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Many real-world image recognition problems, such as diagnostic medical imaging exams, are "long-tailed" - there are a few common findings followed by many more relatively rare conditions. In chest radiography, diagnosis is both a long-tailed and multi-label problem, as patients often present with multiple findings simultaneously. While researchers have begun to study the problem of long-tailed learning in medical image recognition, few have studied the interaction of label imbalance and label co-occurrence posed by long-tailed, multi-label disease classification. To engage with the research community on this emerging topic, we conducted an open challenge, CXR-LT, on long-tailed, multi-label thorax disease classification from chest X-rays (CXRs). We publicly release a large-scale benchmark dataset of over 350,000 CXRs, each labeled with at least one of 26 clinical findings following a long-tailed distribution. We synthesize common themes of top-performing solutions, providing practical recommendations for long-tailed, multi-label medical image classification. Finally, we use these insights to propose a path forward involving vision-language foundation models for few- and zero-shot disease classification., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: R.M.S has received royalties for patent or software licenses from iCAD, Philips, PingAn, ScanMed, Translation Holdings, and MGB as well as research support form CRADA with PingAn. The remaining authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Interventional therapies (ITs) are an emerging treatment modality for pulmonary embolism (PE); however, the degree of racial, sex-based, and sociodemographic disparities in access and timing is unknown., Objectives: To investigate barriers to access and timing of ITs for PE across the United States., Methods: A retrospective cohort study utilizing the Nationwide Inpatient Sample from 2016-2020 included adult patients with PE. The use of ITs (mechanical thrombectomy and catheter-directed thrombolysis) was identified via International Classification of Diseases 10th revision codes. Early IT was defined as procedure performed within the first 2 days after admission., Results: A total of 27 805 273 records from the 2016-2020 Nationwide Inpatient Sample database were examined. There were 387 514 (1.4%) patients with PE, with 14 249 (3.6%) of them having undergone IT procedures (11 115 catheter-directed thrombolysis, 2314 thrombectomy, and 780 both procedures). After multivariate adjustment, factors associated with less use of IT included Black race (odds ratio [OR], 0.90; 95% CI, 0.86-0.94; P < .01), Hispanic race (OR, 0.73; 95% CI, 0.68-0.79; P < .01), female sex (OR, 0.88; 95% CI, 0.85-0.91; P < .01), treatment in a rural hospital (OR, 0.49; 95% CI, 0.44-0.54; P < .01), and lack of private insurance (Medicare OR, 0.77; 95% CI, 0.73-0.80; P < .01; Medicaid OR, 0.65; 95% CI, 0.61-0.69; P < .01; no coverage OR, 0.87; 95% CI, 0.82-0.93; P < .01). Among the patients who received IT, 11 315 (79%) procedures were conducted within 2 days of admission and 2934 (21%) were delayed. Factors associated with delayed procedures included Black race (OR, 1.12; 95% CI, 1.01-1.26; P = .04), Hispanic race (OR, 1.52; 95% CI, 1.28-1.80; P < .01), weekend admission (OR, 1.37; 95% CI, 1.25-1.51; P < .01), Medicare coverage (OR, 1.24; 95% CI, 1.10-1.40; P < .01), and Medicaid coverage (OR, 1.29; 95% CI, 1.12-1.49; P < .01)., Conclusion: Significant racial, sex-based, and geographic barriers exist in overall access to IT for PE in the United States., Competing Interests: Declaration of competing interests There are no competing interests to disclose., (Copyright © 2024 International Society on Thrombosis and Haemostasis. Published by Elsevier Inc. All rights reserved.)

