Early Selection Of Patients Research Articles

Occurrence of Secondary Non-Hodgkin Lymphomas Among Our Classical Hodgkin Lymphoma Patients: A Single-Centre Experience.

Objective Non-Hodgkin lymphoma (NHL) arising as a secondary malignancy in patients treated for classical Hodgkin lymphoma (cHL) is an infrequent and challenging clinical scenario. NHL can be presented synchronously with cHL or may develop later, sequentially, up to years after treatment for cHL. The relationship between the two lymphomas is unclear, and there are no clear guidelines forthe management ofthese patients. We would like to find a better clinical understanding of this issueso this study investigates the occurrence and clinical characteristics of secondary NHL. Materials and methods In this retrospective cohort examination, we collected cHL cases when NHL occurred during or after the course of treating cHL. We performed the histopathologic revisions of the samples, and in every case where the quality of the sample was lower, we performed molecular examinations to find the association between cHL and NHL. We performed next-generation genome sequencing (NGS) and immunoglobulin heavy-chain variable region gene (IgHV) clonality testing. Results In a cohort of 164 cHL patients diagnosed between 2011 and 2020, six patients were identified with NHL during rebiopsy prompted by lymphoma relapse or progression. Among these, five patients were diagnosed with post-germinalcenter-originated diffuse large B-cell lymphoma (post-GC DLBCL), and one patient presented high-grade B-cell lymphoma (HG-BCL). The NHL manifestation differed in its timing: three cases emerged after successful cHL treatment, with at least 18 months of complete remission, while the other three patients faced primary refractory cHL. Notably, the primary refractory cases did not exhibit a confirmed clonal relationship between cHL and NHL, but NGS data raised the possibility of synchronous NHL in one case. In contrast, among the patients with sequentially occurring NHL, polymerase chain reaction (PCR) testing of the IgHV gene affirmed a clonal connection between cHL and secondary DLBCL in one case, while the high morphological similarity suggested a potential clonality between the two lymphomas in another case. Conclusion This study reveals that secondary NHL may manifest both synchronously and sequentially following cHL. Our results suggest that synchronous NHL has a worse prognosis compared to sequentialcaseswhen the different lymphomas are not recognized at the time of diagnosis. As our data showed, in some cases, mutations that accompany the tumor cells throughout their clonal evolution can be identified, with additional mutations later on. In the future, next-generation sequencing (NGS)-based processing of liquid biopsy samples can overcome the limitations resulting from the spatial heterogeneity of lymphoid malignancies. Over the long term, this identification could lead to early patient selection and alternative treatment strategies, ultimately leading to improved prospects for cure.

The added value of ultrasound imaging biomarkers to clinicopathological factors for the prediction of high-risk Oncotype DX recurrence scores in patients with breast cancer.

The Oncotype DX (ODX) recurrence score (RS), a 21-gene assay, has been proven to recognize patients at high risk of recurrence (RS ≥26) who would benefit from chemotherapy. However, it has limited availability and high costs. Our study thus aimed to identify ultrasound (US) imaging biomarkers and develop a prediction model for identifying patients with a high ODX RS. In this retrospective study, consecutive patients with T1-3N0-1M0 breast cancer who were hormone receptor positive and human epidermal growth factor receptor 2 (HER2) negative who had an available ODX RS were reviewed. Patients treated from May 2012 and December 2015 were placed into a training cohort, and those treated from January 2016 to January 2017 were placed in a validation cohort. Clinicopathologic data were collected, and preoperative US scans were analyzed. Univariable and multivariable regression analyses were performed to evaluate the independent predictors for a high-risk of breast cancer in the training cohort, and a nomogram was developed and evaluated with the area under the receiver operating characteristic curve (AUC), calibration curve, and decision curve analysis (DCA). A total of 363 patients were in the training cohort and 160 in the validation cohort, with the proportion with a high RS (RS 26-100) being 14% and 13.1%, respectively. Echogenic halo, enhanced posterior echo, low level of progesterone receptor (PR), and high Ki-67 index were identified as independent risk factors for high RS (all P values <0.05). The nomogram was constructed based on the combined model, which showed a better discrimination ability than did the clinicopathological model [combined model: AUC =0.95, 95% confidence interval (CI): 0.93-0.97; clinicopathological model: AUC =0.89, 95% CI: 0.86-0.92; P=0.001] and greater clinical benefit according to DCA. Furthermore, the nomogram was found to be effective in the validation cohort (AUC =0.90, 95% CI: 0.84-0.94), especially in patients with stage T1N0M0 disease (AUC =0.91, 95% CI: 0.84-0.95). US features may serve as valuable imaging biomarkers for the prediction of high recurrence risk in patients with T1-3N0-1M0 breast cancer and hormone receptor (HR)-positive and HER2-negative status. A nomogram incorporating PR status, Ki-67 index, and US imaging biomarkers showed a good discrimination ability in the early selection of patients at high risk of recurrence, especially in those with stage T1N0M0 disease.

