Lysyl oxidase-like 1-antisense 1 (LOXL1-AS1) lncRNA differentially regulates gene and protein expression, signaling and morphology of human ocular cells.

Pseudoexfoliation glaucoma (PEXG) is characterized by dysregulated extracellular matrix (ECM) homeostasis that disrupts conventional outflow function and increases intraocular pressure (IOP). Prolonged IOP elevation results in optic nerve head damage and vision loss. Uniquely, PEXG is a form of open angle glaucoma that has variable penetrance, is difficult to treat and does not respond well to common IOP-lowering pharmaceuticals. Therefore, understanding modulators of disease severity will aid in targeted therapies for PEXG. Genome-wide association studies have identified polymorphisms in the long non-coding RNA lysyl oxidase-like 1-antisense 1 (LOXL1-AS1) as a risk factor for PEXG. Risk alleles, oxidative stress and mechanical stretch all alter LOXL1-AS1 expression. As a long non-coding RNA, LOXL1-AS1 binds hnRNPL and regulates global gene expression. In this study, we focus on the role of LOXL1-AS1 in the ocular cells (trabecular meshwork and Schlemm's canal) that regulate IOP. We show that selective knockdown of LOXL1-AS1 leads to cell-type-specific changes in gene expression, ECM homeostasis, signaling and morphology. These results implicate LOXL1-AS1 as a modulator of cellular homeostasis, altering cell contractility and ECM turnover, both of which are well-known contributors to PEXG. These findings support LOXL1-AS1 as a key target for modifying the disease.

Dermatological toxicity associated with the use of gilteritinib in relapsed acute myeloid leukemia with FLT3 mutation: a case report.

We present a case of a patient diagnosed with FLT3 mut+ acute myeloid leukemia with FLT3 and NMP1 mutations who did not respond to standard induction and consolidation treatment with chemotherapy. Due to the FLT3mut+ gene mutation and intermediate cytogenetic risk, treatment with gilteritinib is requested. After treatment she experienced a neutrophilic dermatosis and granuloma annulare that was resolved with gilteritinib dose reduction and specific treatment in coordination with the dermatology department.

Successful Liberation from Acute Kidney Replacement Therapy in Critically Ill Patients: A Prospective Cohort Study.

INTRODUCTION: Recovery of kidney function to liberate patients from acute kidney replacement therapy (AKRT) is recognized as a vital patient-centered outcome. The lack of specific guidelines providing specific recommendations on therapy interruption is an important obstacle. We aimed to determine the prevalence of successful discontinuation of AKRT and its predictive factors after the elaboration of clinical protocol with these recommendations. METHODOLOGY: A prospective cohort study was performed with 156 patients at a public Brazilian university hospital between July 2020 and July 2021. RESULTS: Success and hospital discharge were achieved for most patients (84.6% and 89%, respectively). Multivariable logistic regression analysis showed that C-reactive protein (CRP), urine output, and creatinine clearance at the time of interruption were variables associated with discontinuation success (OR: 0.943, CI: 0.905-0.983, p = 0.006; OR: 1.078, CI: 1.008-1.173, p = 0.009 and OR: 1.091, CI: 1.012-1.213, p = 0.004; respectively). The areas under the curve for CRP, urine output, and creatinine clearance at the time of interruption were 0.78, 0.62, and 0.82, respectively. Both CRP and creatinine clearance were good predictors of successful liberation of AKRT. The optimal cutoff value of them had sensitivity and specificity of 0.88 and 0.87, 0.91 and 0.90, respectively. The use of noradrenalin at the time of interruption (OR: 0.143, CI: 0.047-0.441, p = 0.001) and successful discontinuation (OR: 3.745, CI: 1.047-13.393, p = 0.042) were identified as variables associated with hospital discharge. CONCLUSION: Our results show the factors related to success in discontinuing AKRT are the CRP, creatinine clearances, and urinary output at the time of AKRT interruption and it was associated with lower mortality.

Implementation of a hospital-based end-of-life and bereavement care program in a latin American middle-income country. A source of light and compassion in the midst of cloudy times.

