Carbon Monoxide Exposure Does Not Improve The In Vitro Fertilization Rate of Oocytes Obtained from Heterozygous Hmox1 Knockout Mice.

In our experimental study we explored the impact of maternal reduced heme oxygenase-1 (HO-1) gene (Hmox1) expression on the in vitro fertilization (IVF) rate through the use of heterozygous Hmox1 knockout mice models (HET/Hmox1+/ -). Also, we hypothesized a beneficial role of gametes exposure during fertilization to carbon monoxide (CO), one of HO-1 by-products, that might be relevant for the improvement of IVF rates. IVF technique was performed by using oocytes obtained from wild-type (WT) or Hmox1+/ - dams fertilized with WT, Hmox1+/ - or Hmox1-/ - mice-derived sperm. The fertilization step occurred either in a conventional incubator (37°C, 5% CO2) or in an incubator implemented with CO (500 ppm). The superovulation yield of WT and Hmox1+/ - mice and the number of fertilized oocytes was assessed using an optical microscope. The dams' Hmox1 heterozygous knockout neither impact the superovulation yield, nor did influence the fertilization success rate. Moreover, CO exposure during fertilization could not significantly improve the outcome. Our study showed that the maternal Hmox1+/ -condition is not affecting the IVF rate in mice. Furthermore, we discovered that CO exposure cannot be exploited to ameliorate this critical step of the IVF protocol.

Case series study of nosocomial Legionnaires' disease in Apulia region (southern Italy): The role of different molecular methods in identifying the infection source

BACKGROUND AND AIM: Legionnaires' disease is a severe form of pneumonia caused by the inhalation or aspiration of water droplets contaminated with Legionella pneumophila and other Legionella species. These bacteria are commonly found in natural habitats and man-made water systems. Legionnaires' disease is a significant public health problem, especially in healthcare settings where patients may be exposed to contaminated environmental sources. Nosocomial outbreaks have been reported worldwide, leading to high morbidity and mortality rates, and increased healthcare costs. This study aimed to compare, the clonal relationship of clinical L. pneumophila strains from two different hospitals with L. pneumophila strains isolated from the water supply. METHODS: In the period from 2019 to 2021, clinical and environmental strains involved in three cases of legionellosis were compared by means of pulsed field gel electrophoresis and sequence based typing techniques. RESULTS: Our findings highlight the persistence of clonally distinct strains within each hospital examined. Furthermore, the L. pneumophila strains detected from hospital environmental sources were related to the clinical strains isolated, demonstrating the nosocomial origin of these cases. CONCLUSIONS: Therefore, it is important to implement more accurate surveillance systems both for epidemiological studies and to check the effectiveness of remediation procedures. (www.actabiomedica.it).

Cefiderocol Versus Colistin for the Treatment of Carbapenem-Resistant Acinetobacter baumannii Complex Bloodstream Infections: A Retrospective, Propensity-Score Adjusted, Monocentric Cohort Study.

INTRODUCTION: Bloodstream infections (BSI) caused by carbapenem-resistant Acinetobacter baumannii (CRAB) are associated with high mortality with limited treatment. The aim of this study is to compare effectiveness and safety of colistin-based versus cefiderocol-based therapies for CRAB-BSI. METHODS: This is a retrospective observational study enrolling patients with monomicrobial CRAB-BSIs treated with colistin or cefiderocol from 1 January 2020, to 31 December 2022. The 30-day all-cause mortality rate was the primary outcome. A Cox regression analysis was performed to identify factors independently associated with mortality. A propensity score analysis using inverse probability of treatment weighting (IPTW) was also performed. RESULTS: Overall 118 patients were enrolled, 75 (63%) and 43 (37%) treated with colistin- and cefiderocol-based regimens. The median (q1-q3) age was 70 (62-79) years; 70 (59%) patients were men. The 30-day all-cause mortality was 52%, significantly lower in the cefiderocol group (40% vs 59%, p = 0.045). By performing a Cox regression model, age (aHR = 1.03, 95% CI 1.00-1.05), septic shock (aHR = 1.93, 95% CI 1.05-3.53), and delayed targeted therapy (aHR = 2.42, 95% CI 1.11-5.25) were independent predictors of mortality, while cefiderocol-based therapy was protective (aHR = 0.49, 95% CI 0.25-0.93). The IPTW-adjusted Cox analysis confirmed the protective effect of cefiderocol (aHR = 0.53, 95% CI 0.27-0.98). CONCLUSIONS: Cefiderocol may be a valuable treatment option for CRAB-BSI, especially in the current context of limited treatment options.

