Hasil untuk "Internal medicine"

Takuma Imakita, Kohei Fujita, Yuki Yamamoto et al.

Abstract Tarlatamab, a bispecific T-cell engager (BiTE), effectively activates the immune system but often causes cytokine release syndrome (CRS). To understand the early in vivo cytokine dynamics of post-BiTE therapy, we analyzed serum from three SCLC patients before and after tarlatamab administration using the Bio-Plex Pro Human Cytokine Screening Panel, 48-Plex. CRS occurred once in case 1, twice in case 2, and not at all in case 3. During the initial CRS in cases 1 and 2, IL-6, IL-1Ra, IL-10, granulocyte colony-stimulating factor, MIG, and IP-10 increased from baseline. Of these, MIG and IP-10 were also elevated during the second CRS episode in case 2. Some cytokines (hepatocyte growth factor, IFN-α2, IFN-γ, IL-2Rα, MIP-1α, MCP-1, and TRAIL) rose during CRS in either case 1 or 2 but showed little change in the other. RANTES decreased during CRS in case 1, yet increased and remained high in case 2, and stayed elevated in case 3. This cytokine profiling highlights the complex pathophysiology of CRS and the involvement of diverse cytokine networks beyond the IL-6 axis. These findings may guide future biomarker development, disease classification, and therapeutic strategies beyond IL-6 inhibition, advancing personalized CRS management.

Sjoerd J.D. Tjalsma, Niels J. Rinzema, Marjon J.A.M. Verstegen et al.

Summary: Cell-type-specific gene activation is regulated by enhancers, sometimes located at large genomic distances from target gene promoters. Whether distal enhancers require specific factors to orchestrate gene regulation remains unclear. Here, we used enhancer distance-controlled reporter screens to find candidate factors. We depleted them and employed activity-by-contact predictions to genome-wide classify genes based on enhancer distance. Predicted distal enhancers typically control tissue-restricted genes and often are strong enhancers. We find cohesin, but also mediator, most specifically required for long-range activation, with cohesin repressing short-range gene activation and prioritizing distal over proximal HBB genes competing for shared enhancers. Long-range controlled genes are also most sensitive to perturbations of other regulatory proteins and to BET inhibitor JQ1, this being more a consequence of their distinct enhancer features than distance. Our work predicts that lengthening of intervening sequences can help limit the expression of target genes to specialized cells with optimal trans-factor environments.

Zagalioti SC, Ziaka M, Exadaktylos A et al.

Sofia-Chrysovalantou Zagalioti,1 Mairi Ziaka,2 Aristomenis Exadaktylos,2 Barbara Fyntanidou1 1Department of Emergency Medicine, AHEPA University General Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece; 2Department of Emergency Medicine, Inselspital University Hospital, University of Bern, Bern, SwitzerlandCorrespondence: Sofia-Chrysovalantou Zagalioti, Email sofia_zag@yahoo.comBackground: Accurate decision-making in triage largely determines the amount of time required for a patient to be evaluated and treated while in the emergency department. Nursing staff worldwide have similar learning characteristics with similar working hours and common goals, despite the fact that different triage scales are used globally. The aim of this mini review is to present the different educational methods and identify the most effective for triage training of triage nurses.Materials and Methods: We screened studies concerning triage education for nurses in Emergency Department, in databases including PubMed, CENTRAL and CINAHL. From November 12, 2023 to February 15, 2024, databases were searched for relevant literature. “Triage education” OR “triage training” AND “emergency nurses” OR “triage nurses” were the MeSH terms.Results: There are various educational methods, including traditional, web-based, audiovisual, simulation-based, blended learning, and other specialized approaches. Almost all of the studies that are currently available demonstrate how effectively an educational intervention might improve nurses’ comprehension of triage. Except for one, every study concluded that the educational intervention significantly improved nurses’ triage knowledge. Comparing the included studies is challenging due to their heterogeneity, and applying the results in practice requires caution.Conclusion: The majority of studies reported that educational interventions effectively increased nurses’ triage knowledge. Blended learning in conjunction with refresher courses enhanced triage-related knowledge and decision-making; however, additional research is required to ascertain whether this approach is superior to the others and whether these improvements will last.Keywords: educational method, emergency department, triage education

Peng Luo, Xiankai Chen, Yafan Yang et al.

