The memory trace of an intrusive trauma-analog episode.

Intrusive memories are a core symptom of posttraumatic stress disorder. Compared with memories of everyday events, they are characterized by several seemingly contradictory features: intrusive memories contain distinct sensory and emotional details of the traumatic event and can be triggered by various perceptually similar cues, but they are poorly integrated into conceptual memory. Here, we conduct exploratory whole-brain analyses to investigate the neural representations of trauma-analog experiences and how they are reactivated during memory intrusions. We show that trauma-analog movies induce excessive processing and generalized representations in sensory areas but decreased blood-oxygen-level-dependent (BOLD) responses and highly distinct representations in conceptual/semantic areas. Intrusive memories activate generalized representations in sensory areas and reactivate memory traces specific to trauma-analog events in the anterior cingulate cortex. These findings provide the first evidence of how traumatic events could distort memory representations in the human brain, which may form the basis for future confirmatory research on the neural representations of traumatic experiences.

Mitochondrial DNA as a marker for treatment-response in post-traumatic stress disorder.

Post-traumatic stress disorder (PTSD) is a serious mental health condition thought to be mediated by a dysregulated stress response system. Stress, especially chronic stress, affects mitochondrial activity and their efficiency in duplicating their genomes. Human cells contain numerous mitochondria that harbor multiple copies of their own genome, which consist of a mixture of wild type and variant mtDNA - a condition known as mitochondrial heteroplasmy. Number of mitochondrial genomes in a cell and the degree of heteroplasmy may serve as an indicator of mitochondrial allostatic load. Changes in mtDNA copy number and the proportion of variant mtDNA may be related to mental disorders and symptom severity, suggesting an involvement of mitochondrial dysfunction also in PTSD. Therefore, we examined number and composition of mitochondrial DNA before and after six weeks of inpatient psychotherapy treatment in a cohort of 60 female PTSD patients. We extracted DNA from isolated monocytes before and after inpatient treatment and quantified cellular mtDNA using multiplex qPCR. We hypothesized that treatment would lead to changes in cellular mtDNA levels and that change in mtDNA level would be associated with PTSD symptom severity and treatment response. It could be shown that mtDNA copy number and the ratio of variant mtDNA decreased during therapy, however, this change did not correlate with treatment response. Our results suggest that inpatient treatment can reduce signs of mitochondrial allostatic load, which could have beneficial effects on mental health. The quantification of mtDNA and the determination of cellular heteroplasmy could represent valuable biomarkers for the molecular characterization of mental disorders in the future.

What is the real morbidity after emergency colectomy for Crohn's disease? A propensity score matched study.

BACKGROUND: In the inflammatory bowel disease literature, emergency surgery for Crohn's disease (CD) is associated with worse postoperative outcomes as compared to elective surgery. Previous studies have compared heterogeneous groups only. We hypothesized that this association would be lost after matched analysis. We aimed to compare matched CD patients undergoing elective vs emergency surgery. METHODS: The National Surgical Quality Improvement database (01/2005-12/2019) was utilized to identify adult CD surgical patients. Univariate and conditional logistic regression models were used to analyze unmatched and matched cohorts. Propensity-score matching was performed to match emergency to non-emergency patients 1:1. Our primary outcome was a composite of any complication. Our secondary endpoints were hospital readmission, unplanned reoperation and 30-day morbidity and mortality. RESULTS: In the unmatched analyses (n = 12,181/95.28% elective and n = 603/4.72% emergency) of Crohn's patients undergoing colectomy, 20% of elective and 42% of emergency patients experienced a complication (p < 0.001). Over 20 outcomes measured including length of stay (LOS), readmission, infections and respiratory, cardiovascular and renal complications, were worse in the emergency cohort. In the matched analyses (n = 400 emergency/400 elective patients) only the categories of any complication (OR 1.44, 1.06-1.96 95% CI, p = 0.02), any surgical site infection (SSI, OR 1.53, 1.07-2.19 95% CI, p = 0.02), superficial SSI (OR 2.25, 1.14-4.44 95% CI, p = 0.02), organ space SSI (1.58 OR 1.04-2.4 95% CI, p = 0.03), unplanned intubation (OR 5.0, 1.45-17.27 95% CI, p = 0.01), ventilation > 48 h (OR 9.0, 1.4-38.79 95% CI, p = 0.003) and septic shock (OR 4.5, 1.86-10.9 95% CI, p < 0.001) were higher in the emergency cohort. CONCLUSIONS: Matching CD patients resulted in a loss of the observed increase in cardiovascular and renal complications, reoperation and LOS following emergency surgery; however, SSIs and respiratory complications remained increased despite matching.

