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Intra-abdominal infections (IAIs) account for a major cause of morbidity and mortality, representing the second most common sepsis-related death with a hospital mortality of 23-38%. Prompt identification of sepsis source, appropriate resuscitation, and early treatment with the shortest delay possible are the cornerstones of management of IAIs and are associated with a more favorable clinical outcome. The aim of source control is to reduce microbial load by removing the infection source and it is achievable by using a wide range of procedures, such as definitive surgical removal of anatomic infectious foci, percutaneous drainage and toilette of infected collections, decompression, and debridement of infected and necrotic tissue or device removal, providing for the restoration of anatomy and function. Damage control surgery may be an option in selected septic patients. Intra-abdominal infections can be classified as uncomplicated or complicated causing localized or diffuse peritonitis. Early clinical evaluation is mandatory in order to optimize diagnostic testing and establish a therapeutic plan. Prognostic scores could serve as helpful tools in medical settings for evaluating both the seriousness and future outlook of a condition. The patient's conditions and the potential progression of the disease determine when to initiate source control. Patients can be classified into three groups based on disease severity, the origin of infection, and the patient's overall physical health, as well as any existing comorbidities. In recent decades, antibiotic resistance has become a global health threat caused by inappropriate antibiotic regimens, inadequate control measures, and infection prevention. The sepsis prevention and infection control protocols combined with optimizing antibiotic administration are crucial to improve outcome and should be encouraged in surgical departments. Antibiotic and antifungal regimens in patients with IAIs should be based on the resistance epidemiology, clinical conditions, and risk for multidrug resistance (MDR) and Candida spp. infections. Several challenges still exist regarding the effectiveness, timing, and patient stratification, as well as the procedures for source control. Antibiotic choice, optimal dosing, and duration of therapy are essential to achieve the best treatment. Promoting standard of care in the management of IAIs improves clinical outcomes worldwide. Further trials and stronger evidence are required to achieve optimal management with the least morbidity in the clinical care of critically ill patients with intra-abdominal sepsis.
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The insulin-like growth factor 2 (IGF2) promotes cell growth by overactivating the IGF system in an autocrine loop in adrenocortical carcinomas (ACCs). The cytoskeleton protein filamin A (FLNA) acts as a repressor of IGF2 mitogenic signalling in ACC cells. The aims of this study were to test FLNA expression by immunohistochemistry in 119 ACCs and 26 adrenocortical adenomas (ACAs) and to evaluate its relationship with clinicopathological features and outcome in ACCs. We found that 71.4% of ACCs did not express FLNA, whereas FLNA absence was a rare event in ACAs (15.4%, p < 0.001 vs. ACCs). In addition, the expression of FLNA was associated with a less aggressive tumour behaviour in ACCs. Indeed, the subgroup of ACCs with high FLNA showed a lower ENSAT stage, Weiss score, and S-GRAS score compared to ACCs with low FLNA expression (p < 0.05). Moreover, patients with high FLNA had a longer overall survival than those with low FLNA (p < 0.05). In conclusion, our data suggest that FLNA may represent a "protective" factor in ACCs, and the integration of FLNA immunohistochemical expression in ACC tissues along with other clinical and molecular markers could be helpful to improve diagnostic accuracy and prognosis prediction in ACCs.
