Optimal Timing Of Intervention Research Articles

Bronchopleural fistula management in a pediatric patient requiring extracorporeal membrane oxygenation.

Bronchopleural fistula (BPF) is a connection between the bronchus and pleural cavity. It is associated with high morbidity and mortality and management of BPF has not been well described in the pediatric population. We describe a 2-year-old girl who presented with fever and increased work of breathing, found to have atypical hemolytic uremic syndrome and Streptococcus necrotizing pneumonia with development of persistent air leak due to bronchopleural fistulas requiring extracorporeal membrane oxygenation (ECMO). Three endobronchial valves were placed with successful resolution of bronchopleural fistulas. She required tracheostomy for chronic respiratory failure and endobronchial valves were eventually removed. Approximately 3.5 months after discharge to acute care rehabilitation, tracheostomy was successfully decannulated. This case highlights the successful use of endobronchial valves for resolution of BPF while on ECMO as well as the importance of further studies on optimal candidates, timing and duration of intervention in addition to sequelae of endobronchial valve placement.

Targeted Verifiable Subcision for Management of Cellulite on the Buttock and Thigh: Incorporation Into Real-World Lower Body Rejuvenation Approaches

Abstract Background Cellulite affects 80 to 98% of post-pubertal females, and most patients with the condition are bothered by it. Targeted Verifiable Subcision™ (TVS; Avéli® [Revelle Aesthetics, Inc., Mountain View, CA]) is a minimally invasive mechanical subcision device which reduces the appearance of cellulite dimples in the buttocks and thighs. While clinical trials have demonstrated efficacy, information on real-world, surgical and non-surgical approaches on the buttocks and thighs is needed. Objectives To describe how TVS is being used by the authors to improve patient outcomes in the lower body in both the surgical and non-surgical setting. Methods Each of the authors described their current practices using TVS for lower body rejuvenation. Author practices have varied proportions of surgical vs. non-surgical cases (from 10 to 100% surgical cases) and a variety of focuses, ranging from primarily facial aesthetics to near exclusive focus on body contouring. Results The authors’ diverse approaches to integrating TVS into clinical practice are detailed, along with pearls for clinical success. TVS is discussed as a companion treatment for surgical procedures, while the patient is already under anesthesia, as well as part of a non-surgical approach, where the local anesthesia required for TVS can make additional energy-based procedures more comfortable for the patient. The authors provide several examples and include considerations for optimal timing and ordering of treatments. Conclusions TVS may become a valuable addition to the treatment armamentarium for surgical or nonsurgical buttock and thigh rejuvenation and can be integrated into surgical and non-surgical workflows.

Association between Gastric Cancer and Osteoporosis: A Longitudinal Follow-Up Study Using a National Health Sample Cohort.

Gastric cancer (GC) survivors may be more likely to develop osteoporosis. However, few studies on the relationship between GC and osteoporosis have been conducted on large patient populations. We aimed to determine the incidence of osteoporosis and identify related factors by comparing patients with GC and matched controls using the Korean National Health Insurance Service-National Sample Cohort (KNHIS-NSC). This study included 9078 patients with GC and 36,312 controls (1:4 propensity score-matched for sex, age, residence, and income). The hazard ratio (HR) for osteoporosis was significantly greater for GC patients than for controls according to Charlson Comorbidity Index (CCI) score-adjusted models (adjusted HR = 1.13). Kaplan-Meier analysis revealed that the cumulative incidence of osteoporosis during the follow-up period commencing from the index date was significantly greater in GC patients than in the controls (p = 0.0087). A positive correlation of osteoporosis with GC was detected for those aged < 65 years, males, and those with CCI scores = 0. In conclusion, the study findings suggest that men with GC aged < 65 years may be at an increased risk for osteoporosis. Research into additional risk factors and the optimal timing of interventions are needed to prevent fractures and minimize bone loss in GC survivors.

What interventions are effective in reducing development of hypertension and other cardiovascular complications in women who have had hypertensive disorders of pregnancy? A systematic review.

