The Dual Role of Neutrophil Extracellular Traps (NETs) in Sepsis and Ischemia-Reperfusion Injury: Comparative Analysis across Murine Models.

A better understanding of the function of neutrophil extracellular traps (NETs) may facilitate the development of interventions for sepsis. The study aims to investigate the formation and degradation of NETs in three murine sepsis models and to analyze the production of reactive oxygen species (ROS) during NET formation. Murine sepsis was induced by midgut volvulus (720° for 15 min), cecal ligation and puncture (CLP), or the application of lipopolysaccharide (LPS) (10 mg/kg body weight i.p.). NET formation and degradation was modulated using mice that were genetically deficient for peptidyl arginine deiminase-4 (PAD4-KO) or DNase1 and 1L3 (DNase1/1L3-DKO). After 48 h, mice were killed. Plasma levels of circulating free DNA (cfDNA) and neutrophil elastase (NE) were quantified to assess NET formation and degradation. Plasma deoxyribonuclease1 (DNase1) protein levels, as well as tissue malondialdehyde (MDA) activity and glutathione peroxidase (GPx) activity, were quantified. DNase1 and DNase1L3 in liver, intestine, spleen, and lung tissues were assessed. The applied sepsis models resulted in a simultaneous increase in NET formation and oxidative stress. NET formation and survival differed in the three models. In contrast to LPS and Volvulus, CLP-induced sepsis showed a decreased and increased 48 h survival in PAD4-KO and DNase1/1L3-DKO mice, when compared to WT mice, respectively. PAD4-KO mice showed decreased formation of NETs and ROS, while DNase1/1L3-DKO mice with impaired NET degradation accumulated ROS and chronicled the septic state. The findings indicate a dual role for NET formation and degradation in sepsis and ischemia-reperfusion (I/R) injury: NETs seem to exhibit a protective capacity in certain sepsis paradigms (CLP model), whereas, collectively, they seem to contribute adversely to scenarios where sepsis is combined with ischemia-reperfusion (volvulus).

Surgical Experience Affects the Outcome of Central Venous Access Catheter Implantation in Children: A Retrospective Cohort Study.

INTRODUCTION: Surgical complications occur in up to third of children, limiting the benefits of tunneled central venous catheters (tCVCs) in children. We aimed to identify risk factors for complications related to catheter implantation. METHODS: All children and adolescents undergoing tCVC implantation at a single center over a period of 9 years were analyzed. Infection, thrombosis, dislocation, and catheter dysfunction were defined as complications. Both patient-related (ie, age, sex, vessel characteristics, revision surgery) and surgical factors (ie, sex of surgeon, surgical experience) were analyzed for their association with complications. RESULTS: A total of 1024 catheters were inserted, 887 ports and 137 broviac catheters. In terms of patient-related factors, Broviac catheters, and nononcological patients had a higher complication rate. The use of the internal jugular vein and revision surgery was associated with significantly increased complications in patients with port catheters. Experience of the surgeon correlated with various outcome parameters. Implantation performed by an attending were associated with lower complication rates in comparison to those performed by residents. Within the resident group, insertions performed by experienced residents had more complications compared with those performed by residents during their first years. CONCLUSION: The study suggests that the outcome of tCVCs insertion is affected by the type of catheter used, the utilized vessel and above all by surgical experience. Residents had significantly increased complication rates in comparison to board-certified surgeons and amongst resident's outcome got worse with increasing experience of the residents. The presence of an experienced attending did not compensate for this effect. To improve the outcome of tCVCs, strategies like direct feedback after every procedure to achieve proficiency should be implanted in residency programs.

Clinical outcome, quality of life, and mental health in long-gap esophageal atresia: comparison of gastric sleeve pull-up and delayed primary anastomosis.

