Semi-field evaluation of electrocuting eave tubes for the control of endophagic mosquitoes in south-east Tanzania.

BACKGROUND: Eave spaces are major entry points through which malaria vectors enter houses. Interventions that target mosquitoes at the eaves have recently been developed. However, most of these interventions are based on insecticides for which resistance has been reported. Here we evaluated the efficacy of mosquito electrocuting eave tubes (MEETs) against Anopheles gambiae sensu stricto (An. gambiae s.s.) and Anopheles funestus s.s. under semi-field conditions. METHODS: Experiments were conducted in two semi-field chambers, each containing one experimental hut. Six electrocuting eave tubes were installed in each hut to assess their impact on laboratory-reared An. gambiae s.s. and An. funestus s.s.. Each species was assessed separately over 10 nights by releasing 200 unfed females per night into each chamber. One volunteer slept in each hut from 7 p.m. to 5 a.m. Mosquitoes were collected indoors and outdoors using mouth and Prokopack aspirators. RESULTS: The placement of MEETs significantly reduced the nightly An. gambiae s.s. indoor and outdoor biting, by 21.1% and 37.4%, respectively. Indoor-biting An. funestus s.s. were reduced by 87.5% while outdoor-biting numbers of An. funestus s.s. declined by 10.4%. CONCLUSIONS: MEETs represent a promising tool for controlling mosquitoes at the point of house entry. Further validation of their potential under natural field conditions is necessary. Several advantages over insecticide-based eave tubes are indicated and discussed in this article.

Echinococcal disease can present with giant abdominal cysts at very young age: A case report.

Echinococcus granulosus larvae can cause cystic echinococcosis (CE, also known as hydatid disease) in humans. The latent phase of hydatid disease lasts for years as a result of the slow growth of the cysts, which only become symptomatic when they are large. Therefore, CE is seldomly seen in very young children. Here we present a 4-year-old boy with two giant asymptomatic abdominal cysts. Ultrasound was inconclusive in regard to the nature of the cysts and serology for echinococcosis was negative, rendering CE improbable also in view of the young age. Nevertheless, in the absence of other conclusive explanations, the patient was started on albendazole. A subsequent diagnostic percutaneous puncture with direct microscopy of cyst fluid revealed parasitological evidence of echinococcosis. This case report shows that CE can present with giant cysts also at very young age and should be considered as a possible diagnosis in all children with giant abdominal cysts.

Microglia are dispensable for experience-dependent refinement of mouse visual circuitry.

To test the hypothesized crucial role of microglia in the developmental refinement of neural circuitry, we depleted microglia from mice of both sexes with PLX5622 and examined the experience-dependent maturation of visual circuitry and function. We assessed retinal function, receptive field tuning of visual cortex neurons, acuity and experience-dependent plasticity. None of these measurements detectibly differed in the absence of microglia, challenging the role of microglia in sculpting neural circuits.

Five-year migration of uncemented femoral components in total knee arthroplasty with either highly cross-linked or conventional polyethylene inserts: a blinded randomized controlled trial using radiostereometric analysis.

Aims: The aim of this study was to compare the migration of the femoral component, five years postoperatively, between patients with a highly cross-linked polyethylene (HXLPE) insert and those with a conventional polyethylene (PE) insert in an uncemented Triathlon fixed insert cruciate-retaining total knee arthroplasty (TKA). Secondary aims included clinical outcomes and patient-reported outcome measures (PROMs). We have previously reported the migration and outcome of the tibial components in these patients. Methods: A double-blinded randomized controlled trial was conducted including 96 TKAs. The migration of the femoral component was measured with radiostereometry (RSA) at three and six months and one, two, and five years postoperatively. PROMs were collected preoperatively and at all periods of follow-up. Results: There was no clinically relevant difference in terms of migration of the femoral component or PROMs between the HXLPE and PE groups. The mean difference in migration (maximum total point motion), five years postopeatively, was 0.04 mm (95% CI -0.06 to 0.16) in favour of the PE group. Conclusion: There was no clinically relevant difference in migration of the femoral component, for up to five years between the two groups. These findings will help to establish a benchmark for future studies on migration of femoral components in TKA.

