Publications by authors named "Marco Tinelli"

24 Publications

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Low complication rate and better results for intramedullary nail - arthrodesis for infected knee joints compared to external fixator-a series of one hundred fifty two patients.

Int Orthop 2021 Apr 23. Epub 2021 Apr 23.

BG Trauma Center Ludwigshafen, Department of Trauma and Orthopaedics, Ludwig-Guttmann-Strasse 13, 67071, Ludwigshafen, Germany.

Purpose: Arthrodesis of the knee joint is still a salvage procedure after recurrent prosthetic joint infections (PJI) of total knee arthroplasties (TKA) with substantial bone loss and seems to be a good solution to avoid amputation. Until now, intramedullary arthrodesis has increasingly been performed; no study has yet been published to compare these techniques after septic removal of TKA in terms of functional assessment and quality of daily life.

Methods: In a single-centre retrospective setting, clinical and radiographic evaluation of consecutive patients after knee arthrodesis using intramedullary and external fixation for infected knee joints was performed. All patients were evaluated clinically, with x-ray and questionnaire including analysis regarding any complications at latest follow-up of a minimum 12 months postoperatively.

Results: We included 152 patients (75 females, 77 males) in this study. The mean age of the patients at surgery was 63.6 years (range 12 to 90 years). The minimum follow-up was 12 months (mean 3.1 years, range 12 to 49 months). Arthrodesis with external fixator (83 patients, 52.2%) showed less blood loss and less peri-operative complications (1.6%) but a high rate of post-operative, pin-track infections (35.5%); loose pins (12.7%); and pin fractures (4.8%), and therefore risk factors for instability and nonunion (30.9%). Revision rate was 22.6% for arthrodesis with external fixator, and the primary union rate was 65.6%. Intramedullary arthrodesis (69 patients, 43.4%) showed a similar re-infection rate to external fixation (16.1% and 15.9%, respectively) but a significantly lower revision rate (5.4%, p < 0.001). Eighty percent of patients with intramedullary arthrodesis showed very good patient-related outcomes regarding pain, function and daily life activities in the questionnaire.

Conclusion: Despite similar results regarding patient satisfaction and everyday competences in questionnaires, intramedullary arthrodesis of the knee is superior to the external fixator, as it results in fewer complications, lower revision rate, and union rates/loosening.
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http://dx.doi.org/10.1007/s00264-021-05054-wDOI Listing
April 2021

Therapeutic strategies for severe COVID-19: a position paper from the Italian Society of Infectious and Tropical Diseases (SIMIT).

Clin Microbiol Infect 2021 Mar 18;27(3):389-395. Epub 2021 Jan 18.

Unit of Emerging and Immunosuppressed Infectious Diseases, Department of Gastroenterology and Transplantation, Polytechnic University of Marche, Ancona, Italy.

Scope: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has become pandemic, reaching almost one million death worldwide. At present standard treatment for coronavirus disease 2019 (COVID-19) is not well defined because the evidence, either from randomized or observational studies, with conflicting results, has led to rapid changes in treatment guidelines. Our aim was to narratively summarize the available literature on the management of COVID-19 in order to combine current evidence and interpretation of the data by experts who are treating patients in the frontline setting.

Methods: The panel conducted a detailed review of the literature and eventual press releases from randomized clinical trials for each possible available treatment. Inductive PubMed search waws performed for publications relevant to the topic, including all clinical trials conducted. The result was a flowchart with treatment indications for patients with COVID-19.

Implications: After 6 months of a pandemic situation and before a possible second coronavirus wave descends on Europe, it is important to evaluate which drugs proved to be effective while also considering that results from many randomized clinical trials are still awaited. Indeed, among treatments for COVID-19, only glucocorticoids have resulted in an association with a significant decrease in mortality in published randomized controlled trials. New therapeutic strategies are urgently needed.
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http://dx.doi.org/10.1016/j.cmi.2020.12.011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7833273PMC
March 2021

Quantitative proteomics reveals specific metabolic features of acute myeloid leukemia stem cells.

Blood 2020 09;136(13):1507-1519

Genome Biology Unit, European Molecular Biology Laboratory (EMBL), Heidelberg, Germany.

Acute myeloid leukemia is characterized by the accumulation of clonal myeloid blast cells unable to differentiate into mature leukocytes. Chemotherapy induces remission in the majority of patients, but relapse rates are high and lead to poor clinical outcomes. Because this is primarily caused by chemotherapy-resistant leukemic stem cells (LSCs), it is essential to eradicate LSCs to improve patient survival. LSCs have predominantly been studied at the transcript level, thus information about posttranscriptionally regulated genes and associated networks is lacking. Here, we extend our previous report on LSC proteomes to healthy age-matched hematopoietic stem and progenitor cells (HSPCs) and correlate the proteomes to the corresponding transcriptomes. By comparing LSCs to leukemic blasts and healthy HSPCs, we validate candidate LSC markers and highlight novel and potentially targetable proteins that are absent or only lowly expressed in HSPCs. In addition, our data provide strong evidence that LSCs harbor a characteristic energy metabolism, adhesion molecule composition, as well as RNA-processing properties. Furthermore, correlating proteome and transcript data of the same individual samples highlights the strength of proteome analyses, which are particularly potent in detecting alterations in metabolic pathways. In summary, our study provides a comprehensive proteomic and transcriptomic characterization of functionally validated LSCs, blasts, and healthy HSPCs, representing a valuable resource helping to design LSC-directed therapies.
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http://dx.doi.org/10.1182/blood.2019003654DOI Listing
September 2020

Considerations for the optimal management of antibiotic therapy in elderly patients.

