US Immigration Westernizes the Human Gut Microbiome.

Many US immigrant populations develop metabolic diseases post immigration, but the causes are not well understood. Although the microbiome plays a role in metabolic disease, there have been no studies measuring the effects of US immigration on the gut microbiome. We collected stool, dietary recalls, and anthropometrics from 514 Hmong and Karen individuals living in Thailand and the United States, including first- and second-generation immigrants and 19 Karen individuals sampled before and after immigration, as well as from 36 US-born European American individuals. Using 16S and deep shotgun metagenomic DNA sequencing, we found that migration from a non-Western country to the United States is associated with immediate loss of gut microbiome diversity and function in which US-associated strains and functions displace native strains and functions. These effects increase with duration of US residence and are compounded by obesity and across generations.

Vaccination with prefusion-stabilized respiratory syncytial virus fusion protein induces genetically and antigenically diverse antibody responses.

An effective vaccine for respiratory syncytial virus (RSV) is an unrealized public health goal. A single dose of the prefusion-stabilized fusion (F) glycoprotein subunit vaccine (DS-Cav1) substantially increases serum-neutralizing activity in healthy adults. We sought to determine whether DS-Cav1 vaccination induces a repertoire mirroring the pre-existing diversity from natural infection or whether antibody lineages targeting specific epitopes predominate. We evaluated RSV F-specific B cell responses before and after vaccination in six participants using complementary B cell sequencing methodologies and identified 555 clonal lineages. DS-Cav1-induced lineages recognized the prefusion conformation of F (pre-F) and were genetically diverse. Expressed antibodies recognized all six antigenic sites on the pre-F trimer. We identified 34 public clonotypes, and structural analysis of two antibodies from a predominant clonotype revealed a common mode of recognition. Thus, vaccination with DS-Cav1 generates a diverse polyclonal response targeting the antigenic sites on pre-F, supporting the development and advanced testing of pre-F-based vaccines against RSV.

Intravenous iron: an update.

Iron deficiency is the most common nutritional deficiency worldwide, with significant adverse health consequences in the presence or absence of anaemia. Total dose intravenous iron replacement is recommended for replacement of iron in patients with severe iron deficiency, especially in the presence of anaemia, intolerance or inefficacy following oral iron, or states of inflammation where upregulation of hepcidin may impair gastrointestinal absorption of iron. Currently, available intravenous iron formulations have been demonstrated to have an excellent overall safety profile, but potential adverse effects, including skin staining, infusion-related reactions and hypophosphataemia, have been described. Knowledge of differences in administration and safety profiles of currently available iron formulations will allow appropriate prescription, counselling, as well as recognition and management of adverse events in patients requiring intravenous iron.

Are serious games seriously good at preparing students for clinical practice?: A randomized controlled trial.

PURPOSE: Serious games (SGs) have great potential for pediatric medical education. This study evaluated the efficacy of a SG in improving learner satisfaction, knowledge, and behavior. MATERIALS AND METHODS: This was an investigator-blinded randomized controlled trial (RCT) comparing a SG against two controls: (i) adaptive tutorial (AT), and (ii) low-stimulus control (LSC). SG is a highly immersive role-playing game in a virtual hospital. AT delivers interactive web-based lessons. LSC is paper-based clinical practice guidelines. Metropolitan senior medical students at UNSW were eligible. A total of 154 enrolled and were block randomized to one intervention. Participants had access to one intervention for 8 weeks which taught pediatric acute asthma and seizure assessment and management. Satisfaction was assessed with Likert-scale responses to 5 statements and 2 free-text comments. Knowledge was assessed with 10 multiple-choice questions (MCQs). Clinical behavior was assessed during a 30-point simulated clinical management scenario (CMS). Primary analysis was performed on a modified intention-to-treat basis and compared: (1) SG vs. AT; and (2) SG vs. LSC. RESULTS: A total of 118 participants were included in the primary analysis (modified intention-to-treat model). No significant differences in MCQ results between the SG and control groups. SG group outperformed the LSC group in the CMS, with a moderate effect (score out of 30: 20.8 (3.2) vs. 18.7 (3.2), respectively, d = 0.65 (0.2-1.1), p = 0.005). No statistically significant difference between SG and AT groups in the CMS (score: 20.8 (3.2) vs. 19.8 (3.1), respectively, d = 0.31 (-0.1 to 0.8), p = 0.18). A sensitivity analysis (per-protocol model) was performed with similar outcomes. CONCLUSIONS: This is the first investigator-blinded RCT assessing the efficacy of a highly immersive SG on learner attitudes, knowledge acquisition, and performance in simulated pediatric clinical scenarios. The SG demonstrated improved translation of knowledge to a simulated clinical environment, particularly compared to LSC. SGs show promise in pediatric medical education.