INTRODUCTION: Pediatric surgeons have yet to reach a consensus whether a gastric sleeve pull-up or delayed primary anastomosis for the treatment of esophageal atresia (EA), especially of the long-gap type (LGEA) should be performed. Thus, the aim of this study was to evaluate clinical outcome, quality of life (QoL), and mental health of patients with EA and their parents. METHODS: Clinical outcomes of all children treated with EA from 2007 to 2021 were collected and parents of affected children were asked to participate in questionnaires regarding their Quality of Life (QoL) and their child's Health-Related Quality of Life (HRQoL), as well as mental health. RESULTS: A total of 98 EA patients were included in the study. For analysis, the cohort was divided into two groups: (1) primary versus (2) secondary anastomosis, while the secondary anastomosis group was subdivided into (a) delayed primary anastomosis and (b) gastric sleeve pull-up and compared with each other. When comparing the secondary anastomosis group, significant differences were found between the delayed primary anastomosis and gastric sleeve pull-up group; the duration of anesthesia during anastomosis surgery (478.54 vs 328.82 min, p < 0.001), endoscopic dilatation rate (100% vs 69%, p = 0.03), cumulative time spent in intensive care (42.31 vs 94.75 days, p = 0.03) and the mortality rate (0% vs 31%, p = 0.03). HRQoL and mental health did not differ between any of the groups. CONCLUSION: Delayed primary anastomosis or gastric sleeve pull-up appear to be similar in patients with long-gap esophageal atresia in many key aspects like leakage rate, strictures, re-fistula, tracheomalacia, recurrent infections, thrive or reflux. Moreover, HrQoL was comparable in patients with (a) gastric sleeve pull-up and (b) delayed primary anastomosis. Future studies should focus on the long-term results of either preservation or replacement of the esophagus in children.

[Impact and Temporal Evolution of the Corona Pandemic on Pediatric Emergency Care]. / Auswirkungen der Corona Pandemie auf die Notfallversorgung im Kindesalter und die zeitliche Entwicklung im Verlauf der Pandemie.

HINTERGRUND: Die COVID-19 Pandemie hat zu massiven gesellschaftlichen und wirtschaftlichen Einschränkungen geführt. Im Kindesalter wurden elektive Vorsorgeuntersuchung oftmals nicht wahrgenommen und es zeigte sich eine Reduktion der Zahl der Notfallvorstellungen. MATERIAL UND METHODEN: In einer retrospektiven Studie erfolgte eine quantitative Auswertung aller Notfallpatienten der 5 Kindernotaufnahmen Hamburgs und der Kinder- und Jugendarztpraxen der Jahre 2019 und 2020. Zusätzlich erfolgte die detaillierte Analyse der Notfallbehandlungen des Altonaer Kinderkrankenhauses während der ersten Phase der Pandemie im Vergleich zum Vorjahr. Zusammenhänge zu den Eckpunkten der Pandemieentwicklung wurden analysiert. Die Berechnung signifikanter Unterschiede in Bezug auf die demographischen Daten und Krankheitsbilder erfolgte mittels Chi- Quadrat und t-Test. ERGEBNISSE: In allen 5 pädiatrischen Notaufnahmen Hamburgs zeigte sich eine nahezu gleichförmige Abnahme der Patientenvorstellungen während der Pandemie, ähnlich in den Kinder- und Jugendarztpraxen. Die Zahl der Behandlungen verhielt sich dabei nicht streng gegenläufig zu den Neuinfektionen, sondern korreliert eher mit den Mobilitätsdaten und entsprach somit den gesamtgesellschaftlichen Veränderungen. Während der Pandemie stieg der Anteil häuslicher Unfälle an der Gesamtzahl der Vorstellungen signifikant an. Die Analyse der Diagnosen zeigte unter anderem eine relative Abnahme von (viralen) Infektionskrankheiten. Nicht behandlungspflichtige Erkrankungen führten in der Pandemie seltener zur Vorstellung. Diese Phänomene entlasteten einerseits die Notaufnahmen, bergen aber auch die Gefahr, dass Erkrankungen durch Eltern falsch eingeschätzt werden und eine notwendige ärztliche Vorstellung somit zu spät erfolgt.

Should the processus vaginalis sac be opened or closed in pediatric herniotomy? A two-center cohort study.

