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Background This study evaluates the safety and feasibility of combined resection for patients with synchronous pulmonary and esophageal cancer. Methods Patients undergoing esophagectomy between 1997 and 2019 were identified from prospectively collected databases at three tertiary referral centers, and those with combined anatomic lung resection at the same setting were identified. This cohort was then matched in a 1:3 ratio to esophagectomy alone cases, based on age, sex, pathologic stage, neoadjuvant therapy, and surgical procedure. Demographic data, peri-operative data, post-operative complications were compared. Statistical analysis included unpaired t-test, Fisher’s exact or chi-squared test and Gehan-Breslow analysis. Results Of 4729 esophagectomies, combined anatomic lung resection was performed in 18 patients with discrete pulmonary lesions. Matching yielded 49 patients who underwent esophagectomy only and was statistically similar compared to patients undergoing combined resections. Ivor Lewis esophagectomy and lobectomy were the most frequent procedures. Combined resections did not have a higher overall complication rate than esophagectomy alone, rather these patients had fewer overall complications (56% vs 84%; p=0.02). Specifically, there was not difference in anastomotic leak (17% vs. 18%) or pulmonary complications (39% vs. 33%) between combined resection and esophagectomy alone. No post-operative mortality was identified, and median overall survival was 4.1 years versus 6.5 years (p=0.10). Conclusions Patients with synchronous localized lung and esophageal cancer, although rare, should not be biased towards non-surgical therapy, as the morbidity associated with combined esophagectomy and anatomic lung resection does not differ significantly from esophagectomy alone in this highly selected group of patients.

The immune system is an active component of bone repair. Mast cells influence the recruitment of macrophages, osteoclasts and blood vessels into the repair tissue. We hypothesized that if mast cells and other immune cells are sensitized to recognize broken bone, they will mount an increased response to subsequent fractures that may be translated into enhanced healing. To test this, we created a bone defect on the left leg of anesthetized mice and 2 weeks later, a second one on the right leg. Bone repair in the right legs was then compared to control mice that underwent the creation of bilateral window bone defects at the same time. Mice were euthanized at 14 and 56 days. Mineralized tissue quantity and morphometric parameters were assessed using micro-CT and histology. The activity of osteoblasts, osteoclasts, vascular endothelial cells, mast cells, and macrophages was evaluated using histochemistry. Our main findings were (1) no significant differences in the amount of bone produced at 14- or 56 days post-operative between groups; (2) mice exposed to subsequent fractures showed significantly better bone morphometric parameters after 56 days post-operative; and (3) significant increases in the content of blood vessels, osteoclasts, and the number of macrophages in the subsequent fracture group. Our results provide strong evidence that a transient increase in the inflammatory state of a healing injury promotes faster bone remodelling and increased neo-angiogenesis. This phenomenon is also characterized by changes in mast cell and macrophage content that translate into more active recruitment of mesenchymal stromal cells.

The purpose of this study was to assess the psychometric properties of the Simplified Inguinal Pain Questionnaire (sIPQ) and compare it to the regular Inguinal Pain Questionnaire (IPQ) for external validation. To do so, the IPQ and sIPQ were telephonically administered at 7 and 28 days postoperatively for a cohort of 25 patients who underwent Lichtenstein hernioplasty. A psychometric analysis of the scores was done using Cronbach’s alpha and test–retest assessments. The agreement rate of the mean-standardized values between scores was afterwards calculated. We found closely similar psychometric values for the IPQ and sIPQ. The agreement rate between scores was 97% (p

Grief and bereavement support is a fundamental component of palliative care, yet there is a gap in practice as not all palliative care services offer it. The compassionate communities (CC) approach aims to build community capacity to address grief as grief support is considered everyone's responsibility. This study describes the characteristics, development, growth and attendees of a grief support program that uses a CC approach to bridge the gap of grief support in palliative care.

To validate the Inguinal Pain Questionnaire (IPQ) in the Spanish Language and test its use in a randomized controlled trial (RCT) of hernia repair using the Lichtenstein technique vs. the ONSTEP technique. We simplified the IPQ using a principal component analysis (PCA) approach as a secondary objective. The IPQ was translated into Spanish and validated in a cohort of 21 patients. Thereafter, 40 patients were randomized to undergo hernia repair by the Lichtenstein technique or the ONSTEP technique. IPQ and pain visual analogue (VAS) score trends over time were compared using a repeated-measures mixed-effects model. The Spanish version of the IPQ showed an internal consistency similar to that of the original score. No significant differences were found in the IPQ responses, pain VAS, or the rate of self-reported pain between patients who underwent the Lichtenstein technique and those who underwent the ONSTEP technique. Following PCA analysis, the number of items on the IPQ was reduced from 18 to 10. The Spanish version of the IPQ measures postoperative inguinal pain adequately. Based on our findings, the ONSTEP technique was not superior to the Lichtenstein technique. The simplified version of the IPQ is not significantly different from the full version and it is easier to complete. NCT04138329, registered on October 24, 2019.

Objective To review the clinical and scientific literature on remote monitoring and management of postsurgical wounds using smartphone applications (apps). Data sources MEDLINE, PubMed, EMBASE, and Cochrane libraries were searched for relevant articles on patients who received surgery and were monitored postdischarge via an app. Study selection Articles were selected with the terms "mobile phones," "smartphones," "wounds," "monitor," and "patient preference." Data extraction The authors found 276 review articles related to telemedicine in wound care. Investigators reviewed the titles and abstracts of the search results and selected 83 articles that were relevant to the remote monitoring of wounds using smartphone apps. Data synthesis The topics explored in selected literature included smartphone app importance to telemedicine, benefits (medical and financial), app examples, and challenges in the context of wound monitoring and management. The authors identified several challenges and limitations that future studies in the field need to address. Conclusions Remote monitoring and management of wounds using smartphone apps is a valuable technique to enhance the quality of and access to healthcare. However, although some patients may prefer this technology, some lack technological competence, limiting telemedicine's applicability. In addition, issues remain with the reliable interpretation of data collected through apps.

