Sustained type I interferon signaling after human immunodeficiency virus type 1 infection of human iPSC derived microglia and cerebral organoids.

Human immunodeficiency virus type-1 (HIV-1)-associated neurocognitive disorder (HAND) affects up to half of people living with HIV-1 and causes long term neurological consequences. The pathophysiology of HIV-1-induced glial and neuronal functional deficits in humans remains enigmatic. To bridge this gap, we established a model simulating HIV-1 infection in the central nervous system using human induced pluripotent stem cell (iPSC)-derived microglia combined with sliced neocortical organoids. Incubation of microglia with two replication-competent macrophage-tropic HIV-1 strains (JRFL and YU2) elicited productive infection and inflammatory activation. RNA sequencing revealed significant and sustained activation of type I interferon signaling pathways. Incorporating microglia into sliced neocortical organoids extended the effects of aberrant type I interferon signaling in a human neural context. Collectively, our results illuminate a role for persistent type I interferon signaling in HIV-1-infected microglia in a human neural model, suggesting its potential significance in the pathogenesis of HAND.

Dysregulated neuroimmune interactions and sustained type I interferon signaling after human immunodeficiency virus type 1 infection of human iPSC derived microglia and cerebral organoids.

Human immunodeficiency virus type-1 (HIV-1) associated neurocognitive disorder (HAND) affects up to half of HIV-1 positive patients with long term neurological consequences, including dementia. There are no effective therapeutics for HAND because the pathophysiology of HIV-1 induced glial and neuronal functional deficits in humans remains enigmatic. To bridge this knowledge gap, we established a model simulating HIV-1 infection in the central nervous system using human induced pluripotent stem cell (iPSC) derived microglia combined with sliced neocortical organoids. Upon incubation with two replication-competent macrophage-tropic HIV-1 strains (JRFL and YU2), we observed that microglia not only became productively infected but also exhibited inflammatory activation. RNA sequencing revealed a significant and sustained activation of type I interferon signaling pathways. Incorporating microglia into sliced neocortical organoids extended the effects of aberrant type I interferon signaling in a human neural context. Collectively, our results illuminate the role of persistent type I interferon signaling in HIV-1 infected microglial in a human neural model, suggesting its potential significance in the pathogenesis of HAND.

Minimally invasive, single-stage, multilevel surgery for obstructive sleep apnoea: A systematic review and meta-analysis.

OBJECTIVES: Minimally invasive, single-staged multilevel surgery (MISS MLS) could be an optimal treatment for selected patients with obstructive sleep apnea (OSA). We aim to systematically review the efficacy of MISS MLS for patients with OSA, as well as the clinical outcomes and possible complications in OSA patients before and after MISS MLS. DESIGN AND SETTING: Systematic review and meta-analysis. Six databases were searched, and the PRISMA guideline was followed. PARTICIPANTS: Patients with OSA receiving MISS MLS. MAIN OUTCOME MEASURES: The random-effects model was adopted for the statistical synthesis. The percentage and 95% confidence interval (CI) were adopted as the effect measurements of MISS MLS for OSA. Subgroup analyses and sensitivity analyses were also performed to identify the heterogeneity among the studies. RESULTS: There were initially 154 articles for identification. Eventually, six studies with a total of 848 OSA patients completely met the inclusion criteria and were further enrolled for analysis. The pooled analysis showed statistically significant lower AHI (apnea/hypopnea index, /hr.; mean difference: -8.931, 95% CI: -11.591 to -6.271, I2 = 87.4%), ESS (mean difference: -2.947, 95% CI: -4.465 to -1.429, I2 = 94.9%), and snoring severity with 0-10 visual analog scale after surgery (mean difference: -4.966, 95% CI: -5.804 to -4.128, I2 = 96.4%). The success rate was 46% in mild/moderate OSA; however, 18% in severe OSA. There were no major complications occurred. CONCLUSIONS: The acceptable surgical outcomes, esp. in mild/moderate OSA, and rare complications are the major advantages of MISS MLS. The evidence of this study could aid the decision making in selecting suitable treatment programs for OSA patients.