BACKGROUND: Inguinal hernia repair is one of the most common operations in children. To improve outcome, several techniques are used. However, it has not been established if the open or the closed hernia sac preparation technique is superior in (premature) neonates and older children. METHODS: Retrospective study including all cases of inguinal hernia repair in children at two large centers. Demographic data and outcome parameters including procedure time and intra as well as postoperative complications were evaluated. To compare open vs. closed hernia sack preparation, cases with secondary open preparation were excluded and propensity score matching was performed. Regression analysis was used to determine factors affecting operative time and recurrence rate. RESULTS: In total 2476 cases of inguinal hernia repair were identified. After exclusion of direct hernias as well as revision cases, 2257 cases were analyzed. Overall mean operative time was 25.8 min. Intraoperative complications occurred in 0.1% and. postoperative complications occurred in 3.0% of all cases, the most frequent postoperative complication being recurrence (1.7%). Closed preparation technique resulted in significantly faster procedure time and lower recurrence rates in premature neonates and older children compared to the open hernia sac preparation technique. Operative technique, prematurity, gender and training of the surgeon are highly associated with operative time, whereas operative technique is the main factor affecting recurrence rate. CONCLUSIONS: It appears that closed hernia sack preparation is superior to open regarding speed and recurrence. This was true for premature neonates, neonates and older children. All other outcome parameters including intra- and postoperative complications were similar. Thus, we recommend to use the closed preparation technique whenever possible.

Fetal-Maternal Surgery for Spina Bifida in a HIV-Infected Mother.

INTRODUCTION: In select cases, in utero surgery for myelomeningocele (MMC) leads to better outcomes than postnatal repair. However, maternal HIV infection constitutes a formal exclusion criterion due to the potential of vertical HIV transmission. Encouraged by a previous case of a successful fetal spina bifida repair in a Hepatitis Bs antigen-positive woman, a plan was devised allowing for fetal surgery. CASE REPORT: In utero MMC repair was performed although the mother was HIV-infected. To minimize the risk of in utero HIV transmission, the mother was treated by highly active antiretroviral therapy throughout gestation as well as intravenous zi-dovudine administration during maternal-fetal surgery. The mother tolerated all procedures very well without any sequelae. The currently 20 month-old toddler is HIV negative and has significantly benefitted from fetal surgery. DISCUSSION/CONCLUSION: This case shows that maternal HIV is not a priori a diagnosis that excludes fetal surgery. Rather, it might be a surrogate for moving towards personalized medicine and away from applying too rigorous exclusion criteria in the selection of candidates for maternal-fetal surgery.

On the Reliability of Suction Measurements for Skin Characterization.

in vivo skin characterization methods were shown to be useful in the detection of microstructural alterations of the dermis due to skin diseases. Specifically, the diagnostic potential of skin suction has been widely explored, yet measurement uncertainties prevented so far its application in clinical assessment. In this work, we analyze specific factors influencing the reliability of suction measurements. We recently proposed a novel suction device, called Nimble, addressing the limitations of existing instruments, and applied it in clinical trials quantifying mechanical differences between healthy skin and scars. Measurements were performed with the commercial device Cutometer and with the new device. A set of new suction measurements was carried out on scar tissue and healthy skin, and FE-based inverse analysis was applied to determine corresponding parameters of a hyperelastic-viscoelastic material model. FE simulations were used to rationalize differences between suction protocols and to analyze specific factors influencing the measurement procedure. Tissue stiffness obtained from Cutometer measurements was significantly higher compared to the one from Nimble measurements, which was shown to be associated with the higher deformation levels in the Cutometer and the nonlinear mechanical response of skin. The effect of the contact force exerted on skin during suction measurements was quantified, along with an analysis of the effectiveness of a corresponding correction procedure. Parametric studies demonstrated the inherently higher sensitivity of displacement- over load-controlled suction measurements, thus rationalizing the superior ability of the Nimble to distinguish between tissues.

Role of CD40 and ADAMTS13 in von Willebrand factor-mediated endothelial cell-platelet-monocyte interaction.

