Healthcare-associated infective endocarditis: source of infection and burden of previous healthcare exposure.

Objective: Prevention of healthcare-associated infective endocarditis (HAIE) is based on characterization of underlying factors. Our object was to describe the source of infection, microbiological etiology, and healthcare-related risk factors for HAIE. Design: Retrospective population-based study. Patients: Adult patients diagnosed with HAIE during 2013-2017 who resided in the study area in Southern Finland with adult population of 0.9 million. Results: Ninety-five HAIE episodes were included. Ten episodes were related to cardiac surgery. Of the remaining 85 episodes, 11 were classified as nosocomial (ie, acquired and diagnosed during ongoing hospitalization) and 74 as non-nosocomial HAIE. Staphylococcus aureus caused 45% of nosocomial episodes, but only 16% of non-nosocomial episodes (P = 0.039). Most common sources of infection in non-nosocomial HAIE were previous hospitalization (24%), dialysis (18%), and urologic procedures (15%). Enterococcus spp. caused 23% of non-nosocomial HAIE, and more than half of them were associated with urologic or gastrointestinal procedures. Two-thirds of the non-nosocomial HAIE patients had recent hospitalization or invasive procedure. We counted previous healthcare-related risk factors for IE and those who had two or more of them had higher in-hospital and one-year mortality. Conclusion: Our study indicates the importance of non-nosocomial acquisition of HAIE and S. aureus as the major pathogen in nosocomial episodes. Enterococcal infections dominate in non-nosocomial cases and further studies are needed to identify patients at risk for enterococcal IE after urological or gastrointestinal procedure.

The impact of emotional support on healthcare workers and students coping with COVID-19, and other SARS-CoV pandemics - a mixed-methods systematic review.

BACKGROUND: Pandemics such as COVID-19 pose threats to the physical safety of healthcare workers and students. They can have traumatic experiences affecting their personal and professional life. Increasing rates of burnout, substance abuse, depression, and suicide among healthcare workers have already been identified, thus making mental health and psychological wellbeing of the healthcare workers a major issue. The aim of this systematic review is to synthesize the characteristics of emotional support programs and interventions targeted to healthcare workers and students since the onset of COVID-19 and other SARS-CoV pandemics and to describe the effectiveness and experiences of these programs. METHOD: This was a mixed method systematic review. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed, and the review was registered on PROSPERO [CRD42021262837]. Searches were conducted using Medline, CINAHL, PsycINFO, Cochrane Library, and Scopus databases. The COVIDENCE systematic review management system was used for data selection and extraction by two independent reviewers. The JBI (Joanna Briggs Institute) critical appraisal tools were used to assess the quality of selected studies by two additional reviewers. Finally, data extraction and narrative analysis were conducted. RESULTS: The search retrieved 3161 results including 1061 duplicates. After screening, a total of 19 articles were included in this review. Participants in studies were nurses, physicians, other hospital staff, and undergraduate medical students mostly working on the front-line with COVID-19 patients. Publications included RCTs (n = 4), quasi-experimental studies (n = 2), cross-sectional studies (n = 6), qualitative interview studies (n = 3), and systematic reviews (n = 4). Most (63.4%) of the interventions used online or digital solutions. Interventions mostly showed good effectiveness (support-seeking, positive emotions, reduction of distress symptoms etc.) and acceptance and were experienced as helpful, but there were some conflicting results. CONCLUSION: Healthcare organizations have developed support strategies focusing on providing emotional support for these healthcare workers and students, but it is difficult to conclude whether one program offers distinct benefit compared to the others. More research is needed to evaluate the comparative effectiveness of emotional support interventions for health workers.

Genomic epidemiology of nosocomial carbapenemase-producing Citrobacter freundii in sewerage systems in the Helsinki metropolitan area, Finland.