BACKGROUND Composition of tissue types within a wound is a useful indicator of its healing progression. Tissue composition is clinically used in wound healing tools (eg, Bates-Jensen Wound Assessment Tool) to assess risk and recommend treatment. However, wound tissue identification and the estimation of their relative composition is highly subjective. Consequently, incorrect assessments could be reported, leading to downstream impacts including inappropriate dressing selection, failure to identify wounds at risk of not healing, or failure to make appropriate referrals to specialists. OBJECTIVE This study aimed to measure inter- and intrarater variability in manual tissue segmentation and quantification among a cohort of wound care clinicians and determine if an objective assessment of tissue types (ie, size and amount) can be achieved using deep neural networks. METHODS A data set of 58 anonymized wound images of various types of chronic wounds from Swift Medical’s Wound Database was used to conduct the inter- and intrarater agreement study. The data set was split into 3 subsets with 50% overlap between subsets to measure intrarater agreement. In this study, 4 different tissue types (epithelial, granulation, slough, and eschar) within the wound bed were independently labeled by the 5 wound clinicians at 1-week intervals using a browser-based image annotation tool. In addition, 2 deep convolutional neural network architectures were developed for wound segmentation and tissue segmentation and were used in sequence in the workflow. These models were trained using 465,187 and 17,000 image-label pairs, respectively. This is the largest and most diverse reported data set used for training deep learning models for wound and wound tissue segmentation. The resulting models offer robust performance in diverse imaging conditions, are unbiased toward skin tones, and could execute in near real time on mobile devices. RESULTS A poor to moderate interrater agreement in identifying tissue types in chronic wound images was reported. A very poor Krippendorff α value of .014 for interrater variability when identifying epithelization was observed, whereas granulation was most consistently identified by the clinicians. The intrarater intraclass correlation (3,1), however, indicates that raters were relatively consistent when labeling the same image multiple times over a period. Our deep learning models achieved a mean intersection over union of 0.8644 and 0.7192 for wound and tissue segmentation, respectively. A cohort of wound clinicians, by consensus, rated 91% (53/58) of the tissue segmentation results to be between fair and good in terms of tissue identification and segmentation quality. CONCLUSIONS The interrater agreement study validates that clinicians exhibit considerable variability when identifying and visually estimating wound tissue proportion. The proposed deep learning technique provides objective tissue identification and measurements to assist clinicians in documenting the wound more accurately and could have a significant impact on wound care when deployed at scale.

Patient: Male, 57-year-old Final Diagnosis: Diabetic foot Symptoms: Chronic ulcer • osteomyelitis • polymicrobial infection Medication: — Clinical Procedure: Bone scan • intravenous antibiotic • oral antibiotic • PET-CT • telemedicine Specialty: Dermatology • Infectious Diseases • Podiatry Objective: Unusual setting of medical care Background: Wounds affect millions of people world-wide, with care being costly and difficult to deliver remotely. The ongoing COVID-19 pandemic highlights the urgent need for telehealth solutions to play a larger role as part of remote care strategies for patient monitoring and care. We describe our findings on the use of a patient-facing wound care app (Swift Patient Connect App, Swift Medical, Canada) as an innovative solution in remote wound assessment and management of a diabetic patient’s wound. Case Report: In February 2020, a 57-year-old man with type I diabetes and peripheral arterial disease presented with osteomyelitis in the left foot at the fifth metatarsal, arising from a chronic ulcer. The wound was deep, with purulent discharge and polymicrobial growth. A 6-week course of intravenous antibiotics was administered, with slow improvement of the wound. At a follow-up appointment in June 2020, The Patient Connect app was recommended to the patient to securely share calibrated images of his wound as well to communicate with his doctor. Between June 2020 and January 2021, wound closure was accurately monitored as part of the management of this diabetic foot infection. The app was also used in the management of 2 subsequent wounds and infection episodes. Conclusions: Use of the Swift Patient Connect App designed to monitor and manage wounds by a patient with diabetes and foot ulcer as part of a remote care strategy resulted in numerous benefits expressed by the patient. After initial adoption, 3 successive wounds were managed with a combination of in-person and telehealth visits complemented by the app. Incorporation of this technology as part of a novel telemedicine strategy promises to have an extensive impact on remote care delivery during the current COVID-19 pandemic and beyond.

The Human Immunodeficiency Virus (HIV) Viral Infectivity Factor (Vif) is a 192-amino acid accessory protein essential to viral replication which counteracts host APOBEC3 proteins. APOBEC3 proteins interfere with the replication of HIV, hepatitis C virus, hepatitis B virus and retrotransposons. Vif is a recent candidate target for therapeutic and preventative interventions in HIV/AIDS yet little is known about its clinical relevance. We describe the results of applying different machine learning algorithms (Apriori, Multifactor Dimensionality Reductor, C4.5, Artificial Neural Networks and ID3) to the search of associations between HIV-1 Vif protein attributes and clinical endpoints. Final iterations showed that the presence of mutations in BC Boxes, APOBEC motifs and Cullin5 binding motifs were together associated with higher initial CD4 T cells while mutations of specific APOBEC motifs coupled with the conservation of other APOBEC motifs were associated with lower historic CD4 T cells. Conservation of specific APOBEC motifs and BC boxes were linked to lower initial viral loads while different combinations of mutations in the Nuclear Localisation Inhibition Signal and BC Boxes were associated with higher historic viral loads. Further scrutiny of these combinations through traditional statistical methods revealed striking differences in both CD4 T cells and viral loads in patients stratified into those having the previous combinations. While artificial intelligence algorithms do not phase out traditional statistical methods, our Artificial Intelligence (AI)-based approach highlights their use at reducing the dimensionality of large and complex datasets and at proposing novel, unimaginable, associations of biological patterns with functional relevance or clinical roles.