BACKGROUND: The death of a child is one of the most devastating events a family can face, resulting in significant physical and psychosocial morbidity. Bereavement support programs have been developed in high-income contexts to address this need. However, little is known about implementing bereavement programs in low-and middle-income countries (LMICs). Here, we describe the implementation of a bereavement program for parents whose children died due to cancer or other catastrophic illnesses. METHODS: We conducted a retrospective analysis to describe the implementation of a hospital-based End of Life (EoL) care and bereavement program. This program was developed in several stages, including an assessment of bereaved families, development program guidelines, staff training, piloting of the program, refinement, and standardization. The program was developed between 2019 and 2021 in a nonprofit, teaching hospital and referral center for southwestern Colombia. RESULTS: Several tools were developed as key components of the bereavement program: a virtual bereavement course; guidance for EoL and bereavement communication and care, memory making, and follow-up calls; a condolence letter template, and group support workshops. A total of 956 healthcare professionals were trained, 258 follow-up calls to bereaved parents were made, 150 individual psychological follow-ups to parents with complicated grief occurred, 79 condolence letters were sent, and 10 support group workshops were carried out. Challenges were identified and overcome, such as limited resources and staff, and cultural perceptions of death. In 2021, this program received an award by the hospital as the Best Strategy to Humanize Healthcare. CONCLUSIONS: This study highlights the feasibility of developing and implementing EoL and bereavement care programs for parents and families within hospitals in LMICs. Lack of resources, staff, and training are some of the identified challenges to implementation. Utilizing methodological tools allows us to identify facilitator factors and deliverable outcomes of our EoL and bereavement program. This model provides a valuable framework for resource-limited settings.

Children with cancer at the end of life in a middle-income country: integrated pediatric palliative care improves outcomes.

BACKGROUND: In 2020, the Global Cancer Observatory reported 280,000 cases of childhood cancer worldwide, with a higher burden of disease and mortality rates in low- and middle-income countries. In 2022, the National Institute of Health reported 1708 new cases of childhood cancer in Colombia and an overall survival rate of approximately 55%. The aim of this study is to compare outcomes in children with cancer in the hospital setting during the last 72 h of life who received concurrent Pediatric Palliative Care (PPC) versus oncology care alone. METHODS: An observational descriptive study was conducted between January 2013 and June 2022 in a center for pediatric patients with oncological diagnoses. In 2017, the PPC team was created. Patients between 28 days and 17 years of age who were hospitalized at least 72 h before death were included. A retrospective review of the medical records of patients in the last 72 h of life was performed. Two cohorts were established: oncology-alone group received exclusive management by oncology, and oncology and PPC received concurrent oncology and PPC management since the diagnosis. RESULTS: We evaluated 257 medical records of deceased pediatric patients with cancer diagnoses. For the first cohort (2013-2017), 136 patients were included; for the second cohort (2018 and 2022), 121 patients were evaluated. The most frequent diagnosis was leukemia [47.1% (n = 121)]. No significant difference was found in either group between dyspnea, pain, and seizures. Dyspnea was the most frequent symptom in both groups. Agitation and anxiety were reported more frequently in children from the oncology-alone group (22.1% and 13.2%, respectively). The oncology and PPC group received more psychology and social work consultation (94.2% and 70.2% vs. 84.6 and 54.4% in the oncology alone group) and had a higher percentage of advance care planning (79.3% vs. 62.5% in the oncology alone group). CONCLUSIONS: This retrospective study highlights that PPC at the end of life (EoL) offers a holistic approach to the physical and psychosocial symptoms experienced by children with cancer; these patients received more comfort through symptom management and less aggressive treatment at the EoL. The availability of a PPC team may contribute to improvements in the quality of end-of-life care. TRIAL REGISTRATION: retrospectively registered.

Evaluation of the Renal Angina Index to Predict the Development of Acute Kidney Injury in Children With Sepsis Who Live in Middle-Income Countries.

