Association of clinical factors and recent anticancer therapy with COVID-19 severity among patients with cancer: a report from the COVID-19 and Cancer Consortium.

BACKGROUND: Patients with cancer may be at high risk of adverse outcomes from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. We analyzed a cohort of patients with cancer and coronavirus 2019 (COVID-19) reported to the COVID-19 and Cancer Consortium (CCC19) to identify prognostic clinical factors, including laboratory measurements and anticancer therapies. PATIENTS AND METHODS: Patients with active or historical cancer and a laboratory-confirmed SARS-CoV-2 diagnosis recorded between 17 March and 18 November 2020 were included. The primary outcome was COVID-19 severity measured on an ordinal scale (uncomplicated, hospitalized, admitted to intensive care unit, mechanically ventilated, died within 30 days). Multivariable regression models included demographics, cancer status, anticancer therapy and timing, COVID-19-directed therapies, and laboratory measurements (among hospitalized patients). RESULTS: A total of 4966 patients were included (median age 66 years, 51% female, 50% non-Hispanic white); 2872 (58%) were hospitalized and 695 (14%) died; 61% had cancer that was present, diagnosed, or treated within the year prior to COVID-19 diagnosis. Older age, male sex, obesity, cardiovascular and pulmonary comorbidities, renal disease, diabetes mellitus, non-Hispanic black race, Hispanic ethnicity, worse Eastern Cooperative Oncology Group performance status, recent cytotoxic chemotherapy, and hematologic malignancy were associated with higher COVID-19 severity. Among hospitalized patients, low or high absolute lymphocyte count; high absolute neutrophil count; low platelet count; abnormal creatinine; troponin; lactate dehydrogenase; and C-reactive protein were associated with higher COVID-19 severity. Patients diagnosed early in the COVID-19 pandemic (January-April 2020) had worse outcomes than those diagnosed later. Specific anticancer therapies (e.g. R-CHOP, platinum combined with etoposide, and DNA methyltransferase inhibitors) were associated with high 30-day all-cause mortality. CONCLUSIONS: Clinical factors (e.g. older age, hematological malignancy, recent chemotherapy) and laboratory measurements were associated with poor outcomes among patients with cancer and COVID-19. Although further studies are needed, caution may be required in utilizing particular anticancer therapies. CLINICAL TRIAL IDENTIFIER: NCT04354701.

Evidence against solar influence on nuclear decay constants.

The hypothesis that proximity to the Sun causes variation of decay constants at permille level has been tested and disproved. Repeated activity measurements of mono-radionuclide sources were performed over periods from 200 days up to four decades at 14 laboratories across the globe. Residuals from the exponential nuclear decay curves were inspected for annual oscillations. Systematic deviations from a purely exponential decay curve differ from one data set to another and are attributable to instabilities in the instrumentation and measurement conditions. The most stable activity measurements of alpha, beta-minus, electron capture, and beta-plus decaying sources set an upper limit of 0.0006% to 0.008% to the amplitude of annual oscillations in the decay rate. Oscillations in phase with Earth's orbital distance to the Sun could not be observed within a 10-6 to 10-5 range of precision. There are also no apparent modulations over periods of weeks or months. Consequently, there is no indication of a natural impediment against sub-permille accuracy in half-life determinations, renormalisation of activity to a distant reference date, application of nuclear dating for archaeology, geo- and cosmochronology, nor in establishing the SI unit becquerel and seeking international equivalence of activity standards.

Measurements of the absolute gamma-ray emission intensities from the decay of 166Ho.

166Ho (T1/2≈ 26.8 h) is an emerging theragnostic radionuclide of interest in nuclear medicine due to its peculiar decay scheme, featuring high-energy ß- emission (≈ 1.8 MeV) coupled with the main gamma-ray emission (≈ 80.6 keV). Using the new 166Ho activity standard and the well-calibrated, high-energy resolution HPGe detector, both available at ENEA-INMRI, a new determination of several 166Ho gamma-ray emission intensities, Iγ, was performed with low uncertainty. The new Iγ values contributed to the Decay Data Evaluation Project.

Genotyping of Helicobacter pylori CagA/CagE strains in gastric mucosa and its association with gastric illness.

The aim of this work was associate the presence of the virulence factors of Helicobacter pylori, cagA/cagE, with gastric illness. We found evidence that indicate the contribution of these genotypes with the severity of gastric lesions in patients infected, principally in histological subtypes as atrophic gastritis, and metaplasia.

Megaprosthesis in articular fractures of the lower limbs in fragile patients: a proposal for the therapeutic algorithm.

