High-quality Evidence Research Articles

Cracking the silent gallstone code: Wait or operate?

The widespread availability of abdominal ultrasound has revealed the common occurrence of asymptomatic gallstones. While the treatment for symptomatic gallstones is clear, the benefits of minimally invasive laparoscopic cholecystectomy have sparked debate about the best approach to managing silent gallstones. The potential for asymptomatic gallstones to become symptomatic or lead to complications complicates the decision-making process regarding surgical intervention, as it's uncertain when or which patients might develop complications. Consequently, risk stratification appears to play a critical role in guiding decisions about silent gallstones. However, there is no definitive evidence to direct management, and a consensus-based on high-quality evidence is yet to be established.

Start with muscle mass or muscle strength in diagnosis and management of sarcopenia? A systematic review of guidance documents.

Sarcopenia has garnered extensive attention in clinical practice since its high prevalence and significant impact on clinical outcomes. Multiple organizations have published guidance documents on sarcopenia, offering evidence-based recommendations for clinical practice and/or research. We aimed to appraise the methodological quality of the included documents and synthesize available recommendations for the screening, diagnosis, and intervention of sarcopenia. We conducted a search on PubMed, Embase, Scopus, Cochrane Library, China National Knowledge Infrastructure, guideline database, and guideline organizations and professional societies websites for clinical practices, consensus statements and position papers in terms of sarcopenia, muscle atrophy or muscle loss published before April 17, 2023. The AGREE II instrument was used by three independent reviewers to assess the methodological quality of these documents. Thirty-six guidance documents published between 2010 and 2023 were included. Seven documents fulfilled ≥ 50% of all the AGREE II domains. Seven underwent a Delphi process and six graded the strength of the recommendations. The process of screening (n=21), early diagnosis of sarcopenia (n=12), diagnosis of sarcopenia and severe sarcopenia (n=10), and management (n=21) were increasingly recommended. SARC-F (n=14) was the most recommended screening tool, and the assessment of muscle function was considered the first step in diagnosing sarcopenia. The management strategy for both age-related and disease-related sarcopenia mainly focused on exercise and nutrition intervention. The guidance documents have provided referential recommendations that have great guiding significance. But the inconsistency in recommendations and variation in methodological rigour suggests that high-quality evidence is lacking yet.

The Management of Elevated Blood Pressure in the Acute Care Setting: A Scientific Statement From the American Heart Association.

Over the past 3 decades, a substantial body of high-quality evidence has guided the diagnosis and management of elevated blood pressure (BP) in the outpatient setting. In contrast, there is a lack of comparable evidence for guiding the management of elevated BP in the acute care setting, resulting in significant practice variation. Throughout this scientific statement, we use the terms acute care and inpatient to refer to care received in the emergency department and after admission to the hospital. Elevated inpatient BP is common and can manifest either as asymptomatic or with signs of new or worsening target-organ damage, a condition referred to as hypertensive emergency. Hypertensive emergency involves acute target-organ damage and should be treated swiftly, usually with intravenous antihypertensive medications, in a closely monitored setting. However, the risk-benefit ratio of initiating or intensifying antihypertensive medications for asymptomatic elevated inpatient BP is less clear. Despite this ambiguity, clinicians prescribe oral or intravenous antihypertensive medications in approximately one-third of cases of asymptomatic elevated inpatient BP. Recent observational studies have suggested potential harms associated with treating asymptomatic elevated inpatient BP, which brings current practice into question. Despite the ubiquity of elevated inpatient BPs, few position papers, guidelines, or consensus statements have focused on improving BP management in the acute care setting. Therefore, this scientific statement aims to synthesize the available evidence, provide suggestions for best practice based on the available evidence, identify evidence-based gaps in managing elevated inpatient BP (asymptomatic and hypertensive emergency), and highlight areas requiring further research.

