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Windy Rakhmawati,1,* Henny Suzana Mediani,1,* Meita Dhamayanti,2,* Ida Maryati,3,* Asty Samiaty Setiawan,4,* Sri Hendrawati,1,* Nenden Nur Asriyani Maryam,1,* Alfiah Hasanah,5,* Aep Maulid Mulyana,6,* Dini Mariani,7,* Imat Rochimat8,* 1Department of Pediatric Nursing, Faculty of Nursing, Universitas Padjadjaran, Sumedang, West Java, 45363, Indonesia; 2Department of Child Health, Faculty of Medicine, Universitas Padjadjaran, Sumedang, West Java, 45363, Indonesia; 3Department of Maternity Nursing, Faculty of Nursing, Universitas Padjadjaran, Sumedang, West Java, 45363, Indonesia; 4Department of Public Dental Health, Faculty of Dentistry, Universitas Padjadjaran, Sumedang, West Java, 45363, Indonesia; 5Department of Economics, Faculty of Economics and Business, Universitas Padjadjaran, Sumedang, West Java, 45363, Indonesia; 6Faculty of Nursing, Universitas Padjadjaran, Sumedang, West Java, 45363, Indonesia; 7Department of Nursing, Polytechnic Health Ministry of Health Tasikmalaya, Tasikmalaya, West Java, 46115, Indonesia; 8Department of Pharmacy, Polytechnic Health Ministry of Health Tasikmalaya, Tasikmalaya, 46115, Indonesia*These authors contributed equally to this workCorrespondence: Windy Rakhmawati, Department of Pediatric Nursing, Faculty of Nursing, Universitas Padjadjaran, Sumedang, West Java, 45363, Indonesia, Tel +62 82119492124, Email windy.rakhmawati@unpad.ac.idBackground: Infants are in a critical period during which often occur many problems, such as growth, development, and motor delays. One of the interventions that can potentially reduce these problems is by giving a massage therapy.Purpose: This study aims to conduct a systematic scoping review of massage therapy’s potential for growth and development among infants under nine months.Methods: This study followed a Preferred Reporting Item for Systematic Review and Meta-analysis (PRISMA-ScR). We collected data from three databases, including PubMed, Scopus, and CINAHL with full text, published in 2013– 2022, subjects aged less than nine months, full-text articles, and randomized controlled trials. Studies were excluded if they were not in English.Results: Of the 11 studies found, it shows that therapy massage can effectively increase infants’ growth and development, including body weight, length, visual-motor coordination and integration, hand-eye, hearing, speech, social, vagal activity, language, locomotion, stationary, and reflexes. The interventions include medium chain triglyceride oil massage, Dabur Lal Tail massage, oil massage, massage by mothers, and massage therapy without additives for 5– 45 minutes. In addition, massage therapy has a positive effect on infants with various conditions, including preterm infants, infants with HIV-infected mothers, and infants with Down’s syndrome.Conclusion: Our findings highlight that infants receiving massage therapy were significantly more likely to increase growth and development than the population who were not given massage therapy. However, further investigation into preventing the severity of growth and developmental problems is urgently needed.Keywords: development, growth, infant, intervention, massage therapy

Objective To investigate whether the race and ethnicity of a patient with rheumatoid arthritis (RA) influences rheumatologists’ likelihood of choosing to initiate biologic disease‐modifying antirheumatic drug (bDMARD) treatment. Methods We conducted a randomized survey experiment in which identical brief case vignettes of hypothetical patients with RA were sent to US rheumatologists (respondents). Three of the four cases included some level of treatment decision ambiguity whereas the fourth case strongly favored bDMARD initiation. Each respondent was shown the four case vignettes, with the race and ethnicity (Black, Hispanic, White) randomly assigned for each case. Each vignette offered multiple choices for next therapeutic step, which we summarized using frequencies and proportions by race and ethnicity version. Results Among 159 US rheumatologists, we found that for the three cases with some level of treatment decision ambiguity, there was little to no variability in the proportions of respondents who chose to start a biologic for the Black and Hispanic variants (cases 1, 2, and 3). For case 4, respondents generally agreed to start a biologic with some minimal variability across the variants (92.6% for the Black version, 98.1% for the Hispanic version, and 96.2% for the White version). Conclusion There are conflicting data regarding bDMARD use and initiation in patients with RA based on the sex and race of the patient. This work adds to this conversation by examining how the next therapeutic step chosen by rheumatologists varied by the race and ethnicity of the hypothetical patient.

