Distinct Clinical Entity Research Articles

Abstract 6417: Deciphering aberrant STING pathway and exploring oncolytic viruses therapy in low grade serous ovarian carcinoma

Abstract There are two serous ovarian cancer histotypes, low and high grade (LGSOC and HGSOC), which are distinct clinical and biological entities. LGSOC is a rare histotype with a relatively stable genome, while HGSC is more common and genomically unstable. Somewhat surprisingly LGSOC expresses high levels of the stimulator of the interferon genes (STING). The STING pathway recognizes cytoplasmic double-stranded DNA and mounts innate cellular immunity through interferon-beta type I production. Our objective is to investigate the aberrant STING signaling in LGSOC and test the effectiveness of oncolytic viruses against LGSOC. We used immunohistochemistry on tissue microarrays (TMAs) to assess STING protein expression in different ovarian cancer histotypes. Whole proteome analysis was applied to identify differentially expressed proteins in LGSOC and HGSOC patient samples (both n=9). Further, a semi-targeted proteomics approach was used to evaluate the expression levels of the STING pathway-related proteins in LGSOC, HGSOC, and LGSOC precursor tumors (each subtype, n=20). To evaluate the key transcription, phosphorylation, and translocation events in STING signaling, we treated LGSOC cell lines with an agonist (dsDNA90) and performed qPCR, immunoblotting, and immunofluorescence experiments, respectively. We tested the viability of the LGSOC cell lines in response to Vaccinia Virus (VV), and Vesicular Stomatitis Virus (VSV) based oncolytic vectors with or without immunostimulatory transgenes. Our results show that STING protein levels were consistently higher in LGSOC TMAs relative to other histotypes. Proteomics analysis showed that the half of the 16 most differentially expressed proteins were the effectors of STING signaling with unexpectedly lower expression in LGSOC, suggesting that despite the robust levels of STING in LGSOC tumors, the pathway is not fully active. Attenuated STING translocation and expression of IFNB1 and other cytokines in LGSOC cell lines confirm the aberrancy in the STING pathway. Semi-targeted proteomics revealed the considerable overexpression of STIM1 in LGSOC patient tumors, which has previously been shown to sequester STING in the endoplasmic reticulum. The treatment with VV and VSV oncolytic viruses significantly reduced the proliferation of LGSOC cell lines. In summary, we find attenuated STING signaling in LGSOC, possibly due to overexpression of STIM1 preventing STING translocation. Although oncolytic viruses show promising results in LGSOC cell lines, more research is needed to determine the optimal treatment strategy, testing oncolytic viruses expressing various transgenes and combination therapies. Citation Format: Almira Zhantuyakova, Dawn Cochrane, Gian Negri, Sandra E. Spencer Miko, Taha Azad, Jutta Huvila, Marta Llaurado Fernandez, Mark Carey, Gregg B. Morin, John Bell, David Huntsman. Deciphering aberrant STING pathway and exploring oncolytic viruses therapy in low grade serous ovarian carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 6417.

PD29-09 COMPARISON OF SURVIVAL OUTCOMES AMONG PATIENTS WITH POSITIVE SOFT TISSUE MARGINS VERSUS POSITIVE NON-SOFT TISSUE MARGINS ALONE FOLLOWING RADICAL CYSTECTOMY FOR MUSCLE INVASIVE BLADDER CANCER