Progress of circulating tumor DNA methylation for gastric cancer screening and management

Circulating tumor DNA (ctDNA) is cell-free DNA released by tumors or circulating tumor cells, containing abundant tumor-specific information that can serve as biomarkers for cancer early screening, monitoring, prognosis, and prediction of treatment response. This is particularly attractive in the field of gastric cancer, where high-quality screening, monitoring, and prediction methods are currently lacking. Gastric cancer exhibits significant tumor heterogeneity, with large differences in genetic and epigenetic characteristics among different subgroups. Methylated ctDNA has high sensitivity and specificity, which can help clarify tumor genotyping and facilitate the formulation of precise diagnostic and therapeutic strategies. Furthermore, numerous studies have confirmed the unique advantages of methylated DNA in predicting treatment response, adjuvant therapy, and drug resistance assessment, which may be used in the future to enhance the efficacy of chemotherapy regimens and improve patient chemotherapeutic response, and even treat multidrug resistance. However, there are several challenges associated with methylated ctDNA, such as low sensitivity and specificity at single-target sites, limited association between some gastric cancer subtypes and ctDNA, off-target risks, and the lack of large-scale and high-quality clinical research evidence. This review mainly summarizes current research on the methylation status of ctDNA in gastric cancer and connects these findings to early screening, recurrence monitoring, and potential treatment opportunities for gastric cancer. With advances in technology and the deepening of interdisciplinary research, ctDNA detection will reveal more disease information and become an essential foundation for gastric cancer research and precision medicine treatment.

Management of impacted fetal head at cesarean birth: A systematic review and meta-analysis.

Despite increasing incidence of impacted fetal head at cesarean birth and associated injury, it is unclear which techniques are most effective for prevention and management. A high quality evidence review in accordance with international reporting standards is currently lacking. To address this gap, we aimed to identify, assess, and synthesize studies comparing techniques to prevent or manage impacted fetal head at cesarean birth prior to or at full cervical dilatation. We searched MEDLINE, Emcare, Embase and Cochrane databases up to 1 January 2023 (PROSPERO: CRD420212750016). Included were randomized controlled trials (any size) and non-randomized comparative studies (n ≥ 30 in each arm) comparing techniques or adjunctive measures to prevent or manage impacted fetal head at cesarean birth. Following screening and data extraction, we assessed risk of bias for individual studies using RoB2 and ROBINS-I, and certainty of evidence using GRADE. We synthesized data using meta-analysis where appropriate, including sensitivity analyses excluding data published in potential predatory journals or at risk of retraction. We identified 24 eligible studies (11 randomized and 13 non-randomized) including 3558 women, that compared vaginal disimpaction, reverse breech extraction, the Patwardhan method and/or the Fetal Pillow®. GRADE certainty of evidence was low or very low for all 96 outcomes across seven reported comparisons. Pooled analysis mostly showed no or equivocal differences in outcomes across comparisons of techniques. Although some maternal outcomes suggested differences between techniques (e.g., risk ratio of 3.41 [95% CI: 2.50-4.66] for uterine incision extension with vaginal disimpaction vs. reverse breech extraction), these were based on unreliable pooled estimates given very low GRADE certainty and, in some cases, additional risk of bias introduced by data published in potential predatory journals or at risk of retraction. The current weaknesses in the evidence base mean that no firm recommendations can be made about the superiority of any one impacted fetal head technique over another, indicating that high quality training is needed across the range of techniques. Future studies to improve the evidence base are urgently required, using a standard definition of impacted fetal head, agreed maternal and neonatal outcome sets for impacted fetal head, and internationally recommended reporting standards.

Managing idiopathic intracranial hypertension in the eye clinic.

Idiopathic intracranial hypertension (IIH) is a neuro-ophthalmological condition characterised by a raised intracranial pressure and papilloedema that causes disabling headaches. The main risk factors of female sex and living with obesity have been known for some time, however the knowledge of the underlying pathophysiology is evolving. Papilloedema can impact the visual function, and the majority of people are offered acetazolamide. Those with sight threatening disease need urgent management, though there is little high quality evidence to recommend any particular surgical intervention. Headache treatment is an unmet clinical need and simple medication overuse advice has the potential to reduce the chronification of migraine-like headaches. IIH is emerging as a systemic metabolic disease distinct from people living with obesity alone. While weight loss is the main stay of disease modifying therapy this is challenging to access and many healthcare professionals that manage the condition have no formal training or accessible pathways for weight management. The aim of this "how to do it" article is to present the latest advances in knowledge of IIH that we pragmatically included in routine clinical care for people living with the condition.