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Neoplasias de la Corteza Suprarrenal , Adenoma Corticosuprarrenal , Carcinoma Corticosuprarrenal , Filaminas , Humanos , Neoplasias de la Corteza Suprarrenal/diagnóstico , Adenoma Corticosuprarrenal/diagnóstico , Carcinoma Corticosuprarrenal/diagnóstico , Filaminas/genética , Filaminas/metabolismo , Transducción de Señal , PronósticoRESUMEN
Background and aims: Diversity is a key element of diet quality. The Food Variety Score (FVS) is used to assess diversity, especially in low- and middle-income countries. It sums up the number of foods consumed ignoring their nutrient content. A more suitable index should combine the number of foods consumed and their nutritional composition. We adapted the Nutritional Functional Diversity indicator (NFD), proposed by ecologists, to measure diversity in the human diet. We compared NFD and FVS evaluating subjects' distributions across quartiles of the two diversity indices. To evaluate which one reflected a higher diet quality, we estimated associations between these two diversity indices and diet quality measures, i.e., the Mediterranean Diet Score (MDS) and the Healthy Eating Index-2015 (HEI-2015). Associations were expressed by odds ratios (OR) and corresponding 95% confidence intervals (CI). Materials and methods: We used the data of controls only derived from an integrated series of hospital-based case-control cancer studies conducted in different Italian areas. The NFD identifies groups of foods based on a set of nutrients according to a cluster analysis. Some steps are required: creating a food-nutrient matrix; clustering of the Euclidean food-food distance matrix to identify groups of foods with nutritional (dis)similarities; and calculating the NFD as the ratio between the sum of branch lengths of the dendrogram belonging to the number of foods consumed by individuals (i.e., subject-specific diversity) and the sum of all branch lengths of the dendrogram (i.e., maximal diversity). Results: More than one quarter of individuals (28.4%) were differently classified within quartiles of the two diversity indices. For both indices, increasing the diversity level increased the risk for adhering to MDS (OR for NFD = 11.26; 95% CI: 7.88-16.09, and OR for FVS = 6.80; 95% CI: 4.84-9.54) and to HEI-2015 (OR for NDF = 2.86; 95% CI: 2.39-3.42, and OR for FVS = 2.72; 95% CI: 2.27-3.26). Associations were stronger for NFD. Conclusion: Our findings showed a greater ability of NFD to assess diet quality quantifying the degree of diversity.
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Serum vitamin D (VitD) levels have been inversely related with metabolic syndrome (MetS), although the direct impact of VitD is still debated. This study examined 879 subjects of working age from an obesity and occupational clinic in Milan, Italy. Among these participants, 316 had MetS, while 563 did not. A multiple logistic regression analysis was conducted to determine the odds ratios (ORs) and the corresponding 95% confidence intervals (CIs) for MetS in relation to serum VitD levels. After controlling for age, sex, leisure time physical activity, and body mass index (BMI), individuals with VitD levels between 20 and 29.9 ng/dL, or at least 30 ng/dL, had approximately half the risk of developing MetS (OR: 0.52, 95% CI: 0.32-0.86 and OR: 0.50, 95% CI: 0.25-0.99, respectively) compared to those with VitD levels below 10 ng/dL. This study presents further evidence of the beneficial effect of adequate VitD levels on the risk of MetS in a population of overweight/obese workers, even after adjusting for BMI. This study supports the importance of testing for and-if required-supplementing VitD in individuals with metabolic risk factors.
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Síndrome Metabólico , Deficiencia de Vitamina D , Humanos , Vitamina D , Síndrome Metabólico/epidemiología , Obesidad/epidemiología , Vitaminas , Sobrepeso , Índice de Masa Corporal , Deficiencia de Vitamina D/complicaciones , Deficiencia de Vitamina D/epidemiologíaRESUMEN
Patients with intra-abdominal sepsis suffer from significant mortality and morbidity. The main pillars of treatment for intra-abdominal infections are (1) source control and (2) early delivery of antibiotics. Antibiotic therapy should be started as soon as possible. However, the duration of antibiotics remains a matter of debate. Prolonged antibiotic delivery can lead to increased microbial resistance and the development of nosocomial infections. There has been much research on biomarkers and their ability to aid the decision on when to stop antibiotics. Some of these biomarkers include interleukins, C-reactive protein (CRP) and procalcitonin (PCT). PCT's value as a biomarker has been a focus area of research in recent years. Most studies use either a cut-off value of 0.50 ng/mL or an >80% reduction in PCT levels to determine when to stop antibiotics. This paper performs a literature review and provides a synthesized up-to-date global overview on the value of PCT in managing intra-abdominal infections.
