Inflammatory markers as early predictors of infection after colorectal surgery: the same cut-off values in laparoscopy and laparotomy?

Purpose

C-reactive protein and procalcitonin are reliable early predictors of infection after colorectal surgery. However, the inflammatory response is lower after laparoscopy as compared to open surgery. This study analyzed whether a different cutoff value of inflammatory markers should be chosen according to the surgical approach.

Methods

A prospective, observational study included consecutive patients undergoing elective colorectal surgery in three academic centers. All infections until postoperative day (POD) 30 were recorded. The inflammatory markers were analyzed daily until POD 4. Areas under the ROC curve and diagnostic values were calculated in order to assess their accuracy as a predictor of intra-abdominal infection.

Results

Five-hundred-one patients were included. The incidence of intra-abdominal infection was 11.8%. The median levels of C-reactive protein (CRP) and procalcitonin (PCT) were lower in the laparoscopy group at each postoperative day (p < 0.0001). In patients without intra-abdominal infection, they were also lower in the laparoscopy group (p = 0.0036) but were not different in patients presenting with intra-abdominal infections (p = 0.3243). In the laparoscopy group, CRP at POD 4 was the most accurate predictor of overall and intra-abdominal infection (AUC = 0.775). With a cutoff of 100 mg/L, it yielded 95.7% negative predictive value, 75% sensitivity, and 70.3% specificity for the detection of intra-abdominal infection.

Conclusion

The impact of infection on inflammatory markers is more important than that of the surgical approach. Defining a specific cutoff value for early discharge according to the surgical approach is not justified. A patient with CRP values lower than 100 mg/L on POD 4 can be safely discharged.

     

The role of preoperative C-reactive protein and procalcitonin as predictors of post-pancreaticoduodenectomy infective complications: A prospective observational study

Introduction

The common causes of morbidity after pancreaticoduodenectomy (PD) are infective complications. Till date, no specific preoperative markers have been identified to determine the probability of developing infective complications. We have studied the factors predicting the occurrence of the infective complication/s in the present study.

Methods

The present prospective observational study included 133 consecutive patients who underwent PD from January 2011 to June 2016 at a specialized hepatopancreaticobiliary surgical oncology unit. The surgeries were done using a standardized technique. Postoperative complications were segregated into two categories—(a) infective (e.g. cholangitis) and (b) non-infective (e.g. delayed gastric emptying). Increased age, preoperative serum albumin levels, preoperative biliary stenting, pre-stenting serum bilirubin levels, duration of common bile duct stenting, preoperative C-reactive protein [CRP], and procalcitonin [PCT] were evaluated.

Results

Overall morbidity rate was 48.8%. Morbidity associated with infective complications was 21.8%. Increased age, preoperative serum albumin levels, and pre-stenting serum bilirubin levels did not increase the rate of the infective complications. The association between preoperative PCT and preoperative CRP with the infective complications was significant with a p-value of <0.01 (6.75E-07) and <0.01 (4.80E-10), respectively. In the multivariate analysis, only the elevated preoperative procalcitonin was a statistically significant predictor of postoperative infective complications.

Conclusion

Preoperative PCT and CRP levels done 48 h before surgery are sensitive, specific, easily available, and cost-effective predictors of infective complications after PD.

     

Using CRP to predict anastomotic leakage after open and laparoscopic colorectal surgery: is there a difference?

Aim

C-reactive protein (CRP) has proven to be a useful adjunct in early diagnosis of anastomotic leak (AL) after colorectal surgery. It would be of considerable value to examine whether modality of surgery has influence upon postoperative CRP serum levels and their predictive value in the diagnosis of AL.

Methods

All patients undergoing elective colorectal surgery with anastomosis were enrolled into a prospective database between 2011 and 2014. AL was defined with strict operative and radiological criteria. Outcomes between open and laparoscopic resections were assessed statistically and Receiver Operating Characteristic (ROC) curve analysis performed.