Inflammatory biomarkers of neutrophil-to-lymphocyte and platelet-to-lymphocyte ratios in 563 severe OSA patients before and after surgery.

BACKGROUND: Evidence has proved that high neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) were risk factors for cardiovascular comorbidities. The alterations of NLR and PLR following obstructive sleep apnea (OSA) treatment were under studied and thus should be investigated. This study aimed to evaluate the changes of inflammatory biomarkers including NLR and PLR in severe OSA patients after surgical interventions of the upper airway, and their relationships with improvements in polysomnographic (PSG) parameters. METHODS: This retrospective cohort study included 563 consecutive severe OSA patients at a tertiary academic medical center who received OSA surgery, as well as underwent pre- and post-operative polysomnographic (PSG) examinations and blood tests. The changes of major PSG estimates, NLR, and PLR before and at least 3 months after OSA surgery were analyzed using paired t-tests with subgroup analyses. Pearson's correlations were performed to discover which PSG parameter contributed to the improvement of the values. RESULTS: After OSA surgery, the major PSG estimates, NLR and PLR dropped significantly in the overall population. In those with a higher preoperative NLR (pre-operative NLR≧3) and PLR (pre-operative PLR≧150), the mean (SD) difference of NLR (- 0.8 [1.6], 95% CI - 1.5 to - 0.2) and PLR (- 41.6 [40], 95% CI - 52.8 to - 30.5) were even more substantial. The changes of the "apnea, longest (r = 0.298, P = .037)" and "hypopnea, longest (r = 0.321, P = .026)" were found significantly related to the improvement of PLR. CONCLUSION: NLR and PLR did significantly drop in severe OSA patients following OSA surgery, and this could be related to the alterations of sleep indices. The findings could possess clinical importance for severe OSA patients after OSA surgeries in reducing possible OSA-associated cardiovascular comorbidities.

COVID-related dysphonia and persistent long-COVID voice sequelae: A systematic review and meta-analysis.

PURPOSE: Dysphonia is a common symptom due to the coronavirus disease of the 2019 (COVID-19) infection. Nonetheless, it is often underestimated for its impact on human's health. We conducted this first study to investigate the global prevalence of COVID-related dysphonia as well as related clinical factors during acute COVID-19 infection, and after a mid- to long-term follow-up following the recovery. METHODS: Five electronic databases including PubMed, Embase, ScienceDirect, the Cochrane Library, and Web of Science were systematically searched for relevant articles until Dec, 2022, and the reference of the enrolled studies were also reviewed. Dysphonia prevalence during and after COVID-19 infection, and voice-related clinical factors were analyzed; the random-effects model was adopted for meta-analysis. The one-study-removal method was used for sensitivity analysis. Publication bias was determined with funnel plots and Egger's tests. RESULTS: Twenty-one articles comprising 13,948 patients were identified. The weighted prevalence of COVID-related dysphonia during infection was 25.1 % (95 % CI: 14.9 to 39.0 %), and male was significantly associated with lower dysphonia prevalence (coefficients: -0.116, 95 % CI: -0.196 to -0.036; P = .004) during this period. Besides, after recovery, the weighted prevalence of COVID-related dysphonia declined to 17.1 % (95 % CI: 11.0 to 25.8 %). 20.1 % (95 % CI: 8.6 to 40.2 %) of the total patients experienced long-COVID dysphonia. CONCLUSIONS: A quarter of the COVID-19 patients, especially female, suffered from voice impairment during infection, and approximately 70 % of these dysphonic patients kept experiencing long-lasting voice sequelae, which should be noticed by global physicians.

Homocysteine Levels in Severe OSA Patients Before and After TORS-OSA Surgery.