Hypertensive disorders of pregnancy (HDP) affect approximately 10-15% of pregnancies and pre-eclampsia affects 3-5% of pregnancies. Women with previous pre-eclampsia or HDP are at increased risk of hypertension (2 to 5 times) and major cardiovascular disease (1.5 to 3 times). There is little guidance on how to reduce this risk. To establish if there are interventions in women with previous HDP or pre-eclampsia that reduce the risk of developing adverse cardiovascular outcomes. A protocol was submitted to PROSPERO; inclusion and exclusion criteria were determined and a search strategy implemented. Primary outcomes were: development of hypertension or change in blood pressure and development of other cardiovascular complications. Records and full texts were screened independently by two reviewers. The Cochrane Risk of Bias tool was used for quality assessment. 3593 articles were screened. Nine articles were included. There were seven randomised-controlled trials and two quasi-experimental studies. One study trialled antihypertensive use, two studies looked at blood pressure monitoring and six studies focused on lifestyle interventions. Three trials reported significant reductions in diastolic blood pressure in the experimental group. No studies looked at the optimal time of intervention or the impact of interventions on the development of other long-term cardiovascular complications. Five studies reported participant feedback. The majority of studies were of low quality. Further research needs to explore potential interventions and optimal timing of interventions to reduce cardiovascular risk. Women also need to be consulted about their preferences for discussions about cardiovascular risk and potential interventions.

Structural Violence, Gender, and Post 9-11 Terrorism in Pakistan: Examining the Psychological Impact on the Parents of Army Public School attacks in Pakistan

This study seeks to explore the gender – specific impact of post-9/11 terrorismacts inPakistan, with a particular focus on the parents of the children killed in the terrorist attacks on Army Public School in Peshawar, in 2014. The paper dwells deep intoexploring how the parents have been impacted and examines the many ways by whichthe victims have devised coping strategies in response to traumatic events. This studyuses Galtung’s structural violence theory as a theoretical framework to examine the psychological impact on the parents, with structural violence in this context referring topost-9/11 terrorism acts in Pakistan. This study adopted a sequential exploratory design. By using a stratified random sampling technique, a total of 216 participants were selected, comprising 133 Direct Victims and 83 Indirect Victims. Data collectioninvolved a mixed method approach - both quantitative and qualitative analyses. Primarydata was collected through structured interviews and a standardized questionnaire called Lieber’s scale of Post-Traumatic Stress Disorder (PTSD) to measure the level of post-traumatic stress. Subsequent processing and tabulation followed by statistical examination to assess the psychological impact of post-9/11 terrorism in Peshawar. Finding indicates that the symptoms of PTSD were still evident among all participants even after nine years of terrorist attack. Participants who were directly exposed totrauma displayed more symptoms of psychological distress as compared to those whowere indirectly exposed. The results also indicate a surprising and rather significant development in gender focused research with male parents exhibiting significantly highlevel of PTSD in comparison to women victims. Observations from the primary data showing men demonstrating higher level of PTSD, brings interesting propositions togender research, where explorations around the social and psychological aspects of masculinity, and the multifaceted roles played by men around gender empowerment may prompt intriguing inquiries into gender research. Furthermore, it is recommendedthat future research must focus on factors that should not only identify the optimal timing for PTSD treatment, but also explore factors that can bring natural recovery. Moreover, the research also facilitates the policy recommendation for development work as well as those agencies including, the government, local and international aidorganizations working in the areas affected by violence.

The influence of psychosocial factors on first-time chemotherapy-induced nausea and vomiting: A prospective multicenter cohort study.