Arterial Stiffness in a Cohort of Young People Living With Perinatal HIV and HIV Negative Young People in England.

Background: Antiretroviral therapy (ART) has increased life expectancy and consequently the risk of cardiovascular disease (CVD) in adults living with HIV. We investigated the levels and predictors of arterial stiffness in young people (YP) living with perinatal HIV (PHIV) and HIV negative YP in the Adolescents and Adults Living with Perinatal HIV (AALPHI) study. Methods: AALPHI was a prospective study evaluating the impact of HIV infection and exposure to ART on YP living with PHIV (aged 13-21 years) who had known their HIV status for at least 6 months, and HIV negative YP (aged 13-23 years) who either had a sibling, friend or parent living with HIV. Participants were enrolled from HIV clinics and community services in England. Two hundred and thirteen PHIV and 65 HIV negative YP (42% siblings of PHIV) had pulse wave velocity (PWV) measurements taken (Vicorder software) from the supra-sternal notch to the middle of the thigh cuff, at their second interview in the study between 2015 and 2017. Average PWV was calculated from the three closest readings (≥3 and ≤ 12 m/s) within 0.6 m/s of each other. Linear regression examined predictors of higher (worse) PWV, including age, sex, HIV status and height as a priori, ethnicity, born outside UK/Ireland, alcohol/nicotine/drug use, weight, waist-to-hip-ratio, mean arterial pressure (MAP), caffeine 2 h before PWV and nicotine on day of PWV. A separate PHIV model included CD4, viral load, years taking ART and ART regimen. Findings: One hundred and twenty eight (60%) PHIV and 45 (69%) HIV negative YP were female (p = 0.18), with median (IQR) age 18 (16, 20) and 18 (16, 21) years (p = 0.48) respectively. Most PHIV were taking a combination of three ART drugs from two classes. There was a trend toward higher (worse) mean PWV in the PHIV group than the HIV negative group [unvariable analysis 6.15 (SD 0.83) m/s vs. 5.93 (0.70) m/s, respectively, unadjusted p = 0.058], which was statistically significant in the multivariable analysis [adjusted p (ap) = 0.020]. In multivariable analysis being male (ap = 0.002), older age (ap < 0.001), higher MAP (ap < 0.001) and nicotine use on day of measurement (ap = 0.001) were also predictors of higher PWV. The predictors were the same in the PHIV model. Interpretation: By late adolescence PHIV had worse PWV in comparison to HIV negative peers, and traditional risk factors for CVD (higher arterial pressure, being male and older age) were associated with higher PWV values. Regular detailed monitoring of cardiovascular risk factors should become standard of care for every young person with PHIV worldwide.

Lack of sensitivity of an IVD/CE-labelled kit targeting the S gene for detection of SARS-CoV-2.