OBJECTIVE: The increased risk of cardiovascular diseases owing to a high level of serum homocysteine has been widely reported. Literature has demonstrated that patients with obstructive sleep apnea/hypopnea syndrome (OSA) had a higher homocysteine level than control group. This study aimed to investigate the alteration of serum homocysteine levels in severe OSA patients receiving transoral robotic surgery (TORS). STUDY DESIGN: Retrospective chart review. SETTING: Tertiary academic medical center. METHODS: Data of polysomnography (PSG) and serum homocysteine levels before and at least 3 months after the surgery were collected and analyzed via paired t tests. A subgroup analysis based on the preoperative homocysteine level (≥15 mcmol/L, as hyperhomocysteinemia group) was conducted to compare the intergroup differences of homocysteine decrease. Pearson's correlation was used to survey the relationships between the changes of major PSG parameters and the levels of homocysteine decrease at baseline and after TORS-OSA surgery. RESULTS: Two hundred sixty-one patients with severe OSA were enrolled. There were significant improvements in major PSG parameters after TORS-OSA surgery. Homocysteine levels significantly decreased from 12.1 ± 3.9 to 11.4 ± 3.7 mcmol/L (difference = -0.7 ± 2.8 mcmol/L, p = .001) postoperatively, which was shown in the hyperhomocysteinemia group (difference = -2.9 ± 4.7 mcmol/L, p = .007) to a greater extent. Pearson's correlation revealed that ΔODI (oxygen desaturation index/h) was the predominant estimate with a positive association with Δhomocysteine (r = 0.525, p = .012). CONCLUSION: TORS-OSA surgery could decrease homocysteine levels in OSA patients. The effects were more relevant in severe OSA patients with abnormal preoperative homocysteine levels.

Is Postextubation Dysphagia Underestimated in the Era of COVID-19? A Systematic Review and Meta-analysis.

OBJECTIVE: To investigate the incidence rate of postextubation dysphagia (PED) in patients with COVID-19, as well as relative factors potentially influencing the clinical course of dysphagia. DATA SOURCES: Six databases including PubMed, MEDLINE, Embase, ScienceDirect, the Cochrane Central Register of Controlled Trials (CENTRAL), and Web of Science were searched with no restriction on the language. REVIEW METHODS: The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed. Data were extracted and cross-examined among 3 of the authors. The random-effects model was adopted for the statistical synthesis. The percentage and 95% confidence interval (CI) were adopted as the effect measurements of the PED incidence rate. Subgroup analyses, sensitivity analyses, and metaregression were also performed to identify the heterogeneity among the studies. RESULTS: A total of 594 patients were enrolled and analyzed from the 10 eligible studies. The weighted incidence of PED in patients with COVID-19 was 66.5% (95% CI: 49.7%-79.9%). Age was the potential factor influencing the incidence rate after heterogeneity was adjusted by the metaregression analysis. CONCLUSION: Compared to the current evidence reporting only 41% of the non-COVID patients experienced PED, our study further disclosed that a higher 66.5% of COVID-19 patients suffered from PED, which deserves global physicians' attention. With the association between COVID-19 and dysphagia having been more clearly understood, future clinicians are suggested to identify intubated patients' risk factors earlier to strengthen PED care programs in the era of COVID-19.

Decreased Peripapillary and Macular Vascular Densities in Patients with Moderate/Severe Obstructive Sleep Apnea/Hypopnea Syndrome.

