PET/CT is now integral to the staging pathway for potentially curable esophageal cancer (EC), primarily to identify distant metastases undetected by computed tomography. The aim of this study was to analyze the effect of PET/CT introduction on survival and assess patterns of recurrence after esophagectomy.A longitudinal cohort of EC patients staged between 1998 and 2016 were considered for inclusion. After co-variate adjustment using propensity scoring, a cohort of 496 patients (273 pre-PET/CT and 223 post-PET/CT) who underwent esophagectomy  were included. The primary outcome measure was overall survival (OS) based on intention to treat.2 6.571, df 1, p = 0.004). On multivariable analysis, pT stage , pN stage  and PET/CT staging (HR 0.688 [95% CI 0.53–0.89] p = 0.004) were independently associated with OS. Recurrent cancer was observed in 125 patients (51.4%) pre-PET/CT, compared with 74 patients post-PET/CT , and was less likely to be distant recurrence after PET/CT introduction .Three-year OS pre-PET/CT was 42.5% compared with 57.8% post-PET/CT (ChiEnhanced PET/CT staging is an important modality and independent factor associated with improved survival in patients undergoing esophagectomy for cancer. Imaging is fundamental to improved cancer staging and largely guides treatment decision-making. Radiological staging investigations including computed tomography (CT) and positron emission tomography (PET) provide anatomical and functional information and have greatly impacted clinical practice –3.Positron emission tomography integrated with computed tomography (PET/CT) is now an established and evidence-based part of the modern radiological staging algorithm of esophageal cancer (EC) , 5. RepoYet PET/CT is not without limitations. Endoscopic ultrasound (EUS) has been reported to be superior in staging both the primary tumor and local lymph nodes , and no Propensity score (PS) analysis facilitates measurement of the probability of receiving a particular treatment modality related to a number of variables, and represents a strong and powerful alternative strategy to explore cause, compared with orthodox statistical adjustment . PS analThe aim of this study was to analyze the influence of 18-FDG PET/CT introduction on OS after esophagectomy for cancer when compared with historical controls by means of PS analysis. The hypothesis was that PET/CT introduction into the routine staging algorithm of patients diagnosed with EC was associated with improved OS after potentially curative surgery. The setting was a UK Upper Gastrointestinal (UGI) cancer network serving a population of 1.8 million.All patients diagnosed with EC of any cell type who underwent surgery and had PET/CT imaging during the preoperative staging period in the South East Wales regional UGI cancer network were studied prospectively between January 1, 2009 and August 31, 2016. These patients were compared with a historical cohort of consecutive patients undergoing EC surgery between January 1, 1998 and January 1, 2009, staged with the network’s historical staging algorithm pre-PET/CT. Exclusion criteria included patients undergoing PET/CT for Siewert type III esophagogastric junctional cancer with proximal esophageal extension, and patients undergoing salvage esophagectomy following initial definitive chemoradiotherapy (dCRT).Patients proceeded to PET/CT staging only if they were suitable for potentially curative treatment on the grounds of CT stage and performance status, and was concurrently arranged with EUS examination. PET/CT was used for pre-treatment staging only Fig.  and was PET/CT examinations were performed at two centers. At the first center (site 1), a total of 87 patients had PET/CT examinations performed using a Philips 16 slice Gemini GXL dedicated PET/CT scanner . The uptake time was 60 min. A standard administered activity of 350 MBq of FDG was given. Reconstructions were performed using a 3D acquisition with non-time of flight acquisition for 4 min per bed position.18F-FDG per kilogram of body weight. Uptake time was 90 min. PET images were acquired at 3 min per field of view. The length of the axial field of view was 15.7 cm. Images were reconstructed with the ordered subset expectation maximization algorithm, with 24 subsets and two iterations. Matrix size was 256 × 256 pixels, using the VUE Point ™ time of flight algorithm. CT images were acquired in a helical acquisition with a pitch of 0.98 and a tube rotation speed of 0.5 s. Tube output was 120 kVp with output modulation between 20 and 200 mA. Matrix size for the CT acquisition was 512 × 512 pixels with a 50-cm field of view. At both centers, all patients were starved for a minimum of 6 h prior to imaging and no oral or intravenous contrast was administered.Four hundred and eighty-five patients were imaged at the second center (site 2) using a GE Discovery 690 PET/CT scanner . Serum glucose levels were routinely checked and confirmed to be less than 7.0 mmol/l prior to imaging. Patients received an activity of 4 MBq of The assignment of lymph nodes as involved or uninvolved on PET images at the two centers was based on subjective clinical assessment in each case. In general, nodes were only assigned as involved if they showed discernible tracer uptake above that of background and were identified separately from the primary tumor. Other factors affecting the classification of nodes were the morphology, size, and relative uptake of the node in question in comparison to the primary tumor. No specific SUV or size cut off was used in assignment of nodes as benign or malignant. Lymph nodes considered physiological or related to an alternative etiology were excluded from the N stage.Patients were selected for radical treatment (surgery or dCRT) based on perceived radiologic stage, comorbidity, and patient choice according to algorithms described previously –19. The Patients were reviewed every 3 months for the first year, and 6 monthly thereafter until 5 years or death. Patients underwent clinical assessment and venous blood sampling including carcinoembryonic antigen (CEA) measurements. Patients who were suspected to have disease recurrence based on clinical assessment or a raised venous CEA underwent computed tomography or endoscopy. Patterns of recurrence were defined as loco-regional, distant (metastatic), or both loco-regional and distant, when both were diagnosed concurrently. The time of recurrence was taken as the date of the confirmatory investigation. The patient cohort was analyzed in January 2017. No patients were lost to follow-up and death certification was obtained from the Office for National Statistics via Cancer Network Information System Cymru (CaNISC).t test and defined by |d| > 0.25. The variables were considered by the MDT and comprised age group, gender, tumor histology, pathological T and N stage, operation type, and site of PET/CT examination. The dependent variable was whether the patient underwent PET/CT staging. The probabilities option was chosen to generate propensity scores, which were then used in a regression, covariate adjustment, to estimate the effect of exposure of PET/CT on DFS and OS. DFS was calculated by measuring the interval from a landmark time of 6 months after diagnosis to the date of recurrence; an approach mirroring previous randomized trials [p < 0·010 level were entered into a forward conditional Cox proportional hazards model. All statistical analysis was performed with SPSS® .Grouped data were expressed as median (range) and non-parametric methods used throughout. Propensity scores were generated using appropriate logistic regression model, and included all relevant independent variables thought to be potential confounding factors and those which affect outcome. Co-variate adjustment was performed using the propensity scores, which were assessed for balance across groups using a Student’s d trials , 22 and In total, 1167 patients were diagnosed with EC between 1998 and 2016 . Patient demographics are detailed in Table Following propensity scoring, 496 consecutive patients were eligible for inclusion, 273 pre-PET/CT, and 223 patients post-PET/CT. Twenty-two (9.9%) patients had non-avid tumors on PET/CT, but were included on an intention-to-treat analysis basis. Propensity scores were generated for all 496 patients in the cohort. The propensity scores were balanced across the two groups, Student’s p < 0.0001). The post-PET/CT cohort also underwent marginally more open and close laparotomies for undetected distant metastases  compared with the pre-PET/CT cohort . The median follow-up was 26 months , with 476 patients (96.1%) followed up for 1 year or until death, 447 (90.0%) for 2 years, 418 (84.3%) for 3 years, and 375 (81.4%) for 5 years.The operative approach was trans-thoracic in 233 (47.0%), trans-hiatal in 200 (40.3%), and a three-stage approach was used in six (1.2%) patients. Open and close laparotomy was performed in 57 (11.5%) patients either due to un-resectable tumor or metastatic disease. Pathological examination revealed R1 resection specimens (microscopic margin involvement) in 166 (33.5%) patients. Operative mortality occurred in 17 (3.4%) patients within 30 days of surgery. More trans-hiatal esophagectomies and three-stage esophagogastrectomies were performed in the post-PET/CT cohort than the pre-PET/CT cohort, which contained more trans-thoracic esophagectomies . The site of recurrent cancer was less likely to be distant in location after PET/CT introduction .Recurrent cancer was observed in 125 patients (51.4%) in the pre-PET/CT cohort, compared with 74 patients in the post-PET/CT cohort . Moreover, PET/CT had no significant effect on survival . The difference in survival pre- and post-PET/CT was approximately 2, 6, and 7% at 1, 2, and 3 years, compared with 7.1, 13.1, and 15.3% in this study. Torrance et al. concluded that PET/CT improved the accuracy of EC staging, avoiding potentially unnecessary surgery, and contended that missed occult metastases did not appear to be the primary cause of early EC recurrence.Reports regarding the influence of PET/CT within EC staging algorithms on patient long-term outcomes related to recurrence and durations of survival are few. Torrance et al. , from ChThe current study has potential inherent limitations. The PET/CT examinations were performed at two centers, using different scanners, protocols, and uptake times, with patients in the early part of the study referred to site 1 (Philips 16 slice Gemini GXL), prior to the opening of site 2’s PET/CT in 2010. The main differences between the two centers were firstly, a 60-min uptake time on the first scanner (site 1), and a 90-min uptake time in site 2. Longer uptake times lead to higher tumor-to-background tracer uptake and may therefore increase conspicuity of nodal and distant metastases . SecondlThe study included patients treated over a 17-year period with a variety of treatment strategies. Evolution in UGI cancer practice would have naturally occurred during the time frame of this study, including neoadjuvant therapy regimen modifications, more detailed patient risk profile assessment related to patients’ fitness for surgery including objective assessment of physical fitness with cardiopulmonary exercise testing, centralization of surgical services, and the introduction of an Enhanced Recovery Program, all of which might represent potential confounding factors.Conversely, the strengths of the study are that the data was collected prospectively, from a well-defined geographical area served by an established regional UGI cancer network and multidisciplinary team. This team included six experienced specialist surgeons, with a referring population base of 1.8 million, accepting over 500 cases per year, generating in excess of 100 potentially curative esophagogastric resections, whose outcome data is well audited and of public record . The surMultivariable model analyses have been considered the orthodox and preferred statistical way of assessing the effect of possible predictors on outcomes after controlling for baseline characteristics, yet their suitability depends on consistent assumptions underlying any given model. Regression analyses of DFS and OS by means of propensity scores overcome some potential biases, and although it is considered the most useful statistical method for controlling confounders, providing appropriate estimates even when faced with extreme correlation between confounders and the exposure , it cannIn conclusion, this propensity score regression analysis further supports the use of PET/CT in EC staging pathways, and in the absence of an adequately powered randomized controlled trial, provides the best level of research evidence regarding the influence of PET/CT on outcome after potentially curative esophagectomy for cancer. Risk profile assessment represents an important development in the selection algorithm for patients diagnosed with invasive EC. While this is often assumed to relate to patients’ physical fitness, clearly avoiding hopeless radical, and unnecessary surgery, in patients with undetected occult metastases is an important allied strategy, if EC treatment outcomes are to be optimized. The findings of this study have shown that the introduction of PET/CT into the global patient assessment process changed the risk profile of over one in ten patients, reduced global recurrence by one-quarter, and improved median survival by a full year. A health economic analysis of the cost-effectiveness of PET/CT is now desirable to estimate the potential allied clinical and fiscal benefits available to upper gastrointestinal cancer networks.


