Extrapulmonary Disease Research Articles

Risk factors associated with length of hospital stay and medical expenses in pulmonary abscess patients: retrospective study.

Pulmonary abscess carries a high mortality and requires long-term managements. A better understanding of the risk factors associated with the prolonged hospital stay and high medical expenses in these patients can improve the management strategy in individual patient and optimize the overall healthcare resources. We performed a retrospective study and reviewed the medical records on consecutive patients hospitalized at the Department of Respiratory Medicine of the General Hospital of Northern Theater Command, Shenyang, Liaoning, China, between January 1, 2015, and December 31, 2020. Demographics, comorbidity, clinical symptoms, laboratory tests, length of hospital stay, and medical expenses were recorded. Their relationships with the length of hospital stay and medical expenses in pulmonary abscess patients were analyzed. There were 190 patients with the pulmonary abscess and 12,189 patients without the pulmonary abscess. Compared with patients without the pulmonary abscess, patients with the pulmonary abscess had longer hospital stays (21.8 ± SD vs 12.8 ± SD, P < 0.01), In patients with the pulmonary abscess, the mean length of hospital stay was 5.3 days longer in male vs female patients (P = 0.025). Multivariate linear regression analyses showed that extrapulmonary disease and clinical symptoms were associated with the length of hospital stay and medical expenses, respectively. In addition, anemia was associated with both the length of hospital stay and medical expenses. Sex and hypoproteinemia were associated with the medical expenses. The mean length of hospital stay was longer in patients with the pulmonary abscess than those without the pulmonary abscess. The length of hospital stay and medical expense were associated with sex, clinical symptoms, extrapulmonary disease, and abnormal laboratory tests in patients with the pulmonary abscess.

Myxoid Liposarcoma: How to Stage and Follow.

Myxoid liposarcoma (MLPS) is a rare soft tissue sarcoma, with propensity to metastasize to locations such as soft tissue and bone. Thus, whole-body MRI should be a consideration as part of staging for patients with a new diagnosis of MLPS since PET and CT may not identify extrapulmonary disease. Surveillance imaging should be tailored, with consideration of more frequent and longer duration of monitoring for large tumors or tumors with round cell component. This review focuses on studies evaluating imaging in MLPS as well as recent publications on survival and prognostic tools in MLPS.

ORGANIZING PNEUMONIA: AN UNUSUAL SEQUELA OF COVID-19 INFECTION.

COVID-19 pneumonia is one of the secondary causes of organizing pneumonia (OP).Early initiation of steroids in OP is associated with improvement in symptoms and prognosis.A prolonged course of steroids may be needed in COVID-induced OP.

CircRNAs deregulation in exosomes derived from BEAS-2B cells is associated with vascular stiffness induced by PM2.5

As an environmental pollutant, ambient fine particulate matter (PM2.5) was linked to cardiovascular diseases. The molecular mechanisms underlying PM2.5-induced extrapulmonary disease has not been elucidated clearly. In this study the ambient PM2.5 exposure mice model we established was to explore adverse effects of vessel and potential mechanisms. Long-term PM2.5 exposure caused reduced lung function and vascular stiffness in mice. And chronic PM2.5 induced migration and epithelial-mesenchymal transition (EMT) phenotype in BEAS-2B cells. After PM2.5 treatment, the circRNAs and mRNAs levels of exosomes released by BEAS-2B cells were detected by competing endogenous RNA (ceRNA) array, which contained 1664 differentially expressed circRNAs (DE-circRNAs) and 308 differentially expressed mRNAs (DE-mRNAs). By bioinformatics analysis on host genes of DE-circRNAs, vascular diseases and some pathways related to vascular diseases including focal adhesion, tight junction and adherens junction were enriched. Then, ceRNA network was constructed, and DE-mRNAs in ceRNA network were conducted functional enrichment analysis by Ingenuity Pathway Analysis, which indicated that hsa_circ_0012627, hsa_circ_0053261 and hsa_circ_0052810 were related to vascular endothelial dysfunction. Furthermore, it was verified experimentally that ExoPM2.5 could induce endothelial dysfunction by increased endothelial permeability and decreased relaxation in vitro. In present study, we investigated in-depth knowledge into the molecule events related to PM2.5 toxicity and pathogenesis of vascular diseases.

