Disease Entity Research Articles

Colon and rectal peritoneal carcinomatosis: are we mixing apples with oranges? A propensity score-matched analysis.

Rectal cancer is universally considered a different disease entity as compared to colon cancer, except when dealing with colorectal peritoneal carcinomatosis (PC), in which the two cancers are deemed as the same one. The present study aims to investigate the influence of primary tumor location (colon vs. rectum) on oncologic outcomes in patients undergoing cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) for colorectal peritoneal metastases. Data from three referral centers undergoing CRS plus HIPEC for PC of colorectal origin were prospectively collected. The primary outcomes were overall survival (OS) and disease-free survival (DFS) according to primary tumor location (colic vs. rectal). Univariate and multivariate analyses were performed using the Cox proportional hazard model first on the total number of patients. Then, a propensity score matching using the nearest-neighbour method with a 1:1 ratio was performed. The study included 167 patients: 126 colic and 41 rectal PC. After propensity score matching, rectal primary tumor location was independently predictive of a lower DFS (HR 1.91; 95%CI 1.06-3.45; p = 0.031) but not of a lower OS (HR 1.12; 95%CI 0.57-2.21; p = 0.73). Post-matching 3-year DFS rates were 49.2% (95%CI 34,3-70,5%) and 19.4% (95%CI 9,4-40,2%) for colic and rectal PC, respectively. The present study shows a significantly worse DFS for rectal cancer PC undergoing CRS and HIPEC compared to colon cancer PC, suggesting a possible need for dedicated pathways for rectal PC patients and posing a question for rectal PC to be considered as a unique disease entity.

Are neurasthenia and depression the same disease entity? An electroencephalography study

BackgroundThe neurasthenia–depression controversy has lasted for several decades. It is challenging to solve the argument by symptoms alone for syndrome-based disease classification. Our aim was to identify objective electroencephalography (EEG) measures that can differentiate neurasthenia from major depressive disorder (MDD).MethodsBoth electronic medical information records and EEG records from patients with neurasthenia and MDD were gathered. The demographic and clinical characteristics, EEG power spectral density, and functional connectivity were compared between the neurasthenia and MDD groups. Machine Learning methods such as random forest, logistic regression, support vector machines, and k nearest neighbors were also used for classification between groups to extend the identification that there is a significant different pattern between neurasthenia and MDD.ResultsWe analyzed 305 patients with neurasthenia and 45 patients with MDD. Compared with the MDD group, patients with neurasthenia reported more somatic symptoms and less emotional symptoms (p < 0.05). Moreover, lower theta connectivity was observed in patients with neurasthenia compared to those with MDD (p < 0.01). Among the classification models, random forest performed best with an accuracy of 0.93, area under the receiver operating characteristic curve of 0.97, and area under the precision-recall curve of 0.96. The essential feature contributing to the model was the theta connectivity.LimitationsThis is a retrospective study, and medical records may not include all the details of a patient’s syndrome. The sample size of the MDD group was smaller than that of the neurasthenia group.ConclusionNeurasthenia and MDD are different not only in symptoms but also in brain activities.

Perceptual Disturbances and Disorders in the ICD-11: An Overview and a Proposal for Systematic Classification.

The International Classification of Diseases (ICD) has been developed and edited by the World Health Organisation and represents the global standard for recording health information and causes of death. The ICD-11 is the eleventh revision and came into effect on 1 January 2022. Perceptual disturbances refer to abnormalities in the way sensory information is interpreted by the brain, leading to distortions in the perception of reality. These can manifest as distorted perceptions or as phantom perceptions and can occur in all sensory modalities as visual, auditory, olfactory, gustatory tactile, vestibular, proprioceptory or interoceptory disturbances. There are similar brain mechanisms involved in the generation of these analogous perceptual disturbances and disorders, and they are treated with similar approaches. Perceptual disturbances are highly prevalent, with large variations across the different sensory modalities. They can be associated with significant suffering and cause a high socioeconomic burden. Perceptual disturbances can be symptoms of another disease or disease entities on their own. In the context of pain, this is reflected by the distinction between secondary pain (pain as a symptom of another underlying condition) and primary pain (a disease in its own right, rather than being a symptom of another underlying condition) in the ICD-11. Such a clear distinction is not found in an entirely consistent way across the various sensory modalities. By using the example of auditory phantom perceptions, we propose a framework for the classification of sensory disorders in alignment with the classification of pain in the ICD-11. The descriptions of the sensory disturbances should include (1) a causal aspect (primary versus secondary), (2) a temporal aspect (acute vs. chronic and persistent vs. intermittent), (3) a cognitive, emotional and autonomic interpretation aspect (=suffering) and (4) a social aspect (=disability). If the latter two aspects are present, we propose that the sensory disturbance is called a sensory disorder.

