On-clamp vs off-clamp robot-assisted partial nephrectomy for achieving modified trifecta: inverse probability of treatment weighting analysis from a high-volume tertiary robotic center.

On-clamp partial nephrectomy for the surgical treatment of renal masses poses the risk of ischemia and greater post-operative renal function loss. Conversely, the off-clamp technique might enhance renal function preservation by avoiding any ischemia time. Nevertheless, the debate persists regarding the efficacy of the on- versus off-clamp partial nephrectomy in achieving better surgical, functional, and oncological outcomes. We retrospectively assessed the data from patients undergoing Robot-Assisted Partial Nephrectomy (RAPN) from 2016 and 2023 in a tertiary robotic center. Inverse probability of treatment weighting (IPTW) was used to account for selection bias in treatment allocation. The main objective of the study was assessing the achievement rates of a modified trifecta within the two groups. Multivariable logistic regression analysis (MLRA) was employed to assess the predictors of trifecta achievement. 532 patients were included in the analysis, of whom 74.1% vs. 25.9% underwent on- and off-clamp, respectively. Balancing the two groups for the main predictors of on-clamp surgery, there were no significant differences between on- and off-clamp in terms of estimated blood loss, transfusion rate, intra- and post-operative complications, positive surgical margins, and post-operative mean reduction of eGFR. Finally, no differences were found in the rate of "trifecta" achievement between on-clamp and off-clamp RAPN (24.6% vs. 21%, p = 0.82). At MLRA, off-clamp technique was not a predictor of trifecta achievement compared to the on-clamp technique (off-clamp vs. on-clamp, aOR 1.24, 95% CIs [0.65-2.36], p = 0.58). Our study revealed that clamping technique does not imply clinically relevant differences in reaching trifecta outcomes.

How to improve newborn outcomes in 60 s-delay clamping the umbilical cord.

Deferred umbilical cord clamping (DCC) has been employed with wide variation in the United States over the last few decades. This practice has the potential to improve infant health and outcomes at the population health level. Education campaigns and policy interventions can promote DCC use in a safe manner.

Exosomal GDNF from Bone Marrow Mesenchymal Stem Cells Moderates Neuropathic Pain in a Rat Model of Chronic Constriction Injury.

Both of exosomes derived from mesenchymal stem cells (MSCs) and glial cell line-derived neurotrophic factor (GDNF) show potential for the treatment of neuropathic pain. Here, the analgesic effects of exosomes derived from bone marrow MSCs (BMSCs) were investigated. BMSCs-derived exosomes were isolated and characterized. Chronic constriction injury (CCI) was constructed to induce neuropathic pain in rats, which were then treated with exosomes. Pain behaviors were evaluated by measuring paw withdrawal thresholds and latency. The changes of key proteins, including cytokines, were explored using Western blot and ELISA. Administration of BMSCs-derived exosomes alleviated neuropathic pain, as demonstrated by the decrease of thermal hyperalgesia and mechanical allodynia, as well as the reduced secretion of pro-inflammatory cytokines in CCI rats. These effects were comparable to the treatment of GDNF alone. Mechanically, the exosomes suppressed the CCI-induced activation of TLR2/MyD88/NF-κB signaling pathway, while GDNF knockdown impaired their analgesic effects on CCI rat. BMSCs-derived exosomes may alleviate CCI-induced neuropathic pain and inflammation in rats by transporting GDNF.

Intraarticular TXA Administration with Appropriate Timing of Clamping and Appropriate Dose is More Effective Than IV Administration.

