Spatiotemporal NF-κB dynamics encodes the position, amplitude, and duration of local immune inputs

Infected cells communicate through secreted signaling molecules like cytokines, which carry information about pathogens. How differences in cytokine secretion affect inflammatory signaling over space and how responding cells decode information from propagating cytokines are not understood. By computationally and experimentally studying NF-κB dynamics in cocultures of signal-sending cells (macrophages) and signal-receiving cells (fibroblasts), we find that cytokine signals are transmitted by wave-like propagation of NF-κB activity and create well-defined activation zones in responding cells. NF-κB dynamics in responding cells can simultaneously encode information about cytokine dose, duration, and distance to the cytokine source. Spatially resolved transcriptional analysis reveals that responding cells transmit local cytokine information to distance-specific proinflammatory gene expression patterns, creating "gene expression zones."Despite single-cell variability, the size and duration of the signaling zone are tightly controlled by the macrophage secretion profile. Our results highlight how macrophages tune cytokine secretion to control signal transmission distance and how inflammatory signaling interprets these signals in space and time

Laparoscopic-Assisted Ileocolic Resection for Crohn's Disease

BACKGROUND: This study reviews our experience with laparoscopic-assisted ileocolic resection in patients with Crohn\u27s disease. The adequacy and safety of this procedure as measured by intraoperative and postoperative complications were evaluated. Special attention was paid to the group in which laparoscopy was not feasible and conversion to laparotomy was necessary. METHODS: Between 1992 and 2005, 168 laparoscopic-assisted ileocolic resections were performed on 167 patients with Crohn\u27s ileal or ileocolic disease. Follow-up data were complete in 158 patients. RESULTS: In 38 patients (24%), conversion to laparotomy was necessary. Previous resection was not a predictor of conversion to laparotomy. Average ileal and colonic length of resected specimens was 20.9 cm and 6.5 cm, respectively, in the laparoscopic group, versus 24.9 cm and 10.6 cm in the converted group. Twenty of 120 specimens (16.6%) in the laparoscopic group were found to have margins microscopically positive for active Crohn\u27s disease. None of the 38 specimens in the converted group had positive ileal margins. CONCLUSIONS: Laparoscopic-assisted ileocolic resection can be safely performed in patients with Crohn\u27s disease ileitis. The finding of positive surgical margins following laparoscopic resections compared with none among conventional resections has to be thoroughly evaluated

Association of Accelerometry-Measured Physical Activity and Cardiovascular Events in Mobility-Limited Older Adults: The LIFE (Lifestyle Interventions and Independence for Elders) Study.

BACKGROUND:Data are sparse regarding the value of physical activity (PA) surveillance among older adults-particularly among those with mobility limitations. The objective of this study was to examine longitudinal associations between objectively measured daily PA and the incidence of cardiovascular events among older adults in the LIFE (Lifestyle Interventions and Independence for Elders) study. METHODS AND RESULTS:Cardiovascular events were adjudicated based on medical records review, and cardiovascular risk factors were controlled for in the analysis. Home-based activity data were collected by hip-worn accelerometers at baseline and at 6, 12, and 24 months postrandomization to either a physical activity or health education intervention. LIFE study participants (n=1590; age 78.9±5.2 [SD] years; 67.2% women) at baseline had an 11% lower incidence of experiencing a subsequent cardiovascular event per 500 steps taken per day based on activity data (hazard ratio, 0.89; 95% confidence interval, 0.84-0.96; P=0.001). At baseline, every 30 minutes spent performing activities ≥500 counts per minute (hazard ratio, 0.75; confidence interval, 0.65-0.89 [P=0.001]) were also associated with a lower incidence of cardiovascular events. Throughout follow-up (6, 12, and 24 months), both the number of steps per day (per 500 steps; hazard ratio, 0.90, confidence interval, 0.85-0.96 [P=0.001]) and duration of activity ≥500 counts per minute (per 30 minutes; hazard ratio, 0.76; confidence interval, 0.63-0.90 [P=0.002]) were significantly associated with lower cardiovascular event rates. CONCLUSIONS:Objective measurements of physical activity via accelerometry were associated with cardiovascular events among older adults with limited mobility (summary score >10 on the Short Physical Performance Battery) both using baseline and longitudinal data. CLINICAL TRIAL REGISTRATION:URL: http://www.clinicaltrials.gov. Unique identifier: NCT01072500

