The diagnostic accuracy for imaging infection with a technetium-99m-labeled antigranulocyte Fab' fragment (LeukoScan) was prospectively examined in a multicenter study. Scintigraphy was performed in ...53 patients at 1 to 6 hours and at 24 hours after injection of the labeled antibody fragment. Thirty-nine sites of infection were detected and confirmed by histologic study, cytologic study, other imaging procedures, or by followup. Thirty-eight of the 53 patients also were studied with technetium-99m-Exametazim or indium-111-oxine labeled leukocytes within 1 week of the LeukoScan study. In 21 patients with 25 osteomyelitic lesions, LeukoScan recognized 13 of the lesions as being true positive ones, 10 as being true negative ones, and 2 as being false negative ones, whereas the leukocyte scan showed 9 true positive results, 5 true negative results, and 2 false negative ones. Sensitivity specificity, and diagnostic accuracy of LeukoScan were 90.0 %, 84.6 %, and 87.9 %; and with autologous leukocyte scintigraphy were 83.9%, 76.5%, and 81.3%, respectively. The sensitivity of LeukoScan was independent of the amount of the labeled antibody injected (0.1 - < 0.5 mg, 96.2%; 0.5 - < 0.9 mg, 80.0%; 0.9 - 1.0 mg, 77.8%). False positive lesions were detected in a periprosthetic calcification, a frontal hyperostosis, and 2 periprosthetic hips that had loosened. Human antimouse antibody could not be detected in any of the 13 patients tested 1 or 3 months after injection. LeukoScan is suitable for imaging infectious lesions and may have diagnostic advantages compared with autologous leukocyte scintigraphy.
We have performed a phase IB study of polyinosinic-polycytidylic acid complexed with poly-L-lysine and carboxymethylcellulose (poly-ICLC) in combination with interleukin 2 (IL-2) in 25 patients with ...a variety of cancers. Patients received weekly or biweekly poly-ICLC by i.m. injection, at doses ranging from 0.01 to 1.0 mg/m2, for 1 month. This was followed by 2 months of outpatient therapy with biweekly i.m. poly-ICLC in combination with IL-2 (3 x 10(6) units/m2) given i.v. by 24-h continuous infusion twice weekly, using a portable infusion pump. No objective tumor responses were observed. Toxicity was moderate at all poly-ICLC doses tested and increased only slightly following the addition of IL-2. No increases in peripheral blood natural killer (NK) activity were observed after treatment with poly-ICLC alone. However, high dose poly-ICLC (greater than or equal to 0.3 mg/m2) in combination with IL-2 resulted in NK activity greater than that seen using the same dose of IL-2 in combination with lower poly-ICLC doses. Increases in the number and percentage of CD56+ cells were evident only after initiation of IL-2 therapy and were unaffected by the poly-ICLC dose. In the majority of patients, these increases were preferentially associated with the subset of CD56+ cells coexpressing CD8, while the CD56+/CD16+ population was elevated to a lesser extent. Moderate increases in serum neopterin levels and 2',5'-oligoadenylate synthetase activity in peripheral blood mononuclear cells were noted at 72 h following initial treatment with 1.0 mg/m2 poly-ICLC. No induction of alpha or gamma interferon was detected. This study shows that the addition of poly-ICLC to a well tolerated IL-2 regimen can significantly enhance NK activity. Poly-ICLC can be used to enhance IL-2-induced NK lytic activity without increases in the dose and, therefore, the toxicity of IL-2 treatment.
The objective was to determine the role of arcitumomab (CEA-Scan; Immunomedics, Morris Plains, NJ), an anticarcinoembryonic antigen (CEA) Fab' labeled with technetium-99m, in the presurgical ...evaluation of patients with recurrent or metastatic colorectal carcinoma.
Surgical resection is the only method known to cure recurrent or metastatic colorectal carcinoma. The location and extent of disease must be determined before surgery. The role of antibody imaging, a new cancer detection modality, in preoperative evaluation for resection of locally recurrent or metastatic colorectal cancer has not been established, either alone or in combination with standard diagnostic modalities.
In a blinded analysis of 209 patients with known or suspected colorectal cancer, the accuracy of arcitumomab, alone and combined with computed tomography (CT), was compared to that of CT for predicting abdominopelvic tumor resectability by correlating the results with surgical and histopathologic findings.
Arcitumomab alone or combined with CT was found to be significantly more accurate for predicting surgical outcome than CT alone. When the results of CT and arcitumomab were concordant for abdominopelvic resectability, nonresectability, or absence of disease, the prediction was accurate in 67%, 100%, and 64%, respectively. Thus, the concordance for nonresectability (100% correct) may obviate the need for other diagnostic modalities or exploratory surgery. When the two tests were discordant, arcitumomab was correct substantially more often than CT. Because the liver is the most common site of distant metastasis in colorectal cancer, a subset of patients with hepatic disease was also analyzed; findings were similar to the overall resectability results. The product's safety profile was excellent: the incidence of induction of an immune response against arcitumomab was <1% and that of potentially adverse events was 1.2%.
