Diagnosis Of Primary Disease Research Articles

Targeted high-throughput sequencing technique for the molecular diagnosis of primary immunodeficiency disorders.

The aim of this study was to investigate the usefulness of targeted high-throughput sequencing (HTS) for the molecular diagnosis of primary immunodeficiency diseases (PID).A total of 56 clinically diagnosed or suspected PID patients were divided into 4 groups according to the International Union of Immunological Societies Expert Committee for Primary Immunodeficiency 2015 and their chief clinical presentations. Patients and their biological family members were examined by targeted HTS, which sequenced the exons and ±10 bp flanking introns of 171 PID-related genes panel. All significant variants were confirmed by PCR-Sanger sequencing. Pathogenicity of the variants was evaluated by using bioinformatics.A total of 117 variants in 73 genes were found in 56 patients. Accurate molecular diagnosis of PID was made in 13 (23.2%) patients, and 12 novel mutations were detected in these patients. Twenty-seven patients carried heterozygous variants that are probably pathogenic in ≥2 genes; 16 patients had only 1 missense variant, or had several variants but not >1 variant was deleterious as evaluated by bioinformatics. The meaning of the targeted HTS results of these patients remains to be studied.Targeted HTS can make a precise molecular diagnosis of PID and detect more novel pathogenic mutations. More and more variations with ambiguous significance are discovered and explanation of these variations is a challenge to the clinicians.

RELATIONSHIP BETWEEN BREAKS IN SEDENTARY BEHAVIOR AND FREE LIVING PHYSICAL ACTIVITY ENERGY EXPENDITURE IN INDIVIDUALS WITH CORONARY ARTERY DISEASE

There is a significant association between sedentary behavior and mortality risk factors. Interrupting sedentary time with physical activity (PA) breaks has been shown to be beneficial in improving these risk factors. Further, there is evidence that free living physical activity energy expenditure (PAEE)>770 kcal/day is associated with significantly lower mortality risk. The purpose of this study was to investigate the relationship between breaks in sedentary time and PAEE, and to determine the number and duration of breaks associated with PAEE>770kcal/day. 132 patients (63 ± 9 years, Male: 77.3%) with a primary diagnosis of coronary artery disease (CAD) participated in this study. Sedentary behavior and PA were assessed using multi-sensor accelerometer (SenseWear Mini Armband). Participants wore the accelerometer for average of five days (21.9 ± 1.7 hrs/day) and the minute by minute data on PAEE (>1.5METs) were averaged over the recording period. The number and duration of PA breaks/sedentary hr (i.e., Break #/sedentary hr, Break duration/sedentary hr) were calculated. Pearson correlation analyses were performed and multiple linear regression analyses were used to investigate the relationship between Break #/sedentary hr and Break duration/sedentary hr with PAEE, while adjusting for age and gender. Receiver Operating Characteristic (ROC) curves were used to determine the cut-off values for Break #/sedentary hr and Break duration/sedentary hr associated with PAEE>770kcal/day. Analyses were conducted using SPSS (version 24). There were strong correlations between PAEE with Break #/sedentary hr (r=0.74, p=0.000) and Break duration/sedentary hr (r=0.87, p=0.000). When adjusting for age and gender, linear regression analyses showed significant associations between PAEE with Break #/sedentary hr (Beta=0.653, unstandardised (B)=234, adjusted R square=0.662, p=0.000) and Break duration/sedentary hr (Beta=0.792, unstandardised (B)=20.89, adjusted R square=0.829, p=0.000). ROC analyses showed that the cut-off values of Break #/sedentary hr = 3 and Break duration/sedentary hr = 21min were associated with PAEE>770kcal/day (Break #/sedentary hr: Sensitivity=0.73, Specificity=0.79, AUC=0.84, p=0.000; Break duration/sedentary hr: Sensitivity=0.94, Specificity=0.79, AUC=0.94, p=0.000). There were strong correlations between breaks in sedentary time and PAEE. For every increase (n=1) in the number of Breaks/sedentary hr, PAEE increased by 234 kcal; and for every minute increase in Break duration/sedentary hr, PAEE increased by ∼21 kcal. Findings indicate that spending 21min in PA, accumulated through 3 breaks, for every hour of being sedentary, is associated with meeting PAEE>770kcal/day. Thus, in order to improve PAEE, CAD patients should be encouraged to interrupt sedentary behavior every 20min with a PA break of seven minutes.