OBJECTIVE: The renal angina index (RAI) provides a clinically feasible and applicable tool to identify critically ill children at risk of severe acute kidney injury (AKI) in high-income countries. Our objective was to evaluate the performance of the RAI as a predictor of the development of AKI in children with sepsis in a middle-income country and its association with unfavorable outcomes. METHODS: This is a retrospective cohort study in children with sepsis hospitalized in the pediatric intensive care unit (PICU) between January 2016 and January 2020. The RAI was calculated 12 hours after admission to predict the development of AKI and at 72 hours to explore its association with mortality, the need for renal support therapy, and PICU stay. RESULTS: We included 209 PICU patients with sepsis with a median age of 23 months (interquartile range, 7-60). We found that 41.1% of the cases (86/209) developed de novo AKI on the third day of admission (KDIGO 1, 24.9%; KDIGO 2, 12.9%; and KDIGO 3, 3.3%).Overall mortality was 8.1% (17/209), higher in patients with AKI (7.7% vs 0.5%, P < 0.01). The RAI on admission was able to predict the presence of AKI on day 3 (area under the curve (AUC), 0.87; sensitivity, 94.2%; specificity, 100%; P < 0.01), with a negative predictive value greater than 95%. An RAI greater than 8 at 72 hours was associated with a greater risk of mortality (adjusted odds ratio [aOR], 2.6; 95% confidence interval [CI], 2.0-3.2; P < 0.01), a need for renal support therapy (aOR, 2.9; 95% CI, 2.3-3.6; P < 0.01), and a PICU stay of more than 10 days (aOR, 1.54; 95% CI, 1.1-2.1; P < 0.01). CONCLUSIONS: The RAI on the day of admission is a reliable and accurate tool for predicting the risk of developing AKI on day 3, in critically ill children with sepsis in a limited resource context. A score greater than eight 72 hours after admission is associated with a higher risk of death, the need for renal support therapy, and PICU stay.

Do 3D-printed and milled tooth-supported complete monolithic zirconia crowns differ in accuracy and fit? A systematic review and meta-analysis of in vitro studies.

STATEMENT OF PROBLEM: Additive (3-dimensional printing) and subtractive (milling) methods are digital approaches to fabricating zirconia restorations. Comparisons of their resultant fabrication accuracy and restoration fit are lacking. PURPOSE: The purpose of this systematic review and meta-analysis was to evaluate the accuracy and fit of monolithic zirconia crowns fabricated by 3-dimensional printing and milling. MATERIAL AND METHODS: The PubMed (Medline), Scopus, Embase, Web of Science, Cochrane Library, and Google Scholar databases were searched up to August 2023. Eligible records were included, and the standardized mean difference (SMD) analyzed 4 outcomes: marginal fit, intaglio fit, trueness, and precision. Publication bias was analyzed with Trim-and-fill, the Egger regression test, and Begg funnel plot. Methodological quality was rated using the QUIN tool. RESULTS: A total of 15 publications were found eligible out of the initial 6539 records. The 3-dimensional printing group demonstrated a lower marginal fit (SMD=1.46, 95% CI=[0.67, 2.26], P<.001; I2=83%, P<.001) and trueness (SMD=0.69, 95% CI=[0.20, 1.18], P=.006; I2=88%, P<.001) and a significantly higher precision (SMD=-2.19, 95% CI=[-2.90, -1.48], P<.001; I2=56%, P=.045). The intaglio fit did not differ significantly across the study groups (SMD=0.77, 95% CI=[-0.22, 1.77], P=.127; I2=87%, P<.001). CONCLUSIONS: Given the high degree of heterogeneity, it can be cautiously concluded that while 3-dimensional printing led to greater precision, the outcomes of the 2 accuracy and adaptation parameters most crucial to the longevity of the restorations-trueness and marginal fit-showed the superiority of the milling technique.

Development of an in-house bone marrow collection kit: The Catalan bone marrow transplantation group experience.

