Focus Of Infection Research Articles

The [99mTc]Tc-HMPAO-labelled white blood cell SPECT/CT as a novel criterion for infective endocarditis diagnosis

Aims: Infective endocarditis (IE) poses a significant clinical challenge, necessitating nuanced diagnostic tools for early and accurate detection. The diagnostic role of the hybrid technique of single-photon emission tomography-computed tomography with technetium-99 m-hexamethylpropyleneamine oxime–labelled leukocytes ([99mTc]Tc-HMPAO-SPECT/CT) has evolved in recent years. This single-center study assessed whether the recent inclusion in the 2023 European Society of Cardiology modified diagnostic criteria of IE (2023 ESC) of infectious lesions detected with [99mTc]Tc-HMPAO-SPECT/CT affects their diagnostic performance.Methods and results: Between 2015 and 2019, we enrolled 205 consecutive adults with suspected IE. All participants underwent [99mTc]Tc-HMPAO-SPECT/CT scans (370–740 MBq). Scans were deemed positive in the presence of intracardiac abnormal tracer uptake and/or within the cardiac implantable electronic device. Patients were prospectively followed-up for 12 ± 10 months. Local device infection (LDI) or IE was diagnosed in 75 (36.6 %) patients, while 72 (35.1 %) [99mTc]Tc-HMPAO-SPECT/CT results returned positive. Moreover, extracardiac infectious foci were detected in 25 % of [99mTc]Tc-HMPAO-SPECT/CT scans. The inclusion of both intracardiac and extracardiac lesions detected with [99mTc]Tc-HMPAO-SPECT/CT yields significantly higher sensitivity (p = 0.003) and negative predictive value (NPV) (p = 0.009).Conclusion: The inclusion of [99mTc]Tc-HMPAO-SPECT/CT into the IE diagnostic work-up improves the appropriate classification of patients. For patients with IE, the extended inclusion of lesions detected with [99mTc]Tc-HMPAO-SPECT/CT in the ESC 2023 diagnostic criteria significantly improves sensitivity and NPV while reducing potential IE misdiagnoses. This pioneering imaging modality is poised to become an integral component of clinical practice, promising to advance IE diagnosis and management.

Impact of Oral Infection on Organ Transplantation: A Systematic Review

ObjectivesPosttransplant infections may lead to dire consequences in immunocompromised organ recipients. Oral foci of infection are therefore often eliminated prior to solid organ transplantation to reduce posttransplant morbidity. However, despite increasing numbers of organ transplantations the necessity of pretransplant dental treatment and its effect on transplant outcome remains uncertain. The aim of the present systematic review was to evaluate the impact of oral foci of infection and pretransplant dental treatment on adverse events following solid organ transplantation. MethodsStudies on adult patients undergoing solid organ transplantation with/without oral infection or with/without pretransplant dental treatment were eligible. An electronic search in PubMed, Scopus, Web of Science, CINAHL and Cochrane was conducted up to June 11, 2024. Screening of eligibility, data extraction and risk-of-bias assessment of the included studies with the Newcastle-Ottawa Scale were done independently by two reviewers. Data were synthesized with a narrative approach. ResultsIn total, 4035 unique publications were identified. After full text assessment of 75 studies nine cohort studies on liver, kidney, heart and/or lung transplantation based on 727 patients were included. Two studies based on 161 patients found a significant increase of infectious complications after liver transplantation when no dental treatment was performed. Presence of oral foci increased the risk of hospitalization after kidney transplantation in one study but was associated with lower infection rate after lung transplantation in another study. No studies found significant impact on mortality or on organ rejection. Overall, the quality of the included studies was good with low or medium risk-of-bias. ConclusionTo our knowledge, this is the first systematic review on the impact of oral infection on organ transplantation. The results suggest a possible link between persisting oral infection and posttransplant infectious complications, thus lending support to the elimination of oral infectious foci before solid organ transplantation.

