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Background: Pain is multifactorial, and pain intensity has been shown to be influenced by patients' thoughts. The Negative Pain Thoughts Questionnaire Short Form (NPTQ-SF) can be used to quantify unhelpful negative cognitive biases about pain, but the relationship between negative pain thoughts and orthopaedic surgery outcomes is not known., Purpose: To evaluate the prevalence of negative pain thoughts in patients undergoing arthroscopic meniscectomy using the NPTQ-SF survey and assess the relationship these thoughts have to knee function, general health, pain, and satisfaction before and after surgery., Study Design: Case series; Level of evidence, 4., Methods: In total, 146 patients undergoing arthroscopic meniscectomy were administered the 4-item NPTQ-SF, 12-item Short Form Survey (SF-12), International Knee Documentation Committee (IKDC) questionnaire, and visual analog scale pain survey preoperatively between July 2021 and August 2022. The same surveys were completed at a minimum of 3 months and no later than 1 year postoperatively by 92 patients confirmed to have undergone meniscectomy., Results: NPTQ-SF scores were correlated with IKDC, SF-12, and satisfaction score preoperatively and at least 3 months postoperatively (mean, 108.5 ± 43.7 days). Preoperative NPTQ-SF scores were significantly negatively correlated with postoperative IKDC ( R = -0.284), SF-12 ( R = -0.266 and -0.328), and visual analog scale pain ( R = 0.294) scores, while a relationship with postoperative satisfaction did not reach statistical significance ( P = .067). Patients with a preoperative NPTQ-SF score >8 were less likely to achieve a Patient Acceptable Symptom State on the postoperative IKDC questionnaire (39% vs 63%; P = .03). Patients with a history of a psychiatric or chronic pain diagnoses have worse NPTQ-SF, SF-12, and IKDC scores pre- and postoperatively., Conclusion: The level of negative pain thoughts in patients undergoing meniscectomy is related to knee function, general health, and pain. Patients with a high level of negative pain thoughts are less likely to achieve a favorable outcome from meniscectomy, with a score ≥8 representing a clinically significant threshold for preoperative screening., Competing Interests: One or more of the authors has declared the following potential conflict of interest or source of funding: B.G. has received consulting fees from Medical Device Business Services and Zimmer Biomet Holdings; and support for education from Legacy Ortho. AOSSM checks author disclosures against the Open Payments Database (OPD). AOSSM has not conducted an independent investigation on the OPD and disclaims any liability or responsibility relating thereto.

Aims: The accomplishment of value-based healthcare (VBHC) models could save up to $1 trillion per year for healthcare systems worldwide while improving patients' wellbeing and experience. Nevertheless, its adoption and development are challenging. This review aims to provide an overview of current literature pertaining to the implementation of VBHC models used in cardiology, with a focus on cardiac electrophysiology., Methods and Results: This scoping review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-analysis for Scoping Reviews. The records included in this publication were relevant documents published in PubMed, Mendeley, and ScienceDirect. The search criteria were publications about VBHC in the field of cardiology and electrophysiology published between 2006 and 2023. The implementation of VBHC models in cardiology and electrophysiology is still in its infant stages. There is a clear need to modify the current organizational structure in order to establish cross-functional teams with the patient at the centre of care. The adoption of new reimbursement schemes is crucial to moving this process forward. The implementation of technologies for data analysis and patient management, among others, poses challenges to the change process., Conclusion: New VBHC models have the potential to improve the care process and patient experience while optimizing the costs. The implementation of this model has been insufficient mainly because it requires substantial changes in the existing infrastructures and local organization, the need to track adherence to guidelines, and the evaluation of the quality of life improvement and patient satisfaction, among others., Competing Interests: Conflict of interest: R.C-A. has received small amounts for educational meetings from Abbott and Boston Scientific. M.M.Z. reports lecture fees/honoraria and travel support by Medtronic, Boston Scientific, Bayer Vital, Pfizer, and ZOLL CMS. F.L., F.B., J.F., L.O., H.P., J.L.M., and G.B. have not declared any conflict of interest., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Congenital erythropoietic porphyria (CEP) is a rare autosomal recessive disease due to the deficient, but not absent, activity of uroporphyrinogen III synthase (UROS), the fourth enzyme in the heme biosynthesis pathway. Biallelic variants in the UROS gene result in decreased UROS enzymatic activity and the accumulation of non-physiologic Type I porphyrins in cells and fluids. Overproduced uroporphyrins in haematopoietic cells are released into the circulation and distributed to tissues, inducing primarily hematologic and dermatologic symptoms. The clinical manifestations vary in severity ranging from non-immune hydrops fetalis in utero to mild dermatologic manifestations in adults. Here, the biochemical, molecular and clinical features of CEP as well as current and new treatment options, including the rescue of UROS enzyme activity by chaperones, are presented., (© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

The porphyrias are a group of rare inborn errors of metabolism associated with various clinical presentations and long-term complications, making them relevant differential diagnoses to consider for many clinical specialities, especially hepatologists, gastroenterologists and dermatologists. To diagnose a patient with porphyria requires appropriate biochemical investigations, as clinical features alone are not specific enough. Furthermore, it is important to be aware that abnormalities of porphyrin accumulation and excretion occur in many other disorders that are collectively far more common than the porphyrias. In this review, we provide an overview of porphyria-related tests with their strengths and limitations, give recommendations on requesting and diagnostic approaches in non-expert and expert laboratories for different clinical scenarios and discuss the role of genetic testing in the porphyrias. To diagnose porphyria in a currently symptomatic patient requires analysis of biochemical markers to demonstrate typical patterns of haem precursors in urine, faeces and blood. The use of genomic sequencing in diagnostic pathways for porphyrias requires careful consideration, and the demonstration of increased porphyrin-related markers is necessary prior to genomic testing in symptomatic patients. In the acute porphyrias, genomic testing is presently a useful adjunct for genetic counselling of asymptomatic family members and the most common cutaneous porphyria, porphyria cutanea tarda, is usually a sporadic, non-hereditary disease. Getting a correct and timely porphyria diagnosis is essential for delivering appropriate care and ensuring best patient outcome., (© 2024 The Author(s). Liver International published by John Wiley & Sons Ltd.)

