SARS-CoV-2 breakthrough infections among vaccinated individuals with rheumatic disease: results from the COVID-19 Global Rheumatology Alliance provider registry.

OBJECTIVE: While COVID-19 vaccination prevents severe infections, poor immunogenicity in immunocompromised people threatens vaccine effectiveness. We analysed the clinical characteristics of patients with rheumatic disease who developed breakthrough COVID-19 after vaccination against SARS-CoV-2. METHODS: We included people partially or fully vaccinated against SARS-CoV-2 who developed COVID-19 between 5 January and 30 September 2021 and were reported to the Global Rheumatology Alliance registry. Breakthrough infections were defined as occurring ≥14 days after completion of the vaccination series, specifically 14 days after the second dose in a two-dose series or 14 days after a single-dose vaccine. We analysed patients' demographic and clinical characteristics and COVID-19 symptoms and outcomes. RESULTS: SARS-CoV-2 infection was reported in 197 partially or fully vaccinated people with rheumatic disease (mean age 54 years, 77% female, 56% white). The majority (n=140/197, 71%) received messenger RNA vaccines. Among the fully vaccinated (n=87), infection occurred a mean of 112 (±60) days after the second vaccine dose. Among those fully vaccinated and hospitalised (n=22, age range 36-83 years), nine had used B cell-depleting therapy (BCDT), with six as monotherapy, at the time of vaccination. Three were on mycophenolate. The majority (n=14/22, 64%) were not taking systemic glucocorticoids. Eight patients had pre-existing lung disease and five patients died. CONCLUSION: More than half of fully vaccinated individuals with breakthrough infections requiring hospitalisation were on BCDT or mycophenolate. Further risk mitigation strategies are likely needed to protect this selected high-risk population.

Analytical Considerations in Nanoscale Flow Cytometry of Extracellular Vesicles to Achieve Data Linearity.

BACKGROUND: Platelet microparticles (PMPs) and their abundance in the blood are a prognostic biomarker in thrombotic disorders and cancer. Nanoscale flow cytometry (nFC) is ideal for high-throughput analysis of PMPs but these clinical assays have not been developed previously. OBJECTIVE: This article demonstrates that nFC is a suitable technology to enumerate PMPs present in plasma samples in a clinical setting. MATERIALS AND METHODS: nFC was performed using the Apogee A50-Micro instrument. Instrument settings and acquisition parameters were developed with the use of fluorescent beads and plasma samples. Sample preparation and handling was also optimized. RESULTS: nFC allows for linear detection of particles between approximately 200 and 1,000 nm based on calibration beads and was dependent on dilution factor and flow rate. Linearity in event analysis as samples became more diluted was lost when events approximately 100 nm were gated while linearity was maintained despite dilution of sample in events larger than 200 nm in diameter. Higher flow rates lead to an under-estimation of events analysed per microlitre of analyte and this was more pronounced when plasma samples were not diluted more than 1/20×. CONCLUSION: nFC offers multi-parametric analysis of PMPs when optimal calibration of acquisition and sample processing settings is performed. Analysis of plasmas from metastatic prostate cancer patients and leukaemia patients revealed that PMP levels were larger than 100 nm and were equally abundant in patients that responded to or failed androgen deprivation therapy or between patients representing different stages of leukaemia.

Digital documentation of the physical examination: moving the clinical breast exam to the electronic medical record.

BACKGROUND: Documentation of the clinical breast examination (CBE) has consisted of simple hand-drawings and stick figures without a common lexicon. There is a need for a device that can accurately depict the CBE in digital format while being objective, reproducible over time, and useable in the electronic medical record. This new device is called palpation imaging (PI). METHODS: We examined 110 patients with a complaint of a breast mass using PI. This laptop-sized device creates a real-time digital display of the palpable area in both video and still formats. The size, hardness, shape, homogeneity, and mass location may be extracted from the image. RESULTS: Of those with a true mass, PI identified the mass in 94% while physical examination identified 86%. The positive predictive value (PPV) for breast cancer using PI was 94% and 78% for physical examination. A survey of primary care physicians revealed the inclusion of the PI record in a consultation note implied competence, experience, and skill by the surgeon. CONCLUSIONS: PI documented the CBE in a timely, efficient, and accurate manner. A reproducible record allows objective review by multiple examiners at varied times. Continued work will optimize examination methods.

