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The accurate understanding of the origin of overpressure is the basis of formation pressure research and the core work of determining the distribution of formation pore pressure in drilling design. The deep water area of Baiyun Sag in the Pearl River Mouth Basin in the northern margin of the South China Sea has been proved to be a hydrocarbon rich depression. In recent years, overpressure has been encountered in the middle and deep layers, but the geological origin of the overpressure in the deep water area are still unclear. Therefore, the pore pressure profile of the Baiyun Sag was evaluated using the data of drilling and seismic velocity, and the relationship between overpressure and the generation mechanism was established. Most of the surrounding and shallow strata of Baiyun Sag show normal pressure, while the middle and deep strata generally show overpressure, with the maximum pressure coefficient up to 1.55. The overpressure zone mainly develops from the middle of Zhujiang Formation to the upper member of Enping Formation. The mudstone resistivity and density values of the two typical Wells deviated from the normal trend. The density showed a constant trend with the increase of depth, while the resistivity showed a certain degree of reversal. The upper layer of the overpressure zone showed abnormally high resistivity values, corresponding to the overgland and transition zone formed by high carbonate content. There is no obvious increase of porosity in the overpressured sandstone strata of Baiyun sag, which does not have the characteristics of undercompaction. The velocity in the overpressure section of the two Wells varies greatly, and the density is basically unchanged or slightly decreased. It is concluded that the overpressure is caused by fluid expansion from hydrocarbon-generation. The large-scale and long-term fluid expansion caused by hydrocarbon generation and expulsion of source rocks provides the power source for the formation of overpressure in Baiyun sag. The distribution of effective source rocks has a controlling effect on the distribution range of overpressure. The tight sandstone strata in the Zhuhai, Wenchang and Enping formations become the cover layer of the overpressure system in the longitudinal direction.

The rapid development in the advanced manufacturing industry asks for better tempering softening resistance (TSR) of Hot work die steels. In this work, a modified H13 steel (CXN03 steel) with additional tungsten, molybdenum, and lowering chromium was prepared. The TSR of CXN03 is significantly better than H13. After quenching at 1040 °C, the hardness and strength of H13 were larger than those of CXN03. However, the hardness and strength of CXN03 exceeded those of H13 after 2 h tempering at 600 °C. A mathematical model was utilized to correlate microstructural characteristics with yield strength during tempering. The calculated results indicated that the superior tempering softening resistance of CXN03 steel mainly results from the excellent stability of dispersive nano-sized M2C, which could prevent dislocation recovery. Recrystallization softening was observed in H13 but not in CXN03. The recrystallization of H13 is driven by dislocation movement, and the rearrangement of dislocations contributed to the formation of sub-boundaries. These sub-boundaries could divide martensite lath as well as form sub-grains. As the tempering time increased, sub-boundaries transformed into high-angle grain boundaries by absorbing the vicinal dislocations. Therefore, martensite lath collapsed, and massive recrystallized grains occurred. The massive stable M2C in CXN03 hindered the dislocation rearrangement, thus preventing the recrystallization.

China’s most successful horizon for shale-gas exploration and development is the Upper Ordovician Wufeng Formation through the Lower Silurian Longmaxi Formation in its Upper Yangtze Region. In this study, the Wufeng–Longmaxi Formation black shales in the Upper Yangtze Region are analysed to determine their microstructural characteristics, total organic carbon (TOC) content, and well log characteristics and to identify information on the parameters of Earth’s orbit from its gamma-ray (GR) data series. Then, paleoenvironmental modes are established over a long time scale. On this basis, the Earth’s orbital control on organic matter enrichment in the black shales is examined. The black shales of the Wufeng Formation and the lower Longmaxi Formation are rich in biogenic siliceous fossils and framboidal pyrite. Their TOC content, GR value, and uranium (U) content increase gradually from the bottom of the Wufeng Formation to the Guanyinqiao Member at its top, peak at the Guanyinqiao Member, and then decrease gradually up to the Longmaxi Formation. Approximately six and seven long eccentricity cycles can be identified from the GR curves of the Wufeng Formation and the lower Longmaxi Formation, respectively. During the long eccentricity minima, corresponding to Earth’s cold period, the black shales have a relatively high level of enrichment of organic matter. This study can provide an important reference for investigating the mechanism by which Earth’s orbits control the climate and sedimentary environment, as well as the mechanism of organic matter enrichment.

Aiming at the problem of insufficient data acquisition for steep carbonate outcrops, we used unmanned aerial vehicle oblique photogrammetry to quantitatively evaluate Jiantianba outcrops from a global perspective. This method can quickly and flexibly acquire, process and interpret outcrop data, establish the three-dimensional digital outcrop model and quantitative reservoir geological knowledge database. Through the fine analysis and comparative study of multiple outcrop sections, we use lithofacies combination, hierarchical interface, sequential indicator stochastic simulation and multiple-point geostatistical simulation methods to establish a three-dimensional multi-point statistical model of the outcrop area. The results show that the model of the Jiantianba carbonate outcrop has three-dimensional coordinates that correspond to oblique photograph image data, allowing for both the accurate location of any point and the measurement of the rock body, and thus providing a base for studying the stratigraphic architecture of the outcrop. Through fine-scale geological and statistical analyses of the geological parameters of three geologic sections, we established a database and model of a typical outcrop, including the types, continuity and scale of lithology, as well as different lithological combinations and the geological evolution of the region. And we established a geological model and quantitative geological database via sequential indicator simulation, using virtual well location, lithological combination, stratigraphic correlation, three-dimensional stratigraphic and lithological models of a typical outcrop. Subsequently, we analyzed the training images of different microfacies based on these models combined with the outcrop geometry. Finally, we established a three-dimensional geological model of reef–shoal facies that is more in line with our current understanding of the geology of the outcrop area by multi-point geostatistical simulations.