Prospective analysis of optic nerve diameter and NSE values in patients with refractory headaches

Purpose: This study aims to investigate the usability of ultrasonographic optic nerve diameter measurement and plasma neuron-specific enolase (NSE) levels in detecting secondary causes of headaches in patients with refractory headaches in emergency department.&#x0D; Materials and Methods: The study was conducted in a university-based adult emergency department over 3 years. Sixty-six consecutive patients presenting to the emergency department with refractory headaches and 50 healthy volunteers for the control group were included. Information recorded included the duration of complaints, type and location of headache, symptoms, co-morbidities, results of imaging studies, optic nerve diameters, results of lactate, arterial blood gas and NSE levels.&#x0D; Results: A total of 66 patients were included, comprising 33 females. The mean age was 43.05 ± 17.06 years. Secondary causes of headache were identified in 45 patients (68.2%). Evaluation of ultrasonographic optic nerve diameter revealed that 17 (25.8%) right and 21 (31.8%) left optic nerve diameters were ≥5 mm. Optic nerve diameter values were significantly higher in patients diagnosed with secondary headache compared to those with primary headache, with no statistically significant difference observed in NSE values. Lactate levels in patients with secondary headaches were significantly higher than those in patients with primary headaches.&#x0D; Conclusion: In patients admitted to the emergency department with refractory headaches and normal imaging, ultrasonographic optic nerve diameter measurement may be preferred as an easily accessible method to guide the detection of secondary causes. NSE was not an effective in the early selection of patients with secondary headaches.

Getting to the heart of Lewy body disease.

Early identification of neurodegenerative diseases before extensive neuronal loss or disabling symptoms have occurred is imperative for effective use of disease-modifying therapies. Emerging data indicate that central Lewy body diseases - Parkinson disease and dementia with Lewy bodies - can begin in the peripheral nervous system, opening up a therapeutic window before central involvement. In this issue of the JCI, Goldstein et al. report that cardiac 18F-dopamine positron emission tomography reveals lower activity selectively in individuals with several self-reported Parkinson disease risk factors who later develop Parkinson disease or dementia with Lewy bodies. Accurately identifying which at-risk individuals will develop central Lewy body disease will optimize early patient selection for disease-modifying therapies.

Evaluating the impact of timing to rib fixation in patients with traumatic brain injury: A nationwide analysis.

Early surgical stabilization of rib fractures (SSRF) is associated with improved inpatient outcomes in patients with multiple rib fractures. However, there is still a paucity of data examining the optimal timing of SSRF in patients with concomitant traumatic brain injury (TBI). This study aimed to assess whether earlier SSRF was associated with improved outcomes in patients with multiple rib fractures and TBI. We performed a retrospective analysis of the American College of Surgeons Trauma Quality Improvement Program 2017-2020, including adult patients with TBI and multiple rib fractures who had undergone SSRF. The outcomes were post-procedural length of stay (LOS), hospital LOS, intensive care unit (ICU) LOS, in-hospital mortality, ventilator days, and tracheostomy rate. Multilevel mixed-effects regression analyses accounting for patient, injury, and hospital characteristics as well as institutional SSRF volume were used to assess the association between timing to SSRF and the outcomes of interest. As a sensitivity analysis, propensity-score matching was performed to compare patients who underwent early (<72 hours) versus late SSRF (≥72 hours). Of 1,041 patients included in this analysis, 430 (41.3%) underwent SSRF within the first 72 hours from admission. Delay to SSRF was associated with an increase in post-procedural LOS (partial regression coefficient (β) = 0.011; p = 0.036; 95% confidence interval [CI], 0.001-0.023), longer hospital LOS (β = 0.053; p < 0.001; 95% CI, 0.042-0.064), prolonged ICU LOS (β = 0.032; p < 0.001; 95% CI, 0.025-0.038), and more ventilator days (β = 0.026, p < 0.001; 95% CI, 0.020-0.032). In patients with concurrent multiple rib fractures and TBI, a delay in SSRF is associated with an increase in postprocedural LOS, hospital LOS, ICU LOS, and ventilator days. These findings suggest that the early patient selection and implementation of SSRF may play a beneficial role in patients presenting with concomitant TBI and multiple rib fractures. Therapeutic/Care Management; Level IV.

Increasing the dose of ibuprofen with postnatal age to close a hemodynamically significant patent ductus arteriosus in very preterm infants.

