Retrospective Investigations Research Articles

Homicidal poisoning series in a nursing home: retrospective toxicological investigations in bone marrow and hair.

Homicidal poisonings remain rare and can be difficult to detect, especially in the elderly or in medical settings. In this atypical poisoning series, a young nursing assistant purposely poisoned thirteen residents of a nursing home and killed ten of them. The medications used were a mix of psychotropic medications (cyamemazine, loxapine, tiapride, risperidone, and mirtazapine), under liquid formulation, which were inducing malaise and coma. The forensic investigation included analysis of blood, urine, hair, and bone marrow and exhumations of seven corpses up to 3years after the inhumation. Hair collected from a hairbrush of a cremated victim have been analyzed. Bone marrow sample preparation was based on a liquid/liquid triple extraction. Hair were incubated after decontamination overnight at 55°C in methanol. Segmentation was possible for seven samples, except for delayed exhumation samples (n = 4) and hairbrush hair sample (n = 1). The extracts were then analyzed using gas chromatography coupled with mass spectrometry (GC-MS) for unknown screening and using liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) for a targeted screening and quantification. Screenings revealed the presence of the same mix of psychotropic medications. Cyamemazine, mirtazapine, loxapine, tiapride, and risperidone hair concentrations were 6-17,458pg/mg, 74-1271pg/mg, 9-1346pg/mg, 13-148pg/mg, and 3-5pg/mg, respectively. Cyamemazine bone marrow concentrations were 229 and 681ng/g and 152-717ng/mL in blood. Patients' medications were also identified and quantified. This poisoning series provide analytical data that could support subsequent toxicological result interpretation in similar forensic cases.

Canine Distemper Virus (CDV) – The COVID-19 of the Wild Cats

In the year 1994, the Serengeti lion population was decimated by a canine distemper disease outbreak. Retrospective investigations showed that this host population had already been in contact with the pathogen in 1981 without any detected sign of disease. As an alternative to the virus mutation hypothesis to explain this difference in virulences observed in 1981 and 1994, we propose a novel mechanism of disease emergence based on variation in population immunity. We use a stochastic model to show that stochastic fluctuations in pathogen circulation, owing to a low probability of virus transmission from its reservoir to the target host and thereby resulting in variations in the global immunity level of the target host population, can explain the observations made in Serengeti. This mechanism may also be involved in other infectious disease emergences or re-emergences.

Factors influencing the sinus membrane thickness in edentulous regions: a cone-beam computed tomography study

BackgroundDuring implant treatment in the maxillary molar area, maxillary sinus floor augmentation is often performed to ameliorate the reduced alveolar bone height attributable to bone remodeling and pneumatization-induced expansion of the maxillary sinus. However, this augmentation may cause complications such as misplaced implants, artery damage, and maxillary sinus mucosal perforation; infections like maxillary sinusitis; and postsurgical complications such as bone graft leakage and postoperative nasal hemorrhaging. To reduce the complications during maxillary sinus floor augmentation and postoperative infections, we performed retrospective investigations of various systemic and local factors that influence pre-operative sinus mucosal thickness (SMT) by using cone-beam computed tomography (CBCT). Subjects included patients who underwent maxillary sinus floor augmentation in an edentulous maxillary molar area with a lateral approach. Pre-operative SMT, existing bone mass, and nasal septum deviation were measured using CBCT images. Relationships between SMT and the following influencing factors were investigated: (1) age, (2) sex, (3) systemic disease, (4) smoking, (5) period after tooth extraction, (6) reason for tooth extraction, (7) residual alveolar bone height (RBH), (8) sinus septa, and (9) nasal septum deviation. Correlations were also investigated for age and RBH (p < 0.05).ResultsWe assessed 35 patients (40 sinuses; 11 male, 24 female). The average patient age was 58.90 ± 9.0 years (males, 57.9 ± 7.7 years; females, 59.9 ± 9.4 years; age range, 41–79 years). The average SMT was 1.09 ± 1.30 mm, incidence of SMT > 2 mm was 25.0%, incidence of SMT < 0.8 mm was 50.0%, and the average RBH was 2.14 ± 1.02 mm. The factors that influenced SMT included sex (p = 0.0078), period after tooth extraction (p = 0.0075), reason for tooth extraction (p = 0.020), sinus septa (p = 0.0076), and nasal septum deviation (p = 0.038).ConclusionsFactors associated with higher SMT included male sex, interval following tooth extraction < 6 months, periapical lesions, sinus septa, and nasal septum deviation. Factors associated with SMT > 2 mm were sex and reason for tooth extraction, while factors associated with SMT < 0.8 mm were time following tooth extraction and nasal septum deviation. Despite the limitations of this study, these preoperative evaluations may be of utmost importance for safely conducting maxillary sinus floor augmentation.

