Incidence of long COVID and associated psychosocial characteristics in a large U.S. city.

PURPOSE: Persistent residual effects from Coronavirus Disease-2019 (COVID-19) have been observed with varying definitions of "Long COVID" and little comprehensive examination. This study examined the incidence and psychosocial correlates of Long COVID using different definitions. METHODS: Data were analyzed from a citywide sample of 3595 adults with lab-confirmed cases of COVID-19 that were surveyed over 3 months. Rates of Long COVID were examined in terms of Post-Acute COVID (PAC), defined as at least one symptom lasting for 4 weeks, and three levels of Post-COVID Syndrome (PCS) that included experiencing at least one symptom for 3 months (PCS-1), experiencing three or more symptoms for 3 months (PCS-2), or experiencing at least one of the same symptoms for 3 months (PCS-3). RESULTS: Among the 686 participants who completed baseline, 1-month, and 3-month follow-up assessments, 75.7% had PAC, 55.0% had PSC-1, 26.5% had PSC-2, and 19.0% had PSC-3. Comparing participants with PAC and PSC-3 in the total sample with inverse probability weighting, multivariable analyses revealed being female, Asian or Native American, greater reported longlines, and less social support were predictive of PCS-3. CONCLUSION: Residual effects of COVID-19 are very common and nearly one-fifth of our sample met the most restrictive definition of Long COVID warranting concern as a public health issue. Some demographic and social factors may predispose some adults to Long COVID, which should be considered for prevention and population health.

Soluble mesothelin related peptides (SMRP) and osteopontin as protein biomarkers for malignant mesothelioma: analytical validation of ELISA based assays and characterization at mRNA and protein levels.

BACKGROUND: There is a need to identify reliable markers for malignant mesothelioma. Soluble mesothelin related peptides (SMRP) and osteopontin (OPN) have gained interest in recent years for this purpose. METHODS: SMRP (Fujirebio Diagnostics Inc.) and OPN (R&D Inc.) ELISA methods were evaluated for multiple parameters. Concentrations were measured in blood from patients with mesothelioma, normal healthy volunteers, and patients with other (non-mesothelioma) cancers. In silico analysis was performed using the GeoProfiles database. At the protein level, SMRP and OPN were measured in cell culture supernatants, and values were compared in patients pre- and post-extrapleural pneumonectomy. RESULTS: The SMRP assay demonstrates intra-assay CVs of 2.3% and 3% (at 4.6 nM and 13.7 nM, respectively), and inter-assay CVs of 3.5% and 3.7% at the same concentrations. The limit of detection (LOD) is 0.182 nM. The OPN assay demonstrates intra-assay CVs of 5.8%, 4.1%, and 5.2% (at 1.9, 5.1, and 11.1 ng/mL, respectively), and inter-assay CVs of 8.5%, 8.4%, and 12.1% at the same concentrations. The LOD is 0.032 ng/mL. Both SMRP and OPN in mesothelioma patients were significantly higher than in patients with other (non-mesothelioma) cancer and in healthy volunteers. The two markers do not appear to correlate with each other and exhibit different tissue expression patterns. Protein concentrations of these markers are highest in different sets of cell lines. Finally, SMRP but not OPN concentrations were decreased in five of seven consecutive patients after extrapleural pneumonectomy, compared to their respective pre-operative values. CONCLUSIONS: These assays provide reliable and reproducible quantitation of SMRP and OPN proteins. Both are increased in mesothelioma patients compared to non-mesothelioma controls. However, the two analytes do not correlate with each other and show distinct expression profiles and protein expression. Concentrations of SMRP but not OPN are decreased in post-surgical samples. Our results further characterize these markers, establish assay performance characteristics, and lay the groundwork for further studies to measure these markers in blood.

Fluorescence in situ hybridization analysis of circulating tumor cells in metastatic prostate cancer.

PURPOSE: To assess the feasibility of characterizing gene copy number alteration by fluorescence in situ hybridization (FISH) of circulating tumor cells (CTC) isolated using the CellSearch system in patients with progressive castration-resistant metastatic prostate cancer. EXPERIMENTAL DESIGN: We used probe combinations that included the androgen receptor (AR) and MYC genes for FISH analysis of CTC samples collected from 77 men with castration-resistant metastatic prostate cancer. RESULTS: High-level chromosomal amplification of AR was detected in 38% and relative gain of MYC in 56% of samples analyzed. No such abnormalities were detected in samples with CTC counts of <10, reflecting ascertainment difficulty in these lower count samples. CONCLUSION: The CTC isolated from our patient cohort present a very similar molecular cytogenetic profile to that reported for late-stage tumors and show that FISH analysis of CTC can be a valuable, noninvasive surrogate for routine tumor profiling. That as many as 50% of these patients have substantial amplification of the AR locus indicates that androgen signaling continues to play an important role in late-stage prostate cancer.

