Maternal and Fetal Radiation-Induced Cancer Risk From Computed Tomography Pulmonary Angiography During Pregnancy: A Retrospective Cohort Study Across a Multihospital Integrated Health Care Network.

OBJECTIVE: Computed tomography pulmonary angiogram (CTPA) is important to evaluate suspected pulmonary embolism in pregnancy but has maternal/fetal radiation risks. The objective of this study was to estimate maternal and fetal radiation-induced cancer risk from CTPA during pregnancy. METHODS: Simulation modeling via the National Cancer Institute's Radiation Risk Assessment Tool was used to estimate excess cancer risks from 17 organ doses from CTPA during pregnancy, with doses determined by a radiation dose indexing monitoring system. Organ doses were obtained from a radiation dose indexing monitoring system. Maternal and fetal cancer risks per 100,000 were calculated for male and female fetuses and several maternal ages. RESULTS: The 534 CTPA examinations had top 3 maternal organ doses to the breast, lung, and stomach of 17.34, 15.53, and 9.43 mSv, respectively, with a mean uterine dose of 0.21 mSv. The total maternal excess risks of developing cancer per 100,000 were 181, 151, 121, 107, 94.5, 84, and 74.4, respectively, for a 20-, 25-, 30-, 35-, 40-, 45-, and 50-year-old woman undergoing CTPA, compared with baseline cancer risks of 41,408 for 20-year-old patients. The total fetal excess risks of developing cancer per 100,000 were 12.3 and 7.3 for female and male fetuses, respectively, when compared with baseline cancer risks of 41,227 and 48,291. DISCUSSION: Excess risk of developing cancer from CTPA was small relative to baseline cancer risk for pregnant patients and fetuses, decreased for pregnant patients with increasing maternal age, and was greater for female fetuses than male fetuses.

Patient and Fetal Radiation-Induced Malignancy Risk From Imaging For Evaluation of Pulmonary Embolism in Pregnancy.

BACKGROUND: Imaging for diagnosis of suspected pulmonary embolism in pregnancy presents radiation concerns for patient and fetus. OBJECTIVES: Estimate the risks of radiation-induced breast cancer and childhood leukemia from common imaging techniques for the evaluation of suspected pulmonary embolism in pregnancy. METHODS: Breast and uterine absorbed doses for various imaging techniques were input into the National Cancer Institute Radiation Risk Assessment Tool to calculate risk of breast cancer for the patient and childhood leukemia for the fetus. Absorbed doses were obtained by synthesizing data from a recent systematic review and the International Commission on Radiological Protection. Primary outcomes were the estimated excess incidences of breast cancer and childhood leukemia per 100,000 exposures. RESULTS: Baseline incidences of breast cancer for a 30-year-old woman and childhood leukemia for a male fetus were 13,341 and 939, respectively. Excess incidences of breast cancer were 0.003 and 0.275 for a single and two-view chest radiograph, respectively, 9.53 and 20.6 for low- and full-dose computed tomography pulmonary angiography (CTPA), respectively, 0.616 and 2.54 for low- and full-dose perfusion scan, respectively, and 0.732 and 2.66 for low- and full-dose ventilation perfusion scan, respectively. Excess incidences of childhood leukemia were 0.004 and 0.007 for a single and two-view chest radiograph, respectively, 0.069 and 0.490 for low- and full-dose CTPA, respectively, 0.359 and 1.47 for low- and full-dose perfusion scan, respectively, and 0.856 and 1.97 for low- and full-dose ventilation perfusion scan, respectively. CONCLUSION: Excess cancer risks for all techniques were small relative to baseline cancer risks, with CTPA techniques carrying slightly higher risk of breast cancer for the patient and ventilation perfusion techniques a higher risk of childhood leukemia.

Radiofrequency Ablation for the Palliative Treatment of Bone Metastases: Outcomes from the Multicenter OsteoCool Tumor Ablation Post-Market Study (OPuS One Study) in 100 Patients.