OBJECTIVES: New molecular tests for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are being rapidly launched in response to the coronavirus disease 2019 (COVID-19) pandemic. The aim of this study was to evaluate the analytical and clinical performance of the VIASURE SARS-CoV-2 S gene RT-PCR Kit on the BD Max™ system and to compare results with those obtained with the cobas® SARS-CoV-2 test on the cobas® 6800 system. METHODS: For testing the analytical performance, reference material was used. Clinical samples (n = 101) obtained from individuals with symptoms compatible with COVID-19 were studied. Oropharyngeal and nasopharyngeal swabs were collected by using either ESwab™ or UTM™ collection systems. RESULTS: When the analytical performance was evaluated, the sample containing the lowest SARS-CoV-2 concentration tested negative with the VIASURE test whereas results obtained with the cobas® test were found to be concordant with the results expected. Six out of the 101 clinical samples (5.9%) showed an inhibition with the VIASURE test. When analysing the remaining 95 clinical samples, 27 were found to be negative with both assays. Of 68 samples that were positive with the cobas® test, the VIASURE test missed 21 (30.9 %) samples. All of those 21 samples had shown Ct values ≥ 31 with the cobas® 6800 system. None of the samples tested positive with the VIASURE test and negative with the cobas® test. CONCLUSIONS: The VIASURE test was impaired by a lack of sensitivity and a relatively high number of invalid results. When using the VIASURE test for routine testing, a significant number of COVID-19-positive samples would have been missed.

Case-matched Comparison of Postoperative Outcomes Following Surgery for Inflammatory Bowel Disease After Exposure to Vedolizumab vs Other Biologics.

BACKGROUND AND AIM: The effects of vedolizumab [VEDO] exposure on perioperative outcomes following surgery for inflammatory bowel disease [IBD] remain controversial. The aim of our study was to compare postoperative morbidity of IBD surgery following treatment with VEDO vs other biologics or no biologics. METHODS: An institutional review board-approved, prospectively collected database was queried to identify all patients undergoing abdominal surgery for IBD between August 2012 and May 2017. The impact of VEDO within 12 weeks preoperatively on postoperative morbidity was initially assessed with univariate and multivariable analyses on all patients. A case-matched analysis was then carried out comparing patients exposed to VEDO vs other biologic agents, based on gender, age ± 5 years, diagnosis, date of surgery ± 2 years, and surgical procedure. RESULTS: Out of 980 patients, 141 received VEDO. The majority of patients [59%] underwent surgery involving end or diverting ostomy creation. The initial multivariate analysis conducted on all patients indicated that VEDO use was independently associated with increased overall morbidity [p <0.001], but not infectious morbidity [p = 0.30]. However, the case-matched comparison of 95 VEDO-treated patients vs 95 patients treated with adalimumab or infliximab did not indicate any difference in overall morbidity [p = 0.32], infectious complications [p = 0.15], or surgical site infections [p = 0.12]. CONCLUSIONS: In a study population having a high rate of surgery involving ostomy creation, the exposure to preoperative VEDO was not associated with an increased morbidity rate when compared with other biologics.

Control of stem cell response and bone growth on biomaterials by fully non-peptidic integrin selective ligands.

In this communication we report that anchoring αvß3 or α5ß1 integrin-selective RGD peptidomimetics to titanium efficiently tunes mesenchymal stem cell response in vitro and bone growth in rat calvarial defects. Our results demonstrate that this molecular chemistry-derived approach could be successful to engineer instructive coatings for orthopedic applications.

Guidelines for Perioperative Care in Elective Colorectal Surgery: Enhanced Recovery After Surgery (ERAS®) Society Recommendations: 2018.

BACKGROUND: This is the fourth updated Enhanced Recovery After Surgery (ERAS®) Society guideline presenting a consensus for optimal perioperative care in colorectal surgery and providing graded recommendations for each ERAS item within the ERAS® protocol. METHODS: A wide database search on English literature publications was performed. Studies on each item within the protocol were selected with particular attention paid to meta-analyses, randomised controlled trials and large prospective cohorts and examined, reviewed and graded according to Grading of Recommendations, Assessment, Development and Evaluation (GRADE) system. RESULTS: All recommendations on ERAS® protocol items are based on best available evidence; good-quality trials; meta-analyses of good-quality trials; or large cohort studies. The level of evidence for the use of each item is presented accordingly. CONCLUSIONS: The evidence base and recommendation for items within the multimodal perioperative care pathway are presented by the ERAS® Society in this comprehensive consensus review.

The relationship between mesorectal grading and oncological outcome in rectal adenocarcinoma.