Short term outcomes of rotational atherectomy versus orbital atherectomy in patients undergoing complex percutaneous coronary intervention: a systematic review and meta-analysis

Objective Coronary artery calcification (CAC) is one of the paramount hurdles for percutaneous coronary intervention (PCI) since it impedes stent delivery and complete expansion. This study intended to evaluate the short-term clinical and procedural outcomes comparing rotational atherectomy (RA) and orbital atherectomy (OA) in patients with heavily calcified coronary lesions undergoing PCI. Design: This systematic review and meta-analysis included all head-to-head published comparisons of coronary RA versus OA. Procedural endpoints and post-procedural clinical outcomes (30 days/in-hospital), were compared. RevMan 5.3 software was used for data analysis. Results: Seven retrospective observational investigations with a total of 4623 patients, including 3203 patients in the RA group and 1420 patients in the OA group, were incorporated. Compared with OA, the RA group was associated with a higher incidence of myocardial infarction at short-term follow-up (OR: 1.56, 95% CI: 1.07–2.29, p = .02, I 2 = 0%). No difference was noted among other short-term post-procedural clinical outcomes including all-cause mortality, target vessel revascularization, or major adverse cardiac events. Among procedural complications, RA was associated with reduced coronary artery dissection and arterial perforation. Increased fluoroscopy time was observed in the RA cohort as compared with OA (MD: 4.78, 95% CI: 2.25–7.30, p = .0002, I 2 = 80%). Conclusion: RA was associated with fewer vascular complications, but at a cost of higher incidence of myocardial infarction and higher fluoroscopy time compared with OA, at short term follow-up. OA is a safe and effective alternative for the management of CAC.

How the world's collective attention is being paid to a pandemic: COVID-19 related n-gram time series for 24 languages on Twitter.

In confronting the global spread of the coronavirus disease COVID-19 pandemic we must have coordinated medical, operational, and political responses. In all efforts, data is crucial. Fundamentally, and in the possible absence of a vaccine for 12 to 18 months, we need universal, well-documented testing for both the presence of the disease as well as confirmed recovery through serological tests for antibodies, and we need to track major socioeconomic indices. But we also need auxiliary data of all kinds, including data related to how populations are talking about the unfolding pandemic through news and stories. To in part help on the social media side, we curate a set of 2000 day-scale time series of 1- and 2-grams across 24 languages on Twitter that are most ‘important’ for April 2020 with respect to April 2019. We determine importance through our allotaxonometric instrument, rank-turbulence divergence. We make some basic observations about some of the time series, including a comparison to numbers of confirmed deaths due to COVID-19 over time. We broadly observe across all languages a peak for the language-specific word for ‘virus’ in January 2020 followed by a decline through February and then a surge through March and April. The world’s collective attention dropped away while the virus spread out from China. We host the time series on Gitlab, updating them on a daily basis while relevant. Our main intent is for other researchers to use these time series to enhance whatever analyses that may be of use during the pandemic as well as for retrospective investigations.

