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.

Investigating Non-Pharmacological Stress Reduction Interventions in Pediatric Patients Confirmed with Salivary Cortisol Levels: A Systematic Review.

For many children, hospitalization can lead to a state of increased anxiety. Being away from home, the invasive procedures undertaken, and the uncertainty of the outcome cause an uncomfortable situation in anticipation of real or imagined hazards. This systematic review aims to assess current evidence on the types of non-pharmacological interventions used and their impact on children's anxiety or distress levels when they visit the hospital for planned or unplanned admissions. The Databases PubMed, Psych INFO, and Google Scholar were queried for papers published from January 2000 to March 2023 reporting the use of non-pharmacological interventions interacting with children in hospital or clinical environments and confirmed with saliva cortisol levels. A total of nine studies were retrieved. Across these studies, four different strategies of non-pharmacological interventions were used. Anxiety and distress were found to be reduced in the majority of the studies as confirmed with salivary cortisol. Overall, there is evidence that non-pharmacological interventions hold a promising role in reducing levels of anxiety or distress in children as confirmed with saliva cortisol. However, research on saliva cortisol as a tool of anxiety measurement requires higher quality studies to strengthen the evidence base.

Measuring Children's Stress via Saliva in Surgical and Endoscopic Procedures and Its Measurement Intention in the Community: Reality-Future Prospects.

(1) Background: Children who undergo surgical or endoscopic procedures display high levels of stress, and various means are applied to reduce their anxiety. Salivary cortisol (S Cortisol) and salivary alpha-amylase (SAA) are often used as a valid biomarker of stress. The primary purpose of the study was the investigation of stress levels through S Cortisol and S amylase after intervention in surgical or endoscopic procedures (gastroscopy-colonoscopy). The secondary outcomes were the investigation of the intention to adopt new methods of saliva sampling. We collected saliva samples from children subjected to invasive medical procedures, with the aim of applying the Theory of Planned Behavior (TPB) as an intervention means to provide information and education to both parents and children undergoing stressful situations, and assess its efficacy in reducing stress levels. We also aimed at acquiring a better understanding of the acceptability of noninvasive biomarker collection in community settings. (2) Methods: The sample of this prospective study comprised 81 children who underwent surgical or endoscopic procedures at the Attikon General University Hospital, Athens, Greece and 90 parents. The sample was divided into two groups. The first, 'Group Unexplained', was not provided any information or education about the procedures, while the second, 'Group Explained', was informed and educated based on TPB. Thereafter, 8-10 weeks after intervention, the Theory of Planned Behavior questions were re-completed by the 'Group Explained'. (3) Results: Significant differences were detected in cortisol and amylase values between the two groups postoperatively after applying the TPB intervention. Saliva cortisol was reduced by 8.09 ng/mL in the 'Group Explained' while in the 'Group Unexplained' it was reduced by 4.45 ng/mL (p < 0.001). Salivary amylase values decreased by 9.69 ng/mL in the 'Group Explained' after the intervention phase of the study, while in the 'Group Unexplained' they increased by 35.04 ng/mL (p < 0.001). The regression explains 40.3% (baseline) and 28.5% (follow-up) of parental intention. The predictive factor of parental intention (baseline) is attitude (p < 0.001) and follow-up is behavioral control (p < 0.028) and attitude (p < 0.001). (4) Conclusions: Providing proper education and information for parents has a positive effect on reducing children's stress levels. Changing parental attitudes towards saliva collection plays the most important role, since a positive attitude can influence intention and ultimately participation in these procedures.

Ileal bypass for pruritus relief in a 3-year-old boy with advanced progressive familial intrahepatic cholestasis: how effective is it?

Progressive familial intrahepatic cholestasis (PFIC) is a group of liver disorders that manifest in early childhood with cholestasis and pruritus resulting progressively in liver failure. We present a case of a 3-year-old boy with advanced PFIC from refractory pruritus. In order to offer an effective treatment of pruritus, our patient underwent ileal bypass and after a 2-month period free of symptoms, unexpectedly relapsed after a Rota viral infection. Finally, the child underwent orthotopic liver transplantation. Patients with advanced PFIC do not seem to benefit from nontransplant invasive interventions regarding the relief of pruritus.