Results

Seven hundred twenty-seven patients with an intestinal anastomosis were identified including 468 laparoscopic procedures (468/727; 64 %). There were 58 anastomotic leaks (58/727; 7.9 %) of which 29 (6.2 %) were laparoscopic and 29 (11.2 %) were open.Mean CRP levels were significantly higher in patients after open surgery compared with laparoscopic both with AL (p?=?0.013), and without (p?=?0.02).ROC curve analysis revealed postoperative day 3 (cut-off CRP 209) and day 4 (cut-off CRP 123.5) to be most predictive of leak in the open group with an area under the curve (AUC) 0.794 (sensitivity 80 %, specificity 80 %) and AUC 0.806 (sensitivity 94 %, specificity 60 %), respectively. In the laparoscopic group, day 2 proved to be the most accurate day for detection of leak with a cut-off CRP of 146.5 showing 75 % sensitivity and a 70 % specificity (AUC 0.766).

Conclusion

CRP levels are higher after open surgery compared with laparoscopic surgery, both with and without AL. AL generates a significant detectable increase in CRP within 2–4 days after surgery.

     

Surgical team proficiency in minimally invasive esophagectomy is related to case volume and improves patient outcomes

Background

Minimally invasive esophagectomy (MIE) is being increasingly performed; however, it is still associated with high morbidity and mortality. The correlation between surgical team proficiency and patient load lacks clarity. This study evaluates surgical outcomes during the first 3-year period after establishment of a new surgical team.

Methods

A new surgical team was established in September 2013 by two expert surgeons having experience of performing more than 100 MIEs. We assessed 237 consecutive patients who underwent MIE for esophageal cancer and evaluated the impact of surgical team proficiency on postoperative outcomes, as well as the team learning curve.

Results

In the cumulative sum analysis, a point of downward inflection for operative time and blood loss was observed in case 175. After 175 cases, both operative time and blood loss significantly decreased (P < 0.001 and P < 0.001, respectively), and postoperative incidence of pneumonia significantly decreased from 18.9 to 6.5% (P = 0.024). Median postoperative hospital stay also decreased from 20 to 18 days (P = 0.022). Additionally, serum CRP levels on postoperative day 1 showed a significant, but weak inverse association with the number of cases (P = 0.024).

Conclusions

After 175 cases, both operative time and blood loss significantly decreased. In addition, the incidence of pneumonia decreased significantly. Additionally, surgical team proficiency may decrease serum CRP levels immediately after MIE. Surgical team proficiency based on team experience had beneficial effects on patients undergoing MIE.

     

Application of the qSOFA score to predict mortality in patients with suspected infection in a resource-limited setting in Malawi

Purpose

To determine the predictive value of qSOFA (quick Sequential Organ Failure Assessment) in Malawian patients with suspected infection.

Methods

Prospective observational study in a tertiary referral hospital in Malawi.

Results

Predictive ability of qSOFA was reasonable [AUROC 0.73 (95% CI 0.68–0.78)], increasing to 0.77 (95% CI 0.72–0.82) when classifying all patients with altered mental status as high risk. Adding HIV status as a variable to the qSOFA score did not improve predictive value.

Conclusion

qSOFA is a simple tool that can aid risk stratification in resource-limited settings.

     

Prediction Model for Two-Year Risk of Opioid Overdose Among Patients Prescribed Chronic Opioid Therapy

Background

Naloxone is a life-saving opioid antagonist. Chronic pain guidelines recommend that physicians co-prescribe naloxone to patients at high risk for opioid overdose. However, clinical tools to efficiently identify patients who could benefit from naloxone are lacking.

Objective

To develop and validate an overdose predictive model which could be used in primary care settings to assess the need for naloxone.

Design

Retrospective cohort.

Setting

Derivation site was an integrated health system in Colorado; validation site was a safety-net health system in Colorado.

Participants

We developed a predictive model in a cohort of 42,828 patients taking chronic opioid therapy and externally validated the model in 10,708 patients.

