[Outbreak of Raoultella ornithinolytica infection in patients cared at a hemodialysis center]. / Brote de infección por Raoultella ornithinolytica en pacientes atendidos en un centro de hemodiálisis.

OBJECTIVE: In July 2022, an outbreak of Raoultella ornithinolytica infection was detected in users of a hemodialysis center in Granada and central venous catheter (CVC) users. The aim of this study was to describe the development of the outbreak and the control measures implemented as well as to identify the risk factors that may have been related to its origin. METHODS: A study of a series of thirteen cases with positive blood culture for Raoultella ornithinolytica was conducted during July 2022. Two hypotheses were considered: direct transmission through contamination of the antiseptic product or cross-contamination through the hands of healthcare personnel. A descriptive data analysis was carried out, with the calculation of attack rates and attributable risk in the exposed group (CVC users). RESULTS: The center performed dialysis on 117 patients. 36 patients had a CVC, and 81 had an arteriovenous fistula (AVF). The total number of infected cases was 13. The attack rate was 11.1%, being 36.1% in patients with CVC and 0% in patients with AVF. The symptoms occurred between 1 and 3 hours after the start of dialysis, except in three cases that occurred after receiving dialysis in other centers. Samples of water, liquids and antiseptics were negative. CONCLUSIONS: An outbreak of Raoultella ornithinolytica bacteraemia is confirmed, due to possible cross-contamination in the CVC handling and antisepsis process. Possibly, the germ was carried by a container of alcoholic chlorhexidine that contaminated the catheter and caused bacteremia during the hemodialysis process.

OBJETIVO: En julio de 2022 se detectó un brote de infección por Raoultella ornithinolytica en usuarios de un centro de hemodiálisis de Granada y portadores de catéter venoso central (CVC). El objetivo del estudio fue describir el desarrollo del brote y las medidas de control que se implantaron al respecto, así como identificar los factores de riesgo que pudieron estar relacionados con su origen. METODOS: Se realizó un estudio de una serie de trece casos con hemocultivo positivo para Raoultella ornithinolytica durante julio de 2022. Se plantearon dos hipótesis: transmisión directa a través de la contaminación del producto antiséptico o transmisión cruzada a través de las manos del personal sanitario del centro. Se llevó a cabo un análisis descriptivo de los datos y se calcularon tasas de ataque y riesgo atribuible en expuestos (portadores de CVC). RESULTADOS: El centro realizó diálisis a 117 pacientes. 36 enfermos portaban un CVC y 81 tenían una fístula arterio-venosa (FAV). El número total de casos infectados fue de 13. La tasa de ataque fue del 11,1%, siendo del 36,1% en pacientes portadores de CVC y del 0% en pacientes con FAV. La sintomatología se presentó entre 1 a 3 horas tras el inicio de la diálisis, salvo en tres casos que fue posterior a recibir diálisis en otros centros. Las muestras de agua, líquidos y antisépticos fueron negativas. CONCLUSIONES: Se confirma un brote de bacteriemia por Raoultella ornithinolytica debido a posible contaminación cruzada durante la manipulación y antisepsia del CVC. Posiblemente, el germen fue vehiculizado por un envase de clorhexidina alcohólica que contaminó el catéter y provocó la bacteriemia en el proceso de hemodiálisis.

Stiff Person Syndrome and Brittle Type 1 Diabetes: Report of 2 Cases.

