Propensity Score-matched Analysis Comparing Robotic Versus Laparoscopic Minor Liver Resections of the Anterolateral Segments: an International Multi-center Study of 10,517 Cases.

OBJECTIVE: To compare the outcomes of robotic minor liver resections (RMLR) versus laparoscopic (L) MLR of the anterolateral segments. BACKGROUND: Robotic liver surgery has been gaining prominence over the years with increasing usage for a myriad of hepatic resections. Robotic liver resections(RLR) has demonstrated non-inferiority to laparoscopic(L)LR while illustrating advantages over conventional laparoscopy especially for technically difficult and major LR. However, the advantage of RMLR for the anterolateral(AL) (segments II, III, IVb, V and VI) segments, has not been clearly demonstrated. METHODS: Between 2008 to 2022, 15,356 of 29,861 patients from 68 international centres underwent robotic(R) or laparoscopic minor liver resections (LMLR) for the AL segments Propensity score matching (PSM) analysis was performed for matched analysis. RESULTS: 10,517 patients met the study criteria of which 1,481 underwent RMLR and 9,036 underwent LMLR. A PSM cohort of 1,401 patients in each group were identified for analysis. Compared to the LMLR cohort, the RMLR cohort demonstrated significantly lower median blood loss (75ml vs. 100ml, P<0.001), decreased blood transfusion (3.1% vs. 5.4%, P=0.003), lower incidence of major morbidity (2.5% vs. 4.6%, P=0.004), lower proportion of open conversion (1.2% vs. 4.5%, P<0.001), shorter post operative stay (4 days vs. 5 days, P<0.001), but higher rate of 30-day readmission (3.5% vs. 2.1%, P=0.042). These results were then validated by a 1:2 PSM analysis. In the subset analysis for 3,614 patients with cirrhosis, RMLR showed lower median blood loss, decreased blood transfusion, lower open conversion and shorter post operative stay than LMLR. CONCLUSION: RMLR demonstrated statistically significant advantages over LMLR even for resections in the AL segments although most of the observed clinical differences were minimal.

Dexmedetomidine directly binds to and inhibits Toll-like receptor 4.

BACKGROUND: While a number of anesthetics has been shown potentially associated with neurotoxicity in the developing brain, dexmedetomidine, a drug that was rather recently introduced into the perioperative setting, is considered beneficial from neurological wellbeing. However, the underlying mechanism of how dexmedetomidine affects brain health remains to be determined. Based on our recent study, we hypothesized that dexmedetomidine would directly bind to and inhibit Toll-like receptor 4 (TLR4), a critical receptor largely expressed in microglia and responsible for neurological insult. METHODS: We used TLR4 reporter assays to test if dexmedetomidine attenuates TLR4 activation. Furthermore, a direct binding of dexmedetomidine on TLR4 was tested using photoactivatable medetomidine. Lastly, the effect of dexmedetomidine on ketamine (anesthetic)-induced neurotoxicity was tested in rat pups (P7). RESULTS: We showed that dexmedetomidine attenuated TLR4 activation using reporter assay (IC50 = 5.8 µg/mL). Photoactivatable dexmedetomidine delineated its direct binding sites on TLR4. We also showed that dexmedetomidine attenuated microglia activation both in vitro and in vivo. DISCUSSION: We proposed a novel mechanism of dexmedetomidine-mediated neuroprotection.

Systematic Review and Meta-Analysis of the Outcomes After Hepatic Artery Reconstruction in Pediatric Liver Transplantation Using a Microscope Versus Surgical Loupe.