Analysis of clinical characters of female vulvar Paget disease

Objective: To investigate the clinical and pathological features, diagnosis and treatment of primary vulvar Paget disease (VPD) , and analyze the related factors that may affect the recurrence. Methods: A retrospective study was carried out on 36 patients diagnosed as VPD pathologically from January 1983 to December 2017 at Peking Union Medical College Hospital, Chinese Academy of Medical Sciences. The clinical and pathological features, diagnosis, treatment and prognosis and the factors influencing recurrence rate of VPD were analyzed. Results: (1) Totally 94% (34/36) of VPD occurred in postmenopausal women. Pruritus was counted 86% (31/36) of the main complaint. Lesions of vulvar were main symptom which had no specificity, acting as ulcer (67%, 24/36) , erythema (50%, 18/36) , depigmentation (42%, 15/36) , sclerosis (31%, 11/36) , and pigmentation (17%, 6/36) . The lesions invaded labium majus (97%, 35/36) , sometimes labium minus (53%, 19/36) , clitoris (28%, 10/36) , perianal (25%, 9/36) , orificium vaginae (3%, 1/36) , and meatus urinarius (3%, 1/36) . Approximately 19% (7/36) of VPD coexisted with intraepithelial neoplasia or adenocarcinoma of vulvar or other part of body. (2) Diagnosis and treatment: diagnosis was confirmed histologically by biopsy or pathologies after surgery, and immunohistochemical results were helpful for differential diagnosis. Surgery was the mean treatment method, 34 of all the 36 patients (94%, 34/36) underwent surgery for at least once, while 2 patients (6%, 2/36) were performed non-operative treatment. The surgical treatment included excision of focus, wide local excision, simple vulvectomy, and extensive vulvectomy. The non-operative treatment included radiotherapy, chemotherapy, laser, photodynamic therapy, and so on. (3) Prognosis: among 36 VPD patients, 4 were lost to follow-up with a 89% (32/36) follow-up rate. Median follow-up was 35.3 months (range,1 month to 31 years) . During the follow-up period, 2 patients were unable to judge whether they will relapse for the follow-up time did not reach half a year, 8 cases were unsuccessful operation, 20 cases succeeded, the achievement ratio was 71% (20/28) . Nine of twenty cases relapsed, the recurrence rate was 45% (9/20) . The median recurrence time was 14 months after operation. One patient of the 32 followed-up patients died, the mortality rate was 3% (1/32) . (4) The related factors affected the recurrence of VPD: t test was applied to the analysis of patients' age, rank test was used in the statistics of the time of confirmed diagnosis, the length and thickness of the resection focus. Fisher test was used to calculate whether the focus were limited to the epidermis, type of surgical procedures, distance between the margin and the focus, whether tumor cells infiltrated the margin. The results showed that none of the above terms in the first operation had significant contribution to recurrence (all P>0.05) . Conclusions: VPD may be a low potential malignancy, which could slowly progress into deep invasive disease. VPD is often associated with intraepithelial neoplasia or primary tumors of the vulva or somewhere else. Operations is the first choice for VPD, but consider for its high recurrence rate after operation, close follow-up should be strongly suggested.

Outcomes of infants receiving chronic peritoneal dialysis: an analysis of the USRDS registry

Outcome data for infants on chronic peritoneal dialysis (CPD) is limited and has been based primarily on the analyses of voluntary entry registry data. In contrast, the United States Renal Data Systems (USRDS) collects data on all infants with end-stage kidney disease (ESKD) on chronic dialysis in the USA. We aimed to describe the clinical characteristics of this population and to determine the associated patient mortality. The USRDS database was reviewed retrospectively for data on infants who initiated CPD at ≤ 12months of age from 1990 to 2014. Infants were categorized into four groups, CPD initiation age (≤ 1month of age or neonates and > 1-12months of age or older infants) and initiation era (1990-1999 and 2000-2014). A total of 1723 infants (574 neonates and 1149 older infants) were identified. Overall, 20.9% of infants (147 neonates and 213 older infants) died on dialysis during the follow-up. The most commonly identified causes of death on dialysis were cardiorespiratory disease (25.8%) and infection (22.8%). There was an increased risk for mortality in all infants who initiated CPD in the earlier initiation era (1990-1999) vs the later era (2000-2014) (aHR of 1.95), for females vs males (aHR 1.43), and for those with a primary diagnosis of cystic kidney diseases vs congenital anomalies of the kidney and urinary tract (CAKUT) (aHR 1.84). In 2000-2014, patient survival at 1 and 5years was 86.8% and 74.6% for those who initiated CPD as neonates and 89.6% and 79.3% for those who did so as older infants. In this large cohort of infants who received chronic peritoneal dialysis over more than two decades, the probability of survival after initiating CPD in the first year of life has significantly improved. There is no difference in the probability of death for neonates compared to older infants. However, the mortality rate remains substantial in association with multiple risk factors.