Influenza generates a significant societal impact on morbidity, mortality, and associated costs. The study objective was to identify factors associated with influenza-like-illness (ILI) episodes during seasonal influenza epidemics among the general population.GrippeNet.fr crowdsourced cohort between 2012/13 and 2017/18. After having completed a yearly profile survey detailing socio-demographic, lifestyle and health characteristics, participants reported weekly data on symptoms. Factors associated with at least one ILI episode per influenza epidemic, using the European Centre for Disease Prevention and Control case definition, were analyzed through a conditional logistic regression model.A prospective study was conducted with the n = 4258). From 11% (n = 469/4140 in 2013/14) to 29% (n = 866/2943 in 2012/13) of individuals experienced at least one ILI during an influenza epidemic. Factors associated with higher risk for ILI were: gender female , young age ; from 5 to 14 years old: 1.53 ), respiratory allergies , receiving a treatment for chronic disease , being overweight  or obese , using public transport  and having contact with pets . Older age  and being vaccinated against influenza  were found to be protective factors for ILI.From 2012/13 to 2017/18, 6992 individuals participated at least once, and 61% of them were women  contains supplementary material, which is available to authorized users. Seasonal influenza represents a major cause of morbidity and mortality worldwide, responsible for 3 to 5 million of serious illnesses , and for(i) individual characteristics, such as age  [(ii) individual’s household features, such as living with children [(iii) individual’s profession like having contacts with children [Documented influenza risk factors are related to der age) , 5, immuder age) , pregnander age) , chronicder age) ; (ii) inchildren ; or  days of work lost per influenza episode and person , 12.Risk factors analyses based on the general population have been already addressed, but most were implemented during the 2009 A/H1N1pdm09 pandemic . Since 2https://www.grippenet.fr). Consent is informed and implied through registration and voluntarily completing a profile survey. This profile survey can be updated throughout the season, and covers socio-demographic ; lifestyle ; and health-related characteristics (height and weight to estimate the body mass index (BMI), chronic treatments for at least one comorbidity including asthma, diabetes, immunosuppression, heart, kidney or pulmonary diseases, influenza vaccination status for the current and past seasons, respiratory allergies) [GN is a crowdsourced surveillance system operating each year from November to April in mainland France since 2012. It is part of a broader European platform Influenzanet, where ten countries are involved . Individlergies) , 18. Aftlergies) –16. If slergies) . The prolergies)  and symplergies) ). ParticAlthough GN participants were not representative of the French general population in terms of age and gender , all age classes were represented (data from 2011/12 season ). The GNThe analysis was conducted on six GN seasons from 2012/13 to 2017/18.Sentinelles network [Each season, GN participants who provided regular information were included in the current study. Regular information was defined as having filled at least one profile survey and three weekly symptoms surveys for a given season. At least one symptoms survey should have been completed before, another during and one after the influenza epidemic period as stated by the French national surveillance network in primary care, called  network . A simil network . IndividECDC), which is often used by other Influenzanet studies [Sentinelles network, stated as GNILI- and defined by (i) sudden onset of symptoms, AND (ii) fever ≥38 °C or fever (when the body temperature level was not available) AND pain or headache, AND (iii) sore throat or cough or shortness of breath [Different case definitions have been built from symptoms declared on GN . For the studies , 21, 22. studies . The anaf breath . The latSentinelles network.As demonstrated in previous research, ILI represents a good proxy for influenza estimates , 24. As p-value below 0.2 were tested in multivariate analyses. Covariates were selected through a backward stepwise selection. The final model included all covariates associated with having at least one ILI episode with a p-value below or equal to 0.05. Same analyses were conducted using the more specific definition (GNILI-). All statistical analyses were performed using the R software (3.2.5 version) and the geepack package [Characteristics of the study participants between 2012/13 to 2017/18 were described depending on the last profile survey completed over the study period. As GN is an observational cohort, most of the participants are returning participants season after season, and so one participant can be counted in the study from one to six times. A person-season was defined as an individual having participated in the study during one season. Determinants associated with having at least one ILI episode during a follow-up season were estimated through a conditional logistic regression model, using the generalized estimated equations for longitudinal correlated data, based on the person-seasons. Explanatory variables  were tested in univariate analyses. All covariates with a  package , 26.Participation description is available in Table n = 4258), living in urban area , and having a mean age of 51 years old. Regarding daily contacts, 32% (n = 2268) were in contact with groups of ≥10 individuals, 26% (n = 1788) with children (beyond their own ones), 10% (n = 728) with patients and 10% (n = 721) with elderly. Vaccination against influenza for the current season was done in 36% (n = 2517) of the individuals followed . Concerning the underlying health conditions, 22% (n = 1504) of the participants were treated for at least one comorbidity . One third (n = 2413) had respiratory allergies and 11% (n = 766) were smokers. Further details are available in Table Socio-demographic, lifestyle and health-related characteristics of the 6992 participants included in the study were described in Table ECDC episode during the influenza epidemic. Using the more specific GNILI- definition, this range reduced from 3% (111/4140 in 2013/14) to 8% (231/2943 in 2012/13)  to 29% (866/2943 in 2012/13) of individuals experienced at least one ILIECDC episode during the influenza epidemic period with a p-value below 0.2 were: gender, age, household composition, occupation, use of public transport, pets at home, contacts with patients, contact with a group of individuals, contact with children, influenza vaccination status regarding the current and past seasons, being treated for health comorbidities, respiratory allergy, and body mass index . Children experienced more ILIECDC episodes compared to adults from 45 to 64 . Individuals using public transport , having pets at home , treated for health comorbidities , having respiratory allergy , or being overweight or obese  were also more prone to experience an ILIECDC episode. On the contrary, individuals aged 75 years or older tended to have fewer ILIECDC episodes compared to those in the range of 45 to 64 . Individuals vaccinated for the current season were also found to be at lower risk .In the final multivariate model Table , women tILI- definition showed similar results . Female vs. male differences regarding influenza have been previously evaluated: at younger (< 20 years) and older (> 80) ages, morbidity rates seem to be higher for males than females, however during the reproductive age (from 20 to 49 age group) women were found to have higher morbidity rates [In our analyses, women were found to be at higher risk for ILI, independently of the case definition used  to 19% (ILIECDC). International studies have provided estimates in the same ballpark  [In addition to the risk factor analysis, we estimated here the average fraction of individuals presenting at least one ILI episode during a season, ranging from 5% , howeven the US , a lowerinition) .ECDC) and a more specific one (GNILI-).The strength of this study is the identification of ILI determinants in the general population. Fine scale data have been collected through a large panel of individuals during several seasons allowing the evaluation of a wide range of ILI determinants. Little-known risk factors for ILI were identified in addition to well-known factors indicating that GrippeNet.fr is effective to study ILI determinants at the population level. However, a few limitations can be highlighted. First, the cohort was not representative of the French population as it is a crowdsourced system. Nevertheless, all ages and gender were represented. Second, no virological confirmation was available to ensure influenza follow-up. Thus, risk factors found here were not specifically associated with influenza infection but with a broader set of respiratory viruses causing similar symptoms. To limit the impact of this aspect, we decided to include only ILI episodes occurring during the influenza epidemic period, and also to explore two ILI case definitions, namely a more sensitive one Additional file 2:Factors associated with at least one ILI episode (GNILI-) during six influenza epidemic periods, GrippeNet.fr. This table highlights the factors associated with an ILI episode using a more specific definition. (DOCX 25 kb)