A variety of biological, mechanical, and physical therapeutic modalities of varying complexity, efficacy, cost, and safety profile have been developed to enhance bone healing. There have been sporadic reports of spontaneous bone formation after repeated cold exposure. In this study we report for the first time, the anabolic effect of cold exposure on bone healing

Background Use of therapeutic cannabinoids in the pediatric population has increased in recent years within areas of epilepsy, palliative care, and cancer. Given the endocannabinoid system plays a crucial role in gastrointestinal (GI) homeostasis, exogenous cannabinoids have the potential to develop GI related side effects. While some GI adverse events have been reported with the use of therapeutic cannabinoids, the full profile of GI adverse events in the pediatric population is still unknown. Aims To understand the impact of therapeutic cannabinoids on the GI system of pediatric patients, we performed a systematic review and meta-analysis to assess the prevalence of various GI-related adverse events arising from cannabinoid usage within pediatric populations. Methods Searches were conducted from OVID MEDLINE, EMBASE, CINAHL, Web of Science, and The Cochrane Library for study screening. The included studies were quantitatively assessed for GI adverse events including nausea, diarrhea, increased appetite, decreased appetite, weight gain, weight loss, constipation, abdominal pain, and unspecified events. The prevalence along with their relation towards diagnosis, type of cannabinoid, dosage, duration of treatment, and study type were also assessed. Results Among a total of 1201 patients across 25 included studies, an overall prevalence of 33.91% GI adverse events was observed in patients. The statistical analysis of the pediatric population displayed no relation between therapeutic cannabinoid usage and GI adverse events, bearing a large heterogeneity (I2 = 91%, P < 0.01). Upon analysis based on study type, a significant difference was observed between prospective and retrospective studies in categories of all GI adverse events, diarrhea, and decreased appetite, with prospective studies displaying a higher prevalence in all three categories. Nausea symptoms showed a significant negative correlation with maximum dosage of cannabinoid used. In addition, diarrhea was found to have a higher prevalence in Dravet syndrome related to an ion channel gene mutation (SCN1A) compared to other epilepsy patients. Conclusions While the meta-analysis did not identify any significant associations between therapeutic cannabinoid usage and GI adverse events, there remains the potential for interactions of cannabinoids on GI symptoms depending on dosage and underlying patient factors. Funding Agencies Farncombe Family Digestive Health Research Institute

Objectives Age-related changes in blood composition have been found to affect overall health. Thus, this study aimed to understand the effect of these changes on bone healing by assessing how plasma derived from young and old rats affect bone healing using a rat model. Methods . Blood plasma was collected from 6-month and 24-month old rats. Differences in elemental composition and metabolome were assessed using optical emission spectrometry and liquid mass spectrometry, respectively. Bilateral tibial bone defects were created in eight rats. Young plasma was randomly applied to one defect, while aged plasma was applied to the contralateral one. Rats were euthanized after two weeks, and their tibiae were analyzed using micro-CT and histology. The proteome of bone marrow was analyzed in an additional group of three rats. Results Bone-defects treated with aged-plasma were significantly bigger in size and presented lower bone volume/tissue volume compared to defects treated with young-plasma. Histomorphometric analysis showed fewer mast cells, macrophages, and lymphocytes in defects treated with old versus young plasma. The proteome analysis showed that young plasma upregulated pathways required for bone healing (e.g. RUNX2, platelet signaling, and crosslinking of collagen fibrils) whereas old plasma upregulated pathways, involved in disease and inflammation (e.g. IL-7, IL-15, IL-20, and GM-CSF signaling). Plasma derived from old rats presented higher concentrations of iron, phosphorous, and nucleotide metabolites as well as lower concentrations of platelets, citric acid cycle, and pentose phosphate pathway metabolites compared to plasma derived from young rats. Conclusion bone defects treated with plasma-derived from young rats showed better healing compared to defects treated with plasma-derived from old rats. The application of young and old plasmas has different effects on the proteome of bone defects.

Neutrophil-to-lymphocyte ratio (NLR) has been identified as a biomarker for multiple malignancies. There is emerging evidence that implicates neutrophils in cancer progression. Alterations of neutrophil counts and NLR during treatment may reflect a change in oncologic outcome that is more important than baseline values. The aim of this study is to investigate the prognostic role of NLR changes during the treatment trajectory of patients with esophageal adenocarcinoma. NLR values of patients with esophageal adenocarcinoma who underwent surgery between 2005 and 2016 were measured at baseline and in the late postoperative period. Primary outcomes were overall survival (OS) and disease-free survival (DFS). The secondary outcome was pathological response to neoadjuvant chemotherapy. 330 patients were included; mean age was 65.6 years, and 82% were male. Most patients had cT3 (74.8%), cN-positive (59.7%) disease. Two-thirds (65.2%) received neoadjuvant chemotherapy. The independent predictors of OS were pathological N-stage, size of primary tumor, and delta NLR (late – baseline NLR). Patients with persistently elevated NLR did worse than those with decreasing NLR trends between baseline and postoperative time points (3-year OS 43.4% versus 71.3%, p

Orthopedic tumor resection, trauma, or degenerative disease surgeries can result in large bone defects and often require bone grafting. However, standard autologous bone grafting has been associated with donor site morbidity and/or limited quantity. As an alternate, allografts with or without metallic or polyether-etherketone have been used as grafting substitutes. However, these may have drawbacks as well, including stress shielding, pseudarthrosis, disease-transmission, and infection. There is therefore a need for alternative bone substitutes, such as the use of mechanically compliant three-dimensional (3D)-printed scaffolds. Several off-the-shelf materials are available for low-cost fused deposition 3D printing such as polylactic acid (PLA) and polycaprolactone (PCL). We have previously described the feasibility of 3D-printed PLA scaffolds to support cell activity and extracellular matrix deposition. In this study, we investigate two medical-grade filaments consistent with specifications found in American Society for Testing and Materials (ASTM) standard for semi-crystalline polylactide polymers for surgical implants, a pure polymer (100M) and a copolymeric material (7415) for their cytocompatibility and suitability in bone tissue engineering. Moreover, we assessed the impact on osteo-inductive properties with the addition of beta-tricalcium phosphate (β-TCP) minerals and assessed their mechanical properties. 100M and 7415 scaffolds with the additive β-TCP demonstrated superior mesenchymal stem cells (MSCs) differentiation detectedviaincreased alkaline phosphatase activity (6-fold and 1.5-fold, respectively) and mineralized matrix deposition (14-fold and 5-fold, respectively)in vitro. Furthermore, we evaluatedin vivocompatibility, biosafety and bone repair potential in a rat femur window defect model. 100M+β-TCPimplants displayed a positive biosafety profile and showed significantly enhanced new bone formation compared to 100M implants evidenced by μCT (39 versus 25% bone volume/tissue volume ratio) and histological analysis 6 weeks post-implantation. These scaffolds are encouraging composite biomaterials for repairing bone applications with a great potential for clinical translation. Further analyses are required with appropriate evaluation in a larger critical-sized defect animal model with long-term follow-up.

