Association between pediatric postoperative delirium and regional cerebral oxygen saturation: a prospective observational study.

BACKGROUND: Postoperative delirium (POD) represents a prevalent and noteworthy complication in the context of pediatric surgical interventions. In recent times, a hypothesis has emerged positing that cerebral ischemia and regional cerebral oxygen desaturation might serve as potential catalysts in the pathogenesis of POD. The primary aim of this study was to methodically examine the potential relationship between POD and regional cerebral oxygen saturation (rSO2) and to assess the predictive and evaluative utility of rSO2 in the context of POD. METHODS: This prospective observational study was conducted at the Children's Hospital, Zhejiang University School of Medicine, Zhejiang, China, spanning the period from November 2020 to March 2021. The research cohort comprised children undergoing surgical procedures within this clinical setting. To measure rSO2 dynamics, cerebral near-infrared spectroscopy (NIRS) was used to monitor rSO2 levels both before and after surgery. In addition, POD was assessed in the paediatric patients according to the Diagnostic and Statistical Manual of Mental Disorders Fifth Edition (DSM-5) criteria. The analysis of the association between the rSO2 index and the incidence of POD was carried out through the application of either the independent samples t-test or the nonparametric rank-sum test. To ascertain the threshold value of the adjusted rSO2 index for predictive and evaluative purposes regarding POD in the pediatric population, the Receiver Operating Characteristics (ROC) curve was employed. RESULTS: A total of 211 cases were included in this study, of which 61 (28.9%) developed POD. Participants suffering delirium had lower preoperative rSO2mean, lower preoperative rSO2min, and lower postoperative rSO2min, higher ∆rSO2mean, higher amount of ∆rSO2mean, lower ∆rSO2min (P < 0.05). Preoperative rSO2mean (AUC = 0.716, 95%CI 0.642-0.790), ∆rSO2mean (AUC = 0.694, 95%CI 0.614-0.774), amount of ∆rSO2mean (AUC = 0.649, 95%CI 0.564-0.734), preoperative rSO2min (AUC = 0.702, 96%CI 0.628-0.777), postoperative rSO2min (AUC = 0.717, 95%CI 0.647-0.787), and ∆rSO2min (AUC = 0.714, 95%CI 0.638-0.790) performed well in sensitivity and specificity, and the best threshold were 62.05%, 1.27%, 2.41%, 55.68%, 57.36%, 1.29%. CONCLUSIONS: There is a close relationship between pediatric POD and rSO2. rSO2 could be used as an effective predictor of pediatric POD. It might be helpful to measure rSO2 with NIRS for early recognizing POD and making it possible for early intervention.

The Association Between Renal Desaturation Measured Using Near-Infrared Spectroscopy and Postoperative Acute Kidney Injury: A Systematic Review.

OBJECTIVES: The objective of this systematic review was to clarify the status of near-infrared spectroscopy (NIRS) in monitoring perioperative renal regional tissue oxygen saturation (rSO2) and determine whether there is evidence supporting its use in predicting postoperative acute kidney injury (AKI). DESIGN: A systematic search of electronic databases was conducted to identify all clinical studies that utilized NIRS to monitor renal rSO2 during the perioperative period to observe postoperative AKI. SETTING: Studies published online as of May 31, 2024, were included in the review. PARTICIPANTS: Studies involving human participants undergoing surgery with a predefined outcome of AKI were included. INTERVENTIONS: Regional tissue oxygen saturation was measured using NIRS. MEASUREMENTS AND MAIN RESULTS: A total of 144 records were identified in the primary search after removing duplicates. After screening, 18 studies were included in the analysis, consisting of 3 case-control studies and 15 prospective cohort studies. Thirteen reports focused on pediatric surgery, whereas five reports focused on adult surgery. Sixteen studies involved cardiovascular surgery with cardiopulmonary bypass, and two studies focused on liver surgery. All studies received a quality score of 7 or above. Significant heterogeneity and mostly short follow up periods were noted. CONCLUSION: Renal desaturation may indicate AKI in patients; however, further studies are required to substantiate this relationship. Additional clinical trials are necessary to evaluate normal values and establish the exact threshold of renal rSO2 that signifies a meaningful decline in renal function.

Salivary metabolites as potential predictive biomarkers for lung surgery complications: a retrospective cross-sectional study.

