Impact of the COVID-19 pandemic on the education and procedural volume of fellows in critical care medicine - a cross-sectional survey.

BACKGROUND: The COVID-19 pandemic has changed the way medical education is delivered. The purpose of this study was to assess the impact of the COVID-19 pandemic on the education and procedural volume of critical care and pulmonary critical care fellows. METHODS: We conducted a cross-sectional, internet-based, voluntary, anonymous, national survey of adult critical care fellows and academic attending physicians in critical care and pulmonary critical care fellowship programs in the United States between December 2020 and February 2021. Survey questions covered both didactic and non-didactic aspects of education and procedural volumes. Answers were ranked on a 5-point Likert scale. Survey responses were summarized by frequency with percentage. Differences between the responses of fellows and attendings were assessed with the Fisher's exact or Chi-Square test, using Stata 16 software (StataCorp LLC, College Station, TX). RESULTS: Seventy four individuals responded to the survey; the majority (70.3%) were male; less than one-third (28.4%) female. Respondents were evenly split among fellows (52.7%) and attendings (47.3%). 41.9% of survey respondents were from the authors' home institution, with a response rate of 32.6%. Almost two-thirds (62.2%) reported that fellows spend more time in the ICU since the onset of the pandemic. The majority noted that fellows insert more central venous catheters (52.7%) and arterial lines (58.1%), but perform fewer bronchoscopies (59.5%). The impact on endotracheal intubations was mixed: almost half of respondents (45.9%) reported fewer intubations, about one-third (35.1%) more intubations. Almost all respondents (93.0%) described fewer workshops; and one-third (36.1%) fewer didactic lectures. The majority (71.2%) noted less time available for research and quality improvement projects; half (50.7%) noted less bedside teaching by faculty and more than one-third (37.0%) less fellow interaction with faculty. Almost one-half of respondents (45.2%) reported an increase in fellows' weekly work hours. CONCLUSION: The pandemic has caused a decrease in scholarly and didactic activities of critical care and pulmonary critical care fellows. Fellows spend more time in ICU rotations, insert more central and arterial lines, but perform fewer intubations and bronchoscopies. This survey provides insights into changes that have occurred in the training of critical care and pulmonary critical care fellows since the onset of the COVID-19 pandemic.

Development of Compartment Syndrome after Radial Artery Puncture in a Patient with Acute Hypoxemic Respiratory Failure due to COVID-19.

A 71-year-old man who was recently hospitalized for COVID-19 pneumonia complicated by acute hypoxemic respiratory failure and severe ARDS requiring noninvasive ventilation was transferred to our hospital from a rehabilitation facility for new onset right wrist and hand pain and swelling which had been attributed to arterial thrombosis and empirically treated with therapeutic anticoagulation. He developed numbness and paralysis in his right hand and was diagnosed with right forearm compartment syndrome requiring emergent fasciotomy. After a prolonged hospital stay complicated by respiratory failure requiring mechanical ventilation, he was discharged with improved, but not resolved, sensorimotor deficits. Arterial blood gas sampling is commonly performed in patients with acute hypoxemic respiratory failure, for assessment of oxygenation and acid-base status. It is considered a benign procedure, but it can lead to serious complications, such as bleeding and compartment syndrome. Risks and benefits of any procedure need to be weighed carefully and less is often more. Compartment syndrome is characterized by the 5 P's-pain, pallor, paresthesia, pulselessness, and paralysis.

Development of a large spontaneous pneumothorax after recovery from mild COVID-19 infection.