J Glob Antimicrob Resist 2020 09 9;22:325-333. Epub 2020 Mar 9.

Division of Infectious and Tropical Diseases, Hospital of Lodi, Lodi, Italy.

Objectives: To maximise efficacy and minimise toxicity, special considerations are required for antibiotic prescription in elderly patients. This review aims to provide practical suggestions for the optimal management of antibiotic therapy in elderly patients.

Methods: This was a narrative review. A literature search of published articles in the last 15 years on antibiotics and elderly patients was performed using the Cochrane Library and PubMed electronic databases. The three priority areas were identified: (i) pharmacokinetics/pharmacodynamics (PK/PD) for optimising dosage regimens and route of administration; (ii) antibiotic dosages in some special subpopulations; and (iii) treatment considerations relating to different antibiotic classes and their adverse events.

Results: Clinicians should understand the altered PK/PD of drugs in this population owing to co-morbid conditions and normal physiological changes associated with ageing. The body of evidence justifies the need for individualised dose selection, especially in patients with impaired renal and liver function. Clinicians should be aware of the major drug-drug interactions commonly observed in the elderly as well as potential side effects.

Conclusion: Antibiotic therapy in the elderly requires a comprehensive approach, including strategies to improve appropriate antibiotic prescribing, limit their use for uncomplicated infections and ensure the attainment of an optimal PK/PD target. To this purpose, further studies involving the elderly are needed to better understand the PK of antibiotics. Moreover, it is necessary to assess the role therapeutic drug monitoring in guiding antibiotic therapy in elderly patients in order to evaluate its impact on clinical outcome.
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http://dx.doi.org/10.1016/j.jgar.2020.02.022DOI Listing
September 2020

Comparison of pedicle screw misplacement following open vs. percutaneous dorsal instrumentation after traumatic spinal fracture.

Eur J Trauma Emerg Surg 2019 Oct 17. Epub 2019 Oct 17.

ATOS Clinic Heidelberg, Bismarckstr. 9-15, 69115, Heidelberg, Germany.

Objective: Dorsal stabilization is a frequently used procedure in the treatment of acute traumatic vertebral body fractures. Besides the traditional open surgical procedure, the percutaneous positioning of pedicle screws is now widely used. The aim of the current study is to compare pedicle screw misplacement following open vs. percutaneous dorsal instrumentation after traumatic spinal fracture of the thoracic and lumbar spine and to assess possible risk factors associated with pedicle screw misplacement.

Methods: All patients who suffered a traumatic spinal fracture that were treated with dorsal stabilization in our level I trauma center in the period from 01/2007 to 03/2014 were included in this retrospective therapeutic cohort study. From 01/2007 to 06/2009, an open surgical procedure was used, and from 06/2009 to 03/2014, the percutaneous procedure was used for all types of fractures. Retrospectively, the positioning of every single pedicle screw was evaluated in the post-operative computed tomography scan and classified. Epidemiological data were also documented to compare the two treatment groups.

Results: A total of 491 patients with 681 vertebral body fractures were included. Of 733 pedicle screws placed during the open surgery procedure, 96.0% were within the safe zone. There was no significant difference compared with pedicle screws placed percutaneously (95.3% of 1884 screws). In all other categories, the number of misplaced pedicle screws also showed no differences between the two treatment groups. There is a positive correlation between pedicle screw misplacement and duration of the operation. Most pedicle screws are misplaced at the levels T12, L1 and T7, T8.

Conclusion: The current study shows that percutaneous surgery using dorsal stabilization allows the positioning of pedicle screws in an equivalently safe manner compared with an open surgical procedure in the acute care of spinal trauma.
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http://dx.doi.org/10.1007/s00068-019-01245-8DOI Listing
October 2019

Italian recommendations for influenza and pneumococcal vaccination in adult patients with autoimmune rheumatic diseases.

Clin Exp Rheumatol 2020 Mar-Apr;38(2):245-256. Epub 2019 Aug 27.

Infectious Diseases Unit, Sapienza University, S.M. Goretti Hospital, Latina, Italy.

Objectives: To provide evidence-based recommendations for vaccination against influenza virus and S. pneumoniae in patients with autoimmune rheumatic diseases (ARDs).

