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A population pharmacokinetic analysis of dalbavancin was conducted in patients with different infection sites. Non-linear mixed effect modeling was used for pharmacokinetic analysis and covariate evaluation. Monte Carlo simulations assessed the probability of target attainment (PTA) of total dalbavancin concentration ≥ 8.04 mg/L over time (associated with ≥90% probability of optimal pharmacodynamic target attainment of fAUC24h/MIC > 111.1 against S. aureus) associated with a single or double dosage, one week apart, of 1000 or 1500 mg in patients with different classes of renal function. Sixty-nine patients with 289 concentrations were included. Most of them (53/69, 76.8%) had bone and joint infections. A two-compartment model adequately fitted dalbavancin concentration−time data. Creatinine clearance (CLCR) was the only covariate associated with dalbavancin clearance. Monte Carlo simulations showed that, in patients with severe renal dysfunction, the 1000 mg single or double one week apart dosage may ensure optimal PTAs of 2 and 5 weeks, respectively. In patients with preserved renal function, the 1500 mg single or double one-week apart dosage may ensure optimal PTAs of 2 and 4 to 6 weeks, respectively. Therapeutic drug monitoring should be considered mandatory for managing inter-individual variability and for supporting clinicians in long-term treatments of subacute and chronic infections.

Background: Scrub typhus is a vector-borne rickettsial infection, which can cause relevant morbidity and mortality. While the number of cases is around a million per year globally, the infection is seldom diagnosed in travellers from Europe., Methods: We herein report three cases diagnosed in Italian travellers and review the literature about imported cases in Europe in the last 60 years., Results: Three participants to the same hiking trip to the forest of northern Laos presented fever and other symptoms, including eschars (2 individuals) and skin rash (2 individuals). Overall, they didn't report complications, and recovered soon after doxycycline treatment. Diagnosis was retrospectively confirmed with PCR in one of them. The review collected data from 40 patients. Almost all of them (95%) presented fever, more than a half had headache, skin rash, eschars, arthromyalgias. 73% of them were hospitalized, and 16.2% needed intensive care. Diagnosis was confirmed by serology in almost all cases (94.6%). Most patients (88%) were treated with doxycycline. All patients survived, although one case resulted in incomplete tetraparesis., Conclusions: Scrub typhus should be considered in all travellers coming back from endemic areas and presenting with acute febrile illness. Laboratory diagnosis can be challenging, as specific tests are not widely available. In case of clinical suspicion, a prompt treatment with oral doxycycline could avoid severe complications., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

COVID-19 is characterized by a severe pulmonary disease due to severe acute respiratory syndrome (SARS)-CoV-2 infection. For clinicians involved in the management of patients with chronic autoimmune diseases the risk linked to the conditions itself and to drug-induced immunosuppression during the COVID-19 pandemic is a major topic. Pemphigus is a rare autoimmune blistering disease (AIBD) of the skin and mucous membranes caused by autoantibodies to desmosomal components, desmoglein 1 and 3. Among immunosuppressant therapies, rituximab (RTX) is considered a highly effective treatment with a favorable safety profile, but it induces a prolonged B-cell depletion that can lead to higher susceptibility to infections. For this reason, concerns about its use during the pandemic have been raised. We describe a case of a pemphigus patient in which RTX-induced B cell depletion led to the severe inflammatory phase, whereas corticosteroid treatment allowed a favorable outcome., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Sinagra, Vedovelli, Binazzi, Salemme, Moro, Mazzanti, Didona and Di Zenzo.)

We report a case of a woman who experienced psychiatric disorders after switching her antiretroviral therapy (c-ART) to dolutegravir (DTG). She is a 59-year-old HIV-1 positive woman with a recent story of cardiovascular disorders treated with beta-blockers, clopidogrel, and rosuvastatin. She underwent a c-ART switch from darunavir/cobicistat and maraviroc to emtricitabine/tenofovir alafenamide fumarate in association with dolutegravir due to drug-drug interactions. One week later, she started to show psychiatric symptoms that required admission to the psychiatric unit. These disorders resolved within a couple of days after DTG discontinuation to allow a regular discharge. With this case-report, we would like to analyse the possible correlation between integrase inhibitor and severe psychiatric disorders in order to confirm the evidences already published in literature., Competing Interests: The authors declare that there are no conflicts of interest regarding the publication of this paper., (Copyright © 2020 Daniele Mengato et al.)