Main Measures

Potential predictors and outcomes (nonfatal pharmaceutical and heroin overdoses) were extracted from electronic health records. Fatal overdose outcomes were identified from state vital records. To match the approximate shelf-life of naloxone, we used Cox proportional hazards regression to model the 2-year risk of overdose. Calibration and discrimination were assessed.

Key Results

A five-variable predictive model showed good calibration and discrimination (bootstrap-corrected c-statistic?=?0.73, 95% confidence interval [CI] 0.69–0.78) in the derivation site, with sensitivity of 66.1% and specificity of 66.6%. In the validation site, the model showed good discrimination (c-statistic?=?0.75, 95% CI 0.70–0.80) and less than ideal calibration, with sensitivity and specificity of 82.2% and 49.5%, respectively.

Conclusions

Among patients on chronic opioid therapy, the predictive model identified 66–82% of all subsequent opioid overdoses. This model is an efficient screening tool to identify patients who could benefit from naloxone to prevent overdose deaths. Population differences across the two sites limited calibration in the validation site.

     

Paricalcitol reduces oxidative stress and inflammation in hemodialysis patients

Background

Treatment with selective vitamin D receptor activators such as paricalcitol have been shown to exert an anti-inflammatory effect in patients on hemodialysis, in addition to their action on mineral metabolism and independently of parathyroid hormone (PTH) levels. The objective of this study was to evaluate the additional antioxidant capacity of paricalcitol in a clinical setting.

Methods

The study included 19 patients with renal disease on hemodialysis, of whom peripheral blood was obtained for analysis at baseline and three months after starting intravenous paricalcitol treatment. The following oxidizing and inflammatory markers were quantified: malondialdehyde (MDA), nitrites and carbonyl groups, indoleamine 2,3-dioxygenase (IDO), tumor necrosis factor alfa (TNF-α), interleukin-6 (IL-6), interleukin-18 (IL-18) and C-reactive protein (CRP). Of the antioxidants and anti-inflammatory markers, superoxide dismutase (SOD), catalase, reduced glutathione (GSH), thioredoxin, and interleukin-10 (IL-10) levels were obtained.

Results

Baseline levels of oxidation markers MDA, nitric oxide and protein carbonyl groups significantly decreased after three months on paricalcitol treatment, while levels of GSH, thioredoxin, catalase and SOD activity significantly increased. After paricalcitol treatment, levels of the inflammatory markers CRP, TNF-α, IL-6 and IL-18 were significantly reduced in serum and the level of anti-inflammatory cytokine IL-10 was increased.

Conclusions

In renal patients undergoing hemodialysis, paricalcitol treatment significantly reduces oxidative stress and inflammation, two well known factors leading to cardiovascular damage.

     

Alterations in colonic transit time after laparoscopic versus open cholecystectomy: a clinical study

Purpose

Postoperative enteral paresis constitutes a common problem for surgeons around the world. Evidence by many authors suggests that colonic inertia constitutes a major component of postoperative enteral paresis. This study aims at comparing the effect of laparoscopic versus open cholecystectomy on colonic transit time in humans.

Materials and methods

In this study, were included a total of 29 patients suffering from cholelithiasis, divided into two groups, a laparoscopic cholecystectomy and an open cholecystectomy group. All patients ingested one capsule containing 24 radiopaque markers on the day of the operation, and plain abdominal films were obtained on the 3rd postoperative day. The number of remaining markers was counted, and the percentage of rejected markers was calculated. For the statistical analysis, SPSS for windows version 12 was used.

Results and discussion

The study’s results show a significant difference in postoperative colonic motility, in favor of the laparoscopic cholecystectomy group (P = 0,001). Causative interpretation of these results is difficult, mainly due to the multifactorial nature of postoperative colonic hypomotility.

Conclusion

The present study suggests an advantage of laparoscopic cholecystectomy, as far as the duration of postoperative colonic paresis is concerned.

     

Metachronous colorectal cancer

Aim

In this study, we present our patients with metachronous colorectal cancer.

Patients and methods

In the period between 1990 and 2009, 670 patients with colorectal cancer were treated.