Impact of opioid-free analgesia on pain severity and patient satisfaction after discharge from surgery: multispecialty, prospective cohort study in 25 countries

Background: Balancing opioid stewardship and the need for adequate analgesia following discharge after surgery is challenging. This study aimed to compare the outcomes for patients discharged with opioid versus opioid-free analgesia after common surgical procedures.Methods: This international, multicentre, prospective cohort study collected data from patients undergoing common acute and elective general surgical, urological, gynaecological, and orthopaedic procedures. The primary outcomes were patient-reported time in severe pain measured on a numerical analogue scale from 0 to 100% and patient-reported satisfaction with pain relief during the first week following discharge. Data were collected by in-hospital chart review and patient telephone interview 1 week after discharge.Results: The study recruited 4273 patients from 144 centres in 25 countries; 1311 patients (30.7%) were prescribed opioid analgesia at discharge. Patients reported being in severe pain for 10 (i.q.r. 1-30)% of the first week after discharge and rated satisfaction with analgesia as 90 (i.q.r. 80-100) of 100. After adjustment for confounders, opioid analgesia on discharge was independently associated with increased pain severity (risk ratio 1.52, 95% c.i. 1.31 to 1.76; P < 0.001) and re-presentation to healthcare providers owing to side-effects of medication (OR 2.38, 95% c.i. 1.36 to 4.17; P = 0.004), but not with satisfaction with analgesia (beta coefficient 0.92, 95% c.i. -1.52 to 3.36; P = 0.468) compared with opioid-free analgesia. Although opioid prescribing varied greatly between high-income and low- and middle-income countries, patient-reported outcomes did not.Conclusion: Opioid analgesia prescription on surgical discharge is associated with a higher risk of re-presentation owing to side-effects of medication and increased patient-reported pain, but not with changes in patient-reported satisfaction. Opioid-free discharge analgesia should be adopted routinely

Does Shared Decision Making in Cancer Treatment Improve Quality of Life? A Systematic Literature Review.

BACKGROUND: The growing consensus espousing the use of shared decision making (SDM) in cancer treatment has coincided with the rise of health care evaluation paradigms that emphasize quality of life (QOL) as a central outcome measure. This review systematically examines the association between treatment SDM and QOL outcomes in cancer. METHODS: A range of bibliographic databases and gray literature sources was searched. The search retrieved 16,726 records, which were screened by title, abstract, and full text to identify relevant studies. The review included 17 studies with a range of study designs and populations. Data were extracted on study methods, participants, setting, study or intervention description, outcomes, main findings, secondary findings, and limitations. Quality appraisal was used, in conjunction with a narrative approach, to synthesize the evidence. RESULTS: The review found weak, but suggestive, evidence for a positive association between perceived patient involvement in decision making, a central dimension of SDM, and QOL outcomes in cancer. The review did not find evidence for an inverse association between SDM and QOL. The poor methodological quality and heterogeneity of the extant literature constrained the derived conclusions. In addition, the literature commonly treated various subscales of QOL instruments as separate outcomes, increasing the probability of spurious findings. CONCLUSIONS: There is weak evidence that aspects of shared decision-making approaches are positively associated with QOL outcomes and very little evidence of a negative association. The extant literature largely assessed patient involvement, only capturing one aspect of the shared decision-making construct, and is of poor quality, necessitating robust studies examining the association

Incidence and progression of trachomatous scarring in a cohort of children in a formerly hyper-endemic district of Tanzania.

BackgroundTrachoma is the leading infectious cause of blindness. Repeated or persistent ocular infection with Chlamydia trachomatis in childhood leads to conjunctival scarring, usually in adulthood but often earlier in areas with greater disease burden. There are limited longitudinal data examining change in scarring in children, especially where trachoma rates are low.Methodology/principal findingsA cohort of children, ages 1-9 years, were randomly selected at baseline from 38 communities in Kongwa, Tanzania and followed for 2 years. Rates of trachomatous inflammation-follicular (TF) were Conclusions/significanceIn this formerly hyper-endemic district, the incidence of new scarring in children ages 1-9 years is low, although 21% of those who had scarring at baseline progressed in severity over the 2-year follow-up period. These data provide support for the thesis that while incident scarring more closely reflects ongoing exposure, progression may involve factors independent of ongoing transmission of trachoma

Patient perceived barriers to surgical follow-up: Study of 6-month post-operative trichiasis surgery follow-up in Tanzania.