Predictive Factors for the Discontinuation of Pressurized Intraperitoneal Aerosol Chemotherapy: Enhancing Patient Selection to Improve Oncological Outcomes-A Single-Center Experience.

Background: Since 2011, Pressurized Intraperitoneal Aerosol Chemotherapy (PIPAC) has emerged as a promising treatment option for patients with peritoneal surface malignancies (PSM) who are not eligible for cytoreductive surgery (CRS). Repeated minimal-invasive treatment is one of the key features and the current empirical standard treatment (ST) consists of at least three administrations over about three months. However, many patients are unable to complete the full course, limiting the potential benefits of PIPAC. Method: This retrospective, single-center study assessed the completion rate of ST and identified the main causes and predictive factors for discontinuation. This study also evaluated the feasibility, safety, and efficacy of PIPAC and investigated whether improved patient selection over the years has resulted in better oncological outcomes. Result: Data from 168 patients treated with PIPAC between January 2017 and March 2023 for a total of 336 procedures showed that only 29% completed ST. Multivariate analysis identified ascites >500 mL and a prior history of bowel obstruction as significant predictors of discontinuation. Conclusions: Patients with radiological or clinical signs of obstruction should not be considered for PIPAC treatment, and ascites increases the risk of incomplete treatment. Larger studies are eagerly awaited to corroborate these findings and refine the selection criteria by disease entity.

Proteomic Profiling Towards a Better Understanding of Genetic Based Muscular Diseases: The Current Picture and a Look to the Future.

Proteomics accelerates diagnosis and research of muscular diseases by enabling the robust analysis of proteins relevant for the manifestation of neuromuscular diseases in the following aspects: (i) evaluation of the effect of genetic variants on the corresponding protein, (ii) prediction of the underlying genetic defect based on the proteomic signature of muscle biopsies, (iii) analysis of pathophysiologies underlying different entities of muscular diseases, key for the definition of new intervention concepts, and (iv) patient stratification according to biochemical fingerprints as well as (v) monitoring the success of therapeutic interventions. This review presents-also through exemplary case studies-the various advantages of mass proteomics in the investigation of genetic muscle diseases, discusses technical limitations, and provides an outlook on possible future application concepts. Hence, proteomics is an excellent large-scale analytical tool for the diagnostic workup of (hereditary) muscle diseases and warrants systematic profiling of underlying pathophysiological processes. The steady development may allow to overcome existing limitations including a quenched dynamic range and quantification of different protein isoforms. Future directions may include targeted proteomics in diagnostic settings using not only muscle biopsies but also liquid biopsies to address the need for minimally invasive procedures.

Clinical and imaging features of co-existent pulmonary tuberculosis and lung cancer: a population-based matching study in China