Objective: Health inequities can be influenced by demographic factors such as race and ethnicity, proficiency in English, and biological sex. Disparities may manifest as differential likelihood of testing which correlates directly with the likelihood of an intervention to address an abnormal finding. Our retrospective observational study evaluated the presence of variation in glucose measurements in the Intensive Care Unit (ICU)., Methods: Using the MIMIC-IV database (2008-2019), a single-center, academic referral hospital in Boston (USA), we identified adult patients meeting sepsis-3 criteria. Exclusion criteria were diabetic ketoacidosis, ICU length of stay under 1 day, and unknown race or ethnicity. We performed a logistic regression analysis to assess differential likelihoods of glucose measurements on day 1. A negative binomial regression was fitted to assess the frequency of subsequent glucose readings. Analyses were adjusted for relevant clinical confounders, and performed across three disparity proxy axes: race and ethnicity, sex, and English proficiency., Results: We studied 24,927 patients, of which 19.5% represented racial and ethnic minority groups, 42.4% were female, and 9.8% had limited English proficiency. No significant differences were found for glucose measurement on day 1 in the ICU. This pattern was consistent irrespective of the axis of analysis, i.e. race and ethnicity, sex, or English proficiency. Conversely, subsequent measurement frequency revealed potential disparities. Specifically, males (incidence rate ratio (IRR) 1.06, 95% confidence interval (CI) 1.01 - 1.21), patients who identify themselves as Hispanic (IRR 1.11, 95% CI 1.01 - 1.21), or Black (IRR 1.06, 95% CI 1.01 - 1.12), and patients being English proficient (IRR 1.08, 95% CI 1.01 - 1.15) had higher chances of subsequent glucose readings., Conclusion: We found disparities in ICU glucose measurements among patients with sepsis, albeit the magnitude was small. Variation in disease monitoring is a source of data bias that may lead to spurious correlations when modeling health data., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Whether intubation should be initiated early in the clinical course of critically ill patients remains a matter of debate. Results from prior observational studies are difficult to interpret because of avoidable flaws including immortal time bias, inappropriate eligibility criteria, and unrealistic treatment strategies., Research Question: Do treatment strategies that intubate patients early in the critical care admission improve 30-day survival compared with strategies that delay intubation?, Study Design and Methods: We estimated the effect of strategies that require early intubation of critically ill patients compared with those that delay intubation. With data extracted from the Medical Information Mart for Intensive Care-IV database, we emulated three target trials, varying the flexibility of the treatment strategies and the baseline eligibility criteria., Results: Under unrealistically strict treatment strategies with broad eligibility criteria, the 30-day mortality risk was 7.1 percentage points higher for intubating early compared with delaying intubation (95% CI, 6.2-7.9). Risk differences were 0.4 (95% CI, -0.1 to 0.9) and -0.9 (95% CI, -2.5 to 0.7) percentage points in subsequent target trial emulations that included more realistic treatment strategies and eligibility criteria., Interpretation: When realistic treatment strategies and eligibility criteria are used, strategies that delay intubation result in similar 30-day mortality risks compared with those that intubate early. Delaying intubation ultimately avoids intubation in most patients., (Copyright © 2023 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Background: Evidence regarding acute kidney injury associated with concomitant administration of vancomycin and piperacillin-tazobactam is conflicting, particularly in patients in the ICU., Research Question: Does a difference exist in the association between commonly prescribed empiric antibiotics on ICU admission (vancomycin and piperacillin-tazobactam, vancomycin and cefepime, and vancomycin and meropenem) and acute kidney injury?, Study Design and Methods: This was a retrospective cohort study using data from the eICU Research Institute, which contains records for ICU stays between 2010 and 2015 across 335 hospitals. Patients were enrolled if they received vancomycin and piperacillin-tazobactam, vancomycin and cefepime, or vancomycin and meropenem exclusively. Patients initially admitted to the ED were included. Patients with hospital stay duration of < 1 h, receiving dialysis, or with missing data were excluded. Acute kidney injury was defined as Kidney Disease: Improving Global Outcomes stage 2 or 3 based on serum creatinine component. Propensity score matching was used to match patients in the control (vancomycin and meropenem or vancomycin and cefepime) and treatment (vancomycin and piperacillin-tazobactam) groups, and ORs were calculated. Sensitivity analyses were performed to study the effect of longer courses of combination therapy and patients with renal insufficiency on admission., Results: Thirty-five thousand six hundred fifty-four patients met inclusion criteria (vancomycin and piperacillin-tazobactam, n = 27,459; vancomycin and cefepime, n = 6,371; vancomycin and meropenem, n = 1,824). Vancomycin and piperacillin-tazobactam was associated with a higher risk of acute kidney injury and initiation of dialysis when compared with that of both vancomycin and cefepime (Acute kidney injury: OR, 1.37 [95% CI, 1.25-1.49]; dialysis: OR, 1.28 [95% CI, 1.14-1.45]) and vancomycin and meropenem (Acute kidney injury: OR, 1.27 [95%, 1.06-1.52]; dialysis: OR, 1.56 [95% CI, 1.23-2.00]). The odds of acute kidney injury developing was especially pronounced in patients without renal insufficiency receiving a longer duration of vancomycin and piperacillin-tazobactam therapy compared with vancomycin and meropenem therapy., Interpretation: VPT is associated with a higher risk of acute kidney injury than both vancomycin and cefepime and vancomycin and meropenem in patients in the ICU, especially for patients with normal initial kidney function requiring longer durations of therapy. Clinicians should consider vancomycin and meropenem or vancomycin and cefepime to reduce the risk of nephrotoxicity for patients in the ICU., (Published by Elsevier Inc.)

