Watch-and-wait approach for inactive echinococcal cysts: scoping review update since the issue of the WHO-IWGE Expert Consensus and current perspectives.

PURPOSE OF REVIEW: This work aims to provide an update of knowledge on the evolution of inactive cystic echinococcosis (CE) cysts (CE4-CE5) managed by 'watch-and-wait', by means of a scoping review of the literature published after the publication of the WHO-IWGE (Informal Working Group on Echinococcosis) Expert Consensus document in 2010. RECENT FINDINGS: A total of 31 articles were included. Population ultrasound-based studies showed that spontaneously inactivated CE cysts represent 50.2% (95% confidence interval 38.7-61.8) of all detected untreated CE cysts, and that the prevalence of CE4-CE5 cysts tends to increase with age. Four longitudinal population-based studies showed that CE cysts naturally tend to evolve towards inactivation and that spontaneously inactivated cysts reactivate in a minority of cases. This was confirmed by four hospital-based studies, showing that spontaneously inactivated cysts reactivate rarely, while rate of reactivation is higher if inactivity was obtained posttreatment. It was not possible to drive conclusions on any difference in the clinical course of infection in immunocompromised or pregnant patients. SUMMARY: CE cysts tend to evolve spontaneously to inactivation over time. The published literature supports the safety of the watch-and-wait approach for inactive cysts, sparing treatment to a substantial proportion of asymptomatic patients. A regular follow-up with ultrasound of all inactive cysts is required to detect reactivations.

Computer-automated design of mode-locked fiber lasers.

We automate the mode-locked fiber laser design process using a modified genetic algorithm and an intuitive optimization loss function to control highly accurate polarization-resolved simulations of laser start-up dynamics without user interaction. We reconstruct both the cavity designs and output pulse characteristics of experimentally demonstrated Yb-fiber all-normal dispersion, dispersion-managed, and wavelength-tuneable all-anomalous dispersion Tm-fiber femtosecond lasers with exceptional accuracy using minimal prior knowledge, and show that our method can be used to predict new cavity designs and novel mode locking states that meet target pulse requirements. Our approach is directly applicable to a broad range of mode locking regimes, wavelengths, pulse energies, and repetition rates, requires no training or knowledge of the loss function gradients, and is scalable for use on supercomputers and inexpensive desktop computers.

Telemedicine-assisted care of an older patient with COVID-19 and dementia: bridging the gap between hospital and home.

Hospital at Home (HaH) has been proposed as a solution to relieve pressure on hospital beds during the COVID-19 pandemic; however, caregivers' feelings of inadequacy and concerns on the need for tighter clinical monitoring might lead to unnecessary and potentially harmful hospital admissions in frail older patients with mild or atypical COVID-19. Here we report the case of a 91-year old woman with severe dementia and atypical COVID-19 that could be successfully managed by our HaH thanks to her highly motivated caregivers and the support of a telemedicine solution (TMS) to provide caregiver training and support as well as supplementary telemonitoring. Despite some well-known issues on TMS use, the hybrid in-person and tele-visit approach of TMS-assisted HaH could help to create a "secure" environment, empowering caregivers to manage frail older adults with COVID-19 at home, avoiding unnecessary admissions to closed wards and their negative physical, functional and psychological outcomes.

An eight-year experience of Nocardia infection in Italy: does immunosuppression matter?

Nocardia has always been considered a pathogen of the immunocompromised host, but recent evidence has also highlighted its role as a pathogen in the immunocompetent. We aim to assess the role of immunosuppression in the disease. We reviewed all the cases of infections due to Nocardia spp. in our center that occurred from 1 January 2012 to 30 September 2019. Patients were divided into three groups: typical immunocompromised (PLWHIV, solid organ or hematopoietic cell transplant recipients, individuals under immunosuppressive drugs), atypical immunocompromised (ongoing chronic diseases involving the lung, kidney, liver and diabetes) and immunocompetent. We identified 53 patients with an infection by Nocardia spp. Thirty-four (60.4%) of them were immunocompromised, 22 (64.7%) typical and 12 (35.3%) atypical immunocompromised. Nineteen (35.8%) were immunocompetent. The two conditions most frequently associated with infection were chronic lung disease (41.5%) and ongoing treatment with immunosuppressive drugs (33.9%). In our cohort a remarkable prevalence of nocardiosis in immunocompetent and atypical immunosuppressed patients was observed.