A previously healthy 37-year-old man presented with fevers and myalgias for a week with a minimal dry cough. Initial SARS-CoV-2 nasopharyngeal testing was negative, but in light of high community prevalence, he was diagnosed with COVID-19, treated with supportive care and self-quarantined at home. Three days after resolution of all symptoms, he developed sudden onset chest pain. Chest imaging revealed a large right-sided pneumothorax and patchy subpleural ground glass opacities. IgM and IgG antibodies for SARS-CoV-2 were positive. His pneumothorax resolved after placement of a small-bore chest tube, which was removed after 2 days.This case demonstrates that patients with COVID-19 can develop a significant pulmonary complication, a large pneumothorax, despite only minimal lower respiratory tract symptoms and after resolution of the original illness. Medical professionals should consider development of a pneumothorax in patients who have recovered from COVID-19 and present with new respiratory symptoms.

Filaggrin Expression and Processing Deficiencies Impair Corneocyte Surface Texture and Stiffness in Mice.

Abundant corneocyte surface protrusions, observed in patients with atopic dermatitis with filaggrin loss-of-function mutations, are inversely associated with levels of natural moisturizing factors (NMFs) in the stratum corneum. To dissect the etiological role of NMFs and filaggrin deficiency in surface texture alterations, we examined mouse models with genetic deficiencies in the synthesis or degradation of filaggrin monomers for NMFs, cell stiffness (elastic modulus) and corneocyte surface protrusion density (dermal texture index). Five neonatal and adult mouse models carrying inactivating mutations of SASPase (Sasp-/-), filaggrin (Flgft/ft and Flg-/-), filaggrin-hornerin (FlgHrnr-/-), and bleomycin hydrolase (Blmh-/-) were investigated. Sasp-/- and Flg-/- were on the hairless mouse background. Atomic force microscopy was used to determine elastic modulus and dermal texture index. Corneocytes of each neonatal as well as hairless adult knockout mouse exhibited an increased number of protrusions and decreased elastic modulus. In these mice, NMFs were reduced except for Sasp-/-. Dermal texture index was inversely correlated with NMFs and elastic modulus. Our findings demonstrate that any filaggrin-NMF axis deficiency can affect corneocyte mechanical properties in mice and likely in humans. Differences in NMFs and corneocyte surface texture between neonatal and adult as well as hairless and hairy mice emphasize the need for carefully selecting the most appropriate animal models for studies.

Transient epidermal barrier deficiency and lowered allergic threshold in filaggrin-hornerin (FlgHrnr-/- ) double-deficient mice.

BACKGROUND: Filaggrin (Flg) and hornerin (Hrnr) share similar structural and functional features. Both proteins have been implicated as essential proteins for skin barrier maintenance. Loss-of-function mutations of these genes constitute a risk factor for atopic dermatitis and eczema-related asthma. Furthermore, both FLG and HRNR protein levels are downregulated in patients with atopic dermatitis. Thus, mice deficient for Flg and Hrnr provide a novel model to study skin barrier impairment and the susceptibility for cutaneous inflammation. METHODS: By using appropriate targeting vectors and breeding strategies, we established a homozygous FlgHrnr double-deficient (FlgHrnr-/- ) mouse model lacking both genes including the intergenomic sequence. RESULTS: Neonates appeared normal, but developed a transient scaly phenotype with overall flaky appearance, but no overt skin phenotype in adulthood, thereby reflecting a subclinical barrier defect seen in humans. Structurally, FlgHrnr-/- mice displayed a markedly reduced granular layer and a condensed cornified layer. Functionally, FlgHrnr-/- mice showed permeability abnormalities and metabolic aberrations regarding the production of natural moisturizing factors (NMFs) in the stratum corneum. Surprisingly, although the immune system revealed no aberrations under steady-state conditions, FlgHrnr-/- mice are predisposed to mount an allergic contact dermatitis, especially at hapten threshold levels eliciting allergic reactions. CONCLUSIONS: Together, our FlgHrnr-/- mouse model nicely reflects the epicutaneous sensitization susceptibilities and inflammatory reactions to environmental insults in humans with impaired skin barrier functions.

A Yin and Yang in Epithelial Immunology: The Roles of the αE(CD103)ß7 Integrin in T Cells.