Refractory Pneumonia in a 12-year-old Girl with Hemoglobin SS Disease

Refractory Pneumonia in a 12-year-old Girl with Hemoglobin SS Disease

Are CT-based exacerbation prediction models ready for use in chronic obstructive pulmonary disease?

Quantitative CT imaging extracts information that reflects the severity, degree of change, or status of a disease.1 There is growing interest, and scientific evidence, for the use of quantitative CT to improve understanding of disease pathophysiology and prognosis in patients with chronic obstructive pulmonary disease (COPD).2 In patients with COPD, quantitative CT provides numerous measurements that represent a wide range of pulmonary and extrapulmonary disease features. Therefore, a growing number of studies are investigating the inclusion of quantitative CT into prediction models for COPD outcomes.

Solid organ transplant recipients with tuberculosis disease in California, 2010 to 2020

Using California Tuberculosis (TB) Registry data from 2010-2020, we compared the presentation and outcomes of patients with TB aged >15 years with and without solid organ transplantation (SOT). We matched to the United Network for Organ Sharing registry for 1987-2020 and the estimated time from transplantation to the diagnosis of TB, the incidence of posttransplant TB, and the probability of death and graft failure in SOT recipients with TB, compared to those without TB. From 2010-2020, there were 148 posttransplant TB cases. Patients with posttransplant TB were more likely to have extrapulmonary disease and more than twice as likely to die as TB patients without SOT (relative risk [RR], 2.2; 95% confidence interval [CI], 1.6-2.9). The median time from transplantation to TB diagnosis was 1.2 years, with the shortest time among lung transplant recipients. The incidence of TB disease among Californians with SOT was 56.0 per 100 000 person-years. The risk of death was higher among SOT recipients with posttransplant TB than those without (adjusted hazard ratio, 2.8; 95% CI, 2.0-4.1); the risk of graft failure was higher among kidney transplant recipients with posttransplant TB than those without (adjusted hazard ratio, 3.4; 95% CI, 1.7-6.9). An increased risk of death and graft failure in SOT recipients with posttransplant TB highlights the need for enhanced pretransplant TB prevention.

DIFFERENTIATION OF SPINAL TUBERCULOSIS AND METASTATIC SPINAL TUMOR USING MRI FEATURE: A SYSTEMATIC REVIEW

Highlights1. Lesions that are regularly diagnosed in the spine include TB of the spine and tumors that have spread throughout the body.2. The examined papers included 35 individuals with tuberculous spondylitis and 31 patients with metastatic spinal malignancies.3. A methodology for MRI imaging and an accurate medical history will aid in establishing an accurate diagnosis. AbstractBackground: Spinal tuberculosis and metastatic tumors are commonly diagnosed lesions in the spine. Tuberculosis spondylitis, also known as Pott's Disease, is the most common extrapulmonary tuberculosis disease. MRI is the gold standard for early diagnosis because there is no significant difference in the results of clinical manifestations and histopathological examination. A biopsy will usually be used for a final exam for diagnosis. Objective: To provide information to confirm the diagnosis of TB spondylitis cases and metastatic spinal tumors. Method: A literature search was conducted via PubMed, Science Direct, and Scopus by selecting studies according to inclusion and exclusion criteria. The quality and risk of bias assessments were performed using Joanna Briggs Institute (JBI) tools. Overall, 35 spinal tuberculosis and 31 metastatic spinal tumor patients from 2 studies were reviewed. Result: Of the 35 patients with tuberculous spondylitis and 31 patients with metastatic spinal tumors from the two studies reviewed. It was found that the thorax was the most common region. The following imaging findings were of statistical significance (p&lt;0.05): skip lesion, solitary lesion, intraspinal lesion, concentric collapse, abscess formation (paraspinal, intraosseous, and epidural lesions), and syrinx formation. Conclusion: An MRI imaging protocol and correct medical history will help establish an accurate diagnosis. Skip lesions, abscesses, and modular lesion margins are considered for diagnosis.

Characterizing the Spectrum of Latent Mycobacterium tuberculosis in the Cynomolgus Macaque Model: Clinical, Immunologic, and Imaging Features of Evolution.

