Relationship between HRV measurements and demographic and clinical variables in a population of patients with atrial fibrillation

Little is known about the role of HRV in atrial fibrillation (AF) patients. Aim of our study was to assess the relationship between HRV measurements and demographic and clinical variables in a population of 274 AF patients. We selected all consecutive patients with persistent/permanent AF among whom had performed a Holter ECG in our Department from April 2010 to April 2015. Time-domain analysis of HRV was evaluated. Demographic and clinical variables were collected for each patient. At multivariable logistic regression, a higher pNN50 was associated with ACE inhibitors/ARBs (p = 0.016) and a lower pNN50 with obesity (p = 0.037) and higher heart rate (HR) (p < 0.0005). A higher RMSSD was associated with ACE inhibitors/ARBs (p = 0.001), digitalis (p < 0.0005) and beta-blockers (p = 0.002) and a lower RMSSD with a higher HR (p < 0.0005). A higher SDNN_i was associated with ACE inhibitors/ARBs (p < 0.0005), digitalis (p < 0.0005) and beta-blockers (p = 0.002) and a lower SDNN_i with dysthyroidism (p = 0.048) and higher HR (p < 0.0005). A higher SDANN was associated with non-dihydropyiridine calcium-channel-blockers (p = 0.002) and ACE inhibitors/ARBs (p = 0.002) and a lower SDANN with hypertension (p = 0.034), obesity (p = 0.011), stroke (p = 0.031), pneumonia (p = 0.005) and higher HR (p < 0.0005). A higher SDNN was associated with ACE inhibitors/ARBs (p < 0.0005), digitalis (p < 0.0005) and beta-blockers (p = 0.022) and a lower SDNN with obesity (p = 0.012), pneumonia (p = 0.049) and higher HR (p < 0.0005). Our study showed that, in AF patients, there is a direct relationship between some clinical variables and HRV measurements; as for patients with sinus rhythm, even in AF patients this relationship seemed to reflect the autonomic nervous system activity.     

Surgical Resection for Pulmonary Carcinoid: Long-Term Results of Multicentric Study—The Importance of Pathological N Status,More Than We Thought

Background

Histological subdivision into typical (TC) and atypical (AC) is crucial for treatment and prognosis of lung carcinoids but can be also very challenging, even for experts. In this study, we aimed to strengthen or reduce the prognostic value of several pathological, clinical, or per-operative factors some of which are still controversial.

Methods

We retrospectively reviewed clinical records related to 195 patients affected by TC (159) or AC (36) surgically treated between 2000 and 2014, in three different centers. Survival and subtypes comparison analyses were performed to identify potential prognostic factors.

Results

TCs showed a lower rate of nodal involvement than ACs (N0 = 94.9%; N1 = 1.9%; N2 = 3.2% in typical and N0 = 63.8%; N1 = 16.6%; N2 = 19.4% in atypical carcinoids, respectively, p < 0.0001). Long-term oncological results of resected carcinoids were significantly better in TCs than ACs with higher 5- and 10-year overall survival rates (97.2 and 88.2% vs. 77.9 and 68.2%, respectively; p = 0.001) and disease-free survival rates (98.2 and 90.3% in typical and 80.8 and 70.7% atypical carcinoids, respectively; p = 0.001). Risk factors analysis revealed that AC subtype [HR 4.33 (95% CI 1.72–8.03), p = 0.002], pathological nodal involvement [HR 3.05 (95% CI 1.77–5.26), p < 0.0001], and higher SUV_max [HR 4.33 (95% CI 1.03–7.18), p = 0.002] were independently and pejoratively associated with overall survival. Factors associated with a higher risk of recurrence were AC subtype [HR 6.13 (95% CI 1.13–18.86), p = 0.002]; nodal involvement [HR 5.48 (95% CI 2.85–10.51), p < 0.0001]; higher Ki67 expression level [HR 1.09 (95% CI 1.01–1.20), p = 0.047]; and SUV_max [HR 1.83 (95% CI 1.04–3.23), p = 0.035].

Conclusion

Surgery for lung carcinoids allows satisfactory oncological results which mainly depend on carcinoid subtype dichotomy, pathological nodal status, and SUV_max.