Return to Work After Primary Rotator Cuff Repair: A Systematic Review and Meta-analysis

Background: Rotator cuff tears are a prevalent pathology in injured workers, causing significant economic ramifications and time away from work. To date, published articles on work outcomes after rotator cuff repair have not been cumulatively assessed and analyzed. Purpose: To systematically review reports on return to work after rotator cuff repair and perform a meta-analysis on factors associated with improved work outcomes. Study Design: Systematic review and meta-analysis; Level of evidence, 4. Methods: A systematic review of return-to-work investigations was performed using PubMed, Embase, and the Cochrane Database of Systematic Reviews in accordance with the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. Individual studies reporting rates of return to previous work with level of evidence 1 to 4 were independently screened by 2 authors for inclusion, and study quality was assessed using the Methodologic Index for Non-randomized Studies and Newcastle-Ottawa Scale. Work outcome data were synthesized and analyzed using random effects modeling to identify differences in rates of return to previous work as a function of operative technique, work intensity, and workers’ compensation status. Results: Thirteen retrospective investigations comprising 1224 patients who underwent rotator cuff repair met inclusion criteria for this investigation. Across all investigations, a weighted average of 62.3% of patients returned to previous level of work at 8.15 ± 2.7 months (mean ± SD) after surgery. Based on random effects modeling, higher rates of return to previous work were identified with decreasing work intensity (P < .001), while rates were similar between open and arthroscopic repair technique (P = .418) and between workers’ compensation and non–workers’ compensation cohorts (P = .089). All shoulder pain and functional outcome assessments demonstrated significant improvements at final follow-up when compared with baseline across all investigations. Conclusion: The majority of injured workers undergoing rotator cuff repair return to previous work at approximately 8 months after surgery. Despite this, >35% of patients are unable to return to their previous work level after their repair procedure. Similar rates of return to work can be anticipated regardless of workers’ compensation status and operative technique, while patients in occupations with higher physical intensity experience inferior work outcomes.

The importance of long-term studies on wildlife diseases and their interfaces with humans and domestic animals: A review.

Long-term wildlife disease research (LTWDR) and its interfaces with humans and domestic animals provide perspective to understand the diseases' main drivers and how they operate. In a systematic review, we analysed the temporal trend of the studies on LTWDR, their aims, and the hosts, pathogens and geographic areas studied. We also evaluated the added value that such studies provide. For analysis, we selected a total of 538 articles from 1993 to 2017 with a study period greater than or equal to 4 consecutive years. A marked increase in the number of studies published during the last 20years was observed that reflects a growing awareness of the outstanding role of wildlife as a reservoir of diseases. The most studied pathogen agents were viruses (39.2%), bacteria (38.5%) and protozoans (15.8%). Concerning the hosts, mammals (84.9%), particularly ungulates (40%) and carnivores (30.9%), and birds (12.5%) were the most represented in these long-term studies. Most articles reached conclusions concerning the effect of the disease on the infection/host dynamics (98.7%) and over 40% considered the economic consequences or proposed management and control measures. The research was mainly located in the Northern Hemisphere. While the definition of LTWDR is not only determined by the duration of the monitoring, the study must be long enough to: (a) address ecological and epidemiological questions that cannot be resolved with short-term observations or experiments, and (b) clarify the effects of different drivers. This review demonstrates that LTWDR has provided information about the causes and consequences of disease change that otherwise could not have been obtained. It may be used to inform decisions related to the emergence of disease and might help to design early warning systems of disease based on retrospective investigations.

Case studies on the association of Iron Deficiency Anemia with Thrombocytopenia and Reactive Thrombocytosis

Iron Deficiency Anemia (IDA) is the most prevalent blood disorder. Iron deficiency stands as a major cause for most of the anemia cases in the country. So, suggestions and efforts are being made to signify the importance of iron in regular diet and in the form of supplementation. Iron deficiency can be addressed effectively but when untreated it can lead to other severe disorders. Thrombocytosis and Thrombocytopenia are two interlinked related to iron deficiency in most cases. Literature suggests that Reactive thrombocytosis (RT) is common in patients with iron deficiency. This study focusses on the retrospective investigations and correlation of the relationship between the ferritin content, anemia, platelet counts and normalization of the same with iron supplementation. Out of the 165 patients, 72 were fit for the study after subjecting to the exclusion criteria of inflammatory diseases, infections, neoplasms etc. These 72 were segregated on the basis of the diagnosis of Thrombocytosis or Thrombocytopenia to establish proper correlation. 61 of 72 patients were diagnosed with thrombocytosis which constituted about 84.72% of the selected patients. 11 of 72 patients were diagnosed with thrombocytopenia. In this study it is clearly evident that both reactive thrombocytosis and thrombocytopenia are resultant of IDA. The platelet levels were elevated in many patients and in few their levels were lowered . The determining factor of platelets count is ferritin saturation. The changes in the iron saturation resulted in both elevation and depression in the platelet count. The platelet morphology lead to the changes in the platelet parameters. it can be advocated that both the conditions are rare and can occur concurrently in patients with IDA.