A novel smartphone App to support the clinical practice of pediatric ophthalmology and strabismus: the validation of visual acuity tests.

This study is aimed at describing the TreC Oculistica novel smartphone App that facilitated the clinical practice of pediatric ophthalmology and strabismus during the COVID-19 pandemic and at reporting on the validation of visual acuity tests in a home setting. The Trec Oculistica smartphone App was prescribed to eligible patients at the Pediatric Ophthalmology and Strabismus Clinic, Ophthalmology Unit of Rovereto Hospital, between September 2020 and March 2022. Four key indicators were identified for monitoring visual and visuo-motor functions remotely: visual acuity, ocular motility, head posture, and color vision. Clinicians selected few mobile applications (iOS, Android) and printable materials within the Trec Oculistica App: the Snellen Chart Visual Acuity App, the 9Gaze App, the eyeTilt App, the Color Blind test App, the LEA Symbols pdf, and the Snellen Chart pdf. All patients, aged 4 and older, were screened at home for visual acuity at 3 m and later in the clinic (LEA Symbols cabinet or Snellen computerized optotype). The 9Gaze, the eyeTilt, and the Color Blind test Apps were only recommended to a subset of patients based on clinical suspicion or diagnosis. The Wilcoxon signed rank sum test and weighted Cohen's kappa coefficient were applied to compare pairs of scores from different settings. The Trec Oculistica App was downloaded and activated by 97 patients or their caregiver. 40 patients were tested at home using the 9Gaze App, 7 used the eyeTilt App, and 11 used the Color-Blind test App. Families reported that all the Apps were easy and intuitive to use; clinicians reported that measurements were reliable. 82 eyes of 41 patients (mean age 5.2 years, SD ± 0.4, range 4.4-6.1) were tested for visual acuity using the self-administered LEA Symbols pdf. 92 eyes of 46 patients (mean age 11.6 years, SD ± 5.2, range 6-35) were evaluated using the self-administered Snellen Chart Visual Acuity App or the Snellen Chart pdf. Home median visual acuity score was statistically different from that registered in clinical setting for both the LEA Symbols pdf (P-value = 0.0074) and the Snellen Chart App and pdf (P-value = 0.0001). The strength of agreement was 0.12 (slight) for the LEA Symbols pdf, 0.50 (moderate) for the Snellen Chart Visual Acuity App, and 0.69 (substantial) for the Snellen Chart pdf. CONCLUSION: The novel TreC Oculistica smartphone App was a useful tool for facilitating the clinical practice of pediatric ophthalmology and strabismus during the COVID-19 pandemic. In the follow-up of strabismus patients and patients with suspected inherited retinal diseases, the 9Gaze, eyeTilt, and Color Blind test applications were deemed to be intuitive and easy to use by families and were considered reliable by clinicians. In a home setting, visual acuity tested by means of Snellen Charts was moderately congruent with the in-office examination. On the contrary, agreement was poor in younger children tested with the LEA Symbols pdf. WHAT IS KNOWN: • Teleophthalmology enables clinicians to evaluate patients' ocular diseases remotely and various tools are helpful for screening, follow-ups and treatment. • Smartphones can currently be used to obtain ocular images and vision measurements of patients' eyes and this information can be shared with the ophthalmologist for further evaluations and medical management (mhealth). WHAT IS NEW: • Smartphone Apps can be successfully used in a hybrid teleophthalmology service concerning first visits and follow-ups. • Apps and printable materials are easy, intuitive to use for patients and  also reliable for  clinicians.

Effectiveness of First-Line Therapy with Old and Novel Antibiotics in Ventilator-Associated Pneumonia Caused by Carbapenem-Resistant Acinetobacter baumannii: A Real Life, Prospective, Observational, Single-Center Study.

