Rishi Raj

Correlation of EGFR Mutation Status With Predominant Histologic Subtype of Adenocarcinoma According to the New Lung Adenocarcinoma Classification of the International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society

CONTEXT Epidermal growth factor receptor (EGFR) mutations have been identified as predictors of response to EGFR tyrosine kinase inhibitors in non-small cell lung cancer. OBJECTIVE To investigate the relationship of EGFR mutation status to the histologic subtype of adenocarcinoma according to the new International Association for the Study of Lung Cancer (IASLC)/American Thoracic Society (ATS)/European Respiratory Society (ERS) classification. DESIGN We screened EGFR mutation in 200 consecutive lung adenocarcinoma resection specimens diagnosed between 2008 and 2011. RESULTS Among 200 lung adenocarcinomas, EGFR mutations were identified in 41 tumors (20.5%). The mean age in the EGFR-mutant group was 64.8 years and this group consisted of 78% females and 22% males. Most patients with EGFR-positive lung cancers were never-smokers (51%) as compared to 8% with EGFR-negative cancers (P < .001). The most common mutations identified in our population were deletions in exon 19 (22 patients) and L858R in exon 21 (12 patients). Five patients had double mutations. The predominant pattern of adenocarcinoma was lepidic (44%) in EGFR-mutant lung cancers as compared to 69% with acinar pattern in EGFR wild-type lung cancers (P < .001). Of 22 minimally invasive adenocarcinomas, 8 (36%) had EGFR mutations, accounting for 20% of adenocarcinomas with EGFR mutations (P < .05). CONCLUSIONS Based on the new IASLC/ATS/ERS classification, the predominant subtype of adenocarcinoma was lepidic (44%) in EGFR-mutant lung cancers (P < .001). However, histologic subtype should not be used to exclude patients from tyrosine kinase inhibitor therapy, since EGFR mutations are found in lung adenocarcinomas of other subtypes.

The Frequency of Frailty in Ambulatory Patients With Chronic Lung Diseases

Objectives: To determine the prevalence of frailty in patients with chronic lung diseases. Methods: We studied 120 patients with chronic lung disease using Fried’s criteria (gait speed, weight loss, exhaustion, grip strength, and physical activity). Results: The study population (56% women) had a mean age of 64 ± 13 years, mean body mass index of 31± 9 kg/m2, and a mean FEV1 (forced expiratory volume in 1 second) of 60% ± 25% of predicted. The average gait speed was 52.1 ± 14.3 m/min; 18% were frail, 64% prefrail, and 18% robust. Gait speed correlated with frailty status and decreased as frailty worsened (57 m/min in robust subjects and 41 m/min in frail subjects). Slow gait speeds (<60 m/min) had a 95% sensitivity and 34% specificity to predict frailty. Conclusions: Patients with chronic lung disease frequently meet Fried’s criteria for frailty. Gait speed can be used to screen these patients to determine if a more detailed evaluation is needed.

Mortality Related to Surgical Lung Biopsy in Patients with Interstitial Lung Disease. The Devil Is in the Denominator

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Surgical Lung Biopsy for Interstitial Lung Diseases

&NA; This review addresses common questions regarding the role of surgical lung biopsy (SLB) in the diagnosis and treatment of interstitial lung disease (ILD). We specifically address when a SLB can be diagnostic as well as when it may be avoided; for example, when the combination of the clinical context and the imaging pattern seen on high‐resolution CT (HRCT) chest scans can provide a confident diagnosis. Existing studies on the diagnostic utility as well as the complications associated with SLB are reviewed; also reviewed are the performance characteristics and reliability of HRCT scans of the chest in predicting the underlying histopathologic findings of the lung. The review is formatted in the form of answers to questions that clinicians regularly ask when considering an SLB in a patient with ILD.

Peripheral lung adenocarcinomas with KRAS mutations are more likely to invade visceral pleura.

