Diagnosis Of Primary Disease Research Articles

Inflammatory Bowel Disease: Predictors and Causes of Early and Late Hospital Readmissions.

The rate of hospital readmission after discharge has been studied extensively in chronic conditions such as hepatic cirrhosis, diabetes mellitus, chronic obstructive pulmonary disease, and heart failure. Causative factors associated with hospital readmission have not been adequately investigated in patients with inflammatory bowel disease (IBD). We studied the rate, causes, and factors that predict readmissions at 1 month, 3 months, and 1 year in patients with IBD. We performed a retrospective cohort study using the electronic medical record of a tertiary academic medical center, encompassing 3 large hospitals to identify patients discharged between January 2007 and December 2010 with a primary discharge diagnosis of either ulcerative colitis or Crohn's disease. The index admission was defined as the first unplanned admission during this period. Readmission was defined as unplanned admission (because of any cause) occurring within 1 week, 1 month, 3 months, and 1 year from the index admission. To identify factors predictive of readmissions, we compared social, demographic, and clinical features at the index admission of patients with readmission and those with no readmissions. Multivariate logistic regression analyses were performed to identify variables associated with 1-month, 3-month, and 1-year readmissions. A total of 439 index admissions with a primary discharge diagnosis of either ulcerative colitis or Crohn's disease were eligible for inclusion in the study. These patients accounted for a total of 785 admissions to the health system during the study period. The unplanned readmission rates were 5% at 1 week, 14% at 1 month, 23.7% at 3 months, and 39.2% at 1 year. The most common reasons for readmissions were IBD exacerbations, infections, and abdominal pain. On multivariate analysis, receiving total parenteral nutrition (odds ratio [OR] = 2.3; 95% confidence interval [CI], 1.22-4.30) and intensive care unit stay during index admission (OR = 3.61; 95% CI, 1.38-9.46) predicted both early and late readmissions, whereas sex, race, insurer, and outside hospital transfers predicted 1-year readmission. Receiving steroids (OR = 0.52; 95% CI, 0.23-1.15) at index admission was protective against 1-month readmission; being discharged on biologics (OR = 0.44; 95% CI, 0.19-1.02) was protective against 3-month readmission. Both early and late hospital readmissions are common in patients with IBD. Because frequent readmissions are indicators of poor quality of care, future prospective studies using larger cohorts of patients are needed to identify modifiable factors in patient care before discharge to improve quality of care, prevent readmissions, and consequently reduce health care costs.

A Radiological Analysis of Oncological Safety of Whole Brain Radiation Therapy With Hippocampus Avoidance in Patients With Brain Metastasis

Whole brain radiotherapy (WBRT) remains reference treatment in patients with brain metastasis (BM), especially with multiple lesions. Hippocampus avoidance in WBRT (HA-WBRT) offers the feasibility of less impaired cognitive function than conventional WBRT and better intracranial control than SBRT. Oncological safety is critical in defining the proper role of HA-WBRT. The study aims to investigate the frequency of intracranial substructure involvement based on large series of radiological data and to optimize the margin definition in treatment planning. Consecutive patients with diagnosis of BM from enhanced MRI between 03/2011 and 07/2016 in RuiJin Hospital were analyzed. Lesions of each patient were confirmed by a senior radiologist and the closest distances from tumor to the hippocampal area were measured. A total of 226 patients (male 115/226, female 111/226) with 1080 metastatic sites are reviewed. The distribution of the primary tumors were: 72.6% from lung cancer (164/226), 19.9% from breast cancer (45/226) and 7.5% from other malignancies (17/226). Seventy-one patients had BM before or simultaneously with their primary malignancy, among them, 64 were with primary lung cancer. In the other 155 patients, the average and median time from the diagnosis of primary disease to the diagnosis of BM were 14 m and 9 m in patients with lung cancer (100/155), 59 m and 34 m in patients with breast cancer (42/100). In total, 758/1080(70.2%) lesions were situated beyond the tentorium. The average maximum diameters of single lesion were 13.82mm ±14.67mm and median diameters were 10mm(1.2mm-162mm).The distribution of the lesions were as follows: 322(29.8%) in the cerebellum, 268(24.8%)in the frontal lobe,168(15.6%)in the temporal lobe,128(11.9%) in the parietal lobe, 131(12.1%)in the occipital lobe, 45(4.2%)in the thalamus and 18(1.6%) in the brainstem. After measuring the closest distance from lesions to the Hippocampus area in each patients, the definition and the frequency of Hippocampus involvemt can be classifed into 3 catogories: 7/226(3.1%) within 5mm or less, 13/226(5.7%) within 10mm or less and 19/226(8.4%) within 20mm or less. 18 of 45 patients who had complete radiological follow-up after WBRT in the same hospital were founded progress of BM. The median time of follow-up is 11 months. There was only one new lesions in area of Hippocampus (less than 5mm). With complete radiological diagnosis, HA-WBRT can be delivered with oncological safety. Proper margin definition of HA in delineation is to be confirmed with individual technique.