Evidence-based, standard antibiotic therapy for ventilator-associated pneumonia (VAP) caused by carbapenem-resistant Acinetobacter baumannii (CRAB) is a relevant unmet clinical need in the intensive care unit (ICU). We aimed to evaluate the effectiveness of first-line therapy with old and novel CRAB active antibiotics in monomicrobial VAP caused by CRAB. A prospective, observational study was performed in a mixed non-COVID-19 ICU. The primary outcome measure was clinical failure upon first-line targeted therapy. Features independently influencing failure occurrence were also investigated via Cox proportional multivariable analysis. To account for the imbalance in antibiotic treatment allocation, a propensity score analysis with an inverse probability treatment weighting approach was adopted. Of the 90 enrolled patients, 34 (38%) experienced clinical failure. Compared to patients who experienced a clinical resolution of VAP, those who had clinical failure were of an older age (median age 71 (IQR 64-78) vs. 62 (IQR 52-69) years), and showed greater burden of comorbidities (median Charlson comorbidity index 8 (IQR 6-8) vs. 4 (IQR 2-6)), higher frequency of immunodepression (44% vs. 21%), and greater clinical severity at VAP onset (median SOFA score 10 (IQR 9-11) vs. 9 (IQR 7-11)). Lower rates of use of fast molecular diagnostics for nosocomial pneumonia (8.8% vs. 30.3%) and of timely CRAB active therapy administration (65% vs. 89%), and higher rates of colistin-based targeted therapy (71% vs. 46%) were also observed in patients who failed first-line therapy. Overall, CRAB active iv regimens were colistin-based in 50 patients and cefiderocol-based in 40 patients, both always combined with inhaled colistin. According to the backbone agent of first-line regimens, clinical failure was lower in the cefiderocol group, compared to that in the colistin group (25% vs. 48%, respectively). In multivariable Cox regression analysis, the burden of comorbid conditions independently predicted clinical failure occurrence (Charlson index aHR = 1.21, 95% CI = 1.04-1.42, p = 0.01), while timely targeted antibiotic treatment (aHR = 0.40, 95% CI = 0.19-0.84, p = 0.01) and cefiderocol-based first-line regimens (aHR = 0.38, 95% CI = 0.17-0.85, p = 0.02) strongly reduced failure risk. In patients with VAP caused by CRAB, timely active therapy improves infection outcomes and cefiderocol holds promise as a first-line therapeutic option.

Coinfections in intensive care units. Has anything changed with Covid-19 pandemia?

BACKGROUND AND AIM: Since December 2019, the Coronavirus disease 2019, caused by severe acute respiratory syndrome coronavirus 2 (Sars-CoV-2), has spread from China, becoming a pandemic. Bacterial and fungal co-infections may lead to increase in COVID-19 severity with a decrease in patients survive. The aim of this work was to evaluate bacterial and fungal co-infections in COVID-19 patients admitted to ICU in comparison with patients recovered in ICU in pre-COVID-19 era in order to understand whether the pandemic had changed the incidence of overinfections in patients admitted to ICU. In fact, the epidemiological data should guide the choice of empirical therapy. METHODS: During pandemic, AOUC Policlinico of Bari organized dedicated ICUs for patient with SARS-CoV-2. Blood cultures, urine, and tracheobronchial aspirate were included in the analysis. RESULTS: Specimens of 1905 patients were analysed in this work. Comparing clinical isolates prevalence by material and COVID-19 vs. non-COVID-19 patients statistically significant differences were detected for A. baumannii complex, Aspergillus fumigatus, Escherichia coli, Haemophilus influenzae and Serratia marcescens isolated from tracheobronchial aspirates; C. albicans from urine samples, A. baumannii complex, Enterococcus faecalis and Enterococcus faecium isolated from blood culture. CONCLUSIONS: Although the organisms isolated in COVID-19 patients are consistent with those frequently associated with healthcare associated infection, our data suggest a particular prevalence in COVID-19 patients of A. baumannii, Stenotrophomonas maltophilia and Aspergillus spp. in the respiratory tract, C. albicans in urine and  A. baumannii, E. faecalis and E. faecium in blood cultures.

Thoracic aorta graft infection by avibactam-resistant KPC-producing K. pneumoniae treated with meropenem/vaborbactam: a case report and literature review.