12135 Background: Previous studies have suggested that if cancer patients experience no chemotherapy-induced nausea and vomiting (CINV) or mild symptoms during their first chemotherapy cycle, they are less likely to experience CINV in subsequent cycles, suggesting that the optimal intervention time may be before the first chemotherapy cycle. Consequently, attention should be paid to relevant risk factors. Currently, there is a lack of data on psychosocial risk factors related to chemotherapy among cancer patients in China. Methods: This study was a multicenter, prospective cohort study that included cancer patients from seven hospitals' oncology departments who were scheduled to undergo their first chemotherapy cycle. The chemotherapy regimens administered were either highly or moderately emetogenic protocols. Demographic and baseline clinical characteristics were recorded by clinical oncologists. Participants were asked to complete the Distress Thermometer (DT), the Mini-Mental Adjustment to Cancer (Mini-MAC), and a risk factor questionnaire the day before chemotherapy, and to keep a daily diary describing their CINV experiencing for 21 days after chemotherapy. Results: Between October 2022 and November 2023, a total of 1100 cancer patients were enrolled in this study and 972 cancer patients completed all the questionnaires. A total of 64.1% reported CINV during the first chemotherapy cycle. In logistic regression analysis, CINV was predicted by higher PS score (OR=1.411, p=0.049), highly emetogenic regimens (OR=1.846, p=0.004), failure to follow anti-emetics guidelines (OR=2.323, p&lt;0.001), history of nausea/vomiting for other reasons(OR=1.817, p=0.001), lower number of hours slept before the night of chemotherapy (OR=8.987, p&lt;0.001), expectancy of CINV(OR=1.505, p=0.032), maladaptive coping (OR = 1.03, p = 0.024) and distress (OR = 1.157, p =0.021). Conclusions: Psychosocial factors significantly correlate with chemotherapy-induced nausea and vomiting (CINV) among Chinese cancer patients. These findings underscore the importance of integrating psychosocial assessments into the management of CINV, potentially improving treatment outcomes and patient experiences.

Identification of symptom clusters and sentinel symptoms during the first cycle of chemotherapy in patients with lung cancer

PurposeTo identify symptom clusters (SCs) in patients with lung cancer who are undergoing initial chemotherapy and to identify the sentinel symptoms of each SC.MethodsA convenience sampling method was used to recruit patients with lung cancer who were undergoing their initial chemotherapy treatment. Patient information was collected using the General Demographic Questionnaire, MD Anderson Symptom Inventory (including the lung cancer module) and a schedule documenting the initial occurrence of symptoms. The Walktrap algorithm was employed to identify SCs, while sentinel symptoms within each SC were identified using the Apriori algorithm in conjunction with the initial occurrence time of symptoms.ResultsA total of 169 patients with lung cancer participated in this study, and four SCs were identified: the psychological SC (difficulty remembering, sadness, dry mouth, numbness or tingling, and distress), somatic SC (pain, fatigue, sleep disturbance, and drowsiness), respiratory SC (coughing, expectoration, chest tightness, and shortness of breath), and digestive SC (nausea, poor appetite, constipation, vomiting, and weight loss). Sadness, fatigue, and coughing were identified as sentinel symptoms of the psychological, somatic, and respiratory SCs, respectively. However, no sentinel symptom was identified for the digestive SC.ConclusionPatients with lung cancer who are undergoing chemotherapy encounter a spectrum of symptoms, often presenting as SCs. The sentinel symptom of each SC emerges earlier than the other symptoms and is characterized by its sensitivity, significance, and driving force. It serves as a vital indicator of the SC and assumes a sentry role. Targeting sentinel symptoms might be a promising strategy for determining the optimal timing of interventions and for mitigating or decelerating the progression of the other symptoms within the SC.

Progression of swine fecal microbiota during early stages of life and its association with performance: a longitudinal study

BackgroundIt is vital to understand healthy gut microbiota composition throughout early life stages when environments are changing, and immunity is developing. There are limited large-scale longitudinal studies classifying healthy succession of swine microbiota. The objectives of this study were to (a) determine the microbiota composition of fecal samples collected from piglets within a few days after birth until one-week post-weaning, and (b) investigate the associations of early fecal microbiota with pig growth performance in nursery and later growing stages. Fecal samples were collected from nine cohorts of 40 pigs (n = 360) from distinct farrowing sources in Ontario and Quebec, Canada at four timepoints from birth to one-week post-weaning, with pig body weight was recorded at each fecal sampling.ResultsMicrobiota was dominated by the phyla Firmicutes, Bacteroides and Proteobacteria. There were notable differences in genera abundance between pigs from different provinces and farming systems. Over the early life stage, the genera Bacteroides, Escherichia/Shigella, and Clostridium cluster XIVa were abundant preweaning, while Prevotella dominated post-weaning. Hierarchical clustering identified three major stages of microbiota development, each associated with distinct composition. Stage one occurs from birth to 7 days, stage two from 7 days after birth until weaning, and stage three from weaning to one-week post-weaning. Three enterotypes were identified in stage two that showed differences in growth before weaning, and in the grower production stage. Piglets with a microbiota enterotype characterized by higher abundance of Prevotella and unclassified Ruminococcaceae had lower growth performance in the pre-weaning stage, and the growing stage.ConclusionThese findings help identify the timing of microbiota shifts across early swine life which may be the optimal time for external intervention to shift the microbiota to a beneficial state. The project findings should help decrease antimicrobial use, increase animal welfare, and have positive economic impacts.