You have accessJournal of UrologyCME1 Apr 2023PD29-09 COMPARISON OF SURVIVAL OUTCOMES AMONG PATIENTS WITH POSITIVE SOFT TISSUE MARGINS VERSUS POSITIVE NON-SOFT TISSUE MARGINS ALONE FOLLOWING RADICAL CYSTECTOMY FOR MUSCLE INVASIVE BLADDER CANCER Julian Rowe, Andrew Gabrielson, Una Choi, Sunil Patel, Trinity Bivalacqua, Max Kates, and Noah Hahn Julian RoweJulian Rowe More articles by this author , Andrew GabrielsonAndrew Gabrielson More articles by this author , Una ChoiUna Choi More articles by this author , Sunil PatelSunil Patel More articles by this author , Trinity BivalacquaTrinity Bivalacqua More articles by this author , Max KatesMax Kates More articles by this author , and Noah HahnNoah Hahn More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003315.09AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Radical cystectomy (RC) is a mainstay treatment for patients with muscle-invasive bladder cancer. While positive soft tissue surgical margins (STSM) portend worse outcomes compared to negative margins, outcomes from positive STSM vs positive non-STSM alone remain understudied. We compare outcomes among patients with positive STSM, positive non-STSM alone, and negative margins following RC. METHODS: A retrospective cohort study was conducted using a single-institution RC registry from 2000-2018. Inclusion criteria included age>18, histologically confirmed urothelial carcinoma, RC with curative intent, and available pathology report. We defined 3 patient groups: 1) positive STSM (adjacent muscle or pelvic organs) ±positive non-STSM, 2) positive non-STSM (urethra or ureter) alone, 3) negative margins. Kaplan-Meier (KM) analysis with log-rank test was used to compare recurrence-free survival (RFS) and overall survival (OS). RESULTS: A total of 236 patients with positive margins and 1,138 patients with negative margins after RC were included. Of those with positive margins, 83 (35.2%) had positive STSM and 153 (64.9%) had positive non-STSM alone. There was no difference in age, adjuvant chemotherapy use, pN+rate between those with positive STSM compared to non-STSM. There was significantly higher variant histology (25.9% vs 8.4%, p<0.001) as well as NAC utilization (43.2% vs 25.2%, p=0.009) in positive STSM compared to non-STSM. Patients with positive STSMs demonstrated significantly worse median RFS (10.5 months vs 35.1 months, p=0.009) and OS (13.7 vs 27.8 months, p=0.013) compared to those with positive non-STSMs alone. Patients with positive non-STSM alone had significantly worse median RFS (35.1 vs 150.8 months, p<0.001) and OS (27.8 vs 87.7 months, p<0.001) compared to those with negative margins. KM analysis demonstrated distinct RFS and OS outcomes between the 3 groups (Figure 1). CONCLUSIONS: Positive STSM were associated with worse RFS and OS compared to positive non-STSM however positive non-STSM alone represents a distinct clinical entity from those with negative margins, and these data can inform patient counseling. This study was limited by differential rates of variant histology and NAC use. Source of Funding: NA © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e827 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Julian Rowe More articles by this author Andrew Gabrielson More articles by this author Una Choi More articles by this author Sunil Patel More articles by this author Trinity Bivalacqua More articles by this author Max Kates More articles by this author Noah Hahn More articles by this author Expand All Advertisement PDF downloadLoading ...

Primary Bone Lymphoma: A Review of the Literature with Emphasis on Histopathology and Histogenesis.

Primary bone lymphoma (PBL) is a rare neoplasm of malignant lymphoid cells presenting with one or more bone lesions without nodal or other extranodal involvement. It accounts for approximately 1% of all lymphomas and 7% of malignant primary bone tumors. Diffuse large B-cell lymphoma (DLBCL), not otherwise specified (NOS) represents the predominant histological type and constitutes over 80% of all cases. PBL may occur at all ages with a typical diagnosis age of 45-60 years and a slight male predominance. Local bone pain, soft tissue edema, palpable mass and pathological fracture are the most common clinical features. Diagnosis of the disease, which is frequently delayed due to its non-specific clinical presentation, is based on the combination of clinical examination and imaging studies and confirmed by combined histopathological and immunohistochemical examination. PBL can develop in any part of the skeleton, although it occurs most commonly in the femur, humerus, tibia, spine and pelvis. The imaging appearance of PBL is highly variable and unspecific. In terms of the cell-of-origin, most cases of primary bone DLBCL (PB-DLBCL), NOS belong to the germinal center B-cell-like subtype and specifically originate from germinal center centrocytes. PB-DLBCL, NOS has been considered a distinct clinical entity based on its particular prognosis, histogenesis, gene expression and mutational profile and miRNA signature. PBL carries a favorable prognosis, especially when treated with combined chemoradiotherapy.