Results

Metachronous cancer was developed in 4 (0.6%) patients. The time interval between index and metachronous cancer was 28 months to 22 years (mean 146 months).

Conclusion

Metachronous colorectal cancer is a potential risk that proves the necessity of postoperative colonoscopic control of all patients with colorectal cancer.

     

Does serum procalcitonin aid in the diagnosis of bloodstream infection regardless of whether patients exhibit the systemic inflammatory response syndrome?

Background

Physicians frequently rely on the systemic inflammatory response syndrome (SIRS) criteria to detect bloodstream infections (BSIs). We evaluated the diagnostic performance of procalcitonin (PCT) in detecting BSI in patients with and without SIRS.

Methods

We tested the association between BSI, serum PCT levels, contemporaneous SIRS scores and serum lactate using logistic regression in a dataset of 4279 patients. The diagnostic performance of these variables was assessed.

Results

In multivariate regression analysis, only log(PCT) was independently associated with BSI (p < 0.05). The mean area under the curve (AUC) of PCT in detecting BSI (0.683; 95% CI 0.65–0.71) was significantly higher than serum lactate (0.615; 95% CI 0.58–0.64) and the SIRS score (0.562; 95% CI 0.53–0.58). The AUC of PCT did not differ significantly by SIRS status. PCT of less than 0.1 ng/mL had a negative predictive value (NPV) of 97.4 and NPV of 96.2% for BSI in the SIRS-negative and SIRS-positive patients, respectively. A PCT of greater than 10 ng/mL had a LR of 6.22 for BSI in SIRS-negative patients. The probability of BSI increased exponentially with rising PCT levels regardless of SIRS status.

Conclusion

The performance of PCT for the diagnosis of BSI was not affected by SIRS status. Only PCT was independently associated with BSI, while the SIRS criterion and serum lactate were not. A low PCT value may be used to identify patients at a low risk for having BSI in both settings. An elevated PCT value even in a SIRS negative patient should prompt a careful search for BSI.

     

Three-dimensional versus two-dimensional laparoscopic right colectomy: a systematic review and meta-analysis

Background

Three-dimensional (3D) vision technology has recently been validated for the improvement of surgical skills in a simulated setting. Clinical studies on specific operations have been published in the field of general, urologic, and gynecologic laparoscopic surgery. We hypothesized that 3D vision laparoscopic right colectomy has better intra and short-term postoperative outcomes than two-dimensional (2D) vision.

Aim

The outcomes of this review and meta-analysis were to compare the 3D vision and the 2D vision laparoscopic right colectomy.

Methods

A systematic search of the literature was performed on Pubmed, WOS, Google Scholar, and Scopus databases (Prospero reg. nr. 42016047704) for comparative studies between 2D and 3D laparoscopic right colectomy. Primary endpoints were safety issues and secondarily patients’ related and surgeons’ comfort outcomes. Meta-analyses, when possible, were conducted with a random-effects model.

Results

Two retrospective comparative studies (for a total of 56 patients in the 2D arm and 52 patients for the 3D arm) were selected out of 680 screened records. Methodological quality was fair. Three-dimensional laparoscopic right colectomy has similar safety and secondary outcomes when compared to 2D, with not statistically significant shorter operating times (mean difference 11.81 min). The results are comparable also for anastomosis leakage. The results for other outcomes were not aggregated for heterogeneity.

Conclusions

3D laparoscopic right colectomy shows equivalent patients’ outcomes compared to 2D operation, but the scarce clinical data and the potential amelioration of surgeons’ skills, especially on difficult intracorporeal tasks like suturing, suggest the publication of further trials.

     

T-tube drainage stimulates the healing of choledochocholedochostomies. An experimental study in pigs

Background/Purpose

We investigated the effect of T-tube drainage on the healing of choledocho-choledochostomies in pigs.

