Analysis of systemic and airway inflammation in obstructive sleep apnea

Purpose

The presence of both systemic and airway inflammation has been suggested in obstructive sleep apnea (OSA) by increased levels of inflammatory biomarkers in the circulation and respiratory specimens. We aimed to investigate the relationship between systemic and airway inflammation in OSA.

Methods

This study was conducted by simultaneously measuring various biomarkers both in serum and induced sputum of 43 patients. We compared the relationships of these biomarker levels with polysomnographic data and obesity measurements and also investigated their interrelationships between systemic and local compartments. We also assessed the relation of inflammatory markers with proximal airway resistance measured by impulse oscillometry.

Results

In multiple regression analyses, each measured serum biomarker [leptin, interleukin-6 (IL-6), IL-8, tumor necrosis factor-α (TNF-α), and vascular endothelial growth factor (VEGF)] significantly correlated with waist circumference or fat area determined by computed tomography. In contrast, regarding airway inflammation, sputum IL-6, IL-8, TNF-α, and VEGF significantly correlated with OSA severity as indicated by the respiratory disturbance index or oxygen desaturation indices. Sputum IL-6, IL-8, TNF-α, and VEGF were significantly related to sputum neutrophil number, and sputum IL-8 and TNF-α were related to proximal airway resistance independently of body mass index. There were no significant interrelationships between the same biomarkers in serum and induced sputum.

Conclusions

Systemic and airway inflammation in OSA might be differently regulated by OSA itself and comorbid obesity, depending on the type of cytokine. Although we did not find apparent interrelationships between systemic and local compartments, further studies are needed to clarify this concept.     

PLATELET KINETICS AFTER TRANSFUSION

A kinetics model is proposed for platelet disposition after transfusion of platelets. In this model, transfusion of platelets and production of endogenous platelets contribute to an increase in the number of platelets in patients, and the life span and age of each platelet contribute to a decrease. The time course of the number of platelets after transfusion of platelets is theoretically described by this model to be a straight line followed by a concave curve. When the platelets have a life span without any variation, a linear pattern is observed in spite of their different ages at the transfusion. This model with a constant life span was applied to three patients receiving platelet transfusion, and the model parameters were calculated by curve fitting the observed platelet levels to the model using the nonlinear least-squares method. As a result, the life span, distribution volume per body weight, and endogenous platelet level (averages for three patients) were calculated as 6·29 d, 0·137 L kg⁻¹, and 1·40×10⁴ counts μL⁻¹, respectively. The calculated platelet levels in individual patients were compared with the observed ones during the next transfusions, and the relative and absolute differences between calculated and observed values were 2·0±15.3% and −0·075±0·443×10⁴ counts μL⁻¹ (mean±SD, 15 observed points for three patients), respectively. These case studies suggest that the model could be clinically useful for individual platelet transfusion.     

食管上皮源性恶性肿瘤误诊病例的内镜超声及组织病理学特点分析

为了分析误诊为食管黏膜下肿瘤的食管上皮源性恶性肿瘤的内镜超声及组织病理学特点,回顾性分析2012年1月—2020年12月在南京鼓楼医院术前诊断为食管黏膜下肿瘤但术后病理证实为食管上皮源性恶性肿瘤的患者资料,记录患者的年龄、性别、病变大小、病变部位、超声下病变起源、病变回声、内镜治疗方式以及术后病理等临床资料。11例患者中男9例、女2例,年龄（65.5±6.2）岁,9例病变长径≤2 cm,8例病变位于胸中段食管。11例患者中10例术前行内镜超声检查,病变起源于黏膜下层6例、固有肌层2例、黏膜肌层2例,病变回声9例为低回声改变,仅1例为等回声病变。11例患者中3例行内镜黏膜切除术,6例行内镜黏膜下剥离术,2例行隧道法内镜黏膜下肿物切除术。组织病理学类型包括3例中低分化鳞癌,3例基底细胞样鳞癌,2例腺样囊性癌（其中1例为腺样囊性癌碰撞鳞癌）,2例腺癌,1例食管肉瘤样癌合并基底细胞样鳞癌。食管上皮源性恶性肿瘤内镜下表现为黏膜下隆起极为罕见,内镜超声有助于鉴别诊断,诊断性治疗可明确诊断。     

Dialysate Vascular Endothelial Growth Factor Is an Independent Determinant of Serum Albumin Levels and Predicts Future Withdrawal From Peritoneal Dialysis in Uremic Patients