Objective: To investigate whether the race and ethnicity of a patient with rheumatoid arthritis (RA) influences rheumatologists' likelihood of choosing to initiate biologic disease‐modifying antirheumatic drug (bDMARD) treatment. Methods: We conducted a randomized survey experiment in which identical brief case vignettes of hypothetical patients with RA were sent to US rheumatologists (respondents). Three of the four cases included some level of treatment decision ambiguity whereas the fourth case strongly favored bDMARD initiation. Each respondent was shown the four case vignettes, with the race and ethnicity (Black, Hispanic, White) randomly assigned for each case. Each vignette offered multiple choices for next therapeutic step, which we summarized using frequencies and proportions by race and ethnicity version. Results: Among 159 US rheumatologists, we found that for the three cases with some level of treatment decision ambiguity, there was little to no variability in the proportions of respondents who chose to start a biologic for the Black and Hispanic variants (cases 1, 2, and 3). For case 4, respondents generally agreed to start a biologic with some minimal variability across the variants (92.6% for the Black version, 98.1% for the Hispanic version, and 96.2% for the White version). Conclusion: There are conflicting data regarding bDMARD use and initiation in patients with RA based on the sex and race of the patient. This work adds to this conversation by examining how the next therapeutic step chosen by rheumatologists varied by the race and ethnicity of the hypothetical patient. [ABSTRACT FROM AUTHOR]

Extraperitoneal endometriosis is the presence of ectopic, functional endometrium outside the peritoneal cavity, and its occurrence is exceedingly rare. Diagnostic imaging--including ultrasound, duplex ultrasonography, and magnetic resonance imaging--in the preoperative assessment of patients with suspected abdominal wall endometriosis (AWE) is helpful for detection and accurate determination of the extent of disease. The treatment of choice for AWE is surgical excision. In addition, medical therapies can be used. We present one case of AWE treated with percutaneous radiofrequency ablation under ultrasound guidance. There were no major complications, and the patient's symptoms improved. In selected patients, radiofrequency ablation can be used safely for the treatment of AWE; however, further studies are needed to confirm this hypothesis. [ABSTRACT FROM AUTHOR]

Foreign bodies (FBs) retained in the soft tissues are a common reason for medical consultation, and usually consist of wooden or metal splinters or glass shards. Failure to remove foreign bodies is likely to give rise to acute or late complications, such as allergies, inflammation or infection, that may be severe. The surgical removal of an FB is invasive, costly and technically challenging. The procedure may fail in some cases and carries the risk of complications. Our study describes a technique for the ultrasound-guided removal of an FB, devised from our experience, and demonstrates its advantages over the standard surgical procedure. Sixty-two patients (43 males and 19 females aged from 9 to 65 years, median age 31 years) presented at our institution between October 2005 and June 2008 with suspected foreign bodies retained in the soft tissues of various body districts. Radiographic and/or ultrasound diagnosis was established by a radiologist expert in musculoskeletal sonography. The same radiologist helped by a nurse subsequently undertook the ultrasound-guided removal in the outpatient's clinic according to the technique described in the paper. ATL 5000 and PHILIPS iu22 ultrasound systems were used with high-frequency linear-array probes, sterile material, local anaesthetic (lidocaine 2%), scapels and surgical forceps. Antibiotic prophylaxis with amoxicillin and clavulanic acid were prescribed to all patients for 7 days after the procedure. Ninety-five FBs (39 glass, 35 metal, 17 vegetable, 2 plastic, 2 stone) were successfully removed under ultrasound guidance in all patients and the procedure took between 15 and 30 min. No complications arose either during or after the procedure. Seventy-five skin incisions were made and the wounds closed with Steri-Strips in 73/75 cases, whereas skin sutures were used in 2/75 cases. No complications arose either during or after the procedure. Ultrasound-guided removal of an FB retained in the soft tissues is a good alternative to surgery as is its relatively straightforward, inexpensive, repeatable and carries a low risk of complications. In addition, failure to remove an FB does not preclude traditional surgical removal. The advantages of this real-time procedure and the use of small instruments minimize bleeding time and avoid injury to surrounding structures. Patient compliance is enhanced by the fact that the procedure has little or no aesthetic impact. These encouraging results suggest ultrasound-guided removal as a first-choice procedure for the extraction of foreign bodies. [ABSTRACT FROM AUTHOR]