PURPOSE: To evaluate the effectiveness of radiofrequency (RF) ablation as measured by change in worst pain score from baseline to 3 mo after RF ablation for the palliative treatment of painful bone metastases. MATERIALS AND METHODS: One hundred patients (mean age, 64.6 y) underwent RF ablation for metastatic bone disease and were followed up to 6 mo. Subjects' pain and quality of life were measured before RF ablation and postoperatively by using the Brief Pain Index and European Quality of Life questionnaires. Opioid agent use and device-, procedure-, and/or therapy-related adverse events (AEs) were collected. RESULTS: Eighty-seven patients were treated for tumors involving the thoracolumbar spine and 13 for tumors located in the pelvis and/or sacrum. All ablations were technically successful, and 97% were followed by cementoplasty. Mean worst pain score decreased from 8.2 ± 1.7 at baseline to 3.5 ± 3.2 at 6 mo (n = 22; P < 0.0001 for all visits). Subjects experienced significant improvement for all visits in average pain (P < .0001), pain interference (P < .0001), and quality of life (P < .003). Four AEs were reported, of which 2 resulted in hospitalization for pneumonia and respiratory failure. All 30 deaths reported during the study were attributed to the underlying malignancy and not related to the study procedure. CONCLUSIONS: Results from this study show rapid (within 3 d) and statistically significant pain improvement with sustained long-term relief through 6 mo in patients treated with RF ablation for metastatic bone disease.

Causation's nuclear future: applying proportional liability to the Price-Anderson Act.

For more than a quarter century, public discourse has pushed the nuclear-power industry in the direction of heavier regulation and greater scrutiny, effectively halting construction of new reactors. By focusing on contemporary fear of significant accidents, such discourse begs the question of what the nation's court system would actually do should a major nuclear incident cause radiation-induced cancers. Congress's attempt to answer that question is the Price-Anderson Act, a broad statute addressing claims by the victims of a major nuclear accident. Lower courts interpreting the Act have repeatedly encountered a major stumbling block: it declares that judges must apply the antediluvian preponderance-of-the-evidence logic of state tort law, even though radiation science insists that the causes of radiation-induced cancers are more complex. After a major nuclear accident, the Act's paradoxically outdated rules for adjudicating "causation" would make post-incident compensation unworkable. This Note urges that nuclear-power-plant liability should not turn on eighteenth-century tort law. Drawing on modern scientific conclusions regarding the invariably "statistical" nature of cancer, this Note suggests a unitary federal standard for the Price-Anderson Act--that a defendant be deemed to have "caused" a plaintiff's injury in direct proportion to the increased risk of harm the defendant has imposed. This "proportional liability" rule would not only fairly evaluate the costs borne by injured plaintiffs and protect a reawakening nuclear industry from the prospect of bank-breaking litigation, but would prove workable with only minor changes to the Price-Anderson Act's standards of "injury" and "fault."

Behavioral Health Workforce Development in Washington State: Addition of a Behavioral Health Support Specialist.

The mental and behavioral health workforce shortage has hindered access to care in the United States, resulting in long waitlists for persons who need behavioral health care. Global models for task sharing, combined with U.S.-led studies of nonspecialists delivering interventions for depression and anxiety, support the development of this workforce in a stepped care system. This Open Forum highlights an innovative effort in Washington State to initiate a bachelor's-level behavioral health support specialist curriculum leading to credentialing to expand the mental health workforce and improve access to care for people with depression and anxiety.

Discovery of SQSTM1/p62-dependent P-bodies that regulate the NLRP3 inflammasome.

Autophagy and ribonucleoprotein granules, such as P-bodies (PBs) and stress granules, represent vital stress responses to maintain cellular homeostasis. SQSTM1/p62 phase-separated droplets are known to play critical roles in selective autophagy; however, it is unknown whether p62 can exist as another form in addition to its autophagic droplets. Here, we found that, under stress conditions, including proteotoxicity, endotoxicity, and oxidation, autophagic p62 droplets are transformed to a type of enlarged PBs, termed p62-dependent P-bodies (pd-PBs). p62 phase separation is essential for the nucleation of pd-PBs. Mechanistically, pd-PBs are triggered by enhanced p62 droplet formation upon stress stimulation through the interactions between p62 and DDX6, a DEAD-box ATPase. Functionally, pd-PBs recruit the NLRP3 inflammasome adaptor ASC to assemble the NLRP3 inflammasome and induce inflammation-associated cytotoxicity. Our study shows that p62 droplet-to-PB transformation acts as a stress response to activate the NLRP3 inflammasome process, suggesting that persistent pd-PBs lead to NLRP3-dependent inflammation toxicity.