The shear-compression deformation of GH4169 superalloy at 1000–1200 °C and 0.01–1 s−1 was investigated by physical and numerical simulation based on a specific shear-compression sample (SCS). OM, EBSD, and TEM analysis revealed the three typical regions in SCS. Dynamic recrystallization (DRX) preferred to occur in the slot region due to the strain concentration, where the Mises equivalent strain was about 4–6 times higher than the pre-set ones. Mixed grains were observed in the transition region because of insufficient deformation. In contrast, equiaxial grains were preserved in the cylindrical region with negligible deformation. Experimental stress decreased with the increase of temperature and decrease of strain rate. The maximum stress was 180 MPa, which was only 30% of that under single compression deformation. Furthermore, four DRX mechanisms were observed in GH4169. Discontinuous dynamic recrystallization (DDRX) and continuous dynamic recrystallization (CDRX) were the dominant and auxiliary mechanisms, respectively. Twinning dynamic recrystallization (TDRX) occurred in the annealing twins with a fast nucleation rate, and the intersected nano-twins provided favorable nucleation sites for DRX. Lastly, secondary dynamic recrystallization (SDRX) with unique nucleation mechanism of triangularly intersecting subgrain boundaries emerged in SCS, which nucleated in the DRX grains and further refined the microstructure of GH4169.

The diagenesis and pore evolution process of tight sandstone reservoirs in the Upper Triassic Bagong Formation of the North Qiangtang Depression were studied by means of physical properties, casting thin slice, SEM, X-ray-diffraction and fluid inclusion temperature measurement. The compositional maturity and structural maturity of the Bagong sandstones are moderately low. Their physical properties are extremely tight. The main diagenetic effects include compaction, cementation, dissolution and metasomatism. The cement components are mainly siliceous, clay minerals and carbonate minerals, and the dissolution component is feldspar. According to the comprehensive analysis of various characteristics, the shallow buried area near the uplift is in the middle diagenesis stage B, and the deep buried area inside the depression is in the late diagenetic stage. Under the premise of considering the apparent volume change and compaction of rock, a quantitative calculation of pore evolution of different diagenetic facies is carried out. The calculation results show that compaction is the primary cause of reservoir porosity reduction, followed by cementation, while dissolution and the formation of chlorite lining are beneficial to reservoir porosity.

Strong heterogeneity, poor pay reservoir connectivity, and complex micro-pore structure are the reasons behind the high difficulty and low accuracy in the productivity evaluation of tight sandstone gas reservoirs. This paper utilized various well logging and mud logging curve data, summarizes the typical curve type, and made use of a mathematical method to form quantitative characterization. Additionally, a logging curve evaluation method is proposed based on the test of production capacity. The total hydrocarbon curve can be divided into six types as shown by the results: box shape, half box shape, upright triangle, inverted triangle, sawtooth shape, single peak, etc. The above is closely related to the level of oil and gas in the reservoir layer. Six types of total hydrocarbon curve can be quantified by amplitude, relative centroid, relative sawtooth, variance, and the parameter value of the autocorrelation function. The box-shaped total hydrocarbon gas logging curve is full and has a large scale. The half box-shaped total hydrocarbon gas logging curve peak scale is significantly smaller than that of the reservoir thickness. The triangularly-shaped total hydrocarbon gas logging curve may either be an upright or inverted triangle. The sawtooth-shaped total hydrocarbon gas logging curve has high and low tendencies that show a number of spikes. Single peak-shaped total hydrocarbon gas logging curve is small with a single peak. There is a good relationship between the six kinds of total hydrocarbon gas logging curve and the tight sandstone gas reservoir production capacity. The high and middle gas pay layers are mainly box-shaped and triangular, whereas the lower production layer is half box-shaped, triangular, and has a zigzag pattern. However, the low gas pay layers mainly possess a sawtooth pattern, while the non-production layer is mainly single peak in shape. The comprehensive interpretation of the total hydrocarbon gas logging curve and log resistivity curve can more accurately distinguish the production capacity of tight sandstone gas reservoirs. Finally, the quantitative model is used for automatic interpretation. Through data verification and analysis, it is found that the coincidence rate of the production gas pay layer is 80.95%, whereas the coincidence rate of production capacity is 78.05%. It is proven by practice that the gas formation capacity of tight sandstone gas reservoirs can be predicted based on the logging and mud logging well curve shapes. Keywords: Method of total hydrocarbon gas mud logging curve, Tight sandstone gas, Reservoir, Fracturing production well capacity

The article presents a research study which aims to evaluate the prevalence of Candida vaginal colonization in pregnant women and to investigate if this is influenced by pregnancy. It provides a background on vulvovaginitis. Methods used are reported regarding specimen collection, culture and identification, and statistical analysis. Results are discussed showing colonization to be significantly higher in pregnant patients and the significant association of pregnancy to asymptomatic infection.

Given the ongoing COVID-19 pandemic, there is a need to identify SARS-CoV-2 and to differentiate it from other respiratory viral infections, especially influenza A and B, in various critical settings. Since their introduction, the use of rapid antigen tests has spread worldwide, but there is variability in their diagnostic accuracy. In the present study, we evaluated the clinical performance of the ID NOW™ COVID-19 2.0, a molecular point-of-care test (POCT) based on enzymatic isothermal amplification for the differential diagnosis of SARS-CoV-2 and influenza A/B in a pediatric emergency setting. A cohort of pediatric patients admitted between December 2022 and February 2023 were simultaneously tested with the POCT and standard laboratory molecular assay. Our findings showed high negative agreement of the POCT assay across the different age groups for SARS-CoV-2, influenza A, and influenza B (more than 98.0%), while its positive agreement varied significantly for the abovementioned viral species from 50.0% to 100%. These results highlight the potential of the ID NOW™ COVID-19 2.0 POCT assay as a reliable and rapid tool for excluding SARS-CoV-2 and influenza A/B infections in symptomatic pediatric patients, although its variable positive agreement suggests a need for confirmatory RT-qPCR testing in certain clinical and epidemiological settings in order to ensure accurate diagnosis and appropriate patient management.

