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Abstract Patients with cancer have many psychosocial needs, some of which may be addressed by implementation of a screening tool. However, it is unknown what ultimately happens (i.e., the “care cascade”) to patients following these interventions. The objective of this study was to evaluate the care cascade for patients following the implementation of a psychosocial needs screening tool. This was a prospective cohort study conducted at a university hospital radiation oncology clinic. Participants who were 18 years or older and presenting for their initial radiation oncology appointment were asked to complete a screening survey. From December 2019 to January 2021, 242 patients completed the survey. 70% of patients were seen for consideration of definitive therapy. 62% of patients checked “yes” to at least one item, most commonly supportive/palliative care (33%), exercise/PT (26%) and advance care planning (26%). Among definitive patients, the most common were supportive/palliative care (33%) and exercise/PT (26%). Among palliative patients, the most common were supportive/palliative care (42%) and advance care planning (32%). Participants were followed for 6 months after taking the survey. 74% of patients with a positive screening survey were contacted by a social worker and/or had a new referral placed with 47% of those patients ultimately attending a new appointment. Screening tools are commonly implemented to quickly identify needs in oncology patients. This study tracked patients following this type of intervention to determine what proportion of patients ultimately received care related to the identified need. Despite the majority of patients being referred to a relevant provider, fewer than half ultimately attended appointments. The combination of a screening tool with social work triage may be an effective way to distribute resources and properly route patients to supportive care providers.

Introduction: The objective of this study was to assess the bi-exponential relaxation times and fractions of the short and long components of the human patellar tendon ex vivo using three-dimensional ultrashort echo time T1ρ (3D UTE-T1ρ) imaging. Materials and Methods: Five cadaveric human knee specimens were scanned using a 3D UTE-T1ρ imaging sequence on a 3T MR scanner. A series of 3D UTE-T1ρ images were acquired and fitted using single-component and bi-component models. Single-component exponential fitting was performed to measure the UTE-T1ρ value of the patellar tendon. Bi-component analysis was performed to measure the short and long UTE-T1ρ values and fractions. Results: The single-component analysis showed a mean single-component UTE-T1ρ value of 8.4 ± 1.7 ms for the five knee patellar tendon samples. Improved fitting was achieved with bi-component analysis, which showed a mean short UTE-T1ρ value of 5.5 ± 0.8 ms with a fraction of 77.6 ± 4.8%, and a mean long UTE-T1ρ value of 27.4 ± 3.8 ms with a fraction of 22.4 ± 4.8%. Conclusion: The 3D UTE-T1ρ sequence can detect the single- and bi-exponential decay in the patellar tendon. Bi-component fitting was superior to single-component fitting.

Irrespective of the reason for hypoperfusion, hypocoagulable and/or hyperfibrinolytic hemostatic aberrancies afflict up to one-quarter of critically ill patients in shock. Intensivists and traumatologists have embraced the concept of SHock-INduced Endotheliopathy (SHINE) as a foundational derangement in progressive shock wherein sympatho-adrenal activation may cause systemic endothelial injury. The pro-thrombotic endothelium lends to micro-thrombosis, enacting a cycle of worsening perfusion and increasing catecholamines, endothelial injury, de-endothelialization, and multiple organ failure. The hypocoagulable/hyperfibrinolytic hemostatic phenotype is thought to be driven by endothelial release of anti-thrombogenic mediators to the bloodstream and perivascular sympathetic nerve release of tissue plasminogen activator directly into the microvasculature. In the shock state, this hemostatic phenotype may be a counterbalancing, yet maladaptive, attempt to restore blood flow against a systemically pro-thrombotic endothelium and increased blood viscosity. We therefore review endothelial physiology with emphasis on glycocalyx function, unique biomarkers, and coagulofibrinolytic mediators, setting the stage for understanding the pathophysiology and hemostatic phenotypes of SHINE in various etiologies of shock. We propose that the hyperfibrinolytic phenotype is exemplified in progressive shock whether related to trauma-induced coagulopathy, sepsis-induced coagulopathy, or post-cardiac arrest syndrome-associated coagulopathy. Regardless of the initial insult, SHINE appears to be a catecholamine-driven entity which early in the disease course may manifest as hyper- or hypocoagulopathic and hyper- or hypofibrinolytic hemostatic imbalance. Moreover, these hemostatic derangements may rapidly evolve along the thrombohemorrhagic spectrum depending on the etiology, timing, and methods of resuscitation. Given the intricate hemochemical makeup and changes during these shock states, macroscopic whole blood tests of coagulative kinetics and clot strength serve as clinically useful and simple means for hemostasis phenotyping. We suggest that viscoelastic hemostatic assays such as thromboelastography (TEG) and rotational thromboelastometry (ROTEM) are currently the most applicable clinical tools for assaying global hemostatic function—including fibrinolysis—to enable dynamic resuscitation with blood products and hemostatic adjuncts for those patients with thrombotic and/or hemorrhagic complications in shock states.