PURPOSE: Saliva is often used as a tool for identifying systemic diseases because of the noninvasive nature of its collection. Moreover, salivary metabolites can be potential predictive factors for postoperative survival. We conducted the present study to establish whether salivary metabolites can function as predictive biomarkers for lung surgery complications. METHODS: Unstimulated salivary samples were collected from 412 patients before lung surgery. Salivary metabolites were analyzed comprehensively by capillary electrophoresis mass spectrometry. Clinical data with the discriminatory ability of biomarkers were assessed to predict lung surgery complications using multivariate logistic regression analysis. The primary endpoint was the risk factors for postoperative complications of Clavien-Dindo grade ≥ III. RESULTS: Postoperative complications of Clavien-Dindo grade ≥ III developed in 36 patients (8.7%). There was no postoperative 30-day mortality. Male sex (odds ratio [OR], 3.852; 95% confidence interval CI 1.455-10.199; p = 0.007) and salivary gamma-butyrobetaine (OR, 0.809; 95% CI 0.694-0.943; p = 0.007) were identified as significant risk factors for postoperative complications of Clavien-Dindo grade ≥ III. CONCLUSION: Salivary metabolites are potential noninvasive biomarkers for predicting postoperative complications of lung surgery.

Protein kinase D1 promotes the survival of random-pattern skin flaps in rats.

BACKGROUND: In reconstructive surgery, random skin flaps are commonly used tools to cover skin defects, however, their applicability and size are limited by post-operative complications such as marginal ischemia-reperfusion injury and flap necrosis. Protein kinase D1 (PKD1), a calcium/calmodulin-dependent serine/threonine kinase, is known to induce angiogenesis and has been shown to mitigate ischemia in cardiovascular diseases. However, the role of PKD1 has not been investigated in skin flaps. METHOD: Seventy-five male Sprague-Dawley rats with skin flaps were randomly divided into three groups: control, PKD1, and CID755673. Seven days following surgery, we assessed the general view and survival rate of the flap using histological analysis. Laser Doppler and lead oxide/gelatin angiography were used to evaluate microcirculation blood flow. Histopathological changes, neovascularization and microvascular density (MVD). were examined and calculated using microscopy after H&E staining. Protein expression levels were determined using immunoblotting and immunohistochemistry techniques. RESULT: PKD1 significantly improved flap survival by upregulating angiogenic factors VEGF and cadherin5 and increasing antioxidant enzymes SOD, eNOS, and HO1, as well as reducing caspase 3, cytochrome c, and Bax expression, and attenuating IL-1ß, IL-6, and TNF-α. In the PKD1 group, PKD1 increased neovascularization, and blood flow and flap survival areas were larger as compared to the control and CID755673 groups. CONCLUSION: These findings show that PKD1 accelerates angiogenesis, reduces oxidative stress, and impedes apoptosis and inflammation, thus resulting in improved flap survival. Our observations indicated that PKD1 could be a therapeutic target for flap failure treatment.

Damage-induced NAD release activates intestinal CD4+ and CD8+ T cell via P2X7R signaling.

BACKGROUND: Postoperative ileus (POI) is characterized by the activation of inflammation triggered by tissue damage. Damage-associated molecular patterns (DAMPs) reportedly induce local inflammation after injury. However, the impact of DAMPs on intestinal resident lymphocytes during POI remains poorly elucidated. METHODS: POI in mice was induced via intestinal manipulation (IM). The concentration of nicotinamide adenine dinucleotide (NAD) was detected after IM. The gastrointestinal motility of the mice was assessed after IM or NAD injection. Cytokine production and calcium influx in T cells were investigated after NAD stimulation using flow cytometry. RESULTS: The concentration of extracellular NAD significantly increased after IM administration, and NAD directly impaired gastrointestinal motility. Intraperitoneal injection of NAD promoted the expression of TNF-α in intestinal CD8+ and CD4+ T cells, but only IFN-γ production by CD8+ T cells was significantly promoted by NAD injection. Granzyme B production in CD8+ and CD4+ T cells decreased after administration. Concordantly, the same results were observed in NAD stimulation of intestinal CD3+ T cells in vitro. Blocking the P2X7R-related membrane enzyme ART2.2 significantly diminished the pro-inflammatory effect of NAD. CONCLUSION: IM includes the release of NAD derived from damaged tissues, consequently promoting pro-inflammatory cytokine production in intestinal CD4+ and CD8+ T lymphocytes. NAD-induced intestinal T cells activation may be associated with POI progression in the mouse.

Temporal and Spatial Patterns of Inflammation and Tissue Injury in Patients with Postoperative Respiratory Failure after Lung Resection Surgery: A Nested Case-Control Study.