Despite evidence supporting the effectiveness of best practices in infection prevention and management, many healthcare workers fail to implement them and evidence-based practices tend to be underused in routine practice. Prevention and management of infections across the surgical pathway should always focus on collaboration among all healthcare workers sharing knowledge of best practices. To clarify key issues in the prevention and management of infections across the surgical pathway, a multidisciplinary task force of experts convened in Ancona, Italy, on May 31, 2019, for a national meeting. This document represents the executive summary of the final statements approved by the expert panel.

The presence of conspecifics can affect alarm calls and in particular the signaller's behaviour. This study investigated the anti-predator response in males of a monogamous species, the red-legged partridge (Alectoris rufa), in relation to the audience. Aerial alarm calls and nonvocal behaviour were analyzed, in order to assess whether they were affected by the presence of an audience, and in particular by the audience's composition: unfamiliar males, unfamiliar females and signallers’ mates. Rate and spectrographic characteristics of the alarm calls, as well as behavioural responses to a dummy avian raptor, were analyzed in a sample of 18 farm-reared males. Our findings show that the presence of conspecifics was able to alter the number and structure of male alarm calls. In addition, the number of alarm calls drastically decreased when no audience was present: when the male was alone, it might even not vocalize, thus reducing predation risk. The audience composition was also important; the presence of the signaller's mate elicited more calls than that of an unfamiliar male. The spectrographic structure of alarm calls was affected by the audience, mainly in terms of peak frequency. This study shows that alarm calls of red-legged partridge males are influenced by the audience, and in particular by the presence of the signaller's mate: red-legged partridge males in presence of their mates not only warn them by increasing alarm calling rate, but also produce less detectable calls. [ABSTRACT FROM PUBLISHER]

Toxigenic Clostridium difficile is responsible for antibiotic-associated diarrhoea and other diseases. The increasing frequency and severity is attributed to highly-virulent ribotypes such as 027. The aim of the study was to collect epidemiological and molecular data for C. difficile isolates during 2009-2013 in the Central Hospital of Bolzano, Northern Italy. Stool samples from inpatients of the Bolzano Central Hospital were screened for toxins A and B, and C. difficile was cultured and tested for antibiotic susceptibility. PCRs were performed for genes of toxin A, toxin B, binary toxin and ribotyping. During the period 2009-13 from 320 patients (9% of patients tested) at least one stool sample proved positive for C. difficile toxins, and incidences for all hospital inpatients per 10,000 patient days (per 1,000 admissions) varied between 2.2 (1.5) and 4.3 (3.0). Out of 138 isolates (43% of total isolates were studied), 24 different ribotypes were identified. Isolates with ribotype 027 were predominant (38%), followed by 018 (13%) and 607 (10%). Whereas for ribotype 018 a significant decrease was seen during the five-year period, ribotype 027 increased significantly from 0% in 2009 to 64% in 2012, decreasing then to 10% in 2013. Isolates were sensitive to metronidazole and vancomycin, whereas isolates of the three major ribotypes were resistant to moxifloxacin. Our data indicates a significant change in C. difficile incidence rates and ribotype frequencies during the five-year period in the Central Hospital in Bolzano.

