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1.
IEEE/ACM Trans Comput Biol Bioinform ; 19(3): 1472-1483, 2022.
Article in English | MEDLINE | ID: mdl-33226952

ABSTRACT

The remarkable growth of multi-platform genomic profiles has led to the challenge of multiomics data integration. In this study, we present a novel network-based multiomics clustering founded on the Wasserstein distance from optimal mass transport. This distance has many important geometric properties making it a suitable choice for application in machine learning and clustering. Our proposed method of aggregating multiomics and Wasserstein distance clustering (aWCluster) is applied to breast carcinoma as well as bladder carcinoma, colorectal adenocarcinoma, renal carcinoma, lung non-small cell adenocarcinoma, and endometrial carcinoma from The Cancer Genome Atlas project. Subtypes were characterized by the concordant effect of mRNA expression, DNA copy number alteration, and DNA methylation of genes and their neighbors in the interaction network. aWCluster successfully clusters all cancer types into classes with significantly different survival rates. Also, a gene ontology enrichment analysis of significant genes in the low survival subgroup of breast cancer leads to the well-known phenomenon of tumor hypoxia and the transcription factor ETS1 whose expression is induced by hypoxia. We believe aWCluster has the potential to discover novel subtypes and biomarkers by accentuating the genes that have concordant multiomics measurements in their interaction network, which are challenging to find without the network inference or with single omics analysis.


Subject(s)
Breast Neoplasms , Carcinoma, Renal Cell , Kidney Neoplasms , Breast Neoplasms/genetics , Carcinoma, Renal Cell/genetics , Cluster Analysis , DNA Methylation/genetics , Female , Humans , Kidney Neoplasms/genetics
2.
J Clin Endocrinol Metab ; 106(3): 826-842, 2021 03 08.
Article in English | MEDLINE | ID: mdl-33221858

ABSTRACT

CONTEXT: Pituitary corticotroph adenomas are rare tumors that can be associated with excess adrenocorticotropin (ACTH) and adrenal cortisol production, resulting in the clinically debilitating endocrine condition Cushing disease. A subset of corticotroph tumors behave aggressively, and genomic drivers behind the development of these tumors are largely unknown. OBJECTIVE: To investigate genomic drivers of corticotroph tumors at risk for aggressive behavior. DESIGN: Whole-exome sequencing of patient-matched corticotroph tumor and normal deoxyribonucleic acid (DNA) from a patient cohort enriched for tumors at risk for aggressive behavior. SETTING: Tertiary care center. PATIENTS: Twenty-seven corticotroph tumors from 22 patients were analyzed. Twelve tumors were macroadenomas, of which 6 were silent ACTH tumors, 2 were Crooke's cell tumors, and 1 was a corticotroph carcinoma. INTERVENTION: Whole-exome sequencing. MAIN OUTCOME MEASURE: Somatic mutation genomic biomarkers. RESULTS: We found recurrent somatic mutations in USP8 and TP53 genes, both with higher allelic fractions than other somatic mutations. These mutations were mutually exclusive, with TP53 mutations occurring only in USP8 wildtype (WT) tumors, indicating they may be independent driver genes. USP8-WT tumors were characterized by extensive somatic copy number variation compared with USP8-mutated tumors. Independent of molecular driver status, we found an association between invasiveness, macroadenomas, and aneuploidy. CONCLUSIONS: Our data suggest that corticotroph tumors may be categorized into a USP8-mutated, genome-stable subtype versus a USP8-WT, genome-disrupted subtype, the latter of which has a TP53-mutated subtype with high level of chromosome instability. These findings could help identify high risk corticotroph tumors, namely those with widespread CNV, that may need closer monitoring and more aggressive treatment.


Subject(s)
ACTH-Secreting Pituitary Adenoma/genetics , Adenoma/genetics , DNA Copy Number Variations , Endopeptidases/genetics , Endosomal Sorting Complexes Required for Transport/genetics , Tumor Suppressor Protein p53/genetics , Ubiquitin Thiolesterase/genetics , ACTH-Secreting Pituitary Adenoma/epidemiology , ACTH-Secreting Pituitary Adenoma/pathology , Adenoma/epidemiology , Adenoma/pathology , Adolescent , Adult , Case-Control Studies , Cell Transformation, Neoplastic/genetics , Cohort Studies , DNA Copy Number Variations/physiology , Female , Gene Frequency , Genetic Association Studies , Genetic Predisposition to Disease , Humans , Male , Middle Aged , Mutation , Neoplasm Invasiveness , Neoplasm Metastasis , Exome Sequencing , Young Adult
3.
AACE Clin Case Rep ; 5(2): e150-e153, 2019.
Article in English | MEDLINE | ID: mdl-31967022