Does the Timing of Surgical Intervention Impact Outcomes in Necrotizing Enterocolitis?

The optimal time for intervention in surgical necrotizing enterocolitis (sNEC) remains to be elucidated. Surgical management varies between peritoneal drain (PD), laparotomy (LAP), and PD with subsequent LAP (PD + LAP). We propose that some infants with surgical NEC benefit from late (>48h) operative intervention to allow for resuscitation. A retrospective comparison of clinical information in infants with sNEC from 2012 to 2022 was performed. Early intervention was defined as less than 48 hours from time of NEC diagnosis to surgical intervention. 118 infants were identified, 92 underwent early intervention (62 LAP; 22 PD; 8 PD + LAP) and 26 underwent late intervention (20 LAP; 2 PD; 4 PD + LAP). Infants with early intervention were diagnosed younger (DOL 8 [6, 15] vs 20 [11, 26]; P=< .05) with more pneumoperitoneum (76% vs 23%; P=< .05). The early intervention group had a higher mortality (35% vs 15%; P=< .05). When excluding infants with pneumoperitoneum, the early intervention group had a higher mortality rate (10/22 (45%), 4/26 (15%); P < .05) and had more bowel resected (29 ± 17cm vs 9 ± 8cm; P < .05), with the same number of patients scoring above 3 on the MD7 criteria. Infants with NEC who underwent early surgical intervention had a higher mortality and more bowel resected. While this study has a provocative finding, it is severely limited by the non-specific 48-hour cut off. However, our data suggests that a period of medical optimization may improve outcomes in infants with sNEC and thus more in-depth studies are needed.

Mapping an intelligent algorithm for predicting female adolescents' cervical vertebrae maturation stage with high recall and accuracy.

The present study was designed to define a novel algorithm capable of predicting female adolescents' cervical vertebrae maturation stage with high recall and accuracy. A total of 560 female cephalograms were collected, and cephalograms with unclear vertebral shapes and deformed scales were removed. 480 films from female adolescents (mean age: 11.5 years; age range: 6-19 years) were used for the model development phase, and 80 subjects were randomly and stratified allocated to the validation cohort to further assess the model's performance. Derived significant predictive parameters from 15 anatomic points and 25 quantitative parameters of the second to fourth cervical vertebrae (C2-C4) to establish the ordinary logistic regression model. Evaluation metrics including precision, recall, and F1 score are employed to assess the efficacy of the models in each identified cervical vertebrae maturation stage (iCS). In cases of confusion and mispredictions, the model underwent modification to improve consistency. Four significant parameters, including chronological age, the ratio of D3 to AH3 (D3:AH3), anterosuperior angle of C4 (@4), and distance between C3lp and C4up (C3lp-C4up) were administered into the ordinary regression model. The primary predicting model that implements the novel algorithm was built and the performance evaluation with all stages of 93.96% for accuracy, 93.98% for precision, 93.98% for recall, and 93.95% for F1-score were obtained. Despite the hybrid logistic-based model achieving high accuracy, the unsatisfactory performance of stage estimation was noticed for iCS3 in the primary cohort (89.17%) and validation cohort (85.00%). Through bivariate logistic regression analysis, the posterior height of C4 (PH4) was further selected in the iCS3 to establish a corrected model, thus the evaluation metrics were upgraded to 95.83% and 90.00%, respectively. An unbiased and objective assessment of the cervical vertebrae maturation (CVM) method can function as a decision-support tool, assisting in the evaluation of the optimal timing for treatment in growing adults. Our novel proposed logistic model yielded individual formulas for each specific CVM stage and attained exceptional performance, indicating the capability to function as a benchmark for maturity evaluation in clinical craniofacial orthopedics for Chinese female adolescents.