Anaerobic Microbiota Derived from the Upper Airways Impact Staphylococcus aureus Physiology.

Staphylococcus aureus is associated with the development of persistent and severe inflammatory diseases of the upper airways. Yet, S. aureus is also carried asymptomatically in the sinonasal cavity of ∼50% of healthy adults. The causes of this duality and host and microbial factors that tip the balance between S. aureus pathogenesis and commensalism are poorly understood. We have shown that by degrading mucins, anaerobic microbiota support the growth of airway pathogens by liberating metabolites that are otherwise unavailable. Given the widely reported culture-based detection of anaerobes from individuals with chronic rhinosinusitis (CRS), here we tested our hypothesis that CRS microbiota is characterized by a mucin-degrading phenotype that alters S. aureus physiology. Using 16S rRNA gene sequencing, we indeed observed an increased prevalence and abundance of anaerobes in CRS relative to non-CRS controls. PICRUSt2-based functional predictions suggested increased mucin degradation potential among CRS microbiota that was confirmed by direct enrichment culture. Prevotella, Fusobacterium, and Streptococcus comprised a core mucin-degrading community across CRS subjects that generated a nutrient pool that augmented S. aureus growth on mucin as a carbon source. Finally, using transcriptome sequencing (RNA-seq), we observed that S. aureus transcription is profoundly altered in the presence of mucin-derived metabolites, though expression of several key metabolism- and virulence-associated pathways varied between CRS-derived bacterial communities. Together, these data support a model in which S. aureus metabolism and virulence in the upper airways are dependent upon the composition of cocolonizing microbiota and the metabolites they exchange.

A real-life comparative effectiveness study into the addition of antibiotics to the management of asthma exacerbations in primary care.

BACKGROUND: Asthma exacerbations are major contributors to asthma morbidity and mortality. They are usually managed with bronchodilators and oral corticosteroids (OCS), but clinical trial evidence suggests that antibiotics could be beneficial. We aimed to assess whether treatment of asthma exacerbations with antibiotics in addition to OCS improved outcomes in larger, more representative routine-care populations. METHOD: A retrospective comparative effectiveness study into managing asthma exacerbations with OCS alone versus OCS plus antibiotics was conducted using the Optimum Patient Care Research Database. The dataset included 28 637 patients; following propensity score matching 20 024 adults and 4184 children were analysed. RESULTS: Antibiotics in addition to OCS were prescribed for the treatment of asthma exacerbations in 45% of adults and 32% of children. Compared to OCS alone, OCS plus antibiotics was associated with reduced risk of having an asthma/wheeze consultation in the following 2 weeks (children hazard ratio (HR) 0.84 (95% CI 0.73-0.96), p=0.012; adults HR 0.86 (95% CI 0.81-0.91), p<0.001), but an increase in risk of a further OCS prescription for a new/ongoing exacerbation within 6 weeks in adults (HR 1.11 (95% CI 1.01-1.21), p=0.030), but not children. Penicillins, but not macrolides, were associated with a reduction in the odds of a subsequent asthma/wheeze consultation compared to OCS alone, in both adults and children. CONCLUSION: Antibiotics were frequently prescribed in relation to asthma exacerbations, contrary to guideline recommendations. Overall, the routine addition of antibiotics to OCS in the management of asthma exacerbations appeared to confer little clinical benefit, especially when considering the risks of antibiotic overuse.

Withdrawal of inhaled corticosteroids versus continuation of triple therapy in patients with COPD in real life: observational comparative effectiveness study.