Radiofrequency Ablation Provides Rapid and Durable Pain Relief for the Palliative Treatment of Lytic Bone Metastases Independent of Radiation Therapy: Final Results from the OsteoCool Tumor Ablation Post-Market Study.

PURPOSE: The OsteoCool Tumor Ablation Post-Market Study (OPuS One) was a prospective, multi-national, single-arm study to investigate safety and effectiveness of radiofrequency ablation (RFA) for palliation of painful lytic bone metastases with 12 months of follow-up. RFA has demonstrated effective palliation of osseous metastases in small clinical studies with short-term follow-up; however, a long-term assessment with robust subject numbers is lacking. MATERIALS AND METHODS: Prospective assessments were conducted at Baseline, 3 days, 1 week, and 1, 3, 6, and 12-months. Pain and quality of life were measured prior to RFA and postoperatively using the Brief Pain Inventory, European Quality of Life-5 Dimension, and European Organization for Research and Treatment of Cancer Care Quality of Life Questionnaire for palliative care. Radiation, chemotherapy and opioid usage, and related adverse events were collected. RESULTS: 206 subjects were treated with RFA at 15 institutions in OPuS One. Worst pain, average pain, pain interference and quality of life significantly improved at all visits starting 3 days post-RFA and sustained to 12 months (P < 0.0001). Post hoc analysis found neither systemic chemotherapy nor local radiation therapy at the index site of RFA influenced worst pain, average pain, or pain interference. Six subjects had device/procedure-related adverse events. CONCLUSION: RFA for lytic metastases provides rapid (within 3 days) and statistically significant pain and quality of life improvements with sustained long-term relief through 12 months and a high degree of safety, independent of radiation. LEVEL OF EVIDENCE: 2B, PROSPECTIVE, NON-RANDOMIZED, POST-MARKET STUDY: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

A Small Blemish: Isotretinoin-Induced Microscopic Colitis.

Microscopic colitis is a form of colonic inflammation that presents with chronic nonbloody diarrhea that can only be diagnosed histologically with biopsies obtained during colonoscopy. We report a rare case of isotretinoin-induced microscopic colitis in a patient who was prescribed this medication for nodular acne with a 1-year history of nonbloody diarrhea, bloating, cramping, and foul-smelling gas. Cessation of this medication in addition to initiating treatment with budesonide resulted in remission of the patient's symptoms. The presence of chronic diarrhea in patients who are taking isotretinoin should raise suspicion for this condition and warrant further investigation.

CT pulmonary angiography in pregnancy: Specific conversion factors to estimate effective radiation dose from dose length product: A retrospective cross-sectional study across a multi-hospital integrated healthcare network.

PURPOSE: Effective dose describes radiation-related cancer risk from CT scans and is estimated using a readily available conversion factor (k-factor), which varies by body part and study type. To purpose of this study is to determine the specific k-factor for CTPA in pregnant patients and its predictive factors. METHODS: This retrospective cross-sectional study evaluates CTPA in pregnancy across a multihospital integrated healthcare network from January 2012 to April 2017. Patient and CTPA-related data were obtained from the electronic health record and a radiation dose index monitoring system. Each patient's effective dose was determined by patient-specific Monte-Carlo simulation with Cristy phantoms and divided by patient dose-length-product to determine the k-factor. K-factor for pregnant patients was compared to the k-factor for adults of standard physique with a one-sample t-test. Bivariate and multivariable analyses were performed for patient and CT predictors of k-factor. RESULTS: A total of 534 patients were included. The mean k-factor for all patients was 0.0249 (mSv·mGy-1·cm-1), 78% greater than k-factor of 0.014 (p < 0.001) suggested for the general adult population. Multivariable analysis demonstrated lower k-factors with increasing pitch (p = 0.0002), patient size (p < 0.001), and scan length (p < 0.0001). The 120 kVp (p < 0.001) and 140 kVp (p = 0.0028) analyses showed a larger k-factor than 80 and 100 kVp studies combined. CONCLUSIONS: Specific k-factor for CTPA in pregnant patients is greater than the previously used generic chest CT k-factor and should be used to estimate the effective dose for CTPA exams in pregnancy.

Serological profiles of pan-coronavirus-specific responses in COVID-19 patients using a multiplexed electro-chemiluminescence-based testing platform.