Multi-drug resistance is emerging in Citrobacter freundii, which is the third most common carbapenemase-producing (CP) Enterobacteriaceae in humans in Finland due to recent outbreaks. The objective of this study was to determine if wastewater surveillance (WWS) could detect CP C. freundii strains causing infections in humans. Selective culturing was used to isolate CP C. freundii from the hospital environment, hospital wastewater, and untreated municipal wastewater in Helsinki, Finland, between 2019 and 2022. Species were identified using MALDI-TOF, and presumptive CP C. freundii isolates were subjected to antimicrobial susceptibility testing and further characterized by whole genome sequencing. A genomic comparison was conducted to compare isolates collected from the hospital environment, untreated municipal wastewater, and a selection of isolates from human specimens from two hospitals in the same city. We also examined the persistence of CP C. freundii in the hospital environment and the impact of our attempts to eradicate it. Overall, 27 blaKPC - 2-carrying C. freundii were detected in the hospital environment (ST18; n = 23 and ST8; n = 4), while 13 blaKPC - 2-carrying C. freundii (ST8) and five blaVIM - 1-carrying (ST421) C. freundii were identified in untreated municipal wastewater. CP C. freundii was not identified in hospital wastewater. We found three clusters (cluster distance threshold ≤ 10 allelic difference) after comparing the recovered isolates and a selection of isolates from human specimens. The first cluster consisted of ST18 isolates from the hospital environment (n = 23) and human specimens (n = 4), the second consisted of ST8 isolates from the hospital environment (n = 4), untreated municipal wastewater (n = 6), and human specimens (n = 2), and the third consisted of ST421 isolates from the untreated municipal wastewater (n = 5). Our results support previous studies suggesting that the hospital environment could act as a source of transmission of CP C. freundii in clinical settings. Furthermore, the eradication of CP Enterobacteriaceae from the hospital environment is challenging. Our findings also showed that CP C. freundii is persistent throughout the sewerage system and demonstrate the potential of WWS for detecting CP C. freundii.

Immunogenicity and safety of the non-typable Haemophilus influenzae-Moraxella catarrhalis (NTHi-Mcat) vaccine administered following the recombinant zoster vaccine versus administration alone: Results from a randomized, phase 2a, non-inferiority trial.

A candidate AS01-adjuvanted vaccine containing four surface proteins from non-typable Haemophilus influenzae and Moraxella catarrhalis (NTHi-Mcat) has been developed to help prevent exacerbations of chronic obstructive pulmonary disease (COPD). Sequential administration of different vaccines containing the same AS01-adjuvant system could lead to immune interference. We compared administration of NTHi-Mcat following AS01-adjuvanted recombinant zoster vaccine (RZV) versus NTHi-Mcat alone. This phase 2a, open-label trial (NCT03894969) randomized healthy current or former smokers (50-80 years) without COPD to administration of NTHi-Mcat at 1, 3 or 6 months after RZV or to NTHi-Mcat alone (2-dose for both vaccines). Primary outcome was non-inferiority of the humoral immune response to NTHi-Mcat administered 1 month after RZV versus NTHi-Mcat alone, evaluated by specific antibody geometric mean concentration (GMC) ratio with 95% confidence intervals (CIs). The per-protocol set included 411 participants. Primary objective was met; lower limit of the 95%CI for the GMC ratio above 0.667 for all four vaccine antigens, 1 month after the second NTHi-Mcat dose. NTHi-Mcat induced similar immune response regardless of whether administered alone or 1, 3 or 6 months following RZV. Safety and reactogenicity profiles were acceptable; adverse event frequency was similar among study groups. Injection site pain was the most common symptom. No new safety concerns were identified. The study demonstrated non-inferiority of the immune response elicited by NTHi-Mcat administered sequentially to RZV versus NTHi-Mcat alone, indicating no immune interference. Starting from 1 month, no specific interval is required between RZV and NTHi-Mcat containing the same AS01-adjuvant system components in different quantities.

Mental well-being of healthcare workers in 2 hospital districts during the first wave of the COVID-19 pandemic in Finland: a cross-sectional study.