Artificial intelligence (AI) has experienced explosive growth in oncology and related specialties in recent years. The improved expertise in data capture, the increased capacity for data aggregation and analytic power, along with decreasing costs of genome sequencing and related biologic "omics", set the foundation and need for novel tools that can meaningfully process these data from multiple sources and of varying types. These advances provide value across biomedical discovery, diagnosis, prognosis, treatment, and prevention, in a multimodal fashion. However, while big data and AI tools have already revolutionized many fields, medicine has partially lagged due to its complexity and multi-dimensionality, leading to technical challenges in developing and validating solutions that generalize to diverse populations. Indeed, inner biases and miseducation of algorithms, in view of their implementation in daily clinical practice, are increasingly relevant concerns; critically, it is possible for AI to mirror the unconscious biases of the humans who generated these algorithms. Therefore, to avoid worsening existing health disparities, it is critical to employ a thoughtful, transparent, and inclusive approach that involves addressing bias in algorithm design and implementation along the cancer care continuum. In this review, a broad landscape of major applications of AI in cancer care is provided, with a focus on cancer research and precision medicine. Major challenges posed by the implementation of AI in the clinical setting will be discussed. Potentially feasible solutions for mitigating bias are provided, in the light of promoting cancer health equity., Competing Interests: Declaration of Competing Interest CCo and MC have no potential conflicts of interest to disclose. ECD is funded in part through the NIH/NCI Support Grant P30 CA008748. CCr reports personal fees for consulting, advisory role and speakers’ bureau from Lilly, Roche, Novartis, MSD, Seagen, Gilead and Pfizer. All the competing interests were outside the submitted work. SMT reports the following consulting or advisory role: Novartis, Pfizer, Merck, Lilly, Nektar, NanoString Technologies, AstraZeneca, Puma Biotechnology, Genentech/Roche, Eisai, Sanofi, Bristol Myers Squibb, Seattle Genetics, Odonate Therapeutics, OncoPep, Kyowa Hakko Kirin, Samsung Bioepis, CytomX Therapeutics, Daiichi Sankyo, Athenex, Gilead, Mersana, Certara, Chugai Pharma, Ellipses Pharma, Infinity, 4D Pharma, OncoSec Medical Inc., BeyondSpring Pharmaceuticals, OncXerna, Zymeworks, Zentalis, Blueprint Medicines, Reveal Genomics, ARC Therapeutics; Institutional Research Funding: Genentech/Roche, Merck, Exelixis, Pfizer, Lilly, Novartis, Bristol Myers Squibb, Eisai, AstraZeneca, NanoString Technologies, Cyclacel, Nektar, Gilead, Odonate Therapeutics, Sanofi, Seattle Genetics. All the competing interests were outside the submitted work. LAC is funded by the National Institute of Health through NIBIB R01 EB017205. GC reports the following honoraria for speaker's engagement: Roche, Seattle Genetics, Novartis, Lilly, Pfizer, Foundation Medicine, NanoString, Samsung, Celltrion, BMS, MSD; Honoraria for providing consultancy: Roche, Seattle Genetics, NanoString; Honoraria for participating in Advisory Board: Roche, Lilly, Pfizer, Foundation Medicine, Samsung, Celltrion, Mylan; Honoraria for writing engagement: Novartis, BMS; Honoraria for participation in Ellipsis Scientific Affairs Group; Institutional research funding for conducting phase I and II clinical trials: Pfizer, Roche, Novartis, Sanofi, Celgene, Servier, Orion, AstraZeneca, Seattle Genetics, AbbVie, Tesaro, BMS, Merck Serono, Merck Sharp Dome, Janssen-Cilag, Philogen, Bayer, Medivation, Medimmune. All the competing interests were