Meropenem/vaborbactam (M/V) is a new carbapenem-carbapenemase inhibitor combination drug active against extensively drug resistant Gram-negative pathogens. Studies about its efficacy and place in therapy are limited in "real-life" and no data are available for deep site infections, like vascular graft infections. We present a case of a patient successfully treated with M/V for a thoracic aorta graft infection, placed for a traumatic penetrating aortic ulcer, due to an extensively KPC-producing Klebsiella pneumoniae resistant to ceftazidime/ avibactam. Furthermore, we conducted a systematic literature review concerning vascular graft infections caused by carbapenem-resistant Klebsiella pneumoniae and the papers published until now about the use of M/V for the treatment of ceftazidime/avibactam-resistant K. pneumoniae. Meropenem/vaborbactam is a promising antibiotic for difficult-to-treat Gram-negative bacteria with limited therapeutic options. Only few reports have been published and more studies are needed to assess which is the best place in therapy of M/V.

Predictors for Pulmonary Tuberculosis Outcome and Adverse Events in an Italian Referral Hospital: A Nine-Year Retrospective Study (2013-2021).

Background: The COVID-19 pandemic has undone years of progress in providing essential TB services and controlling the TB burden. Italy, a low TB burden country, has an incidence of 7.1 cases per 100,000 people. To control the TB spreading in Italy is critical to investigate the characteristics of patients with the worst outcomes and the highest risk of adverse events related to antituberculosis therapy. Therefore, we conducted a large retrospective study in TB patients admitted to the Clinic of Infectious Diseases University of Bari, Italy, in order to describe the clinical presentation and the factors associated with adverse events and outcomes. Methods: We retrospectively evaluated the patients admitted to the Clinic of Infectious Diseases from January 2013 to 15 December 2021. We stratified our cohort into two groups: <65 years of age and ≥65 years in order to assess any differences between the two groups. Two logistic regression models were implemented considering the dependent variables as: (I) the adverse events; and (II) the unsuccessful treatments. Results: In total, 206 consecutive patients [60% (n = 124) M, median age 39 years, range 16-92] were diagnosed and admitted with TB at Clinic of Infectious Diseases. Of the whole sample, 151 (74%) were <65 years and 55 (26%) were ≥65. Statistically significant differences between the two groups were detected (p-value < 0.05) for nationality (p-value = 0.01), previous contact with TB patient (p-value = 0.00), type of TB (p-value = 0.00), unsuccessful treatment (p-value = 0.00), length of hospitalization (p-value = 0.02) and diagnostic delay (p-value = 0.01). Adverse events related to TB drug regimen were reported in 24% (n = 49). Age < 65 years (O.R. = 3.91; 95% CI 1.72-4.21), non-Italian nationality (O.R. = 4.45; 95% CI 2.22-4.98.), homeless (O.R. = 3.23; 95% CI 2.58-4.54), presence of respiratory symptoms (O.R. = 1.23; 95% CI 1.10-1.90), diagnostic delay (O.R = 2.55; 95% CI 1.98-3.77) resulted associated with unsuccessful treatment outcome (death, failure or lost to follow up). Finally, age < 65 years (O.R. = 1.73; 95% CI 1.31-2.49), presence of pulmonary TB (O.R. = 1.15; 95% CI 1.02-1.35), length of hospitalization (O.R. = 1.82; 95% CI 1.35-2.57) and TB culture positive (O.R. = 1.35; 95% CI 1.12-1.82) were associated with adverse events in our populations. Conclusions: The pharmacological approach alone seems insufficient to treat and cure a disease whose ethiopathogenesis is not only due to the Mycobacterium tuberculosis, but also to the poverty or the social fragility. Our data suggest that young foreigners, the homeless, and the people with low social and economic status are at higher risk of an unfavorable outcome in low incidence TB countries. Targeted actions to support this highly vulnerable population both in terms of outcome and occurrence of adverse events are needed.

Impact of Vitamin D in Prophylaxis and Treatment in Tuberculosis Patients.

