Cold ischemia time in liver transplantation: An overview.

The standard approach to organ preservation in liver transplantation is by static cold storage and the time between the cross-clamping of a graft in a donor and its reperfusion in the recipient is defined as cold ischemia time (CIT). This simple definition reveals a multifactorial time frame that depends on donor hepatectomy time, transit time, and recipient surgery time, and is one of the most important donor-related risk factors which may influence the graft and recipient's survival. Recently, the growing demand for the use of marginal liver grafts has prompted scientific exploration to analyze ischemia time factors and develop different organ preservation strategies. This review details the CIT definition and analyzes its different factors. It also explores the most recent strategies developed to implement each timestamp of CIT and to protect the graft from ischemic injury.

From evidence to practice: A systematic review-based diagnostic algorithm for paediatric eosinophilia across socioeconomic context.

AIM: Paediatric eosinophilia is a common clinical dilemma, often leading to resource- and time-consuming assessments. We aim to evaluate the main aetiologies of eosinophilia in children from different socioeconomic settings and propose a diagnostic algorithm. METHODS: A systematic literature review was conducted through PubMed, Embase and the Cochrane Library. Studies published from January 2012 to June 2023 reporting the incidence and aetiology of peripheral eosinophilia in children were included. Evidence from studies on children originating from low- or high-income countries was compared. RESULTS: A total of 15 observational studies, encompassing 3409 children, were included. The causes of eosinophilia varied based on the children's origin and the eosinophilia severity. In children from high-income countries, allergic diseases were the leading cause, with a prevalence of 7.7%-78.2%, while parasitosis ranged from 1.0% to 9.1%. In children from low-income countries, parasitosis was predominant, ranging from 17.7% to 88.3%, although allergic diseases were found in 2.5%-4.8% of cases. Concerning severity, allergic diseases were the leading cause of mild-to-moderate eosinophilia; parasitosis was associated with moderate-to-severe eosinophilia, while immunological disorders were mostly found in severe cases. CONCLUSION: We developed a step-up diagnostic algorithm that considers the child's origin and eosinophilia severity and could optimise resource allocation.

Does multiple gastric aspirate collection increase sensitivity of M. tuberculosis detection in children with pulmonary tuberculosis?

This study aims to investigate the sensitivity of microscopy, culture and polymerase chain reaction on three gastric aspirates (GAs) in the microbiological confirmation of active pulmonary tuberculosis (TB) and to identify possible changes in sensitivity derived from the collection of a different number of aspirates. Children with clinical and radiological diagnoses of active pulmonary TB who underwent three GAs between March 2007 and June 2019 were retrospectively evaluated. Clinical, radiological, and microbiological data were collected. The sensitivity of microbiological tests on GAs was calculated. Moreover, differences in sensitivity according to age and radiological pattern were investigated. Overall, 156 children with active pulmonary TB were enrolled with a median age of 51.5 (IQR: 25.2-113.2) months. Microbiological investigations on the first GA showed a sensitivity of 34% (95%CI 26.7, 42), the cumulative sensitivity of first and second GAs was 40.4% (95%CI 32.7, 48.5) and of the three GAs was 47.4% (95%CI 39.8, 55.2). The collection of three GAs leads to an overall increase in sensitivity of the first GA by 13.4% (95%CI 2.8, 24.1%; p=0.014). Moreover, the increase in sensitivity was significantly higher in children ≤ 4 years of age and in those with uncomplicated TB (p=0.008).Conclusions: Performing a higher number of GAs increases the sensitivity of microbiological confirmation of active pulmonary TB, particularly in children ≤ 4 years and with an uncomplicated radiological pattern. What is known: • The diagnosis of paediatric tuberculosis is a challenge for paediatricians • Despite their low sensitivity gastric aspirates represent the standard sample for microbiological confirmation of active pulmonary tuberculosis in children • Most international guidelines recommend performing three sequential gastric aspirates on three consecutive days What is new: • A significant increase in global sensitivity by 13.4% was found by the collection of three gastric aspirates compared to the first one • Performing a higher number of gastric aspirates increases the sensitivity of microbiological confirmation, particularly in children ≤ 4 years and with an uncomplicated radiological pattern.

