Mutational signatures in esophageal squamous cell carcinoma from eight countries with varying incidence.

Esophageal squamous cell carcinoma (ESCC) shows remarkable variation in incidence that is not fully explained by known lifestyle and environmental risk factors. It has been speculated that an unknown exogenous exposure(s) could be responsible. Here we combine the fields of mutational signature analysis with cancer epidemiology to study 552 ESCC genomes from eight countries with varying incidence rates. Mutational profiles were similar across all countries studied. Associations between specific mutational signatures and ESCC risk factors were identified for tobacco, alcohol, opium and germline variants, with modest impacts on mutation burden. We find no evidence of a mutational signature indicative of an exogenous exposure capable of explaining differences in ESCC incidence. Apolipoprotein B mRNA-editing enzyme, catalytic polypeptide-like (APOBEC)-associated mutational signatures single-base substitution (SBS)2 and SBS13 were present in 88% and 91% of cases, respectively, and accounted for 25% of the mutation burden on average, indicating that APOBEC activation is a crucial step in ESCC tumor development.

Survival of COVID-19 Patients With Respiratory Failure is Related to Temporal Changes in Gas Exchange and Mechanical Ventilation.

Background: Respiratory failure due to coronavirus disease of 2019 (COVID-19) often presents with worsening gas exchange over a period of days. Once patients require mechanical ventilation (MV), the temporal change in gas exchange and its relation to clinical outcome is poorly described. We investigated whether gas exchange over the first 5 days of MV is associated with mortality and ventilator-free days at 28 days in COVID-19. Methods: In a cohort of 294 COVID-19 patients, we used data during the first 5 days of MV to calculate 4 daily respiratory scores: PaO2/FiO2 (P/F), oxygenation index (OI), ventilatory ratio (VR), and Murray lung injury score. The association between these scores at early (days 1-3) and late (days 4-5) time points with mortality was evaluated using logistic regression, adjusted for demographics. Correlation with ventilator-free days was assessed (Spearman rank-order coefficients). Results: Overall mortality was 47.6%. Nonsurvivors were older (P < .0001), more male (P = .029), with more preexisting cardiopulmonary disease compared to survivors. Mean PaO2 and PaCO2 were similar during this timeframe. However, by days 4 to 5 values for all airway pressures and FiO2 had diverged, trending lower in survivors and higher in nonsurvivors. The most substantial between-group difference was the temporal change in OI, improving 15% in survivors and worsening 11% in nonsurvivors (P < .05). The adjusted mortality OR was significant for age (1.819, P = .001), OI at days 4 to 5 (2.26, P = .002), and OI percent change (1.90, P = .02). The number of ventilator-free days correlated significantly with late VR (-0.166, P < .05), early and late OI (-0.216, P < .01; -0.278, P < .01, respectively) and early and late P/F (0.158, P < .05; 0.283, P < .01, respectively). Conclusion: Nonsurvivors of COVID-19 needed increasing intensity of MV to sustain gas exchange over the first 5 days, unlike survivors. Temporal change OI, reflecting both PaO2 and the intensity of MV, is a potential marker of outcome in respiratory failure due to COVID-19.

Deep learning prediction of likelihood of ICU admission and mortality in COVID-19 patients using clinical variables.

BACKGROUND: This study aimed to develop a deep-learning model and a risk-score system using clinical variables to predict intensive care unit (ICU) admission and in-hospital mortality in COVID-19 patients. METHODS: This retrospective study consisted of 5,766 persons-under-investigation for COVID-19 between 7 February 2020 and 4 May 2020. Demographics, chronic comorbidities, vital signs, symptoms and laboratory tests at admission were collected. A deep neural network model and a risk-score system were constructed to predict ICU admission and in-hospital mortality. Prediction performance used the receiver operating characteristic area under the curve (AUC). RESULTS: The top ICU predictors were procalcitonin, lactate dehydrogenase, C-reactive protein, ferritin and oxygen saturation. The top mortality predictors were age, lactate dehydrogenase, procalcitonin, cardiac troponin, C-reactive protein and oxygen saturation. Age and troponin were unique top predictors for mortality but not ICU admission. The deep-learning model predicted ICU admission and mortality with an AUC of 0.780 (95% CI [0.760-0.785]) and 0.844 (95% CI [0.839-0.848]), respectively. The corresponding risk scores yielded an AUC of 0.728 (95% CI [0.726-0.729]) and 0.848 (95% CI [0.847-0.849]), respectively. CONCLUSIONS: Deep learning and the resultant risk score have the potential to provide frontline physicians with quantitative tools to stratify patients more effectively in time-sensitive and resource-constrained circumstances.