The proper function(s) of cell-surface receptors is crucial for the regulation of adaptive immune responses. One such receptor is the αE(CD103)ß7 integrin, whose history in science is closely linked with the evolution of our knowledge of immune regulation. Initially described as a marker of intraepithelial T-lymphocytes, this leukocyte integrin is now seen as a dynamically regulated receptor involved in the functional differentiation of some cytotoxic T cells as well as regulatory T cells, thus presumably contributing to the fine-tuning of immune reactions in epithelial compartments. In this brief overview, we delineate our current view on αE(CD103)ß7 in T-cell-mediated immune responses.

Preferencia de pacientes niños y sus padres respecto a la vestimenta y sexo del odontopediatra / Children's and parent’s preferences regarding the attire and sex of the pediatric dentists

Objetivo: evaluar si los niños y sus padres consideran que la vestimenta del odontopediatra es un aspecto importante en la relación paciente-profesional y cuál sería la de su preferencia. Métodos: se realizó un estudio transversal, analítico en 270 niños/as de 4 y 12 años y uno de sus respectivos padres, en una Clínica Privada y una Institución de Asistencia Colectivizada en Montevideo, Uruguay. El estudio incluyó un cuestionario dirigido a padres/madres y otro a niños/as, y fotografías de odontopediatras con diferente vestimenta: túnica blanca (Imagen 1 y 6), ambo de color lila para la mujer (I-2) y ambo de color verde para el hombre (I-7), equipo con diseños infantiles (I-3, I-8), vestimenta informal ( I-4, I-9) y vestimenta formal (I-5, I-10). Se les solicitó a los niños/as y padres/madres por separado que clasificaran sus preferencias. Resultados: el 29% de los niños/as manifestó preferencia por la imagen 2, seguida por un 25% por la imagen 3. Tanto para las madres como los padres, la imagen más elegida fue la número 3 con 47% y 10% respectivamente. En relación a las opiniones de los padres/madres con respecto a si la vestimenta del odontopediatra influye en el vínculo con su hijo/a, el 83% manifestó que sí, un 16% expresó que no y un 1% opinó “da igual”. Conclusiones: la vestimenta más elegida por los niños/as encuestados fue el ambo de color lila seguida por la vestimenta con diseño infantil, y la de menos preferencia fue la informal. Para los padres/madres la más elegida fue la vestimenta con diseño infantil. Los padres en general opinaron que la vestimenta influye en el vínculo entre el odontopediatra y su hijo/a; y el comportamiento del niño/a en el consultorio.

Objective: assess whether the children and their parents believe that the dentist’s attire is an important aspect of patient-professional relationship and, if so, which do they consider to be the most confidence-inspiring attire. Methods: a cross-sectional, analytical study was conducted on 270 children aged 4 -12 years old and one of their respective parents at one private clinic and an institution of assistance collectivized in Montevideo, Uruguay. The study included a questionnaire and photographs of pediatric dentists in different attire: white coat (picture 1 and 6), green scrub for man and violet scrub for women (picture 2 and 7), children's design on the scrubs (picture 3 and 8), casual attire (picture 4 and 9) and formal attire (picture 5 and 10). Children and parents separately asked to rate their preferences. Results: 29% of children expressed a preference for the image 2, followed by 25% by the image 3. For both mothers and fathers, the image was chosen n°3 with 47% and 10% respectively. With regard to the views of parents on whether the dentist dress influences in the bond between the professional and the child , the 83% said it has influence, while 16% said it doesn ́t matter. Only 1% said "do not care". Conclusions: the attire more chosen by children was the violet scrub followed by the scrub with children's design, and the less preference was the casual attire. For fathers and mothers the attire more chosen was the scrub with children's design, Both father and mother felt that clothing affects the bold between the pediatric dentist and his daughter/son; and behavior of the child in the dentist clinic.

Improving the Quality of Handoffs in Patient Care Between Critical Care Providers in the Intensive Care Unit.