Endogenous Endophthalmitis in the Setting of Kidney Disease: A Case Series

Blood stream infections (BSI) are common in patients with kidney disease. Metastatic foci of infections are one of the known complications of BSI. Endophthalmitis which is defined as infection and inflammation of the inner coats of the eye ball and intraocular fluids (aqueous and vitreous), is one such focus. We discuss the clinical profile of five patients who had endogenous endophthalmitis in the setting of kidney disease and their management and outcome. All five had diabetes mellitus; the source was central venous catheter in two and urinary tract infection in two. Microbial cause was Staphylococcus aureus in two, Pseudomonas aeruginosa in one, Klebsiella pneumoniae in one and Candida albicans in one. All five required dialysis. Recovery of vision was poor with partial recovery only in two patients. A vision-threatening emergency, this condition requires early identification and management for better recovery of vision.

49533 308-nm excimer light is effective for palmoplantar pustulosis regardless of the presence or absence of focal infection: Single-center real-world experience of treatment for palmoplantar pustulosis

49533 308-nm excimer light is effective for palmoplantar pustulosis regardless of the presence or absence of focal infection: Single-center real-world experience of treatment for palmoplantar pustulosis

Anorectal Pathologies in the Course of Acute Leukaemias; Predictive Parameters.

Patients with leukaemia are exposed to infections as long as they are neutropenic. During this period, anorectal pathologies are among the common foci of infection with high mortality. In this study, we aim to investigate the factors that may have a predictive effect on early diagnosis and rapid intervention in perianal complications occurring in neutropenic patients diagnosed with leukaemia. A total of 90 patients with acute leukaemia, including 45 patients with anorectal pathology and 45 patients without anorectal pathology, were analysed. Demographics, blood group, BMI, haemogram and biochemical parameters at the time of diagnosis, and types of perianal pathology were recorded. In the group of patients with anorectal pathology, WBC, lymphocytes, monocytes, and LDH were significantly (p<0.05) higher, and platelets, MPV, and PCT were significantly (p<0.05) lower. The multivariate model showed significant-independent (p<0.05) efficacy of WBC and MPV values in differentiating patients with and without anorectal pathology. A significant efficacy was observed at the WBC cut-off of 17000 [area under the curve 0.656 (0.542-0.770)] and the MPV cut-off of 10 [area under the curve 0.667 (0.554-0.780)] in differentiating patients with and without anorectal pathology. Anorectal pathologies are common foci of infection in patients with acute leukaemia. Having predictive parameters that may help for early intervention will help the clinician. This is the first study in the literature to compare a control group with a group with anorectal pathologies in leukaemia patients providing a cut-off for WBC.

Fatigue and depression at 8 weeks and 1 year after bacterial brain abscess and their relationship with cognitive status

ABSTRACT A bacterial brain abscess (BA) is a focal brain infection with largely unknown long-term implications. This prospective study assessed the frequency of fatigue and symptoms of depression at 8 weeks and 1 year after BA and examined the relationship between fatigue, depressive symptoms, and cognitive status. Twenty BA-patients (age 17–73; 45% female) were assessed for fatigue, depression, memory, and executive functions. Fatigue rates were 40-65% at 8 weeks and 25-33% at 1 year on various fatigue questionnaires. Patient Health Questionnaire indicated symptoms of depression in 10% at the 8-week follow-up only. Relevant comorbidities and vocational outcomes were not associated with fatigue or symptoms of depression. Mean fatigue scores improved significantly between the two-time points. Greater fatigue was related to subjective problems with working memory, inhibition, self-monitoring, and emotional control and worse objective verbal memory performance. Symptoms of depression were associated with one out of two fatigue measures. We conclude that fatigue is common in the first year after BA, and higher levels of fatigue are related to more cognitive problems. Symptoms of clinical depression were rare. These findings underscore fatigue as an important consequence of BA and emphasize the necessity for targeted rehabilitation interventions.

