Five-Year Subjective Outcomes of Obstructive Sleep Apnea Surgery: A Multiinstitutional Study

Objectives

To evaluate the effect of obstructive sleep apnea (OSA) surgery on long-term (5-year) subjective outcomes, including sleep disordered breathing (SDB) symptoms and other complications, in patients with OSA.

Methods

We enrolled patients who underwent diagnostic polysomnography for OSA between January 2006 and December 2006 in ten hospitals. Patients either were treated for OSA or were not treated for OSA. All patients completed a brief telephone survey regarding their SDB signs and symptoms (e.g., snoring, apnea, nocturnal arousals, and daytime sleepiness), positive airway pressure (PAP) compliance, and any adverse effects of either the surgery or PAP. A positive subjective outcome for either surgery or no treatment was taken to be the alleviation of apnea, defined as a ≥50% increase in score. A positive subjective outcome (compliance) for PAP was defined as a PAP usage of ≥4 hours per night and ≥5 days per week.

Results

A total of 229 patients were included in this study. Patients were divided into three groups: a surgery group (n=87), a PAP group (n=68), and a control (untreated) group (n=74). The surgery group exhibited significant improvement in all SDB symptoms compared with the control group. The long-term subjective outcomes of the surgery (52.9%) and PAP (54.4%) groups were significantly better than those of the control group (25.0%). The subjective outcome of the surgery group was not significantly different from that of the PAP group. The overall surgical complication rate was 23.0% (20 of 87) in the surgery group, and 55.0% (22 of 40) of all patients with PAP experienced adverse effects.

Conclusion

The extent of SDB symptoms was consistently improved in patients with OSA at 5 years postsurgery. Information about the potential long-term subjective outcomes should be provided to patients when considering surgery.     

Comparison of Preoperative and Postoperative Ocular Biometry in Eyes with Phakic Intraocular Lens Implantations

Purpose

To compare preoperative and postoperative ocular biometry in patients with iris-fixated phakic intraocular lens (pIOLs): Artisan and Artiflex.

Materials and Methods

This study included 40 eyes with Artisan and 36 eyes with Artiflex pIOL implants. Anterior chamber depth (ACD) and axial length (AL) were measured by applanation ultrasonography (A-scan) and partial coherence interferometry (IOLMaster) preoperatively and 3 months after pIOL implantation.

Results

ACD measurements after Artisan or Artiflex pIOL implantation were smaller than preoperative measurements. Specifically, the difference after Artisan pIOL implantation was -1.07±0.17 mm by A-scan and -0.08±0.08 mm by IOLMaster. The difference after Artiflex pIOL implantation was -1.31±0.15 mm by A-scan and -0.05±0.07 mm by IOLMaster. After Artisan pIOL implantation, differences in AL measurements by A-scan were insignificant (difference: -0.03±0.15 mm), whereas postoperative AL measurements by IOLMaster were significantly longer than preoperative measurements (difference: 0.12±0.07 mm). After Artiflex pIOL implantation, AL measurements by both A-scan and IOLMaster were significantly longer than preoperative measurements (difference: 0.09±0.16 mm by A-scan and 0.07±0.10 mm by IOLMaster). In the Artiflex group, differences in AL measurements by A-scan correlated with the central thickness of the Artiflex pIOL.

Conclusion

ACD and AL measurements were influenced by iris-fixated phakic IOL implantation.     