Methods

Twenty pigs with a median weight of 56 kg were used for the experiments. The pigs were randomized to two groups of ten. In all pigs the gallbladder was removed and the common bile duct was transected. In both groups continuity was re-established by standardized single-line, interrupted, and inverted sutures. In one group a T-tube for decompression was inserted. On postoperative day 6, a laparotomy was performed. Pigs were investigated for signs of cholascos, and an intraoperative cholangiography was performed. The excised anastomosis was examined for breaking strength and collagen content. Blood samples were drawn prior to the first and the final operations.

Results

In both groups standard liver parameters were unaffected by surgery, and cholangiography showed no signs of extrahepatic stenosis or intrahepatic dilatation. The T-tubedrained choledocho-choledochostomies showed a significantly higher breaking strength (P = 0.035) compared to the group which had no drainage. Collagen content per volume was unaffected by T-tube drainage.

Conclusions

T-tube drainage had a significant stimulatory effect on the breaking strength of choledocho-choledochostomies in pigs on postoperative day 6, but was without effect on collagen content.

     

Enhancement of colonic anastomotic strength in rats by short-chain fatty acids

Background

The present study is aiming at elucidating the effect of intraoperative lavage with short-chain fatty acids (SCFAs) on colonic anastomosis in rats.

Methods

Forty male Wistar rats were randomized into four groups (10 rats each). After resection of a segment of transverse colon, an end-to-end anastomosis was performed. In the 1st group, no intraoperative large bowel lavage was performed; in the 2nd, a lavage with normal saline solution; in the 3rd, the animals received a diet rich in SCFAs pre- and postoperatively, and a lavage with normal saline was performed; and in the 4th group, an intraoperative lavage with SCFAs was carried out. On the 4th postoperative day, the animals were sacrificed. Septic complications, adhesions and anastomoses were graded macroscopically and histologically, and bursting pressure of the anastomoses, CRP, IL-6 and TNF-a was measured.

Results

Fewer septic complications (abscesses and minimal ruptures) and adhesions were observed in the 4th group with the intraoperative lavage with SCFAs. The bursting pressure also, in the same group, was higher (73.3 mmHg), followed by the 1st group (67.1 mmHg).

Conclusion

Intraoperative lavage with SCFAs increases the bursting pressure of colonic anastomoses, while lavage with saline solution decreases it, in comparison to the group without lavage.

     

Postoperative infectious complications-driven recurrence after radical resection for esophageal cancer

Background

Few reports have reported the long-term outcome of esophageal cancer patients suffering from postoperative infectious complications. Here, we investigated the impact of postoperative infectious complications in patients who had undergone curative resection for esophageal cancer.

Methods

The study population comprised 97 patients who underwent radical resection for esophageal cancer with curative intent between 2001 and 2008. Postoperative infectious complications were defined as surgical site infections and pneumonia. We compared clinical features, tumor histology, recurrence, and overall survival between patients with postoperative infections and those who did not.

Results

Of the 97 patients studied, 37 had postoperative infectious complications. The disease-free and overall survival rates of the entire cohort did not significantly differ between patients with and without postoperative infectious complications. Univariate analysis revealed that among patients with stage III esophageal cancer, those with postoperative infectious complications demonstrated significantly shorter disease-free survival than those without. Multivariate analysis demonstrated that postoperative infectious complications were independent prognostic indicators for disease-free survival of stage III esophageal cancer patients.

Conclusions

Our findings suggest that postoperative infectious complications in stage III esophageal cancer patients have a negative impact on disease-free survival.

     

Provider Recommendations in the Face of Scientific Uncertainty: An Analysis of Audio-Recorded Discussions about Vitamin D

BACKGROUND

Little is known about how providers communicate recommendations when scientific uncertainty exists.

OBJECTIVES

To compare provider recommendations to those in the scientific literature, with a focus on whether uncertainty was communicated.

DESIGN

Qualitative (inductive systematic content analysis) and quantitative analysis of previously collected audio-recorded provider–patient office visits.

PARTICIPANTS

Sixty-one providers and a socio-economically diverse convenience sample of 603 of their patients from outpatient community- and academic-based primary care, integrative medicine, and complementary and alternative medicine provider offices in Southern California.

