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A 37-year-old man developed persistent hemoptysis after sustaining a gunshot wound to the right shoulder and lung. A right upper lobectomy was performed, in which Aspergillus species microorganisms were identified within retained bullet fragments. The role of infected bullet fragments in the pathogenesis of hemoptysis in this patient is discussed.

Genome-wide platelet transcriptomics is increasingly used to uncover new aspects of platelet biology and as a diagnostic and prognostic tool. Nevertheless, platelet isolation methods for transcriptomic studies are not standardized, introducing challenges for cross-study comparisons, data integration, and replication. In this prospective multicenter study, called "Standardizing Platelet Transcriptomics for Discovery, Diagnostics, and Therapeutics in the Thrombosis and Hemostasis Community (STRIDE)" by the International Society on Thrombosis and Haemostasis Scientific and Standardization Committees, we assessed how 3 of the most commonly used platelet isolation protocols influence metrics from next-generation bulk RNA sequencing and functional assays. Compared with washing alone, more stringent removal of leukocytes by anti-CD45 beads or PALL filters resulted in a sufficient quantity of RNA for next-generation sequencing and similar quality of RNA sequencing metrics. Importantly, stringent removal of leukocytes resulted in the lower relative expression of known leukocyte-specific genes and the higher relative expression of known platelet-specific genes. The results were consistent across enrolling sites, suggesting that the techniques are transferrable and reproducible. Moreover, all 3 isolation techniques did not influence basal platelet reactivity, but agonist-induced integrin αIIbβ 3 activation is reduced by anti-CD45 bead isolation compared with washing alone. In conclusion, the isolation technique chosen influences genome-wide transcriptional and functional assays in platelets. These results should help the research community make informed choices about platelet isolation techniques in their own platelet studies., Competing Interests: Declaration of competing interests M.T.R. reports patents pending or issued on using platelet transcriptomics. All other authors have no conflicts to declare., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: Coronavirus disease 2019 (COVID-19) is associated with derangement in biomarkers of coagulation and endothelial function and has been likened to the coagulopathy of sepsis. However, clinical laboratory metrics suggest key differences in these pathologies. We sought to determine whether plasma coagulation and fibrinolytic potential in patients with COVID-19 differ compared with healthy donors and critically ill patients with sepsis. Approach and Results: We performed comparative studies on plasmas from a single-center, cross-sectional observational study of 99 hospitalized patients (46 with COVID-19 and 53 with sepsis) and 18 healthy donors. We measured biomarkers of endogenous coagulation and fibrinolytic activity by immunoassays, thrombin, and plasmin generation potential by fluorescence and fibrin formation and lysis by turbidity. Compared with healthy donors, patients with COVID-19 or sepsis both had elevated fibrinogen, d-dimer, soluble TM (thrombomodulin), and plasmin-antiplasmin complexes. Patients with COVID-19 had increased thrombin generation potential despite prophylactic anticoagulation, whereas patients with sepsis did not. Plasma from patients with COVID-19 also had increased endogenous plasmin potential, whereas patients with sepsis showed delayed plasmin generation. The collective perturbations in plasma thrombin and plasmin generation permitted enhanced fibrin formation in both COVID-19 and sepsis. Unexpectedly, the lag times to thrombin, plasmin, and fibrin formation were prolonged with increased disease severity in COVID-19, suggesting a loss of coagulation-initiating mechanisms accompanies severe COVID-19., Conclusions: Both COVID-19 and sepsis are associated with endogenous activation of coagulation and fibrinolysis, but these diseases differently impact plasma procoagulant and fibrinolytic potential. Dysregulation of procoagulant and fibrinolytic pathways may uniquely contribute to the pathophysiology of COVID-19 and sepsis.

Case Description: A 1-year-old male eclectus parrot ( Eclectus roratus ) with a 3- to 4-month history of blepharospasm in the right eye was referred to a veterinary medical teaching hospital for further evaluation. Conventional medical treatments had been ineffective. The referring avian specialist had plucked a suspected ectopic feather from the right eye 6 weeks prior to the referral evaluation., Clinical Findings: The parrot was sedated, and ophthalmic examination of the right eye with slit-lamp biomicroscopy revealed a 3 × 2 × 2-mm raised vascular mass with a focally pigmented center associated with the temporal aspect of the leading edge of the third eyelid. No abnormalities were detected in the left eye., Treatment and Outcome: The parrot was anesthetized, and the right eye mass was excised and submitted for histologic examination. Histologically, there was a single pigmented feather follicle bulb surrounded by multiple discrete lymphoid follicles and moderate lymphoplasmacytic inflammation within the substantia propria of the third eyelid conjunctiva. The histologically normal feather follicle in an abnormal location classified the lesion as a choristoma. Nine months after surgery, the parrot had no signs of ocular discomfort and no overt regrowth of the feather follicle., Clinical Relevance: For the eclectus parrot of this report, a lesion caused by normal differentiation of an ectopic feather follicle in the right third eyelid was successfully treated. A third eyelid choristoma appears to be a hitherto unreported pathological finding in avian species. Although rare, the presence of a choristoma should be considered as a differential diagnosis for birds with blepharospasm.