Competing Interests: No declaration of competing interests.

A variety of methodologies have been developed to help health systems increase the 'value' created from their available resources. The urgency of creating value is heightened by population ageing, growth in people with complex morbidities, technology advancements, and increased citizen expectations. This study develops a policy framework that seeks to reconcile the various approaches towards value-based policies in health systems. The distinctive contribution is that we focus on the value created by the health system as a whole, including health promotion, thus moving from value-based health care towards a value-based health system perspective. We define health system value to be the contribution of the health system to societal wellbeing. We adopt a framework of five dimensions of value, embracing health improvement, health care responsiveness, financial protection, efficiency and equity, which we map onto a society's aggregate wellbeing. Actors within the health system make different contributions to value, and we argue that their perspectives can be aligned with a unifying concept of health system value. We provide examples of policy levers and highlight key actors and how they can promote certain aspects of health system value. We discuss advantages of value-based approach based on the notion of wellbeing and some practical obstacles to its implementation., Competing Interests: Declaration of Competing Interest We have no conflict of interest to declare., (Copyright © 2023. Published by Elsevier B.V.)

Defects in hydroxymethylbilane synthase (HMBS) can cause acute intermittent porphyria (AIP), an acute neurological disease. Although sequencing-based diagnosis can be definitive, ∼⅓ of clinical HMBS variants are missense variants, and most clinically reported HMBS missense variants are designated as "variants of uncertain significance" (VUSs). Using saturation mutagenesis, en masse selection, and sequencing, we applied a multiplexed validated assay to both the erythroid-specific and ubiquitous isoforms of HMBS, obtaining confident functional impact scores for >84% of all possible amino acid substitutions. The resulting variant effect maps generally agreed with biochemical expectations and provide further evidence that HMBS can function as a monomer. Additionally, the maps implicated specific residues as having roles in active site dynamics, which was further supported by molecular dynamics simulations. Most importantly, these maps can help discriminate pathogenic from benign HMBS variants, proactively providing evidence even for yet-to-be-observed clinical missense variants., Competing Interests: Declaration of interests F.P.R. is an investor in Ranomics, Inc., and is an investor in and advisor for SeqWell, Inc., BioSymetrics, Inc., and Constantiam Biosciences, Inc., and has accepted conference travel support from Illumina, Inc. L.F., A.C., and R.N. are employed by and invested in Invitae. R.J.D. has received both a grant and royalties and has also served as a consultant for Alnylam Pharmaceuticals., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Syngas biomethanation is a promising technology in the process chain converting wastes to methane. However, gas-liquid mass transfer is a limiting factor of the biomethanation process. To reach high methane productivity, increasing the pressure is an interesting strategy to improve mass transfer. However, the CO content in the syngas raises concerns about a potential inhibition of the microorganisms. Therefore, the aim of the research was to assess the ability to work at high CO partial pressures. In this regard, a pressurized continuous stirred column with a working volume of 10L was implemented and a consortium adapted for syngas-biomethanation for 22 months was submitted to 100% CO and increasing pressure. No inhibition phenomenon was observed for logarithmic P CO as high as 1.8 bar (inlet pressure 5.0 bar), which was the first time that such a high CO partial pressure was tested in continuous mode. Mass transfer limitations allowed for the carboxydotrophic microorganisms to consume CO faster than it was transferred, allowing for the dissolved CO concentration to remain under inhibitory concentrations. These results question the habitual consensus that CO inhibition is a limiting factor of syngas biomethanation., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Syngas biomethanation is a promising technology for waste to energy conversion. However, it had not yet been tested at high syngas flow rates. The aim of this study was to assess the possibility for syngas biomethanation to reach high methane productivity at higher syngas inflow rate. A pressurized stirred column was implemented. The syngas inflow rate was gradually increased, and two different increase strategies were compared. The highest methane productivity achieved yet with syngas-biomethanation was obtained, with 23.2 L CH4 /L/d, with high conversion efficiencies of 89% for H 2 and 82% for CO. The mass transfer performances of the process were investigated, and the existence of a biological enhancement factor was observed. Considering an enhancement factor in bioprocesses is a pioneering concept that could change the way we design bioreactor to improve mass transfer. The high methane productivity obtained in this study paves the way for the process industrialization., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Case: We report the case of a healthy 17-year-old female softball player with a subacute full-thickness intramuscular tear of the pectoralis major (PM) muscle. A successful muscle repair was obtained using a modified Kessler technique., Conclusions: Despite initially being a rare injury pattern, the incidence of PM muscle rupture is likely to increase as interest in sports and weight training increases, and although this injury pattern is more common in men, it is becoming more common in women as well. Furthermore, this case presentation provides support for operative treatment of intramuscular ruptures of the PM muscle., Competing Interests: Disclosure: The Disclosure of Potential Conflicts of Interest forms are provided with the online version of the article (http://links.lww.com/JBJSCC/C38)., (Copyright © 2023 by The Journal of Bone and Joint Surgery, Incorporated.)

Patients with major forms of acute hepatic porphyria present acute neurological attacks with overproduction of porphobilinogen (PBG) and δ-aminolevulinic acid (ALA). Even if ALA is considered the most likely agent inducing the acute symptoms, the mechanism of its accumulation has not been experimentally demonstrated. In the most frequent form, acute intermittent porphyria (AIP), inherited gene mutations induce a deficiency in PBG deaminase; thus, accumulation of the substrate PBG is biochemically obligated but not that of ALA. A similar scenario is observed in other forms of acute hepatic porphyria (i.e., porphyria variegate, VP) in which PBG deaminase is inhibited by metabolic intermediates. Here, we have investigated the molecular basis of δ-aminolevulinate accumulation using in vitro fluxomics monitored by NMR spectroscopy and other biophysical techniques. Our results show that porphobilinogen, the natural product of δ-aminolevulinate deaminase, effectively inhibits its anabolic enzyme at abnormally low concentrations. Structurally, this high affinity can be explained by the interactions that porphobilinogen generates with the active site, most of them shared with the substrate. Enzymatically, our flux analysis of an altered heme pathway demonstrates that a minimum accumulation of porphobilinogen will immediately trigger the accumulation of δ-aminolevulinate, a long-lasting observation in patients suffering from acute porphyrias.

