrolingual collapse is present. Our findings suggest that in-office awake endoscopy may have certain predictive value to select surgical patients.

Fibro-osseous Pseudotumor of the Distal Phalanx.

Fibro-osseous pseudotumor of the digit is an unusual benign tumor that appears on the extremities. A 45-year-old, human immunodeficiency virus-positive man presented with a painful lesion on the tip of the fourth toe of his right foot. The tumor was completely excised without any connection to the underlying bone being observed, although the phalanx had to be extirpated. Histopathology confirmed the diagnosis of fibro-osseous pseudotumor. At the follow-up visit, 12 months later, no abnormalities were found.

One-Stage Multilevel Surgery for Treatment of Obstructive Sleep Apnea Syndrome.

We report the results of one-stage multilevel upper airway surgery for patients who could not tolerate continuous positive airway pressure (CPAP). Patients treated with multilevel surgery at a University Hospital in 2015-2019 were identified from a prospectively maintained database. The inclusion criteria were aged 18-70 years, body mass index (BMI) < 35 kg/m2, apnea-hypopnea index (AHI) > 20, and lingual tonsil hypertrophy grade 3 or 4. Drug-induced sleep endoscopy was performed before surgery in all patients. Multilevel surgery was performed in one stage and included expansion sphincter pharyngoplasty (ESP), coblation tongue base reduction (CTBR), and partial epiglottectomy (PE) as required. The outcome measures were postoperative AHI, time percentage oxygen saturation < 90%, and Epworth Sleepiness Scale (ESS) score. A total of 24 patients were included: median age 49.1 years, average BMI 27.26 kg/m2, and 90% men. Ten patients received ESP plus CTBR plus PE, eight received ESP plus CTBR, and six received ESP plus PE. The mean preoperative AHI was 33.01 at baseline and improved to 17.7 ± 13 after surgery (p < 0.05). The ESS score decreased from 11 ± 5.11 to 7.9 ± 4.94 (p < 0.05). The surgical success rate according to Sher's criteria was 82.3%. The median follow-up was 23.3 months (range 12-36). These findings suggest that multilevel surgery is a safe and successful treatment of OSAHS.

Prehabilitation for Bariatric Surgery: A Randomized, Controlled Trial Protocol and Pilot Study.

Bariatric surgery is the most efficacious treatment for obesity, though it is not free from complications. Preoperative conditioning has proved beneficial in various clinical contexts, but the evidence is scarce on the role of prehabilitation in bariatric surgery. We describe the protocol and pilot study of a randomized (ratio 1:1), parallel, controlled trial assessing the effect of a physical conditioning and respiratory muscle training programme, added to a standard 8-week group intervention based on therapeutical education and cognitive-behavioural therapy, in patients awaiting bariatric surgery. The primary outcome is preoperative weight-loss. Secondary outcomes include associated comorbidity, eating behaviour, physical activity, quality of life, and short-term postoperative complications. A pilot sample of 15 participants has been randomized to the intervention or control groups and their baseline features and results are described. Only 5 patients completed the group programme and returned for assessment. Measures to improve adherence will be implemented and once the COVID-19 pandemic allows, the clinical trial will start. This is the first randomized, clinical trial assessing the effect of physical and respiratory prehabilitation, added to standard group education and cognitive-behavioural intervention in obese patients on the waiting list for bariatric surgery. Clinical Trial Registration: NCT0404636.

Generation of light-producing somatic-transgenic mice using adeno-associated virus vectors.

We have previously designed a library of lentiviral vectors to generate somatic-transgenic rodents to monitor signalling pathways in diseased organs using whole-body bioluminescence imaging, in conscious, freely moving rodents. We have now expanded this technology to adeno-associated viral vectors. We first explored bio-distribution by assessing GFP expression after neonatal intravenous delivery of AAV8. We observed widespread gene expression in, central and peripheral nervous system, liver, kidney and skeletal muscle. Next, we selected a constitutive SFFV promoter and NFκB binding sequence for bioluminescence and biosensor evaluation. An intravenous injection of AAV8 containing firefly luciferase and eGFP under transcriptional control of either element resulted in strong and persistent widespread luciferase expression. A single dose of LPS-induced a 10-fold increase in luciferase expression in AAV8-NFκB mice and immunohistochemistry revealed GFP expression in cells of astrocytic and neuronal morphology. Importantly, whole-body bioluminescence persisted up to 240 days. We have validated a novel biosensor technology in an AAV system by using an NFκB response element and revealed its potential to monitor signalling pathway in a non-invasive manner in a model of LPS-induced inflammation. This technology complements existing germline-transgenic models and may be applicable to other rodent disease models.

Association Between Use of Enhanced Recovery After Surgery Protocol and Postoperative Complications in Total Hip and Knee Arthroplasty in the Postoperative Outcomes Within Enhanced Recovery After Surgery Protocol in Elective Total Hip and Knee Arthroplasty Study (POWER2).

