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1.
Respir Investig ; 59(5): 589-595, 2021 Sep.
Article in English | MEDLINE | ID: mdl-34246581

ABSTRACT

Rapid eye movement (REM) related obstructive sleep apnea (OSA) is defined by the presence of episodes of apnea or hypopnea predominantly or exclusively during REM sleep. Epidemiology of this disorder shows a complex interaction with age, sex, and body mass index. The prevalence is variable and depends on the criteria used to define this disorder. Moreover, the clinical significance of this entity remains poorly defined. However, episodes of apnea or hypopnea encountered during REM sleep are longer and are associated with a more profound drop in oxygen saturation than non-REM sleep. Likewise, this disorder may be independently associated with hypertension and poor glycemic control. More importantly, positive airway pressure therapy as currently prescribed may not treat the majority of apnea episodes during REM sleep. The treatment is further complicated by the different definitions used for the diagnosis of this disorder and the lack of consensus if patients with this diagnosis should be treated if their overall apnea-hypopnea index does not meet the threshold for the clinical diagnosis of OSA. The definition and treatment used for the diagnosis and management of REM-related OSA needs to be standardized. Moreover, a consensus needs to be developed as to whether patients with this disorder should be treated if their overall apnea-hypopnea index does not meet the threshold for the clinical diagnosis of OSA. Further investigation may help answer if this disorder is independently associated with neurocognitive and cardiometabolic adverse outcomes and help guide the therapeutic approach.


Subject(s)
Hypertension , Sleep Apnea, Obstructive , Sleep, REM , Humans , Polysomnography , Prevalence , Sleep Apnea, Obstructive/epidemiology , Sleep Apnea, Obstructive/therapy
2.
Respirol Case Rep ; 9(4): e00739, 2021 Apr.
Article in English | MEDLINE | ID: mdl-33732471

ABSTRACT

Complete lung collapse associated with sarcoidosis is exceedingly rare. Although lymphoma should be ruled out when patients with mediastinal lymphadenopathy develop lung collapse, sarcoidosis should be considered in the differential, especially when associated with fibrosing mediastinitis.

3.
J Am Acad Dermatol ; 83(6): 1581-1589, 2020 Dec.
Article in English | MEDLINE | ID: mdl-32682027

ABSTRACT

BACKGROUND: The incidence of cutaneous squamous cell carcinoma (SCC) in patients with chronic lymphocytic leukemia (CLL) is significantly higher compared with age- and sex-matched controls. OBJECTIVE: To evaluate the association of factors associated with SCC risk. METHODS: Clinical CLL and SCC data were obtained from Mayo Clinic CLL Resource and self-reported questionnaires among patients with newly diagnosed CLL. We computed the CLL International Prognostic Index (CLL-IPI) from CLL prognostic factors, and a polygenic risk score from SCC susceptibility variants. We used Cox regression to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). RESULTS: Among 1269 patients with CLL, the median follow-up was 7 years, and SCC subsequently developed in 124 patients. Significant associations with SCC risk were history of skin cancer (HR=4.80; 95% CI: 3.37-6.83), CLL-IPI (HR=1.42; 95% CI: 1.13-1.80), and polygenic risk score (HR=2.58; 95% CI: 1.50-4.43). In a multivariable model, these factors were independent predictors (C statistic = 0.69; 95% CI: 0.62-0.76). T-cell immunosuppressive treatments were also associated with SCC risk (HR=2.29; 95% CI: 1.47-3.55; adjusted for age, sex, and prior SCC). LIMITATIONS: The sample size decreases when combining all risk factors in a single model. CONCLUSION: SCC risk includes history of skin cancer, an aggressive disease at time of CLL diagnosis, receiving T-cell immunosuppressive treatments, and high polygenic risk score. Future studies should develop prediction models that include these factors to improved screening guidelines.


Subject(s)
Carcinoma, Squamous Cell/epidemiology , Leukemia, Lymphocytic, Chronic, B-Cell/epidemiology , Skin Neoplasms/epidemiology , Adult , Aged , Aged, 80 and over , Biomarkers, Tumor/genetics , Carcinoma, Squamous Cell/diagnosis , Carcinoma, Squamous Cell/genetics , Carcinoma, Squamous Cell/immunology , Dermatology/standards , Female , Follow-Up Studies , Genetic Predisposition to Disease , Humans , Immunosuppressive Agents/adverse effects , Incidence , Leukemia, Lymphocytic, Chronic, B-Cell/drug therapy , Leukemia, Lymphocytic, Chronic, B-Cell/immunology , Male , Mass Screening/standards , Medical History Taking , Medical Oncology/standards , Middle Aged , Practice Guidelines as Topic , Prognosis , Risk Assessment/statistics & numerical data , Risk Factors , Skin/immunology , Skin/pathology , Skin Neoplasms/diagnosis , Skin Neoplasms/genetics , Skin Neoplasms/immunology , T-Lymphocytes/drug effects , T-Lymphocytes/immunology , Young Adult
4.
Blood Cancer J ; 9(8): 59, 2019 08 05.
Article in English | MEDLINE | ID: mdl-31383849