Arthroscopic rotator cuff repair (RCR) is a popular treatment for rotator cuff tears. Retear after RCR remains a significant concern even with modern techniques. Augmentation of RCR has been described using multiple different grafts, one option including a cannulated dermal allograft implant (DePuy Mitek). The utilization of this implant avoids significantly increased surgical time, allows for augmentation at the weakest area of repair, and does not lead to any wasted allograft material., (© 2022 The Authors.)

Worldwide responses to the COVID-19 pandemic have shown that it is possible for politicians to come together across departmental boundaries. To this end, in many countries, heads of government and their health ministers work closely with all other ministries, departments, and sectors, including social affairs, internal affairs, foreign affairs, research and education, transport, agriculture, business, and state aid. In this Viewpoint, we ask if and how the Sustainable Development Goals (SDGs) can support intersectoral collaboration to promote health, since governments have already committed to achieving them. We contend that SDGs can do so, ultimately advancing health while offering co-benefits across society., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Previous studies proposed the Triggering Receptor Expressed on Myeloid Cells 2 (TREM2), a receptor expressed in myeloid cells including microglia in brain and osteoclasts in bone, as a link between brain and bone disease. The TREM2 R47H variant is a known risk factor for Alzheimer's disease (AD), the most common form of dementia. To investigate whether altered TREM2 signaling could contribute to bone and skeletal muscle loss, independently of central nervous system defects, we used mice globally hemizygous for the TREM2 R47H variant (TREM2 R47H/+ ), which do not exhibit AD pathology, and wild-type (WT) littermate control mice. Dxa/Piximus showed bone loss in female TREM2 R47H/+ animals between 4 and 13 months of age and reduced cancellous and cortical bone (measured by micro-computed tomography [μCT]) at 13 months, which stalled out by 20 months of age. In addition, they exhibited decreased femoral biomechanical properties measured by three-point bending at 13 months of age, but not at 4 or 20 months. Male TREM2 R47H/+ animals had decreased trabecular bone geometry but increased ultimate strain and failure force at 20 months of age versus WT. Only male TREM2 R47H/+ osteoclasts differentiated more ex vivo after 7 days with receptor activator of nuclear factor κB ligand (RANKL)/macrophage colony-stimulating factor (M-CSF) compared to WT littermates. Yet, estrogen receptor alpha expression was higher in female and male TREM2 R47H/+ osteoclasts compared to WT mice. However, female TREM2 R47H/+ osteoclasts expressed less complement 3 (C3), an estrogen responsive element, and increased protein kinase B (Akt) activity, suggesting altered estrogen signaling in TREM2 R47H/+ cells. Despite lower bone volume/strength in TREM2 R47H/+ mice, skeletal muscle function measured by plantar flexion and muscle contractility was increased in 13-month-old female mutant mice. Overall, these data demonstrate that an AD-associated TREM2 variant can alter bone and skeletal muscle strength in a sex-dimorphic manner independent of central neuropathology, potentially mediated through changes in osteoclastic intracellular signaling. © 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR)., (© 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).)

Background and Purpose: Complex surgery and radiotherapy are the central pillars of loco-regional oncology treatment. This paper describes the reimbursement schemes used in radiation and complex surgical oncology, reports on literature and policy reviews., Material and Methods: A systematic review of the literature of the reimbursement models has been carried out separately for radiotherapy and complex cancer surgery based on PRISMA guidelines. Using searches of PubMed and grey literature, we identified articles from scientific journals and reports published since 2000 on provider payment or reimbursement systems currently used in radiation oncology and complex cancer surgery, also including policy models., Results: Most European health systems reimburse radiotherapy using a budget-based, fee-for-service or fraction-based system; while few reimburse services according to an episode-based model. Also, the reimbursement models for cancer surgery are mostly restricted to differences embedded in the DRG system and adjustments applied to the fees, based on the complexity of each surgical procedure. There is an enormous variability in reimbursement across countries, resulting in different incentives and different amounts paid for the same therapeutic strategy., Conclusion: A reimbursement policy, based on the episode of care as the basic payment unit, is advocated for. Innovation should be tackled in a two-tier approach: one defining the common criteria for reimbursement of proven evidence-based interventions; another for financing emerging innovation with uncertain definitive value. Relevant clinical and economic data, also collected real-life, should support reimbursement systems that mirror the actual cost of evidence-based practice., Competing Interests: Declaration of competing interest The authors have no conflict of interest., (Copyright © 2021 Josep M. Borras, Julieta Corral, Ajay Aggarwal, Riccardo Audisio, Josep Alfons Espinas, Josep Figueras, Peter Naredi, Dimitra Panteli, Nicolas Pourel, Joan Prades, Yolande Lievens. Published by Elsevier Ltd.. All rights reserved.)

Background and Purpose: Complex surgery and radiotherapy are the central pillars of loco-regional oncology treatment. This paper describes the reimbursement schemes used in radiation and complex surgical oncology, reports on literature and policy reviews., Material and Methods: A systematic review of the literature of the reimbursement models has been carried out separately for radiotherapy and complex cancer surgery based on PRISMA guidelines. Using searches of PubMed and grey literature, we identified articles from scientific journals and reports published since 2000 on provider payment or reimbursement systems currently used in radiation oncology and complex cancer surgery, also including policy models., Results: Most European health systems reimburse radiotherapy using a budget-based, fee-for-service or fraction-based system; while few reimburse services according to an episode-based model. Also, the reimbursement models for cancer surgery are mostly restricted to differences embedded in the DRG system and adjustments applied to the fees, based on the complexity of each surgical procedure. There is an enormous variability in reimbursement across countries, resulting in different incentives and different amounts paid for the same therapeutic strategy., Conclusion: A reimbursement policy, based on the episode of care as the basic payment unit, is advocated for. Innovation should be tackled in a two-tier approach: one defining the common criteria for reimbursement of proven evidence-based interventions; another for financing emerging innovation with uncertain definitive value. Relevant clinical and economic data, also collected real-life, should support reimbursement systems that mirror the actual cost of evidence-based practice., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Josep M. Borras, Julieta Corral, Ajay Aggarwal, Riccardo Audisio, Josep Alfons Espinas, Josep Figueras, Peter Naredi, Dimitra Panteli, Nicolas Pourel, Joan Prades, Yolande Lievens. Published by Elsevier B.V. All rights reserved.)