Methods: A Consensus Committee including physicians with expertise in rheumatic and infectious diseases was established by two Italian scientific societies, Società Italiana di Reumatologia (SIR) and Società Italiana di Malattie Infettive e Tropicali (SIMIT). The experts were invited to develop evidence-based recommendations concerning vaccinations in ARDs patients, based on their clinical status before and after undergoing immunosuppressive treatments. Key clinical questions were formulated for the systematic literature reviews, based on the clinical pathway. A search was made in Medline (via PubMed) according to the original MeSH strategy from October 2009 and a keyword strategy from January 2016 up to December 2017, updating existing EULAR recommendations. Specific recommendations were separately voted and scored from 0 (no agreement with) to 100 (maximal agreement) and supporting evidence graded. The mean and standard deviation of the scores were calculated to determine the level of agreement among the experts' panel for each recommendation. Total cumulative agreement ≥70 defined consensus for each statement.

Results: Nine recommendations, based on 6 key clinical questions addressed by the expert committee, were proposed. The aim of this work is to integrate the 2011 EULAR recommendations on vaccination against influenza and S. pneumoniae in ARDs patients. An implementation plan was proposed to improve the vaccination status of these patients and their safety during immunosuppressive treatments.

Conclusions: Influenza and pneumococcus vaccinations are effective and safe in patients with ARDs. More efforts should be made to translate the accumulated evidence into practice.
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April 2020

Role of place of acquisition and inappropriate empirical antibiotic therapy on the outcome of extended-spectrum β-lactamase-producing Enterobacteriaceae infections.

Int J Antimicrob Agents 2019 Jul 12;54(1):49-54. Epub 2019 Apr 12.

Experimental and Clinical Medicine Department, Università degli Studi di Firenze, Florence, Italy; USC Microbiologia e Virologia, AOSP Papa Giovanni XXIII, Piazza OMS 1, Bergamo, Italy; Institute of Infectious Diseases, Catholic University of Rome, Rome, Italy; Clinical Microbiology and Virology Unit, Alessandro Manzoni Hospital, Lecco, Italy; Infectious Diseases Department, Azienda Socio Sanitaria Territoriale di Cremona, Cremona, Italy; Emergency Department, Azienda Socio Sanitaria Territoriale di Cremona, Cremona, Italy; Microbiology and Virology Unit, Azienda Ospedaliero-Universitaria Careggi, Florence, Italy.

The impact of inappropriate empirical antibiotic therapy (IEAT) on the outcome of severe infections due to extended-spectrum β-lactamase-producing Enterobacteriaceae (ESBL-Ent) remains unclear. Current evidence is limited by study design and lack of confounder control. The main objective of this study was to define the outcome of severe infections due to ESBL-Ent according to clinical parameters and place of infection acquisition. Adult hospitalised patients with ESBL-Ent infections were included in a 3-year multicentre prospective study. Primary outcomes were IEAT rates and crude mortality of severe infections, adjusted by place of acquisition [community-acquired infection (CAI), healthcare-associated infection (HCAI) and hospital-acquired infection (HAI)]. Among 729 patients, 519 (71.2%) were diagnosed with HAI, 176 (24.1%) with HCAI and 34 (4.7%) with CAI. Moreover, 32.9% of patients received IEAT; higher rates of IEAT were observed in pneumonia (23%) and deep surgical site infections (19%). HCAIs were more frequently associated with IEAT than HAIs (48.3% vs. 27.9%; OR = 1.7, 95% CI 1.2-2.4). The overall mortality rate for severe infections (n = 264) was 12.1% and was significantly higher in HCAIs (20%) than HAIs (10%) (RR = 2.3, 95% CI 1.01-5.3). IEAT significantly increased the risk of mortality in bloodstream infections (RR = 8.3, 95% CI 2-46.3). Rates of IEAT and overall mortality of ESBL-Ent severe infections were higher in HCAIs than HAIs. Prompt diagnosis of patients with severe HCAIs due to ESBL-Ent is essential since these infections receive high rates of IEAT and significantly higher mortality than HAIs [ClinicalTrials.gov Identifier: NCT00404625].
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http://dx.doi.org/10.1016/j.ijantimicag.2019.04.007DOI Listing
July 2019

Daptomycin Resistant Clinical Strain With Novel Non-synonymous Mutations in the and Genes: A New Insight Into Daptomycin Resistance.

Front Microbiol 2018 6;9:2705. Epub 2018 Nov 6.

Department of Medical Microbiology, University Medical Center Groningen, University of Groningen, Groningen, Netherlands.

Daptomycin (DAP) resistance in is uncommon but there are increasing reports of the emergence of resistance during DAP therapy. Most clinical DAP-resistant isolates investigated carried mutations in the gene. The aim of this study was to identify mutations between a clinical pair of methicillin-susceptible (MSSA) isolates (DAP-susceptible and DAP-resistant). Additionally, the activity of genes previously associated with DAP resistance was assessed. Two MSSA isolates from patient with left-sided endocarditis were analyzed by whole genome sequencing (WGS) and reverse transcription-quantitative real-time PCR (RT-qPCR). The first isolate, DAP-susceptible, was obtained before initiation of treatment and the second isolate, DAP-resistant, was recovered after 4 weeks of DAP therapy. Comparison of complete genomes of DAP-susceptible and its DAP-resistant variant identified two non-synonymous and one synonymous mutations. The non-synonymous mutations consisted of a S829L substitution in and a T331I substitution in . The RT-qPCR experiments revealed an increased expression of , and genes in DAP-resistant variant. Strikingly, the expression of and genes was significantly downregulated by DAP. The and genes were previously associated with DAP resistance, however, none of the mutations described in this study had been previously identified and linked to DAP resistance. Moreover, we provide a new insight into the DAP action on , in which the expression of key genes in DAP resistance is decreased by the antibiotic.
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http://dx.doi.org/10.3389/fmicb.2018.02705DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6232378PMC
November 2018

Minimally invasive reduction and percutaneous posterior fixation of one-level traumatic thoraco-lumbar and lumbar spine fractures.