Acute pharyngitis in children and adults: descriptive comparison of current recommendations from national and international guidelines and future perspectives.

This study aims to provide a comparison of the current recommendations about the management of acute pharyngitis. A literature search was conducted from January 2009 to 2023. Documents reporting recommendations on the management of acute pharyngitis were included, pertinent data were extracted, and a descriptive comparison of the different recommendations was performed. The quality of guidelines was assessed through the AGREE II instrument. Nineteen guidelines were included, and an overall moderate quality was found. Three groups can be distinguished: one group supports the antibiotic treatment of group A ß-hemolytic Streptococcus (GABHS) to prevent acute rheumatic fever (ARF); the second considers acute pharyngitis a self-resolving disease, recommending antibiotics only in selected cases; the third group recognizes a different strategy according to the ARF risk in each patient. An antibiotic course of 10 days is recommended if the prevention of ARF is the primary goal; conversely, some guidelines suggest a course of 5-7 days, assuming the symptomatic cure is the goal of treatment. Penicillin V and amoxicillin are the first-line options. In the case of penicillin allergy, first-generation cephalosporins are a suitable choice. In the case of beta-lactam allergy, clindamycin or macrolides could be considered according to local resistance rates.    Conclusion: Several divergencies in the management of acute pharyngitis were raised among guidelines (GLs) from different countries, both in the diagnostic and therapeutic approach, allowing the distinction of 3 different strategies. Since GABHS pharyngitis could affect the global burden of GABHS disease, it is advisable to define a shared strategy worldwide. It could be interesting to investigate the following issues further: cost-effectiveness analysis of diagnostic strategies in different healthcare systems; local genomic epidemiology of GABHS infection and its complications; the impact of antibiotic treatment of GABHS pharyngitis on its complications and invasive GABHS infections; the role of GABHS vaccines as a prophylactic measure. The related results could aid the development of future recommendations. What is Known: • GABHS disease spectrum ranges from superficial to invasive infections and toxin-mediated diseases. • GABHS accounts for about 25% of sore throat in children and its management is a matter of debate. What is New: • Three strategies can be distinguished among current GLs: antibiotic therapy to prevent ARF, antibiotics only in complicated cases, and a tailored strategy according to the individual ARF risk. • The impact of antibiotic treatment of GABHS pharyngitis on its sequelae still is the main point of divergence; further studies are needed to achieve a global shared strategy.

Acute graft versus host disease after liver transplantation: where do we stand?

Graft-versus-host disease (GVHD) is a rare complication after liver transplantation (LT), with an estimated incidence rate of 0.5% to 2% and a mortality rate as high as 75%. The classical target organs of GVHD include the intestines, liver, and skin. The damage of these organs is not easy to detect for the clinician as there is no widely accepted clinical or laboratory diagnostic tests; as a result, diagnosis and initiation of therapy are often delayed. Moreover, without prospective clinical trials to reference, evidence guiding therapy is limited. This review summarized the current knowledge, the potential applications and the clinical relevance of GVHD after LT, highlighting novel approaches in grading and management of GVHD.

Management of pulmonary aspergillosis in children: a systematic review.

Invasive pulmonary aspergillosis (IPA) is a severe condition in immunocompromised children, but the optimal management is still under debate. In order to better clarify this issue, a literature search was performed through MEDLINE/PubMed database to describe current risk factors and diagnostic, therapeutic and prophylactic tools for invasive pulmonary aspergillosis (IPA) in the paediatric age. Observational studies and clinical trials regarding diagnosis, treatment and prophylaxis were considered, and results were summarised. Five clinical trials and 25 observational studies (4453 patients) were included.Haematological malignancies, previous organ transplant and other primary or acquired immunodeficiency were identified as risk factors for IPA in children.Current diagnostic criteria distinguish between "proven", "probable" and "possible" disease. Consecutive galactomannan assays have good sensitivity and specificity, especially when performed on broncho-alveolar lavage. At the same time, ß-D-glucan should not be used since cut-off in children is unclear. PCR assays cannot currently be recommended for routine use.Voriconazole is the recommended first-line agent for IPA in children older than 2 years of age. Liposomal amphotericin B is preferred in younger patients or cases of intolerance to voriconazole. Its plasma concentrations should be monitored throughout the treatment. The optimal duration of therapy has yet to be determined. Posaconazole is the preferred prophylactic agent in children older than 13 years old, whereas oral voriconazole or itraconazole are the drugs of choice for those between 2-12 years. Further good-quality studies are warranted to improve clinical practice.