Acute intermittent porphyria (AIP) is an inherited rare hepatic disorder due to mutations within the hydroxymethylbilane gene. AIP patients with active disease overproduce aminolevulinic acid (ALA) and porphobilinogen (PBG) in the liver which are exported inducing severe neurological attacks. Different hepatic metabolic abnormalities have been described to be associated with this condition. The goal of this research was to explore the metabolome of symptomatic AIP patients by state-of-the art liquid chromatography-tandem mass spectrometry (LC-MS/MS). A case versus control study including 18 symptomatic AIP patients and 33 healthy controls was performed. Plasmatic levels of 51 metabolites and 16 ratios belonging to four metabolic pathways were determined. The results showed that the AIP patients presented significant changes in the two main areas of the metabolome under study: (a) the tryptophan/kynurenine pathway with an increase of tryptophan in plasma together with increase of the kynurenine/tryptophan ratio; and (b) changes in the tricarboxylic acid cycle (TCA) including increase of succinic acid and decrease of the fumaric acid/succinic acid ratio. We performed a complementary in vitro study adding ALA to hepatocytes media that showed some of the effects on the TCA cycle were parallel to those observed in vivo. Our study confirms in plasma previous results obtained in urine showing that AIP patients present a moderate increase of the kynurenine/tryptophan ratio possibly associated with inflammation. In addition, it also reports changes in the mitochondrial TCA cycle that, despite requiring further research, could be associated with an energy misbalance due to sustained overproduction of heme-precursors in the liver.

Hoverboards and electric scooters have surged in popularity in the past decade. These devices carry their own injury profiles and have caused increasing emergency department visits for injury. The purpose of this study was to compare both hoverboards and electric scooters to more traditional scooters and evaluate seasonal variations in their injury patterns. The National Electronic Injury Surveillance System (NEISS) database was used, downloading cases with the appropriate consumer product codes. Four distinct scooter groups were created, and were: non-powered scooters, powered scooters, electric scooters, and hoverboards. Statistical analyses were first performed with SUDAAN software to account for the stratified and weighted nature of the data to obtain national estimates of injuries and associated demographic variables. Cosinor analyses were performed to analyze the estimated number of emergency department (ED) visits for rhythmic variation by month and weekday of injury. Weekday by month analyses were studied using a three-dimensional topographic concept. Overall, there were over 1 million ED visits over the 20 years for injuries due to the four different types of scooters (75.8% nonmotorized scooters, 12.4% motorized scooters, 6.8% hoverboards, and 2.4% electric scooters). Cosinor analyses demonstrated that there was a peak in injuries in the summer and on weekends for all scooters, except for hoverboards. For hoverboards 21% of all ED visits occurred in December, with mostly occurring exactly around Christmas Day. This study confirms previous findings that scooter injuries occur mostly in warmer months and is the first to demonstrate a topographical "Christmas Effect" of hoverboard injuries. This information can be used in health care resource allocation as well as design of potential prevention strategies.

The COVID-19 pandemic is a catastrophe. It was also preventable. The potential impacts of a novel pathogen were foreseen and for decades scientists and commentators around the world warned of the threat. Most governments and global institutions failed to heed the warnings or to pay enough attention to risks emerging at the interface of human, animal, and environmental health. We were not ready for COVID-19, and people, economies, and governments around the world have suffered as a result. We must learn from these experiences now and implement transformational changes so that we can prevent future crises, and if and when emergencies do emerge, we can respond in more timely, robust and equitable ways, and minimize immediate and longer-term impacts. In 2020-21 the Pan-European Commission on Health and Sustainable Development assessed the challenges posed by COVID-19 in the WHO European region and the lessons from the response. The Commissioners have addressed health in its entirety, analyzing the interactions between health and sustainable development and considering how other policy priorities can contribute to achieving both. The Commission's final report makes a series of policy recommendations that are evidence-informed and above all actionable. Adopting them would achieve seven key objectives and help build truly sustainable health systems and fairer societies., (Copyright © 2021. Published by Elsevier B.V.)

In a circular economy approach, heterogeneous wastes can be upgraded to energy in the form of syngas via pyrogasification, and then to methane via biomethanation. Working at high pressure is a promising approach to intensify the process and to reduce gas-liquid transfer limitations. However, raising the pressure could lead to reaching the CO inhibition threshold of the microorganisms involved in syngas-biomethanation. To investigate the impact on pressure on the process, a 10L continuous stirred tank reactor working at 4 bars and 55 °C was implemented. Syngas (40% CO, 40% H 2 , 20% CO 2 ) biomethanation was performed successfully and methane productivity as high as 6.8 mmol CH4 /L reactor /h with almost full conversion of CO (97%) and H 2 (98%) was achieved. CO inhibition was investigated and carboxydotrophs appeared less resistant to high CO exposition than methanogens., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Purpose: To evaluate the safety and efficacy of hip arthroscopy immediately following gunshot wound (GSW) to the hip., Methods: Patients who received hip arthroscopy for GSWs from 2006 to 2020 by 2 surgeons at a level I trauma center were identified by Current Procedural Terminology codes. Inclusion criteria were those patients who suffered a GSW to the hip, received hip arthroscopy for treatment, and had a minimum follow-up of 2 months. The exclusion criteria were any patients younger than 18 years of age. Medical records were reviewed for patient demographics, surgical details, clinical outcomes, and complications., Results: A total of 50 hip arthroscopy cases were identified by Current Procedural Terminology codes. Of the 50 cases identified, 8 patients met the inclusion criteria. All 8 patients were male, African-American, and the mean age was 31 years (range, 19-54 years) with mean follow-up of 14 months. Five of 8 cases were noted to have poor visualization with arthroscopy. Common reasons for poor visualization were difficult access to the bullet fragments, morbid obesity, hematoma formation, and pre-existing arthritis. Of these 5 cases, 2 were converted to open procedures to retrieve the remaining bullet fragments. One patient developed abdominal compartment syndrome, most likely due to increased pulse pressure over a prolonged operative period and involvement of the acetabular fovea. Emergent exploratory laparotomy and abdominal compartment fluid release were performed, and the patient had an otherwise unremarkable hospital course., Conclusions: There are risks with the use of arthroscopic methods to remove GSW fragments, which may be greater than elective hip arthroscopy. Certain factors, such as the surgeon's arthroscopic experience, locations of bullets fragments, visual quality, length of procedure, and concomitant acetabular fractures, must be considered before proceeding with arthroscopy., Level of Evidence: Therapeutic case series., (© 2021 by the Arthroscopy Association of North America. Published by Elsevier Inc.)

