Steatohepatitic hepatocellular Carcinoma:A new approach to classifying morphological subtypes of hepatocellular carcinoma.

Histological subtyping of hepatocellular carcinoma (HCC) is challenging in the presence of histological heterogeneity, where distinctly different morphological patterns are present within the same tumor. Current approaches rely on percent cut-offs. We hypothesized that morphologic intratumor heterogeneity is a non-random biological feature and that incorporating recurrent patterns would improve histological subtyping of HCC. Resected HCC were studied and the overall frequency of morphologic intratumor heterogeneity was 45% in 242 specimens. Steatohepatitic HCC (SH-HCC) had the highest frequency of morphologic intratumor heterogeneity (91%); this was confirmed in additional cohorts of SH-HCC from different medical centers (overall frequency of 78% in SH-HCC). Morphologic intratumor heterogeneity in SH-HCC showed distinct and recurrent patterns that could be classified as early, intermediate, and advanced. Incorporating these patterns into the definition of SH-HCC allowed successful resolution of several persistent challenges: the problem of the best cut-off for subtyping SH-HCC, the problem of the relationship between SH-HCC and scirrhous HCC, and the classification for HCC with abundant microvesicular steatosis. This approach also clarified the relationship between SH-HCC and CTNNB1 mutations, showing that CTNNB1 mutations occur late in a subset of SH-HCC. In summary, there is a high frequency of morphologic intratumor heterogeneity in HCC. Incorporating this finding into histological subtyping resolved several persistent problems with the SH-HCC subtype.

Epidemiology of respiratory viruses among children during the SARS-CoV-2 pandemic: A systematic review and meta-analysis.

OBJECTIVE: This meta-analysis aimed to assess the prevalence of respiratory viruses among children under the special conditions of the COVID-19 pandemic. METHODS: Five databases were systematically searched to assess the pooled prevalence of various respiratory viruses in different age groups, regions, seasons, and in patients with and without confirmed SARS-CoV-2 coinfection. Moreover, we looked at the virus distribution in the first and second half of the pandemic and countries with distinct economic status. Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines were followed, and the systematic review was registered on PROSPERO (CRD42022379297). RESULTS: Enterovirus/rhinovirus and human respiratory syncytial virus (HRSV) were the most prevalent pathogens among children. The prevalence of HRSV increased in the second half of the pandemic. The prevailing viruses vary according to the SARS-CoV-2-coinfection status, season, region, and country´s economic status. CONCLUSION: This meta-analysis shows the epidemiology of respiratory viruses other than SARS-CoV-2 in children aged 0 to 12 years during the COVID-19 pandemic. Because major events, such as a pandemic, can alter epidemiology patterns, it is important to know them to improve health education measures, develop vaccines and medicines for vulnerable groups, as a guide for prevention strategies, and help with clinical decisions.

New Insights into the Fluid Management in Patients with Septic Shock.

The importance of fluid resuscitation therapy during the early stages of sepsis management is a well-established principle. Current Surviving Sepsis Campaign (SSC) guidelines recommend the early administration of intravenous crystalloid fluids for sepsis-related hypotension or hyperlactatemia due to tissue hypoperfusion, within the first 3 h of resuscitation and suggest using balanced solutions (BSs) instead of normal saline (NS) for the management of patients with sepsis or septic shock. Studies comparing BS versus NS administration in septic patients have demonstrated that BSs are associated with better outcomes including decreased mortality. After initial resuscitation, fluid administration has to be judicious in order to avoid fluid overload, which has been associated with increased mortality, prolonged mechanical ventilation, and worsening of acute kidney injury. The "one size fits all" approach may be "convenient" but it should be avoided. Personalized fluid management, based on patient-specific hemodynamic indices, provides the foundations for better patient outcomes in the future. Although there is a consensus on the need for adequate fluid therapy in sepsis, the type, the amount of administered fluids, and the ideal fluid resuscitation strategy remain elusive. Well-designed large randomized controlled trials are certainly needed to compare fluid choices specifically in the septic patient, as there is currently limited evidence of low quality. This review aims to summarize the physiologic principles and current scientific evidence regarding fluid management in patients with sepsis, as well as to provide a comprehensive overview of the latest data on the optimal fluid administration strategy in sepsis.