Estimating the diagnostic accuracy of the ankle-brachial pressure index for detecting peripheral arterial disease in people with diabetes: A systematic review and meta-analysis.

To systematically evaluate research investigating the accuracy of the ankle-brachial index (ABI) for diagnosing peripheral artery disease (PAD) in people with diabetes, as the accuracy is thought to be reduced in this cohort. A database search of EBSCO Megafile Premier, Embase and The Cochrane Library was conducted to 28 February 2019. Prospective and retrospective investigations of the diagnostic accuracy of the ABI for PAD in people with diabetes using an imaging reference standard were eligible. Sensitivity and specify of the ABI and bivariate meta-analysis against reference tests, or a standard summary receiver operating curve analysis (SROC) was performed. Thirty-three studies met the inclusion criteria. ABI was compared with angiography in 12 studies and with colour duplex ultrasound (CDUS) in 21 studies. A SROC analysis of studies using angiography as the reference standard found a diagnostic odds ratio (DOR) of 9.06 [95% confidence interval (CI) 3.61 to 22.69], and area under the curve (AUC) of 0.76 (95% CI 0.66 to 0.86). Bivariate analysis of studies using CDUS demonstrated mean sensitivity of 0.60 (95% CI 0.48 to 0.71; P=0.097) and mean specificity of 0.87 (95% CI 0.78 to 0.92; P<0.001) with a DOR of 9.76 (95% CI 5.24 to 18.20; P<0.0001) and AUC 0.72. These results suggest the ABI has a high specificity but lower sensitivity in detecting imaging diagnosed PAD in people with diabetes. The low probability of the testing being able to rule diagnosis in or out suggest that the ABI has limited effectiveness for early detection of PAD in this cohort.

Comprehensive Analysis of Multiple Primary Cancers in Patients With Esophageal Squamous Cell Carcinoma Undergoing Esophagectomy.

The aim of this study was to elucidate the latest epidemiology and risk factors for multiple primary cancers (MPCs), and the association between neoadjuvant chemotherapy (NAC) and postoperative metachronous cancer (PMC) in patients with esophageal squamous cell carcinoma (ESCC) who underwent esophagectomy. Background data to derive appropriate screening strategies are insufficient. This study consisted of 3 retrospective investigations. A total of 766 consecutive patients with ESCC who underwent esophagectomy between April 2005 and December 2019 were eligible for epidemiological analysis. Of these, 688 patients without missing data were analyzed for the risk of MPCs. In total, 364 patients who underwent NAC (115) and no preoperative treatments (249) were investigated for the association between NAC and PMC. Of 766 patients, 288 (38%) patients experienced 357 MPCs in their life. PMCs identified after the completion of 5-year postoperative follow-up were significantly more advanced (P = 0.019). Male sex [hazard ratio (HR) = 3.04, P = 0.038], older age (HR = 2.39, P < 0.001), and diabetes mellitus (HR = 1.76, P = 0.034) were risk factors for preoperative metachronous cancers. Heavy smoking (HR = 1.70, P = 0.014) and drinking (HR = 1.61, P = 0.029) were risk factors for synchronous cancers. NAC significantly reduced PMC incidence ( P = 0.043). NAC showed a trend to contribute to improved survival via reduced deaths from PMCs, although this did not reach significance ( P = 0.082). ESCC is associated with a high risk of MPCs. Continuing follow-up for PMCs after the completion of 5-year postoperative follow-up is important. NAC may reduce PMCs, representing a novel mechanism for improving survival in patients with locally advanced ESCC.