Purpose: To compare peripapillary and macular vascular densities (PVDs and MVDs) between patients with obstructive sleep apnea/hypopnea syndrome (OSA) and control subjects with symptoms of sleep-related breathing disorders only by swept-source optical coherence tomography angiography (OCTA). Participants and Methods: In this prospective study, 192 participants underwent a full-night polysomnography to determine OSA severity and subsequently received OCTA measurements as well as AngioTool software analysis. Results: A total of 146 patients with OSA (51 mild, 43 moderate, 52 severe) and 24 control subjects (apnea/hypopnea index, AHI <5) were enrolled. PVDs and MVDs in the superficial and choroidal layers were significantly different among the four groups. When participants with simple snoring/mild OSA (AHI <15) were grouped together and compared with moderate/severe OSA (AHI ≥15), PVDs were significantly lower for the latter group in the superficial layer (p = 0.0003), deep layer (p = 0.004), and choroidal layer (p = 0.003). MVDs were also lower for the moderate/severe OSA group in the superficial (p = 0.012) and choroidal layer (p = 0.004). Negative correlations were identified between AHI and PVDs in the superficial layer (ρ = -0.257, p = 0.0007), deep layer (ρ = -0.197, p = 0.0102) and choroidal layer (ρ = -0.220, p = 0.0039) and between AHI and MVDs in the superficial layer (ρ = -0.199, p = 0.0094) and choroid layer (ρ = -0.186, p = 0.0152). Conclusion: PVDs and MVDs were significantly lower in patients with moderate/severe OSA as compared to subjects with simple snoring/mild OSA. Furthermore, decreased PVDs and MVDs significantly correlated with OSA severity.

Zbtb20 identifies and controls a thymus-derived population of regulatory T cells that play a role in intestinal homeostasis.

The expression of BTB-ZF transcription factors such as ThPOK in CD4+ T cells, Bcl6 in T follicular helper cells, and PLZF in natural killer T cells defines the fundamental nature and characteristics of these cells. Screening for lineage-defining BTB-ZF genes led to the discovery of a subset of T cells that expressed Zbtb20. About half of Zbtb20+ T cells expressed FoxP3, the lineage-defining transcription factor for regulatory T cells (Tregs). Zbtb20+ Tregs were phenotypically and genetically distinct from the larger conventional Treg population. Zbtb20+ Tregs constitutively expressed mRNA for interleukin-10 and produced high levels of the cytokine upon primary activation. Zbtb20+ Tregs were enriched in the intestine and specifically expanded when inflammation was induced by the use of dextran sodium sulfate. Conditional deletion of Zbtb20 in T cells resulted in a loss of intestinal epithelial barrier integrity. Consequently, knockout (KO) mice were acutely sensitive to colitis and often died because of the disease. Adoptive transfer of Zbtb20+ Tregs protected the Zbtb20 conditional KO mice from severe colitis and death, whereas non-Zbtb20 Tregs did not. Zbtb20 was detected in CD24hi double-positive and CD62Llo CD4 single-positive thymocytes, suggesting that expression of the transcription factor and the phenotype of these cells were induced during thymic development. However, Zbtb20 expression was not induced in "conventional" Tregs by activation in vitro or in vivo. Thus, Zbtb20 expression identified and controlled the function of a distinct subset of Tregs that are involved in intestinal homeostasis.

Alterations of Ocular Surface and Tear Film in Patients with Obstructive Sleep Apnea/Hypopnea Syndrome.