Studies of rare genetic variation have identified molecular pathways conferring risk for developmental neuropsychiatric disorders. To date, no published whole-exome sequencing studies have been reported in obsessive-compulsive disorder (OCD). We sequenced all the genome coding regions in 20 sporadic OCD cases and their unaffected parents to identify rare de novo (DN) single-nucleotide variants (SNVs). The primary aim of this pilot study was to determine whether DN variation contributes to OCD risk. To this aim, we evaluated whether there is an elevated rate of DN mutations in OCD, which would justify this approach toward gene discovery in larger studies of the disorder. Furthermore, to explore functional molecular correlations among genes with nonsynonymous DN SNVs in OCD probands, a protein–protein interaction (PPI) network was generated based on databases of direct molecular interactions. We applied Degree-Aware Disease Gene Prioritization (DADA) to rank the PPI network genes based on their relatedness to a set of OCD candidate genes from two OCD genome-wide association studies (Stewart et al., 2013; Mattheisen et al., 2014). In addition, we performed a pathway analysis with genes from the PPI network. The rate of DN SNVs in OCD was 2.51 × 10−8 per base per generation, significantly higher than a previous estimated rate in unaffected subjects using the same sequencing platform and analytic pipeline. Several genes harboring DN SNVs in OCD were highly interconnected in the PPI network and ranked high in the DADA analysis. Nearly all the DN SNVs in this study are in genes expressed in the human brain, and a pathway analysis revealed enrichment in immunological and central nervous system functioning and development. The results of this pilot study indicate that further investigation of DN variation in larger OCD cohorts is warranted to identify specific risk genes and to confirm our preliminary finding with regard to PPI network enrichment for particular biological pathways and functions.

Worldwide attention is focused on microplastics environmental pollution, primarily for its potential negative effects on biota and human health. It is of great importance to identify standardized analytical methods to have an objective feedback about this concern. The recent regulation regarding the intentionally added microplastics content and the attention for the unintentional microplastics release are the basis of this work, whose topic is the development of an analytical method for microbeads (spheres) and microparticles (fragments) determination in certain cosmetic samples, in particular creamy samples. The method is based on Accelerated Solvent Extraction technique to remove all the sample matrix ingredients. The final suspension was then filtered on silicon membrane, for the following quali-quantitative micro-FTIR analysis, and on glass fibre membranes, for the gravimetric analysis. The method was developed for a theoretical microplastics concentration of 0.025 % (w/w) and allows a good recovery percentage. Working both by gravimetric evaluation and by micro-FTIR analysis gives more confident results and guaranties a proper identification and characterization of the filtered materials., 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 © 2024 Elsevier B.V. All rights reserved.)

Stress granules (SG) are part of a cellular protection mechanism where untranslated messenger RNAs and RNA-binding proteins are stored upon conditions of cellular stress. Compositional variations due to qualitative or quantitative protein changes can disrupt their functionality and alter their structure. This is the case of different forms of amyotrophic lateral sclerosis (ALS) where a causative link has been proposed between the cytoplasmic de-localization of mutant proteins, such as FUS (Fused in Sarcoma), and the formation of cytotoxic inclusions. Here, we describe the SG transcriptome in neuroblastoma cells and define several features for RNA recruitment in these condensates. We demonstrate that SG dynamics and RNA content are strongly modified by the incorporation of mutant FUS, switching to a more unstructured, AU-rich SG transcriptome. Moreover, we show that mutant FUS, together with its protein interactors and their target RNAs, are responsible for the reshaping of the mutant SG transcriptome with alterations that can be linked to neurodegeneration. Our data describe the molecular differences between physiological and pathological SG in ALS-FUS conditions, showing how FUS mutations impact the RNA and protein composition of these condensates., (© The Author(s) 2024. Published by Oxford University Press on behalf of Nucleic Acids Research.)

Purpose: European training pathways for surgeons dedicated to treating severely injured and critically ill surgical patients lack a standardized approach and are significantly influenced by diverse organizational and cultural backgrounds. This variation extends into the realm of mentorship, a vital component for the holistic development of surgeons beyond mere technical proficiency. Currently, a comprehensive understanding of the mentorship landscape within the European trauma care (visceral or skeletal) and emergency general surgery (EGS) communities is lacking. This study aims to identify within the current mentorship environment prevalent practices, discern existing gaps, and propose structured interventions to enhance mentorship quality and accessibility led by the European Society for Trauma and Emergency Surgery (ESTES)., Methods: Utilizing a structured survey conceived and promoted by the Young section of the European Society of Trauma and Emergency Surgery (yESTES), we collected and analyzed responses from 123 ESTES members (both surgeons in practice and in training) across 20 European countries. The survey focused on mentorship experiences, challenges faced by early-career and female surgeons, the integration of non-technical skills (NTS) in mentorship, and the perceived role of surgical societies in facilitating mentorship., Results: Findings highlighted a substantial mentorship experience gap, with 74% of respondents engaging in mostly informal mentorship, predominantly centered on surgical training. Notably, mentorship among early-career surgeons and trainees was less reported, uncovering a significant early-career gap. Female surgeons, representing a minority within respondents, reported a disproportionately poorer access to mentorship. Moreover, while respondents recognized the importance of NTS, these were inadequately addressed in current mentorship practices. The current mentorship input of surgical societies, like ESTES, is viewed as insufficient, with a call for structured programs and initiatives such as traveling fellowships and remote mentoring., Conclusions: Our survey underscores critical gaps in the current mentorship landscape for trauma and EGS in Europe, particularly for early-career and female surgeons. A clear need exists for more formalized, inclusive mentorship programs that adequately cover both technical and non-technical skills. ESTES could play a pivotal role in addressing these gaps through structured interventions, fostering a more supportive, inclusive, and well-rounded surgical community., Competing Interests: Declarations. Conflict of interest: Stefano P. B. Cioffi, Marit Herbolzheimer, Enrico Marrano, Gabriele Bellio, Wouter Kluijfhout, Frans-Jasper Wijdicks and Annika Hättich are founding members of Young ESTES. Jonathan Tilsed is Chair of the UEMS European Board of Surgery Examination in Emergency Surgery. Diego Mariani is the ESTES Chair of Education, Christine Rey Valcarel is Chair of the ESTES Advisory Council. Shahin Mohseni is Chair of the Visceral Trauma Section of ESTES and is a Section Editor for the European Journal of Trauma and Emergency Surgery (EJTES). Carlos Yanez is Chair of the Emergency Surgery Section of ESTES. Jan P.A.M. Verbruggen is Chair of the Skeletal Trauma and Sports Medicine Section, and President-Elect of ESTES. Frank Hildebrand is Vice-Chair of the ESTES Research Committee and Immediate Past-President of ESTES. Christine Gaarder is President of ESTES. Hayato Kurihara is Vice-President of ESTES. Gary Alan Bass is the ESTES Chair of Research and is a Section Editor for EJTES. All other authors declare no competing interests., (© 2024. The Author(s).)