Monocyte extravasation into the vessel wall is a key step in atherogenesis. It is still elusive how monocytes transmigrate through the endothelial cell (EC) monolayer at atherosclerosis predilection sites. Platelets tethered to ultra-large von Willebrand factor (ULVWF) multimers deposited on the luminal EC surface following CD40 ligand (CD154) stimulation may facilitate monocyte diapedesis. Human ECs grown in a parallel plate flow chamber for live-cell imaging or Transwell permeable supports for transmigration assay were exposed to fluid or orbital shear stress and CD154. Human isolated platelets and/or monocytes were superfused over or added on top of the EC monolayer. Plasma levels and activity of the ULVWF multimer-cleaving protease ADAMTS13 were compared between coronary artery disease (CAD) patients and controls and were verified by the bioassay. Two-photon intravital microscopy was performed to monitor CD154-dependent leukocyte recruitment in the cremaster microcirculation of ADAMTS13-deficient versus wild-type mice. CD154-induced ULVWF multimer-platelet string formation on the EC surface trapped monocytes and facilitated transmigration through the EC monolayer despite high shear stress. Two-photon intravital microscopy revealed CD154-induced ULVWF multimer-platelet string formation preferentially in venules, due to strong EC expression of CD40, causing prominent downstream leukocyte extravasation. Plasma ADAMTS13 abundance and activity were significantly reduced in CAD patients and strongly facilitated both ULVWF multimer-platelet string formation and monocyte trapping in vitro. Moderate ADAMTS13 deficiency in CAD patients augments CD154-mediated deposition of platelet-decorated ULVWF multimers on the luminal EC surface, reinforcing the trapping of circulating monocytes at atherosclerosis predilection sites and promoting their diapedesis.

Patient- and Physician-Reported Outcome of Combined Fractional CO2 and Pulse Dye Laser Treatment for Hypertrophic Scars in Children.

BACKGROUND: Hypertrophic scars are commonly seen in children and associated with pruritus, pain, functional impairment, and aesthetic disfigurement. Ablative fractional CO2 and pulse dye laser are emerging techniques to improve scar quality. Only limited data are available on children, nonburn scars, and patient-reported outcome. We aimed to investigate safety and outcome of repeated laser therapy for hypertrophic scars originating from burns and other conditions by means of patient- and physician-reported outcome measures. METHODS: This was a retrospective before-after analysis of laser treatments in children with hypertrophic scars. Outcome was measured using Patient and Observer Scar Assessment Scale, Vancouver Scar Scale and Itch Man Scale. With respect to safety, laser- and anesthesia-related complications were analyzed. RESULTS: Seventeen patients, aged 11.37 ± 4.82 years with 27 scars, underwent 102 distinct laser treatments, mainly combined CO2 and pulse dye laser (94%), with few CO2 only (6%). Vancouver Scar Scale total score before the first and after the first session decreased significantly from 7.65 ± 2.12 to 4.88 ± 1.73; Patient and Observer Scar Assessment Scale observer overall opinion also dropped from 5.88 ± 1.57 to 4.25 ± 1.70. Pruritus improved significantly. Patient age and timing of laser intervention did not have an impact on treatment response. Complications related to laser treatment were seen in 2% (wound infection, n = 2) and to anesthesia in 4% (insignificant n = 2, minor n = 1). CONCLUSIONS: Combined laser therapy significantly improves quality, pain, and pruritus of hypertrophic scars in children. When provided by experienced laser and anesthesia teams, it is safe with a low rate of complications.

In utero Hepatitis B Immunization during Fetal Surgery for Spina Bifida.

BACKGROUND: Fetal surgery for spina bifida aperta may lead to significantly better outcomes than postnatal repair, particularly regarding shunt-dependent hydrocephalus, independent ambulation, and voiding functions. The "Management of Myelomeningocele Study" (MOMS) represents the current benchmark, also in terms of eligibility criteria. CASE REPORT: A positive maternal hepatitis B virus (HBV) status is a MOMS exclusion criterion. Here, we report on the first successful active and passive in utero HBV vaccination of a spina bifida fetus carried by a HBV-positive mother undergoing maternal-fetal surgery. The now 2-year-old infant is healthy, HBV negative, and drew maximal benefit from prenatal surgery. DISCUSSION AND CONCLUSION: Taken together, this patient benefitted maximally from fetal surgery for spina bifida, despite meeting an exclusion criterion. Thus, generally speaking, eligibility criteria for fetal surgery can be challenged under certain circumstances for the benefit of the patient.

