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Herbaspirillum spp. is a common environmental bacterium usually found in soil, plant roots, and water. It is rarely associated with infection in immunocompromised patients, and rarely reported infections in immunocompetent patients. We report the first case of a Herbaspirillum huttiense bacteraemia in a non‐neutropenic home haemodialysis patient. A 57‐year‐old male presented to our hospital with a 3‐day history of malaise, fevers, rigours, and anorexia following dialysis through his central line. On examination, he was pyrexic (temperature 38.7°C) with splinter haemorrhages noted, but no other signs of infection were present. Blood cultures revealed a polymicrobial infection, with Serratia liquefaciens and Corynebacterium jeikeium isolated from the central line and Herbaspirillum sp. was isolated from both the central line and a peripheral culture. A later peripheral blood culture following central line removal isolated Herbaspirillum huttiense. Regular biological testing of his home water supply and dialysate detected no colony forming units of non‐fermenting gram‐negative bacilli. He was initially treated with ceftriaxone and vancomycin initially, followed by ertapenem and vancomycin. Intravenous antibiotics were ceased following 5 days after central line removal and he made an uneventful recovery. [ABSTRACT FROM AUTHOR]

Background: SARS-CoV-2 is responsible for the ongoing global pandemic, and the continuous emergence of novel variants threatens fragile populations, such as immunocompromised patients. This subgroup of patients seems to be seriously affected by intrahost viral changes, as the pathogens, which are keen to cause replication inefficiency, affect the impaired immune system, preventing efficient clearance of the virus. Therefore, these patients may represent an optimal reservoir for the development of new circulating SARS-CoV-2 variants. The following study aimed to investigate genomic changes in SARS-CoV-2-positive immunocompromised patients over time. Methods: SARS-CoV-2-positive nasopharyngeal swabs were collected at different time points for each patient (patient A and patient B), extracted and then analyzed through next-generation sequencing (NGS). The resulting sequences were examined to determine mutation frequencies, describing viral evolution over time. Case presentation: Patient A was a 53-year-old patient with onco-hematological disease with prolonged infection lasting for 51 days from May 28th to July 18th, 2022. Three confirmed SARS-CoV-2-positive samples were collected on May 28th, June 15th and July 4th. Patient B was 75 years old and had onco-hematological disease with prolonged infection lasting for 146 days. Two confirmed positive SARS-CoV-2 samples were collected at the following time points: May 21st and August 18th. Conclusion: Heat map construction provided evidence of gain and/or loss of mutations over time for both patients, suggesting within-host genomic evolution of the virus. In addition, mutation polymorphisms and changes in the SARS-CoV-2 lineage were observed in Patient B. Sequence analysis revealed high mutational pattern variability, reflecting the high complexity of viral replication dynamics in fragile patients. [ABSTRACT FROM AUTHOR]

AbstractPseudomonas aeruginosa (PA), an opportunistic human pathogen that is frequently linked with chronic infections in immunocompromised individuals, is also metabolically versatile, and thrives in diverse environments. Additionally, studies report that PA can interact with other microorganisms, such as bacteria, and fungi, producing unique metabolites that can modulate the host immune response, and contribute to disease pathogenesis. This review summarizes the current knowledge related to the metabolic interactions of PA with other microorganisms (Staphylococcus, Acinetobacter, Klebsiella, Enterococcus, and Candida) and human hosts, and the importance of these interactions in a polymicrobial context. Further, we highlight the potential applications of studying these metabolic interactions toward designing better diagnostic tools, and therapeutic strategies to prevent, and treat infections caused by this pathogen. [ABSTRACT FROM AUTHOR]

Objective: To assess the screening efficiency of an multi-cancer early detection (MCED) test added to standard of care (SoC) screening, compared to SoC screening alone, among immunocompromised individuals, and to estimate the diagnostic workup costs associated with positive screening results. Methods: We estimated the potential impact of cancer screening among immunocompromised individuals aged 50–79 years within the University of Utah Health system who underwent a stem cell/solid organ transplant or were diagnosed with a primary or secondary immunodeficiency disorder between January 2000 and February 2018. We derived cancer incidence rates from the Huntsman Cancer Institute Tumor Registry, and screening performance of SoC screening and an MCED test from published literature. Outcomes of screening efficiency included the true-positive to false-positive (TP:FP) ratio, diagnostic yield (DY), and cancer detection rate (CDR) for SoC screening alone and an incremental MCED test. Scenario and probabilistic sensitivity analyses were conducted. Results: Among 4932 immunocompromised individuals aged 50–79 years, we estimated that 2595 tests would be done under SoC screening and assumed that all individuals received an additional MCED test. Adding an MCED test to SoC screening substantially improved screening efficiency (TP:FP = 1:1, DY = 5.15/1000 tests, CDR = 42.0%), compared to SoC screening alone (TP:FP = 1:99, DY = 1.23/1000 tests, CDR = 5.3%), assuming an MCED test with 100% uptake. Our findings were also robust to parameter uncertainty. Conclusion: Adding an MCED test to complement existing screening may be a highly efficient strategy to increase the detection of cancers among immunocompromised individuals. These results could help to improve cancer prevention and detection efforts among individuals with multiple cancer risk factors. [ABSTRACT FROM AUTHOR]

A 67-year-old woman with anti-neutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis was not vaccinated against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and was on multiple immunosuppressive drugs. She was hospitalized because of interstitial shadowing in the lungs and diagnosed with persistent coronavirus disease 2019 (COVID-19). Despite treatment with a recombinant monoclonal antibody and antivirals, her symptoms persisted and she lacked a specific antibody response. She tested negative for SARS-CoV-2 antigen after the second antiviral treatment, and a subsequent chest radiograph showed improvement. However, the antibody levels did not change. This case highlights the importance of careful monitoring of the SARS-CoV-2 antigen and antibody levels during COVID-19 treatment in patients with immunosuppression. [ABSTRACT FROM AUTHOR]

Pneumocystis jirovecii pneumonia is an opportunistic infection that affects HIV-infected and immunocompromised persons and rarely affects immunocompetent patients. However, after the advent of the COVID-19 pandemic, some COVID-19 patients without immunocompromise or HIV were infected with P. jirovecii. Clinical manifestations were atypical, easily misdiagnosed, and rapidly progressive, and the prognosis was poor. [ABSTRACT FROM AUTHOR]

Introduction: Immunocompromised host pneumonia (ICHP) is an important cause of morbidity and mortality, yet usual care (UC) diagnostic tests often fail to identify an infectious etiology. A US-based, multicenter study (PICKUP) among ICHP patients with hematological malignancies, including hematological cell transplant recipients, showed that plasma microbial cell-free DNA (mcfDNA) sequencing provided significant additive diagnostic value. Aim: The objective of this study was to perform a cost-effectiveness analysis (CEA) of adding mcfDNA sequencing to UC diagnostic testing for hospitalized ICHP patients. Methods: A semi-Markov model was utilized from the US third-party payer's perspective such that only direct costs were included, using a lifetime time horizon with discount rates of 3% for costs and benefits. Three comparators were considered: (1) All UC, which included non-invasive (NI) and invasive testing and early bronchoscopy; (2) All UC & mcfDNA; and (3) NI UC & mcfDNA & conditional UC Bronch (later bronchoscopy if the initial tests are negative). The model considered whether a probable causative infectious etiology was identified and if the patient received appropriate antimicrobial treatment through expert adjudication, and if the patient died in-hospital. The primary endpoints were total costs, life-years (LYs), equal value life-years (evLYs), quality-adjusted life-years (QALYs), and the incremental cost-effectiveness ratio per QALY. Extensive scenario and probabilistic sensitivity analyses (PSA) were conducted. Results: At a price of $2000 (2023 USD) for the plasma mcfDNA, All UC & mcfDNA was more costly ($165,247 vs $153,642) but more effective (13.39 vs 12.47 LYs gained; 10.20 vs 9.42 evLYs gained; 10.11 vs 9.42 QALYs gained) compared to All UC alone, giving a cost/QALY of $16,761. NI UC & mcfDNA & conditional UC Bronch was also more costly ($162,655 vs $153,642) and more effective (13.19 vs 12.47 LYs gained; 9.96 vs 9.42 evLYs gained; 9.96 vs 9.42 QALYs gained) compared to All UC alone, with a cost/QALY of $16,729. The PSA showed that above a willingness-to-pay threshold of $50,000/QALY, All UC & mcfDNA was the preferred scenario on cost-effectiveness grounds (as it provides the most QALYs gained). Further scenario analyses found that All UC & mcfDNA always improved patient outcomes but was not cost saving, even when the price of mcfDNA was set to $0. Conclusions: Based on the evidence available at the time of this analysis, this CEA suggests that mcfDNA may be cost-effective when added to All UC, as well as in a scenario using conditional bronchoscopy when NI testing fails to identify a probable infectious etiology for ICHP. Adding mcfDNA testing to UC diagnostic testing should allow more patients to receive appropriate therapy earlier and improve patient outcomes. [ABSTRACT FROM AUTHOR]