OBJECTIVE: The use of megaprosthetic implants could provide substantial advantages in elderly population affected by complex fractures. The aim of the study was to identify the patients suitable to megaprosthetic implants in the treatment of lower limbs fractures, as well as periprosthetic fractures. PATIENTS AND METHODS: From January 1st, 2015, to December 31st, 2021, all patients affected by femoral fractures with severe bone loss or previous surgery failure were retrospectively reviewed. ADL, IADL, SF-12 values pre- and post-operative were recorded. Hemoglobin value, NLR, PLR were recorded pre- and peri-operatively for all patients. Complications were recorded. All patients underwent a radiological follow-up. Significance was set at p ≤ 0.05. RESULTS: 23 patients were considered eligible, 10 males and 13 females; the mean age was 72.87 years old (± 12.33), while the mean BMI was 27.2 points (± 5.2). The mean follow-up was 2 years (± 1.4). The mean preoperative ADL and IADL scores were correlated with a positive independence of the patient, while the mean postoperative scores corresponded to a moderate-low independence. Also the mean Mental and Physical SF12 scores saw a decrease in values. NLR values were higher in the first group of patients with complications. CONCLUSIONS: A careful multiparametric and multidisciplinary patient selection is required to identify the suitable patient to this treatment.

Correlation between Neutrophil-to-lymphocyte ratio and Euthyroid Sick Syndrome in elderly patients with proximal femur fractures.

OBJECTIVE: Proximal femur fractures are among the most common type of trauma in elderly patients, and Euthyroid sick syndrome has already been related to fractures and trauma. The evidence of a consistent inflammatory state occurring during hip fracture, made us consider as a potential marker also the neutrophil-to-lymphocyte ratio (NLR), which is already in use to measure the prognosis and guide the therapeutic management in various conditions. PATIENTS AND METHODS: A retrospective observational analysis on patients affected by proximal femur fractures was conducted. Patients were divided between affected and non-affected by Euthyroid Sick Syndrome (ESS). Standard follow up was conducted at 1, 3, 6 and 12 months. RESULTS: 79 patients were enrolled in this study. There were 19 males and 60 females, the mean age was 83.8 ± 6.5 y.o., and 44 patients were affected by ESS. Affected patients showed higher NLR values (10.2 ± 9.4 vs. 6.9 ± 3.9; p= 0.001) and higher decrease in fT3 values in the 1st post-operative day (1.8 ± 0.4 vs. 2.2 ± 0.3; p= 0.001), higher values of PTH (97.9 ± 46.2 vs. 70.1 ± 36.2; p=0.004) and lower levels of Vitamin D (18.8 ± 7.8 vs. 23.5 ± 12.9; p= 0.04). As regards complications, we found them in 27% of patients in group A, while only in 8% in Group B, with a statistically significant difference (p= 0.03). CONCLUSIONS: ESS and NLR are promising prognostic markers in PFF in the elderly patients. If used together, they could help in the pre- and post-operative management of the patients.

GENDER, SEXUALITY, AND ETHNICITY AS FACTORS OF CLUB DRUG USE AMONG ASIAN AMERICANS.

This article examines the relationship between substance use and gender, sexuality, ethnicity, and nativity among 250 Asian American youths involved in the dance club/rave scene. We find distinct patterns of drug use differing by country of origin and ethnicity. However, contrary to some literature we do not find significant differences corresponding to immigration status, or number of years in the U.S. The most significant differences between subgroups are related to gender and sexuality: male respondents consume more drugs, more frequently than female respondents, and non-heterosexual respondents consume more than heterosexual respondents, with differing patterns for men's and women's sexual subgroups. There were also significant gender and sexuality differences with respect to the contexts in which respondents consume drugs, with the most significant differences being between heterosexual and non-heterosexual men. As we discuss, these findings illustrate the need for further investigation of drug use patterns of gender and sexuality within Asian American communities.

Measurement of absolute γ-ray emission probabilities in the decay of 227Ac in equilibrium with its progeny.

The emission probabilities of γ rays produced in the 227Ac decay series were determined by high-resolution γ-ray spectrometry of sources with standardised activity. The sources were prepared quantitatively on glass discs by drop deposition of a solution with 227Ac in radioactive equilibrium with its daughter nuclides. Their activity was measured by a primary standardisation technique based on alpha-particle counting at a defined low solid angle. Four laboratories performed γ-ray spectrometry and derived absolute γ-ray intensities. Mean values were calculated and compared with literature data and the currently recommended evaluated data. New values on certain γ-ray emission probabilities are proposed.

