Visualizing Engrafted Human Cancer and Therapy Responses in Immunodeficient Zebrafish.

Xenograft cell transplantation into immunodeficient mice has become the gold standard for assessing pre-clinical efficacy of cancer drugs, yet direct visualization of single-cell phenotypes is difficult. Here, we report an optically-clear prkdc-/-, il2rga-/- zebrafish that lacks adaptive and natural killer immune cells, can engraft a wide array of human cancers at 37°C, and permits the dynamic visualization of single engrafted cells. For example, photoconversion cell-lineage tracing identified migratory and proliferative cell states in human rhabdomyosarcoma, a pediatric cancer of muscle. Additional experiments identified the preclinical efficacy of combination olaparib PARP inhibitor and temozolomide DNA-damaging agent as an effective therapy for rhabdomyosarcoma and visualized therapeutic responses using a four-color FUCCI cell-cycle fluorescent reporter. These experiments identified that combination treatment arrested rhabdomyosarcoma cells in the G2 cell cycle prior to induction of apoptosis. Finally, patient-derived xenografts could be engrafted into our model, opening new avenues for developing personalized therapeutic approaches in the future.

Therapeutic targeting of LCK tyrosine kinase and mTOR signaling in T-cell acute lymphoblastic leukemia.

Relapse and refractory T-cell acute lymphoblastic leukemia (T-ALL) has a poor prognosis, and new combination therapies are sorely needed. Here, we used an ex vivo high-throughput screening platform to identify drug combinations that kill zebrafish T-ALL and then validated top drug combinations for preclinical efficacy in human disease. This work uncovered potent drug synergies between AKT/mTORC1 (mammalian target of rapamycin complex 1) inhibitors and the general tyrosine kinase inhibitor dasatinib. Importantly, these same drug combinations effectively killed a subset of relapse and dexamethasone-resistant zebrafish T-ALL. Clinical trials are currently underway using the combination of mTORC1 inhibitor temsirolimus and dasatinib in other pediatric cancer indications, leading us to prioritize this therapy for preclinical testing. This combination effectively curbed T-ALL growth in human cell lines and primary human T-ALL and was well tolerated and effective in suppressing leukemia growth in patient-derived xenografts (PDX) grown in mice. Mechanistically, dasatinib inhibited phosphorylation and activation of the lymphocyte-specific protein tyrosine kinase (LCK) to blunt the T-cell receptor (TCR) signaling pathway, and when complexed with mTORC1 inhibition, induced potent T-ALL cell killing through reducing MCL-1 protein expression. In total, our work uncovered unexpected roles for the LCK kinase and its regulation of downstream TCR signaling in suppressing apoptosis and driving continued leukemia growth. Analysis of a wide array of primary human T-ALLs and PDXs grown in mice suggest that combination of temsirolimus and dasatinib treatment will be efficacious for a large fraction of human T-ALLs.

Performance Metrics of Screening Digital Breast Tomosynthesis Based on Years Since a Prior Breast Cancer Diagnosis.