The Fall of Icarus: Post-psychotic depression - Apropros a clinical case

IntroductionDepressive symptoms occur in different phases of psychosis, including prodromal, acute and post-psychotic. Post-psychotic depression (PPD) is a phenomenon that presents as a diagnostic and therapeutic challenge. Having been ascribed various descriptions in the past, PPD has been used in a broad manner to describe depressive symptoms that appear in patients with history of psychosis. PPD unveils itself as a separate nosological entity, differing from the adverse effects typically associated with antipsychotics, the negative symptoms of psychosis, and other psychiatric disorders that present with both psychotic and depressive symptoms (e.g. bipolar disorder, schizoaffective disorder, or psychotic depression).ObjectivesThe authors present a case of a 64 year-old man hospitalized due to inaugural psychosis with persecutory and grandiose delusions as well as auditory hallucinatory activity, who began to develop a depressive clinical picture whilst under treatment. A brief discussion on post-psychotic depression, from its clinical presentation to its treatment and implications in prognosis is also presented.MethodsA brief non-systematized literature review using the Pubmed platform as well as presentation of a clinical case.ResultsDepressive complaints are a common complication of psychotic episodes, with the literature estimating that approximately a quarter of psychotic patients present with PPD. Although typically described in association with schizophrenia, recent literature describes PPD occurring alongside other psychotic presentations, including first-episode psychosis. A division between affect and psychosis has been attempted in terms of psychiatric classification, however, the blurred lines between the two continue to contribute to difficulties in differential diagnosis. This becomes a challenge when distinguishing between extrapyramidal symptoms associated with antipsychotics, negative symptoms (i.e apathy, abulia and alogia) and psychiatric disorders with affective-psychotic overlap. Having only recently been considered a distinct clinical entity in psychiatric classification systems, research on its etiology, course, treatment and prognosis are scarce. In regards to the previously described patient, a depressive disorder whilst in treatment for psychosis was identified, and through early recognition of the symptoms treatment with an antidepressant was initiated with favourable response.ConclusionsPPD is a relatively common phenomenon which is gaining more attention in recent literature. As classifications have begun to consider PPD as a distinct clinical entity, as well as unifying defining criteria, further studies can be developed so as to clarify aspects which remain to be defined. The clinician should be aware of this entity as well as the potentially confounding symptom presentations, so as to provide adequate early treatment thus contributing to improved patient outcomes.Disclosure of InterestNone Declared

Outcomes of Lung Transplantation in Patients With Combined Pulmonary Fibrosis and Emphysema: A Single-Center Experience

Combined pulmonary fibrosis and emphysema (CPFE) is a distinct clinical entity that can progress to end-stage lung disease. Patients with CPFE may develop pulmonary hypertension and face a predicted 1-year mortality of 60%. Lung transplantation is the only curative therapeutic option for CPFE. This report describes our experience after lung transplantation in patients with CPFE. This retrospective, single-center study describes short- and long-term outcomes for adult patients who underwent lung transplant for CPFE. The study included 19 patients with explant pathology-proven diagnosis of CPFE. The patients were transplanted between July 2005 and December 2018. Sixteen recipients (84%) had pulmonary hypertension before transplant. Of the 19 patients, 7 (37%) had primary graft dysfunction at 72 hours post-transplant. 1-, 3-, and 5-year freedom from bronchiolitis obliterans syndrome was 100%, 91% (95% CI, 75%-100%), and 82% (95% CI, 62%-100%), respectively. One-, 3-, and 5-year survival was 94% (95% CI, 84%-100%), 82% (95% CI, 65%-100%), and 74% (95% CI, 54%-100%), respectively. Our experience demonstrates the safety and feasibility of lung transplant for patients with CPFE. Significant morbidity and mortality without lung transplant coupled with favorable post-transplant outcomes merit prioritization of CPFE in the Lung Allocation Score algorithm for lung transplant candidacy.