The efficacy of cuff-shaving combined with negative pressure wound therapy in refractory exit-site and tunnel infections: a single center experience

BackgroundRefractory exit-site infections (ESIs) and tunnel infections (TIs) are challenging complications for patients undergoing peritoneal dialysis (PD). This study compared the outcomes of surgical intervention, notably the cuff-shaving (CS) procedure coupled with negative-pressure wound therapy (NPWT), and conservative management strategies for patients with refractory ESI and TI.MethodsWe retrospectively reviewed patients who underwent PD at our center, focusing on the incidence and management of ESI and TI. We evaluated and compared treatment outcomes, including ESI scores, frequency of ESI and/or TI, identification of causative microorganisms, and duration of catheter survival or time until removal.ResultsWe identified 97 episodes of catheter-related ESI and/or TI across 71 patients with an incidence rate of 0.15 episodes per patient-year. Of the 23 patients with refractory ESI and/or TI, surgical intervention was performed in 8, while 15 chose conservative management. In the one-month follow-up, patients who underwent CS combined with NPWT showed no complications such as leakage, and their local symptoms resolved completely. The mean PD catheter survival time was significantly longer in the surgical group (29.38 ± 7.25 months) than in the conservative group (7.86 ± 2.13 months). Surgical intervention demonstrated a significantly higher therapeutic efficacy and extended catheter survival.ConclusionsThe combination of CS and NPWT as a surgical approach is crucial for eradicating infectious foci and significantly improving the longevity of PD catheter function. This integrated surgical strategy offers a promising solution for the management of refractory ESI and TI in patients undergoing PD.

Infectious Foci, Comorbidities and Its Influence on the Outcomes of Septic Critically Ill Patients.

Sepsis is among the most frequent diagnoses on admission to the intensive care unit (ICU). A systemic inflammatory response, activated by uncontrolled infection, fosters hypoperfusion and multiorgan failure and often leads to septic shock and mortality. These infections arise from a specific anatomic source, and how the infection foci influence the outcomes is unknown. All patients admitted to the ICU of Hospital de Vila Franca de Xira, between 1 January 2017 and 31 June 2023, were screened for sepsis and categorized according to their infection foci. During the study period, 1296 patients (32.2%) had sepsis on admission. Their mean age was 67.5 ± 15.3 and 58.1% were male; 73.0% had community-acquired infections. The lung was the main focus of infection. Septic shock was present in 37.9% of the patients and was associated with hospital mortality. Severe imbalances were noted in its incidence, and there was lower mortality in lung infections. The hospital-acquired infections had a slightly higher mortality but, after adjustment, this difference was non-significant. Patients with secondary bacteremia had a worse prognosis (one-year adjusted hazard ratio of 1.36, 95% confidence interval 1.06-1.74, p = 0.015), especially those with an isolated non-fermenting Gram-negative infection. Lung, skin, and skin structure infections and peritonitis had a worse prognosis, whilst urinary, biliary tract, and other intra-abdominal infections had a better one-year outcome.

Source Control and Antibiotics in Intra-Abdominal Infections.

Intra-abdominal infections (IAIs) account for a major cause of morbidity and mortality, representing the second most common sepsis-related death with a hospital mortality of 23-38%. Prompt identification of sepsis source, appropriate resuscitation, and early treatment with the shortest delay possible are the cornerstones of management of IAIs and are associated with a more favorable clinical outcome. The aim of source control is to reduce microbial load by removing the infection source and it is achievable by using a wide range of procedures, such as definitive surgical removal of anatomic infectious foci, percutaneous drainage and toilette of infected collections, decompression, and debridement of infected and necrotic tissue or device removal, providing for the restoration of anatomy and function. Damage control surgery may be an option in selected septic patients. Intra-abdominal infections can be classified as uncomplicated or complicated causing localized or diffuse peritonitis. Early clinical evaluation is mandatory in order to optimize diagnostic testing and establish a therapeutic plan. Prognostic scores could serve as helpful tools in medical settings for evaluating both the seriousness and future outlook of a condition. The patient's conditions and the potential progression of the disease determine when to initiate source control. Patients can be classified into three groups based on disease severity, the origin of infection, and the patient's overall physical health, as well as any existing comorbidities. In recent decades, antibiotic resistance has become a global health threat caused by inappropriate antibiotic regimens, inadequate control measures, and infection prevention. The sepsis prevention and infection control protocols combined with optimizing antibiotic administration are crucial to improve outcome and should be encouraged in surgical departments. Antibiotic and antifungal regimens in patients with IAIs should be based on the resistance epidemiology, clinical conditions, and risk for multidrug resistance (MDR) and Candida spp. infections. Several challenges still exist regarding the effectiveness, timing, and patient stratification, as well as the procedures for source control. Antibiotic choice, optimal dosing, and duration of therapy are essential to achieve the best treatment. Promoting standard of care in the management of IAIs improves clinical outcomes worldwide. Further trials and stronger evidence are required to achieve optimal management with the least morbidity in the clinical care of critically ill patients with intra-abdominal sepsis.

