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

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

IL1B and DEFB1 Polymorphisms Increase Susceptibility to Invasive Mold Infection After Solid-Organ Transplantation.

BACKGROUND: Single-nucleotide polymorphisms (SNPs) in immune genes have been associated with susceptibility to invasive mold infection (IMI) among hematopoietic stem cell but not solid-organ transplant (SOT) recipients. METHODS: Twenty-four SNPs from systematically selected genes were genotyped among 1101 SOT recipients (715 kidney transplant recipients, 190 liver transplant recipients, 102 lung transplant recipients, 79 heart transplant recipients, and 15 recipients of other transplants) from the Swiss Transplant Cohort Study. Association between SNPs and the end point were assessed by log-rank test and Cox regression models. Cytokine production upon Aspergillus stimulation was measured by enzyme-linked immunosorbent assay in peripheral blood mononuclear cells (PBMCs) from healthy volunteers and correlated with relevant genotypes. RESULTS: Mold colonization (n = 45) and proven/probable IMI (n = 26) were associated with polymorphisms in the genes encoding interleukin 1β (IL1B; rs16944; recessive mode, P = .001 for colonization and P = .00005 for IMI, by the log-rank test), interleukin 1 receptor antagonist (IL1RN; rs419598; P = .01 and P = .02, respectively), and β-defensin 1 (DEFB1; rs1800972; P = .001 and P = .0002, respectively). The associations with IL1B and DEFB1 remained significant in a multivariate regression model (P = .002 for IL1B rs16944; P = .01 for DEFB1 rs1800972). The presence of 2 copies of the rare allele of rs16944 or rs419598 was associated with reduced Aspergillus-induced interleukin 1β and tumor necrosis factor α secretion by PBMCs. CONCLUSIONS: Functional polymorphisms in IL1B and DEFB1 influence susceptibility to mold infection in SOT recipients. This observation may contribute to individual risk stratification

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

40-nm SPAD-Array System for Ultra-Fast Raman Spectroscopy

The PoteinID (ProID) European project focuses on the development of a novel detection system that can perform ultra-fast Raman Spectroscopy (RS) with the aim of protein identification. The protein comprised of an amino acid (aa) chain is first denatured and then passed through a plasmonic nanopore. Each aa molecule is excited with a monochromatic laser and such excitation is followed by a Raman scattering process and subsequent autofluorescence. The goal of the detector developed by us, is to collect only the Raman photons while rejecting the fluorescence signal. By exploiting the fact that the fluorescence signal has a characteristic time constant in the order of few nanoseconds, while the Raman signal has a characteristic time constant in the order of few hundreds of picoseconds, we can reject the fluorescence signal by employing time-filtering techniques. The time- filtering technique used in this system is the Time-Gated Single-Photon Counting (TG-SPC). With this gating strategy we can define a temporal window (referred to as gate) where the SPADs are photosensitive and outside this window the photons are not detected. By using a sub-ns gate generated internally by the array, we can make the SPADs photosensitive only to the Raman photons. After the photons are detected and counted by each pixel, the sum of the four pixels inside a column is available at the output as an 8-bit word. The sums of the columns are outputted sequentially starting from the last one and then scanned in a shift-register pattern. Each column has a readout time of around 10 ns, so by using a 100 MHz reading clock, a full readout of 1.28 μs can be achieved. Thanks to the innovative jump readout modality, it is possible to select a specific subset of the column to read and thus reducing the overall readout time by 10 ns per each disabled column. By disabling 28 columns it is possible to reach sub-μs readout time. This technique was inspired by results shown presented in [1]. In this paper, we present the characterization of a detector developed as a preliminary version to the 128 x 4 SPAD array. The detector tested in this paper is based on a 16 x 4 SPAD array developed in the same 40 nm planar technology

Multipass wide-field phase imager

Advances in optical imaging always look for an increase in sensitivity and resolution among other practicability aspects. Within the same scope, in this work we report a versatile interference contrast imaging technique, with high phase sensitivity and a large field-of-view of several mm2. Sensitivity is increased through the use of a self-imaging non-resonant cavity, which causes photons to probe the sample in multiple rounds before being detected, where the configuration can be transmissive or reflective. Phase profiles can be resolved individually for each round thanks to a specially designed single-photon camera with time-of-flight capabilities and true pixels-off gating. Measurement noise is reduced by novel data processing combining the retrieved sample profiles from multiple rounds. Our protocol is especially useful under extremely low light conditions as required by biological or photo-sensitive samples. Results demonstrate more than a four-fold reduction in phase measurement noise, compared to single round imaging, and values close to the predicted sensitivity in case of the best possible cavity configuration, where all photons are maintained until n rounds. We also find good agreement with the theoretical predictions for low number of rounds, where experimental imperfections would play a minor role. The absence of a laser or cavity lock-in mechanism makes the technique an easy to use inspection tool

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