Any surgeon providing care to patients with congenital, oncologic, infectious, or traumatic processes impacting the head and neck should have an intimate knowledge of the local anatomy. The complex fascial system in this region results in a series of loosely and tightly bound spaces that can both harbor and/or facilitate the rapid spread of infections through these fascial planes and potential spaces. Deep neck space infections may occur spontaneously from cutaneous, lymphatic, odontogenic, otologic, salivary gland, sinus, and hematogenous sources or develop as the result of surgical/iatrogenic manipulation. These infections are typically polymicrobial, involving a mixture of Gram-positive cocci, Gram-negative rods, and beta-lactam-resistant anaerobes commonly found in the oropharyngeal flora. Other populations, such as immunocompromised or hospitalized patients, are particularly vulnerable to infection by certain opportunistic and antibiotic-resistant pathogens. Understanding the deep neck anatomy is crucial for predicting the spread of infection and guiding treatment strategies. The superficial and deep cervical fascial planes form a series of compartments and spaces including the retropharyngeal, danger, prevertebral, carotid, parapharyngeal, submandibular, sublingual, parotid, masticator, temporal, and infrahyoid spaces. Despite their rarity in the post-antibiotic era, deep neck space infections pose a significant threat as they progress rapidly and can quickly lead to life-threatening complications. Delayed clinical presentation is common due to the compartmentalization by fascial planes, therefore early recognition requires a high index of suspicion, thorough clinical examination, and diagnostic imaging studies, typically contrast-enhanced computed tomography (CECT). Treatment requires a multidisciplinary approach, including advanced airway management, administration of empirical broad-spectrum antibiotics, and surgical drainage when indicated. This review provides a comprehensive overview of deep neck space anatomy and its defining fascial planes, as well as discussions on epidemiology, specific microbiology, clinical presentation, diagnosis, antibiotic selection, and surgical treatment options. [ABSTRACT FROM AUTHOR]

Pneumocystis jirovecii is a prevalent opportunistic fungal pathogen that can lead to life-threatening Pneumocystis pneumonia in immunocompromised individuals. Given that timely and accurate diagnosis is essential for initiating prompt treatment and enhancing patient outcomes, it is vital to develop a rapid, simple, and sensitive method for P. jirovecii detection. Herein, we exploited a novel detection method for P. jirovecii by combining recombinase polymerase amplification (RPA) of nucleic acids isothermal amplification and the trans cleavage activity of Cas12a. The factors influencing the efficiency of RPA and Cas12a-mediated trans cleavage reaction, such as RPA primer, crRNA, the ratio of crRNA to Cas12a and ssDNA reporter concentration, were optimized. Our RPA-Cas12a-based fluorescent assay can be completed within 30–40 min, comprising a 25–30 min RPA reaction and a 5–10 min trans cleavage reaction. It can achieve a lower detection threshold of 0.5 copies/µL of target DNA with high specificity. Moreover, our RPA-Cas12a-based fluorescent method was examined using 30 artificial samples and demonstrated high accuracy with a diagnostic accuracy of 93.33%. In conclusion, a novel, rapid, sensitive, and cost-effective RPA-Cas12a-based detection method was developed and demonstrates significant potential for on-site detection of P. jirovecii in resource-limited settings. [ABSTRACT FROM AUTHOR]

Cryptococcal infection of central nervous system commonly involves meningitis or meningoencephalitis, but rarely mimics inflammatory myelitis. We present short segment myelitis as a dominant manifestation caused by Cryptococcus neoformans in a patient with nephrotic syndrome under immunosuppressive therapy. This case report highlights Cryptococcus neoformans as a potential etiological factor for short segment myelitis in immunocompromised hosts. [ABSTRACT FROM AUTHOR]

Background: Listeria monocytogenes brain abscess is a rare phenomenon that is common in immunocompromised patients. Streptococcus equinus brain abscess has never been reported in the literature to our knowledge. In this case report, we describe a case of brain abscess secondary to Listeria monocytogenes and Streptococcus equinus in an immunocompetent patient with transient low CD4 count. Case presentation: A 27-year-old white, male patient, previously healthy, nonalcoholic, and occasional smoker, presented to the emergency department for confusion and headache. The patient was found to have a left parietal abscess, which was drained and the fluid was sent for culture. Culture grew Listeria monocytogenes and Streptococcus equinus. The patient was treated with intravenous ampicillin followed by oral amoxicillin for a total of 6 weeks. The CD4 count was low initially. However, after the resolution of the infection, the CD4 count came back within normal range. Another brain magnetic resonance imaging was done that showed a significantly decreased hyperintensity within the left parietal subcortical white matter at the site of surgery with significantly decreased enhancement and almost total resolution of the previous abscess. Conclusion: Transient low CD4 count is a rare phenomenon that exposes patients to unusual and atypical infections. Since low CD4 count is transient, patients treated promptly recover from their illness. Our patient developed a Listeria monocytogenes and Streptococcus equinus brain abscess, which is considered rare and has not been previously described in the literature to our knowledge. [ABSTRACT FROM AUTHOR]

Microsporidia are intracellular eukaryotic pathogens that pose a substantial threat to immunocompromised hosts. The way these pathogens manipulate host cells during infection remains poorly understood. Using a proximity biotinylation strategy we established that microsporidian EnP1 is a nucleus-targeted effector that modifies the host cell environment. EnP1's translocation to the host nucleus is meditated by nuclear localization signals (NLSs). In the nucleus, EnP1 interacts with host histone H2B. This interaction disrupts H2B monoubiquitination (H2Bub), subsequently impacting p53 expression. Crucially, this inhibition of p53 weakens its control over the downstream target gene SLC7A11, enhancing the host cell's resilience against ferroptosis during microsporidian infection. This favorable condition promotes the proliferation of microsporidia within the host cell. These findings shed light on the molecular mechanisms by which microsporidia modify their host cells to facilitate their survival. [ABSTRACT FROM AUTHOR]

Reports on cases of strongyloidiasis and tuberculosis or aspergillosis coinfection are fragmented in the literature and no large-scale reviews are describing its occurrence across the globe. We identified a total of 230 cases of strongyloidiasis and tuberculosis coinfection amongst 2376 participants with tuberculosis disease from eight epidemiological surveys conducted in Ethiopia (n = 4, 50%); Tanzania (n = 3, 37.5%) and Malaysia (n = 1, 12.5%). Clinical outcomes in these studies were not stated as they were largely descriptive. In addition, there were ten individual case reports of strongyloidiasis and tuberculosis coinfection. Of the ten, four were from the USA (40%), two each from India (20%) and Japan (20%), and one each from the UK (10%) and Argentina (10%). Of the ten, six had favourable outcomes, two were fatal and outcomes were unclear in the remainder. Ten cases of strongyloidiasis and aspergillosis coinfection were identified, five were reported from the USA (50%), and one each from the Netherlands (10%), China (10%), Iran (10%), Colombia (10%) and Italy (10%). Five each had favourable and fatal outcomes. Fatal outcomes in strongyloidiasis and tuberculosis or aspergillosis coinfection were associated with steroid therapy (n = 3), decline for treatment (n = 1), delayed diagnosis (n = 2) and delayed presentation (n = 1). Our findings suggest a significant proportion of individuals living with tuberculosis are also affected with strongyloidiasis, especially in sub-Saharan Africa. However, more studies are required to ascertain the burden of strongyloidiasis and tuberculosis coinfection as few cases were reported from other highly burdened tuberculosis regions. In addition, the role of the attending clinician is critical to reduce morbidities from the coexistence of these clinical entities as a significant number of cases with documented outcomes were fatal. [ABSTRACT FROM AUTHOR]