Coagulation Factor XI (FXI) contributes to the pathobiology of sepsis-associated thrombosis and is a target for new therapeutics. Through cleavage of disulfide bonds, FXI becomes reduced (rFXI), accelerating intrinsic coagulation cascade activation. The role of rFXI in human sepsis has never been studied. We determined levels of total FXI and rFXI in critically-ill septic patients with and without overt disseminated intravascular coagulation (DIC, a dysregulated pro-thrombotic condition). Total FXI and rFXI plasma levels were measured on ICU admission in prospectively enrolled septic patients (n = 32) from three academic medical centers and matched, healthy controls (n = 15). In septic patients, hematologic and physiologic parameters and pathological thrombosis (presence or absence of overt DIC) were determined. rFXI was higher in septic patients than controls (p < 0.05). In septic patients, rFXI was significantly associated with platelet count (r = 0.3511, p < 0.05) and APACHE II score (r = - 0.359, p < 0.05), indices of illness severity. rFXI was lower in patients with overt DIC (p = 0.088), suggesting a consumptive coagulopathy. In contrast, while total FXI levels were reduced in sepsis, they failed to correlate with illness severity, thrombosis, or hematologic parameters. We establish, for the first time, that rFXI is increased in patients with sepsis and correlates with illness severity (APACHE II score and platelet count) and pathological coagulopathy (overt DIC). Total FXI levels, in contrast, are decreased in sepsis but fail to associate with any indices. These findings suggest that rFXI has unique activity in human sepsis.

The timely management of diabetic ketoacidosis (DKA) is essential to avoid lengthy hospitalizations and poor clinical outcomes. There is often an absence of ownership for glycemic management in hospitalized patients, most notably in those with a diagnosis other than diabetes. Evidence supports the use of evidence-based DKA protocols. The purpose of this project was to determine whether utilization of an evidence-based order set versus an individualized provider approach for the treatment and management of DKA decreases resolution time and occurrences of hypoglycemia and improves clinical outcomes. Preintervention and postintervention retrospective reviews of the electronic medical record of 150 nonpregnant adult patients diagnosed with DKA allowed retrieval of relevant outcome data. Multiple events provided an intensive orientation and development of health care professionals for a systems approach to utilization of the evidence-based order set. Implementation of the institutionally approved evidence-based order set affirmed anticipated outcomes. Results showed improvements in the (a) total length of stay, (b) arrival to intravenous fluid time, (c) intravenous insulin initiation to discontinuation (resolution) time, (d) arrival to subcutaneous insulin administration time, (e) time from initial to sequential laboratory testing, (f) use of a basal, prandial, and correction insulin approach (physiological mimic), and (g) the incidence of hypoglycemia. Outcomes substantiate the importance and need for maintaining an evidence-based and systems approach for the management of DKA.

Human tumors, including gastric cancer, frequently express high levels of epidermal growth factor receptors (EGFRs), which are associated with a poor prognosis. Targeted delivery of anticancer drugs to cancerous tissues shows potential in sparing unaffected tissues. However, it has been a major challenge for drug penetration in solid tumor tissues due to the complicated tumor microenvironment. We have constructed a recombinant protein named anti-EGFR-iRGD consisting of an anti-EGFR VHH (the variable domain from the heavy chain of the antibody) fused to iRGD, a tumor-specific binding peptide with high permeability. Anti-EGFR-iRGD, which targets EGFR and αvβ3, spreads extensively throughout both the multicellular spheroids and the tumor mass. The recombinant protein anti-EGFR-iRGD also exhibited antitumor activity in tumor cell lines, multicellular spheroids, and mice. Moreover, anti-EGFR-iRGD could improve anticancer drugs, such as doxorubicin (DOX), bevacizumab, nanoparticle permeability and efficacy in multicellular spheroids. This study draws attention to the importance of iRGD peptide in the therapeutic approach of anti-EGFR-iRGD. As a consequence, anti-EGFR-iRGD could be a drug candidate for cancer treatment and a useful adjunct of other anticancer drugs., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Purpose: The Frederick Restaurant Challenge is an innovative project based on a collaborative effort among community organizations and partners designed to offer delicious healthful meal options at local restaurants during the month of November for American Diabetes Month. Local restaurants were challenged to participate and submitted recipes for healthful meals to the Frederick County Diabetes Coalition for review by registered dietitians. Diners voted on meals to determine the challenge winner(s), and were eligible to win prizes as well. Publicity prior to and during the month was effective in creating positive news about healthful meals when eating out, raised awareness about diabetes, and provided restaurants with desirable advertising opportunities. Feedback from restaurants and diners was overwhelmingly positive. The purpose of this article is to describe this successful low-budget project to encourage its replication in local communities., Conclusions: The Frederick Restaurant Challenge proved to be a very successful, innovative, low-budget project that met its intended goals: to develop healthful meal options for people with diabetes (or for anyone wishing to eat healthier); to demonstrate that healthful food can taste delicious; and to encourage restaurants to continue offering healthful options on their menus beyond the challenge month. Community interventions such as the Frederick Restaurant Challenge offer unique and important strategies for affecting change and raising awareness not only for people with diabetes but also for the entire community.