Neutrophil Extracellular Traps: A Crucial Factor in Post-Surgical Abdominal Adhesion Formation.

Post-surgical abdominal adhesions, although poorly understood, are highly prevalent. The molecular processes underlying their formation remain elusive. This review aims to assess the relationship between neutrophil extracellular traps (NETs) and the generation of postoperative peritoneal adhesions and to discuss methods for mitigating peritoneal adhesions. A keyword or medical subject heading (MeSH) search for all original articles and reviews was performed in PubMed and Google Scholar. It included studies assessing peritoneal adhesion reformation after abdominal surgery from 2003 to 2023. After assessing for eligibility, the selected articles were evaluated using the Critical Appraisal Skills Programme checklist for qualitative research. The search yielded 127 full-text articles for assessment of eligibility, of which 7 studies met our criteria and were subjected to a detailed quality review using the Critical Appraisal Skills Programme (CASP) checklist. The selected studies offer a comprehensive analysis of adhesion pathogenesis with a special focus on the role of neutrophil extracellular traps (NETs) in the development of peritoneal adhesions. Current interventional strategies are examined, including the use of mechanical barriers, advances in regenerative medicine, and targeted molecular therapies. In particular, this review emphasizes the potential of NET-targeted interventions as promising strategies to mitigate postoperative adhesion development. Evidence suggests that in addition to their role in innate defense against infections and autoimmune diseases, NETs also play a crucial role in the formation of peritoneal adhesions after surgery. Therefore, therapeutic strategies that target NETs are emerging as significant considerations for researchers. Continued research is vital to fully elucidate the relationship between NETs and post-surgical adhesion formation to develop effective treatments.

As time goes by - Overlooking 40 years of inpatient burn treatment at a national pediatric burn center in Switzerland.

BACKGROUND: Despite extensive prevention programs, burns remain a frequent cause of injury in Switzerland with a known age peak in children. Pediatric burns may cause substantial morbidity, a psyochological burden and therapy related high economic costs. To improve preventive measures, precise knowledge of etiology and treatment of pediatric burns in Switzerland as well as their temporal evolution is indispensable. METHODS: The present retrospective analysis included pediatric burn patients admitted for acute treatment to the Pediatric Burn Center of the University Children`s Hospital Zurich over the last four decades. Sociodemographic, injury related, and treatment related data were extracted from medical records. Linear regression analysis was applied to determine temporal changes during the past four decades and chi-square and t-tests were applied wherever applicable. RESULTS: A total of 3425 acute burn patients were included in the study between 1977 and 2020, corresponding to a mean of 89 patients/year. Mean age was 3.60 ± 4.12 years, three quarters of all patients were preschool children (0-5 years) and mean total body surface area (TBSA) burned was 8.01% ± 9.57%, however only around one fifth had severe burns (>10% TBSA). Scald burns (65.31%) and flame burns (32.99%) were most commonly seen. Linear regression analysis showed the total number of thermal injuries treated at our center to have increased significantly as of 2004 (p < 0.001). Separate analysis showed the same for small and medium (<10% TBSA) burns (p < 0.001), whereas the number of severe burns did not increase significantly. Length of stay (LOS) was highly associated with %TBSA burned. The percentage of female patients amongst all patients increased over time (p = 0.012). LOS per TBSA burned decreased significantly (p < 0.001). CONCLUSION: The present data show pediatric burns to remain a major health burden in Switzerland, especially small and medium burns in preschool children. Prevention programs should focus on this age population as well as on scald and flame burns as most common etiologies. The observed decrease in length of stay suggests a major improvement in overall quality of care in pediatric burns and supports centralization of care.

Evaluation of 4DryField® as an Adhesion Prophylaxis in Pediatric Patients: a Propensity-Score Matched Study.