The accuracy of arcitumomab for assessing resectability status is greater than that of CT, both in all patients undergoing evaluation for curative abdominopelvic resection of colorectal cancer and in the subset of patients with suspected or proven liver metastases. The additional use of arcitumomab with CT potentially doubles the number of patients who could be saved the cost, morbidity, and mortality of unnecessary abdominopelvic surgery and increases those who are potentially resectable for cure by 40%.
The impact of diagnostic stewardship and testing algorithms on the utilization and performance of the FilmArray meningitis/encephalitis (ME) panel has received limited investigation. We performed a ...retrospective single-center cohort study assessing all individuals with suspected ME between February 2017 and April 2019 for whom the ME panel was ordered. Testing was restricted to patients with cerebrospinal fluid (CSF) pleocytosis. Positive ME panel results were confirmed before reporting through correlation with direct staining (Gram and calcofluor white) and CSF cryptococcal antigen or by repeat ME panel testing. Outcomes included the ME panel test utilization rate, negative predictive value of nonpleocytic CSF samples, test yield and false-positivity rate, and time to appropriate deescalation of acyclovir. Restricting testing to pleocytic CSF samples reduced ME panel utilization by 42.7% (263 versus 459 tests performed) and increased the test yield by 61.8% (18.6% versus 11.5% positivity rate;
< 0.01) with the application of criteria. The negative predictive values of a normal CSF white blood cell (WBC) count for ME panel targets were 100% (195/195) for nonviral targets and 98.0% (192/196) overall. All pathogens detected in nonpleocytic CSF samples were herpesviruses. The application of a selective testing algorithm based on repeat testing of nonviral targets avoided 75% (3/4) of false-positive results without generating false-negative results. The introduction of the ME panel reduced the duration of acyclovir treatment from an average of 66 h (standard deviation SD, 43 h) to 46 h (SD, 36 h) (
= 0.03). The implementation of the ME panel with restriction criteria and a selective testing algorithm for nonviral targets optimizes its utilization, yield, and accuracy.
Sixteen patients with non-Hodgkin's lymphoma were infused with 6.2 to 58.2 mCi (0.2 to 3.9 mg) doses of radioactive iodine (131I)-labeled LL2 immunoglobulin G (IgG) or F(ab')2, in order to study ...antibody distribution, pharmacokinetics, dosimetry, toxicity, tumor targeting, and therapy. LL2 is a murine IgG2a monoclonal antibody (MAb) reactive with B cells and non-Hodgkin's B-cell lymphoma. In a series of five assessable therapy patients, doses as small as 30 mCi 131I-LL2 IgG or F(ab')2 resulted in tumor responses (two partial remissions, two mixed and minor responses, and one no response), while one patient receiving diagnostic doses as low as 6.2 mCi showed a partial remission for 1 year and a complete remission after a second low radiation dose. No acute toxicities were noted, and only myelotoxicity accompanied therapeutic doses, with grade IV marrow toxicity seen in three of seven patients receiving total doses of about 50 mCi. Dosimetry calculations showed spleen and tumor dose rules of about 4.6 cGy/mCi, which was three to four times the dose to other organs. Despite the administration of relatively low doses of LL2 (0.2 to 3.9 mg), 82% of 60 known extrasplenic lymphoma sites were imaged. Serum clearance showed an average distribution half-life (T1/2) of 2.1 hours and an elimination T1/2 of 32.0 hours. The average total-body clearance T1/2 was 43 to 45 hours. LL2's antigenic target does not appear to be shed in high amounts into the circulation. Three of eight patients having at least two injections showed a human antimouse antibody response. These patients may have been presensitized to animal protein. An interesting observation in this study was the marked drop in circulating B lymphocytes after the administration of radioiodinated LL2 or anticarcinoembryonic antigen MAbs, suggesting that this is a nonspecific radiation effect and not necessarily related to the binding of MAb to normal B cells.
We examined the relation of carcinoembryonic antigen levels to time, site and extent of recurrence in 358 patients with colorectal cancer. The recurrence rate was higher in patients with Dukes' B and ...Dukes' C lesions who had preoperative levels higher than 5 ng per milliliter. There was a linear inverse correlation between preoperative levels and estimated mean time to recurrence in patients with Dukes' B and C lesions, ranging from 30 months for a level of 2 to 9.8 months for a level of 70 ng per milliliter. In patients with Dukes' C lesions the median time to recurrence was 13 months if preoperative levels were higher than 5 ng per milliliter, and 28 months if they were lower. Preoperative carcinoembryonic antigen levels in patients with resectable Dukes' B and C cancer provided an additional criterion for allocating these patients to groups at high or low risk for recurrence.
During the initial months of the COVID-19 pandemic, rapidly rising disease prevalence in the United States created a demand for patient-facing information exchanges that addressed questions and ...concerns about the disease. One approach to managing increased patient volumes during a pandemic involves the implementation of telephone-based triage systems. During a pandemic, telephone triage hotlines can be employed in innovative ways to conserve medical resources and offer useful population-level data about disease symptomatology and risk factor profiles.