BACKGROUND: Inhaled corticosteroids (ICS) are indicated for prevention of exacerbations in patients with COPD, but they are frequently overprescribed. ICS withdrawal has been recommended by international guidelines in order to prevent side effects in patients in whom ICS are not indicated. METHOD: Observational comparative effectiveness study aimed to evaluate the effect of ICS withdrawal versus continuation of triple therapy (TT) in COPD patients in primary care. Data were obtained from the Optimum Patient Care Research Database (OPCRD) in the UK. RESULTS: A total of 1046 patients who withdrew ICS were matched 1:4 by time on TT to 4184 patients who continued with TT. Up to 76.1% of the total population had 0 or 1 exacerbation the previous year. After controlling for confounders, patients who discontinued ICS did not have an increased risk of moderate or severe exacerbations (adjusted HR: 1.04, 95% confidence interval (CI) 0.94-1.15; p = 0.441). However, rates of exacerbations managed in primary care (incidence rate ratio (IRR) 1.33, 95% CI 1.10-1.60; p = 0.003) or in hospital (IRR 1.72, 95% CI 1.03-2.86; p = 0.036) were higher in the cessation group. Unsuccessful ICS withdrawal was significantly and independently associated with more frequent courses of oral corticosteroids the previous year and with a blood eosinophil count ≥ 300 cells/µL. CONCLUSIONS: In this primary care population of patients with COPD, composed mostly of infrequent exacerbators, discontinuation of ICS from TT was not associated with an increased risk of exacerbation; however, the subgroup of patients with more frequent courses of oral corticosteroids and high blood eosinophil counts should not be withdrawn from ICS. Trial registration European Network of Centres for Pharmacoepidemiology and Pharmacovigilance (EUPAS30851).

Co-occurrence of Anaerobes in Human Chronic Wounds.

Chronic wounds are wounds that have failed to heal after 3 months of appropriate wound care. Previous reports have identified a diverse collection of bacteria in chronic wounds, and it has been postulated that bacterial profile may contribute to delayed healing. The purpose of this study was to perform a microbiome assessment of the Wound Healing and Etiology (WE-HEAL) Study cohort, including underlying comorbidities less commonly studied in the context of chronic wounds, such as autoimmune diseases, and investigate possible relationships of the wound microbiota with clinical healing trends. We examined chronic wound specimens from 60 patients collected through the WE-HEAL Study using 16S ribosomal RNA gene sequencing. A group of co-occurring obligate anaerobes was identified from taxonomic analysis guided by Dirichlet multinomial mixtures (DMM) modeling. The group includes members of the Gram-positive anaerobic cocci (GPAC) of the Clostridia class (i.e., Anaerococcus, Finegoldia, and Peptoniphilus) and additional strict anaerobes (i.e., Porphyromonas and Prevotella). We showed that the co-occurring group of obligate anaerobes not only co-exists with commonly identified wound species (such as Staphylococcus aureus, Staphylococcus epidermidis, Pseudomonas, Corynebacterium, and Streptococcus), but importantly, they could also predominate the wound microbiota. Furthermore, examination of clinical comorbidities of the WE-HEAL specimens showed that specific obligate and facultative anaerobes were significantly reduced in wounds presented with autoimmune disease. With respect to future healing trends, no association with the wound microbiome community or the abundance of individual wound species could be established. In conclusion, we identified a co-occurring obligate anaerobic community type that predominated some human chronic wounds and underrepresentation of anaerobes in wounds associated with autoimmune diseases. Possible elucidation of host environments or key factors that influence anaerobe colonization warrants further investigation in a larger cohort.

Glucose and lactate as metabolic constraints on presynaptic transmission at an excitatory synapse.

KEY POINTS: Synapses have high energy demands which increase during intense activity. We show that presynaptic terminals can utilise extracellular glucose or lactate to generate energy to maintain synaptic transmission. Reducing energy substrates induces a metabolic stress: presynaptic ATP depletion impaired synaptic transmission through a reduction in the number of functional synaptic vesicle release sites and a slowing of vesicle pool replenishment, without a consistent change in release probability. Metabolic function is compromised in many pathological conditions (e.g. stroke, traumatic brain injury and neurodegeneration). Knowledge of how synaptic transmission is constrained by metabolic stress, especially during intense brain activity, will provide insights to improve cognition following pathological insults. ABSTRACT: The synapse has high energy demands, which increase during intense activity. Presynaptic ATP production depends on substrate availability and usage will increase during activity, which in turn could influence transmitter release and information transmission. We investigated transmitter release at the mouse calyx of Held synapse using glucose or lactate (10, 1 or 0 mm) as the extracellular substrates while inducing metabolic stress. High-frequency stimulation (HFS) and recovery paradigms evoked trains of EPSCs monitored under voltage-clamp. Whilst postsynaptic intracellular ATP was stabilised by diffusion from the patch pipette, depletion of glucose increased EPSC depression during HFS and impaired subsequent recovery. Computational modelling of these data demonstrated a reduction in the number of functional release sites and slowed vesicle pool replenishment during metabolic stress, with little change in release probability. Directly depleting presynaptic terminal ATP impaired transmitter release in an analogous manner to glucose depletion. In the absence of glucose, presynaptic terminal metabolism could utilise lactate from the aCSF and this was blocked by inhibition of monocarboxylate transporters (MCTs). MCT inhibitors significantly suppressed transmission in low glucose, implying that lactate is a presynaptic substrate. Additionally, block of glycogenolysis accelerated synaptic transmission failure in the absence of extracellular glucose, consistent with supplemental supply of lactate by local astrocytes. We conclude that both glucose and lactate support presynaptic metabolism and that limited availability, exacerbated by high-intensity firing, constrains presynaptic ATP, impeding transmission through a reduction in functional presynaptic release sites as vesicle recycling slows when ATP levels are low.