Patent ductus arteriosus (PDA) is associated with neonatal morbidities in high-risk preterm infants. Early neonatal treatment by ibuprofen induces the ductus arteriosus (DA) closure in approximatively 60% of infants. Dose escalation of ibuprofen according to postnatal age has been suggested for improving the DA closure rate. The aim of this study was to assess the efficacy and tolerance of an increasing dose regimen of ibuprofen. This single-center retrospective cohort study involved infants hospitalized from 2014 to 2019 in our neonatal unit. Selection criteria were gestational age < 30weeks, birth weight < 1000g, and treatment by ibuprofen. Three dose levels were used and consisted of a daily intravenous injection of ibuprofen-tris-hydroxymethyl-aminomethane (ibuprofen-THAM) for three consecutive days: (i) 10 -5 -5mg/kg before the 70th h of life (H70) (dose level 1), (ii) 14 -7 -7mg/kg between H70 and H108 (dose level 2), (iii) 18 -9 -9mg/kg after H108 (dose level 3). The ibuprofen-induced DA closure was compared between ibuprofen schedules, and the Cox proportional-hazard regression was performed to identify factors associated with the ibuprofen efficacy. Tolerance was assessed through renal function, acidosis, and platelet count. One hundred forty-three infants met the inclusion criteria. The ibuprofen-induced DA closure was observed in 67 infants (46.8%). One course of ibuprofen at dose level 1 was more efficient in closing the DA than other schedules (dose level 1, one course (n = 70): 71%, dose level 2 or 3, one course (n = 20): 45%, two-course schedules (n = 53): 15%, p < 0.0001). Independent factors associated with ibuprofen-induced DA closure were a complete antenatal schedule of steroids (p = 0.001), a lower CRIB II score (p = 0.009), and a lower and earlier exposure to ibuprofen (p < 0.0001 and p = 0.002). No severe side effects were observed. Neonatal mortality and morbidities were similar regardless of the infant's response to ibuprofen. Conclusion: Increasing ibuprofen doses with postnatal age failed to reach an efficacy similar to earlier treatment. Although the infant response to ibuprofen was likely to depend on multiple factors, the optimal use of ibuprofen included its early initiation. What is Known: • Ibuprofen is the current first-line treatment for patent ductus arteriosus during the early neonatal period in very preterm infants. • However, the ibuprofen efficacy rapidly declined with postnatal age during the first week of life. A dose escalation of ibuprofen according to postnatal age has been suggested to improve the ibuprofen-induced ductus arteriosus closure. What is New: • The rapid drop of ibuprofen's ability to close hemodynamically significant patent ductus arteriosus persisted beyond the postnatal day 2 despite the dose adjustment arguing for an early initiation to optimize its efficacy. • The early selection of patients who will suffer from patent ductus arteriosus-related morbidities and who will positively respond to ibuprofen is an issue that could determine the future place of ibuprofen in the patent ductus arteriosus management.

MP73-02 FOCAL THERAPY - 7 YEARS EXPERIENCE WITH FOCAL HIGH INTENSITY FOCUSED ULTRASOUND IN 164 PATIENTS WITH PROSTATE CANCER: SINGLE CENTER RESULTS