The actions of sodium 4-hydroxybutyrate, gamma-aminobutyric acid and meprobamate have been studied in unanaesthetized animals, in local anaesthetic tests, on isolated organ preparations, on convulsions induced by picrotoxin and strychnine, and on monosynaptic (patellar) and polysynaptic (plantar) reflexes of the spinal cord. Sodium 4-hydroxybutyrate induced a sleep-like state with three unusual features: the righting reflex was remarkably persistent, respiration was good throughout and recovery was abrupt. gamma-Aminobutyric acid was inactive and meprobamate caused flaccid paralysis with loss of the righting reflex. None of the agents affected the responses of the rat diaphragm either to direct stimulation of the muscle or to indirect stimulation through the phrenic nerve. Only meprobamate reduced the responses of theguinea-pig isolated ileum preparation, showed local anaesthetic action and had an anticonvulsant action. All three compounds were capable, after intravenous or topical application, of blocking plantar reflexes in doses which did not affect the patellar reflex. The spinal animal responded in the same way, to the same dose of sodium 4-hydroxybutyrate, as the decerebrate preparation. Topical application to the motor cortex had no effect on spinal reflexes. We conclude that sodium 4-hydroxybutyrate acts preferentially on the internuncial neurones in the spinal cord but differs from meprobamate in its other actions. The similarity between the actions of sodium 4-hydroxybutyrate and of gamma-aminobutyric acid provides furtherevidence in support of the hypothesis that sodium 4-hydroxybutyrate is involved in the gamma-aminobutyric acid metabolic pathways.

The analgesic potency of a series of new compounds related to pethidine has been measured in rats. The replacement of the methyl group on the nitrogen atom of pethidine by groups containing ether linkages produces an increase in potency. Two different positions for the oxygen atom are particularly beneficial, but the effects, in these two positions, appear to be exerted in different ways and are not additive. Simple toxicity tests in mice and rats and tests on respiration in rats of five of the more potent compounds revealed no unexpected adverse action.

In confirmation of the results of Croxatto and his co-workers, plasma proteins incubated with pepsin yielded a substance (pepsitensin) with pressor activity. Euglobulin gave a much higher yield than the other plasma protein fractions. Incubation for 4 hr at pH 4 gave high yields of pressor activity (pepsitensin) but no antidiuretic activity; incubation of euglobulin for 4 hr at pH 2.5 yielded extracts with antidiuretic as well as pressor activity. Incubation for 8 to 11 hr at pH 2.5 produced the highest yield of both activities. Further incubation, at the same pH, up to 20 hr caused a rapid decline in the pressor activity of the extracts, but the antidiuretic activity was much more resistant to destruction by pepsin. Pepsitensin was found to be very soluble in water and poorly soluble in organic solvents. It is not inactivated by thioglycollate. In blood pressure assays some animals did not respond to pepsitensin, and nephrectomized (17 to 24 hr) rats were found to be more suitable preparations. Pepsitensin was shown to exert pressor effect by direct action on the blood vessels. Its pressor action could be differentiated from that of tyramine, dimethylphenylpiperazine, nicotine, noradrenaline and Pitressin but not from that of angiotensin. The isolated guinea-pig ileum and the rat uterus were equally sensitive to angiotensin and pepsitensin. In paper chromatograms, in the solvent system butanol-acetic acid-water, the R(F) of pepsitensin was very similar to that of angiotensin.