Undetectable SARS-CoV-2 in a nasopharyngeal swab but persistent viral RNA from deep lung swabs: findings from an autopsy.

During the global pandemic of COVID-19 accurate diagnosis of the infection by demonstrating SARS-CoV-2 viral RNA by PCR in specimens is crucial for therapeutic and preventative interventions. There have been instances where nasal and throat swabs have been negative despite the patient having typical clinical and radiological findings compatible with the disease. We report a case of a man in his late 50s, brought to the hospital following a cardiac arrest and prolonged unsuccessful resuscitation. The history was typical for COVID-19 with fever for 10 days and worsening shortness of breath. His throat and nasal swabs (after death) were negative for SARS-CoV-2. A limited diagnostic autopsy was performed after 27 days, and lung swabs confirmed presence of SARS-CoV-2. This case highlights the importance of lung swabs when initial upper respiratory tract swabs are negative and proves that the virus can be detected from dead human tissue almost a month later.

Continued In-Hospital Angiotensin-Converting Enzyme Inhibitor and Angiotensin II Receptor Blocker Use in Hypertensive COVID-19 Patients Is Associated With Positive Clinical Outcome.

BACKGROUND: This study investigated continued and discontinued use of angiotensin-converting enzyme inhibitors (ACEi) or angiotensin II receptor blockers (ARB) during hospitalization of 614 hypertensive laboratory-confirmed COVID-19 patients. METHODS: Demographics, comorbidities, vital signs, laboratory data, and ACEi/ARB usage were analyzed. To account for confounders, patients were substratified by whether they developed hypotension and acute kidney injury (AKI) during the index hospitalization. RESULTS: Mortality (22% vs 17%, P > .05) and intensive care unit (ICU) admission (26% vs 12%, P > .05) rates were not significantly different between non-ACEi/ARB and ACEi/ARB groups. However, patients who continued ACEi/ARBs in the hospital had a markedly lower ICU admission rate (12% vs 26%; P = .001; odds ratio [OR] = 0.347; 95% confidence interval [CI], .187-.643) and mortality rate (6% vs 28%; P = .001; OR = 0.215; 95% CI, .101-.455) compared to patients who discontinued ACEi/ARB. The odds ratio for mortality remained significantly lower after accounting for development of hypotension or AKI. CONCLUSIONS: These findings suggest that continued ACEi/ARB use in hypertensive COVID-19 patients yields better clinical outcomes.

Prediction model and risk scores of ICU admission and mortality in COVID-19.

This study aimed to develop risk scores based on clinical characteristics at presentation to predict intensive care unit (ICU) admission and mortality in COVID-19 patients. 641 hospitalized patients with laboratory-confirmed COVID-19 were selected from 4997 persons under investigation. We performed a retrospective review of medical records of demographics, comorbidities and laboratory tests at the initial presentation. Primary outcomes were ICU admission and death. Logistic regression was used to identify independent clinical variables predicting the two outcomes. The model was validated by splitting the data into 70% for training and 30% for testing. Performance accuracy was evaluated using area under the curve (AUC) of the receiver operating characteristic analysis (ROC). Five significant variables predicting ICU admission were lactate dehydrogenase, procalcitonin, pulse oxygen saturation, smoking history, and lymphocyte count. Seven significant variables predicting mortality were heart failure, procalcitonin, lactate dehydrogenase, chronic obstructive pulmonary disease, pulse oxygen saturation, heart rate, and age. The mortality group uniquely contained cardiopulmonary variables. The risk score model yielded good accuracy with an AUC of 0.74 ([95% CI, 0.63-0.85], p = 0.001) for predicting ICU admission and 0.83 ([95% CI, 0.73-0.92], p<0.001) for predicting mortality for the testing dataset. This study identified key independent clinical variables that predicted ICU admission and mortality associated with COVID-19. This risk score system may prove useful for frontline physicians in clinical decision-making under time-sensitive and resource-constrained environment.

Outcomes of Introducing a Mobile Interactive Learning Resource in a Large Medical School Course.