Circulating prostate tumor cells detected by reverse transcription-PCR in men with localized or castration-refractory prostate cancer: concordance with CellSearch assay and association with bone metastases and with survival.

BACKGROUND: Reverse transcription-PCR (RT-PCR) assays have been used for analysis of circulating tumor cells (CTCs), but their clinical value has yet to be established. We assessed men with localized prostate cancer or castration-refractory prostate cancer (CRPC) for CTCs via real-time RT-PCR assays for KLK3 [kallikrein-related peptidase 3; i.e., prostate-specific antigen (PSA)] and KLK2 mRNAs. We also assessed the association of CTCs with disease characteristics and survival. METHODS: KLK3, KLK2, and PSCA (prostate stem cell antigen) mRNAs were measured by standardized, quantitative real-time RT-PCR assays in blood samples from 180 localized-disease patients, 76 metastatic CRPC patients, and 19 healthy volunteers. CRPC samples were also tested for CTCs by an immunomagnetic separation system (CellSearch; Veridex) approved for clinical use. RESULTS: All healthy volunteers were negative for KLK mRNAs. Results of tests for KLK3 or KLK2 mRNAs were positive (> or =80 mRNAs/mL blood) in 37 patients (49%) with CRPC but in only 15 patients (8%) with localized cancer. RT-PCR and CellSearch CTC results were strongly concordant (80%-85%) and correlated (Kendall tau, 0.60-0.68). Among CRPC patients, KLK mRNAs and CellSearch CTCs were closely associated with clinical evidence of bone metastases and with survival but were only modestly correlated with serum PSA concentrations. PSCA mRNA was detected in only 7 CRPC patients (10%) and was associated with a positive KLK mRNA status. CONCLUSIONS: Real-time RT-PCR assays of KLK mRNAs are highly concordant with CellSearch CTC results in patients with CRPC. KLK2/3-expressing CTCs are common in men with CRPC and bone metastases but are rare in patients with metastases diagnosed only in soft tissues and patients with localized cancer.

Determination of busulfan in human plasma using an ELISA format.

High-dose busulfan is an important component of many bone marrow transplantation-preparative regimens. High busulfan plasma levels have been shown to increase the chance of venoocclusive disease and low levels are associated with recurrence of disease or graft rejection. Currently, busulfan levels are monitored by physical methods that are expensive and time consuming, resulting in relatively low overall use of busulfan testing for dose adjustment. Novel highly selective antibodies for busulfan have been generated and a microtiter plate immunoassay capable of quantifying busulfan levels in plasma has been developed. The assay was configured using a busulfan-horseradish peroxidase (HRP) conjugate as the reporter group and busulfan monoclonal antibodies. The assay requires 30 microL of plasma with no sample preparation. The immunoassay has a standard curve based on busulfan with a range of 75-2000 ng/mL. The time to first result is 30 minutes with up to 40 patient samples in duplicate; multiple plates can be run at once. The coefficient of variation (CV) on signal is <5% for an entire plate, and the 95% confidence interval for negative samples (n = 78) is below the lowest calibrator of 75 ng/mL. Cross-reactivity with the major inactive metabolites (tetrahydrothiophene, tetramethyl sulfone, and tetrahydrothiophene-3-ol-1,1-dioxide) was <0.1%. Results generated with clinical samples (n = 35 and n = 70) correlate well to gas chromatography-mass spectrometry (R = 0.976 and 0.985, respectively) with a slope of 1.05 +/- 0.05. This immunoassay method is suitable for determining levels of busulfan in human plasma. It offers the advantages of using a smaller sample size, does not require sample preparation, and is less labor intensive than other methods. The ability to make 240 determinations per hour enables effective and timely routine monitoring of busulfan levels in clinical practice.

Circulating tumor cell number and prognosis in progressive castration-resistant prostate cancer.