You have accessJournal of UrologyCME1 Apr 2023MP73-02 FOCAL THERAPY - 7 YEARS EXPERIENCE WITH FOCAL HIGH INTENSITY FOCUSED ULTRASOUND IN 164 PATIENTS WITH PROSTATE CANCER: SINGLE CENTER RESULTS Yamini Nagaraj, Fabian Falkenbach, Valia Veleva, Randi Marisa Pose, Jonas Ekrutt, Raisa Abrams-Pompe, Jaideep Ratkal, Pierre Tennstedt, Derya Tilki, Hans Heinzer, Markus Graefen, and Georg Salomon Yamini NagarajYamini Nagaraj More articles by this author , Fabian FalkenbachFabian Falkenbach More articles by this author , Valia VelevaValia Veleva More articles by this author , Randi Marisa PoseRandi Marisa Pose More articles by this author , Jonas EkruttJonas Ekrutt More articles by this author , Raisa Abrams-PompeRaisa Abrams-Pompe More articles by this author , Jaideep RatkalJaideep Ratkal More articles by this author , Pierre TennstedtPierre Tennstedt More articles by this author , Derya TilkiDerya Tilki More articles by this author , Hans HeinzerHans Heinzer More articles by this author , Markus GraefenMarkus Graefen More articles by this author , and Georg SalomonGeorg Salomon More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003341.02AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Focal therapy aims to selectively ablate tumor lesions and preserve prostate tissue, thus minimizing side effect whilst providing oncological control. The experience of the first 2 years lead to improved diagnostic work up prior to HIFU with better patient selection and less tumor recurrence in the following 5 years. The strong recommendation of control biopsy in the follow up, lead to a reliable and early selection of patients requiring salvage therapy and thus improving oncological results. METHODS: This is a prospective evaluation of 164 patients undergoing focal high intensity focused ultrasound (HIFU) in our institution from July 2015 till June 2022. Patients were required to have a unilateral Gleason score (GS) ≤7, stage T1 or T2 and a PSA level of≤15 ng/ml. Tumor localization was done using multiparametric MRI followed by mainly transrectal targeted and systematic biopsies of any lesion PI-RADS≥3. Systematic biopsy was recommended 1 year after HIFU with PSA levels every 3 months. An MRI was scheduled at 3 years post HIFU. In the control biopsy significant cancer recurrence was defined as >3mm GS 3+3, >3 positive cores or any GS≥3+4; these patients were offered further treatment; either a repeat HIFU, radical prostatectomy (RP) or radiation therapy (RT). Urinary and erectile function were assessed using validated questionnaires. RESULTS: Median PSA prior to HIFU was 6 ng/ml, the median follow-up was 61 months. 38% of the patients had low, 60% intermediate and 2% high risk disease. Median PSA level 2 years post HIFU was 1.9 ng/ml. Of the 119 control biopsies 50% had no evidence of tumor, 36% had insignificant tumor evidence and 14 % showed evidence of significant prostate cancer according to the above defined criteria. Significant infield recurrence occurred in 6 patients (4%) and significant outfield recurrence was seen in 10 patients (6%). 5 patients received a repeat HIFU, 4 patients a RT and 7 had a RP. There were no cases of distant metastasis, no need for palliative antiandrogen therapy (ADT) and no major complications. Urinary continence and erectile function were preserved in 99.5% and 85% respectively. CONCLUSIONS: At 7 years, HIFU therapy showed efficient oncological control rates with a radical treatment free survival rate of 93%. Significant infield recurrence was seen in 4% and significant outfield recurrence in 6% of patients. There was no distant metastasis and no need for palliative ADT. HIFU is associated with excellent preservation of continence and erectile function with very low morbidity. Source of Funding: Non funded © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e1034 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Yamini Nagaraj More articles by this author Fabian Falkenbach More articles by this author Valia Veleva More articles by this author Randi Marisa Pose More articles by this author Jonas Ekrutt More articles by this author Raisa Abrams-Pompe More articles by this author Jaideep Ratkal More articles by this author Pierre Tennstedt More articles by this author Derya Tilki More articles by this author Hans Heinzer More articles by this author Markus Graefen More articles by this author Georg Salomon More articles by this author Expand All Advertisement PDF downloadLoading ...

Hypertrophic, Dilated, and Arrhythmogenic Cardiomyopathy: Where Are We?

Cardiomyopathies are a heterogeneous group of structural, mechanical, and electrical heart muscle disorders which often correlate with life-threatening arrhythmias and progressive heart failure accounting for significant cardiovascular morbidity and mortality. Currently, cardiomyopathies still represent a leading reason for heart transplantation worldwide. The last years have brought remarkable advances in the field of cardiomyopathies especially in terms of understanding the molecular basis as well as the diagnostic evaluation and management. Although most cardiomyopathy treatments had long focused on symptom management, much of the current research efforts aim to identify and act on the disease-driving mechanisms. Regarding risk assessment and primary prevention of sudden cardiac death, additional data are still pending in order to pave the way for a more refined and early patient selection for defibrillator implantation. This review summarizes the current knowledge of hypertrophic, dilated and arrhythmogenic cardiomyopathy with a particular emphasis on their pathophysiology, clinical features, and diagnostic approach. Furthermore, the relevant ongoing studies investigating novel management approaches and main gaps in knowledge are highlighted.

Extracorporeal resuscitation-criteria, prerequisites, outcome : A reality check

Für ausgewählte Patienten, in denen die konventionelle kardiopulmonale Reanimation (cCPR) erfolglos bleibt, sprechen die europäischen Leitlinien zur Reanimation 2021 erstmals eine Empfehlung zur extrakorporalen Reanimation (eCPR) als mögliche Rettungstherapie aus. Die eCPR wird im therapierefraktären Kreislaufstillstand etabliert, um Diagnostik und Therapie reversibler Ursachen, wie Herzinfarkt, Lungenembolie, akzidentielle Hypothermie, Intoxikationen mit herzwirksamen Substanzen und akute Hypoxie, zu ermöglichen. Selektionskriterien für eCPR umfassen prognostische Reanimationsfaktoren, wie beobachteter Kreislaufstillstand, Start von Reanimationsmaßnahmen in < 5 min, schockbarer Erstrhythmus, Zeichen effektiver cCPR wie Lebenszeichen während der Reanimation, anhaltendes Kammerflimmern, intermittierende Phasen von Spontankreislauf oder anhaltendes endtidales CO2 > 10 mm Hg, Patientenalter und Gesundheitszustand. Die Zeitspanne vom Kreislaufstillstand bis zur eCPR ist eine der wichtigsten Determinanten für neurologisch gutes Überleben und sollte < 60 min liegen. Für die Einhaltung dieser Zielvorgabe muss eine entschlossene „Load-and-Go“-Strategie mit frühzeitiger Patientenselektion und raschem Transport unter mechanischer cCPR in ein eCPR-Zentrum verfolgt werden, oder es wird versucht, die eCPR präklinisch zum Einsatz zu bringen. Zwei randomisierte kontrollierte eCPR-Studien demonstrierten Überlebensraten von 43 % bzw. 31,5 % bei Patienten mit anhaltendem Kammerflimmern bzw. kardialem Kreislaufstillstand. Ob diese Ergebnisse außerhalb einzelner hochspezialisierter Zentren anwendbar sind, ist wie die Frage nach der besten präklinischen und innerklinischen Strategie Gegenstand zukünftiger Studien.