Mobile devices are an integral part of modern medical education, as convenient platforms for access to online interactive learning resources; students' use of textbooks has correspondingly declined. We designed an interactive iBook© for pre-clinical students encompassing the content of the pulmonary segment in an organ-based multidisciplinary course. We found, via a survey-based study, that students preferred the iBook to other faculty-supplied materials (PowerPoints and PDFs), mainly due to its interactive images, animations, and study questions. Students' test performance did not change significantly after introducing the iBook. This study suggests that expanded use of interactive learning resources may enhance students' engagement with pre-clinical courses.

Exercise Capacity in Unilateral Diaphragm Paralysis: The Effect of Obesity.

PURPOSE: Healthy patients with unilateral diaphragm paralysis (UDP) are often asymptomatic; those with UDP and comorbidities that increase work of breathing are often dyspneic. We report the effect of obesity on exercise capacity in UDP patients. METHODS: All obese and nonobese patients with UDP undergoing cardiopulmonary exercise testing (CPET) during a 32-month period in the exercise laboratory of an academic hospital were compared to a retrospectively identified cohort of obese and nonobese controls without UDP, matched for key features. CPET used a modified Bruce treadmill protocol with breath-to-breath expired gas analysis. O2 uptake, minute ventilation, exercise time, and work rate were recorded at peak exercise. Static pulmonary functions were measured. Kruskal-Wallis, Wilcoxon rank sum, and Fisher's exact tests were used to compare continuous and categorical variables, respectively. Stratified linear regression was used to quantify the effect of UDP and obesity on CPET variables. RESULTS: Twenty-two UDP patients and 46 controls were studied. The BMI of obese and nonobese patients was 33.0±4.2 and 25.8±2.4 kg/m2, respectively. UDP subjects with obesity, compared to controls with neither condition, showed significantly reduced peak O2 uptake normalized to actual body weight (1.57±0.64 versus 2.01±0.88 L/min), shorter exercise time (5.7±2.0 versus 8.5±2.9 minutes), and lower peak ventilation. This was not observed in UDP alone or obesity alone. Peak work rate trended lower in the combined UDP-obesity group. CONCLUSION: Neither UDP nor obesity alone significantly reduced exercise capacity. Superimposed UDP and obesity interact to create a ventilatory limitation to exercise, with reduced peak-VO2, exercise time, and work rate.

Use of student feedback to drive quality improvement (QI) in a preclinical U.S. medical school course.

Medical educators are continually looking for ways to enhance integrated learning and help students see how the material taught in their various courses is inter-related. . At Stony Brook School of Medicine, we embarked on a school-wide new curriculum called the Learning focused, Experiential, Adaptive, Rigorous and Novel (LEARN) curriculum and developed several integrated courses that were not based in specific departments. As part of this process, the pre-clinical (Phase-1) curriculum was shortened to 17 months to accommodate an expanded set of clinical offerings. The new structure called for teachers from different departments to lead and conduct the integrated blocks of pre-clinical courses. In this paper, we describe our discouraging experience with the first iteration of an integrated course in Cardiology, Pulmonology and Renal organ systems (CPR), and its transformation into a highly successful second iteration. This involved a systematic course quality improvement (QI) process within the context of a larger school wide curricular reform. As a result, student overall satisfaction with the course increased from 22% (28 of 127 responders) to 83% (111 of 134 responders); the mean score on a standardized NBME content exam increased by 6.7%. We report the systematic process we used to collect data from students and faculty that helped facilitate quality improvement in a key course in Phase-1 of our LEARN curriculum.

Impact of advanced endoscopic imaging on Barrett's esophagus in daily clinical practice.