BACKGROUND. Mammography surveillance protocols after breast cancer treatment vary widely. Some practices recommend performing diagnostic mammography for a certain number of years or indefinitely, whereas others recommend returning immediately to screening. OBJECTIVE. This study's objective was to determine performance metrics of screening digital breast tomosynthesis (DBT) in patients who resume screening mammography immediately after breast cancer treatment, based on the number of years since the breast cancer diagnosis. METHODS. This retrospective study included screening DBT examinations performed from January 2013 to June 2019 in patients who resumed screening mammography immediately after a prior breast cancer diagnosis. Multivariable logistic regression models with generalized estimating equations were used to evaluate associations between screening performance metrics and years since the prior breast cancer diagnosis, controlling for age, race and ethnicity, breast density, presence of a prior screening mammogram, and interpreting radiologist. RESULTS. The study included 8090 patients (mean age, 65 ± 11 [SD] years) with a prior breast cancer diagnosis who underwent 30,812 screening DBT examinations during the study period. The cancer detection rate (CDR) was 8.6 per 1000 examinations (265/30,812), abnormal interpretation rate (AIR) was 5.7% (1750/30,812), PPV1 was 15.1% (265/1750), sensitivity was 80.3% (265/330), specificity was 95.1% (28,997/30,482), and false-negative rate was 2.1 per 1000 examinations (65/30,812). CDR showed a significant independent positive association with years since breast cancer diagnosis (adjusted OR, 1.03; 95% CI, 1.01-1.05; p < .001), being lowest more than 2 to up to 3 years after diagnosis (4.9 per 1000 examinations) and highest more than 8 to up to 9 years after diagnosis (11.2 per 1000 examinations). AIR showed a significant independent negative association with years since breast cancer diagnosis (adjusted OR, 0.99; 95% CI, 0.98-1.00; p = .01), being highest 1 year or less after diagnosis (7.5%) and lowest more than 5 to up to 6 years after diagnosis (5.0%). CONCLUSION. Among 8090 patients with a prior breast cancer diagnosis, even though the AIR was higher during the year after diagnosis compared with subsequent years, the AIR remained acceptably low (< 10%) in all years. CLINICAL IMPACT. These results support the study institution's mammographic surveillance protocol for patients with a prior breast cancer diagnosis of returning immediately to DBT screening.

Nuestra Recuperación [Our Recovery]: using photovoice to understand the factors that influence recovery in Latinx populations.

BACKGROUND: Photovoice is a form of visual ethnography intended to engage impacted communities in research followed by action to ameliorate the injustices under study. Photovoice has increased in use, especially in collaboration with Latinx communities addressing health inequities. The Latinx population comprises nearly 18% of the overall United States population and according to the census is projected to reach just under 30% by 2060. This diverse panethnic community faces significant structural barriers in accessing services. Racism and the resulting marginalization, specifically, contributes to limited access to recovery services and treatment. Making meaningful advances in substance use disorder training, intervention and policy necessitates learning alongside the Latinx community. METHODS: We partnered with a Latinx serving integrated behavioral health and primary care setting in Boston Massachusetts to explore barriers and facilitators to recovery using photovoice. Spanish-speaking Latinx adults with a substance use disorder participated. The group met for three photovoice sessions over a six-week period. Together group members critically analyzed photographs using the SHOWeD method. RESULTS: Findings indicate a sense of purpose and meaning, security, faith and housing are important elements of recovery. The results illustrated the importance of sources of connection in maintaining sobriety. Through this photovoice project, Latinx Spanish speaking participants highlighted barriers and facilitators to their substance use disorder recovery which spanned individual, community, and structural levels. CONCLUSIONS: The experiences and voices of the Latinx community are crucial to drive discussions that advance policy (e.g., housing stability and access), enhance providers' understanding of Latinx Spanish-speakers' substance use disorder recovery, and inform culturally and linguistically appropriate services. This study demonstrated that photovoice is highly acceptable and feasible among Latinx clients receiving substance use disorder services. Visual images related to housing, faith, etc. communicate challenges, power structures, as well as hopes to policymakers at multiple levels (e.g., institution/ agency, state).

Venovenous bypass in adult liver transplant recipients: A single-center observational case series.

