Increased basal nitric oxide amplifies the association of inflammation with all-cause and cardiovascular mortality in prevalent hemodialysis patients

Purpose

We tested the hypothesis that the basal nitric oxide (NO) levels in prevalent hemodialysis (HD) patients may associate with inflammatory cytokines, predisposing them to increased mortality risk.

Methods

We performed a prospective cohort study of 76 prevalent HD patients (42 % women), with a mean age of 65.3 ± 11.8 years with a follow-up for almost 4 years (median—47 months, interquartile range ?19–75 months). We measured basal NO, proinflammatory cytokines (TNF-α, IL-1, IL-6, and IL-10), dietary intake, biochemical parameters of nutrition, and body composition (anthropometry and bioimpedance analysis).

Results

Among various cytokines studied, only IL-6 exhibited a statistically significant linear association (adjusted r = 0.31, p = 0.014) with NO. Statistical interaction analysis showed a departure from multiplicity of effects of high NO (above the median) with high IL-6 (above the median) levels: crude Cox hazard ratios for all-cause and cardiovascular mortality for the product termed IL-6 × NO were 2.73 with a 95 % CI of 1.38–5.40 (p = 0.004) and 5.03 with a 95 % CI of 1.76–14.40 (p = 0.003), respectively. Across the four IL-6 NO categories, the group with high IL-6 and high NO (above their median levels) exhibited worse outcomes in both, all-cause and cardiovascular mortality (multivariable adjusted hazard ratios were 3.06, 95 % CI of 1.24–7.54 and 3.95, 95 % CI of 1.02–15.32, respectively).

Conclusions

Chronic inflammation, as measured by higher serum IL-6 levels, in combination with high basal NO is associated with worse clinical outcomes in terms of all-cause and cardiovascular death in clinically stable prevalent HD patients.     

Cytokine responses following laparoscopic or open pyeloplasty in children

Background

The present study evaluated the cytokine response in children following laparoscopic pyeloplasty (LP) or open pyeloplasty (OP). A series of cytokines were measured postoperatively, including interkin1-β (IL-1β), interleukin-6 (IL-6), interleukin-8 (IL-8), interleukin-10 (IL-10), tumor necrosis factor-alpha (TNF-α), and C-reactive protein (CRP).

Methods

A total of 31 patients, with an average age of 9.1 ± 3.0 years (range 2.5–14 years) were studied. Fourteen patients underwent LP and 17 underwent OP. Blood serum concentrations of IL-1β, IL-6, IL-8, IL-10, TNF-α, and CRP were measured via enzyme-linked immunosorbent assay (ELISA) before surgery as well as 4, 24, and 48 h following the operation. In addition, the procedure duration, hospital stay, incidence of wound infection, and the recurrence rate of stenosis in both groups were compared.

Results

Serum IL-6 and CRP concentrations were significantly elevated in both groups at 4, 24, and 48 h relative to preoperative levels. However, the rise in IL-6 and CRP in OP group was significantly more robust than in LP group. No significant changes were observed in serum levels of IL-1β, IL-8, IL-10, or TNF-α in either group. The procedure duration was significantly longer for LP (193.6 ± 74.7 min, range 120–360 min) versus OP (120.1 ± 27.5 min, range 90–165 min, p < 0.05), but the hospital stay following LP was shorter (LP group: 5.3 ± 1.1 days versus OP group: 9.3 ± 2.1 days, p < 0.05). No severe complications were noted in either group, however, one child experienced wound infection following OP procedure. An incident of recurrent stenosis following the operation occurred in both groups. There was no postoperative morbidity or severe implications at 12 month follow-up in either group.

Conclusions

Both OP and LP are safe and effective procedures for the treatment of ureteropelvic junction obstruction in the pediatric population. However, the shorter hospital stay and decreased cytokine response following LP indicates potential benefits over traditional invasive procedures.     

Plasma Cytokine Analysis in Patients with Advanced Extremity Melanoma Undergoing Isolated Limb Infusion

Background

Preprocedure clinical and pathologic factors have failed to consistently differentiate complete response (CR) from progressive disease (PD) in patients after isolated limb infusion (ILI) with melphalan for unresectable in-transit extremity melanoma.