PURPOSE OF THE STUDY: Our aim was to compare the effects of intraarticular and intravenous (IV) tranexemic acid (TXA) application on bleeding and complication rates in patients who underwent total knee arthroplasty (TKA). MATERIAL AND METHODS: Between 2017 and 2021, 406 patients who underwent TKA with 2 g of IV TXA and retrograde 1.5 g of TXA applied through the drain were included in the study. Of the patients, 206 were in the IV TXA group. Preoperative and postoperative hemoglobin levels, drain output, BMI, ASA score, blood loss, and the number of transfused patients were recorded. Complications such as symptomatic venous thromboembolism were also recorded. RESULTS: There was no significant difference between the two groups in terms of age, sex, American Society of Anesthesiologists (ASA) score, or BMI (p = 0.68, 0.54, 0.28, 0.45). Total drain output and blood loss were significantly higher in the IV TXA group than in the intraarticular TXA group (p < 0.0001, p < 0.0001). Eighteen patients in the IV TXA group and 1 patient in the intraarticular TXA group received a blood transfusion (p < 0.0001). There was no difference between the two groups in terms of preoperative hemoglobin or platelet count (p = 0.24). However, postoperative hemoglobin level was higher in the patients who received intraarticular TXA (p=0.0005). More thromboembolism events were seen in the IV TXA group (p < 0.0001). CONCLUSIONS: Intraarticular TXA application reduces blood loss more than IV application, reduces the blood transfusion rate, and causes fewer complications. KEY WORDS: tranexemic acid, total knee arthroplasty, intraarticular injection, blood loss, blood transfusion.

Comparison of Beating-Heart Technique Versus Aortic Cross-Clamping in Tricuspid Valve Surgery.

OBJECTIVE: Tricuspid valve surgery can be performed on a beating heart or on an arrested heart. We aimed to compare the outcomes of tricuspid valve surgery using these two different approaches. METHODS: Between January 2015 and February 2020, 204 patients who underwent tricuspid valve surgery along with concomitant cardiac surgical procedures were included in the study. Techniques of cross-clamping and beating-heart tricuspid surgery were applied to 103 and 101 patients, respectively. Concomitant valvular and/or coronary interventions were performed under cross clamping in both groups. Results from the preoperative period, immediate postoperative period, and six-month postoperative interval were compared between the groups. RESULTS: There were no differences in demographic characteristics or preoperative grades of tricuspid valve regurgitation between the groups. Duration of mechanical ventilation, and stays in the intensive care unit and hospital were significantly shorter in patients operated on using the beating-heart technique. Additionally, re-exploration surgery and mortality rates were significantly lower in the beating-heart group. Postoperative six-month echocardiography findings related to tricuspid valve regurgitation, maximum and minimum gradients of the tricuspid valve, and pulmonary arterial pressure were also lower in the beating-heart group. CONCLUSION: Beating-heart tricuspid valve surgery may be preferable to the cross-clamping technique to avoid clamp-induced ischemia, which can lead to worsened postoperative outcomes.

Soft robotic platform for progressive and reversible aortic constriction in a small-animal model.

Our understanding of cardiac remodeling processes due to left ventricular pressure overload derives largely from animal models of aortic banding. However, these studies fail to enable control over both disease progression and reversal, hindering their clinical relevance. Here, we describe a method for progressive and reversible aortic banding based on an implantable expandable actuator that can be finely tuned to modulate aortic banding and debanding in a rat model. Through catheterization, imaging, and histologic studies, we demonstrate that our platform can recapitulate the hemodynamic and structural changes associated with pressure overload in a controllable manner. We leveraged soft robotics to enable noninvasive aortic debanding, demonstrating that these changes can be partly reversed because of cessation of the biomechanical stimulus. By recapitulating longitudinal disease progression and reversibility, this animal model could elucidate fundamental mechanisms of cardiac remodeling and optimize timing of intervention for pressure overload.

Robot-assisted Partial Nephrectomy With Selective Artery Clamping for Renal Cell Carcinoma in Horseshoe Kidney.

BACKGROUND: Robot-assisted partial nephrectomy (RAPN) has become the standard treatment for small renal tumors, including highly complex cases. However, applying RAPN to renal tumors in the horseshoe kidney (HSK) is clinically challenging due to malformations and complex blood supply. Herein, we present two cases of RAPN in patients with HSK treated using selective artery clamping methods. CASE REPORTS: A 61-year-old male with a 15 mm renal tumor located on the upper pole of the right HSK was referred to our Department. The patient underwent RAPN via the transperitoneal approach, following a three-dimensional computed tomography (3D-CT) assessment. Additionally, before surgery, we confirmed which renal arteries would be clamped in surgery by examining the kidney regions supplied by each renal artery. The second patient referred to our Department, a 45-year-old male, had a 46 mm renal tumor located on the isthmus of the HSK. His tumor received blood supply from two renal arteries, with the bilateral collecting systems converging and forming a ureter on 3D-CT. The patient underwent RAPN through an intraperitoneal approach in the semi-lateral position, with port placement lower than in standard RAPN. Pathological examinations revealed clear-cell renal cell carcinoma with negative surgical margins in both cases. Both patients had no recurrences or metastases at 53 and 13 months post-surgery, respectively. CONCLUSION: We present cases successfully treated with RAPN with selective artery clamping methods for HSK using 3D-CT without encountering complications, even in isthmus tumors.