BACKGROUND AND AIMS: Several advanced imaging techniques have been proposed to improve the visualization of dysplastic regions within Barrett's epithelium, with some evidence for the use of narrow-band imaging (NBI) and acetic acid chromoendoscopy (AAC). METHODS: We retrospectively analyzed consecutive cases of Barrett's esophagus, diagnosed using white-light endoscopy and confirmed histologically by the presence of intestinal metaplasia, between April 2007 and April 2010 in a large community hospital. A change in practice was then instituted, whereby a Barrett's team consisting of specialist endoscopists was formed in an attempt to standardize and improve the quality of surveillance. Barrett's epithelium was inspected with both white-light imaging and NBI in all patients. Where the length of Barrett's epithelium was 3 cm or more, AAC was also used. One and a half percent acetic acid was sprayed onto the Barrett's segment and loss of aceto-whitening observed after a 2-minute period. Any abnormal areas noted during advanced imaging underwent target biopsy sampling. We subsequently compared the dysplasia detection rate in Barrett's epithelium identified between April 2011 and April 2014 after these changes. Observed differences between the cohorts were analyzed with the Fisher exact test and the Student t test. RESULTS: From 2007 to 2010 Barrett's esophagus was identified during 560 gastroscopies in 392 individual patients. The mean maximal Barrett's esophagus recorded length was 4.4 cm (range, 1-10), with an average of 4.7 esophageal biopsy specimens taken per endoscopy. In comparison, from 2011 to 2014 Barrett's esophagus was identified during 856 endoscopies in 630 patients. From 2011 to 2014 the Barrett's team performed 85% of all procedures using the aforementioned techniques. The mean maximal Barrett's esophagus length was 3.8 cm (range, 1-16), with an increased average of 5.8 biopsy specimens per endoscopy taken (P < .01). Both cohorts were comparable in age and gender distribution. Our data demonstrated no significant difference in the relative frequencies of occurrence of dysplasia detected between both cohorts of patients. From 2007 to 2010 dysplasia was detected in 11.0% (n = 43) of patients. This consisted of low-grade dysplasia in 7.7% of patients and high-grade dysplasia or cancer 3.3%. From 2011 to 2014 this compared with dysplasia in 11.3% (n = 71) of patients, with low-grade dysplasia in 9.4% and high-grade dysplasia or cancer in 1.9%. CONCLUSIONS: Our data show that the use of NBI and AAC in the imaging of Barrett's esophagus did not result in an increased detection rate of dysplasia in routine clinical practice. These findings concur with the recommendations of existing Barrett's esophagus surveillance guidelines, which advocate the continued use of quadratic biopsy sampling within general surveillance programs.

Cerebral Oximetry During Cardiac Arrest: A Multicenter Study of Neurologic Outcomes and Survival.

OBJECTIVES: Cardiac arrest is associated with morbidity and mortality because of cerebral ischemia. Therefore, we tested the hypothesis that higher regional cerebral oxygenation during resuscitation is associated with improved return of spontaneous circulation, survival, and neurologic outcomes at hospital discharge. We further examined the validity of regional cerebral oxygenation as a test to predict these outcomes. DESIGN: Multicenter prospective study of in-hospital cardiac arrest. SETTING: Five medical centers in the United States and the United Kingdom. PATIENTS: Inclusion criteria are as follows: in-hospital cardiac arrest, age 18 years old or older, and prolonged cardiopulmonary resuscitation greater than or equal to 5 minutes. Patients were recruited consecutively during working hours between August 2011 and September 2014. Survival with a favorable neurologic outcome was defined as a cerebral performance category 1-2. INTERVENTIONS: Cerebral oximetry monitoring. MEASUREMENTS AND MAIN RESULTS: Among 504 in-hospital cardiac arrest events, 183 (36%) met inclusion criteria. Overall, 62 of 183 (33.9%) achieved return of spontaneous circulation, whereas 13 of 183 (7.1%) achieved cerebral performance category 1-2 at discharge. Higher mean ± SD regional cerebral oxygenation was associated with return of spontaneous circulation versus no return of spontaneous circulation (51.8% ± 11.2% vs 40.9% ± 12.3%) and cerebral performance category 1-2 versus cerebral performance category 3-5 (56.1% ± 10.0% vs 43.8% ± 12.8%) (both p < 0.001). Mean regional cerebral oxygenation during the last 5 minutes of cardiopulmonary resuscitation best predicted the return of spontaneous circulation (area under the curve, 0.76; 95% CI, 0.69-0.83); regional cerebral oxygenation greater than or equal to 25% provided 100% sensitivity (95% CI, 94-100) and 100% negative predictive value (95% CI, 79-100); regional cerebral oxygenation greater than or equal to 65% provided 99% specificity (95% CI, 95-100) and 93% positive predictive value (95% CI, 66-100) for return of spontaneous circulation. Time with regional cerebral oxygenation greater than 50% during cardiopulmonary resuscitation best predicted cerebral performance category 1-2 (area under the curve, 0.79; 95% CI, 0.70-0.88). Specifically, greater than or equal to 60% cardiopulmonary resuscitation time with regional cerebral oxygenation greater than 50% provided 77% sensitivity (95% CI,:46-95), 72% specificity (95% CI, 65-79), and 98% negative predictive value (95% CI, 93-100) for cerebral performance category 1-2. CONCLUSIONS: Cerebral oximetry allows real-time, noninvasive cerebral oxygenation monitoring during cardiopulmonary resuscitation. Higher cerebral oxygenation during cardiopulmonary resuscitation is associated with return of spontaneous circulation and neurologically favorable survival to hospital discharge. Achieving higher regional cerebral oxygenation during resuscitation may optimize the chances of cardiac arrest favorable outcomes.