     

Late gadolinium enhancement on cardiac magnetic resonance predicts coronary vasomotor abnormality and myocardial lactate production in patients with chronic heart failure

Myocardial fibrosis and microvascular dysfunction are key determinants of outcome in heart failure (HF); we examined their relationship in patients with HF. Our study included 61 consecutive patients with HF but without coronary stenosis. All underwent gadolinium-enhanced cardiac magnetic resonance to evaluate late gadolinium enhancement (LGE) and an acetylcholine (ACh) provocation test to evaluate microvascular dysfunction. During the ACh provocation test, we sampled blood simultaneously from the coronary sinus and aortic root to compare lactate concentrations. We quantified coronary blood flow volume using an intracoronary Doppler-tipped guidewire. We detected LGE in 34 patients (LGE-positive); 27 were LGE-negative. Coronary blood flow volume increased significantly after the ACh provocation test only in LGE-negative patients (before vs. after ACh, 47.5 ± 36.8 vs. 69.2 ± 48.0 ml/min, respectively; p = 0.004). The myocardial lactate extraction ratio (LER) significantly decreased after the ACh test in both groups (LGE-negative, p = 0.001; LGE-positive, p < 0.001), significantly more so in the LGE-positive group (p = 0.017). Multivariate logistic regression analysis showed that a post-ACh LER < 0 (indicating myocardial lactate production) was a significant predictor of LGE-positivity (odds ratio 4.54; 95 % confidence interval 1.38–14.93; p = 0.013). In the LGE-positive group, an LGE volume greater than the median significantly predicted a post-ACh LER of <0 (p = 0.042; odds ratio 6.02; 95 % confidence interval 1.07–33.86). ACh-provoked coronary vasomotor abnormality is closely correlated with myocardial fibrosis in patients with HF but without organic coronary stenosis. Coronary vasomotor abnormalities in fibrotic myocardium may worsen HF.     

Changes in collagen metabolism account for ventricular functional recovery following beta-blocker therapy in patients with chronic heart failure

While beta blockade improves left ventricular (LV) function in patients with chronic heart failure (CHF), the mechanisms are not well known. This study aimed to examine whether changes in myocardial collagen metabolism account for LV functional recovery following beta-blocker therapy in 62 CHF patients with reduced ejection fraction (EF). LV function was echocardiographically measured at baseline and 1, 6, and 12 months after bisoprolol therapy along with serum markers of collagen metabolism including C-terminal telopeptide of collagen type I (CITP) and matrix metalloproteinase (MMP)-2. Deceleration time of mitral early velocity (DcT) increased even in the early phase, but LVEF gradually improved throughout the study period. Heart rate (HR) was reduced from the early stage, and CITP gradually decreased. LVEF and DcT increased more so in patients with the larger decreases in CITP (r = ?0.33, p < 0.05; r = ?0.28, p < 0.05, respectively), and HR (r = ?0.31, p < 0.05; r = ?0.38, p < 0.05, respectively). In addition, there were greater decreases in CITP, MMP-2 and HR from baseline to 1, 6, or 12 months in patients with above-average improvement in LVEF than in those with below-average improvement in LVEF. Similar results were obtained in terms of DcT. There was no significant correlation between the changes in HR and CITP. In conclusion, improvement in LV systolic/diastolic function was greatest in patients with the larger inhibition of collagen degradation. Changes in myocardial collagen metabolism are closely related to LV functional recovery somewhat independently from HR reduction.     

SOFA score and left ventricular systolic function as predictors of short-term outcome in patients with sepsis

In a group of septic patients, we assess the short-term prognostic value of LV systolic performance, evaluated through conventional left ventricular ejection fraction (LVEF) and left ventricular global longitudinal strain (LV GLS). One hundred forty-seven patients with sepsis were recruited; LVEF by planimetry and peak GLS by 2D speckle tracking could be assessed within 24 h. The study population was stratified according to SOFA tertiles assessed at the time of the echocardiogram (G1: SOFA score <5; G2: SOFA score 5–7; G3: SOFA score >7). Day-7 follow-up data were used as reference. Patients in G2 and G3 show a significant hemodynamic derangement, paralleling the more pronounced organ damage by definition; nevertheless, LVEF and GLS are comparable among the three groups (both p > 0.1). All-cause mortality at day-7 follow-up is slightly lower in G1 (9%) versus G2 and G3 (14 and 26%, respectively, p = NS). Analyses through ROC curves focusing on day-7 mortality show that the SOFA score fairly correlates with events (AUC 0.635, p = 0.037), while low LVEF (AUC 0.35, p = 0.022) and less negative GLS (AUC 0.73, p = 0.001) do so. In multivariate analyses, mortality by day-7 follow-up is more likely per higher GLS (i.e., indicative of worst systolic dysfunction, HR 1.22/%, p = 0.005) and per increasing SOFA score (HR 1.22/unit, p = 0.010), whereas LVEF, adjusted for age and SOFA score, does not enter the prognostic model. In the very short term in patients with severe sepsis, LV systolic function assessment by means of GLS predicts the short-term prognosis, independent of SOFA.     

Prognostic Impact of Node-Spreading Pattern in Surgically Treated Small-Cell Lung Cancer: A Multicentric Analysis

Objective

Although surgery in selected small-cell lung cancer (SCLC) patients has been proposed as a part of multimodality therapy, so far, the prognostic impact of node-spreading pattern has not been fully elucidated. To investigate this issue, a retrospective analysis was performed.