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.

Clinical significance of interleukin-18 in the course of burn injured children.

BACKGROUND: Burn injury (BI) is one of the most serious causes of morbidity and mortality in the pediatric population. BI triggers an initial stage of hyperinflammation, followed by hypersecretion of both pro- and anti-inflammatory cytokines. IL- 18 is a vital pro-inflammatory cytokine, the effect of which has been investigated not only in animal models but also in adult patients. No study has yet examined the association of serum IL- 18 levels and the clinical significance in the course of pediatric BI. METHODS: We conducted a prospective study including all children with burn injuries who were hospitalized from December 2015 to December 2018 in a tertiary Children's Hospital. RESULTS: A total of 55 children with BI were included. In the present study, we found a strong positive correlation between total body surface area (TBSA) and the levels of IL-18 at admission and on the third day postburn, respectively. The WBC count, the number of lymphocytes and the CRP levels at admission revealed a strong, positive correlation with IL-18 levels. The correlation between IL-18 levels at admission and the length of stay (LOS) was moderate. CONCLUSIONS: This study has shown that the levels of IL-18 collected at admission correlate positively with the extent of TBSA and inflammatory indices in pediatric patients. Moreover, IL-18 levels at admission may not be the most accurate prognostic factor regarding the LOS. However, further research is needed in order to establish more accurate predictive factors for the outcome of BIs in pediatric patients.

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.

Inflammatory fibroid polyp of the anus in a 12-month-old girl: Case report and review of the literature.

Inflammatory fibroid polyp (IFP) is a rare, usually solitary and intraluminal polypoid benign tumour that can affect any part of the gastrointestinal (GI) tract. Its aetiology is unknown and clinical presentation depends on the site of involvement. We present the case of a 12-month-old girl with IFP and review all reported cases of IFP in children and adolescents <18 years. A 12-month-old girl presented with rectal bleeding. The patient underwent colonoscopy which revealed an anus polyp. Surgical resection was performed and histopathological examination of the specimen showed features of IFP. A literature review of 20 cases (including ours) between 1966 and January 2022 is also presented. To our knowledge, this is the youngest reported patient with IFP and the first in the anal area.

Antibacterial Activity of Copper Nanoparticles against Xanthomonas campestris pv. vesicatoria in Tomato Plants.

Copper-based bactericides have appeared as a new tool in crop protection and offer an effective solution to combat bacterial resistance. In this work, two copper nanoparticle products that were previously synthesized and evaluated against major bacterial and fungal pathogens were tested on their ability to control the bacterial spot disease of tomato. Growth of Xanthomonas campestris pv. vesicatoria, the causal agent of the disease, was significantly suppressed by both nanoparticles, which had superior function compared to conventional commercial formulations of copper. X-ray fluorescence spectrometry measurements in tomato leaves revealed that bioavailability of copper is superior in the case of nanoparticles compared to conventional formulations and is dependent on synthesis rather than size. This is the first report correlating bioavailability of copper to nanoparticle efficacy.

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.

A Review of History and Challenges of Evidence-Based Pediatric Surgery.

PURPOSE: Evidence-based pediatric surgery (EBPS) refers to the use of the best available evidence in making personalized decisions concerning the management of each pediatric surgical patient. This study aims to provide a comprehensive review on past and present evidence-based clinical decision, and challenges in pediatric surgery. MATERIAL AND METHODS: A literature search was conducted according to a set of criteria in PubMed for historical and current peer-reviewed studies regarding EBPS. RESULTS: One hundred forty-five full-text published articles focusing on EPBS findings over the past 25 years were included. The rarity of many congenital anomalies, the inability to establish multicenter collaborations, the failure to perform double-blinded studies in children, the pediatric surgeons' reluctance to perform ethically unacceptable sham operations and their skepticism shown in accepting and implementing the documented results instead of applying their personal clinical practice methods and surgical techniques are among problems that hamper the accomplishment of randomized controlled trials (RCTs). CONCLUSIONS: RCTs remain limited in clinical pediatric surgery practice due to problems in the design and publication of these trials. Moreover, skepticism exists regarding acceptance and implementation of the documented results of RCTs. Notwithstanding, pediatric surgeons must establish evidence-based centers in order to increase the number of well-designed RCTs, properly evaluate clinical research, make effective evidence-based clinical decisions and develop high-quality of pediatric surgeries care in the future.

