Placenta Growth Factor in Eyes with Neovascular Glaucoma Is Decreased after Intravitreal Ranibizumab Injection

Purpose

To evaluate changes in the concentrations of placental growth factor (PlGF) and vascular endothelial growth factor-A (VEGF-A) in aqueous humor of patients with neovascular glaucoma (NVG) before and after an intravitreal injection of ranibizumab (IVR) and to determine the underlying correlation between the levels.

Methods

The prospective interventional comparative study involved 20 eyes of 20 patients with surgery-required advanced NVG and 20 control subjects from January 2013 to November 2013. The NVG eyes received the IVR treatment before glaucoma surgery. Aqueous humor was collected at the time of the IVR injection (pre- IVR) and at the time of antiglaucomatous surgery (post-IVR). Aqueous humor was also collected at the time of cataract surgery in normal control. Aqueous humor and plasma VEGF-A and PlGF levels were measured with an enzyme-linked immunosorbent assay methods, respectively.

Results

The mean aqueous humor PlGF and VEGF-A concentrations in the pre-IVR eyes were significantly higher than in those of the control subjects (p<0.001), whereas the plasma levels showed no significant difference. There was a statistically significant correlation between the aqueous humor PlGF and the VEGF-A concentration (r = 0.612, p = 0.003). The mean aqueous humor PlGF in the post-IVR eyes dramatically decreased from 1078.36 ± 755.83 to 177.64 ± 151.73 pg/mL (p<0.001). The VEGF-A level showed a similar trend from 3697.64 ± 2104.47 pg/mL to 183.54 ± 130.35 pg/mL (p<0.001).

Conclusions

Aqueous humor concentrations of VEGF-A and PlGF were significantly elevated in the eyes with NVG, and there was a positive correlation between the levels. After an IVR treatment, VEGF-A and PlGF were significantly decreased in NVG eyes.     

Long-Term Outcomes and Complications of Trabeculectomy for Secondary Glaucoma in Patients with Familial Amyloidotic Polyneuropathy

Objective

Secondary glaucoma is a serious complication in patients with transthyretin (TTR)-related familial amyloidotic polyneuropathy (FAP). We assessed the long-term outcomes and complications of trabeculectomy with mitomycin C (MMC) for secondary glaucoma associated with FAP.

Methods

Medical case records of Kumamoto University Hospital were retrospectively reviewed. Twenty-one eyes of 13 patients (10 with FAP ATTR Val30Met; 3 with FAP ATTR Tyr114Cys) underwent trabeculectomy with MMC and follow-up of at least 2 years. The primary outcome measure was Kaplan-Meier survival, with failure of this treatment being defined as an intraocular pressure (IOP) of ≤5 mm Hg or ≥22 mm Hg on two consecutive visits or as additional operations needed to reduce IOP. Secondary outcome measures included complications, bleb characteristics, and additional postoperative interventions required.

Results

The mean postoperative follow-up period was 5.7 years (range, 2.2–12.7 years). Kaplan-Meier analysis indicated probabilities of success of 0.76, 0.67, and 0.53 at 1, 2, and 3 years after operation, respectively. Significant complications included ocular decompression retinopathy in 7 eyes (33%) and bleb encapsulation in 10 eyes (48%). Twelve eyes (57%) needed additional surgery, such as bleb revision or trabeculectomy with MMC, to reduce IOP.

Conclusions

Trabeculectomy with MMC may not be optimal for patients with FAP-related glaucoma and may have several significant complications.     

Factors Influencing Aqueous Proinflammatory Cytokines and Growth Factors in Uveitic Glaucoma

Purpose

To analyze the effects of factors on aqueous humor proinflammatory cytokine and growth factor levels in patients with uveitic glaucoma (UG).

Methods

In this cross-sectional study, we enrolled 143 participants: 1) UG patients (n = 39); 2) primary open-angle glaucoma (POAG) patients (n = 36); and 3) cataract surgery patients, as a comparative group (n = 68). Aqueous humor samples were obtained at the start of surgery. Aqueous cytokine levels were determined using a multiplex immunoassay (xMAP and the Human Cytokine/Chemokine Panel I).