Mycobacterium tuberculosis infection outcomes have been described as active tuberculosis or latent infection but a spectrum of outcomes is now recognized. We used a nonhuman primate model, which recapitulates human infection, to characterize the clinical, microbiologic, and radiographic patterns associated with developing latent M. tuberculosis infection. Four patterns were identified. "Controllers" had normal erythrocyte sedimentation rate (ESR) without M. tuberculosis growth in bronchoalveolar lavage or gastric aspirate (BAL/GA). "Early subclinicals" showed transient ESR elevation and/or M. tuberculosis growth on BAL/GA for 60 days postinfection, "mid subclinicals" were positive for 90 days, and "late subclinicals" were positive intermittently, despite the absence of clinical disease. Variability was noted regarding granuloma formation, lung/lymph node metabolic activity, lung/lymph node bacterial burden, gross pathology, and extrapulmonary disease. Like human M. tuberculosis infection, this highlights the heterogeneity associated with the establishment of latent infection, underscoring the need to understand the clinical spectrum and risk factors associated with severe disease.

Isolated cervical lymph node sarcoidosis: a diagnostic challenge of a case report

Sarcoidosis is a granulomatous disorder involving multi-systemic organs. Patients invariably have lung involvement but some may have extrapulmonary disease. Rarely, cervical lymphadenopathy is the only sign without mediastinal or pulmonary abnormalities. We report a Malay male who complained of neck swelling exclusively. On imaging, multiple enlarged cervical lymph nodes deep to the sternocleidomastoid muscle were seen. An excision biopsy revealed non-caseating granulomas with epithelioid macrophages. Extensive investigations led to the diagnosis of isolated cervical lymph node sarcoidosis. Sarcoidosis can present as cervical lymphadenopathy alone, without mediastinal or lung disease. The presence of epithelioid granulomas on histopathology warrants the exclusion of other granulomatous diseases. Isolated cervical lymph node sarcoidosis is only diagnosed in the presence of consistent clinical and radiological findings. In this case, close monitoring for systemic sarcoidosis is important as it can manifest later in life.

Diagnosis and biomarkers for ocular tuberculosis: From the present into the future.

Tuberculosis is an airborne disease caused by Mycobacterium tuberculosis (Mtb) and can manifest both pulmonary and extrapulmonary disease, including ocular tuberculosis (OTB). Accurate diagnosis and swift optimal treatment initiation for OTB is faced by many challenges combined with the lack of standardized treatment regimens this results in uncertain OTB outcomes. The purpose of this study is to summarize existing diagnostic approaches and recently discovered biomarkers that may contribute to establishing OTB diagnosis, choice of anti-tubercular therapy (ATT) regimen, and treatment monitoring. The keywords ocular tuberculosis, tuberculosis, Mycobacterium, biomarkers, molecular diagnosis, multi-omics, proteomics, genomics, transcriptomics, metabolomics, T-lymphocytes profiling were searched on PubMed and MEDLINE databases. Articles and books published with at least one of the keywords were included and screened for relevance. There was no time limit for study inclusion. More emphasis was placed on recent publications that contributed new information about the pathogenesis, diagnosis, or treatment of OTB. We excluded abstracts and articles that were not written in the English language. References cited within the identified articles were used to further supplement the search. We found 10 studies evaluating the sensitivity and specificity of interferon-gamma release assay (IGRA), and 6 studies evaluating that of tuberculin skin test (TST) in OTB patients. IGRA (Sp = 71-100%, Se = 36-100%) achieves overall better sensitivity and specificity than TST (Sp = 51.1-85.7%; Se = 70.9-98.5%). For nuclear acid amplification tests (NAAT), we found 7 studies on uniplex polymerase chain reaction (PCR) with different Mtb targets, 7 studies on DNA-based multiplex PCR, 1 study on mRNA-based multiplex PCR, 4 studies on loop-mediated isothermal amplification (LAMP) assay with different Mtb targets, 3 studies on GeneXpert assay, 1 study on GeneXpert Ultra assay and 1 study for MTBDRplus assay for OTB. Specificity is overall improved but sensitivity is highly variable for NAATs (excluding uniplex PCR, Sp = 50-100%; Se = 10.5-98%) as compared to IGRA. We also found 3 transcriptomic studies, 6 proteomic studies, 2 studies on stimulation assays, 1 study on intraocular protein analysis and 1 study on T-lymphocyte profiling in OTB patients. All except 1 study evaluated novel, previously undiscovered biomarkers. Only 1 study has been externally validated by a large independent cohort. Future theranostic marker discovery by a multi-omics approach is essential to deepen pathophysiological understanding of OTB. Combined these might result in swift, optimal and personalized treatment regimens to modulate the heterogeneous mechanisms of OTB. Eventually, these studies could improve the current cumbersome diagnosis and management of OTB.