ABSTRACT

OBJECTIVE: Crooke cell adenoma (CCA) is a rare tumor of the anterior pituitary. It is highly aggressive and carries significant risk of morbidity and mortality. METHODS: This report focuses on the presentation of this disease process and review diagnosis and treatment. The patient is a 64-year-old male with a history of resected pituitary adenoma of unknown pathology. RESULTS: The patient underwent serial magnetic resonance imaging surveillance for numerous years without recurrence of tumor, however eventually developed symptoms of worsening left ear pain over 3 weeks that rapidly evolved to include ptosis. Imaging revealed a new pituitary macroadenoma. Urgent surgical resection revealed histopathological diagnosis of CCA. Corticotroph adenomas represent a rare subset of pituitary tumors. Clinically silent pituitary tumors demonstrate relatively higher rates of cavernous sinus invasion (30% versus 18%) and progression or recurrence (34% versus 6%) when compared to nonfunctioning adenomas. In CCA, only 65% of patients have clinical features of Cushing disease at presentation. Twenty-four-hour urinary free cortisol is discussed in the literature as a potential tool, where a value 4 times the upper limit of normal was predictive of higher risk of having Crooke cell changes. With a recurrence rate of up to 60%, multimodal treatment (surgery and radiation) is preferred. CONCLUSION: This case highlights early detection and treatment as keys to reducing the risk of morbidity and mortality from CCA. Currently, there are limited tools for identifying patients who are high risk for developing Crooke cell changes. Treatment modalities classically include surgery and radiotherapy. Adjuvant and novel chemotherapies are being explored.

4.
Tanaffos ; 18(2): 169-172, 2019 Feb.
Article in English | MEDLINE | ID: mdl-32440306

ABSTRACT

A 35- year- old man with a prior history of liver transplantation 18 months ago was admitted to our Intensive Care Unit (ICU) with fever and worsening dyspnea and was diagnosed with severe pneumonia leading to Acute Respiratory Distress Syndrome (ARDS). He had a prolonged hospitalization and was treated with empiric broad spectrum intravenous antibiotics, oseltamivir, trimethoprim/sulfamethoxazole, and subsequently caspofungin and ganciclovir. Blood, nasopharyngeal, as well as Bronchoalveolar Lavage (BAL) culture and Polymerase Chain Reaction (PCR) were negative for all viral, bacterial, and fungal causes of pulmonary infection except Enterovirus-Human Rhinovirus (EV-HRV) that was positive with high titers on BAL and swab specimens. Consequently, the diagnosis of EV-HRV pneumonia complicated by ARDS was established. The patient gradually improved and was discharged from the hospital after 3 weeks. This report highlights EV-HRV as a cause of ARDS in immunocompromised adults.

5.
Endocrinol Metab Clin North Am ; 47(2): 313-333, 2018 06.
Article in English | MEDLINE | ID: mdl-29754634

ABSTRACT

Cushing's syndrome is associated with increased morbidity and mortality. Cardiovascular events, sepsis, and thromboembolism are the leading causes of mortality. Patient's with Cushing's due to a pituitary adenoma and those with Cushing's due to benign adrenal adenoma have relatively good survival outcomes often mirroring that of the general population. Persistent or recurrent disease is associated with high mortality risk. Ectopic Cushing's syndrome and Cushing's due to adrenocortical carcinoma confer the highest mortality risk among Cushing's etiologies. Prompt diagnosis and treatment, and specific monitoring for and treatment of associated comorbidities are essential to decrease the burden of mortality from Cushing's.


Subject(s)
Adrenal Gland Neoplasms/mortality , Cushing Syndrome/mortality , Pituitary Neoplasms/mortality , Adrenal Gland Neoplasms/complications , Cushing Syndrome/etiology , Humans , Pituitary Neoplasms/complications
6.
Clin Respir J ; 12(1): 62-67, 2018 Jan.
Article in English | MEDLINE | ID: mdl-27059900