Endoscopic versus surgical treatment for thoracopancreatic fistulas complicating chronic pancreatitis: A systematic review.

BACKGROUND: Thoracopancreatic fistulae are a rare complication of chronic pancreatitis. The aim of the present study is to evaluate potential risk factors for endoscopic treatment failure and explore the safety of surgery when utilized either upfront or as a "bail-out" procedure after failed endoscopic treatment. METHOD: A comprehensive literature search was conducted on the MedLine, Scopus, Embase, and Web of Knowledge databases for cases of thoracopancreatic fistulae. Data regarding patient demographics, fistula anatomy, and treatment interventions performed were extracted for further analysis. RESULTS: The study pool consisted of 75 case reports and 19 case series published between the years 1972 and 2020. Duct disruption in the pancreatic body was most commonly encountered (41.1%), and a left pleural effusion was the most common manifestation (46%). Endoscopic treatment was attempted for 104 patients with an overall success rate of 42.3% (n = 44). Predictive factors for eventual success of endoscopic treatment were the ability of endoscopic retrograde cholangiopancreatography to diagnose the thoracopancreatic leak (odds ratio 9.76, 95% confidence interval 2.71-35.09, P < .001), the use of pancreatic duct stents (odds ratio 22.1, 95% confidence interval 7.92-61.61, P < .001), and the use of sphincterotomy (odds ratio 7.96, 95% confidence interval 2.1-30.1, P < .001). Conversely, the presence of pancreatic duct calculi was associated with endoscopic treatment failure (odds ratio 0.34, 95% confidence interval 0.12-0.94, P = .03). Pooled results suggest that surgical outcomes were comparable between the primary and salvage surgery groups. CONCLUSION: A step-up approach from endoscopic management to salvage surgery may be effectively employed in cases of thoracopancreatic fistulae refractory to endoscopic treatment.

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.

Shifting Perspectives of Translational Research in Bio-Bactericides: Reviewing the Bacillus amyloliquefaciens Paradigm.

Bacterial biological control agents (BCAs) have been increasingly used against plant diseases. The traditional approach to manufacturing such commercial products was based on the selection of bacterial species able to produce secondary metabolites that inhibit mainly fungal growth in optimal media. Such species are required to be massively produced and sustain long-term self-storage. The endpoint of this pipeline is large-scale field tests in which BCAs are handled as any other pesticide. Despite recent knowledge of the importance of BCA-host-microbiome interactions to trigger plant defenses and allow colonization, holistic approaches to maximize their potential are still in their infancy. There is a gap in scientific knowledge between experiments in controlled conditions for optimal BCA and pathogen growth and the nutrient-limited field conditions in which they face niche microbiota competition. Moreover, BCAs are considered to be safe by competent authorities and the public, with no side effects to the environment; the OneHealth impact of their application is understudied. This review summarizes the state of the art in BCA research and how current knowledge and new biotechnological tools have impacted BCA development and application. Future challenges, such as their combinational use and ability to ameliorate plant stress are also discussed. Addressing such challenges would establish their long-term use as centerfold agricultural pesticides and plant growth promoters.

Direct Antibiotic Activity of Bacillibactin Broadens the Biocontrol Range of Bacillus amyloliquefaciens MBI600.