BACKGROUND AND OBJECTIVES: Bone marrow (BM) harvesting is one of the essential sources of stem cells for haematopoietic stem cell transplantation. In 2019, commercial BM collection kits became unavailable in Europe. Consequently, we created an in-house BM collection kit as an alternative. MATERIALS AND METHODS: We compared two groups of BM collections. The first collections were taken using an in-house kit from June 2022 through February 2023 and the second with a commercial kit from February 2021 through May 2022. These all took place at seven collection centres (CC). We analysed the harvest quality (cell blood count, CD34+ cells, viability, potency and sterility), the incidents occurring with each kit and the time to neutrophil and platelet engraftment in recipients. RESULTS: A total of 23 donors underwent BM harvesting with the in-house kit and 23 with the commercial one. Both cohorts were comparable regarding donor characteristics, CC and time to procedure. No statistical differences were found in harvest quality between the in-house and commercial kits. A new transfusion set was required in three BM harvests (13%) with the in-house kit because of filter clogging. The median time to neutrophil and platelet engraftment was 21 days for both cohorts and 29 days (in-house) and 33 days (commercial), p = 0.284, respectively. CONCLUSION: The in-house BM collection kit offers a real approach to solve the diminished supply of commercial kits. A higher risk of filter clogging was observed compared with commercial kits due to the lack of 850 and 500 µm filters.

Factors predicting successful discontinuation of acute kidney replacement therapy: A retrospective cohort study.

BACKGROUND: Treatment for severe acute kidney injury (AKI) typically involves the use of acute kidney replacement therapy (AKRT) to prevent or reverse complications. METHODOLOGY: We aimed to determine the prevalence of successful discontinuation of AKRT and its predictive factors. A retrospective cohort study was performed with 316 patients hospitalized at a public Brazilian university hospital between January 2011 and June 2020. RESULTS: Success and hospital discharge were achieved for most patients (85% and 74%, respectively). Multivariable logistic regression analysis showed that C-reactive protein (CRP), urine output, and need mechanical ventilation at the time of interruption were variable associated with discontinuation success (OR 0.969, CI 0.918-0.998, p = 0.031; OR 1.008, CI 1.001-1.012, p = 0.041 and OR 0.919, CI 0.901-0.991, p = 0.030; respectively), while the absence of comorbidities such as chronic kidney disease (OR 0.234, CI 0.08-0.683, p = 0.008), cardiovascular disease (OR 0.353, CI 0.134-0.929, p = 0.035) and hypertension (OR 0.278, CI 0.003-0.882, p = 0.009), as well as pH values at the time of AKRT indication (OR 1.273, CI 1.003-1.882, p = 0.041), mechanical ventilation at the time of interruption (OR 0.19, CI 0.19-0.954, p = 0.038) and successful discontinuation (OR 8.657, CI 3.135-23.906, p < 0.001) were identified as variables associated with hospital discharge. CONCLUSION: These results show that clinical conditions such as comorbidities, urine output, and mechanical ventilation, and laboratory variables such as pH and CRP are factors associated with hospital discharge and AKRT discontinuation success, requiring larger studies for confirmation.

Forest and woodland replacement patterns following drought-related mortality.

Forest vulnerability to drought is expected to increase under anthropogenic climate change, and drought-induced mortality and community dynamics following drought have major ecological and societal impacts. Here, we show that tree mortality concomitant with drought has led to short-term (mean 5 y, range 1 to 23 y after mortality) vegetation-type conversion in multiple biomes across the world (131 sites). Self-replacement of the dominant tree species was only prevalent in 21% of the examined cases and forests and woodlands shifted to nonwoody vegetation in 10% of them. The ultimate temporal persistence of such changes remains unknown but, given the key role of biological legacies in long-term ecological succession, this emerging picture of postdrought ecological trajectories highlights the potential for major ecosystem reorganization in the coming decades. Community changes were less pronounced under wetter postmortality conditions. Replacement was also influenced by management intensity, and postdrought shrub dominance was higher when pathogens acted as codrivers of tree mortality. Early change in community composition indicates that forests dominated by mesic species generally shifted toward more xeric communities, with replacing tree and shrub species exhibiting drier bioclimatic optima and distribution ranges. However, shifts toward more mesic communities also occurred and multiple pathways of forest replacement were observed for some species. Drought characteristics, species-specific environmental preferences, plant traits, and ecosystem legacies govern postdrought species turnover and subsequent ecological trajectories, with potential far-reaching implications for forest biodiversity and ecosystem services.