#2153 Difelikefalin: a new solution against itching in CKD-aP patients

Abstract Background and Aims Chronic kidney disease-associated pruritus (CKD-aP) is one of the most common and burdensome symptom affecting patients with advanced chronic kidney disease, with an estimated prevalence of 53.3%. The clinical presentation is extremely variable, from minor lesions to true scratch injuries, and significantly affects the patient's quality of life (QoL), sleep quality and mood, as well as being associated with increased mortality. At present, high-quality evidence on which to base treatment is limited. Currently proposed first-line therapeutic options include optimization of dialysis treatment, emollient agents, UVB light, antihistamines, gabapentin and pregabalin. Recently difelikefalin, a k-opioid receptor agonist, has been the first Food and Drug Administration (FDA) approved drug for moderate-severe CKD-aP treatment. The aim of our study is to demonstrate the efficacy of this drug in relieving symptoms in CKD-aP patients. Method For this preliminary retrospective observational study, 19 patients (9 females, 10 males) with CKD-aP performing dialysis at our Dialysis Center were recruited. All of them had appropriate Kt/V values and had previously been treated with first-line medications. The other main demographic and clinical characteristics of our population, such as calcium-phosphate metabolism and inflammation's indexes, can be seen in Table 1. Our population underwent the Worst Itch Numeric Rating Scale (WI-NRS) by which the presence, intensity, and impact on sleep of this symptom were investigated. They also were subjected to questions that investigate their quality of life (SF-PCS12, SF-MCS12). All patients completed those questionnaires before starting Difelikefalin treatment (t0) and after one month of treatment (t1), 15 of them were evaluated also after three months (t3) and 10 patients, those who first started therapy, reached the assessment at six months (t6). Results Statistical analysis of our preliminary study shows very encouraging data regarding the efficacy of difelikefalin on CKD-aP and sleep quality. As shown in Table 2, we recorded a significant decrease (p value <.001, ƞ2 0.552) in the intensity of itching, most noticeable in the first month, confirming that the effect of this drug is evident and considerable already after four weeks. Our data also demonstrate a significant and lasting positive effect of difelikefalin on sleep quality (p value 0.006, ƞ2 0.592), as shown in Table 3. We found no significant data on the improvement in the QoL of the patients in the study, probably due to the difficulty in standardising this complex feature and due to the limited size of the statistical sample. Furthermore, it should be considered that 3 of the patients enrolled in the study had to discontinue the medication due to the onset of side effects such as diarrhea and headache. Conclusion The most influential limitation of this retrospective observational study is the small number of recruited patients, in addition to the fact that not all of them reached a 6-months treatment evaluation. Our aim is to complete the study by enrolling a larger number of patients from our Dialysis Centre and to monitor the effect of difelikefalin during a longer treatment period, in order to achieve a more accurate analysis and significative results applicable on a larger scale. As far as we can currently evaluate, this drug is significantly effective in reducing CKD-aP and thus in improving the quality of sleep.

Efficacy of acupuncture treatment for breast cancer-related insomnia: study protocol for a multicenter randomized controlled trial

BackgroundInsomnia is one of the most common symptoms among breast cancer patients, which can be present throughout all stages of breast cancer. As a non-pharmacological alternative treatment, acupuncture has been suggested to improve sleep situations in patients with cancer suffering from insomnia. However, there is a lack of well-designed, high-quality clinical evidence regarding the efficacy of acupuncture in the treatment of breast cancer-related insomnia. This study is conducted to evaluate the efficacy and safety of acupuncture treatment for breast cancer-related insomnia.MethodsThis study was designed as a multicenter, randomized, sham-controlled clinical trial. A total of 264 eligible patients with breast cancer-related insomnia will be randomized into an acupuncture group and a sham acupuncture group in a 1:1 ratio. In the trial, patients in the acupuncture and sham acupuncture groups will receive 12 sessions over a consecutive 4-week period. The primary outcome will be the treatment response rate of Insomnia Severity Index (ISI) at week 4; secondary outcomes include treatment remission rate of ISI, Sleep Efficiency (SE) obtained by the use of Sleep diary, treatment response rate of ISI at 8th and 16th weeks of follow-up, the mean changes of ISI, Generalized Anxiety Disorder Scale (GAD-7), Patient Health Questionnaire-9 (PHQ-9), Quality of Life Questionnaire - Core 30 (QLQ-C30), sleep parameters recorded in Actigraphy and weekly usage of remedial drugs. Adverse events will be recorded throughout the study. All analyses will be based on the ITT principle and performed with SAS 9.4 statistical software.DiscussionThis trial will evaluate the clinical efficacy and safety of acupuncture for breast cancer-related insomnia. If proven effective, acupuncture will provide an effective option for patients with breast cancer-related insomnia, which will play a positive role in helping patients reduce their use of sleeping medications.Clinical trial registrationClinicalTrials.gov, identifier NCT05510700.