1424. Central Nervous System Tuberculosis in a Large Healthcare System

Abstract Background Central nervous system tuberculosis (CNS-TB) accounts for 5-10% of extrapulmonary TB cases. It takes 3 clinical forms: meningitis, tuberculoma, and arachnoiditis. Modern case descriptions of the presentation of CNS-TB are rare. The goal of this study is to examine the presentation, diagnostic studies, and associated comorbidities of CNS-TB. Methods In our academic healthcare system, cases of culture confirmed CNS-TB were identified in a database maintained by the infection control group. This is a retrospective case series of the 11 adults with confirmed CNS-TB. Results 273 patients were identified with TB infection from 2008 to 2022. 104 (38%) had extra pulmonary disease. 11 (4%) had CNS infection. Patient characteristics are described in Table 1. 5 (45%) of the patients with CNS disease also had pulmonary disease. Mean age of diagnosis was 42. 5 (45%) were male and 9 (82%) were African American. 5 (45%) had HIV; mean CD4 count was 100 (8-255). Diagnostics are shown in Table 2. CSF studies revealed a mean WBC of 295/mm3 (4-808), protein of 605 mg/dL (27-4476), and Glucose of 31 (12-64) mg/dL. 4 (36%) patients presented with British Research Medical Council (BMRC) clinical stage I disease and 7 (64%) with stage II disease. 8 (73%) patients had an abnormal CT or MRI scan of the head, with representative images seen in Figure 1. 5 patients (45%) had lesions consistent with tuberculomas. 1 (9%) had arachnoiditis identified on imaging. 1 (9%) patient died. Conclusion 38% of patients diagnosed with TB at our center had extrapulmonary disease compared to 17.5% reported in the literature. The 4% rate of CNS-TB was similar to previously reported. Our series describes abnormal imaging as well as CSF studies showing leukocytosis, pleocytosis, and hypoglycorrhachia consistent with previously described findings. Though numbers were small, no significant difference was found between HIV positive and negative patients. Although mortality was rare in our series, the patient who died had advanced AIDS and multidrug resistant meningitis. Given the significant global mortality of this disease, this series highlights the need for more current studies describing the presentation and diagnostic characteristics of modern CNS-TB so clinicians can better recognize and treat the condition without delay. Disclosures All Authors: No reported disclosures.

Prothrombotic state, endothelial injury, and echocardiographic changes in non-active sarcoidosis patients.

Sarcoidosis is a multisystem inflammatory granulomatous disease of unknown cause that most commonly affects lungs and lymph nodes, with frequent yet asymptomatic cardiac involvement. The epidemiologically associated cardiovascular risk suggests an underlying prothrombotic state and endothelial dysfunction, currently understudied in the available literature. Therefore, we aimed to investigate prothrombotic plasma properties together with selected echocardiographic and laboratory biomarkers of cardiovascular injury in that disease. N = 53 patients with pulmonary sarcoidosis in clinical remission and N = 66 matched controls were assessed for inflammatory and endothelial injury biomarkers, plasma thrombin generation profile, and echocardiographic and lung function parameters. Sarcoidosis cases had impaired systolic and diastolic left ventricular function, higher concentrations of inflammatory markers, D-dimer and factor VIII activity compared to the controls. The coexistence of extrapulmonary disease was associated with elevated circulating vascular cell adhesion molecule 1, while cases with hypercalcemia had higher thrombomodulin concentration. Sarcoidosis was characterized by the unfavorably altered thrombin generation profile, reflected by the 16% higher endogenous thrombin potential (ETP), 24% increased peak thrombin concentration, and 12% shorter time to thrombin peak in comparison to the control group. ETP was higher in cases with proxies of pulmonary restriction, extrapulmonary-extracutaneous manifestation, and need for corticosteroids use. Despite the clinical remission, sarcoidosis is related to prothrombotic plasma properties and signs of endothelial injury, likely contributing to the higher risk of cardiovascular events. In addition, subclinical cardiac involvement may play an additional role, although further clinical and experimental studies are needed to verify these findings.