Case series of 18 patients with lower extremity wounds treated with a concentrated surfactant–based gel dressing

The purpose of this case series was to assess the performance of a concentrated surfactant-based gel (CSG) dressing on 18 patients in the outpatient setting over 4weeks. Wounds selected were full thickness, had been presented for greater than 4weeks, and were located on the lower extremities. Patients were given the CSG dressing and instructed on its use. On follow-up clinic visits, the wound was assessed, measurements were obtained, Pressure Ulcer Scale for Healing (PUSH) Tool scores completed, and satisfaction with the dressing was solicited. Individual analysis of each subject's wound was conducted to determine if there was a healing trend over time with a decrease in total PUSH score. Descriptive statistics were used to analyze the results. Eighteen patients participated in this case series involving 9 women and 9 men with a mean age of 66 years (range from 52 to 91). All 18 of the patients had a primary diagnosis of peripheral vascular disease with 7 patients having venous leg ulcers and 11 patients with lower extremity arterial ulcers. The mean Total PUSH score before the CSG dressing was applied was 10.7 (range from 5 to 15) (standard deviation [SD] 3.09) and posttreatment was 8.3 (range from 0 to 14) (SD 4). All 18 patients had a decrease in their pretreatment score from the first clinic visit compared with the posttreatment PUSH Tool score, indicating that the CSG dressing may be an effective dressing in the management of lower extremity wounds.

Outcomes and Patterns of Relapse Following Definitive Radiation Therapy for Treatment of Oligometastatic Cervical Cancer

Survival rates are low for women with metastatic cervical cancer. Definitive radiation therapy to sites of oligometastatic disease has been reported to result in prolonged survival in other malignancies but has not been systematically studied in women with cervical cancer. The goal of this study was to report on clinical outcomes for women with cervical cancer treated with definitive radiation to isolated sites of recurrence. From 2001 to 2015, a total of 41 patients were treated with definitive radiation therapy using IMRT (n = 15), stereotactic (n = 6), or 3D (n = 20) photon therapy for oligometastatic cervical cancer. Patients presented either with synchronous oligometastatic disease to mediastinum (n = 1) or supraclavicular (SCV) lymph nodes (n = 8) with intact pelvic primary, or with recurrent disease to mediastinum (n = 10), SCV (n = 15), lung (n = 6), or bone (n = 1). Patients with recurrent disease were diagnosed at a median 21 months following initial diagnosis of primary disease (range: 2-177 months). Overall survival (OS) and progression-free survival (PFS) were evaluated via Kaplan-Meier method. Median follow-up time was 31.5 months (range: 1-104 months). Thirty-two patients presented with squamous cell carcinoma, 7 with adenocarcinoma, 1 with neuroendocrine, and 1 with papillary serous histology. The median age at diagnosis of patients in the cohort was 45 years (range: 24-77 years). Seven of 41 patients received induction chemotherapy prior to radiation (17.1%). Median overall survival (OS) from end of radiation treatment was 42 months (95% CI: 21-63 months), with an OS rate at 2-years of 72.2%. Median progression-free survival (PFS) was 13 months (95% CI: 4.2-21.8 months). Of the 41 patients treated, a total of 9 experienced disease progression (22%), with a median time-to-progression of 13 months (range: 4-42 months). Relapses occurred in the mediastinum (n = 5), lungs (n = 2), pelvis (n = 1), or brain (n = 1). All mediastinal recurrences occurred following treatment of SCV nodal basins. There were no local or in-field recurrences. There were no statistically significant associations with age (≥50 vs. <50 years), race (white vs. non), histology (SCC vs. non-squamous), induction chemotherapy, oligometastatic presentation (synchronous vs. recurrent), radiation technique (IMRT/stereotactic vs. 3D), radiation dose (≥50 vs. <50 Gy), or metastatic site (distant vs. mediastinal vs. SCV) in regard to either OS or PFS; however, a trend towards increased mortality was noted for patients presenting with pulmonary or osseous metastasis (HR 2.908, P = .062). Treatment with definitive radiation therapy to sites of oligometastatic cervical cancer can result in durable survival and excellent local control. Randomized trials are needed to determine if higher rates of survival can be attributed to treatment effect or patients selection.