INTRODUCTION: Abdominal adhesions following surgery can lead to complications like intestinal obstruction and pelvic pain. While no molecular therapies currently target the underlying adhesion formation process, various barrier agents exist. 4DryField® has shown promise in reducing bleeding and adhesions in adults. This study aimed to assess its effectiveness in children. METHODS: The study examined all pediatric patients who underwent laparotomy between January 2018 and February 2022. It compared outcomes between those treated with 4DryField® and a control group. Key endpoints included surgical revision, adhesion recurrence, infections, insufficiencies, fever, CRP levels, and time to gastrointestinal passage. RESULTS: In total, 233 children had surgery for bowel adhesions. After propensity score matching, 82 patients were included in the analysis: 39 in the control and 43 in the 4DryField® group. 4DryField® did not affect re-adhesion rate. Children in the treatment group had significantly more complications (47% vs. 15%, p=0.002), more often fever and higher CRP levels. CONCLUSIONS: 4DryField® did not show potential in reducing adhesion formation, but it was associated with significantly more complications in pediatric patients. Thus, future prospective studies to evaluate the safety and effectiveness of 4DryField® in children.

Barriers and prospects for skin grafting in burn treatment across African countries.

INTRODUCTION: The current standard management of full-thickness or deep dermal burns is early tangential excision and skin grafting. A conservative approach to deep burns without the option of skin grafting results in delayed wound healing, possibly leading to wound infection and is associated with hypertrophic scarring and increased morbidity and mortality. The aim of this study was to improve the understanding of the management and availability to perform skin grafting for burns on the African continent. It also sought to identify challenges and perceived improvements. METHODS: A web-based, structured, closed-formatted, multinational survey was designed to gather information on the current state and availability of skin grafting of burn wounds on the African continent. The questionnaire consisted of 27 questions, available in English and French. It was reviewed within the GAP-Burn collaboration network and sent to 271 health care professionals who had participated in a previous study and had initially been recruited by means of the snowball system. RESULTS: The questionnaire was completed 84 times (response rate: 31.0%), of which 3 were excluded. Responses originated from 22 African countries. The majority 71 (87.7%) resulted from countries with a low Human Development Index (HDI), 7 (8.6%) from medium HDI countries. Split thickness skin grafting (STSG) is performed in 51 (63.0%) centers. The majority considers STSG to reduce length of stay (72.8%) and improve scarring (54.3%), yet some indicated that STSG is associated with increased risk of donor site infection (8.6%) and severe bleeding (7.4%). Factors preventing increased grafting included lack of equipment and training. CONCLUSION: Skin grafting is not performed in a significant number of hospitals treating burns. The majority of the staff believe that more skin grafting would lead to a better outcome. Advocacy and improved infrastructure, human resources coupled with introduction to well-structured health coverage for all in African countries could help to better access and affordability in burn care.

Fetal MRI-Based Mediastinal Shift Angle (MSA) and Percentage Area of Left Ventricle (pALV) as Prognostic Parameters for Congenital Diaphragmatic Hernia.

OBJECTIVE: Fetal magnetic resonance imaging (MRI) is broadly used as a method for assessing prognosis in congenital diaphragmatic hernia (CDH). In addition to the extent of lung hypoplasia, determined by measuring the lung volume, cardiac impairment due to pulmonary hypertension and left cardiac hypoplasia is decisive for the prognosis. The percentage area of left ventricle (pALV) describes the percentage of the inner area of the left ventricle in relation to the total area, whereas the mediastinal shift angle (MSA) quantifies the extent of cardiac displacement. The prognostic value of pALV and MSA should be evaluated in terms of survival, the need for extracorporeal membrane oxygenation (ECMO) therapy, and the development of chronic lung disease (CLD). METHODS: In a total of 122 fetal MRIs, the MSA and pALV were measured retrospectively and complete outcome parameters were determined regarding survival for all 122 subjects, regarding ECMO therapy in 109 cases and about the development of CLD in 78 cases. The prognostic value regarding the endpoints was evaluated using logistic regression and ROC analysis. RESULTS: The MSA was significantly higher in children who received ECMO therapy (p = 0.0054), as well as in children who developed CLD (p = 0.0018). ROC analysis showed an AUC of 0.68 for ECMO requirement and 0.77 with respect to CLD development. The pALV showed a tendency towards higher levels in children who received ECMO therapy (p = 0.0824). The MSA and the pALV had no significant effect on survival (MSA: p = 0.4293, AUC = 0.56; pALV: p = 0.1134, AUC = 0.57). CONCLUSIONS: The MSA determined in fetal MRI is a suitable prognostic parameter for ECMO requirement and CLD development in CDH patients and can possibly be used as a supplement to the established parameters.