Simple Summary: Ischemia-reperfusion injury (IRI) is the source of significant graft inflammation in liver transplantation. Such injuries can lead to increased recurrence of both benign and malignant diseases of the biliary tree after transplant. Herein, we review the mechanisms and risk factors for the link between IRI and biliary recurrence, as well as evidence for strategies to mitigate this damage. Liver transplantation is known to generate significant inflammation in the entire organ based on the metabolic profile and the tissue's ability to recover from the ischemia-reperfusion injury (IRI). This cascade contributes to post-transplant complications, affecting both the synthetic liver function (immediate) and the scar development in the biliary tree. The new occurrence of biliary strictures, and the recurrence of malignant and benign liver diseases, such as cholangiocarcinoma (CCA) and primary sclerosing cholangitis (PSC), are direct consequences linked to this inflammation. The accumulation of toxic metabolites, such as succinate, causes undirected electron flows, triggering the releases of reactive oxygen species (ROS) from a severely dysfunctional mitochondrial complex 1. This initiates the inflammatory IRI cascade, with subsequent ischemic biliary stricturing, and the upregulation of pro-tumorigenic signaling. Such inflammation is both local and systemic, promoting an immunocompromised status that can lead to the recurrence of underlying liver disease, both malignant and benign in nature. The traditional treatment for CCA was resection, when possible, followed by cytotoxic chemotherapy. Liver transplant oncology is increasingly recognized as a potentially curative approach for patients with intrahepatic (iCCA) and perihilar (pCCA) cholangiocarcinoma. The link between IRI and disease recurrence is increasingly recognized in transplant oncology for hepatocellular carcinoma. However, smaller numbers have prevented similar analyses for CCA. The mechanistic link may be even more critical in this disease, as IRI causes the most profound damage to the intrahepatic bile ducts. This article reviews the underlying mechanisms associated with biliary inflammation and biliary pathology after liver transplantation. One main focus is on the link between transplant-related IRI-associated inflammation and the recurrence of cholangiocarcinoma and benign liver diseases of the biliary tree. Risk factors and protective strategies are highlighted. [ABSTRACT FROM AUTHOR]

Background Although the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines are highly efficacious at preventing severe disease in the general population, current data are lacking regarding vaccine efficacy (VE) for individuals with mild immunocompromising conditions. Methods A post hoc, cross-protocol analysis of participant-level data from the blinded phase of four randomized, placebo-controlled, coronavirus disease 2019 (COVID-19) vaccine phase 3 trials (Moderna, AstraZeneca, Janssen, and Novavax) was performed. We defined a "tempered immune system" (TIS) variable via a consensus panel based on medical history and medications to determine VE against symptomatic and severe COVID-19 cases in TIS participants versus non-TIS individuals starting at 14 days after completion of the primary series through the blinded phase for each of the 4 trials. An analysis of participants living with well-controlled human immunodeficiency virus was conducted using the same methods. Results A total of 3852/30 351 (12.7%) Moderna participants, 3088/29 868 (10.3%) Novavax participants, 3549/32 380 (11.0%) AstraZeneca participants, and 5047/43 788 (11.5%) Janssen participants were identified as having a TIS. Most TIS conditions (73.9%) were due to metabolism and nutritional disorders. Vaccination (vs placebo) significantly reduced the likelihood of symptomatic and severe COVID-19 for all participants for each trial. VE was not significantly different for TIS participants versus non-TIS for either symptomatic or severe COVID-19 for each trial, nor was VE significantly different in the symptomatic endpoint for participants with human immunodeficiency virus. Conclusions For individuals with mildly immunocompromising conditions, there is no evidence of differences in VE against symptomatic or severe COVID-19 compared with those with non-TIS in the 4 COVID-19 vaccine randomized controlled efficacy trials. [ABSTRACT FROM AUTHOR]

Background We aimed to determine if pre-existing immunocompromising conditions (ICCs) were associated with the presentation or outcome of patients with acute coronavirus disease 2019 (COVID-19) admitted for pediatric intensive care. Methods Fifty-five hospitals in 30 US states reported cases through the Overcoming COVID-19 public health surveillance registry. Patients <21 years admitted 12 March 2020–30 December 2021 to the pediatric intensive care unit (PICU) or high-acuity unit for acute COVID-19 were included. Results Of 1274 patients, 105 (8.2%) had an ICC, including 33 (31.4%) hematologic malignancies, 24 (22.9%) primary immunodeficiencies and disorders of hematopoietic cells, 19 (18.1%) nonmalignant organ failure with solid-organ transplantation, 16 (15.2%) solid tumors, and 13 (12.4%) autoimmune disorders. Patients with ICCs were older, had more underlying renal conditions, and had lower white blood cell and platelet counts than those without ICCs, but had similar clinical disease severity upon admission. In-hospital mortality from COVID-19 was higher (11.4% vs 4.6%, P =.005) and hospitalization was longer (P =.01) in patients with ICCs. New major morbidities upon discharge were not different between those with and without ICC (10.5% vs 13.9%, P =.40). In patients with ICCs, bacterial coinfection was more common in those with life-threatening COVID-19. Conclusions In this national case series of patients <21 years of age with acute COVID-19 admitted for intensive care, existence of a prior ICCs were associated with worse clinical outcomes. Reassuringly, most patients with ICCs hospitalized in the PICU for severe acute COVID-19 survived and were discharged home without new severe morbidities. [ABSTRACT FROM AUTHOR]

Porokeratoses (PK) are a group of uncommon dermatoses characterized by abnormal epidermal differentiation due to a disorder of the mevalonate metabolic pathway. Several clinical subtypes exist that can be associated with the same patient or affect different patients within a family and could, therefore, be different expressions of one disease. All PK subtypes share a common histopathologic finding, the cornoid lamella, a vertical stack of parakeratotic corneocytes embedded in an orthokeratotic horny layer. PK often affects immunosuppressed patients, in whom the course may parallel the level of immunosuppression. The pathogenesis of PK, which had long remained mysterious, has been recently unraveled after discovering pathogenic variants of genes involved in the mevalonate metabolic pathway. The disease is due to germline pathogenic variants of genes of this pathway but requires a second‐hit event to manifest; therefore, PK is considered a dominantly inherited but recessively expressed condition. The prognosis of PK is usually favorable, even though the lesions progress to keratinocyte carcinomas in 7%–16% of patients. The treatment of PK was based on physical (ablative) procedures and various (topical or systemic) treatments, whose efficacy is nevertheless inconsistent and often temporary. The discovery of the metabolic pathway involved in the pathogenesis of PK paved the way for the elaboration of new topical treatments (combination of statins and cholesterol), which are more regularly efficacious compared with older treatments, even though the management of some patients with PK may still be challenging. [ABSTRACT FROM AUTHOR]

Immunocompromised patients are at high risk to fail clearance of SARS‐CoV‐2. Prolonged COVID‐19 constitutes a health risk and a management problem as cancer treatments often have to be disrupted. As SARS‐CoV‐2 evolves, new variants of concern have emerged that evade available monoclonal antibodies. Moreover, antiviral therapy promotes SARS‐CoV‐2 escape mutations, particularly in immunocompromised patients. These patients frequently suffer from prolonged infection. No successful treatment has been established for persistent COVID‐19 infection. Here, we report on a series of 21 immunocompromised patients with COVID‐19—most of them hematologic malignancies—treated with plasma obtained from recently convalescent or vaccinated donors or a combination thereof. Repeated dosing of SARS‐CoV‐2‐antibody‐containing plasma could clear SARS‐CoV‐2 infection in 16 out of 21 immunocompromised patients even if COVID‐19‐specific treatments failed to induce sustained viral clearance or to improve clinical course of SARS‐CoV‐2 infection. Ten patients were major responders defined as an increase delta(d)Ct of > = 5 after the first administration of convalescent and/or vaccinated plasma (C/VP). On average, SARS‐CoV‐2 PCR Ct values increased from a median value of 22.55 (IQR = 19.10–24.25) to a median value of 29.57 (IQR = 27.55–34.63; p = <.0001) in the major response subgroup. Furthermore, when treated a second time with C/VP, even 4 out of 5 of the initial nonresponders showed an increase in Ct‐values from a median value of 23.13 (IQR = 17.75–28.05) to a median value of 32.79 (IQR = 31.75–33.75; p =.013). Our results suggest that C/VP could be a feasible treatment of COVID‐19 infection in patients with hematologic malignancies who did not respond to antiviral treatment. [ABSTRACT FROM AUTHOR]