Therapeutic management of allergic rhinitis: a survey of otolaryngology and allergology specialists.

PURPOSE: To describe the current management of allergic rhinitis (AR) in Spain's specialized care according to the next-generation ARIA guidelines. METHODS: An ad hoc online survey was distributed to AR specialists to appraise their perceptions of pathology management, knowledge of next-generation ARIA guidelines (including four case clinics), and their views on the principal barriers and the actions to proper AR management. RESULTS: one hundred nine specialists (38.5% allergists and 61.5% otolaryngologists) completed the study survey. Most respondents (87.2%) had read all or part of the Next-Generation ARIA Guidelines, and 81.6% stated that they considered the patient's treatment choice preferences. However, only 20.2% of specialists answered according to the recommendations in at least three of the four case clinics. Most participants failed to fulfill the treatment duration according to the guidelines. They regarded the lack of multidisciplinary teams (21.7%) and the lack of patients' AR treatment adherence (30.6%) as the most critical healthcare system- and patient-related barriers to the correct management of AR, respectively. Promoting patients' education was considered the most crucial action to improve it. CONCLUSION: Despite specialists' awareness, there is a gap between the evidence-based guidelines' recommendations and their implementation in clinical practice.

Mechanical harvesting at dawn in a super-high-density table olive orchard: effect on the quality of fruits.

BACKGROUND: Mechanical harvesting with over-the-row harvesters in super-high-density (SHD) table olive orchards increases the effectiveness of fruit removal, although bruising can limit the fruit quality. Additionally, an early harvest in periods less favourable to quality production is increasingly frequent as a result of global warming. The present study explores the impact on olive quality of harvesting at dawn when the environmental temperature is low. The study was carried out for 2 years on two cultivars with different tolerance to bruising ('Manzanilla de Sevilla' and 'Manzanilla Cacereña'), grown in SHD conditions and harvested at two timepoints: dawn and morning. RESULTS: Fruit morphology was not modified by the moment of harvest in either of the cultivars. Fruit harvested at dawn produced less CO2 and ethylene and was less damaged externally and internally compared to fruit harvested in the morning. However, environmental conditions throughout development influenced the response because the highest values of bruising (incidence, area and volume of damaged area), total internal damage and the number of tissue ruptures increased in the year with the hottest summer, and the differences between harvest treatments were less evident. CONCLUSION: Mechanical harvesting at dawn contributes to reducing the damage in olive fruit. © 2022 The Authors. Journal of The Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.

Role of cholesterol metabolism in the anticancer pharmacology of selective estrogen receptor modulators.

Selective estrogen receptor modulators (SERMs) are a class of compounds that bind to estrogen receptors (ERs) and possess estrogen agonist or antagonist actions in different tissues. As such, they are widely used drugs. For instance, tamoxifen, the most prescribed SERM, is used to treat ERα-positive breast cancer. Aside from their therapeutic targets, SERMs have the capacity to broadly affect cellular cholesterol metabolism and handling, mainly through ER-independent mechanisms. Cholesterol metabolism reprogramming is crucial to meet the needs of cancer cells, and different key processes involved in cholesterol homeostasis have been associated with cancer progression. Therefore, the effects of SERMs on cholesterol homeostasis may be relevant to carcinogenesis, either by contributing to the anticancer efficacy of these compounds or, conversely, by promoting resistance to treatment. Understanding these aspects of SERMs actions could help to design more efficacious therapies. Herein we review the effects of SERMs on cellular cholesterol metabolism and handling and discuss their potential in anticancer pharmacology.

Electrochemical Detection for Isothermal Loop-Mediated Amplification of Pneumolysin Gene of Streptococcus pneumoniae Based on the Oxidation of Phenol Red Indicator.