ABSTRACT

OBJECTIVE: To screen for Tuberculosis (TB) in human immunodeficiency virus (HIV) people in an effort to improve early TB diagnosis and reduce TB transmission. METHODS: A prospective study was conducted on adult HIV people from 2008 to 2011. Three samples of sputum, cell blood count, tuberculin skin test (TST) and chest X-ray were obtained from all patients. The characteristics of HIV patients with TB and HIV patients without TB were compared to each other. RESULTS: Of the 154 HIV patients included, 58 (38%) had tuberculosis with a mean CD4 cell count of 68 cells/mm3 . Active TB was found in 56 (47%) patients with a history of intravenous drug use. Cough (OR = 3.1, 95% CI 1.2-7.79), positive TST (OR = 8.15, 95% CI 3.28-20.25) and an abnormal chest X-ray (OR = 5.1, 95% CI 1.84-14.2) were the predicting factors for detecting active TB among HIV patients. The sensitivity and specificity of a combination of any symptoms with chest X-ray, smear, TST or all of these were 96.5% and 86.5%, respectively. CD4 cell count <100 (OR = 2.67; 95% CI 1.23-5.78) and smoking (OR = 13.4; 95% CI 3.04-59.4) remained independently associated with TB in a multivariate analysis. CONCLUSION: There was a high prevalence of TB within the HIV population. Screening for TB among these patients can be carried out at every clinic or health facility using a combination of symptoms, TST, chest X-ray and smear sample.


Subject(s)
HIV Infections/epidemiology , HIV , Latent Tuberculosis/epidemiology , Mycobacterium tuberculosis/isolation & purification , Sputum/microbiology , Tuberculosis, Pulmonary/epidemiology , Adult , Comorbidity/trends , Female , Follow-Up Studies , HIV Infections/virology , Humans , Iran/epidemiology , Latent Tuberculosis/microbiology , Male , Prevalence , Prospective Studies , Tuberculin Test , Tuberculosis, Pulmonary/microbiology
7.
Endocrine ; 59(1): 16-29, 2018 01.
Article in English | MEDLINE | ID: mdl-29177641

ABSTRACT

Prolactinomas are the most common secretory pituitary adenoma. They typically occur in women in the 3rd-6th decade of life and rarely in the pediatric population or after menopause. Most women present with irregular menses and/or infertility. Dopamine (DA) agonists, used in their treatment, are safe during pregnancy, but in most cases are discontinued at conception with close monitoring for signs or symptoms of tumor growth. Breastfeeding is safe postpartum, provided there was no significant growth during pregnancy. Some women will experience normalization of prolactin levels postpartum. Menopause may also decrease prolactin levels and even those with macroprolactinomas may consider discontinuing their DA agonist with close follow-up. Prolactinomas may be associated with decreased quality of life scores in women, and play a role in bone health and cardiovascular risk factors. This review discusses the current literature and clinical understanding of prolactinomas throughout the entirety of the female life cycle.


Subject(s)
Aging/physiology , Pituitary Neoplasms , Prolactinoma , Adult , Child , Female , Humans , Menopause/blood , Menopause/physiology , Pituitary Gland/embryology , Pituitary Neoplasms/diagnosis , Pituitary Neoplasms/epidemiology , Pregnancy , Pregnancy Complications, Neoplastic/epidemiology , Pregnancy Complications, Neoplastic/etiology , Prolactin/blood , Prolactinoma/diagnosis , Prolactinoma/epidemiology , Quality of Life , Risk Factors
9.
J Glob Antimicrob Resist ; 4: 1-4, 2016 03.
Article in English | MEDLINE | ID: mdl-27436384

ABSTRACT

The objectives of this study were to determine the impact of diabetes mellitus (DM) on antituberculosis drug resistance in new cases of tuberculosis (TB). A case-control study was conducted on all newly diagnosed pulmonary TB adult patients with DM as cases and without DM as controls who were hospitalised from May 2013 to October 2013 in Iran. A molecular resistance test for rapid detection of resistance to isoniazid and rifampicin was done. Multivariate analysis was performed to determine the impact of DM on any anti-TB drug resistance. In total, 62 TB cases with DM and 64 TB cases without DM were included. TB cases with DM were more likely to be older (59 years vs. 43 years; P=0.001). Two TB-DM patients had multidrug-resistant TB (MDR-TB) (3.2%) compared with no cases of MDR-TB in the control group, and more TB-DM cases had isolates that were resistant to at least one drug (12.9% vs. 10.9%). DM [odds ratio (OR)=4.82, 95% confidence interval (CI) 1-23.57], age <40 years (OR=5.48, 95% CI 1.19-25.29) and history of TB contact (OR=5.86, 95% CI 1.69-20.36) remained significantly associated with any drug resistance in the multivariate analysis. In conclusion, new TB patients with DM are at increased risk of anti-TB drug resistance. More studies are needed to confirm these results.