Invasive fungal disease (IFD) presents a life-threatening condition in immunocompromised patients, thus often prompting empirical administration of antifungal treatment, without adequate mycological evidence. Over the past years, wide use of antifungal prophylaxis resulted in decreased occurrence of IFD but has contributed to changes in the spectrum of fungal pathogens, revealing the occurrence of previously rare fungal genera causing breakthrough infections. The expanding spectrum of clinically relevant fungal pathogens required the implementation of screening approaches permitting broad rather than targeted fungus detection to support timely onset of pre-emptive antifungal treatment. To address this diagnostically important aspect in a prospective setting, we analyzed 935 serial peripheral blood (PB) samples from 195 pediatric and adult patients at high risk for IFD, involving individuals displaying febrile neutropenia during treatment of hematological malignancies or following allogeneic hematopoietic stem cell transplantation. Two different panfungal-PCR-screening methods combined with ensuing fungal genus identification by Sanger sequencing were employed. In the great majority of PB-specimens displaying fungal DNAemia, the findings were transient and revealed fungi commonly regarded as non-pathogenic or rarely pathogenic even in the highly immunocompromised patient setting. Hence, to adequately exploit the diagnostic potential of panfungal-PCR approaches for detecting IFD, particularly if caused by hitherto rarely observed fungal pathogens, it is necessary to confirm the findings by repeated testing and to identify the fungal genus present by ensuing analysis. If applied appropriately, panfungal-PCR-screening can help prevent unnecessary empirical therapy, and conversely, contribute to timely employment of effective pre-emptive antifungal treatment strategies. [ABSTRACT FROM AUTHOR]

Introduction: Although pets provide several social-emotional benefits for children, the risk of zoonosis must be considered among immunocompromised individuals. Methods: A prospective study was conducted in a tertiary hospital including immunocompromised patients younger than 20 years owning dogs and/or cats. Colonization and/or infection was evaluated by stool studies, bacterial swabs, blood polymerase chain reaction and serological studies in both patients and their pets, to evaluate potential zoonotic transmission occurrence. Results: We included 74 patients and their 92 pets (63 dogs, 29 cats). Up to 44.6% of the patients and 31.5% of the pets had at least 1 positive result. Up to 18.4% of pets' fecal samples were positive (bacteria, parasites or hepatitis E virus). No helminths were observed despite the high frequency of incorrect intestinal deworming practices. Among children, gastrointestinal microorganisms were found in 37.3% (primarily Clostridium difficile). Colonization by Staphylococcus pseudintermedius was common among pets (8.0%) but not among children (0.0%). No shared colonization between owners and pets was observed, except in one case (Blastocystis in both patient and pet feces). Among patients, serologies were positive for Strongyloides stercoralis (14.8%), Toxocara canis (3.2%), Bartonella henselae (19.1%) and hepatitis E (5.6%). Serology was positive for Rickettsia spp. (22.6%) and Babesia spp. (6.5%) in dogs and for Leishmania spp. (14.3%) and Toxoplasma spp. (14.3%) in cats. Conclusion: Exposure to zoonotic agents was detected in both patients and pets; however, shared colonization events were almost nonexistent. In our cohort, dogs and cats do not appear to entail high zoonosis transmission risk for immunocompromised patients. [ABSTRACT FROM AUTHOR]

Introduction: This study aims to share the experience of the Ministry of Health (Singapore) in deploying a centrally managed Telemedicine service to triage, and manage COVID-19 cases in the community during the COVID-19 Omicron wave. Material and methods: Data from the deployed telemedicine system, Telemedicine Allocation and Reconciliation System, over a 14-week period (3 January 2022–10 April 2022) was analysed to determine the safety and efficacy of both the (i) National COVID-19 sorting logic algorithm and (ii) the use of a centralised telemedicine platform with privacy protection in a pandemic. Results: There was a total of 47,754 children (aged 1–11 years old), 75,702 adolescents and adult patients (aged 12–69 years old) and 55,774 geriatric patients (aged > = 70 years old) who were directly managed by this platform. Amongst them, 64,961 were from the higher-risk special populations (pregnant, end-stage renal failure and immunocompromised and geriatric population). The total number of patients requiring escalations to public health institutions were 4212. This accounts for 1.32%, 3.00% and 2.35% of the children, teenagers and adults, and geriatric population respectively. [ABSTRACT FROM AUTHOR]

Background: COVID-19 continues to pose a threat to immunocompromised individuals, even with vaccination. The monoclonal antibodies (mAbs) tixagevimab/cilgavimab (TXG/CIL) provide targeted prophylaxis against SARS-CoV-2 with the benefit of a prolonged half-life. Although approved for COVID-19 prevention, there is limited data on their effectiveness among heavily immunocompromised populations. Methods: We conducted a prospective, observational study at Laiko General Hospital, Athens, Greece, from August to December 2022 to investigate the efficacy of TXG/CIL as a form of pre-exposure prophylaxis in immunocompromised patients. Data on breakthrough SARS-CoV-2 infections were collected over a six-month follow-up period. Results: Of the 375 participants (mean age 61.3 ± 14.1 years; 59.7% male), 76 (20.3%) developed breakthrough SARS-CoV-2 infections, with an incidence of 3.81 cases/100 patient months. Hospitalization was required for 21 patients (5.6%), with a median stay of 14 days. Seven deaths were recorded, with only one attributed to COVID-19. Previous infection (OR 0.46, 95% CI 0.26–0.82) and hybrid immunity (OR 0.52, 95% CI 0.29–0.92) can protect against new infection. Solid organ malignancy significantly increased the risk of severe outcomes among those infected (OR 7.4, 95% CI 2.2–24.7, p = 0.001). Conclusions: TXG/CIL provides effective prophylaxis against COVID-19 in immunocompromised patients. Future strategies should focus on developing new mAb combinations to address emerging SARS-CoV-2 variants and protect vulnerable populations. [ABSTRACT FROM AUTHOR]

Adenovirus infections of immunocompromised patients can cause life-threatening disseminated disease. While there are presently no drugs specifically approved to treat these infections, there are several compounds that showed efficacy against adenovirus in preclinical studies. For any such compound, low toxicity is an essential requirement. As cumulative drug effects can accentuate pathology, especially in patients with other morbidities, it is important to limit antiviral exposure to what is absolutely necessary. This is achievable by monitoring the virus burden of the patients and administering antivirals to suppress virus replication to a non-pathogenic level. We modeled such a system using Syrian hamsters infected with a replication-competent adenovirus vector, in which luciferase expression is coupled to virus replication. We found that virus replication could be followed in vivo in the same animal by repeated measurement of luciferase expression. To test the utility of an interrupted treatment regimen, we used NPP-669 and valganciclovir, two antiviral compounds with high and moderate anti-adenoviral efficacy, respectively. We found that short-term treatment of adenovirus-infected hamsters at times of peak virus replication can prevent virus-associated pathology. Thus, we believe that this animal model can be used to model different treatment regimens for anti-adenoviral compounds. [ABSTRACT FROM AUTHOR]