Emergency Department, Hospital Inpatient, and Mortality Burden of Atrial Fibrillation in the United States, 2006 to 2014

The prevalence of atrial fibrillation (AF) is increasing in the United States as the population ages, but national surveillance is lacking. This cross-sectional study (2006 to 2014) analyzed data from the Healthcare Cost and Utilization Project's Nationwide Emergency Department Sample, the National (Nationwide) Inpatient Sample, and the National Vital Statistics System. Event totals were estimated independently for emergency department (ED) visits, hospitalizations, and mortality, and then collectively after applying criteria to identify mutually exclusive events. Rates were calculated for AF as primary diagnosis or underlying cause of death (primary AF), as well as secondary diagnosis or contributing cause of death (co-morbid AF), and standardized by age to the 2010 US population. From 2006 to 2014, event rates increased for primary AF (249 to 268 per 100,000) and co-morbid AF (1,473 to 1,835 per 100,000). In 2014, an estimated 599,790 ED visits, 453,060 hospitalizations, and 21,712 deaths listed AF as primary. A total of 684,470 mutually exclusive primary AF and 4,695,997 mutually exclusive co-morbid AF events occurred. Among ED visits and hospitalizations with primary AF, the most common secondary diagnoses were hypertension, heart failure, ischemic heart disease, and diabetes. The mean cost per hospitalization with primary AF was $8,819. Mean costs were higher for those with co-morbid AF versus those without co-morbid AF among hospitalizations with a primary diagnosis of ischemic heart disease, heart failure, stroke, hypertension, or diabetes (all p ≤0.01). In conclusion, with the substantial health and economic impact of AF and an aging US population, improved diagnosis, prevention, management, and surveillance of AF are increasingly important.

Long-term disability and progression in spinal onset multiple sclerosis.

The aim of this study is to investigate the long-term effects of the initial spinal cord (SC) involvement in MS patients. In this retrospective, single-center study, 824 patients with definite MS were screened. A total of 348 patients were excluded for ambiguous documentation of the initial relapse, pediatric onset, diagnosis of primary progressive disease, irregular assessments or visits causing doubt on the onset of progression time, and clinical follow-up duration less than 12months. Eventually, 476 MS patients were included. Data regarding the demographics, initial symptoms, the degree of recovery from the initial relapse, neuroimaging, cerebrospinal fluid analysis, long-term disability, and progression were collected from the medical registry. The mean duration of follow-up was 7.49±5.30years. The percentage of patients entering the progressive disease course was 23.3 in the whole group. A total of 157 patients (33.0%) had SC involvement during the first clinical relapse. These patients were significantly older at disease onset (31.69±10.18 vs. 29.55±9.49; p=0.028), had higher rates of progression (32.5 vs. 18.8%; p=0.001), and had higher disability scores in long-term follow-up (3.41±2.19 vs. 2.62±1.81; p<0.001). Mean age at the transition of progressive phase was 41.4±11.2years. The degree of recovery from the initial relapse significantly affected the long-term disability. The poor recovery from the initial relapse was associated with older onset age and higher EDSS scores. Being older than 40years during MS onset and poor recovery from the initial relapse exerted an increased risk for progression. The initial SC involvement was related to a more severe relapse with less chance of complete recovery and higher risk for progression. Confirmation of risk factors in different MS cohorts would increase our understanding of the complex disease mechanisms.

Recrudescence of Deficits After Stroke

Reemergence of previous stroke-related deficits (or poststroke recrudescence [PSR]) is an underrecognized and inadequately characterized phenomenon. To investigate the clinical features, triggers, and risk factors for PSR. This retrospective study incorporated a crossover cohort study to identify triggers and a case-control study to identify risk factors. The study used the Massachusetts General Hospital Research Patient Data Repository to identify patients for the period January 1, 2000, to November 30, 2015, who had a primary or secondary diagnosis of cerebrovascular disease, who underwent magnetic resonance imaging of the brain at least once, and whose inpatient or outpatient clinician note or discharge summary stated the term recrudescence. In all, 153 patients met the preliminary diagnostic criteria for PSR: transient worsening of residual poststroke focal neurologic deficits or transient recurrence of prior stroke-related focal deficits, admission magnetic resonance imaging showing a chronic stroke but no acute infarct or hemorrhage, no evidence of transient ischemic attack or seizure, no acute lesion on diffusion-weighted imaging, and no clinical or electroencephalographic evidence of seizure around the time of the event. Clinical and imaging features of PSR; triggers (identified by comparing PSR admissions with adjacent admissions without PSR); and risk factors (identified by comparing PSR cases with control cases from the Massachusetts General Hospital Stroke Registry). Of the 153 patients, 145 had prior infarct, 8 had hypertensive brain hemorrhage, and 164 admissions for PSR were identified. The patients' mean (SD) age was 67 (16) years, and 92 (60%) were women. Recrudescence occurred a mean (SD) of 3.9 (0.6) years after the stroke, lasted 18.4 (20.4) hours, and was resolved on day 1 for 91 of the 131 episodes with documented resolution time (69%). Deficits were typically abrupt and mild and affected motor-sensory or language function. No patient had isolated gaze paresis, hemianopia, or neglect. During PSR, the National Institutes of Health Stroke Scale (NIHSS) score worsened by a mean (SD) 2.5 (1.9) points, and deficits were limited to a single NIHSS item in 62 episodes (38%). The underlying chronic strokes were variably sized, predominantly affected white matter tracts, and involved the middle cerebral artery territory for 112 patients (73%). Infection, hypotension, hyponatremia, insomnia or stress, and benzodiazepine use were higher during PSR admissions. Compared with the control group (patients who did not experience recrudescence), the PSR group (patients who were hospitalized for recrudescence) had more women, African American individuals, and those who self-identified as being from "other" race. The PSR group also had more diabetes, dyslipidemia, smoking, infarcts from small-vessel disease, and "other definite" causes and worse onset NIHSS scores. Six patients (4%) received intravenous tissue plasminogen activator without complications. The PSR features identified in the study should enable prompt diagnosis and distinguish recrudescence from mimics, such as transient ischemic attacks, migraine, Todd paralysis, and Uhthoff phenomenon. Prospective studies are required to validate the proposed diagnostic criteria and to decipher underlying mechanisms.