Background/Objective: Stiff person syndrome (SPS) and type 1 diabetes (T1D) are heterogeneous disorders characterized by antibodies (Abs) against glutamic acid decarboxylase (GAD). Case Report: We describe 2 patients with T1D and autoimmune thyroid disease who presented with muscle rigidity and intermittent spasms that affected gait and with elevated circulating anti-GAD titers. Classic SPS and stiff limb syndrome were diagnosed, respectively. Muscle spasms resolved with immunotherapy and muscle relaxants in both patients, and the ability to ambulate without an assistive device was restored in 1 patient. Patients also had brittle diabetes with high glycemic variability, requiring the use of flash glucose monitoring with an insulin pump and a second-generation basal insulin analog, respectively. Discussion: GAD Ab-associated syndromes include SPS, T1D, and other endocrinopathies. The clinical heterogeneity implies variable susceptibility of γ-aminobutyric acid-ergic neurons and pancreatic beta cells to anti-GAD or other autoantibodies. Conclusion: Our case series represent the heterogeneity in natural history, clinical course, and response to therapy in patients with Abs against GAD-spectrum disorders.

Enucleation of insulinoma using laparoscopic distal pancreatectomy with a focus on vascular and splenic preservation: a case report.

Insulinomas represent <10% of pancreatic tumors. It is a functional neuroendocrine tumor that can cause recurrent and severe episodes of loss of consciousness due to hypoglycemia. Surgical removal is the only curative treatment. The selection of the optimal surgical technique must be individualized for each patient. Currently, there are emerging innovations in less invasive techniques that reduce morbidity. We present the case of a 23-year-old woman who underwent enucleation of an insulinoma localized at the tip of the pancreatic tail after laparoscopic surgery, with a focus on vascular and splenic preservation. The tumor was safely identified during surgery and enucleated without injury to the spleen and adjacent vascular structures or postoperative complications.

Towards Digital Quantification of Ploidy from Pan-Cancer Digital Pathology Slides using Deep Learning.

Abnormal DNA ploidy, found in numerous cancers, is increasingly being recognized as a contributor in driving chromosomal instability, genome evolution, and the heterogeneity that fuels cancer cell progression. Furthermore, it has been linked with poor prognosis of cancer patients. While next-generation sequencing can be used to approximate tumor ploidy, it has a high error rate for near-euploid states, a high cost and is time consuming, motivating alternative rapid quantification methods. We introduce PloiViT, a transformer-based model for tumor ploidy quantification that outperforms traditional machine learning models, enabling rapid and cost-effective quantification directly from pathology slides. We trained PloiViT on a dataset of fifteen cancer types from The Cancer Genome Atlas and validated its performance in multiple independent cohorts. Additionally, we explored the impact of self-supervised feature extraction on performance. PloiViT, using self-supervised features, achieved the lowest prediction error in multiple independent cohorts, exhibiting better generalization capabilities. Our findings demonstrate that PloiViT predicts higher ploidy values in aggressive cancer groups and patients with specific mutations, validating PloiViT potential as complementary for ploidy assessment to next-generation sequencing data. To further promote its use, we release our models as a user-friendly inference application and a Python package for easy adoption and use.

Effects of adding graphene fibers to polymethyl methacrylate on biocompatibility and surface characterization.

STATEMENT OF PROBLEM: Interim fixed prostheses are used provisionally to provide esthetics and maintain function until placement of the definitive prosthesis. Polymethyl methacrylate (PMMA) has been widely used as an interim material but has mechanical limitations that can be improved with the addition of nanomaterials such as graphene fibers (PMMA-G). However, studies on the biocompatibility of this material are lacking. PURPOSE: The purpose of this in vitro study was to determine the biocompatibility and cytotoxic effects of PMMA compared with PMMA-G in periodontal ligament stem cells (PDLSCs) by measuring the viability and cell apoptosis of those cells subjected to different concentrations of both compounds by elution, as well as the surface characterization of these materials. MATERIAL AND METHODS: Sterile Ø20×15-mm specimens of PMMA and PMMA-G were covered with Dulbecco modified Eagle medium for 24 hours to be the subsequent eluent. PDLSCs were seeded in 6 plates of 96 wells at dilutions 1/1, 1/2, 1/4, and 1/8 for each material. Three plates for the cell viability assay with MTT and 3 plates for the cell apoptosis assay with Hoechst 33342 staining were used in turn to subdivide the measurements at 24, 48, and 72 hours. The Kruskal-Wallis test was used to compare the data obtained in the different dilutions at different times and the Mann-Whitney test to compare both materials. Topography and wetting were analyzed for surface characterization. The Student t test of paired measurements was used to compare the different surfaces for each parameter (α=.05 for all tests). RESULTS: In both the cell viability assay (MTT) and the cell apoptosis assay, the test did not identify statistically significant differences in PMMA and PMMA-G with respect to the control group in the different dilutions at different times (P>.05). When comparing both materials, no statistically significant differences (P=.268) were found in either trial. PMMA-G had lower roughness and kurtosis and higher wetting than PMMA. CONCLUSIONS: Both PMMA and PMMA-G were found to be biocompatible materials with no significant differences between them after cell viability and apoptosis testing. PMMA-G had higher wettability and lower roughness than PMMA.