BackgroundCo-existent pulmonary tuberculosis and lung cancer (PTB-LC) represent a unique disease entity often characterized by missed or delayed diagnosis. This study aimed to investigate the clinical and radiological features of patients diagnosed with PTB-LC.MethodsPatients diagnosed with active PTB-LC (APTB-LC), inactive PTB-LC (IAPTB), and LC alone without PTB between 2010 and 2022 at our institute were retrospectively collected and 1:1:1 matched based on gender, age, and time of admission. Symptoms and clinicopathological features were compared among the three groups of patients. Logistic regression was employed for risk factor analysis.ResultsCompared to LC or IAPTB-LC, patients with APTB-LC exhibited higher proportions of weight loss (p < 0.001) and fever (p < 0.001) at the time of diagnosis. Additionally, radiological features such as nodules (p = 0.007), tree-in-bud (p < 0.001), cavitation (p < 0.001), and calcification (p < 0.001) were significantly more prevalent in APTB-LC patients compared to the other groups. Patients with APTB-LC were more susceptible to lymph node involvement (p < 0.001) and distant metastasis (p = 0.006) compared to those with IAPTB-LC or LC alone. Additionally, in comparison to LC alone, patients with IAPTB-LC exhibited more complex symptoms, imaging features, and lymph node metastases. Logistic regression results indicated that factors such as BMI, fever, patchy shadow, cavitation, neck or supraclavicular lymph node metastasis, and liver injury favor the diagnosis of APTB-LC over LC alone. The pre-diagnostic model exhibited robust performance, achieving area under the curve (AUC) values of 0.864 in the training set and 0.830 in the test set.ConclusionOur results indicate that PTB-LC is a distinct disease characterized by complex clinicopathological features and a more aggressive nature. Based on our findings, we recommend conducting TB-related tests for LC patients who exhibit relevant risk factors or are identified as high-risk cases according to the pre-diagnostic model.

Synopsis of European Society of Pediatric astroenterology, Hepatology and Nutrition (ESPGHAN) Guidelines (2024) on the Diagnosis and Treatment of Eosinophilic Esophagitis.

The European Society of Pediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) 2024 guidelines on eosinophilic esophagitis in children provide a systematic approach to the diagnosis and management of this rising disease entity in children. We present a concise update of the guideline to simplify management protocols, thus improving patient outcome.

Preventive Effects of Botulinum Neurotoxin Long-Term Therapy: Comparison of the 'Experienced' Benefits and 'Suspected' Worsening Across Disease Entities.

Background: Repetitive intramuscular injections of botulinum neurotoxin (BoNT) have become the treatment of choice for a variety of disease entities. But with the onset of BoNT therapy, the natural course of a disease is obscured. Nevertheless, the present study tries to analyze patients' "suspected" course of disease severity under the assumption that no BoNT therapy had been performed and compares that with the "experienced" improvement during BoNT treatment. Methods: For this cross-sectional study, all 112 BoNT long-term treated patients in a botulinum toxin out-patient department were recruited who did not interrupt their BoNT/A therapy for more than two injection cycles during the last ten years. Patients had to assess the remaining severity of their disease as a percentage of the severity at onset of BoNT therapy and to draw three different graphs: (i) the CoDB-graph showing the course of severity of patient's disease from onset of symptoms to onset of BoNT/A therapy, (ii) the CoDA-graph illustrating the course of severity from onset of BoNT/A therapy until recruitment, and (iii) the CoDS-graph visualizing the suspected development of disease severity from onset of BoNT/A therapy until recruitment under the assumption that no BoNT/A therapy had been performed. Three different types of graphs were distinguished: the R-type indicated a rapid manifestation or improvement, the C-type a continuous worsening or improvement, and the D-type a delayed manifestation or response to BoNT therapy. Four patient subgroups (cervical dystonia, other cranial dystonia, hemifacial spasm, and the migraine subgroup) comprised 91 patients who produced a complete set of graphs which were further analyzed. The "experienced" improvement and "suspected" worsening of disease severity since the onset of BoNT/A therapy were compared and correlated with demographical and treatment related data. Results: Improvement was significant (p < 0.05) and varied between 45 and 70% in all four patient subgroups, the "suspected" worsening was also significantly (p < 0.05) larger than 0, except in the migraine patients and varied between 10 and 70%. The "total benefit" (sum of improvement and prevented "suspected" worsening) was the highest in the other cranial dystonia group and the lowest in the migraine subgroup. The distributions of R-,C-,D-type graphs across CoDB-, CoDS-, and CoDB-graphs and across the four patient subgroups were significantly different. Conclusions: (i) Most BoNT long-term treated patients have the opinion that their disease would have further progressed and worsened if no BoNT/A therapy had been performed, (ii) The type of response to BoNT/A is different across different subgroups of BoNT/A long-term treated patients.