Bacteriophage ISP eliminates Staphylococcus aureus in planktonic phase, but not in the various stages of the biofilm cycle.

Metal-implant associated bacterial infections are a major clinical problem due to antibiotic treatment failure. As an alternative, we determined the effects of bacteriophage ISP on clinical isolates of Staphylococcus aureus in various stages of its life cycle in relation to biofilm formation and maturation. ISP effectively eliminated all planktonic phase bacteria, whereas its efficacy was reduced against bacteria attached to the metal implant and bacteria embedded within biofilms. The biofilm architecture hampered the bactericidal effects of ISP, as mechanical disruption of biofilms improved the efficacy of ISP against the bacteria. Phages penetrated the biofilm and interacted with the bacteria throughout the biofilm. However, most of the biofilm-embedded bacteria were phage-tolerant. In agreement, bacteria dispersed from mature biofilms of all clinical isolates, except for LUH15394, tolerated the lytic activity of ISP. Lastly, persisters within mature biofilms tolerated ISP and proliferated in its presence. Based on these findings, we conclude that ISP eliminates planktonic phase Staphylococcus aureus while its efficacy is limited against bacteria attached to the metal implant, embedded within (persister-enriched) biofilms, and dispersed from biofilms.

Association of Vitamin A and D Deficiencies with Infectious Outcomes in Children Undergoing Intensive Induction Therapy for Acute Lymphoblastic Leukemia.

OBJECTIVE: To evaluate the association between deficiency of vitamin A or D at diagnosis of pediatric acute lymphoblastic leukemia (ALL) and subsequent infectious complications during induction therapy. STUDY DESIGN: We conducted an institutional review board-approved, retrospective cohort study of children with newly diagnosed ALL from 2007 to 2017 at St. Jude Children's Research Hospital. We measured vitamin D, vitamin D binding protein, retinol binding protein as a surrogate for vitamin A, and immunoglobulin isotypes in serum obtained at ALL diagnosis, and we assessed the association between vitamin deficiencies or levels and infection-related complications during the 6-week induction phase using Cox regression models. RESULTS: Among 378 evaluable participants, vitamin A and D deficiencies were common (43% and 17%, respectively). Vitamin D deficiency was associated with higher risks of febrile neutropenia (adjusted hazard ratio [aHR], 1.7; P = .0072), clinically documented infection (aHR, 1.73; P = .025), and likely bacterial infection (aHR, 1.86; P = .008). Conversely, vitamin A deficiency was associated solely with a lower risk of sepsis (aHR, 0.19; P = .027). CONCLUSIONS: In this retrospective study, vitamin D deficiency was associated with an increased risk of common infection-related complications during induction therapy for ALL. Additional studies are warranted to evaluate whether vitamin D supplementation could mitigate this effect.

HEX17(Neumifil): An intranasal respiratory biotherapeutic with broad-acting antiviral activity.

Broad-acting antiviral strategies to prevent respiratory tract infections are urgently required. Emerging or re-emerging viral diseases caused by new or genetic variants of viruses such as influenza viruses (IFVs), respiratory syncytial viruses (RSVs), human rhinoviruses (HRVs), parainfluenza viruses (PIVs) or coronaviruses (CoVs), pose a severe threat to human health, particularly in the very young or old, or in those with pre-existing respiratory conditions such as asthma or chronic obstructive pulmonary disease (COPD). Although vaccines remain a key component in controlling and preventing viral infections, they are unable to provide broad-spectrum protection against recurring seasonal infections or newly emerging threats. HEX17 (aka Neumifil), is a first-in-class protein-based antiviral prophylactic for respiratory viral infections. HEX17 consists of a hexavalent carbohydrate-binding module (CBM) with high affinity to sialic acids, which are typically present on terminating branches of glycans on viral cellular receptors. This allows HEX17 to block virus engagement of host receptors and inhibit infection of a wide range of viral pathogens and their variants with reduced risk of antiviral resistance. As described herein, HEX17 has demonstrated broad-spectrum efficacy against respiratory viral pathogens including IFV, RSV, CoV and HRV in multiple in vivo and in vitro studies. In addition, HEX17 can be easily administered via an intranasal spray and is currently undergoing clinical trials.