Intraoperative digital specimen mammography: prompt image review speeds surgery.

Specimen mammograms are often a time-consuming event for image-guided surgery. The use of an intraoperative imaging device may improve the speed of surgery, but comparison must be made to ensure accuracy is maintained. One hundred fifty consecutive image localized patients underwent both intraoperative digital specimen mammogram (in the operating room) and standard specimen mammogram (in radiology). Intraoperative mammograms as read by breast surgeons were as accurate as standard films while saving an average of 19 minutes per operative procedure. Intraoperative digital specimen mammograms can accurately identify target lesions while saving operating room time.

Intraoperative ultrasonography guidance is accurate and efficient according to results in 100 breast cancer patients.

BACKGROUND: The frequency of nonpalpable breast cancer has doubled in the last 10 years. Surgical use of high quality portable ultrasound units has made it possible to evaluate the time-saving method of intraoperative ultrasonography localization. METHODS: Ultrasonography localization in the operating room immediately prior to definitive surgery was performed by the surgeon. All tissue underwent specimen mammography and ink orientation. The presence of negative margins, the closest margins, the need for reexcision, and the cosmetic result were examined for each patient. RESULTS: Ultrasonography correctly localized all breast cancers at surgery (100% sensitivity). Negative margins for invasive carcinoma were found in 90% of patients. Negative margins were at least 10 mm in 27%, at least 5 mm in 62%, and at least 1 mm in 90%. Positive margins were due to the presence of noncalcified ductal carcinoma in-situ (4 of 10) or multifocal invasive disease (6 of 10) noted at final histology. Reexcisions were performed in 9% of patients. CONCLUSIONS: Surgical use of intraoperative ultrasonography for localization of breast cancer is accurate and efficient. Ultrasonography localization is easier on the patient, is time and cost efficient, and convenient to schedule. Surgeons should embrace this new skill and utilize this tool whenever a nonpalpable breast cancer can be seen with ultrasonography.

Encircling guidewire facilitates complete excision of image-localized breast lesions.

BACKGROUND: An innovative encircling guidewire defines three sides of a target lesion with a single puncture to achieve negative margins. METHODS: Twenty-five patients requiring image-guided surgery were localized with an encircling guidewire. Although the deployed wire is circular, it is straight when placed, using a straight outer needle. After image-guided placement of the wire around the lesion, all patients underwent standard surgical excision. Each patient was categorized by proper localization of the target lesion, presence of negative margins, closest margin, and need for reexcision. RESULTS: The circlewire wire identified the target lesion in all cases. There were no complications relative to either version of the leading tip on the guidewire. Negative margins were achieved in all pure invasive ductal carcinomas. Positive margins were found in all 3 patients with extensive noncalcified in-situ disease and 1 patient with multifocal invasive lobular carcinoma. CONCLUSIONS: An innovative encircling localizing guidewire device gives the surgeon a new option to completely remove a nonpalpable breast lesion.

Intraoperative digital specimen mammography: rapid, accurate results expedite surgery.

INTRODUCTION: Specimen mammography during image guided breast surgery is a daily occurrence. The process of specimen travel, imaging and reporting may take 20-30 minutes. An intraoperative method to obtain digital specimen mammograms may expedite the process. We compared intraoperative digital specimen mammography (IDSM) as well as standard specimen mammography (SSM) on 121 consecutive image guided lumpectomies. METHODS: Each lumpectomy specimen had IDSM obtained followed by travel to radiology for SSM. Surgical decisions were based on all imaging obtained. Data included 1) the ability of each imaging method to identify the target lesion, 2) degree of concordance of surgical interpretation of IDSM compared to radiologist interpretation of SSM, 3) the time required from lumpectomy to surgical review of images from each method, and 4) potential operative time savings. RESULTS: Intraoperative digital specimen mammography (IDSM) was equally as accurate as standard x-ray film specimen mammography. There was no significant difference between 1) the frequency of identification of the target lesion by surgeon or radiologist, 2) lack of identification of any lesion, or 3) frequency of involved margins using imaging criteria. However, there was a marked difference in 1) the time needed to obtain images ready to read, 2) the ability to re-excise tissue promptly, and 3) the overall operating room time with an average decrease of 19 minutes. CONCLUSIONS: Intraoperative digital specimen mammography (IDSM) was equally accurate as SSM obtained in this study. Use of this new technology allows surgeons to quickly view specimen images which translate into shorter more efficient operations.