Background: Silicone implants have been successfully used for breast augmentation and reconstruction in millions of women worldwide. The reaction to the silicone implant is highly variable; it can lead to local inflammatory symptoms, and sometimes to systemic symptoms and disease. Over 80 cases of anaplastic lymphoma kinase-negative anaplastic large cell lymphoma have been reported in patients with silicone breast implants and have been accepted as a new clinical entity. To the best of our knowledge, an intravascular large B-cell lymphoma associated with a silicone breast implant has not been reported previously., Case Presentation: A 48-year-old Caucasian woman who presented with high fever was found to have splenomegaly on physical examination. A laboratory diagnosis revealed pancytopenia, hypertriglyceridemia, and hyperferritinemia. She developed signs of altered sensorium, hemiparesis, aphasia, and cauda equina syndrome. On further evaluation, she fulfilled the necessary five out of eight criteria for diagnosis of macrophage activation syndrome/hemophagocytic lymphohistiocytosis. Dexamethasone administration was followed by prompt improvement; however, 3 days later she again manifested high fever, which persisted despite administration of immunoglobulin and cyclosporine A. Her silicone breast implant was considered a possible contributor to her macrophage activation syndrome and was therefore removed. A histological examination of the capsule tissue showed an extensive lymphohistiocytic/giant cell foreign body reaction suggestive of autoimmune/inflammatory syndrome induced by adjuvants. However, the histological examination unexpectedly also revealed an intravascular large B-cell lymphoma., Conclusions: The genetic background of our patient with silicone breast implants might have predisposed her to three rare and difficult to diagnose syndromes/diseases: macrophage activation syndrome/hemophagocytic lymphohistiocytosis, autoimmune/inflammatory syndrome induced by adjuvants, and intravascular large B-cell lymphoma. The simultaneous manifestation of all three syndromes suggests causal interrelationships. Human leukocyte antigen testing in all women who undergo silicon breast implantation could in the future enable us to better evaluate the risk of potential side effects.

This study is intended to investigate the differences in anti-predator behavioural and acoustic response to terrestrial and aerial predators as well as the behavioural differences between sexes in the red-legged partridge. To this aim we observed the response of 114 partridge (57 males and 57 females) to dummy terrestrial and aerial predators, a raptor and a fox. We divided behavioural responses to predators into four mutually exclusive categories: vigilance, freezing, escape and non-anti-predator behaviours. We also recorded and analysed the vocalizations emitted during tests. The animals reacted differently to aerial and terrestrial stimuli. The reactions elicited by the terrestrial predator were ranked as follows: vigilance, escape, non-anti-predator behaviours, and freezing. Those elicited by the aerial predator were ranked as follows: vigilance, freezing, escape and non-anti-predator behaviours. Vigilance and escape were elicited more frequently by the terrestrial predator than by the aerial predator (vigilance: p < 0.001; escape: p < 0.001). Freezing was the most frequent behaviour following the appearance of the aerial predator (p < 0.001). In fact, freezing may represent an effective strategy in an open space, combining camouflage from and detection by the predator. On the other hand, vigilance is an effective behaviour to detect and avoid a terrestrial predator hunting by ambush. We did not find clear-cut differences between sexes. The analysis of vocalizations revealed that the fox and the raptor elicited significantly different calls (p = 0.003); the fox evoked significantly more vocalizations than the raptor (p< 0.001), differing in addition in frequency parameters. Thus partridges not only discriminate between aerial and terrestrial predators and behave consequently, but are also able to tune alarm calls in relation to the context of predation. [ABSTRACT FROM AUTHOR]

High developmental dysplasia of the hip is commonly treated with total hip arthroplasty and shortening osteotomy. We present a two stage technique, consisting of progressive femoral lowering followed by total hip arthroplasty. The clinico-radiographic results of eleven patients (twelve hips) who were operated on with the two-stage technique were evaluated at a mean follow-up of 11 ± 5 years. At the final follow-up, ten patients (eleven hips) had a mean Harris hip score of 85 ± 5 points with no implant loosening. One patient (one hip) was revised at 5 years due to infection. No neurovascular complications were observed in any patients. With this technique, we could place the cup in the anatomical position and obtain complete limb symmetry with excellent clinical results at long-term., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Purpose: The two most commonly used techniques for gap balancing in robot-assisted total knee arthroplasty (RA-TKA) are measured resection (MR) and ligament balancing (LB). There are limited studies have reported differences in intraoperative and postoperative outcomes between MR-TKA and LB-TKA in RA-TKA. This study aims to compare the intraoperative and postoperative outcomes of primary RA-TKA between LB and MR techniques. Methods: This cohort study utilized prospectively collected data from a single center, spanning from January 2021 to December 2022. We compared the intraoperative procedures and postoperative clinical and imaging results between two groups. Results: The LB group had a thinner distal femur cut and a lower usage of thicker polyethylene. Additionally, the LB group exhibited a higher mean femoral component external rotation and greater tibial posterior slope. The rate of soft tissue release and bone recut was lower in the LB group, as was the mean C-reactive protein level. Conclusion: In RA-TKA, LB offers advantages in soft tissue protection and bone mass preservation. However, no differences were observed in clinical and radiographic outcomes after a 2-year follow-up. [ABSTRACT FROM AUTHOR]