Diagnosing acute encephalitis in patients with hematological disorders: caveats and pitfalls.

The aim of this study was to review the quality of the diagnostic work-up for acute encephalitis carried out at our center in a cohort of patients with hematological disorders. Our data showed substantial heterogeneity in investigating patients. Not all patients had their CSF tested for viruses commonly responsible for encephalitis in immunocompetent individuals (e.g., VZV, enterovirus). A blood sample for the calculation of the CSF/blood replication ratio was collected in 74% of cases. CSF cultures and immunophenotyping of CSF cells were performed in 77% and 21% of patients, respectively. A multidisciplinary consensus is needed to improve current guidelines and standardize diagnostic protocols.

Noise-related polarization dynamics for femto and picosecond pulses in normal dispersion fibers.

We report how the complex intra-pulse polarization dynamics of coherent optical wavebreaking and incoherent Raman amplification processes in all-normal dispersion (ANDi) fibers vary for femto and picosecond pump pulses. Using high temporal resolution vector supercontinuum simulations, we identify deterministic polarization dynamics caused by wavebreaking and self-phase modulation for femtosecond pulses and quasi-chaotic polarization evolution driven by Raman amplification of quantum noise for picosecond pulses. In contrast to cross-phase modulation instability, the Raman-based polarization noise has no power threshold and is reduced by aligning the higher energy polarization component with the lower index axis of the fiber. The degree of polarization stability is quantified using new time domain parameters that build on the spectrally averaged degree of coherence used in supercontinuum research to quantify the output spectral stability. We show that the spectral coherence is intrinsically linked to polarization noise, and that the noise will occur in both polarization maintaining (PM) and non-PM fibers, spanning a broad range of pulse energies, durations, and fiber birefringence values. This analysis provides an in-depth understanding of the nonlinear polarization dynamics associated with coherent and incoherent propagation in ANDi fibers.

Cryptococcosis in an HIV-negative, HCV positive, immunosenescent patient: a case report.

Cryptococcus species is still a very common opportunistic infection in AIDS patients. However, it is increasingly responsible for disease in otherwise immunocompromised individuals, such as transplant recipients and the heterogeneous group of patients with underlying immunologic diseases, hematologic disorders and organ failure syndromes. Clinical presentation, prognosis, and outcomes are difficult to define given these varied host groups, and tailoring treatments to fit the necessities of each patient is likewise challenging. Our patient was on treatment with steroids and direct-acting antiviral agents (DAAs) for a chronic HCV-related hepatitis, worsened by cryoglobulinemia, membranoproliferative glomerulonephritis and a lowgrade B cells lymphoma. We report a case of systemic cryptococcal infection in an immunosenescent, HIV-negative patient.

Oral anticoagulant therapy in atrial fibrillation older patients with previous bleeding.

Oral anticoagulant therapy (OAT) with direct oral anticoagulant (DOACs) is the established treatment to reduce thromboembolic risk in patients with atrial fibrillation (AF). Bleeding risk scores are useful to identify and correct factors associated with bleeding risk in AF patients on OAT. However, the clinical scenario is more complex in patients with previous bleeding event, and the decision about whether and when starting or re-starting OAT in these patients remains a contentious issue. Major bleeding is associated with a subsequent increase in both short- and long-term mortality, and even minimal bleeding may have prognostic importance because it frequently leads to disruption of antithrombotic therapy. There is an unmet need for guidance on how to manage antithrombotic therapy after bleeding has occurred. While waiting for observational and randomized data to accrue, this paper offers a perspective on managing antithrombotic therapy after bleeding in older patients with AF.

Cryptococcosis in an HIV-negative, HCV positive, immunosenescent patient: a case report.