Methods

Multiplex immunobead assay technology (Milliplex MAP Human Cytokine/Chemokine Magnetic Bead Panel, Millipore Corp., Billerica, MA; and Magpix analytical test instrument, Luminex Corp., Austin, TX) was performed on pre-ILI plasma to determine concentrations of selected cytokines (MIP-1α, IL-1Rα, IP-10, IL-1β, IL-1α, MCP-1, IL-6, IL-17, EGF, IL-12p40, VEGF, GM-CSF, and MIP-1β) on a subset of patients (n = 180) who experienced CR (n = 23) or PD (n = 24) after ILI. Plasma from normal donors (n = 12) was also evaluated.

Results

Of 180 ILIs performed, 28 % (95 % confidence interval 22–35, n = 50) experienced a CR, 14 % (n = 25) experienced a partial response, 11 % (n = 21) had stable disease, 34 % (n = 61) had PD, and 13 % (n = 23) were not evaluable for response. Tumor characteristics and pharmacokinetics appeared similar between CR (n = 23) and PD (n = 24) patients who underwent cytokine analysis. Although there were no differences in cytokine levels between CR and PD patients, there were differences between the melanoma patients and controls. MIP-1α, IL-1Rα, IL-1β, IL-1α, IL-17, EGF, IL-12p40, VEGF, GM-CSF, and MIP-1β were significantly higher in normal controls compared to melanoma patients, while IP-10 was lower (p < 0.001) in controls compared to melanoma patients.

Conclusions

Patients with unresectable in-transit melanoma appear to have markedly decreased levels of immune activating cytokines compared to normal healthy controls. This further supports a potential role for immune-targeted therapies and immune monitoring in patients with regionally advanced melanoma.     

Single-port cholecystectomy in obese patients: our experience and a review of the literature

Purpose

The objective of the present study was to compare the postoperative outcomes between obese and normal-weight patients undergoing single-port cholecystectomy (SPC) for gallstone disease.

Methods

A prospectively maintained SPC-database was retrospectively analyzed, and the outcomes of obese [body mass index (BMI) ≥30 kg/m²] and normal-weight patients were compared. All patients underwent SPC using the reusable X-Cone? device.

Results

A total of 100 patients underwent SPC between July 2009 and September 2011. Seventeen obese patients (17 %) (median BMI 33.9 kg/m², range 30.0–38.8) were compared to 83 normal-weight patients (median BMI 24.1 kg/m², range 17.3–29.5). The length of the operation (median 75.5 min, range 42–156 vs. median 72.0 min, range 42–129; p = 0.51), conversion rate (N = 2 vs. N = 0; p = 1), postoperative complication rate (9.6 vs. 11.8%; p = 0.68), and postoperative hospital stay (median 3 days, range 1–14 vs. median 3 days, range 2–5; p = 0.74), were comparable for the normal-weight and obese patients.

Conclusion

The postoperative outcome of obese patients after SPC is not inferior to that of normal-weight patients undergoing the same operation. Therefore, the BMI should not be considered a key criterion in the patient selection for single-port surgery.     

Hippocampal volume reduction in elderly patients at risk for postoperative cognitive dysfunction

Purpose

Postoperative cognitive dysfunction (POCD) is a formidable public health issue, which would not only affect the quality of life among elderly patients but also lead to pulmonary infection and increased mortality. While, there is a lack of an effective indicator in predicting POCD. As one pivotal part of the limbic system in brain, hippocampus is associated with cognitive function. Hippocampal atrophy could indicate the degree of changes in cognitive function.

Methods

Forty-one ASA II or III patients (23 male, 18 female) aged ≥65 years undergoing open gastrointestinal tract surgery were enrolled in this study. MRI was performed to measure the volume of hippocampal formation before surgery and the results were standardized according to individual intracranial volume. All patients underwent a battery of neuropsychological tests including sensitive tests on the Wechsler adult memory scale and Wechsler adult intelligence scale, trail making test and the grooved pegboard test. We used the Z score to identify POCD as recommended by ISPOCD. All patients were then divided into POCD group and non-POCD group according to the results of the neuropsychological tests. The results of the tests were correlated with the volume of hippocampal formation measured by MRI. The value of MRI measurement of hippocampal volume in predicting POCD was analyzed. Multivariate linear correlation analyses of compositive Z score using potential contributing factors such as age, duration of anesthesia, education and hippocampal volume was carried out.

Results

Thirty-six patients completed the whole battery of neuropsychological tests after surgery. Thirteen of the 36 patients were found to have POCD (36 %) on the postoperative 4th day. The hippocampal volume was significantly smaller in POCD group (4.75 ± 0.23) than in non-POCD group (5.06 ± 0.31). Hippocampal volume had great influence on Z score, and had negative correlation with Z score.