Fecal Microbiota Transplantation (FMT) represents a promising therapeutic tool under study for several purposes and is currently applied to the treatment of recurrent Clostridioides difficile infection. However, since the use of fresh stool was affected by several issues linked to donor screening, the development of a frozen stool bank is a reliable option to standardize FMT procedures. Nevertheless, different environmental factors impact microbial viability. Herein, we report the effect of different thawing temperatures and storage conditions on bacterial suspensions in the FMT procedure. In total, 20 stool samples were divided into aliquots and tested across a combination of different storing periods (15, 30; 90 days) and thawing procedures (4 °C overnight, room temperature for 1 h; 37 °C for 5 min). Focusing on storage time, our data showed a significant reduction in viability for aerobic and anaerobic bacteria after thawing for 15 days, while no further reductions were observed until after 90 days. Instead, among the different thawing procedures, no significant differences were observed for aerobic bacteria, while for anaerobes, thawing at 37 °C for 5 min was more effective in preserving the bacterial viability. In conclusion, the frozen fecal microbiota remained viable for at least three months, with an excellent recovery rate in all three thawing conditions., Competing Interests: The authors declare no conflicts of interest.

To carry out effective and quick identification of SARS-CoV-2 from nasopharyngeal swabs and contain outbreaks, reliable and rapid tools are needed. Herein, we compared a rapid antigen test based on active microfluidic technology to an RT-qPCR assay in pediatric and young adult patients admitted to the Pediatric Emergency Unit of a Children's Hospital. Nasopharyngeal swabs collected from patients with suspected COVID-19 disease and from those without COVID-19 related symptoms, but requiring hospitalization, were performed with both antigen test and RT-qPCR assays. We included 375 patients with a median age of 5 years in the study, with an estimated overall prevalence of 7.2%. Overall, we observed a specificity of 97.4% (95% CI: 94.9-98.7) and a sensitivity of 66.6% (95% CI: 46.0-82.7) with a positive likelihood ratio (LR+) of 25.8 (95% CI: 12.8-51.8). In the subgroup of symptomatic patients, the specificity and the sensitivity were 95.2% (95% CI: 89.4-98.0) and 80.0% (95% CI: 44.2-96.5) respectively; LR+ was 16.6 (95% CI: 7.19-38.6). In the asymptomatic subset, the performance showed a specificity of 98.7% (95% CI: 95.8-99.7), a sensitivity of 58.8% (95% CI: 33.5-80.6), and an LR+ of 43.7 (95% CI: 13.3-144.0). Compared to RT-qPCR, the new microfluidic-based antigen test showed higher specificity (>95%) in the pediatric population, thus representing a suitable point-of-care testing (POCT) in a clinical setting with low prevalence of COVID-19.

Background: Advanced breast cancer (ABC) is characterized by multidimensional clinical complexity that is usually not considered in randomized clinical trials. In the present real-life study, we investigated the link between clinical complexity and quality of life of patients with HR + /HER2 - ABC treated with CDK4/6 inhibitors., Methods: We evaluated multimorbidity burden assessed with the Cumulative Illness Rating Scale (CIRS), polypharmacy and patient-reported outcomes (PROs). PROs were assessed at baseline (T0), after 3 months of therapy (T1), and at disease progression (T2) using EORTC QLC-C30 and QLQ-BR23 questionnaires. Baseline PROs and changes between T0 and T1 were evaluated amongst patients with different multimorbidity burden (CIRS <5 and ≥5) and polypharmacy (<2 or ≥2 drugs)., Results: From January 2018 to January 2022, we enrolled 54 patients (median age 66 years, IQR 59-74). The median CIRS score was 5 (IQR 2-7), whilst the median number of drugs taken by patients was 2 (IQR 0-4). No changes in QLQ-C30 final scoring between T0 and T1 were observed in the overall cohort ( p =0.8944). At T2, QLQ-C30 global score deteriorated with respect to baseline ( p =0.0089). At baseline, patients with CIRS ≥5 had worse constipation than patients without comorbidities ( p <0.05) and a lower trend in the median QLQ-C30 global score. Patients on ≥2 drugs had lower QLQ-C30 final scores and worse insomnia and constipation ( p <0.05). No change in QLQ-C30 final score from T0 to T1 was observed ( p >0.05)., Conclusion: Multimorbidity and polypharmacy increase the clinical complexity of patients with ABC and may affect baseline PROs. The safety profile of CDK4/6 inhibitors seems to be maintained in this population. Further studies are needed to assess clinical complexity in patients with ABC.This article is part of the Tackling clinical complexity in breast cancer Special Issue: https://www.drugsincontext.com/special&#95;issues/tackling-clinical-complexity-in-breast-cancer/., Competing Interests: Disclosure and potential conflicts of interest: The authors declare that they have no conflicts of interest relevant to this article. The International Committee of Medical Journal Editors (ICMJE) Potential Conflicts of Interests form for the authors is available for download at: https://www.drugsincontext.com/wp-content/uploads/2023/05/dic.2023-1-7-COI.pdf, (Copyright © 2023 Tagliaferri B, Mollica L, Palumbo R, Leli C, Malovini A, Terzaghi M, Quaquarini E, Teragni C, Maccarone S, Premoli A, Sottotetti F.)