Neurological involvement has been widely reported in SARS-CoV-2 infection. However, viral identification in the cerebrospinal fluid (CSF) is rarely found. The aim of this study is to evaluate the accuracy of virological and immunological biomarkers in CSF for the diagnosis of neuroCOVID-19. We analyzed 69 CSF samples from patients with neurological manifestations: 14 with suspected/confirmed COVID-19, with 5 additional serial CSF samples (group A), and as a control, 50 non-COVID-19 cases (group B-26 with other neuroinflammatory diseases; group C-24 with non-inflammatory diseases). Real-time reverse-transcription polymerase chain reaction (real-time RT-PCR) was used to determine SARS-CoV-2, and specific IgG, IgM, neopterin, and protein 10 induced by gamma interferon (CXCL-10) were evaluated in the CSF samples. No samples were amplified for SARS-CoV-2 by real-time RT-PCR. The sensitivity levels of anti-SARS-CoV-2 IgG and IgM were 50% and 14.28%, respectively, with 100% specificity for both tests. CXCL-10 showed high sensitivity (95.83%) and specificity (95.83%) for detection of neuroinflammation. Serial CSF analysis showed an association between the neuroinflammatory biomarkers and outcome (death and hospital discharge) in two cases (meningoencephalitis and rhombencephalitis). The detection of SARS-CoV-2 RNA and specific immunoglobulins in the CSF can be used for neuroCOVID-19 confirmation. Additionally, CXCL-10 in the CSF may contribute to the diagnosis and monitoring of neuroCOVID-19.

Background: Nurses play a pivotal role in combating antimicrobial resistance (AMR). However, the success of local and national AMR containment efforts hinges on the knowledge, attitude, and practice (KAP) of nursing staff and undergraduate students. Objectives: This study aims to explore the determinants of nurses' KAP regarding AMR, offering insights to control the emergence and spread of drug-resistant pathogens. Methods: This cross-sectional, multicenter survey involving Italian nurses, nursing students, and healthcare professionals was conducted administering an anonymous online questionnaire focusing on AMR. The median score of 12 was taken as the cutoff for "good KAP." The association between study variables and good KAP was assessed using chi-square or t-tests, followed by multivariable logistic regression analysis for statistically significant ( p < 0.05) variables. Findings: Among 848 participants, 61.9% ( n = 525) were students, and 39.6% ( n = 336) scored as having "low KAP." High KAP was associated with being female and studying AMR independently. Conversely, living in southern Italy and receiving AMR training from pharmaceutical companies were associated with low KAP. Conclusions: Among Italian nurses, AMR awareness relies on those who have studied AMR as self-taught and is affected by gender and region. Italian universities lack in lectures on AMR management, and much needs to be done to improve awareness of antimicrobial stewardship among nonmedical health workers., Competing Interests: The authors have no competing interests to declare., (Copyright: © 2024 The Author(s).)

Emergency general surgeons often provide care to severely ill patients requiring surgical interventions and intensive support. One of the primary drivers of morbidity and mortality is perioperative bleeding. In general, when addressing life threatening haemorrhage, blood transfusion can become an essential part of overall resuscitation. However, under all circumstances, indications for blood transfusion must be accurately evaluated. When patients decline blood transfusions, regardless of the reason, surgeons should aim to provide optimal care and respect and accommodate each patient's values and target the best outcome possible given the patient's desires and his/her clinical condition. The aim of this position paper was to perform a review of the existing literature and to provide comprehensive recommendations on organizational, surgical, anaesthetic, and haemostatic strategies that can be used to provide optimal peri-operative blood management, reduce, or avoid blood transfusions and ultimately improve patient outcomes., (© 2024. The Author(s).)