Cryptococcus species is still a very common opportunistic infection in AIDS patients. However, it is increasingly responsible for disease in otherwise immunocompromised individuals, such as transplant recipients and the heterogeneous group of patients with underlying immunologic diseases, hematologic disorders and organ failure syndromes. Clinical presentation, prognosis, and outcomes are difficult to define given these varied host groups, and tailoring treatments to fit the necessities of each patient is likewise challenging. Our patient was on treatment with steroids and direct-acting antiviral agents (DAAs) for a chronic HCV-related hepatitis, worsened by cryoglobulinemia, membranoproliferative glomerulonephritis and a low-grade B cells lymphoma. We report a case of systemic cryptococcal infection in an immunosenescent, HIV-negative patient.

Structural and Immunodiagnostic Characterization of Synthetic Antigen B Subunits From Echinococcus granulosus and Their Evaluation as Target Antigens for Cyst Viability Assessment.

Background: Several tools have been proposed for serodiagnosis of cystic echinococcosis (CE), but none seems promising for cyst viability assessment. Antigens with stage-specific diagnostic value have been described, but few studies with well-characterized antigens and human serum samples have been performed. Antigen B (AgB) proteoforms hold promise as markers of viability, due to their differential stage-related expression and immunoreactivity. Methods: Four AgB subunits (AgB1, AgB2, AgB3, AgB4) were synthesized and structurally characterized. Based on the preliminary evaluation of the subunits by western immunoblotting and enzyme-linked immunosorbent assay (ELISA), AgB1 and AgB2 were further tested in two ELISA setups and extensively validated on 422 human serum samples. Results: All subunits showed a high degree of spontaneous oligomerization. Interacting residues within oligomers were identified, showing that both the N-terminal and C-terminal of each subunit are involved in homo-oligomer contact interfaces. No hetero-oligomer was identified. AgB1 and AgB2 ELISAs revealed different sensitivities relative to cyst stage. Of note, besides high specificity (97.2%), AgB1 revealed a higher sensitivity for active-transitional cysts (100% for CE1, 77.8% for CE2, 81.5% for CE3a, and 86.3% for CE3b) than for inactive cysts (41.7% for CE4 and 11.1% for CE5) and postsurgical patients (44%). Interestingly, 19 of 20 patients with spontaneously inactive cysts and 6 of 9 treated with albendazole >5 years earlier were negative on the AgB1 assay. Conclusions: The structural characterization of subunits provides insights into the synthetic antigen conformation. The stage-related sensitivity of synthetic AgB1 holds promise as part of a multiantigen setting and deserves further longitudinal evaluation as marker of cyst viability.

Effects of oral anticoagulant therapy in older medical in-patients with atrial fibrillation: a prospective cohort observational study.

BACKGROUND: Uncertainties about efficacy and safety of oral anticoagulant therapy (OAT) among older and frail medical patients with atrial fibrillation (AF) largely contribute to under-prescription of these drugs. AIMS: In this prospective observational cohort study, we investigated mortality, and ischemic and hemorrhagic events, in hospital-discharged older patients with AF. METHODS: Stroke and bleeding risk were evaluated using CHA2DS2-VASC and HAS-BLED scores. Comorbidity, frailty, cognitive and nutritional status and functional autonomy were evaluated using standardized scales. Independent associations between clinical variables, including OAT use, and all-cause mortality, fatal and non-fatal ischemic and hemorrhagic events, were evaluated. Further clinical outcomes comparison between patients treated with OAT and those untreated was performed after adjustment for significant differences in patient baseline characteristics with propensity score matching. RESULTS: Of 452 patients included (mean age 81.6 years, 54.9 % women, roughly 30 % cognitively impaired and/or functionally dependent, mean CHA2DS2-VASC and HAS-BLED scores 4.6 and 2.8, respectively), 151 (33.4 %) died during a mean follow-up period of 300.5 days; ischemic and hemorrhagic stroke occurred in 4.0 and 0.4 % of patients, respectively, and major bleedings in 6.2 %. DISCUSSION: After multivariate analysis, OAT at discharge was associated with lower overall mortality and reduced occurrence of ischemic stroke, the first finding being confirmed in propensity score matched analysis. CONCLUSIONS: Among older vulnerable AF patients with high post discharge death rate, OAT was associated, among other multiple factors, with reduced mortality and lower occurrence of ischemic stroke.

First evaluation of QuantiFERON-TB Gold Plus performance in contact screening.