Methods

From 01/1996 to 12/2012, clinico-pathological, surgical, and oncological features were retrospectively reviewed in a multicentric cohort of 154 surgically treated SCLC patients. A multivariate Cox proportional hazard model was developed using stepwise regression, in order to identify independent outcome predictors. Overall (OS), cancer-specific (CSS), and Relapse-free survival (RFS) were calculated by Kaplan-Meier method.

Results

Overall, median OS, CSS, and RFS were 29 (95 % CI 18–39), 48 (95 % CI 19–78), and 22 (95 % CI 17–27) months, respectively. Lymphadenectomy was performed in 140 (90.9 %) patients (median number of harvested nodes: 11.5). Sixty-seven (47.9 %) pN0-cases experienced the best long-term survival (CSS: 71, RFS: 62 months; p < 0.0001). Among node-positive patients, no prognostic differences were found between pN1 and pN2 involvement (CSS: 22 vs. 15, and RFS: 14 vs. 10 months, respectively; p = 0.99). By splitting node-positive SCLC according to concurrent N1-invasion, N0N2-patients showed a worse CSS compared to those cases with combined N1N2-involvement (N0N2: 8 months vs. N1N2: 22 months; p = 0.04). On the other hand, the number of metastatic stations (p = 0.80) and the specific node-level (p = 0.85) did not affect CSS. At multivariate analysis, pN+ (HR: 3.05, 95 % CI 1.21–7.67, p = 0.02) and ratio between metastatic and resected lymph-nodes (RL, HR: 1.02, 95 % CI 1.00–1.04, p = 0.03) were independent predictors of CSS. Moreover, node-positive patients (HR: 3.60, 95 % CI 1.95–6.63, p < 0.0001) with tumor size ≥5 cm (HR: 1.85, 95 % CI 0.88–3.88, p = 0.10) experienced a worse RFS.

Conclusions

In selected surgically treated SCLC, the long-term survival may be stratified according to the node-spreading pattern.

     

Three-question set from Michigan Neuropathy Screening Instrument adds independent prognostic information on cardiovascular outcomes: analysis of ALTITUDE trial

Aims/hypothesis

The self-administered Michigan Neuropathy Screening Instrument (MNSI) is used to diagnose diabetic peripheral neuropathy. We examined whether the MNSI might also provide information on risk of death and cardiovascular outcomes.

Methods

In this post hoc analysis of the Aliskiren Trial in Type 2 Diabetes Using Cardio-Renal Endpoints (ALTITUDE) trial, we divided 8463 participants with type 2 diabetes and chronic kidney disease (CKD) and/or cardiovascular disease (CVD) into independent training (n = 3252) and validation (n = 5211) sets. In the training set, we identified specific questions that were independently associated with a cardiovascular composite outcome (cardiovascular death, resuscitated cardiac arrest, non-fatal myocardial infarction/stroke, heart failure hospitalisation). We then evaluated the performance of these questions in the validation set.

Results

In the training set, three questions (‘Are your legs numb?’, ‘Have you ever had an open sore on your foot?’ and ‘Do your legs hurt when you walk?’) were significantly associated with the cardiovascular composite outcome. In the validation set, after multivariable adjustment for key covariates, one or more positive responses (n = 3079, 59.1%) was associated with a higher risk of the cardiovascular composite outcome (HR 1.54 [95% CI 1.28, 1.85], p < 0.001), heart failure hospitalisation (HR 1.74 [95% CI 1.29, 2.35], p < 0.001), myocardial infarction (HR 1.81 [95% CI 1.23, 2.69], p = 0.003), stroke (HR 1.75 [95% CI 1.20, 2.56], p = 0.003) and three-point major adverse cardiovascular events (MACE) (cardiovascular death, non-fatal myocardial infarction, non-fatal stroke) (HR 1.49 [95% CI 1.20, 1.85], p < 0.001) relative to no positive responses to all questions. Associations were stronger if participants answered positively to all three questions (n = 552, 11%). The addition of the total number of affirmative responses to existing models significantly improved Harrell’s C statistic for the cardiovascular composite outcome (0.70 vs 0.71, p = 0.010), continuous net reclassification improvement (+22% [+10%, +31%], p = 0.027) and integrated discrimination improvement (+0.9% [+0.4%, +2.1%], p = 0.007).

Conclusions/interpretation

We identified three questions from the MNSI that provide additional prognostic information for individuals with type 2 diabetes and CKD and/or CVD. If externally validated, these questions may be integrated into the clinical history to augment prediction of CV events in high-risk individuals with type 2 diabetes.