Eur J Orthop Surg Traumatol 2018 Dec 16;28(8):1581-1587. Epub 2018 May 16.

Department of Orthopaedics and Trauma Surgery, University Medical Center Mannheim, Medical Faculty Mannheim of Heidelberg University, Theodor-Kutzer-Ufer 1-3, 68167, Mannheim, Germany.

Introduction: Although open procedures are the gold standard, the alternative approach of minimal invasive reduction using percutaneous screws for thoracic and lumbar spine fractures is under discussion. Aim of this study was to investigate the results of reduction and the accuracy of screw placement in minimally invasive percutaneous posterior instrumentation for these fractures.

Materials And Methods: One hundred and twenty-seven patients with thoraco-lumbar and lumbar burst fractures and minimal invasive dorsal instrumentation were analyzed retrospectively in terms of the accuracy of pedicle screw placement and results of fracture reduction.

Results: In total, 542 screws were placed. Thirty-four (6.3%) screws of 22 patients (17.3%) were misplaced, but misplacement was minimal, replacement of any screw position due to instability was not necessary, and no new neurological deficit occurred. In thoraco-lumbar fractures (82/64.5%), reduction succeeded from 2.5 ± 6° kyphosis to 5.6 ± 5.7° lordosis (p < 0.001) and in lumbar spine fractures from 6.9° ± 10.3° lordosis to 14.5° ± 8.8° lordosis (p < 0.001).

Conclusion: Minimal invasive percutaneous dorsal instrumentation of burst fractures of the thoraco-lumbar and lumbar spine provides adequate reduction and reliable regular screw placement.

Level Of Evidence: Level IV (retrospective series).
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http://dx.doi.org/10.1007/s00590-018-2224-9DOI Listing
December 2018

An outbreak of skin infections in neonates due to a Staphylococcus aureus strain producing the exfoliative toxin A.

Infection 2018 Feb 6;46(1):49-54. Epub 2017 Nov 6.

Department of Infectious Diseases, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161, Rome, Italy.

Purpose: Staphylococcus aureus is an important cause of infections in hospitalized neonates. Preterm or low birthweight infants are especially at risk to develop a S. aureus infection due to the immaturity of the immune system, length of hospital stay and invasive procedures. Exfoliative toxin (ET)-producing S. aureus is often responsible for neonatal infections, causing clinical manifestations such as staphylococcal scalded skin syndrome, characterized by both localized blisters or generalized exfoliation of the skin.

Methods: We describe an outbreak due to an S. aureus strain producing ETA occurring in a local hospital in Northern Italy. Molecular typing of the isolates included spa typing and multilocus sequence typing. DNA microarray hybridization was also performed on one representative strain.

Results: In the period from July 2013 to February 2014, 12 neonates presented with skin infections, mainly bullae or pustules. Cultures of skin swabs yielded methicillin-susceptible S. aureus (MSSA). By molecular typing, an epidemic strain (t1393/ST5) was identified in nine neonates; microarray analysis and PCR revealed that it contained the ETA encoding gene. Screening of staff, mothers and healthy neonates and environmental cultures did not reveal the presence of the epidemic strain. However, the father of an infected neonate was found to be a carrier of MSSA t1393 five months after the outbreak started.

Conclusion: Implementation of hygiene procedures and sanitization of the ward twice terminated the outbreak. Timely surveillance of infections, supported by molecular typing, is fundamental to prevent similar episodes among neonates.
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http://dx.doi.org/10.1007/s15010-017-1084-2DOI Listing
February 2018

High early post-operative complication rate after elective aseptic orthopedic implant removal of upper and lower limb.

J Orthop Res 2018 03 27;36(3):1035-1039. Epub 2017 Sep 27.

Department of Trauma and Orthopaedics, BG Trauma Center Ludwigshafen, Ludwig-Guttmann-Strasse 13, Ludwigshafen, 67071, Germany.