Results

In UG cases, mean interleukin (IL)-6, IL-8, monocyte chemotactic protein (MCP)-1, tumor necrosis factor (TNF)-α, platelet-derived growth factor (PDGF)-AA, PDGF-AB/BB, and VEGF levels were 171.1, 214.5, 2791.7, 3.5, 23.9, 5.4, and 168.9 pg/mL, respectively, and were higher than those in cataract (non-glaucomatous) cases except PDGF. Levels of IL-6, MCP-1, and VEGF were higher in UG cases than in POAG cases. UG cases with a history of phacoemulsification displayed significantly higher levels of IL-6 (P = 0.0164), IL-8 (P = 0.0003), MCP-1 (P = 0.0465), and PDGF-AB/BB (P = 0.0062) compared to the phakic cases. The presence of cells in the anterior chamber was related to higher levels of IL-8 (P = 0.0002), TNF-α (P = 0.0037), and PDGF-AB/BB (P = 0.0009). The level of PDGF-AB/BB was higher in infectious uveitis than in non-infectious uveitis (P = 0.0211). The level of transforming growth factor (TGF)-β2 was negatively correlated with the levels of MCP-1 (adjusted R² = 0.28, t = -2.45, P = 0.031) and TNF-α (adjusted R² = 0.27, t = -2.43, P = 0.032).

Conclusion

A history of phacoemulsification, the presence of cells in the anterior chamber, and infectious uveitis were related to aqueous proinflammatory cytokine levels in patients with UG. TGF-β2 might be an anti-inflammatory factor in aqueous humor of UG patients.     

Prediction of Perioperative Cardiac Events through Preoperative NT-pro-BNP and cTnI after Emergent Non-Cardiac Surgery in Elderly Patients

Objectives

Clinical risk stratification has an important function in preoperative evaluation of patients at risk for cardiac events prior to non-cardiac surgery. The aim of this study was to determine whether the combined measurement of pre-operative N-terminal pro-brain natriuretic peptide (NT-pro-BNP) and cardiac troponin I (cTnI) could provide useful prognostic information about postoperative major adverse cardiac events (MACE) within 30 days in patients aged over 60 years undergoing emergent non-cardiac surgery.

Methods

The study group comprised 2519 patients aged over 60 years that were undergoing emergent non-cardiac surgery between December 2007 and December 2013. NT-pro-BNP and cTnI were measured during hospital admission. The patients were monitored for MACE (cardiac death, non-fatal myocardial infarction, or cardiac arrest) during the 30-day postoperative follow-up period.

Results

MACE occurred in 251 patients (10.0%). Preoperative NT-pro-BNP and cTNI level were significantly higher in the individuals that experienced MACE than in those who did not (P < 0.001). The confounding factors of age, sex, co-morbidities and preoperative medications were adjusted in a multivariate logistic regression analysis. This analysis showed that preoperative NT-proBNP level > 917 pg/mL (OR 4.81, 95% CI 3.446–6.722, P < 0.001) and cTnI ≥ 0.07 ng/mL (OR 8.74, 95% CI 5.881–12.987, P < 0.001) remained significantly and independently associated with MACE after the adjustment of the confounding factors. Kaplan-Meier event-free survival curves demonstrated that patients with preoperative simultaneous NT-proBNP level > 917 pg/mL and cTnT ≥0.07 ng/mL had worse event-free survival than individual assessments of either biomarker.

Conclusion

Preoperative plasma NT-proBNP and cTnI are both independently associated with an increased risk of MACE in elderly patients after emergent non-cardiac surgery. The combination of these biomarkers provides better prognostic information than using either biomarker separately.     

Inflammatory Kidney and Liver Tissue Response to Different Hydroxyethylstarch (HES) Preparations in a Rat Model of Early Sepsis

Background

Tissue hypoperfusion and inflammation in sepsis can lead to organ failure including kidney and liver. In sepsis, mortality of acute kidney injury increases by more than 50%. Which type of volume replacement should be used is still an ongoing debate. We investigated the effect of different volume strategies on inflammatory mediators in kidney and liver in an early sepsis model.

Material and Methods

Adult male Wistar rats were subjected to sepsis by cecal ligation and puncture (CLP) and assigned to three fluid replenishment groups. Animals received 30mL/kg of Ringer’s lactate (RL) for 2h, thereafter RL (75mL/kg), hydroxyethyl starch (HES) balanced (25mL/kg), containing malate and acetate, or HES saline (25mL/kg) for another 2h. Kidney and liver tissue was assessed for inflammation. In vitro rat endothelial cells were exposed to RL, HES balanced or HES saline for 2h, followed by stimulation with tumor necrosis factor-α (TNF-α) for another 4h. Alternatively, cells were exposed to malate, acetate or a mixture of malate and acetate, reflecting the according concentration of these substances in HES balanced. Pro-inflammatory cytokines were determined in cell supernatants.

