Managing patients with severe symptomatic tricuspid regurgitation (TR) remains extremely challenging, with a lack of consensus on when and how to treat it. Tricuspid valve pathology has been disregarded for a very long time because of the established belief that treating left-sided heart diseases would lead to the resolution or significant improvement of TR. Initially considered benign, severe TR has been found to be a strong predictor of prognosis. Despite the increasing prevalence and the disabling nature of this disease, the great majority of patients with clinically significant TR have seldom been considered for structural interventions. Numerous surgical and transcatheter treatment options are now available; however, optimal timing and procedural selection remain crucial aspects influencing outcomes. According to recent evidence in the literature, early referral is associated with good short and long-term outcomes, and various predictors of favorable outcomes following either surgical or transcatheter treatment have been identified. Evaluation by a multidisciplinary heart team with expertise in tricuspid valve disease is of paramount importance to identify adequate treatment for every patient.

BACKGROUND: Infections caused by multi-drug resistant Gram-negative pathogens are associated with worse clinical outcomes in critically ill patients. We evaluated hospital outcomes based on adequacy of overall and newer antibacterial therapy for Enterobacterales (ENT) and Pseudomonas aeruginosa (PsA) in US patients.
METHODS: Hospitalized adults ≥ 18 years old with facility-reported antibiotic susceptibility from 2018-2022 across 161 facilities in the BD Insights Research Database were identified as ENT- or PsA-positive. Generalized linear mixed models were used to evaluate the impact of inadequate empiric therapy (IET) and time to initiate newer antibacterials (ceftazidime-avibactam; ceftolozane-tazobactam; cefiderocol; meropenem-vaborbactam; eravacycline; and imipenem-cilcastatin-relebactam) on hospital mortality and post-culture length of stay (LOS).
RESULTS: Among 229,320 ENT and 36,027 PsA susceptibility results, 1.7% and 16.8% were carbapenem non-susceptible (carb-NS), respectively. Median time to first susceptibility result was longer for carb-NS vs. carb susceptible in ENT (64 h vs. 48 h) and PsA (67 h vs. 60 h). For ENT, IET was associated with significantly higher mortality (odds ratio [OR],1.29 [95% CI, 1.16-1.43, P < 0.0001]) and longer hospital LOS (14.8 vs. 13.3, P < 0.0001). Delayed start to newer antibacterial therapy was associated with significantly greater hospital mortality for ENT (P = 0.0182) and PsA (P = 0.0249) and significantly longer post-culture LOS for ENT (P < 0.0001) and PsA (P < 0.0001).
CONCLUSIONS: Overall, IET and delayed use of newer antibacterials are associated with significantly worse hospital outcomes. More rapid identification of high-risk patients can facilitate adequate therapy and timely use of newer antibacterials developed for resistant Gram-negative pathogens.

Background: Nitroglycerin is suggested to improve flap survival based on promising results; however, there are no data on the effectiveness of treatment initiation time. This study aimed to compare the effect of various nitroglycerin treatment initiation times on partial flap survival. Materials and Methods: The study included 50 Sprague-Dawley rats. Modified McFarlane flaps were elevated on the dorsum of each rat. Group A received placebo treatment. Groups B, C, D, and E received topical nitroglycerin 2% starting 1 day before surgery, on the day of surgery, postoperative d 2, and postoperative d 4, respectively. After 7 days, the flap survival rates were calculated. Afterward, the severity and extent of inflammation and ischemia, and the severity of edema were evaluated histologically. Results: The flap survival rate was highest in group B, followed by groups C, D, E, and A. The difference between groups B and C was not significant, whereas the difference between group B and groups A, D, and E was. In addition, the difference between groups A, D, and E was not significant. Histological analysis showed that inflammation was less severe in groups B and C than in groups A, D, and E. Ischemia was the most severe in groups A and D and was the least severe in group C. Conclusion: Topical nitroglycerin treatment increases flap survival when initiated before or on the day of surgery, but has no benefit when initiated on postsurgery d 2 or 4. Preoperative initiation of nitroglycerin treatment positively affects flap survival.
Contexte: L’utilisation de la nitroglycérine a été proposée pour améliorer la survie d’un lambeau à partir de résultats prometteurs. Il n’y a cependant aucune donnée sur l’efficacité du délai d’instauration du traitement. Cette étude a visé à comparer l’effet de différents moments d’instauration du traitement avec la nitroglycérine sur la survie d’un lambeau partiel. Matériels et méthodes: L’étude a inclus 50 rats Sprague-Dawley. Des lambeaux modifiés de McFarlane ont été surélevés sur le dos de chaque rat. Le groupe A a reçu un placebo, tandis que les groupes B, C, D et E ont reçu de la nitroglycérine topique à 2% en commençant, respectivement, la veille de la chirurgie, le jour de la chirurgie, 2 jours et 4 jours postopératoires. Les taux de survie du volet ont été calculés après 7 jours. Ensuite, la sévérité et l’étendue de l’inflammation et de l’ischémie ainsi que la sévérité de l’œdème ont été évaluées histologiquement. Résultats: Le taux de survie des volets a été le plus élevé dans le groupe B, suivi des groupes C, D, E et A. La différence entre les groupes B et C n’était pas significative, tandis que la différence entre le groupe B et les groupes A, D et E l’était. En outre, la différence entre les groupes A, et E n’était pas significative. L’analyse histologique a montré que l’inflammation était moins sévère dans les groupes B et C que dans les groupes A, D et E. L’ischémie a été la plus importante dans les groupes A et D et la moins importante dans le groupe C. Conclusion: Le traitement topique avec la nitroglycérine augmente la survie d’un lambeau quand il est commencé le jour de la chirurgie ou avant, mais il n’apporte pas d’avantage s’il est instauré au 2e ou au 4e jour postopératoire. L’instauration d’un traitement par la nitroglycérine en préopératoire a un effet positif sur la survie des lambeaux.