Vitamin D plays a crucial role in many infectious diseases, such as tuberculosis (TB), that remains one of the world's top infectious killers with 1.5 million deaths from TB in 2021. Vitamin D suppresses the replication of Mycobacterium tuberculosis in vitro and showed a promising role in TB management as a result of its connection with oxidative balance. Our review encourages the possible in vivo benefit of a joint administration with other vitamins, such as vitamin A, which share a known antimycobacterial action with vitamin D. However, considering the low incidence of side effects even at high dosages and its low cost, it would be advisable to assess vitamin D level both in patients with active TB and high-risk groups and administer it, at least to reach sufficiency levels.

Emerging issue of fluconazole-resistant candidemia in a tertiary care hospital of southern italy: time for antifungal stewardship program.

An increased number of patients is at risk of Candida spp. bloodstream infection (CBSI) in modern medicine. Moreover, the rising of antifungal resistance (AR) was recently reported. All consecutive CBSI occurred in our Hospital (consisting of 1,370 beds) between 2015 and 2018, were reviewed. For each case, Candida species, AR pattern, ward involved and demographic data of patients were recorded. Overall, 304 episodes of CBSI occurred, with a median (q1:first-,q3:third quartile) of 77 (71-82) CBSI/year. Over the years, a significant increase of CBSI due to C. albicans compared to non-albicans strains was recorded in medical wards (from 65% to 71%, p=0.030), while this ratio remained stable in others. An increase of resistant strains to multiple antifungals such as C. guillermondii was noticed in recent years (from 0% to 9.8%, p=0.008). Additionally, from 2015 to 2018 an increase in fluconazole-resistance was recorded in our Hospital (from 7.4% to 17.4%, p=0.025) and a slight increase in voriconazole-resistance (from 0% to 7% in 2018, p=0.161) was observed, while resistance to echinocandin and amphotericin B remained firmly below 2%. This study suggests a rapid spread of antifungal resistance in our Hospital; therefore, an appropriate antifungal stewardship programs is urgently warranted.

Implementation of tele visit healthcare services triggered by the COVID-19 emergency: the Trentino Province experience.

AIM: In response to the SARS-CoV-2 emergency, the Competence Centre on digital health 'TrentinoSalute4.0' has developed TreC_Televisita, a tele visit solution that meets the needs of the Trentino healthcare system and maintains high-quality patient-doctor interactions while respecting social distancing. This paper highlights how 'TreC_Televisita' was integrated into the Trentino healthcare system and its potential to become a structural and durable solution for the future local healthcare service provisioning. SUBJECT AND METHODS: This paper presents the multifactorial context that TreC_Televisita has faced for its implementation and the strategies adopted for its structural integration into the healthcare system. The analysis focuses on the main issues faced for the integration of the tele visits (e.g. privacy, payments) and how the context of TrentinoSalute4.0 permitted responding quickly to its implementation during the pandemic. It also describes how TreC_Televisita fits into the healthcare continuum from the organisational and technological standpoint, the end-user perspective and the barriers that could hamper the solution scalability. RESULTS: TreC_Televisita has demonstrated to be a technological solution that can be contextualised for different clinical domains beyond SARS-CoV-2. Moreover, it has shown its potential to scale up the solution beyond the COVID-19 emergency to the whole healthcare provisioning system in the long term. CONCLUSION: Being a positive experience in the first months of its implementation, the long-term goal is to transform TreC_Televisita into a structural pillar of the Trentino healthcare system, setting the bases for a sustainable, win-win situation for all the stakeholders involved in healthcare service provisioning.

Efficacy of plasmapheresis as treatment for bilateral hyperviscosity syndrome related retinopathy in multiple myeloma.

PURPOSE: To report a case of good clinical response to plasmapheresis as therapy for a bilateral hyperviscosity syndrome related retinopathy in a young patient with undiagnosed multiple myeloma (MM). METHODS: Case report. RESULTS: A 48-year-old caucasian man, previously diagnosed with monoclonal gammopathy of undetermined significance (MGUS), presented for medical attention for back ache and vision decrease, worst in the left eye. Ophthalmological examination revealed presence of bilateral CRVO-like retinopathy which raised the hypothesis of hyperviscosity syndrome (HVS). After confirmation of MM diagnosis, plasmapheresis were promptly begun. The right eye regained a good visual acuity and an anatomical restoration already notable 5 days from the first plasmapheresis. CONCLUSIONS: Fundoscopy lead to diagnosis of HVS, it is therefore advisable in all patients with MM in order to perform plasmapheresis as soon as possible if necessary. In case of atypical CRVO, haematological and inflammatory causes, should be always ruled out.