Results

Cytokine mRNA in kidney and liver was increased in CLP animals treated with HES balanced compared to RL, but not after application of HES saline. MCP-1 was 3.5fold (95% CI: 1.3, 5.6) (p<0.01) and TNF-α 2.3fold (95% CI: 1.2, 3.3) (p<0.001) upregulated in the kidney. Corresponding results were seen in liver tissue. TNF-α-stimulated endothelial cells co-exposed to RL expressed 3529±1040pg/mL MCP-1 and 59±23pg/mL CINC-1 protein. These cytokines increased by 2358pg/mL (95% CI: 1511, 3204) (p<0.001) and 29pg/ml (95% CI: 14, 45) (p<0.01) respectively when exposed to HES balanced instead. However, no further upregulation was observed with HES saline. PBS supplemented with acetate increased MCP-1 by 1325pg/mL (95% CI: 741, 1909) (p<0.001) and CINC-1 by 24pg/mL (95% CI: 9, 38) (p<0.01) compared to RL. Malate as well as HES saline did not affect cytokine expression.

Conclusion

We identified HES balanced and specifically its component acetate as pro-inflammatory factor. How important this additional inflammatory burden on kidney and liver function is contributing to the sepsis-associated inflammatory burden in early sepsis needs further evaluation.     

Soluble Isoform of the Receptor for Advanced Glycation End Products as a Biomarker for Postoperative Respiratory Failure after Cardiac Surgery

Purpose

Postoperative respiratory failure is a major problem which can prolong the stay in the intensive care unit in patients undergoing cardiac surgery. We measured the serum levels of the soluble isoform of the receptor for advanced glycation end products (sRAGE), and we studied its association with postoperative respiratory failure.

Methods

Eighty-seven patients undergoing elective cardiac surgery were enrolled in this multicenter observational study in three university hospitals. Serum biomarker levels were measured perioperatively, and clinical data were collected for 7 days postoperatively. The duration of mechanical ventilation was studied for 28 days.

Results

Serum levels of sRAGE elevated immediately after surgery (median, 1751 pg/mL; interquartile range (IQR) 1080–3034 pg/mL) compared with the level after anesthetic induction (median, 884 pg/mL; IQR, 568–1462 pg/mL). Postoperative sRAGE levels in patients undergoing off-pump coronary artery bypass grafting (median, 1193 pg/mL; IQR 737–1869 pg/mL) were significantly lower than in patients undergoing aortic surgery (median, 1883 pg/mL; IQR, 1406–4456 pg/mL; p = 0.0024) and valve surgery (median, 2302 pg/mL; IQR, 1447–3585 pg/mL; p = 0.0005), and postoperative sRAGE correlated moderately with duration of cardiopulmonary bypass (r_s = 0.44, p<0.0001). Receiver operating characteristic curve analysis demonstrated that postoperative sRAGE had a predictive performance with area under the curve of 0.81 (95% confidence interval 0.71–0.88) for postoperative respiratory failure, defined as prolonged mechanical ventilation >3 days. The optimum cutoff value for prediction of respiratory failure was 3656 pg/mL, with sensitivity and specificity of 62% and 91%, respectively.

Conclusions

Serum sRAGE levels elevated immediately after cardiac surgery, and the range of elevation was associated with the morbidity of postoperative respiratory failure. Early postoperative sRAGE levels appear to be linked to cardiopulmonary bypass, and may have predictive performance for postoperative respiratory failure; however, large-scale validation studies are needed.     

Overall Survival of Stage III Colon Cancer with Only One Lymph Node Metastasis Is Independently Predicted by Preoperative Carcinoembryonic Antigen Level and Lymph Node Sampling Status

Background

This study identified predictors of favorable overall survival (OS) for stage III colon cancer patients who had only one lymph node (LN) metastasis (N1a).

Methods

Variables, including preoperative carcinoembryonic antigen (CEA) level, LN sampling status, and the choices of postoperative adjuvant chemotherapy, were recorded. Prognostic significance was determined using the log-rank test and multivariate Cox regression analysis.

Results

The median 42-month follow-up period included 363 eligible patients. Among them, 230 (63.3%) received only 5-flurouracil (5-FU) adjuvant chemotherapy; 76 (20.9%) underwent oxaliplatin-based regimens; and 57 (15.7%) chose surgery alone. The 5-year survival rate of these evaluated patients was 75%, 63%, and 77%, respectively (P = 0.823). Multivariate analysis revealed that normal preoperative CEA level (≦5 ng/mL) and adequate LN sampling (LN ≧ 12) were significant predictors for higher 5-year OS (P < 0.001; P = 0.007, respectively). However, the use of postoperative adjuvant chemotherapy in these N1a colon cancer patients did not significantly affect their 5-year OS.

Conclusions

A preoperative CEA level of less than or equal to 5 ng/mL, and curative surgery with an adequate lymphadenectomy determined a favorable OS outcome in stage III colon cancer with only one LN metastasis.     