Risk of Severe Cardiovascular Events From Add-On Tiotropium in Chronic Obstructive Pulmonary Disease

ObjectiveTo examine the risk of cardiovascular disease (CVD) from tiotropium added to inhaled long-acting β2 agonists (LABAs) and inhaled corticosteroids (ICSs) in a nationwide population with chronic obstructive pulmonary disease (COPD). Patients and MethodsThis nested case-control study included 65,966 patients with COPD treated with LABAs and ICSs identified from the Taiwan nationwide health care claims database from January 1, 2007, through June 30, 2011. Cases were all patients with a first primary diagnosis of ischemic heart disease, heart failure, stroke, or arrhythmia from inpatient or emergency care settings during follow-up, and each was matched with 4 disease risk score–matched controls from risk sets. The use of tiotropium in the year before the index/event date was measured, stratified by duration since therapy initiation, concomitant COPD medications, and dosage form. Conditional logistic regression models were used to estimate odds ratios of the CVD risk from add-on tiotropium therapy. ResultsFrom the study cohort, with a mean age of 70.3 years (interquartile range, 61.8-79.4 years), 3188 CVD cases (incidence rate, 6.2 [95% CI, 6.0-6.4] cases per 100 person-years) and 12,349 matched controls were identified. The new use of tiotropium was associated with a 1.88-fold (95% CI, 1.44-2.46) increased CVD risk within 30 days of therapy initiation, and the association was sustained up to 60 days after treatment initiation (adjusted odds ratio, 1.71; 95% CI, 1.08-2.70). The risk persisted across all tiotropium regimens, with a case-crossover analysis, and in comparison with new add-on theophylline therapy. ConclusionTiotropium newly added to LABA/ICS combination therapy was associated with an increased cardiovascular risk in patients with COPD.

Newborn screening using TREC/KREC assay for severe T and B cell lymphopenia in Iran.

T-cell receptor excision circles (TRECs) and κ-deleting recombination excision circles (KRECs) are recently used for detection of T or B cell lymphopenia in neonates based on region-specific cutoff levels. Here, we report cutoffs for TREC and KREC copies useful for newborn screening and/or diagnosis of primary immunodeficiency diseases (PID) in Iran. DNA was extracted from a single 3.2mm punch of dried blood spots collected from 2160 anonymized newborns referred to two major referral health centres between 2014 and 2016. For refinement of the cutoffs, 51 patients with a definite diagnosis of severe combined immunodeficiency, X-linked agammaglobulinaemia and combined immunodeficiency, including ataxia telangiectasia, human phosphoglucomutase 3 and Janus kinase-3 deficiency, as well as 47 healthy controls were included. Samples from patients with an X-linked hyper-IgM-syndrome, Wiskott-Aldrich syndrome and DNA ligase 4 deficiency were considered as disease controls. Triplex-quantitative real-time PCR was used. Cutoffs were calculated as TRECs<11 and KRECs<6 copies with an ACTB > 700 copies with sensitivity of 100% for TREC and 97% for KREC. Among thirty anonymized newborn samples (1.5%) with abnormal results for TREC and/or KREC, only twenty-one available cases were retested and shown to be in the normal range except for three samples (0.15%). All of the patients with a definitive diagnosis were correctly identified based on our established TREC/KREC copy numbers. Determining cutoffs for TREC/KREC is essential for correctly identifying children with PID in newborn screening. Early diagnosis of PID patients enables appropriate measures and therapies like stem cell transplantation.

Validated uroflowmetry-based predictive model for the primary diagnosis of urethral stricture disease in men.

To define a uroflowmetry-based non-invasive predictive tool for the primary diagnosis of urethral stricture disease. A total of 300 male patients (150 with urethral stricture disease and 150 with benign prostatic obstruction), treated surgically between 2005 and 2015, and 75 healthy males were included in this study. Patients were randomly assigned to one of two groups (75 benign prostatic obstruction patients and 75 urethral stricture disease patients in each group). A model, able to objectively differentiate between benign prostatic obstruction and urethral stricture disease, was created by use of original and hybrid uroflowmetry variables in logistic regression in groupA (test group). Receiver operating characteristics curve analysis was used for validation in groupB (validation group) and to calculate cut-off values to distinguish healthy individuals from benign prostatic obstruction as a result of urethral stricture disease. Receiver operating characteristics area under the curve values of the created model were 0.841 (0.777-0.905) and 0.807 (0.735-0.879) in groups A and B, respectively. Optimal cut-off values were 2.2847 and 0.1182 to distinguish healthy individuals versus benign prostatic obstruction and benign prostatic obstruction versus urethral stricture disease. A triphasic uroflowmetry-based model is able to objectively distinguish voiding patterns of healthy individuals, benign prostatic obstruction and urethral stricture disease. The probability of urethral stricture disease can be objectively calculated for each individual patient based on a non-invasive uroflowmetry test. Uroflowmetry pattern interpretation by use of statistical models could become a new standard.