A highly sensitive electrochemical methodology for end-point detection of loop-mediated isothermal nucleic acid amplification reactions was developed. It is based on the oxidation process of phenol red (PR), commonly used as a visual indicator. The dependence of its redox process on pH, which changes during amplification, allows performing quantitative measurements. Thus, the change in the oxidation potential of PR during the amplification is used, for the first time, as the analytical signal that correlates with the number of initial DNA copies. As a proof-of-concept, the amplification of the pneumolysin gene from Streptococcus pneumoniae, one of the main pathogens causing community-acquired pneumonia, is performed. Combination of isothermal amplification with electrochemical detection, performed on small-size flexible electrodes, allows easy decentralization. Adaptation to the detection of other pathogens causing infectious diseases would be very useful in the prevention of future epidemics.

Glycosphingolipid metabolism and its role in ageing and Parkinson's disease.

It is well established that lysosomal glucocerebrosidase gene (GBA) variants are a risk factor for Parkinson's disease (PD), with increasing evidence suggesting a loss of function mechanism. One question raised by this genetic association is whether variants of genes involved in other aspects of sphingolipid metabolism are also associated with PD. Recent studies in sporadic PD have identified variants in multiple genes linked to diseases of glycosphingolipid (GSL) metabolism to be associated with PD. GSL biosynthesis is a complex pathway involving the coordinated action of multiple enzymes in the Golgi apparatus. GSL catabolism takes place in the lysosome and is dependent on the action of multiple acid hydrolases specific for certain substrates and glycan linkages. The finding that variants in multiple GSL catabolic genes are over-represented in PD in a heterozygous state highlights the importance of GSLs in the healthy brain and how lipid imbalances and lysosomal dysfunction are associated with normal ageing and neurodegenerative diseases. In this article we will explore the link between lysosomal storage disorders and PD, the GSL changes seen in both normal ageing, lysosomal storage disorders (LSDs) and PD and the mechanisms by which these changes can affect neurodegeneration.

The digestive tract sections of the sea cucumber Isostichopus badionotus reveal differences in composition, diversity, and functionality of the gut microbiota.

For the first time, this study analyses the composition and diversity of the gut microbiota of Isostichopus badionotus in captivity, using high-throughput 16S rRNA sequencing, and predicts the metagenomic functions of the microbiota. The results revealed a different composition of the gut microbiota for the foregut (FG) and midgut (MG) compared to the hindgut (HG), with a predominance of Proteobacteria, followed by Actinobacteria, Bacteroidetes, and Firmicutes. The FG and MG demonstrated a greater bacterial diversity compared to the HG. In addition, a complex network of interactions was observed at the genus level and identified some strains with probiotic and bioremediation potentials, such as Acinetobacter, Ruegeria, Streptococcus, Lactobacillus, Pseudomonas, Enterobacter, Aeromonas, Rhodopseudomonas, Agarivorans, Bacillus, Enterococcus, Micrococcus, Bifidobacterium, and Shewanella. Predicting metabolic pathways revealed that the bacterial composition in each section of the intestine participates in different physiological processes such as metabolism, genetic and environmental information processing, organismal systems, and cellular processes. Understanding and manipulating microbe--host-environment interactions and their associated functional capacity could substantially contribute to achieving more sustainable aquaculture systems for I. badionotus.

Effects of dietary marine sulphated polysaccharides (Algimun®) on growth performance, immune responses and disease resistance of juvenile gilthead seabream (Sparus aurata) to Photobacterium damselae subsp. piscicida.

The present study evaluated the effects of a dietary mix of marine sulphated polysaccharides, named Algimun® (AL), supplementation to gilthead seabream (Sparus aurata) juveniles in terms of growth performance, immune responses, and resistance against Photobacterium damselae subsp. piscicida. A total of 240 fish (initial mean weight of 6.00 ± 0.03 g) was randomly separated into 12 tanks (400 L, 20 fish per tank) distributed in four replicates. Fish were fed three experimental diets: a basal diet (Control), and a basal diet with two inclusion rates of Algimun® as 3 g/kg (AL0.3) and 5 g/kg (AL0.5) for 30 days before bacterial infection with P. damselae subsp. piscicida. After a 30-day feeding-period, growth performance was significantly improved in AL0.3 and AL0.5 groups compared to the control group (P < 0.05). AL0.3 and AL0.5 groups showed significantly higher lysozyme activity and myeloperoxidase activity when compared to the control group (P < 0.05). The gene expression of immune mediators (IL-1ß, IL-6, IL-10, IL-18, TNF-α and COX-2) was significantly upregulated in the intestine, spleen and head kidney in AL0.3 and AL0.5 groups when compared to the control group (P < 0.05). Eight days post-challenge, the survival rate against P. damselae subsp. piscicida was numerically higher in fish within AL0.3 and AL0.5 groups compared to control (+20%). The study findings suggest that marine sulphated polysaccharides (Algimun®) could be used as an immunomodulator in gilthead seabream to support animal's health and boost resistance in case of disease outbreak.