OBJECTIVES: The COVID-19 pandemic has caused unseen pressure on healthcare systems in many countries, jeopardizing the mental well-being of healthcare workers. The authors aimed to assess the mental well-being of Finnish healthcare workers from 2 hospital districts (Helsinki University Hospital [HUS] and Social and Health Services in Kymenlaakso [Kymsote]) with differing COVID-19 incidence rates during the first wave of the COVID-19 pandemic in spring 2020. MATERIAL AND METHODS: A total number of 996 healthcare workers (HUS N = 862, Kymsote N = 134) participated in this prospectively conducted survey study during summer 2020. Symptom criteria of self-reported mental health symptoms followed ICD-10 classification, excluding duration criteria. Participants were divided into symptom categories "often/sometimes", and "rarely/never". These groups were compared to sociodemographic factors and factors related to work, workload, and well-being. RESULTS: The degree of mental health symptoms did not differ between the 2 healthcare districts despite differing COVID-19 incidences (p = 1). The authors observed a significant relationship between self-reported diagnostic mental health symptoms and experiences of insufficient instructions for protection against COVID-19 (in HUS cohort p < 0.001), insufficient recovery from work (p < 0.001), and subjective increased workload (p < 0.001). CONCLUSIONS: The authors' results show the importance of well-planned and sufficient instructions for protection from SARS-CoV-2 for healthcare workers, indicating their need to feel safe and protected at work. The workload of healthcare workers should be carefully monitored to keep it moderate and ensure sufficient recovery. Sufficient control of the epidemic to keep the burden of the healthcare system low is vital for healthcare workers' well-being. Int J Occup Med Environ Health. 2022;35(6):708-18.

SARS-CoV-2 indoor environment contamination with epidemiological and experimental investigations.

SARS-CoV-2 has been detected both in air and on surfaces, but questions remain about the patient-specific and environmental factors affecting virus transmission. Additionally, more detailed information on viral sampling of the air is needed. This prospective cohort study (N = 56) presents results from 258 air and 252 surface samples from the surroundings of 23 hospitalized and eight home-treated COVID-19 index patients between July 2020 and March 2021 and compares the results between the measured environments and patient factors. Additionally, epidemiological and experimental investigations were performed. The proportions of qRT-PCR-positive air (10.7% hospital/17.6% homes) and surface samples (8.8%/12.9%) showed statistical similarity in hospital and homes. Significant SARS-CoV-2 air contamination was observed in a large (655.25 m3 ) mechanically ventilated (1.67 air changes per hour, 32.4-421 L/s/patient) patient hall even with only two patients present. All positive air samples were obtained in the absence of aerosol-generating procedures. In four cases, positive environmental samples were detected after the patients had developed a neutralizing IgG response. SARS-CoV-2 RNA was detected in the following particle sizes: 0.65-4.7 µm, 7.0-12.0 µm, >10 µm, and <100 µm. Appropriate infection control against airborne and surface transmission routes is needed in both environments, even after antibody production has begun.

A machine learning approach to predict resilience and sickness absence in the healthcare workforce during the COVID-19 pandemic.

During the COVID-19 pandemic, healthcare workers (HCWs) have faced unprecedented workloads and personal health risks leading to mental disorders and surges in sickness absence. Previous work has shown that interindividual differences in psychological resilience might explain why only some individuals are vulnerable to these consequences. However, no prognostic tools to predict individual HCW resilience during the pandemic have been developed. We deployed machine learning (ML) to predict psychological resilience during the pandemic. The models were trained in HCWs of the largest Finnish hospital, Helsinki University Hospital (HUS, N = 487), with a six-month follow-up, and prognostic generalizability was evaluated in two independent HCW validation samples (Social and Health Services in Kymenlaakso: Kymsote, N = 77 and the City of Helsinki, N = 322) with similar follow-ups never used for training the models. Using the most predictive items to predict future psychological resilience resulted in a balanced accuracy (BAC) of 72.7-74.3% in the HUS sample. Similar performances (BAC = 67-77%) were observed in the two independent validation samples. The models' predictions translated to a high probability of sickness absence during the pandemic. Our results provide the first evidence that ML techniques could be harnessed for the early detection of COVID-19-related distress among HCWs, thereby providing an avenue for potential targeted interventions.