     

Identifying Subpopulations with Distinct Response to Treatment Using Plasma Biomarkers in Acute Heart Failure: Results from the PROTECT Trial

Background

Over the last 50 years, clinical trials of novel interventions for acute heart failure (AHF) have, with few exceptions, been neutral or shown harm. We hypothesize that this might be related to a differential response to pharmacological therapy.

Methods

We studied the magnitude of treatment effect of rolofylline across clinical characteristics and plasma biomarkers in 2033 AHF patients and derived a biomarker-based responder sum score model. Treatment response was survival from all-cause mortality through day 180.

Results

In the overall study population, rolofylline had no effect on mortality (HR 1.03, 95% CI 0.82–1.28, p = 0.808). We found no treatment interaction across clinical characteristics, but we found interactions between several biomarkers and rolofylline. The biomarker-based sum score model included TNF-R1α, ST2, WAP four-disulfide core domain protein HE4 (WAP-4C), and total cholesterol, and the score ranged between 0 and 4. In patients with score 4 (those with increased TNF-R1α, ST2, WAP-4C, and low total cholesterol), treatment with rolofylline was beneficial (HR 0.61, 95% CI 0.40–0.92, p = 0.019). In patients with score 0, treatment with rolofylline was harmful (HR 5.52, 95% CI 1.68–18.13, p = 0.005; treatment by score interaction p < 0.001). Internal validation estimated similar hazard ratio estimates (0 points: HR 5.56, 95% CI 5.27–7–5.87; 1 point: HR 1.31, 95% CI 1.25–1.33; 2 points: HR 0.75, 95% CI 0.74–0.76; 3 points: HR 1.13, 95% CI 1.11–1.15; 4 points, HR 0.61, 95% CI 0.61–0.62) compared to the original data.

Conclusion

Biomarkers are superior to clinical characteristics to study treatment heterogeneity in acute heart failure.

     

Factors affecting the postoperative morbidity and survival of patients with liver cirrhosis following colorectal cancer surgery

Purpose

Data are lacking on the appropriate risk stratification of patients undergoing surgery for colorectal cancer (CRC). This study aimed to evaluate the predictive factors for perioperative morbidity and oncological outcomes in CRC patients with liver cirrhosis (LC).

Methods

A retrospective analysis of prospectively collected data was conducted. A total of 161 LC patients who underwent surgery for CRC were identified between January 2001 and December 2010.

Results

The mean patient age was 60 ± 10 years, and the median follow-up period was 54.0 months (range 0.5–170.0). The proportions of patients with Child-Pugh classifications for LC were as follows: A (n = 118; 73.3%), B (n = 39; 24.2%), and C (n = 4; 2.5%). The median model for end-stage liver disease (MELD) score was 8 (range 6–21). The postoperative morbidity rate was 37.3% (60/161). Hyperbilirubinemia (p = 0.002), prothrombin time (PT) prolongation (p = 0.020), and intraoperative transfusion (p = 0.003) were the significant factors for postoperative morbidity in multivariate analysis. The postoperative mortality rate was 3.1% (5/161), and the 5-year cancer-specific and 5-year overall survival rates were 86.1 and 59.9%, respectively. The significant clinical risk factors by multivariate analysis that influenced overall survival were the TNM stage of CRC (p = 0.035), MELD score (>8 points) (p < 0.001), and the coexistence of hepatocellular carcinoma (HCC) (p = 0.012).

Conclusions

Hyperbilirubinemia, PT prolongation, and intraoperative transfusion are significant risk factors for postoperative morbidity in LC patients who undergo surgery for CRC. Additionally, not only advanced TNM stage but also a high MELD score and the coexistence of HCC are associated with poor overall survival in CRC patients with LC.

     

Risk factors and outcomes of acute lower gastrointestinal bleeding in intestinal Behçet’s disease

Background

Intestinal Behçet’s disease (BD) can cause acute lower gastrointestinal bleeding, which is sometimes fatal.

Aim

We aimed to identify the risk factors and outcomes of acute lower gastrointestinal bleeding and factors associated with rebleeding in intestinal BD patients.

Methods

Of the total of 588 intestinal BD patients, we retrospectively reviewed the medical records of 66 (11.2%) patients with acute lower gastrointestinal bleeding and compared them with those of 132 matched patients without bleeding.

Results

The baseline characteristics were comparable between the bleeding group (n = 66) and the non-bleeding group (n = 132). On multivariate analysis, the independent factors significantly associated with lower gastrointestinal bleeding were older age (>52 years) (hazard ratio [HR] 2.2, 95% confidence interval [CI] 1.058–4.684, p = 0.035) and a nodular ulcer margin (HR 7.1, 95% CI 2.084–24.189, p = 0.002). Rebleeding occurred in 23 patients (34.8%). Female patients (p = 0.044) and those with previous use of corticosteroids or azathioprine (p = 0.034) were more likely to develop rebleeding. On multivariate analysis, only use of steroids or azathioprine was significantly associated with rebleeding (HR 3.2, 95% CI 1.070–9.462, p = 0.037).