With the ever-increasing adoption of shift models for intensive care unit (ICU) staffing, improving shift-to-shift handoffs represents an important step in reducing medical errors. The authors developed an electronic handoff tool integrated within the existing electronic medical record to improve handoffs in an adult ICU. First, stakeholder (staff intensivists, fellows, and nurse practitioners/physician assistants) input was sought to define what elements they perceived as being essential to a quality handoff. The principal outcome measure of handoff accuracy was the concordance between data transmitted by the outgoing team and data received by the incoming team (termed as agreement). Based on stakeholder input, the authors developed the handoff tool and provided regular education on its use. Handoffs were observed before and after implementation of the tool. There was an increase in the level of agreement for tasks and other important data points handed off without an increase in the time required to complete the handoff.

The effect of epidermal levels of urocanic acid on 25-hydroxyvitamin D synthesis and inflammatory mediators upon narrowband UVB irradiation.

BACKGROUND/PURPOSE: Urocanic acid (UCA) absorbs ultraviolet (UV)B radiation in the epidermis which may interfere with phototherapy. Therefore, the influence of individual levels of UCA on immune reactivity and vitamin D synthesis induced by narrowband UVB radiation was assessed. METHODS: Twenty-eight subjects with irritant contact dermatitis of the hands were irradiated with suberythemal doses of narrowband UVB radiation on their unaffected lower forearms on three consecutive days. Stratum corneum tape strips and epidermal interstitial fluid (ISF) as well as blood samples were analyzed. RESULTS: Narrowband UVB irradiation led to the conversion of trans-UCA into its cis-isomer in the epidermis. The observed increase in 25-hydroxyvitamin D serum concentrations was inversely correlated with the baseline levels of trans-UCA. Furthermore, UVB irradiation induced significant changes in the levels of CXCL10/IP-10, CCL2/MCP-1, CCL4/MIP-1ß, and the IL-1RA/IL-1α ratio. The levels of IL-1α and CXCL9/MIG showed a trend toward increase. The changes in the levels of inflammatory and immunomodulatory mediators did not depend on baseline levels of trans-UCA. CONCLUSION: The results suggest that epidermal levels of trans-UCA affect vitamin D synthesis, but not cutaneous immune reactivity upon repeated exposure to suberythemal doses of narrowband UVB radiation. However, this requires further exploration.

Integrin αE (CD103) is induced but plays no pathogenic role in psoriasiform skin lesions of TGFß1 transgenic mice.

T-cells expressing αE (CD103), an integrin induced by TGFß on T-cells in vitro, accumulate within epithelia in inflammatory disorders, including psoriasis. However, it is unclear, if and how αE (CD103) contributes to skin inflammation. Using two complementary approaches, we have investigated αE (CD103) in psoriasis-like skin inflammation of mice with transgenic epidermal expression of human TGFß1: αE (CD103) was inhibited by function-blocking antibodies in vivo, and double-mutants with additional αE (CD103)-depletion were generated in two different genetic backgrounds. Epidermal hTGFß1 expression was associated with prominent expression of αE (CD103) on infiltrating cells. However, neither treatment with αE (CD103)-blocking antibodies nor deficiency of αE (CD103) in double-mutant mice altered the psoriasis-like phenotype. In addition, histopathological and flow cytometric analyses revealed similar pathological skin alterations and lymphocyte subgroups in the different mouse strains. Thus, while αE (CD103) expression is indeed associated with hTGFß1 in vivo, it has little, if any, influence on the course of the psoriasis-like phenotype in K5.hTGFß1 transgenic mice.

Impact of runoff water from an experimental agricultural field applied with Vertimec® 18EC (abamectin) on the survival, growth and gill morphology of zebrafish juveniles.