Sports-Related Oral and Maxillofacial Injuries: A 5-Year Retrospective Study, Pusan National University Dental Hospital

The incidence of sports trauma is gradually increasing, and its importance is therefore also increasing. The present study was conducted to analyze the types, proportions, and tendencies of sports trauma associated with the oral and maxillofacial regions. Patients who visited the Emergency Department of Pusan National University Dental Hospital between 2014 and 2018 for more than 5years were surveyed through retrospective epidemiologic investigations. Type of sports was classified according to American Academy of Pediatrics classification. For statistical analysis, age and gender distribution, cause of trauma, and annual trends data were collected. Of the 517 patients, most of the patients were teenagers (27.9%), followed by those younger than 10years (23.2%) (χ2= 22.897; P=.002), and noncontact sports, which is cycling, was the most common (43.5%) cause for trauma in both adult and children groups (χ2= 91.824; P<.001). The most common sports associated with contact sports, limited-contact sports, and noncontact sports were football (47.7%), baseball (50.0%), and cycling (74.8%), respectively. The causes for trauma injury were as follows: contact sports, other person's body (53.4%); limited-contact sports, other objects (60.9%); and noncontact sports, slip down (77.4%) (χ2= 298.901; P<.001). The prevalence and incidence of sports injuries increase every year, and the proportion of injured patients in May was the highest (χ2= 52.360; P=.181). The high percentage of traumatic sports demonstrated statistically significant trends (χ2=43.073; P=.002). Kickboard injuries showed a rapid increase recently (P for linear trend=.045), whereas other sports showed no significant trends. Considering the increasing incidence of sports-related injuries, oral and maxillofacial surgeons should be more concerned with maxillofacial trauma during sports.

Comparative Effectiveness Between Primary and Revision Foraminotomy for the Treatment of Lumbar Foraminal Stenosis.

Foraminotomy has demonstrated clinical benefit in patients with lumbar foraminal stenosis (LFS), as evidenced by several small retrospective investigations. However, there is a subset of patients who have recurrent symptoms following the operation and therefore require revision surgery. Yet, despite this phenomenon, the relative efficacy of revision foraminotomy (RF) is not well elucidated due to limited literature on the quality of life (QOL) outcomes and cost associated with primary foraminotomy (PF) and RF. To compare the effectiveness of PF and RF in terms of QOL outcomes and relative costs. This is a retrospective cohort study conducted at a single tertiary-care institution. The patient sample consisted of patients undergoing foraminotomy for the treatment of LFS between 2008 and 2016. The primary outcome measure was improvement in postoperative QOL, as measured by EuroQol 5-Dimensions (EQ-5D), and secondary outcome measures included Pain Disability Questionnaire (PDQ) and Patient Health Questionnaire-9 (PHQ-9) perioperative cost as well as minimum clinically important difference (MCID). A retrospective chart review was conducted to identify individuals who underwent PF or RF for LFS and to collect clinical, operative, and demographic data. QOL scores (EQ-5D, PDQ, and PHQ-9) were collected between 2008 and 2016, and perioperative financial data were extracted via the institution's cost utilization engine. Paired t tests were used to assess changes within treatment groups, and Fisher exact tests were used for intercohort comparisons. Five hundred seventy-nine procedures were eligible: 476 (82%) PF and 103 (18%) RF. A significantly higher proportion of males underwent RF than PF (71% versus 59%, P = .03), and PF was done on a significantly higher number of vertebral levels (2.2 versus 2.0, P = .04). There were no other significant differences in demographics. Preoperatively, mean PDQ-Functional scores (50 versus 54, P = .04) demonstrated significantly poorer QOL in the RF cohort. Postoperatively, EQ-5D index showed significant improvement in both the PF (0.547→0.648, P < .0001) and the RF (0.507→0.648, P < .0001) cohorts. Similarly, total PHQ-9 improved significantly in the PF cohort (7.84→5.91, P < .001) and in the RF cohort (8.55→5.53, P = .02), as did total PDQ (PF: 77→63, P < .0001; RF: 85→70, P = .04). QOL scores were also compared between groups preoperatively and postoperatively, and the only significant difference between PF and RF was observed in the preoperative PDQ-Functional score (49.7 versus 54.3, P = .04). The proportion of patients achieving MCID was not significantly associated with cohort. Finally, perioperative cost did not differ significantly between cohorts (PF: $13,383 versus RF: $13,595, P = .82). Both PF and RF produced significant improvement in nearly all measures in patients with LFS. There was no significant difference in cost between PF and RF, but both PF and RF showed postoperative QOL improvements as compared with preoperative scores, indicating that RF remains a reasonable treatment option for patients with recurrent symptoms of LFS.