Introduction: Dalbavancin (DAL) is a long-acting lipoglycopeptide active against Gram-positive bacteria, including multidrug-resistant isolates. A growing body of evidence supports its efficacy in various difficult-to-treat infections. DAL shows time-dependent bactericidal activity in vitro at free drug concentrations equal to 4×MIC values. However, the optimal dosing scheme for achieving the PK/PD target in multidose treatment has not been fully established. Methods: Pharmacokinetic analysis was based on a nonlinear mixed effects modelling approach performed in NONMEM v7.5/Pirana, while R was used for data management and graphical summaries. Final model parameters were used to simulate the plasma disposition of DAL by Monte Carlo simulations to determine the multidose DAL regimen associated with a 90% target attainment of 100% fT > 4×MIC. Results: A two-compartmental model with first-order elimination and allometric-scaled bodyweight best described DAL disposition in patients with CLcr > 30 mL/min. Monte Carlo simulations showed that two 1500 mg DAL doses 7 days apart granted an optimal PTA > 90% of 100% fT > 4×MIC up to 5, 4, and 3 weeks in patients weighting from 40–80 kg, 80–120 kg and 120–200 kg, respectively. An additional third 1500 mg dose at the above time points by weight bands may extend the optimal PTA up to 9, 7, and 6 weeks of total treatment. Conclusions: Two 1500 mg DAL doses administered 7 days apart could be a valuable starting strategy for patients of all weight classes with CLcr > 30 mL/min. In patients requiring long-term DAL treatment, the optimal timing of additional administrations should be guided by routine TDM or empirically through patients' total body weight when TDM is unavailable. [ABSTRACT FROM AUTHOR]

Objectives: The aim of this work was to perform a systematic review assessing the pharmacokinetic/pharmacodynamic (PK/PD) properties of dalbavancin and the clinical use for in-label and off-label indications in pediatric patients. Methods: Two authors independently searched the PubMed-MEDLINE and Scopus databases and clinicaltrials.gov up to 20 November 2024, to retrieve randomized controlled trials (RCTs), observational studies, PK studies, and case series/reports assessing dalbavancin PK/PD properties or the clinical use for both in-label and off-label indications in pediatric patients. Data were independently extracted by the two authors, and the quality of the included studies was independently assessed by means of specific tools according to study design. Clinical success was selected as the primary outcome. Descriptive statistics were used for summarizing the retrieved data. Subgroup analysis according to PK/PD data, as well as in-label and off-label indications, was performed. Results: After screening 206 articles, nine studies were included in the systematic review (one RCT, three PK studies, and five case series/reports; n = 267). Dalbavancin exposure was 30% lower in pediatric patients compared to adults. In acute bacterial skin and skin structure infections (ABSSSIs), the overall clinical success of dalbavancin was 96.1-97.3% and 92.9% in RCT and case series, respectively. Bone and joint infections (60.7%) and central-line-associated bloodstream infections (14.3%) represented the most common dalbavancin off-label indications in pediatric patients. Overall, the clinical success for off-label indications was 92.9%. The rate of adverse events ranged from 7.1% to 10.7%. Conclusions: Our systematic review summarized evidence concerning the PK/PD properties of dalbavancin and its use for in-label or off-label indications in pediatric patients. The available findings suggest that dalbavancin may be a valuable alternative for the management of ABSSSIs and/or off-label indications in pediatric patients according to efficacy and safety data, allowing for a potential minimized duration of hospital stay. [ABSTRACT FROM AUTHOR]