Inflammatory, Metabolic, and Coagulation Effects on Medial Arterial Calcification in Patients with Peripheral Arterial Disease

Calcium deposits in the vessel wall in the form of hydroxyapatite can accumulate in the intimal layer, as in atherosclerotic plaque, but also in the medial layer, as in medial arterial calcification (MAC) or medial Möenckeberg sclerosis. Once considered a passive, degenerative process, MAC has recently been shown to be an active process with a complex but tightly regulated pathophysiology. Atherosclerosis and MAC represent distinct clinical entities that correlate in different ways with conventional cardiovascular risk factors. As both entities coexist in the vast majority of patients, it is difficult to estimate the relative contribution of specific risk factors to their development. MAC is strongly associated with age, diabetes mellitus, and chronic kidney disease. Given the complexity of MAC pathophysiology, it is expected that a variety of different factors and signaling pathways may be involved in the development and progression of the disease. In this article, we focus on metabolic factors, primarily hyperphosphatemia and hyperglycemia, and a wide range of possible mechanisms by which they might contribute to the development and progression of MAC. In addition, we provide insight into possible mechanisms by which inflammatory and coagulation factors are involved in vascular calcification processes. A better understanding of the complexity of MAC and the mechanisms involved in its development is essential for the development of potential preventive and therapeutic strategies.

Long-term prognosis of out-of-hospital cardiac arrest due to idiopathic ventricular arrhythmias.

Life-threatening ventricular arrhythmias (VA) may occur in patients with unknown cardiac disease. A sizable part of them remains labeled as Idiopathic VA and limited data is available regarding their natural history. Our aim was to evaluate the long-term clinical outcomes of survivors of an idiopathic life-threatening VA. Patients who survived an idiopathic life-threatening VA referred to an ICD were included and followed for a median follow-up of 7 years. Clinical and device data were collected and a comparison between genders was made. A total of 29 patients, 41% female, mean age of 50 (19) years were studied; all were implanted with an ICD at index hospitalization. At follow-up, an etiological diagnosis was established in 38% of patients. Genetic testing improved the diagnosis and allowed the identification of a distinct clinical entity in 60% of patients (p=0.04, OR=7.0), especially in women. Regarding ICD data, 31% received appropriate therapies with a median time to first appropriate shock of 39 months (IQR 12-46 months). Men had a significantly higher prevalence of appropriated shocks (50% vs 8%, p=0.04), with a similar time to the first arrhythmic event between genders. Two of the patients died, both from non-arrhythmic causes. Etiologic diagnosis and recurrence prediction in patients with idiopathic VA is challenging, even with long-term follow-up and sophisticated diagnostic evaluation. Genetic testing significantly improved the diagnostic yield, especially in women. Arrhythmia recurrence occurred in about one-third of patients and is significantly higher in men, underscoring the importance of ICD implantation.

Large parathyroid adenomas: Potential mechanisms to reconcile adenoma size and disease phenotype.

Parathyroid adenomas weighing more than 3.5g are reported variously as "atypical", "large" or "giant" parathyroid adenomas. All such adenomas are rare variants accounting for no more than 1.5% of all parathyroid adenomas. Large parathyroid adenomas are often associated with more severe form of the disease, including osteitis fibrosa cystica (OFC) and share many biochemical, histological, and molecular features of both benign and malignant parathyroid neoplasms, and are considered a distinct clinical entity. However, the pathogenesis of oversized parathyroid adenomas and the often-associated skeletal phenotype remains unclear. We present 5 cases of primary hyperparathyroidism (PHPT) with OFC, an uncommon manifestation of contemporary PHPT, associated with larger parathyroid adenomas, seen in the Bone and Mineral Disorders Clinic of the Henry Ford Health in the last 30 years to illustrate the critical role of vitamin D nutrition in the pathogenesis of both the OFC and adenoma size. The estimated prevalence of OFC was very low 0.2%, 5 of the >3000 surgically confirmed cases of PHPT seen during this time. The mean ± SD values were: age: 36.8 ± 22.1 years (4 of the 5 <36years), serum calcium 11.6 ± 1.1 mg/dl, alkaline phosphatase 799 ± 487 IU/L, PTH 1440 ± 477 pg/ml, 25-hydroxyvitamin D 13.0 ± 8.9 ng/ml, 1,25-dihyroxyvitamin D 26.5 ± 13.7 pg/ml, urine calcium 562 ± 274 mg/day, and parathyroid adenoma weight 4.53 ± 2.2g. Parathyroidectomy led to the resolution of both the biochemical indices and OFC in each patient without recurrence over >10 years of follow-up. Because OFC is a very rare in the West, but very common areas of endemic vitamin D deficiency, we also examined the relationship between vitamin D nutrition, as assessed by serum 25-hydroxyvitamin D level, and parathyroid adenoma weight as well as prevalence of OFC in two large secularly diverse cohorts of patients with PHPT (Detroit, USA and Chandigarh, India). Based on this relationship and the relative prevalence of OFC in these two large cohorts, we propose that vitamin D nutrition (and perhaps calcium nutrition) best explains both the adenoma size and prevalence of OFC.

