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19 pages, 1914 KB  
Article
Hospital-Based Genomic Surveillance of Klebsiella pneumoniae: Trends in Resistance and Infection
by Erica Olund-Matos, Ricardo Franco-Duarte, André Santa-Cruz, Maria Nogueira, Margarida Correia-Neves, Diana Lopes, Rui Jorge Silva, Margarida Ribeiro Araújo, Inês Monteiro Araújo, Ana Filipa Martins, Carolina Maia Nogueira, Alberta Faustino, Pedro G. Cunha, Pedro Soares and Teresa Rito
Biology 2025, 14(12), 1795; https://doi.org/10.3390/biology14121795 - 16 Dec 2025
Viewed by 277
Abstract
Klebsiella pneumoniae (Kp) is a leading cause of hospital-acquired infections representing a growing threat driven by emerging multidrug resistance (MDR) and hypervirulence. In this study, we aim to characterise the genomic and epidemiological landscape of Kp in a Portuguese regional hospital (Braga) lacking [...] Read more.
Klebsiella pneumoniae (Kp) is a leading cause of hospital-acquired infections representing a growing threat driven by emerging multidrug resistance (MDR) and hypervirulence. In this study, we aim to characterise the genomic and epidemiological landscape of Kp in a Portuguese regional hospital (Braga) lacking prior genomic data. We performed whole-genome sequencing of 115 Kp isolates collected from colonisation and infection cases. Phylogenetic, resistance, and virulence profiles were integrated with clinical and epidemiological data. Genomic analysis revealed high diversity, with 83.5% of isolates forming evolutionary clusters. Several novel sequence types (STs), as ST2623 and ST1562, were detected for the first time in Portugal to our knowledge. ST45, uncommonly associated with carbapenem resistance, emerged as dominant with multiple blaKPC-3-positive isolates. Results suggest active transmission of carbapenem resistance genes. One hypervirulent carbapenem-resistant ST13 warrants careful surveillance. Virulence-associated yersiniabactin was common (66.9%) but other hypervirulence loci were rare. Epidemiologically, MDR-Kp was associated with older hospitalised patients with prior antibiotic use and invasive procedures, while community-acquired infections were genetically diverse and affected younger patients with comorbidities. An unusually low number of respiratory infections was observed, likely reflecting strict COVID-19 mitigation measures. Although widespread dissemination of hypervirulent or MDR clones was not evident, the emergence of high-risk lineages and the detection of ongoing gene transmission episodes underscore the need for ongoing genomic surveillance. Immediate mitigation strategies could include reducing device use and hospital transfers, given the high prevalence of colonisation. Full article
(This article belongs to the Section Microbiology)
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26 pages, 5734 KB  
Article
AI-Based Quantitative HRCT for In-Hospital Adverse Outcomes and Exploratory Assessment of Reinfection in COVID-19
by Xin-Yi Feng, Fei-Yao Wang, Si-Yu Jiang, Li-Heng Wang, Xin-Yue Chen, Shi-Bo Tang, Fan Yang and Rui Li
Diagnostics 2025, 15(24), 3156; https://doi.org/10.3390/diagnostics15243156 - 11 Dec 2025
Viewed by 297
Abstract
Background/Objectives: Quantitative computed tomography (CT) metrics are widely used to assess pulmonary involvement and to predict short-term severity in coronavirus disease 2019 (COVID-19). However, it remains unclear whether baseline artificial intelligence (AI)-based quantitative high-resolution computed tomography (HRCT) metrics of pneumonia burden provide [...] Read more.
Background/Objectives: Quantitative computed tomography (CT) metrics are widely used to assess pulmonary involvement and to predict short-term severity in coronavirus disease 2019 (COVID-19). However, it remains unclear whether baseline artificial intelligence (AI)-based quantitative high-resolution computed tomography (HRCT) metrics of pneumonia burden provide incremental prognostic value for in-hospital composite adverse outcomes beyond routine clinical factors, or whether these imaging-derived markers carry any exploratory signal for long-term severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) reinfection among hospitalized patients. Most existing imaging studies have focused on diagnosis and acute-phase prognosis, leaving a specific knowledge gap regarding AI-based quantitative HRCT correlates of early deterioration and subsequent reinfection in this population. To evaluate whether combining deep learning-derived, quantitative, HRCT features and clinical factors improve prediction of in-hospital composite adverse events and to explore their association with long-term reinfection in patients with COVID-19 pneumonia. Methods: In this single-center retrospective study, we analyzed 236 reverse-transcription polymerase chain reaction (RT-PCR)-confirmed COVID-19 patients who underwent baseline HRCT. Median follow-up durations were 7.65 days for in-hospital outcomes and 611 days for long-term outcomes. A pre-trained, adaptive, artificial-intelligence-based, prototype model (Siemens Healthineers) was used for pneumonia analysis. Inflammatory lung lesions were automatically segmented, and multiple quantitative metrics were extracted, including opacity score, volume and percentage of opacities and high-attenuation opacities, and mean Hounsfield units (HU) of the total lung and opacity. Patients were stratified based on receiver operating characteristic (ROC)-derived optimal thresholds, and multivariable Cox regression was used to identify predictors of the composite adverse outcome (intensive care unit [ICU] admission or all-cause death) and SARS-CoV-2 reinfection, defined as a second RT-PCR-confirmed episode of COVID-19 occurring ≥90 days after initial infection. Results: The composite adverse outcome