Development of a primary standard for calibration of (64)Cu activity measurement systems.

A (64)Cu national primary standard, was developed by the National Institute for Ionising Radiation Metrology (INMRI) of the ENEA (ENEA-INMRI) using the CIEMAT/NIST method of 4pibeta liquid scintillation spectrometry with (3)H-standard efficiency tracing. Relatively short (64)Cu half-life is required for the work to be performed at the production site. It was produced at the Scanditronix MC40 Cyclotron of the Joint Research Centre (JRC) of the European Commission (Ispra, Italy) through the (64)Zn(d,2p) (64)Cu reaction. Significant efforts were made to identify and quantify the impurities of (61)Cu and (65)Zn in the mother solution, which were activated through the (64)Zn(d,alphan) (61)Cu and (64)Zn(d,p) (65)Zn reactions, respectively. To this purpose, a new procedure for the determination of pure beta-emitter impurities by the CIEMAT/NIST method has been applied. A transfer standard portable well-type ionisation chamber was also calibrated with minimum uncertainty.

An intercomparison of Monte Carlo codes used in gamma-ray spectrometry.

In an intercomparison exercise, the Monte Carlo codes most commonly used in gamma-ray spectrometry today were compared with each other in order to gauge the differences between them in terms of typical applications. No reference was made to experimental data; instead, the aim was to confront the codes with each other, as they were applied to the calculation of full-energy-peak and total efficiencies. Surprising differences between the results of different codes were revealed.

99mTc by 99Mo produced at the ENEA-FNG facility of 14MeV neutrons.

A severe supply crisis of 99Mo, precursor of 99mTc a diagnostic radionuclide largely used in Nuclear Medicine, occurred in 2008-2009 due to repeated shut-down of the two main (aged) fission reactors. An alternative route for producing 99Mo by 100Mo(n,2n)99Mo reaction was investigated at ENEA. The experiment, designed according to Monte Carlo simulations performed with the Fluka code, produced 99Mo by irradiating a natural Molybdenum powdered target with 14MeV neutrons produced at the Frascati Neutron Generator. The 99Mo specific activity was measured at metrological level by γ-ray spectrometry.

Comparison of 131I activity measurements at the NCBJ RC POLATOM and the ENEA-INMRI linked to the BIPM SIR system.

A bilateral comparison between ENEA-INMRI (Italy) and NCBJ RC POLATOM (Poland) of 131I-solution activity measurements was organized in the year 2015 and piloted by POLATOM, which provided the sources for the comparison. The 131I master solution was standardized independently at both institutes by using Liquid Scintillation Counting and ionization chamber techniques. The 131I master solution was then sent by POLATOM to the BIPM International Reference System (SIR). The comparison was registered as an EURAMET.RI(II)-K2.I-131 key comparison allowing the ENEA-INMRI result to enter in the SIR database.

Experimental determination of calibration settings of a commercially available radionuclide calibrator for various clinical measurement geometries and radionuclides.

Following the approach of the National Primary Laboratory of the UK (NPL) for the calibration of radionuclide calibrators, but using a commercially available instrument with no data available in the literature, the radionuclide calibrator response was investigated as a function of different measurement geometries at the "Regina Elena" National Cancer Institute (IRE) in Rome. Working with Italian National Metrology Institute for ionising radiation quantities (ENEA-INMRI), specific calibration factors with traceability to national primary standards were determined for different types of glass vials, solid capsules and plastic syringes, investigating three radionuclides with different energy spectra (Tc-99m, In-111, I-131). For each kind of syringe, calibration correction factors for different filling volumes were calculated. For Tc-99m and I-131 the difference between measured and true activity was in the range 2-7%, depending on measurement geometry. For In-111 a large percentage deviation from the true activity value was found in each geometry considered, reaching 35%. The magnitude of this difference is particularly dependent on the energies of the emitted photons.

Characterization and calibration of a novel detection system for real time monitoring of radioactive contamination in water processed at water treatment facilities.

Characterization and calibration measurements were carried out at the National Institute of Ionizing Radiation Metrology of ENEA on the TAp WAter RAdioactivity (TAWARA) Real Time Monitor system recently developed for real time monitoring of radioactive contamination in water processed at water treatment facilities. Reference radiations and radionuclides were chosen in order to reflect energy ranges and radiation types of the major water radioactive contaminants possibly arising from environmental, industrial or terroristic origin. The following instrument parameters were tested: sensitivity, selectivity, background, short/long term stability, linearity with respect to activity.