Conclusion

The MRI measurement of hippocampal volume is suggested to be valuable as a predictor of POCD in the elderly.     

Reduction of intercellular adhesion molecule 1 may play a role in anti-inflammatory effect of hyaluronic acid in a rat model of severe non-bacterial cystitis

Purpose

To evaluate the impact of intercellular adhesion molecule 1 (ICAM-1) in hyaluronic acid (HA) therapy in rats model of severe non-bacterial cystitis.

Methods

Cystitis models in Sprague–Dawley female rats were produced by combination of intraperitoneal cyclophosphamide (CYP) with intravesical protamine/lipopolysaccharide (PS/LPS). HA or heparin (0.5 ml) was introduced intravesically to rats’ bladders followed PS/LPS. Bladder tissue was prepared for histology including mast cell presence and measurement of ICAM-1, tumor necrosis factor (TNF)-α, and interleukin 6 (IL-6).

Results

Cystitis model using intraperitoneal CYP and intravesical SP/LPS showed serious inflammation, higher mast cell count with elevated ICAM-1, TNF-α, and IL-6 levels. After intravesical heparin or HA treatment, incidence of grades 3–4 bladder inflammation and tissue ICAM-1 level were only significantly lower in HA group (P = 0.017, P = 0.021, respectively), but not in heparin group (P = 0.12, P = 0.798, respectively). Remarkably lower level of TNF-α (P = 0.003) and ICAM-1 (P = 0.006) was detected in HA-treated rats compared with heparin-treated rats. Inflammation grade and ICAM-1 level had strong correlation (P < 0.001). IL-6 level after HA or heparin instillation had no difference.

Conclusions

Intravesical administration of HA decreased the severity of bladder inflammation, mast cell presence, and levels of ICAM-1 and TNF-α in a rat model of severe non-bacterial cystitis; its effect was more obvious than that of heparin. Reduction of ICAM-1 may play a role in the anti-inflammatory effect of HA.     

Relationship Between Cytokine Gene Polymorphisms and Risk of Postoperative Pneumonia with Esophageal Cancer

Background

We retrospectively evaluated the relationship between cytokine gene polymorphisms and development of postoperative pneumonia after esophagectomy.

Methods

In 120 patients who underwent esophagectomy, serum samples were obtained to measure levels of serum interleukin (IL)-6 and IL-10 at four time points (preoperatively, postoperative day (POD)0, POD1, and POD3). DNA extracted from peripheral blood in all patients was analyzed to determine polymorphisms of cytokines such as tumor necrosis factor-α -1031 T/C, IL-1β -511C/T, IL-6 -634C/G, and IL-10 -819 T/C.

Results

Postoperative pneumonia arose in 34 patients (28.3 %). Perioperative serum IL-10 levels were significantly higher for IL-10 -819 C/T?+?C/C genotypes than for T/T genotypes (POD0 16.7?±?2.84 vs. 8.54?±?0.87 pg/ml, p?=?0.0002; POD1 14.0?±?2.64 vs. 8.8?±?0.87 pg/ml, p?=?0.0143; POD3 8.9?±?2.67 vs. 4.4?±?0.52 pg/ml, p?=?0.0076). The frequency of the IL-10 -819 T/T genotype was significantly higher in patients with postoperative pneumonia than in patients without pneumonia (p?=?0.0323). Multivariate analysis of factors such as sex, smoking, length of operation, field of lymph node dissection, and IL-10 polymorphism identified IL-10 polymorphism as independent predictor of postoperative pneumonia.

Conclusions

Patients with IL-10 -819 T/T genotype may be at high risk for postoperative pneumonia after esophagectomy.     

Propofol attenuates lipopolysaccharide-induced monocyte chemoattractant protein-1 production through p38 MAPK and SAPK/JNK in alveolar epithelial cells

Purpose

Propofol is widely used in sedation and surgical procedures involving patients with acute lung injury (ALI), a common complication in critically ill patients. Monocyte chemoattractant protein-1 (MCP-1) plays an important role in pathological changes in ALI. The present study investigated the anti-inflammatory effect and mechanism of propofol on MCP-1 production and mitogen-activated protein kinase (MAPK) phosphorylation induced by lipopolysaccharide (LPS) in alveolar epithelial cells (AECs).