The aim of this study is to describe and evaluate the COVID-19 telephone triage hotline used by a large academic medical center in the midwestern United States.
Michigan Medicine established a telephone hotline to triage inbound patient calls related to COVID-19. For calls received between March 24, 2020, and May 5, 2020, we described total call volume, data reported by callers including COVID-19 risk factors and symptomatology, and distribution of callers to triage algorithm endpoints. We also described symptomatology reported by callers who were directed to the institutional patient portal (online medical visit questionnaire).
A total of 3929 calls (average 91 calls per day) were received by the call center during the study period. The maximum total number of daily calls peaked at 211 on March 24, 2020. Call volumes were the highest from 6 AM to 11 AM and during evening hours. Callers were most often directed to the online patient portal (1654/3929, 42%), nursing hotlines (1338/3929, 34%), or employee health services (709/3929, 18%). Cough (126/370 of callers, 34%), shortness of breath (101/370, 27%), upper respiratory infection (28/111, 25%), and fever (89/370, 24%) were the most commonly reported symptoms. Immunocompromised state (23/370, 6%) and age >65 years (18/370, 5%) were the most commonly reported risk factors.
The triage algorithm successfully diverted low-risk patients to suitable algorithm endpoints, while directing high-risk patients onward for immediate assessment. Data collected from hotline calls also enhanced knowledge of symptoms and risk factors that typified community members, demonstrating that pandemic hotlines can aid in the clinical characterization of novel diseases.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Background. The authors previously reported that an anticarcinoembryonic antigen antibody against a carcinoembryonic antigen (CEA)‐specific epitope is preferred for clinical investigations. They ...developed a second generation, CEA‐specific murine monoclonal antibody (MoAb), MN‐14 (IMMU‐14), that has a tenfold higher affinity. This report summarizes the initial clinical experience with the new MoAb.
Methods. MN‐14 immunoglobulin G (IgG) (0.5–6.0 mg) was labeled with radioactive iodine (I131) (5–80 mCi) and injected into 22 patients with cancer. External scinti‐graphy was used to determine targeting in patients with low and highly elevated plasma CEA. Quantitative external scintigraphy methods were used to determine organ and tumor clearance rates and absorbed radiation doses. Targeting data were correlated with several factors, including MoAb protein dose, plasma CEA, and relative tumor burden.
Results. Despite more than 80% complexation with plasma CEA of more than 500 ng/ml, all known tumor sites were disclosed by external scintigraphy. The overall sensitivity of tumor targeting on a lesion basis was 89%. The residence time in the blood was predicted by body weight (P = 0.05) and the log of plasma CEA (P = 0.043). The absorbed dose to the red marrow and total body could be predicted by the body weight of the patient, but no other factor contributed significantly to the clearance rate or absorbed dose to the organs. Individual tumors received an average dose of 9.3 ± 6.4 cGy/mCi. The absorbed dose to the tumors was negatively correlated to the weight of the tumor, and the percent uptake in the tumor was positively correlated to the estimated total tumor burden. Patients injected with approximately 5 mg of MN‐14 IgG were more likely to have anti‐mouse antibodies (HAMA) develop than were patients who were injected with less MoAb.
Conclusions. These results suggest that MN‐14 targets tumors effectively, even in the presence of elevated circulating CEA. Additional studies are necessary to determine if an advantage for the higher affinity MN‐14 MoAb, compared with the lower affinity NP‐4 MoAb, can be appreciated clinically.
To describe and identify factors associated with mortality rate and quality of life 1 yr after prolonged mechanical ventilation.
Prospective, observational cohort study with patient recruitment over ...26 months and follow-up for 1 yr.
Intensive care units at a tertiary care university hospital.
Adult patients receiving prolonged mechanical ventilation.
None.
We measured mortality rate and functional status, defined as the inability to perform instrumental activities of daily living (IADLs) 1 yr following prolonged mechanical ventilation. The study enrolled 817 patients. Their median age was 65 yrs, 46% were women, and 44% were alive at 1 yr. Median ages at baseline of 1-yr survivors and nonsurvivors were 53 and 71 yrs, respectively. At the time of admission to the hospital, survivors had fewer comorbidities, lower severity of illness score, and less dependence compared with nonsurvivors. Severity of illness on admission to the intensive care unit and prehospitalization functional status had a significant association with short-term mortality rate, whereas age and comorbidities were related to long-term mortality. Fifty-seven percent of the surviving patients needed caregiver assistance at 1 yr of follow-up. The odds of having IADL dependence at 1-yr among survivors was greater in older patients (odds ratio 1.04 for 1-yr increase in age) and those with IADL dependence before hospitalization (odds ratio 2.27).
Mortality rate after prolonged mechanical ventilation is high. Long-term mortality rate is associated with older age and poor prehospitalization functional status. Many survivors needed assistance after discharge from the hospital, and more than half still required caregiver assistance at 1 yr. Interventions providing support for caregivers and patients may improve the functional status and quality of life of both groups and thus need to be evaluated.
PDF