Acute intermittent porphyria (AIP) is a rare metabolic disease caused by mutations within the hydroxymethylbilane synthase gene. Previous studies have reported increased levels of plasma total homocysteine (tHcy) in symptomatic AIP patients. In this study, we present long-term data for tHcy and related parameters for an AIP patient cohort (n = 37) in different clinical disease-states. In total, 25 patients (68%) presented with hyperhomocysteinemia (HHcy; tHcy > 15 μmol/L) during the observation period. HHcy was more frequent in AIP patients with recurrent disease receiving heme arginate, than in nonrecurrent (median tHcy: 21.6 μmol/L; range: 10-129 vs median tHcy: 14.5 μmol/L; range 6-77). Long-term serial analyses showed a high within-person tHcy variation, especially among the recurrent patients (coefficient of variation: 16.4%-78.8%). HHcy was frequently associated with low blood concentrations of pyridoxal-5'-phosphate and folate, while cobalamin concentration and the allele distribution of the methylene-tetrahydrofolate-reductase gene were normal. Strikingly, 6 out of the 9 recurrent patients who were later included in a regime of givosiran, a small-interfering RNA that effectively reduced recurrent attacks, showed further increased tHcy (median tHcy in 9 patients: 105 μmol/L; range 16-212). Screening of amino acids in plasma by liquid-chromatography showed co-increased levels of methionine (median 71 μmol/L; range 23-616; normal <40), suggestive of acquired deficiency of cystathionine-β-synthase. The kynunerine/tryptophan ratio in plasma was, however, normal, indicating a regular metabolism of tryptophan by heme-dependent enzymes. In conclusion, even if HHcy was observed in AIP patients receiving heme arginate, givosiran induced an aggravation of the dysregulation, causing a co-increase of tHcy and methionine resembling classic homocystinuria., (© 2021 SSIEM.)

Background: Amphetamine urine drug screening by immunoassay is prone to cross-react with other compounds leading to false positive results. Tetracaine is a local anesthetic drug used in the clinical setting as an ointment during urinary catheterization. In our laboratory, tetracaine is often detected by gas chromatography-mass spectrometry in the urine of patients admitted in the emergency department with false positive amphetamine results. The objectives of this study were to investigate if there was cross-reactivity to tetracaine in an amphetamine immunoassay and to retrospectively evaluate the potential contribution of tetracaine to false positive amphetamine results., Methods: An interference study was conducted using negative urine samples spiked with increasing concentrations of tetracaine hydrochloride and analyzed with the CEDIA Amphetamine/Ecstasy immunoassay. Retrospectively, urine samples of patients which yielded positive amphetamine immunoassay results and were analyzed by gas chromatography-mass spectrometry were reviewed ( n  = 417). The presence of tetracaine and/or other drugs by gas chromatography-mass spectrometry were gathered., Results: Tetracaine caused false positive amphetamine results by immunoassay (cut-off 1000 µg/L) with a concentration of above 40 mg/L. Retrospective analysis of all positive amphetamine immunoassay samples showed that in 45 out of the 417 (10.8%) urine samples no amphetamine-like derivative was identified by gas chromatography - mass spectrometry. In 37 out of 45 (82.2%) of these false positive cases tetracaine was detected, of whom 59.5% (22/37) had an estimated tetracaine concentration of ≥40 mg/L., Conclusions: This study confirmed the interference of tetracaine in the CEDIA Amphetamine/Ecstasy immunoassay and that tetracaine may have contributed to around 80% of the false positive amphetamine cases in the urine samples of patients admitted to the emergency department at our institution.

Objective: To stratify major hepatectomies (MajHs) according to their outcomes., Summary of Background Data: MajHs are associated with non-negligible operative risks, but they include a wide range of procedures. Detailed depiction of the outcomes of different MajHs is the basis for a new classification of liver resections., Methods: We retrospectively considered patients that underwent hepatectomy in 17 high-volume centers. Patients with an associated digestive/biliary resection were excluded. We analyzed open MajHs in non-cirrhotic patients. MajHs were classified according to the Brisbane nomenclature. Right hepatectomies (RHs) were reference standards. Outcomes were adjusted for potential confounders, including indication, liver function, preoperative portal vein embolization, and enrolling center., Results: We analyzed a series of 2212 patients. In comparison with RH, left hepatectomy had lower mortality [0.6% vs 2.2%, odds ratio (OR) = 0.25], severe morbidity (11.7% vs 14.4%, OR = 0.62), and liver failure rates (2.1% vs 11.6%, OR = 0.16). Left hepatectomy+Sg1 and mesohepatectomy+/-Sg1 had outcomes similar to RH, except for higher bile leak rate (31.3% and 13.5% vs 6.7%, OR = 4.36 and OR = 2.29). RH + Sg1 had slightly worse outcomes than RH. Right and left trisectionectomies had higher mortality (5.0% and 7.3% vs 2.2%, OR = 2.07 and OR = 2.71) and liver failure rates than RH (19.0% and 22.0% vs 11.6%, OR = 2.03 and OR = 2.21). Left trisectionectomy had even higher severe morbidity (25.6% vs 14.4%, OR = 2.07) and bile leak rates (14.6% vs 6.7%, OR = 2.31)., Conclusions: The term "major hepatectomy" includes resections having heterogeneous outcome. Different MajHs can be stratified according to their mortality, severe morbidity, liver failure, and bile leak rates.