Impact of early versus delayed umbilical cord clamping on term neonates' haemoglobin levels: a randomized controlled trial.

OBJECTIVE: To compare the effects of early and delayed cord clamping on the haemoglobin levels of neonates delivered at term. METHODS: This randomized controlled trial enrolled pregnant women during the second stage of labour. They were randomized into either the early cord clamping (ECC) group or the delayed cord clamping (DCC) group in the ratio of 1:1. Following delivery of the baby, the umbilical cords of participants in the ECC group were clamped within 30 s of delivery of the neonate while those of participants in the DCC group were clamped after 2 min from the delivery of the neonate. The primary outcome measure was the effect of ECC and DCC on the haemoglobin levels of neonates delivered at term. RESULTS: A total of 270 pregnant women were enrolled in the study. Their baseline sociodemographic and clinical characteristics were similar in both groups. There was no significant difference in the mean haemoglobin level between ECC and DCC groups at birth. The mean haemoglobin level of the neonates at 48 h postpartum was significantly higher in the DCC group than the ECC group. CONCLUSION: DCC at birth was associated with a significant increase in neonatal haemoglobin levels at 48 h postpartum when compared with ECC.Trial Registration: The trial was registered at Pan African Clinical Trial Registry with approval number PACTR202206735622089.

6-Methoxyflavone antagonizes chronic constriction injury and diabetes associated neuropathic nociception expression.

Neuropathy is a disturbance of function or a pathological change in nerves causing poor health and quality of life. A proportion of chronic pain patients in the community suffer persistent neuropathic pain symptoms because current drug therapies may be suboptimal so there is a need for new therapeutic modalities. This study investigated the neuroprotective flavonoid, 6-methoxyflavone (6MF), as a potential therapeutic agent and gabapentin as the standard comparator, against neuropathic models. Thus, neuropathic-like states were induced in Sprague-Dawley rats using sciatic nerve chronic constriction injury (CCI) mononeuropathy and systemic administration of streptozotocin (STZ) to induce polyneuropathy. Subsequent behaviors reflecting allodynia, hyperalgesia, and vulvodynia were assessed and any possible motoric side-effects were evaluated including locomotor activity, as well as rotarod discoordination and gait disruption. 6MF (25-75 mg/kg) antagonized neuropathic-like nociceptive behaviors including static- (pressure) and dynamic- (light brushing) hindpaw allodynia plus heat/cold and pressure hyperalgesia in the CCI and STZ models. 6MF also reduced static and dynamic components of vulvodynia in the STZ induced polyneuropathy model. Additionally, 6MF reversed CCI and STZ suppression of locomotor activity and rotarod discoordination, suggesting a beneficial activity on motor side effects, in contrast to gabapentin. Hence, 6MF possesses anti-neuropathic-like activity not only against different nociceptive modalities but also impairment of motoric side effects.

The application of a single-hand-operated hepatic pedicle clamping clamp in laparoscopic hepatectomy.

OBJECTIVE: In this paper, a single-hand-operated hepatic pedicle clamp was introduced, and its application value in laparoscopic liver tumor resection was preliminarily discussed. METHODS: The clinical data of 67 patients who underwent laparoscopic liver tumor resection at the First Affiliated Hospital of Wannan Medical College from March 2019 to October 2023 were retrospectively analyzed. The Pringle maneuver was performed with a hepatic pedicle clamp during the operation. The preoperative, intraoperative and postoperative clinical data were observed and recorded. RESULTS: Sixty-seven patients had a median block number, block time, intraoperative blood loss, and postoperative length of hospital stay of 4, 55 min, 400 ml, and 7 days, respectively. The average operation time was 304.9±118.4 min, the time required for each block was 3.2±2.4 s, and the time required for each removed block was 2.6±0.7 s. None of the patients developed portal vein thrombosis or hepatic artery aneurysm formation. CONCLUSION: The hepatic pedicle clamping clamp is simple to use in laparoscopic hepatectomy, optimizes the operation process, and has a reliable blocking effect. It is recommended for clinical application.