Employment after heart transplantation among adults with congenital heart disease.

Adults with congenital heart disease may require heart transplantation for end-stage heart failure. Whereas heart transplantation potentially allows adults with congenital heart disease to resume their usual activities, employment outcomes in this population are unknown. Therefore, we investigated the prevalence and predictors of work participation after heart transplantation for congenital heart disease. Retrospective review of a prospective registry. United Network for Organ Sharing registry of transplant recipients in the United States. Adult recipients of first-time heart transplantation with a primary diagnosis of congenital heart disease, performed between 2004 and 2015. None. Employment status reported by transplant centers at required follow-up intervals up to 5y posttransplant. Among 470 patients included in the analysis (mean follow-up: 5±3y), 127 (27%) worked after transplant, 69 (15%) died before beginning or returning to work, and 274 (58%) survived until censoring, but did not participate in paid work. Multivariable competing-risks regression analysis examined characteristics associated with posttransplant employment, accounting for mortality as a competing outcome. In descriptive and multivariable analysis, pretransplant work participation was associated with a greater likelihood of posttransplant employment, while the use of Medicaid insurance at the time of transplant was associated with a significantly lower likelihood of working after transplant (subhazard ratio compared to private insurance: 0.55; 95% confidence interval: 0.32, 0.95; P=.032). Employment was rare after heart transplantation for congenital heart disease, and was significantly less common than in the broader population of adults with congenital heart disease. Differences in return to work were primarily related to pretransplant employment and the use of public insurance, rather than clinical characteristics.

Oral health of pediatric liver transplant recipients

To evaluate oral health conditions in pediatric liver transplant recipients, with special focus on caries, green staining of the teeth, gingival bleeding, and gingival overgrowth. 40 patients (mean age 11.6years) were examined at a routine follow-up visit, 6months to 16years after liver transplantation at the Swiss Center for Liver Disease in Children. After the medical examination, participants were further examined for the presence of dental caries, periodontal disease, GE, and GTC. The mean decay, missing, and filled teeth (dmft/DMFT) score was 3.8. 45% of the participants presented at least one carious lesion. Two-third of the participants had more than 20% of sites with the presence of plaque and gingival inflammation. Signs of GE were found in 18% and GTC in 30% of the participants. A positive correlation was identified between GTC and peak serum bilirubin (P<.001) and primary diagnosis of cholestatic disease (P=.04). Gingival inflammation was associated with plaque (P<.001), use of immunosuppressive medication (P=.04), and was more pronounced in children with cholestatic disease (P=.007). Children and young adults with liver transplants presented a rather poor oral health status. Liver transplant physicians should counsel patients for regular dental follow-up in order to avoid serious dental infections.

Multicolor Flow Cytometry for the Diagnosis of Primary Immunodeficiency Diseases.

Primary immunodeficiency diseases (PIDDs) are rare inherited diseases that impair the human immune system. We established a multicolor flow cytometric assay to comprehensively evaluate the immune status and immunological characteristics of patients with PIDDs. Fifty-nine normal controls and 75 patients with PIDDs, including X-linked severe combined immunodeficiency (X-SCID), X-linked agammaglobulinemia (XLA), X-linked hyper IgM syndrome (X-HIGM), ataxia telangiectasia (AT), Wiskott-Aldrich syndrome (WAS), hyper IgE syndrome (HIES), and chronic mucocutaneous candidiasis disease (CMCD), were enrolled in this study. Immunophenotyes were evaluated by multicolor flow cytometry using seven different panels that allowed the detection of major leukocyte populations in peripheral blood. Multicolor flow cytometry revealed distinct leukocyte populations and immunological features of patients with X-SCID, XLA, X-HIGM, AT, WAS, HIES, and CMCD. Immunophenotyping by multicolor flow cytometry is useful to evaluate immune status and contributes to the diagnosis and management of patients with PIDDs.