AIM: The prognostic association between mesorectal grading and oncological outcome in patients undergoing resection for rectal adenocarcinoma is controversial. The aim of this retrospective chart review was to determine the individual impact of mesorectal grading on rectal cancer outcomes. METHOD: We compared oncological outcomes in patients with complete, near-complete and incomplete mesorectum who underwent rectal excision with curative intent from 2009 to 2014 for Stage cI-III rectal adenocarcinoma. We also assessed the independent association of mesorectal grading and oncological outcome using multivariate models including other relevant variables. RESULTS: Out of 505 patients (339 men, median age of 60 years), 347 (69%) underwent a restorative procedure. There were 452 (89.5%), 33 (6.5%) and 20 (4%) patients with a complete, near-complete and incomplete mesorectum, respectively. Local recurrence was seen in 2.4% (n = 12) patients after a mean follow-up of 3.1 ± 1.7 years. Unadjusted 3-year Kaplan-Meier analysis by mesorectal grade showed decreased rates of overall, disease-free and cancer-specific survival and increased rates of overall and distant recurrence with a near-complete mesorectum, while local recurrence was increased in cases of an incomplete mesorectum (all P < 0.05). On multivariate analyses, a near-complete mesorectum was independently associated with decreased cancer-specific survival (hazard ratio 0.26, 95% CI 0.1-0.7; P = 0.007). There were no associations between mesorectal grading and overall survival, disease-free survival, overall recurrence or distant recurrence (all P > 0.05). CONCLUSION: Mesorectal grading is independently associated with oncological outcome. It provides unique information for optimizing surgical quality in rectal cancer.

Fluorescence imaging of invasive head and neck carcinoma cells with integrin αvß6-targeting RGD-peptides: an approach to a fluorescence-assisted intraoperative cytological assessment of bony resection margins.

We assessed the use of peptides containing arginylglycylaspartic acid (RGD) that target integrin αvß6 as a potential approach for a fluorescence-assisted intraoperative cytological assessment of bony resection margins (F-AICAB) in patients who had bone-infiltrating squamous cell carcinoma (SCC) of the head and neck. This was assessed to demarcate invasive carcinoma cells that stained for αvß6. Specimens from bony resection margins (n=362) were defined as either malignant or benign according to the results of cytological and histological examinations. Integrin αvß6-targeting fluorescence-labelled RGD peptides were added to the cytological samples and the accuracy of the resulting signal assessed by comparing it with the cytological findings. The value of F-AICAB was evaluated to find out if it could help to improve future diagnoses, tests, and treatments. Integrin αvß6 was strongly expressed in invasive SCC cells and qualified as a marker for bone-infiltrating carcinoma cells. It showed a high affinity to bind to invasive SCC cells and enabled swift and specific demarcation of αvß6-stained carcinoma cells. It was also diagnostic, with a sensitivity of 100% (95% CI 81.3% to 99.3%), specificity of 98.3% (95% CI 94.4% to 99.0%), positive predictive value of 92% (95% CI 70.2% to 94.3%), and negative predictive value of 100% (95% CI 96.9% to 99.9%), compared with the cytological findings. The targeting of specific integrin subtypes with selective, synthetic ligands, adapted for multimodal imaging, is a promising new approach to diagnosis. Further studies are necessary to provide more evidence for successful clinical translation and to establish the impact on clinical procedures.

Laparoscopy reduces iatrogenic splenic injuries during colorectal surgery.