Introduction Despite being widely used as a screening tool, a rigorous scientific evaluation of infrared thermography for the diagnosis of minimally symptomatic patients suspected of having COVID‐19 infection has not been performed. Methods A consecutive sample of 60 adult individuals with a history of close contact with COVID‐19 infected individuals and mild respiratory symptoms for less than 7 days and 20 confirmed COVID‐19 negative healthy volunteers were enrolled in the study. Infrared thermograms of the face were obtained with a mobile camera, and RT‐PCR was used as the reference standard test to diagnose COVID‐19 infection. Temperature values and distribution of the face of healthy volunteers and patients with and without COVID‐19 infection were then compared. Results Thirty‐four patients had an RT‐PCR confirmed diagnosis of COVID‐19 and 26 had negative test results. The temperature asymmetry between the lacrimal caruncles and the forehead was significantly higher in COVID‐19 positive individuals. Through a random forest analysis, a cut‐off value of 0.55°C was found to discriminate with an 82% accuracy between patients with and without COVID‐19 confirmed infection. Conclusions Among adults with a history of COVID‐19 exposure and mild respiratory symptoms, a temperature asymmetry of ≥ 0.55°C between the lacrimal caruncle and the forehead is highly suggestive of COVID‐19 infection. This finding questions the widespread use of the measurement of absolute temperature values of the forehead as a COVID‐19 screening tool.

Post-esophagectomy anastomotic complications can result in high morbidity/mortality. Those with necrosis and sepsis have traditionally resulted in conduit loss and cervical esophagostomy. We sought to examine our management and outcomes of anastomotic complications, with a focus on an approach that stresses conduit salvage. Methods Conduit complications were identified from a prospectively collected esophagectomy database (2006–17) at a high-volume referral center. Patient/tumor/treatment details and surgical outcomes were collected. Conduit complications were defined as Leak/Conduit Necrosis/Tracheoesophageal Fistula (TEF) and graded according to the Clavien-Dindo classification. Successful treatment was defined when sepsis/leak control was achieved and no further intervention was required. Statistical analysis was done using Cox regression, logistic regression, ANOVA or Chi-square tests, *p Results Of 647 esophagectomies, conduit complications occurred in 103 (16%) [Leak:73 (11%); Necrosis:24 (4%), (TEF):6(1%)]. Antibiotics (C-D = 2) was successful in 28 (38%) of Leaks. Endoscopic stent alone (C-D = 3A) was successful in 20 (27%) Leak, 7(29%) Necrosis, and 1(17%) TEF cases. Early conduit revision+re-anastomosis (C-D = 3B/4) was successfully performed in 22 (30%) Leak, 13 (54%) Necrosis, and 5(83%) TEF cases. Only 6 patients [2(3%) Leak, 4(16%) Necrosis] had conduit loss+cervical esophagostomy. 90-day mortality was: Minor (C-D = 2-3A) Leak = 3%, Major (C-D = 3B-4) Leak = 8%, and Necrosis = 21%*. Necrosis, but not Leak or TEF, was associated with lower 3-year survival compared to patients who did not have conduit complication (30% vs 55%, p Conclusion The vast majority of conduit complications, including conduit necrosis, can be managed successfully with conduit salvage with endoscopic treatment or early surgical re-anastomosis. Cervical esophagostomy is rarely required.

Dense collagen (DC) gels facilitate the osteoblastic differentiation of seeded dental pulp stem cells (DPSCs) and undergo rapid acellular mineralization when incorporated with bioactive glass particles, both in vitro and subcutaneously in vivo. However, the potential of DC-bioactive glass hybrid gels in delivering DPSCs for bone regeneration in an osseous site has not been investigated. In this study, the efficacies of both acellular and DPSC-seeded DC-S53P4 bioactive glass [(53)SiO2-(23)Na2O-(20)CaO-(4)P2O5, wt%] hybrid gels were investigated in a critical-sized murine calvarial defect. The incorporation of S53P4, an osteostimulative bioactive glass, into DC gels led to its accelerated acellular mineralization in simulated body fluid (SBF), in vitro, where hydroxycarbonated apatite was detected within 1 day. By day 7 in SBF, micro-mechanical analysis demonstrated an 8-fold increase in the compressive modulus of the mineralized gels. The in-situ effect of the bioactive glass on human-DPSCs within DC-S53P4 was evident, by their osteogenic differentiation in the absence of osteogenic supplements. The production of alkaline phosphatase and collagen type I was further increased when cultured in osteogenic media. This osteostimulative effect of DC-S53P4 constructs was confirmed in vivo, where after 8 weeks implantation, both acellular scaffolds and DPSC-seeded DC-S53P4 constructs formed mineralized and vascularized bone matrices with osteoblastic and osteoclastic cell activity. Surprisingly, however, in vivo micro-CT analysis confirmed that the acellular scaffolds generated larger volumes of bone, already visible at week 3 and exhibiting superior trabecular architecture. The results of this study suggest that DC-S53P4 scaffolds negate the need for stem cell delivery for effective bone tissue regeneration and may expedite their path towards clinical applications.