Apathetic Thyrotoxicosis Presenting With New-Onset Pulmonary Hypertension

Apathetic thyrotoxicosis is a distinct clinical entity of hyperthyroidism that occurs in elderly patients. Manifestations include depression, weight loss, mild tachycardia, and symptoms of heart failure. Noteworthy is the absence of typical hyperkinetic motor symptoms. Pulmonary hypertension is an often-overlooked manifestation of thyrotoxicosis. Here, we present a case of a 67-year-old woman who presented to the clinic with complaints of dyspnea on exertion, orthopnea, leg edema, and 20-lb weight loss. Further work-up revealed pulmonary hypertension with thyrotoxicosis, without the typical sympathetic symptoms. After achieving a euthyroid state with methimazole therapy, she experienced resolution of her symptoms, and her pulmonary artery pressures normalized.

Anti-Ku antibody syndrome: is it a distinct clinical entity? A cross-sectional study of 75 patients.

Anti-Ku antibody syndrome: is it a distinct clinical entity? A cross-sectional study of 75 patients.

DSP-Related Cardiomyopathy as a Distinct Clinical Entity? Emerging Evidence from an Italian Cohort.

Variants in desmoplakin gene (DSP MIM *125647) have been usually associated with Arrhythmogenic Cardiomyopathy (ACM), or Dilated Cardiomyopathy (DCM) inherited in an autosomal dominant manner. A cohort of 18 probands, characterized as heterozygotes for DSP variants by a target Next Generation Sequencing (NGS) cardiomyopathy panel, was analyzed. Cardiological, genetic data, and imaging features were retrospectively collected. A total of 16 DSP heterozygous pathogenic or likely pathogenic variants were identified, 75% (n = 12) truncating variants, n = 2 missense variants, n = 1 splicing variant, and n = 1 duplication variant. The mean age at diagnosis was 40.61 years (IQR 31-47.25), 61% of patients being asymptomatic (n = 11, New York Heart Association (NYHA) class I) and 39% mildly symptomatic (n = 7, NYHA class II). Notably, 39% of patients (n = 7) presented with a clinical history of presumed myocarditis episodes, characterized by chest pain, myocardial enzyme release, 12-lead electrocardiogram abnormalities with normal coronary arteries, which were recurrent in 57% of cases (n = 4). About half of the patients (55%, n = 10) presented with a varied degree of left ventricular enlargement (LVE), four showing biventricular involvement. Eleven patients (61%) underwent implantable cardioverter defibrillator (ICD) implantation, with a mean age of 46.81 years (IQR 36.00-64.00). Cardiac magnetic resonance imaging (CMRI) identified in all 18 patients a delayed enhancement (DE) area consistent with left ventricular (LV) myocardial fibrosis, with a larger localization and extent in patients presenting with recurrent episodes of myocardial injury. These clinical and genetic data confirm that DSP-related cardiomyopathy may represent a distinct clinical entity characterized by a high arrhythmic burden, variable degrees of LVE, Late Gadolinium Enhancement (LGE) with subepicardial distribution and episodes of myocarditis-like picture.

Large Bowel Perforation in Patients with Colorectal Cancer: A South African Perspective.