Interrelationship Between Borderline Personality, PTSD and Complex PTSD

This article contains a presentation of the most important elements of the definition of Complex PTSD (Complex Post-traumatic Stress Disorder). Since it is possible to discuss the new aspects of the disease which consists on: Borderline Personality Disorder (BPD), Post-traumatic Stress Disorder (PTSD), and - as a new disease - Complex PTSD (cPTSD). The text is showing on the accuracy to make distinctions of the Complex PTSD from other known disease entities, because modern studies are clearly demonstrating this need. This is evidenced by studies of people exposed to chronic social stress combined with depression relationships. The experiences referred to as "boundary" for the human psyche and making up this type of disorder are long-lasting and leaving significant traces in the psyche of the patients (affective dysregulation). The introduction of a new disease entity is caused by the necessity to adjust clinical diagnoses to new observations, which significantly beyond the accepted definition of PTSD (range: symptoms, treatment time). It seems legitimate to define a new comprehensive trauma; the symptoms largely depend on the characteristics of the individual patient.

Identification of Biomarkers of Arrhythmogenic Cardiomyopathy (ACM) by Plasma Proteomics.

Background and Objectives: The pathophysiology of arrhythmogenic cardiomyopathy (ACM), previously known as arrhythmogenic right ventricular cardiomyopathy (ARVC), and its specific biological features remain poorly understood. High-throughput plasma proteomic profiling, a powerful tool for gaining insights into disease pathophysiology at the systems biology level, has not been used to study ACM. This study aimed at characterizing plasmatic protein changes in patients with ACM, which were compared with those of healthy controls, and at exploring the potential role of the identified proteins as biomarkers for diagnosis and monitoring. Materials and Methods: Blood samples were collected from six ACM patients, four patients with other cardiomyopathies, and two healthy controls. Plasma was processed to remove high-abundance proteins and analyzed by two-dimensional gel electrophoresis. Differential protein expressions were assessed using PDQuest software, Bio-Rad US version 8.0.1. Results: The analysis revealed several proteins with altered expressions between ACM patients and controls, including plakophilin-2, junctional plakoglobin, desmoplakin, desmin, transmembrane protein 43, and lamin A/C. Conclusions: The plasma proteomic profiling of ACM suggests that ACM is a distinct disease entity characterized by a unique dysregulation of desmosomal proteins. The identification of plasma biomarkers associated with ACM underscores their potential to improve diagnostic accuracy and facilitate early intervention strategies. Further exploration of mutations in desmosomal proteins and their phosphorylation states may provide deeper insights into the pathophysiology of ACM.

Female Oncofertility and Immune Checkpoint Blockade in Melanoma: Where Are We Today?

The incidence of melanoma among young adults has risen, yet mortality has declined annually since the introduction of immune checkpoint inhibitors (ICI). The utilization of peri-operative ICI has significantly altered the treatment landscape in melanoma, with PD-1 inhibitors showing promising efficacy in improving relapse-free survival rates in high-risk stage II-III disease. With the increasing use of ICI, secondary concerns have emerged regarding the impact of cancer drugs on fertility and reproductive health among women of childbearing potential, especially in early-stage cancer settings. The exclusion of pregnant women from trials contributes to limited human data and clinical uncertainties, such as maternal and fetal toxicities related to ICI exposure during pregnancy, as well as the value of fertility preservation before ICI therapy. Uncertainty persists regarding pregnancy post-adjuvant immunotherapy, given the potential detrimental effects of hormonal and immunological changes during pregnancy on melanoma relapse. There is additional uncertainty about whether pregnancy-associated melanoma (PAM) represents a distinct disease entity that warrants tailored management compared to non-pregnant cases. Our review aims to give an overview of oncofertility practices among female melanoma patients after immunotherapy. We also focus on the literature gap in the published evidence and synthesize summaries regarding ICI toxicities on reproductive health and fetal development, pregnancy planning, and recurrence risks after melanoma treatment.