Background: Lack of education and training in palliative care has been described to be one of the most important barriers to pediatric palliative care implementation. Objective: To examine what factors determine the degree of knowledge and level of comfort Mexican pediatricians have providing pediatric palliative care. Methods: A questionnaire that assessed palliative care concepts was developed and applied online to Mexican pediatricians, both generalists and specialists. Results: A total of 242 pediatricians responded. The majority had not received palliative care education (92.6%) and felt uncomfortable discussing palliative needs with patients and families (92.1%). The mean score of the questionnaire was 6.8 (±1.4) of 10 correct answers. Knowledge in palliative care was associated with exposure to oncologic patients ( P = .01) and previous palliative care education ( P = .02) but inversely related to the pediatrician’s age ( P = .01). Comfort addressing patient’s palliative care needs was associated with knowledge in palliative care ( P < .01), exposure to oncologic patients ( P = .03), and previous education in palliative care ( P = .02). Conclusions: Although Mexican pediatricians have basic knowledge of palliative care concepts, they do not feel comfortable addressing palliative care needs, suggesting that the main barrier for implementing palliative care is not the lack of knowledge but rather feeling uncomfortable when addressing these issues with patients and families. Educational programs should incorporate strategies that could help physicians develop comfort in approaching palliative care patients.

Bone repair after trauma or surgical intervention involves a tightly regulated cascade of events that starts with hemostasis and an inflammatory response, which are critical for successful healing. Nonsteroidal anti-inflammatory drugs (NSAID) are routinely prescribed for pain relief despite their potential inhibitory effect on bone repair. The goal of this study was to determine the impact of administration of the non-selective NSAID diclofenac in the inflammatory phase of bone repair in mice with or without lipopolysaccharide-induced systemic inflammation. Repair of femoral window defects was characterized using micro computed tomography imaging and histological analyses at 2 weeks postoperative. The data indicate (a) impaired bone regeneration associated with reduced osteoblast, osteoclast, and macrophage activity; (b) changes in the number, activity, and distribution of mast cells in regenerating bone; and (c) impaired angiogenesis due to a direct toxic effect of diclofenac on vascular endothelial cells. The results of this study provide strong evidence to support the conjecture that administration of NSAIDs in the first 2 weeks after orthopaedic surgery disrupts the healing cascade and exacerbates the negative effects of systemic inflammation on the repair process.

Tissue hypoxia is a critical driving force for angiogenic and osteogenic responses in bone regeneration and is, at least partly, under the control of the Hypoxia Inducible Factor-1α (HIF-1α) pathway. Recently, the widely used iron chelator deferoxamine (DFO) has been found to elevate HIF-1α levels independent of oxygen concentrations, thereby, creating an otherwise normal environment that mimics the hypoxic state. This has the potential to augment the biological properties of inorganic scaffolds without the need of recombinant growth factors. This pilot study investigates the effect of local delivery of DFO on bone formation and osseointegration of an anatomically matched bone graft substitute, in the treatment of segmental bone defects. Three-dimensional printing was used to create monetite grafts, which were implanted into 10 mm midshaft ulnar defects in eight rabbits. Starting postoperative day 4, one graft site in each animal was injected with 600 μL (200 μM) of DFO every 48 h for six doses. Saline was injected in the contralateral limb as a control. At 8 weeks, micro-CT and histology were used to determine new bone growth, vascularity, and assess osseointegration. Six animals completed the protocol. Bone metric analysis using micro-CT showed a significantly greater amount of new bone formed (19.5% vs. 13.65% p = 0.042) and an increase in bone-implant contact area (63.1 mm2 vs. 33.2 mm2 p = 0.03) in the DFO group compared with control. Vascular channel volume was significantly greater in the DFO group (20.9% vs. 16.2% p = 0.004). Histology showed increased bone formation within the osteotomy gap, more bone integrated with the graft surface as well as more matured soft tissue callus in the DFO group. This study demonstrates a significant increase in new bone formation after delivery of DFO in a rabbit long bone defect bridged by a 3D-printed bioresorbable bone graft substitute. Given the safety, ease of handling, and low expense of this medication, the results of this study support further investigation into the use of iron chelators in creating a biomimetic environment for bone healing in segmental bone loss.

Large bone defects represent a significant challenge for clinicians and surgeons. Tissue engineering for bone regeneration represents an innovative solution for this dilemma and may yield attractive alternate bone substitutes. Three-dimensional (3D) printing with inexpensive desktop printers shows promise in generating high-resolution structures mimicking native tissues using biocompatible, biodegradable, and cost-effective thermoplastics, which are already FDA-approved for food use, drug delivery, and many medical devices. Microporous 3D-printed polylactic acid scaffolds, with different pore sizes (500, 750, and 1000 μm), were designed and manufactured using an inexpensive desktop 3D printer, and the mechanical properties were assessed. The scaffolds were compared for cell growth, activity, and bone-like tissue formation using primary human osteoblasts. Osteoblasts showed high proliferation, metabolic activity, and osteogenic matrix protein production, in which 750 μm pore-size scaffolds showed superiority. Further experimentation using human mesenchymal stem cells on 750 μm pore scaffolds showed their ability in supporting osteogenic differentiation. These findings suggest that even in the absence of any surface modifications, low-cost 750 μm pore-size 3D-printed scaffolds may be suitable as a bone substitute for repair of large bone defects.

Introduction. Childhood depression is a disease that is becoming more frequent. Few reports address parental perception of children depressive symptoms, and these studies have not been carried out in community samples. Objective. To evaluate the correlation and agreement of depressive symptoms in school-age children, and their parent’s perception about emotional and conduct abnormalities. Method. A transversal study was performed in 284 children who filled a Children Depression Inventory. One of their parents filled a Strengths and Difficulty Questionnaire, and correlation between scores and subcomponent scores were assessed. Agreement between presence of depressive symptoms in children and their parent’s perception of abnormal emotional and/or conduct reports was also obtained. Results. 47 children were identified with depressive symptoms. We found moderate correlation between scores. We did not find agreement between the presence of depressive symptoms in the children and the report of emotional and conduct abnormalities by parents. Discussion and conclusion. There is a modest correlation between depressive symptom severity and parental perception of abnormal emotions and/or behaviors. We found no evidence of agreement between these domains in our study, which suggests that parents fail to perceive negative emotions or conducts as depressive symptoms in their children. Parental reports should be addressed by healthcare workers, and their emotional significance should be interpreted. An intentional search of depressive symptomatology in children should be a priority.