ABSTRACT

Chronic lymphocytic leukemia (CLL) and its precursor, monoclonal B-cell lymphocytosis (MBL), are heritable. Serumfree light-chain (sFLC) measures are a prognostic factor for CLL, but their role in susceptibility to CLL is not clear. We investigated differences between sFLC measurements in pre-treatment serum from five groups to inform the association of sFLC with familial and sporadic CLL: (1) familial CLL (n = 154), (2) sporadic CLL (n = 302), (3) familial MBL (n = 87), (4) unaffected first-degree relatives from CLL/MBL families (n = 263), and (5) reference population (n = 15,396). The percent of individuals having elevated monoclonal and polyclonal sFLCs was compared using age-stratified and age- and sex-adjusted logistic regression models. In age groups >50 years, monoclonal sFLC elevations were increased in sporadic and familial CLL cases compared to the reference population (p's < 0.05). However, there were no statistically significant differences in sFLC monoclonal or polyclonal elevations between familial and sporadic CLL cases (p's > 0.05). Unaffected relatives and MBL cases from CLL/MBL families, ages >60 years, showed elevated monoclonal sFLC, compared to the reference population (p's < 0.05). This is the first study to demonstrate monoclonal sFLC elevations in CLL cases compared to controls. Monoclonal sFLC levels may provide additional risk information in relatives of CLL probands.


Subject(s)
B-Lymphocytes/pathology , Immunoglobulin Light Chains/blood , Leukemia, Lymphocytic, Chronic, B-Cell/immunology , Lymphocytosis/immunology , Adult , Aged , Aged, 80 and over , B-Lymphocytes/immunology , Biomarkers, Tumor/blood , Biomarkers, Tumor/immunology , Case-Control Studies , Cohort Studies , Female , Humans , Leukemia, Lymphocytic, Chronic, B-Cell/blood , Leukemia, Lymphocytic, Chronic, B-Cell/epidemiology , Leukemia, Lymphocytic, Chronic, B-Cell/genetics , Lymphocytosis/blood , Lymphocytosis/epidemiology , Lymphocytosis/genetics , Male , Middle Aged , Minnesota/epidemiology
5.
Leukemia ; 33(2): 499-507, 2019 02.
Article in English | MEDLINE | ID: mdl-30201985

ABSTRACT

We and others have shown increased risk of monoclonal gammopathy of undetermined significance (MGUS) in first-degree relatives of patients with multiple myeloma (MM). Whether familial risk of MGUS differs by the MM proband's age at onset, tumor or clinical characteristics is unknown. MM and smoldering MM (SMM) cases (N = 430) were recruited from the Mayo Clinic in Rochester, Minnesota between 2005-2015. First-degree relatives over age 40 provided serum samples for evaluation of MGUS (N = 1179). Age and sex specific rates of MGUS among first-degree relatives were compared to a population-based sample. Cytogenetic subtypes were classified by Fluorescence in situ hybridization. MGUS was detected in 75 first-degree relatives for an age- and sex- adjusted prevalence of 5.8% (95% CI: 4.5-7.2). Prevalence of MGUS in first-degree relatives was 2.4 fold (95% CI: 1.9-2.9) greater than expected rates. Familial risk did not differ by proband's age at diagnosis, gender, isotype, IgH translocation, or trisomy. This study confirms first-degree relatives of MM cases have a significantly higher risk of MGUS compared to the general population, regardless of age, gender, or tumor characteristics. In selected situations, such as multiple affected first-degree relatives, screening of first-degree relatives of MM cases could be considered for follow-up and prevention strategies.


