Multi-wavelength SPAD photoplethysmography for cardio-respiratory monitoring

There is a growing interest in photoplethysmography (PPG) for the continuous monitoring of cardio-respiratory signals by portable instrumentation aimed at the early diagnosis of cardiovascular diseases. In this context, it is conceivable that PPG sensors working at different wavelengths simultaneously can optimize the identification of apneas and the quantification of the associated heart-rate changes or other parameters that depend on the PPG shape (e.g., systematic vascular resistance and pressure), when evaluating the severity of breathing disorders during sleep and in general for health monitoring. Therefore, the objective of this work is to present a novel pulse oximeter that provides synchronous data logging related to three light wavelengths (green, red, and infrared) in transmission mode to optimize both heart rate measurements and a reliable and continuous assessment of oxygen saturation. The transmission mode is considered more robust over motion artifacts than reflection mode, but current pulse oximeters cannot employ green light in transmission mode due to the high absorbance of body tissues at this wavelength. For this reason, our device is based on a Single-Photon Avalanche Diode (SPAD) with very short deadtime (less than 1 ns) to have, at the same time, the single photon sensitivity and high-count rate that allows acquiring all the wavelengths of interest on the same site and in transmission mode. Previous studies have shown that SPAD cameras can be used for measuring the heart rate through remote PPG, but oxygen saturation and heart-rate measures through contact SPAD-based PPG sensors have never been addressed so far. The results of the preliminary validation on six healthy volunteers reflect the expected physiological phenomena, providing rms errors in the Inter Beat Interval estimation smaller than 70 ms (with green light) and a maximum error in the oxygen saturation smaller than 1% during the apneas. Our prototype demonstrates the reliability of SPAD-based devices for continuous long-term monitoring of cardio-respiratory variables as an alternative to photodiodes especially when minimal area and optical power are required

A stringent preemptive protocol reduces cytomegalovirus disease in the first 6 months after kidney transplantation

Background: The optimal strategy to prevent cytomegalovirus (CMV) disease after kidney transplantation continues to be open to debate. The preemptive approach requires regular determination of CMV viremia and prompt initiation of therapy. Methods: We retrospectively compared the incidence of CMV disease during two periods at our center: A first phase (P1, n=84 kidney recipients), during which time the intensity of surveillance was determined by the responsible physician, was compared to a second phase (P2, n=74), when a stringent protocol of CMV surveillance was required for all patients. The preemptive approach was applied for all CMV risk groups; prophylaxis was optional in the case of treatment for rejection or delayed graft function in the intermediate- and high-risk group. Follow-up was truncated at 6months after transplant surgery. CMV syndrome was differentiated from asymptomatic replication by the presence of at least one systemic symptom, while diagnosis of CMV end-organ disease required histological confirmation. Results: Immunosuppression was similar in the two periods. CMV prophylaxis was used equally (26%) in both periods. The probability for asymptomatic viremia episodes was not different for patients in P1 and P2 regardless of the prevention strategy. For patients following the preemptive strategy, the probability for CMV disease was increased during P1 (p=0.016), despite fewer PCR assays being performed in phase 2. Protocol violations were only observed during P1. Conclusions: The probability of CMV disease episodes (CMV syndrome and CMV end-organ disease) was substantially reduced using a very stringent protocol. This study highlights the crucial importance of a stringent protocol with optimal adherence by all caregivers if the preemptive strategy is to be successfu

Spatially Resolved Event-Driven 24 × 24 Pixels SPAD Imager with 100% Duty Cycle for Low Optical Power Quantum Entanglement Detection

Quantum microscopy requires efficient detectors able to identify temporal correlations among photons. Photon coincidences are usually detected by postprocessing their timestamps measured by means of time-To-digital converters (TDCs), through a time and power-consuming procedure, which impairs the overall system performance. In this article, we propose an innovative single-photon sensitive imager based on single-photon avalanche diodes (SPADs), able to signal coincident photon pairs along with their position through a TDC-free, event-driven architecture. The result is a highly efficient detector (25.8%) with a 100% duty cycle and minimized data throughput. The modular architecture and the 330 ns readout time, independent of pixel number, pave the way to large format imagers based on the same paradigm. The detector enabled quantum imaging at extremely low, microwatt-level optical pump powers, four orders of magnitude lower than previous experiments with similar optical setups

Viral Escape in the Central Nervous System with Multidrug-Resistant Human Immunodeficiency Virus-1

In this study, we report the case of a patient infected with human immunodeficiency virus (HIV)-1 who developed ataxia and neurocognitive impairment due to viral escape within the central nervous system (CNS) with a multidrug-resistant HIV-1 despite long-term viral suppression in plasma. Antiretroviral therapy optimization with drugs with high CNS penetration led to viral suppression in the CSF, regression of ataxia, and improvement of neurocognitive symptom