Purpose: Obstructive sleep apnea/hypopnea syndrome (OSA) results in repeated oxygen desaturation, repeated arousals, and episodic nocturnal activation of sympathetic nervous system during sleep. Untreated OSA is strongly associated with an increase of cardio- and cerebrovascular disorders, as well as the damages of ophthalmological microstructures. However, previous literature only simply studied the association between the ophthalmic disorders and OSA. In the present study, we first investigated the alterations of ocular surface and tear film non-invasively with the innovated corneal topographer in untreated OSA patients and normal control subjects. Furthermore, we analyzed in depth whether the correlations between OSA severity and ocular surface exams exist. Participants and Methods: Participants underwent a full-night polysomnography to determine OSA occurrence and severity. All participants subsequently received Ocular Surface Disease Index questionnaire and comprehensive ocular exams, including floppy eyelid syndrome (FES) assessment, oculus scan for tear meniscus height, non-invasive keratograph tear film breakup time (NIKBUT), and ocular surface redness, endothelial cell density, and corneal fluorescein staining. Results: One hundred eighty-one participants were prospectively enrolled in the study. FES was found in 11.5% of the normal control group and 60.0% of the severe OSA group (p=0.0005). There were significant differences in the first-NIKBUT (F-NIKBUT) (p < 0.0001), average-NIKBUT (A-NIKBUT) (p = 0.0007), and redness scores over the nasal bulbar (p = 0.032), temporal bulbar (p < 0.0001), nasal limbal (p = 0.014), and temporal limbal (p < 0.0001) areas among the four groups. F-NIKBUT and A-NIKBUT were significantly shorter in the moderate/severe OSA group (apnea/hypopnea index (AHI) ≥15) than in the normal/mild OSA group (AHI <15) (both p < 0.0001). The redness scores over the temporal bulbar (p < 0.0001) and temporal limbal (p < 0.0001) areas were also significantly different in these two OSA groups. Moreover, F-NIKBUT and A-NIKBUT negatively correlated with AHI. Nasal bulbar redness, temporal bulbar redness, nasal limbal redness, and temporal limbal redness positively correlated with AHI. Conclusion: OSA patients had higher occurrence of FES. The NIKBUT was significantly shorter, and the temporal conjunctival redness scores over bulbar and limbal areas were higher in the moderate/severe OSA group than in the normal/mild OSA group. NIKBUT and conjunctival hyperemia significantly correlated with the severity of untreated OSA.

Effects of TORS-OSA Surgery on Lower Urinary Tract Symptoms, Overactive Bladder Symptoms, and Nocturia in Male Patients with Obstructive Sleep Apnea/Hypopnea Syndrome.

Objective: To determine the presence of lower urinary tract symptoms (LUTS), and overactive bladder (OAB) symptoms in men with obstructive sleep apnea/hypopnea syndrome (OSA) and the effects of transoral robotic surgery (TORS) for the treatment of OSA on these conditions. Materials and Methods: One hundred twenty-three patients with a diagnosis of OSA were prospectively enrolled. The evaluations of LUTS and OAB symptoms were based on self-administered questionnaires containing international prostate symptom score (IPSS) and OAB symptom score (OABSS), respectively. Men with an OABSS urgency score of ≥2 and sum score of ≥3 were considered to have OAB. The therapeutic outcomes were assessed at baseline, and 12 weeks after TORS-OSA Surgery. Results: There were significant differences in IPSS, and OABSS according to OSA severity. After TORS-OSA surgery, significant improvements on OSA severity, daytime quality of life (QoL) and nighttime sleep quality were observed. TORS-OSA surgery was also associated with a statistically significant improvement of LUTS, LUTS QoL score, and OAB symptoms (IPSS 22.1% decrease; IPSS QoL score 21.1% decrease; OABSS17.4% decrease) at post-operative 3 months' follow-up. The presence of OAB, and severe nocturia was significantly reduced from 22.8% to 11.4% (p=0.001), 5.7% to 0.8% (p=0.031) after TORS-OSA surgery. There were no patients who had acute airway compromise or massive bleeding peri- or post-operatively. Conclusion: TORS upper airway surgery could improve LUTS and OAB symptoms on male patients with OSA in addition to improvement of major parameters of sleep study and sleep-related QoL.

Systematic review and updated meta-analysis of multi-level surgery for patients with OSA.