Androgen and Cortisol Cosecreting Adrenal Adenoma and Tuberculous Lymphadenitis.

The differential diagnosis between malignant and benign adrenal cortical tumors is challenging, and concurrent androgen and cortisol production should raise  suspicion of a malignant tumor. We present the case of a 36-year-old woman who exhibited pronounced hirsutism, clitoromegaly, and secondary amenorrhea. A contrast-enhanced computed tomography (CT) scan revealed a 35 × 27 mm right adrenal mass with unenhanced CT attenuation of 40 Hounsfield units (HUs). The mass exhibited absolute and relative washout rates of 50% and 28%, respectively, and was accompanied by a 25 × 20 mm adenopathy located in the hepatogastric space. Total testosterone was elevated by 247 ng/dL (8.56 nmol/L) (normal reference range, 10-75 ng/dL; 0.34-2.6 nmol/L). A 1-mg dexamethasone suppression test revealed an elevated serum morning cortisol concentration of 10.57 µg/dL (291.58 nmol/L) (reference range, <1.8 µg/dL; < 49.66 nmol/L). A fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) scan revealed increased uptake in both the adrenal mass and the adenopathy. Subsequently, the patient underwent an open right adrenalectomy and lymphadenectomy. Histological examination revealed the presence of an adrenal adenoma with myelolipomatous metaplasia, as well as a positive polymerase chain reaction (PCR) for Mycobacterium tuberculosis in the adenopathy.

A Hemorrhagic Brain Mass in a Child With Encephalocraniocutaneous Lipomatosis.

Encephalocraniocutaneous lipomatosis (ECCL) is a rare genetic condition with well-described skin, ocular, and central nervous system findings. Several case reports have been documented demonstrating the presence of low-grade gliomas in patients with ECCL and the association with certain FGFR1 mutations. We report on a case of diffuse low-grade glioma, mitogen activated protein kinase pathway altered in a patient with ECCL, who was found to have a distinct FGFR1 mutation.

How can we optimize the diagnostic and therapeutic approach to pneumonia? Expert opinion-based recommendations.

Pneumonia continues to be one of the most frequent infectious syndromes and a relevant cause of death and health resources utilization. The OPENIN ("Optimización de procesos clínicos para el diagnóstico y tratamiento de infecciones") Group is composed of Infectious Diseases specialists and Microbiologists and aims at generating recommendations that can contribute to improve the approach to processes with high impact on the health system. Such task relies on a critical review of the available scientific evidence. The first Group meeting (held in October 2023) aimed at answering the following questions: Can we optimize the syndromic and microbiological diagnosis of pneumonia? Is it feasible to safely shorten the length of antibiotic therapy? And, is there any role for the immunomodulatory strategies based on the adjuvant use of steroids, macrolides or immunoglobulins? The present review summarizes the literature reviewed for that meeting and offers a series of expert recommendations.

Exploring the CIEDE2000 thresholds for lightness, chroma, and hue differences in dentistry.