Since its first appearance in late 2019 in Wuhan, China, severe acute respiratory syndrome caused by Coronavirus 2 (SARS-CoV-2) has had a major impact on healthcare facilities around the world. Although in the past year, mass vaccination and the development of monoclonal antibody treatments have reduced the number of deaths and severe cases, the circulation of SARS-CoV-2 remains high. Over the past two years, diagnostics have played a crucial role in virus containment both in health care facilities and at the community level. For SARS-CoV-2 detection, the commonly used specimen type is the nasopharyngeal swab, although the virus can be identified in other matrices such as feces. Since fecal microbiota transplantation (FMT) assumes significant importance in the treatment of chronic gut infections and that feces may be a potential vehicle for transmission of SARS-CoV-2, in this study we have evaluated the performance of the rapid cartridge-based RT-PCR test STANDARD™ M10 SARS-CoV-2 (SD Biosensor Inc., Suwon, South Korea) using fecal samples. The results obtained indicates that STANDARD™ M10 SARS-CoV-2 can detect SARS-CoV-2 in stool samples even at low concentration. For this reason, STANDARD™ M10 SARS-CoV-2 could be used as reliable methods for the detection of SARS-CoV-2 in fecal samples and for the screening of FMT donors., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 Published by Elsevier Ltd.)

Fungemia is a life-threatening condition associated with high mortality; the most frequently isolated genus is Candida. Candida glabrata is of particular concern because of its increasing resistance to azoles. We evaluated common lab tests accessible by almost all healthcare professionals to estimate the post-test probability of recovery of C. glabrata from a blood culture collected by venipuncture, positive for fungi identified by microscopic examination. Patients with blood cultures positive for C. glabrata had significantly higher median values of serum creatinine (P=0.006), and a value of ≥1.45 mg/dL was the best cut-off in discriminating C. glabrata from other Candida spp., with 0.67 [95% Confidence Interval (CI): 0.49-0.85] sensitivity and 0.75 (95% CI: 0.66-0.84) specificity; Youden's J statistic: 0.42. The receiver operator characteristic curve analysis showed an area under the curve of 0.718 (95% CI: 0.603-0.833); P=0.001. Therefore, given a pre-test probability of 24% and applying the Bayes' theorem, the post-test probability of C. glabrata fungemia with creatinine values ≥1.45 mg/dL increased to 45.8%. In conclusion, we showed how the probability of recovery of C. glabrata from blood cultures collected by venipuncture and positive for fungi can be better estimated using concurrent creatinine values.

Tumour markers have no established role in the monitoring of the course of metastatic breast cancer during antineoplastic therapy, yet cancer antigen 15.3 (CA15.3) and carcinoembryonic antigen (CEA) are commonly used in clinical practice to aid in the early detection of progression of disease (PD). In our multicentre, prospective, real-life study, we enrolled 142 consecutive patients with advanced breast cancer receiving endocrine therapy in combination with a CDK4/6 inhibitor from January 2017 to October 2020; 75 patients had PD at the time of database closure. We measured serum marker concentrations at regular 4-month intervals together with radiological tumour response assessments and in cases of clinical suspicion of PD. Appropriate descriptive and inferential statistical methods were used to analyse serum marker level trends amongst prespecified subgroups and at specific time points (baseline, best radiologically documented tumour response and first detection of PD) in the subpopulation of patients with PD at the time of database closure. Notably, the median time from treatment initiation to best tumour response was 4.4 months. We evaluated the presence of an association between baseline CA15.3 and CEA levels and prespecified clinical characteristics but found no clinically meaningful correlation. We assessed marker level variations at the time of best radiologically documented disease response and PD: in the subgroup of patients who responded to treatment before progressing, we detected a statistically significant correlation with tumour marker variation between the time of best response and progression; this finding was not confirmed in the subgroup of patients that did not benefit from treatment. In conclusion, serum tumour marker flares can be useful in the early diagnosis of PD but should not be used as the sole factor prompting a change in treatment strategy without radiological confirmation., Competing Interests: Disclosure and potential conflicts of interest: The authors declare that they have no conflicts of interest relevant to this manuscript. The International Committee of Medical Journal Editors (ICMJE) Potential Conflicts of Interests form for the authors is available for download at: https://www.drugsincontext.com/wp-content/uploads/2022/08/dic.2022-1-3-COI.pdf, (Copyright © 2022 Sottotetti F, Ferraris E, Tagliaferri B, Palumbo R, Quaquarini E, Teragni C, Balletti E, Leli C, Premoli A, Mollica L, Puglisi S, Sardi S, Malovini A, Pedrazzoli P, Bernardo A.)

Introduction: Exercise training improves walking capacity in patients with intermittent claudication (IC). Endothelial progenitor cells (EPCs), endothelial microparticles (EMPs), and endothelial dysfunction could play a role in this process., Methods: We measured EPCs and EMPs in a group of 60 patients with IC, and in a control group of 20 individuals without IC, before a treadmill test and 2, 24, and 48 hours after the test. Thirty patients with IC were randomly assigned to perform a 12-week home-based exercise training program. The EPC count, flow-mediated dilation (FMD) of the brachial artery, pain-free walking time (PFWT), and maximum walking time (MWT) were measured at the baseline and after the exercise training program., Results: In patients with IC, EMPs significantly increased 2 hours after the treadmill test, whereas EPCs significantly increased after 24 hours. Among the subjects assigned to complete the training program, we observed a significant increase in the number of EPCs after 12 weeks, as well as an improvement in FMD, PFWT, and MWT. A significant correlation between the variation of EPCs, FMD, and MWT was found. The increase of EPCs and FMD were independent determinants of the walking capacity improvement, without significant interaction., Conclusion: Our results suggest that EPCs mobilization contributes to the improvement of walking capacity in patients with IC undergoing structured physical training. A number of different, partly independent, mechanisms are involved in this process, and our results highlight the potential role of EMPs release and endothelial function improvement. ClinicalTrials.gov Identifier: NCT04302571 .