Comparison of the pathogenesis of SARS-CoV-2 infection in K18-hACE2 mouse and Syrian golden hamster models.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the etiological agent of COVID-19, causes life-threatening disease. This novel coronavirus enters host cells via the respiratory tract, promoting the formation of severe pulmonary lesions and systemic disease. Few animal models can simulate the clinical signs and pathology of COVID-19 patients. Diverse preclinical studies using K18-hACE2 mice and Syrian golden hamsters, which are highly permissive to SARS-CoV-2 in the respiratory tract, are emerging; however, the systemic pathogenesis and cellular tropism of these models remain obscure. We intranasally infected K18-hACE2 mice and Syrian golden hamsters with SARS-CoV-2, and compared the clinical features, pathogenesis, cellular tropism and infiltrated immune-cell subsets. In K18-hACE2 mice, SARS-CoV-2 persistently replicated in alveolar cells and caused pulmonary and extrapulmonary disease, resulting in fatal outcomes. Conversely, in Syrian golden hamsters, transient SARS-CoV-2 infection in bronchial cells caused reversible pulmonary disease, without mortality. Our findings provide comprehensive insights into the pathogenic spectrum of COVID-19 using preclinical models.

Baseline Eosinophil Count as a Potential Clinical Biomarker for Clinical Complexity in EGPA: A Real-Life Experience.

Eosinophilic granulomatosis with polyangiitis (EGPA) is a small-vessel necrotizing vasculitis with multiple organ involvement. Despite improvements in clinical management, biomarkers for organ involvement and disease prognosis are still an unmet need. EGPA patients referred to our immunology clinic were retrospectively reviewed. Demographic/clinical features, eosinophils, ANCA status, eosinophil cationic protein (ECP) and total serum IgE were evaluated at the baseline. Eosinophils, total serum IgE, ECP and ANCA were studied as possible biomarkers for lung and extrapulmonary disease. In total, 167 EGPA patients were recruited for our study. A positive association between eosinophils and peripheral nervous system (PNS) involvement was demonstrated (p &lt;0.001; chi-squared test). Receiver operating characteristic (ROC) curves using the eosinophil count or percentage as predictors of PNS involvement yielded AUC values of 0.75 and 0.67, respectively. ANCA positivity was associated with PNS involvement, while no correlations with clinical parameters were found for ECP and total serum IgE. Patients without extrapulmonary involvement had lower eosinophils (eosinophils: 2844.7 ± 1698 vs. 6373 ± 5468, p &lt; 0.001; eosinophil percentage: 24.6 ± 10% vs. 36.2 ± 15.8, p &lt; 0.001) and were less likely to be ANCA+ (p &lt; 0.001, chi-squared test). Eosinophils in EGPA are an important biomarker and are associated with extrapulmonary involvement. These findings could strengthen the role of anti-eosinophilic drugs in improving extrapulmonary disease.

Autoantibody profile in sarcoidosis, analysis from the GRADS sarcoidosis cohort.

BackgroundSarcoidosis, a multi-systemic granulomatous disease, is a predominantly T-cell disease but evidence for a role for humoral immunity in disease pathogenesis is growing. Utilizing samples from the Genomic Research in Alpha-1 anti-trypsin Deficiency and Sarcoidosis (GRADS) study, we examined the prevalence of autoantibodies in sarcoidosis patients with pulmonary-only and extra-pulmonary organ involvement compared to normal controls.Study design and methodsWe analyzed serum samples from sarcoidosis patients who participated in the GRADS study utilizing an autoantigen microarray platform for both IgM and IgG antibodies. The cohort included sarcoidosis patients with pulmonary-only disease (POS, n = 106), sarcoidosis patients with extra-pulmonary disease (EPS, n = 120) and a normal control cohort (NC, n = 101). Organ involvement was assessed following a standardized format across all GRADS participating centers.ResultsSarcoidosis patients overall had increased levels of IgM and IgG autoantibodies compared to normal controls. In addition, several autoantibodies were elevated in the POS and EPS cohorts compared to the NC cohort. Differences in autoantibody levels were also noted between the POS and the EPS cohorts. When comparing organ involvement with sarcoidosis, bone, spleen and ear, nose and throat involvement had higher IgM expression than other organs.ConclusionSarcoidosis patients have elevated IgM and IgG autoantibody levels compared to normal controls. In addition, individuals with pulmonary as well as additional organ involvement had higher IgM expression. Further research is needed focusing on specific organ-autoantibody pairs and role of autoantibodies in disease pathogenesis.