Palliative and end-of-life educational practices in US pulmonary and critical care training programs.

PURPOSE: To describe educational features in palliative and end-of-life care (PEOLC) in pulmonary/critical care fellowships and identify the features associated with perceptions of trainee competence in PEOLC. METHODS: A survey of educational features in 102 training programs and the perceived skill and comfort level of trainees in 6 PEOLC domains: communication, symptom control, ethical/legal, community/institutional resources, specific syndromes, and ventilator withdrawal. We evaluated associations between perceived trainee competence/comfort in PEOLC and training program features, using regression analyses. RESULTS: Fifty-five percent of program directors (PDs) reported faculty with training in PEOLC; 30% had a written PEOLC curriculum. Neither feature was associated with trainee competence/comfort. Program directors and trainees rated bedside PEOLC teaching highly. Only 20% offered PEOLC rotations; most trainees judged these valuable. Most PDs and trainees reported that didactic teaching was insufficient in communication, although sufficient teaching of this was associated with perceived trainee competence in communication. Perceived trainee competence in managing institutional resources was rated poorly. Program directors reporting significant barriers to PEOLC education also judged trainees less competent in PEOLC. Time constraint was the greatest barrier. CONCLUSION: This survey of PEOLC education in US pulmonary/critical care fellowships identified associations between certain program features and perceived trainee skill in PEOLC. These results generate hypotheses for further study.

Impact of critical care medicine training programs' palliative care education and bedside tools on ICU use at the end of life.

BACKGROUND: Intensive care unit (ICU) use at the end of life is rising. Little research has focused on associations among critical care fellows' training, institutional support, and bedside tools with ICU use at the end of life. OBJECTIVE: We evaluated whether hospital and critical care medicine program interventions were associated with ICU use in the last 6 months of life for patients with chronic illness. METHODS: Our observational, retrospective study explored associations between results from a survey of critical care program directors and hospital-level Medicare data on ICU use in the last 6 months of life. Program directors evaluated quality of palliative care education in their critical care fellowships and reported on the number of bedside tools and the presence or absence of an inpatient palliative care consultation service. RESULTS: For the 89 hospitals and 71 affiliated training programs analyzed, there were statistically significant relationships between 2 of the explanatory variables-the quality of palliative care education and the number of bedside tools-in ICU use. Each level of increased educational quality (1-5 Likert scale) was associated with a 0.57-day decrease in ICU days, whereas, for each additional, evidence-based bedside tool, there was a 0.31-day decrease. The presence of an inpatient palliative care program was not a significant predictor of ICU use. CONCLUSIONS: We found that the quality of palliative care training in critical care medicine programs and the use of bedside tools were independently associated with reduced ICU use at the end of life.

A feasibility study of cerebral oximetry during in-hospital mechanical and manual cardiopulmonary resuscitation*.