Prevalence and clinical presentation of long COVID in children: a systematic review.

A systematic literature review was conducted up to 15th February 2022 to summarize long COVID evidence and to assess prevalence and clinical presentation in children and adolescents. Articles reporting long COVID prevalence and symptoms based on original data in the paediatric population were included. Case series quality was assessed through the JBI Critical Appraisal Checklist. For observational studies, adherence to STROBE checklist was evaluated. Twenty-two articles were included: 19 observational studies (12 cohort/7 cross-sectional) and 3 case series. Nine studies provided a control group. We found a high variability in terms of prevalence (1.6-70%). The most frequently reported symptoms were fatigue (2-87%), headache (3.5-80%), arthro-myalgias (5.4-66%), chest tightness or pain (1.4-51%), and dyspnoea (2-57.1%). Five studies reported limitations in daily function due to long COVID. Alterations at brain imaging were described in one study, transient electrocardiographic abnormalities were described in a minority of children, while most authors did not evidence long-term pulmonary sequelae. Older age, female sex, and previous long-term pathological conditions were more frequently associated with persistent symptoms. CONCLUSION: Long COVID evidence in children is limited, heterogeneous, and based on low-quality studies. The lockdown consequences are difficult to distinguish from long COVID symptoms. High-quality studies are required: WHO definition of long COVID should be used, controlled clinical studies should be encouraged, and the impact of new variants on long COVID prevalence should be investigated to ensure an objective analysis of long COVID characteristics in children and a proper allocation of healthcare system resources. WHAT IS KNOWN: • Children rarely develop a severe respiratory disease in the acute phase of COVID-19. • A limited number of patients develop a multisystem inflammatory condition that can lead to multiorgan failure and shock. WHAT IS NEW: • Persistent symptoms after SARS-CoV-2 infection are reported in children and limitations in daily function due to long COVID symptoms affect school attendance. • Functional complaints of post-acute COVID are difficult to be distinguished from those due to social restrictions.

Risk factors for severe COVID-19 in people with cystic fibrosis: A systematic review.

Background: People with cystic fibrosis (CF) are considered a clinically fragile population with an intrinsic higher risk of developing severe COVID-19, though a certain variability in terms of outcomes and hospitalization has been noticed. Aim: To highlight the main risk factors for severe COVID-19 in patients with CF. Methods: A systematic review of the current literature was conducted through PubMed and EMBASE databases. English-written articles reporting clinical data on CF subjects with SARS-CoV2 infection were included and analyzed. Selected reports were evaluated for adherence to STROBE recommendations. Results: After the selection phase, 9 observational studies were included, 5 of which reported data from CF Registry Global Harmonization Group. The hospitalization rate ranged from 18.2 to 58.1%. The main risk factors for severe outcome were as follows: FEV1 < 70%p, CF-related diabetes, age > 40 years, pancreatic insufficiency, underweight, previous transplant, azithromycin use. Use of dornase alfa was associated with decreased risk for severe disease, while there was insufficient evidence to establish the role of inhaled steroids or CFTR modulators. No solid data regarding specific SARS-CoV-2 therapies in patients with CF emerged. Conclusion: Most people with CF experience a mild course of SARS-CoV-2 infection, nevertheless subgroups with higher risk of severe outcome emerged. Maintenance therapies for CF overall did not show a clear preventive effect against severe outcomes, although dornase alfa seems to give some protection. Due to the current lack of data on specific COVID-19 therapies and immunization in patients with CF, further studies are needed to establish their impact in this population.

COVID-19 pandemic: Supply chain risk management by integrating Interpretive Structural Modeling and Bayesian belief network.