Large bowel perforation (LBP) occurs in up to 10% of colorectal cancer (CRC) patients and is a potential surgical emergency. Data on LBP in CRC patients from resource-limited countries are required to improve the management of this condition in these settings. Our study aimed to describe LBP amongst CRC patients in KwaZulu-Natal, South Africa. This was a descriptive sub-analysis of LBP data from an ongoing CRC registry. This study explores free and contained perforations and describes LBP characteristics, surgical management, histological findings, overall survival, and CRC recurrence. Ninety-four out of 2523 CRC patients had LBP (3.7%). The median age was 53.0 years (interquartile range: 43.0-64.0). The male-to-female ratio was 1.4:1. Thirty-three patients (35.1%) had a coexisting bowel obstruction. Tumor site perforations occurred in 87 patients (92.6%) and were mostly in the sigmoid colon (36.2%). Perforations were contained in 77 patients (81.9%). Eighty-nine patients (94.7%) underwent resection (elective resection: 76/89 patients, 85.4%). The post-operative inpatient mortality rate was 2.2%. Most patients had Stage III CRC (46 patients, 48.9%) and moderately differentiated tumors (77 patients, 81.9%). Overall survival at 12 months following CRC diagnosis was 55.4%. The early recurrence rate for CRC disease was 5.4%. Tumor site perforations predominated, and most were contained. Patients were younger when compared with the international literature. We reaffirm that diastatic-free and contained perforations are two distinct clinical entities.

Mutation Status Defines Subtypes of Essential Thrombocythemia and Relation to Polycythemia Vera in Iraqi Patients

Background: Polycythemia vera (PV) and essential thrombocythemia (ET) are a part of the BCR-ABL1-negative myeloproliferative neoplasms (MPNs) that harbor mutation in Janus kinase 2 (JAK2), CALR, or MPL gene. Objectives: The objective of this study was to investigate the impact of JAK2 and CALR mutations on the clinical course and hematological phenotype of ET patients and to evaluate the biological and clinical features of ET and PV sharing the same type of mutation in JAK2V617F. Materials and Methods: This was a cross-sectional study that included 94 patients diagnosed with MPN, of them 47 had PV and 47 had ET. JAK2V617F mutation was assessed using either allele-specific PCR or JAK-2 quantitative real-time PCR kit. JAK2-negative patients were further assessed for the existence of CALR mutations using SNP biotechnology MPN screening kit. Results: JAK2 mutation was identified in 29 ET patients, whereas CALR mutations were confirmed in 18 patients. JAK2-mutated ET patients were significantly older than those with CALR mutations. Seventy-six were reported to have a mutation in JAKV617F, of them 47 were diagnosed as PV and 29 as ET. JAK2V617F-mutated PV patients had significantly higher levels of hemoglobin, hematocrit, and WBC than JAK2-mutated ET patients. On the other hand, JAK2-mutated PV patients exhibited lower platelet count than ET harboring the same mutation. Conclusion: JAK2-mutated ET represents a distinct clinical entity that has a hematological and clinical phenotype ranging between JAK2-mutated PV and CALR-mutated ET. The analysis of the mutational status is essential in discriminating subtypes of MPN and confirming the diagnosis in ET and PV patients.

Cluneal neuropathy: Background, diagnosis, and treatment.

Cluneal neuropathy is encompassed by three distinct clinical entities. Superior, middle, and inferior cluneal neuralgia make up the constellation of symptoms associated with cluneal neuropathy. Each has its own variable anatomy. We compiled a narrative review including a review of available literature. We conducted searches on PubMed/MEDLINE, Embase and Google Scholar on the topics of cluneal neuropathy and treatment therein. We collected source articles regarding original descriptions of the disease entities in addition to articles focused on treatment. Adjusted incidence rates of superior cluneal neuropathy are 1.6%-11.7%. Accurate diagnosis remains challenging due to the lack of standardized criteria and the aforementioned variability. Treatment may include therapeutic nerve blocks, ablative techniques, neuromodulation, and surgical decompression. Gaps including those related to true incidence and work up exist. Outcomes from interventional studies are limited and mixed due to significant population heterogeneity and non-standardized treatment approaches coupled with very small sample sizes.