Conclusions

Age >52 years and the presence of a nodular margin of the ulcer were found to be related to increased risk of bleeding in patients with intestinal BD. Rebleeding is not uncommon and not effectively prevented with currently available medications. Further studies are warranted to identify effective measures to decrease rebleeding in intestinal BD.

     

Increased <Emphasis Type="Italic">p</Emphasis>-cresyl sulfate level is independently associated with poor outcomes in patients with heart failure

Amino acid-derived metabolites, including protein-bound uremic toxins, may have prognostic value for patients with heart failure (HF). The aim of this study was to investigate whether p-cresyl sulfate (PCS), indoxyl sulfate (IS), and arginine metabolites provided prognostic values in addition to the traditional biomarker, B-type natriuretic peptide (BNP), in patients with HF. Chromatography mass spectrometry was performed to measure tyrosine, tryptophan, arginine, PCS, IS, and asymmetric (ADMA) and symmetric dimethylarginine (SDMA) in the plasma from 51 normal controls and 136 HF patients. Compared to the normal controls, PCS levels significantly increased in HF patients (p = 0.003). During the follow-up (2.3 ± 1.1 years), 35 (25.7 %) patients experienced a composite event of death or HF-related re-hospitalization. In univariable analysis, PCS, estimated glomerular filtration rate (eGFR), BNP, DMA/arginine ratio, and ADMA/arginine ratio were associated with a higher rate of composite events. In the multivariable analysis, PCS was the only independent predictor of composite events [hazard ratio (HR) 1.06 (per 10 μM), 95 % confidence interval (CI) 1.01–1.11, p = 0.02]. Kaplan–Meier curves showed that a PCS level of ≥50 μM was significantly associated with a higher composite event rate than those with a PCS level of <50 μM (Log rank = 5.11, p = 0.024; HR 2.13, 95 % CI 1.09–4.16, p = 0.02). In conclusion, among protein-bound uremic toxins, eGFR, and DMA metabolites, increased PCS is the only independent predictor of HF-related events in patients with HF. A combination of PCS and BNP should better risk-stratify patients with HF.     

Effects of Effortful Swallow on Cardiac Autonomic Regulation

Swallowing-induced changes in heart rate have been recently reported. However, it is not apparent the responses of heart rate variability (HRV) elicited by effortful swallow maneuver. We investigated the acute effects of effortful swallowing maneuver on HRV. This study was performed on 34 healthy women between 18 and 35 years old. We assessed heart rate variability in the time (SDNN, RMSSD, and pNN50) and frequency (HF, LF, and LF/HF ratio) domains and, visual analysis through the Poincaré plot. The subjects remained at rest for 5 min during spontaneous swallowing and then performed effortful swallowing for 5 min. HRV was analyzed during spontaneous and effortful swallowing. We found no significant differences for SDNN, pNN50, RMSSD, HF in absolute units (ms²). There is a trend for increase of LF in absolute (p = 0.05) and normalized (p = 0.08) units during effortful swallowing. HF in normalized units reduced (p = 0.02) during effortful swallowing and LF/HF ratio (p = 0.03) increased during effortful swallowing. In conclusion effortful swallow maneuver in healthy women increased sympathetic cardiac modulation, indicating a cardiac overload.     

Characteristics of rheumatoid arthritis patients undergoing reverse shoulder arthroplasty

The risks and complication profile of reverse total shoulder arthroplasty (RSA) in rheumatoid arthritis (RA) patients has yet to be clearly defined as most studies have small cohorts. Using a large inpatient database, the purpose on our study was to determine the overall demographics, hospitalization characteristics, and early complication rates in rheumatoid patients and compared these to rotator-cuff arthropathy patients without RA undergoing RSA. Utilizing United States Nationwide Inpatient Sample from 2010 to 2013, we evaluated a total of 919 RA RSA and compared them to 8097 patients without RA undergoing RSA. The outcomes included demographic characteristics like age, race, sex, Deyo comorbidity score, perioperative complications, and mean length-of-stay. The RA cohort had 81% females versus 60% in the comparison cohort. This cohort was younger (p = 0.006) and had longer hospitalization time (p = 0.001), but the total inpatient costs were not significantly different (p = 0.15). In regards to Deyo index, rheumatoid patients had significantly higher scores (p < 0.001). The inpatient complication rates for infection (p = 0.9), nerve injury (p = 0.9), and instability (p = 0.19) were similar, but the RA cohort had more prosthetic-related (p = 0.001) and greater tuberosity-related (p = 0.008) complications. The mortality rates were also similar (p = 0.625). In RSA for RA patients, surgeons should be mindful of preoperative risk factors and demographic characteristics that may influence their outcomes. Caution should specifically be paid to the possibility of longer hospitalization time and increased incidence of certain complications, including intraoperative fracture, when compared to non-rheumatoid patients. Close collaboration between rheumatologists, surgeons, and primary care physicians is a must for optimizing and managing these patients.     