The necessity of orthopedic implant removal is under intense discussion and even if it is performed as an elective procedure, the risk of complications is present. Aim of the study was to identify parameters responsible for an increased risk of early post-operative complications after elective aseptic orthopedic implant removal. We reviewed 1,545 cases of aseptic and elective orthopedic implant removal between 2009 and 2011. The patient́s demographic data, time and duration of operation, patient́s comorbidities, and presence of complications in the first 4 weeks after implant removal were evaluated. Patients with signs of infection at the time of the surgical procedure were excluded from this study. 579 women and 966 men who underwent elective aseptic orthopedic implant removal were identified. Mean age at implant removal was 42 years and mean duration of the surgical procedure was 37 min. In this cohort, 70 patients (4.5%) underwent elective aseptic implant removal after 6pm. 52 patients (3.37%) operated on during daytime suffered from complications post-operatively and five patients (0.3%) who were operated on during the night experienced complications. The parameters age, sex, BMI, and surgeon showed no statistically significant differences for the risk of post-operative complications. Patients' comorbidities such as diabetes seem to have influence but were not statistically significant either. Patients with revision surgery since their first operation, nocturnal surgery and longer duration of the procedure showed a statistically significant higher risk for complications, especially in the lower leg. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:1035-1039, 2018.
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http://dx.doi.org/10.1002/jor.23718DOI Listing
March 2018

Is it time to revise linezolid dose in elderly patients?

Eur J Clin Pharmacol 2017 Oct 15;73(10):1335-1336. Epub 2017 Jul 15.

Unit of Clinical Pharmacology, L. Sacco University Hospital, Milan, Italy.

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http://dx.doi.org/10.1007/s00228-017-2303-6DOI Listing
October 2017

Good isometric and isokinetic power restoration after distal biceps tendon repair with anchors.

Arch Orthop Trauma Surg 2017 Jul 2;137(7):939-944. Epub 2017 Jun 2.

Department of Trauma and Orthopaedics, BG Trauma Center Ludwigshafen, Ludwig-Guttmann-Strasse 13, 67071, Ludwigshafen, Germany.

Introduction: Distal biceps brachii tendon rupture can lead to 30-40% power loss of elbow flexion and up to 50% of forearm supination. Re-fixation of the distal biceps brachii tendon is recommended to warrant an adequate quality of the patient's life. This study reports the isometric and isokinetic results after anchor re-fixation 2.5 years after surgery.

Patients And Methods: Between 2007 and 2010, 69 patients with distal biceps brachii tendon tear underwent a suture anchor reattachment. During the follow-up examination, a questionnaire and DASH score were filled in, the circumferences of the arm were measured, range of motion was collected, and different trials were conducted at the BTE Primus RS™ (Baltimore Therapeutic Equipment) on both arms.

Results: 49 patients (71%) were reinvestigated with a follow-up of 32 months (11-58 months). A significant difference was found in the ability of elbow flexion between the affected arm and the opposite side as well as in pronation and supination. In elbow flexion and extension as well as in pronation and supination of the forearm, the strength was significantly diminished.

Conclusions: 32 months after surgical re-fixation of the distal biceps brachii tendon rupture, strength in all exercises is marginally reduced in comparison to the opposite arm. Re-fixation of the distal biceps brachii tendon is an adequate method to return the range of motion and the strength in the elbow joint to an almost normal level and that gives rise to a high level of patient satisfaction.

Level Of Evidence: Level III, case-control study.
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http://dx.doi.org/10.1007/s00402-017-2724-9DOI Listing
July 2017

Diagnosis and management of skin and soft-tissue infections (SSTI). A literature review and consensus statement: an update.

J Chemother 2017 Aug 5;29(4):197-214. Epub 2017 Apr 5.

n Infectious Diseases Division , University of Genoa and IRCCS San Martino-IST , Genoa , Italy.

Skin and soft-tissue infections (SSTIs) are among the most common bacterial infections, posing considerable diagnostic and therapeutic challenges. Fourteen members of the Italian Society of Infectious Diseases, after a careful review of the most recent literature using Medline database and their own clinical experience, updated a previous paper published in 2011 by preparing a draught manuscript of the statements. The manuscript was successively reviewed by all members and ultimately re-formulated the present manuscript during a full day consensus meeting. The microbiological and clinical aspects together with diagnostic features were considered for necrotizing and not necrotizing SSTIs in the light of the most recent guidelines and evidences published in the last five years. The antimicrobial therapy was considered as well - both empirical and targeted to methicillin-resistant Staphylococcus aureus and/or other pathogens, also taking into account the epidemiological and bacterial resistance data and the availability of new antibacterial agents.
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http://dx.doi.org/10.1080/1120009X.2017.1311398DOI Listing
August 2017

Diagnosis of periprosthetic joint infection using alpha-defensin test or multiplex-PCR: ideal diagnostic test still not found.

Int Orthop 2017 07 4;41(7):1307-1313. Epub 2017 Feb 4.

Department of Trauma and Orthopaedics, BG Trauma Center Ludwigshafen, Ludwig-Guttmann-Strasse 13, 67071, Ludwigshafen, Germany.

Purpose: Diagnosing periprosthetic infection remains a challenge. Multiplex-PCR and biomarkers such as alpha-defensin are potentially useful and fast methods for detecting periprosthetic infection. This study compared these new methods with clinical assessment, conventional microbiological methods and histo-pathological examination.

Methods: Twenty-eight consecutive patients with 30 joints and a mean age of 67.7 years (range 39 to 88) with removal of total hip arthroplasty (THA) or total knee replacement (TKR) were included in this study. Patients were classified according to the modified Musculoskeletal Infection Society score (MSIS) for infected joints. Punction fluid and tissue specimens were taken for conventional microbiological examination, alphadefensin test was performed, a synovial membrane specimen was used for multiplex-PCR and histopathological examination was carried out.