Abstract Objective To explore whether the upper and/or middle mediastinal nodes (UMMN) should be dissected in Siewert type II adenocarcinoma (AC) according to the incidence of lymph node metastasis. Additionally, to investigate the association between the length of esophageal involvement (LEI) and the UMMN metastases. Methods A cohort with Siewert type II AC who were operated on by a surgical team that routinely treated esophagogastric junction (EGJ) tumors with esophagectomy and extended lymphadenectomy were assessed retrospectively. The primary endpoint of the research was the metastasis rate of UMMN. Results A total of 94 patients with EGJ tumor from July 2018 to September 2022 were enrolled. Station 106recR (6.4%, 6/94) was the only station among upper mediastinal nodes (UMN) that presented positive nodes. Middle mediastinal nodes (MMN) metastases of station 107, 109 and station 108 were 2.1% (2/94) and 5.0% (4/80), respectively. Among the 11 patients with MMN or UMN metastases, 63.6% (7/11) had lesser than seven metastatic nodes, and 54.5% (6/11) had a pathological N stage ≤2. LEI >3 cm (p = 0.042) showed a higher risk for MMN metastases in univariable logistic analysis. However, no independent risk factor for mediastinal node metastases was detected. Conclusion This study demonstrated that the incidence of positive MMN and UMN is relatively low in resectable Siewert type II AC, which indicated that it is not necessary to perform a routine dissection upon these stations. LEI >3 cm might be associated with higher risk for mediastinal node metastasis. Certain patients could benefit from extended lymphadenectomy since most of the patients with positive MMN or UMN have a limited number of metastatic nodes.

Ovidio A. García-Villarreal

La reparación transcatéter borde a borde constituye un enfoque terapéutico que cambia el paradigma para los pacientes con regurgitación mitral grave que se consideran de alto riesgo para cirugía de la válvula mitral convencional. A pesar de su creciente popularidad, las consecuencias a largo plazo del gradiente transmitral elevado posterior al procedimiento en cuanto a las tasas de mortalidad y morbilidad siguen siendo un tema de intenso debate. La relación recíproca entre la reducción del área mitral y el aumento del gradiente transmitral, resultante de la colocación de un clip sobre ambas valvas de la mitral, puede potencialmente socavar la eficacia y la viabilidad del procedimiento. Es esencial una consideración cuidadosa para sopesar los beneficios y riesgos de reducir la regurgitación mitral residual a ≤ 1+ a expensas de un aumento del gradiente de la válvula mitral > 5 mm Hg. El efecto que un gradiente elevado de la válvula mitral después del procedimiento puede tener sobre el resultado final, como las tasas de muerte por cualquier causa o de hospitalización por regurgitación cardíaca, actualmente es un tema polémico. En esta revisión, se analizan cada uno de estos factores para ofrecer una visión más completa de las complejidades involucradas.

Yan Gu, Chunhua Song, Sinisa Dovat et al.

A. L. Chilingaryan, L. G. Tunyan, K. G. Adamyan et al.

Aim. To study the structural and functional left heart parameters in patients with severe aortic stenosis (AS) and preserved ejection fraction (EF) in order to determine the risk of atrial fibrillation (AF).Material and methods. The study included 84 patients (men, 37; mean age, 68±8 years) with severe AS and EF >55%. All patients had sinus rhythm and were asymptomatic. Echocardiography was performed to assess longitudinal strain of the left ventricle (LVLS), right ventricle, left atrium (LALS) and the left atrial stiffness (LAS) using the speckle tracking method. Left ventricular mass index (LVMI) and maximum left atrium volume index (LAVI) were also determined. Patients were followed up for 1 year.Results. AF was reported in 27 (32%) patients, of which 9 (33%) had asymptomatic AF episodes detected by 48-hour electrocardiography. Eighteen (67%) patients with AF felt palpitations. Patients with and without episodes of atrial fibrillation had non-significant differences in LVMI, LAVI, and LVLS. Patients with atrial fibrillation had a lower LALS and a higher LAS compared with patients without atrial fibrillation. Regression analysis revealed that LALS and LAS were independent predictors of AF.Conclusion. AF develops in about one third of asymptomatic patients with severe AS and normal EF. The development of AF predisposes to the onset of AS symptoms in most patients. LALS and LAS were predictors of AF in these patients. Identification of patients at risk of AF will allow for earlier aortic valve replacement.