Edge-of-field waterbodies in tropical agroecosystems have been reported to be especially prone to pesticide contamination through runoff resulting from intensive irrigation practices and tropical rainfall. In the present study, the effects of runoff from an experimental agricultural field applied with Vertimec(®) 18EC (active ingredient: abamectin) on zebrafish were evaluated. To this end, the experimental field was applied with the Vertimec(®) 18EC dose recommended for strawberry crop in Brazil, whereas another field was treated with water only to serve as control. No effects of runoff water from either plot were recorded on survival. Water from the treated field led to increased growth and gill alterations. In general, these alterations were of the first and second degree, including proliferation of cells between the secondary lamellae, dilation at the lamellar apex, detachment of the respiratory epithelium and aneurism. These results confirm the high toxic potential of Vertimec(®) 18EC and provide evidence that environmental risks are likely to occur in areas subject to runoff containing this pesticide.

Pain reduced by low-level laser therapy during use of orthodontic separators in early mixed dentition.

OBJECTIVE: The purpose of this work was to investigate whether low-level laser therapy (LLLT) applied at a defined distance from the gingiva has a pain-reducing effect in young patients undergoing orthodontic separation during the early mixed-dentition stage. MATERIALS AND METHODS: A total of 40 children in early mixed dentition (mean age 8.05 years) who required separation of molars were included. The study comprised a group of 20 patients whose treatment included laser application on the day of separation and a control group of 20 patients not receiving LLLT. All patients recorded their maximum pain intensities on the day of separation (day 1) and on the following 4 days. RESULTS: Compared to the control group, pain perception was significantly reduced (p < 0.05) in the LLLT group on day 1 and continued to be reduced on day 2. Equivalent pain levels were recorded in both groups on days 3-5. CONCLUSION: Given our findings of a pain-reducing effect in young patients undergoing orthodontic separation during the early mixed-dentition stage, LLLT is an interesting alternative option of providing analgesia even in very young patients.

Integrin αE(CD103) Is Involved in Regulatory T-Cell Function in Allergic Contact Hypersensitivity.

Murine contact hypersensitivity (CHS) is a dendritic cell (DC)-dependent T-cell-mediated inflammation with CD8+ T cells as effectors and CD4+ T cells as regulators (Treg cells) that models human allergic contact dermatitis. The integrin αE(CD103) is expressed by some T-cell and DC subsets and has been implicated in epithelial lymphocyte localization, but its role in immune regulation remains enigmatic. We have identified a function for CD103 in the development of cutaneous allergic immune responses. CHS responses, but not irritant contact dermatitis, were significantly augmented in CD103-deficient mice in hapten-challenged skin. Phenotype and function of skin DCs during sensitization were normal, whereas adoptive transfer experiments revealed that the elevated CHS response in CD103-deficient mice is transferred by primed T cells and is independent of resident cells in recipient mice. While T-cell counts were elevated in challenged skin of CD103-deficient mice, the FoxP3 expression level of CD4+CD25+ Treg cells was significantly reduced, indicating impaired functionality. Indeed, Treg cells from CD103-deficient mice were not able to suppress CHS reactions during the elicitation phase. Further, CD103 on FoxP3+ Treg cells was involved in Treg retention to inflamed skin. These findings indicate an unexpected dichotomous functional role for CD103 on Treg cells by modulating FoxP3 expression.

Association of low serum 25-hydroxyvitamin D levels and sepsis in the critically ill.