Meibomian gland dysfunction (MGD) is one of the possible conditions underlying ocular surface disorders (OSD). Prevalence of MGD in dogs affected by OSD has not yet been reported. We aimed to evaluate the prevalence of MGD among OSD canine patients, which had been assessed by non-contact infrared meibography and interferometry, and to identify MGD associated factors that might guide its diagnosis. Medical records of canine patients examined for OSD between 2016 and 2019 were reviewed. The frequency of MGD was evaluated within different categories . The putative MGD risk factors and frequency of MGD within grades of interferometry were evaluated in a regression analysis model and reported as odd ratios (ORs).adj = 3.015 (95% CI: 1.395–6.514) (P = 0.005) and older patients ORadj = 1.207 (95% CI: 1.081–1.348) (P = 0.001). No significant differences were found between left and right eyes (P = 0.66) or between the two types of skull conformation (P = 0.477) and MGD presence. MGD was associated to the lowest lipid layer (LL) thickness, as assessed by interferometry (grade 0) OR = 16.00 (95% CI: 2.104–121.68) (P < 0.001). STT values were not significantly associated with the presence of MGD (P > 0.05).One hundred fifty eyes from 81 dogs with OSD were included with median age 75 months (range 3–192) and female representation with 52%. MGD was present in 70% of the examined eyes. MGD risk was higher in males ORMGD is a common underlying pathology in OSD. Being male and higher age are risk factors for MGD. An interferometry grade 0 may guide OSD diagnosis towards MGD. Ocular surface homeostasis is maintained by the lacrimal functional unit, an integrated system comprising the lacrimal glands, ocular surface  and lids, and the sensory and motor nerves that connect them .Any disorder in these structures can be classified as an ocular surface disorder (OSD), which includes also conditions like dry eye disease, and meibomian gland dysfunction (MGD) .The main role of the lacrimal functional unit is to provide the ocular surface with an adequate and protective tear film (TF). The precorneal TF is composed of a thin superficial lipid layer (LL) and an underlying mucoaqueous layer, which occupies the bulk of the TF thickness and interacts directly with the glycocalyx of the epithelium via the membrane-spanning mucins , 4. LipiMGD is a chronic, diffuse abnormality involving most of the meibomian glands , and chaThe tear film-lipid layer (TF-LL) can be assessed by interferometry with the observation of interference patterns , which pThe study aimed to retrospectively review the common meibographic and interferometric findings in the eyes of dogs affected by OSD to find out the proportion of cases with concomitant MGD, and to identify possible risk factors for MGD. In addition, the possible relationship of interferometry and MGD was studied.In a period of 3 years 2016–2019), 150 eyes from 81 dogs were examined. Median age was 75 months (range 3–192) and gender distribution was female for 52%  of eyes and male for 48% (100% entire). Twenty-seven different breeds were represented in this study with mixed-breed and English bulldog as the most frequent ones, with an equal representation of 12 dogs each. Brachycephalic breeds were represented by 59 eyes and non-brachycephalic by 91 eyes  eyes, and it was the most common diagnosis among OSD eyes, followed by macroblepharon (16.7%) and exposure keratitis 12.7%) (Table .7% (TablP = 0.66).No significant association was found between right or left eyes with regards to MGD presence  = 3.015 (95% CI: 1.395–6.514) (P = 0.005), while there was not difference between neutered or intact females presenting MGD OR = 1.122 (95% CI: 0.422–2.987) (P = 0.817). The risk of developing MGD increased with age with an estimated ORadj of 1.207 (95% CI: 1.081–1.348) for any additional year (P = 0.001). However, no significant association was observed between skull conformation and MGD (P = 0.477) , followed by grade 2 (22%), grade 0 (19.4%), grade 3 (7.3%) and the last one grade 4 (2%).P < 0.001 and P = 0.007 respectively) .The distribution of skull conformation and gender within the grades of interferometry were significantly different . A higher risk of MGD was observed at grade 0 with thinner LL OR = 16.00 (95% CI: 2.104–121.68) (P < 0.001), and a lower risk was found for grade 2 OR = 0.414 (95% CI: 0.186–0.922) (P = 0.032) corresponding to thicker LL. The OR for grade 3 OR = 0.325 (95% CI: 0.094–1.127) (P = 0.078) was not significant, probably due to the small sample size (n = 11). Likewise, the OR of grade 4 was could not be assessed due to the small number of patients (n = 3), none of which had MGD. Thus, MGD incidence seems to decrease with increasing interferometry grades, as was suggested by the absence of the disease in grade 4.The presence of MGD was significantly associated with interferometry grades Table . A higheP > 0.05). In grade 1, eyes with MGD showed a STT-1 value of 22.7 mm/min (SD = 8.6) versus a value of 21.6 mm/min (SD = 8.6) in eyes free of MGD (P = 0.626). Also in grade 2, eyes with MGD showed a very similar STT-1 value when compared to eyes free of MGD  respectively (P = 0.948). In the remaining grades  the number of cases was too low to be analyzed.STT-1 values were not significantly associated with the presence of MGD and grades of interferometry , followed by macroblepharon (16.7%) and eye exposure keratitis (12.7%), also considered potential causes of altered TF distribution.Several techniques have been used to study the meibomian gland function. Slit-lamp biomicroscopy allows the assessment of the meibomian glands openings and may provide morphological evaluation of the glands in non-pigmented eyelids; however, it is limited as an indirect measure of meibomian gland structure and function . MeibomeMeibography had been performed between the upper eyelid of the examined eyes. Human studies on MGD demonstrated no significant differences on examining either the upper or lower eyelid for MGD diagnosis, since when MGD was present, there was a good correlation between upper and lower meibomian gland loss . FurtherThe risk of developing MGD in humans increases with age, androgen deficiency and several other factors, including ophthalmic risk factors like dry eye and blepharitis –19. HoweInterferometry allows visualization of the kinetics of the oily layer of the TF that can be partially influenced by its composition, not only by its thickness –23. LL cBrachycephalic dogs are reported to be prone to OSD ; howeverIn the presence of MGD, no association was observed between tear production (measured by STT-1) and grades of interferometry. A compensatory system has been described in humans by which the reduced oily layer of the TF, in case of MGD, is compensated by an increased secretion of aqueous component . In the The balance of TF components is important for TF stability, and a compensatory system is thought to operate in response to changes in these components . FurtherOne limitation of our study is the inability to investigate goblet cells and their mucin secretion. Human studies speculate that an increase of TF stability by mucin production may require longer times .In addition, it was not possible to standardize environmental important parameters, such as temperature and humidity . Since aMGD is a common underlying pathology in OSD. Being male and of older age are risk factors for MGD. A low grade of interferometry (grade 0) is associated with MGD, and thus, together with the presence of risk factors, might guide the OSD diagnosis towards MGD before confirmation by meibography.Medical records of canine patients that had undergone TF examination after a diagnosis of OSD at the Ophthalmology Referrals Unit of the Turin Veterinary Centre, Italy from 2016 to 2019 were reviewed. Informed consent form was obtained from the owners for the use of the patient data. Diagnosis of OSD was made after a complete ophthalmic examination and was based on clinical signs of loss of ocular surface homeostasis caused by anatomical and/or functional alterations of one or more components of the lacrimal functional unit including: the ocular surface (cornea and conjunctiva) with sensory nerve endings, the afferent and efferent innervation to stimulate tear secretion, the lacrimal gland, the meibomian gland, the conjunctival goblet cells and the eyelids.Information from each case included gender, breed, skull conformation , age, eye examined (left or right), concurrent ocular diseases, meibography and interferometry.All dogs in this study had undergone a complete and bilateral ophthalmic examination by a board-certified veterinary ophthalmologist. The examination included assessments of the palpebral reflex, menace response, pupillary light and dazzle reflexes, Schirmer tear test 1 (STT-1) , slit-lamp biomicroscopy , fluorescein staining , applanation tonometry , and indirect ophthalmoscopy .Patients that were on any kind of OSD treatment met inclusion criteria only if treatment had been suspended ≥2 days before performing the TF examination. Records of dogs with orbital or nictitating membrane disorders, with intraocular diseases , or with a recent history of surgery (less than 1 month) were excluded from the study..A hand-held ocular surface analyzer , equipped with infrared and white led lights for meibography and interferometry, respectively, was used to perform non-contact infrared meibography of the upper lid and interferometry Fig. .Fig. 2S).Meibography was mainly directed at the diagnosis of MGD, and only 2 categories were considered: MGD affected or unaffected. A diagnosis of MGD was achieved when terminal duct obstruction was present along over 75% of the eyelid margins and/or when meibomian glands dilatation, shortening, atrophy or dropout affected more than 50% of the eyelid [Meibomian gland expression has been used in some cases to evaluate the color and consistency of the expressed meibum or to confirm ductal occlusion.Interferometry was used to assess the TF-LL patterns, each one reflecting a specific thickness of the TF-LL. The patterns were classified according to a grading scale recommended by the instrument manufacturer, with categories adopted for humans , 9, 29, STT-1 was used to assess tear production. The continuous variable was subdivided into three categories: < 10 mm/min, 10–15 mm/min and > 15 mm/min.In order to avoid excessive inter-observer differences in the assignment of ranks the interferometry was done by the same experienced operator.The data were retrospectively collected and reviewed, and elaborated for statistical analysis.Normality of the underlying distribution of the continuous variables was assessed using the Shapiro-Wilk test.Continuous variables with normal distribution were presented as mean and standard deviation (SD), and those with non-normal distribution were presented as median (range), while absolute frequencies and percentage were used for categorical variables.The MGD frequency distribution was evaluated within different categories  using the Chi-squared test.Independent variables  were evaluated as risk factors for developing MGD (dependent variable) in a logistic regression model and reported as odd ratios (ORs) with their 95% confidence (95% CI) intervals. ORs were adjusted by gender and age. The skull conformation was considered as a categorical variable and brachycephaly was used as the reference level to which nonbrachycephaly was compared. Association between the presence of MGD and interferometry grades was analyzed by ORs.Probability values of < 0.05 were considered significant.Statistical analysis was performed with R software  and MedCalc software .