Silver Nanoparticles as a Tool for the Study of Spontaneous Aggregation of Immunoglobulin Monoclonal Free Light Chains.

Some misfolded proteins, e.g., immunoglobulin monoclonal free light chains (FLC), tend to form fibrils. Protein deposits in tissue may lead to amyloidosis and dysfunction of different organs. There is currently no technique allowing for the identification of FLC that are prone to aggregate. The development of such a method would enable the early selection of patients at high risk of developing amyloidosis. The aim of this study was to investigate whether silver nanoparticles (AgNPs) could be a useful tool to study the process of aggregation of FLC and their susceptibility to form the protein deposits. Mixtures of AgNPs and urine samples from patients with multiple myeloma were prepared. To evaluate the aggregation process of nanoparticles coated with proteins, UV-visible spectroscopy, transmission electron microscopy, and the original laser light scattering method were used. It has been shown that some clones of FLC spontaneously triggered aggregation of the nanoparticles, while in the presence of others, the nanoparticle solution became hyperstable. This is probably due to the structure of the chains themselves, unique protein-AgNPs interactions and perhaps correlates with the tendency of some FLC clones to form deposits. Nanoparticle technology has proven to be helpful in identifying clones of immunoglobulin FLC that tend to aggregate.

Early Deaths after Arterial Ischemic Stroke in Pediatric Patients: Incidence and Risk Factors.

In developed countries, cerebrovascular diseases are among the 10 most common causes of death in both the pediatric and adult population. The prevalence of fatal outcomes following arterial ischemic stroke (AIS) in various groups of pediatric patients ranges from 1% to almost 32%. However, a constant improvement in stroke mortality among children has been observed. The extent of the decline differs among studies (from nearly tenfold to twofold decline), as it depends on the study population. While a portion of this variability might be explained by factors such as health care access, population age, diseases related to ethnicity, and different etiologies of stroke in studied populations, the understanding of such differences is still insufficient. Risk factors for death in the early stages of the disease are poorly understood and are usually based on the clinical presentations of relatively small groups of pediatric patients. Familiarity with these factors may be of significant importance for prognosis, but also for the early selection of patients requiring careful supervision. The present study aimed to analyze and discuss the current literature data on the incidence of early death and risk factors for early death in children suffering from stroke.

Multifactorial Predictors of Late Epileptic Seizures Related to Stroke: Evaluation of the Current Possibilities of Stratification Based on Existing Prognostic Models-A Comprehensive Review.

Background: Epilepsy associated with strokes is a significant clinical and public health problem and has a negative impact on prognosis and clinical outcome. A late epileptic seizure occurring seven days after stroke is actually equated with poststroke epilepsy due to the high risk of recurrence. Predictive models evaluated in the acute phase of stroke would allow for the stratification and early selection of patients at higher risk of developing late seizures. Methods: The most relevant papers in this field were reviewed to establish multifactorial predictors of late seizures and attempt to standardize and unify them into a common prognostic model. Results: Clinical and radiological factors have become the most valuable and reproducible predictors in many reports, while data on electroencephalographic, genetic, and blood biomarkers were limited. The existing prognostic models, CAVE and SeLECT, based on relevant, readily available, and routinely assessed predictors, should be validated and improved in multicenter studies for widespread use in stroke units. Conclusions: Due to contradictory reports, a common and reliable model covering all factors is currently not available. Further research might refine forecasting models by incorporating advanced radiological neuroimaging or quantitative electroencephalographic analysis.