occurred in 38 of 236 patients (16.1%). Higher AI-derived opacity burden was significantly associated with poorer outcomes; for example, opacity score cut-off of 5.5 yielded an area under the ROC curve (AUC) of 0.71 (95% confidence interval [CI] 0.62–0.79), and similar performance was observed for the volume and percentage of opacities and high-attenuation opacities (AUCs up to 0.71; all p < 0.05). After adjustment for age and comorbidities, selected HRCT metrics—including opacity score, percentage of opacities, and mean HU of the total lung (cut-off −662.38 HU; AUC 0.64, 95% CI 0.54–0.74)—remained independently associated with adverse events. Individual predictors demonstrated modest discriminatory ability, with C-indices of 0.59 for age, 0.57 for chronic obstructive pulmonary disease (COPD), 0.62 for opacity score, 0.63 for percentage of opacities, and 0.63 for mean total-lung HU, whereas a combined model integrating clinical and imaging variables improved prediction performance (C-index = 0.68, 95% CI: 0.57–0.80). During long-term follow-up, RT-PCR–confirmed reinfection occurred in 18 of 193 patients (9.3%). Higher baseline CT-derived metrics—particularly opacity score and both volume and percentage of high-attenuation opacities (percentage cut-off = 4.94%, AUC 0.69, 95% CI 0.60–0.79)—showed exploratory associations with SARS-CoV-2 reinfection. However, this analysis was constrained by the very small number of events (n = 18) and wide confidence intervals, indicating substantial statistical uncertainty. In this context, individual predictors again showed only modest C-indices (e.g., 0.62 for procalcitonin [PCT], 0.66 for opacity score, 0.66 for the volume and 0.64 for the percentage of high-attenuation opacities), whereas the combined model achieved an apparent C-index of 0.73 (95% CI 0.64–0.83), suggesting moderate discrimination in this underpowered exploratory reinfection sample that requires confirmation in external cohorts. Conclusions: Fully automated, deep learning-derived, quantitative HRCT parameters provide useful prognostic information for early in-hospital deterioration beyond routine clinical factors and offer preliminary, hypothesis-generating insights into long-term reinfection risk. The reinfection-related findings, however, require external validation and should be interpreted with caution given the small number of events and limited precision. In both settings, combining AI-based imaging and clinical variables yields better risk stratification than either modality alone. Full article
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11 pages, 332 KB  
Article
Pathogen-Specific Risk for Iterative Surgical Debridement in Orthopedic Infections: A Prospective Multicohort Analysis
by Flamur Zendeli, Anna Jędrusik, Raymond O. Schaefer, David Albrecht, Michael Betz, Felix W. A. Waibel, Tanja Gröber, Nathalie Kühne, Sören Könneker and İlker Uçkay
J. Clin. Med. 2025, 14(24), 8750; https://doi.org/10.3390/jcm14248750 - 10 Dec 2025
Viewed by 230
Abstract
Background/Objectives: Almost all orthopedic infections require a combination of surgical debridement with targeted antimicrobial treatment. The number of debridement procedures may vary considerably between infection episodes. The case mix is large, and so-called “second looks” are frequent. We investigate which bacteria are [...] Read more.
Background/Objectives: Almost all orthopedic infections require a combination of surgical debridement with targeted antimicrobial treatment. The number of debridement procedures may vary considerably between infection episodes. The case mix is large, and so-called “second looks” are frequent. We investigate which bacteria are associated with second looks to achieve local infection control. Methods: We used a composite database stemming from three prospective randomized controlled trials (RCTs) from 2019 to 2025 with protocoled surgical debridement (initial debridement). In these RCTs, we allowed additional debridement only in the case of persistent or progressive local infection. Results: Overall, 201/1067 (18.8%) orthopedic infections required multiple debridement procedures. The median number of additional debridement procedures was two across all pathogen groups, with a range of 2–8 interventions. Gram-negative pathogens revealed the highest risk for “second looks” (28.2%), followed by implant-related infections (25.4%). Cutibacteria yielded the lowest risk (11.7%). In the multivariable logistic regression model, Gram-negative infections (OR 2.04, 95%CI 1.20–3.47) and infected implants (OR 2.18, 95%CI 1.56–3.03) were independently associated with multiple interventions, in contrast to Staphylococcus aureus, Enterococci, or Streptococci. Conclusions: Gram-negative pathogens were significantly associated with the need for second looks in orthopedic infections. The findings support preoperative counseling, antibiotic stewardship, and operative planning for staged management in infection cases with a high risk of clinical failure. Trials registrations: NCT04048304, NCT04081792, NCT05499481. Full article
(This article belongs to the Section Infectious Diseases)
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11 pages, 214 KB  
Case Report
Challenges and Strategies in Managing Recurrent Clostridioides difficile Infection in Older Adults
by Imaan Hirji, Divya John, Jeena Jith, Hiro Khoshnaw and Myooran Ganeshananthan
Geriatrics 2025, 10(6), 158; https://doi.org/10.3390/geriatrics10060158 - 2 Dec 2025
Viewed by 359
Abstract
Background: Clostridioides difficile infections (CDIs) are caused by a Gram-positive, spore-forming bacillus and are defined by more than three episodes of watery diarrhoea per day. CDI is a major cause of morbidity and mortality in older adults, particularly over 65 years. Recurrent CDI [...] Read more.