Association of physical activity pattern and risk of Parkinson’s disease

Increasing evidence suggests an association between exercise duration and Parkinson’s disease. However, no high-quality prospective evidence exists confirming whether differences exist between the two modes of exercise, weekend warrior and equal distribution of exercise duration, and Parkinson’s risk. Hence, this study aimed to explore the association between different exercise patterns and Parkinson’s risk using exercise data from the UK Biobank. The study analyzed data from 89,400 UK Biobank participants without Parkinson’s disease. Exercise data were collected using the Axivity AX3 wrist-worn triaxial accelerometer. Participants were categorized into three groups: inactive, regularly active, and engaged in the weekend warrior (WW) pattern. The relationship between these exercise patterns and Parkinson’s risk was assessed using a multifactorial Cox model. During a mean follow-up of 12.32 years, 329 individuals developed Parkinson’s disease. In a multifactorial Cox model, using the World Health Organization–recommended threshold of 150 min of moderate-to-vigorous physical activity per week, both the active WW group [hazard ratio (HR) = 0.58; 95% confidence interval (CI) = 0.43–0.78; P < 0.001] and the active regular group (HR = 0.44; 95% CI = 0.34–0.57; P < 0.001) exhibited a lower risk of developing Parkinson’s disease compared with the inactive group. Further, no statistically significant difference was observed between the active WW and the active regular groups (HR = 0.77; 95% CI = 0.56–1.05; P = 0.099). In conclusion, in this cohort study, both the WW exercise pattern and an equal distribution of exercise hours were equally effective in reducing Parkinson’s risk.

#2576 Effect of dialysis versus conservative care on all-cause mortality in older patients with advanced CKD: nationwide Swedish cohort study

Abstract Background and Aims Conservative care is emerging as an alternative to dialysis in older patients with advanced chronic kidney disease (CKD). However, high-quality evidence comparing the effect of dialysis versus conservative care on patient survival is lacking. Previous observational studies suffered from avoidable biases, such as immortal time bias and lead time bias, and adjusted for limited confounders. This study aimed to assess the effects of dialysis versus conservative care on mortality in older patients with advanced CKD. Method The target trial emulation framework was used to design and analyze this observational study. We conducted a nationwide observational cohort study using data from the Swedish Renal Registry between 2007-2021. We included all nephrologist-referred patients with eGFR &amp;lt; 20 ml/min/1.73 m2 who had a registered decision for dialysis or conservative care. Eligible patients were required to be ≥ 65 years with a Davies Comorbidity Score ≥ 2 or ≥ 80 years. The primary endpoint was 5-year all-cause mortality. Inverse probability of treatment weighting was used to adjust for 50 baseline confounders, including demographics, comorbidities, medication use, blood pressure, laboratory measurements, hospitalizations, and calendar year. Patients in the non-overlapping region of the propensity score distribution were excluded since they had an absolute indication for dialysis or conservative care. Cox proportional hazards regression was used to estimate intention-to-treat hazard ratios (HRs) with 95% confidence intervals (CIs), and the Kaplan-Meier estimator was used to estimate absolute risks. Additionally, we calculated the 5-year restricted mean survival times (RMST) and the 5-year RMST difference between dialysis and conservative care arms. To test the robustness and consistency of our main results, we performed a subgroup analysis in patients aged ≥80. Results Of 2834 eligible patients, 1903 had a registered choice for dialysis and 931 for conservative care. The median age was 81 years, 36.1% were female and median eGFR was 13.1 ml/min/1.73 m2. During the 5-year follow-up period, 29 conservative care patients started dialysis and 430 patients died before starting dialysis. After weighting, all confounders were balanced (standardized mean difference &amp;lt; 0.10). Compared to dialysis, conservative care was associated with a higher absolute 5-year risk of death (91.8% vs. 74.1%), corresponding with an absolute risk difference of 17.6% (95% CI 13.3%-21.9%) (Fig. 1). The adjusted hazard ratio for conservative care vs. dialysis was 2.3 (95% CI 2.0-2.6). The 5-year restricted mean survival times were 34.8 (95% CI 33.2-37.3) months for dialysis and 21.5 (95% CI 19.4-23.6) months for conservative care groups. The 5-year RMST difference was 13.3 months (95% CI 10.8-16.6), meaning that dialysis patients would live on average 13.3 months longer over a 5-year follow-up period than conservative care patients (Table 1). The results were consistent among people ≥ 80 years (adjusted HR 2.2, 95% CI 1.9-2.5; 5-year RMST difference 9.4 months, 95% CI 7.2-13.9). Conclusion In older patients with advanced CKD under nephrologist care, conservative care was associated with a higher risk of mortality than dialysis. These findings could improve the shared decision-making process with patients on the choice of kidney failure treatment.