Introduction: In 2020, 368 million people globally were affected by knee osteoarthritis, and prevalence is projected to increase with 74% by 2050. Relatively high rates of dissatisfactory results after total knee arthroplasty (TKA), as reported by approximately 20% of patients, may be caused by sub-optimal knee alignment and balancing. While mechanical alignment has traditionally been the goal, patient-specific alignment strategies are gaining interest. Robotic assistance could potentially facilitate implementation of these alignment strategies through data-based surgical planning, accurate execution of the surgical plan and validation. The clinical value of surgical assistance in diverging from mechanical alignment remains to be investigated. In the present study, robotic-assisted TKA will be performed to pursue inverse kinematic alignment (iKA) within predefined boundaries, focusing on restoring native tibia joint line. Methods: This randomized controlled trial evaluates clinical effectiveness of robotic-assisted TKA (ROSA® Knee System, Zimmer Biomet, Montreal, Quebec, Canada) aiming for iKA compared to conventional TKA aiming for mechanical alignment. A total of 150 participants will be randomized (1:1) to either treatment to provide an 80% power for a 4.8-point clinically important difference in the primary outcome measure, the Oxford Knee Score (OKS) 12 months after surgery. Allocation was achieved using computer-based randomization. Outcomes will be analyzed using linear mixed models with time and group as main factors and interaction-term. Secondary outcomes include clinical metrics (leg alignment, implant and patient survival), surgical parameters (adverse events, surgery duration, blood loss, hospital stay length, medication use), patient-reported outcomes (symptoms, quality of life, pain), mobility and physical activity measurements, metabolic syndrome, cost-efficacy, and gait and continuous glucose monitoring. Ethics and dissemination: This study has been approved by the Medical Ethical Committee Zuyd and Zuyderland Medical Centre (NL79161.096.21/METCZ20220006), September 2022. Trial registration number: NCT05685693 (clinicaltrials.gov). [ABSTRACT FROM AUTHOR]

Leishmaniasis is spreading from mediterranean countries to the north of Europe. The Alps are not an endemic region and there are only few reports of sporadic cases. We report the case of a 72 year old male who presented after a syncope with fever, cough and a sacral skin rash. Clinical examination revealed splenomegaly, elevated liver enzymes and pancytopenia; differential diagnosis included myeloproliferative or lymphoproliferative disorders, infections and auto-immune conditions that cause enlargement of the spleen and liver diseases, however, all tests were negative. In (18)FDG PET computerized tomography, pathological and diffuse uptake in the spleen was seen, with mild and homogeneous FDG uptake in the bone marrow and normal tracer uptake elsewhere in the body. Bone marrow aspiration revealed the presence of numerous intra- and extracellular Leishmania amastigotes. Travel history indicated that he had been in Sardinia for a 7-day vacation several months ago. The patient promptly responded to treatment with liposomal amphotericin B. Imported visceral leishmaniasis is likely to be seen more frequently in non-endemic regions and fever, pancytopenia and splenomegaly are diagnostic clues, whereas diagnostic confirmation may be done by detection of Leishmania spp. amastigotes in the bone marrow.

The immune system protects the organism from foreign invaders and foreign substances and is involved in physiological functions that range from tissue repair to neurocognition. However, an excessive or dysregulated immune response can cause immunopathology and disease. A 39-year-old man was affected by severe hepatosplenic schistosomiasis mansoni and by amyotrophic lateral sclerosis. One question that arose was, whether there was a relation between the parasitic and the neurodegenerative disease. IL-17, a proinflammatory cytokine, is produced mainly by T helper-17 CD4 cells, a recently discovered new lineage of effector CD4 T cells. Experimental mouse models of schistosomiasis have shown that IL-17 is a key player in the immunopathology of schistosomiasis. There are also reports that suggest that IL-17 might have an important role in the pathogenesis of amyotrophic lateral sclerosis. It is hypothesized that the factors that might have led to increased IL-17 in the hepatosplenic schistosomiasis mansoni might also have contributed to the development of amyotrophic lateral sclerosis in the described patient. A multitude of environmental factors, including infections, xenobiotic substances, intestinal microbiota, and vitamin D deficiency, that are able to induce a proinflammatory immune response polarization, might favor the development of amyotrophic lateral sclerosis in predisposed individuals.