Leptomeningeal carcinomatosis (LC) is a rare but challenging manifestation of advanced breast cancer with a severe impact on morbidity and mortality. We performed a systematic review of the evidence published over the last two decades, focusing on recent advances in the diagnostic and therapeutic options of LC. Lobular histology and a triple-negative intrinsic subtype are well-known risk factors for LC. Clinical manifestations are diverse and often aspecific. There is no gold standard for LC diagnosis: MRI and cerebrospinal fluid cytology are the most frequently used modalities despite the low accuracy. Current standard of care involves a multimodal strategy including systemic and intrathecal chemotherapy in combination with brain radiotherapy. Intrathecal chemotherapy has been widely used through the years despite the lack of data from randomized controlled trials and conflicting evidence on patient outcomes. No specific chemotherapeutic agent has shown superiority over others for both intrathecal and systemic treatment. Although endocrine therapy was heuristically considered unable to exert significant control on central nervous system metastatic disease, retrospective data suggest a favourable toxicity profile and even a possible positive impact on survival. In recent years, encouraging data on the use of targeted agents has emerged but further research in this field is required. Palliative treatment in the form of whole brain or stereotactic radiotherapy is associated with improvement in clinical manifestations and quality of life, with no proven impact on survival. The most investigated prognostic factors include performance status, non-triple-negative disease and multimodal treatment. Validation of prognostic scores is necessary to aid clinicians in the identification of patient subgroups that are most likely to benefit from an intensive therapeutic approach., Competing Interests: Disclosure and potential conflicts of interest: The authors declare that they have no conflicts of interest relevant to this manuscript. The International Committee of Medical Journal Editors (ICMJE) Potential Conflicts of Interests form for the authors is available for download at: https://www.drugsincontext.com/wp-content/uploads/2021/09/dic.2021-6-6-COI.pdf, (Copyright © 2021 Mollica L, Leli C, Puglisi S, Sardi S, Sottotetti F.)

Objectives: Given the ongoing pandemic emergency, there is a need to identify SARS CoV-2 infection in various community settings. Rapid antigen testing is spreading worldwide, but diagnostic accuracy is extremely variable. Our study compared a microfluidic rapid antigen test with a reference molecular assay in patients admitted to the emergency department (ED) of a general hospital from October 2020 to January 2021., Methods: Nasopharyngeal swabs collected in patients with suspected COVID-19 and in patients with no symptoms suggesting COVID-19, but requiring hospitalization, were obtained., Results: 792 patients of median age 71 years were included. With a prevalence of 21%, the results showed: 68.7% (95% confidence interval [CI]: 60.9-75.5) sensitivity; 95.2% (95% CI: 93.1-96.7) specificity; 79.2% (95% CI: 71.4-85.3) positive predictive value (PPV); 91.9% (95% CI: 89.5-93.9) negative predictive value; 3.8 (95% CI: 2.7-5.3) positive likelihood ratio (LR+); and 0.09 (95% CI: 0.07-0.1) negative likelihood ratio (LR-). In the symptomatic subgroup, sensitivity increased to 81% (95% CI: 70.3-88.6) and PPV to 96.9% (95% CI: 88.5-99.5), along with an LR+ of 32 (95% CI: 8.2-125.4)., Conclusions: The new rapid antigen test showed an overall excellent diagnostic performance in a challenging situation, such as that of an ED during the COVID-19 emergency., (Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

SARS-CoV-2 is a newly-discovered positive-sense RNA virus, the cause of coronavirus disease 2019 (COVID-19) currently spreading worldwide. The SARS-CoV-2 S glycoprotein is considered a main target for neutralizing antibodies. In order to better understand the kinetics of the antibody response, we evaluated the relation between two consecutive antibody titers determined over an average period of four months. A total of 628 subjects were included in the study. A significant reduction of the antibody titers over time was found: Ab Titer 1: 8.1 Arbitrary Units (AU)/mL (IQR: 4.8-29.3); Ab Titer 2: 6.2 AU/mL (IQR: 0-28.5); p<0.0001. A Receiver Operator Characteristic curve analysis showed an Area Under the Curve (AUC) of 0.973 (95% CI: 0.962-0.984; p<0.0001) with an Ab titer 1 threshold of 110 AU/mL to predict an Ab Titer 2 ≥50 AU/mL with 100% specificity. Likewise, an AUC of 0.952 (95% CI: 0.930-0.974; p<0.0001) with an Ab titer 1 threshold of 185 AU/mL was found to predict an Ab Titer 2 ≥100 AU/mL. This study showed that the SARS-CoV-2 S1/S2 IgG median titer declined over an average period of four months and that the first IgG determination thresholds found can help predict IgG values after the same interval.