Potential Role of Vitamins A, B, C, D and E in TB Treatment and Prevention: A Narrative Review.

(1) Background: Tuberculosis (TB) is one of the world's top infectious killers, in fact every year 10 million people fall ill with TB and 1.5 million people die from TB. Vitamins have an important role in vital functions, due to their anti-oxidant, pro-oxidant, anti-inflammatory effects and to metabolic functions. The aim of this review is to discuss and summarize the evidence and still open questions regarding vitamin supplementation as a prophylactic measure in those who are at high risk of Mycobacterium tuberculosis (MTB) infection and active TB; (2) Methods: We conducted a search on PubMed, Scopus, Google Scholar, EMBASE, Cochrane Library and WHO websites starting from March 1950 to September 2021, in order to identify articles discussing the role of Vitamins A, B, C, D and E and Tuberculosis; (3) Results: Supplementation with multiple micronutrients (including zinc) rather than vitamin A alone may be more beneficial in TB. The WHO recommend Pyridoxine (vitamin B6) when high-dose isoniazid is administered. High concentrations of vitamin C sterilize drug-susceptible, MDR and extensively drug-resistant MTB cultures and prevent the emergence of drug persisters; Vitamin D suppresses the replication of mycobacterium in vitro while VE showed a promising role in TB management as a result of its connection with oxidative balance; (4) Conclusions: Our review suggests and encourages the use of vitamins in TB patients. In fact, their use may improve outcomes by helping both nutritionally and by interacting directly and/or indirectly with MTB. Several and more comprehensive trials are needed to reinforce these suggestions.

Meropenem/vaborbactam activity in vitro: a new option for Klebsiella pneumoniae carbapenemase (KPC)-producing Klebsiella pneumoniae treatment.

Aim: Infections by Klebsiella pneumoniae carbapenemase (KPC)-producing K. pneumoniae represent a major challenge because of limited treatment strategies. New ß-lactam/ß-lactamase inhibitor associations may help to deal with this challenge. The aim of this study is to evaluate the in vitro susceptibility of KPC-producing K. pneumoniae for meropenem/vaborbactam in comparison with ceftazidime/avibactam against. Materials and methods: Twenty-eight strains isolated from blood cultures were evaluated. Testing for susceptibility to meropenem/vaborbactam and ceftazidime/avibactam was performed by E-test gradient strip. Results: All the clinical isolates were susceptible to meropenem/vaborbactam, while one strain was resistant to ceftazidime/avibactam with a MIC of 32 µg/ml. The median MIC of ceftazidime/avibactam evaluated after standardization was higher compared with that of meropenem/vaborbactam. Conclusion: Meropenem/vaborbactam could be an important turning point in the treatment of KPC-producing K. pneumoniae infections, especially considering the emergence of ceftazidime/avibactam resistance.

Lay abstract Carbapenem-resistant Klebsiella pneumoniae is responsible, in critically ill patients, for nosocomial infections that are difficult to treat due to limited therapeutic options. Today, new antibiotics are available for treating these infections. The aim of this study is to evaluate the antimicrobial activity of meropenem/vaborbactam versus ceftazidime/avibactam. The results demonstrate that meropenem/vaborbactam could be an important turning point in the treatment of carbapenem-resistant K. pneumoniae infections, considering the emergence of ceftazidime/avibactam resistance.

Enabling teleophthalmology during the COVID-19 pandemic in the Province of Trento, Italy: Design and implementation of a mHealth solution.