Evolutionary paths of performance measurement and management system: the longitudinal case study of a leading SME

Purpose The literature highlights the relevance of performance measurement and management system in small and medium enterprises (SMEs) to face the current competitive environment. However, a number of studies investigate how performance measurement and management system is effective for evolving and how contingency factors could influence this change. Newer experiences are sporadic and rarely investigated by researchers and practitioners. The purpose of this study is to identify the feasible evolutionary path of performance measurement and management system in leading SMEs to respond to current business challenges. Furthermore, it aims to contribute to the understanding of the role of key contingency factors influencing this evolution. Design/methodology/approach A longitudinal case study, based on retrospective and real-time investigations, is performed to investigate the primary evolutions of the performance measurement and management system and its key determinants. Findings The findings highlight two evolution paths, increasing the maturity of performance measurement. The first path highlights a strong command and control of performance management; the second path shows a democratic and participative of performance management. Moreover, management information system, organizational culture and management style are highlighted as key contingency factors in the change of performance management. Originality/value The authors contribute to knowledge in performance measurement field, showing how the efforts for developing performance measurement and management system in a leading SME could determine two different evolutionary paths. Furthermore, the paper describes the increasing role of organizational culture, management style and management information system in performance management evolution, as well as the relevance of online chats and social media in performance management activities.

Detecting and recording cardiac murmurs in clinically healthy puppies in first opinion veterinary practice at the first health check

BackgroundThe frequency that cardiac murmurs are identified and recorded in first opinion veterinary practices at the first health check in puppies is unknown. The aims of the study were to assess the agreement between first opinion veterinary practitioners, a veterinary student and a veterinary cardiology specialist on detecting murmurs, and to establish whether abnormal auscultation findings had been recorded in the health certificates of clinically healthy puppies. The study included prospective and retrospective investigations, where the prospectively collected auscultation findings from a veterinary cardiology specialist and a trained veterinary student were compared to auscultation findings recorded by first opinion veterinary practitioners.ResultsCardiac auscultation was performed on 331 client-owned, clinically healthy dogs at two time points: at age 34–69 days by a first opinion veterinary practitioner and at age 45–76 days, on average 9 days later, by a veterinary cardiology specialist and a trained veterinary student. Agreement among the three was compared for the presence of a murmur. The degree of inter-observer agreement was evaluated using Cohen’s kappa. Auscultation findings, as noted in the pets’ passports, from 331 puppies and 43 different first opinion veterinary practices, were retrospectively reviewed and prospectively compared with auscultation findings from a veterinary cardiology specialist. Agreement between the veterinary cardiology specialist and the first opinion veterinary practitioners was poor (ϰ = 0.01) and significantly different (P < 0.001). First opinion veterinary practitioners had recorded a cardiac murmur in only 1 of the 97 puppies in which the veterinary cardiology specialist detected a murmur. Two-hundred-and-fifty-two puppies were auscultated by both the veterinary cardiology specialist and the student. Their agreement was fair (ϰ = 0.40) and significantly different (P = 0.024). The agreement between the student and a first opinion veterinary practitioner on these 252 puppies was poor (ϰ = 0.03) and significantly different (P < 0.001).ConclusionsThis study shows that soft cardiac murmurs are rarely documented during the first veterinary health check in puppies by first opinion veterinary practitioners. Although soft murmurs may not be clinically relevant, finding and recording them is evidence of a carefully performed auscultation. Missing a non-pathological murmur is not of clinical importance; however, missing a pathological murmur could prove detrimental for the individual puppy.

Biphasic Outbreak of Invasive Group A Streptococcus Disease in Eldercare Facility, New Zealand.