OBJECTIVE: We hypothesized that deficiency in 25-hydroxyvitamin D prior to hospital admission would be associated with sepsis in the critically ill. DESIGN: Two-center observational study of patients treated in medical and surgical ICUs. SETTING: Two hundred nine medical and surgical intensive care beds in two teaching hospitals in Boston, MA. PATIENTS: Three thousand three hundred eighty-six patients, 18 years old or older, in whom 25-hydroxyvitamin D was measured prior to hospitalization between 1998 and 2011. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: : Preadmission 25-hydroxyvitamin D was categorized as deficiency in 25-hydroxyvitamin D (≤ 15 ng/mL), insufficiency (15-30 ng/mL), and sufficiency (≥ 30 ng/mL). The primary outcome was sepsis as defined by International Classification of Diseases, 9th Edition, Clinical Modification and validated by the 2001 Society of Critical Care Medicine/European Society of Intensive Care Medicine, American College of Chest Physicians, American Thoracic Society, and Surgical Infection Society international sepsis definitions conference guidelines. Logistic regression examined the presence of sepsis 3 days prior to critical care initiation to 7 days after critical care initiation. Adjusted odds ratios were estimated by multivariable logistic regression models. Preadmission 25-hydroxyvitamin D deficiency is predictive for the risk of sepsis. In the full cohort, 25-hydroxyvitamin D deficiency is a significant predictor for the risk of International Classification of Diseases, 9th Edition, Clinical Modification-defined sepsis following multivariable adjustment, including age, gender, race, type (surgical vs medical), and Deyo-Charlson index (adjusted odds ratio, 1.51 [95% CI, 1.17-1.94]; p = 0.001) relative to patients with 25-hydroxyvitamin D sufficiency. In a subset of cohort patients enriched for those with International Classification of Diseases, 9th Edition, Clinical Modification-diagnosed sepsis (n = 444), preadmission 25-hydroxyvitamin D deficiency is a significant predictor for the risk of conference guideline-defined sepsis following multivariable adjustment, including age, gender, race, type (surgical vs medical), and Acute Physiology and Chronic Health Evaluation II (adjusted odds ratio, 2.05 [95% CI, 1.19-3.52]; p = 0.009) relative to patients with 25-hydroxyvitamin D sufficiency. Furthermore, in cohort patients with International Classification of Diseases, 9th Edition, Clinical Modification-defined sepsis (n = 568), the multivariable adjusted risk of 90-day mortality was 1.6-fold higher in those with preadmission 25-hydroxyvitamin D values in the insufficient and deficient range, compared with those with preadmission vitamin D sufficiency (adjusted odds ratio, 1.63 [95% CI, 1.11-2.39]; p = 0.01). CONCLUSION: 25-hydroxyvitamin D deficiency prior to hospital admission is a significant predictor of sepsis in the critically ill. Additionally, patients with sepsis who are not vitamin D sufficient have an increased risk of mortality following critical care initiation.

Internalization routes of cell-penetrating melanoma antigen peptides into human dendritic cells.

Optimized delivery of antigens combined with sustainable maturation of dendritic cells (DCs) is crucial for generation of effective antitumoral immune responses. Multiple approaches for ex vivo antigen loading and improvement in immunogenicity have been described. We have recently established a single-step protocol consisting of a fusion peptide (a sequence of the melanoma antigen Melan-A and a cationic cell-penetrating HIV TAT domain) bound in complexes with a toll-like receptor agonist. As the exact cellular uptake mechanisms of TAT-coupled antigens have been a matter of considerable debate and significantly depend on cell type, cargo and concentrations, we evaluated internalization routes into human immature DCs in comparison with non-phagocytic cell lines. We found that Melan-A-TAT fusion peptide uptake by DCs is mainly energy dependent, superior compared with polylysine-coupled Melan-A and significantly higher in DCs as compared with Jurkat cells or HUVECs. Furthermore, we could track the uptake of the fusion peptide exclusively through early endosomes to lysosome compartments after 90 min by fluorescence microscopy and immunoelectron microscopy. Specific endocytosis inhibitors revealed major internalization of the fusion peptide by DCs via clathrin-mediated endocytosis, whereas uptake by non-phagocytic HUVECs differed significantly, involving macropinocytosis as well as clathrin-mediated endocytosis. As our understanding of the processes involved in internalization of TAT-coupled cargos by human DCs broadens, and DC activation becomes available by single-step procedures as described, further development of simultaneous DC maturation and intra-cellular peptide targeting is warranted.

Immunostimulatory activity of murine keratinocyte-derived exosomes.