PURPOSE: The development of tumor-specific markers to select targeted therapies and to assess clinical outcome remains a significant area of unmet need. We evaluated the association of baseline circulating tumor cell (CTC) number with clinical characteristics and survival in patients with castrate metastatic disease considered for different hormonal and cytotoxic therapies. EXPERIMENTAL DESIGN: CTC were isolated by immunomagnetic capture from 7.5-mL samples of blood from 120 patients with progressive clinical castrate metastatic disease. We estimated the probability of survival over time by the Kaplan-Meier method. The concordance probability estimate was used to gauge the discriminatory strength of the informative prognostic factors. RESULTS: Sixty-nine (57%) patients had five or more CTC whereas 30 (25%) had two cells or less. Higher CTC numbers were observed in patients with bone metastases relative to those with soft tissue disease and in patients who had received prior cytotoxic chemotherapy relative to those who had not. CTC counts were modestly correlated to measurements of tumor burden such as prostate-specific antigen and bone scan index, reflecting the percentage of boney skeleton involved with tumor. Baseline CTC number was strongly associated with survival, without a threshold effect, which increased further when baseline prostate-specific antigen and albumin were included. CONCLUSIONS: Baseline CTC was predictive of survival, with no threshold effect. The shedding of cells into the circulation represents an intrinsic property of the tumor, distinct from extent of disease, and provides unique information relative to prognosis.

Circulating tumor cell analysis in patients with progressive castration-resistant prostate cancer.

PURPOSE: To better direct targeted therapies to the patients with tumors that express the target, there is an urgent need for blood-based assays that provide expression information on a consistent basis in real time with minimal patient discomfort. We aimed to use immunomagnetic-capture technology to isolate and analyze circulating tumor cells (CTC) from small volumes of peripheral blood of patients with advanced prostate cancer. EXPERIMENTAL DESIGN: Blood was collected from 63 patients with metastatic prostate cancer. CTCs were isolated by the Cell Search system, which uses antibodies to epithelial cell adhesion marker and immunomagnetic capture. CTCs were defined as nucleated cells positive for cytokeratins and negative for CD45. Captured cells were analyzed by immunofluorescence, Papanicolau staining, and fluorescence in situ hybridization. RESULTS: Most patients (65%) had 5 or more CTCs per 7.5 mL blood sample. Cell counts were consistent between laboratories (c = 0.99) and did not change significantly over 72 or 96 h of storage before processing (c = 0.99). Their identity as prostate cancer cells was confirmed by conventional cytologic analysis. Molecular profiling, including analysis of epidermal growth factor receptor (EGFR) expression, chromosome ploidy, and androgen receptor (AR) gene amplification, was possible for all prostate cancer patients with >or=5 CTCs. CONCLUSIONS: The analysis of cancer-related alterations at the DNA and protein level from CTCs is feasible in a hospital-based clinical laboratory. The alterations observed in EGFR and AR suggest that the methodology may have a role in clinical decision making.

Frecuencia de perforaciones radiculares en tratamientos endodónticos realizados por estudiantes de postgrados chilenos

Introducción: Este estudio evaluó la frecuencia de perforaciones radiculares provocadas por estudiantes de primer y segundo año de la especialidad de Endodoncia de la Facultad de Odontología de la Universidad Andrés Bello (UNAB), Santiago (Chile), entre 2019 y marzo de 2021. Materiales y Métodos: Se realizó un estudio observacional descriptivo a través de datos recopilados retrospectivamente en fichas clínicas de pacientes atendidos en el área de postgrado en Endodoncia de la universidad, durante 2019, 2020 y hasta marzo de 2021. Resultados: Un total de 569 pacientes fueron atendidos en el período, 118 fueron atendidos por estudiantes de primer año y 451 por los de segundo año. La frecuencia de perforaciones del primer año fue de un 0% y la del segundo año del 2 % (n = 9). Considerando el total general de pacientes, la frecuencia relativa de perforaciones fue de apenas 1,6 %. Con respecto a ubicación, 3 perforaciones fueron en el tercio cervical de la raíz, 3 en el tercio medio, 2 en el tercio apical y 1 en el piso cameral. Ninguna perforación resultó en la indicación inmediata de extracción y todas fueron selladas con materiales a base de silicato de calcio. Conclusiones: La frecuencia de perforaciones radiculares por los estudiantes de postgrado fue muy baja, lo que podría evidenciar la seguridad de los protocolos institucionales de tratamiento y enseñanza. La mayor ocurrencia de perforaciones fue con los estudiantes de segundo año, lo cual puede ser atribuido a que tratan casos de mayor complejidad.