CONTEXT Kirsten-RAS (KRAS) mutations play an important role in the carcinogenesis of a subset of lung adenocarcinomas and are associated with poorer prognosis. OBJECTIVE To investigate the relationship of KRAS mutation status to the histologic subtype of adenocarcinoma according to the recent classification, patient demographics, tumor size, predominant histologic subtype, nodal status, and visceral pleural invasion, in an attempt to uncover the reason for the worse prognosis associated with KRAS mutation. DESIGN A total of 187 consecutive resected lung adenocarcinomas from our institution from 2008 to 2011 that were diagnosed according to the new International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society classification and screened for KRAS mutations were included in the study. RESULTS A total of 32% of the adenocarcinomas harbored the KRAS mutation. The median age in the KRAS mutation group was 69 years (range, 43-86 years), and male to female ratio was 1:2.3. The proportion of heavy smokers was significantly higher in tumors with KRAS mutation compared with wild type (83% versus 62%; P = .01). A total of 27% of tumors with KRAS mutation had pleural invasion versus 11% of tumors without KRAS mutation (P = .009). A total of 59 tumor samples were positive for KRAS mutation (25 for G12C, 14 for G12A, 8 for G12V, 7 for G12D, 3 for G12S, and 1 for G12T), and only 3 tumors harbored codon 13 mutations (G13C). Two tumors had double mutations. CONCLUSIONS KRAS mutations are more common in heavy smokers, and lung adenocarcinomas with KRAS mutation are more likely to invade the visceral pleura. Increased frequency of visceral pleural invasion may explain in part the worse prognosis associated with KRAS mutations.

The Repeatability of Gait Speed and Physiological Cost Index Measurements in Working Adults

Objectives: To determine the performance characteristics of gait speed measurements and the physiological cost index (PCI; heart rate change/gait speed) in working adults. Methods: Gait speeds, heart rate changes, andnon–steady state PCIs were calculated in 61 volunteers who worked in our health sciences center. These subjects completed 9 separate 100-foot walk tests in 3 separate sessions. Results: The mean heart rate change after a 100-foot walk was 16.6 ± 8.1 beats per minute. The mean gait speed was 76.1 ± 9.6 meters per minute, and the mean PCI was 0.22 ± 0.11 beats per meter. There were highly significant correlations among all measurements on the 9 separate tests (correlation coefficients 0.41-0.95); gait speed measurements had the highest correlations (0.91-0.95). In a multivariable model hypertension and arthritis were associated with reduced gait speeds. Conclusion: Gait speed, heart rate changes, and non–steady state PCIs have good repeatability when measured over short walks. This information provides a rapid physiological assessment and a method for measuring changes in functional status in healthy subjects and most patients.

Accelerometer-based devices can be used to monitor sedation/agitation in the intensive care unit

PURPOSE Monitoring sedation/agitation levels in patients in the intensive care unit (ICU) are important to direct treatment and to improve outcomes. This study was designed to determine the potential use of accelerometer-based sensors/devices to objectively measure sedation/agitation in patients admitted to the ICU. MATERIALS AND METHODS Accelerometer-based devices (actigraphs) were placed on nondominant wrists of 86 patients in the ICU after informed consent. The sedation/agitation levels were classified as deep sedation, light sedation, alert and calm, mild agitation and severe agitation, and measured at regular intervals. The sedation/agitation levels were correlated with the accelerometer data (downloaded raw actigraphy data). RESULTS The sedation/agitation levels correlated strongly with the accelerometer readings represented by mean actigraphy counts (r = 0.968; P = .007) and the proportion of time spent moving as determined by actigraphy (r = 0.979; P = .004). CONCLUSIONS Accelerometer data correlate strongly with the sedation/agitation levels of patients in the ICUs, and appropriately designed accelerometer-based sensors/devices have the potential to be used for automating objective and continuous monitoring of sedation/agitation levels in patients in the ICU.