Prophylactic intravenous immunoglobulin use in allogeneic stem cell transplantation; does intravenous immunoglobulin affect survival, sepsis, and engraftment time?

Abstract: BACKGROUND: Stem cell transplant recipients have an increase in various infections depending on the immunosuppression. The purpose is to explore the effect of the use of proflactıc intravenous immunoglobulin (IVIG) on transplant recıpıents. OBJECTIVE: It was aimed to examine the effect of IVIG on allogeneic stem cell transplantation. MATERIALS AND METHODS: In this study, sepsis status, infection focus causing sepsis, neutrophil and platelet engraftment time of patients the length of stay in the hospital at the time of the stem cell transplant, if the patient died, how many days after the transplant the event developed, and the data of the bone marrow transplant unit were reviewed retrospectively. One hundred and eleven patients who were given IVIG (400 mg/kg/week IVIG intravenous was given to the patients as a weekly prophylactic up to 100 days starting on the 7th day after transplantation) and 190 patients who did not receive IVIG were included in the study. RESULTS: There was no statistically significant difference between the IVIG groups in terms of gender, diagnosis, donor characteristics, and event (P &gt; 0.05). Sepsis was observed significantly less in patients who were given IVIG compared to patients who were not given IVIG (P &lt; 0.001). While it was observed that IVIG did not have a significant effect on platelet engraftment and discharge times (P &gt; 0.05), neutrophil engraftment time was significantly higher in patients given IVIG compared to patients not given IVIG (P &lt; 0.009). It was observed that the use of IVIG in patients with sepsis did not have a positive effect on survival. (with sepsis hazard ratio [HR]: 3.890 P = 0.001, IVIG given HR: 3.244 P = 0.035). CONCLUSION: It was observed that the use of IVIG in allogeneic stem cell transplantation was associated with a decrease in sepsis, but the use of IVIG did not have a positive effect on survival and could prolong neutrophil engraftment.

Epidemiological patterns of natural focal diseases of the Voronezh region

Diseases of animals and humans are widespread and are confined to the habitat of the reservoir. Urbanization has led to the expansion of the range of natural focal diseases with the formation of persistent anthropurgic foci.The purpose of the work was to study the epizootic manifestations of natural focal diseases and analyze the morbidity of the population of the Voronezh region. The research material was based on data from federal statistical observation forms No. 2 for 2012–2022, and the results of epizootological monitoring of the department of natural focal infections and laboratories of the Center for Hygiene and Epidemiology in the Voronezh region. A retrospective epidemiological analysis of the morbidity rate of the population of the Voronezh region was carried out, ranking administrative territories based on the method of standard deviations. The results obtained were processed using Microsoft Excel; the long-term average incidence rate, error of the mean, confidence intervals, and significance level (p) less than 0.05 were calculated. The result of the analysis showed that the long-term average incidence rate of natural focal diseases in the Voronezh region was 9.91 per 100,000 population. In the structure of nosological forms, 85.98 % were tick-borne borreliosis and hemorrhagic fever with renal syndrome. The long-term average incidence rate of Lyme disease is 4.45 per 100,000 population, hemorrhagic fever with renal syndrome is 0.87 per 100,000 population. According to the ranking results, the Ramonsky, Ternovsky and Anninsky administrative territories were classified as risk areas for the average long-term incidence of borreliosis, and the Ramonsky, Verkhnekhava and Paninsky administrative territories for hemorrhagic fever with renal syndrome. The results obtained indicate active natural foci of infections in the Voronezh region.