Perioperative outcomes of utilizing infrahepatic inferior vena cava clamping and Pringle maneuver during hepatectomy: a meta-analysis.

PURPOSE: Intraoperative bleeding during hepatectomy is primarily controlled through anaesthesiological interventions or surgical techniques such as Pringle maneuver (PM). Infrahepatic IVC clamping (IIVCC) is an alternative surgical technique to reduce central venous pressure and prevent retrograde hepatic venous bleeding. The aim of the meta-analysis was to compare IIVCC+PM with PM alone in terms of intraoperative outcomes and perioperative complications. METHODS: Medline, Cochrane Library, Scopus, Web of Science, and EMBASE were searched for comparative studies till 16.04.2024, resulting in 679 articles, of which eight studies met inclusion criteria. Data on patient demographics, surgical technique, and perioperative outcomes was assessed. Cochrane Risk of Bias 2.0 (RoB 2.0) Tool and Newcastle-Ottawa Scale (NOS) were used for risk of bias assessment. RESULTS: Two randomized controlled trials, one prospective, and five retrospective cohort studies with 358 patients in IIVCC+PM and 397 patients in PM alone group were included. IIVCC+PM resulted in significantly greater CVP reduction, less intraoperative blood loss (MD (95% CI) = - 233.03 (- 360.48 to - 105.58), P < 0.001), and less intraoperative blood transfusion (OR (95% CI) = 0.38 (0.25 to 0.57), P < 0.001) compared to PM alone. The two groups had comparable total operative time, transection time and total intraoperative fluid infusion. Patients undergoing IIVCC+PM had significantly shorter length of stay (MD (95% CI) = - 0.63 days (- 1.21 to - 0.05 days), P = 0.03) and overall complication rates (OR (95% CI) = 0.63 (0.43-0.92), P = 0.02) compared to PM alone group. CONCLUSION: The utilization of IIVCC along with PM during liver resection may be beneficial in reducing intraoperative bleeding and blood transfusion without adversely influencing operative times or perioperative outcomes compared to PM alone.

Efficacy assessment of novel methanimine derivatives in chronic constriction injury-induced neuropathic model: An in-vivo, ex-vivo and In-Silico approach.

The multicomponent etiology, complex clinical implications, dose-based side effect and degree of pain mitigation associated with the current pharmacological therapy is incapable in complete resolution of chronic neuropathic pain patients which necessitates the perpetual requirement of novel medication therapy. Therefore, this study explored the ameliorative aptitude of two novel methanimine imitative like (E)-N-(4-nitrobenzylidene)-4­chloro-2-iodobenzamine (KB 09) and (E)-N-(4-methylbenzylidene)-4­chloro-2-iodobenzamine (KB 10) in chronic constriction injury (CCI) of sciatic nerve induced neuropathic pain in rat model. Standard behavioral tests like dynamic and static allodynia, cold, thermal and mechanical hyperalgesia along with rotarod activity were performed at various experimental days like 0, 3, 7, 14 and 21. Enzyme linked immunosorbent assay (ELISA) on spinal tissue and antioxidant assays on sciatic nerve were executed accompanied by molecular docking and simulation studies. Prolonged ligation of sciatic nerve expressively induced hyperalgesia as well as allodynia in rats. KB 09 and KB 10 substantially attenuated the CCI elicited hyperalgesia and allodynia. They significantly reduced the biomarkers of pain and inflammation like Interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) in ELISA and while enhanced the GSH, SOD and CAT and diminished the MDA levels during antioxidant assays. KB 09 displayed -9.62 kcal/mol with TNF-α and -7.68 kcal/mol binding energy with IL-6 whereas KB 10 exhibited binding energy of -8.20 kcal/mol with IL-6 while -11.68 kcal/mol with TNF-α and hence both trial compounds ensured stable interaction with IL-6 and TNF-α during computational analysis. The results advocated that both methanimine derivatives might be novel candidates for attenuation of CCI-induced neuropathic pain prospects via anti-nociceptive, anti-inflammatory and antioxidant mechanisms.