Aggressive nutritional strategy, particularly enhancing early provision of energy and protein, has appeared to reduce postnatal growth failure and improve later developmental outcomes. But the amount of macronutrients required remains unclear. The aim of this study was to investigate the impact of protein and energy intakes during the first two weeks after birth on neurodevelopmental outcomes.This retrospective cohort study of very low birth weight infants born between January 2012 and December 2015 was conducted at one tertiary neonatal intensive care unit. The primary outcome was a neurodevelopmental impairment (NDI) at 2 years corrected age defined by a cerebral palsy or a 24 month Ages and Stages Questionnaires score on any of the five domains lower than 2 standard deviation below the mean score. Multivariable logistic regression analysis was used to adjust for perinatal and postnatal confounders.Among 245 (73%) infants discharged home alive, 159 (65%) had follow-up at 2 years. Infants with NDI  were more likely male gender  and experienced more patent ductus arteriosus (PDA) ligation  than control. After adjusting for confounders, first-week protein intake , second-week non-protein energy intake  and PDA ligation  had significant independent association with higher likelihood of NDI at 2 years.Providing nutrition above the optimal level may not be beneficial and may even be harmful. These results confirm the recent recommendation to decrease amino acid intakes published in the latest ESPGHAN guidelines. Over the past decade, improvements in perinatal care have resulted in increased survival rates of very low birth weight  infants, having led to a higher incidence of neurodevelopmental sequelae. Recently, a French population-based study of preterm born at 22 to 34 weeks of gestational age (GA) have shown improvements in survival at 2 years’ corrected age (CA) without neuromotor disabilities between 1997 and 2011 but these children have remained at risk of developmental delay –8. ConseThe aim of the current study was to investigate the impact of protein and energy intakes during the first two weeks after birth on neurodevelopmental outcomes at 2 years’ CA in VLBW infants.This retrospective cohort study was conducted in a 51-bed tertiary level neonatal intensive care unit (NICU) at Rennes’ University Hospital, France. All inborn and outborn VLBW infants admitted within 24 hours of life from January 2012 to December 2015 and who subsequently had neurodevelopmental assessments at 2 years’ CA in the local perinatal follow-up network were eligible. The infants who had severe congenital brain malformations or chromosomal anomalies, those who had hospital stay less than 7 days or died before follow-up and infants who were lost to follow-up were excluded. The ethics committee of the Rennes University Hospital approved the study. Written informed consent was obtained from the parents of each participating infant before their enrollment in the local perinatal follow-up network. All data were fully anonymized.The primary outcome was a neurodevelopmental impairment (NDI) at 2 years’ CA. Parents reported their child’s development using the second edition of the 24 month Ages and Stages Questionnaire (ASQ)  validateSecondary outcomes were anthropometric measurements performed at birth and 2 years’ CA. Weight, length and head circumference (HC) were recorded at birth and at 2 years’ CA. They were converted to standardized Z-scores according to Olsen curves at birth  and to WBaseline clinical data and neonatal comorbidities were retrospectively retrieved from patients' medical records. Nutritional intakes were prospectively collected from our local computerized physician order entry system.The following maternal details were obtained: singleton or multiple pregnancy, preeclampsia, clinical chorioamnionitis, antenatal steroid therapy initiated (at least two injections), and vaginal or cesarean birth. At birth, baseline clinical data included: gestational age, gender, anthropometric measurements  and surfactant replacement therapy.The presence of comorbidities associated with prematurity were collected such as mechanical ventilation duration, bronchopulmonary dysplasia defined as ventilatory or oxygen requirement at 36 weeks’ PMA, PDA confirmed by echocardiography requiring ibuprofen or surgical ligation, NEC defined as a stage 2A or more according to Bell’s modified classification, and retinopathy of prematurity (ROP) defined as a stage 2 or more according to international classification. Cerebral white matter injuries on magnetic resonance imaging at term for survivors or before death were also reported.Nutritional intakes data encompassed parenteral and enteral intakes. The daily protein, total energy, non-protein energy and fluid intakes were summed to obtain the median of daily intakes during the first and the second week after birth.Clinical pathways used in our institution during the study period indicated that parenteral nutrition should be started on the first day of life with 2.4 g/kg/d of AA, 6 g/kg/d of dextrose and 1 g/kg/d of lipids. Subsequent daily increase was 0.5 g/kg/d, 1.2 g/kg/d and 0.5 g/kg/d respectively. Targets for AA intakes were 4 g/kg/d (maximum 4.5 g/kg/d) among infants less than 1000 g at birth or 3.5 g/kg/d (maximum 4 g/kg/d) if birth weight was above 1000g. Target dextrose intake was 15.6 g/kg/d (maximum 18 g/kg/d). Target lipids intake was 3.5 g/kg/d. Early trophic feeding was started within the first day of life, with expressed or pasteurized human milk, for 5 days if the birth weight was less than 1000g or 3 days otherwise. If well tolerated, enteral nutrition was then increased with a daily volume enhancement of 20 to 25 mL/kg/d, PN being replaced gradually. Fortification of maternal or donor human milk was started when enteral intakes reached 80 mL/kg/d. Central line was removed when the infant tolerated 120 mL/kg/d enteral feeding.Patient’s characteristics are reported as numbers (with percentages) for categorical variables and as medians (with interquartile ranges) for continuous variables. Categorical variables were compared with the Chi square or Fisher’s exact test, and continuous variables were compared with a Mann-Whitney U test, as appropriate. To identify independent predictors of NDI at 2 years’ CA, multivariable logistic regression analysis were performed. In models building, nutritional intakes including protein, non-protein energy and fluid intakes were associated with all clinically relevant variables as GA, birth weight, and neonatal comorbidities. Because birth weight and birth weight Z-score were highly correlated, only birth weight was included in the multivariable models. Optimization for variable selection with stepwise method using the Akaike's Information Criterion (AIC) was applied in Model I. Because GA and birth weight are well known as independent factors of neurodevelopmental outcome and were excluded by variable selection method, Model II kept GA and Model I factors, while Model III kept GA, birth weight and Model I factors. All analyses were performed using the R  software. Statistical relevance was considered at P value <0.05.Out of a total of 336 VLBW infants assessed, 245 (73%) were discharged home alive and enrolled in the local perinatal follow-up network . Among tThe median GA was 28.4 weeks (26.9 to 29.6 weeks), the median birth weight was 1050 grams (865 to 1240 grams), 55.1% were male, and 13.1% were considered SGA according to their Z-score. The mortality rate during hospital stay was 14%. There was no statistically significant difference between included and excluded infants for the majority of the reviewed variables, including nutrient intakes. There was a longer mechanical ventilation duration (2 days (0 to 12 days) versus 1 day (0 to 6 days), P = 0.006) for excluded compared to included infants.The characteristics and morbidities of the surviving babies who were assessed at 2 years’ CA were summarized in Protein intake increased from 3.45 g/kg per day (3.06 to 3.80) in week 1 to 3.89 g/kg per day (3.53 to 4.06) in week 2. Non-protein energy intake increased from 59 kcal/kg per day (51 to 68) in week 1 to 103 kcal/kg per day (83 to 120) in week 2. No differences were observed between the two groups in the nutritional intakes on univariate analysis.Multivariable logistic regression analysis were performed to assess the independent contribution of protein and non-protein energy intakes to NDI at 2 years’ CA while controlling for birth weight, GA, gender, fluid intakes and comorbidities associated with neurodevelopmental outcomes (NEC and PDA ligation). In each of our models shown in From birth to 2 years’ CA, growth was similar between groups, except the HC delta Z-score was significantly lower (P = 0.03) in NDI group as compared to control .The objective of postnatal nutrition in VLBW infants is to achieve a postnatal growth that is similar to fetal growth and coupled with adequate long-term developmental outcomes. The correlation between early provision of protein and later outcomes has been widely documented, while the optimal maximum amount of protein still has to be determined.In this retrospective cohort study of 245 VLBW survivors, a higher first-week protein intake and a higher second-week non-protein energy intake were associated with higher odds of NDI at 2 years’ CA. Important comorbidities as NEC and PDA ligation were also associated with NDI. These findings contrast with multiple large cohort studies over the past decade that have strongly associated an increase in early protein and energy intake with an improvement of motor and cognitive scores in childhood.The strengths of this study include the primary outcome assessment method and the adherence to nutritional guidelines recommended over the study period. ASQ was used to assess development delay since is a reliable parent-completed development screening tool which previous studies have indicated high test-retest reliability, inter-observer reliability, and internal consistency . ASQ hasThe observed negative association between NDI and higher AA intakes supports the recently updated current guidelines that recommend AA intake between 2.5 g/kg per day and 3.5 g/kg per day . RegardiRelatively few studies have investigated the direct effects of neonatal nutritional intake on later neurodevelopment. Stephens et al.  were theIn contrast to above findings, Cester et al.  did not Overall these studies, evidence appeared to be insufficient to show an effect from increased early protein intake on neurodevelopment at 18 or 24 months’ CA, as confirm the most recent Cochrane systematic review . It is oStrong observed associations between neonatal comorbidities, as NEC and PDA ligation, corroborated previous observational studies ,22 who fIn addition to the limitations already described, this investigation has the potential bias inherent in observational uncontrolled study. Outcome data reported here were collected retrospectively and some data, such as the primary outcome, were provided by the parents. Even if nutrient intakes were prospectively collected from our local computerized physician order entry system, it is often reported in nutrition studies that actual intake in 24 hours period can be different from prescription.Among a single-center cohort of VLBW infants over a three-year period, a higher early protein intake and non-protein energy intake were associated with higher odds of neurodevelopmental impairment at 2 years’ corrected age. This highlights the contradictory hypothesis that greater protein intakes in early life improve neurodevelopmental outcome like previous studies. However, these results confirm the recent recommendation to decrease amino acid intakes published in the latest ESPGHAN guidelines. When the standard nutrition is below optimal, providing more nutrition may be beneficial. Nevertheless, providing nutrition above the optimal level may not be beneficial and may even be harmful. This study also confirms the strong relationship from neonatal comorbidities to early providing nutrition with an influence on later neurodevelopmental outcome. Further studies are necessary to improve our knowledge and nutritional practices in VLBW infants.S1 Dataset(XLS)Click here for additional data file.