Expression of Cytokines,Chmokines and Growth Factors in Patients Undergoing Cataract Surgery with Femtosecond Laser Pretreatment

Purpose

To describe cytokines, chemokines and growth factors profiles in patients undergoing cataract surgery with femtosecond laser pretreatment and investigate their relationships with the postoperative in vivo inflammation index.

Methods

Aqueous humor was collected from 22 eyes after femtosecond laser pretreatment and from 22 eyes at the beginning of routine cataract surgery. The levels of 45 inflammation-related mediators were measured using multiplex fluorescent bead-based immunoassays. Laser flare photometry was measured preoperatively and at 1 day, 7 days and 30 days postoperatively.

Results

Compared with the control group, the femtosecond laser treatment group showed significantly higher aqueous humor levels of fibroblast growth factor (FGF-2), tumor necrosis factor (TNF)-α, leukemia inhibitor factor (LIF), interleukin (IL)-1ra and IL-18, and significantly lower aqueous humor levels of IL-9, platelet-derived growth factor (PDGF)-BB, eotaxin and TNF-β. Postoperative aqueous flare was significantly greater in the manual cataract surgery group at 1 day (p<0.001), 7days (p<0.001) and 30 days (p = 0.002).No correlation was found between the analyzed mediators and the aqueous flare values.

Conclusions

The expression profiles of cytokines, chemokines and growth factors and the correlations of these profiles with the in vivo inflammatory indexes for patients undergoing cataract surgery with femtosecond laser pretreatment were identified. Our data indicate a disturbance of postoperative inflammation response after femtosecond laser treatment.     

The Influence of Phacoemulsification on Surgical Outcomes of Trabeculectomy with Mitomycin-C for Uveitic Glaucoma

Purpose

To evaluate the influence of phacoemulsification after trabeculectomy on the postoperative intraocular pressure (IOP) in eyes with uveitic glaucoma (UG).

Setting

Kumamoto University Hospital, Kumamoto, Japan.

Design

A retrospective cohort study.

Methods

The medical records of patients with UG who had trabeculectomy with mitomycin-C (MMC) were reviewed. Complete and qualified surgical failures were defined by an IOP of ≥21 mmHg (condition A), ≥18 mmHg (condition B), or ≥15 mmHg (condition C) without and with glaucoma eye drops, respectively. Kaplan-Meier survival analysis, generalized by the Wilcoxon test, and the Cox proportional hazards model analysis were conducted. Post-trabeculectomy phacoemulsification was treated as a time-dependent variable. In 24 (30%) of the included 80 eyes, phacoemulsification was included, and they were divided into two groups: groups I (8 eyes with phacoemulsification within 1 year after trabeculectomy) and group II (16 eyes after 1 year following trabeculectomy).

Results

Multivariable Cox proportional hazards model analysis showed post-trabeculectomy phacoemulsification was a significant factor in both complete success and qualified success based upon condition C (P = 0.0432 and P = 0.0488, respectively), but not for the other conditions. Kaplan–Meier survival analyses indicated significant differences in success probabilities between groups I and group II for complete success and qualified success based upon condition C (P = 0.020 and P = 0.013, respectively). There was also a significant difference for qualified success based upon condition B (P = 0.034), while there was no significant difference for the other conditions.

Conclusion

Post-trabeculectomy phacoemulsification, especially within 1 year, can cause poor prognosis of IOP control of UG eyes after trabeculectomy with MMC.     

Circulating ANGPTL8/Betatrophin Is Increased in Obesity and Reduced after Exercise Training

Objective

ANGPTL8 is a liver and adipose tissue produced protein that regulates the level of triglyceride in plasma as well as glucose homeostasis. This study was designed to evaluate the level of ANGPTL8 in obese and non-obese subjects before and after exercise training.

Methods

A total of 82 non-obese and 62 adult obese were enrolled in this study. Subjects underwent a three months of exercise training. Both full length and C-terminal 139–198 form of ANGPTL8 were measured by ELISA.

Results

Our data show that the full length ANGPTL8 level was increased in obese subjects (1150.04 ± 108.10 pg/mL) compared to non-obese (775.54 ± 46.12) pg/mL (p-Value = 0.002). C-terminal 139–198 form of ANGPTL8 was also increased in obese subjects 0.28 ± 0.04 ng/mL vs 0.20 ± 0.02 ng/mL in non-obese (p-value = 0.058). In obese subjects, the levels of both forms were reduced after three months of exercise training; full length was reduced from 1150.04 ± 108.10 pg/mL to 852.04 ± 51.95 pg/mL (p-Values 0.015) and c-terminal form was reduced from 0.28 ± 0.04 ng/mL to 0.19 ± 0.03 ng/mL (p-Value = 0.058). Interestingly, full length ANGPTL8 was positively associated with fasting blood glucose (FBG) in non-obese (r = 0.317, p-Value = 0.006) and obese subjects (r = 0.346, p-Value = 0.006) C-terminal 139–198 form of ANGPTL8 on the other hand, did not show any correlation in both groups.