A CLINICAL REVIEW OF DIAGNOSTIC BIOMARKERS AND THE ROLE OF THE GUT MICROBIOTA IN PRETERM INFANTS WITH NECROTIZING ENTEROCOLITIS

The purpose of this work is to clarify the latest opinions of clinicians about the pathogenesis, diagnosis and treatment of necrotic enterocolitis, as well as the role of microflora in the pathogenesis of this pathology. Material and methods. Search Strategy: A literature search was conducted in the following electronic databases: PubMed, Web of Science (Thomson Reuters), Scopus, Cochrane Library, SpringerLink, and EBSCOhost ScienceDirect. The search spanned 20 years, from 2000 to 2020. In this review, we included 39 articles on this topic, which were available in full text and analyzed through critical evaluation. Results.According to the literature, necrotizing enterocolitis is primarily attributed to prematurity, compounded by the disruption of intestinal microflora composition due to artificial feeding, leading to an inflammatory reaction in the immature intestine. Delayed detection of the initial signs of necrotizing enterocolitis exacerbates treatment outcomes. In clinical practice, two main dilemmas in necrotizing enterocolitis diagnosis arise. Firstly, distinguishing early necrotizing enterocolitis from sepsis can be challenging, resulting in delayed diagnosis and treatment. Secondly, the optimal timing for surgical intervention remains unclear. Conclusion. There is a need to elucidate the latest opinions of clinicians regarding the pathogenesis, diagnosis, and treatment of necrotizing enterocolitis, including the role of microflora in its pathogenesis. Treatment strategies should integrate various models of clinical prognosis and biomarkers to accurately diagnose and tailor therapy for necrotizing enterocolitis.

Aortic Regurgitation: From Valvular to Myocardial Dysfunction.

Chronic aortic regurgitation (AR) leads to volume overload in the left ventricle (LV), which is well tolerated for years. In this condition, the LV usually dilates with minimal reduction in the ejection fraction (EF), even in the absence of symptoms. Echocardiography is the primary imaging test used to quantify AR. However, no single assessment of Doppler measures is accurate and precise in individual patients; therefore, the integration of multiple parameters is necessary. Recent guidelines recommend surgical treatment for severe AR in patients who are symptomatic or have an LVEF < 55% and an end-systolic diameter > 50 mm. Nevertheless, advances in imaging technology have improved the quantification of AR and the assessment of LV subclinical dysfunction. It is widely recognized that patients who undergo aortic valve replacement/repair (AVR) due to symptoms or a low LVEF experience worse outcomes than those undergoing AVR for non-Class I indications. In fact, subclinical irreversible myocardial damage may occur in clinically well-compensated and closely monitored patients while awaiting formal surgical indications. This condition could be prevented by the use of multimodal imaging parameters, in particular longitudinal LV strain and magnetic resonance imaging. In addition, better cut-off values for mortality predictors should be established. This review aims to identify simple models that integrate several echocardiographic and cardiac magnetic resonance-derived parameters to predict the optimal timing of surgical treatment in asymptomatic patients with chronic severe AR.