Dietary Intake of Yeast-Derived ß-Glucan and Rice-Derived Arabinoxylan Induces Dose-Dependent Innate Immune Priming in Mice.

Beta-glucans and arabinoxylans are known for their immunostimulatory properties. However, in vivo these have been documented almost exclusively following parenteral administration, underemphasizing oral intake. C57BL/6 mice are fed either a control diet or a diet supplemented with yeast-derived whole ß-glucan particle (yWGP) or with rice-derived arabinoxylan (rice bran-1) at a concentration of 1%, 2.5%, or 5% weight/weight (w/w) for 2 weeks. Thereafter, cells from blood, bone marrow, and spleen are collected for ex vivo stimulation with various microbial stimuli. Dietary intake of yWGP for 2 weeks at concentrations of 1% and 2.5% w/w increases ex vivo cytokine production in mouse blood and bone marrow, whereas 5% w/w yWGP shows no effect. In the spleen, cytokine production remains unaffected by yWGP. At a concentration of 1% w/w, rice bran-1 increases ex vivo cytokine production by whole blood, but 2.5% and 5% w/w cause inhibitory effects in bone marrow and spleen. This study demonstrates that dietary yWGP and rice bran-1 induce immune priming in mouse blood and bone marrow, with the strongest effects observed at 1% w/w. Future human trials should substantiate the efficacy of dietary ß-glucans and arabinoxylans to bolster host immunity, focusing on dose optimization.

Effects of interrupting the enterohepatic circulation in amatoxin intoxications.

BACKGROUND: Interruption of the enterohepatic circulation is regarded as an effective way to treat patients with amatoxin poisoning. Nonetheless, its effectiveness has not yet been systematically evaluated. Therefore, we performed a systematic review to investigate the role of enterohepatic circulation on patient outcome and clinical laboratory values. We specifically sought to evaluate the effect of activated charcoal, which absorbs drugs and toxins in the gastrointestinal tract. METHODS: A previously established database with data extracted from case reports and series from literature, supplemented with recent publications, was used. Patient characteristics, outcome, and laboratory values were evaluated. RESULTS: We included 133 publications describing a total of 1,119 unique cases. Survival was 75 per cent in the control group (n = 452), whereas in the group treated with single or multiple doses of activated charcoal (n = 667) survival was 83 per cent (P < 0.001, odds ratio 1.89 [95 per cent confidence interval 1.40-2.56]). Furthermore, no difference in peak values of alanine aminotransferase and aspartate aminotransferase activities were observed, whereas peak values of total serum bilirubin concentration and international normalized ratio were statistically significantly reduced in patients treated with activated charcoal. DISCUSSION: The ability of activated charcoal to enhance the elimination of amatoxin through interruption of the enterohepatic circulation offers a potentially safe and inexpensive therapy for patients in the post-absorptive phase. LIMITATIONS: Limitations include the potential for publication bias, the lack of universal confirmation of amatoxin concentrations, and the inability to directly measure enterohepatic circulation of amatoxin. CONCLUSION: Treatment with activated charcoal in patients with amatoxin poisoning was associated with a greater chance of a successful outcome. Additionally, activated charcoal was associated with a reduction in markers of liver function, but not markers of liver injury.

Using case vignettes to study the presence of outcome, hindsight, and implicit bias in acute unplanned medical care: a cross-sectional study.