outside the submitted work., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: Artificial intelligence (AI) has the potential to personalize treatment strategies for patients with cancer. However, current methodological weaknesses could limit clinical impact. We identified common limitations and suggested potential solutions to facilitate translation of AI to breast cancer management., Methods: A systematic review was conducted in MEDLINE, Embase, SCOPUS, Google Scholar and PubMed Central in July 2021. Studies investigating the performance of AI to predict outcomes among patients undergoing treatment for breast cancer were included. Algorithm design and adherence to reporting standards were assessed following the Transparent Reporting of a multivariable prediction model for Individual Prognosis Or Diagnosis (TRIPOD) statement. Risk of bias was assessed by using the Prediction model Risk Of Bias Assessment Tool (PROBAST), and correspondence with authors to assess data and code availability., Results: Our search identified 1,124 studies, of which 64 were included: 58 had a retrospective study design, with 6 studies with a prospective design. Access to datasets and code was severely limited (unavailable in 77% and 88% of studies, respectively). On request, data and code were made available in 28% and 18% of cases, respectively. Ethnicity was often under-reported (not reported in 52 of 64, 81%), as was model calibration (63/64, 99%). The risk of bias was high in 72% (46/64) of the studies, especially because of analysis bias., Conclusion: Development of AI algorithms should involve external and prospective validation, with improved code and data availability to enhance reliability and translation of this promising approach. Protocol registration number: PROSPERO - CRD42022292495., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: Artificial intelligence (AI) has the potential to personalise mechanical ventilation strategies for patients with respiratory failure. However, current methodological deficiencies could limit clinical impact. We identified common limitations and propose potential solutions to facilitate translation of AI to mechanical ventilation of patients., Methods: A systematic review was conducted in MEDLINE, Embase, and PubMed Central to February 2021. Studies investigating the application of AI to patients undergoing mechanical ventilation were included. Algorithm design and adherence to reporting standards were assessed with a rubric combining published guidelines, satisfying the Transparent Reporting of a multivariable prediction model for Individual Prognosis Or Diagnosis [TRIPOD] statement. Risk of bias was assessed by using the Prediction model Risk Of Bias ASsessment Tool (PROBAST), and correspondence with authors to assess data and code availability., Results: Our search identified 1,342 studies, of which 95 were included: 84 had single-centre, retrospective study design, with only one randomised controlled trial. Access to data sets and code was severely limited (unavailable in 85% and 87% of studies, respectively). On request, data and code were made available from 12 and 10 authors, respectively, from a list of 54 studies published in the last 5 yr. Ethnicity was frequently under-reported 18/95 (19%), as was model calibration 17/95 (18%). The risk of bias was high in 89% (85/95) of the studies, especially because of analysis bias., Conclusions: Development of algorithms should involve prospective and external validation, with greater code and data availability to improve confidence in and translation of this promising approach., Trial Registration Number: PROSPERO - CRD42021225918., (Copyright © 2021 British Journal of Anaesthesia. Published by Elsevier Ltd. All rights reserved.)