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BACKGROUND: Diaphragmatic hernia (DH) presenting acutely can be a potentially life-threatening condition. Its management continues to be debatable. METHODS: A bibliographic search using major databases was performed using the terms "emergency surgery" "diaphragmatic hernia," "traumatic diaphragmatic rupture" and "congenital diaphragmatic hernia." GRADE methodology was used to evaluate the evidence and give recommendations. RESULTS: CT scan of the chest and abdomen is the diagnostic gold standard to evaluate complicated DH. Appropriate preoperative assessment and prompt surgical intervention are important for a clinical success. Complicated DH repair is best performed via the use of biological and bioabsorbable meshes which have proven to reduce recurrence. The laparoscopic approach is the preferred technique in hemodynamically stable patients without significant comorbidities because it facilitates early diagnosis of small diaphragmatic injuries from traumatic wounds in the thoraco-abdominal area and reduces postoperative complications. Open surgery should be reserved for situations when skills and equipment for laparoscopy are not available, where exploratory laparotomy is needed, or if the patient is hemodynamically unstable. Damage Control Surgery is an option in the management of critical and unstable patients. CONCLUSIONS: Complicated diaphragmatic hernia is a rare life-threatening condition. CT scan of the chest and abdomen is the gold standard for diagnosing the diaphragmatic hernia. Laparoscopic repair is the best treatment option for stable patients with complicated diaphragmatic hernias. Open repair is considered necessary in majority of unstable patients in whom Damage Control Surgery can be life-saving.
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Hernia Hiatal , Hernias Diafragmáticas Congénitas , Traumatismos Torácicos , Humanos , Diafragma/lesiones , Tomografía Computarizada por Rayos X , TóraxRESUMEN
Many countries are facing an aging population. As people live longer, surgeons face the prospect of operating on increasingly older patients. Traditional teaching is that with older age, these patients face an increased risk of mortality and morbidity, even to a level deemed too prohibitive for surgery. However, this is not always true. An active 90-year-old patient can be much fitter than an overweight, sedentary 65-year-old patient with comorbidities. Recent literature shows that frailty-an age-related cumulative decline in multiple physiological systems, is therefore a better predictor of mortality and morbidity than chronological age alone. Despite recognition of frailty as an important tool in identifying vulnerable surgical patients, many surgeons still shun objective tools. The aim of this position paper was to perform a review of the existing literature and to provide recommendations on emergency laparotomy and in frail patients. This position paper was reviewed by an international expert panel composed of 37 experts who were asked to critically revise the manuscript and position statements. The position paper was conducted according to the WSES methodology. We shall present the derived statements upon which a consensus was reached, specifying the quality of the supporting evidence and suggesting future research directions.
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Fragilidad , Humanos , Anciano , Anciano de 80 o más Años , Laparotomía , Anciano Frágil , Consenso , ComorbilidadRESUMEN
BACKGROUND AND AIMS: Acute infections cause relevant activation of innate immunity and inflammatory cascade. An excessive response against pathogens has been proved to trigger the pathophysiological process of thrombo-inflammation. Nevertheless, an association between the use of antithrombotic agents and the outcome of critically ill patients with infectious diseases is lacking. The aim of this meta-analysis is to determine the impact of antithrombotic treatment on survival of patients with acute infective disease. METHODS: MEDLINE, Embase, Cinahl, Web of Science and Cochrane Central Register of Controlled Trials (CENTRAL) databases were systematically searched from inception to March 2021. We included randomized controlled trials (RCTs) that evaluated any antithrombotic agent in patients with infectious diseases other than COVID-19. Two authors independently performed study selection, data extraction and risk of bias evaluation. The primary outcome was all-cause mortality. Summary estimates for mortality were calculated using the inverse-variance random-effects method. RESULTS: A total of 16,588 patients participating in 18 RCTs were included, of whom 2141 died. Four trials evaluated therapeutic-dose anticoagulation, 1 trial prophylactic-dose anticoagulation, 4 trials aspirin, and 9 trials other antithrombotic agents. Overall, the use of antithrombotic agents was not associated with all-cause mortality (relative risk 0.96; 95% confidence interval, 0.90-1.03). CONCLUSIONS: The use of antithrombotics is not associated with all-cause mortality in patients with infectious disease other than COVID-19. Complex pathophysiological interplays between inflammatory and thrombotic pathways may explain these results and need further investigation. REGISTRATION: PROSPERO, CRD42021241182.