BACKGROUND AND IMPORTANCE: Various biases can impact decision-making and judgment of case quality in the Emergency Department (ED). Outcome and hindsight bias can lead to wrong retrospective judgment of care quality, and implicit bias can result in unjust treatment differences in the ED based on irrelevant patient characteristics. OBJECTIVES: First, to evaluate the extent to which knowledge of an outcome influences physicians' quality of care assessment. Secondly, to examine whether patients with functional disorders receive different treatment compared to patients with a somatic past medical history. DESIGN: A web-based cross-sectional study in which physicians received case vignettes with a case description and care provided. Physicians were informed about vignette outcomes in a randomized way (no, good, or bad outcome). Physicians rated quality of care for four case vignettes with different outcomes. Subsequently, they received two more case vignettes. Physicians were informed about the past medical history of the patient in a randomized way (somatic or functional). Physicians made treatment and diagnostic decisions for both cases. SETTING AND PARTICIPANTS: One hundred ninety-one Dutch emergency physicians (EPs) and general practitioners (GPs) participated. OUTCOME MEASURES AND ANALYSIS: Quality of care was rated on a Likert scale (0-5) and dichotomized as adequate (yes/no). Physicians estimated the likelihood of patients experiencing a bad outcome for hindsight bias. For the second objective, physicians decided on prescribing analgesics and additional diagnostic tests. MAIN RESULTS: Large differences existed in rated quality of care for three out of four vignettes based on different case outcomes. For example, physicians rated the quality of care as adequate in 44% (95% CI 33-57%) for an abdominal pain case with a bad outcome, compared to 88% (95% CI 78-94%) for a good outcome, and 84% (95% CI 73-91%) for no outcome ( P  < 0.01). The estimated likelihood of a bad outcome was higher if physicians received a vignette with a bad patient outcome. Fewer diagnostic tests were performed and fewer opioids were prescribed for patients with a functional disorder. CONCLUSION: Outcome, hindsight, and implicit bias significantly influence decision-making and care quality assessment by Dutch EPs and GPs.

Breaking the chains of lipoprotein lipase deficiency: A pediatric perspective on the efficacy and safety of Volanesorsen.

RATIONALE: Lipoprotein lipase (LPL) deficiency, a rare inherited metabolic disorder, is characterized by high triglyceride (TG) levels and life-threatening acute pancreatitis. Current treatment for pediatric patients involves a lifelong severely fat-restricted diet, posing adherence challenges. Volanesorsen, an EMA-approved RNA therapy for adults, effectively reduces TG levels by decreasing the production of apolipoprotein C-III. This 96-week observational open-label study explores Volanesorsen's safety and efficacy in a 13-year-old female with LPL deficiency. METHODS: The patient, with a history of severe TG elevations, 53 hospital admissions, and life-threatening recurrent pancreatitis despite dietary restrictions, received weekly subcutaneous Volanesorsen injections. We designed a protocol for this investigator-initiated study, primarily focusing on changes in fasting TG levels and hospital admissions. RESULTS: While the injections caused occasional pain and swelling, no other adverse events were observed. TG levels decreased during treatment, with more measurements below the pancreatitis risk threshold compared to pre-treatment. No hospital admissions occurred in the initial 14 months of treatment, contrasting with 21 admissions in the 96 weeks before. In the past 10 months, two pancreatitis episodes may have been linked to dietary noncompliance. Dietary restrictions were relaxed, increasing fat intake by 65% compared to baseline. While not fully reflected in the PedsQL, both parents and the patient narratively reported an improved quality of life. CONCLUSION: This study demonstrates, for the first time, that Volanesorsen is tolerated in a pediatric patient with severe LPL deficiency and effectively lowers TG levels, preventing life-threatening complications. This warrants consideration for expanded access in this population.

Unexpected Amanita phalloides-Induced Hematotoxicity-Results from a Retrospective Study.