Symptomatic myocarditis is classically featured by a flu-like prodrome, dyspnea on exertion, palpitations, substernal chest pain, and abnormal electrocardiogram (ECG). The clinical diagnosis has often been challenging due to its similarities to acute coronary syndrome. Our case involved a patient who presented with claudication of bilateral lower extremity and ST-segment elevation myocardial infarction (STEMI) in the inferior leads. On cardiac catheterization, nonobstructed coronary arteries with left ventricular ejection fraction (LVEF) of 30% were demonstrated. His clinical presentation was consistent with suspected myocarditis, and he improved with immunosuppression. In addition, his thrombocytopenia and severe symptoms of peripheral neuropathy responded to both immunotherapy and anticoagulation. This case highlights the interplay between history taking, physical examination, and multimodal diagnostic imaging.

Glucosamine (GlcN) is the most widely consumed dietary supplement and exhibits anti-inflammatory effects. However, the influence of GlcN on immune cell generation and function is largely unclear. In this study, GlcN was delivered into mice to examine its biological function in hematopoiesis. We found that GlcN promoted the production of immature myeloid cells, known as myeloid-derived suppressor cells (MDSCs), both in vivo and in vitro. Additionally, GlcN upregulated the expression of glucose transporter 1 in hematopoietic stem and progenitor cells (HSPCs), influenced HSPC functions, and downregulated key genes involved in myelopoiesis. Furthermore, GlcN increased the expression of arginase 1 and inducible nitric oxide synthase to produce high levels of reactive oxygen species, which was regulated by the STAT3 and ERK1/2 pathways, to increase the immunosuppressive ability of MDSCs. We revealed a novel role for GlcN in myelopoiesis and MDSC activity involving a potential link between GlcN and immune system, as well as the new therapeutic benefit.

Abstract Background Weight loss by surgery or lifestyle changes is strongly recommended for obese individuals to improve metabolic health, but the underlying impairments that persist from a history of obesity remain unclear. Recent investigations demonstrate a persistent inflammatory state with weight loss and bariatric surgery, but the mechanism and impact are not fully understood. Additionally, these studies have not been performed in females although women are the majority of individuals undergoing weight loss interventions. Methods The goal of this study was to determine the sex differences in metabolically induced inflammation after dietary weight loss (WL) or bariatric surgery. Following a 60% high-fat diet (HFD) for 12 weeks, C57Bl/6j mice underwent either a dietary switch to normal chow for WL or vertical sleeve gastrectomy (VSG) and were evaluated 8 weeks after intervention. WL effects on myelopoiesis were further evaluated with bone marrow chimeras. Results Both sexes had a decrease in adiposity and total weight following WL or VSG intervention. With HFD, females had very little inflammation and no further increase with WL, but males had persistent inflammation even after WL despite metabolic improvement. Interestingly, after VSG, myeloid inflammation was increased in the livers of males and to a lesser extent in females. Conclusions These studies demonstrate that regardless of sex, it is critical to assess an individuals’ history of obesity rather than just rely on current weight status in medical decision-making. There are long-lasting effects on tissue inflammation in both sexes especially with surgical weight loss. Dietary change is overall most effective to improve meta-inflammation in obese males on its own or in combination with surgical weight loss.