Methods

AECs were treated with 1 μg/ml LPS for 30 min, 1 h, 6 h, or 24 h following pretreatment with 12.5–100 μM propofol for 30 min. Cytokines and chemokines secretion were profiled using cytokine array, and mRNA and protein levels of MCP-1 were measured by RT-PCR and ELISA. The phosphorylation of p38 MAPK, p44/42 MAPK, SAPK/JNK, ATF-2, and c-Jun were measured by Western blot analysis.

Results

Propofol at 50 and 100 μM dose-dependently inhibited MCP-1 mRNA expression (P < 0.05), and also propofol at 50 μM decreased extracellular MCP-1 protein levels (P < 0.05) compared to the LPS group. Propofol at 12.5–50 μM inhibited LPS-induced phosphorylation of p38 MAPK, p44/42 MAPK, SAPK/JNK, ATF-2, and c-Jun in AECs.

Conclusions

Propofol at clinically relevant concentrations attenuated LPS-induced MCP-1 mRNA expression and secretion by inhibiting the phosphorylation of p38 MAPK, SAPK/JNK, ATF-2, and c-Jun exerting its anti-inflammatory effects in AECs. These results suggest that propofol may modulate inflammatory response at clinically achievable concentrations in ALI.     

TNF-α, IL-6, and IL-8 Cytokines and Their Association with TNF-α-308 G/A Polymorphism and Postoperative Sepsis

Introduction

Early prediction of postoperative sepsis remains an enormous clinical challenge. Association of TNF-α-308 G/A polymorphism with sepsis remains controversial. We, therefore, investigated this polymorphism with serum levels of cytokines TNF-α, IL-6, and IL-8 in relation to development of sepsis following major gastrointestinal surgery.

Methods

Two hundred and thirty-nine patients undergoing major gastrointestinal surgery were enrolled. Polymorphism was studied through the analysis of restriction fragments of Nco1-digested DNA with the polymerase chain reaction. All patients were followed for 1 month following surgery for evidence of sepsis. Levels of serum cytokines TNF-α, IL-6, and IL-8 were measured preoperatively and postoperatively by enzyme-linked immunosorbent assay (ELISA).

Results

Forty-seven (19.66 %) patients developed postoperative sepsis. Patients with postoperative sepsis were significantly (p?=?0.002) more likely to possess AA homozygous genotype with higher capacity to produce cytokines TNF-α (p?<?0.0001), IL-6 (p?<?0.0001), and IL-8 (p?<?0.0001) as compared to other genotypes. When compared with patients carrying at least one G allele, the AA genotype was associated with a significantly higher probability (odds ratio (OR)?=?4.17; p?=?0.003; 95 % confidence interval (CI)?=?1.5–11.48) of developing sepsis. Compared with the GG genotype, AA was associated with a significantly higher probability (OR?=?5.18; p?=?0.0008; 95 % CI?=?1.82–14.76) of sepsis development.

Conclusion

TNF-α-308 G/A polymorphism is significantly associated with the development of postoperative sepsis and with increased expression of cytokines TNF-α, IL-6, and IL-8.     

Comparative effects of flurbiprofen and fentanyl on natural killer cell cytotoxicity, lymphocyte subsets and cytokine concentrations in post-surgical intensive care unit patients: prospective, randomized study

Purpose

The purpose of this study was to compare the effect of the long-term administration of flurbiprofen and fentanyl in the intensive care unit on natural killer cell cytotoxicity (NKCC), lymphocyte subsets and cytokine levels.

Methods

In this prospective study, patients scheduled for at least 48 h sedation after neck surgery were randomly assigned to two groups called group N and group F. Group N patients were sedated with propofol and flurbiprofen after surgery (n = 12), while group F patients were sedated with propofol and fentanyl (n = 13). The NKCC, lymphocyte subsets, and plasma levels of tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6, and IL-10 were measured before and at the end of surgery, on postoperative day (POD) 1 and POD2.

Results

The NKCC was significantly higher on POD1 in group N than in group F (14.5 ± 11.2 versus 6.3 ± 4.1 %, p < 0.05), the difference between the groups disappearing on POD2. Lymphocyte subsets and plasma levels of cytokines were not significantly different between the two groups during the study period.

Conclusions

Transient suppressive effects on NKCC were observed in the fentanyl group as compared to the flurbiprofen group. This suggests that when choosing postoperative analgesics, physicians should bear in mind the potential immunosuppressive effects of these agents in patients requiring prolonged sedation in the intensive care unit.     