OBJECTIVE: To evaluate the perceptibility and acceptability CIEDE2000 (KL:KC:KH) thresholds for lightness, chroma and hue differences in dentistry. METHOD: A Python-based program was developed to conduct a psychophysical experiment based on visual assessments of computer-simulated images of human teeth. The experiment was performed on a calibrated display. A 40-observer panel: dentists and laypersons (male and female; n=10), evalu- ated three subsets of simulated human teeth: the lightness subset (%∆L00 ≥ 98 %), the chroma subset (%∆C00 ≥ 98 %) and the hue subset (%∆H00 ≥ 98 %), using ∆E00 ≥ 5 units. A Takagi-Sugeno-Kang Fuzzy Approximation model was used as fitting procedure, and 50:50 % lightness, chroma and hue CIEDE2000 (1:1:1) and CIEDE2000 (2:1:1) perceptibility (PT00) and accept- ability (AT00) thresholds were calculated. Data was statistically analyzed using t-test (p < 0.05). RESULTS: The 50:50 % PT00 for KL=1 were ∆L00=1.04, ∆C00=1.58 and ∆E00=1.01; and for KL=2 were ∆L00=0.51, ∆C00=1.58 and ∆E00=0.71. The 50:50 % AT00 for KL=1 were ∆L00=2.82, ∆C00=3.04 and ∆E00=2.66; and for KL=2 were ∆L00=1.40, ∆C00=3.04 and ∆E00=1.78. PT00 and AT00 ∆H00 may be considered no computable. A significant difference was found between CIEDE2000(1:1:1) and CIEDE2000(2:1:1), between lightness and chroma metrics, and between observer groups. No differences for lightness and chroma PT00 were found between male and female groups. CONCLUSIONS: It is important to use PT00 and AT00 for lightness, chroma and hue specific to evaluate perceptual sensitivity for color changes in the tooth color space. AT00 for lightness and chroma are influenced by the observer's experience and gender. Males and laypersons show more tolerance for changes in chroma (∆C00) and in lightness (∆L00). SIGNIFICANCE: Hue and chroma mismatch are more difficult to be accepted in dental color space.

Reading metacomprehension of Spanish deaf and hard-of-hearing students.

Difficulties in monitoring reading comprehension result in poor comprehension. One key aspect of monitoring is metacomprehension, which refers to one's awareness of one's own reading comprehension. Previous studies have observed difficulties in metacomprehension among the deaf or hard-of-hearing (DHH) population. This study aims to determine whether the metacomprehension of DHH students corresponds to their reading score and whether they are truly capable of adjusting their metacomprehension to the difficulty of the text. We evaluated 25 Spanish-speaking DHH students with reading scores approximately equivalent to Grades 5 or 6 of Primary School. Participants were asked to read a text and answer questions. The texts corresponded to three levels of difficulty (explicit, inferable, and noninferable). The results revealed that the metacomprehension of DHH students corresponded to their reading score. The DHH population may have better reading metacomprehension than is typically assumed, although the manifestation of this skill may depend on the type of task demanded of them (comprehension judgment or knowledge judgment).

GPS Suitability for Physical Frailty Assessment.

The ageing of the population needs the automation of patient monitoring. The objective of this is twofold: to improve care and reduce costs. Frailty, as a state of increased vulnerability resulting from several diseases, can be seen as a pandemic for older people. One of the most common detection tests is gait speed. This article compares the gait speed measured outdoors using smartphones with that measured using manual tests conducted in medical centres. In the experiments, the walking speed was measured over a straight path of 80 m. Additionally, the speed was measured over 2.4 m in the middle of the path, given that this is the minimum distance used in medical frailty tests. To eliminate external factors, the participants were healthy individuals, the weather was good, and the path was flat and free of obstacles. The results obtained are promising. The measurements taken with common smartphones over a straight path of 80 m are within the same order of error as those observed in the manual tests conducted by practitioners.

Pharmacogenetics in Oncology: A useful tool for individualizing drug therapy.