Conclusion

In conclusion, our data demonstrate that ANGPTL8 was increased in obesity and reduced after exercise training supporting the potential therapeutic benefit of reducing ANGPTL8. The various forms of ANGPTL8 associated differently with FBG suggesting that they have different roles in glucose homeostasis.     

Dry Eye Disease in Patients with Functioning Filtering Blebs after Trabeculectomy

Purpose

The aim of this study was to analyze dry eye disease (DED) in patients with functioning filtering blebs and to explore the relationship between the morphology of filtering blebs and ocular surface instability.

Methods

This was a cross-sectional, case-comparison study. Seventy glaucomatous patients (70 eyes) with functioning blebs who had undergone trabeculectomy more than 6 months prior (study group) and 35 control subjects (35 eyes) (control group) were included. All subjects completed an ocular symptom questionnaire that referred to the Shihpai Eye Study. Evaluation of meibomian gland obstruction, a tear film break-up time test (TFBUT), fluorescein corneal staining and a Schirmer’s tear test were then performed. Filtering bleb morphology was analyzed using Wuerzburg bleb classification scoring criteria in the study group. The presence of DED was defined as the concomitant presence of TFBUT <10 seconds and the presence of superficial punctate keratitis.

Results

The patients with functioning blebs presented higher corneal staining scores (P = 0.012) and lower TFBUT values (P = 0.043) than the control group. DED was present in 28/70 patients in the study group and 6/35 patients in the control group (P = 0.018). More patients in the study group complained of dryness (P = 0.001), a gritty or sandy sensation (P < 0.001) and redness (P = 0.048). In the study group, the patients with DED were significantly different from the patients without DED in both TFBUT (P < 0.001) and corneal staining (P < 0.001). More patients in the DED group were likely to report dryness (P = 0.013) and watery or teary eyes (P = 0.012). The differences in meibomian gland obstruction scores between the study and the control group, the DED and the non-DED group were not significant (P = 0.105 and P = 0.077, respectively). The values for microcysts and bleb heights were significantly higher in the DED group (P = 0.040 and P = 0.011, respectively). A Spearman’s rank correlation showed that microcysts were positively correlated with corneal staining (r = 0.270, P = 0.024). Bleb height was negatively correlated with TFBUT (r = -0.299, P = 0.012) and positively correlated with corneal staining (r = 0.275, P = 0.021). The relationships between DED and microcysts and between DED and bleb height were significant (r = 0.247, P = 0.039 and r = 0.307, P = 0.010, respectively).

Conclusion

DED is relatively common in patients with functioning filtering blebs following trabeculectomy. In DED patients, dryness and watery are common symptoms. Microcysts and bleb height are related to ocular surface instability and DED.     

Postoperative Metamorphopsia in Macula-Off Rhegmatogenous Retinal Detachment: Associations with Visual Function,Vision Related Quality of Life,and Optical Coherence Tomography Findings

Purpose

To evaluate postoperative metamorphopsia in macula-off rhegmatogenous retinal detachment (RRD) and its association with visual function, vision related quality of life, and optical coherence tomography (OCT) findings.

Methods

45 patients with primary macula-off RRD were included. At 12 months postoperatively, data on metamorphopsia using sine amsler charts (SAC), best corrected visual acuity (BCVA), letter contrast sensitivity, color vision (saturated and desaturated color confusion indexes), critical print size, reading acuity, the 25-item National Eye Institute Visual Functioning Questionnaire (NEI-VFQ-25), and OCT, were obtained.

Results

Metamorphopsia was present in 39 patients (88.6%), with most of them (n = 35, 77.8%) showing only mild metamorphopsia (SAC score = 1). Patients with metamorphopsia had significantly worse postoperative BCVA (p = 0.02), critical print size (p<0.0005), and reading acuity (p = 0.001) compared to patients without metamorphopsia. Other visual function outcomes and NEI-VFQ-25 overall composite score were all also somewhat lower in patients with metamorphopsia, but this did not reach statistical significance. No association with OCT findings was present.

Conclusion

The prevalence of postoperative metamorphopsia in macula-off RRD patients is high, however, the degree of metamorphopsia is relatively low. When metamorphopsia is present, visual functions seem to be compromised, while vision related quality of life is only mildly affected.     

Difference in Outcomes between First-Operated vs. Fellow-Operated Eyes in Patients Undergoing Bilateral Trabeculectomies

Main Objective

To compare the course and outcome of first- and fellow-operated eyes in patients who underwent bilateral trabeculectomies and to investigate the factors associated with the difference.