Trends of testing for and diagnosis of α1-antitrypsin deficiency in the UK: more testing is needed.

α1-antitrypsin deficiency (AATD) significantly increases the risk of developing chronic obstructive pulmonary disease (COPD), and testing of all COPD patients for AATD is recommended by the World Health Organization, European Respiratory Society and Global Initiative for Chronic Obstructive Lung Disease (GOLD). We aimed to determine trends for testing and diagnosing AATD from 1990 to 2014.This study analysed all patients diagnosed with COPD from about 550 UK Optimum Patient Care Research Database general practices, including a subgroup of those diagnosed before the age of 60 years.We identified 107 024 COPD individuals, of whom 29 596 (27.6%) were diagnosed before 60 years of age. Of them, only 2.2% (95% CI 2.09-2.43%) had any record of being tested for AATD. Of those tested, 23.7% (95% CI 20.5-27.1%) were diagnosed with AATD. Between 1994 and 2013 the incidence of AATD diagnosis generally increased. A diagnosis of AATD was associated with being male, being an ex-smoker, more severe COPD with a lower forced expiratory volume in 1 s % pred and higher GOLD 2017 stages (all p<0.05).Despite an increase in the frequency of AATD testing since 1990, only 2.2% of patients diagnosed with COPD before the age of 60 years were tested. AATD prevalence was 23.7% in those tested. Thus, it appears that AATD remains markedly underdiagnosed in COPD patients.

The TEACHH model to predict life expectancy in patients presenting for palliative spine radiotherapy: external validation and comparison with alternate models.

INTRODUCTION: The TEACHH score was developed to identify patients with predicted short (< 3 months) and long (> 1 year) life expectancy. We aimed to validate this model in an independent group of patients presenting for palliative spine radiotherapy and to compare it to alternate prognostic models. METHODS: We retrospectively reviewed charts of 195 consecutive patients referred for palliative spine radiotherapy. Patients were grouped according to the number of risk factors from the TEACHH model, Chow model, and Oswestry Risk Index. RESULTS: One hundred and eighty patients with a median age of 65 years were included. Follow-up was 5.8 months in all patients and 31.8 months in living patients. For the TEACHH model, patients in groups 1, 2, and 3 had a median (95% CI) overall survival (OS) of 22.3 (15.7-36.1), 4.9 (3.8-6.6), and 1.5 (0.8-5.4) months, respectively. Wilcoxon pairwise comparisons showed statistically different survival between groups 1 and 2, and 1 and 3. In the Chow model, patients in groups 1, 2, and 3 had a median (95% CI) OS of 16.1 (10.0-22.3), 5.9 (3.8-9.2), and 1.9 (1.2-2.5) months, respectively. There was a significant difference between all groups. The Oswestry Risk Index identified five prognostic groups with median OS (95% CI) ranging from 22.2 (12.9-30.2) to 2.1 (0.8-4.0) months. Only group 1 was statistically different from the others. Although the effect of age was small, the TEACHH model performed best with the inclusion of all parameters. CONCLUSIONS: The TEACHH model is useful to identify patients with spinal metastases with predicted short, intermediate, and long LE. Its prognostic ability is similar to the Chow model.

Periplasmic Binding Protein Dimer Has a Second Allosteric Event Tied to Ligand Binding.

The ligand-induced conformational changes of periplasmic binding proteins (PBP) play a key role in the acquisition of metabolites in ATP binding cassette (ABC) transport systems. This conformational change allows for differential recognition of the ligand occupancy of the PBP by the ABC transporter. This minimizes futile ATP hydrolysis in the transporter, a phenomenon in which ATP hydrolysis is not coupled to metabolite transport. In many systems, the PBP conformational change is insufficient at eliminating futile ATP hydrolysis. Here we identify an additional state of the PBP that is also allosterically regulated by the ligand. Ligand binding to the homodimeric apo PBP leads to a tightening of the interface α-helices so that the hydrogen bonding pattern shifts to that of a 310 helix, in-turn altering the contacts and the dynamics of the protein interface so that the monomer exists in the presence of ligand.