Serological assessment of SARS-CoV-2 specific responses are an essential tool for determining the prevalence of past SARS-CoV-2 infections in the population especially when testing occurs after symptoms have developed and limited contact tracing is in place. The goal of our study was to test a new 10-plex electro-chemiluminescence-based assay to measure IgM and IgG responses to the spike proteins from multiple human coronaviruses including SARS-CoV-2, assess the epitope specificity of the SARS-CoV-2 antibody response against full-length spike protein, receptor-binding domain and N-terminal domain of the spike protein, and the nucleocapsid protein. We carried out the assay on samples collected from three sample groups: subjects diagnosed with COVID-19 from the U.S. Army hospital at Camp Humphreys in Pyeongtaek, South Korea; healthcare administrators from the same hospital but with no reported diagnosis of COVID-19; and pre-pandemic samples. We found that the new CoV-specific multiplex assay was highly sensitive allowing plasma samples to be diluted 1:30,000 with a robust signal. The reactivity of IgG responses to SARS-CoV-2 nucleocapsid protein and IgM responses to SARS-CoV-2 spike protein could distinguish COVID-19 samples from non-COVID-19 and pre-pandemic samples. The data from the three sample groups also revealed a unique pattern of cross-reactivity between SARS-CoV-2 and SARS-CoV-1, MERS-CoV, and seasonal coronaviruses HKU1 and OC43. Our findings show that the CoV-2 IgM response is highly specific while the CoV-2 IgG response is more cross-reactive across a range of human CoVs and also showed that IgM and IgG responses show distinct patterns of epitope specificity. In summary, this multiplex assay was able to distinguish samples by COVID-19 status and characterize distinct trends in terms of cross-reactivity and fine-specificity in antibody responses, underscoring its potential value in diagnostic or serosurveillance efforts.

Clinical Approach to and Work-up of Bleeding Patients.

A bleeding patient is a common consult for interventional radiologists. Prompt triage, preprocedural evaluation specific to the site of hemorrhage, and knowledge of resuscitative strategies allow for a potentially life-saving procedure to be appropriately and safely performed. Having a firm understanding of the clinical work-up and management of a bleeding patient has never been more important. In this article, a discussion of the clinical approach and work-up of a bleeding patient for whom interventional radiology is consulted is followed by a discussion of etiology-specific preprocedural work-up.

Safety and feasibility of outpatient transcatheter hepatic arterial embolization for hepatocellular carcinoma.

PURPOSE: To evaluate the feasibility and safety of performing image-guided bland embolization and chemoembolization as an outpatient-based procedure in selected patients with hepatocellular carcinoma (HCC). MATERIALS AND METHODS: This is a retrospective review of the authors' experience with outpatient embolization and chemoembolization from January 2005 to June 2006. Patients with nonresectable HCC not eligible for liver transplantation were enrolled. Patients with Child-Pugh class A and early class B liver disease were treated by using the outpatient protocol, patients with Child-Pugh class C and late class B liver disease and those with elevated bilirubin or creatinine levels were excluded and treated as inpatients or denied embolization therapy. One hundred thirty-three bland embolizations or chemoembolizations were performed in 77 patients on an outpatient basis during the study period. RESULTS: Patients were discharged home on the same day after 131 of the 133 procedures (99%; 95% confidence interval [CI]: +/-2%), in two cases (2%, 95% CI: +/-2%), patients were admitted the day of the procedure. In two of the 131 cases (2%, 95% CI: +/-2%), patients discharged home returned to the emergency department 1-6 days after the procedure. One hundred twenty-nine of the 133 cases (97%, 95% CI: +/-3%) were successfully treated by using the outpatient embolization or chemoembolization protocol, with subsequent hospitalization needed in only four of 133 cases (3%, 95% CI: +/-3%). CONCLUSIONS: Image-guided hepatic bland embolization and chemoembolization performed with an outpatient protocol in carefully selected patients with HCC with aggressive follow-up is safe, with relatively few complications and few requirements for admission or revisitation to the emergency department.

Lung Cancer Screening CT: Sex-Specific Conversion Factors to Estimate Effective Radiation Dose From Dose-Length Product.