#2139 Non-lupus full house nephropathy: a debatable entity

Abstract Background and Aims The presence of a full house (FH) pattern at immunofluorescence on kidney biopsy in a patient without clinical and laboratory features of systemic lupus erythematosus (SLE) has led to the descriptive term non-lupus full house nephropathy (NLFHN). This systematic review and meta-analysis focus on NLFHN nomenclature, clinical findings and outcomes. Method In a reiterative process, all identified terms for NLFHN and other MeSH terms were searched in PubMed. Out of 344 results, 57 records published between 1982 and 2022 were included in the analysis. Clinical data of single patients from different reports were collected and analysed. Results Out of the 57 records, 61% were case reports. NLFHN was addressed with 17 different names; the same name used by different authors could refer to different entities. We identified 148 patients: 75 (51%) were males; median age 35 (23-58) years. Serum creatinine and proteinuria at onset were 1.4 (0.8-2.5)mg/dL and 5.7 (2.7-8.8)g/day. Overall, about half of patients achieved complete response. A causative agent was identified in 51 (44%) patients, predominantly infections(41%). Secondary NLFHN was mostly non-relapsing with worse kidney function at onset compared to idiopathic NLFHN (P = 0.001). Among the 57 (50%) patients with idiopathic NLFHN, complete response was comparable between patients treated with immunosuppression and supportive therapy; however, proteinuria and creatinine at onset were higher in patients treated with immunosuppression (P = 0.089 and P = 0.066). The remaining 7 (6%) patients developed SLE after a median follow-up of 5.0 (1.9-9.0) years. Conclusion The place of NLFHN among glomerular diseases is still uncertain, due to the lack of high-quality evidence and consensus on nomenclature. NLFHN can be evaluated as initial manifestation of SLE, isolated manifestation of SLE or a new disease unrelated to SLE. Data support the classification of SLE and NLFHN as distinct clinical entities, with comparable outcome. However, RCTs are needed to drive strong conclusions on treatments and outcomes.

Review of evidence for treatments of acute non arteritic anterior ischemic optic neuropathy.

To review treatment modalities that have been studied in acute nonarteriticanterior ischemic optic neuropathy (NAION). We performed a comprehensive literature search of English language publications in the last 5 years, with human species and NAION. Articles were reviewed to identify those that described original research on treatment of acute NAION. Study type, setting, duration, interventions, and results were extracted and articles were reviewed for biases and limitations. We identified 22 kinds of treatment varying by compound and modality. These include topical, intravitreal, and systemic drugs as well as surgical approaches. Evidence for efficacy ranges from expert opinion to randomized control trials. Although several treatments are utilized in practice, none of these have high quality evidence of efficacy to improve visual outcomes. Continued collaborative research is necessary to complete high quality studies in order identify effective therapies for this rare and blinding disease.

Factors contributing to sepsis-associated encephalopathy: a comprehensive systematic review and meta-analysis

BackgroundThis study aims to systematically assess the risk factors, the overall strength of association, and evidence quality related to sepsis-associated encephalopathy.MethodsA systematic search was conducted in the Cochrane Library, PubMed, Web of Science, and Embase for cohort or case-control studies published up to August 2023 on risk factors associated with sepsis-related encephalopathy. The selected studies were screened, data were extracted, and the quality was evaluated using the Newcastle–Ottawa Scale. Meta-analysis was performed using RevMan 5.3 software. The certainty of the evidence was assessed using the GRADE criteria.ResultsA total of 13 studies involving 1,906 participants were included in the analysis. Among these studies, 12 were of high quality, and one was of moderate quality. Our meta-analysis identified six risk factors significantly associated with Serious Adverse Events (SAE). These included APACHE II, SOFA, age, tau protein, and IL-6, which were found to be risk factors with significant effects (standard mean difference SMD: 1.24–2.30), and albumin, which was a risk factor with moderate effects (SMD: −0.55). However, the certainty of evidence for the risk factors identified in this meta-analysis ranged from low to medium.ConclusionThis systematic review and meta-analysis identified several risk factors with moderate to significant effects. APACHE II, SOFA, age, tau protein, IL-6, and albumin were associated with sepsis-related encephalopathy and were supported by medium- to high-quality evidence. These findings provide healthcare professionals with an evidence-based foundation for managing and treating hospitalized adult patients with sepsis-related encephalopathy.