Thoracic surgeries involving resection of lung tissue pose a risk of severe postoperative pulmonary complications, including acute respiratory distress syndrome (ARDS) and respiratory failure. Lung resections require one-lung ventilation (OLV) and, thus, are at higher risk of ventilator-induced lung injury (VILI) attributable to barotrauma and volutrauma in the one ventilated lung, as well as hypoxemia and reperfusion injury on the operated lung. Further, we also aimed to assess the differences in localized and systemic markers of tissue injury/inflammation in those who developed respiratory failure after lung surgery versus matched controls who did not develop respiratory failure. We aimed to assess the different inflammatory/injury marker patterns induced in the operated and ventilated lung and how this compared to the systemic circulating inflammatory/injury marker pattern. A case-control study nested within a prospective cohort study was performed. Patients with postoperative respiratory failure after lung surgery (n = 5) were matched with control patients (n = 6) who did not develop postoperative respiratory failure. Biospecimens (arterial plasma, bronchoalveolar lavage separately from ventilated and operated lungs) were obtained from patients undergoing lung surgery at two timepoints: (1) just prior to initiation of OLV and (2) after lung resection was completed and OLV stopped. Multiplex electrochemiluminescent immunoassays were performed for these biospecimen. We quantified 50 protein biomarkers of inflammation and tissue injury and identified significant differences between those who did and did not develop postoperative respiratory failure. The three biospecimen types also display unique biomarker patterns.

Propofol ameliorates acute postoperative fatigue and promotes glucagon-regulated hepatic gluconeogenesis by activating CREB/PGC-1α and accelerating fatty acids beta-oxidation.

Postoperative fatigue (POF) is the most common and long-lasting complication after surgery, which brings heavy burden to individuals and society. Recently, hastening postoperative recovery receives increasing attention, but unfortunately, the mechanisms underlying POF remain unclear. Propofol is a wildly used general anesthetic in clinic, and inspired by the rapid antidepressant effects induced by ketamine at non-anesthetic dose, the present study was undertaken to investigate the anti-fatigue effects and underlying mechanisms of propofol at a non-anesthetic dose in 70% hepatectomy induced POF model in rats. We first showed here that single administration of propofol at 0.1 mg/kg ameliorated acute POF in hepatectomy induced POF rats. Based on metabonomics analysis, we hypothesized that propofol exerted anti-fatigue activity in POF rats by facilitating free fatty acid (FFA) oxidation and gluconeogenesis. We further confirmed that propofol restored the deficit in FFA oxidation and gluconeogenesis in POF rats, as evidenced by the elevated FFA utilization, acetyl coenzyme A content, pyruvic acid content, phosphoenolpyruvic acid content, hepatic glucose output and glycogen storage. Moreover, propofol stimulated glucagon secretion and up-regulated expression of cAMP-response element binding protein (CREB), phosphorylated CREB, peroxlsome prolifeator-activated receptor-γ coactivator-1α (PGC-1α), phosphoenolpyruvate carboxykinade1 and carnitine palmitoltransferase 1A. In summary, our study suggests for the first time that propofol ameliorates acute POF by promoting glucagon-regulated gluconeogenesis via CREB/PGC-1α signaling and accelerating FFA beta-oxidation.

GATA2 participates in the recanalization of lymphatic vessels after surgical lymph node extirpation.

Lymphatic recanalization failure after lymphadenectomy constitutes a major risk of lymphedema in cancer surgery. It has been reported that GATA2, a zinc finger transcription factor, is expressed in lymphatic endothelial cells and is involved in the development of fetal lymphatic vessels. GATA3, another member of the GATA family of transcription factors, is required for the differentiation of lymphoid tissue inducer (LTi) cells and is essential for lymph node formation. However, how GATA2 and GATA3 function in recanalization after the surgical extirpation of lymphatic vessels has not been elucidated. Employing a new model of lymphatic recanalization, we examined the lymphatic reconnection process in Gata2 heterozygous deficient (Gata2+/- ) and Gata3 heterozygous deficient (Gata3+/- ) mice. We found that lymphatic recanalization was significantly impaired in Gata2+/- mice, while Gata3+/- mice rarely showed such abnormalities. Notably, the perturbed lymphatic recanalization in the Gata2+/- mice was partially restored by crossing with the Gata3+/- mice. Our results demonstrate for the first time that GATA2 participates in the regeneration of damaged lymphatic vessels and the unexpected suppressive activity of GATA3 against lymphatic recanalization processes.

Acute peri-operative neurocognitive disorders: a narrative review.

Peri-operative neurocognitive disorders are the most common complication experienced by older individuals undergoing anaesthesia and surgery. Peri-operative neurocognitive disorders, particularly postoperative delirium, result in long-term poor outcomes including: death; dementia; loss of independence; and poor cognitive and functional outcomes. Recent changes to the nomenclature of these disorders aims to align peri-operative neurocognitive disorders with cognitive disorders in the community, with consistent definitions and clinical diagnosis. Possible mechanisms include: undiagnosed neurodegenerative disease; inflammation and resulting neuroinflammation; neuronal damage; and comorbid systemic disease. Pre-operative frailty represents a significant risk for poor postoperative outcomes; it is associated with an increase in the incidence of cognitive decline at 3 and 12 months postoperatively. In addition to cognitive decline, frailty is associated with poor functional outcomes following elective non-cardiac surgery. It was recently shown that 29% of frail patients died or experienced institutionalisation or new disability within 90 days of major elective surgery. Identification of vulnerable patients before undergoing surgery and anaesthesia is the key to preventing peri-operative neurocognitive disorders. Current approaches include: pre-operative delirium and cognitive screening; blood biomarker analysis; intra-operative management that may reduce the incidence of postoperative delirium such as lighter anaesthesia using processed electroencephalography devices; and introduction of guidelines which may reduce or prevent delirium and postoperative neurocognitive disorders. This review will address these issues and advocate for an approach to care for older peri-operative patients which starts in the community and continues throughout the pre-operative, intra-operative, postoperative and post-discharge phases of care management, involving multidisciplinary medical teams, as well as family and caregivers wherever possible.