Hemophagocytic syndrome caused by primary herpes simplex virus 1 infection: report of a first case

Introduction: Hemophagocytic syndrome represents a severe hyperinflammatory condition by activated macrophages. Leading viral triggering agents are Epstein-Barr virus (EBV), cytomegalovirus (CMV), and adenovirus. Materials and methods: We present a patient with Wegener's granulomatosis on azathioprine and prednisone medication, who developed a life-threatening hemophagocytic syndrome. Positive plasma polymerase chain reaction (PCR) with negative serology revealed a primary, disseminated infection with herpes simplex virus-1 as the triggering pathogen. After treatment with acyclovir, high-dose steroids, immunoglobulins, and etoposide, the patient recovered. Conclusion: Early diagnosis of potentially underlying infections of hemophagocytic syndrome influences the therapeutic approach. It is important to consider a variety of infectious agents, particularly in immunosuppressed individuals. The reported case emphasizes the importance of screening for herpes simplex virus

Intra-hospital differences in antibiotic use correlate with antimicrobial resistance rate in <i>Escherichia coli</i> and <i>Klebsiella pneumoniae</i>: a retrospective observational study.

Monitoring antimicrobial use and resistance in hospitals are important tools of antimicrobial stewardship programs. We aimed to determine the association between the use of frequently prescribed antibiotics and the corresponding resistance rates in &lt;i&gt;Escherichia coli&lt;/i&gt; and &lt;i&gt;Klebsiella pneumoniae&lt;/i&gt; among the clinical departments of a tertiary care hospital. We performed a retrospective observational study to analyse the use of nine frequently prescribed antibiotics and the corresponding antimicrobial resistance rates in hospital acquired &lt;i&gt;E. coli&lt;/i&gt; and &lt;i&gt;K. pneumoniae&lt;/i&gt; isolates from 18 departments of our institution over 9 years (2008-2016). The main cross-sectional analysis assessed the hypothetical influence of antibiotic consumption on resistance by mixed logistic regression models. We found an association between antibiotic use and resistance rates in &lt;i&gt;E. coli&lt;/i&gt; for amoxicillin-clavulanic acid (OR per each step of 5 defined daily dose/100 bed-days 1.07, 95% CI 1.02-1.12; &lt;i&gt;p&lt;/i&gt;  = 0.004), piperacillin-tazobactam (OR 2.11, 95% CI 1.45-3.07; &lt;i&gt;p&lt;/i&gt;  &lt; 0.001), quinolones (OR 1.52, 95% CI 1.25-1.86; &lt;i&gt;p&lt;/i&gt;  &lt; 0.001) and trimethoprim-sulfamethoxazole (OR 1.59, 95% CI 1.19-2.13; &lt;i&gt;p&lt;/i&gt;  = 0.002). Additionally, we found a significant association when all nine antibiotics were combined in one analysis. The association between consumption and resistance rates was stronger for nosocomial than for community strains. In &lt;i&gt;K. pneumoniae,&lt;/i&gt; we found an association for amoxicillin-clavulanic acid (OR 1.07, 95% CI 1.01-1.14; &lt;i&gt;p&lt;/i&gt;  = 0.025) and for trimethoprim-sulfamethoxazole (OR 2.02, 95% CI 1.44-2.84; &lt;i&gt;p&lt;/i&gt;  &lt; 0.001). The combined analysis did not show an association between consumption and resistance (OR 1.06, 95% CI 0.99-1.14; &lt;i&gt;p&lt;/i&gt;  = 0.07). We documented an association between antibiotic use and resistance rate for amoxicillin-clavulanic acid, piperacillin-tazobactam, quinolones and trimethoprim-sulfamethoxazole in &lt;i&gt;E. coli&lt;/i&gt; and for amoxicillin-clavulanic acid and trimethoprim-sulfamethoxazole in &lt;i&gt;K. pneumoniae&lt;/i&gt; across different hospital departments. Our data will support stewardship interventions to optimize antibiotic prescribing at a department level

A stringent preemptive protocol reduces cytomegalovirus disease in the first 6 months after kidney transplantation