UNRAVELING GENDER DISPARITIES AND PROGNOSTIC INSIGHTS IN MODERATE AORTIC STENOSIS: A RETROSPECTIVE STUDY

Abstract Aortic stenosis (AS) is the most prevalent valvular heart disease in developed countries, associated with reduced survival if severe AS remains untreated. Recent reports note unfavorable outcomes in moderate AS (mAS) patients, challenging optimal intervention timing. Variations in pathophysiology linked to sex differences, involving sex hormones, activation of the renin–angiotensin–aldosterone system, and dysregulation in collagen synthesis, have been observed. Yet, limited data exists on sex–specific differences in mAS outcomes. This single–center, retrospective study included 150 patients (median age 79±13 years, female sex 48%) diagnosed with mAS who underwent comprehensive echocardiography in IRCCS Fondazione Ca’ Granda Ospedale Maggiore Policlinico of Milan from July 2022 to October 2023. Clinical data, encompassing demographics details and therapy, were obtained via record reviews and phone interviews. Death verification relied on the ‘Sistema Informativo Socio–Sanitario Regione Lombardia’ database. Echocardiographic records were digitally stored and post–processed by four independent investigators using Medimatic ComPACS workstation. Men were significantly younger than women (75±10 vs 79±9.7 years, p= 0.016). They exhibited lower left ventricular (LV) ejection fraction, larger LV end–systolic volume and stroke volume compared to women (54±7 vs 59±10%; p=0.028. 55±36 vs 31±13 ml; p&amp;lt;0.001. 83±18 vs 75±18 ml; p=0.030). Men had significantly smaller aortic valve (AV) area index to body surface area (BSA) (0.6±0.09 vs 0.7±0.1 cmq/mq; p&amp;lt;0.001) and lower doppler velocity index (0.32±0.07 vs 0.38±0.11; p&amp;lt;0.001) than women. Coronary artery disease and smoking were more frequent in men (53.3 vs 46.7%; p=0,002. 52.6 vs 47.4%; p&amp;lt;0.001). In survival analysis, 15% of women and 30.8% of men experienced events, with male gender independently associated with the composite outcome (all–cause mortality and AV replacement) over a mean follow–up time of 200 ± 133 days, showing a median survival of 244±16 vs 255±15 days for females (p–value=0.025). In multivariable analysis including relevant clinical variables (hemoglobin and AV index to BSA), male sex remained independently associated with the composite outcome (hazard ratio 2,01; CI 1.0–4.17; p=0.05). Women diagnosed with mAS exhibited a lower incidence of AV replacement and all–cause mortality. These findings may suggest the existence of different clinical and echocardiographic phenotypes among patients with AS.

Assessing Regurgitation Severity, Adverse Remodeling, and Fibrosis with CMR in Primary Mitral Regurgitation.

This review offers an evidence-based analysis of established and emerging cardiovascular magnetic resonance (CMR) techniques used to assess the severity of primary mitral regurgitation (MR), identify adverse cardiac remodeling and its prognostic effect. The aim is to provide different insights regarding clinical decision-making and enhance the clinical outcomes of patients with MR. Cardiac remodeling and myocardial replacement fibrosis are observed frequently in the presence of substantial LV volume overload, particularly in cases with severe primary MR. CMR serves as a useful diagnostic imaging modality in assessing mitral regurgitation severity, early detection of cardiac remodeling, myocardial dysfunction, and myocardial fibrosis, enabling timely intervention before irreversible damage ensues. Incorporating myocardial remodeling in terms of left ventricular (LV) dilatation and myocardial fibrosis with quantitative MR severity assessment by CMR may assist in defining optimal timing of intervention.

Effects of 4-hydroxy-2(3H)-benzoxazolone on proliferation and apoptosis of pancreatic cancer L3.6 cells

This study explored the effects of 4-hydroxy-2(3H)-benzoxazolone(HBOA) on the proliferation and apoptosis of pancreatic cancer cells and its molecular mechanism. The L3.6 cells cultured in vitro were treated with HBOA of 0-1.0 mmol·L~(-1). The cell viability was detected by the cell counting kit-8(CCK-8) method, and the half inhibitory concentration(IC_(50)) was analyzed to determine the drug concentration and time. The cell morphology was observed under an inverted microscope and by acridine orange(AO) staining. The ability of proliferation and self-renewal were evaluated through live cell counting and colony formation experiments. The cell cycle progression and cell apoptosis rate were detected by flow cytometry. The morphology of cell apoptosis was observed by scanning electron microscopy. The mRNA expression of proliferating cell nuclear antigen(PCNA), cyclinA1, cyclinA2, cyclin dependent kinase 2(CDK2), and cyclin dependent kinase inhibitor 1A(P21) were determined by qPCR. The level of reactive oxygen species(ROS), lipid peroxide, and mitochondrial membrane potential were measured by flow cytometry. The activity of protein kinase B(Akt)/mammalian target of rapamycin(mTOR) signaling pathway was detected by Western blot. Compared with the control group, the cells treated with HBOA exhibited a significant decrease in viability. Then the optimal concentration and intervention time of HBOA were determined to be 0.4 mmol·L~(-1), 0.6 mmol·L~(-1), and 48 h. Compared with the control group, groups with HBOA of 0.4 mmol·L~(-1 )and 0.6 mmol·L~(-1) showed a significant suppression in cell proliferation and colony formation ability, down-regulated mRNA of PCNA, cyclinA1, cyclinA2, and CDK2, up-regulated P21 mRNA, S-phase cell cycle arrest, and increased cell apoptosis rate. There was an appearance of apoptotic bodies, increased ROS and lipid peroxide, decreased mitochondrial membrane potential(with a significant decrease in 0.6 mmol·L~(-1) group), and down-regulated p-Akt and p-mTOR proteins. The results show that HBOA inhibits the proliferation of pancreatic cancer L3.6 cells and induces cell apoptosis, which may be related to the increase in reactive oxygen species and the inhibition of the Akt/mTOR pathway.