Successful treatment with a short course of remdesivir in a case of prolonged COVID-19 in a lymphoma patient.

BACKGROUND: Patients with haematological malignancies have an increased susceptibility for COVID-19 and higher mortality. They may also have prolonged symptoms and viral shedding. Clinical trials have not specifically addressed the management of this patient group. We present a lymphoma patient with COVID-19 who was treated with remdesivir, and a literature review of similar cases. METHODS: SARS-CoV-2 RT-PCR, virus culture and whole-genome sequencing were performed from nasopharyngeal swabs and antibody testing from serum. In addition, SARS-CoV-2 nucleocapsid antigen was tested from serum. Medline was searched for reported cases of lymphoma and COVID-19 treated with remdesivir. RESULTS: The patient was undergoing lymphoma treatment including chemotherapy, rituximab and prednisolone. After diagnosis of COVID-19, broad-spectrum antibiotics were administered due to neutropenia and fever. After 20 d of fever with no signs of co-infection, remdesivir was initiated with rapid response. The treatment was continued for 4 d. Serum SARS-CoV-2 antibody tests were negative 20, 30 and 66 d from symptom onset. Before starting remdesivir, the SARS-CoV-2 PCR and virus culture from the nasopharynx and serum antigen test were positive. From earlier reports, we identified a total of eleven cases of lymphoma and COVID-19 treated with remdesivir accompanied by other antivirals and anti-inflammatory agents. CONCLUSIONS: As shown in this and earlier reports on lymphoma patients, the clinical course of COVID-19 may be protracted and a humoral immune response may remain absent. In addition, optimal management remains undecided. The presented patient responded well to a short course of remdesivir.

Microdebrider is less aerosol-generating than CO2 laser and cold instruments in microlaryngoscopy.

OBJECTIVE: COVID-19 spreads through aerosols produced in coughing, talking, exhalation, and also in some surgical procedures. Use of CO2 laser in laryngeal surgery has been observed to generate aerosols, however, other techniques, such cold dissection and microdebrider, have not been sufficiently investigated. We aimed to assess whether aerosol generation occurs during laryngeal operations and the effect of different instruments on aerosol production. METHODS: We measured particle concentration generated during surgeries with an Optical Particle Sizer. Cough data collected from volunteers and aerosol concentration of an empty operating room served as references. Aerosol concentrations when using different techniques and equipment were compared with references as well as with each other. RESULTS: Thirteen laryngological surgeries were evaluated. The highest total aerosol concentrations were observed when using CO2 laser and these were significantly higher than the concentrations when using microdebrider or cold dissection (p < 0.0001, p < 0.0001) or in the background or during coughing (p < 0.0001, p < 0.0001). In contrast, neither microdebrider nor cold dissection produced significant concentrations of aerosol compared with coughing (p = 0.146, p = 0.753). In comparing all three techniques, microdebrider produced the least aerosol particles. CONCLUSIONS: Microdebrider and cold dissection can be regarded as aerosol-generating relative to background reference concentrations, but they should not be considered as high-risk aerosol-generating procedures, as the concentrations are low and do not exceed those of coughing. A step-down algorithm from CO2 laser to cold instruments and microdebrider is recommended to lower the risk of airborne infections among medical staff.

Aerosol generation during general anesthesia is comparable to coughing: An observational clinical study.