The role of urinary TGF-β1, TNF-α, IL-6 and microalbuminuria for monitoring therapy in posterior urethral valves

Background

Long-term renal deterioration is common in patients with posterior urethral valves (PUV), and early identification of detrimental factors can help in counselling patients as well as in guiding future therapy. The aim of our study was (1) to evaluate urinary transforming growth factor-β₁ (TGF-β₁), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) levels and microalbuminuria before and after ablation of PUV and (2) to examine the effect of early induction of angiotensin-converting enzyme inhibitors (ACE-I) on renal recovery.

Methods

The study included 30 patients with diagnosed PUV. Urinary cytokines were measured pre-operatively and post-operatively for 1 year. The study group was subdivided into two subgroups at 6 months after surgery. Group 1 included 16 patients whose urinary TGF-β₁ level showed a declining trend. Group 2 included 14 patients whose urinary TGF-β₁ showed a rising trend or plateaued; these patients were started on ACE-I therapy, which they received for at least 6 months.

Results

Urinary TGF-β₁, TNF-α and microalbumin levels were high in patients with PUV. In Group 1 patients, urinary TGF-β_1, TNF-α and microalbumin levels fell significantly following valve ablation and continued to decline for 12 months. In Group 2 patients, after an initial fall following valve ablation, urinary TGF-β₁, TNF-α and microalbumin showed a continued rise until 6 months post-surgery. After ACE-I therapy, there was 53.43 % fall in urinary TGF-β₁, 43.15 % fall in microalbuminuria, 28.57 % improvement in split renal function and 35.80 % improvement in GFR.

Conclusions

Based on our results, urinary TGF-β₁, urinary TNF-α and microalbuminuria can be used as biomarkers for the early recognition of ongoing renal damage in patients with PUV. ACE-I plays a role in retarding renal damage in these patients.     

Effects of recombinant human erythropoietin on neuropathic pain and cerebral expressions of cytokines and nuclear factor-kappa B

Purpose

The effect of recombinant human erythropoietin (rhEPO) on neuropathic pain remains unclear. This study aimed to determine the effects of preemptive administration of rhEPO on the behavioural changes and neuroinflammatory responses in a rat model of neuropathic pain.

Methods

Fifty rats were randomly allocated into five groups, sham-operation treated with saline and L5 spinal nerve transection treated with different doses of rhEPO (0 [saline], 1000, 3000, or 5000 U · kg^?1, respectively). The rats were intraperitoneally treated from 1 day before surgery to post-surgery day 7. The mechanical (paw pressure thresholds, PPT) and thermal thresholds (paw withdrawal latencies, PWL) were measured on post-surgery days 1, 3, and 7. The contralateral brain was obtained on post-surgery day 7 to determine the expressions of tumour necrosis factor (TNF-α), interleukin (IL)-1β, IL-6, L-10, and nuclear factor-kappa B (NF-κB) activity.

Results

There were significant decreases in PPT and PWL after L5 spinal nerve transection (P < 0.001). Compared with the saline group, the rhEPO 3000 and 5000 U · kg^?1 groups resulted in significant increases in PPT and PWL (P < 0.001) and reduced the cerebral expressions of TNF-α, IL-1β, IL-6, and NF-κB activity associated with the increase in IL-10 (rhEPO3000 group, P < 0.05, and rhEPO5000 group, P < 0.001, respectively). Administration of rhEPO 1000 U · kg^?1 had no significant effects on these variables.

Conclusions

Preemptive rhEPO dose-dependently attenuated the mechanical and thermal hyperalgesia in L5 spinal nerve transection rats, which correlated with the decreased cerebral expressions of TNF-α, IL-1β, and IL-6 via downregulating NF-κB activity and the increased expression of IL-10.     

Urinary brain-derived neurotrophic factor: a potential biomarker for objective diagnosis of overactive bladder

Purpose

To investigate the diagnostic performance of urinary brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) as potential biomarkers for overactive bladder (OAB).

Methods

Ninety women diagnosed with OAB and 45 normal controls without OAB were enrolled. Urine samples were collected from all subjects. Urinary BDNF and NGF levels were measured using enzyme-linked immunosorbent assays. Results normalized by urinary creatinine (Cr) levels were compared between OAB groups and controls. Symptom severity was assessed using overactive bladder symptom score.