BACKGROUND: Due to the many restrictions imposed during the COVID-19 emergency, the normal clinical activities have been stopped abruptly in view of limiting the circulation of the virus. The extraordinary containment measures have had a dramatic impact on the undertaking and follow-up of ophthalmic outpatients. OBJECTIVE: In order to guarantee proper monitoring and routine care, the Pediatric Ophthalmology equipe of Rovereto Hospital (North-East of Italy) supported by the Competence Center on Digital Health TrentinoSalute4.0, designed and implemented a digital platform, TreC Oculistica, enabling teleophthalmology. We report our innovative-albeit restricted-experience aiming at testing and maximizing the efficacy of remote ophthalmic and orthoptic visits. METHODS: A multidisciplinary team created the TreC Oculistica platform and defined a teleophthalmology protocol. The system consists of a clinician web interface and a patient mobile application. Clinicians can prescribe outpatients with the App and some preliminary measurements to be self-collected before the televisit. The App conveys the clinician's requests (i.e. measurements) and eases the share of the collected information in a secure digital environment, promoting a new health care workflow. RESULTS: Four clinicians took part in the testing phase (2 ophthalmologists and 2 orthoptists) and recruited 37 patients (mostly pediatric) in 3 months. Thanks to a continuous feedback between the testing and the technical implementation, it has been possible to identify pros and cons of the implemented functionalities, considering possible improvements. Digital solutions such as TreC Oculistica advance the digitalization of the Italian health care system, promoting a structured and effective reorganization of the workload supported by digital systems. CONCLUSIONS: The study tested an innovative digital solution in the teleophthalmology context and represented the first experience within the Italian healthcare system. This solution opens up new possibilities and scenarios that can be effective not only during the pandemic, but also in the traditional management of public health services.

Cefiderocol-Based Combination Therapy for "Difficult-to-Treat" Gram-Negative Severe Infections: Real-Life Case Series and Future Perspectives.

Cefiderocol is a new cephalosporin displaying against extensively resistant (XDR) Gram-negative bacteria. We report our experience with cefiderocol-based combination therapies as "rescue" treatments in immunocompromised or critically ill patients or in patients with post-surgical infections who had failed previous regimens. A total of 13 patients were treated from 1 September 2020 to 31 March 2021. In total, 5/13 (38%) patients were classified as critically ill, due to severe COVID-19 lung failure; 4/13 (31%) patients had post-surgical infections and 4/13 (31%) had severe infections in immunocompromised subjects due to solid organ transplantation (2/4) or hematological malignancy (2/4). Overall, 10/13 infections were caused by carbapenem-resistant Acinetobacter baumannii, one by KPC-positive ceftazidime/avibactam-resistant Klebsiella pneumonia and two by Pseudomonas aeruginosa XDR. Based on clinical, microbiological and hematobiochemical evaluation, cefiderocol was associated with different companion drugs, particularly with fosfomycin, high-dose tigecycline and/or colistin. Microbiological eradication was achieved in all cases and the 30-day survival rate was 10/13; two patients died due to SARS-CoV-2 lung failure, whereas one death was attributed to subsequent infections. No recurrent infections within 30 days were reported. Finally, we hereby discuss the therapeutic potential of cefiderocol and the possible place in the therapy of this novel drug.

Validation of the 2WIN Corneal Reflexes App in children.

PURPOSE: To test the reliability and accuracy of the 2Win Refractometer Corneal Reflexes App (CR App) in detecting manifest strabismus in pediatric patients. METHODS: Prospective study involving 167 children with suspected strabismus (mean age 7.6 years; SD = 3.0, range 2-14 years) undergoing the CR App ocular alignment assessment (Pediatric Ophthalmologist) versus the alternate cover test with prism ocular alignment assessment for distance (Orthoptist) as the gold standard. The AAPOS 2013 guidelines for the detection of manifest strabismus in primary position (> 8 PD) were used. RESULTS: Total sensitivity, specificity, PPV, and NPV for the CR App were 79.2%, 86.2%, 86.4%, and 78.9%, respectively. The overall inconclusive rate was 17.9%, but was 36.3% in children younger than 5. Sensitivity and PPV for vertical deviations were poor (33.3% and 12.5%, respectively). The accuracy of the CR App regarding the degree (in prism diopters) of manifest deviations was tested with the Wilcoxon signed rank sum test: correlation with the gold standard was good for esodeviations (p value = 0.765, not statistically significant) and poorer for exodeviations (p value = 0.056, still not statistically significant), whereas a significant difference (p value = 0.0001) was observed for vertical deviations. CONCLUSION: The CR App showed good sensitivity, specificity, PPV, and NPV for manifest strabismus > 8PD in accordance with the AAPOS 2013 guidelines; sensitivity and PPV were poor for vertical deviations. The accuracy of the CR App was good for horizontal deviations, but poor for vertical deviations. The inconclusive result rate was high in younger children.