Background: Clostridioides difficile infections (CDIs) are caused by a Gram-positive, spore-forming bacillus and are defined by more than three episodes of watery diarrhoea per day. CDI is a major cause of morbidity and mortality in older adults, particularly over 65 years. Recurrent CDI leads to higher mortality and prolonged, debilitating illness. Case Presentations: This article presents two patients, aged over 80 years old, who developed recurrent CDI causing complicated and prolonged treatment courses. Patient 1 required an extended course of antibiotics for treatment of discitis and a congruent psoas abscess. Patient 2 developed CDI after multiple short courses of antibiotics for urinary tract infections (UTIs) in the context of multiple comorbidities. Both patients experienced three distinct episodes of CDI and were treated in collaboration with microbiology specialists. Following the third episode, both were successfully treated with oral capsule faecal microbiome transplants (FMTs). Their cases highlight the challenge of balancing systemic antibiotic use against CDI risk. Discussions: These cases underscore known risk factors for recurrent CDI, including advanced age and prolonged antibiotic exposure. Recurrence rates in patients over 65 can reach 58%. The British Society of Gastroenterology and Healthcare Infection Society support the use of FMTs in recurrent cases. Environmental decontamination, including terminal cleaning with sporicidal agents, is critical in reducing reinfection in hospital settings. Conclusions: Recurrent CDI in elderly patients reflects a complex interplay between infection control and managing comorbidities. New guidelines suggest that FMTs can significantly reduce morbidity and mortality. These cases emphasise the need for individualised, multidisciplinary care, adherence to guidelines, and further research to improve safe, effective CDI management in older adults. Full article
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18 pages, 2556 KB  
Article
Identification of Risk Factors in Patients with Recurrent Cystitis May Improve Individualized Management
by Jakhongir F. Alidjanov, Ulugbek A. Khudaybergenov, Khurshid B. Khudayberdiev, Jennifer Kranz, Laila Schneidewind, Fabian P. Stangl, José Medina-Polo, Adrian Pilatz, Tommaso Cai, Kurt G. Naber, Florian M. Wagenlehner and Truls E. Bjerklund Johansen
Diagnostics 2025, 15(22), 2885; https://doi.org/10.3390/diagnostics15222885 - 14 Nov 2025
Viewed by 702
Abstract
Background/Objectives: Management of acute episodes of lower urinary tract infection (LUTI) depends on whether they are sporadic or recurrent. We aimed to define factors that differentiate patients with acute sporadic cystitis (AC) from those with recurrent cystitis (RC) and thereby improve individualized [...] Read more.
Background/Objectives: Management of acute episodes of lower urinary tract infection (LUTI) depends on whether they are sporadic or recurrent. We aimed to define factors that differentiate patients with acute sporadic cystitis (AC) from those with recurrent cystitis (RC) and thereby improve individualized care. Methods: We performed a post hoc analysis of prospectively collected data from the multinational GPIU.COM study. Female patients with an acute LUTI episode completed the Acute Cystitis Symptom Score (ACSS) and underwent a routine clinical and laboratory evaluation, including a physical examination, ultrasonography, urinalysis, and urine culture and antimicrobial susceptibility testing. Risk factors for recurrence were evaluated using the Lower Urinary Tract Infection Recurrence Risk (LUTIRE) nomogram and the ORENUC classification. Statistical analysis followed a robust stepwise approach. Significant variables were assessed by relative risk (RR), and logistic regression was used to estimate odds ratios (ORs). Model performance was evaluated using the area under the curve (AUC), the Hosmer–Lemeshow test, variance inflation factor (VIF), and bootstrap sampling. Results: A total of 106 women were included (AC n = 50; RC n = 56). Patients with RC more frequently presented with a history of constipation, a severe impact of symptoms on daily activities, multiple uropathogens, and trace proteinuria. Pyuria was inversely associated with RC. Logistic regression identified chronic constipation, severe impact of symptoms on daily activities, and multiple uropathogens as independent predictors of RC. Three predictive models showed consistent discrimination between AC and RC (AUC = 0.80, 0.82, and 0.84). Conclusions: AC and RC showed notable differences in certain symptom profiles, quality of life, urinalysis, and microbiological findings. Combining high-value predictors from LUTIRE and ORENUC into a comprehensive prognostic algorithm could improve assessment of recurrence risk. A refined classification of LUTIs with recurrence grading is warranted to guide decision-making and prevention strategies. Full article
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15 pages, 696 KB  
Article
Community-Onset Fungemias: Epidemiology and Genomic Characterization at a Tertiary-Care Hospital in Barcelona, Spain
by Celso Soares Pereira Batista, Alba Rivera, Maria Teresa Alvarez Albarran, Marc Rubio, Iris Belen-Figas, Cristina Lopez-Querol, Elisenda Miró, Ferran Navarro and Ferran Sanchez-Reus
J. Fungi 2025, 11(11), 808; https://doi.org/10.3390/jof11110808 - 14 Nov 2025
Viewed by 602
Abstract
Background: Community-onset fungemia is a clinically significant syndrome frequently linked to recent healthcare exposure and significant morbidity and mortality. Methods: We performed a 21-year, single-centre retrospective cohort of consecutive yeast bloodstream infections diagnosed at the Emergency Department (2004–2024). Clinical/epidemiological data, species identification [...] Read more.