Selective oral ROCK2 inhibitor down-regulates IL-21 and IL-17 secretion in human T cells via STAT3-dependent mechanism.

Rho-associated kinase 2 (ROCK2) regulates the secretion of proinflammatory cytokines and the development of autoimmunity in mice. Data from a phase 1 clinical trial demonstrate that oral administration of KD025, a selective ROCK2 inhibitor, to healthy human subjects down-regulates the ability of T cells to secrete IL-21 and IL-17 by 90% and 60%, respectively, but not IFN-γ in response to T-cell receptor stimulation in vitro. Pharmacological inhibition with KD025 or siRNA-mediated inhibition of ROCK2, but not ROCK1, significantly diminished STAT3 phosphorylation and binding to IL-17 and IL-21 promoters and reduced IFN regulatory factor 4 and nuclear hormone RAR-related orphan receptor γt protein levels in T cells derived from healthy subjects or rheumatoid arthritis patients. Simultaneously, treatment with KD025 also promotes the suppressive function of regulatory T cells through up-regulation of STAT5 phosphorylation and positive regulation of forkhead box p3 expression. The administration of KD025 in vivo down-regulates the progression of collagen-induced arthritis in mice via targeting of the Th17-mediated pathway. Thus, ROCK2 signaling appears to be instrumental in regulating the balance between proinflammatory and regulatory T-cell subsets. Targeting of ROCK2 in man may therefore restore disrupted immune homeostasis and have a role in the treatment of autoimmunity.

Electrochemical detection of Pseudomonas in wound exudate samples from patients with chronic wounds.

In clinical practice, point-of-care diagnostic testing has progressed rapidly in the last decade. For the field of wound care, there is a compelling need to develop rapid alternatives for bacterial identification in the clinical setting, where it generally takes over 24 hours to receive a positive identification. Even new molecular and biochemical identification methods require an initial incubation period of several hours to obtain a sufficient number of cells prior to performing the analysis. Here we report the use of an inexpensive, disposable electrochemical sensor to detect pyocyanin, a unique, redox-active quorum sensing molecule released by Pseudomonas aeruginosa, in wound fluid from patients with chronic wounds enrolled in the WE-HEAL Study. By measuring the metabolite excreted by the cells, this electrochemical detection strategy eliminates sample preparation, takes less than a minute to complete, and requires only 7.5 µL of sample to complete the analysis. The electrochemical results were compared against 16S rRNA profiling using 454 pyrosequencing. Blind identification yielded 9 correct matches, 2 false negatives, and 3 false positives giving a sensitivity of 71% and specificity of 57% for detection of Pseudomonas. Ongoing enhancement and development of this approach with a view to develop a rapid point-of-care diagnostic tool is planned.

Pediatric Cardiac Intensive Care Society 2014 Consensus Statement: Pharmacotherapies in Cardiac Critical Care: Sedation, Analgesia and Muscle Relaxant.

OBJECTIVE: This article reviews pharmacotherapies currently available to manage sedation, analgesia, and neuromuscular blockade for pediatric cardiac critical patients. DATA SOURCES: The knowledge base of an expert panel of pharmacists, cardiac anesthesiologists, and a cardiac critical care physician involved in the care of pediatric cardiac critical patients was combined with a comprehensive search of the medical literature to generate the data source. STUDY SELECTION: The panel examined all studies relevant to management of sedation, analgesia, and neuromuscular blockade in pediatric cardiac critical patients. DATA EXTRACTION: Each member of the panel was assigned a specific subset of the studies relevant to their particular area of expertise (pharmacokinetics, pharmacodynamics, and clinical care) to review and analyze. DATA SYNTHESIS: The panel members each crafted a comprehensive summary of the literature relevant to their area of expertise. The panel, as a whole, then collaborated to cohesively summarize all the available, relevant literature. CONCLUSIONS: In the cardiac ICU, management of the cardiac patient requires an individualized sedative and analgesic strategy that maintains hemodynamic stability. Multiple pharmacological therapies exist to achieve these goals and should be selected based on the patient's underlying physiology, hemodynamic vulnerabilities, desired level of sedation and analgesia, and the projected short- or long-term recovery trajectory.

Real-time sharing and expression of migraine headache suffering on Twitter: a cross-sectional infodemiology study.