Projected Incidence of Hepatobiliary Cancers and Trends Based on Age, Race, and Gender in the United States.

BACKGROUND: Identifying the projected incidence of hepatobiliary cancers and recognizing patient cohorts at increased risk can help develop targeted interventions and resource allocation. The expected incidence of subtypes of hepatobiliary cancers in different age groups, races, and genders remains unknown. METHODS: Historical epidemiological data from the Surveillance, Epidemiology, and End Results (SEER) database was used to project future incidence of hepatobiliary malignancies in the United States and identify trends by age, race, and gender. Patients ≥18 years of age diagnosed with a hepatobiliary malignancy between 2001 and 2017 were included. US Census Bureau 2017 National Population projects provided the projected population from 2017 to 2029. Age-Period-Cohort forecasting model was used to estimate future births cohort-specific incidence. All analyses were completed using R Statistical Software. RESULTS: We included 110381 historical patients diagnosed with a hepatobiliary malignancy between 2001 and 2017 with the following subtypes: hepatocellular cancer (HCC) (68%), intrahepatic cholangiocarcinoma (iCCA) (11.5%), gallbladder cancer (GC) (8%), extrahepatic cholangiocarcinoma (eCCA) (7.6%), and ampullary cancer (AC) (4%). Our models predict the incidence of HCC to double (2001 to 2029) from 4.5 to 9.03 per 100,000, with the most significant increase anticipated in patients 70-79 years of age. In contrast, incidence is expected to continue to decline among the Asian population. Incidence of iCCA is projected to increase, especially in the white population, with rates in 2029 double those in 2001 (2.13 vs. 0.88 per 100,000, respectively; p < 0.001). The incidence of GC among the black population is expected to increase. The incidence of eCCA is expected to significantly increase, especially among the Hispanic population, while that of AC will remain stable. DISCUSSION: The overall incidence of hepatobiliary malignancies is expected to increase in the coming years, with certain groups at increased risk. These findings may help with resource allocation when considering screening, treatment, and research in the coming years.

Smoothing Lexis diagrams using kernel functions: A contemporary approach.

Lexis diagrams are rectangular arrays of event rates indexed by age and period. Analysis of Lexis diagrams is a cornerstone of cancer surveillance research. Typically, population-based descriptive studies analyze multiple Lexis diagrams defined by sex, tumor characteristics, race/ethnicity, geographic region, etc. Inevitably the amount of information per Lexis diminishes with increasing stratification. Several methods have been proposed to smooth observed Lexis diagrams up front to clarify salient patterns and improve summary estimates of averages, gradients, and trends. In this article, we develop a novel bivariate kernel-based smoother that incorporates two key innovations. First, for any given kernel, we calculate its singular values decomposition, and select an optimal truncation point-the number of leading singular vectors to retain-based on the bias-corrected Akaike information criterion. Second, we model-average over a panel of candidate kernels with diverse shapes and bandwidths. The truncated model averaging approach is fast, automatic, has excellent performance, and provides a variance-covariance matrix that takes model selection into account. We present an in-depth case study (invasive estrogen receptor-negative breast cancer incidence among non-Hispanic white women in the United States) and simulate operating characteristics for 20 representative cancers. The truncated model averaging approach consistently outperforms any fixed kernel. Our results support the routine use of the truncated model averaging approach in descriptive studies of cancer.

Factors Influencing Performance in Laparoscopic Suturing and Knot Tying: A Cohort Study.