BACKGROUND: The optimal strategy to prevent cytomegalovirus (CMV) disease after kidney transplantation continues to be open to debate. The preemptive approach requires regular determination of CMV viremia and prompt initiation of therapy. METHODS: We retrospectively compared the incidence of CMV disease during two periods at our center: A first phase (P1, n = 84 kidney recipients), during which time the intensity of surveillance was determined by the responsible physician, was compared to a second phase (P2, n = 74), when a stringent protocol of CMV surveillance was required for all patients. The preemptive approach was applied for all CMV risk groups; prophylaxis was optional in the case of treatment for rejection or delayed graft function in the intermediate- and high-risk group. Follow-up was truncated at 6 months after transplant surgery. CMV syndrome was differentiated from asymptomatic replication by the presence of at least one systemic symptom, while diagnosis of CMV end-organ disease required histological confirmation. RESULTS: Immunosuppression was similar in the two periods. CMV prophylaxis was used equally (26 %) in both periods. The probability for asymptomatic viremia episodes was not different for patients in P1 and P2 regardless of the prevention strategy. For patients following the preemptive strategy, the probability for CMV disease was increased during P1 (p = 0.016), despite fewer PCR assays being performed in phase 2. Protocol violations were only observed during P1. CONCLUSIONS: The probability of CMV disease episodes (CMV syndrome and CMV end-organ disease) was substantially reduced using a very stringent protocol. This study highlights the crucial importance of a stringent protocol with optimal adherence by all caregivers if the preemptive strategy is to be successful

Exposure to avian coronavirus vaccines is associated with increased levels of SARS-CoV-2-cross-reactive antibodies.

BACKGROUND Although avian coronavirus infectious bronchitis virus (IBV) and SARS-CoV-2 belong to different genera of the Coronaviridae family, exposure to IBV may result in the development of cross-reactive antibodies to SARS-CoV-2 due to homologous epitopes. We aimed to investigate whether antibody responses to IBV cross-react with SARS-CoV-2 in poultry farm personnel who are occupationally exposed to aerosolized IBV vaccines. METHODS We analyzed sera from poultry farm personnel, COVID-19 patients, and pre-pandemic controls. IgG levels against the SARS-CoV-2 antigens S1, RBD, S2, and N and peptides corresponding to the SARS-CoV-2 ORF3a, N, and S proteins as well as whole virus antigens of the four major S1-genotypes 4/91, IS/1494/06, M41, and D274 of IBV were investigated by in-house ELISAs. Moreover, live-virus neutralization test (VNT) was performed. RESULTS A subgroup of poultry farm personnel showed elevated levels of specific IgG for all tested SARS-CoV-2 antigens compared with pre-pandemic controls. Moreover, poultry farm personnel, COVID-19 patients, and pre-pandemic controls showed specific IgG antibodies against IBV strains. These antibody titers were higher in long-term vaccine implementers. We observed a strong correlation between IBV-specific IgG and SARS-CoV-2 S1-, RBD-, S2-, and N-specific IgG in poultry farm personnel compared with pre-pandemic controls and COVID-19 patients. However, no neutralization was observed for these cross-reactive antibodies from poultry farm personnel using the VNT. CONCLUSION We report here for the first time the detection of cross-reactive IgG antibodies against SARS-CoV-2 antigens in humans exposed to IBV vaccines. These findings may be useful for further studies on the adaptive immunity against COVID-19

Exposure to avian coronavirus vaccines is associated with increased levels of SARS-CoV-2-cross-reactive antibodies

Background: Although avian coronavirus infectious bronchitis virus (IBV) and SARS-CoV-2 belong to different genera of the Coronaviridae family, exposure to IBV may result in the development of cross-reactive antibodies to SARS-CoV-2 due to homologous epitopes. We aimed to investigate whether antibody responses to IBV cross-react with SARS-CoV-2 in poultry farm personnel who are occupationally exposed to aerosolized IBV vaccines. Methods: We analyzed sera from poultry farm personnel, COVID-19 patients, and pre-pandemic controls. IgG levels against the SARS-CoV-2 antigens S1, RBD, S2, and N and peptides corresponding to the SARS-CoV-2 ORF3a, N, and S proteins as well as whole virus antigens of the four major S1-genotypes 4/91, IS/1494/06, M41, and D274 of IBV were investigated by in-house ELISAs. Moreover, live-virus neutralization test (VNT) was performed. Results: A subgroup of poultry farm personnel showed elevated levels of specific IgG for all tested SARS-CoV-2 antigens compared with pre-pandemic controls. Moreover, poultry farm personnel, COVID-19 patients, and pre-pandemic controls showed specific IgG antibodies against IBV strains. These antibody titers were higher in long-term vaccine implementers. We observed a strong correlation between IBV-specific IgG and SARS-CoV-2 S1-, RBD-, S2-, and N-specific IgG in poultry farm personnel compared with pre-pandemic controls and COVID-19 patients. However, no neutralization was observed for these cross-reactive antibodies from poultry farm personnel using the VNT. Conclusion: We report here for the first time the detection of cross-reactive IgG antibodies against SARS-CoV-2 antigens in humans exposed to IBV vaccines. These findings may be useful for further studies on the adaptive immunity against COVID-19. Keywords: COVID-19; IBV; SARS-CoV-2; cross-reactivity; neutralizatio