BACKGROUND: Very little information is currently available on the use and outcomes of venovenous bypass (VVB) in liver transplantation (LT) in adults in Australia. In this study, we explored the indications, intraoperative course, and postoperative outcomes of patients who underwent VVB in a high-volume LT unit. METHODS: The study was a single-center, retrospective observational case series of adult patients who underwent VVB during LT at Austin Health in Melbourne, Australia between March 2008 and March 2022. Information on baseline preoperative status and intraoperative variables, including specific VVB characteristics as well as postoperative and VVB-related complications was collected. The lengths of intensive care unit and hospital stays as well as intraoperative and in-hospital mortality were recorded. RESULTS: Of the 900 LTs performed at this center during the aforementioned 14-year period, 27 (3%) included a VVB procedure. VVB was performed electively in 16 of these 27 patients (59.3%) and as a rescue technique to control massive bleeding in the other 11 (40.1%). The median (interquartile range [IQR]) age of those who underwent VVB procedures was 48 (39-55) years; the median age was 56 (47-62) years in the non-VVB group (p<0.0001). The median model for end-stage liver disease (MELD) scores were similar between the two patient groups. Complete blood data was available for 622 non-VVB patients. Twenty-six VVB (96.3%) and 603 non-VVB (96.9%) patients required intraoperative blood transfusions. The median (IQR) number of units of packed red blood cells transfused was 7 (4.8-12.5) units in the VVB group compared to 3.0 units (1.0-6.0) in the non-VVB group (p<0.0001). Inpatient mortality was 18.5% and 1.1% for the VVB and non-VVB groups, respectively (p<0.0001). There were no significant differences in length of hospital stay or incidence of acute kidney injury, primary graft dysfunction, or long-term graft failure between the two groups. Patients in the VVB group experienced a higher rate of postoperative non-anastomotic biliary stricture compared to patients in the non-VVB group (33% and 7.9%, respectively; p = 0.0003). CONCLUSIONS: VVB continues to play a vital role in LT. This case series highlights the heightened risk of major complications linked to VVB. However, the global transition to selective use of VVB underscores the urgent need for collaborative multi-center studies designed to address outstanding questions and parameters related to the safe implementation of this procedure.

In vitro evaluation of the insertion force for different dilator tip configurations.

The purpose of this study was to evaluate the tissue penetration insertion force of different dilator tip geometries in simulated tissue. Four different dilator tip designs-conical (control), triangular, diamond, and biconvex-were appraised. The penetration force for each dilator was measured by using an ad hoc device. Each modified dilator required significantly less force necessary for "tissue" insertion compared with the conical control (P < .05 for all designs). These data suggest that angled dilator tips may facilitate insertion and may contribute to new dilator and catheter tip design.

Strategy for effective percutaneous drainage of pancreatic collections: results on 121 patients.

UNLABELLED: There is a lack of technical guidelines for image-guided percutaneous drainage (IGPD) of pancreatic fluid collections (PFCs). To fill that void, we present a strategy and guidelines for systematic IGPD for effective PFCs evacuation. METHODS: Institutional Review Board (IRB)-approved study of 121 pancreatitis patients with symptomatic PFCs that underwent IGPD. IGPD strategy aimed at evacuation of the PFCs compartments using vigorous catheter drainage and manipulations. PFCs resolution and patients' outcome were measured. RESULTS: Pancreatitis pathogenesis and etiology included: necrotizing, 79 patients (alcoholic, 40; biliary, 20; hyperlipidemia, 8; other, 11); traumatic, 32 patients; and chronic ductal, 10 patients (pseudocysts). An ipsilateral retroperitoneal access was used for pararenal spaces PFCs (61, 50% patients), a transabdominal IGPD approach for anterior PFCs (49 patients, 41%), an intercostal/subcostal access for left subphrenic PFCs (22 patients, 18%), and a transgastric drainage route for retrogastric PFCs (9 patients, 7%). Table 1 lists the site of the pancreatic fluid collections and number and size of the catheter(s) used for IGPD of the PFCs in the 121 patients. Fifty-seven (47%) patients had positive cultures PFCs. Of these, 24 (20%) had polymicrobial infections, and 18 (15%) had fungal infections. There were 20 (11%) patients with multi-compartment drainage. PFCs resolution occurred in 102 (84%) patients. PFCs recurrence was treated by surgery (four patients) or IGPD (one patient). Pancreatic fistulas closed, except in one patient. Nine patients (7%) experienced multiorgan failure/death; 5 (4%) were lost to follow-up.

Littoral cell angioma: review of the literature and case report.