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease due to gradual motoneurons (MN) degeneration. Among the processes associated to ALS pathogenesis, there is the formation of cytoplasmic inclusions produced by aggregation of mutant proteins, among which the RNA binding protein FUS. Here we show that, in neuronal cells and in iPSC-derived MN expressing mutant FUS, such inclusions are significantly reduced in number and dissolve faster when the RNA m 6 A content is diminished. Interestingly, stress granules formed in ALS conditions showed a distinctive transcriptome with respect to control cells, which reverted to similar to control after m 6 A downregulation. Notably, cells expressing mutant FUS were characterized by higher m 6 A levels suggesting a possible link between m 6 A homeostasis and pathological aggregates. Finally, we show that FUS inclusions are reduced also in patient-derived fibroblasts treated with STM-2457, an inhibitor of METTL3 activity, paving the way for its possible use for counteracting aggregate formation in ALS., (© 2024. The Author(s).)

There is a need for implementation and maturation of an inclusive trauma system in every country in Europe, with patient centered care by dedicated surgeons. This process should be initiated by physicians and medical societies, based on the best available evidence, and supported and subsequently funded by the government and healthcare authorities. A systematic approach to organizing all aspects of trauma will result in health gain in terms of quality of care provided, higher survival rates, better functional outcomes and quality of life. In addition, it will provide reliable data for both research, quality improvement and prevention programs. Severely injured patients need surgeons with broad technical and non-technical competencies to provide holistic, inclusive and compassionate care. Here we describe the philosophy of the surgical approach and define the necessary skills for trauma, both surgical and other, to improve outcome of severely injured patients. As surgery is an essential part of trauma care, surgeons play an important role for the optimal treatment of trauma patients throughout and after their hospital stay, including the intensive care unit (ICU). However, in most European countries, it might not be obvious to either the general public, patients or even the physicians that the surgeon must assume this responsibility in the ICU to optimize outcomes. The aim of this paper is to define key elements in terms of trauma systems, trauma-specific surgical skills and active critical care involvement, to organize and optimize trauma care in Europe., (© 2022. The Author(s).)

Introduction: Fixation of major fractures plays a pivotal role in the surgical treatment of polytrauma patients. In addition to ongoing discussions regarding the optimal timing in level I trauma centers, it appears that the respective trauma systems impact the implementation of both, damage control and safe definitive surgery strategies. This study aimed to assess current standards of polytrauma treatment in a Europe-wide survey., Methods: A survey, developed by members of the polytrauma section of ESTES, was sent online via SurveyMonkey ® , between July and November 2020, to 450 members of ESTES (European Society of Trauma and Emergency Surgery). Participation was voluntary and anonymity was granted. The questionnaire consisted of demographic data and included questions about the definition of "polytrauma" and the local standards for the timing of fracture fixation., Results: In total, questionnaires of 87 participants (19.3% response rate) were included. The majority of participants were senior consultants (50.57%). The mean work experience was 19 years, and on average, 17 multiple-injured patients were treated monthly. Most of the participants stated that a polytrauma patient is defined by ISS ≥ 16 (44.16%), followed by the "Berlin Definition" (25.97%). Systolic blood pressure < 90 mmHg, tachycardia or vasopressor administration (86.84%), pH deviation, base excess shift (48.68%), and lactate > 4 mmol (40.79%) or coagulopathy defined by ROTEM (40.79%) were the three most often stated indicators for shock. Local guidelines (33.77%) and the S-3 Guideline by the DGU® (23.38%) were mostly stated as a reference for the treatment of polytrauma patients. Normal coagulation (79.69%), missing administration of vasopressors (62.50%), and missing clinical signs of "SIRS" (67.19%) were stated as criteria for safe definite secondary surgery., Conclusion: Different definitions of polytrauma are used in the clinical setting. Indication for and the extent of secondary (definitive) surgery are mainly dependent on the polytrauma patient`s physiology. The «Window of Opportunity» plays a less important role in decision making., (© 2022. The Author(s).)