Geranylgeranyl pyrophosphate amplifies Treg differentiation via increased IL-2 expression to ameliorate DSS-induced colitis

Blocking the mevalonate pathway for cholesterol reduction by using statin may have adverse effects including statin-induced colitis. Moreover, one of the predisposing factors for colitis is an imbalanced CD4⁺ T cell, which can be observed on the complete deletion of HMG-CoA reductase (HMGCR), a target of statins. In this study, we inquired geranylgeranyl pyrophosphate (GGPP) is responsible for maintaining the T-cell homeostasis. Following dextran sulfate sodium (DSS)-induced colitis, simvastatin increased the severity of disease, while cotreatment with GGPP, but not with cholesterol, reversed the disease magnitude. GGPP ameliorated DSS-induced colitis by increasing T_reg cells. GGPP amplified T_reg differentiation through increased IL-2/STAT 5 signaling. GGPP prenylated Ras protein, a prerequisite for extracellular signal-regulated kinase (ERK) pathway activation, leading to increased IL-2 production. Higher simvastatin dose increased the severity of colitis. GGPP ameliorated simvastatin-increased colitis by increasing T_reg cells. T_reg cells, which have the capacity to suppress inflammatory T cells and were generated through IL-2/STAT5 signaling, increased IL-2 production through prenylation and activation of the Ras/ERK pathway.     

Revised Korean Antiviral Guideline Reduces the Hepatitis B-related Hepatocellular Carcinoma Risk in Cirrhotic Patients

BackgroundSince September 2015, the initiation of antiviral therapy (AVT) for patients with chronic hepatitis B (CHB)-related cirrhosis has been reimbursed according to the revised Korean Association for the Study of Liver (KASL) guideline, if the patient had hepatitis B virus DNA level ≥ 2,000 IU/L, regardless of aminotransferase or alanine aminotransferase levels. This study investigated whether the KASL guideline implementation reduced the risk of CHB-related hepatocellular carcinoma (HCC) in patients with cirrhosis in South Korea.MethodsA total of 429 patients with CHB-related cirrhosis who initiated AVT between 2014 and 2016 were recruited. The risk of HCC development was compared between patients who initiated AVT before and after September 2015 (pre-guideline [n = 196, 45.7%] vs. post-guideline implementation [n = 233, 54.3%]).ResultsUnivariate analysis showed that AVT initiation before guideline implementation, older age, male gender, and diabetes significantly predicted increased risk of HCC development (all P < 0.05). Subsequent multivariate analysis showed that AVT initiation before guideline implementation (HR = 1.941), older age (HR = 5.762), male gender (HR = 2.555), and diabetes (HR = 1.568) independently predicted increased risk of HCC development (all P < 0.05). Additionally, multivariate analysis showed that AVT initiation before guideline implementation (HR = 2.309), male gender (HR = 3.058), and lower platelet count (HR = 0.989) independently predicted mortality (P < 0.05). The cumulative incidences of HCC and mortality were significantly higher in patients who initiated AVT before guideline implementation than in those who initiated AVT after guideline implementation (all P < 0.05, log-rank test).ConclusionThe prognosis of patients with CHB-related cirrhosis who initiated AVT improved after guideline implementation according to the revised KASL guideline.     

Chemoradiation-induced changes in systemic inflammatory markers and their prognostic significance in oesophageal squamous cell carcinoma