Corticotropinoma as a Component of Carney Complex

Known germline gene abnormalities cause one-fifth of the pituitary adenomas in children and adolescents, but, in contrast with other pituitary tumor types, the genetic causes of corticotropinomas are largely unknown. In this study, we report a case of Cushing disease (CD) due to a loss-of-function mutation in PRKAR1A, providing evidence for association of this gene with a corticotropinoma. A 15-year-old male presenting with hypercortisolemia was diagnosed with CD. Remission was achieved after surgical resection of a corticotropin (ACTH)-producing pituitary microadenoma, but recurrence 3 years later prompted reoperation and radiotherapy. Five years after the original diagnosis, the patient developed ACTH-independent Cushing syndrome, and a diagnosis of primary pigmented nodular adrenocortical disease was confirmed. A PRKAR1A mutation (c.671delG, p.G225Afs*16) was detected in a germline DNA sample from the patient, which displayed loss of heterozygosity in the corticotropinoma. No other germline or somatic mutations of interest were found. As corticotropinomas are not a known component of Carney complex (CNC), we performed loss of heterozygosity and messenger RNA stability studies in the patient’s tissues, and analyzed the effect of Prkar1a silencing on AtT-20/D16v-F2 mouse corticotropinoma cells. No PRKAR1A defects were found among 97 other pediatric CD patients studied. Our clinical case and experimental data support a role for PRKAR1A in the pathogenesis of a corticotroph cell tumor. This is a molecularly confirmed report of a corticotropinoma presenting in association with CNC. We conclude that germline PRKAR1A mutations are a novel, albeit apparently infrequent, cause of CD.

Pregnancy Outcomes in Patients with Glomerular Disease Attending a Single Academic Center in North Carolina

Background: Contemporary data regarding pregnancy outcomes in US patients with primary glomerular diseases are lacking. We aimed to report fetal and maternal outcomes among women with biopsy-proven primary glomerular disease who received obstetric care at a single large academic US center. Methods: All women with a biopsy-confirmed primary glomerular disease diagnosis and without end-stage kidney disease who received obstetric care at the University of North Carolina (UNC) Hospitals (1996-2015) were identified using the Glomerular Disease Collaborative Network registry and the UNC Hospitals Perinatal Database. The primary study outcome was perinatal death (stillbirth at >20 weeks or neonatal death). Secondary outcomes included premature birth (<37 weeks), birth weight, preeclampsia, and kidney function changes (postpartum vs. baseline). Demographics, clinical characteristics, and outcomes were compared across glomerular disease subtypes. Results: Among 48 pregnancies in 43 women (IgA nephropathy n = 17, focal segmental glomerulosclerosis [FSGS] n = 16, membranous nephropathy n = 6, minimal change disease n = 4), 13% of pregnancies resulted in perinatal death and 48% of babies were born prematurely. From a maternal perspective, 33% of pregnancies were complicated by preeclampsia, 39% by a doubling of urinary protein, and 27% by a ≥50% increase in serum creatinine. Outcome differences across glomerular disease subtypes were not statistically significant, although decline in kidney function appeared most frequent in FSGS. Conclusion: Adverse pregnancy outcomes are frequently observed in women with glomerular disease. The independent influence of glomerular disease subtype on outcomes requires further study. More widespread reporting and analysis of pregnancy outcomes in women with glomerular disease are urgently needed.

GATA3 expression in triple‐negative breast cancers

GATA-binding protein 3 (GATA3) is a well-studied transcription factor found to be essential in the development of luminal breast epithelium and has been identified in a variety of tumour types, including breast and urothelial carcinomas, making it a useful immunohistochemistry marker in the diagnosis of both primary and metastatic disease. We investigated GATA3 protein expression in a 106 primary triple-negative breast carcinomas (100 basal-like, six non-basal-like) using Cell Marque mouse monoclonal anti-GATA3 (L50-823). Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was used to quantify mRNA expression in 22 triple-negative breast cancers (TNBCs) (20 primary and two cell lines), four luminal (three primary and one cell line) and five human epidermal growth factor receptor 2 (HER2) (four primary and one cell line) amplified tumours. In 98 TNBCs where IHC was assessable, 47 (48%) had a 1+ or greater staining with 20 (21%) having high GATA3 expression when using a weighted scoring. Our study has demonstrated that GATA3 expression is common in primary triple-negative breast carcinomas. It also suggests that although GATA3 is an oestrogen receptor (ER) regulated gene, it still proves useful in differentiating between primary and metastatic tumours in patients with a history of breast cancer regardless of its molecular subtype.