Síndrome de Budd-Chiari: etiología, manejo y resultados en una cohorte de 35 pacientes del Hospital Pablo Tobón Uribe

El síndrome de Budd-Chiari (Budd-Chiari syndrome, BCS) es una entidad rara, definida por la obstrucción del flujo venoso del hígado y corresponde a una condición heterogénea tanto en presentación como en manejo terapéutico. A continuación, presentamos un estudio retrospectivo de pacientes con diagnóstico de BCS, atendidos por el grupo de hepatología del el Hospital Pablo Tobón Uribe. Los resultados se expresan como proporciones en las variables categóricas y como medias y rangos para las variables continuas. La edad promedio de presentación fue de 37,7 años y no hubo preponderancia por el género. Los principales síntomas fueron dolor abdominal (91,4 %), ascitis (71,4 %) y hepatomegalia (60 %). Asimismo, 11 pacientes (31,4 %) presentaron hipercoagulabilidad primaria, mientras que en 7 (20 %) se encontró algún síndrome mieloproliferativo. Además, 6 (17,1 %) tenían neoplasias extrahepáticas: 3 con compresión mecánica y 3 por hipercoagulabilidad asociada; solo en 1 caso se documentaron membranas en la vena cava inferior. Y en 5 casos no fue posible determinar la causa de trombosis. De igual forma, 32 pacientes (91,4 %) recibieron anticoagulación como primer manejo; solo 4 sujetos fueron remitidos a procedimientos: 2 a angioplastia, 1 a derivación portosistémica intrahepática transyugular (Transjugular Intrahepatic Portosystemic Shunt, TIPS) y 1 a trasplante ortotópico hepático (TOH). Luego de ello, 17 (48,5 %) recibieron procedimientos invasivos como segunda línea: 8 (22,8 %) se condujeron a angioplastia y endoprótesis (stent), 5 (14,29 %) a TIPS y 4 necesitaron TOH. Así, los 6 pacientes que se llevaron a TIPS no necesitaron trasplante hepático. El BCS continúa siendo una condición poco frecuente que afecta la salud de personas jóvenes, tanto hombres como mujeres, con una presentación clínica heterogénea. Sin embargo, en la mayoría de los casos ocurre por una causa desencadenante clara, entre las cuales predominan las trombofilias y los síndromes mieloproliferativos. El uso de medidas terapéuticas invasivas, especialmente de la selección temprana de los enfermos que se benefician de TIPS, ha cambiado la historia natural y el pronóstico de este grupo de pacientes.&#x0D;

Extracorporeal cardiopulmonary resuscitation at the emergency department: A retrospective patient selection evaluation.

There is an increasing use of extracorporeal life support in refractory cardiac arrest. Recent studies highlighted the importance of an early and accurate patient selection for this invasive procedure. The aim of this study was to retrospectively validate a six-criteria-screening-checklist (witnessed collapse, bystander-cardiopulmonary resuscitation/first medical contact <5 min, shockable, age <70 years, end tidal carbon dioxide >14 mmHg and pupils not anisocoric/distorted/mydriatic) as an early screening tool in patients treated with extracorporeal cardiopulmonary resuscitation (eCPR) at the emergency department. Retrospective observational study. All patients at least 18 years of age with nontraumatic cardiac arrest and without return of spontaneous circulation before eCPR treatment at our department between January 2013 and December 2018 were included in this retrospective observational study. No specific intervention was set in this observational study. Primary outcome was the rate of patients who fulfilled all criteria, secondary outcome was 30-day and 6-month survival in accordance with the criteria. Overall, data from a total of 92 patients were eligible for analyses. Out of these, 27 patients (29%) met all criteria. Patients, who fulfilled all criteria, showed significantly higher odds for 30-day survival [OR 6.0 (95% CI 1.78 to 20.19)] P = 0.004. Patients, who did not fulfil all criteria, showed significantly higher rates of early mortality after eCPR initiation [OR 4.57 (95% CI 1.69 to 12.37)] P = 0.003. Patients fulfilling all inclusion criteria showed higher rates of survival after eCPR. Our results affirm that there is a possibility and even an obvious necessity for early patient selection based on standardised criteria before eCPR treatment. Large randomised trials are urgently needed to answer this question accurately.

Laparoscopic hepatectomy for hepatocellular carcinoma: A study on the adoption at a large academic center