Bioactive Compounds from Medicinal Plants as Potential Adjuvants in the Treatment of Mild Acne Vulgaris

In recent years, there has been a growing interest in the use of medicinal plants and phytochemicals as potential treatments for acne vulgaris. This condition, characterized by chronic inflammation, predominantly affects adolescents and young adults. Conventional treatment typically targets the key factors contributing to its development: the proliferation of Cutibacterium acnes and the associated inflammation. However, these treatments often involve the use of potent drugs. As a result, the exploration of herbal medicine as a complementary approach has emerged as a promising strategy. By harnessing the therapeutic properties of medicinal plants and phytochemicals, it may be possible to address acne vulgaris while minimizing the reliance on strong drugs. This approach not only offers potential benefits for individuals seeking alternative treatments but also underscores the importance of natural remedies of plant origin in dermatological care. The primary aim of this study was to assess the antimicrobial, antioxidant, and anti-inflammatory properties of plants and their phytochemical constituents in the management of mild acne vulgaris. A comprehensive search of scientific databases was conducted from 2018 to September 2023. The findings of this review suggest that medicinal plants and their phytochemical components hold promise as treatments for mild acne vulgaris. However, it is crucial to note that further research employing high-quality evidence and standardized methodologies is essential to substantiate their efficacy and safety profiles.

A systematic literature review of clinical evidence and treatment burden in newly diagnosed high-risk pediatric patients with classical Hodgkin lymphoma.

This systematic literature review evaluated frontline treatment burden in pediatric and adolescent/young adult (AYA) patients with high-risk classical Hodgkin lymphoma (cHL) among studies originating from the United States. Data were extracted from 32 publications (screened: total, n=3115; full-text, n=98) representing 12 studies (randomized controlled trials [RCTs], n=2; non-comparative, non-randomized, n=7; observational, n=3). High-risk disease definitions varied across studies. Five-year event-free survival (EFS)/progression-free survival (PFS) was 86%-100% and 79%-94%, and complete response rates were 35%-100% and 5%-64% for brentuximab vedotin (BV)-containing and chemotherapy-alone regimens, respectively. In identified RCTs, BV-containing compared with chemotherapy-alone regimens demonstrated significantly longer 3-year EFS/5-year PFS. Hematological and peripheral neuropathy were the most commonly reported adverse events of interest, although safety data were inconsistently reported. Few studies evaluated humanistic and no studies evaluated economic burden. Results from studies with the highest quality of evidence indicate an EFS/PFS benefit for frontline BV-containing versus chemotherapy-alone regimens for pediatric/AYA patients with high-risk cHL.

Superiority trial for the development of an ideal method for the closure of midline abdominal wall incisions to reduce the incidence of wound complications after elective gastroenterological surgery: study protocol for a randomized controlled trial

BackgroundThe recent guidelines from the European and American Hernia Societies recommend a continuous small-bite suturing technique with slowly absorbable sutures for fascial closure of midline abdominal wall incisions to reduce the incidence of wound complications, especially for incisional hernia. However, this is based on low-certainty evidence. We could not find any recommendations for skin closure. The wound closure technique is an important determinant of the risk of wound complications, and a comprehensive approach to prevent wound complications should be developed.MethodsWe propose a single-institute, prospective, randomized, blinded-endpoint trial to assess the superiority of the combination of continuous suturing of the fascia without peritoneal closure and continuous suturing of the subcuticular tissue (study group) over that of interrupted suturing of the fascia together with the peritoneum and interrupted suturing of the subcuticular tissue (control group) for reducing the incidence of midline abdominal wall incision wound complications after elective gastroenterological surgery with a clean-contaminated wound. Permuted-block randomization with an allocation ratio of 1:1 and blocking will be used. We hypothesize that the study group will show a 50% reduction in the incidence of wound complications. The target number of cases is set at 284. The primary outcome is the incidence of wound complications, including incisional surgical site infection, hemorrhage, seroma, wound dehiscence within 30 days after surgery, and incisional hernia at approximately 1 year after surgery.DiscussionThis trial will provide initial evidence on the ideal combination of fascial and skin closure for midline abdominal wall incision to reduce the incidence of overall postoperative wound complications after gastroenterological surgery with a clean-contaminated wound. This trial is expected to generate high-quality evidence that supports the current guidelines for the closure of abdominal wall incisions from the European and American Hernia Societies and to contribute to their next updates.Trial registrationUMIN-CTR UMIN000048442. Registered on 1 August 2022. https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000055205

Infective Pleural Effusions-A Comprehensive Narrative Review Article.