A 3-month outbreak of invasive group A Streptococcus disease at an eldercare facility, in which 5 persons died, was biphasic. Although targeted chemoprophylaxis contained the initial outbreak, a second phase of the outbreak occurred after infection control processes ended. To retrospectively investigate the genomic epidemiology of the biphasic outbreak, we used whole-genome sequencing and multiple bioinformatics approaches. Analysis of isolates from the outbreak and isolates prospectively collected during the outbreak response indicated a single S. pyogenes emm81 clone among residents and staff members. Outbreak isolates differed from nonoutbreak emm81 isolates by harboring an integrative conjugative genomic element that contained the macrolide resistance determinant erm(TR). This study shows how retrospective high-resolution genomic investigations identified rapid spread of a closed-facilty clonal outbreak that was controlled, but not readily cleared, by infection control management procedures.

Against All Odds: RNA Extraction From Different Protocols Adapted to Formalin-fixed Paraffin-embedded Tissue.

For the preservation of tissue samples, formalin fixation followed by paraffin embedding (FFPE) has been the method of choice for decades, mainly because it maintains the morphologic characteristics of the original tissue particularly preserved, as well as its genetic material. FFPE cells can be used to perform molecular tests, such as conventional (c) or quantitative (q) reverse transcriptase polymerase chain reaction (RT-PCR), in retrospective investigations. However, extracting RNA from archived FFPE tissues is a challenging procedure, as it requires time and the use of complex extraction methods. As specific FFPE extraction methods are not always available in the laboratories, the objective of this study was to evaluate the performance of a method based on phenol-chloroform (PC) and 2 commercial methods for RNA extraction, adapting their protocols for FFPE tissues. For this study, a pool of FFPE tissues underwent RNA extraction by PC, QIAmp Viral RNA Mini, and RNeasy Mini Kit. Both the RT-cPCR and the RT-qPCR results were favorable, demonstrating the viability of the RNA. As these results expanded the alternatives for low-budget FFPE extraction, the choice of the ideal method to be used will depend on the availability of reagents and kits.

Metabolomics and adductomics of newborn bloodspots to retrospectively assess the early-life exposome.

Exposomics studies can measure health-relevant chemical exposures during a lifetime and estimate the 'internal' environment. However, sampling limitations make these features difficult to capture directly during the critical neonatal time period. We review the use of newborn dried bloodspots (DBS) archived from newborn screening programs for exposomic analysis in epidemiological children's health studies. Emerging 'omics technologies such as adductomics and metabolomics have been adapted for DBS analysis, and these technologies can now provide valuable etiological information on the complex interplay between exposures, biological response, and population phenotypes. Adductomics and metabolomics of DBS can provide robust measurements for retrospective epidemiological investigations. With extensive bioarchiving programs in the United States and other countries, DBS are poised to substantially aid epidemiological studies, particularly for rare and low-frequency childhood diseases and disorders.

Received Cradling Bias During the First Year of Life: A Retrospective Study on Children With Typical and Atypical Development.

A population-level left cradling bias exists whereby 60–90% of mothers hold their infants on the left side. This left biased positioning appears to be mutually beneficial to both the mother and the baby's brain organization for processing of socio-emotional stimuli. Previous research connected cradling asymmetries and Autism Spectrum Disorders (ASD), entailing impairment in socio-communicative relationships and characterized by an early hypo-lateralization of brain functions. In this explorative study, we aimed to provide a contribution to the retrospective investigations by looking for early behavioral markers of neurodevelopmental disorders such as ASD. We hypothesized that an atypical trajectory in maternal cradling might be one of the possible signs of an interference in mother-infant socio-emotional communication, and thus of potential neurodevelopmental dysfunctions. To this aim, we examined photos depicting mother-child early cradling interactions by consulting family albums of 27 children later diagnosed with ASD and 63 typically developing children. As regards the first half of the first year of life, no differences were shown between maternal cradling-side preferences in typical and ASD groups, both exhibiting the left-cradling bias in the 0–3 months period, but not in the 3–6 months period. However, our results show dissimilar patterns of cradling preferences during the second half of the first year of life. In particular, the absence of left-cradling shown in typical mothers was not observed in ASD mothers, who exhibited a significant left-cradling bias in the 6–12 months age group. This difference might reflect the fact that mother-infant relationship involving children later diagnosed with ASD might remain “basic” because mothers experience a lack of social activity in such children. Alternatively, it may reflect the overstimulation in which mothers try to engage infants in response to their lack of responsiveness and social initiative. However, further investigations are needed both to distinguish between these two possibilities and to define the role of early typical and reversed cradling experiences on neurodevelopment.