Identifying latently infected individuals is crucial for the elimination of tuberculosis (TB). We evaluated for the first time the performance of a new type of interferon-γ release assay, QuantiFERON-TB Plus (QFT-Plus), which includes an additional antigen tube (TB2), stimulating both CD4+ and CD8+ T-cells in contacts of TB patients.Contacts were screened for latent TB infection by tuberculin skin test, QFT-Plus and QuantiFERON-TB Gold in Tube (QFT-GIT).In 119 TB contacts, the overall agreement between QFT-Plus and QFT-GIT was high, with a Cohen's κ of 0.8. Discordant results were found in 12 subjects with negative QFT-GIT and positive QFT-Plus results. In analyses of markers of TB exposure and test results, the average time spent with the index case was the strongest risk factor for positivity in each of these tests. The difference in interferon-γ production between the two antigen tubes (TB2-TB1) was used as an estimate of CD8+ stimulation provided by the TB2. TB2-TB1 values >0.6 IU·mL-1 were significantly associated with proximity to the index case and European origin.QFT-Plus has a stronger association with surrogate measures of TB exposure than QFT-GIT in adults screened for latent TB infection. Interferon-γ response in the new antigen tube used an indirect estimate of specific CD8+ response correlates with increased Mycobacterium tuberculosis exposure, suggesting a possible role in identifying individuals with recent infection.

Cystic Echinococcosis.

Echinococcosis is one of the 17 neglected tropical diseases (NTDs) recognized by the World Health Organization. The two major species of medical importance are Echinococcus granulosus and Echinococcus multilocularis. E. granulosus affects over 1 million people and is responsible for over $3 billion in expenses every year. In this minireview, we discuss aspects of the epidemiology, clinical manifestations, and diagnosis of cystic echinococcosis or cystic hydatid disease caused by E. granulosus.

Chest ultrasonography in patients with HIV: a case series and review of the literature.

INTRODUCTION: Pulmonary disease is common in HIV-infected patients. Diagnostic means, however, are often scarce in areas where most HIV patients are living. Chest ultrasonography has recently evolved as a highly sensitive and specific imaging tool for diagnosing chest conditions such as pneumothorax, pneumonia and pulmonary edema in critically ill patients. This article addresses the issue of imaging and differentiating common pulmonary conditions in HIV-infected patients by chest ultrasonography. METHODS: We report chest ultrasound features of five different common pulmonary diseases in HIV-infected patients (bacterial pneumonia, Pneumocystis jirovecii pneumonia, tuberculosis, cytomegalovirus pneumonia and non-Hodgkin lymphoma) and review the respective literature. CONCLUSIONS: We observed characteristic ultrasound patterns especially in Pneumocystis jirovecii pneumonia and pulmonary lymphoma. Further exploration of chest ultrasonography in HIV-infected patients appears promising and may translate into new diagnostic approaches for pulmonary conditions in patients living with HIV.

Acceptance of standardized ultrasound classification, use of albendazole, and long-term follow-up in clinical management of cystic echinococcosis: a systematic review.

PURPOSE OF REVIEW: Cystic echinococcosis is a chronic, complex, and neglected disease. The need for a simple classification of cyst morphology that would provide an accepted framework for scientific and clinical work on cystic echinococcosis has been addressed by two documents issued by the WHO Informal Working Group on Echinococcosis in 2003 (cyst classification) and in 2010 (Expert consensus for the diagnosis and treatment of echinococcosis). RECENT FINDINGS: Here we evaluate the use of the WHO Informal Working Group on Echinococcosis classification of hepatic cystic echinococcosis, the acceptance by clinicians of recommendations regarding the use of albendazole, and the implementation of the long-term follow-up of patients with hepatic cystic echinococcosis in the scientific literature since the WHO Informal Working Group on Echinococcosis recommendations were issued. SUMMARY: Of the publications included in our review, 71.2% did not indicate any classification, whereas 14% used the WHO Informal Working Group on Echinococcosis classification. Seventy-four percent reported the administration of peri-interventional albendazole, although less than half reported its modality, and 51% the length of patient follow-up. A joint effort is needed from the scientific community to encourage the acceptance and implementation of these three key issues in the clinical management of cystic echinococcosis.