Subject(s)
Blood Proteins/analysis , Immunoglobulin Isotypes/genetics , Monoclonal Gammopathy of Undetermined Significance/pathology , Multiple Myeloma/genetics , Adult , Aged , Aged, 80 and over , Disease Progression , Family , Female , Follow-Up Studies , Humans , In Situ Hybridization, Fluorescence , Male , Middle Aged , Monoclonal Gammopathy of Undetermined Significance/blood , Monoclonal Gammopathy of Undetermined Significance/epidemiology , Monoclonal Gammopathy of Undetermined Significance/etiology , Multiple Myeloma/complications , Multiple Myeloma/pathology , Prevalence , Prognosis , Risk Factors , Survival Rate , United States/epidemiology
6.
J Pediatr Gastroenterol Nutr ; 64(5): 726-729, 2017 05.
Article in English | MEDLINE | ID: mdl-28437323

ABSTRACT

OBJECTIVES: Guidelines for diagnosing celiac disease (CD) recommend initial testing with a highly sensitive serologic test for anti-tissue transglutaminase immunoglobulin A antibodies (tTG IgA). When the probability of CD is high, IgA deficiency should be considered. The 2 approaches to address this include measuring "both tTG IgA and tTG IgG" or measuring "total IgA." We aim to assess the utility of an isolated positive tTG IgG result in diagnosing CD. METHODS: We conducted a retrospective review of patients undergoing serologic testing for CD from January 1997 to June 2014. Patients with positive tTG IgG and negative tTG IgA were included. Moreover, all patients who had any other positive CD-specific serologic findings were excluded. Demographics, clinical presentation, tests, and biopsy results were recorded. RESULTS: The indication for checking celiac serology was gastrointestinal symptoms in 172 of 233 patients, iron deficiency anemia in 12, and high-risk screening in 48. Small bowel biopsy was performed in 178 patients (77%); 160 had normal results and 18 had histologic changes suggestive of enteropathy. Nine patients had increased intraepithelial lymphocytes, and 9 had partial villous atrophy. Only 6 cases of CD were, however, confirmed. The utility of isolated tTG IgG in diagnosis of CD was low at 3% (6/178). CONCLUSION: In this cohort of patients, the utility of isolated tTG IgG in diagnosing CD was low at 3%.


Subject(s)
Autoantibodies/blood , Celiac Disease/diagnosis , GTP-Binding Proteins/immunology , Immunoglobulin A/blood , Immunoglobulin G/blood , Transglutaminases/immunology , Adolescent , Adult , Aged , Biomarkers/blood , Celiac Disease/immunology , Child , Female , Humans , Male , Middle Aged , Predictive Value of Tests , Protein Glutamine gamma Glutamyltransferase 2 , Retrospective Studies , Young Adult
7.
Updates Surg ; 68(4): 419-420, 2016 Dec.
Article in English | MEDLINE | ID: mdl-27263101

ABSTRACT

Penetrating trauma to the abdomen can be a potential diagnostic dilemma for the trauma surgeon, and a formal exploratory laparotomy may result in the detection of occult injuries. We report a very unusual case of penetrating trauma to the abdomen resulting in pericardio-diagphragmatic rupture. We have also highlighted the technical aspects of clinical care in this specific scenario.


Subject(s)
Abdominal Injuries/surgery , Laparotomy/methods , Suicide, Attempted , Wounds, Stab/surgery , Abdominal Injuries/diagnosis , Aged , Humans , Male , Wounds, Stab/diagnosis
8.
Expert Rev Gastroenterol Hepatol ; 10(4): 537-46, 2016.
Article in English | MEDLINE | ID: mdl-26603931

ABSTRACT

Refractory celiac disease (RCD) affects patients who have failed to heal after 6-12 months of a strict gluten-free diet (GFD) and when other causes of symptoms (including malignancy) have been ruled out. It may also occur in patients who previously had responded to a long-term GFD. RCD may be categorized as RCD1 (normal immunophenotype) and RCD2 (aberrant immunophenotype). RCD1 usually responds to a continued GFD, nutritional support, and therapeutic agents such as corticosteroids. In contrast, clinical response in RCD2 is incomplete and prognosis is often poor. RCD (particularly RCD2) is associated with serious complications, such as ulcerative jejunitis and enteropathy-associated T-cell lymphoma (EATL). Strict clinical and laboratory criteria should be used to diagnose RCD and specialized tests for aberrancy and clonality should be interpreted in the context of their sensitivity and specificity. Adequate nutritional support and anti-inflammatory treatment may even allow patients with RCD2 to attain a clinical remission.