Littoral cell angioma (LCA), a primary vascular neoplasm originating from splenic red pulp littoral cells, was initially thought to be an extremely rare pathology. There have been an increasing number of cases reported in the literature. However, the etiology and prevalence of LCA is still unclear, partly due to the rarity of cases. The association of LCA with internal organ cancers, specifically lymphoma, has also been reported. In the patients with a history of cancer/lymphoma, the accurate diagnosis of LCA as the cause of the splenomegaly is challenging. Here we present a case of LCA in a patient with non-Hodgkin B-cell lymphoma and alpha-thalassemia trait. To our knowledge, this is the first report of the coexistence of LCA and thalassemia and only the second report of LCA and marginal-zone non-Hodgkin B-cell lymphoma. We review the literature and discuss the radiologic and pathologic findings of this case compared with the previously reported cases.

Postoperative complications and hospital costs following open radical cystectomy: A retrospective study.

OBJECTIVES: To evaluate primarily the relationship between postoperative complications and hospital costs, and secondarily the relationship between postoperative complications and mortality, following radical cystectomy. METHODS: Postoperative complications were retrospectively examined for 147 patients undergoing radical cystectomy at a university hospital between January 2012 and July 2021. Complications were defined and graded using the Clavien-Dindo classification system. In-hospital cost was calculated using an activity-based costing methodology. Regression modelling was used to investigate the relationships among a priori selected perioperative variables, complications, and costs. The effect of complications on postoperative mortality was ascertained using time-dependent coefficients in a Cox proportional hazards regression model. RESULTS: 135 (92%) patients experienced one or more postoperative complications. The medians of hospital cost for patients who experienced no complications and those who experienced complications were $42,796.3 (29,222.9-53,532.5) and $81,050.1 (49,614.8-122,533.6) respectively, p < 0.001. Hospital costs were strongly associated with complication severity: Clavien-Dindo grade II complications increased costs by 45.2% (p < 0.001, 95% CI 19.1%-76.6%), and Clavien-Dindo grade III to V complications increased costs by 107.5% (p < 0.001, 95% CI 52.4%-181.8%). Each additional count of complication and increase in Clavien-Dindo complication grade increased the risk of mortality 1.28-fold (RR = 1.28, p = 0.006, 95% CI 1.08-1.53) and 2.50-fold (RR = 2.50, p = 0.012 95% CI 1.23-5.07) respectively. CONCLUSIONS: These findings demonstrate a high prevalence of complications following cystectomy and significant associated increases in hospital costs and mortality. Postoperative complications are a key target for cost-containment strategies. TRIAL REGISTRATION: Trial Registration: Australian New Zealand Clinical Trials Registry (ACTRN:12622000057785.

A Suture-less Underlay Ventral Herniorrhaphy Technique for High-Risk Complex Abdominal Wall Reconstruction.

INTRODUCTION: Many factors increase the complexity of abdominal wall reconstruction including attenuated fascia, loss-of-domain, prior hernia surgeries, multiple fascial defects, enterocutaneous fistulas, and mesh infections. We describe our experience of using a suture-less mesh fixation underlay ventral herniorrhaphy technique to combat such issues in high-risk ventral hernia repair. METHODS: This is a prospective-observational study. Patients from 2019 onward undergoing emergent or elective cases were included. The technique: A large porcine acellular-dermal-matrix (ADM) alone or sutured to a light-weight, macroporous polypropylene mesh is created and placed with ADM facing the bowel. Fibrin glue is sprayed over the mesh, fascia and skin closed. An abdominal binder is placed pre-extubation and left undisturbed for 5 postoperative days. RESULTS: Of 34 included patients, the average demographic was a Caucasian (62.9%) female (65.7%), with class-I or greater obesity (76.5%), hypertension (74.3%), dyslipidemia (48.6%), non-skin malignancy (40.0%), type II diabetes mellitus (34.3%), a ventral hernia working group class of III-IV (55.9%), a mean of 3 ± 2.2 prior surgeries, and mean fascial defect size of 12.3 x 13.5cm. Five were prior solid-organ transplant recipients. Four patients underwent simultaneous tumor extirpations and herniorrhaphy. Five cases (14.7%) were emergent. Removal of prior mesh was performed in 48.5% of cases-seven had infected mesh. Median length of stay was 7 days, with 141 days median follow-up time. Fifteen patients (44.1%) developed a complication. Hernia-specific complications were limited to healing problems. There were no recurrences. CONCLUSION: This technique is easy and safe to employ in patients requiring high-risk complex abdominal reconstructions with minimal hernia-specific complications.