A radiological and pathological assessment of ileocolic pedicle length as a predictor of lymph node retrieval following right hemicolectomy for caecal cancer

Background

In colon cancer, the number of harvested lymph nodes is critical for pathological staging. It has been proposed that the more central the mesenteric vascular ligation, the greater the nodal yield. The aim of the current study was to determine the association of radiological and pathological ileocolic pedicle length on nodal harvest following right hemicolectomy for caecal cancer.

Methods

A series of 50 patients undergoing right hemicolectomy for adenocarcinoma underwent specimen evaluation. Preoperative computed tomography images were reconstructed and analysed to determine the direct (vessel origin to caecum) ileocolic pedicle length.

Results

The median pathological distance from the tumour to the high vascular tie was 80 mm, and median nodal yield was 16.5 nodes. Radiological pedicle length did not correlate with the pathological distance from the tumour to the high vascular tie or nodal yield; however, the pathological pedicle length did correlate with the total nodal yield (r ²: 0.343, p = 0.015). The median pathologically determined length of colon resected (r ²: 0.153, p = 0.289), ileum resected (r ²: 0.087, p = 0.568) and total specimen length resected (r ²: 0.182, p = 0.205) did not correlate with the total nodal yield. An ileal specimen length ≤25 mm [hazard ratio (HR) 14.8, 95 % confidence interval (CI) 1.1–194.5, p = 0.040] and a well-differentiated tumour (HR 10.5, 95 % CI 1.1–95.9, p = 0.037) increased the likelihood of retrieving <12 lymph nodes.

Conclusions

Based on these data, pathologic pedicle length is a determining factor in lymph node retrieval. Preoperative radiological calculation of pedicle length does not help predict the number of lymph nodes retrieved.

     

Effect of physical activity on heart rate variability and carotid intima-media thickness in older people

We investigated the effect of physical activity on heart rate variability (HRV) and carotid intima-media thickness (IMT) in elderly subjects and the relationship between HRV and IMT. Thirty-two elderly sedentary subjects and 32 age-matched endurance athletes underwent ultrasonography of the carotid wall for measuring IMT, and 24-h ECG monitoring for measuring HRV. Elderly athletes had evidence of increased vagal activity in the time (SDANN, rMSSD, and pNN50; p < 0.01) and frequency domain (HF and LF/HF ratio, p < 0.01) with respect to sedentary subjects. Moreover, athletes showed lower IMT than control subjects (p < 0.01). In the whole population SDNN was inversely related to IMT, respectively (r = ?0.60 and r = ?0.58, p < 0.0001), while LF/HF ratio related positively to IMT. In conclusion, this study demonstrated that in aging HRV is negatively associated with IMT, a putative index of atherosclerosis, confirming cardiac autonomic neuropathy as part of the pathophysiological pathway for atherosclerosis. It confirms that the regular physical activity represents a valuable strategy to counter age-related impairments of cardiac autonomic activity and artery structural changes.     

Impact of distal embolization on myocardial perfusion and survival among patients undergoing primary angioplasty with glycoprotein IIb–IIIa inhibitors: insights from the EGYPT cooperation

Even though primary angioplasty is able to obtain TIMI 3 flow in the vast majority of STEMI patients, epicardial recanalization does not guarantee optimal myocardial perfusion, that remain suboptimal in a relatively large proportion of patients. Large interest has been focused in recent years on the role of distal embolization as major determinant of impaired reperfusion. The aim of the current study was to investigate in a large cohort of STEMI undergoing primary angioplasty with Gp IIb–IIIa inhibitors the impact of distal embolization on myocardial perfusion and survival. Our population is represented by patients undergoing primary angioplasty for STEMI included in the EGYPT database. Distal embolization was defined as an abrupt ‘‘cutoff’’ in the main vessel or one of the coronary branches of the infarct-related artery, distal to the angioplasty site. Myocardial perfusion was evaluated by angiography or ST-segment resolution, whereas infarct size was estimated by using peak CK and CK-MB. Follow-up data were collected between 30 days and 1 year after primary angioplasty. Data on distal embolization were available in a total of 1182 patients (71% of total population). Distal embolization was observed in 132 patients (11.1%). Patients with distal embolization were older (P < 0.001), with larger prevalence of diabetes (P = 0.01), previous MI (P = 0.048) and advanced Killip class at presentation (P = 0.018), abciximab administration (P < 0.001), with a lower prevalence of smoking (P = 0.04). Patients with distal embolization had more often poor preprocedural recanalization (P = 0.061), less often postprocedural TIMI 3 flow (P < 0.001), postprocedural MBG 2–3 (P < 0.001), complete ST-segment resolution (P = 0.021) and larger infarct size (CK-MB: 328 ± 356 U/l vs. 259 ± 226 U/l, P = 0.012). The impact of distal embolization on myocardial perfusion was confirmed after correction for baseline confounding factors as evaluated by MBG 2–3 (adjusted OR [95% CI] = 3.14 [2.06–4.77], P < 0.0001) but not complete ST-segment resolution (adjusted OR [95% CI] = 1.23 [0.84–1.92], P = 0.26). At 208 ± 160 days follow-up, distal embolization was associated with a significantly higher mortality (9.2% vs. 2.7%, HR [95% CI] = 3.41 [1.73–6.71], P < 0.0001), that was confirmed after correction for baseline confounding factors (adjusted HR [95% CI] = 2.23 [1.1–4.7], P = 0.026). This study showed among STEMI patients treated with Gp IIb–IIIa inhibitors, that distal embolization is independently associated with impaired myocardial perfusion and survival.     