Prevalence and determinants of metabolic syndrome among type2 diabetic patients using different diagnosis criteria in ethiopia: systematic review and meta-analysis

BackgroundMetabolic syndrome has become a major public health problem worldwide and is attributable to the spread of different non-communicable diseases such as type 2 diabetes mellitus, coronary artery diseases, stroke, and permanent or temporary disabilities. It is not a single disease entity but encompasses different risk factors. However, there were inconsistencies among previously conducted primary studies, hence this systematic review and meta-analysis aimed to determine the pooled prevalence and determinants of metabolic syndrome among type2 diabetes patients in Ethiopia.MethodFirst-hand studies about the metabolic syndrome among adult type 2 diabetic patients in Ethiopia were searched through known and international databases (PubMed, Scopus, Web of Science, and Cochran Library) and search engines (Google and Google Scholar). Data was extracted using a standard data extraction checklist developed according to Joanna Briggs Institute (JBI). The I2 statistics are used to identify heterogeneity across studies. Funnel plot asymmetry and Egger’s tests were used to check for publication bias. A random effect model was used to estimate the pooled prevalence of the metabolic syndrome among non-insulin-dependent patients in Ethiopia. The STATA version 11 software employed for statistical analysis was conducted using STATA version 11 software.ResultThe overall pooled prevalence of metabolic syndrome among type2 diabetic patients in was 54.56% [95%CI (43.73, 65.38), I2 = 97.0%, P = 0.001] using NCEP-ATP III, 48.32% [95%CI (42.1, 54.44), I2 = 97.0%, P = 0.001] IDF diagnosis criteria, 47.0[95%CI(27.01–66.99)], I2 = 97.5%, p = 0.001 using WHO and 59.37%(95%CI(47.21–71.52), I2 = 91.2%, p = 0.001 using harmonized diagnosis criteria respectively. This meta-analysis identified several significant predictors of metabolic syndrome among type 2 diabetes patients in Ethiopia. The odds of having metabolic syndrome was reduced for females (Adjusted Odds Ratio [AOR] = 0.55, 95% CI: 0.35–0.87) compared to males. However, the odds of metabolic syndrome increased with alcohol intake (AOR = 1.44, 95% CI: 1.03–2.01), the odds of living in urban areas(AOR = 2.12, 95% CI: 1.55–2.88), and the odds of having a diabetes duration of six or more years since diagnosis (AOR = 2.94, 95% CI: 1.17–7.41) were significant predictors.ConclusionThe pooled prevalence was considerably high among type 2 diabetic patients in Ethiopia. The pooled prevalence of metabolic syndrome varies as per the diagnosis criteria used with the highest observed in harmonized diagnosis criteria. Being female, being rural residency, alcohol intake, and duration of diabetes since diagnosis were significant predictors of metabolic syndrome among type 2 diabetic patients in Ethiopia.

Outcome of critically ill patients receiving systemic chemotherapy on the intensive care unit.

Analyze the outcomes of critically ill patients who developed new-onset organ dysfunction and received systemic chemotherapy during their ICU stay. Retrospective cohort study. A tertiary medical center in Germany with an Intensive Care Medicine department consists of 11 intensive care units comprising 140 beds, serving all subspecialties of adult intensive care medicine. 167 patients receiving systemic oncological treatment from January 1st, 2015 to December 31st, 2021, with a data cut-off on December 31st, 2022. None. A total of 167 patients were included. The primary reasons for ICU admission were respiratory failure and shock/sepsis, each accounting for 34% of cases, while complications associated with oncological therapy accounted for less than 8%. The median age of hematological patients (n = 129) was 62 years (IQR 50-70), and for solid tumor patients (n = 38), it was 60 years (IQR 52-65). Predominant disease entities included lymphoma (43%) and acute myeloid leukemia (29%) among hematological patients, and lung cancer (47%) and gastrointestinal malignancies (17%) among solid tumor patients. Hematological patients had a significantly higher median Simplified Acute Physiology Score II (47 vs. 39 points; p=0.013), a higher need for invasive mechanical ventilation (59% vs. 50%; p=0.3), renal replacement therapy (54% vs. 24%; p < 0.001), and a higher 1-year mortality rate (64% vs. 53%; p=0.2) compared to solid tumor patients. The hazard ratio for 1 year survival for male sex was 2.34 (1.31-3.49), for mechanical ventilation 2.01 (1.33-3.04), for vasopressor therapy 1.98 (1.27-3.10), and for renal replacement therapy 1.51 (1.03-2.23), respectively. Administering intravenous chemotherapy in an ICU setting remains challenging, and the experience to establish an indication for systemic chemotherapy is still challenging. However, the study demonstrates that, after careful interdisciplinary decision-making, a substantial number of patients can benefit from it.