OBJECTIVE: A major hurdle limiting the ability to improve the quality of resuscitation has been the lack of a noninvasive real-time detection system capable of monitoring the quality of cerebral and other organ perfusion, as well as oxygen delivery during cardiopulmonary resuscitation. Here, we report on a novel system of cerebral perfusion targeted resuscitation. DESIGN: An observational study evaluating the role of cerebral oximetry (Equanox; Nonin, Plymouth, MI, and Invos; Covidien, Mansfield, MA) as a real-time marker of cerebral perfusion and oxygen delivery together with the impact of an automated mechanical chest compression system (Life Stat; Michigan Instruments, Grand Rapids, MI) on oxygen delivery and return of spontaneous circulation following in-hospital cardiac arrest. SETTING: Tertiary medical center. PATIENTS: In-hospital cardiac arrest patients (n = 34). MAIN RESULTS: Cerebral oximetry provided real-time information regarding the quality of perfusion and oxygen delivery. The use of automated mechanical chest compression device (n = 12) was associated with higher regional cerebral oxygen saturation compared with manual chest compression device (n = 22) (53.1% ± 23.4% vs 24% ± 25%, p = 0.002). There was a significant difference in mean regional cerebral oxygen saturation (median % ± interquartile range) in patients who achieved return of spontaneous circulation (n = 15) compared with those without return of spontaneous circulation (n = 19) (47.4% ± 21.4% vs 23% ± 18.42%, p < 0.001). After controlling for patients achieving return of spontaneous circulation or not, significantly higher mean regional cerebral oxygen saturation levels during cardiopulmonary resuscitation were observed in patients who were resuscitated using automated mechanical chest compression device (p < 0.001). CONCLUSIONS: The integration of cerebral oximetry into cardiac arrest resuscitation provides a novel noninvasive method to determine the quality of cerebral perfusion and oxygen delivery to the brain. The use of automated mechanical chest compression device during in-hospital cardiac arrest may lead to improved oxygen delivery and organ perfusion.

A feasibility study evaluating the role of cerebral oximetry in predicting return of spontaneous circulation in cardiac arrest.

UNLABELLED: To date there has been no reliable noninvasive real time monitoring available to determine cerebral perfusion during cardiac arrest. OBJECTIVES: To investigate the feasibility of using a commercially available cerebral oximeter during in-hospital cardiac arrest, and determine whether this parameter predicts return of spontaneous circulation (ROSC). METHODS: Cerebral oximetry was incorporated in cardiac arrest management in 19 in-hospital cardiac arrest cases, five of whom had ROSC. The primary outcome measure was the relationship between rSO(2) and ROSC. RESULTS: The use of cerebral oximetry was found to be feasible during in hospital cardiac arrest and did not interfere with management. Patients with ROSC had a significantly higher overall mean ± SE rSO(2) (35 ± 5 vs. 18 ± 0.4, p<0.001). The difference in mean rSO(2) between survivors and non-survivors was most pronounced in the final 5 min of cardiac arrest (48 ± 1 vs. 15 ± 0.2, p<0.0001) and appeared to herald imminent ROSC. Although spending a significantly higher portion of time with an rSO(2)>40% was found in survivors (p<0.0001), patients with ROSC had an rSO(2) above 30% for >50% of the duration of cardiac arrest, whereas non-survivors had an rSO(2) that was below 30%>50% of their cardiac arrest. Patients with ROSC also had a significantly higher change in rSO(2) from baseline compared to non-survivors (310% ± 60% vs. 150% ± 27%, p<0.05). CONCLUSION: Cerebral oximetry may have a role in predicting ROSC and the optimization of cerebral perfusion during cardiac arrest.

Early changes in functional dynamic magnetic resonance imaging predict for pathologic response to neoadjuvant chemotherapy in primary breast cancer.

PURPOSE: Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) allows noninvasive, in vivo measurements of tissue microvessel perfusion and permeability. We examined whether DCE-MRI done after two cycles of neoadjuvant chemotherapy could predict final clinical and pathologic response in primary breast cancers. EXPERIMENTAL DESIGN: Thirty-seven patients with primary breast cancer, due to receive six cycles of neoadjuvant 5-fluorouracil, epirubicin and cyclophosphamide chemotherapy, were examined using DCE-MRI before neoadjuvant chemotherapy and after two cycles of treatment. Changes in DCE-MRI kinetic parameters (K(trans), k(ep), v(e), MaxGd, rBV, rBF, MTT) were correlated with the final clinical and pathologic response to neoadjuvant chemotherapy. Test-retest variability was used to determine individual patient response. RESULTS: Twenty-eight patients were evaluable for response (19 clinical responders and 9 nonresponders; 11 pathologic responders and 17 nonresponders). Changes in the DCE-MRI kinetic parameters K(trans), k(ep), MaxGd, rBV, and rBF were significantly correlated with both final clinical and pathologic response (P < 0.01). Change in K(trans) was the best predictor of pathologic nonresponse (area under the receiver operating characteristic curve, 0.93; sensitivity, 94%; specificity, 82%), correctly identifying 94% of nonresponders and 73% of responders. Change in MRI-derived tumor size did not predict for pathologic response. CONCLUSION: Changes in breast tumor microvessel functionality as depicted by DCE-MRI early on after starting anthracycline-based neoadjuvant chemotherapy can predict final clinical and pathologic response. The ability to identify nonresponders early may allow the selection of patients who may benefit from a therapy change.