This paper aims at evaluating refractive outcome and complication profile of sutureless, glueless, flapless, intrascleral fixation of intraocular lens (SFIOL) in pediatric population.  This retrospective study included patients ≤18 years of age who underwent SFIOL for ectopia lentis. Details obtained included preoperative uncorrected visual acuity (UCVA), cycloplegic refraction, and best-corrected visual acuity (BCVA); intraoperative complications; and postoperative UCVA, cycloplegic refraction, and BCVA and complications. p < 0.001). Median pre- and postoperative BCVA was logMAR 0.24 (Snellen 20/34) and logMAR 0.18 (Snellen 20/30), respectively. UCVA ≥20/60 was attained in 90% of eyes. BCVA ≥20/30 was attained in 85.0% of eyes. Most common early postoperative complications were hyphaema (10%), transient vitreous hemorrhage (2.5%), and ocular hypotony (2.5%). None of these developed any long-term sequelae. Only one case of subluxation of IOL was seen. No case of late endophthalmitis or retinal detachment was seen.  Median pre- and postoperative UCVA was logMAR 1.78 (Snellen 20/1200) and logMAR 0.30 (Snellen 20/40), respectively, ( Since refractive error induced is minimal, the procedure is suitable for IOL implantation in children, who are noncompliant with spectacles. The complication profile is similar to that reported in adults. Optical rehabilitation of childhood aphakia, in the presence of an unstable capsule-zonule complex, is one of the most challenging tasks faced by the ophthalmologists. Numerous techniques like anterior chamber IOL (ACIOL), iris-fixated IOL (IFIOL), and scleral fixated IOL (SFIOL) have been developed for such eyes –8. Long-By the virtue of its near physiological anatomical location, such complications are rare in the case of SFIOL , 7, 9–13The results of sutureless SFIOL have been encouraging in adult eyes –23. HoweThis was a retrospective study conducted at Aravind Eye Hospital, Madurai, India. Case records of patients under 18 years of age who underwent SFIOL for congenital ectopia lentis from January 2012 to December 2016 were analyzed.Preoperative evaluation included uncorrected visual acuity (UCVA), best-corrected visual acuity (BCVA), cycloplegic refraction, intraocular pressure, and a comprehensive anterior and posterior segment evaluation to find any pathological cause of decreased BCVA. Any intraoperative and postoperative complication(s), along with their management, were noted. At each follow-up, the examination included UCVA, BCVA, cycloplegic refraction, intraocular pressure, and a comprehensive anterior and posterior segment evaluation to see for any postoperative complications. The intra- and postoperative complication(s) were managed as per the universally accepted protocols. Causes of poor postoperative BCVA were discerned in all cases.All surgeries were done under general anesthesia by a single surgeon (Dr. NB). Superior 270-degree conjunctival peritomy is followed by light scleral cautery to achieve adequate hemostasis. Two partial-thickness scleral pockets are then made, with the help of 25-gauge (G) microvitreoretinal (MVR) trocar blade, for permanent incarceration of the IOL haptics. These pockets are created 180-degree apart, parallel to the limbus, and 1.5–2 mm away from the limbus. A scleral tunnel is made superiorly with the help of a crescent blade. Next, three standard 25G pars plana vitrectomy (PPV) sclerostomy ports are constructed at 2, 10, and 4′o clock. Then, two ciliary sulcus-based sclerotomies are created close to the scleral pockets for externalization of IOL haptics, using a 24G needle. First, lensectomy and anterior vitrectomy are performed.Entry into the anterior chamber is then made through the scleral tunnel with the help of a keratome blade. A standard three-piece nonfoldable IOL  is implanted. With the tailing haptic fixated at the scleral incision, the leading haptic is grasped at the tip with a 25-gauge end-gripping forceps  and pulled out through the sclerotomy. The haptic is then tucked into the scleral pocket. Then, the tailing haptic is inserted into the posterior chamber. The IOL that does not fall as one haptic is already incarcerated in the scleral pocket. The second haptic is visualized with the help of a binocular indirect ophthalmomicroscope (BIOM), grasped, and pulled out through the second sclerotomy. The tailing haptic is also tucked into the limbus-parallel scleral pocket. Finally, centralization of the IOL is done by adjusting the amount of haptic in each pocket. The vitrectomy ports, the sclera tunnel, and the conjunctiva are finally sutured. All the sites were inspected for wound leakage.In case IOL subluxation is seen in the postoperative period, it can be centralized easily by performing a localized peritomy over the 2 scleral pockets and adjusting the length of haptic tucked in the scleral pocket.t-test/Mann–Whitney U test. Change in variables after a procedure was done with the help of the paired t-test. P value less than 0.05 was considered to be statistically significant.Statistical analysis was performed with Stata statistical software, version 11.1 . Continuous variables were expressed as mean (±standard deviation), and categorical variables were expressed as percentages. Any association between categorical data was seen with help of the chi-square/Fisher exact test, while difference in continuous data between 2 groups was seen with help of the Student n = 36/40) attained UCVA ≥20/60, and 67.5% (n = 27/40) attained UCVA ≥20/40. Improvement in BCVA by at least 2 Snellen line was achieved in 47.5% (n = 19/40) of eyes. BCVA ≥20/30 was attained in 34 eyes (85.0%)  with mean age of 13.4 ± 3.7 years .  (85.0%) .n = 13/40) of eyes. Average spherical equivalent (SE) was 0.26 ± 0.97 DS, while average cylindrical correction was 0.68 ± 0.72 DC. SE was ≤1 DS in 88.2% of eyes (n = 33/40), while cylindrical correction was ≤1 DC in 72.5% of eyes (n = 29/40). While 47.5% (n = 19/40) of eyes had no astigmatism, only 12.5% (n = 5/40) of eyes had astigmatism ≥1.5 DC.Postoperative emmetropia was attained in 32.5% , transient vitreous hemorrhage , and ocular hypotony   . HoweverThe median follow-up of the patients was 12 months . The IOL was well centered in all the eyes at the last follow-up and required no active intervention .Scleral fixation of IOL in the posterior chamber is the current procedure of choice for surgical rehabilitation of aphakia in the absence of adequate capsular support –8. HowevThe purpose of visual rehabilitation by IOL implantation is to achieve minimum refractive error. The average astigmatism induced in our study was 0.68 ± 0.77 DC, which is a small value. Nearly half of the eyes were astigmatically neutral while around three-fourth of the eyes had astigmatism less than 1 DC. Around 90% of eyes attained UCVA ≥20/60 and had spherical equivalent less than 1 DS. Since refractive error induced in our study was minimal, the procedure is suitable for implantation of IOL in children who tend to be noncompliant with their spectacles. With good uncorrected vision, chances of patients developing amblyopia in the postoperative period reduce.The technique used in this study for SFIOL was originally described by Gabor and Pavlidis  has multThe postoperative complications associated with the sutureless technique were also less than the conventional technique. No apparent IOL tilt was noticed in any of the patients in our study patients as the haptics were placed in the intrascleral tunnels without any traction. None of the eyes had severe inflammation in the form of fibrin since minimum intraocular manipulation was done during IOL fixation. Reduced postoperative inflammation made the visual rehabilitation faster. Since the tips of the haptics were buried intrasclerally, conjunctival erosion was not seen in any of the eyes. This also reduced the chances of late-onset endophthalmitis as suture erosion can serve as a direct communication channel between the outside environment and the eye .This technique had several advantages over the glued sutureless SFIOL also. Firstly, the scleral tunnels have been demonstrated, using anterior segment ultrasound, to achieve a leak-free closure even without the application of glue . AvoidinThis study is the largest series evaluating the safety and efficacy of sutureless, glueless, intrascleral fixation in the pediatric population. The technique has multiple advantages including reduction in cost of surgery and surgical time, as well as intra and postoperative complications. Also, resurgery is relatively easier. Easy centration of IOL can allow the use of multifocal and toric IOLs. The disadvantages of the technique include its learning curve and requirement for specialized instruments. Limitations of the study include its retrospective nature and short duration of follow-up.


P = 0.013], whereas there was no significant link between CKD and spontaneous HCV clearance , HBV infection , or HBV/HCV co-infection . Notably, after anti-HCV therapy, the serum creatinine concentration was significantly decreased  from the pretreatment level , both in patients who showed an end of treatment virological response (ETVR) and those who did not (P < 0.001). Also, in both the ETVR and non-ETVR groups, the percentages of patients with an estimated glomerular filtration rate (eGFR) ≥90 ml/min/1.73 m2 increased significantly (P < 0.001), whereas the percentages of those with an eGFR <60 ml/min/1.73 m2 significantly decreased (P < 0.001). In conclusion, persistent HCV infection was independently associated with CKD, and antiviral treatment with IFN plus RBV can improve renal function and reverse CKD in HCV-infected patients.Hepatitis C virus (HCV) infection greatly increases the risk of nephropathy. In this observational study, we aimed to explore the relationship between viral hepatitis infection and chronic kidney disease (CKD), identify risk factors, and determine the effect of antiviral treatment on CKD in Chinese patients with chronic HCV infection. A total of 2,435 study subjects were enrolled and divided into four groups: the HCV infection, HBV infection, HBV and HCV co-infection, and uninfected control groups. Of these, 207 patients with chronic hepatitis C (CHC) were given standard dual therapy [subcutaneous injection of recombinant interferon (IFN)-α2b and oral ribavirin (RBV)] for 48 weeks. We found that the prevalence of CKD gradually increased with age in all groups and was significantly increased in patients 60 years or older. Multivariate logistic regression analyses showed that persistent HCV infection was significantly associated with CKD [odds ratio (OR), 1.33; 95% confidence interval (CI), 1.06–1.66;  In the United States, Europe, Australia, and Japan, the incidence of CKD ranges from 6–11%3. It has been demonstrated that CKD is more prevalent among patients infected with hepatitis C virus (HCV) than among the general population4. In fact, chronic HCV infection can raise the risk of developing CKD by 23%5. Two large cohort analyses including more than 150,000 US veterans with chronic HCV infection suggested that this population has a nearly 2-fold greater risk of developing end-stage renal disease (ESRD)7. From a number of recent independent studies, an updated meta-analysis demonstrated a significant increase in the risk of CKD among HCV-infected patients in comparison with uninfected individuals9.Chronic kidney disease (CKD), which is characterized primarily by loss of renal function over time, remains a serious health problem worldwide. A recent cross-sectional survey showed that the overall prevalence of CKD in China is as high as 10.8%, and approximately 120 million individuals suffer from CKD nationwide10. In a recent study in a US population, Park and colleagues assessed the risk of CKD development among those with HCV infection as well as the effects of various antiviral treatments on the incidence of CKD in HCV-infected patients11. Notably, effective HCV treatment significantly reduced the prevalence of CKD in patients with chronic hepatitis C (CHC)11. Similar findings were also demonstrated in several prospective studies, indicating that anti-HCV treatment reduces the risk of developing CKD13. However, whether antiviral treatment in hepatitis can also support an improvement in renal function and reversal of CKD development requires further assessment. A meta-analysis of 11 clinical trials conducted in Western countries and Japan showed that IFN-α–based antiviral therapy led to a significant decrease in proteinuria and stabilization of serum creatinine levels with greater improvement in protein excretion in CHC patients14. The heterogeneity of the demographic data, nature and stage of kidney disease, as well as the severity of liver injury and extrahepatic manifestations may lead to different results, and it remains unknown whether IFN-based dual therapy with IFN plus RBV, the main components of HCV treatment in mainland China due to the high cost of direct-acting antiviral agents (DAAs), can improve renal function or reverse CKD in HCV-infected