Epidemiological situation of natural focal infections in the Volgograd region in 2022

The article is devoted to the analysis of the epidemiological situation of natural focal infections (NFI) in the Volgograd region in 2022. Materials and methods: The work used the official statistics of the institutions of Rospotrebnadzor on NFI for 2022. The main research method is epidemiological analysis. Results and discussion: It has been established that the numbers of small mammals, potential carriers of NFI, as well as ixodid ticks in the territory of the Volgograd region in the season of 2022 were higher than the same indicators of the previous year (SIPY). The number of mosquitoes, carriers of arbovirus infections, did not exceed the average long-term indicators in any species. When examining environmental objects for the presence of markers of NFI pathogens, a slight increase in the proportion of positive samples compared to SIPY in all nosological forms was noted. Sporadic cases of West Nile fever (WNF), Crimean hemorrhagic fever (CHF), hemorrhagic fever with renal syndrome (HFRS), ixodes ricinus-borne diseases (TBDs), Q fever have been registered; no cases of tularemia, rabies, leptospirosis were detected. The morbidity rates of the population of the Volgograd region for all NFI were at the level or lower than those for the Russian Federation and the Southern Federal District.

Early stoppage of empirical antibiotic therapy at clinical improvement in paediatric leukaemia patients with high-risk febrile neutropenia (ESAT-HR-FN study): Study protocol of a single centre investigator initiated randomised open label non-inferiority trial

Background and rationaleFebrile neutropenia (FN) is one of the major causes of early mortality among children undergoing induction chemotherapy for haematological malignancies. FN occurs in up to 80 % of the children undergoing intensive chemotherapy and FN specific mortality is as high as 10 %. The management of high-risk FN (HR-FN) is by early initiation of broad-spectrum empirical antibiotic therapy (EAT) which is continued till blood count recovery. Adverse effects of prolonged EAT among children without proven infective focus have questioned the rationale behind the duration of EAT. The non inferiority of early stoppage of EAT in patients with low-risk FN (LR-FN) when afebrile for 48 h, irrespective of marrow recovery, is proven among adults and children. However, there is paucity of data regarding the same in children with HR-FN. This study aims to determine whether early discontinuation of EAT in children with HR-FN without proven infective focus who become afebrile and awaiting marrow recovery, would reduce antibiotic duration and their adverse effects without any negative consequences for patients. ObjectiveTo compare the rates of recurrent fever in paediatric patients (2–18 years) with HR-FN when EAT is continued till marrow recovery (control group) versus when stopped early at defervescence irrespective of marrow recovery (study group). MethodologyThis is the study protocol of a phase 3, single centre, randomized, open label, non-inferiority clinical trial. The primary outcome is the rate of fever recurrence among patients with HR-FN, when EAT is stopped early irrespective of marrow recovery (study group) and will be compared to the rate of fever recurrence on continuation of EAT till marrow recovery which is defined as an absolute neutrophil count (ANC) ≥ 500/mm3 (control group). Secondary outcomes include the comparison of duration of antibiotic use, mortality rates, hospital re-admission rates, requirement of multiple broad-spectrum antibiotics, therapeutic anti-fungal usage and need for organ support between the study and the control groups. A total of 280 children with acute leukaemia undergoing EAT for grade 3 or severe FN (ANC <500/μL) without clinico-laboratory evidence of infective foci are being randomized in the ratio of 1:1 between the study and the control group after defervescence for 48 h. The patients will be followed up for primary outcome (fever recurrence) till the end of induction period (day 35) or recovery of ANC ≥500/mm3 whichever is earlier. Expected outcomeESAT-HR FN study is the first large phase 3 randomised study to assess the impact of early stoppage of EAT irrespective of marrow recovery among a homogenous paediatric cohort of HR-FN in the setting of induction chemotherapy for acute leukaemia. This study will be seminal in addressing the duration of EAT in HR-FN among children without infective foci and if proven to be non-inferior this strategy will help to reduce the adverse effects from prolonged antibiotic use, the emergence of drug resistance, decrease hospital stay length and overall health care costs.