Christian G. Ziegler, Carina Riediger, Matthias Gruber et al.

Pheochromocytomas (PCCs) are rare but potentially lethal tumors that arise from the adrenal medulla. The clinical suspicion and diagnosis of PCC can be challenging due to the non-specific nature of signs and symptoms. In many patients, infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) could lead to long-term symptoms including fatigue, headaches, and cognitive dysfunction. Here, we present the case of a patient incidentally diagnosed with an adrenal mass that proved to be a PCC after imaging was performed due to persisting complaints after coronavirus disease 2019 (COVID-19) infection. A 37-year-old male patient was referred to our center because of a right-sided inhomogeneous adrenal mass, incidentally found during a computed tomographic scan of the thorax performed due to cough and dyspnea that persisted after COVID-19 infection. Other complaints that were present prior to COVID-19 infection included profuse sweating, dizziness, exhaustion with chronic fatigue, and concentration difficulties. The patient had no history of hypertension, his blood pressure was normal, and the 24-h ambulatory blood pressure monitoring confirmed normotension but with the absence of nocturnal dipping. Plasma normetanephrine was 5.7-fold above the upper limit (UL) of reference intervals (738 pg/ml, UL = 129 pg/ml), whereas plasma metanephrine and methoxytyramine were normal at 30 pg/ml (UL = 84 pg/ml) and <4 pg/ml (UL = 16 pg/ml), respectively. Preoperative preparation with phenoxybenzamine was initiated, and a 4-cm tumor was surgically resected. Profuse sweating as well as dizziness was resolved after adrenalectomy pointing toward PCC and not COVID-19-associated patient concerns. Altogether, this case illustrates the difficulties in recognizing the possibility of PCC due to the non-specific nature of signs and symptoms of the tumor, which in this case did not include hypertension and coincided with some of the symptoms of long COVID-19.

Juan Carlos Ibarrola-Peña, Francisco José Barbosa-Camacho, Yolanda Lorelei Almanza-Mena et al.

IntroductionUnderstanding how Mexicans behave during the pandemic could present a complete picture of the phenomenon in our country and provide better management of it.ObjectiveThis study aimed to analyze the Mexican population's behavior and preventive measures.MethodsThis was a cross-sectional study in which a total of 4,004 participants from the general population responded to the survey.ResultsAlmost 99% of the participants mentioned knowing the symptoms of COVID-19. Although 77.5% of participants considered that they followed proper social distancing measures, 60% of them mentioned that they knew at least six individuals who did not follow social distancing measures. Furthermore, 96.2% of participants reported using preventive measures at least 50% of the time. Only 51.3% used a certified mask.ConclusionThe COVID-19 pandemic outcomes in Mexico are the result of multiple negative factors, such as high rates of comorbidities, high number of people living together at home, many people breaking social isolation, and most of the population using non-certified preventive measures that may not be effective enough.

Francesco Carubbi, Francesco Carubbi, Philipp Bosch et al.