Purpose: Extrapulmonary tuberculosis (EPTB) is frequently seen in human immunodeficiency virus (HIV)-infected individuals in Sub-Saharan Africa and recent work has shown point-of-care (POC) ultrasound to be a diagnostic aid in the resource-limited, highly endemic setting. Its role in industrialized countries, however, has rarely been studied. With international migration, EPTB is increasingly seen in European hospitals. This study reports ultrasound findings and discusses the diagnostic relevance of EPTB in an industrialized country setting., Methods: In this retrospective study, we describe a cohort of 27 patients with a predominantly immigrant background diagnosed with HIV and EPTB in Northern Italy and evaluate the role of ultrasound in their clinical management. All inpatient files of HIV-positive individuals admitted to our hospital with culture-proven diagnosis of EPTB were reviewed, along with chest X-rays and ultrasound studies. The outcome and results of long-term follow-up were extracted., Results: A total of 243 HIV-positive inpatients were identified between January 2005 and November 2011. Twenty-seven of the patients [11.1 %, 95 % confidence interval (CI) 7.4-15.7] were diagnosed with EPTB. Ultrasound showed a typical pattern of enlarged abdominal lymph nodes and focal lesions in the spleen and liver in 22 patients (81.5 %, 95 % CI 7.4-15.7) and, thus, helped to raise the suspicion of mycobacterial infection., Conclusion: As disseminated mycobacterial infections in HIV-positive patients can be treated effectively if diagnosed early, and typical sonographic findings are seen in the majority of these patients, we suggest that POC ultrasound should be integrated in diagnostic and screening algorithms for EPTB in developed countries.

Background: Vancomycin is frequently used in the treatment of methicillin-resistant Staphylococcus aureus (MRSA) bacteraemia; reduced susceptibility to vancomycin is therefore disturbing., Methods: molecular epidemiological analysis of 81 MRSA bacteraemia isolates collected during 2002-10 in the province of Bolzano, northern Italy was performed. MICs of a range of antimicrobials were determined by agar microdilution, screening for hGISA was by Macro-Etest and Etest GRD and confirmed by PAP-AUC with vancomycin and teicoplanin. All isolates were characterised by toxin gene profiling, agr, spa, and SCCmec-typing; MLST and PFGE were carried out on representative strains., Results: The dominant clones identified were ST8-MRSA-IVc (55%) and ST228- and ST111-MRSA-I (25%); most of the latter two lineages (19/20; 95%) were GISA or PAP-AUC confirmed hGISA. One ST8-MRSA-IVc isolate harboured ccrA2B2 together with ccrA4B4. The remainder were diverse genotypically and belonged to MLST clonal complexes 1, 22, 45 and 398., Conclusions: Diverse lineages of MRSA were identified as causing bacteraemia in a province in northern Italy. The association of a specific genotype with the hGISA and GISA phenotypes among representatives of the second most common lineage identified is of clinical concern.

We present a case of a young female athlete with chronic knee instability and constitutional varus limb, in which the failure of an initial stabilising operation required multiple operations to correct the unstable varus knee: in particular valgus osteotomy and ligament reconstruction using contralateral patellar tendon were performed in two staged operations in order to minimise surgical aggression, optimise rehabilitation and prevent postop complications. The final result is evaluated according to the IKDC chart as normal category A.

The B203.13 monoclonal antibody was developed by immunizing mice with the B/monocyte biphenotypic cell line B1b. During normal hematopoiesis B203.13 is expressed on a fraction of CD34+ cells, while on mature cells it is only present on B-lymphocytes. We tested this antibody as a marker of childhood B-acute lymphoblastic leukemia (B-ALL). Bone marrow aspirates from 139 cases of early B-ALL and 25 controls were studied. About 40% of the B-ALL patients expressed B203.13. In these patients, B203.13 was constantly co-expressed with CD10, but never co-expressed with CD20, contrary to the controls. The CD10(+)/B203.13(+) phenotype was specific to B-ALL, since CD10(+)/CD20(+) cells from common acute lymphoblastic leukemia (c-ALL) did not express B203.13. We concluded that the use of B203.13 in association with CD10 and CD20 provides meaningful information for distinguishing normal residual B-cells from leukemic B-lymphoblasts and that recurrence of a CD10(+)/B203.13(+) phenotype after transplantation may be a very early relapse indicator of early B-acute lymphoblastic leukemia.