Objective Diagnosis of acute appendicitis may be challenging. The current imaging methods have modest sensitivities and specificities. This study aimed to evaluate skin infrared thermal (IRT) imaging as a diagnostic adjunct for acute appendicitis in adults. Methods We conducted a prospective observational study in 51 patients with appendicitis, 20. with abdominal pain (no appendicitis) and 51 healthy controls. Temperature of the skin overlying abdominal lower quadrants, right (RLQ) and left (LLQ), were recorded and compared between groups. Using a machine learning algorithm, we identified which parameters discriminated between groups and compared the diagnostic accuracy of IRT to the final diagnosis. Results RLQ temperature >34 °C discriminate healthy controls and patients with acute abdomen; a delta >0.35 °C in RLQ vs LLQ discriminate patients with and without appendicitis. Compared to the ultrasound-based diagnosis, IRT has a sensitivity of 91% and a specificity of 56% to diagnose appendicitis. Conclusions IRT could be an adjunct tool in the diagnosis of appendicitis in settings with limited resources. Further research is needed to confirm and translate our results into clinical practice.

Immunomodulation strategies are believed to improve the integration and clinical performance of synthetic bone substitutes. One potential approach is the modification of biomaterial surface chemistry to mimic bone extracellular matrix (ECM). In this sense, we hypothesized that coating synthetic dicalcium phosphate (DCP) bioceramics with bone ECM proteins would modulate the host immune reactions and improve their regenerative performance. To test this, we evaluated the in vitro proteomic surface interactions and the in vivo performance of ECM-coated bioceramic scaffolds. Our results demonstrated that coating DCP scaffolds with bone extracts, specifically those containing calcium-binding proteins, dramatically modulated their interaction with plasma proteins in vitro, especially those relating to the innate immune response. In vivo, we observed an attenuated inflammatory response against the bioceramic scaffolds and enhanced peri-scaffold new bone formation supported by the increased osteoblastogenesis and reduced osteoclastogenesis. Furthermore, the bone extract rich in calcium-binding proteins can be 3D-printed to produce customized hydrogels with improved regeneration capabilities. In summary, bone extracts containing calcium-binding proteins can enhance the integration of synthetic biomaterials and improve their ability to regenerate bone probably by modulating the host immune reaction. This finding helps understand how bone allografts regenerate bone and opens the door for new advances in tissue engineering and bone regeneration. Statement of Significance Foreign-body reaction is an important determinant of in vivo biomaterial integration, as an undesired host immune response can compromise the performance of an implanted biomaterial. For this reason, applying immunomodulation strategies to enhance biomaterial engraftment is of great interest in the field of regenerative medicine. In this article, we illustrated that coating dicalcium phosphate bioceramic scaffolds with bone-ECM extracts, especially those rich in calcium-binding proteins, is a promising approach to improve their surface proteomic interactions and modulate the immune responses towards such biomaterials in a way that improves their bone regeneration performance. Collectively, the results of this study may provide a conceivable explanation for the mechanisms involved in presenting the excellent regenerative efficacy of natural bone grafts.

Background Early skin-to-skin contact promotes infant physiologic stability, provides warmth and makes breast milk readily available. Despite the known benefits of early skin-to-skin contact, this practice is not included within standard care in the Mexican public healthcare system. After birth, newborns are usually taken to an incubator in the nursery where they transition to extrauterine life and receive either dextrose 5% or infant formula for their first feed. The aim of this study was to assess if a dual educational intervention in a rural hospital in Mexico could modify current practice and accomplish early skin-to-skin contact and early breastfeeding. Methods A two-step educational intervention was designed. The first step was to educate the labor and birthing staff of the hospital, and the second step was to educate all pregnant women with uncomplicated pregnancies at 36 weeks’ gestation. The educational intervention explored the benefits, implications and steps of early skin-to-skin contact and early breastfeeding. All births were registered for the three month period following the intervention. The time of onset of skin-to-skin (SSC) contact, its duration and time of initiation of breastfeeding were recorded and analyzed using ANOVA testing. Results A total of 142 births met our inclusion criteria, from those, 77% (n = 109) received skin-to-skin contact and early breastfeeding. The average time of initiation of skin-to-skin contact in the first and last month of the study was 18.5 (± 2.2) and 9.6 (± 2.2) minutes of life, respectively (p

Clinical trials have shown the positive effects of local insulin therapy in the formation of new vessels and fibrosis in acute and chronic diabetic wounds without major adverse effects.The aim of this study was to investigate the effects of local insulin use on wound healing in non-diabetic patients.A randomized, split-plot, double-blind, placebo-controlled trial was conducted. Ten non-diabetic patients with full-thickness acute wounds were recruited (5 due to trauma, 3 to burns, and 2 to pressure). All wounds received standard bedside treatment. Each wound was divided into 2 zones. One side received a standard care plus insulin, while the other received standard care plus injection of saline solution. A biopsy specimen was taken from both sites on days 0 and 14. The amount of blood vessel growth and the percentage of fibrosis were evaluated.A significant difference in the number of new vessels was observed on the insulin-treated site (70.6 [29.21]) compared to saline only (26.5 [34.3];We suggest that local insulin administration is a safe therapeutic option for angiogenesis in wounds of non-diabetic patients.Les essais cliniques démontrent les effets positifs de l’insulinothérapie localisée pour former de nouveaux vaisseaux ou une fibrose en cas de plaies aiguës ou chroniques causées par le diabète, sans entraîner de réactions indésirables majeures.La présente étude visait à évaluer les effets de l’utilisation localisée d’insuline chez des patients non diabétiques.Les chercheurs ont réalisé un essai aléatoire et contrôlé contre placebo, en parcelles divisées et à double insu. Ils ont recruté dix patients non diabétiques ayant des plaies aiguës de pleine épaisseur (cinq à cause d’un traumatisme, trois à cause de brûlures et deux à cause de pression). Toutes les plaies ont fait l’objet de soins standards au chevet du patient et chacune a été divisée en deux zones. Une zone faisait l’objet de soins standards avec l’ajout d’insuline et l’autre zone, de soins standards avec l’injection de soluté physiologique. Les chercheurs ont prélevé une biopsie dans chaque zone les jours 0 et 14. Ils ont évalué la croissance des vaisseaux sanguins et le pourcentage de fibrose.Les chercheurs ont observé une différence significative dans le nombre de nouveaux vaisseaux de la zone traitée à l’insuline (70,6 ± 29,21) par rapport à celle traitée à l’aide de soluté physiologique (26,5 ± 34,3;Selon les chercheurs, l’administration localisée d’insuline serait sécuritaire pour l’angiogenèse des plaies des patients non diabétiques.