Aberrant splicing of CaV1.2 calcium channel induced by decreased Rbfox1 enhances arterial constriction during diabetic hyperglycemia.

Diabetic hyperglycemia induces dysfunctions of arterial smooth muscle, leading to diabetic vascular complications. The CaV1.2 calcium channel is one primary pathway for Ca2+ influx, which initiates vasoconstriction. However, the long-term regulation mechanism(s) for vascular CaV1.2 functions under hyperglycemic condition remains unknown. Here, Sprague-Dawley rats fed with high-fat diet in combination with low dose streptozotocin and Goto-Kakizaki (GK) rats were used as diabetic models. Isolated mesenteric arteries (MAs) and vascular smooth muscle cells (VSMCs) from rat models were used to assess K+-induced arterial constriction and CaV1.2 channel functions using vascular myograph and whole-cell patch clamp, respectively. K+-induced vasoconstriction is persistently enhanced in the MAs from diabetic rats, and CaV1.2 alternative spliced exon 9* is increased, while exon 33 is decreased in rat diabetic arteries. Furthermore, CaV1.2 channels exhibit hyperpolarized current-voltage and activation curve in VSMCs from diabetic rats, which facilitates the channel function. Unexpectedly, the application of glycated serum (GS), mimicking advanced glycation end-products (AGEs), but not glucose, downregulates the expression of the splicing factor Rbfox1 in VSMCs. Moreover, GS application or Rbfox1 knockdown dynamically regulates alternative exons 9* and 33, leading to facilitated functions of CaV1.2 channels in VSMCs and MAs. Notably, GS increases K+-induced intracellular calcium concentration of VSMCs and the vasoconstriction of MAs. These results reveal that AGEs, not glucose, long-termly regulates CaV1.2 alternative splicing events by decreasing Rbfox1 expression, thereby enhancing channel functions and increasing vasoconstriction under diabetic hyperglycemia. This study identifies the specific molecular mechanism for enhanced vasoconstriction under hyperglycemia, providing a potential target for managing diabetic vascular complications.

Quality improvement efforts directed at optimal umbilical cord management in delivery room.

Delayed or deferred cord clamping (DCC) and umbilical cord milking (UCM) benefit all infants by optimizing fetal-neonatal transition and placental transfusion. Even though DCC is recommended by almost all maternal and neonatal organizations, it has not been universally implemented. There is considerable variation in umbilical cord management practices across institutions. In this article, we provide examples of successful quality improvement (QI) initiatives to implement optimal cord management in the delivery room. We discuss a number of key elements that should be considering among those undertaking QI efforts to implement DCC and UCM including, multidisciplinary team collaboration, development of theory for change, mapping of the current and ideal process and workflow for cord management, and creation of a unit-specific evidence-based protocol for cord management. We also examine important strategies for implementation and provide suggestions for developing a system for measurement and benchmarking.

Murine Left Pulmonary Hilar Clamp Model of Lung Ischemia Reperfusion Injury.

Ischemia reperfusion injury (IRI) during lung transplantation is a major risk factor for post-transplant complications, including primary graft dysfunction, acute and chronic rejection, and mortality. Efforts to study the underpinnings of IRI led to the development of a reliable and reproducible mouse model of left lung hilar clamping. This model involves a surgical procedure performed in an anesthetized and intubated mouse. A left thoracotomy is performed, followed by careful lung mobilization and dissection of the left pulmonary hilum. The hilar clamp involves reversible suture ligation of the pulmonary hilum with a slipknot, which stops the arterial inflow, venous outflow, and airflow through the left mainstem bronchus. Reperfusion is initiated by careful removal of the suture. Our laboratory uses 30 min of ischemia and 1 h of reperfusion for the experimental model in the current investigations. However, these time periods can be modified depending on the specific experimental question. Immediately prior to sacrifice, arterial blood gas can be obtained from the left ventricle after a 4 min period of right hilar clamping to ensure that the PaO2 values obtained are attributed to the injured left lung alone. We also describe a method to measure cell extravasation with flow cytometry, which involves intravenous injection of a fluorochrome-labeled antibody specific for the cell(s) to be studied prior to sacrifice. The left lung can then be harvested for flow cytometry, frozen or fixed, paraffin-embedded immunohistochemistry, and quantitative polymerase chain reaction. This hilar clamp technique allows for detailed study of the cellular and molecular mechanisms underlying IRI. Representative results reveal decreased left lung oxygenation and histologic evidence of lung injury following hilar clamping. This technique can be readily learned and reproduced by personnel with and without microsurgical experience, leading to reliable and consistent results and serving as a widely adoptable model for studying lung IRI.