Consensus and guidelines on diagnosis and management of polypoidal choroidal vasculopathy (PCV) from the Asia-Pacific Vitreo-retina Society (APVRS).

A panel of 21 international experts are formed by the Asia-Pacific Vitreo-retina Society to work out the consensus and guidelines on polypoidal choroidal vasculopathy (PCV). PCV is a common subtype of neovascular age-related macular degeneration and is more prevalent in Asian populations. Recent advancement in imaging technology allows greater understanding of the disease process of PCV. Furthermore, non-indocyanine green angiography features in optical coherence tomography angiography have been validated for PCV diagnosis and treatment response monitoring. Clinical trials provide new data on the safety and efficacy of various anti-vascular endothelial growth factor (anti-VEGF) agents as well as protocols that aim to improve the sustainability of treatments. In view of the myriads of emerging information, the panel gathered, reviewed, discussed, formulated and voted on the consensus and guidelines of PCV on four areas: 1) disease entity, 2) investigation and diagnosis, 3) treatment options, and 4) management protocol and future development in a five-point Likert scale (strongly agree, agree, neutral, disagree and strongly disagree). We proposed using a consensus score in which the maximum was 100. The summation of the respective "percentages" of experts voting for "agree" or "strongly agree" would be counted as the actual score. Consensus was achieved when the actual score of 75 or more was reached, which meant at least 75 % of the experts had voted for "strongly agree" or "agree" on the consensus statement concerned.

Evidence for functional interaction between the CB1 and the mGlu7 receptors mediated signaling in modulation of anxiety behavior and cognition.

Anxiety is a severe social problem. It is a disease entity that occurs alone or accompanies other diseases such as depression, phobia, or post-traumatic stress disorder. Our earlier studies demonstrated that blockage of arachidonic acid (AA) pathway via inhibition of cyclooxygenase-2 (COX-2) enzyme can modulate mGluRs-induced anxiety-like behavior. Here, we hypothesized that modulation of 2-arachidoglycerol (2-AG), a component of the AA pathway, concomitantly with modulation of mGluR7 signaling, should be adequate to trigger a similar response from the test organism. Since 2-AG is an endogenous agonist for CB1 receptors, we used a CB1/GPR55/μ-opioid receptor antagonist (AM251) alone and in combination with mGluR7 allosteric agonist (AMN082). Stress-induced hyperthermia (SIH) test was performed as a behavioral readout. AM251 has a dual mode on AMN082-mediated effects in SIH in CD-1 mice. Furthermore, the CB1 receptor ligand influenced adaptation to stress in repeated SIH procedures and learning possibilities of mice in the Barnes maze. We also found changes in mGluR7 protein expression levels in the prefrontal cortex (PFC) after mice were exposed to AM251, which showed the potential to attenuate the AMN082-induced decline in mGluR7 levels. The changes induced by AM251 on AMN082-mediated behavioral and biochemical effects were confirmed in electrophysiological experiments in which AM251 abolished AMN082-mediated LTP escalation in PFC. The mGluR7 overexpressed cell line was used to exclude the direct involvement of mGluR7 in AM251 activity. All the above results and the co-localization of CB1 and mGlu7 receptors detected in specific brain regions strongly suggest the specific interaction between CB1 and mGlu7 receptors and their signaling.