BACKGROUND: Effective dose (ED) is used to understand radiation-related cancer risk of CT scans. Currently, ED for low-dose CT (LDCT) lung cancer screening (LCS) is estimated by multiplying the CT scan-reported dose-length product (DLP) by a DLP-to-ED conversion factor (k-factor) for general chest CT imaging, which does not account for sex. The purpose of this study was to calculate sex-specific k-factors for LDCT LCS. METHODS: This retrospective study evaluated consecutive LCS patients across a large health system from 2016 to 2017. Patient and CT scan-related data were obtained from the radiology information system, the picture archiving and communication system, and a radiation dose index-monitoring system. Each patient's ED was determined by patient-specific Monte-Carlo simulation using Cristy phantoms and divided by study DLP to determine the k-factor. The k-factors were compared vs the standard of 0.014 mSv·mGy⁻1·cm⁻1 for a chest CT scan by using a one-sample Student t test. Bivariate and multivariable analyses were performed for k-factors based on patient and CT scan factors. RESULTS: A total of 1,890 patients were included in the study. The mean k-factor for all patients was 0.0179 mSv·mGy⁻1·cm⁻1, which was 22% greater than the standard value of 0.014 mSv·mGy⁻1·cm⁻1 for a chest CT scan previously applied to LDCT imaging (P < .001). The mean k-factor in women (0.0213 mSv·mGy⁻1·cm⁻1) was 43% greater than in men (0.0149 mSv·mGy⁻1·cm⁻1) in the multivariable model (P < .001). CONCLUSIONS: The overall k-factor for LCS is higher than the previously used value for chest CT imaging; when stratified according to sex, it was 43% greater in women than in men. Sex- and LCS-specific k-factors should be used to estimate effective radiation dose in LCS programs.

Predictors of radiation dose for CT pulmonary angiography in pregnancy across a multihospital integrated healthcare network.

PURPOSE: There is a large range of published effective radiation dose for CTPA during pregnancy. The purpose of our study is to determine the mean effective radiation dose and predictors of mean effective radiation dose for CTPA in pregnant patients across a multihospital integrated healthcare network. METHODS: This retrospective study evaluates pregnant women who had a CTPA as the first primary advanced imaging test for evaluation of PE in a multihospital integrated healthcare network from January 2012-April 2017. Patient and CT-related data were obtained from the electronic health record and Radimetrics server (Radimetrics Inc, Bayer). DLP was recorded and effective radiation dose in mSv was determined using a conversation factor of 0.014 mSv·mGy-¹·cm-¹. Patient size was determined by water equivalent diameter. Bivariate and multivariate analysis were performed for effective radiation dose based on patient and CT factors. RESULTS: In the 534 CTPA exams, the mean effective radiation dose was 3.96 mSv. Bivariate analysis showed significant differences in radiation dose by trimester, p = 0.042: first trimester 4.52 mSv, second trimester 3.73 mSv, and third trimester 3.95 mSv. Multivariable analysis demonstrated CTPA during first trimester, increasing mAs, kVp, scan length, patient size, and use of mAs modulation, as well as decreasing pitch, to be predictive of higher effective radiation dose. CONCLUSION: Mean effective radiation dose was on the lower end of published studies. Trimester was a statistically significant predictor of effective radiation dose when accounting for known predictors of radiation dose.

Obstruction of the Biliary and Urinary System.

Biliary and urinary obstructions can be managed endoscopically or cystoscopically, surgically or by percutansous intervention or drainage. If the obtructed system is infected, emergent decompression is needed. Early recognition and treatment is paramount in both conditions. Acute cholangitis can present many different ways, from mild symptoms to fulminant sepsis. It is usually a result of ascending bacterial colonization and biliary obstruction resulting in bacterial overgrowth. Therefore, those patients with recent biliary instrumentation or previous biliary modification are at higher risk. Charcot's triad of fever, right upper quadrant abdominal pain, and jaundice is only seen in 50%-70% of patients. Fever is seen in over 90% of cases, pain is seen in 70% of cases, and jaundice is seen in 60% of cases. Altered mental status and hypotension are associated with severe cases. All 5 symptoms of fever, right upper quadrant abdominal pain, jaundice, altered mental status, and hypotension are referred to as Reynold's Pentad. Acute pyonephrosis can also present many different ways, from minimal symptoms to fulminant sepsis. Fever, chills, and flank pain are the classic symptoms, although some patients may be relatively asymptomatic. Pyonephrosis may present with a classic triad of fever, flank pain, and hydronephrosis, or simply hydronephrosis and sepsis. Pyonephrosis usually occurs as a result of urinary obstruction with either an ascending infection of the urinary tract or hematogenous spread of a bacterial pathogen as the culprit. Up to 75% of cases are related to urinary stone disease. Patients are at increased risk for pyonephrosis when they haven anatomic urinary tract obstruction, certain chronic diseases (diabetes meliitus and AIDS), or are immunosuppressed due to immunodeficiency or medications, (chronic steroid therapy).