Comparison of the outcomes of concurrent versus staged TAVR combined with PCI in patients with severe aortic stenosis and coronary artery disease: a systematic review and meta-analysis.

The optimal timing for percutaneous coronary intervention (PCI) in patients undergoing transcatheter aortic valve replacement (TAVR) remains uncertain. This research aims to evaluate the results of patients diagnosed with severe aortic valve stenosis and coronary artery disease who undergo either simultaneous or staged PCI therapy during TAVR procedures. We retrieved all relevant studies from our self-constructed databases up to January 2, 2024, encompassing databases such as Embase, Medline, Cochrane Library, and PubMed. A total of nine studies were included, and the results showed that both surgical modalities had good safety profiles in the early and long-term stages. For early endpoint events, the risk of all-cause mortality and major bleeding within 30 years was similar in the staged TAVR + PCI and the contemporaneous TAVR + PCI (P > 0.05). Additionally, the risk of myocardial infarction, stroke, acute kidney injury and pacemaker implantation within 30 days or perioperatively is similar (P > 0.05). For long-term endpoint events, the risk of all-cause mortality, myocardial infarction and stroke was similar in the two groups at ≥2 years (P > 0.05). In patients undergoing TAVR who required coronary revascularization, no significant differences were observed in the early and long-term outcomes between those receiving concurrent TAVR and PCI versus staged surgery.

Advances in non-invasive treatment of aortic diseases

The current clinical treatment methods for aortic diseases including aortic aneurysm, aortic dissection,etc.,are open surgery and endovascular surgery. Compared to traditional open surgery, endovascular surgery has the advantages of minimal trauma, fast recovery, fewer complications, and better prognosis, which gradually becomes the main trend in the treatment of aortic diseases. However, with the further development and long-term follow-up of endovascular treatment for aortic diseases, increasing evidence shows that in many cases, there are difficulties in the diagnosis of causes, decision-making of treatment timing, and lack of effective evaluation of treatment prognosis in endovascular treatments. Therefore, it is necessary to conduct in-depth research on non-invasive treatment including prevention, diagnosis, treatment, and prediction of aortic diseases. The non-invasive treatment of aortic disease is mainly applied to high-risk populations with aortic dissection, regulating key targets and mechanisms, and adopting drug intervention in advance to achieve the goal of controlling aortic dilation and preventing the occurrence of dissection. Conducting precise multi omics analysis to determine the optimal intervention timing and treatment strategy and targeting complications related to aortic disease or endovascular treatment for patients with a positive family history of aortic dilation or those who have developed aortic dissection. Precise regulation can be achieved to control the progression of aortic aneurysm and aortic dissection, delay or achieve long-term stable coexistence with aortic disease, and even reverse disease progression and achieve benign aortic remodelingthrough new intervention vectors. Ultimately achieving the ideal state of complete thrombosis and mechanized healing of the aortic aneurysm or aortic dissection false lumen.