OBJECTIVES: To perform an updated systematic review for determining the surgical success rate of multilevel upper airway surgery for patients with obstructive sleep apnea/hypopnea syndrome (OSA). METHODS: A systematic review was performed to identify English-language studies that evaluated the treatment of adult OSA patients with multilevel OSA surgery up to January, 2018. We used polysomnography as a metric of treatment success. Articles were only included if the surgery intervention involved at least two of the frequently involved anatomic sites: nose, oropharynx and hypopharynx. Eighty-seven studies fit the inclusion criteria and a meta-analysis was performed to determine the overall success. RESULTS: The meta-analysis included 3931 subjects with a mean age of 46.1 years. The originally reported success rate in the included literature was 59.9%. A meta-analysis was performed to redefine the success rate to be consistent with the commonly agreed upon criteria - namely "a reduction in apnea/hypopnea index (AHI, /hr.) of 50% or more and an AHI of less than 20". The recalculated success rate was 60.2%. Standard meta-analytic techniques for combining p-values between studies after weighting for sample size found significant improvements in AHI, apnea index, % of rapid eye movement sleep, lowest saturation of oxygen (%), and Epworth Sleepiness Scale. CONCLUSION: This study shows the significant improvement of treatment outcomes with multilevel surgery for OSA patients.

OSA Treatment on Cardio- and Cerebrovascular Comorbidities: A Long-term Nationwide Cohort Study.

OBJECTIVE: To compare the cardio- and cerebrovascular outcomes and survival rates of surgical and nonsurgical interventions for patients with obstructive sleep apnea (OSA) based on a national population-based database. STUDY DESIGN: Retrospective cohort study. SETTING: Taiwan National Health Insurance Research Database. METHODS: We analyzed all cases of OSA among adults (age >20 years and confirmed with ICD-9-CM) from January 2001 to December 2013. We compared the patients with OSA who received upper airway surgery with age-, sex-, and comorbidity index-matched controls with continuous positive airway pressure (CPAP) treatment. The risk of myocardial infarction (MI) or stroke after treatment of OSA-related surgery versus CPAP was investigated. RESULTS: During follow-up, 112 and 92 incident cases of MI occurred in the OSA surgery and CPAP treatment groups, respectively (rates of 327 and 298 per 100,000 person-years). Furthermore, 50 and 39 cases were newly diagnosed with stroke in the OSA surgery and CPAP treatment groups (rates of 144 and 125 per 100,000 person-years). Cox proportional hazard regressions showed that the OSA treatment groups (OSA surgery vs CPAP) were not significantly related to MI (hazard ratio, 1.03 [95% CI, 0.781-1.359]; P = .833) and stroke (hazard ratio, 1.12 [95% CI, 0.736-1.706]; P = .596) at follow-up, after adjustment for sex, age at index date, days from diagnosis to treatment, and comorbidities. CONCLUSION: Our study demonstrated that there was no difference of cardio- and cerebrovascular results between CPAP and surgery for patients with OSA in a 13-year follow-up. LEVEL OF EVIDENCE: 3.

H3K23/H3K36 hypoacetylation and HDAC1 up-regulation are associated with adverse consequences in obstructive sleep apnea patients.

The aim of this study is to determine the roles of global histone acetylation (Ac)/methylation (me), their modifying enzymes, and gene-specific histone enrichment in obstructive sleep apnea (OSA). Global histone modifications, and their modifying enzyme expressions were assessed in peripheral blood mononuclear cells from 56 patients with OSA and 16 matched subjects with primary snoring (PS). HIF-1α gene promoter-specific H3K36Ac enrichment was assessed in another cohort (28 OSA, 8 PS). Both global histone H3K23Ac and H3K36Ac expressions were decreased in OSA patients versus PS subjects. H3K23Ac expressions were further decreased in OSA patients with prevalent hypertension. HDAC1 expressions were higher in OSA patients, especially in those with excessive daytime sleepiness, and reduced after more than 6 months of continuous positive airway pressure treatment. H3K79me3 expression was increased in those with high C-reactive protein levels. Decreased KDM6B protein expressions were noted in those with a high hypoxic load, and associated with a higher risk for incident cardiovascular events or hypertension. HIF-1α gene promoter-specific H3K36Ac enrichment was decreased in OSA patients versus PS subjects. In vitro intermittent hypoxia with re-oxygenation stimuli resulted in HDAC1 over-expression and HIF-1α gene promoter-specific H3K36Ac under-expression, while HDAC1 inhibitor, SAHA, reversed oxidative stress through inhibiting NOX1. In conclusions, H3K23/H3K36 hypoacetylation is associated with the development of hypertension and disease severity in sleep-disordered breathing patients, probably through up-regulation of HDAC1, while H3K79 hypermethylation is associated with higher risk of cardiovascular diseases, probably through down-regulation of KDM6B.