Ozone and childhood respiratory disease in three US cities: evaluation of effect measure modification by neighborhood socioeconomic status using a Bayesian hierarchical approach

BackgroundGround-level ozone is a potent airway irritant and a determinant of respiratory morbidity. Susceptibility to the health effects of ambient ozone may be influenced by both intrinsic and extrinsic factors, such as neighborhood socioeconomic status (SES). Questions remain regarding the manner and extent that factors such as SES influence ozone-related health effects, particularly across different study areas.MethodsUsing a 2-stage modeling approach we evaluated neighborhood SES as a modifier of ozone-related pediatric respiratory morbidity in Atlanta, Dallas, & St. Louis. We acquired multi-year data on emergency department (ED) visits among 5–18 year olds with a primary diagnosis of respiratory disease in each city. Daily concentrations of 8-h maximum ambient ozone were estimated for all ZIP Code Tabulation Areas (ZCTA) in each city by fusing observed concentration data from available network monitors with simulations from an emissions-based chemical transport model. In the first stage, we used conditional logistic regression to estimate ZCTA-specific odds ratios (OR) between ozone and respiratory ED visits, controlling for temporal trends and meteorology. In the second stage, we combined ZCTA-level estimates in a Bayesian hierarchical model to assess overall associations and effect modification by neighborhood SES considering categorical and continuous SES indicators (e.g., ZCTA-specific levels of poverty). We estimated ORs and 95% posterior intervals (PI) for a 25 ppb increase in ozone.ResultsThe hierarchical model combined effect estimates from 179 ZCTAs in Atlanta, 205 ZCTAs in Dallas, and 151 ZCTAs in St. Louis. The strongest overall association of ozone and pediatric respiratory disease was in Atlanta (OR = 1.08, 95% PI: 1.06, 1.11), followed by Dallas (OR = 1.04, 95% PI: 1.01, 1.07) and St. Louis (OR = 1.03, 95% PI: 0.99, 1.07). Patterns of association across levels of neighborhood SES in each city suggested stronger ORs in low compared to high SES areas, with some evidence of non-linear effect modification.ConclusionsResults suggest that ozone is associated with pediatric respiratory morbidity in multiple US cities; neighborhood SES may modify this association in a non-linear manner. In each city, children living in low SES environments appear to be especially vulnerable given positive ORs and high underlying rates of respiratory morbidity.

Effect of drinking water source on associations between gastrointestinal illness and heavy rainfall in New Jersey.

Gastrointestinal illness (GI) has been associated with heavy rainfall. Storm events and periods of heavy rainfall and runoff can result in increased microbiological contaminants in raw water. Surface water supplies are open to the environment and runoff can directly influence the presence of contaminants. A time-stratified bi-directional case-crossover study design was used to estimate associations of heavy rainfall and hospitalizations for GI. Cases of GI were identified as in-patient hospitalization with a primary diagnosis of infectious disease associated diarrhea [ICD-9 codes: specified gastrointestinal infections 001–009.9 or diarrhea 787.91] among the residents of New Jersey from 2009 to 2013 resulting in a final sample size of 47,527 cases. Two control days were selected on the same days of the week as the case day, within fixed 21-day strata. Conditional logistic regression was used to estimate odds ratios controlling for temperature and humidity. To determine potential effect modification estimates were stratified by season (warm or cold) and drinking water source (groundwater, surface water, or ‘other’ category). Stratified analyses by drinking water source and season identified positive associations of rainfall and GI hospitalizations in surface water systems during the warm season with no lag (OR = 1.12, 95% CI 1.05–1.19) and a 2-day lag (OR = 1.09, 95% CI 1.03–1.16). Positive associations in ‘Other’ water source areas (served by very small community water systems, private wells, or unknown) during the warm season with a 4-day lag were also found. However, there were no statistically significant positive associations in groundwater systems during the warm season. The results suggest that water systems with surface water sources can play an important role in preventing GI hospitalizations during and immediately following heavy rainfall. Regulators should work with water system providers to develop system specific prevention techniques to limit the impact of heavy rainfall on public health.

Wilson's disease: Experience at a tertiary care hospital.