Patients with Abdominal Aortic Aneurysm Are at Higher Risk of Cancer and Metastasis

Background: Some studies focusing on the endovascular repair of abdominal aortic aneurysms (AAA) have demonstrated that cancer is often found in such patients. Retrospective investigations have also indicated that AAA patients have an increased risk of cancer. However, the incidence rate of cancer and survival rate in patients with AAA compared to the population remains unknown. Methods: We conducted a prospective, single center, non-randomized, comparative cohort study including 223 AAA patients and 1000 Coronary artery disease (CAD) patients enrolled in our department between 01/01/2008 and 31/12/2011 with annual follow-up until 31/12/2018. Based on statistics from the Belgian cancer registry Belgium, the incidence rate of cancer was calculated for both men and women in the general population. The primary endpoint was the cumulative incidence rate of cancer in all three groups and the secondary endpoint was overall survival. Results: After nine years of follow-up, the cancer incidence was 30·1% (95%CI: 21·6-39·3%) in AAA patients and 23·5% (95%CI: 20·0-27·1%) in CAD subjects, markedly higher than the Walloon population (17·4%). Moreover, the development of metastases among patients with AAA was higher compared to CAD patients (38·7% vs.18·6%, P=0·03). In terms of overall survival, the proportion of cancer deaths in AAA patients was twice as high as in CAD patients. Conclusions: This study confirms an increased incidence of cancers and decreased survival in AAA patients compared to the general population. Funding Statement: This work was supported by the European Program FP7 “Fighting aneurysmal diseases” (no. 200647). Audrey Courtois and Jacobine Munten were funded by the Aneurysmal Pathology Foundation. Declaration of Interests: The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article. Ethics Approval Statement: The study was designed and conducted within the framework of the European program “Fighting Aneurysmal Disease (FAD; B70720095774 and B70720095773 9)” approved by the ethics committee (n°200647). All the participants were instructed on the study objectives and provided informed consent. The study was approved by the ethics board of the University hospital of Liege.

Estimating patients’ risk for postoperative delirium from preoperative routine data - Trial design of the PRe-Operative prediction of postoperative DElirium by appropriate SCreening (PROPDESC) study - A monocentre prospective observational trial

BackgroundPostoperative Delirium (POD) is the most common complication of elderly patients after surgery associated with increased postoperative morbidity, persistent care dependency and even mortality. Prevention of POD requires detection of patients at high risk prior to surgery. PROPDESC intends to provide an instrument for preoperative routine screening of patients' risk for POD. MethodsPROPDESC is a monocentric prospective observatory trial including 1000 patients older than 60 years from various disciplines of a university hospital planned for surgery of at least 60 min. To develop a score predicting the risk for POD, anesthesiological stratifications, laboratory values, medication and known risk factors as well as quality of life and cognitive performance are taken into account. POD assessment is performed daily on the first five days after the operation respectively the end of sedation in the intensive care units and normal wards. The score is evaluated from 600 data sets and subsequently validated internally. The most appropriate predictors are determined by a component-wise gradient boosting approach. DiscussionBased on retrospective investigations, etiology of POD is considered multifactorial. By a prospective analysis of various factors, PROPDESC intends to provide an applicable tool to predict the risk for POD from preoperative routine data and assessment of cognitive function. Objective is to establish an automatically generating score in preoperative routine to screen patients for increased risk of POD as starting point for POD reduction and management. Model compilation requires a high significance and enhancement within compound as well as regular availability of the selected predictors. Trial registrationDRKS, DRKS00015715. Registered 13 December 2018 - Retrospectively registered, https://www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00015715.