Subject(s)
Celiac Disease/diet therapy , Diet, Gluten-Free , Adrenal Cortex Hormones/therapeutic use , Anti-Inflammatory Agents/therapeutic use , Biopsy , Celiac Disease/diagnosis , Celiac Disease/immunology , Combined Modality Therapy , Diagnosis, Differential , Humans , Immunophenotyping/methods , Nutrition Assessment , Nutritional Support , Phenotype , Predictive Value of Tests , Remission Induction , Time Factors , Treatment Failure
10.
Dig Dis ; 33(2): 215-220, 2015.
Article in English | MEDLINE | ID: mdl-25925925

ABSTRACT

BACKGROUND/AIMS: Many medications can cause diarrhea by increasing motility, inflammation or enteropathy. Olmesartan and mycophenolic acid (CellCept) are drugs that are capable of increasing inflammation and enteropathy in some individuals and, if not recognized, can lead to chronic diarrhea. It is this type of drug-induced diarrhea that is the focus of this review. METHODS: A summary of our findings (recent and earlier published) as well as a review of published works from other centers were conducted. RESULTS: There is increasing evidence that olmesartan use is associated with enteropathy in a small number of individuals who use angiotensin receptor II blockers, and that this enteropathy is characterized by severe diarrhea capable of inducing severe dehydration and, in some instances, failure of organs such as the kidney. Typical patient demographics are Caucasian individuals who are older (>50 years old) and obese or overweight prior to weight loss. Prolonged exposure to olmesartan use for 1-2 years is typical, although case reports of irbesartan and valsartan have been reported as well. Discontinuing olmesartan leads to improvement of symptoms; however, the period for healing is variable, with some patients requiring steroid therapy and even prolonged parental nutrition support. In addition, many histological features of olmesartan-associated enteropathy are also present in celiac disease, including villi shortening and lymphocyte infiltration. Other drug-associated enteropathies have also been reported with mycophenolate mofetil used in transplantation. CONCLUSIONS: Of the drug-associated enteropathies discussed in this review, olmesartan can generate the most severe symptoms, albeit quite rare. Therefore, with patients who present with severe diarrhea and weight loss, one should consider olmesartan-associated enteropathy. In addition, many of the features associated with olmesartan-associated enteropathy are also found in celiac disease enteropathy; as such, one should review any celiac disease diagnosis for any use of olmesartan at the time of diagnosis.


Subject(s)
Drug-Related Side Effects and Adverse Reactions/pathology , Gastrointestinal Diseases/chemically induced , Antibodies, Monoclonal/adverse effects , Drug-Related Side Effects and Adverse Reactions/diagnosis , Drug-Related Side Effects and Adverse Reactions/therapy , Gastrointestinal Diseases/diagnosis , Gastrointestinal Diseases/therapy , Humans , Imidazoles/adverse effects , Ipilimumab , Mycophenolic Acid/adverse effects , Mycophenolic Acid/analogs & derivatives , Risk Factors , Tetrazoles/adverse effects
11.
Immunology ; 145(3): 313-22, 2015 Jul.
Article in English | MEDLINE | ID: mdl-25913295

ABSTRACT

All vertebrates contain a diverse collection of commensal, symbiotic and pathogenic microorganisms, such as bacteria, viruses and fungi, on their various body surfaces, and the ecological community of these microorganisms is referred to as the microbiota. Mucosal sites, such as the intestine, harbour the majority of microorganisms, and the human intestine contains the largest community of commensal and symbiotic bacteria. This intestinal community of bacteria is diverse, and there is a significant variability among individuals with respect to the composition of the intestinal microbiome. Both genetic and environmental factors can influence the diversity and composition of the intestinal bacteria with the predominant environmental factor being diet. So far, studies have shown that diet-dependent differences in the composition of intestinal bacteria can be classified into three groups, called enterotypes. Other environmental factors that can influence the composition include antibiotics, probiotics, smoking and drugs. Studies of monozygotic and dizygotic twins have proven that genetics plays a role. Recently, MHC II genes have been associated with specific microbial compositions in human infants and transgenic mice that express different HLA alleles. There is a growing list of genes/molecules that are involved with the sensing and monitoring of the intestinal lumen by the intestinal immune system that, when genetically altered, will significantly alter the composition of the intestinal microflora. The focus of this review will be on the genetic factors that influence the composition of the intestinal microflora.


Subject(s)
Immunogenetics , Intestinal Mucosa/immunology , Intestines/immunology , Microbiota/immunology , Genetic Variation/immunology , HLA Antigens/genetics , HLA Antigens/immunology , Host-Pathogen Interactions/genetics , Host-Pathogen Interactions/immunology , Humans , Intestinal Mucosa/metabolism , Intestinal Mucosa/microbiology , Intestines/microbiology , Microbiota/genetics , Microbiota/physiology , Models, Immunological , Toll-Like Receptors/genetics , Toll-Like Receptors/immunology
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