Objectives: To investigate opinion and routine practice of specialists from different disciplines on imaging techniques for interventional procedures related to rheumatic and musculoskeletal diseases (RMDs).Methods: An English-language questionnaire was developed by an international working group and distributed to health care providers of various disciplines involved in the care of people with RMDs via an online survey tool (SoSci Survey®) from December 2019 to May 2020.Results: A total of 1,105 respondents from 56 countries completed the survey, over 60% of participants were rheumatologists. The majority of respondents (88%) performed interventional procedures in RMDs patients and 90% of them used imaging guidance. Ultrasonography was the most frequently used technique, particularly among rheumatologists. X-ray and computed tomography were mainly used by radiologists. A discrepancy emerged between the importance assigned to certain items such as the availability of a second operator and their actual implementation in clinical practice. Local barriers, lack of resources and facilities were mentioned as the most relevant obstacles in this regard. Lack of training on imaging and/or imaging guided procedures did not emerge as a barrier to perform such interventions; in fact, 19% of respondents performing the procedures indicated not to have received adequate training in this field.Conclusions: This is the first multinational multidisciplinary survey exploring in detail the opinions and practice on imaging guidance for interventional procedures in RMDs. A harmonization of protocols based on international guidelines, along with adequate training programmes and interventions on barriers at national/local levels are the main unmet needs requiring attention.

The COMEPA group

Coronavirus disease 2019 (COVID-19) has dramatically changed our lives. In the past months, hospitals were saturated of patients; therefore, it is still important to have simple and standardized prognostic factors and to evaluate the efficacy and safety of medications commonly used for COVID-19. We aimed to collect data of the patients hospitalized in Internal Medicine and Geriatrics Wards at the University Hospital (Policlinico) ‘P. Giaccone’ in Palermo, Italy (COMEPA, COVID-19 Medicina Policlinico Palermo), with the main purpose of finding prognostic tools that can be easily used in clinical practice in order to identify patients hospitalized for/with COVID-19 at higher risk of negative outcomes, such as mortality, transfer to Intensive Care Unit (ICU) and institutionalization, as well as evaluating the efficacy/safety of medications commonly used for COVID-19. For reaching these aims, the medical records of approximately 600 patients will be recorded, having data on several parameters and including as outcomes mortality, ICU placement, institutionalization. With the COMEPA study, we therefore plan to update current literature, giving new data on prognostic factors and on the efficacy/safety of some medications used for COVID-19.

Xiaowen Yu, Xiaowen Yu, Chong Ma et al.

BackgroundUrachal cancer is a rare neoplasm in the urological system. To our knowledge, no published study has explored to establish a model for predicting the prognosis of urachal cancer. The present study aims to develop and validate nomograms for predicting the prognosis of urachal cancer based on clinicopathological parameters.MethodsBased on the data from the Surveillance, Epidemiology, and End Results database, 445 patients diagnosed with urachal cancer between 1975 and 2018 were identified as training and internal validation cohort; 84 patients diagnosed as urachal cancer from 2001 to 2020 in two medical centers were collected as external validation cohort. Nomograms were developed using a multivariate Cox proportional hazards regression analysis in the training cohort, and their performance was evaluated in terms of its discriminative ability, calibration, and clinical usefulness by statistical analysis.ResultsThree nomograms based on tumor–node–metastasis (TNM), Sheldon and Mayo staging system were developed for predicting cancer-specific survival (CSS) of urachal cancer; these nomograms all showed similar calibration and discrimination ability. Further internal (c-index 0.78) and external (c-index 0.81) validation suggested that Sheldon model had superior discrimination and calibration ability in predicting CSS than the other two models. Moreover, we found that the Sheldon model was able to successfully classify patients into different risk of mortality both in internal and external validation cohorts. Decision curve analysis proved that the nomogram was clinically useful and applicable.ConclusionsThe nomogram model with Sheldon staging system was recommended for predicting the prognosis of urachal cancer. The proposed nomograms have promising clinical applicability to help clinicians on individualized patient counseling, decision-making, and clinical trial designing.

Fabien J. Fuche, Jennifer A. Jones, Girish Ramachandran et al.