Background: Palliative ventilator withdrawal (PVW) in the ICU is a common occurrence., Research Question: The goal of this study was to measure the rate of severe tachypnea as a proxy for dyspnea and to identify characteristics associated with episodes of tachypnea., Study Design and Methods: This study assessed a retrospective cohort of ICU patients from 2008 to 2012 mechanically ventilated at a single academic medical center who underwent PVW. The primary outcome of at least one episode of severe tachypnea (respiratory rate > 30 breaths/min) within 6 h after PVW was measured by using detailed physiologic and medical record data. Multivariable logistic regression was used to examine the association between patient and treatment characteristics with the occurrence of a severe episode of tachypnea post extubation., Results: Among 822 patients undergoing PVW, 19% and 30% had an episode of severe tachypnea during the 1-h and 6-h postextubation period, respectively. Within 1 h postextubation, patients with the following characteristics were more likely to experience tachypnea: no pre-extubation opiates (adjusted OR [aOR], 2.08; 95% CI, 1.03-4.19), lung injury (aOR, 3.33; 95% CI, 2.19-5.04), Glasgow Coma Scale score > 8 (aOR, 2.21; 95% CI, 1.30-3.77), and no postextubation opiates (aOR, 1.90; 95% CI, 1.19-3.00)., Interpretation: Up to one-third of ICU patients undergoing PVW experience severe tachypnea. Administration of pre-extubation opiates (anticipatory dosing) represents a key modifiable factor that may reduce poor symptom control., (Copyright © 2020 American College of Chest Physicians. All rights reserved.)

Introduction: The cardiorenal syndrome generally focuses on left ventricular function, and the importance of the right ventricle as a determinant of renal function is described less frequently. In a cohort of critically ill patients with echocardiographic measurements obtained within 24 hours of admission to the intensive care unit, we examined the association of right ventricular function with acute kidney injury (AKI) and AKI-associated mortality. We also examined whether clinical measurement of volume overload modified the association between ventricular function and AKI in a subpopulation with documented admission physical examinations., Methods: Among 1879 critically ill patients with echocardiographic ventricular measurements, 43% ( n  = 807) had ventricular dysfunction-21% ( n  = 388), 9% ( n  = 167), and 13% ( n  = 252) with isolated left ventricular dysfunction, isolated right ventricular dysfunction, and biventricular dysfunction, respectively. Overall, ventricular dysfunction was associated with a 43% higher adjusted risk of AKI (95% confidence interval [CI] 1.14-1.80; P  = 0.002) compared with those with normal biventricular function, whereas isolated left ventricular dysfunction, isolated right ventricular dysfunction, and biventricular dysfunction were associated with a 1.34 (95% CI 1.00-1.77, P  = 0.05), 1.35 (95% CI 0.90-2.10, P  = 0.14) and 1.67 (95% CI 1.23-2.31, P  = 0.002) higher adjusted risk. Although an episode of AKI was associated with an approximately 2-fold greater risk of hospital mortality in those with isolated left ventricular dysfunction and biventricular dysfunction, in those with isolated right ventricular dysfunction, AKI was associated with a 7.85-fold greater risk of death (95% CI 2.89-21.3, P  < 0.001). Independent of ventricular function, peripheral edema was an important determinant of AKI., Discussion: Like left ventricular function, right ventricular function is an important determinant of AKI and AKI-associated mortality. Volume overload, independently of ventricular function, is a risk factor for AKI. Whether establishment of euvolemia might mitigate AKI risk will require further study.