Igg4-related Lung Disease

Pulmonary involvement is common in IgG4-related disease, an idiopathic entity characterized by tumorous growths involving multiple organ systems, elevated IgG4 levels, and characteristic histopathology manifested by lymphoplasmacytic infiltrate, fibrosis, obliterative phlebitis, and tissue infiltration with IgG4-positive plasma cells. Mediastinal adenopathy is present in nearly all patients, and pulmonary involvement takes the form of pulmonary nodules or masses (most common), consolidation, interstitial infiltrates, and thickened bronchovascular bundles. Diagnosis rests on elevated IgG4 levels, characteristic histopathology, and the exclusion of other conditions that may be associated with similar clinical and histopathologic findings. Treatment is usually but not always needed; most patients respond to steroids at least initially, but relapses are common. Experience with other therapies is limited. This review summarizes the current literature on pulmonary manifestations of IgG4-related disease.

Hyperacute Methotrexate Pneumonitis in a Patient With Crohn's Disease

64-year-old woman with Crohn’s colitis preAsented with 2 weeks of intermittent fevers, drenching night sweats, dry cough, and progressively dyspnea on exertion. She had developed a severe flare of Crohn’s colitis 4 months before that was refractory to inpatient infliximab therapy and necessitated surgical management with a segmental colectomy and diverting ileostomy. Postoperatively, she developed peristomal pyoderma gangrenosum for which she was to receive adalimumab and weekly oral methotrexate (MTX) therapy. Two days after her first dose of 10-mg oral MTX, she had onset of the presenting symptoms that worsened after her second dose of MTX. Symptom onset occurred before initiation of adalimumab. On presentation, computed tomography of the chest showed diffuse ground glass opacities with centrilobular prominence (Figure A). Noninvasive workup for infectious etiologies was negative. Bronchoscopy and bronchoalveolar lavage (BAL) antigen testing and cultures did not reveal evidence of bacterial, viral, mycobacterial, or fungal infection. Elevated lymphocyte (54%) and eosinophil (11%) counts were noted on BAL cell differential. A diagnosis of MTX-induced pneumonitis (MIP) was made. She was started on a tapering prednisone course. After 2 weeks of corticosteroid therapy, the patient’s symptoms resolved and a follow-up computed tomography showed resolution of radiographic abnormalities (Figure B). MTX is an immunosuppressive agent with efficacy as monotherapy in induction and remission of Crohn’s disease. Concurrent use of MTX with anti–tumor necrosis factor-a agents can prevent antidrug antibody formation and foster higher drug levels. MTX can be associated with serious lung toxicity with MIP being the most common manifestation. Described mostly among patients with rheumatoid arthritis, MIP generally occurs after months of low-dose oral MTX therapy (<20 mg/ week) and can progress to respiratory failure. MIP is rare in other chronic inflammatory diseases and a recent systematic review of randomized controlled trials of 12 weeks or greater duration of MTX therapy in adults with psoriasis and inflammatory bowel diseases did not find an increased risk of pulmonary adverse events among MTX-treated patients. There are only 2 previous case reports of MTX-related pulmonary disease reported in Crohn’s disease. In both of these, symptom onset was at 2–18 months after initiation of MTX. Described here is the first case of hyperacute MIP in Crohn’s disease with

Bladder pressure measurements in patients admitted to a medical intensive care unit

Background:Intra-abdominal hypertension is identified as an independent risk factor for death. However, this pathophysiological state is not always considered in patients in medical intensive care units and is frequently underdiagnosed. Methods:Serial bladder pressure measurements were recorded in patients admitted to the medical intensive care units to determine the frequency of intra-abdominal hypertension. Results:This study included 53 patients with a mean age of 59.0 ± 17.7 years. The average admission intra-abdominal pressure was 10.0 ± 5.4 mm Hg with a range of 0 to 28 mm Hg. Eleven patients (21%) had an initial pressure reading above normal (>12 mm Hg). Peak airway pressures were higher, and PaO2/FiO2 ratios were lower in patients with an initial pressure >12 mm Hg. Conclusions:Bladder pressure measurements provide an easy method to estimate intra-abdominal pressures and provide an additional tool for the physiologic assessment of critically ill patients.