MAIN MEASURES

Comparison of provider information-giving about vitamin D to professional guidelines and scientific information for which conflicting recommendations or insufficient scientific evidence exists; certainty with which information was conveyed.

RESULTS

Ninety-two (15.3 %) of 603 visit discussions touched upon issues related to vitamin D testing, management and benefits. Vitamin D deficiency screening was discussed with 23 (25 %) patients, the definition of vitamin D deficiency with 21 (22.8 %), the optimal range for vitamin D levels with 26 (28.3 %), vitamin D supplementation dosing with 50 (54.3 %), and benefits of supplementation with 46 (50 %). For each of the professional guidelines/scientific information examined, providers conveyed information that deviated from professional guidelines and the existing scientific evidence. Of 166 statements made about vitamin D in this study, providers conveyed 160 (96.4 %) with certainty, without mention of any equivocal or contradictory evidence in the scientific literature. No uncertainty was mentioned when vitamin D dosing was discussed, even when recommended dosing was higher than guideline recommendations.

CONCLUSIONS AND RELEVANCE

Providers convey the vast majority of information and recommendations about vitamin D with certainty, even though the scientific literature contains inconsistent recommendations and declarations of inadequate evidence. Not communicating uncertainty blurs the contrast between evidence-based recommendations and those without evidence. Providers should explore best practices for involving patients in decision-making by acknowledging the uncertainty behind their recommendations.

     

Hand grip strength as a predictor of postoperative complications in esophageal cancer patients undergoing esophagectomy

Background

Radical esophagectomy remains the primary treatment option for resectable esophageal cancer. However, it sometimes induces postoperative complications due to its invasive nature. Recently, the impact of loss of muscle mass on postoperative complications and survival among cancer patients has been highlighted. This study aimed to identify the impact of low hand grip strength (HGS) on postoperative complications after esophagectomy.

Methods

A total of 188 patients (male: 166, female: 22) who underwent radical esophagectomy with gastric tube reconstruction between 2008 and 2014 were included. The correlation between HGS and age was analyzed using Pearson’s correlation coefficient. Due to the small patient numbers, only male patients were stratified into two groups according to age (<70 years: non-elderly group, ≥70 years: elderly group). Receiver operating characteristic curve analysis was performed for each group using postoperative complication occurrence as the endpoint to determine an optimal HGS cutoff value.

Results

Postoperative complications occurred in 60.9% of the elderly group and 47.4% of the non-elderly group. When the cutoff values were set at 30.5 and 37 kg for the elderly and non-elderly group, respectively, low HGS was an independent predictive factor of postoperative complications on multivariate analysis only in the elderly group (p = 0.008). In the elderly group, the incidence of postoperative pneumonia was 39.5% among patients with low HGS vs. 3.8% among patients with high HGS.

Conclusion

Preoperative HGS is an independent predictive factor of postoperative complications, especially postoperative pneumonia, for elderly male patients with esophageal cancer treated with radical esophagectomy.

     

Fettleberdiagnostik bei Diabetes mellitus Typ 2

Definition of terms

Under the term non-alcoholic fatty liver disease (NAFLD) both simple hepatic fat accumulation and non-alcoholic steatohepatitis (NASH) are combined. NASH is associated with liver fibrosis, cirrhosis and hepatocellular carcinoma (HCC).

Epidemiological importance

In 2020, NAFLD will be the leading cause for liver transplantation in the USA, with rising financial costs for the healthcare system.

Comorbidities, diagnosis, and treatment

Type 2 diabetes (T2D) and metabolic syndrome (MetS) are important risk factors for the development of NAFLD, whereby these three diseases share similar pathophysiologic conditions, e.g., insulin resistance, obesity, and metabolic inflammation. Due to the rising number of patients with T2D and MetS, clinicians should aim to diagnose NAFLD early in this patient population and if necessary start treatment.

Goal

The aim of this work is to give an overview over the topic of NAFLD and diagnostic approaches in patients with T2D.

     

Treatment of acute hepatitis C: recommendations from an expert panel of the Italian Society of Infectious and Tropical Diseases

Aim

This paper is aimed at providing practical recommendations for the management of acute hepatitis C (AHC).