patients in a Chinese population.The presence of HCV also is associated with rapid deterioration of renal function, suggesting that it is necessary to develop treatments to prevent HCV-induced CKD15.Unlike HCV infection, whether HBV infection can increase the risk of CKD development and promote CKD progression has not been appropriately investigated. A meta-analysis found no correlation between HBV sero-positive status and the prevalence of CKD or proteinuria in a cross-sectional survey17. The results gained through this study may provide critical information that will assist in the development of early intervention measures for preventing kidney damage caused by pathogenic hepatic viruses.In the present study, we aimed to investigate the association between HBV infection, HCV infection, or HBV/HCV co-infection and CKD as well as to analyze the effect of anti-HCV therapy with IFN-based dual therapy on CKD recovery. Fuyu is an endemic area for HCV infection and provides an excellent setting for this type of study, as it is suitable for examining the relationship of IFN-based therapy for HCV with CKD due to the high prevalence of both HCV infection and anti-viral treatment9/L], albumin [46.9 (44.8–49.9) g/L], triglycerides [1.7 (1.1–2.8) mmol/L], and cholesterol [5.0 (4.4–5.8) mmol/L] compared with the HCV infection, HBV infection, and HBV/HCV co-infection groups.A total of 2,435 subjects completed the survey and examination in this study. The mean age was 50.3 ± 10.3 years, and 52.5% of patients were women. The study subjects were divided into four groups based on the types of viral hepatitis, according to the following distribution: HCV infection (38.3%), HBV infection (4.8%), HBV/HCV co-infection (2.9%), and uninfected controls (54.0%). The demographic and clinical characteristics of the study subjects in the four groups are summarized in Table P = 0.013), but not spontaneous HCV clearance , HBV infection , or HBV/HCV co-infection . Other independent risk factors significantly associated with CKD included age, female gender, diabetes mellitus, and levels of TBIL, triglycerides, and cholesterol , hemoglobin, albumin, total bilirubin (TBIL), triglycerides, and cholesterol levels were significantly correlated with CKD, and thus, these variables were selected for subsequent multivariable logistic regression analysis. As shown in Table P < 0.001). Additionally, the eGFR was improved after the end of the antiviral treatment; the proportion of patients with an eGFR ≥90 ml/min/1.73 m2 was significantly increased (P < 0.001), whereas that of individuals with an eGFR <60 ml/min/1.73 m2 was decreased significantly in both the ETVR and non-ETVR groups (P < 0.001). Notably, the antiviral treatment led to a significant reduction in the prevalence of CKD (P < 0.001), whereas it did not alter the incidence of albuminuria. We also compared the changes in serum urea nitrogen, serum creatinine, and eGFR before and after antiviral therapy in the ETVR versus non-ETVR groups, and no significant differences between the groups were found. As shown in Fig. P = 0.662); the serum creatinine decreased by 17.10 ± 15.20 mmol/L in the ETVR group and by 18.28 ± 17.37 mmol/L in the non-ETVR group (P = 0.601); and the eGFR increased by 16.45 ± 20.36 mmol/L in the ETVR group and by 16.58 ± 20.08 mmol/L in the non-ETVR group (P = 0.690).Overall, 207 CHC patients received standard dual therapy  for 48 weeks. Upon completion of anti-HCV therapy, 115 (55.6%) patients showed an end of treatment virological response (ETVR), whereas 92 (44.4%) patients did not exhibit an ETVR in our study (not-ETVR). In the total cohort, significant changes in plasma creatinine and estimated glomerular filtration rate (eGFR) were seen after the end of the anti-viral therapy in both the ETVR and non-ETVR groups Table . Further1. This may be due to an inherent bias associated with subject selection, as the mean age of all participants in this study was 47.6 years. Therefore, an older age may have influenced the high rate of CKD found in this study. (2) The prevalence of CKD in the HBV infection group was the lowest, which may be associated with the younger age distribution and lower prevalence of diabetes (5.1%). This finding was consistent with a previous study in which the HBV infection group had a lower prevalence of CKD (14.3%) than an HCV infection group (22.1%) and HBV/HCV co-infection group (17.2%)8. (3) The HCV infection group had the highest prevalence of diabetes (10.8%), which is consistent with several studies, showing that the prevalence of diabetes mellitus was significantly greater in patients with HCV infection20. Although the underlying mechanisms need to be elucidated, it appears that dysregulation of cytokines, intracellular oxidative stress, suppression of insulin downstream signaling, modulation of incretins, and pancreatic β-cell dysfunction are contributing factors23.In the present study, multivariate logistic regression analysis revealed that age >60 years, female gender, diabetes, lower TBIL, higher triglycerides, and higher total cholesterol were significant independent risk factors associated with the development of CKD, and these findings were consistent with other studies25. In this study, we also found that higher levels of TBIL were significantly associated with CKD . Mashitani and colleagues found that the serum bilirubin levels were associated with diabetic nephropathy progression in type 2 diabetes patients26. As bilirubin is a normal metabolite of human hemoglobin, and a number of recent studies have shown that bilirubin has a dose-dependent antioxidant effect, bilirubin production potentially may act as a compensatory defense mechanism when renal function is mildly reduced27.In this study, we investigated the prevalence of CKD in mainland China, a high endemic area of HCV infection, for the first time and determined the risk factors associated with CKD. The major novel findings are summarized as follows. (1) The prevalence of CKD in uninfected controls was 27.7%, which was much higher than that previously reported for the general population of rural areas in northern regions (16.9%)28. Another Taiwanese study found that HCV infection was significantly related to the high prevalence and severity of CKD27. Furthermore, the incidence of ESRD was reported to be 2.14-fold greater in patients with chronic HCV infection than in those without HCV infection29. As CKD is highly prevalent in hepatitis C patients, all of the above findings indicate that HCV infection is an independent risk factor for CKD. Given the aforementioned potential renal involvement, annual screening for CKD in patients with CHC is highly recommended. Our results demonstrate that HCV/HBV co-infection was not associated with CKD, which may due to replication inhibition of HBV and HCV in these patients30. This conjecture is also in good agreement with the possibility that HCV-related kidney diseases may result from HCV directly and immune-mediated kidney damage31.After having adjusted for gender, age, and the other potential confounders, persistent HCV infection was identified as an independent risk factor for CKD in our study. A study of male veterans in the US demonstrated that HCV infection was significantly associated with membrano proliferative glomerulo nephritis (MPGN)14. However, the repair of kidney damage following antiviral therapy was not linked to HCV RNA clearance. Compared with the non-ETVR group, significant decreases in serum creatinine and serum urea nitrogen along with an improvement in eGFR were not observed in the ETVR group in our study. In fact, when we divided the patients into ETVR and non-ETVR groups, the number of cases (115 patients with ETVR and 92 patients without ETVR achieved) in our study was too small for statistical analysis. Therefore, a limitation is the small number of study subjects making it difficult to perform subgroup analysis in our treatment cohort.In the anti-viral treatment cohort, we found that the antiviral therapy consisting of IFNα-2b combined with RBV decreased the serum creatinine level and improved both the eGFR and severity of CKD, which is in agreement with other studies in western countries and JapanThis study has several other limitations. First, the dual therapy with pegylated (PEG)-IFN plus RBV was previously used to treat chronic HCV infection. However, a number of limitations have been well recognized, which include low sustained virologic response (SVR) rates (approximately 50% of SVRs for genotype I), numerous adverse effects associated with the dual therapy, and the requirement of a long treatment duration of the dual therapy (24 or 48 weeks). The treatment of HCV infection has been changing rapidly, and newly developed DAAs have shown greater clinical efficacy than the dual therapy in patients with chronic HCV infection despite their high cost. Therefore, the effects of DAAs on renal function need to be studied in the future. Second, we enrolled 117 patients with HBV infection and 70 individuals with HBV/HCV co-infection, and thus, the sample sizes of these groups were relatively small for evaluating the prevalence of CKD. Third, the status of CKD was determined at the baseline cross-sectional screening survey, while data on the duration of renal damage and decline of GFR in the study subjects were not available in the current study. Furthermore, some other risk factors associated with the development of CKD, such as cigarette smoking, cirrhosis, hypertension, angiotensin-converting enzyme inhibitor (ACEi) use, angiotensin receptor blocker (ARB) use, and cardiovascular diseases, were not taken into consideration in our study. Therefore, further investigation is underway in our center to determine if these parameters have any other confounding effects.In conclusion, this study has provided important scientific evidence that persistent HCV infection is strongly associated with CKD. The findings have also demonstrated that anti-viral therapy in patients with hepatitis C can improve or restore kidney function in our study.This observational study was conducted in Fuyu city , an area with a prevalence of HCV infection as high as 40%. A total of 3,219 participants completed the cross-sectional survey and physical examination in September 2012 at the First Hospital of Jilin University. After excluding 784 participants with no serum creatinine measurement or urine protein results, the remaining 2,435 individuals were included in the final analysis. These patients included 932 with HCV infection, 117 with HBV infection, 70 with HBV/HCV coinfection, and 1,316 uninfected healthy controls. HCV infection was defined by positivity for HCV antibody, HBV infection by positivity for HBsAg, and co-infection with HBV and HCV by positivity for HBsAg and HCV antibody. Uninfected healthy controls had neither HBV infection nor HCV infection. The HCV infection group was further divided into two sub-groups: 110 patients with spontaneously cleared HCV (positive for HCV antibody in the absence of detectable HCV-RNA) and 822 patients with HCV persistence (anti-HCV positive/HCV-RNA positive).Moreover, 207 CHC patients from the above cohort were enrolled in a subsequent cohort of patients who receive anti-HCV treatment consisting of standard dual therapy with subcutaneous injection of recombinant IFN-α2b  in combination with oral RBV  for 48 weeks. During the treatment period, the 207 CHC patients were scheduled for assessment of both the efficacy and safety of the dual therapy at different time points, including baseline and 4, 12, 24, and 48 weeks on the standard dual therapy.Written informed consent was obtained from every participant in this study, and the study protocol was reviewed and approved by the Ethics Committee of the First Hospital of Jilin University.Blood samples were taken in the morning after more than 8 h of fasting, and the laboratory tests for liver function, renal function, blood glucose, fasting insulin, and C peptide were performed using a Synchron LX®20 autoanalyser . At the Clinical Laboratory, the First Hospital of Jilin University. Levels of HCV RNA were examined by quantitative real-time polymerase chain reaction (qRT-PCR) using the COBAS AmpliPrep/COBAS TaqMan HCV Test following the manufacturer’s instructions  with the limit of detectability as low as 15 IU/ml. Levels of anti-HCV and HBsAg were determined on an Abbott ARCHITECT i2000SR. HCV genotyping was conducted using multicolor fluorescence PCR with an HCV RNA genotype kit .33. CKD stage 1 was defined as eGFR ≥ 90 mL/min/1.73 m2 in combination with albuminuria; CKD stage 2 was defined as eGFR of 60–89 mL/min/1.73 m2 with the presence of albuminuria; and CKD stage 3 or above was defined as eGFR < 60 ml/min/1.73 m2. The diagnosis and stages of CKD were assigned at the baseline cross-sectional screening survey in all study participants. Also the diagnosis and stages of CKD were assigned at baseline and at 4, 12, 24, and 48 weeks of the standard dual therapy given to the 207 CHC patients in the anti-HCV treatment cohort.The following Cockcroft-Gault formula was used to calculate the eGFR: eGFR = [(140-age) × weight (kg)]/[0.818 × SCr (μmol/L)] × 0.85 , in which SCr represents serum creatinine. The stages of CKD were determined by the patient’s level of eGFR and the status of albuminuria according to the criteria of the Kidney Disease Outcomes Quality Initiative (K/DOQI)2 test. A P-value < 0.05 was considered statistically significant.Statistical analysis was conducted using SPSS software package 18.0 . Continuous variables are presented as means ± standard deviation (SD) or median (inter quartile), and categorical variables are expressed as frequency (%). Continuous variables were compared among the four groups using analysis of variance (ANOVA) tests, and comparisons between any two groups were performed using the least significant difference (LSD) test. Categorical variables were analyzed using a chi-squared test or the Fisher’s exact test. Univariate and multivariate logistic binary regression analyses were used to identify potential confounding variables. For the analysis of data before and after anti-HCV therapy, we used the Wilcoxon signed-rank test, the McNemar test, or the χ