Background: Invasive fungal diseases (IFD) are high morbidity and mortality infections in children with cancer suffering episodes of high‐risk febrile neutropenia (HRFN). IFD epidemiology has changed in the last two decades, with an increasing incidence in recent years due to the growing number of immunocompromised children at risk for IFD. The aim of this study was to evaluate the incidence of IFD in children with cancer in the period 2016–2020 compared to 2004–2006 in six hospitals in Chile. Methods: Prospective, multicentre study, carried out between 2016 and 2020 in six hospitals in Chile. The defined cohort corresponds to a dynamic group of HRFN episodes in patients <18 years old with cancer, who at the fourth day of evolution still presented fever and neutropenia (persistent HRFN). Each episode was followed until resolution of FN. The incidence of IFD was calculated between 2016 and 2020 and compared with data obtained in the period 2004–2006. The incidence rate was estimated. Results: A total of 777 episodes of HRFN were analysed; 257 (33.1%) were considered as persistent‐HRFN occurring in 174 patients. The median age was 7 years (IQR: 3–12 years) and 52.3% (N = 91) were male. Fifty‐three episodes of IFD were detected: 21 proven, 14 probable and 18 possible. Possible IFD were excluded, leaving 239 episodes of persistent‐HRFN with an IFD incidence of 14.6% (95% CI 10.5–19.9) and an incidence rate of 13.6 IFD cases per 1000 days of neutropenia (95% CI 9.5–20.0). Compared to 2004–2006 cohort (incidence: 8.5% (95% CI 5.2–13.5)), a significant increase in incidence of 6.1% (95% CI 0.2–12.1, p =.047) was detected in cohorts between 2016 and 2020. Conclusion: We observed a significant increase in IFD in 2016–2020, compared to 2004–2006 period. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to investigate the trends in infectious spondylitis over the past two decades. Methods: We included 157 cases, from 2000 to 2020, of infectious spondylitis. The cases were divided into two groups: 00 (cases during 2000–2009; 82 cases:) and 10 (cases during 2010–2020; 75 cases) groups. Patients' age, sex, causative organism, and localization were examined and compared between the two groups. Results: The proportions of women in the 00 and 10 groups were 30.5% and 38.7%, respectively, with no significant difference (P = 0.28). The average age was significantly higher in the 10 group (72.6 years) than in the 00 group (68.8 years; P < 0.01). A compromised host was the cause of infection in 52.4% and 36.0% of the patients in the 00 and 10 groups, respectively, showing a significant difference. The bacterial identification rates were 70.1% and 77.3% in the 00 and 10 groups, respectively (P < 0.01), and the genus Staphylococcus was the most common bacteria. The proportions of resistant bacteria such as methicillin-resistant Staphylococcus aureus in the 00 and 10 groups were 27.3% and 6.7%, respectively (P < 0.01). Conversely, infectious diseases caused by indigenous bacteria in the oral cavity and intestines were more common in the 10group (37.8%) than in the 00 group (13.0%), showing a significant difference (P < 0.01). Conclusion: Recently, infections caused by indigenous bacteria in the oral cavity and intestines have increased more than those caused by resistant bacteria over the past two decade. [ABSTRACT FROM AUTHOR]

Background Candidaemia is associated with poor outcomes including high mortality rates. Controversy remains regarding whether fluconazole or an echinocandin is the optimal choice for initial candidaemia treatment, particularly among high-risk patients such as the immunocompromised or critically ill. Objectives To understand optimal initial treatment of candidaemia. Methods We conducted a retrospective study of immunocompromised or ICU adult patients with candidaemia from 2010 to 2014. Patients who received ≥3 consecutive days of initial treatment with fluconazole or micafungin were included. The primary outcome was complete response at day 14, defined as clinical improvement and blood culture sterilization. Secondary outcomes included microbiological and clinical success, survival and recurrent candidaemia. Results A total of 197 patients were included; 76 received fluconazole and 121 received micafungin. There was no difference in complete response between the fluconazole and micafungin groups (ICU: 38% versus 40%, P  = 0.87; immunocompromised: 57% versus 59%, P  = 0.80). Secondary outcomes including survival were also similar. In multivariable analysis, among ICU patients, Pitt bacteraemia score < 4 (P  = 0.002) and time to antifungal (P  = 0.037) were associated with meeting the primary outcome; white blood cell count > 11 cells × 103/µL on day 0 (P  < 0.001) and Candida isolated from a non-blood site (P  = 0.025) were associated with not meeting the primary outcome. Among immunocompromised patients, white blood cells > 11 × 103/µL (P  = 0.003) and Candida isolated from a non-blood site (P  = 0.026) were associated with not meeting the primary outcome. Conclusions These data suggest that among ICU or immunocompromised patients, severity of illness rather than initial antifungal choice drove clinical outcomes. [ABSTRACT FROM AUTHOR]

Data on the safety and antibody response of the BNT162b2 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mRNA vaccine in children aged 5–11 years with underlying diseases are limited. Thus, our study aimed to address this gap. This prospective observational study investigated the antibody titers for SARS-CoV-2 spike protein receptor-binding domain (S-IgG) and nucleocapsid protein (N-IgG) in patients aged 5–11 years with chronic underlying diseases following two doses of BNT162b2. Additionally, a questionnaire was used to assess adverse events (AEs) arising within 7 days after each dose. Data on severe AEs arising within 28 days after each dose were extracted from the patients' electronic medical records. Among 122 patients, 24.6% (30/122) were immunocompromised. Furthermore, 79 patients experienced at least one AE following vaccination, but all recovered without sequelae, including one severe case after the first dose. The seropositivity rate after the second dose was 99.1% (116/117). Excluding 19 N-IgG-positive patients, the geometric mean antibody titer (GMT) was significantly higher in immunocompetent patients than in immunocompromised patients (1496 U/mL [95% confidence interval 1199–1862] vs. 472 U/mL [200−1119], p = 0.035). Additionally, the GMT of S-IgG was higher in N-IgG-positive patients than in N-IgG-negative patients (8203 [5847–11482] U/mL vs. 1127 [855–1486] U/mL, p < 0.001). BNT162b2 is acceptably safe and immunogenic for children aged 5–11 years with underlying diseases. Although seroconversion was satisfactory in immunocompromised patients, the titers were lower than in immunocompetent patients. [ABSTRACT FROM AUTHOR]

Deficits in T cell immunity translate into increased risk of severe viral infection in recipients of solid organ and hematopoietic cell transplants. Thus, therapeutic strategies that employ the adoptive transfer of virus-specific T cells are being clinically investigated to treat and prevent viral diseases in these highly immunocompromised patients. Posoleucel is an off-the-shelf multivirus-specific T cell investigational product for the treatment and prevention of infections due to adenovirus, BK virus, cytomegalovirus, Epstein–Barr virus, human herpesvirus 6 or JC virus. Herein we perform extensive characterization of the phenotype and functional profile of posoleucel to illustrate the cellular properties that may contribute to its in vivo activity. Our results demonstrate that posoleucel is enriched for central and effector memory CD4+ and CD8+ T cells with specificity for posoleucel target viruses and expressing a broad repertoire of T cell receptors. Antigen-driven upregulation of cell-surface molecules and production of cytokine and effector molecules indicative of proliferation, co-stimulation, and cytolytic potential demonstrate the specificity of posoleucel and its potential to mount a broad, polyfunctional, and effective Th1-polarized antiviral response upon viral exposure. We also show the low risk for off-target and nonspecific effects as evidenced by the enrichment of posoleucel in memory T cells, low frequency of naive T cells, and lack of demonstrated alloreactivity in vitro. The efficacy of posoleucel is being explored in four placebo-controlled clinical trials in transplant recipients to treat and prevent viral infections (NCT05179057, NCT05305040, NCT04390113, NCT04605484). [ABSTRACT FROM AUTHOR]

Among immunocompromised hosts, leukemia patients, and hematopoietic cell transplant recipients are particularly vulnerable, facing challenges in balancing coronavirus disease 2019 (COVID‐19) management with their underlying conditions. In this How I Treat article, we discuss how we approach severe acute respiratory syndrome coronavirus 2 infections in daily clinical practice, considering the existing body of literature and for topics where the available data are not sufficient to provide adequate guidance, we provide our opinion based on our clinical expertise and experience. Diagnostic approaches include nasopharyngeal swabs for polymerase chain reaction testing and chest computed tomography scans for symptomatic patients at risk of disease progression. Preventive measures involve strict infection control protocols and prioritizing vaccination for both patients and their families. Decisions regarding chemotherapy or hematopoietic cell transplantation in leukemia patients with COVID‐19 require careful consideration of factors such as COVID‐19 severity and treatment urgency. Treatment protocols include early initiation of antiviral therapy, with nirmatrelvir/ritonavir or remdesivir. For cases of prolonged viral shedding, distinguishing between viable and non‐viable viruses remains challenging but is crucial for determining contagiousness and guiding management decisions. Overall, individualized approaches considering immune status, clinical presentation, and viral kinetics are essential for effectively managing COVID‐19 in leukemia patients. [ABSTRACT FROM AUTHOR]

Candida albicans is a major fungal pathogen of humans that can cause serious systemic infections in vulnerable immunocompromised populations. One of its virulence attributes is its capacity to transition between yeast and filamentous morphologies, but our understanding of this process remains incomplete. Here, we analyzed data from a functional genomic screen performed with the C. albicans Gene Replacement And Conditional Expression collection to identify genes crucial for morphogenesis in host-relevant conditions. Through manual scoring of microscopy images coupled with analysis of each image using a deep learning-based method termed Candescence, we identified 307 genes important for filamentation in tissue culture medium at 37°C with 5% CO2. One such factor was orf19.5963 , which is predicted to encode the prenyltransferase Nus1 based on sequence homology to Saccharomyces cerevisiae. We further showed that Nus1 and its predicted interacting partner Rer2 are important for filamentation in multiple liquid filament-inducing conditions as well as for wrinkly colony formation on solid agar. Finally, we highlight that Nus1 and Rer2 likely govern C. albicans morphogenesis due to their importance in intracellular trafficking, as well as maintaining lipid homeostasis. Overall, this work identifies Nus1 and Rer2 as important regulators of C. albicans filamentation and highlights the power of functional genomic screens in advancing our understanding of gene function in human fungal pathogens. [ABSTRACT FROM AUTHOR]