Background: Community-onset fungemia is a clinically significant syndrome frequently linked to recent healthcare exposure and significant morbidity and mortality. Methods: We performed a 21-year, single-centre retrospective cohort of consecutive yeast bloodstream infections diagnosed at the Emergency Department (2004–2024). Clinical/epidemiological data, species identification (MALDI-TOF MS), antifungal susceptibility (CLSI M27; Sensititre YO10), and whole-genome sequencing (WGS) were analyzed. Results: Forty-eight episodes (51 isolates) were included; 56.3% were male, median age 74 years (IQR 63–82). Acquisition was healthcare-associated in 38/48 (79.2%). Sources were unknown (36.7%), abdominal (22.4%), urological (22.4%), catheter-related (14.3%), and 2.1% was attributed to a cardiovascular and a joint focus; 18.8% were polymicrobial. Crude mortality was 20.8% at 7 days (10/48) and 29.2% at 30 days (14/48). Species distribution: Candida albicans 41.2%, Nakaseomyces glabratus 27.5%, Candida parapsilosis 11.8%, Candida tropicalis 11.8%, Pichia kudriavzevii 3.9%, Clavispora lusitaniae 1.9%, and Candida orthopsilosis 1.9%. No isolate was resistant to anidulafungin, micafungin, or amphotericin B; one N. glabratus showed reduced susceptibility to caspofungin. Azole resistance was observed in one C. albicans and one N. glabratus isolate. WGS (44 isolates) confirmed MALDI-TOF identifications and characterized resistance markers. All 12 sequenced N. glabratus carried ERG2 I207V, PDR15/PDH1 E839D, and PDR1 V91I/L98S. Notable cases included one N. glabratus caspofungin-intermediate with FKS2 F659C, N. glabratus fluconazole-resistant with multiple PDR1 substitutions including a unique novel G857V, and C. albicans fluconazole-resistant harbouring alterations in MRR1/MRR2, CDR1, and ERG11. Conclusions: In this 21-year cohort, community-onset fungemia was predominantly healthcare-associated, with C. albicans as the predominant species, followed by N. glabratus. Crude mortality reached 29.2% at 30 days. Echinocandin resistance was not observed; azole resistance was uncommon. WGS provided precise speciation and actionable insight into resistance mechanisms, including a putatively novel PDR1 G857V in N. glabratus. Full article
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18 pages, 1064 KB  
Systematic Review
Patient and Professional Perspectives on Long COVID: A Systematic Literature Review and Meta-Synthesis
by Sophia X. Sui and Lei Yu
Int. J. Environ. Res. Public Health 2025, 22(11), 1620; https://doi.org/10.3390/ijerph22111620 - 24 Oct 2025
Viewed by 1194
Abstract
Background: Post-COVID-19 condition (‘long COVID’) involves fluctuating symptoms across multiple organ systems and disability or functional loss, which may be episodic, continuous, or permanent. Qualitative research is essential to capture lived experiences and explain how social and health system contexts may influence improvement, [...] Read more.