Contrast-enhanced computed tomography (CECT) imaging is commonly used to assess pancreatic adenocarcinoma (PAC). However, the value of semiquantitative and quantitative assessments of CECT parameters used to predict survival in PAC remains unknown. This study aims to investigate the prognostic role of pretreatment CECT imaging in patients with locally advanced pancreatic adenocarcinoma (LAPAC).  From June 2013 to May 2017, eighty-six newly diagnosed patients with pathologically and radiologically confirmed LAPAC were retrospectively recruited. All patients were evaluated by CECT and experienced gemcitabine-based chemotherapy. The relationship between overall survival (OS) and clinical factors including age, sex, serum carbohydrate antigen 19-9 value, and CECT findings  was determined using Cox proportional hazard regression models, and a nomogram was constructed for the prediction of 1- and 1.5-year survival rates of patients with LAPAC. p < 0.001). After multivariate Cox regression, a nomogram was established based on a new model containing the predictive variables of high Ca19-9 level, higher clinical stages, larger tumour volume, the presence of peripancreatic involvement, and liver metastases. The model displayed good accuracy in predicting OS with a C-index of 0.614. The calibration plots also showed a good discrimination and calibration of the nomogram between the predicted and observed survival probabilities.  On univariate analysis, patients who had a tumour enhanced rate (TER) less than 80.465% and those who had a TER ≥ 80.465% are with a 3.587-fold increase in OS ( Our results showed that TER can be used to predict survival in LAPAC, and we developed a nomogram for determining the prognosis of patients with LAPAC. However, the purposed nomogram still requires external data verification in future applications. Pancreatic adenocarcinoma (PAC) is one of the most lethal malignancies and is estimated to cause more than 45,750 deaths in the United States in 2019 . As the α (HIF-1α), an endogenous marker of hypoxia, is significantly associated with poor prognosis in PAC [α expression. Although a small amount of pathological tissue can be obtained by biopsy, the expression of HIF-1α cannot accurately reflect the hypoxic state of the tumour due to the heterogeneity of the tumour. Studies have shown that HIF-1α is negatively correlated with microvessel density (MVD) [For malignant tumour, traditional prognostic factors are mainly clinical-pathological features such as performance status, histological grade, serum biomarkers, systemic inflammation and nutritional status, and TNM staging, which are frequently evaluated by contrast-enhanced computed tomography (CECT) and/or magnetic resonance (MR) imaging , 6. In Ps in PAC . Howeverty (MVD) , 10. In ty (MVD) . Therefoty (MVD) , this prWe retrospectively reviewed the medical records of 907 patients with pancreatic lesion admitted in our institute from 1 June 2013 to 31 May 2017. Among this population, the selection criteria for data extraction were as follows: (1) patients who had pathologically proven pancreatic adenocarcinoma; (2) adequate quality of the abdominal contrast-enhanced computed tomography (CT) scan; (3) no history of malignancies of other origin; (4) the availability of laboratory examinations; (5) follow-up for more than three months after the initial diagnosis. The exclusion criteria included patients with neuroendocrine carcinoma of the pancreas, ampulla Vater cancer, or distal common bile duct cancer and patients with a previous history of treatment for PAC. We identified a total of 188 patients and extracted related medical records and data. We further excluded 102 patients among the identified patients due to either the absence of pretreatment CECT scans performed in our institute or absence of multiphase contrast scan. Finally, 86 patients with LAPAC, who all experienced gemcitabine-based chemotherapy, were screened out for analysis. Inclusion details are shown in 2 was delineated, respectively, in three different solid slices for each tumour and peritumoural pancreatic tissue, and then, three CT values were achieved to compute the mean CT value. TER was computed as equation , obtained at 120 kV and 200 mA with collimation of 1 mm and 3 mm reconstruction thickness. Plain and multiphase contrast images were obtained following general clinical settings. Contrast images were acquired in the arterial phase and the venous phase. The delay time for the contrast-enhanced CT images was 35–40 seconds for the arterial phase and 65–70 seconds for the venous phase after the intravenous injection of 80–100 mL Iohexol  at a rate of 3 mL/s. CECT parameters including tumour location, tumour volume (TV), peripancreatic involvement (PPI), blood vessel involvement (BVI), tumour enhanced rate (TER), peritumoural pancreatic parenchyma enhanced rate (PER), and the presence of liver metastasis were evaluated by two radiologists independently. The TV was calculated based on an imaging reconstruction tool (GE AW SERVER 2.0). The contrast-enhanced CT value of tumour and nontumoural pancreatic tissue was measured at the venous phase. The region of interest (ROI) was defined in the solid portion of the mass and pancreatic parenchyma and bypassed peripheral fat, artefacts, necrosis, cystic necrosis/cystic components, and blood vessels and pancreatic ducts. ROI with an area of approximately 50 mmFigures U test. The categorical variables were analysed by the chi-squared test or Student's t-test, where appropriate. Based on the 75th percentile of TER, patients with LAPAC were divided into a relatively abundant blood supply group (TER ≥ 80.465%) and a relatively poor blood supply group (TER < 80.465%). A receiver operating characteristic (ROC) curve was calculated to determine the optimal cutoff value for the TV based on the six-month survival rate. Univariate prognostic factor analysis was performed using the Cox proportional hazard model to estimate the hazard ratio (HR) and 95% confidence interval (CI). Factors associated with survival in the univariate analysis entered into a final multivariate survival analysis with a stepwise Cox regression model for identifying independent prognostic factors. Based on multivariate analyses, nomograms were generated to provide visualized risk prediction using the survival. Discrimination between survival probability and actual observations was evaluated using the C-index. Statistical analyses were performed using SPSS 21.0  or the package of rms in R software version 2.15.2 . Values of p less than 0.05 were considered statistically significant, and all tests were two-sided.Continuous variables were analysed nonparametrically using the Mann–Whitney 3 . Peripancreatic invasion (PPI) was identified in 6 patients (7.0%). The median TER was 53.21% . The median PER was 132.30% . The median overall survival was 6.05 months .Patient baseline characteristics and CT imaging parameters of the 86 treatment naïve patients are shown in r = −0.470, p < 0.001). The chi-squared test showed a statistically significant difference in staging of patients with different TERs (p < 0.001). The more advanced tumour clinical stage was mainly distributed in the TER < 80.465 group. These results suggest that TER is associated with the clinical stages in pancreatic cancer.We further evaluated the correlation between TER and the clinical stages of pancreatic cancer. TER is different among clinical stages, and Pearson correlation analysis suggested that clinical stages were negatively correlated with TER (p < 0.001), presence of PPI (p < 0.05), presence of liver metastases (p < 0.001), TER lower than 80.465% (p < 0.001), TV higher than 24,062.25 (mm3) (p < 0.001), and Ca19-9 ≥1000 (IU/mL) (p < 0.001) significantly predict a poor prognosis, as shown in p value <0.001 and <0.005, respectively), as shown in p < 0.001) is a significant factor for favourable prognoses. TER ≥ 80.465% group enjoys survival benefit (median OS = 13.80 ± 5.71 months) over TER < 80.465% group (median OS = 5.60 ± 3.36 months) (p < 0.001). TER significantly predicts OS in both univariate and multivariate analyses (p < 0.001). The predicting model for poor prognosis in patients with LAPAC is as follows:Data on sex, age, BMI, a family history of malignancies, tumour location, clinical stages, serum Ca19-9, the presence of pancreatic duct dilation (PDD), bile duct dilation (BDD), liver metastasis, TV, and TER were collected. Univariate analysis indicates that more advanced clinical stages  [In our study, a low TER was significantly associated with short survival, which is consistent with the study of Wang et al. . Another< 0.001) . Low MVD< 0.001) . In addi< 0.001) , 14. Wan< 0.001) . Furtherα of the human pancreatic cancer cell can reverse the chemotherapy drug resistance [Recent studies have also reported that hypoxic microenvironment plays a critical role in the acquired chemoresistance of pancreatic cancer cells , 16. Undsistance . TherefoIn contrast, another study showed tumour vascularity assessed by contrast-enhanced ultrasonography before treatment did not correlate with progression-free survival nor with overall survival . The disIn our study, univariate Cox regression analysis found that the presence of PPI, Ca19-9, TER, TV, clinical stages, and the presence of liver metastasis are statistically significant prognostic factors. However, TV and the presence of liver metastasis did not retain prognostic roles in further multivariate Cox regression. These may result from our interpretation that clinical staging is based on TNM staging, which is a combination of tumour size, the presence of local invasion, local lymph node status, and distant metastasis. There is a strong correlation between TV and liver metastasis and clinical stages. Therefore, TV and the presence of liver metastasis are not independent prognostic factors. This may provide an explanation to the difference in statistically significant prognostic factors between univariate and multivariate analyses.A nomogram can integrate several risk factors and provides a more individualized prediction of prognosis and risk assessment for each patient. Compared with the conventional staging system, a nomogram model increased prediction accuracy in some neoplasms such as urothelial carcinoma, intrahepatic cholangiocarcinoma, and breast cancer –22. Our However, in the present study, as with most retrospective studies, our study has a limitation. Further, the absolute number of total subjects studied is relatively small in this study, and the nomogram was constructed without a division for a validation cohort. We, therefore, analysed the C-index of the constructed nomogram and the calibration curve fit at the different time periods of prediction well between nomogram prediction and the actual observation. Moreover, our measurement of TER reflected a relative change of CT value in plain CT and enhanced venous phase instead of an absolute perfusion parameter. This problem can be solved by drawing a time-contrast dose curve by repeated sequential scans of each tumour slice followed by calculating the area under the curve. However, further studies on providing an absolute tumour perfusion parameter may be limited as obtaining this parameter will require a high radiation dose by scanning each one of the CT slices. Dynamic contrasted enhancement MR will address this problem and can provide more perfusion parameters so that further research studies can begin with this respect. Thus, the findings of this study must be interpreted with caution.Taken together, our results indicate that tumour enhanced rate on CECT demonstrated prognostic significance in univariate analysis and maintained its significant roles in multivariable analysis. Our results suggest that pretreatment CECT scans can be used to predict survival in advance pancreatic cancer.