Objective:Chemoradiation (CRT) may induce a change in systemic inflammatory state which could affect clinical outcomes in oesophageal cancer. We aimed to evaluate the changes and prognostic significance of systemic inflammatory markers following definitive CRT in oesophageal squamous cell carcinoma.Methods:A total of 53 patients treated with concurrent CRT were included in this retrospective analysis. We compared neutrophils, lymphocytes, platelets, neutrophil–lymphocyte ratio (NLR) and platelet–lymphocyte ratio (PLR) before and after CRT using Wilcoxon signed-rank test. Overall survival (OS) and progression-free survival (PFS) were calculated. Univariable and multivariable survival analysis were performed using Cox regression analysis. Clinical univariable survival prognostic factors with p < 0.1 were included in a multivariable cox regression analysis for backward stepwise model selection.Results:Both NLR (median ∆+2.8 [IQR −0.11, 8.62], p < 001) and PLR (median ∆+227 [81.3–523.5], p < 0.001) increased significantly after CRT. Higher levels of pre-CRT, post-CRT and change (∆) in NLR and PLR were associated with inferior OS and PFS. Post-CRT NLR (HR 1.04, 95% CI 1.02–1.07, p < 0.001), post-CRT platelets (HR 1.03, 95% CI 1.01–1.05, p = 0.005), cT-stage (HR 3.83, 95% CI 1.39–10.60, p = 0.01) and RT dose (HR 0.41, 95% CI 0.21–0.81, p = 0.01) were independent prognostic factors for OS in multivariable analysis. Change in NLR (HR 1.04, 95% CI 1.01–1.06, p = 0.001), post-CRT platelets (HR 1.03, 95% CI 1.01–1.05, p = 0.002), cT-stage (HR 3.98, 95% CI 1.55–10.25, p = 0.004) and RT dose (HR 0.41, 95% CI 0.21–0.80, p = 0.009) were independent prognostic factors for PFS.Conclusion:Both NLR and PLR increased following definitive CRT. Post-CRT NLR and ∆NLR were associated with adverse survival in oesophageal SCC.Advances in knowledge:We showed that CRT increased PLR and NLR, possibly reflecting a systemic inflammatory state which were associated with poor clinical outcomes in oesophageal SCC.     

Effects of Deletion of ERα in Osteoblast‐Lineage Cells on Bone Mass and Adaptation to Mechanical Loading Differ in Female and Male Mice

Estrogen receptor alpha (ERα) has been implicated in bone's response to mechanical loading in both males and females. ERα in osteoblast lineage cells is important for determining bone mass, but results depend on animal sex and the cellular stage at which ERα is deleted. We demonstrated previously that when ERα is deleted from mature osteoblasts and osteocytes in mixed‐background female mice, bone mass and strength are decreased. However, few studies exist examining the skeletal response to loading in bone cell–specific ERαKO mice. Therefore, we crossed ERα floxed (ERα^fl/fl) and osteocalcin‐Cre (OC‐Cre) mice to generate animals lacking ERα in mature osteoblasts and osteocytes (pOC‐ERαKO) and littermate controls (LC). At 10 weeks of age, the left tibia was loaded in vivo for 2 weeks. We analyzed bone mass through micro‐CT, bone formation rate by dynamic histomorphometry, bone strength from mechanical testing, and osteoblast and osteoclast activity by serum chemistry and immunohistochemistry. ERα in mature osteoblasts differentially regulated bone mass in males and females. Compared with LC, female pOC‐ERαKO mice had decreased cortical and cancellous bone mass, whereas male pOC‐ERαKO mice had equal or greater bone mass than LC. Bone mass results correlated with decreased compressive strength in pOC‐ERαKO female L₅ vertebrae and with increased maximum moment in pOC‐ERαKO male femora. Female pOC‐ERαKO mice responded more to mechanical loading, whereas the response of pOC‐ERαKO male animals was similar to their littermate controls. © 2015 American Society for Bone and Mineral Research. © 2015 American Society for Bone and Mineral Research.     

Transplantation of allogeneic peripheral blood stem cells mobilized by recombinant human granulocyte colony-stimulating factor [see comments]