Bacillus amyloliquefaciens is considered the most successful biological control agent due to its ability to colonize the plant rhizosphere and phyllosphere where it outgrows plant pathogens by competition, antibiosis, and inducing plant defense. Its antimicrobial function is thought to depend on a diverse spectrum of secondary metabolites, including peptides, cyclic lipopeptides, and polyketides, which have been shown to target mostly fungal pathogens. In this study, we isolated and characterized the catecholate siderophore bacillibactin by B. amyloliquefaciens MBI600 under iron-limiting conditions and we further identified its potential antibiotic activity against plant pathogens. Our data show that bacillibactin production restrained in vitro and in planta growth of the nonsusceptible (to MBI600) pathogen Pseudomonas syringae pv. tomato. Notably, it was also related to increased antifungal activity of MBI600. In addition to bacillibactin biosynthesis, iron starvation led to upregulation of specific genes involved in microbial fitness and competition. IMPORTANCE Siderophores have mostly been studied concerning their contribution to the fitness and virulence of bacterial pathogens. In the present work, we isolated and characterized for the first time the siderophore bacillibactin from a commercial bacterial biocontrol agent. We proved that its presence in the culture broth has significant biocontrol activity against nonsusceptible bacterial and fungal phytopathogens. In addition, we suggest that its activity is due to a new mechanism of action, that of direct antibiosis, rather than by competition through iron scavenging. Furthermore, we showed that bacillibactin biosynthesis is coregulated with the transcription of antimicrobial metabolite synthases and fitness regulatory genes that maximize competition capability. Finally, this work highlights that the efficiency and range of existing bacterial biocontrol agents can be improved and broadened via the rational modification of the growth conditions of biocontrol organisms.

Transmission of Infections during Cardiopulmonary Resuscitation.

Cardiopulmonary resuscitation (CPR) is an emergency lifesaving endeavor, performed in either the hospital or outpatient settings, that significantly improves outcomes and survival rates when performed in a timely fashion. As with any other medical procedure, CPR can bear potential risks not only for the patient but also for the rescuer. Among those risks, transmission of an infectious agent has been one of the most compelling triggers of reluctance to perform CPR among providers. The concern for transmission of an infection from the resuscitated subject may impede prompt initiation and implementation of CPR, compromising survival rates and neurological outcomes of the patients. Infections during CPR can be potentially acquired through airborne, droplet, contact, or hematogenous transmission. However, only a few cases of infection transmission have been actually reported globally. In this review, we present the available epidemiological findings on transmission of different pathogens during CPR and data on reluctance of health care workers to perform CPR. We also outline the levels of personal protective equipment and other protective measures according to potential infectious hazards that providers are potentially exposed to during CPR and summarize current guidelines on protection of CPR providers from international societies and stakeholders.

HSP90 affects root growth in Arabidopsis by regulating the polar distribution of PIN1.

Auxin homeostasis and signaling affect a broad range of developmental processes in plants. The interplay between HSP90 and auxin signaling is channeled through the chaperoning capacity of the HSP90 on the TIR1 auxin receptor. The sophisticated buffering capacity of the HSP90 system through the interaction with diverse signaling protein components drastically shapes genetic circuitries regulating various developmental aspects. However, the elegant networking capacity of HSP90 in the global regulation of auxin response and homeostasis has not been appreciated. Arabidopsis hsp90 mutants were screened for gravity response. Phenotypic analysis of root meristems and cotyledon veins was performed. PIN1 localization in hsp90 mutants was determined. Our results showed that HSP90 affected the asymmetrical distribution of PIN1 in plasma membranes and influenced its expression in prompt cell niches. Depletion of HSP90 distorted polar distribution of auxin, as the acropetal auxin transport was highly affected, leading to impaired root gravitropism and lateral root formation. The essential role of the HSP90 in auxin homeostasis was profoundly evident from early development, as HSP90 depletion affected embryo development and the pattern formation of veins in cotyledons. Our data suggest that the HSP90-mediated distribution of PIN1 modulates auxin distribution and thereby auxin signaling to properly promote plant development.