Non-typhoidal Salmonella (NTS) are a leading cause of foodborne infections worldwide, and serogroups B, C1, C2-C3 and D are the most common serogroups associated with human disease. While live vaccine candidates that protect against S. Typhimurium (serogroup B) and S. Enteritidis (serogroup D) have been described by us and others, far less effort has been directed towards vaccines that target either serogroup C1 or C2-C3 Salmonella. Here we describe a Salmonella Newport-based live-attenuated vaccine (serogroup C2-C3). Deletion of the genes clpX or rfaL, previously used in live vaccines to attenuate S. Typhimurium and/or S. Enteritidis, failed to attenuate S. Newport. However, we found that deletion of either guaBA or htrA raised the 50% lethal dose of S. Newport in an intraperitoneal infection model in BALB/c mice. Our live-attenuated vaccine candidate CVD 1966 (S. Newport ΔguaBA ΔhtrA) elicited strong antibody responses against COPS, flagellin and outer membrane proteins when administered intraperitoneally or orally. Following lethal challenge with the parental virulent strain of S. Newport, we observed vaccine efficacies of 53% for immunization via the intraperitoneal route and 47% for immunization via the oral route. Following intraperiteonal immunization, the vaccine also significantly reduced the bacterial burden of challenge organisms in the liver and spleen. Interestingly, reducing the LPS chain length by deleting rfaL did not induce a stronger immune response towards surface antigens, and failed to elicit any protection against lethal homologous challenge. In conclusion, we have developed a live-attenuated Salmonella serogroup C2-C3 vaccine that we are further evaluating.

Shiau-Fu Hsieh, Kuo-Liong Chien, Chu-Hao Weng et al.

Background: The predictors for failure of home discharge after post-acute inpatient stroke rehabilitation need investigation. Methods: With this retrospective case-control study conducted in a stroke rehabilitation unit in one tertiary hospital, data of 297 eligible stroke patients regarding patient demographics, family information, disease and function were collected. The primary outcome was failure of home discharge. Results: One hundred and eighteen of 297 stroke patients (mean age 63 years, 37% women) failed to discharge home, including 109 admitted to rehabilitation hospitals and 9 to long-term care facilities. An inverse trend existed between numbers of daughters and the risk of failure of home discharge: having three or more daughters significantly lowers the risks for poor discharge destination (adjusted odds ratio, 0.23, 95% confidence interval, 0.07–0.72; test for trend, p = 0.002). Conclusion: Having more daughters independently predicts home discharge after post-acute inpatient stroke rehabilitation.

Li Lin, Rakhi Desai, Xiaoying Wang et al.

Abstract Background Microglial cultures comprise a critically important model system for investigating inflammatory mechanisms in almost all CNS disorders. Mild trypsinization and shaking are the two most commonly used methods to isolate primary microglia from mixed glial cultures. In this study, we characterized and compared microglia obtained using these two methods. Methods Primary rat microglia cultures were prepared from cerebral cortices of 1–2-day-old neonatal Sprague-Dawley rats. After achieving confluency at about 14 days in vitro, microglia were isolated from mixed glial cultures via either mild trypsinization or shaking. The purity of microglia was estimated by flow cytometry. Quantitative real-time PCR was used to measure mRNA expression. TNFα, IL-1β, IL-10, and IGF-1 in cell culture supernatant were measured using ELISA kits. Phagocytic function was assessed using fluorescein-labeled Escherichia coli K-12 BioParticles. Results Mild trypsinization generated a higher yield and purity than shaking. Microglia isolated by mild trypsinization appeared to be in a quiescent state with ramified morphology. Microglia isolated by shaking showed a more heterogenous morphology, including cells with rounded shapes suggestive of activation. Compared with shaking, microglia isolated by trypsinization also had lower baseline phenotype markers (iNOS, CD86, CD206, and arginase 1) and lower levels of cytokines (TNFα, IL-1β, IL-10, and IGF-1) as well as reduced phagocytic capability. Both methods yielded microglia that were responsive to various stimuli such as IL-4, lipopolysaccharide (LPS), or interferon-γ (IFNγ). Although stimulated patterns of gene expression and cytokine release were generally similar, there were also significant differences in terms of absolute response. LPS treatment induced significantly higher levels of TNFα and IL-10 in microglia isolated by mild trypsinization versus shaking. IFNγ induced a lower response in TNFα in microglia obtained by mild trypsinization versus shaking. Conclusions Our results suggest that isolating microglia with the shaking method may induce slight activation even at baseline, and this may affect stimulus responses in subsequent experiments. Caution and attention should be warranted when choosing isolation protocols for primary microglia cultures.