Update of European Society of Clinical Microbiology and Infectious Diseases coronavirus disease 2019 guidelines: diagnostic testing for severe acute respiratory syndrome coronavirus 2.

SCOPE: Since the onset of COVID-19, several assays have been deployed for the diagnosis of SARS-CoV-2. The European Society of Clinical Microbiology and Infectious Diseases (ESCMID) published the first set of guidelines on SARS-CoV-2 in vitro diagnosis in February 2022. Because the COVID-19 landscape is rapidly evolving, the relevant ESCMID guidelines panel releases an update of the previously published recommendations on diagnostic testing for SARS-CoV-2. This update aims to delineate the best diagnostic approach for SARS-CoV-2 in different populations based on current evidence. METHODS: An ESCMID COVID-19 guidelines task force was established by the ESCMID Executive Committee. A small group was established, half appointed by the chair, and the remaining selected with an open call. The panel met virtually once a week. For all decisions, a simple majority vote was used. A list of clinical questions using the population, intervention, comparison, and outcome (PICO) format was developed at the beginning of the process. For each PICO, 2 panel members performed a literature search focusing on systematic reviews with a third panellist involved in case of inconsistent results. The panel reassessed the PICOs previously defined as priority in the first set of guidelines and decided to address 49 PICO questions, because 6 of them were discarded as outdated/non-clinically relevant. The 'Grading of Recommendations Assessment, Development and Evaluation (GRADE)-adoption, adaptation, and de novo development of recommendations (ADOLOPMENT)' evidence-to-decision framework was used to produce the guidelines. QUESTIONS ADDRESSED BY THE GUIDELINES AND RECOMMENDATIONS: After literature search, we updated 16 PICO questions; these PICOs address the use of antigen-based assays among symptomatic and asymptomatic patients with different ages, COVID-19 severity status or risk for severe COVID-19, time since the onset of symptoms/contact with an infectious case, and finally, types of biomaterials used.

Performance of point-of care molecular and antigen-based tests for SARS-CoV-2: a living systematic review and meta-analysis.

BACKGROUND: Molecular and antigen point-of-care tests (POCTs) have augmented our ability to rapidly identify and manage SARS-CoV-2 infection. However, their clinical performance varies among individual studies. OBJECTIVES: The evaluation of the performance of molecular and antigen-based POCTs in confirmed, suspected, or probable COVID-19 cases compared with that of laboratory-based RT-PCR in real-life settings. DATA SOURCES: MEDLINE/PubMed, Scopus, Embase, Web of Science, Cochrane Library, Cochrane COVID-19 study register, and COVID-19 Living Evidence Database from the University of Bern. STUDY ELIGIBILITY CRITERIA: Peer-reviewed or preprint observational studies or randomized controlled trials that evaluated any type of commercially available antigen and/or molecular POCTs for SARS-CoV-2, including multiplex PCR panels, approved by the United States Food and Drug Administration, with Emergency Use Authorization, and/or marked with Conformitè Europëenne from European Commission/European Union. PARTICIPANTS: Close contacts and/or patients with symptomatic and/or asymptomatic confirmed, suspected, or probable COVID-19 infection of any age. TEST/S: Molecular and/or antigen-based SARS-CoV-2 POCTs. REFERENCE STANDARD: Laboratory-based SARS-CoV-2 RT-PCR. ASSESSMENT OF RISK OF BIAS: Eligible studies were subjected to quality-control and risk-of-bias assessment using the Quality Assessment of Diagnostic Accuracy Studies 2 tool. METHODS OF DATA SYNTHESIS: Summary sensitivities and specificities with their 95% CIs were estimated using a bivariate model. Subgroup analysis was performed when at least three studies informed the outcome. RESULTS: A total of 123 eligible publications (97 and 26 studies assessing antigen-based and molecular POCTs, respectively) were retrieved from 4674 initial records. The pooled sensitivity and specificity for 13 molecular-based POCTs were 92.8% (95% CI, 88.9-95.4%) and 97.6% (95% CI, 96.6-98.3%), respectively. The sensitivity of antigen-based POCTs pooled from 138 individual evaluations was considerably lower than that of molecular POCTs; the pooled sensitivity and specificity rates were 70.6% (95% CI, 67.2-73.8%) and 98.9% (95% CI, 98.5-99.2%), respectively. DISCUSSION: Further studies are needed to evaluate the performance of molecular and antigen-based POCTs in underrepresented patient subgroups and different respiratory samples.