Subject(s)
Diabetes Mellitus/epidemiology , Drug Resistance, Bacterial , Tuberculosis/complications , Adult , Aged , Case-Control Studies , Female , Humans , Iran , Isoniazid/pharmacology , Male , Middle Aged , Rifampin/pharmacology
10.
Tanaffos ; 15(3): 124-127, 2016.
Article in English | MEDLINE | ID: mdl-28210275

ABSTRACT

Active tuberculosis (TB) is one of the major opportunistic infections that may occur in solid organ transplant recipients. Diagnosis and treatment of latent and active TB are challenging in this population due to lack of randomized clinical trials. In this review, we discuss the clinical manifestations of TB, diagnosis of latent TB and treatment of both latent and active TB.

11.
Saudi J Kidney Dis Transpl ; 26(1): 6-11, 2015 Jan.
Article in English | MEDLINE | ID: mdl-25579709

ABSTRACT

Tuberculosis (TB) is a frequently encountered infection among organ transplant recipients in developing countries, and the incidence of infection after the first year of transplantation is considerably high. In this study, the impact of rifabutin treatment on organ transplant recipients with TB infection was evaluated with respect to the trend of infection, management and outcome. The medical records of 26 post-transplant patients who received an organ transplant between 2004 and 2012 and later diagnosed with TB of different organs were reviewed retrospectively. We retrieved data regarding clinical features as well as treatment and outcomes. The median time interval between transplantation and TB was 36 months (IQR 12-101 months). The most common form of infection was pulmonary/pleural TB. All our subjects received rifabutin instead of rifampin in the anti-TB treatment regime as rifabutin is a less-potent inducer of cytochrome P-450. All patients responded satisfactorily to the treatment and maintained excellent allograft function. Moreover, we did not have any mortality among our recipients. Drug-induced hepatitis was observed in nine (35%) patients. Rifabutin is an excellent alternative medication to rifampin in the setting of TB management. Hepatotoxicity is a potential risk for treatment because of the potential additive toxicity of immunosuppressive drugs.


Subject(s)
Antibiotics, Antitubercular/therapeutic use , Chemical and Drug Induced Liver Injury/etiology , Immunosuppression Therapy/adverse effects , Opportunistic Infections/drug therapy , Rifabutin/therapeutic use , Tuberculosis, Pleural/drug therapy , Tuberculosis, Pulmonary/drug therapy , Adult , Antibiotics, Antitubercular/adverse effects , Bone Marrow Transplantation , Female , Heart Transplantation , Humans , Kidney Transplantation , Lung Transplantation , Male , Middle Aged , Retrospective Studies , Rifabutin/adverse effects
12.
Saudi J Kidney Dis Transpl ; 25(6): 1240-3, 2014 Nov.
Article in English | MEDLINE | ID: mdl-25394441

ABSTRACT

With regard to the significant morbidity and mortality due to tuberculosis in lung transplant recipients, the identification of brain-dead organ donors with latent tuberculosis by use of the QuantiFERON TB Gold (QFT-G) test may be of help to reduce the risk of TB reactivation and mortality in lung recipients. This study was conducted in the National Research Institute of Tuber-culosis and Lung Diseases (NRITLD) in Iran, from January to March 2013. A total of 38 conse-cutive brain-dead donors, not currently infected with active tuberculosis, were recruited. The medi-cal records of all the study enrollees were reviewed. A whole-blood IFN- release assay (IGRA) in reaction to early secreted antigenic target 6 (ESAT-6), culture filtrate protein 10 (CFP-10), and TB7.7 antigens, was performed and the released Interferon- was measured via enzyme-linked immunosorbent assay (ELISA). The data was analyzed with QFT-G software which was provided by the company. The demographic, characteristics and other variables were entered into SPSS version 11.5. The QFT-G test results of three donors (7.9%) turned out to be positive, negative for 24 donors (63.1%), and indeterminate for 11 cases (28.9%). Our study revealed the potential advantages of QFT-G in lowering the incidence of donor-derived post-transplant tuberculosis among lung recipients. However, a high rate of indeterminate results restricted the performance of QFT-G in this study.


Subject(s)
Brain Death , Interferon-gamma Release Tests , Latent Tuberculosis/diagnosis , Lung Transplantation , Lung/microbiology , Mycobacterium tuberculosis/isolation & purification , Tissue Donors , Adult , Cells, Cultured , Enzyme-Linked Immunosorbent Assay , Female , Humans , Iran , Latent Tuberculosis/immunology , Latent Tuberculosis/microbiology , Latent Tuberculosis/transmission , Male , Middle Aged , Mycobacterium tuberculosis/immunology , Predictive Value of Tests , Young Adult
13.
Exp Clin Transplant ; 12(2): 129-32, 2014 Apr.
Article in English | MEDLINE | ID: mdl-24702145