Managing Venous Thromboembolic Disease On-Call.

Managing venous thromboembolic disease on-call requires the interventional radiologist consider not only potential risk and benefit to the patient but also available resources in the IR suite as well as throughout the hospital, such as intensive care monitoring during treatment. We demonstrate how our practice manages these on-call cases ranging from deep venous thrombosis to acute pulmonary embolism and decide which patients need emergent treatment and which can undergo delayed intervention during working hours. In all cases, an adequate preprocedural clinical assessment is crucial.

Costs and utilization of end-stage glaucoma patients receiving visual rehabilitation care: a US multisite retrospective study.

PURPOSE: Glaucoma is a prevalent ophthalmologic disease and leading cause of blindness. A retrospective analysis was conducted to evaluate resources and costs for end-stage glaucoma patients receiving visual rehabilitation care (VRC). MATERIALS AND METHODS: A chart review was conducted in 3 United States VRC centers. Charts of patients with primary open-angle glaucoma as the primary cause of vision loss (1998 to 2003) were selected, yielding 81 records. Data were collected from patient-level billing and reimbursement records (ophthalmologist/optometrist visits, glaucoma medications, procedures, and specialized low-vision and glaucoma-related services). Visual rehabilitation services included utilization of low-vision devices, assessment of daily functioning, orientation and mobility training, and patient counseling. RESULTS: Mean age at baseline was 72.7 years [standard deviation (SD)=17.2, range: 29 to 95]. Of those with known sex (n=77), 55.8% were women. Medicare was the payer type for most patients (59.3%), whereas 20% had Medicaid. Mean number of visits was 7.1 (SD=6.1) in year 1 and 3.7 (SD=4.2) in year 2, for an annual mean of 5.4 (SD=5.0) visits overall. Total mean cost per patient in year 1 was greater than year 2 [$2170 (SD=$2252) vs. $1202 (SD=$1080), respectively]; of the total 2-year costs, 15% were VRC, 37% ophthalmology care, and 48% pharmacy. Analysis of nonpharmacy costs revealed that VRC accounted for 28% and ophthalmology for 72%. CONCLUSIONS: End-stage glaucoma is associated with appreciable resource utilization and costs, because of both vision rehabilitation and ophthalmology care. Advanced primary open-angle glaucoma has a substantial cost-of-illness, warranting improved management in early stages of disease.

Extracellular release of the glycosylphosphatidylinositol (GPI)-linked Leishmania surface metalloprotease, gp63, is independent of GPI phospholipolysis: implications for parasite virulence.

The major zinc metalloprotease of Leishmania (gp63), an important determinant of parasite virulence, is attached to the parasite surface via a glycosylphosphatidylinositol anchor. Here we report the spontaneous release of proteolytically active gp63 from a number of Leishmania isolates, causing cutaneous and visceral disease. To investigate the mechanism(s) of gp63 release, we transfected a gp63-deficient variant of Leishmania amazonensis with constructs expressing gp63 and various mutants thereof. Surprisingly, approximately half of wild type gp63 was found in the culture supernatant 12 h post-synthesis. Biochemical analysis of the extracellular gp63 revealed two forms of the protein, one that is released from the cell surface, and another, that apparently is directly secreted. Release of cell surface gp63 was significantly reduced when the proteolytic activity of the protein was inactivated by site-specific mutagenesis or inhibited by zinc chelation, suggesting that release involves autoproteolysis. The extracellular gp63 does not contain a glycosylphosphatidylinositol moiety or ethanolamine, indicating that phospholipolysis is not involved in the release process. Release of gp63 is also independent of glycosylation. The finding of proteolytically active, extracellular gp63 produced by multiple Leishmania isolates suggests a potential role of the extracellular enzyme in substrate degradation relevant to their survival in both the mammalian host and the insect vector.