Background: Laparoscopic liver resection (LLR) may improve outcomes for cirrhotic patients with hepatocellular carcinoma (HCC) and portal hypertension (PHT). The aim of this study was to compare the short-term outcomes after LLR for HCC in cirrhotic patients with and without PHT., Methods: This multicentric study included 96 HCC patients who underwent LLR. Clinically significant portal hypertension (CSPH) was defined by a hepatic venous pressure gradient ≥10 mmHg. Short-term outcomes and liver-specific complications including post-hepatectomy liver failure (PHLF), ascites and encephalopathy were compared between patients with and without CSPH., Results: Thirty-one patients (32%) had CSPH. The CSPH group had higher post-operative morbidity (52% vs. 15%; p < 0.001), PHLF (10% vs. 0%; p = 0.03) and encephalopathy (10% vs. 0%; p = 0.03). There was no difference in terms of post-operative ascites between the two groups (CSPH: 16% vs. no CPSH: 8%, p = 0.28). The length of stay was longer in patients with CSPH than in those without CSPH (6 vs. 4 days; p < 0.001)., Conclusions: The laparoscopic approach is feasible in selected HCC patients with CSPH, at the price of significant increases in liver-specific complications and length of stay.

Background & Aims: Liver resection (LR) in patients with hepatocellular carcinoma (HCC) and clinically significant portal hypertension (CSPH) defined as a hepatic venous pressure gradient (HVPG) ≥10 mmHg is not encouraged. Here, we reappraised the outcomes of patients with cirrhosis and CSPH who underwent LR for HCC in highly specialised liver centres., Methods: This was a retrospective multicentre study from 1999 to 2019. Predictors for postoperative liver decompensation and textbook outcomes were identified., Results: In total, 79 patients with a median age of 65 years were included. The Child-Pugh grade was A in 99% of patients, and the median model for end-stage liver disease (MELD) score was 8. The median HVPG was 12 mmHg. Major hepatectomies and laparoscopies were performed in 28% and 34% of patients, respectively. Ninety-day mortality and severe morbidity rates were 6% and 27%, respectively. Postoperative and persistent liver decompensation occurred in 35% and 10% of patients at 3 months. Predictors of liver decompensation included increased preoperative HVPG ( p  = 0.004), increased serum total bilirubin ( p  = 0.02), and open approach ( p  = 0.03). Of the patients, 34% achieved a textbook outcome, of which the laparoscopic approach was the sole predictor ( p  = 0.004). The 5-year overall survival and recurrence-free survival rates were 55% and 43%, respectively., Conclusions: Patients with cirrhosis, HCC and HVPG ≥10 mmHg can undergo LR with acceptable mortality, morbidity, and liver decompensation rates. The laparoscopic approach was the sole predictor of a textbook outcome., Lay Summary: Patients with cirrhosis, hepatocellular carcinoma, and clinically significant portal hypertension (defined as a hepatic venous pressure gradient ≥10 mmHg) can undergo resection with acceptable mortality, morbidity, liver decompensation rates, and a textbook outcome. These results can be achieved in selected patients with preserved liver function, good general status, and sufficient remnant liver volume., Competing Interests: The authors declare no conflicts of interest that pertain to this work. Please refer to the accompanying ICMJE disclosure forms for further details., (© 2020 The Author(s).)

Background : The prospective phase IV AVAMET study was undertaken to correlate response evaluation criteria in solid tumors (RECIST)-defined response rates with computed tomography-based morphological criteria (CTMC) and pathological response after liver resection of colorectal cancer metastases. Methods : Eligible patients were aged ≥18 years, with Eastern Cooperative Oncology Group (ECOG) performance status 0/1 and histologically-confirmed colon or rectal adenocarcinoma with measurable liver metastases. Preoperative treatment was bevacizumab (7.5 mg on day 1) + XELOX (oxaliplatin 130 mg/m 2 , capecitabine 1000 mg/m 2 bid on days 1-14 q3w). After three cycles, response was evaluated by a multidisciplinary team. Patients who were progression-free and metastasectomy candidates received one cycle of XELOX before undergoing surgery 3-5 weeks later, followed by four cycles of bevacizumab + XELOX. Results : A total of 83 patients entered the study; 68 were eligible for RECIST, 67 for CTMC, and 51 for pathological response evaluation. Of these patients, 49% had a complete or partial RECIST response, 91% had an optimal or incomplete CTMC response, and 81% had a complete or major pathological response. CTMC response predicted 37 of 41 pathological responses versus 23 of 41 responses predicted using RECIST ( p = 0.008). Kappa coefficients indicated a lack of correlation between the results of RECIST and morphological responses and between morphological and pathological response rates. Conclusion: CTMC may represent a better marker of pathological response to bevacizumab + XELOX than RECIST in patients with potentially-resectable CRC liver metastases.

Introduction: Extreme prematurity is associated with high mortality rates. The probability of death at different points in time is a priority for professionals and parents, and needs to be established on an individual basis. The aim of this study is to carry out a systematic review of predictive models of mortality in premature infants that have been published recently., Methods: A double search was performed for article published in PubMed on models predicting mortality in premature neonates. The population studied were premature neonates with a gestational age of ≤30 weeks and / or a weight at birth of ≤1500g. Works published with new models from June 2010 to July 2019 after a systematic review by Medlock (2011) were included. An assessment was made of the population, characteristics of the model, variables used, measurements of functioning, and validation., Results: Of the 7744 references (1st search) and 1435 (2nd search) found, 31 works were selected, with 8 new models finally being included. Five models (62.5%) were developed in North America and 2 (25%) in Europe. A sequential model (Ambalavanan) enables predictions of mortality to be made at birth, 7, 28 days of life, and 36 weeks post-menstrual. A multiple logistic regression analysis was performed on 87.5% of the models. The population discrimination was measured using Odds Ratio (75%) and the area under the curve (50%). "Internal Validation" had been carried out on 5 models. Three models can be accessed on-line. There are no predictive models validated in Spain., Conclusions: The making of decisions based on predictive models can lead to the care given to the premature infant being more individualised and with a better use of resources. Predictive models of mortality in premature neonates in Spain need to be developed., (Crown Copyright © 2019. Publicado por Elsevier España, S.L.U. All rights reserved.)