Background: Post-COVID-19 condition (‘long COVID’) involves fluctuating symptoms across multiple organ systems and disability or functional loss, which may be episodic, continuous, or permanent. Qualitative research is essential to capture lived experiences and explain how social and health system contexts may influence improvement, recovery, and service use. We synthesised perspectives from people living with long COVID and healthcare professionals to inform service design and policy. Methods: We conducted a systematic review and qualitative meta-synthesis. MEDLINE, Embase, PsycINFO, CINAHL, Scopus, and Web of Science were searched for studies published between 1 January 2020 and 19 August 2025. Eligible studies reported qualitative data from adults with long COVID (≥12 weeks after acute infection) and/or healthcare professionals in any setting. We excluded non-qualitative, non-primary, or non-English reports. Two reviewers independently screened, extracted, and appraised studies using the Critical Appraisal Skills Programme checklist. Data were synthesised thematically. The protocol was registered with the Open Science Framework. Findings: Of 1544 records screened, 49 studies met the inclusion criteria: 41 involving patients, two involving professionals, and six involving both. Eight patient themes (including symptom burden, identity disruption and stigma) and four professional themes (including recognition, care coordination and holistic care models) were identified. Recognition emerged as a cross-cutting mechanism: validation and consistent pacing guidance facilitated engagement and safer activity, whereas invalidation and inconsistent advice were associated with distress, avoidance, and disengagement. Trajectories showed gradual expansion of multidisciplinary care models, but major capacity and equity gaps persisted. Most studies had low methodological concerns, although heterogeneity in populations and settings was substantial. Interpretation: Long COVID is a chronic, biological condition that also intersects with social and psychological dimensions, and may present with episodic, continuous, or progressive trajectories. Healthcare services must prioritise early validation, provide consistent pacing and relapse prevention guidance, expand access to multidisciplinary and peer-supported rehabilitation, integrate mental healthcare, strengthen coordinated pathways, and support graded return to work. Explicit attention to equity is required to avoid widening disparities. Full article
(This article belongs to the Special Issue Long COVID-19 and Its Impact on Public Health)
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6 pages, 3576 KB  
Case Report
Diphtheria-like Pseudomembranous Corynebacterium striatum Chronic Infection of Left Ventricular Assist Device Driveline Bridged to Heart Transplantation with Dalbavancin Treatment
by Tommaso Lupia, Marco Casarotto, Simone Mornese Pinna, Silvia Corcione, Alessandro Bondi, Massimo Boffini, Mauro Rinaldi and Francesco Giuseppe De Rosa
Reports 2025, 8(4), 208; https://doi.org/10.3390/reports8040208 - 19 Oct 2025
Viewed by 1406
Abstract
Background and Clinical Significance: Corynebacterium striatum is an emerging multidrug-resistant pathogen increasingly implicated in infections among immunocompromised patients and patients with indwelling medical devices. Case Presentation: We report the probable first case of pseudomembranous inflammation associated with C. striatum infection in [...] Read more.
Background and Clinical Significance: Corynebacterium striatum is an emerging multidrug-resistant pathogen increasingly implicated in infections among immunocompromised patients and patients with indwelling medical devices. Case Presentation: We report the probable first case of pseudomembranous inflammation associated with C. striatum infection in a 53-year-old male with an implanted left ventricular assist device (LVAD) awaiting heart transplantation. The patient experienced recurrent episodes of C. striatum bacteremia despite multiple courses of targeted antibiotic therapy, including vancomycin, linezolid, tedizolid, teicoplanin, and dalbavancin. During urgent heart transplantation, pseudomembranous tissue surrounding the LVAD driveline was observed, and cultures confirmed C. striatum device infection. Histopathological analysis revealed necrotic elements and Gram-positive organisms consistent with pseudomembranous inflammation. Conclusions: The case describes the diagnosis and treatment of this rare infection, highlighting the pathogenic potential of C. striatum, its role in device-related infections, and the histopathological evidence of pseudomembrane formation. Full article
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10 pages, 5778 KB  
Case Report
Unusual Epidemic of Tyzzer’s Disease in Commercial Rabbit Breeders: Clinical, Pathological, and Therapeutic Observations
by Benedetta Cordioli, Manuel Garbuio, Luca Palazzolo, Francesco Dorigo, Luca Zandonà, Laura Viel, Claudia Zanardello and Luca Bano
Animals 2025, 15(19), 2920; https://doi.org/10.3390/ani15192920 - 8 Oct 2025
Viewed by 667
Abstract
Clostridium piliforme (Cp) is a pleomorphic spore-forming obligate intracellular bacterium and the causative agent of Tyzzer’s disease. The condition affects multiple species, including rabbits, in which the disease is sporadic in recently weaned animals. This report details a case of disease caused by [...] Read more.
Clostridium piliforme (Cp) is a pleomorphic spore-forming obligate intracellular bacterium and the causative agent of Tyzzer’s disease. The condition affects multiple species, including rabbits, in which the disease is sporadic in recently weaned animals. This report details a case of disease caused by Cp observed exclusively in breeding rabbits of a commercial farm. The clinical manifestations were a higher mortality rate in does and late-gestation abortions. We performed necropsy and further microbiological, parasitological and histopathological analyses. Anatomopathological lesions were suggestive of Tyzzer’s disease and the presence of Cp was confirmed by PCR. Parasitological analysis tested negative and standard bacteriological examination of intestines revealed a high load of Escherichia coli and Clostridium perfringens, which were considered secondary pathogens. Chlamydophila sp. and Toxoplasma gondii infections were excluded by PCR as causative agents of abortions. Moreover, in the months following the diagnosed outbreak, episodes of subcutaneous edema occurred in multiple does and young breeders born after the resolution of the epidemic. The constant reduction in the use of antimicrobials in recent years could make some neglected diseases emerge again. Therefore, it is crucial to suspect such uncommon pathologies in commercial rabbitries to properly manage them on farms. Full article
(This article belongs to the Section Veterinary Clinical Studies)
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10 pages, 580 KB  
Article
MIBG Scintigraphy and Arrhythmic Risk in Myocarditis
by Maria Lo Monaco, Margherita Licastro, Matteo Nardin, Rocco Mollace, Flavia Nicoli, Alessandro Nudi, Giuseppe Medolago and Erika Bertella
Biomedicines 2025, 13(8), 1981; https://doi.org/10.3390/biomedicines13081981 - 15 Aug 2025
Cited by 1 | Viewed by 795
Abstract
Background: The widespread use of cardiac magnetic resonance imaging (MRI) in clinical practice has enabled the identification of numerous patients with evident damage from previous myocarditis, whether known or unknown. For years, myocardial fibrosis has been a topic of interest due to its [...] Read more.