Results

Urinary BDNF and NGF levels were elevated in OAB groups but not in controls. Mean (SD) baseline BDNF and NGF levels normalized by Cr levels were significantly higher in OAB subjects than in controls (20.609 ± 23.932 vs. 1.779 ± 0.729, p < 0.01) and (0.258 ± 0.264 vs. 0.081 ± 0.028, p < 0.01), respectively. Urinary BDNF/Cr levels were 80-fold higher than NGF/Cr levels in OAB subjects. Receiver operating characteristic curves for assessing urinary BDNF/Cr levels in OAB groups showed sensitivity and specificity of 93.33 and 88.89 %, respectively. Urinary BDNF levels were associated with OAB symptom severity.

Conclusions

Urinary BDNF/Cr levels are elevated in women with OAB and are significantly associated with symptom severity. No elevation of BDNF is found in women without OAB. BDNF analysis has better sensitivity than NGF in detecting OAB in subjects without other lower urinary tract disorders. Results of the present study suggest a potential role for BDNF as an objective biomarker for OAB diagnosis.     

Mapping the cytokine profile of painful bladder syndrome/interstitial cystitis in human bladder and urine specimens

Purpose

This study investigated the cytokine profile in bladder tissue and urine of painful bladder syndrome/interstitial cystitis (PBS/IC) patients.

Methods

Multiplex analysis of 23 cytokines was performed with a multiple antigen bead assay (Luminex 100 IS) on cold cup bladder biopsy and urine specimens collected during cystoscopy with hydrodistention (HD) under general anesthesia from 10 PBS/IC patients (ICS definition). Collected tissue specimens and urine from pre-HD and post-HD (mean 27 days) were compared to banked urine and tissue specimens (n = 10) collected from control subjects without PBS/IC symptoms.

Results

Univariate comparison of bladder tissue levels found significant elevation of IL-16, IL-18, CTACK, ICAM-1, MCP-3, SCGFβ, TRAIL, and VCAM-1 in PBS/IC relative to controls. Multivariate analysis revealed VCAM-1 and ICAM-1 were responsible for the discrimination of both tissue and urine of PBS/IC from controls. Urine levels of MCP-3 and TRAIL were significantly reduced a month after HD in concert with improvement in standardized measures of clinical symptoms (pain, urgency, and frequency (PUF) overall score [mean 25.8 ± 5.5 vs. 20.3 ± 7, p = 0.04] and symptom score [mean 18.2 ± 3.2 vs. 12.2 ± 5.9; p = 0.009]). Post-HD urine levels of MCSF(r = 0.88; p = 0.003), MCP-3 (r = 0.81; p = 0.01), SDF1α (r = 0.82; p = 0.01), and IL-18 (r = 0.64; p = 0.08) positively correlated with improved symptom scores.

Conclusions

These results indicate significant elevation of cytokines in PBS/IC bladder tissue relative to controls. Significant reduction in post-HD urine levels of MCP-3 and TRAIL relative to pre-HD in PBS/IC was associated with clinical improvement (as measured by PBS/IC symptom scores) to qualify them as biomarker candidates.     

Gastric Bypass and Sleeve Gastrectomy: the Same Impact on IL-6 and TNF-α. Prospective Clinical Trial

Background

Due to the association between the quantity of adipose tissue and concentrations of interleukin-6 (IL-6) and tumor necrosis factor (TNF-α), this work aimed to assess the effects of Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG) procedures on serum IL-6 and TNF-α concentrations.

Methods

This study evaluated serum IL-6 and TNF-α levels, as well as routine anthropometric and biochemical values, before and 1 year post-bariatric surgery. Fifty percent of patients (n?=?24) underwent RYGB, and 50 % (n?=?24) underwent SG. Prior to bariatric surgery, IL-6 and TNF-α mRNA expression levels in subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) were investigated in obese women.

Results

There was a significant reduction (p?<?0.05) in all anthropometric and routine biochemical measurements in patients in the RYGB and SG groups 1 year post-surgery. The serum concentrations of IL-6 and TNF-α were reduced following surgery in both groups (p?<?0.05). No differences in the relative expression levels of IL-6 and TNF-α were found between SAT and VAT prior to bariatric surgery.

Conclusions

RYGB and SG procedures demonstrated a similar impact on adipokine levels in women 1 year post-surgery. Both techniques may improve the course of chronic diseases and the state of inflammation associated with obesity.     

Elevated IL-1β and IL-6 levels in lumbar herniated discs in patients with sciatic pain

Purpose

Previous experimental models have shown that proinflammatory cytokines modulate peripheral and central nociception. However, the direct correlation between inflammation and pain in patients remains unclear. Our aim is to correlate the levels of inflammation in the spine with pre- and postoperative pain scores after discectomy.