Added value of a chest multidetector computed tomography scoring system in the assessment of chronic lung disease among pediatric patients

BackgroundPediatric chronic lung disease (CLD) represents a heterogeneous group of several distinct clinical entities, with its prevalence increasing over the last decade. The current study aimed to identify the role of chest multidetector computed tomography (MDCT) using modified Bhalla scoring for the early diagnosis of CLD in pediatric patients and determine the most common chest MDCT findings. This prospective study involved 45 pediatric patients with chronic respiratory symptoms, all of whom underwent MDCT. Thereafter, data were analyzed using the modified Bhalla score.ResultsChronic lung diseases were classified according to their radiological and clinical criteria. The total CT score, which was the most significant factor for chronic inhalation and chronic recurrent inflammatory lung diseases, varied between 2 and 21 points, with those having autoimmune diseases exhibiting the largest value for the mean CT score. The clinical severity of symptoms was not correlated with CT score.ConclusionOur findings showed that MDCT was a useful tool for diagnosing pediatric CLD and assessing disease extent, severity, and superimposed complications. The modified Bhalla CT scoring system allowed for systematic primary and follow-up assessments of various lung lesions in cases with varying CLD etiologies.

A Sarcomatoid Renal Cell Carcinoma with Clear Cell Papillary-Like Primary Tumor and Lymph Node Metastasis: A Diagnostic Conundrum.

Clear cell papillary renal cell tumor (CCPRCT) is a distinct clinical entity with characteristic pathological features and non-aggressive clinical behavior. Diagnostically challenging cases present when there are immunomorphological findings of CCPRCT associated with heterogeneous morphologies, aggressive histological features, and advanced pathological stages-so-called CCPRCT-like tumors. In this report, we describe a heterogeneous, multifocal renal tumor with immunomorphological characteristics of CCPRCT but with associated aggressive features such as sarcomatoid and necrotic areas, perirenal and sinus fat involvement, and most notably, lymph node metastasis composed entirely of classic CCPRCT morphology and immunophenotype. Immunohistochemical and fluorescence in situ hybridization studies did not support a translocation renal cell carcinoma. Molecular analyses did not identify common mutations or chromosomal abnormalities seen in clear cell renal cell carcinoma or ELOC-mutated renal cell carcinoma. This case highlights that rare renal cell tumors remain difficult to classify and the distinction between CCPRCT and CCPRCT-like tumors remains to be better defined.

The risk of early suicide and diagnostic issues in Cotard's syndrome associated to self-starvation.

Cotard's syndrome is a rare neuropsychiatric disorder in which the patient holds nihilistic delusions concerning his/her own existence, including the conviction of being dead or having lost parts of the body. There are occasional reports of Cotard's syndrome being accompanied by nutritional deficiencies or self-starvation. The authors describe the peculiar case of a 40-year-old man who developed severe malnutrition within a few months. At first, a diagnosis of anorexia nervosa was made. The man was admitted to the hospital where other significant psychopathological symptoms emerged. One of the consequences of Cotard's syndrome is self-starvation because of negation of existence of self. The presented case points out that, although Cotard's syndrome has been reported to be associated with various organic conditions and other forms of psychopathology, loss of appetite and nutritional deficits can erroneously lead to mistake this diagnosis for anorexia nervosa, thus underestimating the high risk of these patients of committing suicide following hospital discharge. Taking into account its rarity and possible subdiagnosis, as a distinct clinical entity the aim of this case report is to emphasize that these patients may initially be addressed to general practitioners, due to the dysmetabolic consequences of malnutrition, rather than to psychiatrists. An early recognition of signs indicative of Cotard's syndrome can be vital to prevent the situation from worsening. In fact, missed diagnoses can put these patients at an higher risk of suicidal behaviour.

The Association of Protein Biomarkers With Incident Heart Failure With Preserved and Reduced Ejection Fraction.