Distinct Patterns of Stromal and Tumor Expression of ROR1 and ROR2 in Histological Subtypes of Epithelial Ovarian Cancer.

OBJECTIVE: The ROR1 and ROR2 receptor tyrosine kinases have both been implicated in ovarian cancer progression and have been shown to drive migration and invasion. There is an increasing importance of the role of stroma in ovarian cancer metastasis; however, neither ROR1 nor ROR2 expression in tumor or stromal cells has been analyzed in the same clinical cohort. AIM: To determine ROR1 and ROR2 expression in ovarian cancer and surrounding microenvironment and examine associations with clinicopathological characteristics. METHODS: Immunohistochemistry for ROR1 and ROR2 was used to assess receptor expression in a cohort of epithelial ovarian cancer patients (n=178). Results were analyzed in relation to clinical and histopathological characteristics and survival. Matched patient sample case studies of normal, primary, and metastatic lesions were used to examine ROR expression in relation to ovarian cancer progression. RESULTS: ROR1 and ROR2 are abnormally expressed in malignant ovarian epithelium and stroma. Higher ROR2 tumor expression was found in early-stage, low-grade endometrioid carcinomas. ROR2 stromal expression was highest in the serous subtype. In matched patient case studies, metastatic samples had higher expression of ROR2 in the stroma, and a recurrent sample had the highest expression of ROR2 in both tumor and stroma. CONCLUSION: ROR1 and ROR2 are expressed in tumor-associated stroma in all histological subtypes of ovarian cancer and hold potential as therapeutic targets which may disrupt tumor and stroma interactions.

To d , or not to d : recent developments and comparisons of regularization schemes.

We give an introduction to several regularization schemes that deal with ultraviolet and infrared singularities appearing in higher-order computations in quantum field theories. Comparing the computation of simple quantities in the various schemes, we point out similarities and differences between them.

Random-summing correction and pile-up rejection in the sum-peak method.

The sum-peak counting method was applied for 125I absolute activity measurement. Count rate-dependent corrections for random summing and dead time effects were experimentally determined at different count rates and in several experimental conditions. Two NaI(Tl) crystals of different volumes were used. They were connected to pulse recording systems with different characteristics, with or without pile-up rejection live-time corrector circuits (PUR/LTC). A theoretical model was proposed to explain the different behaviours found experimentally. It is shown that count rate-dependent effects are drastically reduced by the use of PUR/LTC.

Close-geometry efficiency calibration of p-type HPGe detectors with a Cs-134 point source.

When close-geometry detector calibration is required in gamma-ray spectrometry, single-line emitters are usually used in order to avoid true coincidence summing effects. We managed to overcome this limitation by developing a method for the determination of the efficiency of p-type HPGe detectors in close-geometry with a calibrated Cs-134 point source. No separate determination of coincidence summing correction factors is required and a single measurement furnishes the full-energy-peak efficiencies in the 475-1365 keV energy range.

Quantitative 177Lu SPECT imaging using advanced correction algorithms in non-reference geometry.

Peptide receptor therapy with 177Lu-labelled somatostatin analogues is a promising tool in the management of patients with inoperable or metastasized neuroendocrine tumours. The aim of this work was to perform accurate activity quantification of 177Lu in complex anthropomorphic geometry using advanced correction algorithms. Acquisitions were performed on the higher 177Lu photopeak (208keV) using a Philips IRIX gamma camera provided with medium-energy collimators. System calibration was performed using a 16mL Jaszczak sphere surrounded by non-radioactive water. Attenuation correction was performed using µ-maps derived from CT data, while scatter and septal penetration corrections were performed using the transmission-dependent convolution-subtraction method. SPECT acquisitions were finally corrected for dead time and partial volume effects. Image analysis was performed using the commercial QSPECT software. The quantitative SPECT approach was validated on an anthropomorphic phantom provided with a home-made insert simulating a hepatic lesion. Quantitative accuracy was studied using three tumour-to-background activity concentration ratios (6:1, 9:1, 14:1). For all acquisitions, the recovered total activity was within 12% of the calibrated activity both in the background region and in the tumour. Using a 6:1 tumour-to-background ratio the recovered total activity was within 2% in the tumour and within 5% in the background. Partial volume effects, if not properly accounted for, can lead to significant activity underestimations in clinical conditions. In conclusion, accurate activity quantification of 177Lu can be obtained if activity measurements are performed with equipment traceable to primary standards, advanced correction algorithms are used and acquisitions are performed at the 208keV photopeak using medium-energy collimators.