Methods

This is an expert position paper based on the literature revision. Final recommendations were graded by level of evidence and strength of the recommendations.

Results

Treatment of AHC with direct-acting antivirals (DAA) is safe and effective; it overcomes the limitations of INF-based treatments.

Conclusions

Early treatment with DAA should be offered when available.

     

Quantifying the Severity of a Delirium Episode Throughout Hospitalization: the Combined Importance of Intensity and Duration

Background

The ability to determine which episodes of delirium are likely to lead to poor clinical outcomes has remained a major area of challenge.

Objective

To quantify delirium severity and course over an entire hospitalization using several measures, and to evaluate their predictive validity for 30- and 90-day outcomes post-discharge.

Design

Two prospective cohort studies.

Participants

Analysis was conducted in two independent cohorts of adult patients aged ≥70.

Main Measures

Nine delirium episode severity measures were examined: (1) measures reflecting delirium intensity (peak Confusion Assessment Method-Severity [CAM-S] and mean CAM-S score), (2) a measure reflecting delirium intensity and duration (sum of all CAM-S scores, sum of all CAM-S scores on delirium days only, peak CAM-S score x days with delirium), (3) measures requiring information on delirium duration and delirium at discharge (total number of delirium days, percentage of delirium days, delirium at discharge), and (4) a measure of cognitive change. Associations of the delirium episode severity measures with 30- and 90-day post-hospital outcomes (death, nursing home placement, and readmission) relevant to delirium were examined.

Key Results

The delirium episode severity measure that required information on both delirium intensity and duration (sum of all CAM-S scores) was the most strongly associated with 30- and 90-day post-hospital outcomes. Using this measure, the relative risk [95 % confidence interval] for death at 30-days increased across levels of sum of all CAM-S scores from 1.0 (referent) to 2.1 [0.8, 5.4] for ‘low,’ to 2.9 [1.2, 7.1] for ‘moderate,’ to 6.4 [2.9, 14.0] for ‘high’ (p for trend <.01).

Conclusions

The delirium episode severity measure that included both intensity and duration had the strongest association with important post-hospital outcomes.

     

Role of Angiogenesis in Chronic Radiation Proctitis: New Evidence Favoring Inhibition of Angiogenesis Ex Vivo

Background

Chronic radiation proctitis (CRP), a common complication after radiotherapy for pelvic malignancies, compromises patient quality of life. Vascular damage and aberrant angiogenesis in the mucosal layer are essential histological features, but changes to the submucosal layer are unclear. Thus, we evaluated the histological characteristics and distribution changes of key angiogenic factors in full-layered human CRP samples.

Methods

Thirty paraffin-embedded CRP and twenty-nine non-CRP tissues were used to evaluate histopathological changes. Immunohistochemistry with anti-CD34 antibody was performed to calculate microvascular density (MVD). Frozen tissues from eight CRP patients and five non-CRP controls were collected and analyzed by antibody array, which contained sixty human angiogenesis-related factors. Quality controls with positive and negative controls were performed during antibody array analysis. Two differentially expressed factors were confirmed by ELISA.

Results

CRP lesions showed vasculopathy, fibrosis, mucosal ulceration, edema, and inflammatory cell infiltration. Human angiogenesis antibody array and ELISA confirmed the increased angiostatin in CRP lesions. Immunohistochemical staining showed dispersed distribution of angiostatin throughout the mucosal and submucosal layers in CRP lesions, while angiostatin accumulated within the vessel lumens in non-CRP tissues. MVD significantly decreased in the submucosal layer of CRP, suggesting a potential association with increased angiostatin.

Conclusions

Angiostatin increased and had a distinct distribution in CRP lesions. Compensatory telangiectasia in the mucosa, vessel stenosis, and reduced MVD might attenuate blood flow in the submucosa and contribute to CRP progression. Restoration of vascular functionality by promoting angiogenesis in the submucosal layer may help alleviate CRP in clinical practice.