Mpox is a zoonotic disease historically reported in Africa. Since 2003, limited outbreaks have occurred outside Africa. In 2022, the global spread of cases with sustained interhuman transmission and unusual disease features raised public health concerns. We explore the mpox outbreak in Rio de Janeiro (RJ) state, Brazil, in an observational study of mpox-suspected cases from June to December 2022. Data collection relied on a public healthcare notification form. Diagnosis was determined by MPXV-PCR. In 46 confirmed cases, anti-OPXV IgG was determined by ELISA, and seven MPXV genomes were sequenced. A total of 3095 cases were included, 816 (26.3%) with positive MPXV-PCR results. Most positive cases were men in their 30 s and MSM. A total of 285 (34.9%) MPXV-PCR+ patients live with HIV. Eight were coinfected with varicella-zoster virus. Anogenital lesions and adenomegaly were associated with the diagnosis of mpox. Females and individuals under 18 represented 9.4% and 5.4% of all confirmed cases, respectively, showing higher PCR cycle threshold (Ct) values and fewer anogenital lesions compared to adult men. Anti-OPXV IgG was detected in 29/46 (63.0%) patients. All analyzed sequences belonged to clade IIb. In RJ state, mpox presented a diverse clinical picture, represented mainly by mild cases with low complication rates and prominent genital involvement. The incidence in females and children was higher than usually reported. The observation of a bimodal distribution of Ct values, with few positive results, may suggest the need to review the diagnostic criteria in these groups., (© 2024 Wiley Periodicals LLC.)

Dealing with acute cholecystitis in high-risk, critically ill, and unfit-for-surgery patients is frequent during daily practice and requires complex management. Several procedures exist to postpone and/or prevent surgical intervention in those patients who temporarily or definitively cannot undergo surgery. After a systematic review of the literature, an expert panel from the Italian Society of Emergency Surgery and Trauma (SICUT) discussed the different issues and statements in subsequent rounds. The final version of the statements was discussed during the annual meeting in Rome (September 2022). The present paper presents the definitive conclusions of the discussion. Fifteen statements based on the literature evidence were provided. The statements gave precise indications regarding the decisional process and the management of patients who cannot temporarily or definitively undergo cholecystectomy for acute cholecystitis. Acute cholecystitis management in high-risk, critically ill, and unfit-for-surgery patients should be multidisciplinary. The different gallbladder drainage methods must be tailored according to each patient and based on the expertise of the hospital. Percutaneous gallbladder drainage is recommended as the first choice as a bridge to surgery or in severely physiologically deranged patients. Endoscopic gallbladder drainage (cholecystoduodenostomy and cholecystogastrostomy) is suggested as a second-line alternative especially as a definitive procedure for those patients not amenable to surgical management. Trans-papillary gallbladder drainage is the last option to be reserved only to those unfit for other techniques. Delayed laparoscopic cholecystectomy in patients with percutaneous gallbladder drainage is suggested in all those patients recovering from the conditions that previously discouraged surgical intervention after at least 6 weeks from the gallbladder drainage., (© 2023. Italian Society of Surgery (SIC).)

Since the association between frailty and difficulty in finding venous access (VA) is largely unexplored and unclear in geriatrics, the aim of this study is to demonstrate how multidimensional frailty is associated with bad VA in a population of older hospitalized people. Multidimensional Prognostic Index (MPI), based on eight different domains usually assessed in comprehensive geriatric assessment, was used for identifying multidimensional frailty; VA heritage was investigated using a questionnaire prepared by a trained nurse, based on clinical experience. Overall, 145 patients were included (mean age 78.6 ± 7.6; males 51.0%). Frailer people, identified as an MPI >0.66 (MPI 3), had a significantly higher presence of bad VA (49.0% vs. 27.3% in MPI 3 and MPI 1 groups, p  = 0.045), no success at first attempt (49.0% vs. 22.7% in MPI 3 and MPI 1 groups, p  = 0.03), reported more frequently pain during VA attempts (63.3% in MPI 3 vs. 27.3 in MPI 1, p  = 0.002), and significantly higher scores in the Numeric Rating Scale compared to their robust counterparts. Taking robust participants in MPI 1 as reference, after adjusting for potential confounders, frailer people (MPI 3) were at increased odds of bad VA (odds ratio [OR] = 2.72; 95% confidence interval [CI]: 1.16-6.41; p  = 0.02), not success at first attempt (OR = 3.67; 95% CI: 1.09-12.57; p  = 0.04), and presence of pain during VA attempt (OR = 4.26; 95% CI: 1.30-13.92; p  = 0.02). In conclusion, our study demonstrated an association between multidimensional frailty and bad VA in a population of older hospitalized people.