BACKGROUND: Splenic injury can occur during colorectal surgery especially in cases, where the splenic flexure is mobilized. The aim of this study was to analyze whether the operative approach (laparoscopic vs. open) was associated with an increased risk for splenic injury during colorectal surgery and to compare the outcomes of different management options. METHODS: All accidental injuries that occurred during colorectal resections performed in our department between January 2010 and June 2013 were identified from an administrative database. All patients with iatrogenic splenic injuries were classified into two groups according to the operative approach. Only procedures that required splenic flexure mobilization were included. Splenic injury management options and outcomes were compared. RESULTS: There were 2336 colorectal resections (1520 open, 816 laparoscopic) performed during the study period. There were 25 (1.1%) iatrogenic splenic injuries. 23 out of 25 splenic injuries occurred during open colorectal surgery. Overall, 16 (64%) patients were managed with topical hemostatic methods, 5 (20%) with splenectomy, and 4 (16%) with splenorrhaphy. It was possible to salvage the spleen in both laparoscopic patients. The laparoscopic approach was associated with a lower splenic injury rate (0.25% vs. 1.5%, p = 0.005) and a lower need for splenectomy/splenorrhaphy (p = 0.03). CONCLUSIONS: Our data suggest that laparoscopic colorectal surgery may be associated with a lower risk of iatrogenic splenic injury, and that most splenic injuries can be managed with spleen-preserving approaches.

Outcomes of ileal pouch-anal anastomosis without primary diverting loop ileostomy if postoperative sepsis develops.

BACKGROUND: The aim of the present study was to assess the short-term and long-term consequences of diverting loop ileostomy (DLI) omission in ileal pouch-anal anastomosis (IPAA) surgery complicated by postoperative pelvic sepsis. METHODS: This was a retrospective review of a prospectively maintained database. Of 4031 patients who underwent IPAA in 1983-2014, 357 developed IPAA-related pelvic sepsis with or without anastomotic dehiscence. Patients with Crohn's disease or cancer were excluded. The patient cohort was divided into two groups, depending on the presence or absence of DLI. Patient characteristics, short-term and long-term outcomes were compared. Long-term pouch survival was estimated with the Kaplan-Meier method. Quality of life (QOL) in the groups was compared at the latest follow-up. RESULTS: Three hundred and twenty-six patients developing pelvic sepsis had diversion at the time of IPAA (D group) and in 31 who developed pelvic sepsis DLI had been omitted (O group). The length of hospital stay was significantly longer in the O group 11.5 (3-33) days versus 8 (2-59) days in the D group (p = 0.006). Forty-eight percent of patients from the O group with anastomotic leak underwent reoperation and had a DLI formed at this second procedure versus 12% in the D group requiring reoperation (p < 0.0001). In long-term follow-up, there was no difference in pouch survival between the groups: 99 versus 97% after 5 years and 88 versus 87% after 10 years, in the O group and D group, respectively (p = 0.40). There was no difference in QOL observed between the groups. CONCLUSIONS: Omission of DLI in selected patients who had IPAA surgery did not increase pouch failure or adversely affect QOL in the long term, if pelvic sepsis occurred.

Restorative proctocolectomy: an example of how surgery evolves in response to paradigm shifts in care.

AIM: Surgical technique constantly evolves in response to the pressure of progress. Ileal pouch anal anastomosis (IPAA) is a good example. We analysed the effect of changes in practice on the technique of IPAA and its outcomes. METHOD: Patients undergoing primary IPAA at this institution were divided into three groups by date of the IPAA: those operated from 1983 to 1993, from 1994 to 2004 and from 2005 to 2015. Demographics, patient comorbidity, surgical techniques, postoperative outcomes, pouch function and quality of life were analysed. RESULTS: In all, 4525 patients had a primary IPAA. With each decade, increasing numbers of surgeons were involved (decade I, 8; II, 16; III, 31), patients tended to be sicker (higher American Society of Anesthesiologists score) and three-staged pouches became more common. After an initial popularity of the S pouch, J pouches became dominant and a mucosectomy rate of 12% was standard. The laparoscopic technique blossomed in the last decade. 90-day postoperative morbidity by decade was 38.3% vs 50% vs 48% (P < 0.0001), but late morbidity decreased from 74.2% through 67.1% to 30% (P < 0.0001). Functional results improved, but quality of life scores did not. Pouch survival rate at 10 years was maintained (94% vs 95.2% vs 95.2%; P = 0.06). CONCLUSION: IPAA is still evolving. Despite new generations of surgeons, a more accurate diagnosis, appropriate staging and the laparoscopic technique have made IPAA a safer, more effective and enduring operation.