Viruses are frequent causal agents of acute respiratory infections and the most common are influenza virus, respiratory syncytial virus (RSV), human parainfluenza virus (HPIV), human metapneumovirus (HMPV), rhinovirus (RV), adenovirus (AdV) and the four endemic human coronaviruses (HCoV) -229E, -NL63, -OC43, -HKU1. Multiplex real-time PCR platforms are becoming increasingly common in laboratories mostly in relation to the increased diagnostic sensitivity and reduced turnaround time. The aim of our study was to determine the prevalence of respiratory viruses in a population of patients within the S.S. Antonio e Biagio e Cesare Arrigo General Hospital catchment area of Alessandria, Italy, from January 2016 to June 2020. Therefore, we retrospectively analyzed the results of multiplex real-time PCR performed on nasopharyngeal swabs collected from consecutive patients with symptoms of respiratory infection. A total of 572 patients were included in the study subdivided as follows: pediatric 197/572 (34.4%), adults 200/572 (35%) and elderly 175/572 (30.6%). Among all samples, 235/572 (41.1%) were positive for a respiratory virus, of whom 189/235 (80.4%) were monomicrobial. The prevalence was: 15.5% (89/572) of rhinovirus/enterovirus (RV/EV); 9.4% (54/572) of RSV; 8.9% (51/572) of influenza virus; 5.4% (31/572) of AdV; 3.1% (18/572) of HCoV; 2.8% (16/572) of HPIV; and 2.3% (13/572) of HMPV. RV/EV were the pathogens most frequently involved in coinfections (34.7%, 16/46), followed by AdV (19.6%, 9/46) and influenza virus (19.6%, 9/46). Samples collected from the pediatric group were more frequently positive. The prevalence of positive pediatric samples compared to adults and elderly, respectively was: 28.4% (56/197) for RV/EV vs 10.5% (21/200) vs 6.9% (12/175), p<0.0001; 18.8% (37/197) for RSV vs 2% (4/200) vs 7.4% (13/175), p<0.0001; 13.7% (27/197) for AdV vs 1% (2/200) vs 1.1% (2/175), p<0.0001; and 6.6% (13/197) for HPIV vs 0.5% (1/200) vs 1.1% (2/175), (p<0.0001). With regard to seasonality, a significantly higher prevalence of influenza virus (p<0.0001) and RSV (p=0.029) was found during winter, with peaks in January-February. AdV peaked during winter 2018-2019 (p=0.004), while HCoV were detected with a significantly higher prevalence during winter 2019-2020 (p=0.037). With regard to HPIV, a significant peak from summer to fall 2018 was observed (p=0.016). Most viral respiratory infections have seasonal patterns and the prevalence of respiratory viruses varies according to the method, geographic area and population considered. Knowledge of local epidemiology is therefore crucial for implementation of prevention and treatment strategies.

Light microscopy, immunochromatographic rapid diagnostic tests and molecular methods are widely used to diagnose malaria. The aim of this study was to find variables among commonly available urgent blood tests to identify patients with low probability of having malaria in small-scale healthcare facilities in which none of the described methods is feasible within a short time. Diagnosis of malaria was made by examining both stained thick and thin blood films by light microscopy. Two hundred and eleven samples were included. Reduced platelet count and increased values of C-reactive protein (CRP) and total bilirubin were the variables most strongly associated with malaria (P<0.0001). The best screening cut-off values obtained by receiver operating characteristic curve analysis for a negative result for malaria were: platelets ≥185,000 cells/μl; CRP ≤2 mg/dl; total bilirubin ≤0.28 mg/dl. The logistic regression model of log-transformed variables showed how platelet count was the only independent variable related to the odds of having a negative blood film result for malaria (odds ratio: 2.621; 95% confidence interval: 1.441-4.768; P=0.002). A platelet count of ≥185,000 cells/μl can be considered a screening value to identify patients with high-probability of a negative blood film result for malaria.

Background: Infectious diarrhoea is a significant cause of morbidity worldwide. Culture and microscopy are time-consuming and have a low yield. New rapid molecular methods such as multiplex PCR, have been recently introduced for aetiological diagnosis. Aim of this study was to compare the diagnostic yield of the FilmArray gastrointestinal panel with that of standard culture for aetiological diagnosis of infectious diarrhoea. Methods: We performed a retrospective analysis of results of stool samples already processed as part of routine clinical care in the interval from March 2016 to March 2019. Results: One hundred and eighty-three stool samples from as many patients were both cultured and tested by FilmArray and the comparison of diagnostic accuracy between culture and FilmArray with respect to Campylobacter spp., Salmonella spp., Shigella spp., Yersinia enterocolitica and Shiga-like toxin producing E. coli O157 gave the following results: 100% (95% confidence interval (CI): 85-100%) sensitivity; 93.4% (95% CI: 87.9-96.6%) specificity; 74.3% (95% CI: 57.5-86.4%) positive predictive value; 100% (95% CI: 96.7-100%) negative predictive value; 2.9 (95% CI: 1.6-5.1) positive likelihood ratio; zero negative likelihood ratio. By means of FilmArray gastrointestinal (GI) panel, we could identify 34.5% more pathogens ( p  = .001). Bacteria were mostly detected in patients with 6 or more years of age ( χ 2 =17.1; p  = .009) during summer. Conclusions: FilmArray GI panel showed a very good diagnostic performance compared to culture for diagnosis of infectious diarrhoea and gave a more detailed picture of the spectrum of the pathogens involved.

Infectious meningitis and encephalitis are potentially life-threatening conditions caused mostly by bacterial and viral agents. Rapid diagnosis and prompt treatment are associated with a more favorable outcome. In recent years nucleic acid amplification tests have been developed to speed detection and identification of pathogens directly from cerebrospinal fluid (CSF). The aim of this study was to compare the diagnostic accuracy of a commercially available multiplex PCR assay for etiological diagnosis of infectious meningitis directly from CSF samples with culture. A secondary endpoint was to look for a possible screening threshold based on main CSF indices and urgent blood test results, to define CSF samples with low pre-test probability of PCR and/or culture-positive result. We performed a secondary analysis of results of CSF samples already processed as part of routine clinical care from February 2016 to December 2018. In all, 109 CSF samples were included in the study and a total of 14 bacteria were identified by either PCR, culture or both methods, along with nine samples positive for viruses. The comparison of PCR results with culture showed no significant difference: 7/109 (6.4%) vs 13/109 (11.9%) respectively, p=0.07. After exclusion of the isolates not detectable by the multiplex PCR panel, the diagnostic accuracy was: 100% (95% confidence interval (CI): 54.1% to 100%) sensitivity; 98.9% (95% CI: 93.5% to 99.9%) specificity; 85.7% (95% CI: 42% to 99.2%) positive predictive value; 100% (95% CI: 95.1% to 100%) negative predictive value; 96 (95% CI: 13.6 to 674.6) LR+; Zero LR-; Cohen's kappa: 0.918, p<0.0001. CSF protein value ≤ 28 mg/dl and CSF glucose/blood glucose ratio ≥0.78 were associated with both PCR-negative result for bacteria or viruses and culture-negative result. The multiplex PCR evaluated in this study showed a very good diagnostic performance compared to culture, and the thresholds found can be a useful tool to best choose which samples to test.