Lincoln Sign in Synovitis, Acne, Pustulosis, Hyperostosis, and Osteomyelitis Syndrome.

Synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO) syndrome is characterized by skin lesions and osteomyelitis. Although the pathogenesis of SAPHO syndrome remains unclear, chronic focal infection may play a role in the development of excessive immune responses.

Engineering mesoporous polydopamine-based potentiate STING pathway activation for advanced anti-biofilm therapy

The biofilm-induced “relatively immune-compromised zone” creates an immunosuppressive microenvironment that is a significant contributor to refractory infections in orthopedic endophytes. Consequently, the manipulation of immune cells to co-inhibit or co-activate signaling represents a crucial strategy for the management of biofilm. This study reports the incorporation of Mn2+ into mesoporous dopamine nanoparticles (Mnp) containing the stimulator of interferon genes (STING) pathway activator cGAMP (Mncp), and outer wrapping by M1-like macrophage cell membrane (m-Mncp). The cell membrane enhances the material's targeting ability for biofilm, allowing it to accumulate locally at the infectious focus. Furthermore, m-Mncp mechanically disrupts the biofilm through photothermal therapy and induces antigen exposure through photodynamic therapy-generated reactive oxygen species (ROS). Importantly, the modulation of immunosuppression and immune activation results in the augmentation of antigen-presenting cells (APCs) and the commencement of antigen presentation, thereby inducing biofilm-specific humoral immunity and memory responses. Additionally, this approach effectively suppresses the activation of myeloid-derived suppressor cells (MDSCs) while simultaneously boosting the activity of T cells. Our study showcases the efficacy of utilizing m-Mncp immunotherapy in conjunction with photothermal and photodynamic therapy to effectively mitigate residual and recurrent infections following the extraction of infected implants. As such, this research presents a viable alternative to traditional antibiotic treatments for biofilm that are challenging to manage.

National study reveals gram negative bacteremia on contemporary pediatric AML protocol

Since bacteremia complicates childhood Acute myeloid leukemia (AML) patients, we assessed bacteremia rates in Israeli children with de-novo AML. All chemotherapy courses of patients enrolled in NOPHO-DBH-2012 AML protocol were included. Down syndrome, acute promyelocytic leukemia were excluded. Among 69 patients, seven had focal bacterial infections. Of the remaining 62, 77.4% had 1–8 bacteremias. Of 238 chemotherapy courses, 98 (41.2%) had bacteremia: 66 (67.3%) predominantly Gram-negative rods (GNR); 28 (28.6%) Gram-positive cocci. Escherichia coli; followed by Klebsiella were most common. Older age, Arab ethnicity, and presenting white blood cell count were associated with an increased risk of bacteremia in the univariable analysis, but these associations were not confirmed in the multivariable analysis. Mortality was high (9.7%), and bacteremia increased PICU utilization 7-fold half from GNR. Most isolates were sensitive to vancomycin/meropenem (94.7%), but GNR had low sensitivity to quinolones (61.8%). High mortality and morbidity of de-novo AML patients from predominantly GNR bacteremia require specific interventions but limited susceptibility to quinolones hampers prophylaxis.

Late cholangitis after pancreatoduodenectomy: A common complication with or without anatomical biliary obstruction