BackgroundPost-surgical follow-up is a challenge in low- and middle-income countries. Understanding barriers to trachomatous trichiasis (TT) surgical follow-up can inform program improvements. In this study, patient perceived barriers and enabling factors to follow-up after TT surgery are identified.MethodsA longitudinal study was carried out in a community-based cohort of persons who received TT surgery in Bahi district, Tanzania. Questionnaires were administered before TT surgery and again after the scheduled 6-month follow-up. Those who did not return were examined at their homes.ResultsAt baseline, 852 participants were enrolled. Of these, 633 (74%) returned at 6 months and 128 (15%) did not and were interviewed at home. Prior to surgery, attenders were more likely to report familiarity with a community health worker (CHW) (22% vs. 14%; p = 0.01) and less likely to state that time constraints are a potential reason for failure to follow-up (66% vs. 74%; p = .04). At follow-up, non-attenders were more likely to endorse barriers pertaining to knowledge about the need for follow-up, lack of transportation, and satisfaction with surgery. There was no difference in post-operative TT between attenders and non-attenders (23% vs. 18% respectively; p = 0.25).ConclusionsThe outcome of surgery was not a barrier to follow-up. However, better integration of CHWs into their communities and work at coordinating post-surgical care may improve follow-up rates. Moreover, provision of transportation and implementation of effective reminder systems may address patient-perceived barriers to improve follow-up

Laparoscopic-assisted ileocolic resection for Crohn\u27s disease.

BACKGROUND: This study reviews our experience with laparoscopic-assisted ileocolic resection in patients with Crohn\u27s disease. The adequacy and safety of this procedure as measured by intraoperative and postoperative complications were evaluated. Special attention was paid to the group in which laparoscopy was not feasible and conversion to laparotomy was necessary. METHODS: Between 1992 and 2005, 168 laparoscopic-assisted ileocolic resections were performed on 167 patients with Crohn\u27s ileal or ileocolic disease. Follow-up data were complete in 158 patients. RESULTS: In 38 patients (24%), conversion to laparotomy was necessary. Previous resection was not a predictor of conversion to laparotomy. Average ileal and colonic length of resected specimens was 20.9 cm and 6.5 cm, respectively, in the laparoscopic group, versus 24.9 cm and 10.6 cm in the converted group. Twenty of 120 specimens (16.6%) in the laparoscopic group were found to have margins microscopically positive for active Crohn\u27s disease. None of the 38 specimens in the converted group had positive ileal margins. CONCLUSIONS: Laparoscopic-assisted ileocolic resection can be safely performed in patients with Crohn\u27s disease ileitis. The finding of positive surgical margins following laparoscopic resections compared with none among conventional resections has to be thoroughly evaluated

Spatiotemporal NF-κB dynamics encodes the position, amplitude, and duration of local immune inputs

Infected cells communicate through secreted signaling molecules like cytokines, which carry information about pathogens. How differences in cytokine secretion affect inflammatory signaling over space and how responding cells decode information from propagating cytokines are not understood. By computationally and experimentally studying NF-κB dynamics in cocultures of signal-sending cells (macrophages) and signal-receiving cells (fibroblasts), we find that cytokine signals are transmitted by wave-like propagation of NF-κB activity and create well-defined activation zones in responding cells. NF-κB dynamics in responding cells can simultaneously encode information about cytokine dose, duration, and distance to the cytokine source. Spatially resolved transcriptional analysis reveals that responding cells transmit local cytokine information to distance-specific proinflammatory gene expression patterns, creating "gene expression zones." Despite single-cell variability, the size and duration of the signaling zone are tightly controlled by the macrophage secretion profile. Our results highlight how macrophages tune cytokine secretion to control signal transmission distance and how inflammatory signaling interprets these signals in space and time.ISSN:2375-254

Examples of grades of trachomatous scarring from S1 to S4.

Original source: Wolle MA, Muñoz B, Mkocha H, West SK. Age, sex, and cohort effects in a longitudinal study of trachomatous scarring. Invest Ophthalmol Vis Sci. 2009 Feb;50 [2]:592–6 [15]. Copyright is held by ARVO.</p