Eligibility for live, interactive otolaryngology telemedicine: 19-Month experience before and during the COVID-19 pandemic in Taiwan.

BACKGROUND: Unequal access to healthcare is a global medical problem. Telemedicine, recently made possible by technological advances, may mitigate this inequity. However, the usefulness of telemedicine for procedure-driven disciplines, such as otolaryngology, under infectious conditions (e.g., the COVID-19 pandemic) is unknown. METHODS: Telemedicine was made legal in Taiwan by an amendment to the Physician Act in 2018. Kaohsiung Chang Gung Memorial Hospital was the first hospital in Taiwan to provide the telemedicine service by connecting to the Chenggong Branch of Taitung Hospital (CGBTH) in November 2018. This retrospective cohort study included all new and established otolaryngology outpatient consultations between November 2018 and May 2020 at CGBTH. The Current Procedural Terminology and International Classification of Disease, 10th Revision codes, patient demographic data, and questionnaire data were obtained. RESULTS: The study included 123 patients with 218 encounters over 19 months. The majority of complaints were ear-related (52.6%). Overall, 49% of the encounters required a specialized procedure for diagnosis and treatment; of these, cerumen removal was the most common procedure. The patient subjective improvement rate increased over the study period (from 62.0% to 78.9%). The rates of return and case closure were both around 90% in 2018 and 2019. The number of otolaryngology consultations and rate of return declined after the start of the COVID-19 pandemic; however, the subjective improvement and case closure rates remained stable. The telemedicine service saved at least 2 h driving time per visit. CONCLUSION: Telemedicine for otolaryngology is a promising approach for remote and underserved regions, as well as during an infectious disease pandemic.

Strongyloides stercoralis and HTLV-1 coinfection in CD34+ cord blood stem cell humanized mice: Alteration of cytokine responses and enhancement of larval growth.

Viral and parasitic coinfections are known to lead to both enhanced disease progression and altered disease states. HTLV-1 and Strongyloides stercoralis are co-endemic throughout much of their worldwide ranges resulting in a significant incidence of coinfection. Independently, HTLV-1 induces a Th1 response and S. stercoralis infection induces a Th2 response. However, coinfection with the two pathogens has been associated with the development of S. stercoralis hyperinfection and an alteration of the Th1/Th2 balance. In this study, a model of HTLV-1 and S. stercoralis coinfection in CD34+ umbilical cord blood hematopoietic stem cell engrafted humanized mice was established. An increased level of mortality was observed in the HTLV-1 and coinfected animals when compared to the S. stercoralis infected group. The mortality was not correlated with proviral loads or total viral RNA. Analysis of cytokine profiles showed a distinct shift towards Th1 responses in HTLV-1 infected animals, a shift towards Th2 cytokines in S. stercoralis infected animals and elevated TNF-α responses in coinfected animals. HTLV-1 infected and coinfection groups showed a significant, yet non-clonal expansion of the CD4+CD25+ T-cell population. Numbers of worms in the coinfection group did not differ from those of the S. stercoralis infected group and no autoinfective larvae were found. However, infective larvae recovered from the coinfection group showed an enhancement in growth, as was seen in mice with S. stercoralis hyperinfection caused by treatment with steroids. Humanized mice coinfected with S. stercoralis and HTLV-1 demonstrate features associated with human infection with these pathogens and provide a unique opportunity to study the interaction between these two infections in vivo in the context of human immune cells.