Introduction: The present study evaluated the frequency of root perforations caused by first- and second-year students of the Endodontics specialty of the Faculty of Dentistry of the UNAB University in Santiago (Chile), between January 2019 and March 2021. Materials and Methods: A descriptive observational study was carried out through data collected retrospectively in clinical records of patients treated in the Postgraduate Endodontics Clinic of the Andrés Bello University (UNAB) during 2019, 2020 and until March 2021. Results: A total of 569 patients were treated during the period, 118 patients were seen by first-year students and 451 by second-year students. The frequency of perforations in the first year was 0% and in the second year it was 2% (n=9). Considering the overall total number of patients, the relative frequency of perforations was only 1.6%. Regarding location, 3 perforations were in the cervical third of the root, 3 in the middle third, 2 in the apical third and 1 in the pulp chamber floor. No perforation resulted in the immediate indication of extraction and all were sealed with calcium silicate-based materials. Conclusions: Te frequency of root perforations by postgraduate students was very low, which could evidence the safety of institutional treatment and teaching protocols. The greatest occurrence of perforations was with second-year students, which can be attributed to the fact that they treat cases of greater complexity.

Incidencia del Traumatismo Dentoalveolar en pacientes atendidos por el Sistema de Salud Pública en Chile

Introducción: Los traumas dentoalveolares constituyen un conjunto de lesiones que comprometen los dientes o a sus estructuras periodontales (producto de impactos violentos, directos o indirectos). Constituyen un problema de salud pública a nivel mundial. Objetivo: El objetivo de esta investigación fue: escribir la tendencia de la incidencia del traumatismo dentoalveolar según grupos etarios en pacientes del Fondo Nacional de Salud reportados en Atención Primaria en Salud y Centros de Especialidades en Chile durante el periodo 2008-2018. Métodos: Investigación de tipo descriptivo transversal se calcularon las tasas de incidencia específicas por edad entre 2008 y 2014 de la Atención Primaria de Salud y estas mismas tasas en los Centros de Especialidades entre 2009-2018. Resultados: Los resultados obtenidos nos permiten observar que la tendencia en APS disminuyó de forma progresiva y en Centros de Especialidades aumentó en todos los años, excepto en el rango etario de 20-64 años. En este último caso, el número de años estudiados permitió la estimación de proyecciones de las tasas de incidencia hacia los años 2019-2021, que indican que habría un aumento. Conclusiones: El registro de traumas dentoalveolares en Chile en el Sistema de Salud Pública es deficiente para realizar investigaciones con poblaciones representativas. Lo que dificulta la comprensión de la epidemiología y la determinación de estrategias adecuadas.

Introducción: Dentoalveolar traumas are defined as a set of injuries that compromise the teeth or their periodontal structures, as a consequence of a direct or indirect violent impact. They constitute a public health problem worldwide. Objective. To describe the trend of the incidence of dentoalveolar trauma according to age groups in patients from the National Health Fund reported in Primary Health Care and Specialty Centers in Chile during the period 2008-2018. Methods: The research carried out in the present work is of a descriptive transversal type. Age-specific incidence rates were calculated between 2008 and 2014 for Primary Health Care and these same rates in Specialty Centers between 2009-2018. Results: The results obtained allow us to observe that the trend in PHC decreased progressively and in Specialty Centers it increased in all years, except in the age range of 20-64 years. In the latter case, the number of years studied allowed the estimation of incidence rate projections towards the years 2019-2021, which indicate that there would be an increase. Conclusions: The registry of dentoalveolar traumas in Chile in the Public Health System is deficient to carry out research with representative populations. This makes it difficult to understand epidemiology and determine appropriate strategies.

Serum biomarkers for assessing histology and outcomes in patients with metastatic lung cancer.