Ginkgolide B improved postoperative cognitive dysfunction by inhibiting microgliosis-mediated neuroinflammation in the hippocampus of mice.

BACKGROUND: Postoperative cognitive dysfunction (POCD) are a common complication of the central nervous system following surgery and anesthesia. The specific pathogenesis and effective therapeutics of POCD need to be further studied. Ginkgolide B (GB), a platelet-activating factor receptor-specific antagonist, has been suggested to have strong anti-inflammatory effects. Here we tested the effects and mechanism of GB on POCD of aged rats. METHODS: Neurobehavioral tests were used to investigate the effect of GB pretreatment on POCD. The hippocampus were harvested to test the expression of proinflammatory cytokines by ELISA. The expression of the microglial marker ionized calcium-binding adaptor molecule-1 (Iba-1) in the hippocampus was evaluated by western blot assay and immunohistochemistry. A Nissl staining experiment was used to detect the neuronal numbers in the hippocampus. RESULTS: Surgery might result in the overexpression of platelet activating factor (PAF) in the plasma and hippocampus and might cause hippocampus-dependent memory impairment. GB pretreatment, inhibited the activation of microglia, reduced the levels of IL-1ß and TNF-α, decreased the loss of neurons after surgery, and prevented POCD in aged rats. CONCLUSION: Our findings suggested that PAF was involved in the development of POCD. Improvement of POCD by PAF antagonist GB was associated with the inhibition of microgliosis-mediated neuroinflammation and neuronal apoptosis in aged rats.

A single-center experience of parathyroidectomy in 1500 cases for secondary hyperparathyroidism: a retrospective study.

BACKGROUND: Chronic kidney disease (CKD) is a global public health problem. With the deterioration of renal function, a certain proportion of CKD patients enter the uremic stage, and secondary hyperparathyroidism (SHPT) becomes a challenge. For refractory hyperparathyroidism, parathyroidectomy (PTX) plays a key role in reducing mortality and improving prognosis. Nevertheless, no consensus has been reached on the optimal surgical method. We aimed to provide evidence for the effectiveness of surgical treatment by summarizing the experience from our center. METHODS: Clinical data from 1500 patients undergoing parathyroidectomy were recorded, which included 1419 patients in a total parathyroidectomy without autotransplantation (tPTX) group, 54 patients in a total parathyroidectomy plus autotransplantation (tPTX + AT) group, and 27 patients in the other group. Perioperative basic data, intact parathyroid hormone (i-PTH) levels, serum calcium levels, serum phosphorus levels, pathological reports, coexisting thyroid diseases, short-term outcomes and complications were analyzed. Moreover, postoperative complications were compared between the tPTX and tPTX + AT groups. RESULTS: Parathyroid hormone, serum calcium and phosphorus levels decreased significantly post-surgery. Two patients died during the perioperative period. As the two most common complications, the incidences of severe hypocalcemia and hyperkalemia were 36.20% (543 cases) and 24.60% (369 cases), respectively. Pre-iPTH levels (OR = 1.001, 95% CI: 1.001-1.001, p < 0.01), serum alkaline phosphatase (ALP) levels (OR = 1.002, 95% CI: 1.001-1.002, p < 0.01) and the mass of excised parathyroid gland (OR = 3.06, 95% CI: 1.24-7.55, p = 0.02) were positively associated with postoperative severe hypocalcemia, while age and serum calcium were negatively associated with it. Pathological reports of resected parathyroid and thyroid glands indicated that 96.49% had parathyroid nodular hyperplasia, 13.45% had thyroid nodular hyperplasia, and 4.08% had thyroid papillary carcinoma. CONCLUSIONS: Parathyroidectomy is a safe and effective treatment for refractory secondary hyperparathyroidism. Severe hypocalcemia is the main complication, and coexistent thyroid diseases should never be neglected.

Intestinal dysmotility after bowel resection in rats is associated with decreased ghrelin and vimentin expression and loss of intestinal cells of Cajal.