This study set out to determine the frequency of antiretroviral drug resistance mutations in treatment-naive subjects of the north central Mexican state of San Luis Potosi. Mexican studies of antiretroviral drug resistance mutations have focused mainly on large metropolitan areas and border towns subjected to intense international migrations. This study set forth to describe the frequency of these mutations in a Mexican region less subjected to such migratory influences and more representative of smaller Mexican cities. Thirty-eight full-length pol sequences spanning the protease, reverse-transcriptase, and integrase-encoding regions were obtained from 42 treatment-naive human immunodeficiency virus (HIV)-infected subjects. Most exhibited subtype B homology, but CRF02_AG was also detected. Evidence of APOBEC3 hypermutation was seen in two samples. Calibrated population analysis revealed a surveillance drug resistance mutation prevalence of 4.9% for protease inhibitors, of 2.7% for nucleoside reverse transcriptase inhibitors, of 8.1% for non-nucleoside reverse transcriptase inhibitors, and an overall prevalence of 9.5%. This corresponds to an intermediate level of transmitted drug resistance according to the World Health Organization. The identification of integrase mutations suggests that transmitted drug mutations are being imported, as inhibitors targeting integrase have not been widely used in Mexico. Our results provide a greater understanding of HIV diversity in Mexico and highlight the way internal migrations allow HIV mutations and genetic features to permeate regions less subjected to international migrations. The implications of these findings will become more evident as Mexico hosts increased repatriations of migrants in the coming years.

Background and Objective.Pain evaluation in children can be a difficult task, since it possesses sensory and affective components that are often hard to discriminate. Infrared thermography has previously been used as a diagnostic tool for pain detection in animals; therefore, the aim of this study was to assess the presence of temperature changes during dental extractions and to evaluate its correlation with heart rate changes as markers of pain and discomfort.Methods. Thermographic changes in the lacrimal caruncle and heart rate measurements were recorded in healthy children scheduled for dental extraction before and during the procedure and compared. Afterwards, correlation between temperature and heart rate was assessed.Results. We found significant differences in temperature and heart rate before the procedure and during the dental extraction (mean difference 4.07°C,p<0.001, and 18.11 beats per minute,p<0.001) and no evidence of correlation between both measurements.Conclusion. Thermographic changes in the lacrimal caruncle can be detected in patients who undergo dental extractions. These changes appear to be stable throughout time and to possess very little intersubject variation, thus making them a candidate for a surrogate marker of pain and discomfort. Future studies should be performed to confirm this claim.

The use of solid fuels for cooking and heating is likely to be the largest source of indoor air pollution on a global scale; these fuels emit substantial amounts of toxic pollutants such as polycyclic aromatic hydrocarbons (PAHs) when used in simple cooking stoves (such as open "three-stone" fires). Moreover, indoor air pollution from biomass fuels is considered an important risk factor for human health. The aim of this study was to evaluate the relationship between exposure to PAHs from wood smoke and vascular dysfunction; in a group of Mexican women that use biomass combustion as their main energy source inside their homes. We used 1-hydroxypyrene (1-OHP) as an exposure biomarker to PAHs and it was assessed using high performance liquid chromatography. The endothelium-dependent vasodilation was assessed through a vascular reactivity compression test performed with a pneumatic cuff under visualization of the brachial artery using high resolution ultrasonography (HRU). Assessment of the carotid intima-media thickness (CIMT) was used as an atherosclerosis biomarker (also assessed using HRU); and clinical parameters such as anthropometry, blood pressure, glucose, triglycerides, total cholesterol, HDL cholesterol, LDL cholesterol, among others were also evaluated. The mean concentration of urinary 1-OHP found in exposed women was 0.46±0.32μmol/mol Cr (range: 0.086-1.23μmol/mol Cr). Moreover, vascular dysfunction (diminished endothelium dependent vasodilation) was found in 45% of the women participating in the study. Association between vascular function and 1-OHP levels was found to be significant through a logistic regression analysis (p=0.034; r(2)=0.1329). Furthermore, no association between CIMT and clinical parameters, urinary 1-OHP levels or vascular dysfunction was found. Therefore, with the information obtained in this study, we advocate for the need to implement programs to reduce the risk of exposure to PAHs in communities that use biomass fuels as a main energy source.

Resumen Antecedentes. El autolesionismo comprende las conductas encaminadas al daño físico de la propia persona. Estas conductas son un fenómeno en aumento entre los adolescentes y pueden ser consideradas como predictores de muerte por suicidio, por lo que su identificación oportuna es una necesidad. El Cuestionario de autolesionismo permite identificar la presencia de pensamientos y conductas autolesivas. Objetivo. Validar el cuestionario de autolesionismo al español y determinar su valor diagnóstico para detectar autolesionismo en adolescentes mexicanos que reciben atención psiquiátrica. Método. Se realizó el procedimiento de traducción-retrotraducción para la adaptación de la escala al idioma español. Se seleccionó una muestra de 106 adolescentes de entre 11 y 17 años de edad en seguimiento por trastornos afectivos o ansiedad para la aplicación de la escala. Se evaluó la consistencia interna mediante el coeficiente de fiabilidad α de Cronbach y se determinó el coeficiente de correlación de Spearman por medio de una prueba test-retest tres meses después de la primera administración. Posteriormente, se realizó una revisión del expediente clínico para determinar la presencia de autolesionismo y realizar un análisis de la sensibilidad y especificidad del cuestionario para detectar el fenómeno. Resultados. El cuestionario traducido presentó un α de Cronbach de 0.960 y una estabilidad temporal a tres meses de 0.9787. La sensibilidad para detectar autolesionismo fue de 97.96%, y la especificidad de 54.39%, comparadas con el expediente clínico. Discusión y conclusión. Los resultados de este estudio sugieren que la escala traducida es una herramienta válida y confiable para detectar autolesionismo en adolescentes mexicanos. La identificación rápida y oportuna de esta población es crucial para evitar suicidios. El uso de la escala puede ayudar a identificar a estos pacientes.