Umbilical cord milking and delayed cord clamping for the prevention of neonatal hypoglycaemia: a systematic review and meta-analysis.

BACKGROUND: Placental management strategies such as umbilical cord milking and delayed cord clamping may provide a range of benefits for the newborn. The aim of this review was to assess the effectiveness of umbilical cord milking and delayed cord clamping for the prevention of neonatal hypoglycaemia. METHODS: Three databases and five clinical trial registries were systematically reviewed to identify randomised controlled trials comparing umbilical cord milking or delayed cord clamping with control in term and preterm infants. The primary outcome was neonatal hypoglycaemia (study defined). Two independent reviewers conducted screening, data extraction and quality assessment. Quality of the included studies was assessed using the Cochrane Risk of Bias tool (RoB-2). Certainty of evidence was assessed using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach. Meta-analysis using a random effect model was done using Review Manager 5.4. The review was registered prospectively on PROSPERO (CRD42022356553). RESULTS: Data from 71 studies and 14 268 infants were included in this review; 22 (2 537 infants) compared umbilical cord milking with control, and 50 studies (11 731 infants) compared delayed with early cord clamping. For umbilical cord milking there were no data on neonatal hypoglycaemia, and no differences between groups for any of the secondary outcomes. We found no evidence that delayed cord clamping reduced the incidence of hypoglycaemia (6 studies, 444 infants, RR = 0.87, CI: 0.58 to 1.30, p = 0.49, I2 = 0%). Delayed cord clamping was associated with a 27% reduction in neonatal mortality (15 studies, 3 041 infants, RR = 0.73, CI: 0.55 to 0.98, p = 0.03, I2 = 0%). We found no evidence for the effect of delayed cord clamping for any of the other outcomes. The certainty of evidence was low for all outcomes. CONCLUSION: We found no data for the effectiveness of umbilical cord milking on neonatal hypoglycaemia, and no evidence that delayed cord clamping reduced the incidence of hypoglycaemia, but the certainty of the evidence was low.

Single-Center Prospective Study of Cross-Clamp vs Balloon Occlusion in Robotic Mitral Surgery.

BACKGROUND: Transthoracic aortic cross-clamp and endoaortic balloon occlusion have both been shown to have comparable safety profiles for aortic occlusion. Because most surgeons use only one technique, we sought to compare the outcomes when a homogeneous group of surgeons changed their occlusion technique from aortic cross-clamp to balloon occlusion. METHODS: We changed our technique from aortic cross-clamp to balloon occlusion in November 2022. This allowed us to conduct a prospective treatment comparison study in the same group of surgeons. Propensity score matching was used to match cases (balloon occlusion) 1:3 to controls (aortic cross-clamp) based on age, sex, body mass index, concomitant maze procedure, and tricuspid valve repair. RESULTS: Total of 411 patients underwent robotic mitral surgery from 2020 through 2023. Propensity score matching was used to match 56 balloon occlusion patients to 168 aortic cross-clamp patients. The 224 patients were a median age of 65 years (interquartile range, 55.6-70.0 years), and 119 (53%) were men. All valves were successfully repaired. Balloon occlusion had a shorter median cardiopulmonary bypass (CPB) time compared with aortic cross-clamp (84.0 vs 94.5 minutes, P = .006). Median cross-clamp time (64.0 vs 64.0 minutes, P = .483) and total surgery time (5.9 vs 6.1 hours, P = .495) did not differ between groups. There were no in-hospital deaths. There were 5 surgeons who performed various combinations of console and bedside roles. CPB, cross-clamp, and surgery durations were not significantly affected by the different surgeon combinations. CONCLUSIONS: Compared with aortic cross-clamp, balloon occlusion has similar perioperative and early postoperative outcomes. Additionally, it likely introduces a 10-minute reduction in total CPB time.