With the continuous development of genetics in healthcare, there has been a significant contribution to the development of precision medicine, which is ultimately aimed at improving the care of patients. Generally, drug treatments used in Oncology are characterized by a narrow therapeutic range and by their potential toxicity. Knowledge of pharmacogenomics and pharmacogenetics can be very useful in the area of Oncology, as they constitute additional tools that can help to individualize patients' treatment. This work includes a description of some genes that have been revealed to be useful in the field of Oncology, as they play a role in drug prescription and in the prediction of treatment response.

Unusual Presentation of De Winter's Sign Due to Bezold-Jarisch Reflex in a Patient With Severe Aortic Valve Stenosis.

The de Winter electrocardiogram (ECG) pattern, marked by upsloping ST depression in leads V2-V6, ST elevation in lead aVR, and tall symmetric T waves, typically indicates left anterior descending artery (LAD) occlusion. Traditionally linked to LAD occlusion, it is rare in severe aortic stenosis and the Bezold-Jarisch reflex (BJR). We report an 83-year-old man with severe aortic stenosis who developed hypotension due to bleeding and exhibited the de Winter ECG pattern. This case highlights how severe aortic stenosis and BJR can lead to significant hemodynamic instability and ischemic ECG changes, resolving after hemodynamic stabilization.

Poorly Controlled New-Onset Diabetes Mellitus and Other Atypical Signs as an Early Sign of Pancreatic Adenocarcinoma.

A 50-year-old man presented with poorly controlled new-onset diabetes mellitus. Six months after diagnosis, episodes of intense abdominal pain with vomiting appeared. Abdominal CT revealed signs of acute pancreatitis with structural changes in the pseudocysts. In the absence of biliary lithiasis or a toxic etiology of acute pancreatitis, the patient progressed unfavorably with increased abdominal pain and fever. Control imaging tests (two and 10 months later) showed the evolution of phlegmonous/necrotic collections, together with portal vein thrombosis and splenomegaly. Given the suggestive signs of possible occult malignancy, such as portal thrombosis, histological analysis of the ascitic fluid revealed a pancreatic adenocarcinoma. Despite the initiation of chemotherapy, the patient died 12 months after diagnosis.

PAI-1 Regulates the Cytoskeleton and Intrinsic Stiffness of Vascular Smooth Muscle Cells.

BACKGROUND: Plasma concentration of PAI-1 (plasminogen activator inhibitor-1) correlates with arterial stiffness. Vascular smooth muscle cells (SMCs) express PAI-1, and the intrinsic stiffness of SMCs is a major determinant of total arterial stiffness. We hypothesized that PAI-1 promotes SMC stiffness by regulating the cytoskeleton and that pharmacological inhibition of PAI-1 decreases SMC and aortic stiffness. METHODS: PAI-039, a specific inhibitor of PAI-1, and small interfering RNA were used to inhibit PAI-1 expression in cultured human SMCs. Effects of PAI-1 inhibition on SMC stiffness, F-actin (filamentous actin) content, and cytoskeleton-modulating enzymes were assessed. WT (wild-type) and PAI-1-deficient murine SMCs were used to determine PAI-039 specificity. RNA sequencing was performed to determine the effects of PAI-039 on SMC gene expression. In vivo effects of PAI-039 were assessed by aortic pulse wave velocity. RESULTS: PAI-039 significantly reduced intrinsic stiffness of human SMCs, which was accompanied by a significant decrease in cytoplasmic F-actin content. PAI-1 gene knockdown also decreased cytoplasmic F-actin. PAI-1 inhibition significantly increased the activity of cofilin, an F-actin depolymerase, in WT murine SMCs, but not in PAI-1-deficient SMCs. RNA-sequencing analysis suggested that PAI-039 upregulates AMPK (AMP-activated protein kinase) signaling in SMCs, which was confirmed by Western blotting. Inhibition of AMPK prevented activation of cofilin by PAI-039. In mice, PAI-039 significantly decreased aortic stiffness and tunica media F-actin content without altering the elastin or collagen content. CONCLUSIONS: PAI-039 decreases intrinsic SMC stiffness and cytoplasmic stress fiber content. These effects are mediated by AMPK-dependent activation of cofilin. PAI-039 also decreases aortic stiffness in vivo. These findings suggest that PAI-1 is an important regulator of the SMC cytoskeleton and that pharmacological inhibition of PAI-1 has the potential to prevent and treat cardiovascular diseases involving arterial stiffening.