Methods

Preoperative characteristics, including the interval between surgeries, were compared between the first- and fellow-operated eyes in 42 patients who underwent bilateral trabeculectomies. Postoperative intraocular pressure and bleb vascularity, using postoperative anterior segment photos, were compared at various time points between the first- and fellow-operated eyes. Surgical success was evaluated at 1 year after surgery and at the final follow-up. Factors affecting the difference between the first and fellow eyes were analyzed.

Results

There was no significant difference in success or failure rates at 1 year postoperatively and at the final follow-up between the first- and fellow-operated eyes. Early postoperative IOP and the degree of bleb vascularity were higher in the fellow-operated eyes (P = 0.001 and 0.003, respectively at week 1 postoperative). The difference in IOP between the first- and fellow-operated eyes was greater in patients whose interval between surgeries was shorter than 3 weeks (P = 0.026).

Conclusions

In patients undergoing bilateral trabeculectomies, early postoperative IOP was higher in the fellow-operated eyes than the first-operated eyes; the difference was greater when the interval between surgeries was shorter. The first-operated eye may influence the early postoperative inflammatory response in the fellow-operated eye. Our findings have clinical implications for planning treatment of patients who may need bilateral surgery.     

The Efficacy of Acupuncture in Post-Operative Pain Management: A Systematic Review and Meta-Analysis

Background

Postoperative pain resulting from surgical trauma is a significant challenge for healthcare providers. Opioid analgesics are commonly used to treat postoperative pain; however, these drugs are associated with a number of undesirable side effects.

Objective

This systematic review and meta-analysis evaluated the effectiveness of acupuncture and acupuncture-related techniques in treating postoperative pain.

Data Source

MEDLINE, Cochrane Library, and EMBASE databases were searched until Sep 30, 2014.

Study Eligibility Criteria

Randomized controlled trials of adult subjects (≥ 18 years) who had undergone surgery and who had received acupuncture, electroacupuncture, or acupoint electrical stimulation for managing acute post-operative pain were included.

Results

We found that patients treated with acupuncture or related techniques had less pain and used less opioid analgesics on Day 1 after surgery compared with those treated with control (P < 0.001). Sensitivity analysis using the leave-one-out approach indicated the findings are reliable and are not dependent on any one study. In addition, no publication bias was detected. Subgroup analysis indicated that conventional acupuncture and transcutaneous electric acupoint stimulation (TEAS) were associated with less postoperative pain one day following surgery than control treatment, while electroacupuncture was similar to control (P = 0.116). TEAS was associated with significantly greater reduction in opioid analgesic use on Day 1 post surgery than control (P < 0.001); however conventional acupuncture and electroacupuncture showed no benefit in reducing opioid analgesic use compared with control (P ≥ 0.142).

Conclusion

Our findings indicate that certain modes of acupuncture improved postoperative pain on the first day after surgery and reduced opioid use. Our findings support the use of acupuncture as adjuvant therapy in treating postoperative pain.     

The Placental Protein Syncytin-1 Impairs Antiviral Responses and Exaggerates Inflammatory Responses to Influenza

Background

Pregnancy increases susceptibility to influenza. The placenta releases an immunosuppressive endogenous retroviral protein syncytin-1. We hypothesised that exposure of peripheral monocytes (PBMCs) to syncytin-1 would impair responses to H1N1pdm09 influenza.

Methods and Findings

Recombinant syncytin-1 was produced. PBMCs from non-pregnant women (n=10) were exposed to H1N1pdm09 in the presence and absence of syncytin-1 and compared to responses of PBMCs from pregnant women (n=12). PBMCs were characterised using flow cytometry, release of interferon (IFN)-α, IFN-λ, IFN-γ, IL-10, IL-2, IL-6 and IL-1β were measured by cytometric bead array or ELISA. Exposure of PBMCs to H1N1pdm09 resulted in the release of IFN-α, (14,787 pg/mL, 95% CI 7311-22,264 pg/mL) IFN-λ (1486 pg/mL, 95% CI 756-2216 pg/mL) and IFN-γ (852 pg/mL, 95% CI 193-1511 pg/mL) after 48 hours. This was significantly impaired in pregnant women (IFN-α; p<0.0001 and IFN-λ; p<0.001). Furthermore, in the presence of syncytin-1, PBMCs demonstrated marked reductions in IFN-α and IFN-λ, while enhanced release of IL-10 as well as IL-6 and IL-1β.

Conclusions

Our data indicates that a placental derived protein, syncytin-1 may be responsible for the heightened vulnerability of pregnant women to influenza.     