The modern clinical research on prostatitis started with the work of Stamey and coworkers who developed the basic principles we are still using. They established the segmented culture technique for localizing the infections in the males to the urethra, the bladder, or the prostate and to differentiate the main categories of prostatitis. Such categories with slight modifications are still used according to the NIH classification: acute bacterial prostatitis, chronic bacterial prostatitis, Chronic Pelvic Pain Syndrome (CPPS) and asymptomatic prostatitis. Prostatic inflammation is considered an important factor in influencing both prostatic growth and progression of symptoms of benign prostatic hyperplasia and prostatitis. Chronic inflammation/neuroinflammation is a result of a deregulated acute phase response of the innate immune system affecting surrounding neural tissue at molecular, structural and functional levels. Clinical observations suggest that chronic inflammation correlates with chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) and benign prostatic hyperplasia (BPH) and an history of clinical chronic prostatitis significantly increases the odds for prostate cancer. The NIHNIDDK classification based on the use of the microbiological 4- glasses localization test or simplified 2-glasses test, is currently accepted worldwide. The UPOINT system identifies groups of clinicians with homogeneous clinical presentation and is used to recognize phenotypes to be submitted to specific treatments. The UPOINTS algorithm implemented the original UPOINT adding to the urinary domains (U), psycho-social (P), organspecific (O), infection (I), neurological (N), muscle tension and tenderness (T) a further domain related to sexuality (S). In fact sexual dysfunction (erectile, ejaculatory, libido loss) has been described in 46-92% of cases with a high impact on the quality of life of patients with CP/CPPS. Prostatic ultrasound represents the most popular imaging test in the work-up of either acute and chronic prostatitis although no specific hypo-hyperechoic pattern has been clearly associated with chronic bacterial prostatitis and CPPS. Use of a digital-processing software to calculate the extension of prostatic calcification area at ultrasound demonstrated a higher percentage of prostatic calcification in patients with chronic bacterial prostatitis. Multiparametric Magnetic Resonance Imaging (mpMRI) is the current state-of-the art imaging modality in the assessment of patients with prostate cancer although a variety of benign conditions, including inflammation, may mimic prostate cancer and act as confounding factors in the discrimination between neoplastic and non-neoplastic lesions. Bacteria can infect prostate gland by: ascending the urethra, reflux of urine into the prostatic ducts, direct inoculation of bacteria through inserted biopsy needles or hematogenous seeding. Enterobacteriaceae are the predominant pathogens in acute and chronic bacterial prostatitis, but an increasing role of Enterococci has been reported. Many strains of these uropathogens exhibit the ability to form biofilm and multidrug- resistance. Sexually Transmitted Infections (STI) agents, in particular Chlamydia trachomatis and Mycoplasma genitalium, have been also considered as causative pathogens of chronic bacterial prostatitis. On the contrary the effective role in genital diseases of other "genital mycoplasmas" is still a much debated issue. Sexually Transmitted Infections agents should be investigated by molecular methods in both patient and sexual partner. "Next generation" investigations, such as cytokine analysis, cytological typing of immune cells could help stratifying the immune response. Epigenetic dysregulation of inflammatory factors should be investigated according to systemic and compartment-specific signals. The search for biomarkers should also include evaluation of hormonal pathways, as measurement of estrogen levels in semen. Antimicrobials are the first line agents for the treatment of bacterial prostatitis. The success of antimicrobial treatment depends on the antibacterial activity and the pharmacokinetic characteristics of the drug which must reach high concentrations in prostate secretion and prostate tissue. Acute bacterial prostatitis can be a serious infection with a potential risk for urosepsis For iInitial treatment of severely ill patients, intravenous administration of high doses of bactericidal antimicrobials, such as broad-spectrum penicillins, third-generation cephalosporins or fluoroquinolones, is recommended in combination with an aminoglycoside. Use of piperacillin-tazobactam and meropenem is justified in presence of multiresistant gramnegative pathogens. The antibiotic treatment of chronic prostatitis is currently based on the use of fluoroquinolones that, given for 2 to 4 weeks, cured about 70% of men with chronic bacterial prostatitis. For the treatment of Chlamydial prostatitis macrolides were shown to be more effective than fluoroquinolones, whereas no differences were observed in microbiological and clinical efficacy between macrolides and tetracyclines for the treatment of infections caused by intracellular pathogens. Aminoglycosides and fosfomycin could be considered as a therapeutic alternative for the treatment of quinolone resistant prostatitis. Use of alpha-blockers in CP/CPPS patients with urinary symptoms and analgesics +/- non steroidal anti-inflammatory drugs (NSAID), in presence of pain demonstrated a reduction of symptoms reduction and an improvement of quality of life, although long term use of NSAID is limited by side effect profile. However, the multimodal therapeutic regimen by contemporary use of alphablockers, antibiotics and anti-inflammatory showed a better control of prostatitis symptoms than single drug treatment. Novel therapeutic substances for the treatment of pain, such as the cannabinoid anandamide would be highly interesting to test. An alternative for the treatment of chronic prostatitis/chronic pelvic pain syndrome is phytotherapy, as primary therapy or in association with other drugs. Quercetin, pollen extract, extract of Serenoa repens and other mixtures of herbal extracts showed a positive effect on symptoms and quality of life without side effects. The association of CP/CPPS with alterations of intestinal function has been described. Diet has its effects on inflammation by regulation of the composition of intestinal flora and direct action on the intestinal cells (sterile inflammation). Intestinal bacteria (microbiota) interacts with food influencing the metabolic, immune and inflammatory response of the organism. The intestinal microbiota has protective function against pathogenic bacteria, metabolic function by synthesis of vitamins, decomposition of bile acids and production of trophic factors (butyrate), and modulation of the intestinal immune system. The alteration of the microbiota is called "dysbiosis" causing invasive intestinal diseases pathologies (leaky gut syndrome and food intolerances, irritable bowel syndrome or chronic inflammatory bowel diseases) and correlating with numerous systemic diseases including acute and chronic prostatitis. Administration of live probiotics bacteria can be used to regulate the balance if intestinal flora. Sessions of hydrocolontherapy can represent an integration to this therapeutic approach. Finally, microbiological examination of sexual partners can offer supplementary information for treatment.