Features of dental diseases in children with albinism

Aim. To comparatively characterize the state of local and general immunity in patients with the primary diagnosis of albinism and oral mucosal diseases. Methods. In the dental clinic of FSBEI HE «Kazan SMU MOH Russia» 4 patients aged 16 to 17 years are observed with the primary diagnosis of albinism and comorbid oral mucosal diseases. On initial examination 2 patients from group 1 were diagnosed with chronic recurrent aphthous stomatitis, Sutton’s disease. K12.1. The control group (group 2) included 5 children aged 12 to 15 years diagnosed with chronic recurrent aphthous stomatitis. The state of local immunity was assessed by the level of lysozyme of the oral fluid before and after the treatment. Lysozyme activity in the oral fluid was evaluated and calculated by our newly developed method. The state of local immunity was assessed by immunograms. Patients’ microbiologic status was evaluated by microscopic and bacteriological methods. Results. Among the patients from group 1 with the diagnosis of chronic recurrent aphthous stomatitis, Sutton’s disease, the analysis of immunograms prior to the study revealed severe neutropenia (5.4±0.4×109/l), lymphocytosis (Т-lymphocytes 85±3.5%), leukopenia (2.2±0.1×109/l), increased level of immunoglobulin A (2.69±0.1 g/l), decreased number of phagocytes (2.6) and circulating immune complexes (22±1.48). In patients from the control group leukopenia (2.89±0.23×109/l), lymphocytosis (Т-lymphocytes 74.3±1.32%), insignificant increase of immunoglobulin G level (14.5±0.59 g/l), decreased number of phagocytes (4.5±0.5) and circulating immune complexes (38.67±1.23), and neutropenia (25.5±0.1×109/l) were revealed. Conclusion. Cellular component of the general immunity in albinos insignificantly differs from the patients of the control group but no restoration of the cellular immunity occurs even in long-term remission; to choose the method of treatment for patients diagnosed with chronic recurrent aphthous stomatitis it is necessary to determine the etiology of the disease, particularly, immunologic status of patients before and after the treatment.

Chronic granulomatous disease due to different mutations in patients from the same consanguineous extended family

Chronic granulomatous disease is a primary immunodeficiency disease caused by a genetic mutation in any of the 5 genes encoding the different components of the Nicotinamide Adenine Dinucleotide Phosphate reduced (NADPH)-Oxidase enzyme complex. Since primary immunodeficiency diseases are considered to be rare diseases, the genetic diagnosis of a certain primary immunodeficiency leads to the reasonable assumption that all patients with the same disease within the same family will have the same genetic mutation. We report 2 patients with chronic granulomatous disease from the same extended consanguineous family who had different genetic causes of their disease. Therefore, it is crucial to obtain a definitive genetic diagnosis of primary immunodeficiency disease even in patients from the same family, where the same genetic diagnosis is presumed to be the cause of the disease. Statement of novelty: Genetic causes of chronic granulomatous disease may be different in patients from the same family.

Abstract 216: Hospitalizations of Patients With Heart Failure and Reduced Ejection Fraction Treated With Sacubitril/Valsartan (S/V) vs. Angiotensin-Converting Enzyme Inhibitor or Angiotensin Receptor Blocker (ACEI/ARB)