Category: Ankle, Ankle Arthritis, Hindfoot, Midfoot/Forefoot Introduction/Purpose: Augment is the first Food and Drug Administration approved synthetic bone substitute specifically formulated for foot and ankle procedures and have shown results comparable to autograft. Initial studies on the use of Augment for fusion procedures of the foot and ankle are encouraging but there remains a lack of radiographic outcomes on its use. The purposes of this study were to report on the radiographic fusion rate of Augment and identify risk factors for nonunion in patients treated with Augment. Methods: After institutional review board approval, a retrospective study was performed of all patients ages 18-85 who underwent arthrodesis of the ankle, hindfoot, or midfoot and used Augment alone or in combination with autograft and/or allograft. Patients were excluded if they did not have regular radiographic follow-up. Each operative report was examined for procedure performed and location of the foot involved. Post-operative radiographs were reviewed to look at union rate following surgery. Patient charts were reviewed for age, gender, Body Mass Index (BMI), smoking history, and diabetes to examine potential risk factors for nonunion. Continuous variables were reported in means ± standard deviations and differences determined between those that fused and those that did not using a Wilcoxon Rank Sums test. Categorical variables reported as number of patients (percent of patients) and differences determined between those that fused and those that did not using a Fisher’s exact test. Results: A total of 71 patients (average age at injury 57±14 years; 35 males (49%), 36 females (50%); BMI 31±6) underwent 33 (46%) midfoot arthrodesis, 41 (58%) hindfoot arthrodesis, and 27 (38%) ankle arthrodesis. A total of 58 patients (82%) went on to achieve fusion while 13 (18%) did not. There was no difference in gender (p=0.135), age (p=0.345) or BMI (p=0.196) between those who achieved fusion and those who did not. Patients with diabetes had a greater risk of nonunion compared to those who did not (p=0.033) while current smoking status or revision fusion did not pose a risk factor (p=1.000) (Table 1). There were no differences in part of the foot/ankle involved (p=0.445) or bone graft used (p=0.303). Conclusion: This the first study to examine the radiographic follow up of union using Augment. The most important finding of this study is that the rate of fusion in foot and ankle arthrodesis using Augment is near 82%. Diabetes is a risk factor for nonunion when using Augment. Smoking, gender, age, BMI, autograft vs allograft, and part of the foot or ankle fused did not pose a risk factor.

Globally, HIV/AIDS is a leading cause of morbidity worldwide among reproductive-aged cisgender women, highlighting the importance of understanding effects of contraceptives on HIV-1 risk. Some observational studies suggest there may be an increased risk of HIV-1 acquisition among women using the long-acting injectable progestin contraceptive, depo-medroxyprogesterone acetate. The potential mechanism of this susceptibility is unclear. There are few data on the role of the upper female reproductive tract in HIV-1 transmission, and the mechanisms of HIV-1 infection are likely to differ in the upper compared to the lower reproductive tract due to differences in tissue composition and variable effects of sex steroids on mucosal immune cell distribution and activity. In this study, we measured the susceptibility of mucosal immune cells from the upper female reproductive tract to HIV-1 entry using the virion-based HIV-1 fusion assay in samples from healthy female volunteers. We studied 37 infectious molecular clones for their ability to fuse to cells from endometrial biopsies in three participants and found that subtype (B or C) and origin of the virus (transmitted founder or chronic control) had little influence on HIV-1 fusion susceptibility. We studied the effect of contraceptives on HIV-1 susceptibility of immune cells from the cervix, endometrium and peripheral blood by comparing fusion susceptibility in four groups: users of the copper intrauterine device (IUD), levonorgestrel-containing oral contraceptive, levonorgestrel-containing IUD and unexposed controls (n = 58 participants). None of the contraceptives was associated with higher rates of HIV-1 entry into female reproductive tract cells compared to control samples from the mid-luteal phase.

Predators and prey co-evolve, each maximizing their own fitness, but the effects of predator–prey interactions on cellular and molecular machinery are poorly understood. Here, we study this process using the predator Caenorhabditis elegans and the bacterial prey Streptomyces, which have evolved a powerful defense: the production of nematicides. We demonstrate that upon exposure to Streptomyces at their head or tail, nematodes display an escape response that is mediated by bacterially produced cues. Avoidance requires a predicted G-protein-coupled receptor, SRB-6, which is expressed in five types of amphid and phasmid chemosensory neurons. We establish that species of Streptomyces secrete dodecanoic acid, which is sensed by SRB-6. This behavioral adaptation represents an important strategy for the nematode, which utilizes specialized sensory organs and a chemoreceptor that is tuned to recognize the bacteria. These findings provide a window into the molecules and organs used in the coevolutionary arms race between predator and potential prey.