Peritoneal protein loss due to high peritoneal permeability may contribute to hypoalbuminemia and early withdrawal from peritoneal dialysis (PD) therapy in end stage renal disease (ESRD) patients. We have found that pigment epithelium‐derived factor (PEDF) has anti‐vasopermeability properties both in cell culture and animal models by counteracting the biological actions of vascular endothelial growth factor (VEGF). However, it remains unknown which clinical variables, including dialysate VEGF and PEDF, are associated with decreased serum albumin levels and could predict early withdrawal from the PD in ESRD patients. We address these issues. Twenty‐seven ESRD patients undergoing PD were enrolled. Clinical variables were measured at 6 months after commencing PD. We examined the independent correlates of serum albumin in PD patients and then prospectively investigated the predictors of withdrawal from the PD therapy over 4 years. Dialysate VEGF was associated with peritoneal solute transport rate (P = 0.002), serum albumin (inversely, P < 0.001) and dialysate PEDF levels (P < 0.001). In multiple stepwise regression analysis, age (P = 0.002) and dialysate VEGF levels (P < 0.001) were independent determinants of serum albumin levels. High VEGF (>27 pg/mL), low serum albumin (≤3.31 g/dL) and low hemoglobin (≤11.2 g/dL) were correlated with withdrawal from the PD therapy during the 4 years. The odds ratio of dialysate VEGF for early withdrawal from the PD was 6.310 (P = 0.035). The present study demonstrated that increased dialysate VEGF was associated with decreased serum albumin and early withdrawal from the PD therapy. Inhibition of peritoneal VEGF production may be a therapeutic target in PD patients.     

Peptide vaccination for patients with melanoma and other types of cancer based on pre-existing peptide-specific ctotoxic T-lymphocyte precursors in the periphery

Identification of antigenic peptides expressed on cancer cells enables us to treat cancer patients with peptide-based immunotherapy. Although optimal protocols for peptide-based vaccines have not yet been elucidated, boosting the immune system could be a better approach than priming the immune system to elicit prompt and potent peptide-specific T-cell responses in cancer patients. With this possibility in mind, the authors undertook a clinical trial in which cancer patients were vaccinated with peptides (maximum 4) after confirmation of pre-existing peptide-specific cytotoxic T-lymphocyte (CTL) precursors in the periphery. Fourteen patients (seven with melanoma and seven with other types of cancer) positive for either HLA-A24 or HLA-A2 were enrolled in this study. Fourteen and 16 peptides were used to screen for HLA-A24+ and HLA-A2+ patients, respectively. The vaccination was well tolerated, and the only adverse effects were local pain and fever. Kinetic analysis revealed that peptide-reactive CTLs increased after peptide vaccination in 7 of 14 patients. Immunoglobulin G (IgG) reactive to the administered peptides was detected in 2 patients before vaccination, although it became detectable in 8 of the other 12 patients after the peptide vaccination. Stable disease for more than 6 months was observed in five patients (one with melanoma and four with other types of cancer); all of these patients showed increased levels of peptide-specific IgG. These results indicate that peptide vaccination of patients showing evidence of pre-existing peptide-specific CTL precursors can be applied in further clinical trials aimed at the treatment of melanoma and other types of cancer.     

彩色多普勒超声与数字减影血管造影对比评价不同节段下肢深静脉血栓的诊断价值

目的 探讨彩色多普勒超声对不同节段深静脉血栓形成(DVT)的诊断价值.方法 临床疑为DVT患者58例,应用彩色多普勒超声探测患肢各节段血管,检查结果 与DSA对照,按照四格表分析,评价彩色多普勒超卢诊断不同节段DVT的灵敏性、特异性、准确性等指标.结果 共检测150条不同节段静脉.进行四格表统计分析彩色多普勒超声对各节段血管的检出率:髂总静脉血栓检查灵敏性82.6%,特异性66.7%;髂外静脉血栓灵敏性83.3%,特异性80.0%;髂内静脉血栓灵敏性80.0%,特异性66.7%;胴静脉血栓灵敏性92.6%,特异性92.2%;股静脉血栓灵敏性96.2%,特异性93.8%;胫前静脉血栓灵敏性71.4%,特异性75.0%;胫后静脉血栓灵敏性72.7%,特异性75.0%.结论 彩色多普勒超声作为DVT的首选检查方法 ,对不同节段静脉血栓有不同的诊断价值,对股、胭及髂外静脉灵敏性较高,胫前、胫后静脉血栓检出的灵敏性较低.     

Phlegmasia Cerulea Dolens: Rare Complication of Vena Cava Filter Placement in Man With Paraplegia

Objective: To describe a complication of placement of an inferior vena cava (IVC) filter in a man with paraplegia.

Design: Case report.

Participants/Methods: A 48-year-old man with T11 paraplegia secondary to an L1 burst fracture underwent thoracic spinal fusion. The postoperative course was complicated by deep vein thrombosis (DVT) of the right common femoral vein, which was treated with warfarin.

Results: During rehabilitation, the hematocrit declined, and fluctuance was noted along the surgical site. Computed tomographic scan suggested a hematoma in the paraspinal and latissimus dorsi muscles. Warfarin was discontinued, and an IVC filter was placed. He subsequently developed severe leg pain, followed by hypotension, acute renal failure, and compartment syndrome in bilateral lower extremities requiring fasciotomies. Ultrasound and computed tomographic angiogram showed extensive bilateral lower extremity DVTs and pulmonary emboli. The diagnosis of cerulea dolens was made. Mechanical and pharmacological thrombectomy was aborted secondary to bleeding complications and hypotension. The patient died shortly after care was withdrawn at the family's request. The autopsy revealed multiple thrombi in IVC, bilateral pelvic and femoral veins, and left pulmonary artery embolus, consistent with phlegmasia cerulea dolens.

Conclusions: Inferior vena cava filters may prevent pulmonary embolism but do not affect the underlying thrombotic process. An IVC filter should be recognized as a possible thrombogenic nidus in patients with spinal cord injury who have known DVT.