Adjacent thoracic lymph node metastases originating from two separate primary cancers: case report.

Reported is an unusual case of adjacent thoracic lymph nodes demonstrating metastases from two different primary malignancies. A 51 year-old woman with a previous history of bilateral breast cancer underwent a radical gastro-oesophagectomy for adenocarcinoma of the lower third of the oesophagus. The resection specimen demonstrated breast and oesophageal metastases in adjacent thoracic lymph nodes. Mechanisms for this phenomenon, including the known local immune suppression on lymphoid cells by oesophageal carcinoma cells, are discussed.

Aerosolized antibiotics and ventilator-associated tracheobronchitis in the intensive care unit.

CONTEXT: In critically ill intubated patients, signs of respiratory infection often persist despite treatment with potent systemic antibiotics. OBJECTIVE: The purpose of this study was to determine whether aerosolized antibiotics, which achieve high drug concentrations in the target organ, would more effectively treat respiratory infection and decrease the need for systemic antibiotics. DESIGN: Double-blind, randomized, placebo-controlled study performed from 2003 through 2004. SETTING: The medical and surgical intensive care units of a university hospital. PATIENTS: Critically ill intubated patients were randomized if: 1) > or = 18 yrs of age, intubated for a minimum of 3 days, and expected to survive at least 14 days; and 2) had ventilator-associated tracheobronchitis defined as the production of purulent secretions (> or = 2 mL during 4 hrs) with organism(s) on Gram stain. Of 104 patients monitored, 43 consented for treatment and completed the study. No patients were withdrawn from the study for adverse events. INTERVENTION: Aerosol antibiotic (AA) or aerosol saline placebo was given for 14 days or until extubation. The responsible clinician determined the administration of systemic antibiotics (SA). Patients were followed for 28 days. MAIN OUTCOME MEASURES: Primary: Centers for Disease Control National Nosocomial Infection Survey diagnostic criteria for ventilator-associated pneumonia (VAP) and clinical pulmonary infection score. Secondary: white blood cell count, SA use, acquired antibiotic resistance, and weaning from mechanical ventilation. RESULTS: Most patients had VAP at randomization. With treatment, the AA group had reduced signs of respiratory infection: reduced Centers for Disease Control National Nosocomial Infection Survey VAP (14/19; 73.6%) to (5/14; 35.7%) vs. placebo (18/24; 75%) to (11/14; 78.6%), reduction in clinical pulmonary infection score, lower white blood cell count at day 14, reduced bacterial resistance, reduced use of SA, and increased weaning (all p < or = .05). CONCLUSIONS: In critically ill patients with ventilator-associated tracheobronchitis, AA decrease VAP and other signs and symptoms of respiratory infection, facilitate weaning, and reduce bacterial resistance and use of systemic antibiotics.

Use of the All Patient Refined-Diagnosis Related Group (APR-DRG) Risk of Mortality Score as a Severity Adjustor in the Medical ICU.

OBJECTIVE: To evaluate the performance of APR-DRG (All Patient Refined-Diagnosis Related Group) Risk of Mortality (ROM) score as a mortality risk adjustor in the intensive care unit (ICU). DESIGN: Retrospective analysis of hospital mortality. SETTING: Medical ICU in a university hospital located in metropolitan New York. PATIENTS: 1213 patients admitted between February 2004 and March 2006. MAIN RESULTS: Mortality rate correlated significantly with increasing APR-DRG ROM scores (p < 0.0001). Multiple logistic regression analysis demonstrated that, after adjusting for patient age and disease group, APR-DRG ROM was significantly associated with mortality risk in patients, with a one unit increase in APR-DRG ROM associated with a 3-fold increase in mortality. CONCLUSIONS: APR-DRG ROM correlates closely with ICU mortality. Already available for many hospitalized patients around the world, it may provide a readily available means for severity-adjustment when physiologic scoring is not available.