It has long been known that keratinocytes influence cutaneous immunity through secretion of soluble factors. Exosomes, small membrane vesicles of endocytotic origin, have been implicated in intercellular communication processes such as the transfer of tumor cell antigens and the activation of recipient dendritic cells (DC). However, little is known about immunomodulatory functions of keratinocyte-derived exosomes. To address this question, we analysed exosome secretion of the murine keratinocyte cell line MPEK under steady state as well as inflammatory conditions (+/- IFNγ). These exosomes were readily taken up by bone marrow-derived DC (BMDC) in vitro resulting in a matured phenotype, as evidenced by increased CD40 expression as well as by the production of large amounts of IL-6, IL-10 and IL-12. When the transfer of antigen-specific information through exosomes was investigated, it was found that keratinocytes took up antigen (ovalbumin) and transferred it to their exosomes. However, these antigen-harbouring exosomes failed to induce antigen-specific T cell responses via BMDC. Together, this novel biological function suggests that keratinocytes are able to direct unspecific immune processes but do not elicit specific immune responses.

Vitamin D in acute kidney injury.

Vitamin D deficiency is common in critically ill patients and associated with increased mortality, as well as an increased risk of acute kidney injury. The occurrence of acute kidney injury by itself substantially increases critical care mortality. In addition to regulating calcium and phosphorus homeostasis and bone metabolism, vitamin D has pleotropic effects on the immune response. Potential mechanisms of how a deficiency in vitamin D could predispose individuals to increased risk of acute renal failure include dysregulation of the immune system, predisposing patients to sepsis, endothelial dysfunction and prevention of healing of renal ischemia-reperfusion injury. Toll-like receptors, NF-κB and the renin-angiotensin-aldosterone system are mediators of vitamin D effects.

The difference between critical care initiation anion gap and prehospital admission anion gap is predictive of mortality in critical illness.

OBJECTIVE: We hypothesized that the delta anion gap defined as difference between critical care initiation standard anion gap and prehospital admission standard anion gap is associated with all cause mortality in the critically ill. DESIGN: Observational cohort study. SETTING: Two hundred nine medical and surgical intensive care beds in two hospitals in Boston, MA. PATIENTS: Eighteen thousand nine hundred eighty-five patients, age ≥18 yrs, who received critical care between 1997 and 2007. MEASUREMENTS: The exposure of interest was delta anion gap and categorized a priori as <0, 0-5, 5-10, and >10 mEq/L. Logistic regression examined death by days 30, 90, and 365 postcritical care initiation and in-hospital mortality. Adjusted odds ratios were estimated by multivariable logistic regression models. The discrimination of delta anion gap for 30-day mortality was evaluated using receiver operator characteristic curves performed for a subset of patients with all laboratory data required to analyze the data via physical chemical principles (n = 664). INTERVENTIONS: None. RESULTS: Delta anion gap was a particularly strong predictor of 30-day mortality with a significant risk gradient across delta anion gap quartiles following multivariable adjustment: delta anion gap <0 mEq/L odds ratio 0.75 (95% confidence interval 0.67-0.81; p < 0.0001); delta anion gap 5-10 mEq/L odds ratio 1.56 (95% confidence interval 1.35-1.81; p < 0.0001); delta anion gap >10 mEq/L odds ratio 2.18 (95% confidence interval 1.76-2.71; p < 0.0001); and all relative to patients with delta anion gap 0-5 mEq/L. Similar significant robust associations post multivariable adjustments are seen with death by days 90 and 365 as well as in-hospital mortality. Correcting for albumin or limiting the cohort to patients with standard anion gap at critical care initiation of 10-18 mEq/L did not materially change the delta anion gap-mortality association. Delta anion gap has similarly moderate discriminative ability for 30-day mortality in comparison to standard base excess and strong ion gap. CONCLUSION: An increase in standard anion gap at critical care initiation relative to prehospital admission standard anion gap is a predictor of the risk of all cause patient mortality in the critically ill.