Elevated Serum Level of IL-35 Associated with the Maintenance of Maternal-Fetal Immune Tolerance in Normal Pregnancy

Objectives

IL-35 is a novel inhibitory cytokine. In this study, we investigate the serum levels of inhibitory cytokines IL-35, IL-10 and TGF-β in both normal pregnancies and non-pregnant females, and whether IL-35 is associated with the pathogenesis of recurrent spontaneous abortion. We also try to elucidate the relationships of IL-35 with estrogen and alpha-fetoprotein (AFP).

Methods

The levels of IL-35, IL-10, TGF-β, estradiol (E2), unconjugated estriol (uE3) and AFP were analyzed in 120 normal pregnancies, 40 women suffering recurrent spontaneous abortion, 40 postpartum healthy women and 40 non-pregnant women by enzyme-linked immunosorbent assay (ELISA). The correlations between inhibitory cytokines, estrogen and AFP were assessed with the Spearman rank correlation coefficient.

Results

Data are expressed as median and percentiles (Q1, Q3).The level of serum IL-35 in normal pregnancies was significantly higher than that in non-pregnant women [333.6 (59.32, 1391) pg/mL vs. 123.9 (8.763, 471.7) pg/mL; P < 0.001]. A significantly higher level of TGF-β was observed in the first trimester only as compared to non-pregnant women [473.4 (398.0, 580.5) pg/mL vs. 379.7 (311.0, 441.3) pg/mL, P < 0.01]. The difference in serum IL-10 level between pregnant women and non-pregnant women was not significant [8.602 (5.854, 12.89) pg/mL vs. 9.339 (5.691, 12.07) pg/mL; P > 0.05]. The level of serum IL-35 in recurrent spontaneous abortion was significantly lower than that in normal early pregnancy [220.4 (4.951, 702.0) pg/mL vs. 386.5 (64.37, 1355) pg/mL; P < 0.05]. The higher IL-35 level in first trimester pregnant women correlated with E2 (r = 0.3062, P < 0.01) and AFP (r = 0.3179, P < 0.01).

Conclusion

Serum levels of IL-35 increased in normal pregnancy and decreased in recurrent spontaneous abortion. Increased IL-35 correlated with estrogen and AFP levels in early pregnancy. IL-35 is becoming recognized as an active player in the maintenance of a successful pregnancy, but this is not the case for IL-10 or TGF-β.     

Impact of Obstructive Sleep Apnea on the Levels of Placental Growth Factor (PlGF) and Their Value for Predicting Short-Term Adverse Outcomes in Patients with Acute Coronary Syndrome

Background

Placental growth factor (PlGF) induces angiogenesis and promotes tissue repair, and plasma PlGF levels change markedly during acute myocardial infarction (AMI). Currently, the impact of obstructive sleep apnea (OSA) in patients with AMI is a subject of debate. Our objective was to evaluate the relationships between PlGF levels and both the severity of acute coronary syndrome (ACS) and short-term outcomes after ACS in patients with and without OSA.

Methods

A total of 538 consecutive patients (312 OSA patients and 226 controls) admitted for ACS were included in this study. All patients underwent polygraphy in the first 72 hours after hospital admission. The severity of disease and short-term prognoses were evaluated during the hospitalization period. Plasma PlGF levels were measured using an electrochemiluminescence immunoassay.

Results

Patients with OSA were significantly older and more frequently hypertensive and had higher BMIs than those without OSA. After adjusting for age, smoking status, BMI and hypertension, PlGF levels were significantly elevated in patients with OSA compared with patients without OSA (19.9 pg/mL, interquartile range: 16.6–24.5 pg/mL; 18.5 pg/mL, interquartile range: 14.7–22.7 pg/mL; p<0.001), and a higher apnea-hypopnea index (AHI) was associated with higher PlGF concentrations (p<0.003). Patients with higher levels of PlGF had also an increased odds ratio for the presence of 3 or more diseased vessels and for a Killip score>1, even after adjustment.

Conclusions

The results of this study show that in patients with ACS, elevated plasma levels of PlGF are associated with the presence of OSA and with adverse outcomes during short-term follow-up.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT01335087","term_id":"NCT01335087"}}NCT01335087     

Serum Levels of Monocyte Chemoattractant Protein-1 and All-Cause and Cardiovascular Mortality among Patients with Coronary Artery Disease

Background

Monocyte chemoattractant protein-1 (MCP-1) is an important chemokine at multiple phases of atherosclerosis in animals, but human studies are few and inconsistent. The aim of this study is to investigate the association of serum MCP-1with all-cause and cardiovascular disease (CVD) mortality among coronary artery disease (CAD) patients and determine whether this biomarker can add secondary prognostic value to standard risk predictors.

Methods

MCP-1 was measured at baseline in 1411 CAD patients who were 40–85 years of age. Cox proportional hazards regression models were used to estimate the association of MCP-1 levels with death risk.