Wilson's disease (WD) is a rare autosomal recessive disorder of copper metabolism. Data regarding WD is not available from Pakistan. A cross-sectional study was conducted at The Aga Khan University Hospital, Karachi, and all patients admitted with primary and secondary diagnosis of Wilson's disease were added. A total of 47 patients were seen; 68% (n = 32) were male. The mean age was 26.6 ± 9.97 years. Most of the patients presented with hepatic, (n = 22, 46.8%), neurological, (n = 17, 36.2%) and psychiatric (n = 8, 17%) symptoms. Mean ceruloplasmin level was 0.17 ± 0.13 g/dl; it was < 0.25 g/dl in 39 (86.6%) patients. Serum copper (Cu) was reduced in 32 (68.1%) patients and 24-hr-urinary Cu was raised in 22 (47.6%) patients. Slit lamp examination for Kayser-Fleischer (KF) rings was done on 15 (31.9%) patients and 9 (60%) of them had KF rings. Mean serum aspartate transaminase (AST) / alanine transaminases (ALT) ratio was 1.92 and median alkaline phosphatase / total bilirubin ratio was 79.30 (IQR 35.05; 166.50).

Targeting Prostate Cancer Stem Cells with Alpha-Particle Therapy.

Modern molecular and radiopharmaceutical development has brought the promise of tumor-selective delivery of antibody–drug conjugates to tumor cells for the diagnosis and treatment of primary and disseminated tumor disease. The classical mode of discourse regarding targeted therapy has been that the antigen targeted must be highly and homogenously expressed in the tumor cell population, and at the same time exhibit low expression in healthy tissue. However, there is increasing evidence that the reason cancer patients are not cured by current protocols is that there exist subpopulations of cancer cells that are resistant to conventional therapy including radioresistance and that these cells express other target antigens than the bulk of the tumor cells. These types of cells are often referred to as cancer stem cells (CSCs). The CSCs are tumorigenic and have the ability to give rise to all types of cells found in a cancerous disease through the processes of self-renewal and differentiation. If the CSCs are not eradicated, the cancer is likely to recur after therapy. Due to some of the characteristics of alpha particles, such as short path length and high density of energy depositions per distance traveled in tissue, they are especially well suited for use in targeted therapies against microscopic cancerous disease. The characteristics of alpha particles further make it possible to minimize the irradiation of non-targeted surrounding healthy tissue, but most importantly, make it possible to deliver high-absorbed doses locally and therefore eradicating small tumor cell clusters on the submillimeter level, or even single tumor cells. When alpha particles pass through a cell, they cause severe damage to the cell membrane, cytoplasm, and nucleus, including double-strand breaks of DNA that are very difficult to repair for the cell. This means that very few hits to a cell by alpha particles are needed in order to cause cell death, enabling killing of cells, such as CSCs, exhibiting cellular resistance mechanisms to conventional therapy. This paper presents and evaluates the possibility of using alpha-particle emitting radionuclides in the treatment of prostate cancer (PCa) and discusses the parameters that have to be considered as well as pros and cons of targeted alpha-particle therapy in the treatment of PCa. By targeting and eradicating the CSCs responsible of tumor recurrence in patients who no longer respond to conventional therapies, including androgen deprivation and castration, it may be possible to cure the disease, or prolong survival significantly.

Comparing airways clearance techniques in chronic obstructive pulmonary disease and bronchiectasis: positive expiratory pressure or temporary positive expiratory pressure? A retrospective study

BackgroundAirway clearance techniques include positive expiratory pressure, commonly used in our clinical practice, and a recently introduced temporary positive expiratory pressure device called UNIKO®. It is unclear which one provides the best benefit to patients. ObjectivesThe aim of this observational 4-year study was to retrospectively compare the efficacy of and specific indications for temporary positive expiratory pressure compared to positive expiratory pressure in a standard rehabilitation program. MethodWe retrospectively collected data from 162 subjects (107 males, mean age 70±9 years, 97 with primary diagnosis of chronic obstructive pulmonary disease, 65 with bronchiectasis), 51 treated with temporary positive expiratory pressure and 111 with positive expiratory pressure. ResultsSubjects showed significant improvement in ratio of partial pressure arterial oxygen and fraction of inspired oxygen (p<0.001), forced vital capacity, forced expiratory volume in one second, peak expiratory flow, arterial oxygen saturation, and partial pressure arterial oxygen with no significant difference between positive expiratory pressure and temporary positive expiratory pressure groups apart from forced expiratory flow, which increased only in the positive expiratory pressure group. Evaluating specific subgroups, temporary positive expiratory pressure was more effective than positive expiratory pressure in improving gas transfer in subjects with emphysema and in those on oxygen therapy, as the effective supplement oxygen flow decreased significantly (p=0.034 and 0.046 respectively for temporary positive expiratory pressure vs. positive expiratory pressure). In subjects on mechanical ventilation, positive expiratory pressure was superior to temporary positive expiratory pressure in increasing forced expiratory flow (p=0.018). ConclusionThe physiological parameters of both groups improved significantly and similarly. Subgroup analysis suggests that temporary positive expiratory pressure could provide some advantage to subjects with emphysema and those on oxygen therapy, while positive expiratory pressure would benefit patients on mechanical ventilation. Randomized clinical trials are necessary to confirm our preliminary results indicating that different subgroups/phenotypes can benefit more from one type of treatment.