Introduction The Modified Merle d'Aubigne-Postel Score and the Harris Hip Score are commonly used to assess the functional outcomes after acetabular fractures. A previous report showed that correlation between scores is good, that there is poor concordance among functional classes, and that the distribution of the scores is highly asymmetrical. Several issues were not addressed in this report, mainly that the data set was treated as transversal data without comparison of scores through time; therefore the objective of this article is to assess the degree of correlation and concordance between the Modified Merle d'Aubigne-Postel Score and the Harris Hip Score during the first 9 months after acetabular fracture treatment. Methods Both scores were recorded in a cohort of 23 previously healthy patients after 3, 6 and 9 months after fixation of acetabular fractures. Through a mixed-effects repeated measures model, we assessed differences between standardized scores. Pearson’s interclass correlation coefficients for full scores and each of their domains, as well as agreement for clinical graduation classification was calculated. Results Between score correlation was 89%. We found no differences between scores at 3, 6 and 9 month follow-ups. Agreement between scores was 0.95, while agreement for clinical graduation classification was 0.67. Discussion Very short term correlation and concordance between scores is excellent, while concordance for clinical graduation classification is modest. We suggest the widespread use of the simpler score.

Certain genotypic combinations of killer-cell immunoglobulin-like receptors (KIR) and human leukocyte antigens (HLA) have been associated with favourable outcomes after exposure to human immunodeficiency virus in Caucasoid and African populations. Human immunodeficiency virus (HIV) infection is characterized by a rapid exhaustion of CD4 cells, which results in impaired cellular immunity. During this early phase of infection, it is thought that the natural killer (NK) cells represent the main effector arm of the host immune response to HIV. This study investigates whether KIR and HLA factors are associated to CD4 T cell numbers after HIV infection in Mexican mestizos as assessed at the time of initial medical evaluation and subsequent clinical follow-up. KIR and HLA-B gene carrier frequency differences were compared between groups of patients stratified by CD4 T cell numbers as assessed during their first medical evaluation (a point in time at which all patients were anti-retroviral therapy naive). In addition, the influence that these genetic factors have on averaged historical CD4 cell counts in patients subjected to follow-up (mostly therapy-experienced) was also evaluated. Our results suggest a protective role for the HLA-Bw4 and KIR3D + Bw4 combination in both therapy-naive and therapy-experienced patients. This report furthers our understanding on the way that immune genes modulate HIV disease progression in less-studied human populations such as the Mexican mestizos with a special focus on CD4 T cell number and behaviour.

17 Background: Neutrophil-to-lymphocyte ratio (NLR) has been identified as a biomarker for a number of malignancies, with higher ratios being associated with poorer oncologic outcomes. Rather than purely an indicator of advanced disease there is emerging evidence that neutrophils are directly implicated in facilitating cancer progression, and thus alterations and trends of neutrophil counts and NLR during different phases of treatment may reflect a change in oncologic outcome that is as important, or more so, as the absolute count or NLR at baseline. The aim of this study is to investigate the prognostic role of neutrophil-to-lymphocyte ratio trends during the treatment trajectory of patients with esophageal adenocarcinoma. Methods: This is a retrospective study of patients who underwent esophagectomy for esophageal adenocarcinoma between 2005-2016. NLR was measured at three time points: baseline, during neoadjuvant chemotherapy (NAC), and in the late postoperative period. Primary outcomes were overall (OS) and disease-free survival (DFS). Results: 333 patients met our inclusion criteria. Mean age was 65.6 years and 82% of patients were males. The majority of patients had locally advanced disease; 75% had clinical T3 disease and 59% had clinical N-positive disease. NAC was administered in 65.6% of patients. Increasing NLR trends between baseline and late postoperative periods was associated with worse OS (3-year OS 56.1% vs. 71.9%, p=0.045). Patients in the high NLR group before and after treatment did worse than those who moved from high to low groups (3-year OS 42.8% vs. 69.2%, p=

180 Background: Esophago-gastric cancers are aggressive malignancies requiring numerous investigations to plan complex multi-modal therapy. The path from initial diagnosis to treatment can be associated with a long delay. This delay and complex patient trajectory may impact quality of life. Given the poor prognosis and highly symptomatic nature of upper GI cancer, a clear and timely access to treatment of crucial importance. We sought to determine the impact of a newly implemented streamlined and structure interdisciplinary pathway for newly diagnosed esophageal and gastric cancer on access times to treatment and quality of life (QoL). Methods: A streamlined pathway for patients referred to a high volume Upper GI Cancer clinic was generated with input from physicians, nutritionists, specialized nurses, and social workers. New diagnosis of esophageal or gastric cancer from 2014-16 were enrolled in this program and consenting patients completed serial QoL questionnaires (ESAS) at baseline, pre-treatment, 1 month post treatment. Dysphagia (DS) was quantified on a 5 point scale. Time intervals (days) were evaluated at various points between diagnosis and start of treatment (diagnosis, CT imaging, first visit with upper GI program, start of treatment). Data presented as median(IQR), * p < 0.05. Results: Of the 251 patients with Upper GI cancer, 153 (61%) consented to participate including 140 esophageal/EGJ and 13 gastric cancer patients. Clinical stage distribution was 17.9% I, 30.7% II, 42.6% III, 8.7% IV. Of the 82 Esoph/EGJ patients with completed QoL questionnaires, 15 (18.3%) patients had severe dysphagia (DS = 3-4) and were prioritized for treatment. Patients with severe dysphagia had reduced time from index endoscopy to treatment (29 (16.3-39.3) vs 43 (32.8-68.0)days)* and first Upper GI clinic to treatment (15 (8.0-23.0) vs 25 (21.0-36.0)*. ESAS surveys showed increased QoL for both patients with and without dysphagia from baseline to pre-treatment indicating that simply entry into the streamlined program improved QoL. Conclusions: Structured interdisciplinary investigative and treatment programs for upper GI cancers can expedite time to treatment and improve QoL.