Methods

Paravertebral muscle, annulus fibrosus (AF) and nucleus pulposus (NP) biopsies were intraoperatively collected from ten lumbar disc hernia (LDH) patients suffering from chronic sciatic pain and, as painless controls, five scoliosis patients. IL-1β and IL-6 expressions in these biopsies were assessed by qPCR and western blot. The amount of pain, indicated on a 0–10 point visual analogue scale (VAS), was assessed 1 day before surgery and 6 weeks and 1 year after surgery. For analysis purposes, LDH patients were grouped into painful (VAS ≥ 3.5) and non-painful (VAS < 3.5). LDH painful patient group showed a onefold increased mRNA expression of IL-1β in the NP, and IL-6 in the AF and NP (p < 0.05 vs. controls).

Results

By western blot analysis, both cytokines were clearly visible in all LDH biopsies, but not in controls. However, cytokine expression of the painful patient group did not differ from those of the non-painful patient group. In addition, there was no correlation between VAS scores and either marker.

Conclusions

These findings support the idea that LDH is accompanied by a local inflammatory process. Yet, the lack of correlation between IL-1β or IL-6 expression and the severity pain suggests that these cytokines may not play a leading role in maintaining a pain generating network.     

Hypothyroidism After Hemithyroidectomy

Background

The risk of hypothyroidism after hemithyroidectomy is variable, and most estimates come from single institutional studies. The purpose of the present study was to determine the incidence of hypothyroidism at the population level, and to evaluate predictive factors for hypothyroidism after hemithyroidectomy.

Methods

This retrospective study identified euthyroid patients who underwent hemithyroidectomy between 2000 and 2010 for benign disease in Kaiser Permanente Southern California regional hospitals. The incidence of hypothyroidism [thyroid stimulating hormone (TSH) levels >4 μIU/ml] was analyzed. The independent effect of age-quartile, gender, race, thyroiditis, and preoperative TSH level on the development of hypothyroidism was evaluated.

Results

Of 1,240 euthyroid patients identified, 417 (34 %) developed hypothyroidism, and 314 (25 % of total group) needed levothyroxine. Hypothyroidism was more common in age-quartile 2 (32 %), age-quartile 3 (37 %), and age-quartile 4 (42 %) than in age-quartile 1 (25 %) [adjusted odds ratio (OR) = 1.87; 95 % confidence interval (CI) 1.27–2.76, p = 0.002; age-quartile 4 compared to age-quartile 1]. Hypothyroidism was more frequent with increasing preoperative TSH levels 36, 72, and 92 % in patients with TSH levels of 1.0–2, 2.01–3, and 3.01–4 μIU/ml, respectively, compared to 17 % in those with TSH levels <1 μIU/ml [adjusted OR = 45.1; 95 % CI 13.5–151, p < 0.0001; 3.01–4 μIU/ml compared to <1 μIU/ml]. Thyroiditis was also an independent predictor of hypothyroidism.

Conclusions

About one third of euthyroid patients who undergo hemithyroidectomy develop hypothyroidism. The most significant predictor is the preoperative TSH level, with an approximate doubling of risk for each 1 unit of TSH increase over 1 μIU/ml. Our categorical scale is simple and allows for easy recall when counseling patients preoperatively.     

Cytokines in chronic kidney disease: potential link of MCP-1 and dyslipidemia in glomerular diseases

Background

Many studies have indicated a role for cytokines in chronic kidney disease (CKD). The aim of this study was to evaluate plasma and urinary levels of monocyte chemoattractant protein-1 (MCP-1/CCL2), transforming growth factor-beta1 (TGF-β1), and interleukin-8 (IL-8/CXCL8) in pediatric patients with CKD stages 2–4.

Methods

Cytokines were measured in 37 healthy controls and in 42 CKD patients by enzyme-linked immunoassay. Patients were divided into groups according to CKD etiology: glomerular disease (group 1, n?=?11) and congenital anomalies of the kidney and urinary tract (group 2, n?=?31). Urinary cytokine measurements were standardized for creatinine.

Results

Plasma and urinary levels of MCP-1/CCL2 were significantly higher in both CKD groups compared to the control group. Between the two CKD groups, only urinary MCP-1/CCL2 levels were significantly different, with MCP-1/CCL2 levels higher in group 1 patients. Plasma and urinary levels of IL-8/CXCL8 and TGF-β1 were undetectable in the control group but comparable between the two CKD groups. In group 1 patients, urinary MCP-1/CCL2 levels were negatively correlated to serum albumin levels and positively correlated to the levels of total cholesterol and triglycerides. In group 2 patients, urinary levels of IL-8/CXCL8 were negatively correlated with the estimated glomerular filtration rate and positively correlated with body mass index.