The coagulation system provides a primitive but effective defense against hemorrhage. Soluble fibrinogen (Fg) monomers, composed of α, β and γ chains, are recruited to provide structural support for the formation of a hemostatic plug. Fg binds to platelets and is processed into a cross-linked fibrin polymer by the enzymatic clotting factors, thrombin and Factor XIII (FXIII). The newly formed fibrin-platelet clot can act as barrier to protect against pathogens from entering the bloodstream. Further, injuries caused by bacterial infections can be confined to the initial wound site. Many pathogenic bacteria have Fg-binding adhesins that can circumvent the coagulation pathway and allow the bacteria to sidestep containment. Fg expression is upregulated during lung infection providing an attachment surface for bacteria with the ability to produce Fg-binding adhesins. Fg binding by leptospira might play a crucial factor in Leptospira-associated pulmonary hemorrhage, the main factor contributing to lethality in severe cases of leptospirosis. The 12th domain of Leptospira immunoglobulin-like protein B (LigB12), a leptospiral adhesin, interacts with the C-terminus of FgαC (FgαCC). In this study, the binding site for LigB12 was mapped to the final 23 amino acids at the C-terminal end of FgαCC (FgαCC8). The association of FgαCC8 with LigB12 (ELISA, KD = 0.76 μM; SPR, KD = 0.96 μM) was reduced by mutations of both charged residues (R608, R611 and H614 from FgαCC8; D1061 from LigB12) and hydrophobic residues (I613 from FgαCC8; F1054 and A1065 from LigB12). Additionally, LigB12 bound strongly to FXIII and also inhibited fibrin formation, suggesting that LigB can disrupt coagulation by suppressing FXIII activity. Here, the detailed binding mechanism of a leptospiral adhesin to a host hemostatic factor is characterized for the first time and should provide better insight into the pathogenesis of leptospirosis.

Patients receiving anti–tumor necrosis factor-α (anti–TNF-α) therapy are at increased risk for tuberculosis and other granulomatous diseases, but little is known about illness caused by nontuberculous mycobacteria (NTM) in this setting. We reviewed the US Food and Drug Administration MedWatch database for reports of NTM disease in patients receiving anti–TNF-α therapy. Of 239 reports collected, 105 (44%) met NTM disease criteria. Median age was 62 years; the majority of patients (66, 65%) were female, and most (73, 70%) had rheumatoid arthritis. NTM infections were associated with infliximab (n = 73), etanercept (n = 25), and adalimumab (n = 7); most patients were taking prednisone (n = 68, 65%) or methotrexate (n = 58, 55%) concurrently. Mycobacteria avium (n = 52, 50%) was most commonly implicated, and 9 patients (9%) had died at the time their infections were reported. A high rate of extrapulmonary manifestations (n = 46, 44%) was also reported.

To build large collections of medical terms from semi-structured information sources (e.g. tables, lists, etc.) and encyclopedia sites on the web. The terms are classified into the three semantic categories, Medical Problems, Medications, and Medical Tests, which were used in i2b2 challenge tasks. We developed two systems, one for Chinese and another for English terms. The two systems share the same methodology and use the same software with minimum language dependent parts. We produced large collections of terms by exploiting billions of semi-structured information sources and encyclopedia sites on the Web. The standard performance metric of recall (R) is extended to three different types of Recall to take the surface variability of terms into consideration. They are Surface Recall (R(S)), Object Recall (R(O)), and Surface Head recall (R(H)). We use two test sets for Chinese. For English, we use a collection of terms in the 2010 i2b2 text. Two collections of terms, one for English and the other for Chinese, have been created. The terms in these collections are classified as either of Medical Problems, Medications, or Medical Tests in the i2b2 challenge tasks. The English collection contains 49,249 (Problems), 89,591 (Medications) and 25,107 (Tests) terms, while the Chinese one contains 66,780 (Problems), 101,025 (Medications), and 15,032 (Tests) terms. The proposed method of constructing a large collection of medical terms is both efficient and effective, and, most of all, independent of language. The collections will be made publicly available.