Time between onset of symptoms and definitive treatment in children with acute appendicitis: How it affects length of hospital stay?

Purpose: Any delay in treatment of acute appendicitis (AA) could lead to complications increasing morbidity and length of hospital stay (LHS). The aim of this study was to determine the time interval between onset of symptoms and seeking medical attention and definitive treatment in children with AA and its impact on LHS. Materials and Methods: A prospective study was conducted from December 2017 to March 2018. All patients diagnosed with AA and who underwent surgical procedure were enrolled. A questionnaire leaflet completed by parents was used to collect clinical data and information about seeking medical attention and children's management. Time was divided into six different intervals (1-2 h, 3-6 h, 7-12 h, 13-24 h, >24 h and >48 h) to estimate the time between onset of symptoms and seeking medical attention and time between hospital admission and surgical procedure. LHS was recorded. Results: During the study period, 125 children were enrolled. Over half of the patients sought for medical assistance relatively soon (3-12 h) after the onset of symptoms, whereas 17.6% sought late healthcare (>24 h). The time between the medical examination and surgical procedure was <24 h in approximately 80% of the children. LHS was affected by time between onset of symptoms and seeking medical attention and time between medical examination and surgical procedure (P = 0.001 and P = 0.017, respectively). Conclusions: The majority of the children with AA admitted to hospital were treated relatively soon after the onset of symptoms. However, a significant proportion of children delayed to seek medical advice and undergo appendectomy, increasing LHS.

Recognizing and Managing Pancreaticopleural Fistulas in Children.

Background: Pancreaticopleural fistula, an abnormal communication between the pancreas and the pleural cavity, is a rare complication of pancreatic disease in children and is mainly associated with acute pancreatitis, chronic pancreatitis, trauma or iatrogenicinjury. The present review presents the current available data concerning the pathogenesis, clinical features, diagnosis and management of this unusual but difficult clinical problem among children, in order to shed light on its pathologic manifestation and raise clinical suspicion.Methods: The review of the literature was performed through a PubMed search of pediatric original articles and case reports, using the key words "pancreaticopleural fistula", "pancreatitis", "pleural effusion", "pseudocyst" and "children". The literature search revealed 47 cases of pediatric patients with pancreaticopleural fistula.Results: Diagnosis is based on the patient's medical history, physical examination and imaging, while the cornerstone of diagnosis is the presence of high pleural effusion amylase levels. The management of this disorder includes conservative, endoscopic and surgical treatment options. If treated promptly and properly, this clinical entity could have a lower rate of complications.Conclusions: The incidence of pancreaticopleural fistula in children may be underestimated in the literature, due to a reduced degree of clinical suspicion. A more heightened awareness of this entity is needed to improve the quality of life in children that suffer from this condition, as early diagnosis is essential for effective treatment and improved outcome.

Benign anorectal disease in children: What do we know?

Benign anorectal disease refers to a diverse group of frequent anorectal complaints that cause considerable discomfort, disability, and often constitute a significant problem for the child and his or her family. Hemorrhoids, fissures, rectal prolapse, and perianal abscess and fistulas are the most common anorectal disorders in pediatric population and their appearance may be age-specific. Although they generally follow a benign course, a careful examination must be performed in order to exclude other serious and complicated underlying pathology. Their diagnosis is based on the patient's medical history, physical examination, endoscopy, and imaging. Moreover, the management of these disorders includes medical and surgical treatment options, and if they are treated promptly and properly may be limited and short lived. This review presents the currently available data in the literature on the diverse aspects of these disorders, including the definition, epidemiology, clinical presentation, pathogenesis, diagnosis, indications for surgery, and long-term outcomes.

Primary Duodenal Melanoma: Challenges in Diagnosis and Management of a Rare Entity.