BACKGROUND: Serum biomarkers are not in routine clinical use for diagnosis, prognosis, or treatment selection in lung cancer. OBJECTIVE: We examined serum protein biomarkers from patients with metastatic lung cancer to determine whether they correlate with progression-free survival (PFS), overall survival (OS), or histologic subtype. METHODS: Serum samples were collected prior to chemotherapy from 153 patients with metastatic lung cancer treated at Memorial Sloan-Kettering Cancer Center. Serum biomarkers were selected for ELISA testing based on their availability in a CLIA-certified clinical laboratory: ProGRP, SCC-Ag, NSE, CYFRA 21-1, TIMP1, and HE4. Pretreatment biomarker levels were correlated with outcome using proportional hazards analysis and tumor histology using logistic regression analysis. RESULTS: Univariate analysis indicated that only higher levels of CYFRA 21-1 were significantly associated with worsened PFS (HR 1.3, 95% CI 1.1--1.5, p< 0.01) and OS (HR 1.4, 95% CI 1.2-1.7, p< 0.001). Multivariate analysis of NSE, CYFRA 21-1, and TIMP1 indicated that CYFRA 21-1 remained independently associated with lower OS (HR 1.3, 95% CI 1.1-1.6, p< 0.01). Univariate analysis indicated that ProGRP (OR 3.3, 95% CI 1.7-6.5, p< 0.001) and NSE (OR 4.8, 95% CI 2.6-8.8, p< 0.0001) had the highest probabilities of differentiating SCLC from NSCLC. Multivariate analysis of these two markers demonstrated that they predicted SCLC histology with 94% accuracy. Univariate analysis showed that only SCCL-Ag distinguished squamous cell histology from adenocarcinoma (OR 4.4, 95% CI 1.7-11.5, p< 0.01). CONCLUSIONS: Serum CYFRA 21-1 may be useful in predicting patient survival, and serum ProGRP, NSE 21-1, and SCCL-Ag may be helpful in distinguishing between lung cancer sub-types.

Rare cell capture technology for the diagnosis of leptomeningeal metastasis in solid tumors.

OBJECTIVE: To evaluate the utility of rare cell capture technology (RCCT) in the diagnosis of leptomeningeal metastasis (LM) from solid tumors through identification of circulating tumor cells (CTCs) in the CSF. METHODS: In this pilot study, CSF samples from 60 patients were analyzed. The main patient cohort consisted of 51 patients with solid tumors undergoing lumbar puncture for clinical suspicion of LM. Those patients underwent initial MRI evaluation and had CSF analyzed through conventional cytology and for the presence of CTCs using RCCT, based on immunomagnetic platform enrichment utilizing anti-epithelial cell adhesion molecule antibody-covered magnetic nanoparticles. An additional 9 patients with CSF pleocytosis but without solid tumors were separately analyzed to ensure accurate differentiation between CTCs and leukocytes. RESULTS: Among the 51 patients with solid tumors, 15 patients fulfilled criteria for LM. CSF CTCs were found in 16 patients (median 20.7 CTCs/mL, range 0.13 to >150), achieving a sensitivity of 100% as compared with 66.7% for conventional cytology and 73.3% for MRI. One patient had a false-positive CSF CTC result (specificity = 97.2%); however, that patient eventually met LM criteria 6 months after the tap. CSF CTCs were not found in any of the additional 9 patients with CSF pleocytosis. CONCLUSION: RCCT is an accurate, novel method for the detection of LM in solid tumors, potentially providing earlier diagnostic confirmation and sparing patients from repeat lumbar punctures.

Measles outbreak associated with an international youth sporting event in the United States, 2007.

BACKGROUND: Despite elimination of endemic measles in the United States (US), outbreaks associated with imported measles continue to occur. In 2007, the initiation of a multistate measles outbreak was associated with an imported case occurring in a participant at an international youth sporting event held in Pennsylvania. METHODS: Case finding and contact tracing were conducted. Control measures included isolating ill persons and administering postexposure prophylaxis to exposed persons without documented measles immunity. Laboratory evaluation of suspected cases and contacts included measles serologic testing, viral culture, detection of viral RNA by reverse-transcription polymerase chain reaction, and viral genotyping. RESULTS: The index case occurred in a child from Japan aged 12 years. Contact tracing among 1250 persons in 8 states identified 7 measles cases; 5 (71%) cases occurred among persons without documented measles vaccination. Epidemiologic and laboratory investigation supported a single chain of transmission, linking the outbreak to contemporaneous measles virus genotype D5 transmission in Japan. Of the 471 event participants, 193 (41%) lacked documentation of presumed measles immunity, 94 (49%) of 193 were US-resident adults, 19 (10%) were non-US-resident adults (aged >18 years), and 80 (41%) were non-US-resident children. DISCUSSION: Measles outbreaks associated with imported disease are likely to continue in the US. Participants in international events, international travelers, and persons with routine exposure to such travelers might be at greater risk of measles. To reduce the impact of imported cases, high measles, mumps, and rubella vaccine coverage rates should be maintained throughout the US, and support should continue for global measles control and elimination.

Identical genotype B3 sequences from measles patients in 4 countries, 2005.

Surveillance of measles virus detected an epidemiologic link between a refugee from Kenya and a Dutch tourist in New Jersey, USA. Identical genotype B3 sequences from patients with contemporaneous cases in the United States, Canada, and Mexico in November and December 2005 indicate that Kenya was likely to have been the common source of virus.