BACKGROUND: Intubation, laryngoscopy, and extubation are considered highly aerosol-generating procedures, and additional safety protocols are used during COVID-19 pandemic in these procedures. However, previous studies are mainly experimental and have neither analyzed staff exposure to aerosol generation in the real-life operating room environment nor compared the exposure to aerosol concentrations generated during normal patient care. To assess operational staff exposure to potentially infectious particle generation during general anesthesia, we measured particle concentration and size distribution with patients undergoing surgery with Optical Particle Sizer. METHODS: A single-center observative multidisciplinary clinical study in Helsinki University Hospital with 39 adult patients who underwent general anesthesia with tracheal intubation. Mean particle concentrations during different anesthesia procedures were statistically compared with cough control data collected from 37 volunteers to assess the differences in particle generation. RESULTS: This study measured 25 preoxygenations, 30 mask ventilations, 28 intubations, and 24 extubations. The highest total aerosol concentration of 1153 particles (p)/cm³ was observed during mask ventilation. Preoxygenations, mask ventilations, and extubations as well as uncomplicated intubations generated mean aerosol concentrations statistically comparable to coughing. It is noteworthy that difficult intubation generated significantly fewer aerosols than either uncomplicated intubation (p = .007) or coughing (p = 0.006). CONCLUSIONS: Anesthesia induction generates mainly small (<1 µm) aerosol particles. Based on our results, general anesthesia procedures are not highly aerosol-generating compared with coughing. Thus, their definition as high-risk aerosol-generating procedures should be re-evaluated due to comparable exposures during normal patient care. IMPLICATION STATEMENT: The list of aerosol-generating procedures guides the use of protective equipments in hospitals. Intubation is listed as a high-risk aerosol-generating procedure, however, aerosol generation has not been measured thoroughly. We measured aerosol generation during general anesthesia. None of the general anesthesia procedures generated statistically more aerosols than coughing and thus should not be considered as higher risk compared to normal respiratory activities.

JC polyomavirus DNA detection in clinical practice.

BACKGROUND: There are limited data about the use and clinical value of JC polyomavirus (JCPyV) DNA detection in various clinical indications. METHODS: We reviewed the clinical records of 410 patients from whom cerebrospinal fluid (CSF), plasma, urine, or tissue samples had been collected for JCPyV DNA polymerase chain reaction (PCR) between 2012 and 2018. RESULTS: JCPyV DNA was analyzed in 224 plasma, 190 CSF-, 32 urine and 10 tissue samples. 240 patients had a history of hematopoietic stem cell or solid organ transplantation, 159 had nephrological disease, 90 had hematologic malignancies, 58 had neurological disease, 37 had infectious disease and 23 had AIDS/HIV as underlying disease. Six patients had no underlying disease. The main reasons to take CSF or plasma samples were neurological symptoms of unknown etiology. Most urine samples were taken to monitor kidney transplantation patients. JCPyV DNA PCR contributed to the diagnosis of progressive multifocal leukoencephalopathy in eight patients (2.0%), of which seven had hematologic malignancy as an underlying disease. CONCLUSIONS: JCPyV PCR is most informative among immunosuppressed patients with neurologic symptoms. CSF and brain biopsy are useful when there is clinical suspicion of PML, whereas plasma samples are not useful. The value of plasma samples is a matter of dispute in the screening of JCPyV-associated nephropathy, as BK polyomavirus is the causative agent in most polyomavirus-associated nephropathy cases. JCPyV detection is valuable in case the patient has past, current or planned treatment with immunosuppressive drugs.

Adjuvanted recombinant zoster vaccine in adult autologous stem cell transplant recipients: polyfunctional immune responses and lessons for clinical practice.

Immunocompromised individuals, particularly autologous hematopoietic stem cell transplant (auHSCT) recipients, are at high risk for herpes zoster (HZ). We provide an in-depth description of humoral and cell-mediated immune (CMI) responses by age (protocol-defined) or underlying disease (post-hoc) as well as efficacy by underlying disease (post-hoc) of the adjuvanted recombinant zoster vaccine (RZV) in a randomized observer-blind phase III trial (ZOE-HSCT, NCT01610414). 1846 adult auHSCT recipients were randomized to receive a first dose of either RZV or placebo 50-70 days post-auHSCT, followed by the second dose at 1-2 months (M) later. In cohorts of 114-1721 participants, at 1 M post-second vaccine dose: Anti-gE antibody geometric mean concentrations (GMCs) and median gE-specific CD4[2+] T-cell frequencies (CD4 T cells expressing ≥2 of four assessed activation markers) were similar between 18-49 and ≥50-year-olds. Despite lower anti-gE antibody GMCs in non-Hodgkin B-cell lymphoma (NHBCL) patients, CD4[2+] T-cell frequencies were similar between NHBCL and other underlying diseases. The proportion of polyfunctional CD4 T cells increased over time, accounting for 79.6% of gE-specific CD4 T cells at 24 M post-dose two. Vaccine efficacy against HZ ranged between 42.5% and 82.5% across underlying diseases and was statistically significant in NHBCL and multiple myeloma patients. In conclusion, two RZV doses administered early post-auHSCT induced robust, persistent, and polyfunctional gE-specific immune responses. Efficacy against HZ was also high in NHBCL patients despite the lower humoral response.

