Understanding the patient journey to diagnosis of lung cancer

OBJECTIVE: This research describes the clinical pathway and characteristics of two cohorts of patients. The first cohort consists of patients with a confirmed diagnosis of lung cancer while the second consists of patients with a solitary pulmonary nodule (SPN) and no evidence of lung cancer. Linked data from an electronic medical record and the Louisiana Tumor Registry were used in this investigation. MATERIALS AND METHODS: REACHnet is one of 9 clinical research networks (CRNs) in PCORnet®, the National Patient-Centered Clinical Research Network and includes electronic health records for over 8 million patients from multiple partner health systems. Data from Ochsner Health System and Tulane Medical Center were linked to Louisiana Tumor Registry (LTR), a statewide population-based cancer registry, for analysis of patient\u27s clinical pathways between July 2013 and 2017. Patient characteristics and health services utilization rates by cancer stage were reported as frequency distributions. The Kaplan-Meier product limit method was used to estimate the time from index date to diagnosis by stage in lung cancer cohort. RESULTS: A total of 30,559 potentially eligible patients were identified and 2929 (9.58%) had primary lung cancer. Of these, 1496 (51.1%) were documented in LTR and their clinical pathway to diagnosis was further studied. Time to diagnosis varied significantly by cancer stage. A total of 24,140 patients with an SPN were identified in REACHnet and 15,978 (66.6%) had documented follow up care for 1 year. 1612 (10%) had no evidence of any work up for their SPN. The remaining 14,366 had some evidence of follow up, primarily office visits and additional chest imaging. CONCLUSION: In both cohorts multiple biopsies were evident in the clinical pathway. Despite clinical workup, 70% of patients in the lung cancer cohort had stage III or IV disease. In the SPN cohort, only 66% were identified as receiving a diagnostic work-up

Anatomic segmentectomy for stage I non–small-cell lung cancer: Comparison of video-assisted thoracic surgery versus open approach

ObjectivesAnatomic segmentectomy is increasingly being considered as a means of achieving an R0 resection for peripheral, small, stage I non–small-cell lung cancer. In the current study, we compare the results of video-assisted thoracic surgery (n = 104) versus open (n = 121) segmentectomy in the treatment of stage I non–small-cell lung cancer.MethodsA total of 225 consecutive anatomic segmentectomies were performed for stage IA (n = 138) or IB (n = 87) non–small-cell lung cancer from 2002 to 2007. Primary outcome variables included hospital course, complications, mortality, recurrence, and survival. Statistical comparisons were performed utilizing the t test and Fisher exact test. The probability of overall and recurrence-free survival was estimated with the Kaplan-Meier method, with significance being estimated by the log-rank test.ResultsMean age (69.9 years) and gender distribution were similar between the video-assisted thoracic surgery and open groups. Average tumor size was 2.3 cm (2.1 cm video-assisted thoracic surgery; 2.4 cm open). Mean follow-up was 16.2 (video-assisted thoracic surgery) and 28.2 (open) months. There were 2 perioperative deaths (2/225; 0.9%), both in the open group. Video-assisted thoracic surgery segmentectomy was associated with decreased length of stay (5 vs 7 days, P < .001) and pulmonary complications (15.4% vs 29.8%, P = .012) compared with open segmentectomy. Overall mortality, complications, local and systemic recurrence, and survival were similar between video-assisted thoracic surgery and open segmentectomy groups.ConclusionsVideo-assisted thoracic surgery segmentectomy can be performed with acceptable morbidity, mortality, recurrence, and survival. The video-assisted thoracic surgery approach affords a shorter length of stay and fewer postoperative pulmonary complications compared with open techniques. The potential benefits and limitations of segmentectomy will need to be further evaluated by prospective, randomized trials

Succinic semialdehyde dehydrogenase deficiency: Lessons from mice and men

Succinic semialdehyde dehydrogenase (SSADH) deficiency, a disorder of GABA degradation with subsequent elevations in brain GABA and GHB, is a neurometabolic disorder with intellectual disability, epilepsy, hypotonia, ataxia, sleep disorders, and psychiatric disturbances. Neuroimaging reveals increased T2-weighted MRI signal usually affecting the globus pallidus, cerebellar dentate nucleus, and subthalamic nucleus, and often cerebral and cerebellar atrophy. EEG abnormalities are usually generalized spike-wave, consistent with a predilection for generalized epilepsy. The murine phenotype is characterized by failure-to-thrive, progressive ataxia, and a transition from generalized absence to tonic-clonic to ultimately fatal convulsive status epilepticus. Binding and electrophysiological studies demonstrate use-dependent downregulation of GABA(A) and (B) receptors in the mutant mouse. Translational human studies similarly reveal downregulation of GABAergic activity in patients, utilizing flumazenil-PET and transcranial magnetic stimulation for GABA(A) and (B) activity, respectively. Sleep studies reveal decreased stage REM with prolonged REM latencies and diminished percentage of stage REM. An ad libitum ketogenic diet was reported as effective in the mouse model, with unclear applicability to the human condition. Acute application of SGS–742, a GABA(B) antagonist, leads to improvement in epileptiform activity on electrocorticography. Promising mouse data using compounds available for clinical use, including taurine and SGS–742, form the framework for human trials

Gene Expression Profiling during Early Acute Febrile Stage of Dengue Infection Can Predict the Disease Outcome

Background: We report the detailed development of biomarkers to predict the clinical outcome under dengue infection. Transcriptional signatures from purified peripheral blood mononuclear cells were derived from whole-genome gene-expression microarray data, validated by quantitative PCR and tested in independent samples. Methodology/Principal Findings: The study was performed on patients of a well-characterized dengue cohort from Recife, Brazil. The samples analyzed were collected prospectively from acute febrile dengue patients who evolved with different degrees of disease severity: classic dengue fever or dengue hemorrhagic fever (DHF) samples were compared with similar samples from other non-dengue febrile illnesses. The DHF samples were collected 2-3 days before the presentation of the plasma leakage symptoms. Differentially-expressed genes were selected by univariate statistical tests as well as multivariate classification techniques. The results showed that at early stages of dengue infection, the genes involved in effector mechanisms of innate immune response presented a weaker activation on patients who later developed hemorrhagic fever, whereas the genes involved in apoptosis were expressed in higher levels. Conclusions/Significance: Some of the gene expression signatures displayed estimated accuracy rates of more than 95%, indicating that expression profiling with these signatures may provide a useful means of DHF prognosis at early stages of infection. © 2009 Nascimento et al

International relations: perspectives and themes

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