Recurrent CT imaging is believed to significantly increase lifetime malignancy risk. We previously reported that high acuity, admitted trauma patients who received a whole-body CT in the emergency department (ED) had a history of prior CT imaging in 14% of cases. The primary objective of this study was to determine the CT imaging history for trauma patients who received a whole-body CT but were ultimately deemed safe for discharge directly home from the ED.This was a retrospective cohort study conducted at an academic ED. All trauma patients who were discharged directly home from the ED after whole-body CT were analyzed. The decision to utilize whole-body CT was at the discretion of the caring physician during the study period. Clinical data for the most recent trauma visit was recorded in a structured fashion on a standardized data collection instrument utilizing the hospital system electronic medical record (EMR). Subsequently, study investigators reviewed a shared, electronic radiological archive for the 6-hospital system to evaluate prior CT exposure for each patient.165 patients were in the study group. The mean age of the study group was 39+/− 16 years old, 40% were female and 64% were Hispanic. The most common mechanism of injury in our study group was motor vehicle crash (MVC) (66%). In our study group, 25% had at least one prior CT. The most common prior studies performed were: CT abdomen/pelvis (13%), CT head (9.1%), CT face (6.7%), and CT chest (1.8%). Within a multivariate logistic regression model we found that the large majority of patient characteristics and mechanisms of injury were not associated with a positive prior CT imaging history.We found a positive history for prior CT for 25% of trauma patients who received whole-body CT scan but were discharged from the ED to home. CT imaging has the capacity to detect a variety of different pathologies encountered in the emergency department (ED). Rosen described that CT is beneficial to the emergency medicine physician by increasing the certainty of diagnosis within a short period of time and significantly decreasing the need for surgical exploration . In lighOne area, in particular, for which there has been significant expansion in CT utilization is the evaluation of trauma patients. From 1998 to 2007 there was a national 3-fold increase in the use of CT scans in the ED for injury-related conditions . Such anWhen considering the increased use of CT imaging, clinicians must weigh the risks inherent to this modality. A single whole-body CT provides significantly more radiation exposure than a conventional x-ray, and at a dose in excess of which is felt to be safe within a one-year period, by the International Symposium on the System of Radiological Protection. (20 mSv) . ReviewsA recent study published at our center in 2015 revealed that 14% of trauma patients that received whole-body CT and were admitted to the hospital had prior CT imaging before their traumatic injury . This stThis was a multicenter, retrospective cohort study to assess the prior imaging history for patients with significant trauma mechanisms and clinical suspicion for important traumatic injuries that were ultimately deemed to be safe for discharge from the ED to home following whole-body CT. Data from all trauma patients who were discharged directly home from the ED after whole-body CT from 3/25/2016 to 10/25/2016 were analyzed.The study was conducted at Christus Spohn Memorial Hospital (site of patient enrollment) and electronic records were reviewed from Memorial Hospital along with five other Christus Spohn hospital sites. Christus Spohn Memorial is a major teaching affiliate of Texas A&M College of Medicine, a level-two trauma center, and serves an inner city population. The annual ED census is 45,000 patients. The six affiliated hospitals comprise 192,073 annual ED visits, which, based on administrative data available locally, constitutes approximately 70% of all ED visits within our twelve-county region of southern Texas. The study was approved by the Spohn Institutional Review Board prior to initiation of data collection.The study included all adult ED patients, age > 17 years, from 3/25/16–10/25/16 for whom there was clinical suspicion for important traumatic injuries but were ultimately deemed by the emergency physician to be safe for discharge home following whole-body CT (i.e. patients discharged home from the ED). Patients were excluded if they were pregnant, prisoners, admitted to the hospital from the ED, or had less than a full whole-body CT to evaluate their traumatic injuries. Inclusive electronic radiological logs were reviewed on a weekly basis by study authors to include any patients that were not identified at point of care.Evaluation of trauma patients and the decision to utilize whole-body CT was at the discretion of the caring physician during the study period. Clinical data for the current visit were recorded in a structured fashion on a standardized data collection instrument utilizing data from the hospital system EMR with all study data points determined a priori. In a similar structured fashion, study investigators reviewed a shared, electronic radiological archive for the 6-hospital system to evaluate prior CT exposure for each patient.Data were entered into Excel 2013 for Windows , and, then, transported into STATA 11 software  for statistical analysis. Continuous data are presented as means +/− standard deviations and were analyzed by t-tests. Categorical data are presented as frequency of occurrence and were analyzed by chi-square. We calculated odds ratios with 95% CIs.Our primary outcome parameter was the percentage of patients who were discharged from the hospital from the ED following whole-body CT and determined to have had a prior history of CT(s) before their traumatic event. Prior CT was defined as CT imaging of any protocol/body area identified on a dedicated page within our system-wide EMR. Data was available for review from this system from 2009 to the present time.As bivariate analyses often mask confounding of other independent variables, we utilized multivariate logistic regression to delineate the effect of each independent variable. The dependent variable was whether patients had any CT(s) performed previously, The independent variables were sex, age, race/ethnicity and mechanism of injury. In view of our methodology for data collection that involved chart review, we were limited to analyzing patient characteristic variables available in the EMR. Physician and examination characteristics were not included within the model.Over the seven-month period, 165 patients were discharged home from the ED after receiving whole-body CT scan. The mean age of the study group was 39 (SD+/− 16) years old, 40% were female (66/165), and 64% (106/165) were Hispanic. The most common mechanism of injury in our study group was MVC . Other mechanisms included fall , stab head , and other .Within the study group, one-fourth  had at least one prior CT. The prior studies performed in order of frequency were: CT abdomen/pelvis 13% (21/165), CT head 9.1% (15/165), CT face 6.7% (11/165), CT cervical spine 5.5% (9/165), CT limb 4.2% (7/165), CT thoracic spine 3%(5/165), CT lumbar spine 3%(5/165), CT neck 1.8% (3/165), and CT chest 1.8% (3/165).With respect to aggregate exposure to chest and/or abdominal CT, studies with typically higher doses of radiation, we found 11 patients (6.7%) had at least one previous study prior to enrollment in our study, five (3%) had two previous studies, and one patient (0.6%) has 13 previous CT studies.p = .025, OR = 2.6; 95% CI 1.12–6.14) and “other” trauma mechanisms  were associated with positive prior CT history We did not find that other patient characteristics were associated with a prior CT history, including age > 64 years  female gender , Hispanic race , non-white/non-Hispanic race , fall mechanism , and stab wound head .A multivariate model which included patient characteristics and mechanism injury found that age 41–64 years  was associated with positive prior CT abdomen and/or chest history. We did not find that other patient characteristics were associated with such an imaging history, including age > 64 years , female gender , Hispanic race , non-white/non-Hispanic race , stab wound head , and other non-MVC, no stab wound head mechanisms .A similar multivariate model found that age 41–64 years , we are confident that errors in the structured abstraction were likely minimal.The characteristics of our study group may also raise concerns for external validity. Our local population is largely indigent and predominately Hispanic. It is unclear if patients from different socioeconomic and ethnic groups would be more or less at risk to have had prior imaging. Another source of potential concern for the generalizability of our results is with respect to our definition of low risk patients. We defined low risk patients as those discharged after ED evaluation. Future studies could improve upon our methods by utilizing low risk criteria identified previously .We found a positive history for prior CT for 25% of trauma patients who received whole-body CT scan but were discharged from the ED to home. Our results should encourage clinicians to evaluate prior CT imaging history and consider shared decision making/use of selective CT algorithms in case for which pretest assessment for risk of serious injury is relatively low.