This study provides novel insight into the mechanisms of intestinal dysmotility following massive small bowel resection. We show that 2 wk after bowel resection in rats, impaired intestinal motility was associated with loss of interstitial cells of Cajal (ICC; downregulation of transmembrane member 16A (TMEM16A) and c-kit expression) as well as with decreased vimentin, desmin, and ghrelin levels. Impaired intestinal motility led to a decrease in final body weight, suggesting less effective nutrient absorption. The purpose of this study was to evaluate the mechanisms of intestinal motility in a rat model of short bowel syndrome (SBS). Rats were divided into three groups: Sham rats underwent bowel transection; SBS-NSI rats underwent a 75% bowel resection and presented with normal intestinal size (NSI) at euthanasia and hypermotility patterns; SBS-DYS showed dysmotile (DYS) enlarged intestine and inhibited motility patterns. Animals were euthanized after 2 wk. Illumina's digital gene expression (DGE) analysis was used to determine the intestinal motility-related gene expression profiling in mucosal samples. Intestinal motility-related and ICC genes and protein expression in intestinal muscle layer were determined using real-time PCR, Western blotting, and immunohistochemistry. Gastrointestinal tract motility was studied by microcomputer tomography. From 10 Ca2+ signaling pathway-related genes, six genes in jejunum and seven genes in ileum were downregulated in SBS vs. Sham animals. Downregulation of TMEM16A mRNA and protein was confirmed by real-time PCR. Rapid intestinal transit time in SBS-NSI rats correlated with a mild decrease in TMEM16A, c-kit, and vimentin mRNA and protein expression (vs/. Sham animals). SBS-DYS rats demonstrated enlarged intestinal loops and delayed small intestinal emptying (on imaging studies) that were correlated with marked downregulation in TMEM16A, c-kit, vimentin, and ghrelin mRNA and protein levels compared with the other two groups. In conclusion, 2 wk following massive bowel resection in rats, impaired intestinal motility was associated with decreased vimentin and ghrelin gene and protein levels as well as loss of ICC (c-kit and TMEM16A).NEW & NOTEWORTHY This study provides novel insight into the mechanisms of intestinal dysmotility following massive small bowel resection. We show that 2 weeks after bowel resection in rats, impaired intestinal motility was associated with loss of interstitial cells of Cajal (downregulation of TMEM 16A, and c-kit expression) as well as with decreased vimentin, desmin, and ghrelin levels. Impaired intestinal motility led to decrease in final body weight, suggesting less effective nutrient absorption.

Biomarker Evidence of the Persistent Inflammation, Immunosuppression and Catabolism Syndrome (PICS) in Chronic Critical Illness (CCI) After Surgical Sepsis.

OBJECTIVE: To analyze serial biomarkers of the persistent inflammation, immunosuppression, and catabolism syndrome (PICS) to gain insight into the pathobiology of chronic critical illness (CCI) after surgical sepsis. BACKGROUND: Although early deaths after surgical intensive care unit sepsis have decreased and most survivors rapidly recover (RAP), one third develop the adverse clinical trajectory of CCI. However, the underlying pathobiology of its dismal long-term outcomes remains unclear. METHODS: PICS biomarkers over 14 days from 124 CCI and 225 RAP sepsis survivors were analyzed to determine associations and prediction models for (1) CCI (≥14 intensive care unit days with organ dysfunction) and (2) dismal 1-year outcomes (Zubrod 4/5 performance scores). Clinical prediction models were created using PIRO variables (predisposition, insult, response, and organ dysfunction). Biomarkers were then added to determine if they strengthened predictions. RESULTS: CCI (vs RAP) and Zubrod 4/5 (vs Zubrod 0-3) cohorts had greater elevations in biomarkers of inflammation (interleukin [IL]-6, IL-8, interferon gamma-induced protein [IP-10], monocyte chemoattractant protein 1), immunosuppression (IL-10, soluble programmed death ligand-1), stress metabolism (C-reactive protein, glucagon-like peptide 1), and angiogenesis (angiopoietin-2, vascular endothelial growth factor, vascular endothelial growth factor receptor-1, stromal cell-derived factor) at most time-points. Clinical models predicted CCI on day 4 (area under the receiver operating characteristics curve [AUC] = 0.89) and 1 year Zubrod 4/5 on day 7 (AUC = 0.80). IL-10 and IP-10 on day 4 minimally improved prediction of CCI (AUC = 0.90). However, IL-10, IL-6, IL-8, monocyte chemoattractant protein 1, IP-10, angiopoietin-2, glucagon-like peptide 1, soluble programmed death ligand-1, and stromal cell-derived factor on day 7 considerably improved the prediction of Zubrod 4/5 status (AUC = 0.88). CONCLUSIONS: Persistent elevations of PICS biomarkers in the CCI and Zubrod 4/5 cohorts and their improved prediction of Zubrod 4/5 validate that PICS plays a role in CCI pathobiology.

MD2 contributes to the pathogenesis of perioperative neurocognitive disorder via the regulation of α5GABAA receptors in aged mice.