Background: The PARADIGM-HF clinical trial showed a significant reduction in heart failure (HF) hospitalizations and cardiovascular (CV) death in patients with heart failure and reduced ejection fraction (HF r EF) and treated with S/V compared to enalapril. The impact of S/V on real-world outcomes is not well studied. Objective: To assess the association of hospitalization and therapy with S/V vs. ACEI/ARB in patients with HF r EF in the US. Methods: Adult patients with ≥1 claim for S/V or ACEI /ARB from 7/7/2015-5/31/2016 were selected from the MarketScan databases. Patients with S/V were assumed to have HF r EF based on its prescribing information. Patients with ACEI/ARB had claims-based evidence of HF r EF. The index date was the 1 st claim for S/V (searched first) or ACEI/ARB. All patients had data for ≥24 months pre-index and ≥6 months post-index, unless inpatient death occurred within 6 months post-index. HF, HF-related, and all-cause hospitalizations in the 6 months pre- and post-index were examined. HF hospitalizations had a primary diagnosis or a diagnosis-related group code for HF. HF-related hospitalizations had a non-primary HF diagnosis and a primary diagnosis of CV or chronic kidney disease, diabetes, chronic obstructive pulmonary disease, pneumonia or signs/symptoms related to HF. All-cause hospitalizations had any diagnosis. Multivariable regressions with scaled Poisson distribution tested the association between number of hospitalizations post-index and therapy with S/V vs. ACEI/ARB, controlling for patients’ characteristics, baseline costs and hospitalizations. Results: A total of 956 patients had ≥1 claim for S/V (median age 64 years, 71% male, mean Charlson Comorbidity Index [CCI] score 3.1); 55,492 patients had ≥1 claim for ACEI/ARB (median age 70 years, 62% male, CCI 3.3). There were significantly fewer hospitalizations in the 6 months post-index than pre-index for all patients, with a greater reduction observed in patients with S/V vs. ACEI/ARB. The pre-post differences for % of patients with HF hospitalizations (S/V vs. ACEI/ARB) were -9.5% vs. -3.2%; HF-related hospitalizations -13.0% vs. -6.3%; and all cause hospitalizations -14.5% vs. -8.0%. Although multivariate analyses demonstrated that HF hospitalizations post-index in S/V patients were not significantly different (rate ratio [95% confidence interval] 0.91 [0.78-1.06], p=0.23), there were significantly fewer HF-related (0.82 [0.71-0.94]) and all-cause hospitalizations (all-cause 0.78 [0.69-0.89]); both p &lt;0.05, compared to ACEI/ARB. Conclusions: Compared to ACEI/ARB, S/V therapy among patients with HF r EF is related to reduction of costly hospitalizations, which may translate to potential cost saving in HF care. The lack of HF hospitalization significance may represent the disparity in the sample size. Sponsorship: The study was funded by Novartis Pharmaceuticals Corp., East Hanover, NJ.

Kidney Transplant Recipients With Rheumatic Diseases: Epidemiological Data From the Polish Transplant Registries 1998–2015

Chronic kidney disease (CKD) is a common complication of rheumatic disorders. We analyzed the incidence of different rheumatic conditions as a primary diagnosis of end-stage renal disease (ESRD) in kidney transplant recipients in Poland.Data were received from the national waiting list for organ transplantation (Poltransplant) registries. Primary diagnosis leading to ESRD were analyzed in 15,984 patients who received kidney transplants between 1998 and 2015. There was no information about primary diagnosis in 4981 cases (31%) and in 1482 cases (9%) the diagnosis was described as unknown.Rheumatic diseases were specified in 566 (5.14%) kidney transplant recipients: lupus erythematosus, (systemic lupus erythematous nephritis) in 211 (1.92%), vasculitis in 176 (1.60%), amyloidosis AA in 82 (0.75%), hemolytic uremic syndrome in 59 (0.54%), secondary glomerulonephritis in 24 (0.22%), scleroderma in 9 (0.08%), rheumatoid arthritis in 4 (0.04%) and Sjögren syndrome in 1 (0.01%). Graft survival at 1 and 5 years were significantly better in the nonrheumatic versus rheumatic group (90 vs 87% and 76 vs 72% respectively, P = .04). Recipient survival at 5 years was significantly better in the nonrheumatic versus the rheumatic group (88 vs 84%, P = .02).Our study showed that systemic lupus erythematosus and systemic vasculitides are the major rheumatic causes of ESRD in the Polish population. Long-term graft and recipient survival were significantly better in the nonrheumatic versus the rheumatic group in the Poltransplant cohort.

Referral of individuals with cardiovascular disease to secondary prevention programmes.

secondary prevention programmes help manage risk factors, prevent progression of disease, minimise complications and reduce readmissions to hospitals. Referrals to these programmes are suboptimal even though they improve survival and quality of life. to explore referral of individuals with a primary diagnosis of acute coronary syndrome, cerebrovascular disease or peripheral vascular disease to secondary prevention programmes. a non-experimental descriptive retrospective design was used to analyse 176 patient records from a tertiary referral hospital in Melbourne, Australia. The study population consisted of individuals over 18 years of age admitted to hospital with a primary diagnosis of acute coronary syndrome, cerebrovascular disease or peripheral vascular disease within a 12-month period in 2009. from the patient records reviewed, 34% (n=60) were referred to secondary prevention programmes compared with 66% (n=116) not referred. Individuals with acute coronary syndrome were more likely to be referred than those with peripheral vascular disease or cerebrovascular disease. Those most likely to be referred were young males, married, living in a rural area and English speaking. the study highlights that referrals to secondary prevention programmes are suboptimal. There is a need to investigate reasons for under-referral and the best approach to manage referrals. referrals to secondary prevention programmes are an important area of research: these are beneficial, yet some individuals are not being referred. Nurses are well placed to promote referrals to these programmes potentially. reducing under-referral.