Presenter: Xavier Pereira MD | Montefiore Medical Center Background: Laparoscopic Hepatectomy (LH) for hepatocellular carcinoma (HCC) represents a major change in surgical practice for the established liver surgeon. LH has gradually evolved through the steps of surgical innovation: proof of concept, procedure development, procedure refinement, and now phasing into widespread adoption at most academic centers. However, technical challenges impacting operative outcomes and effects on R0 resection have slowed the adoption of laparoscopy in liver surgery. While landmark studies have confirmed the safety of laparoscopy to early adopters, they often fail to capture the efficacy, safety, and comparable oncologic outcomes that can be seen with the widespread adoption of LH at most academic centers. We sought to describe the adoption of LH for HCC at our institution with an emphasis on early patient selection, a safe and gradual increase in case complexity, and it effects on procedural and oncologic outcomes. Methods: Patients undergoing hepatectomy for HCC between July 2016 to December 2018 were reviewed. Patient demographics, indications for surgery, hepatic disease burden, co-morbidities, intraoperative and postoperative data were reviewed retrospectively. Open (OH) vs. laparoscopic procedures (LH) were matched for comparison od endpoints using Chi square, Student’s T-test, and Mann-Whitney U tests. Results: Comparative distribution of 177 cases on a quarterly timeline is presented (Figure 1), highlighting a steady adoption of LH. Of the 56 patients matched for analysis, 27 underwent open hepatectomy (OH) while 26 underwent LH. These cohorts were well matched without notable difference in the Charlson Comorbidities Index (CCI) (p-value 0.943) or Childs class (p-value 0.077). The LH group showed less tumor burden (p<0.0639) less segments involved (p<0.0063) and less complex resections based on the Iwate difficulty scoring (p<0.0013) indicating an expected bias in patient selection, more conservative for LH. The average LOS, EBL, and intraoperative transfusions were lower in the laparoscopic group vs. the open group (P < 0.0115 and p<0.0483). The proportion of R0/R1 resections was no different between both groups (p<0.2771) achieving R0 resections in 92% of LLRs vs. 80% of OLRs. The median recurrence-free survival and median patient survival was not different between groups. As the study period went on, progression in the learning curve of LH correlated with an increase in the proportion of CCI score >70% and the Iwate difficulty scoring per case, as well as an increase in operative time and a rate of conversions with more challenging cases. Conclusion: Widespread adoption of LH on diseased livers with HCC relies on progressive patient selection reassuring the surgical team on taking more challenging cases. Even with increasingly difficult cases, the complication rate and oncologic outcomes remain comparable to open surgery.

Early Enrichment of ESR1 Mutations and the Impact on Gene Expression in Presurgical Primary Breast Cancer Treated with Aromatase Inhibitors.

To investigate the presence of ESR1 mutations in primary estrogen-receptor-positive (ER+) breast cancer treated with extended (>4 weeks) neoadjuvant (presurgical) aromatase inhibitor (NAI) therapy and to identify patients who may gain less benefit from aromatase inhibition (AI) alone based upon on-treatment changes in gene expression. We evaluated ER, progesterone receptor, and Ki67 by immunostaining, ESR1 mutations by droplet-digital PCR and expression of over 800 key breast cancer genes in paired pre- and post-NAI tumor samples from 87 ER+ breast cancer patients. Cell proliferation and estrogen-regulated genes (ERG) remained suppressed in most tumors indicative of persistent response to NAI. Enrichment of ESR1 mutations was found in five tumors and predominantly in patients receiving therapy for >6 months. ESR1-mutant tumors showed increased expression of ESR1 transcript and limited suppression of ERGs and proliferation-associated genes in response to NAI. ESR1 wild-type tumors with high residual proliferation (Ki67r ≥10%; 15/87 tumors) showed lower ESR1/ER expression pre- and post-therapy and lower ERGs. Tumors with ESR1 mutations or Ki67r ≥10% showed less inhibition of estrogen response, cell cycle, and E2F-target genes. Ligand-independent ER signaling, as a result of ESR1 mutation or reduced ER dependence, identified after extended NAI therapy, can guide early selection of patients who would benefit from combination therapy.

Prediction of poor outcome in Clostridioides difficile infection: A multicentre external validation of the toxin B amplification cycle

Classification of patients according to their risk of poor outcomes in Clostridioides difficile infection (CDI) would enable implementation of costly new treatment options in a subset of patients at higher risk of poor outcome. In a previous study, we found that low toxin B amplification cycle thresholds (Ct) were independently associated with poor outcome CDI. Our objective was to perform a multicentre external validation of a PCR-toxin B Ct as a marker of poor outcome CDI. We carried out a multicentre study (14 hospitals) in which the characteristics and outcome of patients with CDI were evaluated. A subanalysis of the results of the amplification curve of real-time PCR gene toxin B (XpertTM C. difficile) was performed. A total of 223 patients were included. The median age was 73.0 years, 50.2% were female, and the median Charlson index was 3.0. The comparison of poor outcome and non–poor outcome CDI episodes revealed, respectively, the following results: median age (years), 77.0 vs 72.0 (p = 0.009); patients from nursing homes, 24.4% vs 10.8% (p = 0.039); median leukocytes (cells/μl), 10,740.0 vs 8795.0 (p = 0.026); and median PCR-toxin B Ct, 23.3 vs 25.4 (p = 0.004). Multivariate analysis showed that a PCR-toxin B Ct cut-off <23.5 was significantly and independently associated with poor outcome CDI (p = 0.002; OR, 3.371; 95%CI, 1.565–7.264). This variable correctly classified 68.5% of patients. The use of this microbiological marker could facilitate early selection of patients who are at higher risk of poor outcome and are more likely to benefit from newer and more costly therapeutic options.

Therapeutic Advances in Emergency Cardiology: A Focus on Acute Myocarditis.