Aim: Ureaplasma parvum, Ureaplasma urealyticum and Mycoplasma hominis are also known as genital mycoplasmas. Acute chorioamnionitis is an inflammation of the placenta associated with miscarriage. We retrospectively evaluated a possible association between genital mycoplasmas detection, acute chorioamnionitis and fetal pneumonia from second and third trimester spontaneous abortions., Methods: One hundred and thirty placenta and fetal lung samples were evaluated for histological examination. The placenta samples, along with corresponding fetal tracheo-bronchial aspirates, also underwent bacterial and fungal culture and real-time polymerase chain reaction (PCR) assay for the detection of genital mycoplasmas., Results: Acute chorioamnionitis and pneumonia were diagnosed in 80/130 (61.5%) and 22/130 (16.9%) samples, respectively. Among samples positive for acute chorioamnionitis, the proportion of samples positive by real-time PCR and/or culture, was significantly higher than that of negative controls [54/80 (67.5%) vs. 26/80 (32.5%); P<0.001]. Ureaplasma parvum detection was significantly associated with acute chorioamnionitis compared to controls [9/11 (81.8%) vs. 2/11 (18.2%); P=0.019], as well as U. urealyticum [6/7 (85.7%) vs. 1/7 (14.3%); P=0.039]. Among tracheo-bronchial aspirates from abortions with pneumonia, the proportion of real-time PCR and/or culture positive samples was significantly higher than that of controls [13/22 (59.1%) vs. 9/22 (40.9%); P=0.029]., Conclusions: A strong association was found between acute histologic chorioamnionitis and microbial invasion with U. parvum and/or U. urealyticum.

Background: Mycoplasmas are frequently isolated from the genital tract. New molecular PCR-based methods for the detection of mycoplasmas can better define the real epidemiology of these microorganisms. The aim of this study was to evaluate the prevalence of mycoplasmas in a population of childbearing age women by means of PCR., Methods: This 21-month multicentre observational study was conducted at four Italian clinical microbiology laboratories. Women reporting symptoms of vaginitis/cervicitis, or with history of infertility, pregnancy, miscarriage or preterm birth were included. Detection of Ureaplasma parvum, Ureaplasma urealyticum, Mycoplasma hominis, Mycoplasma genitalium was performed from cervical swabs by means of a commercially available multiplex real-time PCR., Results: a total of 1761 women fulfilled the inclusion criteria and were included in the study. The overall prevalence was: U. parvum 38.3%, U. urealyticum 9%, M. hominis 8.6% and M. genitalium 0.6%. The proportion of foreign patients positive for U. parvum was significantly higher compared to Italian patients (37% vs 30.1%, p = 0.007) and also for overall mycoplasma colonization (53.4% vs 45.8%, p = 0.011). The number of symptomatic patients positive for M. hominis was significantly higher than that of negative controls (2.9% vs 1%, p = 0.036). A significant positive trend in mycoplasma colonization was found in relation to the pregnancy week for U. urealyticum (p = 0.015), M. hominis (p = 0.044) and for overall mycoplasma colonization (p = 0.002)., Conclusion: multiplex RT-PCR can be a valuable tool to evaluate the real epidemiology of cervical mycoplasma colonization., (Copyright © 2017. Published by Elsevier B.V.)

Background: Peak of bone mass (PBM) is generally reached about the age of 18 both in boys and girls. Maximizing PBM during growth may contribute to fracture risk reduction in adulthood and in the elderly. The aim of our study was to evaluate the effects on bone mineral density (BMD) of global physical activity (PA), carried out in the past 15 years, in a population of 70 healthy, young male and female subjects aged 22 to 25., Methods: BMD of the lumbar spine and total hip was measured using dual-energy X-ray absorptiometry (DEXA); global PA, resulting from sports-related, occupational and commuting PA, was evaluated using validated questionnaires., Results: Women spent more time than men both in sports-related, occupational and commuting PA in the age range between 10-15 years. In the female group global PA positively correlated with BMD of the lumbar spine (r=0.38; P=0.02) and the total hip (r=0.36; P=0.04) and BMD of the lumbar spine was independently predicted by global PA and Body Mass Index., Conclusions: Our retrospective cross-sectional study indicates that global PA, not only sports-related PA, performed during prepubertal age, is associated with a greater PBM in women.