Newly Diagnosed Carney Complex in 3 Young Adults with Primary Adrenal Cushing Syndrome – A Case Series and Review of the Literature

ABSTRACT Objective: Carney complex (CNC) is a very rare cause of adrenocorticotropic hormone (ACTH)-independent Cushing syndrome (CS). We describe 3 cases of CNC diagnosed through the evaluation of CS, with no other major manifestations of CNC. Methods: We present the relevant history, laboratory, and pathologic data of the current cases, and review relevant documentation from the literature. Results: Among all 3 patients, CS symptomatology was the main clinical characteristic, which was also supported by a diminished diurnal rhythmicity of plasma cortisol and ACTH levels. The paradoxical increase in cortisol after both low and high dose dexamethasone suppression tests (Liddle's test) proved to be the most useful biochemical clue for the diagnosis of primary pigmented nodular adrenocortical disease (PPNAD) in these patients. The absence of bilateral macronodular or unilateral adrenal lesion led to the possible diagnosis of PPNAD/CNC. None of the 3 patients demonstrated any of the other described major man...

Overall and Free-Event Survival of Patients Taken to Hematopoietic Stem Cell Transplantation in a Colombian Reference Center

INTRODUCTION:Hematopoietic cell transplantation is a standard care procedure, frequently curative where no other treatment is an option.OBJETIVE:Describe the clinical and sociodemographic characteristics of patients taken to HSCT at Fundación Oftalmológica de Santander - Clínica Carlos Ardila Lülle (FOSCAL) in Santander, Colombia, and determine the overall survival (OS) and free-event survival (FES) of patients at 100 days, 1 year and 4 years, according to the base illness stateMATERIALS AND METHODS:Observational descriptive open prospective cohort study of consecutive patients who underwent HSTC at FOSCAL (Santander, Colombia). Information on sociodemographic and clinical characteristics was collected from medical records between November of 2009 and July of 2015. Normality analysis was made through Shapiro-Wilk test, and survival function was estimated with Kaplan and Meier. This protocol was reviewed and approved by the committee of ethic, investigation or its equivalents of Universidad Autónoma de Bucaramanga and FOSCAL.RESULTS:56 patients constituted the total sample, 50% were women with an average age of 46 (±15 years). Most frequent indications for HCT were multiple myeloma (41%), lymphoma (37.5%) and acute leukemia (12.5%). According to the type of transplant made and its indication, autologous transplant occupied the first place (85.7%) along with multiple myeloma (48%). In allogeneic transplant the most frequent cause of HCT was acute leukemia (75%). The sources of hematopoietic progenitors in 98% of the transplants were taken from peripheral blood. Nineteen patients died (33.9%). The principal cause of death was related to the primary illness, while three deaths were directly related to the HCT. OS at day 100 was 96.4 (CI95%, 86.2 - 99.1), at 1 year, 85.4 (CI95%, 73.03 - 92.4) and at 4 years, 68.6 (CI95%, 52.4 - 80.3). FES at day 100 was 94.5 (CI95%, 83.9 - 98.2), at 1 year, 86.8 (CI95%, 74.4 - 93.2) and at 4 years, 61.0 (CI95%, 45.1 - 73.6). OS and FES at 4 years of autologous HCT was 71.5 (CI95%, 72.6 - 83.1) and 62.6 (CI95%, 45.6 - 75.6) respectively, and OS and FES at 4 years of allogeneic HCT was 50.0 (CI95%, 8.05 - 82.6) and 48.6 (CI95%, 22.6 - 81.6) respectively. There were no significant differences in OS and FES according to the state of the pretransplant disease: OS of 69.5 (CI95%, 38.8 - 87.0) and FES of 57.5 (CI95%, 30.1 - 77.5) for multiple myeloma, 65.0 (CI95%, 40.3 - 81.5) and 57.8 (CI95%, 33.2 - 76.2) for lymphoma and 47.6 (CI95%, 7.5 - 80.8) and 45.7 (CI95%, 6.9 - 79.5) for acute leukemia.CONCLUSIONS:The indications of HCT in our center are similar to published international literature. The principal cause of death was primary illness and a low incidence of transplant related death was registered (1.57%). OS and FES are similar to international registries according to primary disease diagnosis. DisclosuresNo relevant conflicts of interest to declare.