Epitheliosis is a histopathological finding associated with malignancy and poor prognosis in dogs with mammary tumors.

Canine mammary epitheliosis (ME) is a poorly studied dysplasia that may have premalignant potential. In this study, the clinicopathological relevance of ME was prospectively studied in 90 female dogs with mammary tumors (MTs) that underwent radical mastectomy. ME distribution, extent, and coexistence with benign and malignant MTs were evaluated for each case (505 mammary glands). ME was macroscopically undetectable and was present in 47/90 (52%) cases, frequently bilateral. In dogs with malignant MTs and ME, diffuse ME throughout the mammary chain was present in 10/39 (26%) cases. A histological ME-carcinoma transition was evident in certain histotypes. By immunohistochemistry (AE1/AE3, cytokeratin 14 [CK-14], CK-8/18, vimentin, calponin, p63, Ki-67, estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2), ME was a slow-growing, triple-negative process with a strong predominance of basal-like nonmyoepithelial cells. ME was associated with older dogs (P = .016), malignant tumors (P = .044), worse clinical stages (P = .013), lymph node metastasis (LNM, P = .021), higher histological grade tumors (P = .035), and shorter overall survival (OS) in univariate analysis (P = .012). Interestingly, ME was distantly located to the malignant tumor in most cases (P = .007). In multivariate analyses, LNM (P = .005), histological grade (P = .006), and tumor size (P = .006) were independent predictors of OS. For the pathologist, the observation of ME should be clearly stated in the MT biopsy report to alert the surgeon/oncologist. Given the differences between canine ME and its human histopathological counterpart (atypical ductal hyperplasia), "epitheliosis" should remain the preferred term for the dog.

Use of ultrasound and targeted physiotherapy to manage nerve sutures placed under joint flexion: a case series.

BACKGROUND: Joint flexion to diminish the gap and avoid nerve grafts fell into disuse for decades, but recently attention for using this technique was regained. We report a case series of nerve suture under joint flexion, ultrasound monitoring, and physiotherapy. Our main objective was to determine how effective this multimodality treatment is. METHODS: A retrospective review of 8 patients treated with direct repair with joint flexion was done. Depending on the affected nerve, either the knee or the elbow was flexed intraoperatively to determine if direct suturing was possible. After surgery, the limb was held immobilized. Through serial ultrasounds and a physiotherapy program, the limb was fully extended. If a nerve repair rupture was observed, the patient was re-operated and grafts were used. RESULTS: Of the eight nerve sutures analyzed, four sustained a nerve rupture revealed by US at an early stage, while four did not show any sign of dehiscence. In the patients in whom the nerve suture was preserved, an early and very good response was observed. Ultrasound was 100% accurate at identifying nerve suture preservation. Early detection of nerve failure permitted early re-do surgery using grafts without flexion, ultimately determining good final results. CONCLUSIONS: We observed a high rate of dehiscence in our group of patients treated with direct repair and joint flexion. We believe this was due to an incorrect use of the immobilization device, excessive movement, or a broken device. In opposition to this, we observed that applying direct nerve sutures and joint flexion offers unusually good and fast results. If this technique is employed, it is mandatory to closely monitor suture status with US, together with physiotherapy providing progressive, US-guided extension of the flexed joint. If nerve rupture occurs, the close monitoring dictated by this protocol should ensure the timely application of a successful graft repair.