BACKGROUND: Perioperative neurocognitive disorder (PND) is a long-term postoperative complication in elderly surgical patients. The underlying mechanism of PND is unclear, and no effective therapies are currently available. It is believed that neuroinflammation plays an important role in triggering PND. The secreted glycoprotein myeloid differentiation factor 2 (MD2) functions as an activator of the Toll-like receptor 4 (TLR4) inflammatory pathway, and α5GABAA receptors (α5GABAARs) are known to play a key role in regulating inflammation-induced cognitive deficits. Thus, in this study, we aimed to investigate the role of MD2 in PND and determine whether α5GABAARs are involved in the function of MD2. METHODS: Eighteen-month-old C57BL/6J mice were subjected to laparotomy under isoflurane anesthesia to induce PND. The Barnes maze was used to assess spatial reference learning and memory, and the expression of hippocampal MD2 was assayed by western blotting. MD2 expression was downregulated by bilateral injection of AAV-shMD2 into the hippocampus or tail vein injection of the synthetic MD2 degrading peptide Tat-CIRP-CMA (TCM) to evaluate the effect of MD2. Primary cultured neurons from brain tissue block containing cortices and hippocampus were treated with Tat-CIRP-CMA to investigate whether downregulating MD2 expression affected the expression of α5GABAARs. Electrophysiology was employed to measure tonic currents. For α5GABAARs intervention experiments, L-655,708 and L-838,417 were used to inhibit or activate α5GABAARs, respectively. RESULTS: Surgery under inhaled isoflurane anesthesia induced cognitive impairments and elevated the expression of MD2 in the hippocampus. Downregulation of MD2 expression by AAV-shMD2 or Tat-CIRP-CMA improved the spatial reference learning and memory in animals subjected to anesthesia and surgery. Furthermore, Tat-CIRP-CMA treatment decreased the expression of membrane α5GABAARs and tonic currents in CA1 pyramidal neurons in the hippocampus. Inhibition of α5GABAARs by L-655,708 alleviated cognitive impairments after anesthesia and surgery. More importantly, activation of α5GABAARs by L-838,417 abrogated the protective effects of Tat-CIRP-CMA against anesthesia and surgery-induced spatial reference learning and memory deficits. CONCLUSIONS: MD2 contributes to the occurrence of PND by regulating α5GABAARs in aged mice, and Tat-CIRP-CMA is a promising neuroprotectant against PND.

Urinary Diversion: Core Curriculum 2021.

Urinary diversion after cystectomy has been a historical standard for the treatment of numerous benign and malignant diseases of the bladder. Since the first published description in the early 1900s, improvements in surgical technique and a better understanding of the metabolic sequelae postoperatively have greatly enhanced patient outcomes. Both continent and incontinent diversions are available to patients after cystectomy. In appropriately selected patients, orthotopic neobladder reconstruction can offer preservation of body image and continence, and continent cutaneous diversions represent a reasonable alternative. Conduit diversion, which remains the most commonly performed diversion technique, is ideal for patients who would benefit from a less morbid surgical procedure that negates the need for self-catheterization. This installment of the Core Curriculum in Nephrology outlines numerous aspects of urinary diversion, in which a multidisciplinary approach to postoperative management at the intersection of nephrology and urology is required to effectively optimize patient outcomes. This article includes a discussion of the various reconstructive options after cystectomy as well as a comprehensive review of frequently encountered short-term and long-term metabolic abnormalities associated with altered electrolyte and acid-base homeostasis.

Endoscopic endoclip papilloplasty preserves sphincter of oddi function.

BACKGROUND: Endoscopic sphincterotomy (EST) can destroy sphincter of Oddi (SO) structure and function. The purpose of this study was to assess the feasibility of endoscopic endoclip papilloplasty (EEPP) in restoring SO function after EST. METHODS: Seven 26-week-old domestic pigs were divided into control and EEPP groups. Necropsy and haematoxylin-eosin staining plus anti-α-smooth muscle actin (α-SMA) staining of papilla and sphincter of Oddi manometry (SOM) were conducted in animals at three independent time points. RESULTS: EST and EEPP were safely performed in all 7 pigs without serious adverse events. For primary outcome, compared to the controls, EEPP generated smaller dilation and less inflammation. Fibrous repair of the papilla was observed at 24 weeks after EEPP. For secondary outcome, in the control group, SO basal pressure (17.25 ± 18.14 to 5.50 ± 0.71 mmHg), SO contraction amplitude (46.00 ± 19.20 to 34.50 ± 48.79 mmHg), peak (4.50 ± 4.04 to 1.50 ± 2.12) and frequency (3.05 ± 3.29 to 1.41 ± 2.19/min) were reduced after EST. Further reductions to almost 0 of these SOM parameters were observed 3 weeks later, including common bile duct pressure and SO contraction period. In contrast, in the EEPP group, these manometric data were recovered to pre-EST levels, including CBD pressure (11.5 ± 7.31 vs 11 ± 2.16 mmHg), SO pressure (17.50 ± 17.75 vs 18.20 ± 21.39 mmHg) and SO contraction amplitude (53.67 ± 21.54 vs 60.00 ± 36.08 mmHg). However, no significant differences were observed between control and EEPP groups by Student t test. CONCLUSIONS: In this porcine study, EEPP accelerated and improved papillary healing after EST, further preserved SO function.