RABBIT risk score and ICU admission due to infection in patients with rheumatoid arthritis

Rheumatoid arthritis (RA) patients are at increased risk of infection. Aim of the present study was to investigate whether RA patients admitted to an intensive care unit (ICU) due to infection have higher Rheumatoid Arthritis Observation of Biologic Therapy (RABBIT) risk scores compared to control RA patients. Seventy-four RA patients (32.4% male) admitted to an ICU due to infection (from January 2002 to December 2013) and 74 frequency-matched control RA patients (16.2% male) were included in this cross-sectional study. There was strong evidence for a higher RABBIT risk score in ICU patients (median 2.0; IQR 1.3–3.2) as compared to controls (1.3; IQR 0.8–2.0; p < 0.0001). Traditional disease-modifying anti-rheumatic drugs (DMARDs) (82.4 vs 64.9%; p = 0.015) and biological DMARDs (28.4 vs 14.9%; p = 0.012) were more frequently given to RA patients without ICU admission. Glucocorticoid users were more frequently found in the ICU group (51.4 vs 31.1%; p = 0.012). In a multivariable analysis tDMARD use was associated with lower (OR 0.38; 95% CI 0.15–0.93; p = 0.034) and glucocorticoid use with borderline higher odds of ICU admission (OR 2.05; 95% CI 0.92–4.58; p = 0.078). Chronic obstructive pulmonary disease (OR 2.89; 95% CI 1.10–7.54; p = 0.03), chronic kidney disease (OR 16.08; 95% CI 2.00–129.48; p = 0.009), and age category (OR 2.67; 95% CI 1.46–4.87; p = 0.001) were strongly associated with ICU admission. There was a strong trend towards higher odds of ICU admission with increasing RABBIT risk score. Use of tDMARDs was associated with lower odds of ICU admission. In an adjusted analysis, bDMARDs were not associated with ICU admission. COPD, CKD, and age were strong risk factors for ICU admission.     

Improved prognostic stratification power of CIBMTR risk score with the addition of absolute lymphocyte and eosinophil counts at the onset of chronic GVHD

The CIBMTR chronic graft-versus-host disease (cGVHD) risk score can be refined and improved for better prognostic stratification. Three hundred and seven consecutive patients diagnosed with cGVHD by the NIH consensus criteria were retrospectively reviewed and had the CIBMTR risk score applied and analyzed. The CIBMTR risk score was successfully validated in our cohort (n = 307). The 3-year overall survival (OS) rates in each risk group (RG) were 82.5 ± 11.3% (RG1), 79.4 ± 3.0% (RG2), 71.8 ± 6.3% (RG3), and 27.3 ± 13.4% (RG4). A significantly lower OS rate and higher non-relapse mortality (NRM) were noted in RG4 compared to the other RGs. However, there were no differences in OS or NRM among RG1 to 3. To improve prognostic stratification power of the CIBMTR risk score, we incorporated the absolute lymphocyte (ALC) and eosinophil count (EC) at time of cGVHD into the CIBMTR risk score. Lower ALC (<1.0 × 10⁹/L, HR 1.94, p = 0.014) and lower EC (<0.5 × 10⁹/L, HR 3.27, p = 0.014) were confirmed as adverse risk factors for OS. Patients were stratified into four revised risk groups (rRG). The 3-year OS rates were 93.3 ± 6.4% (rRG1, score 0–3), 84.9 ± 3.4% (rRG2, score 4–6), 70.9 ± 4.4% (rRG3, score 7–9), and 32.0 ± 1.1% (rRG4, score ≥ 10) (p < 0.001). The 3-year NRM rates were 0.0% (rRG1), 6.7 ± 0.4% (rRG2), 18.4 ± 0.7% (rRG3), and 57.7 ± 5.1% (rRG4) (p < 0.001). The revised CIBMTR risk score was superior to the original CIBMTR risk score for OS (p < 0.001). The revised CIBMTR risk score including ALC and EC at the onset of cGVHD improved the prognostic stratification power of the CIBMTR risk score for long-term outcomes.     