BACKGROUND: Laparoscopic suturing and knot tying are regarded as some of the most difficult laparoscopic skills to learn. Training is essential to reach proficiency, but available training opportunities are limited. Various techniques to improve training have been evaluated. It appears that individual-related factors affect initial performance and response to training. Thus, the current study aimed to assess factors influencing laparoscopic-suturing and knot-tying performances. METHODS: All patients were trained one-on-one (teacher-student) for 3 hours. Patients were tested before training (bowel anastomosis model) and directly after training (congenital diaphragmatic hernia or esophageal atresia model) to evaluate transferability. Primary endpoints were time, knot quality, precision, knot strength, and overall laparoscopic knotting performance. Moreover, factors such as (1) age, (2) gender, (3) handedness, (4) previous training or operative experience, (5) playing an instrument, (6) sportive activities, and (7) computer gaming which may influence the primary endpoints were assessed. RESULTS: In total, 172 medical students or novice surgical residents were included. Training significantly improved all outcome parameters assessed in the current study. More than 50% of the patients reached proficiency after 3 hours of training. Personal factors like operative experience, playing music instruments, sportive activities, and computer gaming affected some outcome parameters. Handedness and gender affected initial performance but differences partially subsided after training. Younger participants showed a much better response to training. CONCLUSION: In conclusion, several factors influence initial performance and response to the training of laparoscopic suturing and knot tying. Surgeons who want to improve their laparoscopic performance, should concentrate on playing a musical instrument and performing sports rather than playing videos gaming. It appears that training is a key and more practice opportunities should be incorporated into medical school and surgical curricula. Moreover, handedness may affect the outcome but only if the training concepts are not tailored to the dominant hand of the surgeon. Future training and surgical curricula should adapt to this and tailor their concepts accordingly.

State of burns management in Africa: Challenges and solutions.

INTRODUCTION: Understand the availability of human resources, infrastructure and medical equipment and perceived improvement helps to address interventions to improve burn care. METHODS: Online survey covering human resources, infrastructure, and medical equipment of burn centers as well as perceived challenges and points for improvement. The survey was distributed in English and French via snowball method. Descriptive statistics and AI-based technique random forest analysis was applied to identify determinants for a reduction of the reported mortality rate. RESULTS: 271 questionnaires from 237 cities in 40 African countries were analyzed. 222 (81.9 %) from countries with a very low Human Development Index (HDI) (4th quartile). The majority (154, 56.8 %) of all responses were from tertiary health care facilities. In only 18.8 % (n = 51) therapy was free of charge for the patients. The majority (n = 131, 48.3 %) had between 1 and 3 specialist doctors (n = 131, 48.3 %), 1 to 3 general doctors (n = 138, 50.9 %) and more than 4 nurses (n = 175, 64.6 %). A separate burn ward was available in 94 (34.7 %) centers. Regular skin grafting was performed in 165 (39.1 %) centers. Random forest-based analysis revealed a significant association between HDI (feature importance: 0.38) and mortality. The most important reason for poor outcome was perceived late presentation (212 institutions, 78.2 %). The greatest perceived potential for improvement was introduction of intensive care units (229 institutions, 84.5 %), and prevention or education (227 institutions, 83.7 %). INTERPRETATION: A variety of factors, including a low HDI, delayed hospital presentation e.g. due to prior care by non-physicians and lack of equipment seem to worsen the outcome. Introduction of an intensive care unit and communal education are perceived to be important steps in improving health care in burns.

Radiomics-Assisted Computed Tomography-Based Analysis to Evaluate Lung Morphology Characteristics after Congenital Diaphragmatic Hernia.

Purpose: Children with congenital diaphragmatic hernia suffer from long-term morbidity, including lung function impairment. Our study aims to analyze lung morphology characteristics via radiomic-assisted extraction of lung features in patients after congenital diaphragmatic hernia repair. Materials and Methods: 72 patients were retrospectively analyzed after approval by the local research ethics committee. All the image data were acquired using a third-generation dual-source CT (SOMATOM Force, Siemens Healthineers, Erlangen, Germany). Dedicated software was used for image analysis, segmentation, and processing. Results: Radiomics analysis of pediatric chest CTs of patients with status after CDH was possible. Between the ipsilateral (side of the defect) and contralateral lung, three shape features and two higher-order texture features were considered statistically significant. Contralateral lungs in patients with and without ECMO treatment showed significant differences in two shape features. Between the ipsilateral lungs in patients with and without the need for ECMO 1, a higher-order texture feature was depicted as statistically significant. Conclusions: By adding quantitative information to the visual assessment of the radiologist, radiomics-assisted feature analysis could become an additional tool in the future to assess the degree of lung hypoplasia in order to further improve the therapy and outcome of CDH patients.