BACKGROUND: Although population studies have greatly improved our understanding of migraine, they have relied on retrospective self-reports that are subject to memory error and experimenter-induced bias. Furthermore, these studies also lack specifics from the actual time that attacks were occurring, and how patients express and share their ongoing suffering. OBJECTIVE: As technology and language constantly evolve, so does the way we share our suffering. We sought to evaluate the infodemiology of self-reported migraine headache suffering on Twitter. METHODS: Trained observers in an academic setting categorized the meaning of every single "migraine" tweet posted during seven consecutive days. The main outcome measures were prevalence, life-style impact, linguistic, and timeline of actual self-reported migraine headache suffering on Twitter. RESULTS: From a total of 21,741 migraine tweets collected, only 64.52% (14,028/21,741 collected tweets) were from users reporting their migraine headache attacks in real-time. The remainder of the posts were commercial, re-tweets, general discussion or third person's migraine, and metaphor. The gender distribution available for the actual migraine posts was 73.47% female (10,306/14,028), 17.40% males (2441/14,028), and 0.01% transgendered (2/14,028). The personal impact of migraine headache was immediate on mood (43.91%, 6159/14,028), productivity at work (3.46%, 486/14,028), social life (3.45%, 484/14,028), and school (2.78%, 390/14,028). The most common migraine descriptor was "Worst" (14.59%, 201/1378) and profanity, the "F-word" (5.3%, 73/1378). The majority of postings occurred in the United States (58.28%, 3413/5856), peaking on weekdays at 10:00h and then gradually again at 22:00h; the weekend had a later morning peak. CONCLUSIONS: Twitter proved to be a powerful source of knowledge for migraine research. The data in this study overlap large-scale epidemiological studies, avoiding memory bias and experimenter-induced error. Furthermore, linguistics of ongoing migraine reports on social media proved to be highly heterogeneous and colloquial in our study, suggesting that current pain questionnaires should undergo constant reformulations to keep up with modernization in the expression of pain suffering in our society. In summary, this study reveals the modern characteristics and broad impact of migraine headache suffering on patients' lives as it is spontaneously shared via social media.

3D-Printed Model in Preoperative Planning of Sciatic Nerve Decompression Because of Heterotopic Ossification: A Case Report.

CASE: A 31-year-old patient presented with an encapsulated sciatic nerve secondary to extensive hip heterotopic ossification (HO), which prevented visualization of a safe osteotomy site to avoid nerve damage. The 3D-printed model demonstrated an easily identifiable osseous reference point along the inferior aspect of the heterotopic mass, allowing for a vertical osteotomy to be safely performed. CONCLUSION: HO is associated with loss of normal anatomic topography. The current case report illustrates the use of a 3D-printed model to identify pertinent anatomic landmarks required for safe decompression of an encapsulated sciatic nerve within the anatomic region of the hip.

Dopamine-resistant hypotension and severe retinopathy of prematurity.

OBJECTIVE: To examine the relationship between the cause or severity of hypotension and the development of severe ROP (sROP) (≥stage 3 or stage 2 with plus disease in zone I or II). STUDY DESIGN: Infants (<28 weeks' gestation, n = 242) were observed for hypotension and treated with a standardized hypotension-treatment protocol. Hypotension was classified as resulting from one of the following causes: (1) culture-positive infection and/or necrotizing enterocolitis; (2) patent ductus arteriosus ligation; or (3) "idiopathic" (no cause identified other than prematurity), and as being either dopamine responsive or dopamine resistant. Cortisol levels were measured for infants with dopamine-resistant hypotension. Eye examinations were performed until the retinopathy of prematurity resolved or the vasculature matured. Multivariable logistic regression analysis was performed to determine the relationship between the cause/severity of hypotension and sROP. RESULTS: Overall, 66% of infants developed hypotension (41% were dopamine responsive and 25% were dopamine resistant). sROP developed in 19% of infants. "Idiopathic" dopamine-resistant hypotension was the only cause significantly related to sROP. Of the infants with dopamine-resistant hypotension, 66% had low serum cortisol (≤10 µg/dL). Low cortisol, in the presence of dopamine-resistant hypotension, was significantly associated with sROP and accounted for the relationship between "idiopathic" hypotension and sROP. When low cortisol was included in statistical models, other known risk factors, such as immature gestation, were no longer significantly related to sROP. CONCLUSION: Low cortisol, in the presence of dopamine-resistant hypotension, has the greatest magnitude of association with sROP.