The effects of prescribing varenicline on two-year health outcomes: an observational cohort study using electronic medical records.

AimsTo investigate whether smokers prescribed varenicline had lower risks of serious ill‐health during the 4 years following treatment compared with those prescribed nicotine replacement therapy (NRT).DesignObservational cohort study of electronic medical records.SettingA total of 370 UK general practices sampled from the Clinical Practice Research Datalink.ParticipantsA total of 126 718 patients aged 18 and over who were issued smoking cessation prescriptions between 1 September 2006 and 31 March 2014.MeasurementsOur primary outcome was all‐cause mortality within 2 years of first prescription as indicated by linked Office of National Statistics data. Our secondary outcomes were cause‐specific mortality, all‐cause, cause‐specific hospitalization, primary care diagnosis of myocardial infarction or chronic obstructive pulmonary disease (COPD), body mass index and attendance rate to primary care within 2 years of first prescription. Risk differences and 95% confidence intervals were estimated by multivariable adjusted regression and propensity score matched regression. We used instrumental variable analysis to overcome residual confounding.FindingsPeople prescribed varenicline were healthier at baseline than those prescribed NRT in almost all characteristics, highlighting the potential for residual confounding. Our instrumental variable analysis results found that people prescribed varenicline had a similar risk of mortality at 2 years [risk difference per 100 patients treated = 0.67, 95% confidence interval (CI) = ‐0.11 to 1.46)] to those prescribed NRT, and there were similar rates of all‐cause hospitalization, incident primary‐care diagnoses of myocardial infarction and COPD. People prescribed varenicline subsequently attended primary care less frequently.ConclusionsSmokers prescribed varenicline in primary care in the United Kingdom do not appear to be less likely to die, be hospitalized or experience a myocardial infarction or chronic obstructive pulmonary disease during the following 2 years compared with smokers prescribed nicotine replacement therapy, but they gain more weight and attend primary care less frequently.

Endocrine Disorders in Primary Mitochondrial Disease.

ContextEndocrine disorders are common in individuals with mitochondrial disease. To develop evidence-based screening practices in this high-risk population, updated age-stratified estimates of the prevalence of endocrine conditions are needed.ObjectiveTo measure the point prevalence of selected endocrine disorders in individuals with mitochondrial disease.Design, Setting, and PatientsThe North American Mitochondrial Disease Consortium Patient Registry is a large, prospective, physician-curated cohort study of individuals with mitochondrial disease. Participants (n = 404) are of any age, with a diagnosis of primary mitochondrial disease confirmed by molecular genetic testing.Main Outcome MeasuresAge-specific prevalence of diabetes mellitus (DM), abnormal growth and sexual maturation (AGSM), hypoparathyroidism, and hypothyroidism.ResultsThe majority of our sample was pediatric (<18 years; 60.1%), female (56.9%), and white (85.9%). DM affected 2% of participants aged <18 years [95% confidence interval (CI): 0.4% to 5.7%] and 24.4% of adult participants (95% CI: 18.6% to 30.9%). DM prevalence was highest in individuals with mitochondrial encephalomyopathy, lactic acidosis, and strokelike episodes syndrome (MELAS; 31.9%, of whom 86.2% had the m.3243A>G mutation). DM occurred more often with mitochondrial DNA defects (point mutations and/or deletions) than with nuclear DNA mutations (23.3% vs 3.7%, respectively; P < 0.001). Other prevalence estimates were 44.1% (95% CI: 38.8% to 49.6%) for AGSM; 0.3% (95% CI: 0% to 1.6%) for hypoparathyroidism; and 6.3% (95% CI: 4% to 9.3%) for hypothyroidism.ConclusionDM and AGSM are highly prevalent in primary mitochondrial disease. Certain clinical mitochondrial syndromes (MELAS and Kearns-Sayre/Pearson syndrome spectrum disorders) demonstrated a higher burden of endocrinopathies. Clinical screening practices should reflect the substantial prevalence of endocrine disorders in mitochondrial disease.

End-Stage Liver Disease in Patients with Intracranial Hemorrhage Is Associated with Increased Mortality: A Cohort Study.