Infective pleural effusions are mainly represented by parapneumonic effusions and empyema. These conditions are a spectrum of pleural diseases that are commonly encountered and carry significant mortality and morbidity rates reaching upwards of 50%. The causative etiology is usually an underlying bacterial pneumonia with the subsequent seeding of the infectious culprit and inflammatory agents to the pleural space leading to an inflammatory response and fibrin deposition. Radiographical evaluation through a CT scan or ultrasound yields high specificity and sensitivity, with features such as septations or pleural thickening indicating worse outcomes. Although microbiological yields from pleural studies are around 56% only, fluid analysis assists in both diagnosis and prognosis by evaluating pH, glucose, and other biomarkers such as lactate dehydrogenase. Management centers around antibiotic therapy for 2-6 weeks and the drainage of the infected pleural space when the effusion is complicated through tube thoracostomies or surgical intervention. Intrapleural enzymatic therapy, used to increase drainage, significantly decreases treatment failure rates, length of hospital stay, and surgical referrals but carries a risk of pleural hemorrhage. This comprehensive review article aims to define and delineate the progression of parapneumonic effusions and empyema as well as discuss pathophysiology, diagnostic, and treatment modalities with aims of broadening the generalist's understanding of such complex disease by reviewing the most recent and relevant high-quality evidence.

Comparison of apixaban versus aspirin for the prevention of latent bioprosthetic aortic valve thrombosis: study protocol for a prospective randomized trial.

The optimal antithrombotic strategy early after aortic valve replacement surgery with a biological valve remains controversial due to lack of high-quality evidence. Either oral anticoagulants or acetylsalicylic acid should be considered for the first 3 months. Hypo-attenuated leaflet thickening on cardiac computed tomography has been associated with latent bioprosthetic valve thrombosis and may be prevented with anticoagulation. We hypothesize that anticoagulation with apixaban is superior to single antiplatelet therapy with acetylsalicylic acid in reducing hypo-attenuated leaflet thickening of bioprosthetic aortic valve prostheses. In this prospective, open-label, randomized trial, patients undergoing isolated aortic valve replacement surgery with rapid deployment bioprosthetic valves will be randomized. The treatment group will receive 5 mg of apixaban twice a day for the first 3 months and 100 mg of acetylsalicylic acid thereafter. The control group will be administered 100 mg of acetylsalicylic acid once a day, indefinitely. After the 3-month treatment period, a contrast-enhanced electrocardiogram-gated cardiac computed tomography will be performed to identify hypo-attenuated leaflet thickening of the bioprosthetic valve. The primary objective of the study is to assess the impact of apixaban on the prevention of hypo-attenuated leaflet thickening at 3 months. The secondary and exploratory endpoints will be clinical outcomes and safety profiles of the two strategies. Antithrombotic therapy after aortic valve replacement is used to prevent valve thrombosis and systemic thromboembolism. Latent bioprosthetic valve thrombosis is a precursor of clinically significant prosthetic valve dysfunction or thromboembolic events. The hallmark feature of latent bioprosthetic valve thrombosis is hypo-attenuated leaflet thickening on cardiac computed tomography. Subclinical leaflet thrombosis occurs frequently in bioprosthetic aortic valves, more commonly in transcatheter than in surgical valves. There is no evidence on the effect of direct oral anticoagulants on the incidence of hypo-attenuated leaflet thickening after surgical aortic valve replacement with rapid deployment bioprostheses. ClinicalTrials.gov NCT06184113. Registered on December 28, 2023.

European Stroke Organisation (ESO) Guidelines on the diagnosis and management of patent foramen ovale (PFO) after stroke.