Background: To investigate the use of palliative care (PC) in patients with end-stage COPD receiving home oxygen hospitalized for an exacerbation., Methods: A retrospective nationwide cohort analysis was performed, using the Nationwide Inpatient Sample. All patients ≥ 18 years of age with a diagnosis of COPD, receiving home oxygen, and admitted for an exacerbation were included., Results: A total of 55,208,382 hospitalizations from the 2006-2012 Nationwide Inpatient Sample were examined. There were 181,689 patients with COPD, receiving home oxygen, and admitted for an exacerbation; 3,145 patients (1.7%) also had a PC contact. There was a 4.5-fold relative increase in PC referral from 2006 (0.45%) to 2012 (2.56%) (P < .01). Patients receiving PC consultations compared with those who did not were older (75.0 years [SD 10.9] vs 70.6 years [SD 9.7]; P < .01), had longer hospitalizations (4.9 days [interquartile range, 2.6-8.2] vs 3.5 days [interquartile range, 2.1-5.6]), and more likely to die in hospital (32.1% vs 1.5%; P < .01). Race was significantly associated with referral to palliative care, with white patients referred more often than minorities (P < .01). Factors associated with PC referral included age (OR, 1.03; 95% CI, 1.02-1.04; P < .01), metastatic cancer (OR, 2.40; 95% CI, 2.02-2.87; P < .01), nonmetastatic cancer (OR, 2.75; 95% CI, 2.43-3.11; P < .01), invasive mechanical ventilation (OR, 4.89; 95% CI, 4.31-5.55; P < .01), noninvasive mechanical ventilation (OR, 2.84; 95% CI, 2.58-3.12; P < .01), and Do Not Resuscitate status (OR, 7.95; 95% CI, 7.29-8.67; P < .01)., Conclusions: The use of PC increased dramatically during the study period; however, PC contact occurs only in a minority of patients with end-stage COPD admitted with an exacerbation., (Copyright © 2016 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Background: Indwelling arterial catheters (IACs) are used extensively in the ICU for hemodynamic monitoring and for blood gas analysis. IAC use also poses potentially serious risks, including bloodstream infections and vascular complications. The purpose of this study was to assess whether IAC use was associated with mortality in patients who are mechanically ventilated and do not require vasopressor support., Methods: This study used the Multiparameter Intelligent Monitoring in Intensive Care II database, consisting of > 24,000 patients admitted to the Beth Israel Deaconess Medical Center ICU between 2001 and 2008. Patients requiring mechanical ventilation who did not require vasopressors or have a diagnosis of sepsis were identified, and the primary outcome was 28-day mortality. A model based on patient demographics, comorbidities, vital signs, and laboratory results was developed to estimate the propensity for IAC placement. Patients were then propensity matched, and McNemar test was used to evaluate the association of IAC with 28-day mortality., Results: We identified 1,776 patients who were mechanically ventilated who met inclusion criteria. There were no differences in the covariates included in the final propensity model between the IAC and non-IAC propensity-matched groups. For the matched cohort, there was no difference in 28-day mortality between the IAC group and the non-IAC group (14.7% vs 15.2%; OR, 0.96; 95% CI, 0.62-1.47)., Conclusions: In hemodynamically stable patients who are mechanically ventilated, the presence of an IAC is not associated with a difference in 28-day mortality. Validation in other datasets, as well as further analyses in other subgroups, is warranted.

Background: Observational studies have found an increased risk of adverse effects such as hemorrhage, stroke, and increased mortality in patients taking selective serotonin reuptake inhibitors (SSRIs). The impact of prior use of these medications on outcomes in critically ill patients has not been previously examined. We performed a retrospective study to determine if preadmission use of SSRIs or serotonin norepinephrine reuptake inhibitors (SNRIs) is associated with mortality differences in patients admitted to the ICU., Methods: The retrospective study used a modifiable data mining technique applied to the publicly available Multiparameter Intelligent Monitoring in Intensive Care (MIMIC) 2.6 database. A total of 14,709 patient records, consisting of 2,471 in the SSRI/SNRI group and 12,238 control subjects, were analyzed. The study outcome was in-hospital mortality., Results: After adjustment for age, Simplified Acute Physiology Score, vasopressor use, ventilator use, and combined Elixhauser score, SSRI/SNRI use was associated with significantly increased in-hospital mortality (OR, 1.19; 95% CI, 1.02-1.40; P=.026). Among patient subgroups, risk was highest in patients with acute coronary syndrome (OR, 1.95; 95% CI, 1.21-3.13; P=.006) and patients admitted to the cardiac surgery recovery unit (OR, 1.51; 95% CI, 1.11-2.04; P=.008). Mortality appeared to vary by specific SSRI, with higher mortalities associated with higher levels of serotonin inhibition., Conclusions: We found significant increases in hospital stay mortality among those patients in the ICU taking SSRI/SNRIs prior to admission as compared with control subjects. Mortality was higher in patients receiving SSRI/SNRI agents that produce greater degrees of serotonin reuptake inhibition. The study serves to demonstrate the potential for the future application of advanced data examination techniques upon detailed (and growing) clinical databases being made available by the digitization of medicine.