The effect of sex on the mouse lens transcriptome.

The transcriptome of mammalian tissues differs between males and females, and these differences can change across the lifespan, likely regulating known sexual dimorphisms in disease prevalence and severity. Cataract, the most prevalent disease of the ocular lens, occurs at similar rates in young individuals, but its incidence is elevated in older women compared to men of the same age. However, the influence of sex on the lens transcriptome was unknown. RNAseq based transcriptomic profiling of young adult C57BL/6J mouse lens epithelial and fiber cells revealed that few genes are differentially expressed between the sexes. In contrast, lens cells from aged (24 month old) male and female C57BL/6J mice differentially expressed many genes, including several whose expression is lens preferred. Like cataracts, posterior capsular opacification (PCO), a major sequela of cataract surgery, may also be more prevalent in women. Lens epithelial cells isolated from mouse eyes 24 h after lens fiber cell removal exhibited numerous transcriptomic differences between the sexes, including genes implicated in complement cascades and extracellular matrix regulation, and these differences are much more pronounced in aged mice than in young mice. These results provide an unbiased basis for future studies on how sex affects the lens response to aging, cataract development, and cataract surgery.

Preoperative Nutritional Scores as Host-Related Prognostic Factors for Both Overall Survival and Postoperative Complications in Patients With Stage II to III Colorectal Cancer.

BACKGROUND: In the TNM eighth edition, nutritional status and inflammatory scores are newly described as host-related prognostic factors for esophageal cancer, hepatocellular carcinoma, and pancreatic cancer. However, only age and race are listed as host-related prognostic factors for colorectal cancer. OBJECTIVE: The purpose of this study was to evaluate the prognostic significance of nutritional and inflammatory scores for postoperative outcomes in patients with colorectal cancer. DESIGN: This was a retrospective study using a database that prospectively collects data. SETTINGS: The study was conducted at a high-volume multidisciplinary tertiary cancer center in Japan. PATIENTS: Study participants were 1880 consecutive patients with stage II to III colorectal cancer who underwent curative resection at the National Cancer Center Hospital between 2004 and 2012. Two nutritional scores (prognostic nutritional index and controlling nutritional status score) and 4 inflammatory scores (modified Glasgow prognostic score, neutrophil:lymphocyte ratio, platelet:lymphocyte ratio, and C-reactive protein:albumin ratio) were calculated. MAIN OUTCOME MEASURES: Correlations of nutritional scores and inflammatory scores with overall survival and postoperative complications were measured. RESULTS: After adjusting for key clinical and pathologic factors by multivariable analysis, 2 nutritional scores (prognostic nutritional index and controlling nutritional status score) and 2 inflammatory scores (neutrophil:lymphocyte ratio and C-reactive protein:albumin ratio) were independent prognostic factors for overall survival. With respect to discriminative ability, time-dependent receiver operating characteristic curves and Harrell concordance index revealed that prognostic nutritional index and controlling nutritional status score were superior to the 4 inflammatory scores for predicting overall survival. Multivariable logistic regression analyses also revealed that prognostic nutritional index, controlling nutritional status score, and C-reactive protein:albumin ratio were independent predictors for postoperative complications. LIMITATIONS: The retrospective design of the study was a limitation. CONCLUSIONS: Preoperative nutritional scores are promising host-related prognostic factors for overall survival and postoperative complications in patients with stage II and III colorectal cancer. See Video Abstract at http://links.lww.com/DCR/B587. EVALUACIN DE SCORE NUTRICIONALES PREOPERATORIOS COMO FACTORES PRONSTICOS PARA SOBREVIDA Y COMPLICACIONES POSTOPERATORIAS EN PACIENTES CON CANCER COLORECTAL ETAPA II Y III: ANTECEDENTES:En las últimas etapificaciones T-N-M, tanto el estado nutricional como inflamatorio han sido descritos como factores pronósticos en cáncer de esófago, hepático y pancreático. Sin embargo en cáncer colorectal solo la edad y la raza son enumerados como factores pronósticos.OBJETIVO:Evaluar la importancia pronóstica de los scores nutricionales e inflamatorias para los resultados posoperatorios en pacientes con cáncer colorrectal.DISEÑO:Estudio retrospectivo utilizando una base de datos.AJUSTE:Centro oncológico teciario en Japón.PACIENTES:Fueron incluidos en el estudio 1880 pacientes, consecutivos, con cancer colorectal etapa II y III sometidos a reseeción curativa en el National Cancer Center Hospital entre 2004 y 2012. Se aplicaron dos scores: nutricional (índice nutricional pronóstico y puntuación del estado nutricional) e inflamatorias (Glasgow modificada, proporción de neutrófilos a linfocitos, de plaquetas a linfocitos y de proteína C reactiva a albúmina).PRINCIPALES MEDIDAS DE RESULTADO:Evaluar scores nutricional e inflamatorio con sobrevida y complicaciones postoperatoria.RESULTADOS:Después de ajustar los factores clínicos y patológicos clave mediante análisis multivariable, dos scores nutricionales (índice nutricional pronóstico y puntuación del estado nutricional de control) y dos inflamatorias (proporción de neutrófilos a linfocitos y proporción de proteína C reactiva a albúmina) fueron pronósticos independientes factores para la sobrevida. Con respecto a la capacidad discriminativa, las curvas de características operativas del receptor, dependientes del tiempo y el índice de concordancia de Harrell, revelaron que el índice nutricional pronóstico y del estado nutricional de control eran superiores a las cuatro inflamatorias para predecir la sobrevida general. Los análisis de regresión logística multivariable también revelaron que el índice nutricional pronóstico, el estado nutricional de control y la relación proteína C reactiva / albúmina fueron predictores independientes de complicaciones postoperatorias.LIMITACIONES:Estudio de tipo retrospectivo.CONCLUSIONES:Los scores nutricionales preoperatorias son factores pronósticos prometedores relacionados con la sobrevida y las complicaciones postoperatorias en pacientes con cáncer colorrectal en estadio II y III. Consulte Video Resumen en http://links.lww.com/DCR/B587.