Patent foramen ovale (PFO) is frequently identified in young patients with cryptogenic ischaemic stroke. Potential stroke mechanisms include paradoxical embolism from a venous clot which traverses the PFO, in situ clot formation within the PFO, and atrial arrhythmias due to electrical signalling disruption. The purpose of this guideline is to provide recommendations for diagnosing, treating, and long-term managing patients with ischaemic stroke and PFO. Conversely, Transient Ischaemic Attack (TIA) was not considered an index event in this context because only one RCT involved TIA patients. However, this subgroup analysis showed no significant differences between TIA and stroke outcomes. The working group identified questions and outcomes, graded evidence, and developed recommendations following the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach and the European Stroke Organisation (ESO) standard operating procedure for guideline development. This document underwent peer-review by independent experts and members of the ESO Guideline Board and Executive Committee. The working group acknowledges the current evidentiary gap in delineating an unequivocal diagnostic algorithm for the detection of PFO. Although transoesophageal echocardiography is conventionally held as the most accurate diagnostic tool for PFO identification, its status as the 'gold standard' remains unsubstantiated by rigorously validated evidence. We found high-quality evidence to recommend PFO closure plus antiplatelet therapy in selected patients aged 18-60 years in whom no other evident cause of stroke is found but a PFO (i.e. PFO-associated stroke). The PASCAL classification system can be used to select such candidates for PFO closure. Patients with both a large right-to-left shunt and an atrial septal aneurysm benefit most from PFO closure. There is insufficient evidence to make an evidence-based recommendation on PFO closure in patients older than 60 and younger than 18 years. We found low quality evidence to suggest against PFO closure in patients with unlikely PFO-related stroke according to the PASCAL classification, except in specific scenarios (Expert Consensus). We suggest against long-term anticoagulation in patients with PFO-associated stroke unless anticoagulation is indicated for other medical reasons. Regarding the long-term AF monitoring after PFO closure, the working group concluded that there remains significant uncertainty regarding the risks and benefits associated with the use of long-term cardiac monitoring, such as implantable loop recorders. This document provides additional guidance, in the form of evidence-based recommendations or expert consensus statements, on diagnostic methods for PFO detection, and medical management after PFO closure.

Management of childbearing with hypermobile Ehlers-Danlos syndrome and hypermobility spectrum disorders: A scoping review and expert co-creation of evidence-based clinical guidelines.

To co-create expert guidelines for the management of pregnancy, birth, and postpartum recovery in the context of hypermobile Ehlers-Danlos syndrome (hEDS) and hypermobility spectrum disorders (HSD). Scoping Review and Expert Co-creation. United Kingdom, United States of America, Canada, France, Sweden, Luxembourg, Germany, Italy, and the Netherlands. Co-creators (n = 15) included expertise from patients and clinicians from the International Consortium on the Ehlers-Danlos syndromes and Hypermobility Spectrum Disorders, facilitated by the Ehlers-Danlos Society. A scoping review using Embase, Medline, the Cochrane Central Register of Controlled Trials and CINHAL was conducted from May 2022 to September 2023. Articles were included if they reported primary research findings in relation to childbearing with hEDS/HSD, including case reports. No language limitations were placed on our search, and our team had the ability to translate and screen articles retrieved in English, French, Spanish, Italian, Russian, Swedish, Norwegian, Dutch, Danish, German, and Portuguese. The Mixed Methods Appraisal Tool was used to assess bias and quality appraise articles selected. The co-creation of guidelines was based on descriptive evidence synthesis along with practical and clinical experience supported by patient and public involvement activities. Primary research studies (n = 14) and case studies (n = 21) including a total of 1,260,317 participants informed the co-creation of guidelines in four overarching categories: 1) Preconceptual: conception and screening, 2) Antenatal: risk assessment, management of miscarriage and termination of pregnancy, gastrointestinal issues and mobility, 3) Intrapartum: risk assessment, birth choices (mode of birth and intended place of birth), mobility in labor and anesthesia, and 4) Postpartum: wound healing, pelvic health, care of the newborn and infant feeding. Guidelines were also included in relation to pain management, mental health, nutrition and the common co-morbidities of postural orthostatic tachycardia syndrome, other forms of dysautonomia, and mast cell diseases. There is limited high quality evidence available. Individualized strategies are proposed for the management of childbearing people with hEDS/HSD throughout pregnancy, birth, and the postpartum period. A multidisciplinary approach is advised to address frequently seen issues in this population such as tissue fragility, joint hypermobility, and pain, as well as common comorbidities, including dysautonomia and mast cell diseases.