Seyoum Aklilu, Sikaala Chadwick H, Chanda Javan et al.

<p>Abstract</p> <p>Background</p> <p>Current front line malaria vector control methods such as indoor residual spraying (IRS) and long-lasting insecticidal nets (LLINs), rely upon the preference of many primary vectors to feed and/or rest inside human habitations where they can be targeted with domestically-applied insecticidal products. We studied the human biting behaviour of the malaria vector <it>Anopheles funestus</it> Giles and the potential malaria vector <it>Anopheles quadriannulatus</it> Theobald in Luangwa valley, south-east Zambia.</p> <p>Methods</p> <p>Mosquitoes were collected by human landing catch in blocks of houses with either combined use of deltamethrin-based IRS and LLINs or LLINs alone. Human behaviour data were collected to estimate how much exposure to mosquito bites indoors and outdoors occurred at various times of the night for LLIN users and non-users.</p> <p>Results</p> <p><it>Anopheles funestus</it> and <it>An. quadriannulatus</it> did not show preference to bite either indoors or outdoors: the proportions [95% confidence interval] caught indoors were 0.586 [0.303, 0.821] and 0.624 [0.324, 0.852], respectively. However, the overwhelming majority of both species were caught at times when most people are indoors. The proportion of mosquitoes caught at a time when most people are indoors were 0.981 [0.881, 0.997] and 0.897 [0.731, 0.965], respectively, so the proportion of human exposure to both species occuring indoors was high for individuals lacking LLINs (<it>An. funestus</it>: 0.983 and <it>An. quadriannulatus</it>: 0.970, respectively). While LLIN users were better protected, more than half of their exposure was nevertheless estimated to occur indoors (<it>An. funestus</it>: 0.570 and <it>An. quadriannulatus</it>: 0.584).</p> <p>Conclusions</p> <p>The proportion of human exposure to both <it>An. funestus</it> and <it>An. quadriannulatus</it> occuring indoors was high in the area and hence both species might be responsive to further peri-domestic measures if these mosquitoes are susceptible to insecticidal products.</p>

Dowling Catherine, Gill Catherine, O'Neill Amanda J et al.

<p>Abstract</p> <p>Background</p> <p>Manipulating apoptotic resistance represents an important strategy for the treatment of hormone refractory prostate cancer. We hypothesised that the Inhibitor of Apoptosis (IAP) Proteins may be mediating this resistance and knockdown of cIAP-1, cIAP-2 and XIAP would increase sensitivity to apoptosis.</p> <p>Methods</p> <p>cIAP-1, cIAP-2 and XIAP where knocked down either individually or in combination using siRNA in androgen independent prostate cancer PC-3 cells as confirmed by real-time PCR and western blotting. Cells were then treated with TRAIL, Etoposide, or Tunicamycin, and apoptosis assessed by PI DNA staining. Apoptosis was confirmed with Annexin V labelling and measurement of PARP cleavage, and was inhibited using the pan-caspase inhibitor, zVAD.fmk. Clonogenic assays and assessment of ID-1 expression by western blotting were used to measure recovery and proliferation.</p> <p>Results</p> <p>PC-3 are resistant to TRAIL induced apoptosis and have elevated expression of cIAP-1, cIAP-2 and XIAP. Combined knockdown sensitised PC-3 to TRAIL induced apoptosis, but not to Etoposide or Tunicmycin, with corresponding increases in caspase activity and PARP cleavage which was inhibited by ZVAD.fmk. Triple knock down decreased proliferation which was confirmed by decreased ID-1 expression.</p> <p>Conclusion</p> <p>Simultaneous knock down of the IAPs not only sensitised the PC-3 to TRAIL but also inhibited their proliferation rates and clonogenic survival. The inability to alter sensitivity to other triggers of apoptosis suggests that this effect is specific for death receptor pathways and knock down might facilitate immune-surveillance mechanisms to counter cancer progression and, in combination with therapeutic approaches using TRAIL, could represent an important treatment strategy.</p>