Recurrent neurosurgical site infection by extensively drug-resistant P. aeruginosa treated with cefiderocol: a case report and literature review.

INTRODUCTION: Cefiderocol is a new siderophore cephalosporin designed to be active against extensively resistant Gram-negative bacteria; however, clinical studies are limited to complicated urinary tract infections, pneumonia, and intra-abdominal infections. To date, no data are available on neurosurgical site infections. CASE PRESENTATION: We present a case of a patient successfully cured with Cefiderocol for a neurosurgical site infection due to extensively resistant P. aeruginosa, who had failed a previous treatment based on combined antimicrobial therapy and right parietal bone excision. CONCLUSIONS: Cefiderocol is a promising antibiotic for complicated infections due to multidrug resistant gram-negative bacteria.

In Vitro Activity of Ceftazidime/Avibactam Alone and in Combination With Fosfomycin and Carbapenems Against KPC-producing Klebsiella Pneumoniae.

KPC-producing Klebsiella pneumonia (KPC-Kp) represents a major therapeutic challenge in critically ill patients. Ceftazidime-avibactam (CAZ-AVI) is a new effective drug against KPC-Kp but, due to emerging resistant strains during monotherapy, the association with a second antibiotic has been advocated. Therefore, intravenous fosfomycin may be a possible choice for combination therapy. The aim of this study was to evaluate the in vitro susceptibility of CAZ-AVI alone and in combination with fosfomycin and carbapenems against KPC-Kp clinical isolates by E-test method. The combination of CAZ-AVI with carbapenems showed synergistic activity, whereas with fosfomycin showed addictive activity, suggesting that fosfomycin may be a carbapenem-sparing strategy in antimicrobial stewardship programs.

Spectral-domain optical coherence tomography findings in idiopathic lamellar macular hole.

BACKGROUND: To evaluate demographic, functional, and morphological parameters of idiopathic lamellar macular hole (ILMH). METHODS: Observational longitudinal retrospective study. Optical coherence tomography examinations and corresponding clinical charts of a series of consecutive patients affected by ILMH, between January 2010 and March 2015, from the database of the Department of Ophthalmology of Trento Hospital, Italy, have been collected and examined. Demographic and functional parameters were: age (year), gender (male/female), eye (right/left), lens status, best-corrected visual acuity (BCVA) in logarithm of the minimum angle of resolution (LogMAR). Tomographic parameters were: LMH shape pattern (intraretinal splitting LMH, IR split LMH, and V-shaped LMH, V LMH), posterior vitreous detachment (PVD yes/ PVD no), ERM type (conventional ERM and atypical ERM), integrity of ellipsoid zone (EZ) and external limiting membrane (ELM), residual foveal thickness (RFT) micron (µ), maximal diameter of intraretinal splitting (MDIRS) (µ). RESULTS: One hundred and eighty-nine eyes of 175 patients were included. The mean age was 72.84 ± 9.6, range 41-96 years. BCVA mean was 0.24 ± 0.25, range 0 -1.3 LogMAR. One hundred and forty-one eyes (74.6 %) were affected by IR split LMH, 48 eyes (25.4 %) were affected by V LMH. Every cases of ILMH were associated with ERM: 117 (61.9 %) conventional ERM, 72 (38.1 %) atypical ERM. A significant prevalence of female gender, phakic condition, and PVD in conventional ERM ILMH subgroup (P = 0.000) was found. BCVA mean was better in the conventional ERM ILMH subgroup (P = 0.000). An association between the interruption of the outer retinal layers (EZ and ELM) and atypical ERM ILMH subgroup was highlighted (P = 0.000). The statistical analysis showed a correlation between BCVA and integrity of ELM (P = 0.000). RFT significantly decreased in atypical ERM ILMH subgroup at 24 months compared to time point 0 (P = 0.027). A progressive increase of MDIRS in both subgroups at 12 months and in atypical ERM ILMH subgroup at 24 months (P = 0.007) was highlighted. CONCLUSIONS: This study demonstrated that ILMH was not a stable condition, showing morphological changes and an involvement of the outer retinal layers during the 2 years of follow-up.