Viral vectors are being used for the treatment of cancer. Yet, their efficacy varies among tumors and their use poses challenges in immunosuppressed patients, underscoring the need for alternatives. We report striking antitumoral effects by a nonlytic viral vector based on attenuated lymphocytic choriomeningitis virus (r3LCMV). We show in multiple tumor models that injection of tumor-bearing mice with this vector results in improved tumor control and survival. Importantly, r3LCMV improved tumor control in immunodeficient Rag mice and MyD88 mice, suggesting that multiple pathways contributed to the antitumoral effects. The antitumoral effects of r3LCMV were also observed when this vector was administered several weeks before tumor challenges, suggesting the induction of trained immunity. Single-cell RNA sequencing analyses, antibody blockade experiments, and knockout models revealed a critical role for host-intrinsic IFN-I in the antitumoral efficacy of r3LCMV vectors. Collectively, these data demonstrate potent antitumoral effects by r3LCMV vectors and unveil multiple mechanisms underlying their antitumoral efficacy. [ABSTRACT FROM AUTHOR]

Key Clinical Message: Cutaneous leishmaniasis is caused by protozoan parasites of the genus leishmania. Atypical presentation and widespread progression of the lesions may be seen in an immunocompromised patient. We report a case of atypical and widespread cutaneous leishmaniasis in a young woman with breast cancer. [ABSTRACT FROM AUTHOR]

Key Clinical Message: Although rare, crusted scabies can affect immunocompetent individuals with no identifiable risk factors. A high index of suspicion, regardless of an individual's immunological status or absence of traditional risk factors, should be maintained by health professionals to facilitate prompt referral to a dermatologist. Crusted scabies is an uncommon variant of human scabies characterized by extensive crusted and scaly hyperkeratotic papules, and plaques resulting from profound proliferation of mites in the skin. It is highly contagious and typically occurs in immunocompromised individuals. Reports of cases in healthy adults are rare. It is often resistant to routine treatment. We report a case of a 30‐year‐old immunocompetent male who presented to us with an extensive pruritic papular rash that started in the inter‐digital web spaces of his hands. Within 3 months from onset, the lesions progressed, and became hyperkeratotic, scaly, non‐pruritic, spreading to involve his entire body (sparing his face only). Crusty scabies was eventually diagnosed and treated by a dermatologist after months of misdiagnosis at peripheral facilities. Although rare, crusted scabies can affect immunocompetent individuals. A high index of suspicion is required, regardless of immunological status. Among immunocompetent individuals, a thorough search for traditional risk factors is imperative. [ABSTRACT FROM AUTHOR]

During October 2021-June 2023, a total of 392 cases of acute hepatitis of unknown etiology in children in the United States were reported to Centers for Disease Control and Prevention as part of national surveillance. We describe demographic and clinical characteristics, including potential involvement of adenovirus in development of acute hepatitis, of 8 fatally ill children who met reporting criteria. The children had diverse courses of illness. Two children were immunocompromised when initially brought for care. Four children tested positive for adenovirus in multiple specimen types, including 2 for whom typing was completed. One adenovirus-positive child had no known underlying conditions, supporting a potential relationship between adenovirus and acute hepatitis in previously healthy children. Our findings emphasize the importance of continued investigation to determine the mechanism of liver injury and appropriate treatment. Testing for adenovirus in similar cases could elucidate the role of the virus. [ABSTRACT FROM AUTHOR]

The risk of Trypanosoma cruzi reactivation is poorly understood. Previous studies evaluating the risk of reactivation report imprecise findings, and recommendations for monitoring and management from clinical guidelines rely on consensus opinion. We conducted a systematic review and meta-analysis to estimate the cumulative T. cruzi reactivation incidence in immunosuppressed adults, summarize the available evidence on prognostic factors for reactivation, and examine its prognostic effect on mortality. MEDLINE, Embase, LILACS, Clinical Trials, and CENTRAL from inception to 4 July 2022. Studies reporting the incidence of T. cruzi reactivation. Immunosuppressed adults chronically infected by T. cruzi. Two authors independently extracted data (including, but not limited to, incidence data, reactivation definition, follow-up, treatment, monitoring schedule, examined prognostic factors) and evaluated the risk of bias. We pooled cumulative incidence using a random-effects model. Twenty-two studies (806 participants) were included. The overall pooled incidence of T. cruzi reactivation was 27% (95% CI, 19–36), with the highest pooled proportion in the sub-group of transplant recipients (36%; 95% CI, 25–48). The highest risk period was in the first 6 months after transplant (32%; 95% CI, 17–58), decreasing drastically the number of new cases later. People living with HIV and patients with autoimmune diseases experienced significantly lower cumulative reactivation incidences (17%; 95% CI, 8–29 and 18%; 95% CI, 9–29, respectively). A single study explored the independent effect of benznidazole and found benefits for preventing reactivations. No studies evaluated the independent association between reactivation and mortality, while sensitivity analysis results using unadjusted estimates were inconclusive. The heterogeneity of diagnostic algorithms was substantial. Reactivation occurs in three out of ten T. cruzi -seropositive immunosuppressed adults. These findings can assist clinicians and panel guidelines in tailoring monitoring schedules. There is a great need for an accurate definition of reactivation and targeted monitoring. [ABSTRACT FROM AUTHOR]

Anti-spike monoclonal antibodies represent one of the most tolerable prophylaxis and therapies for COVID-19 in frail and immunocompromised patients. Unfortunately, viral evolution in Omicron has led all of them to failure. We review here the current pipeline of anti-spike mAb's, discussing in detail the most promising candidates. We scanned PubMed, ClinicalTrials.gov and manufacturers' press releases for clinical studies on anti-spike monoclonal antibodies. We present state-of-art data clinical progress for AstraZeneca's AZD3152, Invivyd's VYD222, Regeneron's REGN-17092 and Aerium Therapeutics' AER-800. The anti-spike monoclonal antibody clinical pipeline is currently limited to few agents (most being single antibodies) with unknown efficacy against the dominant JN.1 sublineage. The field of antibody-based therapies requires boosting by both manufacturers and institutions. [ABSTRACT FROM AUTHOR]

Immunocompromised patients with impaired humoral immunity are at risk for persistent COVID-19 (pCOVID), a protracted symptomatic disease with active viral replication. To establish a national consensus statement on the diagnosis, treatment, management, isolation, and prevention of pCOVID in adults. We base our suggestions on the available literature, our own experience, and clinical reasoning. Literature on the treatment of pCOVID is scarce and consists of few case reports and case series. The available studies provide low-quality evidence for monoclonal antibodies, convalescent plasma, antiviral drugs, and immunomodulators. Different combination therapies are described. Continuous viral replication and antiviral treatment may lead to the development of mutations that confer resistance to therapy. To reduce the risk of resistance and improve outcomes, we suggest treating pCOVID with a combination of antibody-based therapy and two antiviral drugs for duration of 5–10 days. Immunomodulatory therapy can be added in patients with an inflammatory clinical picture. In cases of treatment failure or relapse, prolonged antiviral treatment can be considered. For the prevention of pCOVID, we suggest active and passive vaccination and early initiation of treatment for acute COVID-19. Additional research on pCOVID treatment is urgently needed. [ABSTRACT FROM AUTHOR]