PLAIN LANGUAGE SUMMARYWhat is the context?After haematopoietic stem cell transplantation, patients have impaired immunity from conditioning chemotherapy regimens, often exacerbated by underlying diseases, putting them at high risk of developing herpes zoster. In this population, antiviral prophylaxis is the current standard of care to reduce herpes zoster risk. Vaccination provides an additional means to prevent herpes zoster. Live-attenuated vaccines are generally contraindicated in immunocompromised patients. A non-live, adjuvanted recombinant zoster vaccine (RZV, Shingrix, GSK), has been approved for use in adults ≥50 years of age in the European Union, United States, Canada, Australia, Japan, and China. This vaccine is highly efficacious at preventing herpes zoster in adults over 50 years of age, as demonstrated in large, placebo-controlled randomised trials. Importantly, Shingrix use is not contraindicated in immunocompromised conditions, and was found to be highly efficacious in adults who had recently undergone autologous haematopoietic stem cell transplant.What is new?In autologous haematopoietic stem cell transplant recipients in whom Shingrix has demonstrated efficacy, two doses elicited high and persistent immune responses. Date presented here further support our understanding of the impact of specific factors such as age or underlying diseases on the vaccine's effect in the population studied, as well as the characteristics of the elicited cell-mediated immune responses.What is the impact?These results indicate that Shingrix, given shortly after haematopoietic stem cell transplant, can induce robust immune responses and reduce the risk of herpes zoster, even in individuals with immunosuppression due to underlying disease and/or use of immunosuppressive therapies, regardless of age or underlying disease.

Three clusters of carbapenemase-producing Citrobacter freundii in Finland, 2016-20.

OBJECTIVES: Carbapenemase-producing Enterobacterales (CPE) have spread widely into health care facilities (HCF) but clusters caused by carbapenemase-producing (CP) Citrobacter freundii have been uncommon until recent years. Here we describe CP C. freundii clusters detected in Finland during 2016-20. METHODS: As a part of the national CPE surveillance, clinical microbiology laboratories send potential CP C. freundii isolates to the reference laboratory for confirmation and further characterization. Whole genome sequencing (WGS) with Illumina MiSeq sequencer was used to detect clusters. Resistance genes and STs were analysed using SRST2 and typing with core genome (cg) MLST. A case was defined as a patient with a CP C. freundii isolate belonging to one of the detected clusters. RESULTS: We detected three CP C. freundii clusters: cluster 1 included 16 cases in five HCFs during 2016-20, cluster 2 had two cases in two HCFs during 2018-19 and cluster 3 had two cases in one HCF in 2020. The isolates (11 clinical and 5 screening) in cluster 1 had KPC-2 carbapenemase and were sequence type (ST)18. Cluster 2 (2 clinical isolates) had OXA-181/GES-5 carbapenemases and were ST604 and cluster 3 (two screening isolates) had KPC-3 carbapenemase and were ST116. None of the cases had a history of recent travel abroad. CONCLUSIONS: CP C. freundii also causes outbreaks and can be a reservoir of carbapenemase genes. The long intervals between successive cases, mostly found in clinical specimens in two clusters, suggest that besides unknown carriers, environmental contamination may play a role in transmission.

Sources of healthcare workers' COVID­19 infections and related safety guidelines.