BackgroundPostoperative cholangitis is a common complication after pancreatoduodenectomy that can occur with or without anatomical biliary obstruction. This study aimed to investigate the incidence, diagnosis, treatment, and risk factors of cholangitis after pancreatoduodenectomy. MethodsWe performed a retrospective cohort study of consecutive patients who underwent pancreatoduodenectomy in 2 Dutch tertiary pancreatic centers (2010–2019). Primary outcome was postoperative cholangitis, defined as systemic inflammation with abnormal liver tests without another focus of infection, at least 1 month after resection. Diagnostic and therapeutic strategies were evaluated. Two types of postoperative cholangitis were distinguished; obstructive cholangitis (benign stenosis of the hepaticojejunostomy) and nonobstructive cholangitis. Potential risk factors were identified using logistic regression analysis. ResultsPostoperative cholangitis occurred in 93 of 900 patients (10.3%). Median time to first episode of cholangitis was 8 months (interquartile range 4–16) after pancreatoduodenectomy. Multiple episodes of cholangitis occurred in 44 patients (47.3%) and readmission was necessary in 83 patients (89.2%). No cholangitis-related mortality was observed. Obstructive cholangitis was seen in 37 patients (39.8%) and nonobstructive cholangitis in 56 patients (60.2%). Surgery was performed for cholangitis in 7 patients (7.5%) and consisted of revision of the hepaticojejunostomy or elongation of the biliary limb. Postoperative biliary leakage (odds ratio 2.56; 95% confidence interval 1.42–4.62; P = .0018) was independently associated with postoperative cholangitis. ConclusionPostoperative cholangitis unrelated to cancer recurrence was seen in 10% of patients after pancreatoduodenectomy. Nonobstructive cholangitis was more common than obstructive cholangitis. Postoperative biliary leakage was an independent risk factor.

Parenteral chronic viral hepatitis in the Arctic zone of the Republic of Sakha (Yakutia) as the most important medical and social problem

Background. The severe course of parenteral viral hepatitis and their further chronicity are associated with the presence of immunodeficiency disorders, frequency of which increases significantly in harsh climate. The article discusses the spread of parenteral viral hepatitis in the Arctic zone of the Republic of Sakha (Yakutia) and the issues of organizing medical care for patients with chronic viral hepatitis at the regional level.The aim of the study. To analyze the incidence rates of parenteral viral hepatitis in the Arctic regions of Yakutia in order to improve the health care system using the example of remote areas of hard access.Methods. The work uses materials from official statistics of the territorial department of Rospotrebnadzor for the Republic of Sakha (Yakutia) for 2000–2022 and information from the “Chronic viral hepatitis in the Republic of Sakha (Yakutia)” register. Results. In the Arctic regions of Yakutia, problems are observed in chronic forms of viral hepatitis B, C and D, as well as in their outcomes, such as cirrhosis and liver cancer, leading to early disability and mortality. In the general structure, hepatitis B infection prevails, which indicates the presence of family foci of infection. All this requires a complex of not only therapeutic, but also advanced anti-epidemiological measures.Conclusion. The difficult epidemiological situation regarding parenteral viral hepatitis, caused by extreme natural and climatic conditions, genetic characteristics of the indigenous population and the lack of medical institutions specializing in the treatment of chronic viral hepatitis, dictates the need to strengthen systematic on-site monitoring studies and telemedicine consultations in the Arctic zone of Yakutia. Thanks to this, residents of hard-to-reach areas of the Arctic zone of the Republic of Sakha (Yakutia) will be able to receive targeted subsidized care for the treatment of chronic hepatitis without traveling to Yakutsk.

Highly restrictive and directional penetration of the blood cerebral spinal fluid barrier by JCPyV.

The human polyomavirus JCPyV is an opportunistic pathogen that infects greater than 60% of the world's population. The virus establishes a persistent and asymptomatic infection in the urogenital system but can cause a fatal demyelinating disease in immunosuppressed or immunomodulated patients following invasion of the CNS. The mechanisms responsible for JCPyV invasion into CNS tissues are not known but direct invasion from the blood to the cerebral spinal fluid via the choroid plexus has been hypothesized. To study the potential of the choroid plexus as a site of neuroinvasion, we used an adult human choroid plexus epithelial cell line to model the blood-cerebrospinal fluid (B-CSF) barrier in a transwell system. We found that these cells formed a highly restrictive barrier to virus penetration either as free virus or as virus associated with extracellular vesicles (EVJC+). The restriction was not absolute and small amounts of virus or EVJC+ penetrated and were able to establish foci of infection in primary astrocytes. Disruption of the barrier with capsaicin did not increase virus or EVJC+ penetration leading us to hypothesize that virus and EVJC+ were highly cell-associated and crossed the barrier by an active process. An inhibitor of macropinocytosis increased virus penetration from the basolateral (blood side) to the apical side (CSF side). In contrast, inhibitors of clathrin and raft dependent transcytosis reduced virus transport from the basolateral to the apical side of the barrier. None of the drugs inhibited apical to basolateral transport suggesting directionality. Pretreatment with cyclosporin A, an inhibitor of P-gp, MRP2 and BCRP multidrug resistance transporters, restored viral penetration in cells treated with raft and clathrin dependent transcytosis inhibitors. Because choroid plexus epithelial cells are known to be susceptible to JCPyV infection both in vitro and in vivo we also examined the release of infectious virus from the barrier. We found that virus was preferentially released from the cells into the apical (CSF) chamber. These data show clearly that there are two mechanisms of penetration, direct transcytosis which is capable of seeding the CSF with small amounts of virus, and infection followed by directional release of infectious virions into the CSF compartment.