Myocarditis, defined as an inflammation of the myocardium, is an important cause of dilated cardiomyopathy and congestive heart failure. Unfortunately, its diagnosis and etiology is often challenging in clinical practice, and thus, improving diagnosis and therapeutic approach of this cardiac pathology is a matter of great interest. The etiology of the disease may be represented by not only infectious agents, usually with viral determination, but also autoimmune and systemic diseases or drugs. Regarding diagnostic techniques, endomyocardial biopsy remains the gold standard; but beyond histological findings, an important step in achieving an accurate diagnosis was represented by the use immunohistochemical criteria and noninvasive diagnostic tests such as cardiac magnetic resonance imaging. We reviewed current data on the current diagnosis and therapeutic approach of acute myocarditis. In addition to the standard heart failure therapy, some specific therapeutic options are available in selected cases. Viral myocarditis with persistent inflammation and viral clearance may be responsive to immunosuppressive therapy with azathioprine and cortisone or to immunoadsorption technique. Also, some chronic viral myocardial infections may benefit from 6 months of interferon-β therapy. The diagnosis of acute myocarditis still remains a great challenge, despite advances related to new diagnostic procedures. Endomyocardial biopsy, an invasive diagnostic tool that is not always usually available in clinical practice, still remains the standard diagnostic technique. Due to the potential evolution of acute myocarditis, identifying new parameters that may allow an early selection of patients with great risk of evolution toward myocardial fibrosis and dilated cardiomyopathy may be a field of great interest for future studies.

Quantitative Lesion Water Uptake in Acute Stroke Computed Tomography Is a Predictor of Malignant Infarction.

Background and Purpose- Early selection of patients with acute middle cerebral artery infarction at risk for malignant edema is critical to initiate timely decompressive surgery. Net water uptake (NWU) per brain volume is a quantitative imaging biomarker of space-occupying ischemic edema which can be measured in computed tomography. We hypothesize that NWU in early infarct lesions can predict development of malignant edema. The aim was to compare NWU in acute brain infarct against other common predictors of malignant edema. Methods- After consecutive screening of single-center registry data, 153 patients with acute proximal middle cerebral artery occlusion fulfilled the inclusion criteria. A total of 29 (18.2%) patients developed malignant edema defined as end point in follow-up imaging leading to decompressive surgery and death as a direct implication of mass effect. Early infarct lesion volume and NWU were quantified in multimodal admission computed tomography; time from symptom onset to admission imaging was recorded. Results- Mean time from onset to admission imaging was equivalent between patients with and without malignant infarcts (mean±SD: 3.3±1.4 hours and 3.3±1.7 hours, respectively). Edematous tissue expansion by NWU within infarct lesions occurred across all patients in this cohort (NWU: 9.1%±6.8%; median, 7.9%; interquartile range, 8.8%; range, 0.1%-35.6%); 7.0% (±5.2) in nonmalignant and 18.0% (±5.7) in malignant infarcts. Based on univariate receiver operating characteristic curve analysis, NWU >12.7% or an edema rate >3.7% NWU/h identified malignant infarcts with high discriminative power (area under curve, 0.93±0.02). In multivariate binary logistic regression, the probability of malignant infarct was significantly associated with early infarct volume and NWU. Conclusions- Computed tomography-based quantitative NWU in early infarct lesions is an important surrogate marker for developing malignant edema. Besides volume of early infarct, the measurements of lesion water uptake may further support identifying patients at risk for malignant infarction.

A Scoring System to Predict the Severity of Hirschsprung Disease at Diagnosis and Its Correlation With Molecular Genetics.

Objectives Hirschsprung disease (HSCR) has a wide range of severity. There are nonsevere forms treated conservatively until surgery and severe forms that require an early stoma and prolonged hospitalization. Our objective was to establish a clinical scoring system to predict the severity of HSCR and to evaluate the possible existence of a clinical-genetic correlation. Methods We carried out a retrospective observational study including all HSCR cases treated in our hospital. The sample was divided into severe and nonsevere disease according to the number of surgical procedures, hospitalization time, and episodes of enterocolitis. The proposed score was applied at diagnosis, and the sensitivity, specificity, and optimal cut-point were determined. We conducted a prospective molecular study of RET, EDNRB, and EDN3 on all patients, as well as SOX10 in Waardenburg Syndrome type 4 forms. Results Among the 42 patients treated between 1983 and 2013, 15 met the severe disease criteria. This group had a higher mean score (13.15 ± 2.36) than the nonsevere group (8.15 ± 2.13; p < 0.001). A score ≥11 had a sensitivity of 87% and a specificity of 81% in detecting the severe cases. Causative mutations were identified in 12 patients, 8 of them in the severe group ( p = 0.015). Most of these mutations (75%) were located in the RET proto-oncogene. Conclusion The proposed scoring system enables the early selection of patients with severe behavior of HSCR. A value ≥11 showed good sensitivity and specificity for this purpose. Causative mutations were identified in more than 50% of patients who met the criteria for severe disease.