Results: The alpha-defensin test and multiplex-PCR showed a sensitivity of 76.9 vs. 30.8% and a specificity of 82.4 vs. 100%, respectively. We found a significant difference between the positive and negative results (p = 0.0023). The conventional microbiological methods were not significantly different from the alpha-defensin test (p = 0.244) with a sensitivity of 84.6% and a specificity of 100% but did differ significantly from the multiplex PCR (p = 0.0030). There was a significant difference between modified MSIS classification and multiplex PCR (p = 0.0007).

Conclusions: Neither alpha-defensin test nor multiplex-PCR could detect periprosthetic infection immediately and reliably. Multiplex-PCR was suitable for detecting the non-infected but not the truly infected. Alpha-defensin test was helpful but showed no satisfactory results. Conventional microbiological methods remain the most reliable for periprosthetic infection diagnosis.
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http://dx.doi.org/10.1007/s00264-017-3412-7DOI Listing
July 2017

Analysis of complications and perioperative data after open or percutaneous dorsal instrumentation following traumatic spinal fracture of the thoracic and lumbar spine: a retrospective cohort study including 491 patients.

Eur Spine J 2017 05 15;26(5):1535-1540. Epub 2016 Dec 15.

Department of Trauma Surgery and Orthopedic Surgery, BG Trauma Centre Ludwigshafen, Ludwig-Guttmann-Str. 13, 67071, Ludwigshafen, Germany.

Purpose: The aim of the current study is to analyze perioperative data and complications of open vs. percutaneous dorsal instrumentation after dorsal stabilization in patients suffering from fractures of the thoracic or lumbar spine.

Methods: In the time period from 01/2007 to 06/2009, open surgical approach was used for dorsal stabilization. The percutaneous surgical approach was used from 05/2009 to 03/2014. In every time period, all types of fractures were treated only by open or by percutaneous approach, respectively, to avoid any selection bias. Retrospectively, epidemiological data, complications and perioperative data were documented and statistically analyzed.

Results: A total of 491 patients met the inclusion criteria. Open surgery procedure was carried out on 169 patients, and percutaneous surgery procedure was carried out on 322 patients. Fracture level ranged from T1 to L5, and fractures were classified types A, B, and C. In 91.4% of all patients, no complication occured following dorsal stabilization after traumatic spine fracture during their hospital stay. However, 42 complications related to dorsal stabilization have been documented during the hospital stay. The complication rate was 14.8% if open surgical approach has been used and was significantly reduced to 5.3% using percutaneous surgical approach. Post-operative hospital stay was also reduced significantly using the percutaneous surgical approach.

Conclusions: According to the current study, percutaneous dorsal stabilization of the spine could also be safely used in trauma cases and is not restricted to degenerative spinal surgery.
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http://dx.doi.org/10.1007/s00586-016-4911-8DOI Listing
May 2017

Staphylococcus aureus toxic shock syndrome toxin-1 endocarditis with muscular metastatic abscesses.

New Microbiol 2014 Jan 15;37(1):113-8. Epub 2014 Jan 15.

Division of Infectious and Tropical Diseases, Hospital of Lodi, Italy.

A 42-year-old woman, living in a nursing home for the mentally disabled, with congenital ventricular septal defect and multiple comorbidities, developed endocarditis with vegetations of the interventricular septum and the right coronary aortic leaflet. The main feature of this case was the metastatic embolism leading to multiple and muscular abscesses. Methicillin-sensitive S. aureus, spa type 253 and ST30, producing toxin shock syndrome toxin-1 was isolated from blood cultures. The patient was initially treated with beta-lactam antibiotics without showing clinical response and subsequently with daptomycin and linezolid that improved the patient's clinical symptoms. The effectiveness of treatment with daptomycin and linezolid was partly due to the ability of linezolid to reduce TSST-1 secretion. The portal of entry of the infection was not recognized. TSST-1 production by the strain might have favoured the formation of large cardiac vegetations and the subsequent metastatic dissemination to the muscles.
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January 2014

Epidemiology and genetic characteristics of extended-spectrum β-lactamase-producing Gram-negative bacteria causing urinary tract infections in long-term care facilities.

J Antimicrob Chemother 2012 Dec 3;67(12):2982-7. Epub 2012 Aug 3.

Division of Infectious and Tropical Diseases, Hospital of Lodi, Lodi, Italy.

Objectives: To assess risk factors for acquiring extended-spectrum β-lactamase-producing Gram-negative bacteria (ESBL+ GN) causing urinary tract infections (UTIs) in long-term care facilities (LTCFs).

Methods: A prospective case-case-control study was carried out. In the first study, cases were defined as patients harbouring ESBL+ GN, while, in the second study, cases were defined as patients harbouring ESBL-negative (ESBL-) GN. Controls were selected by simple random sampling from patients without GN infection. ESBL determinants were characterized by hybridization, and confirmed by PCR and sequencing.