OBJECTIVES: To evaluate the effectiveness of safety guidelines in the workplace, the authors analyzed the work-related exposure to SARS-CoV-2 and the source of COVID­19 infections among healthcare workers (HCWs), together with the use of personal protective equipment (PPE). MATERIAL AND METHODS: A cross-sectional prospective study was conducted in tertiary hospitals in the Uusimaa region, Finland, with 1072 volunteers being enrolled in the study from among the HCWs at the Helsinki University Hospital. Overall, 866 (80.8%) HCWs (including 588 nurses, 170 doctors, and 108 laboratory and medical imaging nurses) completed the questionnaire by July 15, 2020, with 52% of the participants taking care of COVID­19 patients. The participants answered a structured questionnaire regarding their use of PPE, the ability to follow safety guidelines, exposure to COVID­19, and the source of potential COVID­19 infections. The participants with COVID­19 symptoms were tested with the SARS-CoV-2 realtime polymerase chain reaction method. All infected participants were contacted, and their answers were confirmed regarding COVID­19 exposure. RESULTS: In total, 41 (4.7%) participants tested positive for SARS-CoV-2, with 22 (53.6%) of infections being confirmed or likely occupational, and 12 (29.3%) originating from colleagues. In 14 cases (63.6%), occupational infections occurred while using a surgical mask, and all infections originating from patients occurred while using a surgical mask or no mask at all. No occupational infections were found while using an FFP2/3 respirator and following aerosol precautions. The combined odds ratio for working at an intensive care unit, an emergency department, or a ward was 3.4 (95% CI: 1.2-9.2, p = 0.016). CONCLUSIONS: A high infection rate was found among HCWs despite safety guidelines. Based on these findings, the authors recommend the use of FFP2/3 respirators in all patient contacts with confirmed or suspected COVID­19, along with the use of universal masking, also in personnel rooms. Int J Occup Med Environ Health. 2021;34(2):239-49.

Gemtuzumab-Ozogamicin-Related Impaired Hemoglobin-Haptoglobin Scavenging as On-Target/Off-Tumor Toxicity of Anti-CD33 AML Therapy: A Report of Two Cases.

Gemtuzumab-ozogamicin (GO) is a humanized anti-CD33 antibody, which is conjugated to a cytotoxic calicheamicin. It is used to treat acute myeloid leukemia (AML) in combination with chemotherapy. We describe here two GO-treated acute myeloid leukemia (AML) cases: both patients suffered from a toxic syndrome, which manifested as impaired hemoglobin-haptoglobin scavenging and accumulation of hemolysis-related products. Our observations and earlier reports indicated that the reaction was caused by GO-targeted destruction of CD33 + CD163+ monocytes/macrophages, which are responsible for the clearance of hemoglobin-haptoglobin complexes. The rise of plasma lactate dehydrogenase was an early sign of the reaction, and both patients had high levels of free plasma hemoglobin, but plasma haptoglobin and bilirubin levels were paradoxically normal. Symptoms included septic fever and abnormalities in cardiac tests and in the case of the first patient, severe neurological symptoms which required intensive care unit admittance. Therapeutic plasma exchanges supported the patients until the recovery of normal hematopoiesis. The symptoms may be easily confounded with infectious complications-related organ damage. Regarding the increasing use of gemtuzumab-ozogamicin and other emerging CD33-targeted cell therapies, we want to highlight this mostly unknown and probably underdiagnosed toxicity.

A randomized, controlled trial comparing the immunogenicity and safety of a 23-valent pneumococcal polysaccharide vaccination to a repeated dose 13-valent pneumococcal conjugate vaccination in adult liver transplant recipients.