Background: The survival benefit of sentinel lymph node biopsy (SLNB) in immunocompetent and immunosuppressed patients with high‐risk cutaneous squamous cell carcinoma (cSCC) has not been established. Objective: To determine whether SLNB improves disease‐specific survival (DSS) in high‐risk cSCC. Secondary objectives were to analyse disease‐free survival, nodal recurrence‐free survival and overall survival (OS). Methods: Multicentre, retrospective, observational cohort study comparing survival outcomes in immunosuppressed and immunocompetent patients treated with SLNB or watchful waiting. Inverse probability of treatment weighting was used to adjust for possible confounding effects. Results: We studied 638 tumours in immunocompetent patients (SLNB n = 42, observation n = 596) and 173 tumours in immunosuppressed patients (SLNB n = 28, observation n = 145). Overall, SLNB was positive in 15.7% of tumours. SLNB was associated with a reduced risk of nodal recurrence (NR) (hazard ratio [HR], 0.05 [95% CI, 0.01–0.43]; p = 0.006), disease specific mortality (HR, 0.17 [95% CI, 0.04–0.72]; p = 0.016) and all‐cause mortality (HR, 0.33 [95% CI, 0.15–0.71]; p = 0.004) only in immunocompetent patients. Conclusions: SLNB was associated with improvements in NR, DSS and OS in immunocompetent but not in immunosuppressed patients with high‐risk cSCC. [ABSTRACT FROM AUTHOR]

Antibodies for treatment and prophylaxis against SARS-CoV-2 are needed particularly for immunocompromised individuals, who cannot adequately benefit from vaccination. To address this need, Aerium Therapeutics is developing antibodies targeting the SARS-CoV-2 spike protein. A bioanalytical method to quantify fully human monoclonal antibodies in a population with widely varying anti-spike antibody titers is required to investigate the pharmacokinetics of these antibodies in clinical trials. To eliminate interference from endogenous anti-spike protein antibodies, an HPLC–MS/MS assay was developed to quantify the investigational monoclonal antibodies (AER001 and AER002) by targeting signature peptides spanning the monoclonal antibodies' CDR regions. By optimizing and comparing affinity capture and ammonium sulphate precipitation, it was demonstrated that both procedures allowed accurate and precise quantification of AER001 and AER002 in human serum with comparable sensitivity. Ammonium sulphate precipitation outperformed immunocapture due to its simplicity and speed at lower cost and a full bioanalytical method validation was performed in human serum. The assay was also validated for human nasal lining fluid extract with a 50-fold lower limit of quantification and was shown to deliver similar sensitivity to previously published affinity capture HPLC–MS/MS assays. Finally, the CDR-derived signature peptides were also generated by tryptic digestion of blank serum in some individuals, an important caveat for HPLC–MS/MS strategies targeting human monoclonal antibodies. In summary, the presented results show that ammonium sulphate precipitation and HPLC–MS/MS allow accurate and precise quantification of monoclonals in clinical studies. The developed methods demonstrate that HPLC–MS/MS can reliably quantify human monoclonal antibodies even when endogenous antibodies with overlapping specificities are present and are crucial for the clinical testing of two investigational COVID-19 monoclonals. [ABSTRACT FROM AUTHOR]

The World Health Organization has disclosed that the hybrid-immune and immunodeficient individuals are two distinct classes of individuals susceptible to the COVID-19 virus. To model this unique characteristics of two distinct categories of susceptible individuals and the dynamics of the three phases of a vaccination program implemented by the World Health Organization in Malaysia, which have not been accounted for in previous studies, a twelve compartmental SSVEIHQR-D epidemiological model was developed. This model aimed to accurately capture the spread of the COVID-19 virus by fitting real-life data to the model and obtaining updated estimates of the reproduction number. The study also focused on assessing current control measures and exploring strategies to eradicate the virus and mitigate future outbreaks. Mathematical analyses of the model included investigations into stability, equilibrium points, the basic reproduction number R0, optimal control strategies, and sensitivity analyses. Estimation and fitting of the model parameters were conducted using daily situation reports from the Ministry of Health of Malaysia. The obtained value of the basic reproduction number, based on fitted parameter values, indicated stability and reflected the current pandemic situation more realistically. Additionally, the herd immunity threshold was calculated and interpreted in the context of the study findings. Finally, practical insights and recommendations derived from the model’s results were provided to inform government agencies, public health organizations, and intervention bodies, aimed at controlling the spread of the COVID-19 virus. [ABSTRACT FROM AUTHOR]

Introduction: Capnocytophaga ochracea is found in the human oral microbiome and is a rare cause of antibiotic-resistant, opportunistic septicemia in immunocompromised hosts. The zoonotic transmission of C ochracea from canines to humans has not yet been reported in the literature. Cohabitation with people is associated with oral colonization in dogs and may be a reservoir for Capnocytophaga infections, which have a decreased susceptibility to first-line antibiotics commonly used to treat animal exposures. Case Report: This is the case of a 70-year-old male with a remote history of lymphoma status post splenectomy, in remission, who presented with stigmata of Capnocytophaga septicemia after a dog bite, which included purpura fulminans on physical examination. Initial broad-spectrum coverage with cefepime failed to slow the progression into multiorgan failure. A Capnocytophaga strain with extended resistance was suspected. Antibiotics were transitioned to meropenem, and the patient eventually made a good recovery. Blood cultures isolated C ochracea. Conclusion: Capnocytophaga infections should be suspected in patients with severe sepsis and purpura fulminans after a canine exposure. Canine pets may be a reservoir for Capnocytophaga species with increased antibiotic resistances, such as C ochracea, which trace their origins to the human oral microbiome. A thorough medical history is essential to identify risk factors such as asplenia and active immune compromise that are associated with infections from antibiotic-resistant strains and worse outcomes. For Capnocytophaga infections that fail initial therapies, cephalosporins should be avoided because of high resistance rates, and the use of carbapenems may be favored over combination beta-lactam/beta-lactamase inhibitors in select clinical scenarios. [ABSTRACT FROM AUTHOR]

Jumbo phages are a group of tailed bacteriophages with large genomes and capsids. As a prototype of jumbo phage, ΦKZ infects Pseudomonas aeruginosa, a multi-drug-resistant (MDR) opportunistic pathogen leading to acute or chronic infection in immunocompromised individuals. It holds potential to be used as an antimicrobial agent and as a model for uncovering basic phage biology. Although previous low-resolution structural studies have indicated that jumbo phages may have more complicated capsid structures than smaller phages such as HK97, the detailed structures and the assembly mechanism of their capsids remain largely unknown. Here, we report a 3.5-Å-resolution cryo-EM structure of the ΦKZ capsid. The structure unveiled ten minor capsid proteins, with some decorating the outer surface of the capsid and the others forming a complex network attached to the capsid's inner surface. This network seems to play roles in driving capsid assembly and capsid stabilization. Similar mechanisms of capsid assembly and stabilization are probably employed by many other jumbo viruses. Here, the authors present the 3.5-Å-resolution cryo-EM structure of the jumbo phage ΦKZ capsid, revealing ten minor capsid proteins that are hypothesized to contribute to capsid assembly and stabilization. [ABSTRACT FROM AUTHOR]

Severe fever with thrombocytopenia syndrome (SFTS) has a high mortality rate compared to other infectious diseases. SFTS is particularly associated with a high risk of mortality in immunocompromised individuals, while most patients who die of SFTS exhibit symptoms of severe encephalitis before death. However, the region of brain damage and mechanisms by which the SFTS virus (SFTSV) causes encephalitis remains unknown. Here, we revealed that SFTSV infects the brainstem and spinal cord, which are regions of the brain associated with respiratory function, and motor nerves in IFNAR1‐/‐ mice. Further, we show that A1‐reactive astrocytes are activated, causing nerve cell death, in infected mice. Primary astrocytes of SFTSV‐infected IFNAR1‐/‐ mice also induced neuronal cell death through the activation of A1‐reactive astrocytes. Herein, we showed that SFTSV induces fatal neuroinflammation in the brain regions important for respiratory function and motor nerve, which may underlie mortality in SFTS patients. This study provides new insights for the treatment of SFTS, for which there is currently no therapeutic approach. [ABSTRACT FROM AUTHOR]

Introduction: Human Erythrovirus (parvovirus) B19 infection can produce symptoms similar to those produced by Dengue, Chikungunya, and Zika viruses, making clinical diagnosis difficult. The importance of erythrovirus B19 in human pathology has been increased and reported in numerous studies published globally. Methods: The B19V infection was investigated by real-time PCR in sera samples from patients with signs and symptoms related to classic arboviral symptoms. This study was conducted to provide information on the genetic diversity of Human Erythrovirus B19 (B19V) circulating in the state of Mato Grosso do Sul, Midwest region of Brazil, from 2017 to 2022. A total of 773 sera samples of patients with negative diagnostic results for Dengue, Chikungunya, and Zika, during the study period were analyzed. Results: Erythrovirus DNA was found in 10.6% (82/773) of patients, among them 10 were pregnant women. Four samples were completely sequenced, and the other five partially, to genotype by phylogenetic reconstruction. All samples belong to worldwide dispersed genotype 1, subgenotype 1a. Discussion: The findings of the study demonstrate the importance of including B19V in differential laboratory diagnosis for epidemiological purposes and appropriate patient management. The diagnosis for B19V should be performed, particularly among pregnant women, immunocompromised patients, and individuals with hemolytic diseases, given that the infection is more severe in these cases. [ABSTRACT FROM AUTHOR]