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COVID-19 , Fibrinolíticos , Humanos , Anticoagulantes/efectos adversos , Aspirina , Fibrinolíticos/uso terapéutico , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
BACKGROUND: Timely access to the operating room for emergency general surgery (EGS) indications remains a challenge across the globe, largely driven by operating room availability and staffing constraints. The "timing in acute care surgery" (TACS) classification was previously published to introduce a new tool to triage the timely and appropriate access of EGS patients to the operating room. However, the clinical and operational effectiveness of the TACS classification has not been investigated in subsequent validation studies. This study aimed to improve the TACS classification and provide further consensus around the appropriate use of the new TACS classification through a standardized Delphi approach with international experts. METHODS: This is a validation study of the new TACS by a selected international panel of experts using the Delphi method. The TACS questionnaire was designed as a web-based survey. The consensus agreement level was established to be ≥ 75%. The collective consensus agreement was defined as the sum of the percentage of the highest Likert scale levels (4-5) out of all participants. Surgical emergency diseases and correlated clinical scenarios were defined for each of the proposed classes. Subsequent rounds were carried out until a definitive level of consensus was reached. Frequencies and percentages were calculated to determine the degree of agreement for each surgical disease. RESULTS: Four polling rounds were carried out. The new TACS classification provides 6 colour-code classes correlated to a precise timing to surgery, defined scenarios and surgical condition. The WHITE colour-code class was introduced to rapidly (within a week) reschedule cancelled or postponed surgical procedures. Haemodynamic stability is the main tool to stratify patients for immediate surgery or not in the presence of sepsis/septic shock. Fifty-one surgical diseases were included in the different colour-code classes of priority. CONCLUSION: The new TACS classification is a comprehensive, simple, clear and reproducible triage system which can be used to assess the severity of the patient and the surgical disease, to reduce the time to access to the operating room, and to manage the emergency surgical patients within a "safe" timeframe. By including well-defined surgical diseases in the different colour-code classes of priority, validated through a Delphi consensus, the new TACS improves communication among surgeons, between surgeons and anaesthesiologists and decreases conflicts and waste and waiting time in accessing the operating room for emergency surgical patients.
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Cirujanos , Triaje , Humanos , Técnica Delphi , Triaje/métodos , Consenso , QuirófanosRESUMEN
Current evidence of an association of breast cancer (BC) risk with air pollution exposure, in particular from traffic exhaust, remains inconclusive, and the exposure assessment methodologies are heterogeneous. This study aimed to conduct a systematic review and meta-analysis on the association between traffic-related air pollution (TRAP) and BC incidence (PROSPERO CRD42021286774). We systematically reviewed observational studies assessing exposure to TRAP and BC risk published until June 2022, available on Medline/PubMed and Web of Science databases. Studies using models for assessing exposure to traffic-related air pollutants or using exposure proxies (including traffic density, distance to road, etc.) were eligible for inclusion. A random-effects meta-analysis of studies investigating the association between NO2/NOx exposure and BC risk was conducted. Overall, 21 studies meeting the inclusion criteria were included (seven case-control, one nested case-control, 13 cohort studies); 13 studies (five case-control, eight cohort) provided data for inclusion in the meta-analyses. Individual studies provided little evidence of an association between TRAP and BC risk; exposure assessment methods and time periods of traffic emissions were different. The meta-estimate on NO2 exposure indicated a positive association (pooled relative risk per 10 µg/m3 of NO2: 1.015; 95% confidence interval, CI: 1.003; 1.028). No association between NOx exposure and BC was found (three studies). Although there was limited evidence of an association for TRAP estimated with proxies, the meta-analysis showed a significant association between NO2 exposure, a common TRAP pollutant marker, and BC risk, yet with a small effect size. Our findings provide additional support for air pollution carcinogenicity.
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BACKGROUND: Severe traumatic brain-injured (TBI) patients should be primarily admitted to a hub trauma center (hospital with neurosurgical capabilities) to allow immediate delivery of appropriate care in a specialized environment. Sometimes, severe TBI patients are admitted to a spoke hospital (hospital without neurosurgical capabilities), and scarce data are available regarding the optimal management of severe isolated TBI patients who do not have immediate access to neurosurgical care. METHODS: A multidisciplinary consensus panel composed of 41 physicians selected for their established clinical and scientific expertise in the acute management of TBI patients with different specializations (anesthesia/intensive care, neurocritical care, acute care surgery, neurosurgery and neuroradiology) was established. The consensus was endorsed by the World Society of Emergency Surgery, and a modified Delphi approach was adopted. RESULTS: A total of 28 statements were proposed and discussed. Consensus was reached on 22 strong recommendations and 3 weak recommendations. In three cases, where consensus was not reached, no recommendation was provided. CONCLUSIONS: This consensus provides practical recommendations to support clinician's decision making in the management of isolated severe TBI patients in centers without neurosurgical capabilities and during transfer to a hub center.