Multiple Instance Neuroimage Transformer.

For the first time, we propose using a multiple instance learning based convolution-free transformer model, called Multiple Instance Neuroimage Transformer (MINiT), for the classification of T1-weighted (T1w) MRIs. We first present several variants of transformer models adopted for neuroimages. These models extract non-overlapping 3D blocks from the input volume and perform multi-headed self-attention on a sequence of their linear projections. MINiT, on the other hand, treats each of the non-overlapping 3D blocks of the input MRI as its own instance, splitting it further into non-overlapping 3D patches, on which multi-headed self-attention is computed. As a proof-of-concept, we evaluate the efficacy of our model by training it to identify sex from T1w-MRIs of two public datasets: Adolescent Brain Cognitive Development (ABCD) and the National Consortium on Alcohol and Neurodevelopment in Adolescence (NCANDA). The learned attention maps highlight voxels contributing to identifying sex differences in brain morphometry. The code is available at https://github.com/singlaayush/MINIT.

If You Pay, Will They Come? Evaluating the Impact of Subsidies on Cessation Outcomes in the Walk or Run to Quit Program.

Introduction: Exercise interventions may assist smoking cessation attempts. One such publicly available 10-week program, Walk or Run to Quit (WRTQ), demonstrated success in smoking cessation and physical activity (PA) outcomes. However, initial WRTQ participants (2016-2017) were fairly homogenous in their demographic profile. To increase diversity, subsidies for participation were offered in 2018. This study assessed how the subsidies affected participant demographics, running frequency, smoking cessation, intention to quit, and program attendance and completion. Methods: The $70 registration fee was subsidized for 41% of participants in 2018. A pre-postdesign was used, with participants completing surveys on their demographics and smoking and physical activity behaviours. Descriptive statistics compared the year subsidies were available (2018) and unsubsidized years (2016-2017) and subsidized and unsubsidized participants' data from 2018. Results: The 2018 participants had lower average attendance and program completion rates compared to 2016-2017 and no statistically significant differences in demographics or smoking cessation and PA outcomes. There were no differences in smoking cessation, run frequency, or demographic variables between the subsidized and unsubsidized participants in 2018. Conclusions: Offering subsidies did not diversify the participant profile. Subsidies did not have a negative impact on attendance nor primary outcomes. Subsidies may not have addressed barriers that prevented a more diverse sample from participating in WRTQ, such as program location, timing, and design. Equitable access to smoking cessation programs remains essential. As subsidies may play a role in reducing financial barriers disproportionately faced by marginalized groups, the implementation of, and recruitment for, such subsidized programs requires further investigation.

Single-cell analysis and functional characterization uncover the stem cell hierarchies and developmental origins of rhabdomyosarcoma.

Rhabdomyosarcoma (RMS) is a common childhood cancer that shares features with developing skeletal muscle. Yet, the conservation of cellular hierarchy with human muscle development and the identification of molecularly defined tumor-propagating cells has not been reported. Using single-cell RNA-sequencing, DNA-barcode cell fate mapping and functional stem cell assays, we uncovered shared tumor cell hierarchies in RMS and human muscle development. We also identified common developmental stages at which tumor cells become arrested. Fusion-negative RMS cells resemble early myogenic cells found in embryonic and fetal development, while fusion-positive RMS cells express a highly specific gene program found in muscle cells transiting from embryonic to fetal development at 7-7.75 weeks of age. Fusion-positive RMS cells also have neural pathway-enriched states, suggesting less-rigid adherence to muscle-lineage hierarchies. Finally, we identified a molecularly defined tumor-propagating subpopulation in fusion-negative RMS that shares remarkable similarity to bi-potent, muscle mesenchyme progenitors that can make both muscle and osteogenic cells.