Gender differences in clinicopathological features and prognosis of squamous cell carcinoma of the esophagus

Background

Esophageal squamous cell carcinoma (ESCC) is more frequent in male, and female ESCC patients have better prognosis and tend to diagnose at an earlier stage than male. Regarding these female advantages, gender differences of immunological reaction and sex hormone relations were investigated previously. However, the gender differences of clinicopathological features and prognostic factors of ESCC remain well unknown.

Methods

A total of consecutive 170 Japanese patients, including 28 females with ESCC who newly diagnosed and underwent esophagectomy between January 2004 and March 2013 in our institute, were examined. Clinicopathological features and p53 expression, a potent biomarker reflecting chemoresistance and prognosis, were compared. Prognostic factors were analyzed using a multivariate analysis.

Results

The rates of current drinking, flusher, smoking habits, and Brinkman index in female were lower than those in male (p < 0.001). Tumor location, tumor differentiation, T factor, N factor, clinical stage, and contents of initial treatment had no gender differences. Especially, in the population that received neoadjuvant chemotherapy, excellent pathological effectiveness (>Grade2) was seen much more in female significantly (36.1:66.7 %, p = 0.048). Immunohistostaining revealed positive rates of p53 expression were significantly high in male (50.4:30.5 %, p = 0.007). Postoperative complication occurred more frequently in male than female (52.8:28.6 %, p = 0.024). Estimated 5-year disease-specific survivals by Kaplan–Meier method were worse in male than female at rates of 46.2 and 76.7 %, respectively (p = 0.045). Multivariate analysis by Cox’s proportional hazards model showed that female gender (HR: 0.508, p = 0.023) and tumor depth (HR: 0.572, p = 0.018) were independent prognostic factors of ESCC after resection.

Conclusions

Female ESCC showed prefer prognosis to male ESCC. Low p53 imunohistochemical expression in the female ESCC patients might be related with higher sensitivity to neoadjuvant chemotherapy.

     

Autoantibodies against myelin sheath and S100β are associated with cognitive dysfunction in patients with rheumatoid arthritis

Rheumatoid arthritis (RA) has been associated with cognitive impairment and peripheral production of autoantibodies. Autoantibodies against central nervous system (CNS) proteins and S100 calcium-binding β (S100β) were found increased in diseases characterized by cognitive impairment like Alzheimer disease and Neuropsychiatric Systemic Lupus Erythematosus (NPSLE). The aim of this study was to investigate the plasma levels of autoantibodies against myelin basic protein (anti-MBP), myelin oligodendrocyte glycoprotein (anti-MOG) and S100β, and their relationships with cognitive performance in RA patients. Twenty patients with active rheumatoid arthritis and 19 age-, sex-, and schooling-matched healthy controls were recruited. Multiple dimensions of cognitive function were evaluated by structured clinical questionnaires. Autoantibodies and S100β levels were assessed by ELISAs. Patients had significantly higher levels of anti-MBP IgG (17.51 ± 1.36 vs. 5.24 ± 0.53 ng/mL), anti-MOG IgG (5.68 ± 1.34 vs. 0.51 ± 0.49 ng/mL), and S100β protein (2.24 ± 0.50 vs. 0.47 ± 0.06) than controls (all p < 0.0001). After adjusting for potential confounders, RA group presented worse cognitive performance involving the working memory and executive functions such as inhibition, flexibility, and mental control in parallel to higher autoantibodies and S100β levels than healthy controls (all p < 0.001). Levels of anti-MBP were negatively associated with delayed verbal recall (DVR; r = ?0.42, p = 0.005), Stroop Color-Word (r = ?0.48, p = 0.004), and N-Back Total scores (r = ?0.59, p < 0.0001) and positively with Trail Making Test B (TMB, r = 0.53, p = 0.001). Negative correlation was found between levels of anti-MOG and DVR (r = ?0.64, p < 0.0001), N-Back Total scores (r = ?0.35, p = 0.03), Stroop Color-Word (r = ?0.51, p = 0.001), and positively with TMB (r = 0.50, p = 0.003). S100β levels were associated with DVR (r = ?0.51, p = 0.002), TMB (r = 0.46, p = 0.008), Stroop Color-Word (r = ?0.67, p < 0.0001), and N-Back Total (r = ?0.52, p = 0.003). RA is associated with impaired cognitive performance associated with higher levels of CNS-related autoantibodies and S100β levels. Given the importance of myelin integrity to cognition, our data indicate that these autoantibodies may be harmful to proper cognitive function.