Aims: In the EXPLORER-HCM trial, mavacamten reduced left ventricular outflow tract obstruction (LVOTO) and improved functional capacity of symptomatic hypertrophic obstructive cardiomyopathy (HOCM) patients. We sought to define the potential use of mavacamten by comparing real-world HOCM patients with those enrolled in EXPLORER-HCM and assessing their eligibility to treatment., Methods and Results: We collected information on HOCM patients followed up at 25 Italian HCM outpatient clinics and with significant LVOTO (i.e. gradient ≥30 mmHg at rest or ≥50 mmHg after Valsalva manoeuvre or exercise) despite pharmacological or non-pharmacological therapy. Pharmacological or non-pharmacological therapy resolved LVOTO in 1044 (61.2%) of the 1706 HOCM patients under active follow-up, whereas 662 patients (38.8%) had persistent LVOTO. Compared to the EXPLORER-HCM trial population, these real-world HOCM patients were older (62.1 ± 14.3 vs. 58.5 ± 12.2 years, p = 0.02), had a lower body mass index (26.8 ± 5.3 vs. 29.7 ± 4.9 kg/m 2 , p < 0.0001) and a more frequent history of atrial fibrillation (21.5% vs. 9.8%, p = 0.027). At echocardiography, they had lower left ventricular ejection fraction (LVEF, 66 ± 7% vs. 74 ± 6%, p < 0.0001), higher left ventricular outflow tract gradients at rest (60 ± 27 vs. 52 ± 29 mmHg, p = 0.003), and larger left atrial volume index (49 ± 16 vs. 40 ± 12 ml/m 2 , p < 0.0001). Overall, 324 (48.9%) would have been eligible for enrolment in the EXPLORER-HCM trial and 339 (51.2%) for treatment with mavacamten according to European guidelines., Conclusions: Real-world HOCM patients differ from the EXPLORER-HCM population for their older age, lower LVEF and larger atrial volume, potentially reflecting a more advanced stage of the disease. About half of real-world HOCM patients were found eligible to mavacamten., (© 2023 The Authors. European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

In hemodynamically stable adults sustaining a splenic trauma, non-operative management (NOM) represents the standard approach even in high-severity injuries. However, knowledge, structural, and logistic limitations still reduce its wider diffusion. This study aims to identify such issues to promote the safe and effective management of these injuries.A survey was developed using the SurveyMonkey ® software and spread nationally in Italy. The survey was structured into: (1) Knowledge of classification systems; (2) Availability to refer patients; (3) Patients monitoring and follow-up; (4) Center-related.The survey was filled in by 327 surgeons, with a completeness rate of 63%. Three responders out of four are used to manage trauma patients. Despite most responders knowing the existing classifications, their use is still limited in daily practice. If a patient needs to be centralized, the concern about possible clinical deterioration represent the main obstacle to achieving a NOM. The lack of protocols does not allow standardization of patient surveillance according to the degree of injury. The imaging follow-up is not standardized as well, varying between computed tomography, ultrasound, and contrast-enhanced ultrasound.The classification systems need to be spread to all the trauma-dedicated physicians, to speak a common language. A more rational centralization of patients should be promoted, ideally through agreements between peripheral and reference centers, both at regional and local level. Standardized protocols need to be shared nationally, as well as the clinical and imaging follow-up criteria should be adapted to the local features., (© 2023. Italian Society of Surgery (SIC).)

Biomolecular condensates serve as membrane-less compartments within cells, concentrating proteins and nucleic acids to facilitate precise spatial and temporal orchestration of various biological processes. The diversity of these processes and the substantial variability in condensate characteristics present a formidable challenge for quantifying their molecular dynamics, surpassing the capabilities of conventional microscopy. Here, we show that our single-photon microscope provides a comprehensive live-cell spectroscopy and imaging framework for investigating biomolecular condensation. Leveraging a single-photon detector array, single-photon microscopy enhances the potential of quantitative confocal microscopy by providing access to fluorescence signals at the single-photon level. Our platform incorporates photon spatiotemporal tagging, which allowed us to perform time-lapse super-resolved imaging for molecular sub-diffraction environment organization with simultaneous monitoring of molecular mobility, interactions, and nano-environment properties through fluorescence lifetime fluctuation spectroscopy. This integrated correlative study reveals the dynamics and interactions of RNA-binding proteins involved in forming stress granules, a specific type of biomolecular condensates, across a wide range of spatial and temporal scales. Our versatile framework opens up avenues for exploring a broad spectrum of biomolecular processes beyond the formation of membrane-less organelles., (© 2023. The Author(s).)

Background: In 2022, an outbreak of mpox that started in European countries spread worldwide through human-to-human transmission. Cases have been mostly mild, but severe clinical presentations have been reported. In these cases, tecovirimat has been the drug of choice to treat patients with aggravated disease., Objectives: Here we investigated the tecovirimat susceptibility of 18 clinical isolates of monkeypox virus (MPXV) obtained from different regions of Brazil., Methods: Different concentrations of tecovirimat were added to cell monolayers infected with each MPXV isolate. After 72 hours, cells were fixed and stained for plaque visualization, counting, and measurement. The ortholog of F13L gene from each MPXV isolate was polymerase chain reaction (PCR)-amplified, sequenced, and the predicted protein sequences were analyzed., Findings: The eighteen MPXV isolates generated plaques of different sizes. Although all isolates were highly sensitive to the drug, two showed different response curves and IC50 values. However, the target protein of tecovirimat, F13 (VP37), was 100% conserved in all MPXV isolates and therefore does not explain the difference in sensitivity., Main Conclusions: Our results support screening different MPXV isolates for tecovirimat susceptibility as an important tool to better use of the restricted number of tecovirimat doses available in low-income countries to treat patients with mpox.