Single-cell imaging of T cell immunotherapy responses in vivo.

T cell immunotherapies have revolutionized treatment for a subset of cancers. Yet, a major hurdle has been the lack of facile and predicative preclinical animal models that permit dynamic visualization of T cell immune responses at single-cell resolution in vivo. Here, optically clear immunocompromised zebrafish were engrafted with fluorescent-labeled human cancers along with chimeric antigen receptor T (CAR T) cells, bispecific T cell engagers (BiTEs), and antibody peptide epitope conjugates (APECs), allowing real-time single-cell visualization of T cell-based immunotherapies in vivo. This work uncovered important differences in the kinetics of T cell infiltration, tumor cell engagement, and killing between these immunotherapies and established early endpoint analysis to predict therapy responses. We also established EGFR-targeted immunotherapies as a powerful approach to kill rhabdomyosarcoma muscle cancers, providing strong preclinical rationale for assessing a wider array of T cell immunotherapies in this disease.

Single-cell imaging of human cancer xenografts using adult immunodeficient zebrafish.

Zebrafish are an ideal cell transplantation model. They are highly fecund, optically clear and an excellent platform for preclinical drug discovery studies. Traditionally, xenotransplantation has been carried out using larval zebrafish that have not yet developed adaptive immunity. Larval engraftment is a powerful short-term transplant platform amenable to high-throughput drug screening studies, yet animals eventually reject tumors and cannot be raised at 37 °C. To address these limitations, we have recently developed adult casper-strain prkdc-/-, il2rgα-/- immunocompromised zebrafish that robustly engraft human cancer cells for in excess of 28 d. Because the adult zebrafish can be administered drugs by oral gavage or i.p. injection, our model is suitable for achieving accurate, preclinical drug dosing. Our platform also allows facile visualization of drug effects in vivo at single-cell resolution over days. Here, we describe the procedures for xenograft cell transplantation into the prkdc-/-, il2rgα-/- model, including refined husbandry protocols for optimal growth and rearing of immunosuppressed zebrafish at 37 °C; optimized intraperitoneal and periocular muscle cell transplantation; and epifluorescence and confocal imaging approaches to visualize the effects of administering clinically relevant drug dosing at single-cell resolution in vivo. After identification of adult homozygous animals, this procedure takes 35 d to complete. 7 days are required to acclimate adult fish to 37 °C, and 28 d are required for engraftment studies. Our protocol provides a comprehensive guide for using immunocompromised zebrafish for xenograft cell transplantation and credentials the model as a new preclinical drug discovery platform.

Transrectal and transvaginal catheter drainages and aspirations for management of pelvic fluid collections: technique, technical success rates, and outcomes in 150 patients.

PURPOSE: To evaluate outcomes of image-guided transrectal/transvaginal (TR/TV) drainage for symptomatic pelvic fluid collections (SPFCs). MATERIALS AND METHODS: Single-center retrospective study of 150 consecutive patients (36 males, 114 females, average age 41 years) who underwent attempted TR/TV drainages of SPFCs during an 11-year, 5-month period. All patients presented with pain and had SPFCs with rectal or vaginal contact on preceding diagnostic CT. Routine technique included Foley catheter insertion, image-guidance with ultrasound and fluoroscopy, 18 g/20 cm Chiba needles, and Seldinger technique for catheter insertion. No anoscope or speculum was used. SPFCs causes were classified by etiology including postoperative-70 (47%); gynecologic-49 (33%); and gastrointestinal-31 (21%). Resolutions of the SPFCs without the need for surgical intervention, collection recurrence, and complications were assessed. Surgical management after attempted TR/TV drainage was considered a failure. RESULTS: Technical success was achieved in 172/180 procedures [TR 128/134 (95%); TV 44/46 (96%)]. TR/TV drainage successfully managed SPFCs in 141/150 patients (94% success rate) and 145/150 patients (97%) did not require surgical intervention; 4 patients with failed TR/TV drainage attempts were managed conservatively. In 5 patients requiring surgery, 4 were after technically successful TR/TV and 1 was after a failed TR attempt. Complications occurred in 4 (3%) patients: 2 bladder punctures (both resolved with medical management), 1 propagation of sepsis, and 1 hemorrhagic return from TR drainage that prompted surgical exploration. CONCLUSION: Transrectal and transvaginal drainage had high technical success rates and were successful in managing the majority (141/150; 94%) of patients with pelvic fluid collections.