Markers of Infection-Mediated Cardiac Damage in Influenza and COVID-19.

Introduction: Influenza and the coronavirus disease 2019 (COVID-19) are two potentially severe viral infections causing significant morbidity and mortality. The causative viruses, influenza A/B and the severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) can cause both pulmonary and extra-pulmonary disease, including cardiovascular involvement. The objective of this study was to determine the levels of cardiac biomarkers in hospitalized patients infected with influenza or COVID-19 and their correlation with secondary outcomes. Methods: We performed a retrospective comparative analysis of cardiac biomarkers in patients hospitalized at our department with influenza or COVID-19 by measuring high-sensitivity troponin-T (hs-TnT) and creatinine kinase (CK) in plasma. Secondary outcomes were intensive care unit (ICU) admission and all-cause in-hospital mortality. Results: We analyzed the data of 250 influenza patients and 366 COVID-19 patients. 58.6% of patients with influenza and 46.2% of patients with COVID-19 presented with increased hs-TnT levels. Patients of both groups with increased hs-TnT levels were significantly more likely to require ICU treatment or to die during their hospital stay. Compared with COVID-19, cardiac biomarkers were significantly higher in patients affected by influenza of all age groups, regardless of pre-existing cardiovascular disease. In patients aged under 65 years, no significant difference in ICU admission and mortality was detected between influenza and COVID-19, whereas significantly more COVID-19 patients 65 years or older died or required intensive care treatment. Conclusions: Our study shows that increased cardiac biomarkers are associated with higher mortality and ICU admission in both, influenza and SARS-CoV-2-infected patients. Cardiac biomarkers are higher in the influenza cohort; however, this does not translate into worse outcomes when compared with the COVID-19 cohort.

S2172 A Unique Case of Disseminated Histoplasmosis Presenting as Colonic Ulcers

Introduction: Histoplasmosis is the most common endemic mycosis in the United States with a disseminated form usually only seen in immunocompromised patients. While localized infections are usually self-limiting and often asymptomatic, some patients present with extra-pulmonary disseminated disease. Although case reports have described colonic and ileal involvement, gastrointestinal manifestations are uncommon. Here we report isolated colonic involvement of disseminated histoplasmosis in an asymptomatic patient. Case Description/Methods: A 62-year-old male with a history of end stage renal disease secondary to IgA nephropathy status post living donor renal transplant on chronic immunosuppressive therapy presented for a routine screening colonoscopy. The patient denied gastrointestinal and pulmonary symptoms to include: cough, shortness of breath, fever, abdominal pain, diarrhea and gastrointestinal bleeding. He grew up in the state of Mississippi and currently resides in Texas working in landscaping. Within the cecum, there were 2 discrete areas of abnormal appearing tissue (Figure A). A 10mm irregular, superficial ulcer with no high-risk stigmata for bleeding was also noted within the distal transverse colon (Figure B). Cold forceps biopsies were obtained at both sites. Surgical pathology with Grocott’s methenamine silver stain demonstrated abundant intra-histiocytic and extracellular organisms morphologically compatible with histoplasmosis. Given a potential for fungal morphological mimicry, the patient was serologically tested for histoplasmosis, coccidioides, and blastomyces. Ultimately, PCR from the tissue sample taken during the biopsy tested positive for Histoplasma capsulatum. The patient was started on itraconazole for 12 months duration which he tolerated without side effects and remained asymptomatic on follow up. Discussion: This case demonstrates an unusual presentation of disseminated histoplasmosis with asymptomatic colonic involvement including the variable endoscopic appearance of this fungal infection. With a mortality rate as high as 31% in the immunocompromised population gastroenterologists need to remain cognizant when encountering colonic ulcerations or abnormal mucosa in high risk patients. In addition, this case highlights the importance of tissue sampling to secure the diagnosis along with the efficacy of itraconazole in treating this potentially deadly infection.Figure 1.: A. Discrete area of anomalous tissue in the cecum B. Area of ulceration along the distal transverse colon.