Conclusions

Differences in cytokine profiles may be related to CKD etiology and other disease-associated alterations.     

IL-17A-mediated sRANK ligand elevation involved in postmenopausal osteoporosis

Summary

The role of proinflammatory IL-17 cytokine was studied in postmenopausal bone loss between 31 osteopenic and 41 osteoporotic women. The effect of serum IL-17A, soluble receptor activator of NF-κB (sRANK) ligand, and osteoprotegerin (OPG) levels on lumbar bone mineral densities was measured. The results demonstrated an increased IL-17A-mediated sRANK ligand elevation in postmenopausal osteoporotic bone loss.

Introduction

IL-17 proinflammatory cytokine is a new inducer of bone loss. Postmenopausal osteoporosis represents a cross talk between estrogen deprivation and increased immune reactivity. The role of IL-17 was studied in the bone loss of postmenopausal osteoporosis.

Methods

Serum IL-17A, sRANK ligand, and OPG levels were investigated on bone mineral densities (BMDs) in the total lumbar (L1–L4) region in 18 pre- and 72 postmenopausal women. IL-17A, sRANK ligand, OPG levels, and BMDs were measured with enzyme-linked immunosorbent assay (ELISA) and dual-energy X-ray absorptiometry (DXA).

Results

Increased serum IL-17A, sRANK ligand, and OPG levels were demonstrated in postmenopausal osteoporotic women compared to osteopenic women (3.65?±?0.61 vs 3.31?±?0.43 ng/ml for IL-17A, P?<?0.007; 2.88?±?0.84 vs 2.49?±?0.61 ng/ml for sRANK ligand, P?<?0.027; and 1.43?±?0.07 vs 1.39?±?0.07 ng/ml for OPG, P?<?0.038). In postmenopausal women, IL-17A levels correlated inversely with total lumbar BMDs (P?<?0.008, r?=??0.279) and positively with sRANK ligand levels (P?<?0.0001, r?=?0.387) or the ratio of sRANK ligand and OPG (P?<?0.013, r?=?0.261), but did not with OPG levels alone.

Conclusion

Increased IL-17A levels are involved in postmenopausal osteoporosis, playing a role in the bone-resorpting processes.     

Circulating Cell-Free DNA: A Promising Marker of Pathologic Tumor Response in Rectal Cancer Patients Receiving Preoperative Chemoradiotherapy

Purpose

The circulating cell-free DNA (cfDNA) in plasma has been reported to be a marker of cancer detection. The aim of this study was to investigate whether the cfDNA has a role as response biomarker in patients receiving preoperative chemoradiotherapy (CRT) for rectal cancer.

Methods

Sixty-seven patients (median age 61 years; male/female 42/25) who underwent CRT for rectal cancer were evaluated. After tumor regression grade (TRG) classification was made, the patients were classified as having disease that responded (TRG 1–2) and that did not respond (TRG 3–5) to therapy. Plasma samples were obtained from patients before and after CRT. The cfDNA levels were analyzed by quantitative real-time polymerase chain reaction of β-globin. On the basis of the Alu repeats, the cfDNA was considered as either total (fragments of 115 bp, Alu 115) or tumoral (fragments of 247 bp, Alu 247). The association between the pre- or post-CRT levels and between variations during CRT of the Alu 247, Alu 115 repeat, and Alu 247/115 ratio (cfDNA integrity index) and the pathologic tumor response was analyzed.

Results

The baseline levels of cfDNA were not associated with tumor response. The post-CRT levels of the cfDNA integrity index were significantly lower in responsive compared to nonresponsive disease (P = 0.0009). Both the median value of the Alu 247 repeat and the cfDNA integrity index decreased after CRT in disease that responded to therapy (P < 0.005 and P < 0.005, respectively) compared to disease that did not respond to therapy (P = 0.83 and P = 0.726, respectively). The results of the multivariable logistic regression analysis showed that only the cfDNA integrity index was significantly and independently associated with tumor response to treatment.

Conclusions

The plasma levels of the longer fragments (Alu 247) of cfDNA and the cfDNA integrity index are promising markers to predict tumor response after preoperative CRT for rectal cancer.