Underrepresentation of Small Lymphocytic Lymphoma in Clinical Trials for Chronic Lymphocytic Leukemia.

Although chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL) are the same biologic disease entity and warrant identical treatment approaches, patients with SLL have frequently been excluded from clinical trials in CLL. This study assessed the representation of patients with SLL among Phase II or III clinical trials cited in the 2024 National Comprehensive Cancer Network (NCCN) treatment guidelines. Patients with SLL were explicitly eligible for only 21 (38%) of the 56 clinical trials for CLL, comprising 222 (6%) of the 3440 enrolled patients. Notably, 380 patients with SLL were enrolled in 16 separate non-CLL clinical trials alongside patients with indolent B-cell lymphomas such as follicular lymphoma. In CLL trials, patients with SLL were included in a greater proportion of studies evaluating BTK inhibitors (67%) or BTK/BCL2 inhibitor combinations (67%) compared to BCL2 inhibitors (0%) or chemoimmunotherapy (0%). Although recent and upcoming trials show a promising trend toward the inclusion of patients with SLL, further advocacy is needed to raise awareness of the biological similarities between CLL and SLL and to promote the representation of patients with SLL in CLL/SLL clinical research.

Single-Cell RNA Sequencing Reveals the Tumor Heterogeneity and Immunosuppressive Microenvironment in Urothelial Carcinoma.

Urothelial carcinoma (UC) can arise from either the lower urinary tract or the upper tract; they represent different disease entities and require different clinical treatment strategies. A full understanding of the cellular characteristics in UC may guide the development of novel therapies. Here, we performed single-cell transcriptome analysis from four patients with UC of the bladder (UCB), five patients with UC of the ureter (UCU), and four patients with UC of the renal pelvis (UCRP) to develop a comprehensive cell atlas of UC. We found the rare epithelial cell subtype EP9 with epithelial-to-mesenchymal transition (EMT) and cancer stem cell (CSC) features, and specifically expressed SOX6, which was associated with poor prognosis. We also found that ACKR1+ endothelial cells and inflammatory cancer-associated fibroblasts (iCAFs) were more enriched in UCU, which may promote pathogenesis. While ESM1+ endothelial cells may more actively participate in UCB and UCRP tumorigenesis by promoting angiogenesis. Additionally, CD8 + effector T cells were more enriched in UCU and UCRP patients, while Tregs were mainly enriched in UCB tumors. C1QC+ macrophages and LAMP3+ dendritic cells were more enriched in UCB, which is closely related to the formation of the heterogeneous immunosuppressive microenvironment. Furthermore, we found strong interactions between iCAFs, EP9, and Endo_ESM1, and different degrees of activation of the FGF-FGFR3 axis and immune checkpoint pathway were observed in different UC subtypes. Our study elucidated the cellular heterogeneity and the components of the microenvironment in UC arising from the upper and lower urinary tracts and provided novel therapeutic targets.

The Potential of Metabolomics as a Tool for Identifying Biomarkers Associated with Obesity and Its Complications: A Scoping Review.