INTRODUCTION: Amanita phalloides poisoning is a serious health problem with a mortality rate of 10-40%. Poisonings are characterized by severe liver and kidney toxicity. The effect of Amanita phalloides poisonings on hematological parameters has not been systematically evaluated thus far. METHODS: Patients with suspected Amanita phalloides poisonings were retrospectively selected from the hospital database of the University Medical Center Groningen (UMCG). Medical data-including demographics; liver, kidney, and blood parameters; treatment; and outcomes-were collected. The severity of the poisoning was scored using the poison severity score. RESULTS: Twenty-eight patients were identified who were admitted to the UMCG with suspected Amanita phalloides poisoning between 1994 and 2022. A time-dependent decrease was observed for hemoglobin and hematocrit concentrations, leukocytes, and platelets. Six out of twenty-eight patients developed acute liver failure (ALF). Patients with ALF showed a higher increase in liver enzymes, international normalized ratios, and PSS compared to patients without ALF. Conversely, hemoglobin and platelet numbers were decreased even further in these patients. Three out of six patients with ALF died and one patient received a liver transplant. CONCLUSION: Our study shows that Amanita phalloides poisonings may be associated with hematotoxicity in patients. The quantification of hematological parameters is of relevance in intoxicated patients, especially in those with ALF.

The influence of soil organic matter content and substance lipophilicity on the toxicity of pesticides to the earthworm Eisenia andrei.

To account for potential differences in bioavailability (and toxicity) due to different soil organic matter (OM) contents in natural and artificial soil (AS), in the current European environmental risk assessment (ERA) a correction factor (CF) of 2 is applied to toxicity endpoints for so called lipophilic pesticides (i.e. log Kow > 2) generated from laboratory tests with soil invertebrates. However, the appropriateness of a single CF is questioned. To improve the accuracy of ERA, this study investigated the influence of soil OM content on the toxicity to the earthworm Eisenia andrei of five active substances used in pesticides covering a wide range of lipophilicity. Laboratory toxicity tests were performed in AS containing 10 %, 5 % and 2.5 % peat, and a natural LUFA 2.2 soil (4.5 % OM), assessing effects on survival, biomass change and reproduction. Pesticide toxicity differed significantly between soils. For all pesticides, toxicity values (LC50, EC50) strongly correlated with soil OM content in AS (r2 > 0.82), with toxicity decreasing with increasing OM content. Obtained regression equations were used to calculate the toxicity at OM contents of 10.0 % and 5.0 %. Model-estimated toxicity between these soils differed by factors of 1.9-3.6, and 2.1-3.2 for LC50 and EC50 values, respectively. No clear relationships between pesticide lipophilicity and toxicity-OM relationships were observed: the toxicity of non-lipophilic and lipophilic pesticides was influenced by OM content in a similar manner. The results suggest that the CF of 2 may not be appropriate as it is based on incorrect assumptions regarding the relationships between lipophilicity, OM content and toxicity. Further research should be conducted to understand the mechanistic link between toxicity and soil OM content to better define more chemically and ecologically appropriate CFs for ERA.

Noninvasive scores are poorly predictive of histological fibrosis in paediatric fatty liver disease.

OBJECTIVES: Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in children. Roughly a quarter of paediatric patients with NAFLD develop nonalcoholic steatohepatitis and fibrosis. Here, we evaluated the diagnostic accuracy of previously published noninvasive fibrosis scores to predict liver fibrosis in a large European cohort of paediatric patients with NAFLD. METHODS: The 457 patients with biopsy-proven NAFLD from 10 specialized centers were included. We assessed diagnostic accuracy for the prediction of any (F ≥ 1), moderate (F ≥ 2) or advanced (F ≥ 3) fibrosis for the AST/platelet ratio (APRI), Fibrosis 4 score (FIB-4), paediatric NAFLD fibrosis score (PNFS) and paediatric NAFLD fibrosis index (PNFI). RESULTS: Patients covered the full spectrum of fibrosis (F0: n = 103; F1: n = 230; F2: n = 78; F3: n = 44; F4: n = 2). None of the scores were able to accurately distinguish the presence of any fibrosis from no fibrosis. For the detection of moderate fibrosis, area under the receiver operating characteristic curve (AUROC) were: APRI: 0.697, FIB-4: 0.663, PNFI: 0.515, PNFS: 0.665, while for detection of advanced fibrosis AUROCs were: APRI: 0.759, FIB-4: 0.611, PNFI: 0.521, PNFS: 0.712. Fibrosis scores showed no diagnostic benefit over using ALT ≤ 50/ > 50 IU/L as a cut-off. CONCLUSIONS: Established fibrosis scores lack diagnostic accuracy to replace liver biopsy for staging of fibrosis, giving similar results as compared to using ALT alone. New diagnostic tools are needed for Noninvasive risk-stratification in paediatric NAFLD.