BACKGROUND: There are increased indications that physical activity timing, irrespective of intensity, impacts insomnia and circadian clock function. Here, we describe the rationale and design of a randomized cross-over study, called ON TIME, to examine the effects of (changing) physical activity timing on insomnia severity and on multiple exploratory outcomes that are linked to circadian clock function.
METHODS: We will conduct a randomized cross-over trial in 40 healthy older adults (aged 65 to 75 years) with subclinical or clinical insomnia (Insomnia Severity Index (ISI) scores of ≥ 10) from the Dutch municipality of Leiden and surroundings. Participants will undergo 3 intervention periods (14 days each) consecutively: one sedentary period and two periods of increased physical activity (one period with morning activity and one period with evening activity). The intervention periods are separated by a wash-out period of 1 week. In both active intervention arms, participants will follow coached or uncoached outdoor physical exercise sessions comprising endurance, strength, and flexibility exercises for 14 days. The primary outcome is change in insomnia severity as measured by the ISI. Additional exploratory outcomes include multiple components of objective sleep quality measured with tri-axial accelerometry and subjective sleep quality assessed by questionnaires as well as dim light melatonin onset and 24-h rhythms in heart rate, heart rate variability, breathing rate, oxygen saturation, mood, and objective emotional arousal and stress. Additionally, we will collect diary data on eating patterns (timing and composition). Finally, fasting blood samples will be collected at baseline and after each intervention period for measurements of biomarkers of metabolic and physiological functioning and expression of genes involved in regulation of the biological clock.
CONCLUSIONS: We anticipate that this study will make a significant contribution to the limited knowledge on the effect of physical activity timing. Optimizing physical activity timing has the potential to augment the health benefits of increased physical exercise in the aging population.
BACKGROUND: Trial was approved by the Medical Ethics Committee Leiden, The Hague, Delft, The Netherlands (June, 2023). The trial was registered in the CCMO-register https://www.toetsingonline.nl/to/ccmo_search.nsf/Searchform?OpenForm under study ID NL82335.058.22 and named (\"Ouderen op tijd in beweging\" or in English \"Older adults exercising on time\"). At time of manuscript submission, the trial was additionally registered at ClinicalTrials.gov under study ID: NL82335.058.22 and is awaiting approval.