To determine if end-stage liver disease (ESLD) in patients with intracranial hemorrhage (ICH) is associated with increased mortality. This single-center, retrospective cohort study included 53 patients (33 in ESLD cohort and 20 in non-ESLD cohort) who received neurosurgical care between 2006 and 2017. ESLD was defined clinically as severely impaired liver function and at least 1 major complication of liver failure. The primary outcome was mortality. Overall, in-hospital, and 30-day mortality rates were higher in the ESLD cohort versus the non-ESLD cohort (79 vs. 30%, 79 vs. 20%, and 64 vs. 25%, all P ≤ 0.01). We identified a significant difference in overall survival between ESLD and non-ESLD cohorts on Kaplan-Meier analysis (P= 0.004 with log-rank and Wilcoxon tests). Odds of overall, in-hospital, and 30-day mortality in the ESLD cohort were 8.67 (95% confidence interval [CI], 2.44-30.84), 14.86 (95% CI, 3.75-58.90), and 5.25 (95% CI, 1.53-18.08). Other predictors of overall mortality included primary admission diagnosis of liver disease (odds ratio [OR]= 9.60; 95% CI, 3.75-58.90), higher Child-Pugh (OR= 1.64; 95% CI, 2.66-34.67) and Model for End-Stage Liver Disease (OR= 1.12; 95% CI, 1.04-1.20) scores, lower Glasgow Coma Scale score (OR= 0.73; 95% CI, 0.61-0.88), ICH that developed in the hospital (OR= 4.11; 95% CI, 1.21-13.98), and intraparenchymal hemorrhage (OR= 9.23; 95% CI, 1.72-49.56). ESLD in patients with ICH is associated with increased mortality.

Prevalence of Nephrolithiasis in Patients with Chronic Liver Disease: A Case–Control Study

Nephrolithiasis is known to be associated with several systemic diseases including chronic kidney disease and renal failure, which can also occur as a complication of chronic liver disease (CLD). This study aimed to assess the prevalence of nephrolithiasis in patients with CLD. A short survey was completed by 198 patients with CLD and 322 controls matched by age, sex, and state of residence. A primary diagnosis of liver disease was confirmed with health record review. The median age of the liver disease group was 63 years and 128 (65%) were male; the median age of the control group was 63 and 199 (63%) were male. Body mass index was higher in the liver disease group (27.8 vs 26.7, P<.01). The most common liver disease diagnosis was hepatitis C (60 [30%]) followed by alcoholic cirrhosis (42 [21.2%]). The self-reported prevalence of nephrolithiasis in the liver disease group was 26%, compared to 14% in the control group (P<.01). This association remained significant after adjusting for age, sex, body mass index, and family history of kidney stones or liver disease. In this case-control, survey-based study, the prevalence of nephrolithiasis was 2 times higher in patients with CLD.

Anterior Cervical Discectomy and Fusion Outcomes over 10 Years: A Prospective Study.

Prospective cohort study with >10-year follow-up. To assess the long-term, >10-year clinical outcomes of anterior cervical discectomy and fusion (ACDF) and to compare outcomes based on primary diagnosis of disc herniation, stenosis or advanced degenerative disc disease (DDD), number of levels treated, and preexisting adjacent level degeneration. ACDF is a proven treatment for patients with stenosis and disc herniation and results in significantly improved short- and intermediate-term outcomes. Motion preservation treatments may result in improved long-term outcomes but need to be compared to long-term ACDF outcomes reference. Patients who had disc herniation, stenosis, and DDD and underwent ACDF with or without decompression were prospectively enrolled and followed for a minimum of 10 years with outcome assessment at various intervals. All 159 consecutive patients had autogenous tricortical iliac crest bone graft and plate instrumentation used. Outcomes included visual analog scale for neck and arm pain. pain drawing, Oswestry Disability Index, and self-assessment of procedure success. Preoperative adjacent-level disc degeneration, pseudarthrosis, and secondary operations were analyzed. For all diagnostic groups, significant outcomes improvement was seen at all follow-up periods for all scales relative to preoperative scores. Outcomes were not related to age, gender, number of levels treated, and minimally to preexisting degeneration at the adjacent level. The use of narcotic pain medication decreased substantially. Neurological deficits almost all resolved. Patient self-reported success ranged from 85% to 95%. Over the long term, additional surgery for pseudarthrosis (10%) occurred in the early follow-up period, and for adjacent segment degeneration (21%), which occurred linearly during the >10-year follow-up period. ACDF leads to significantly improved outcomes for all primary diagnoses and was sustained for >10 years' follow-up. Secondary surgeries were performed for pseudarthrosis repair and for symptomatic adjacent-level degeneration. 2.

Brain metastases in breast cancer: analysis of the role of HER2 status and treatment in the outcome of 94 patients.