The paper proposes a theoretical framework, based on a literature review, that analyzes the links between COVID-19 impacts and supply chain risk mitigation strategies, investigating the role of digitalization as a potential key resource to improve the effectiveness of supply chain resilience. Then, the paper empirically tests the framework through a hybrid causal mapping technique using the frameworks of Interpretive Structural Modelling and Bayesian Belief Networks methods to support supply chain decision making approaches. The findings of this paper can support managers in developing simple and traciable models for assessing interdependences among supply chain disruption sources and to invest effectively in resilience strategies.

A Cost Decision Model Supporting Treatment Strategy Selection in BRCA1/2 Mutation Carriers in Breast Cancer.

In this paper, a cost decision-making model that compares the healthcare costs for diverse treatment strategies is built for BRCA-mutated women with breast cancer. Moreover, this model calculates the cancer treatment costs that could potentially be prevented, if the treatment strategy with the lowest total cost, along the entire lifetime of the patient, is chosen for high-risk women with breast cancer. The benchmark of the healthcare costs for diverse treatment strategies is selected in the presence of uncertainty, i.e., considering, throughout the lifetime of the patient, the risks and complications that may arise in each strategy and, therefore, the costs associated with the management of such events. Our results reveal a clear economic advantage of adopting the cost decision-making model for benchmarking the healthcare costs for various treatment strategies for BRCA-mutated women with breast cancer. The cost savings were higher when all breast cancer patients underwent counseling and genetic testing before deciding on any diagnostic-therapeutic path, with a probability of obtaining savings of over 75%.

Multi-criteria decision-making for sustainable metropolitan cities assessment.

The recent development of metropolitan cities, especially in Europe, requires an effective integrated management of city services, infrastructure, and communication networks at a metropolitan level. A preliminary step towards a proper organizational and management strategy of the metropolitan city is the analysis, benchmarking and optimization of the metropolitan areas through a set of indicators coherent with the overall sustainability objective of the metropolitan city. This paper proposes the use of the Analytic Hierarchy Process multi-criteria decision making technique for application in the smart metropolitan city context, with the aim of analysing the sustainable development of energy, water and environmental systems, through a set of objective performance indicators. Specifically, the 35 indicators defined for the Sustainable Development of Energy, Water and Environment Systems Index framework are used. The application of the approach to the real case study of four metropolitan areas (Bari, Bitonto, Mola, and Molfetta) in the city of Bari (Italy) shows its usefulness for the local government in benchmarking metropolitan areas and providing decision indications on how to formulate the sustainable development strategy of the metropolitan city. Based on the Analytic Hierarchy Process characteristics, the results highlight that although one specific area (Mola in the considered case) is globally ranked at the first place, it is only ranked first with respect to some dimensions. Such a result has strong implications for the metropolitan city's manager who has the possibility to identify and implement targeted actions, which may be designed ad hoc to improve specific dimensions based on the current state of the city, thus maximizing the efficiency and effectiveness of the actions undertaken for the sustainable development of energy, water and environmental systems of the whole metropolitan city.

Intracorporeal Anastomosis Reduces Surgical Stress Response in Laparoscopic Right Hemicolectomy: A Prospective Randomized Trial.

Total laparoscopic right hemicolectomy is a procedure that involves an intracorporeal anastomosis. This approach may reduce tissue injury resulting in a significant lower surgical stress response (SSR) compared with the same procedure performed with an extracorporeal anastomosis. The purpose of this study was to compare the SSR level between 2 groups of patients undergoing laparoscopic right hemicolectomy with intracorporeal or extracorporeal anastomosis. From June 2015 to December 2016, 60 patients were enrolled and randomized. Interleukin-6, C-reactive protein, procalcitonin, white blood cell count, cortisol, prolactin, prealbumin, albumin, triglycerides, and transferrin were analyzed preoperatively and at 1, 3, and 5 days postoperatively. Interleukin-6 and C-reactive protein levels were significantly lower in the intracorporeal group on days 1, 3, and 5 postoperatively compared with the extracorporeal group. Gastrointestinal recovery was significantly earlier in the intracorporeal group. The intracorporeal anastomosis in laparoscopic right hemicolectomy reduces SSR, which may play a role in bowel recovery.