Surface Microdialysis for Detection of Colorectal Anastomosis Ischemia-An Experimental Study.

BACKGROUND: Inadequate blood supply is one of the major risk factors for anastomotic leak after low anterior rectal resection. Early detection of ischemia might predict complicated healing and enable anastomotic salvage, which is associated with better outcomes. A microdialysis offers a real-time evaluation of adequate bowel perfusion through monitoring of tissue metabolism. In this experimental study, we assessed the role of microdialysis in detecting early ischemia after colorectal anastomosis. MATERIALS AND METHODS: Colorectal anastomosis was performed in six miniature pigs. A microdialysis catheter was placed on the bowel serosa 5 mm proximal to the anastomosis. Metabolic changes were monitored hourly before and after initiating ischemia, which was induced by ligation of the inferior mesenteric artery and skeletonization of the mesocolon. RESULTS: Significant increase in tissue levels of lactate was detected after 60 min of ischemia (13.6 [10.4-16.1] versus 6.75 [1.8-9.6] mmol/L at baseline; P < 0.005). The lactate/pyruvate ratio increased accordingly. The concentration of glycerol increased significantly after 2 hours-from a baseline value of 29.5 (3-84) to 125 (79-201) mmol/L (P < 0.005). The decrease in glucose levels was also significant after 60 minutes-0 (0-0.2) versus 4.7 (3.3-6.8) mmol/L at baseline. However, its values started to decline before ischemia. CONCLUSIONS: Surface microdialysis can detect ischemic changes early and may be a promising method in postoperative monitoring of colorectal anastomosis.

Early postoperative decrease of albumin is an independent predictor of major complications after oncological esophagectomy: A multicenter study.

BACKGROUND AND OBJECTIVES: Serum albumin perioperative decrease (∆Alb) may reflect the magnitude of the physiological stress induced by surgery. Studies highlighted its value to predict adverse postoperative outcomes, but data in esophageal surgery are scant. This study aimed to investigate the role of ∆Alb to predict major complications after esophagectomy for cancer. METHODS: Multicenter retrospective study conducted in five high-volume centers, including consecutive patients undergoing an esophagectomy for cancer between 2006 and 2017. Patients were randomly assigned to a training (n = 696) and a validation (n = 350) cohort. Albumin decrease was calculated on postoperative day 1 and defined as ΔAlb. The primary endpoint was major complications according to Clavien classification. RESULTS: In the training cohort, esophagectomy induced a rapid drop of albumin. Cut-off of ΔAlb was established at 11 g/L and allowed to distinguish patients with adverse outcomes. On multivariable analysis, ΔAlb was identified as an independent predictor of major complications (OR, 1.06; 95% CI, 1.01-1.11; p = .014). Higher BMI and laparoscopy were associated with lower ΔAlb. Analysis of the validation cohort provided consistent findings. CONCLUSIONS: ΔAlb appeared as a promising biomarker after oncological esophagectomy, allowing prediction of potential adverse outcomes.