Inferior vena cava filling defects on CT and MRI.

OBJECTIVE: The purpose of this article is to describe the appearance and causes of inferior vena cava (IVC) filling defects, how such findings may be accurately characterized, and the clinical significance of IVC filling defects. Filling defects in the IVC observed at MDCT and MRI may be a result of flow artifacts, anatomic variants, or bland or malignant thrombus. CONCLUSION: Familiarity with anatomy and flow effects is critical for distinguishing true from false filling defects in the IVC. Delayed imaging after administration of IV contrast material and dedicated MRI sequences may be helpful for further characterization of such findings. Once a true filling defect of the IVC is established, identification of the cause, whether benign or malignant, and extent will guide clinical treatment.

Intraoperative ultrasound facilitates surgery for early breast cancer.

BACKGROUND: Mammogram-directed wire localization for nonpalpable cancer requires surgeon's time and coordination and some patient discomfort. Up to half of these nonpalpable lesions can be visualized by ultrasound. Use of intraoperative ultrasound streamlines the process of image-guided surgery. METHODS: We prospectively visualized 69 nonpalpable breast cancers between January 1998 and July 2001. Ultrasound localization was performed in the operating room immediately before definitive surgery. Breast cancers were localized using either blue dye or a guide wire. RESULTS: Ultrasound correctly localized all lesions at surgery. Negative margins for invasive carcinoma were found in 97% (67 of 69) of patients. Re-excisions were performed in only 6% (4 of 69) of patients. Overall negative margins were found in 90% (62 of 69) of patients. Most positive margins (71%) were due to the presence of noncalcified ductal carcinoma in situ. Mastectomy was necessary in 4% of patients, usually due to multifocal invasive carcinoma. CONCLUSIONS: Increased familiarity with ultrasound has allowed the surgeon to localize breast cancer in the operating room, improving the process of image-guided surgery. Ultrasound localization is accurate, time efficient, technically feasible, and easier for the patient. The re-excision rate is very low and is similar to that for mammographic localization. Intraoperative ultrasound localization should be considered whenever a breast cancer needs image-guided excision.

Metallic marker placement after stereotactic core biopsy of breast calcifications: comparison of two clips and deployment techniques.

OBJECTIVE: Two methods of deployment of metallic clips at the site of stereotactic core biopsy for breast calcifications are compared retrospectively. MATERIALS AND METHODS: One hundred nineteen clips deployed through an 11-gauge vacuum-assisted biopsy probe at core biopsy sites were compared with 109 vascular ligating clips deployed at biopsy sites using an 18-gauge spinal needle. The distance of each clip from the position of the target calcification was assessed using stereotactic coordinates in 52 sequential cases and was measured on mammograms before and after biopsy in 108 clips deployed through an 11-gauge probe and 98 clips deployed using an 18-gauge needle. Variance in clip position between postbiopsy and follow-up mammograms was measured in 43 clips placed with an 11-gauge probe and in 44 clips placed with an 18-gauge needle. Comparable measurements of variance in position of fat necrosis calcifications between screening mammograms were used as controls. RESULTS: Ninety-seven percent of the clips placed with an 11-gauge probe and 98% of the clips placed using an 18-gauge needle were within 1 cm of the target calcifications using stereotactic coordinates. On mammograms obtained after biopsy, 70% of the clips placed with an 11-gauge probe and 63% of the clips placed using an 18-gauge needle were within 1 cm of the target calcifications, and the position of 91% of the clips placed with an 11-gauge probe and 90% of the clips placed using an 18-gauge needle varied less than 15 mm on follow-up mammograms. Both clips provided accurate targets for wire-localized excisions. The cost of the 11-gauge needle and clip is $320. The 14-gauge probe, vascular clip, and 18-gauge spinal needle cost $191.58. CONCLUSION: A vascular ligating clip delivered to a stereotactic core biopsy site by an 18-gauge spinal needle is comparable in apparent accuracy and stability to a clip deployed through an 11-gauge probe. This technique allows core biopsies to be performed with instruments smaller than 11-gauge and at a 40% savings in equipment cost.

Stereotactic core breast biopsy of malignant calcifications: diagnostic yield of cores with and cores without calcifications on specimen radiographs.