Results: The study involved 297 LTCF patients (99 with ESBL+ GN UTI, 99 with ESBL- GN UTI and 99 without GN infection). ESBL+ GN UTIs were due to Escherichia coli (64%), Proteus mirabilis (25%) and Klebsiella pneumoniae (11%). The CTX-M-type enzymes were the most prevalent (73% of isolates), whereas TEM- and SHV-type ESBLs and AmpC-type enzymes were less prevalent (10%, 2% and 15% of isolates, respectively). Patients with ESBL+ GN UTI were more likely to have a permanent urinary catheter (OR 15, 95% CI 6.9-30.5) and to have received antimicrobial therapy in the previous 30 days (OR 4, 95% CI 1.2-10.9). After adjusting for type, dosage and duration of antibiotic, exposure to ≥7 days of quinolones and third-generation cephalosporins was associated with the highest risk of ESBL+ GN UTI development (OR 7, 95% CI 1.2-40). Independent risk factors for acquiring ESBL- GN UTIs were previous surgical procedures (OR 2, 95% CI 1.1-4) and the presence of a urinary catheter (OR 8, 95% CI 4-16). No specific antibiotics remained a significant risk for ESBL- GN UTI after adjusting for demographic and clinical risk factors.

Conclusions: Exposure to ≥7 days of quinolones and third-generation cephalosporins significantly increases the risk of ESBL+ GN UTI. Interventions aimed at improving compliance with antimicrobial stewardship principles should be further developed and implemented in LTCFs.
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http://dx.doi.org/10.1093/jac/dks300DOI Listing
December 2012

Nef-specific CD45RA+ CD8+ T cells secreting MIP-1beta but not IFN-gamma are associated with nonprogressive HIV-1 infection.

AIDS Res Ther 2010 Jul 2;7:20. Epub 2010 Jul 2.

Institute of Virology, Helmholtz Zentrum München - German Research Center for Environmental Health, 85764 Neuherberg, Germany.

Background: Long-term survival of HIV-1 infected individuals is usually achieved by continuous administration of combination antiretroviral therapy (ART). An exception to this scenario is represented by HIV-1 infected nonprogressors (NP) which maintain relatively high circulating CD4+ T cells without clinical symptoms for several years in the absence of ART. Several lines of evidence indicate an important role of the T-cell response in the modulation of HIV-1 infection during the acute and chronic phase of the disease.

Results: We analyzed the functional and the differentiation phenotype of Nef- and Tat-specific CD8+ T cells in a cohort of HIV-1 infected NP in comparison to progressors, ART-treated seropositive individuals and individuals undergoing a single cycle of ART interruption. We observed that a distinctive feature of NP is the presence of Nef-specific CD45RA+ CD8+ T cells secreting MIP-1beta but not IFN-gamma. This population was present in 7 out of 11 NP. CD45RA+ IFN-gammaneg MIP-1beta+ CD8+ T cells were not detected in HIV-1 infected individuals under ART or withdrawing from ART and experiencing a rebounding viral replication. In addition, we detected Nef-specific CD45RA+ IFN-gammaneg MIP-1beta+ CD8+ T cells in only 1 out of 10 HIV-1 infected individuals with untreated progressive disease.

Conclusion: The novel antigen-specific CD45RA+ IFN-gammaneg MIP-1beta+ CD8+ T cell population represents a new candidate marker of long-term natural control of HIV-1 disease progression and a relevant functional T-cell subset in the evaluation of the immune responses induced by candidate HIV-1 vaccines.
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http://dx.doi.org/10.1186/1742-6405-7-20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2909146PMC
July 2010

Methicillin-susceptible Staphylococcus aureus in skin and soft tissue infections, Northern Italy.

Emerg Infect Dis 2009 Feb;15(2):250-7

Hospital of Lodi, Lodi, Italy.

During February 2004-September 2006, familial clusters and sporadic cases of Staphylococcus aureus skin and soft tissue infections were observed in a suburban area near Milan in northern Italy. Molecular typing of the isolates showed an epidemic methicillin-susceptible S. aureus (MSSA) strain, spa type 005 and sequence type 22 that harbored Panton-Valentine leukocidin (PVL) genes. The first case-patients were neonates or mothers who had recently delivered in the local hospital. Examination of the medical records showed a cluster of postpartum mastitis and neonatal skin infections antedating the emergence of infections in the community. Nasal swabs of neonates, mothers, and hospital staff were positive for the epidemic MSSA. Hospital circulation of the strain was interrupted by implementation of infection control measures, although infections continued to occur in the community. The PVL-positive MSSA strain resembles typical community-acquired methicillin-resistant S. aureus in its ability to cause prolonged community and hospital outbreaks of skin infections.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2657610PMC
http://dx.doi.org/10.3201/eid1502.080010DOI Listing
February 2009

The intracellular detection of MIP-1beta enhances the capacity to detect IFN-gamma mediated HIV-1-specific CD8 T-cell responses in a flow cytometric setting providing a sensitive alternative to the ELISPOT.

AIDS Res Ther 2008 Oct 6;5:22. Epub 2008 Oct 6.