Importance: The Enhanced Recovery After Surgery (ERAS) care protocol has been shown to improve outcomes compared with traditional care in certain types of surgery. Objective: To assess the association of use of the ERAS protocols with complications in patients undergoing elective total hip arthroplasty (THA) and total knee arthroplasty (TKA). Design, Setting, and Participants: This multicenter, prospective cohort study included patients recruited from 131 centers in Spain from October 22 through December 22, 2018. All consecutive adults scheduled for elective THA or TKA were eligible for inclusion. Patients were stratified between those treated in a self-designated ERAS center (ERAS group) and those treated in a non-ERAS center (non-ERAS group). Data were analyzed from June 15 through September 15, 2019. Exposures: Total hip or knee arthroplasty and perioperative management. Sixteen individual ERAS items were assessed in all included patients, whether they were treated at a center that was part of an established ERAS protocol or not. Main Outcomes and Measures: The primary outcome was postoperative complications within 30 days after surgery. Secondary outcomes included length of stay and mortality. Results: During the 2-month recruitment period, 6146 patients were included (3580 women [58.2%]; median age, 71 [interquartile range (IQR), 63-76] years). Of these, 680 patients (11.1%) presented with postoperative complications. No differences were found in the number of patients with overall postoperative complications between ERAS and non-ERAS groups (163 [10.2%] vs 517 [11.4%]; odds ratio [OR], 0.89; 95% CI, 0.74-1.07; P = .22). Fewer patients in the ERAS group had moderate to severe complications (73 [4.6%] vs 279 [6.1%]; OR, 0.74; 95% CI, 0.56-0.96; P = .02). The median overall adherence rate with the ERAS protocol was 50.0% (IQR, 43.8%-62.5%), with the rate for ERAS facilities being 68.8% (IQR, 56.2%-81.2%) vs 50.0% (IQR, 37.5%-56.2%) at non-ERAS centers (P < .001). Among the patients with the highest and lowest quartiles of adherence to ERAS components, the patients with the highest adherence had fewer overall postoperative complications (144 [10.6%] vs 270 [13.0%]; OR, 0.80; 95% CI, 0.64-0.99; P < .001) and moderate to severe postoperative complications (59 [4.4%] vs 143 [6.9%]; OR, 0.62; 95% CI, 0.45-0.84; P < .001) and shorter median length of hospital stay (4 [IQR, 3-5] vs 5 [IQR, 4-6] days; OR, 0.97; 95% CI, 0.96-0.99; P < .001). Conclusions and Relevance: An increase in adherence to the ERAS program was associated with a decrease in postoperative complications, although only a few ERAS items were individually associated with improved outcomes.

Nasal Surgery May Improve Upper Airway Collapse in Patients With Obstructive Sleep Apnea: A Drug-Induced Sleep Endoscopy Study.

OBJECTIVE: The aim of this study is to evaluate the effects of nasal surgery in the upper airway (UA) collapse using drug induced sleep endoscopy (DISE) in a group of patients with obstructive sleep apnea hypopnea syndrome (OSAHS). METHODS: Prospective cohort of patients treated with nasal surgery between 2015 and 2016. All patients were diagnosed with mild to severe OSAHS. The inclusion criteria were age between 18 and 70 years, apnea-hypopnea index (AHI) higher than 15, and septal deviation. All patients had a DISE performed before surgery and 3 months after. The DISE findings were evaluated through the NOHL scale. RESULTS: Thirty-four patients were included. Surgical success with subjective and objective improvement in nasal obstructions was achieved in all cases. The pattern of UA obstruction did change significantly following nasal surgery (P < 0.05). Before nasal surgery, 74% of the patients demonstrated multilevel obstruction. After nasal surgery, only 50% patients showed multilevel collapse (P < 0.05). Among patients with single-level collapse, the oropharynx was the most common location of obstruction. It became more frequent after nasal surgery was done (41% vs 21%, P < 0.05). Significant improvement was shown in hypopharyngeal collapse. Postoperative AHI decreased from a mean of 26.7 to 19 events/h, but this change was not significant. CONCLUSION: Nasal surgery may improve hypopharyngeal collapses observed during DISE in patients with OSAHS. Thus, an improvement in nasal obstruction may also modify the surgical plan based on UA functional findings in OSAHS patients.

Oncogenic Rag GTPase signaling enhances B cell activation and drives follicular lymphoma sensitive to pharmacological inhibition of mTOR.