Interstitial lung disease (ILD) comprises a group of respiratory diseases affecting the interstitium of the lungs, which occur when a lung injury triggers an abnormal healing response, and an inflammatory process leads to altered diffusion and restrictive respiratory dysfunction. The term "interstitial" may be misleading, as other components of the lungs are usually also involved (epithelium, airways, endothelium, and so on). Pediatric conditions (childhood interstitial lung disease, chILD) are different from adult forms, as growing and developing lungs are affected and more diverse and less prevalent diseases are seen in childhood. Diffuse parenchymal lung disease (DPLD) and diffuse lung disease (DLD) can be used interchangeably with ILD. Known etiologies of chILD include chronic infections, bronchopulmonary dysplasia, aspiration, genetic mutations leading to surfactant dysfunction, and hypersensitivity pneumonitis due to drugs or environmental exposures. Many forms are seen in disorders with pulmonary involvement (connective tissue disorders, storage diseases, malignancies, and so on), but several conditions have unknown origins (desquamative pneumonitis, pulmonary interstitial glycogenosis, neuroendocrine cell hyperplasia in infancy, and so on). Currently, there is no consensus on pediatric classification; however, age grouping is proposed as some specific forms are more prevalent in infancy (developmental and growth abnormalities, surfactant dysfunction mutations, etc.) and others are usually seen in older cohorts (disorders in normal or immunocompromised hosts, systemic diseases, etc.). Clinical manifestations vary from mild nonspecific symptoms (recurrent respiratory infections, exercise intolerance, failure to thrive, dry cough, etc.) to a severe clinical picture (respiratory distress) and presentation related to the child's age. The diagnostic approach relies on imaging techniques (CT), but further investigations including genetic tests, BAL, and lung biopsy (VATS) are needed in uncertain cases. Pharmacological treatment is mostly empiric and based on anti-inflammatory and immunomodulatory drugs. Lung transplantation for selected cases in a pediatric transplantation center could be an option; however, limited data and evidence are available regarding long-term survival. International collaboration is warranted to understand chILD entities better and improve the outcomes of these patients. [ABSTRACT FROM AUTHOR]

Toxoplasmosis, caused by the protozoan parasite Toxoplasma gondii (T. gondii), presents a significant global health concern, particularly for immunocompromised individuals and congenitally infected newborns. Despite its widespread prevalence, there are limited data on T. gondii seroprevalence and ocular toxoplasmosis in Romania. This review aims to summarize the research accomplished on the prevalence and epidemiology of human ocular toxoplasmosis in Romania. Ocular toxoplasmosis, a leading cause of infectious posterior uveitis worldwide, involves complex interactions between host immune responses and parasite factors. Clinically, it presents as focal necrotizing retinitis, characterized by active focal retinal lesions with adjacent chorioretinal scarring, often accompanied by vitreous inflammation and anterior chamber reactions. Diagnosis relies on clinical examination supported by fundus photography, optical coherence tomography (OCT), and serological assays. The authors followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) standards, conducting a literature review on PubMed, Google Scholar, and Scopus. Our focus was on ocular toxoplasmosis in Romania, and we used keywords and specific MeSH terms. Finally, 17 articles met all the criteria, as summarized in the PRISMA diagram. This study underscores the need for improved diagnostic methods, increased research efforts, and comprehensive public health education to mitigate the burden of toxoplasmosis and ocular toxoplasmosis in Romania. [ABSTRACT FROM AUTHOR]

The investigation's goal was to obtain further knowledge about the connection between Herpes Zoster infection and dentistry therapy for the osteonecrosis of the jaws, combining the review with a case report relevant to the purpose. It is important to study this association because it is a possible additional factor to be considered in the causes of the osteonecrosis of the jaws. We limited our search to English-language papers published between 1 January 2004 and 7 June 2024 in PubMed, Scopus, and Web of Science that were relevant to our topic. In the search approach, the Boolean keywords "Herpes Zoster AND osteonecros*" were used. Results: This study analyzed 148 papers from Web of Science, PubMed, and Scopus, resulting in 95 articles after removing duplicates. Of these, 49 were removed because they were off topic, and 46 were confirmed. This study includes a qualitative analysis of the final 12 articles, removing 34 articles that were off topic. The literature highlights severe oral complications from Herpes Zoster reactivation, emphasizing the need for early diagnosis, comprehensive management, and multidisciplinary care. Treatment strategies include antiviral therapy, pain management, surgical debridement, and antibiotics. Immunocompromised individuals require vigilant monitoring and balanced immunosuppressive therapy. Further research is needed to enhance therapeutic approaches. [ABSTRACT FROM AUTHOR]

Background: The accuracy of a diagnostic test depends on its intrinsic characteristics and the disease incidence. This study aims to depict post-test probability of Pneumocystis pneumonia (PJP), according to results of PCR and Beta-D-Glucan (BDG) tests in patients with acute respiratory failure (ARF). Materials and methods: Diagnostic performance of PCR and BDG was extracted from literature. Incidence of Pneumocystis pneumonia was assessed in a dataset of 2243 non-HIV immunocompromised patients with ARF. Incidence of Pneumocystis pneumonia was simulated assuming a normal distribution in 5000 random incidence samples. Post-test probability was assessed using Bayes theorem. Results: Incidence of PJP in non-HIV ARF patients was 4.1% (95%CI 3.3-5). Supervised classification identified 4 subgroups of interest with incidence ranging from 2.0% (No ground glass opacities; 95%CI 1.4–2.8) to 20.2% (hematopoietic cell transplantation, ground glass opacities and no PJP prophylaxis; 95%CI 14.1–27.7). In the overall population, positive post-test probability was 32.9% (95%CI 31.1–34.8) and 22.8% (95%CI 21.5–24.3) for PCR and BDG, respectively. Negative post-test probability of being infected was 0.10% (95%CI 0.09–0.11) and 0.23% (95%CI 0.21–0.25) for PCR and BDG, respectively. In the highest risk subgroup, positive predictive value was 74.5% (95%CI 72.0-76.7) and 63.8% (95%CI 60.8–65.8) for PCR and BDG, respectively. Conclusion: Although both tests yield a high intrinsic performance, the low incidence of PJP in this cohort resulted in a low positive post-test probability. We propose a method to illustrate pre and post-test probability relationship that may improve clinician perception of diagnostic test performance according to disease incidence in predefined clinical settings. [ABSTRACT FROM AUTHOR]

Background: Recently, there is increasing evidence that the proportion of odontogenic brain abscesses is greater than previously known. In this study, we aim to differentiate the oral infections as triggers more precisely and to classify them in the clinical setting. Methods: For analysis, we conducted a retrospective single center study. We reviewed patients with brain abscesses who have undergone treatment in the University Hospital of Freiburg, Germany in the period between 2000–2021. Inclusion required two main criteria: 1. The brain abscess must not have an other focus than odontogenic. 2. The microbial spectrum identified in the brain abscess must be consistent with an odontogenic origin. Results: Of 217 brain abscess patients, 26 met the inclusion criteria. 42% (11 patients) suffered from immunosuppressive conditions. Odontogenic foci were diagnosed in 18 cases (69%). Neurologic deficits included vigilance reduction and hemiparesis. Pathogens of the Streptococcus anginosus group were the most frequent causative agent (21 cases, 81%). Metronidazole (54%) and ceftriaxone (42%) were part of the targeted antibiotic therapy. All brain abscesses were surgically treated. Teeth were extracted in 14 of 17 cases for focus control. 18 cases (72%) showed complete or partial resolution of neurologic symptoms and 3 cases were fatal. Conclusion: Apparently silent or chronic oral infections are sufficient to cause bacterial colonization of the brain, especially in immunocompromised patients. Therefore, special care should be taken to maintain good oral health. An interdisciplinary management should become a standard to prevent and treat the occurrence of brain abscesses. [ABSTRACT FROM AUTHOR]