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Lesiones Traumáticas del Encéfalo , Humanos , Lesiones Traumáticas del Encéfalo/cirugía , Hospitales , Encéfalo , Procedimientos Neuroquirúrgicos , HospitalizaciónRESUMEN
BACKGROUND: Minimally invasive surgery (MIS), including laparoscopic and robotic approaches, is widely adopted in elective digestive surgery, but selectively used for surgical emergencies. The present position paper summarizes the available evidence concerning the learning curve to achieve proficiency in emergency MIS and provides five expert opinion statements, which may form the basis for developing standardized curricula and training programs in emergency MIS. METHODS: This position paper was conducted according to the World Society of Emergency Surgery methodology. A steering committee and an international expert panel were involved in the critical appraisal of the literature and the development of the consensus statements. RESULTS: Thirteen studies regarding the learning curve in emergency MIS were selected. All but one study considered laparoscopic appendectomy. Only one study reported on emergency robotic surgery. In most of the studies, proficiency was achieved after an average of 30 procedures (range: 20-107) depending on the initial surgeon's experience. High heterogeneity was noted in the way the learning curve was assessed. The experts claim that further studies investigating learning curve processes in emergency MIS are needed. The emergency surgeon curriculum should include a progressive and adequate training based on simulation, supervised clinical practice (proctoring), and surgical fellowships. The results should be evaluated by adopting a credentialing system to ensure quality standards. Surgical proficiency should be maintained with a minimum caseload and constantly evaluated. Moreover, the training process should involve the entire surgical team to facilitate the surgeon's proficiency. CONCLUSIONS: Limited evidence exists concerning the learning process in laparoscopic and robotic emergency surgery. The proposed statements should be seen as a preliminary guide for the surgical community while stressing the need for further research.
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Laparoscopía , Procedimientos Quirúrgicos Robotizados , Cirujanos , Humanos , Curriculum , Procedimientos Quirúrgicos Mínimamente InvasivosRESUMEN
Canned fish is a widely consumed and affordable food whose effect on cancer risk has been little investigated. We studied its effect on risk of upper digestive tract cancers using data from a network of hospital-based case-control studies from Northern Italy providing information about canned fish consumption as a separate item and including a total of 946 patients with oral cavity and pharynx cancer, 304 patients with esophageal cancer, 230 patients with gastric cancer and 3273 controls. Twenty-three percent of patients with cancer of the oral cavity or pharynx and 26% of those with cancer of the stomach consumed ≥1 serving per week of canned fish, compared to 40% and 49% of the respective control group. Among cases of esophageal cancer and controls 22% consumed ≥1 serving per week of canned fish. Odds ratios for ≥1 vs <1 portion per week were 0.79 (95% Confidence Interval, CI: 0.64-0.97) for cancer of the oral cavity and pharynx, and 0.59 (95% CI: 0.41-0.86) for stomach cancer, whereas there was no inverse association with esophageal cancer. These findings suggest a favorable role of canned fish for selected upper digestive tract cancers.
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Neoplasias Esofágicas , Neoplasias Gastrointestinales , Neoplasias Gástricas , Animales , Factores de Riesgo , Neoplasias Gástricas/epidemiología , Estudios de Casos y ControlesRESUMEN
BACKGROUND: The optimal timing of PCI for NSTE-ACS with CKD is unclear. The aim of our study was to assess whether early percutaneous coronary intervention (PCI) (within 24 hours from admission) is associated with improved in-hospital (mortality or acute kidney injury) and long-term events (composite of mortality, myocardial infarction, stroke and bleeding events) in patients with non-ST-elevation acute coronary syndromes (NSTE-ACS) with chronic kidney disease (CKD). METHODS: We retrospectively studied NSTE-ACS patients who underwent PCI in large tertiary centers. CKD was defined as estimated glomerular filtration rate (eGFR)<60 mL/min/1.73 m2. A propensity score for the likelihood of an early invasive strategy was calculated. Relative risks (RR) and adjusted hazard ratios (HR) were estimated for in-hospital and follow-up events. RESULTS: We included 821 patients, mean age was 69±12 years; 492 (60%) received an early PCI, and 273 (33%) had an eGFR <60. Median follow-up was 391 days. At univariate analysis, early treatment was associated with significantly lower in-hospital and follow-up events. However, after adjustment for major prognostic factors, there was no significant association with both in-hospital (RR=1.06; 95% CI 0.83-1.36) and follow-up events (RR=1.07; 95% CI 0.83-1.37). When the association was assessed in strata of CKD, lack of statistically significant association was confirmed, even if a trend emerged in patients with preserved renal function both on primary outcome (RR=0.47, 95% 0.18-1.22) and time to secondary outcome (HR=0.62, 95% CI 0.36-1.08). CONCLUSIONS: In conclusion in a cohort of NSTE-ACS patients, an early invasive strategy does not independently affect prognosis.