Although case reports link proton-pump inhibitor (PPI) use and hypomagnesemia, no large-scale studies have been conducted. Here we examined the serum magnesium concentration and the likelihood of hypomagnesemia (<1.6 mg/dl) with a history of PPI or histamine-2 receptor antagonist used to reduce gastric acid, or use of neither among 11,490 consecutive adult admissions to an intensive care unit of a tertiary medical center. Of these, 2632 patients reported PPI use prior to admission, while 657 patients were using a histamine-2 receptor antagonist. PPI use was associated with 0.012 mg/dl lower adjusted serum magnesium concentration compared to users of no acid-suppressive medications, but this effect was restricted to those patients taking diuretics. Among the 3286 patients concurrently on diuretics, PPI use was associated with a significant increase of hypomagnesemia (odds ratio 1.54) and 0.028 mg/dl lower serum magnesium concentration. Among those not using diuretics, PPI use was not associated with serum magnesium levels. Histamine-2 receptor antagonist use was not significantly associated with magnesium concentration without or with diuretic use. The use of PPI was not associated with serum phosphate concentration regardless of diuretic use. Thus, we verify case reports of the association between PPI use and hypomagnesemia in those concurrently taking diuretics. Hence, serum magnesium concentrations should be followed in susceptible individuals on chronic PPI therapy.

We performed a double-blind placebo-controlled trial to study whether early treatment with erythropoietin could prevent the development of acute kidney injury in patients in two general intensive care units. As a guide for choosing the patients for treatment we measured urinary levels of two biomarkers, the proximal tubular brush border enzymes gamma-glutamyl transpeptidase and alkaline phosphatase. Randomization to either placebo or two doses of erythropoietin was triggered by an increase in the biomarker concentration product to levels above 46.3, with a primary outcome of relative average plasma creatinine increase from baseline over 4 to 7 days. Of 529 patients, 162 were randomized within an average of 3.5 h of a positive sample. There was no difference in the incidence of erythropoietin-specific adverse events or in the primary outcome between the placebo and treatment groups. The triggering biomarker concentration product selected patients with more severe illness and at greater risk of acute kidney injury, dialysis, or death; however, the marker elevations were transient. Early intervention with high-dose erythropoietin was safe but did not alter the outcome. Although these two urine biomarkers facilitated our early intervention, their transient increase compromised effective triaging. Further, our study showed that a composite of these two biomarkers was insufficient for risk stratification in a patient population with a heterogeneous onset of injury.

Spontaneous hemothorax in neurofibromatosis type 1 rarely occurs, is potentially life-threatening, and requires expedient management. We present a case of massive hemothorax in a patient with neurofibromatosis type 1 caused by spontaneous rupture of the right internal mammary artery. A subsequently diagnosed underlying pheochromocytoma may be implicated in rupture of the arterial wall.

Adenoviruses are efficient gene delivery agents for a variety of neoplasms. In the present study, we have investigated the use of adenoviruses for the delivery of the thymidine kinase (tk) gene into multiple myeloma (MM) cells. We first demonstrated that MM cell lines and MM patient cells express both adenovirus receptors as well as the DF3/MUC1 protein, thus providing a rationale for using adenoviruses to selectively deliver genes under the control of the DF3 promoter. By using an adenoviral construct containing beta-galactosidase (beta-gal) gene driven by the DF3 promoter (Ad. DF3-betagal), we demonstrate greater than 80% transduction efficiency in OCI-My5 and RPMI 8226 MM cell lines at a multiplicity of infection of 1 to 100. Importantly, transduction with the tk gene driven by the DF3 promoter (Ad.DF3-tk) followed by treatment with 50 micromol/L ganciclovir (GCV) purged >/=6 log of contaminating OCI-My5 and RPMI 8226 MM cells within bone marrow mononuclear cells. In contrast, normal human hematopoietic progenitor cell number was unaffected under these conditions. Selectivity of DF3/MUC1 promoter was further confirmed, because Ad.DF3-betagal or Ad.DF3-tk did not transduce MUC1-negative HeLa cervical carcinoma cells. In addition, GCV treatment of Ad.DF3-tk-transduced RPMI 8226 MM cells did not induce a significant bystander effect. These findings demonstrate that transduction with Ad vectors using a tumor-selective promoter provides a highly efficient and selective approach for the ex vivo purging of MM cells.