Rice-derived arabinoxylan fibers are particle size-dependent inducers of trained immunity in a human macrophage-intestinal epithelial cell co-culture model.

Arabinoxylans have been identified for a wide range of purported health-promoting applications, primarily attributed to its immunomodulatory effects. Previously, we have reported the ability of arabinoxylans to induce non-specific memory in innate immune cells, commonly referred to as "trained innate immunity". In the present study, we investigated the effect of particle size on innate immune training and resilience in primary human macrophages as well as in a more physiologically relevant macrophage-intestinal epithelial cell co-culture model. We demonstrated that smaller (>45 & < 90 µm) compared to larger (>90 µm) particle size fractions of rice bran-derived arabinoxylan preparations have a higher enhancing effect on training and resilience in both models. Smaller particle size fractions elevated TNF-α production in primary macrophages and enhanced Dectin-1 receptor activation in reporter cell lines compared to larger particles. Responses were arabinoxylan source specific as only the rice-derived arabinoxylans showed these immune-supportive effects. This particle size-dependent induction of trained immunity was confirmed in the established co-culture model. These findings demonstrate the influence of particle size on the immunomodulatory potential of arabinoxylans, provide further insight into the structure-activity relationship, and offer new opportunities to optimize the immune-enhancing effects of these dietary fibers.

Unraveling Hematotoxicity of α-Amanitin in Cultured Hematopoietic Cells.

Amanita phalloides poisonings account for the majority of fatal mushroom poisonings. Recently, we identified hematotoxicity as a relevant aspect of Amanita poisonings. In this study, we investigated the effects of the main toxins of Amanita phalloides, α- and ß-amanitin, on hematopoietic cell viability in vitro. Hematopoietic cell lines were exposed to α-amanitin or ß-amanitin for up to 72 h with or without the pan-caspase inhibitor Z-VAD(OH)-FMK, antidotes N-acetylcysteine, silibinin, and benzylpenicillin, and organic anion-transporting polypeptide 1B3 (OATP1B3) inhibitors rifampicin and cyclosporin. Cell viability was established by trypan blue exclusion, annexin V staining, and a MTS assay. Caspase-3/7 activity was determined with Caspase-Glo assay, and cleaved caspase-3 was quantified by Western analysis. Cell number and colony-forming units were quantified after exposure to α-amanitin in primary CD34+ hematopoietic stem cells. In all cell lines, α-amanitin concentration-dependently decreased viability and mitochondrial activity. ß-Amanitin was less toxic, but still significantly reduced viability. α-Amanitin increased caspase-3/7 activity by 2.8-fold and cleaved caspase-3 by 2.3-fold. Z-VAD(OH)-FMK significantly reduced α-amanitin-induced toxicity. In CD34+ stem cells, α-amanitin decreased the number of colonies and cells. The antidotes and OATP1B3 inhibitors did not reverse α-amanitin-induced toxicity. In conclusion, α-amanitin induces apoptosis in hematopoietic cells via a caspase-dependent mechanism.

Technology assistance in primary total knee replacement: hype or hope?