ABSTRACT

OBJECTIVES: Evaluation for latent tuberculosis infection is advised before organ transplant. The interferon-gamma release assay has been shown to be more specific than the tuberculin skin test for screening for latent tuberculosis infection. We compared the tuberculin skin test and QuantiFERON-TB Gold In-Tube test for screening for latent tuberculosis infection and agreement between the tests in heart and lung transplant recipients before transplant. MATERIALS AND METHODS: Fifty-five adult patients who had been evaluated for heart and lung transplant between September 2011 and September 2012 at Masih Daneshvari Hospital in Iran were prospectively enrolled. We performed the tuberculin skin test and QuantiFERON-TB Gold In-Tube test. RESULTS: Of the 55 patients, 3 (5%) had positive tuberculin skin test results, and 11 (20%) had positive QuantiFERON-TB Gold In-Tube test results. Agreement between the tuberculin skin test and QuantiFERON-TB Gold In-Tube test was fair (Kappa=0.061; 95% CI: - 0.185-0.307) (P = .56). CONCLUSIONS: The positivity for QuantiFERON-TB Gold In-Tube test was greater than the positivity for the tuberculin skin test, and QuantiFERON-TB Gold In-Tube test more accurately determined the risk for latent tuberculosis infection. However, a further longitudinal study is necessary to verify that the QFT-G test would predict developing tuberculosis after heart and lung transplant.


Subject(s)
Heart Transplantation , Interferon-gamma Release Tests , Latent Tuberculosis/diagnosis , Lung Transplantation , Tuberculin Test , Adolescent , Adult , Female , Humans , Iran , Latent Tuberculosis/immunology , Latent Tuberculosis/microbiology , Male , Middle Aged , Predictive Value of Tests , Prospective Studies , Reproducibility of Results , Young Adult
14.
J Diabetes Metab Disord ; 12(1): 58, 2013 Dec 20.
Article in English | MEDLINE | ID: mdl-24360398

ABSTRACT

Tuberculosis (TB) and diabetes mellitus (DM) are both important health issues. A bidirectional association between them has been demonstrated by many researchers. The link of DM and TB is more prominent in developing countries where TB is endemic and the burden of diabetes mellitus is increasing. The association between diabetes and tuberculosis may be the next challenge for global tuberculosis control worldwide. Proper planning and collaboration are necessary to reduce the dual burden of diabetes and TB. One model similar to the TB-HIV program for prevention, screening and treatment of both diseases can be the best approach. In this paper, we review existing data and discuss the matters of controversy that would be helpful for determining research priorities in different countries.

15.
Exp Clin Transplant ; 10(3): 278-81, 2012 Jun.
Article in English | MEDLINE | ID: mdl-22631066

ABSTRACT

OBJECTIVES: This study sought to compare the sensitivities of serum galactomannan and bronchoalveolar lavage galactomannan in diagnosing invasive aspergillosis in solid-organ transplant recipients (lung and heart). MATERIALS AND METHODS: This study took place in the lung transplant center of the National Research Institute for Tuberculosis and Lung Disease. All patients with clinical and radiologic manifestations suggestive of pulmonary infection were included. Serum and bronchoalveolar lavage galactomannan were measured. RESULTS: Seventeen patients were included (lung, 15; heart, 1; heart-lung, 1). Probable or definite invasive aspergillosis was diagnosed in 9 patients. With a cutoff ≥ 0.5, serum galactomannan sensitivity and specificity for diagnosing invasive aspergillosis were 77.18% and 100%. Negative predictive value and positive predictive value were 80% and 100%. The sensitivity and specificity of bronchoalveolar lavage galactomannan for diagnosing invasive aspergillosis with cutoff of ≥ 0.5 was 100%. CONCLUSIONS: Regarding the high levels of mortality and problems in diagnosing this disease, using bronchoalveolar lavage galactomannan could be a suitable option.


Subject(s)
Bronchoalveolar Lavage Fluid/chemistry , Heart Transplantation , Invasive Pulmonary Aspergillosis/diagnosis , Lung Transplantation , Mannans/analysis , Mannans/blood , Transplantation , Adult , Antifungal Agents/therapeutic use , Biomarkers/metabolism , Caspofungin , Drug Therapy, Combination , Echinocandins/therapeutic use , Galactose/analogs & derivatives , Humans , Invasive Pulmonary Aspergillosis/drug therapy , Invasive Pulmonary Aspergillosis/metabolism , Lipopeptides , Male , Middle Aged , Predictive Value of Tests , Prospective Studies , Pyrimidines/therapeutic use , Retrospective Studies , Sensitivity and Specificity , Triazoles/therapeutic use , Voriconazole
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