Obesity and its related diseases, such as type 2 diabetes (T2DM), cardiovascular disease (CVD), and metabolic fatty liver disease (MAFLD), require new diagnostic markers for earlier detection and intervention. The aim of this study is to demonstrate the potential of metabolomics as a tool for identifying biomarkers associated with obesity and its comorbidities in every age group. The presented systematic review makes an important contribution to the understanding of the potential of metabolomics in identifying biomarkers of obesity and its complications, especially considering the influence of branched-chain amino acids (BCAAs), amino acids (AAs) and adipokines on the development of T2DM, MAFLD, and CVD. The unique element of this study is the combination of research results from the last decade in different age groups and a wide demographic range. The review was based on the PubMed and Science Direct databases, and the inclusion criterion was English-language original studies conducted in humans between 2014 and 2024 and focusing on the influence of BCAAs, AAs or adipokines on the above-mentioned obesity complications. Based on the PRISMA protocol, a total of 21 papers were qualified for the review and then assigned to a specific disease entity. The collected data reveal that elevated levels of BCAAs and some AAs strongly correlate with insulin resistance, leading to T2DM, MAFLD, and CVD and often preceding conventional clinical markers. Valine and tyrosine emerge as potential markers of MAFLD progression, while BCAAs are primarily associated with insulin resistance in various demographic groups. Adipokines, although less studied, offer hope for elucidating the metabolic consequences of obesity. The review showed that in the case of CVDs, there is still a lack of studies in children and adolescents, who are increasingly affected by these diseases. Moreover, despite the knowledge that adipokines play an important role in the pathogenesis of obesity, there are no precise findings regarding the correlation between individual adipokines and T2DM, MAFLD, or CVD. In order to be able to introduce metabolites into the basic diagnostics of obesity-related diseases, it is necessary to develop panels of biochemical tests that will combine them with classical markers of selected diseases.

Electroconvulsive Therapy - History and Current Use in Psychiatry: A Literature Review

Despite the numerous controversies associated with electroconvulsive therapy, in its favor is the relatively low number of contraindications, side effects and high level of safety. Purpose: The purpose of the publication was to collect and organize information on the use of electroconvulsive therapy in psychiatry and its effectiveness in specific disease entities, such as depression, schizophrenia, bipolar affective disorder and PTSD. Methods: A literature review was conducted using PubMed and Google Scholar containing information on the use of ECT in psychiatry. The search focused on the words electroconvulsive therapy, ECT, schizophrenia, depression, PTSD, bipolar affective disorder. Priority was given to using recent articles. Results: According to the most reliable sources, electroconvulsive therapy has a beneficial therapeutic effect in patients with depression, PTSD, schizophrenia and bipolar affective disorder. Conclusions: Due to the commonness of mental illnesses and the co-occurring resistance to pharmacological treatment, modern psychiatry is looking for alternative methods. One of them is electroconvulsive therapy, which has undergone modifications over time and is today considered a method with a high safety profile. Beneficial effects of the use of ECT can be observed in patients with bipolar disorder, schizophrenia and depression, and research on its effectiveness in the case of PTSD is still ongoing. ECT can be used in pregnant women, in patients with treatment-resistant depression and at high risk of suicide.

Ultrasound in Patients With Clinically Suspected Submandibular Gland Disease

Background: The submandibular gland is quite common to be affected by various disease processes in all age groups that may be difficult to differentiate clinically. Its superficial location makes it readily accessible to ultrasound evaluation. Objective: To evaluate sonographic features of abnormal submandibular gland. Methods: Ultrasound images and medical records of patients who presented with clinically suspected submandibular gland disease at a single institution were retrospectively reviewed. Demographic data, final diagnoses, further management, and sonographic findings were evaluated. Results: Eighty-one patients were identified, 56 females and 25 males (mean [SD] age, 53 [16] years; range, 1 - 87 years). The main presenting symptoms were palpable mass (31 [38.3%]) and pain (23 [28.4%]) involving the left (30 [37.0%]), the right (27 [33.3%]), and bilateral submandibular area (24 [29.6%]). Only 6 patients (8.1%) underwent further imaging. The most common final diagnoses were acute sialadenitis (38 [46.9%]), Sjögren syndrome (14 [17.3%]), tumor (6 [7.4%]), and stone (4 [4.9%]). Submandibular glands were normal in 17 of 81 patients (21%); 9 of 17 (52.9%) had abnormal lymph nodes. Among various disease entities, a significant correlation was found between Sjögren syndrome and small gland size, stone and ductal dilatation, and abnormal lymph nodes with enlarged nodal size (P &lt; .001). Conclusions: Two-thirds of the patients had inflammatory/infectious diseases, with tumor and stone in minority. Certain ultrasound findings can suggest diagnosis. Less than 10% underwent further imaging, suggesting that ultrasound can be used to detect and guide further management of submandibular disease.