Heart failure with preserved ejection fraction (HFpEF) and heart failure with reduced ejection fraction (HFrEF) are distinct clinical entities, yet there is scant evidence for associations of proteomic signatures with future development of HFpEF versus HFrEF. We evaluated the association of 71 protein biomarkers with incident HFpEF versus HFrEF (left ventricular ejection fraction ≥ versus <50%) among Framingham Heart Study participants using multivariable Cox models. Among 7038 participants (mean age 49 years; 54% women), 5 biomarkers were associated with increased risk of incident HFpEF (false discovery rate q<0.05): NT-proBNP (N-terminal pro-B-type natriuretic peptide; hazard ratio [HR], 2.13; 95% CI, 1.52-2.99; P<0.001), growth differentiation factor-15 (HR, 1.67; 95% CI, 1.32-2.12; P<0.001), adrenomedullin (HR, 1.58; 95% CI, 1.23-2.04; P<0.001), uncarboxylated matrix Gla protein (HR, 1.55; 95% CI 1.23-1.95; P<0.001), and C-reactive protein (HR, 1.46; 95% CI, 1.17-1.83; P=0.001). Fourteen biomarkers were associated with incident HFrEF (multivariable P<0.001, q<0.05 for all). Of these, 3 biomarkers were associated with both HF subtypes (NT-proBNP, growth differentiation factor-15, and C-reactive protein). When compared directly, myeloperoxidase, resistin, and paraoxanase-1 were more strongly associated with HFrEF than HFpEF. We identified 5 protein biomarkers of new-onset HFpEF representing pathways of inflammation, cardiac stress, and vascular stiffness, which partly overlapped with HFrEF. We found 14 biomarkers associated with new-onset HFrEF, with some distinct associations including myeloperoxidase, resistin, and paraoxanase-1. Taken together, these findings provide insights into similarities and differences in the development of HF subtypes. URL: https://clinicaltrials.gov/ct2/show/NCT00005121; Unique identifier: NCT0005121.

A Case of Middle Aged Women with Isolated Left Coronary ostial stenosis with Non ST Elevation Myocardial Infarction

Background: The stenosis of the ostial left anterior descending artery represents one of the challenges for the interventional cardiologist. In contrast ostial stenosis of the left main trunk shows very good results after percutaneous interventions and implantation of drug-eluting stents. The indications for percutaneous transluminal coronary angioplasty (PTCA) of an ostial lesion correspond to the indications for treatment of all other lesions. Case: A-56-year-old woman was admitted to our hospital who was initially admitted in the intensive care unit for a severe acute chest pain. She had no coronary risk factors. No hormonal disorders were observed. Physical and laboratory examinations revealed that she had not suffered from syphilis or aortitis syndrome or any other inflammatory diseases. An electrocardiogram (ECG) was immediately performed and showed ST segment non elevation in the precordial leads (Figure 1) suggesting an acute anterior ST Non elevation myocardial infarction (NSTEMI). On coronary angiography, a 80% stenosis of the left coronary ostial stenosis was found, but no abnormality was found in other arterial trees. (Figure 2) The patient was diagnosed as having isolated coronary ostial stenosis. Conclusion: The patients are almost always middle aged woman with no coronary risk factors. , the involved coronary artery is the left main coronary artery, so its obstruction results in a serious condition. Therefore, though its pathogenesis remains to be determined, isolated left coronary ostial stenosis seems to be a distinct clinical entity.

Prevalence, comorbidities and mortality of generalized pustular psoriasis: A literature review.

Generalized pustular psoriasis (GPP) is a rare auto-inflammatory skin disease characterised by acute episodes of sterile pustule formation. Diagnosis and treatment of the disease have historically been complicated by a lack of awareness, and no consistent global definition or clinical coding standards. Now acknowledged as a distinct clinical entity with a recognised genetic component, GPP can take a serious and life-threatening course due to systemic inflammatory complications and its association with various comorbidities. As with other rare diseases, there are significant challenges to understanding the epidemiology of GPP, notably a small patient population, non-standardised study methodologies and ethnic differences in its presentation. A clearer understanding of GPP is therefore required for clinicians to better manage patients with this rare condition. In this review article, we present an overview of the available data on GPP prevalence estimates in key demographics and report the frequency of genetic mutations associated with the disease. We detail the incidence of known comorbidities and summarise the data on mortality and assigned causes of death. Lastly, we discuss the various factors that impact the collection, interpretation and comparison of these data.