Introduction: 6-Monoacetylmorphine (6-MAM) is a specific metabolite of heroin. Thus, the presence of 6-MAM in urine is a definitive indication of heroin intake. The possibility of having an immunoassay procedure to measure 6-MAM would be a diagnosis tool to discriminate, among opiates-positive, those patients who have consumed heroin and those who have not. Methods: EMIT ® II Plus 6-Acetylmorphine Assay was used to measure 6-MAM in urine. The positive opiate screening results were confirmed at the Toxicology laboratory of our hospital by GC-MS. Results: This study includes 63 urine samples from subjects admitted to emergency department with suspicion of opiate consumption. Specificity was evaluated in the two groups of samples studied. In the first group all samples which resulted negative by opiate immunoassay (n = 33) were negative for 6-MAM immunoassay test. Thus, the specificity obtained for 6-MAM immunoassay in this group was 100%. Regarding the second specificity study, performed in positive samples by opiate immunoassay which were negative to 6 MAM by GC-MS, the specificity decreased down to 75%. In the study of sensitivity all samples confirmed as positive to 6-MAM by confirmatory method (GC-MS) resulted positive by the screening method, thus sensitivity obtained was 100%. Discussion: In this study no FN for 6-MAM was observed and therefore the new Emit ® II Plus 6- Acetylmorphine Assay procedure has a high NPV, thus a negative result with 6-MAM immunoassay practically excludes heroine consume. The positive results to 6-MAM by immunoassay should be confirmed by a more analytically specific method, such as GCMS.

Background: The outcomes of liver resection (LR) with a narrow margin in patients with transplantable hepatocellular carcinoma (HCC) have not been studied. The aim was to assess whether narrow margin following up-front LR impacts the incidence, timing, pattern, and transplantability of tumor recurrence in patients with initially transplantable HCC., Methods: All initially transplantable HCC patients undergoing hepatectomy with either narrow (<10 mm) or wide (≥10 mm) margins from 2007 to 2016 at four Western university centers were compared in terms of recurrence, transplantability of recurrence, recurrence-free survival (RFS), and intention-to-treat overall survival (ITT-OS). Independent predictors of non-transplantability of recurrence were assessed., Results: This study included 187 patients (narrow group, n = 107 vs. wide group, n = 80). Recurrence was significantly more frequent in the narrow margin group (44% vs. 26%; p = 0.01) with a shorter RFS (p = 0.03). The transplantability of recurrence and ITT-OS were, however, not different between the two groups. The presence of satellite nodules on the resected specimens emerged as the sole independent predictor of non-transplantability of tumor recurrence. The stratification of the analysis according to the presence of cirrhosis achieved essentially the same results as in the whole study population., Conclusions: Narrow margin was associated with a higher tumor recurrence rate and a shorter RFS for patients with initially transplantable HCC. However, transplantability of recurrence and long-term ITT-OS were not impaired.

Background: Hepatitis C virus (HCV) is a risk factor for porphyria cutanea tarda (PCT), a rare disease originating in the liver characterised by overproduction of porphyrins. Although hepatitis C infection is highly prevalent among patients with porphyria, only a minority of hepatitis C patients develop PCT., Aims: To explore the presence of porphyrin abnormalities in a cohort of asymptomatic hepatitis C-infected patients and the impact of anti-viral therapy., Methods: Eighty-four consecutive patients with HCV infection treated with direct-acting antivirals after 1 January 2018 were longitudinally evaluated for the presence of porphyrin abnormalities. Those patients with biochemical abnormalities at baseline were additionally evaluated at follow-up. Porphyrins in urine were screened by fluorometry and isomer separation was performed by liquid chromatography., Results: In five patients, all of them asymptomatic, porphyrin profile abnormalities were detected: three presented significant increased urinary porphyrins with a typical PCT profile, and two showed normal levels of urinary porphyrins, but abnormal porphyria-like profiles. Urine evaluation after hepatitis C cure showed complete normalisation of the urinary porphyrins in all patients, confirming the biochemical cure of the disease., Conclusions: We document the existence of rare cases of hepatitis C-infected patients with significant uroporphyrinuria in the absence of dermatological manifestations. Anti-viral therapy normalises the biochemical disorder, preventing patients from presenting PCT associated complications., (© 2020 John Wiley & Sons Ltd.)

Objective: To elucidate minor hepatectomy (MiH) outcomes., Summary Background Data: Liver surgery has moved toward a parenchyma-sparing approach, favoring MiHs over major resections. MiHs encompass a wide range of procedures., Methods: We retrospectively evaluated consecutive patients who underwent open liver resections in 17 high-volume centers., Exclusion Criteria: cirrhosis and associated digestive/biliary resections. Resections were classified as (Brisbane nomenclature): limited resections (LR); (mono)segmentectomies/bisegmentectomies (Segm/Bisegm); right anterior and right posterior sectionectomies (RightAnteriorSect/RightPosteriorSect). Additionally, we defined: complex LRs (ComplexLR = LRs with exposed vessels); postero-superior segmentectomies (PosteroSuperiorSegm = segment (Sg)7, Sg8, and Sg7+Sg8 segmentectomies); and complex core hepatectomies (ComplexCoreHeps = Sg1 segmentectomies and combined resections of Sg4s+Sg8+Sg1). Left lateral sectionectomies (LLSs, n = 442) and right hepatectomies (RHs, n = 1042) were reference standards. Outcomes were adjusted for potential confounders., Results: Four thousand four hundred seventy-one MiHs were analyzed. Compared with RHs, MiHs had lower 90-day mortality (0.5%/2.2%), severe morbidity (8.6%/14.4%), and liver failure rates (2.4%/11.6%, P < 0.001), but similar bile leak rates. LR and LLS had similar outcomes. ComplexLR and Segm/Bisegm of anterolateral segments had higher bile leak rates than LLS rates (OR = 2.35 and OR = 3.24), but similar severe morbidity rates. ComplexCoreHeps had higher bile leak rates than RH rates (OR = 1.94); the severe morbidity rate approached that of RH. PosteroSuperiorSegm, RightAnteriorSect, and RightPosteriorSect had severe morbidity and bile leak rates similar to RH rates. MiHs had low liver failure rates, except RightAnteriorSect (vs LLS OR = 4.02)., Conclusions: MiHs had heterogeneous outcomes. Mortality was low, but MiHs could be stratified according to severe morbidity, bile leak, and liver failure rates. Some MiHs had postoperative outcomes similar to RH.