UNASSIGNED: Patients with non-ST-elevation acute coronary syndrome (NSTE-ACS) consists of a heterogenic population and improvement in identification of a specific risk profile is needed. In this study we aimed to obtain better insight in the role of different biomarkers for patients undergoing a routine invasive diagnostic strategy within 24 hours after admission.
UNASSIGNED: An Immediate or Early Invasive Strategy in Non-ST-Elevation Acute Coronary Syndrome (OPTIMA-2) study was a randomized controlled prospective open-label multicentre trial, randomizing NSTE-ACS patients. An invasive strategy was either immediate ( < 3 hours) or early (12-24 hours). Peak high-sensitive TroponinT (hsTropT) value was determined within the first 48 hours of admission. N-terminal proB-type natriuretic peptide (NTpro-BNP) and high-sensitivity C-reactive protein (hsCRP) values were determined at admission and at discharge. These biomarkers were then divided into tertiles and related to clinical outcomes up to one year. The relation between these biomarkers and myocardial function recovery established by echocardiography was analyzed as a secondary endpoint.
UNASSIGNED: The OPTIMA-2 study included 249 patients. Overall, there was no significant increase in the risk of developing an adverse cardiovascular event in the first year if biomarker tertiles at admission were compared. However, mean NT-proBNP levels at admission were higher for patients that experienced all-cause death withing the first year (1.93 ± 0.49 vs 1.42 ± 0.58, p = 0.05). Also, peak hs-cTnT (232.0 ± 2846.0 vs 71.5 ± 1152.0, p = 0.06) values at baseline were higher in patients experiencing a myocardial infarction within 1-year. NT-proBNP levels at admission and at discharge correlated with recovery of the left ventricular (LV) function at 30 days (coefficient 0.021 (95% CI = 0.009-0.033) and coefficient 0.016 (95% CI = 0.005-0.027)).
UNASSIGNED: In NSTE-ACS patients treated by an early invasive strategy and administration of modern anticoagulant and antiplatelet therapy, multiple biomarker measurements during admission could not predict the occurrence of recurrent cardiovascular events within the first year of follow-up.

The optimal timing for actively discontinuing immune checkpoint inhibitor therapy in long-term responders with recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC) remains unresolved. We conducted a retrospective study of 246 patients with R/M HNSCC treated with nivolumab to determine the optimal timing to actively discontinue nivolumab therapy. We examined the point at which progression-free survival (PFS) plateaued in all cases. We compared the prognosis of 19 (7.7%) ongoing cases and 227 (92.3%) discontinued cases and analyzed treatment duration and treatment-free interval (TFI). The 6-year overall survival was 11.8% (median, 12.1), and the 6-year PFS was 15.3% (median, 3.0). The PFS curve remained stable for 3 years. The median duration of nivolumab treatment was 2.9 months (range 0.03-81.9): Ongoing group, 41.8 (5.6-81.9); Decision group, 36.8 (4.0-70.1); Toxicity group, 30.6 (2.8-64.8); and progressive disease group, 2.0 (0.03-42.9). TFI in the Decision group was 15.1 months (0.6-61.6) and 30.6 months (2.8-64.8) in the Toxicity group. Long-term responses in R/M HNSCC patients treated with nivolumab are rare but gradually increasing. For this patient group, our best estimate of the optimal time to end treatment is 3 years, as the PFS in this study reached a plateau at that timepoint.

UNASSIGNED: Although there have been several studies describing risk factors for complications after outpatient total hip arthroplasty (THA), data describing the timing of such complications is lacking.
UNASSIGNED: Patients who underwent outpatient or inpatient primary THA were identified in the 2012-2019 National Surgical Quality Improvement Program database. For 9 different 30-day complications, the median postoperative day of diagnosis was determined. Multivariable regressions were used to compare the risk of each complication between outpatient vs inpatient groups. Multivariable Cox proportional hazards modeling was used to evaluate the differences in the timing of each adverse event between the groups.
UNASSIGNED: After outpatient THA, the median day of diagnosis for readmission was 12.5 (interquartile range 5-22), surgical site infection 15 (2-21), urinary tract infection 13.5 (6-19.5), deep vein thrombosis 13 (8-21), myocardial infarction 4.5 (1-7), pulmonary embolism 15 (8-25), sepsis 16 (9-26), stroke 2 (0-7), and pneumonia 6.5 (3-10). On multivariable regressions, outpatients had a lower relative risk (RR) of readmission (RR = 0.73), surgical site infection (RR = 0.72), and pneumonia (RR = 0.1), all P < .05. On multivariable cox proportional hazards modeling, there were no statistically significant differences in the timing of each complication between outpatient vs inpatient procedures (P > .05).
UNASSIGNED: The timing of complications after outpatient THA was similar to inpatient procedures. Consideration should be given to lowering thresholds for diagnostic testing after outpatient THA for each complication during the at-risk time periods identified here. Although extremely rare, this is especially important for catastrophic adverse events, which tend to occur early after discharge.