Background: The widespread use of cardiac magnetic resonance imaging (MRI) in clinical practice has enabled the identification of numerous patients with evident damage from previous myocarditis, whether known or unknown. For years, myocardial fibrosis has been a topic of interest due to its established correlation with arrhythmic events in various clinical settings, including ischemic heart disease, dilated cardiomyopathy, and hypertrophic cardiomyopathy. MIBG scintigraphy is a method widely used in patients who are candidates for defibrillator implantation or have experienced heart failure. This examination evaluates the sympathetic innervation of the myocardium. Objective: To assess the real arrhythmogenic risk of non-ischemic scars identified in symptomatic or asymptomatic patients through the use of MIBG. Methods: Patients were retrospectively selected based on the presence of non-ischemic myocardial fibrosis detected by cardiac MRI, consistent with a myocarditis outcome (even in the absence of a clear history of myocarditis). These patients underwent myocardial scintigraphy with MIBG using a tomographic technique. Results: A total of 50 patients (41 males, mean age 51 ± 16 years) who underwent MRI from 2019 to June 2024 were selected. The primary indication for MRI was ventricular ectopic extrasystoles detected on Holter ECG (n = 12, 54%), while five patients underwent MRI following a known acute infectious event (23%, including three cases of COVID-19 infection). All symptomatic patients presented with chest pain in the acute phase, accompanied by elevated hsTNI levels (mean value: 437 pg/mL). The MRI findings showed normal ventricular volumes (LV: 80 mL/m2, RV: 81 mL/m2) and normal ejection fractions (56% and 53%, respectively). The mean native T1 mapping value was 1013 ms (normal range: 950–1050). T2 mapping values were altered in the 5 patients who underwent MRI during the acute phase (mean value: 57 ms), without segmentation. Additionally, three patients had non-tamponade pericardial effusion. All patients exhibited LGE (nine subepicardial, seven midwall, six patchy). All patients underwent myocardial scintigraphy with MIBG at least 6 months after the acute event, with only one case yielding a positive result. This patient, a 57-year-old male, had the most severe clinical presentation, including more than 65,000 premature ventricular beats (PVBs) and multiple episodes of paroxysmal supraventricular tachycardia (PSVT) recorded on Holter ECG. MRI findings showed severe left ventricular dysfunction, a slightly dilated LV, and midwall LGE at the septum, coinciding with hypokinetic areas. Conclusions: MIBG scintigraphy could be a useful tool in assessing arrhythmic risk in patients with previous myocarditis. It could help reduce the clinical burden of incidental findings of non-ischemic LGE, which does not appear to be independently associated with an increased risk profile. Full article
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15 pages, 9593 KB  
Article
EBV-Driven HLH and T Cell Lymphoma in a Child with X-Linked Agammaglobulinemia: A Genetically Confirmed Case Report and Literature Review
by Jose Humberto Perez-Olais, Elizabeth Mendoza-Coronel, Jose Javier Moreno-Ortega, Jesús Aguirre-Hernández, Gabriela López-Herrera, Marco Antonio Yamazaki-Nakashimada, Patricia Baeza-Capetillo, Guadalupe Fernanda Godínez-Zamora, Omar Josue Saucedo-Ramírez, Laura C. Bonifaz and Ezequiel M. Fuentes-Pananá
J. Pers. Med. 2025, 15(8), 365; https://doi.org/10.3390/jpm15080365 - 9 Aug 2025
Viewed by 1366
Abstract
Introduction: X-linked agammaglobulinemia (XLA) is a prototypical inborn error of immunity (IEI) caused by mutations in the BTK gene, leading to a profound deficiency of mature B cells and severe pan-hypogammaglobulinemia. The Epstein-Barr virus (EBV), which primarily infects B lymphocytes, is believed [...] Read more.