Neonatal mortality among outborn versus inborn babies.

BACKGROUND: Most previous studies reported there were higher survival rates if low birth weight babies were born in tertiary perinatal centers (inborn) than elsewhere (outborn). The objective of this study is to examine whether the number and ratio of outborn babies decrease and the neonatal mortality differs between inborn and outborn babies. METHODS: We used the pooled data of the Taiwan Clinical Effectiveness Index for the years 2011-2016 obtained from the Joint Commission of Taiwan to study the outborn/inborn number and neonatal mortality rate. RESULTS: We found that the number of outborn babies did not decrease year by year. The ratio of outborn to total babies was lower in the groups of birth body weight 750-999 g and ≧ 2500 g than the other groups. The neonatal mortality rate in outborns was significantly higher than the inborns in the groups of birth body weight 1000-1499 g, 2000-2499 g and ≧ 2500 g (6.9 ± 2.4 vs. 3.8 ± 0.9, P = 0.009, 2.6 ± 0.6 vs. 0.6 ± 0.3, P = 0.002 and 1.52 ± 0.67 vs. 0.08 ± 0.02, P = 0.002, respectively) in medical centers. CONCLUSION: Improved maternal transport which promotes in utero transfer of patients may further improve neonatal outcome.

Transoral robotic OSA surgery.

Continuous positive airway pressure (CPAP) is the primary treatment of obstructive sleep apnea/hypopnea syndrome (OSA). Most sleep physicians are in agreement that a certain number of OSA patients cannot or will not use CPAP. Although other conservative therapies such as oral appliance, sleep hygiene and sleep positioning may help some of these patients, there are many who fail all conservative treatments. As experts of upper airway diseases, we often view an airway clearly and help OSA patients understand the importance of assessment and treatment for OSA. Surgery for OSA is not a substitute for CPAP but is an alternative treatment for those who failed conservative therapies and therefore have no other options. Transoral robotic surgery (TORS) is a relatively new technique and a valid option with minor post-operative morbidities for selected OSA patients. In the article, we provide an updated overview of the role and evidence of TORS for the treatment of OSA.

A novel algorithm to predict oxygen desaturation in sedated patients with obstructive sleep apnea utilizing polysomnography: A STROBE-compliant article.

This retrospective study aimed at identifying the predictors of oxygen desaturation (OD) (i.e., SpO2 < 95%) in patients with obstructive sleep apnea (OSA) requiring deep sedation and developing an algorithm to predict OD.We studied 66 OSA patients undergoing propofol-induced deep sedation for drug-induced sleep endoscopy (DISE). The patients were divided into prediction (n = 35) and validation (n = 31) groups. Patient characteristics and polysomnographic parameters were analyzed with receiver operating characteristic curve and Chi-squared test to identify significant predictors of OD for developing an algorithm in the prediction group. The predictive accuracy, sensitivity, positive predictive value, and negative predictive value of the algorithm were determined in the validation group.Six polysomnographic predictors of OD were identified, including Apnea-Hypopnea Index of total sleep time (AHI-TST), AHI at the stage of rapid eye movement (AHI-REM), percentage of time with oxygen saturation <90% (mO2 < 90%), average SpO2, lowest SpO2, and desaturation index. Stepwise multiple logistic regression analysis demonstrated that low average SpO2 (<95.05%) and high AHI-REM (>16.5 events/h) were independent predictors of OD. The algorithm thus developed showed that patients with an average SpO2 < 95.05% and those with an average SpO2 ≥ 95.05% together with an AHI-REM > 16.5 events/h would be at risk of OD under sedation. The predictive accuracy, sensitivity, positive predictive value, and negative predictive value were 84%, 100%, 83%, 100%, respectively.For patients with OSA, average SpO2 and AHI-REM may enable clinicians to predict the occurrence of oxygen desaturation under deep sedation. Future large-scale studies are needed to validate the findings.