PURPOSE: To retrospectively compare core biopsy diagnosis with final diagnosis at surgical excision in cores with and cores without calcification on specimen radiographs. MATERIALS AND METHODS: One hundred thirteen consecutive patients underwent vacuum-assisted 11- or 14-gauge needle stereotactic core biopsy for calcifications with malignant histologic results in core samples from 116 lesions. For each lesion, calcification was identified in at least one core at specimen radiography. Cores with and those without calcification seen on magnified specimen radiographs were separately submitted to and reported on by pathologists, who obtained additional levels in cores with calcification. All patients underwent surgical excision of the lesion area within 7 weeks. The pathologic diagnosis in core samples with and those without calcification on specimen radiographs was compared with final diagnosis at surgical excision. Fisher exact test was used for all chi(2) determinations of statistical significance. RESULTS: Cores with calcification on specimen radiographs were more likely to enable a final diagnosis of malignancy than were cores without calcification (98 [84%] vs 82 [71%] of 116; P =.02). Cores without calcification were significantly more likely to cause a diagnosis of cancer to be missed than were those with calcification on specimen radiographs (13 [11%] vs one [1%] of 116; P <.001). Underestimates of malignancy were more frequent in 14- than in 11-gauge specimens (11 [18%] of 60 vs six [10%] of 56; P =.30). Regardless of needle size, there was no significant difference in underestimation of malignancy between cores with and without radiographically evident calcification (17 [15%] vs 21 [18%] of 116; P =.60). CONCLUSION: Specimen radiography is essential to document calcification retrieval. Cores without radiographically demonstrated calcification may fail to show a malignant lesion. Separate identification of calcium-containing cores may assist the pathologist, who can more thoroughly evaluate these cores with additional levels of section.

Detachable balloon-modified reducing stent to treat hepatic insufficiency after transjugular intrahepatic portosystemic shunt creation.

A patient developed severe hepatic insufficiency after creation of a transjugular intrahepatic portosystemic shunt, which was treated unsuccessfully with a constrained Wallstent ("reducing stent"). After a failed attempt at occluding the shunt with an occlusion balloon, a detachable balloon was placed at the portal end of the constrained stent. This balloon-modified reducing stent reduced flow while maintaining shunt patency, and the patient's hepatic insufficiency improved. She went on to undergo successful liver transplantation several months later.

Do simultaneous bilateral tunneled infusion catheters in patients undergoing bone marrow transplantation increase catheter-related complications?

PURPOSE: Secure venous access with multiple lumens is necessary for the care of allogeneic hematopoietic stem cell transplant (HSCT) recipients. The outcomes associated with simultaneous bilateral tunneled internal jugular infusion catheter placement in the HSCT recipient population were investigated in an attempt to determine whether simultaneous introduction of these catheters compounds or magnifies the risks (infection, venous thrombosis) associated with tunneled catheters. MATERIALS AND METHODS: Patients undergoing HSCT and receiving bilateral tunneled infusion catheters in a single procedure were identified using a quality assurance data base. Medical records for the duration of catheterization were reviewed; 43 patients were included in the study (mean age, 42 years; range, 22-56). Diagnoses included acute lymphocytic leukemia (n = 4), acute myelogenous leukemia (n = 8), aplastic anemia (n = 2), chronic myelogenous leukemia (n = 17), chronic lymphocytic leukemia (n = 1), Hodgkin lymphoma (n = 1), myelodysplasia (n = 4), myelofibrosis (n = 2), and non-Hodgkin lymphoma (n = 4). Cox proportional hazards regression analysis was performed to determine differences in infection rates between dual- and triple-lumen catheters. RESULTS: Forty-three pairs of catheters were placed. All met venous access needs for HSCT recipient care. Complete follow-up was achieved for 77 of 87 (89%) catheters. The overall infection rate was 0.25 per 100 catheter-days. The rate was 0.19 and 0.33 for dual- and triple-lumen catheters, respectively (P =.15). Mechanical failure did not differ between catheter types (dual: 0.14 episodes per 100 days, triple: 0.05 per 100 days, P =.2). CONCLUSIONS: Bilateral multilumen tunneled infusion catheter placement in a single procedure using imaging guidance is safe with acceptable outcomes and meets venous access needs for HSCT. There is a trend toward higher infection rates, with more lumens and more mechanical failure with dual-lumen catheters.