A strategy based on integer programming for optimal dosing and timing of preventive hypoglycemic treatments in type 1 diabetes management

Background and objectivesOne of the major problems related to type 1 diabetes (T1D) management is hypoglycemia, a condition characterized by low blood glucose levels and responsible for reduced quality of life and increased mortality. Fast-acting carbohydrates, also known as hypoglycemic treatments (HT), can counteract this event. In the literature, dosage and timing of HT are usually based on heuristic rules. In the present work, we propose an algorithm for mitigating hypoglycemia by suggesting preventive HT consumption, with dosages and timing determined by solving an optimization problem. MethodsBy leveraging integer programming and linear inequality constraints, the algorithm can bind the amount of suggested carbohydrates to standardized quantities (i.e., those available in “off-the-shelf” HT) and the minimal distance between consecutive suggestions (to reduce the nuisance for patients). ResultsThe proposed method was tested in silico and compared with competitor algorithms using the UVa/Padova T1D simulator. At the cost of a slight increase of HT consumed per day, the proposed algorithm produces the lowest median and interquartile range of the time spent in hypoglycemia, with a statistically significant improvement over most competitor algorithms. Also, the average number of hypoglycemic events per day is reduced to 0 in median. ConclusionsThanks to its positive performances and reduced computational burden, the proposed algorithm could be a candidate tool for integration in a DSS aimed at improving T1D management.

Association of hemorrhage-to-treatment time with outcomes in patients with brainstem cavernous malformations: a nationwide cohort study.

Brainstem cavernous malformations (BSCMs) often present with haemorrhage, but the optimal timing for microsurgical intervention remains unclear. This study aims to explore how intervention timing relates to neurological outcomes in haemorrhagic BSCM patients undergoing microsurgery, offering insights for clinical decisions. A total of 293 consecutive patients diagnosed with BSCMs, who underwent microsurgery were identified between March 2011 and January 2023 at two comprehensive centres in China, with a postoperative follow-up duration exceeding 6 months. Utilizing logistic regression models with restricted cubic splines, distinct time groups were identified. Subsequently, matching weight analysis compared these groups in terms of outcomes, new haemorrhage rates, cranial nerve deficits, and perioperative complications. The primary outcome was an unfavourable outcome, which was defined as a mRS score greater than 2 at the latest follow-up. Among the 293 patients, 48.5% were female, median age was (39.9±14.3) years, and median haemorrhage-to-treatment time was 42 days. Patients were categorized into acute (≤21days), subacute (22-42days), and delay (>42days) intervention groups. After matching, 186 patients were analyzed. Adjusted analysis showed lower unfavourable outcome rates for acute [adjusted odds ratio (OR), 0.73; 95% CI, 0.65-0.82; P<0.001] and subacute (adjusted OR, 0.83; 95% CI, 0.72-0.95; P=0.007) groups compared to the delay group. Subacute intervention led to fewer cranial nerve deficits (adjusted OR, 0.76; 95% CI, 0.66-0.88, P<0.001). New haemorrhage incidence didn't significantly differ among groups. For haemorrhagic BSCMs patients, delayed microsurgical intervention that exceeded 42 days after a prior haemorrhage were associated with an increased risk of unfavourable neurological outcomes.

Optimal timing of percutaneous coronary intervention for non-ST elevated myocardial infarction with congestive heart failure

ObjectivesThis study investigated the optimal timing for percutaneous coronary intervention (PCI) in patients with NSTEMI complicated by heart failure (HF). MethodsIn total, 762 patients with NSTEMI and HF in a multicenter, prospective registry in South Korea were classified according to the Killip classification (Killip class 2, n = 414 and Killip class 3, n = 348) and underwent early (within 24 h) and delayed (after 24 h) PCI. The primary outcome was all-cause mortality which was further analyzed with landmark analysis with two months as a cut-off. Secondary outcomes were cardiovascular death, in-hospital cardiogenic shock (CS), readmission due to HF, and acute myocardial infarction during follow-up. ResultsDelayed PCI was associated with lower rates of 2-month mortality (6.1 % vs. 15.8 %, p = 0.007) and in-hospital CS (4.3 % vs. 14.1 %, p = 0.003), along with lower risks of 2-month mortality (hazard ratio [HR] = 0.38, 95 % confidence interval [CI] = 0.18–0.83, p = 0.014), in-hospital CS (HR = 0.29, 95 % CI = 0.12–0.71, p = 0.006) in multivariate Cox models of Killip class 3 patients. There was no statistical difference of incidence and risk of all predefined outcomes according to varying timing of PCI in Killip 2 patients. ConclusionsBased on these results, the timing of PCI in patients with NSTEMI complicated by HF should be determined based on HF severity. Delayed PCI should be considered in patients with NSTEMI and more severe HF.