Short-term outcomes of laparoscopic versus open total colectomy with ileorectal anastomosis: a case-matched analysis from a nationwide database.

BACKGROUND: In the current study, we aimed to compare peri- and postoperative 30-day outcomes of patients undergoing laparoscopic versus open total colectomy with ileorectal anastomosis in a case-matched design using data procedure-targeted database. METHODS: Patients who underwent elective total colectomy with ileorectal anastomosis in 2012 and 2013 were identified from the American College of Surgeons National Surgical Quality Improvement Program database. Patients were divided into two groups according to the type of surgical approach (laparoscopic and open). Laparoscopic and open groups were matched (1:1) based on age, gender, diagnosis, body mass index, and American Society of Anesthesiologists classification. Comorbidities, perioperative, and short-term (30-day) postoperative outcomes were compared between the matched groups. RESULTS: We identified 1442 patients-549 in the laparoscopic group and 893 patients in the open group. After case matching, there were 326 patients in each group. There were 48 (14.7%) patients who had conversion in the laparoscopic group. The open group had a higher proportion of patients with ascites [0 (0%) vs. 7 (2.1%) p = 0.015], preoperative weight loss [26 (8.0%) vs. 45 (13.8%) p = 0.018], and contaminated wound classifications [Clean/Contaminated 261 (80%) vs. 240 (74%), Contaminated 55 (16.9%) vs. 54 (16.6%), and Dirty/Infected 8 (2.5%) vs. 28 (8.6%), (p = 0.003)]. The laparoscopic group had a significantly longer operative time (242 ± 98 vs. 202 ± 116 min, p < 0.001), shorter hospital stay (9.4 ± 8.5 vs. 13.3 ± 10.7 days, p < 0.001), and lower ileus rate (23.9 vs. 31.0%, p = 0.045) than the open group. After adjusting for covariates, the differences in terms of operative time and hospital stay remained significant [odds ratio (OR): 0.79, confidence interval (CI) 0.74-0.85 and OR 1.36, CI 1.21-1.52, p < 0.001, respectively]. CONCLUSIONS: Laparoscopic approach for total colectomy with ileorectal anastomosis is associated with a shorter hospital stay but longer operative time compared with an open approach.

Predictors of wound dehiscence and its impact on mortality after abdominoperineal resection: data from the National Surgical Quality Improvement Program.

BACKGROUND: Wound dehiscence is a known complication following abdominoperineal resection (APR) and can have a negative impact on recovery and outcome. The aim of this study was to determine the predictors of post-APR 30-day abdominal and/or perineal wound dehiscence, readmission, and reoperation, and to assess the impact of wound dehiscence on 30-day mortality. METHODS: All patients undergoing APR between 2005 and 2012 were analyzed using the American College of Surgeons National Surgical Quality Improvement Program. RESULTS: There were 5161 patients [male = 3076 (59.6 %)] with a mean age of 61.9 ± 14.3 years. Mean body mass index was 27.4 ± 6.6 kg/m(2). The most common indication for surgery was rectal cancer (79.1 %), followed by inflammatory bowel disease (8.2 %). The overall rate of wound dehiscence was 2.7 % (n = 141). Older age (p = 0.013), baseline dyspnea (p = 0.043), smoking history (p = 0.009), and muscle flap creation (p ≤ 0.001) were independently associated with the risk of dehiscence. No association was observed between omental flap creation and dehiscence risk (p = 0.47). The 30-day readmission rate (15.6 vs. 5.6 %, p ≤ 0.001) and need for reoperation (39 vs. 6.6 %, p ≤ 0.001) were significantly higher in patients who experienced dehiscence. Dehiscence was an independent risk factor for 30-day mortality [OR = 2.69 (1.02-7.08), p = 0.045)]. CONCLUSIONS: Older age, baseline dyspnea, smoking, and the use of muscle flap were associated with higher risk of wound dehiscence following APR. Patients with wound dehiscence had a higher rate of readmission and need for reoperation, and an increased risk of 30-day mortality.