Primary melanoma of the duodenum is an extremely rare, aggressive and life-threatening malignant neoplasm. Published data regarding the effectiveness of current treatment strategies is limited, and our knowledge relies mostly on sporadic case reports. The diagnosis of primary duodenal melanoma is challenging and is based on the patient's medical history and findings from physical examination and radiological and endoscopic imaging as well as proper and careful pathological examinations of the tumor. Despite the many advances in cancer treatment, the prognosis for patients with this type of melanoma remains extremely poor. Delayed diagnosis at advanced disease stage, the general aggressive behavior of this neoplasm, the technical difficulty in achieving complete surgical resection, along with the rich vascular and lymphatic drainage of the intestinal mucosa, all have a negative impact on patients' outcome. In the present review, we aimed to collect and summarize the currently available data in the literature regarding the pathogenesis, clinical features, diagnosis, management and long-term outcomes of this rare, malignant tumor, in order to expand knowledge of its biological behavior and investigate optimal therapeutic options for these patients. Additionally, we present our experience of a case involving a 73-year-old female with primary duodenal melanoma, who was successfully treated with complete surgical resection.

Medullary thyroid carcinoma in children: current state of the art and future perspectives.

Medullary thyroid carcinoma (MTC) is a distinct type of malignant thyroid tumor in cell origin, biological behavior, and natural history. It accounts for 1.6% of all thyroid cancers and presents either sporadically or as a hereditary disease, the latter occurring as a part of multiple endocrine neoplasia (MEN) 2A and MEN2B syndromes or as a familial MTC disease with no other manifestations. The gene responsible for the hereditary form is the rearranged during transfection (RET) gene, a proto-oncogene located to human chromosome 10. Most pediatric MTC cases have been discovered after genetic testing investigations, leading to the concept of prophylactic surgery in presymptomatic patients. Therefore, the genetic status of the child, along with serum calcitonin levels and ultrasonographic findings, determine the appropriate age for prophylactic surgical intervention. Nevertheless, a diagnosis at an early stage of MTC warrants total thyroidectomy and central lymph node dissection with the addition of lateral/contralateral lymph node dissection depending on the tumor size, ultrasonographic evidence of neck disease, or calcitonin levels. Conversely, locally advanced/unresectable or metastatic MTC is primarily treated with multikinase inhibitors, while more specific RET inhibitors are being tested in clinical trials with promising results.

Effects of cabergoline on hyperprolactinemia, psychopathology, and sexual functioning in schizophrenic patients.

Antipsychotic medications are associated to different degrees with sexual dysfunction mainly through their potential to induce hyperprolactinemia. Prolactin (PRL) secretion is mainly regulated by the hypothalamic dopaminergic systems. We conducted this 6-month, parallel-group study to prospectively investigate the effects of the dopamine agonist cabergoline on sexual dysfunction in clinically stable patients with schizophrenia (DSM-IV, AP 194) and hyperprolactinemia (PRL > 20 ng/ml for men and PRL > 25 ng/ml for women). In total 80 patients were enrolled; 33 were receiving risperidone, 17 haloperidol, 11 amisulpride, and 8 risperidone microspheres long acting. Based on PRL levels (< 50, 50-99, or > 100 ng/ml), patients were assigned in 3 cabergoline doses (0.25, 0.5, and 1 mg/day in 38, 23, and 19 patients, respectively). The psychopathology was evaluated using the Positive and Negative Syndrom Scale (PANSS), and sexual dysfunction was evaluated using the Arizona Sexual Experiences Scale (ASEX). PRL levels were reduced in all patients, from 73.3 (± 46.8) to 42.0 (± 27.8) at Month 3 and 27.1 (± 20.4) at Month 6 (p < .001). ASEX scores declined from 19.1 (± 5.1) to 17.6 (± 5.5) at Month 3 and 15.0 (± 6.5) at Month 6 (p < .001). PANSS scores were reduced in the third and in the sixth month (p = .001 at 6 month vs. baseline). The decrease in PRL was not statistically different between groups. Our data suggest that cabergoline administration to clinically stable patients with schizophrenia may improve sexual functioning without adversely affecting their psychopathologic status, provided that the dose has been suited to the severity of the hyperprolactinemia.