BACKGROUND: Solid organ transplant (SOT) patients are at significant risk for invasive pneumococcal disease. The optimal pneumococcal vaccination strategy for SOT patients is not known. METHODS: The potential adult liver transplant recipients were randomised into two arms: to receive a 23-valent pneumococcal polysaccharide vaccine (PPV23) before the transplantation or to receive a 13-valent pneumococcal conjugate vaccine (PCV13) before the transplantation and a second dose of PCV13 six months after the transplantation. Serotype-specific antibody concentrations and opsonophagocytic activity (OPA) were measured before and after the first vaccination (visits V1,V2) and six and seven months after the transplantation, e.g. before and after the second PCV13 (visits V3,V4). RESULTS: Out of 47 patients, 19 (PCV13 arm) and 17 (PPV23 arm) received a liver transplant and all these patients completed the study (36/47, 76,6%). Each vaccine schedule elicited a good immune response. At V2, the geometric mean concentrations (GMCs) of antibodies for serotypes 6A, 7F and 23F, and the geometric mean titers (GMT́s) of OPA for serotypes 4, 6A, 6B and 23F were significantly higher for PCV13, but the proportions of patients reaching OPA cut-off ≥ 8 or ELISA cut-off ≥ 1.0 µg/ml did not differ between the arms. At V3 the antibody concentrations and the OPA had declined to baseline in both arms. The second PCV13 vaccination elicited an immune response. There was no difference in adverse events. No vaccine-related allograft rejection was detected. CONCLUSIONS: The immunogenicity of PPV23 and PCV13 was comparable in this patient material, but the seroresponses waned after transplantation. The second dose of PCV13 restored the immune responses and was well tolerated.

Characteristics of late recurrent candidemia in adult patients.

BACKGROUND AND OBJECTIVES: Candida species are one of the most common causes of health care-associated bloodstream infections. However, recurrent candidemia is rare, and the characteristics of late recurrent (LR) candidemia are partly unclear. Our aim was to evaluate the characteristics of LR candidemia in adult patients. PATIENTS AND METHODS: A retrospective cohort study was performed in the hospital district of Helsinki and Uusimaa in Finland (2007-2016). All candidemia cases were searched in an electronic database during the study period. Patients with LR candidemia were compared with patients with a single candidemia episode to evaluate the characteristics of LR candidemia. LR candidemia was defined as having at least two episodes of candidemia more than 30 days apart. RESULTS: We identified 24 episodes of LR candidemia in 20 patients. Patients with LR candidemia represented 6% of all patients with candidemia during the study period, and most of these cases were nosocomial. The median time between the first and the recurrent episode was 5.1 months. One-year mortality in LR candidemia was 45%. Underlying gastrointestinal disease (OR 7.21, 95% CI 2.52-20.61) and history of intra-venous drug use (IVDU) (OR 3.62, 95% CI 1.03-12.69) were independent risk factors for LR candidemia in the multivariable analysis. CONCLUSION: Our study indicates that the gastrointestinal tract may be a continuous source of infection in patients with chronic gastrointestinal diseases. Gastrointestinal diseases and IVDU should be regarded as risk factors for LR candidemia.

Heterozygous TLR3 Mutation in Patients with Hantavirus Encephalitis.

Puumala hantavirus (PUUV) hemorrhagic fever with renal syndrome (HFRS) is common in Northern Europe; this infection is usually self-limited and severe complications are uncommon. PUUV and other hantaviruses, however, can rarely cause encephalitis. The pathogenesis of these rare and severe events is unknown. In this study, we explored the possibility that genetic defects in innate anti-viral immunity, as analogous to Toll-like receptor 3 (TLR3) mutations seen in HSV-1 encephalitis, may explain PUUV encephalitis. We completed exome sequencing of seven adult patients with encephalitis or encephalomyelitis during acute PUUV infection. We found heterozygosity for the TLR3 p.L742F novel variant in two of the seven unrelated patients (29%, p = 0.0195). TLR3-deficient P2.1 fibrosarcoma cell line and SV40-immortalized fibroblasts (SV40-fibroblasts) from patient skin expressing mutant or wild-type TLR3 were tested functionally. The TLR3 p.L742F allele displayed low poly(I:C)-stimulated cytokine induction when expressed in P2.1 cells. SV40-fibroblasts from three healthy controls produced increasing levels of IFN-λ and IL-6 after 24 h of stimulation with increasing concentrations of poly(I:C), whereas the production of the cytokines was impaired in TLR3 L742F/WT patient SV40-fibroblasts. Heterozygous TLR3 mutation may underlie not only HSV-1 encephalitis but also PUUV hantavirus encephalitis. Such possibility should be further explored in encephalitis caused by these and other hantaviruses.