Institute of Virology, Helmholtz Zentrum München, German Research Center for Environmental Health, 85764 Neuherberg, Germany.

Background: T-cell mediated immunity likely plays an important role in controlling HIV-1 infection and progression to AIDS. Several candidate vaccines against HIV-1 aim at stimulating cellular immune responses, either alone or together with the induction of neutralizing antibodies, and assays able to measure CD8 and CD4 T-cell responses need to be implemented. At present, the IFN-gamma-based ELISPOT assay is considered the gold standard and it is broadly preferred as primary assay for detection of antigen-specific T-cell responses in vaccine trials. However, in spite of its high sensitivity, the measurement of the sole IFN-gamma production provides limited information on the quality of the immune response. On the other hand, the introduction of polychromatic flow-cytometry-based assays such as the intracellular cytokine staining (ICS) strongly improved the capacity to detect several markers on a single cell level.

Results: The cumulative analysis of 275 samples from 31 different HIV-1 infected individuals using an ICS staining procedure optimized by our laboratories revealed that, following antigenic stimulation, IFN-gamma producing T-cells were also producing MIP-1beta whereas T-cells characterized by the sole production of IFN-gamma were rare. Since the analysis of the combination of two functions decreases the background and the measurement of the IFN-gamma+ MIP-1beta+ T-cells was equivalent to the measurement of the total IFN-gamma+ T-cells, we adopted the IFN-gamma+ MIP-1beta+ data analysis system to evaluate IFN-gamma-based, antigen-specific T-cell responses. Comparison of our ICS assay with ELISPOT assays performed in two different experienced laboratories demonstrated that the IFN-gamma+ MIP-1beta+ data analysis system increased the sensitivity of the ICS up to levels comparable to the sensitivity of the ELISPOT assay.

Conclusion: The IFN-gamma+ MIP-1beta+ data evaluation system provides a clear advantage for the detection of low magnitude HIV-1-specific responses. These results are important to guide the choice for suitable highly sensitive immune assays and to build reagent panels able to accurately characterize the phenotype and function of responding T-cells. More importantly, the ICS assay can be used as primary assay to evaluate HIV-1-specific responses without losing sensitivity in comparison to the ELISPOT assay.
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http://dx.doi.org/10.1186/1742-6405-5-22DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2569082PMC
October 2008

Epidemiology of bacterial meningitis in Lombardy Region in the period 2000-2006.

New Microbiol 2007 Jul;30(3):340-5

Regional Working Group on Surveillance and Control of Bacterial Meningitis, Regional Health Office, Lombardy, Italy.

Epidemiological study of bacterial meningitis, particularly those forms susceptible to vaccination, is an indispensable tool in choosing vaccination strategies. Lombardy Region, where approximately 20% of the Italian population resides, has conducted an in-depth study on invasive meningococcal diseases and pneumococcal meningitis using available health statistics and performing a control of single cases to achieve complete knowledge of the phenomenon. The results, relating to the period 2000-2006, indicate limited incidence rates both for the general population and childhood age groups that do not justify hypotheses of a universal offering of the specific vaccines. However, the healthcare system must equip itself with additional tools for the identification of the serogroups and serotypes responsible for disease as a further support for possible choices modifying the current vaccination policies.
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July 2007

Naturally occurring C-terminally truncated STAT5 is a negative regulator of HIV-1 expression.

Blood 2007 Jun 1;109(12):5380-9. Epub 2007 Mar 1.

AIDS Immunopathogenesis Unit and the Division of Infectious Diseases, San Raffaele Scientific Institute, Milano, Italy.

CD4(+) cells of most individuals infected with HIV-1 harbor a C-terminally truncated and constitutively activated form of signal transducer and activator of transcription-5 (STAT5 Delta). We report that the chronically HIV-infected U1 cell line expresses STAT5 Delta but not full-length STAT5. Granulocyte-macrophage colony-stimulating factor (GM-CSF) stimulation of U1 cells promoted early activation of STAT5 Delta and of extracellular signal regulated kinases (ERKs), followed by later activation of activator protein 1 (AP-1) and HIV expression. Inhibition of ERK/AP-1 by PD98,059 abolished, whereas either tyrphostin AG490 or a STAT5 small interfering RNA (siRNA) enhanced, virion production in GM-CSF-stimulated U1 cells. Chromatin immunoprecipitation demonstrated the induction of STAT5 Delta binding to STAT consensus sequences in the HIV-1 promoter together with a decreased recruitment of RNA polymerase II after 1 hour of GM-CSF stimulation of U1 cells. Down-regulation of STAT5 Delta by siRNA resulted in the up-regulation of both HIV-1 gag-pol RNA and p24 Gag antigen expression in CD8-depleted leukocytes of several HIV-positive individuals cultivated ex vivo in the presence of interleukin-2 but not of interleukin-7. Thus, the constitutively activated STAT5 Delta present in the leukocytes of most HIV-positive individuals acts as a negative regulator of HIV expression.
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http://dx.doi.org/10.1182/blood-2006-08-042556DOI Listing
June 2007