Results

During a median follow-up of 3.3 years, 117 deaths were recorded, 88 of which were due to CVD. The multivariable-adjusted hazard ratios across tertiles of MCP-1 were 1.51 (95% confidence intervals [CI] 0.89–2.58), 1.00, and 2.11 (95% CI 1.31–3.40) for all-cause mortality, and 1.50 (95% CI 0.80–2.81), 1.00, and 2.21 (95% CI 1.27–3.87) for CVD mortality. The addition of serum MCP-1 to the fully adjusted model increased the C-index by 0.009 (p<0.0001) for all-cause mortality and 0.008 (p<0.0001) for CVD mortality and significantly improved the predictive ability by 12.1% (P = 0.006) on all-cause mortality and 12.6% (P = 0.003) on CVD mortality using the net reclassification improvement method.

Conclusions

Both lower and higher MCP-1 levels are associated with an increased risk of all-cause and CVD mortality among CAD patients. More research is needed to confirm its clinical relevance.     

Presepsin (Soluble CD14 Subtype): Reference Ranges of a New Sepsis Marker in Term and Preterm Neonates

Objective

Presepsin (soluble CD14 subtype) has been shown to be beneficial as a sepsis marker in adults. Nevertheless, very few data are available in neonates. The aim of the present study was to determine reference ranges of presepsin in term and preterm neonates.

Methods

Healthy term neonates and preterm neonates without clinical signs of infection admitted to the Neonatal Unit were consecutively enrolled. Presepsin concentrations in whole blood were measured using a point-of-care assay system located in the Unit. Demographic data, antenatal and perinatal variables commonly affecting C-reactive protein and procalcitonin values were considered.

Results

Of the 684 neonates enrolled in the study, 484 (70.8%) were born at term and 200 (29.2%) were preterm (24–36 weeks’ gestation). In term infants, presepsin median value was 603.5 pg/mL (interquartile range: 466.5–791 pg/mL; 5th and 95th centiles: 315 and 1178 pg/mL respectively). In preterm infants, presepsin median value was slightly higher, equal to 620 pg/mL (interquartile range: 503–864 pg/mL; 5th and 95th centiles: 352 and 1370 pg/mL respectively). The reference ranges of presepsin we determined were much higher than those seen in healthy adults. No correlation between presepsin levels and postnatal age was observed, as well as no significant difference was demonstrated in preterm neonates at different gestational ages. None of the variables analyzed affected presepsin levels at a clinical significant extent.

Conclusion

For the first time, this study provides reference ranges of presepsin in term and preterm neonates. Having reliable reference values is crucial for obtaining an adequate diagnostic accuracy. Based on our results, most variables commonly affecting C-reactive protein and procalcitonin values do not affect presepsin levels, which suggests that presepsin could be an effective sepsis marker. Further investigations in large groups of neonates with sepsis are needed to determine the diagnostic and prognostic value of this biomarker.     

Transient but Significant Visual Field Defects after Robot-Assisted Laparoscopic Radical Prostatectomy in Deep Trendelenburg Position

Background

Robot-assisted laparoscopic radical prostatectomy (RALP) is a minimally invasive surgical procedure for prostate cancer. During RALP, the patient must be in a steep Trendelenburg (head-down) position, which leads to a significant increase in intraocular pressure (IOP). The association of RALP with visual field sensitivity, however, has not been prospectively studied. The purpose of this study was to evaluate prospectively the visual field, retinal nerve fiber layer (RNFL) thickness, and optic disc morphology in 50 normal eyes of 25 male patients that underwent RALP.

Methods

The subjects were 25 males among 33 consecutive patients who underwent uneventful RALP under general anesthesia in our hospital. Visual field tests using the Humphrey visual field analyzer 30-2 SITA-standard program were performed before, 7 days after, and 1-3 months after RALP. IOP was measured before, during, and after RALP; and ophthalmologic examinations, including slit-lamp, fundus examination, and optical coherence tomography (OCT), were scheduled before and 7 days after surgery.

Results

IOP was significantly increased during RALP up to 29.4 mmHg (P<0.01). Postoperative local visual field defects were detected in 7 eyes of 7 subjects dominantly in the lower hemifield without abnormal findings in the optic nerve head or retina, and the visual field recovered to normal within 3 months after surgery. General factors associated with RALP, IOP, RNFL thickness, or optic disc parameters did not differ significantly between eyes with and without postoperative visual field defects, and parameters of OCT measurements were not altered after surgery.

Conclusion

Transient but significant unilateral visual field defects were found in 28% of the subjects examined. The probable cause are the increased IOP and altered perfusion during surgery and ophthalmologic examinations are therefore suggested before and after RALP.