N6-Methyladenosine (m 6 A) is well-known for controlling different processes of linear RNA metabolism. Conversely, its role in the biogenesis and function of circular RNAs (circRNAs) is still poorly understood. Here, we characterize circRNA expression in the pathological context of rhabdomyosarcoma (RMS), observing a global increase when compared to wild-type myoblasts. For a set of circRNAs, such an increase is due to the raised expression of the m 6 A machinery, which we also find to control the proliferation activity of RMS cells. Furthermore, we identify the RNA helicase DDX5 as a mediator of the back-splicing reaction and as a co-factor of the m 6 A regulatory network. DDX5 and the m 6 A reader YTHDC1 are shown to interact and to promote the production of a common subset of circRNAs in RMS. In line with the observation that YTHDC1/DDX5 depletion reduces RMS proliferation, our results provide proteins and RNA candidates for the study of rhabdomyosarcoma tumorigenicity., (© 2023. The Author(s).)

Long noncoding RNAs (lncRNAs) are emerging as critical regulators of heart physiology and disease, although the studies unveiling their modes of action are still limited to few examples. We recently identified pCharme, a chromatin-associated lncRNA whose functional knockout in mice results in defective myogenesis and morphological remodeling of the cardiac muscle. Here, we combined Cap-Analysis of Gene Expression (CAGE), single-cell (sc)RNA sequencing, and whole-mount in situ hybridization analyses to study pCharme cardiac expression. Since the early steps of cardiomyogenesis, we found the lncRNA being specifically restricted to cardiomyocytes, where it assists the formation of specific nuclear condensates containing MATR3, as well as important RNAs for cardiac development. In line with the functional significance of these activities, pCharme ablation in mice results in a delayed maturation of cardiomyocytes, which ultimately leads to morphological alterations of the ventricular myocardium. Since congenital anomalies in myocardium are clinically relevant in humans and predispose patients to major complications, the identification of novel genes controlling cardiac morphology becomes crucial. Our study offers unique insights into a novel lncRNA-mediated regulatory mechanism promoting cardiomyocyte maturation and bears relevance to Charme locus for future theranostic applications., Competing Interests: VT, GB, FD, AS, TS, SG, LS, DM, GF, VV, SS, EP, CN, AM, MB No competing interests declared, (© 2023, Taliani, Buonaiuto et al.)

Background: The American College of Surgeons NSQIP surgical risk calculator provides an estimation of 30-day postoperative adverse outcomes. It is useful in the identification of high-risk patients needing clinical optimization and supports the informed consent process. The purpose of this study is to validate its predictive value in the Italian emergency setting., Study Design: Six Italian institutions were included. Inclusion diagnoses were acute cholecystitis, appendicitis, gastrointestinal perforation or obstruction. Areas under the receiving operating characteristic curves, Brier score, Hosmer-Lemeshow index, and observed-to-expected event ratio were measured to assess both discrimination and calibration. Effect of the Surgeon Adjustment Score on calibration was then tested. A patient's personal risk ratio was obtained, and a cutoff was chosen to predict mortality with a high negative predicted value., Results: A total of 2,749 emergency procedures were considered for the analysis. The areas under the receiving operating characteristic curve were 0.932 for death (0.921 to 0.941, p < 0.0001; Brier 0.041) and 0.918 for discharge to nursing or rehabilitation facility (0.907 to 0.929, p < 0.0001; 0.070). Discrimination was also strong (area under the receiving operating characteristic curve >0.8) for renal failure, cardiac complication, pneumonia, venous thromboembolism, serious complication, and any complication. Brier score was informative (<0.25) for all the presented variables. The observed-to-expected event ratios were 1.0 for death and 0.8 for discharge to facility. For almost all other variables, there was a general risk underestimation, but the use of the Surgeon Adjustment Score permitted a better calibration of the model. A risk ratio >3.00 predicted the onset of death with sensitivity = 86%, specificity = 77%, and negative predicted value = 99%., Conclusions: The American College of Surgeons NSQIP surgical risk calculator has proved to be a reliable predictor of adverse postoperative outcomes also in Italian emergency settings, with particular regard to mortality. We therefore recommend the use of the surgical risk calculator in the multidisciplinary care of patients undergoing emergency abdominal surgery., (Copyright © 2022 by the American College of Surgeons. Published by Wolters Kluwer Health, Inc. All rights reserved.)