DNA binding and bridging by human CtIP in the healthy and diseased states.

The human DNA repair factor CtIP helps to initiate the resection of double-stranded DNA breaks for repair by homologous recombination, in part through its ability to bind and bridge DNA molecules. However, CtIP is a natively disordered protein that bears no apparent similarity to other DNA-binding proteins and so the structural basis for these activities remains unclear. In this work, we have used bulk DNA binding, single molecule tracking, and DNA bridging assays to study wild-type and variant CtIP proteins to better define the DNA binding domains and the effects of mutations associated with inherited human disease. Our work identifies a monomeric DNA-binding domain in the C-terminal region of CtIP. CtIP binds non-specifically to DNA and can diffuse over thousands of nucleotides. CtIP-mediated bridging of distant DNA segments is observed in single-molecule magnetic tweezers experiments. However, we show that binding alone is insufficient for DNA bridging, which also requires tetramerization via the N-terminal domain. Variant CtIP proteins associated with Seckel and Jawad syndromes display impaired DNA binding and bridging activities. The significance of these findings in the context of facilitating DNA break repair is discussed.

Bifocal diffractive lenses based on the aperiodic Kolakoski sequence.

In this work, we present a new family of Zone Plates (ZPs) designed using the self-generating Kolakoski sequence. The focusing and imaging properties of these aperiodic diffractive lenses coined Kolakoski Zone Plates (KZPs) are extensively studied. It is shown that under monochromatic plane-wave illumination, a KZP produces two main foci of the same intensity along the axial axis. Moreover, one of the corresponding focal lengths is double the other, property correlated with the involved aperiodic sequence. This distinctive optical characteristic is experimentally confirmed. We have also obtained the first images provided by these bifocal new diffractive lenses.

Near-pair patch generative adversarial network for data augmentation of focal pathology object detection models.

Purpose: The limited volume of medical training data remains one of the leading challenges for machine learning for diagnostic applications. Object detectors that identify and localize pathologies require training with a large volume of labeled images, which are often expensive and time-consuming to curate. To reduce this challenge, we present a method to support distant supervision of object detectors through generation of synthetic pathology-present labeled images. Approach: Our method employs the previously proposed cyclic generative adversarial network (cycleGAN) with two key innovations: (1) use of "near-pair" pathology-present regions and pathology-absent regions from similar locations in the same subject for training and (2) the addition of a realism metric (Fréchet inception distance) to the generator loss term. We trained and tested this method with 2800 fracture-present and 2800 fracture-absent image patches from 704 unique pediatric chest radiographs. The trained model was then used to generate synthetic pathology-present images with exact knowledge of location (labels) of the pathology. These synthetic images provided an augmented training set for an object detector. Results: In an observer study, four pediatric radiologists used a five-point Likert scale indicating the likelihood of a real fracture (1 = definitely not a fracture and 5 = definitely a fracture) to grade a set of real fracture-absent, real fracture-present, and synthetic fracture-present images. The real fracture-absent images scored 1.7±1.0, real fracture-present images 4.1±1.2, and synthetic fracture-present images 2.5±1.2. An object detector model (YOLOv5) trained on a mix of 500 real and 500 synthetic radiographs performed with a recall of 0.57±0.05 and an F2 score of 0.59±0.05. In comparison, when trained on only 500 real radiographs, the recall and F2 score were 0.49±0.06 and 0.53±0.06, respectively. Conclusions: Our proposed method generates visually realistic pathology and that provided improved object detector performance for the task of rib fracture detection.