Characterization of the mature form of a ß-defensin-like peptide, Hoa-D1, in the lobster Homarus americanus.

We report on the characterization of the native form of an American lobster, Homarus americanus, ß-defensin-like putative antimicrobial peptide, H. americanus defensin 1 (Hoa-D1), sequenced employing top-down and bottom-up peptidomic strategies using a sensitive, chip-based nanoLC-QTOF-MS/MS instrument. The sequence of Hoa-D1 was determined by mass spectrometry; it was found to contain three disulfide bonds and an amidated C-terminus. The sequence was further validated by searching publicly-accessible H. americanus expressed sequence tag (EST) and transcriptome shotgun assembly (TSA) datasets. Hoa-D1, SYVRScSSNGGDcVYRcYGNIINGAcSGSRVccRSGGGYamide (with c representing a cysteine participating in a disulfide bond), was shown to be related to ß-defensin-like peptides previously reported from Panulirus japonicas and Panulirus argus. We found Hoa-D1 in H. americanus hemolymph, hemocytes, the supraoesophageal ganglion (brain), eyestalk ganglia, and pericardial organ extracts, as well as in the plasma of some hemolymph samples. Using discontinuous density gradient separations, we fractionatated hemocytes and localized Hoa-D1 to hemocyte sub-populations. While Hoa-D1 was detected in semigranulocytes and granulocytes using conventional proteomic strategies for analysis, the direct analysis of cell lysates exposed evidence of Hoa-D1 processing, including truncation of the C-terminal tyrosine residue, in the granulocytes, but not semigranulocytes. These measurements demonstrate the insights regarding post-translational modifications and peptide processing that can be revealed through the MS analysis of intact peptides. The identification of Hoa-D1 as a widely-distributed peptide in the lobster suggests the possibility that it may be pleiotropic, with functions in addition to its proposed role as an antimicrobial molecule in the innate immune system.

Observations on failed retrieval of optional inferior vena cava filters.

PURPOSE: To evaluate causes of failed optional inferior vena cava filter (IVCF) retrievals. METHODS: Single-center retrospective study. RESULTS: IVCF retrievals were attempted in 26/211 (12%) patients at a mean 42.9 days. There were 9 failures (all OptEase) due to: inability to snare the hook (n=5), noncollapsible IVCF (n=3), and unusual procedural pain (n=1). Median duration of retrieved IVCFs was 31 days compared to 53 days for failures (P<.05). IVCFs aligned with the IVC's cephalocaudal axis were retrieved in 13/16 cases, while misaligned IVCFs were retrieved 4/10 cases (P<.05). CONCLUSION: Filter duration and misalignment were significantly associated with retrieval failures.

Primary retroperitoneal paraganglioma simulating a pancreatic mass: a case report and review of the literature.

Paragangliomas are extra-adrenal tumors of the autonomic nervous system and may be found within the skull base, neck, chest, and abdomen. When presenting within the abdominal cavity, they may arise as a primary retroperitoneal neoplasm and can mimic vascular malformations or other conditions related to specific retroperitoneal organs such as the pancreas, kidneys, or adrenals. Retroperitoneal paragangliomas are mostly benign with good prognosis; however, they can present with abdominal pain, palpable mass, or hypertensive episodes. Patients should be initially evaluated with catecholamine levels, followed by computed tomography or magnetic resonance imaging to locate the primary lesion. Surgical excision remains the mainstay of treatment, although advanced disease and proximity to vital organs can make excision difficult or impossible. This case report describes a patient who initially underwent work up for a suspected pancreatic head mass which was discovered to be a retroperitoneal paraganglioma by frozen section.