The humoral immune response demands that B cells undergo a sudden anabolic shift and high cellular nutrient levels which are required to sustain the subsequent proliferative burst. Follicular lymphoma (FL) originates from B cells that have participated in the humoral response, and 15% of FL samples harbor point, activating mutations in RRAGC, an essential activator of mTORC1 downstream of the sensing of cellular nutrients. The impact of recurrent RRAGC mutations in B cell function and lymphoma is unexplored. RRAGC mutations, targeted to the endogenous locus in mice, confer a partial insensitivity to nutrient deprivation, but strongly exacerbate B cell responses and accelerate lymphomagenesis, while creating a selective vulnerability to pharmacological inhibition of mTORC1. This moderate increase in nutrient signaling synergizes with paracrine cues from the supportive T cell microenvironment that activates B cells via the PI3K-Akt-mTORC1 axis. Hence, Rragc mutations sustain induced germinal centers and murine and human FL in the presence of decreased T cell help. Our results support a model in which activating mutations in the nutrient signaling pathway foster lymphomagenesis by corrupting a nutrient-dependent control over paracrine signals from the T cell microenvironment.

Prospective multi-center study on expansion sphincter pharyngoplasty.

BACKGROUND AND OBJECTIVE: The aim of this study was to demonstrate the long-term effectiveness of Expansion Sphincter Pharyngoplasty (ESP) as a standalone surgical treatment of obstructive sleep apnea-hypopnea syndrome (OSAHS) patients through a prospective multi-center study. MATERIAL AND METHODS: A prospective non-comparative multicenter study of patients suffering from OSHAS selected after drug-induced sleep endoscopy, with ESP as standing alone procedure was performed. Inclusion criteria were lateral collapse on oropharynx and preoperative AHI between 5 and 70. Minimum follow-up was >12 months. Outcome measures were Epworth sleepiness scale (ESS), AHI, success rate and CPAP need after surgery. RESULTS: A total of 75 ESP were performed. Mean patient age was 46.7 ± 10.5 years. Mean pre-operative and post-operative AHI was 22.1 ± 12.2 and 8.6 ± 6.7, respectively (p < .001). Mean pre-operative and post-operative ESS score was 11.5 ± 4.7 and 4.6 ± 6.6, respectively (p < .001). AHI <5 was obtained in 25 patients (33.3%), and CPAP was not further needed after surgery in a total of 62 patients (82.6%). CONCLUSIONS AND SIGNIFICANCE: In this prospective multi-center study, patients undergoing ESP standing alone for the treatment of OSAHS have a reasonable expectation for success with minimal morbidity.

Expansion sphincter pharyngoplasty: Usefulness of DISE. / Faringoplastia de expansión: utilidad de la somnoscopia (DISE).

OBJECTIVES: The aim of this study was first to present the indications and results using expansion sphincter pharyngoplasty to treat obstructive sleep apnoea-hypopnoea syndrome (OSAHS). And second, to compare the findings of drug-induced sleep endoscopy (DISE) before and after the surgery. MATERIAL AND METHODS: The study design was a prospective cohort of patients surgically treated between 2015 and 2016. All patients were diagnosed with mild to severe obstructive sleep apnoea and did not tolerate CPAP. All had pre- and post-surgery DISE and polysomnography. The inclusion criteria were age, between 18 years and 70 years, small tonsils (sizes 1 and 2), Friedman II and III clinical stage, and lateral collapse in preoperative DISE. We performed surgery to the palate only, using expansion sphincter pharyngoplasty. RESULTS: Seventeen patients were included, 52.94% had severe OSAHS. Average age was 42 years, average body mass index was 28. The surgical success rate according to Sher criteria was 82.35%. 41.17% had a postoperative apnoea-hypopnoea index of less than 10. Seventy-five percent of the patients had no further need for CPAP. CONCLUSION: Expansion sphincter pharyngoplasty is a safe technique for treating OSAHS, in patients with small tonsils, Friedman grade I and II and collapse of lateral walls in DISE, in the absence of multilevel collapse. The postoperative DISE showed improvement of the lateral collapse was achieved with the expansion.

R-Ras2 is required for germinal center formation to aid B cells during energetically demanding processes.

Upon antigen recognition within peripheral lymphoid organs, B cells interact with T cells and other immune cells to transiently form morphological structures called germinal centers (GCs), which are required for B cell clonal expansion, immunoglobulin class switching, and affinity maturation. This process, known as the GC response, is an energetically demanding process that requires the metabolic reprogramming of B cells. We showed that the Ras-related guanosine triphosphate hydrolase (GTPase) R-Ras2 (also known as TC21) plays an essential, nonredundant, and B cell-intrinsic role in the GC response. Both the conversion of B cells into GC B cells and their expansion were impaired in mice lacking R-Ras2, but not in those lacking a highly related R-Ras subfamily member or both the classic H-Ras and N-Ras GTPases. In the absence of R-Ras2, activated B cells did not exhibit increased oxidative phosphorylation or aerobic glycolysis. We showed that R-Ras2 was an effector of both the B cell receptor (BCR) and CD40 and that, in its absence, B cells exhibited impaired activation of the PI3K-Akt-mTORC1 pathway, reduced mitochondrial DNA replication, and decreased expression of genes involved in glucose metabolism. Because most human B cell lymphomas originate from GC B cells or B cells that have undergone the GC response, our data suggest that R-Ras2 may also regulate metabolism in B cell malignancies.