With the advent of precision and genomic medicine, a critical issue is whether a disease gene variant is pathogenic or benign. Such is the case for the three autosomal dominant acute hepatic porphyrias (AHPs), including acute intermittent porphyria, hereditary coproporphyria, and variegate porphyria, each resulting from the half-normal enzymatic activities of hydroxymethylbilane synthase, coproporphyrinogen oxidase, and protoporphyrinogen oxidase, respectively. To date, there is no public database that documents the likely pathogenicity of variants causing the porphyrias, and more specifically, the AHPs with biochemically and clinically verified information. Therefore, an international collaborative with the European Porphyria Network and the National Institutes of Health/National Center for Advancing Translational Sciences/National Institute of Diabetes and Digestive and Kidney Diseases (NIH/NCATS/NIDDK)-sponsored Porphyrias Consortium of porphyria diagnostic experts is establishing an online database that will collate biochemical and clinical evidence verifying the pathogenicity of the published and newly identified variants in the AHP-causing genes. The overall goal of the International Porphyria Molecular Diagnostic Collaborative is to determine the pathogenic and benign variants for all eight porphyrias. Here we describe the overall objectives and the initial efforts to validate pathogenic and benign variants in the respective heme biosynthetic genes causing the AHPs.

Porphyria cutanea tarda (PCT) arises from a deficiency of uroporphyrinogen decarboxylase (UROD) in the liver. Several exogenous risk factors are associated with the acquired form of the disease. In Southern Europe, PCT is strongly linked to hepatitis C virus (HCV) infection to the point that a high prevalence of viral infection in some geographic areas generated an increase of PCT cases as a complication. In spite of the association, PCT is a rare complication of HCV infection, thus suggesting the existence of susceptibility factors operating in only some patients. Investigation of liver specimens of PCT patients showed iron accumulation, which albeit moderate, was higher in comparison with HCV-infected patients without PCT. Measurements of hepcidin in serum of HCV-infected patients with and without PCT and calculation of hepcidin/ferritin ratio were compatible with the hypothesis that HCV induced inadequate response of hepcidin to iron accumulation. Administration of direct-acting antivirals (DAA) to HCV-infected patients with active PCT showed that eradication of the virus was followed by resolution of PCT and rapid disappearance of urinary porphyrins. This suggests a direct participation of the virus in the oxidative mechanism leading to UROD inhibition. If clinical evolution of HCV- PCT-patients is placed within a time-frame, rapid PCT resolution by DAA is in striking contrast with a long-delay (in most cases of decades) between viral infection and appearance of overt porphyria. This could be explained if HCV infection (a): enhanced an oxidative environment in the vicinity of UROD and (b): facilitated iron accumulation through hepdicin down-regulation. Thus, only when iron accumulation reached a threshold, inhibition of UROD attained a critical level. However, the enigma is why only a minority of HCV-infected patients develop PCT. If additional risk factors (i.e. alcohol abuse) are not concurring, it should be concluded that modifier genes or epigenetic mechanisms related to iron homeostasis, facilitate iron progressive accumulation in only a minority susceptible patients., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Reduction of left ventricular (LV) dilation (RD) beyond the first year after ST-segment-elevation myocardial infarction (STEMI) is unknown. We investigated its potential occurrence in comparison with stationary (SD) and progressive (PD) dilation., Methods and Results: Perfusion gated SPECT features at 1 and 3 years were evaluated in 168 3-year survivors of a first anterior STEMI. Comparisons were made among patients with RD (≥15% reduction of LV end-systolic volume [LVESV]), SD (<15% reduction or increase), and PD (≥15% increase). There were 35 patients with RD (21%), 84 with SD (50%), and 49 with PD (29%). At 1 year, ejection fraction, wall motion and perfusion scores, and LV volumes were similar. In RD patients, the fall in LVESV, nearly 22%, was apparent in those with frank (>51 mL; P < .001) or little/moderate LV dilation at 1 year (LVESV ≤51 mL; P = .002) and was associated with increased ejection fraction (P values .008 and .009, respectively). In the 3 groups, however, LVESV changes were unrelated to 1-year LV volumes, ejection fraction, or contractility score., Conclusions: At 3 years following anterior STEMI there is reduction of LV dilation in about 21% of patients associated with increases in ejection fraction in those with or without clearly dilated ventricles at 1year. These findings add to the complexity of LV remodeling and possibly suggest very late changes in infarct size., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Whether patients with incomplete myocardial rupture (IMR) present distinctive clinical and cardiac magnetic resonance features from those with moderate-severe pericardial effusion (⩾10 mm (PE)) remains unknown., Methods: We compared the clinical, angiographic and cardiac magnetic resonance characteristics of nine patients with IMR (diagnosed angiographically and/or by cardiac magnetic resonance) with 29 with PE, and also with 38 without IMR or PE with evidence of transmural necrosis (reference group) matched for age, gender and year of admission., Results: Patients with IMR were younger than those with PE ( p <0.001) but the two groups shared a higher rate of admission delay (78% and 41%) than those without IMR/PE (5%, p <0.001) and lower frequency of reperfusion therapy (44%, 55% and 100%, respectively, p <0.001). Thirteen patients with PE (45%) but only one IMR (11%) presented recurrent chest pain. IMR patients tended to present smaller infarct size at cardiac magnetic resonance ( p =0.153 and 0.036) and number of segments with ⩾75% necrosis than PE patients and those without IMR/PE ( p =0.098 and 0.029, respectively). Ten PE patients presented cardiac tamponade (35%). A control 2D-echocardiogram performed within two years in 71 patients (93%) documented a pseudoaneurysm in one PE and in one IMR patient., Conclusions: IMR is generally silent and occurs in younger patients with smaller infarct size than those with PE although both present late and are often untreated with reperfusion therapy. These findings may warrant imaging assessment in ST elevation myocardial infarction patients with delayed admission, particularly in absence of reperfusion, to rule out an IMR.