First-in-human infection imaging with 89Zr-labelled leukocytes and comparison of scan quality with [99mTc]Tc-HMPAO-labelled leukocytes.

Nuclear medicine infection imaging is routinely performed with the use of leukocytes radiolabelled with technetium-99m hexamethylpropyleneamine oxime ([99mTc]Tc-HMPAO) and single-photon emission computed tomography (SPECT). Positron emission tomography (PET) is more sensitive than SPECT and results in higher-quality images. Zirconium-89 (89Zr) is a positron emitter with a half-life of 78.4 h, which translates to the biological half-life and slow biodistribution of intact cells and allows delayed PET imaging for more accurate biodistribution of the labelled leukocytes to infection foci. A first-in-human study with [89Zr]Zr-oxine-leukocytes in four healthy volunteers was reported in 2022. Our first-in-human study utilising the cell surface labelling approach aimed to image infection in patients with the use of 89Zr-labelled leukocytes, using p-isothiocyanatobenzyl-desferrioxamine B (Df-Bz-NCS) as a bifunctional chelating agent, and to compare the scan quality and biodistribution of [89Zr]Zr-Df-Bz-NCS-labelled leukocytes on PET images to SPECT images obtained with [99mTc]Tc-HMPAO-labelled leukocytes. Leukocytes were isolated from whole-blood samples of eight patients with clinically and/or radiologically confirmed infection. Isolated leukocytes were labelled with [99mTc]Tc-HMPAO according to standardised methods, and [89Zr]Zr-Df-Bz-NCS according to our previously published radiolabelling method. Whole-body SPECT imaging was performed 2 and 18 h post injection of [99mTc]Tc-HMPAO-labelled leukocytes, and whole-body PET/CT was performed 3 and 24 h post injection of [89Zr]Zr-Df-Bz-NCS-labelled leukocytes in seven patients. Successful [89Zr]Zr-Df-Bz-NCS-leukocyte labelling was achieved. High labelling efficiencies were obtained (81.7% ± 3.6%; n = 8). A mean high viability of [89Zr]Zr-Df-Bz-NCS-labelled leukocytes was observed (88.98% ± 12.51%). The [89Zr]Zr-Df-Bz-NCS-leukocyte labelling efficiency was not significantly affected by the white blood cell count of the patient. The performance of [99mTc]Tc-HMPAO- and [89Zr]Zr-Df-Bz-NCS-labelled leukocytes, in terms of the ability to accurately detect infection, were similar in two out of seven patients, and [99mTc]Tc-HMPAO-labelled leukocytes outperformed [89Zr]Zr-Df-Bz-NCS-labelled leukocytes in one patient with femoral osteomyelitis. However, in two cases of pulmonary pathology, [89Zr]Zr-Df-Bz-NCS-labelled leukocytes demonstrated improved pathological uptake. No skeletal activity was observed in any of the patients imaged with [89Zr]Zr-Df-Bz-NCS-labelled leukocytes, illustrating the in vivo stability of the radiolabel. Although the [89Zr]Zr-Df-Bz-NCS-leukocyte labelling aspect of this study was noteworthy, infection imaging did not yield convincingly positive results due to the pulmonary trapping of intravenously administered [89Zr]Zr-Df-Bz-NCS-labelled leukocytes.