Peripheral blood stem cells (PBSCs) are widely used in autologous transplantation because of ease of collection and rapid hematopoietic reconstitution. However, PBSCs have rarely been used for allogeneic transplantation because of concerns about donor toxicities from cytokine administration and the theoretical increased risk of graft- versus-host-disease (GVHD) from the large number of T cells infused. Eight patients with advanced malignancies received allogeneic PBSC transplants from genotypically HLA-identical sibling donors. All donors received 5 days of recombinant human granulocyte colony-stimulating factor (rhG-CSF; 16 micrograms/kg/day) subcutaneously and were leukapheresed for 2 days. After treatment of the patient with total body irradiation and cyclophosphamide (n = 7) or etoposide, thiotepa, and cyclophosphamide (n = 1), PBSCs were infused immediately after collection and without modification. All patients received cyclosporine and either methotrexate (n = 6) or prednisone (n = 2) for GVHD prophylaxis, rhG-CSF was well tolerated with mild bone pain requiring acetaminophen occurring in two donors. All patients engrafted and in seven hematopoietic recovery was rapid, with 500 neutrophils/microL achieved by day 18 and 20,000 platelets/microL by day 12. Complete donor engraftment was documented by Y chromosome analysis in all four sex-mismatched donor-recipient pairs tested and by DNA analysis in two sex-matched pairs. One patient died on day 18 of veno-occlusive disease of the liver with engraftment but before chromosome analysis could be performed (results are pending in 1 patient). A second patient died of fungal infection 78 days after transplant. Grade 2 acute GVHD occurred in two patients and grade 3 GVHD occurred in one patient. One patient is 301 days from transplant in remission with chronic GVHD; the remaining five patients are alive and disease free 67 to 112 days after transplantation. Preliminary results indicate that allogeneic PBSCs mobilized by rhG-CSF can provide rapid hematologic recovery without an appreciably greater incidence of acute GVHD than would be expected with marrow. Further follow-up is required to determine the incidence of chronic GVHD and any potential beneficial effects on relapse after transplant.     

Functional recovery guided by an electrospun silk fibroin conduit after sciatic nerve injury in rats

The aim of this study was to evaluate the regenerative capacity of a newly developed nerve guidance conduit using electrospun silk fibroin (SFNC) implanted in a 10‐mm defect of the sciatic nerve in rats. After evaluating the physical properties and cytocompatibility of SFNC in vitro, rats were randomly allocated into three groups: defect only, autograft and SFNC. To compare motor function and abnormal sensation among groups, ankle stance angle (ASA) and severity of autotomy were observed for 10 weeks after injury. Immunostaining with axonal neurofilament (NF) and myelin basic protein (MBP) antibodies were performed to investigate regenerated nerve fibres inside SFNC. ASA increased significantly in the SFNC group at 1, 7 and 10 weeks after injury compared to the defect only group (p < 0.05). At one week, mean ASA of the SFNC group was significantly higher than that of the autograft group (p < 0.05). Onset and severity of autotomy decreased significantly in the SFNC group compared to other groups (p < 0.05). Autotomy in the SFNC group started at 4 weeks and maximally reached toe level. However, the defect only and autograft groups first showed autotomy at 2 and 1 weeks following injury, respectively, and then reached the sole level. Well myelinated nerve fibres stained with NF and MBP were found inside SFNC. In conclusion, SFNC could be helpful in restoring motor function and preventing abnormal sensations after nerve injury. Copyright © 2012 John Wiley & Sons, Ltd.     

The influences of position and forced respiratory maneuvers on spinal stability muscles

[Purpose] The purposes of this study were to investigate the influences of position on %MVIC of spinal stability muscles to establish for the most effective breathing pattern for activation of spinal stability muscles in order to provide an additional treatment method for use in spinal stability exercise programs. [Subjects and Methods] Thirty-three healthy subjects performed quiet breathing and four different forced respiratory maneuvers (FRM); [pursed lip breathing (PLB), diaphragmatic breathing (DB), combination breathing (CB) and respiration muscle endurance training (RMET)] in both standing and sitting positions. %MVIC of them (the multifidus (MF), erector spinae (ES), internal oblique/transversus abdominis (IO/TrA), external oblique (EO), rectus abdominis (RA) measured. [Results] IO/TrA, MF and EO showed greater activation in standing than in sitting, while RA and ES showed greater activation in sitting than in standing. RMET induced significantly greater activation of spinal stability muscles then other breathing patterns. %MVIC changes of muscle activities induced by FRM were independent of position with a few exceptions. [Conclusion] The increased respiratory demands of FRM induced greater activation of spinal stability muscles than QB. RMET was found to be the most effective breathing pattern for increasing the activation of the spinal stability muscles.Key words: Spinal stability muscles, Position, Forced respiratory maneuvers