Current scientific literature is deficient in detailing the optimal timing for conducting bariatric surgery in relation to kidney transplantation. In this study, we performed a retrospective evaluation of kidney transplant recipients with BMI >35 kg/m2. It aimed to provide data on those who received both sleeve gastrectomy (SG) and kidney transplantation (KT) simultaneously, as well as on patients who underwent SG and KT at different times, either before or after. In addition, the acceptance levels of the bariatric surgery among different scenarios were assessed. Our findings demonstrated that combined KT and SG led to successful weight loss, in contrast to undergoing kidney transplant alone, while maintaining comparable rates of graft and patient survival. Weight loss was similar between recipients who had a combined operation and those who underwent SG following the transplant. Additionally, over a median time frame of 1.7 years, patients who underwent SG before KT exhibited a statistically significant reduction in BMI at the time of the transplant. Notably, our study highlights that patients offered the combined procedure were significantly more likely to undergo SG compared to those for whom SG was presented at a different operative time than the transplant.

BACKGROUND: The effects of the timing of surgical repair on the outcomes of traumatic and non-traumatic rotator cuff injuries (RCI) remain elusive. Thus, this study aimed to compare differences in outcomes following the repair of traumatic and non-traumatic RCI at varying time points.
METHODS: The study population comprised 87 patients with traumatic and non-traumatic RCI who underwent arthroscopic rotator cuff repair and were followed up for a minimum of 6 months. Next, the trauma and the non-trauma groups were stratified into subgroups according to the time of injury (early repair: occurring within 3 months; delayed repair: occurring after 3 months). Measurements before and after surgical interventions were compared to evaluate the effect of the duration of RCI on the functional status of patients in the trauma and non-trauma groups. Primary evaluation indices included the Visual Analog Scale (VAS) pain score, American Shoulder and Elbow Surgeons (ASES) score, Constant shoulder function score, and the University of California, Los Angeles (UCLA) shoulder score. Secondary evaluation indices consisted of shoulder range of motion (ROM), postoperative rotator cuff retear rate, and incidence of joint stiffness.
RESULTS: Among the 40 patients in the trauma group, 22 underwent early repair, whereas the remaining 18 underwent delayed repair. In the non-trauma group consisting of 47 patients, 18 underwent early repair, whereas the remaining 29 underwent delayed repair. The minimum clinical follow-up time was 6 months, with an average follow-up time of 10.2 months. During postoperative follow-up, 1 and 6 patients who underwent early and delayed repair experienced re-tear in the trauma group, respectively. Contrastingly, 3 and 8 patients who underwent early and delayed repair presented with re-tear in the non-trauma group, respectively.
CONCLUSIONS: Early repair of traumatic RCI yielded superior outcomes, including improved range of motion, lower pain symptoms, and lower risk of postoperative re-tears compared to delayed repair. Additionally, non-surgical treatment is recommended as the preferred approach for patients with non-traumatic RCI.

BACKGROUND: Surgery is often indicated in the treatment of medically recalcitrant chronic rhinosinusitis (CRS). There is conflicting evidence on the impact of timeliness of sinus surgery on the degree of perceived symptom improvement in CRS.
OBJECTIVE: The goal of this study was to systematically evaluate the available literature on the relationship between patient wait times for endoscopic sinus surgery (ESS) and postoperative changes in patient-reported outcome measures.
METHODS: Ovid, MEDLINE, CINAHL, and Cochrane Library of Systematic Reviews between January 2000 and September 1, 2023, were searched. A total of 931 studies were independently screened by 2 reviewers. Two studies were included in the meta-analysis, while 4 others were included in a narrative review.
RESULTS: Two studies consisting of 1606 patients were included in the meta-analysis. A mean difference in 22-Item Sino-Nasal Outcome Test (SNOT-22) of -0.3 (95% CI = -3.9 to 3.3, I2 = 89%, P < .01 was observed between \"long\" and \"short\" groups, while a mean difference in SNOT-22 of -0.1 (95% CI = -2.5 to 2.3, I2 = 80%, P = .03) was observed between \"long\" and \"mid\" groups. Patients who receive surgery earlier on their disease process (ie, earlier from the time of diagnosis to eventual surgery) appear to require less access to healthcare resources including prescription medications, thus suggesting better disease control.
CONCLUSIONS: There is conflicting evidence to conclude whether timing of ESS affects disease-specific measures in patients with CRS. Patients who receive surgery earlier appear to have lower demands on healthcare utilization including visits and prescription use. Our study suggests there is a need for increased access to surgical specialists who manage patients with CRS, and better understanding by primary care specialists in how to manage CRS when specialist access is not available.