We investigated the impact of human epidermal growth factor receptor 2 (HER2) and prognostic factors in the outcome of patients with breast cancer that developed brain metastases. . The data from 94 patients who received multidisciplinary therapy from 2001 to 2007 were retrospectively reviewed. Patients were assigned according to their HER2 status, and overall survival and time to brain metastases recurrence/progression were evaluated. The prognostic value of age, presence of extracerebral metastases, recursive partitioning analysis class, hormone therapy, systemic therapy and trastuzumab was assessed. The median overall survival and time to brain disease progression were 7.1 and 6.5 months, respectively. HER2 positivity (P = 0.006), treatment with trastuzumab (P = 0.025), chemotherapy (P = 0.011) and recursive partitioning analysis class I-II (P <0.001) were associated with prolonged survival on univariate analysis. On multivariate analysis, only recursive partitioning analysis class I-II (P <0.001) and triple-negative disease (P = 0.04) remained significant for overall survival, whereas time to brain metastases progression was only associated with recursive partitioning analysis class I-II (P = 0.001). The time from the diagnosis of primary disease to brain metastasis was slightly shorter in the HER2+ patients than in HER2- patients (36 vs 39 months). Intensified local treatment of brain metastasis incorporating whole-brain radiotherapy and/or radiosurgery and neurosurgery did not affect survival. Patients with triple-negative disease presented a significantly lower survival than the rest of the cohort (4 vs 8 months; P = 0.012). Recursive partitioning analysis class I-II was found to be the strongest independent predictive factor. Treatment with trastuzumab in HER2+ patients appeared to improve overall survival, probably due to the better control of systemic metastatic disease, but did not maintain significance in multivariate analysis. The dismal prognosis of patients with triple-negative breast cancer highlights the need to develop novel therapies to improve the poor survival.

Fluorine-18-fluorodeoxyglucose positron emission tomography/computed tomography: A diagnostic imaging modality in renal cancer patients

PurposeThe aim of this study is to clarify the role of 18-F-FDG PET/CT over CT alone in the detection of primary, recurrent and metastatic disease in renal cancers patients. Patients and methodsIn this study; 18-F-PET/CT scans were performed for 25 patients (19 males and 6 females) with renal cancer. A patient-based analysis was performed in a dedicated manner to pick up lesions on CT, PET and PET/CT fused images. Statistical analysis was calculated. A final diagnosis of disease extent was affirmed by clinical, radiologic workup and histopathological correlation. ResultsPET/CT has 100% sensitivity, 93% specificity, 100% PPV, 91% NPV and 96% accuracy; compared to 100% sensitivity and 70% specificity, 83% PPV, 100% NPV and 88% accuracy for CT in diagnosis of primary, recurrent and metastatic disease in renal cancer. ConclusionIncorporated 18-F FDG PET/CT is a very versatile and accurate imaging technique for renal cancers. It significantly improves the accuracy and predictive values over CT alone for detection of primary, recurrent and metastatic disease in renal cancer thus change the treatment decision.

Efficacy of dexamethasone suppression test during the diagnosis of primary pigmented nodular adrenocortical disease in Chinese adrenocorticotropic hormone-independent Cushing syndrome

ObjectiveTo evaluate the cut-off value of the ratio of 24 h urinary free cortisol (24 h UFC) levels post-dexamethasone to prior-dexamethasone in dexamethasone suppression test (DST) during the diagnosis of primary pigmented nodular adrenocortical disease in Chinese adrenocorticotropic hormone-independent Cushing syndrome.DesignRetrospective study.ParticipantsThe patients diagnosed with primary pigmented nodular adrenocortical disease (PPNAD, n = 25), bilateral macronodular adrenal hyperplasia (BMAH, n = 27), and adrenocortical adenoma (ADA, n = 84) were admitted to the Peking Union Medical College Hospital from 2001 to 2016.EstimationsSerum cortisol, adrenocorticotropic hormone (ACTH), and 24 h UFC were measured before and after low-dose dexamethasone suppression test (LDDST) and high-dose dexamethasone suppression test (HDDST).ResultsAfter LDDST and HDDST, 24 h UFC elevated in patients with PPNAD (paired t-test, P = 0.007 and P = 0.001), while it remained unchanged in the BMAH group (paired t-test, P = 0.471 and P = 0.414) and decreased in the ADA group (paired t-test, P = 0.002 and P = 0.004). The 24 h UFC level after LDDST was higher in PPNAD and BMAH as compared to ADA (P < 0.017), while no significant difference was observed between PPNAD and BMAH. After HDDST, 24 h UFC was higher in patients with PPNAD as compared to that of ADA and BMAH (P < 0.017). The cut-off value of 24 h UFC (Post-L-Dex)/(Pre-L-Dex) was 1.16 with 64.0% sensitivity and 77.9% specificity, and the cut-off value of 24 h UFC (Post-H-Dex)/(Pre-H-Dex) was 1.08 with 84.0% sensitivity and 75.6% specificity.ConclusionThe ratio of post-dexamethasone to prior-dexamethasone had a unique advantage in distinguishing PPNAD from BMAH and ADA.