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Síndrome Coronario Agudo , Intervención Coronaria Percutánea , Insuficiencia Renal Crónica , Humanos , Persona de Mediana Edad , Anciano , Anciano de 80 o más Años , Pronóstico , Síndrome Coronario Agudo/cirugía , Intervención Coronaria Percutánea/efectos adversos , Estudios Retrospectivos , Insuficiencia Renal Crónica/complicacionesRESUMEN
Introduction. Sepsis is an overwhelming reaction to infection with significant morbidity, requiring urgent interventions in order to improve outcomes. The 2016 Sepsis-3 guidelines modified the previous definitions of sepsis and septic shock, and proposed some specific diagnostic and therapeutic measures to define the use of fluid resuscitation and antibiotics. However, some open issues still exist. Methods. A literature research was performed on PubMed and Cochrane using the terms "sepsis" AND "intra-abdominal infections" AND ("antibiotic therapy" OR "antibiotic treatment"). The inclusion criteria were management of intra-abdominal infection (IAI) and effects of antibiotic stewardships programs (ASP) on the outcome of the patients. Discussion. Sepsis-3 definitions represent an added value in the understanding of sepsis mechanisms and in the management of the disease. However, some questions are still open, such as the need for an early identification of sepsis. Sepsis management in the context of IAI is particularly challenging and a prompt diagnosis is essential in order to perform a quick treatment (source control and antibiotic treatment). Antibiotic empirical therapy should be based on the kind of infection (community or hospital acquired), local resistances, and patient's characteristic and comorbidities, and should be adjusted or de-escalated as soon as microbiological information is available. Antibiotic Stewardship Programs (ASP) have demonstrated to improve antimicrobial utilization with reduction of infections, emergence of multi-drug resistant bacteria, and costs. Surgeons should not be alone in the management of IAI but ideally inserted in a sepsis team together with anaesthesiologists, medical physicians, pharmacists, and infectious diseases specialists, meeting periodically to reassess the response to the treatment. Conclusion. The cornerstones of sepsis management are accurate diagnosis, early resuscitation, effective source control, and timely initiation of appropriate antimicrobial therapy. Current evidence shows that optimizing antibiotic use across surgical specialities is imperative to improve outcomes. Ideally every hospital and every emergency surgery department should aim to provide a sepsis team in order to manage IAI.
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Background. Antibiotic treatment in emergency general surgery (EGS) is a major challenge for surgeons, and a multidisciplinary approach is necessary in order to improve outcomes. Intra-abdominal infections are at high risk of increased morbidity and mortality, and prolonged hospitalization. An increase in multi-drug resistance bacterial infections and a tendency to an antibiotic overuse has been described in surgical settings. In this clinical scenario, antibiotic de-escalation (ADE) is emerging as a strategy to improve the management of antibiotic therapy. The objective of this article is to summarize the available evidence, current strategies and unsolved problems for the optimization of ADE in EGS. Methods. A literature search was performed on PubMed and Cochrane using "de-escalation", "antibiotic therapy" and "antibiotic treatment" as research terms. Results. There is no universally accepted definition for ADE. Current evidence shows that ADE is a feasible strategy in the EGS setting, with the ability to optimize antibiotic use, to reduce hospitalization and health care costs, without compromising clinical outcome. Many studies focus on Intensive Care Unit patients, and a call for further studies is required in the EGS community. Current guidelines already recommend ADE when surgery for uncomplicated appendicitis and cholecystitis reaches a complete source control. Conclusions. ADE in an effective and feasible strategy in EGS patients, in order to optimize antibiotic management without compromising clinical outcomes. A collaborative effort between surgeons, intensivists and infectious disease specialists is mandatory. There is a strong need for further studies selectively focusing in the EGS ward setting.