Introduction: X-linked agammaglobulinemia (XLA) is a prototypical inborn error of immunity (IEI) caused by mutations in the BTK gene, leading to a profound deficiency of mature B cells and severe pan-hypogammaglobulinemia. The Epstein-Barr virus (EBV), which primarily infects B lymphocytes, is believed to be unable to establish persistence in these patients due to the lack of its natural reservoir. Indeed, current evidence supports that EBV infection is typically refractory in individuals with XLA. Methods: We describe the clinical and molecular characterization of a 10-year-old male patient with genetically confirmed XLA who developed EBV viremia, hemophagocytic lymphohistiocytosis (HLH), and EBV-positive cutaneous T cell lymphoma. Diagnosis was supported by flow cytometry, serology, quantitative PCR, EBER in situ hybridization, histopathology, and whole-exome sequencing. Results: Despite the complete absence of peripheral B cells, EBV was detected in leukocytes and multiple tissues, indicating active infection. The patient developed HLH and a T cell lymphoma with EBER-positive infiltrates. Genetic analysis revealed a nonsense mutation in BTK (1558C>T, R520*), confirming XLA. The clinical course included multiple episodes of neutropenia, viral and bacterial infections, and severe systemic inflammation. Conclusions: This is the first documented case of an XLA patient with confirmed BTK mutation presenting with clinical features more consistent with chronic active EBV infection. These findings challenge the prevailing paradigm that XLA confers protection against EBV-related diseases and further support the possibility of EBV noncanonical reservoirs leading to immune dysregulation. EBV should also be considered in the differential diagnosis of XLA patients presenting with systemic inflammation or lymphoproliferative disease. Full article
(This article belongs to the Section Personalized Therapy in Clinical Medicine)
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12 pages, 1562 KB  
Article
Intra-Host Evolution During Relapsing Parvovirus B19 Infection in Immunocompromised Patients
by Anne Russcher, Yassene Mohammed, Margriet E. M. Kraakman, Xavier Chow, Stijn T. Kok, Eric C. J. Claas, Manfred Wuhrer, Ann C. T. M. Vossen, Aloys C. M. Kroes and Jutte J. C. de Vries
Viruses 2025, 17(8), 1034; https://doi.org/10.3390/v17081034 - 23 Jul 2025
Viewed by 1103
Abstract
Background: Parvovirus B19 (B19V) can cause severe relapsing episodes of pure red cell aplasia in immunocompromised individuals, which are commonly treated with intravenous immunoglobulins (IVIGs). Few data are available on B19V intra-host evolution and the role of humoral immune selection. Here, we report [...] Read more.
Background: Parvovirus B19 (B19V) can cause severe relapsing episodes of pure red cell aplasia in immunocompromised individuals, which are commonly treated with intravenous immunoglobulins (IVIGs). Few data are available on B19V intra-host evolution and the role of humoral immune selection. Here, we report the dynamics of genomic mutations and subsequent protein changes during relapsing infection. Methods: Longitudinal plasma samples from immunocompromised patients with relapsing B19V infection in the period 2011–2019 were analyzed using whole-genome sequencing to evaluate intra-host evolution. The impact of mutations on the 3D viral protein structure was predicted by deep neural network modeling. Results: Of the three immunocompromised patients with relapsing infections for 3 to 9 months, one patient developed two consecutive nonsynonymous mutations in the VP1/2 region: T372S/T145S and Q422L/Q195L. The first mutation was detected in multiple B19V IgG-seropositive follow-up samples and resolved after IgG seroreversion. Computational prediction of the VP1 3D structure of this mutant showed a conformational change in the proximity of the antibody binding domain. No conformational changes were predicted for the other mutations detected. Discussion: Analysis of relapsing B19V infections showed mutational changes occurring over time. Resulting amino acid changes were predicted to lead to a conformational capsid protein change in an IgG-seropositive patient. The impact of humoral response and IVIG treatment on B19V infections should be further investigated to understand viral evolution and potential immune escape. Full article
(This article belongs to the Collection Parvoviridae)
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10 pages, 398 KB  
Brief Report
SARS-CoV-2 Vaccine Breakthrough Reinfections in Fully Vaccinated Healthcare Workers in Davao City, Philippines: A Retrospective Cohort Study
by Alfredo A. Hinay, Jennifer Ashley H. Reyes, Rvin John T. Servillon and Ace Ronald C. Sarabia
COVID 2025, 5(7), 106; https://doi.org/10.3390/covid5070106 - 9 Jul 2025
Viewed by 1276
Abstract
Background: Breakthrough infections (BTIs) continue to occur among healthcare workers (HCWs) despite full COVID-19 vaccination, raising concerns about ongoing vulnerability in this high-risk group. In addition to initial BTIs, breakthrough reinfections (BTRs) have emerged as a challenge, with some HCWs experiencing multiple episodes [...] Read more.