INTRODUCTION: Total knee replacement (TKR) reduces pain, it increases quality of life and it generally lasts a long time with revision rates of less than 5% at 10 years. Some authors have suggested that outcomes may be further improved by technology assistance. AREAS COVERED: Technology assistance in primary TKR includes technologies such as navigated TKR, patient specific instrumentation TKR and robotic TKR. EXPERT OPINION: In general, technology assistance results in higher accuracy of component positioning and alignment, but this is likely not clinically relevant as no clinically important difference in clinical outcomes, quality of life and complications such as revisions has been demonstrated in meta-analyses of randomized controlled trials. As technology assistance in primary TKR is increasingly used to capture patient and surgeon data, surgeons have an increasingly important role in protecting their patients' data and their own data. Real world evidence of implant registries has shown that TKR without technologically assistance can achieve perfectly acceptable outcomes. Although there is a genuine hope that technology-assisted TKR may further improve these outcomes, this hope is based on promises rather than solid evidence. At the same time, technology assisted TKR is heavily promoted including direct patient marketing, which are aspects of a hype.

A multisociety Delphi consensus statement on new fatty liver disease nomenclature.

The principal limitations of the terms NAFLD and NASH are the reliance on exclusionary confounder terms and the use of potentially stigmatising language. This study set out to determine if content experts and patient advocates were in favor of a change in nomenclature and/or definition. A modified Delphi process was led by three large pan-national liver associations. The consensus was defined a priori as a supermajority (67%) vote. An independent committee of experts external to the nomenclature process made the final recommendation on the acronym and its diagnostic criteria. A total of 236 panelists from 56 countries participated in 4 online surveys and 2 hybrid meetings. Response rates across the 4 survey rounds were 87%, 83%, 83%, and 78%, respectively. Seventy-four percent of respondents felt that the current nomenclature was sufficiently flawed to consider a name change. The terms "nonalcoholic" and "fatty" were felt to be stigmatising by 61% and 66% of respondents, respectively. Steatotic liver disease was chosen as an overarching term to encompass the various aetiologies of steatosis. The term steatohepatitis was felt to be an important pathophysiological concept that should be retained. The name chosen to replace NAFLD was metabolic dysfunction-associated steatotic liver disease. There was consensus to change the definition to include the presence of at least 1 of 5 cardiometabolic risk factors. Those with no metabolic parameters and no known cause were deemed to have cryptogenic steatotic liver disease. A new category, outside pure metabolic dysfunction-associated steatotic liver disease, termed metabolic and alcohol related/associated liver disease (MetALD), was selected to describe those with metabolic dysfunction-associated steatotic liver disease, who consume greater amounts of alcohol per week (140-350 g/wk and 210-420 g/wk for females and males, respectively). The new nomenclature and diagnostic criteria are widely supported and nonstigmatising, and can improve awareness and patient identification.

Machine Learning assisted systematic reviewing in orthopaedics.

Background: Machine learning assisted systematic reviewing may help to reduce the work burden in systematic reviews. The aim of this study is therefore to determine by a non-developer the performance of machine learning assisted systematic reviewing on previously published orthopaedic reviews in retrieving relevant papers. Methods: Active learning for Systematic Reviews (ASReview) was tested against the results from three previously published systematic reviews in the field of orthopaedics with 20 iterations for each review. The reviews covered easy, intermediate and advanced scenarios. The outcomes of interest were the percentage work saved at 95% recall (WSS@95), the percentage work saved at 100% recall (WSS@100) and the percentage of relevant references identified after having screened the first 10% of the records (RRF@10). Means and corresponding [95% confidence intervals] were calculated. Results: The WSS@95 was respectively 72 [71-74], 72 [72-73] and 50 [50-51] for the easy, intermediate and advanced scenarios. The WSS@100 was respectively 72 [71-73], 62 [61-63] and 37 [36-38] for the easy, intermediate and advanced scenarios. The RRF@10 was respectively 79 [78-81], 70 [69-71] and 58 [56-60] for the easy, intermediate and advanced scenarios. Conclusions: Machine learning assisted systematic reviewing was efficient in retrieving relevant papers for systematic review in orthopaedics. The majority of relevant papers were identified after screening only 10% of the papers. All relevant papers were identified after screening 30%-40% of the total papers meaning that 60%-70% of the work can potentially be saved.