Comparison of two chemotherapy regimens in patients with newly diagnosed Ewing sarcoma (EE2012): an open-label, randomised, phase 3 trial

Internationally, a single standard chemotherapy treatment for Ewing sarcoma is not defined. Because different chemotherapy regimens were standard in Europe and the USA for newly diagnosed Ewing sarcoma, and in the absence of novel agents to investigate, we aimed to compare these two strategies. EURO EWING 2012 was a European investigator-initiated, open-label, randomised, controlled phase 3 trial done in 10 countries. We included patients aged 2-49 years, with any histologically and genetically confirmed Ewing sarcoma of bone or soft tissue, or Ewing-like sarcomas. The eligibility criteria originally excluded patients with extrapulmonary metastatic disease, but this was amended in the protocol (version 3.0) in September, 2016. Patients were randomly assigned (1:1) to either the European regimen of vincristine, ifosfamide, doxorubicin, and etoposide induction, and consolidation using vincristine, actinomycin D, with ifosfamide or cyclophosphamide, or busulfan and melphalan (group 1); or the US regimen of vincristine, doxorubicin, cyclophosphamide, ifosfamide, and etoposide induction, plus ifosfamide and etoposide, and consolidation using vincristine and cyclophosphamide, or vincristine, actinomycin D, and ifosfamide, with busulfan and melphalan (group 2). All drugs were administered intravenously. The primary outcome measure was event-free survival. We used a Bayesian approach for the design, analysis, and interpretation of the results. Patients who received at least one dose of study treatment were considered in the safety analysis. The trial was registered with EudraCT, 2012-002107-17, and ISRCTN, 54540667. Between March 21, 2014, and May 1, 2019, 640 patients were entered into EE2012, 320 (50%) randomly allocated to each group. Median follow-up of surviving patients was 47 months (range 0-84). Event-free survival at 3 years was 61% with group 1 and 67% with group 2 (adjusted hazard ratio [HR] 0·71 [95% credible interval 0·55-0·92 in favour of group 1). The probability that the true HR was less than 1·0 was greater than 0·99. Febrile neutropenia as a grade 3-5 treatment toxicity occurred in 234 (74%) patients in group 1 and in 183 (58%) patients in group 2. More patients in group 1 (n=205 [64%]) required at least one platelet transfusion compared with those in group 2 (n=138 [43%]). Conversely, more patients required blood transfusions in group 2 (n=286 [89%]) than in group 1 (n=277 [87%]). Dose-intensive chemotherapy with vincristine, doxorubicin, cyclophosphamide, ifosfamide, and etoposide is more effective, less toxic, and shorter in duration for all stages of newly diagnosed Ewing sarcoma than vincristine, ifosfamide, doxorubicin, and etoposide induction and should now be the standard of care for Ewing sarcoma. The European Union's Seventh Framework Programme for Research, Technological Development, and Demonstration; The National Coordinating Centre in France, Centre Léon Bérard; SFCE; Ligue contre le cancer; Cancer Research UK.

Convolutional Neural Network as an Image Processing Technique for Classification of Bacilli Tuberculosis Extra Pulmonary (TBEP) Disease

Tuberculosis Extra Pulmonary (TBEP) is an infectious disease caused by the bacterium Mycobacterium tuberculosis and can cause death. Patients suffering from this disease must be treated quickly without waiting for a long time. Biopsy is one of the techniques used to take the patient's lung fluid and given Ziehl Neelsen chemical dye and then observed using a microscope to determine this TBEP disease. In this research, the TBEP detection process was developed using a classification method, namely CNN with feature extraction and feature selection. The feature uses 5 features where these features are a combination of shape features and texture features with the highest information gain value. From the results of research conducted through the training and testing stages of the classification method using feature selection, the accuracy rate is higher than not using feature selection with a comparison of the feature selection stage increasing 0.6536% for the training process, and 0.8942% for the testing process.