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Background and Aims: The content of fatty acids (FA) in human milk may be influenced by maternal nutrition. We evaluated the role of a Mediterranean diet in influencing the content of FA in human milk among 282 breastfeeding mothers participating in the MEDIDIET study. Materials and Methods: Mediterranean Diet Score (MDS), a composite index, was used to evaluate adherence to the Mediterranean diet. It includes 9 components (i.e., vegetables, fruit, cereals, legumes, monounsaturated to saturated FA ratio - MUFA/SFA, fish, dairy products, meat, and alcohol) and therefore potentially ranges from 0 (no adherence) to 9 (complete adherence) points. None of the mothers obtained the highest score due to the low alcohol consumption in the study population. Mothers were categorized in approximate tertiles of adherence: 0-3 (34.4%), 4 (26.2%), and 5-8 points (39.4%). The mean content of FA across categories of MDS was compared using ANOVA and test for trend. Results: A high adherence of breastfeeding mothers to the Mediterranean diet was associated with lower content of SFA in human milk (42.58 ± 4.36 for MDS = 0-3, 42.58 ± 4.89 for MDS = 4, and 40.92 ± 5.22% of fats for MDS = 5-8 points; p ANOVA and p for trend = 0.02). Conversely, a high adherence was associated with higher content of MUFA in human milk (43.27 ± 4.27 for MDS = 0-3, 43.27 ± 4.47 for MDS = 4, and 45.24 ± 5.22% of fats for MDS = 5-8 points; p ANOVA and p for trend < 0.01), ω-3 FA (1.07 ± 0.25 for MDS = 0-3, 1.22 ± 0.49 for MDS = 4, and 1.31 ± 0.51% of fats for MDS = 5-8 points; p ANOVA and p for trend < 0.01), and the major types of ω-3 FA (i.e., α-linolenic acid - ALA, eicosapentaenoic acid - EPA, docosahexaenoic acid - DHA, docosapentaenoic acid - DPA). These associations were mainly driven by the adherence to the vegetables, MUFA/SFA, fish, and dairy products components of the Mediterranean diet. Conclusion: A high adherence to the Mediterranean diet was associated with human milk showing a lower content of SFA and higher content of MUFA and ω-3 FA, including DHA. The Mediterranean diet may contribute in human milk production with higher content of specific FA which is directly involved in infant's neural and visual development, as reported by previous studies.
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Somatic mutations in the ubiquitin specific peptidase 8 (USP8) gene have been associated with higher levels of somatostatin (SS) receptor subtype 5 (SSTR5) in adrenocorticotroph hormone (ACTH)-secreting pituitary neuroendocrine tumors (PitNETs). However, a correlation between the USP8 mutational status and favourable responses to pasireotide, the somatostatin multi-receptor ligand acting especially on SSTR5, has not been investigated yet. Here, we studied the impact of USP8 mutations on pasireotide responsiveness in human and murine corticotroph tumor cells. SSTR5 upregulation was observed in USP8 wild-type primary tumor cells transfected with S718del USP8 mutant. However, cell transfection with S718del USP8 and C40-USP8 mutants in in vitro sensitive cultures from USP8 wild-type tumors abolished their ability to respond to pasireotide and did not confer pasireotide responsiveness to the in vitro resistant culture. Pasireotide failed to reduce ACTH secretion in primary cells from one S718P USP8-mutated tumor but exerted a strong antisecretory effect in primary cells from one P720R USP8-mutated tumor. In agreement, AtT-20 cells transfection with USP8 mutants led to SSTR5 expression increase but pasireotide could reduce ACTH production and cyclin E expression in P720R USP8 overexpressing cells, only. In situ Proximity Ligation Assay and immunoflurescence experiments revealed that P720R USP8 mutant is still able to bind 14-3-3 proteins in AtT-20 cells, without affecting SSTR5 localization. In conclusion, P720R USP8 mutation might be considered as a molecular predictor of favourable response to pasireotide in corticotroph tumor cells.