Background: Breakthrough infections (BTIs) continue to occur among healthcare workers (HCWs) despite full COVID-19 vaccination, raising concerns about ongoing vulnerability in this high-risk group. In addition to initial BTIs, breakthrough reinfections (BTRs) have emerged as a challenge, with some HCWs experiencing multiple episodes of infection after vaccination. This study investigated the factors influencing breakthrough infection and reinfection rates among HCWs between January 2021 and December 2022 in Davao City, Philippines. Methods: This retrospective cohort study was conducted using secondary data from the Davao City Epidemiological Surveillance Unit, approved by the Department of Health. This study included 1011 fully vaccinated HCWs from various congressional districts. Results: BTI was observed in all HCWs included in the study. However, BTRs varied across occupational groups: medical technologists showed the highest reinfection rate (22.37%), followed by physicians (13.48%), and nurses/nurse aides (10.14%). Booster vaccination significantly reduced BTRs (5.83% vs. 11.18%, p = 0.0267). Occupation and institutional type were significant factors, with higher rates reported by physicians and in public hospitals (p = 0.0002 and p = 0.0041, respectively). The vaccine manufacturer, sex, age, and booster type showed no significant differences. Conclusion: These findings highlight the importance of targeted interventions for high-risk HCWs and emphasize the effectiveness of the booster vaccination. Full article
(This article belongs to the Section COVID Public Health and Epidemiology)
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14 pages, 600 KB  
Case Report
Emergence of Multidrug-Resistant Campylobacter jejuni in a Common Variable Immunodeficiency Patient: Evolution of Resistance Under the Selective Antibiotic Pressure
by Tajana Juzbašić, Nataša Andrijašević, Ivana Ferenčak, Dragan Jurić, Silvija Šoprek, Vlatka Poje Janeš, Ljiljana Žmak, Arjana Tambić Andrašević and Ana Gverić Grginić
Trop. Med. Infect. Dis. 2025, 10(6), 165; https://doi.org/10.3390/tropicalmed10060165 - 12 Jun 2025
Cited by 1 | Viewed by 981
Abstract
Campylobacter jejuni is a leading cause of bacterial gastroenteritis worldwide which usually presents as mild, and self-limiting disease in immunocompetent individuals. However, in immunocompromised patients, such as those with common variable immunodeficiency, C. jejuni can cause severe recurrent infections requiring antibiotic treatment. Our [...] Read more.
Campylobacter jejuni is a leading cause of bacterial gastroenteritis worldwide which usually presents as mild, and self-limiting disease in immunocompetent individuals. However, in immunocompromised patients, such as those with common variable immunodeficiency, C. jejuni can cause severe recurrent infections requiring antibiotic treatment. Our study reports a case of a 37-year-old male patient with CVID, who had multiple episodes of C. jejuni intestinal infections over a 3.5-year period. A total of 27 stool samples were collected and analyzed between December 2020 and July 2024 during acute febrile diarrheal episodes, with C. jejuni isolated in 15 samples. Antimicrobial susceptibility testing (AST) during the course of the disease revealed three different antimicrobial resistance profiles including multi-drug-resistant phenotype. Whole genome sequencing was performed on three representative isolates, all identified as MLST type 367, ST-257 complex, with minimal genetic divergence, indicating a clonal origin. Genes and point mutations conferring resistance to macrolides, fluoroquinolones, beta-lactams, and tetracycline were identified in different C. jejuni isolates, along with key virulence factors linked to adherence, invasion, motility, and immune evasion. The genetic analysis of macrolide phenotypic resistance revealed different resistance mechanisms. Genotypic and phenotypic analyses of the same C. jejuni clone from single patient, and identified multidrug resistance pattern, present the first documented case of in vivo resistance development of C. jejuni in Croatia. This case highlights the role of prolonged antibiotic pressure in driving resistance evolution and underscores the need for careful antimicrobial stewardship and genomic monitoring in immunocompromised patients. Further research is needed to correlate phenotypic resistance with genetic determinants in Campylobacter spp. Full article
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15 pages, 800 KB  
Review
Genetic Factors Related to the Development or Progression of Mesoamerican Endemic Nephropathy
by Alejandro Marín-Medina, Ingrid Patricia Dávalos-Rodríguez, Emiliano Peña-Durán, Luis Eduardo de la Torre-Castellanos, Luis Felipe González-Vargas and José Juan Gómez-Ramos
Int. J. Mol. Sci. 2025, 26(10), 4486; https://doi.org/10.3390/ijms26104486 - 8 May 2025
Viewed by 1412
Abstract
Over the past two decades, Mesoamerican endemic nephropathy (MeN) has become a major public health problem in certain regions of Mexico and Central American countries. The etiology of this disease is multifactorial, and important environmental factors have been described, such as chronic heat [...] Read more.
Over the past two decades, Mesoamerican endemic nephropathy (MeN) has become a major public health problem in certain regions of Mexico and Central American countries. The etiology of this disease is multifactorial, and important environmental factors have been described, such as chronic heat stress, recurrent episodes of dehydration, infections, and exposure to toxins of chemical and biological origin. Genetic and epigenetic factors have been proposed to play significant roles in MeN. Recent studies have analyzed the role of these factors in MeN. In some cases, these factors appear to be associated with accelerated deterioration of established kidney disease due to preexisting endothelial dysfunction and tubulopathy. In other cases, they appear to be associated with early kidney damage, even before occupational exposure, suggesting that they may play a relevant role in the genesis of the disease. Other factors appear to act as risk reducers for developing MeN in areas with a high prevalence of the disease. Therefore, this disease has a rather complex multifactorial etiology, with possible polygenic contributions, possible epigenetic phenomena, and multiple environmental factors. Full article
(This article belongs to the Special Issue Genetic Variations in Human Diseases: 2nd Edition)
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