BACKGROUND: To review the impact of the operating microscope (OM) for reconstruction of the hepatic artery (HA) by comparing the outcomes with standard loupe reconstruction (SL) in pediatric liver transplantation (LT). METHODS: Studies comparing the application of OM and SL for the reconstruction of the HA in primary pediatric LT were included from a systematic search of MEDLINE, Cochrane Library and EMBASE from inception to June 2022. Re-transplantation, dual grafts and auxiliary transplants were excluded. Primary outcome was the rate of HA thrombosis (HAT). Secondary outcomes were graft loss and mortality. RESULTS: There were 1261 liver recipients from 9 included studies published until June 2022. There were 484 patients in the OM group and 777 patients in the SL group. HAT incidence with OM was significantly lower with OR = 0.18 (95% CI: 0.07-0.48). The 1-year graft survival was significantly better in the OM group with OR = 2.77 (95% CI: 1.13-6.80). 1-year overall mortality was also significantly lower with OM with OR = 0.39 (0.18-0.86). The use of OM did not significantly impact the incidence of HAT in the living donor liver transplant subgroup. Differences in time for hepatic HA reconstruction, total operating time and length of hospital stay did not reach statistical significance. CONCLUSION: The use of OM has reduced the risk of HAT, graft loss and mortality in pediatric liver transplantation. Adoption of microsurgical principles in general may have contributed to the improved outcomes with SL reconstruction of HA in pediatric LT.

Robotic, laparoscopic and open surgery for gallbladder cancer: a systematic review and network meta-analysis.

INTRODUCTION: Minimally invasive oncological resections have become increasingly widespread in the surgical management of cancers. However, the role of minimally invasive surgery (MIS) for gallbladder cancer (GBC) remains unclear. We aim to perform a systematic review and network meta-analysis of existing literature to evaluate the safety and feasibility of laparoscopic and robotic surgery in the management of GBC compared to open surgery (OS) by comparing outcomes. METHODS: A literature search of the PubMed/MEDLINE (2000 to December 2021) and EMBASE (2000 to December 2021) databases was conducted. The primary outcome studied was overall survival, and secondary outcomes studied were postoperative morbidity, severe complications, incidence of bile leak, length of hospital stay, operation time, R0 resection rate, local recurrence and lymph node yield. RESULTS: Thirty-two full-text articles met the eligibility criteria and were included in the final analysis with a total of 5883 patients undergoing either OS or MIS (laparoscopic or robotic) for GBC. 1- and 2-stage meta-analyses did not reveal any significant differences between OS, laparoscopic and robotic surgery in terms of overall survival, R0 resection, lymph node harvest, local recurrence and post-operative complications. Patients who underwent OS had significantly longer hospitalization stay and intra-operative blood loss compared to those who underwent laparoscopic or robotic surgery. Network meta-analysis did not reveal any significant differences between post-operative and survival outcomes of laparoscopic vs robotic surgery groups. CONCLUSION: This network meta-analysis suggests that both laparoscopic and robotic surgery are safe and effective approaches in the surgical management of GBC, with post-operative and survival outcomes comparable to OS. An MIS approach may also lead to shorter hospitalization stay, less intraoperative blood loss and post-operative complications compared to OS. There was no obvious benefit of either MIS approach (laparoscopic versus robotic) over the other.

CP-Net: Instance-aware part segmentation network for biological cell parsing.

Instance segmentation of biological cells is important in medical image analysis for identifying and segmenting individual cells, and quantitative measurement of subcellular structures requires further cell-level subcellular part segmentation. Subcellular structure measurements are critical for cell phenotyping and quality analysis. For these purposes, instance-aware part segmentation network is first introduced to distinguish individual cells and segment subcellular structures for each detected cell. This approach is demonstrated on human sperm cells since the World Health Organization has established quantitative standards for sperm quality assessment. Specifically, a novel Cell Parsing Net (CP-Net) is proposed for accurate instance-level cell parsing. An attention-based feature fusion module is designed to alleviate contour misalignments for cells with an irregular shape by using instance masks as spatial cues instead of as strict constraints to differentiate various instances. A coarse-to-fine segmentation module is developed to effectively segment tiny subcellular structures within a cell through hierarchical segmentation from whole to part instead of directly segmenting each cell part. Moreover, a sperm parsing dataset is built including 320 annotated sperm images with five semantic subcellular part labels. Extensive experiments on the collected dataset demonstrate that the proposed CP-Net outperforms state-of-the-art instance-aware part segmentation networks.

No Difference in Short-Term Surgical Outcomes from Semaglutide Treatment for Type 2 Diabetes Mellitus after Cervical Decompression and Fusion: A Propensity Score-Matched Analysis.

STUDY DESIGN: Retrospective cohort. OBJECTIVE: To evaluate the impact of semaglutide treatment for Type 2 Diabetes Mellitus (T2DM) on the risk of short-term (<6 months) postoperative complications in patients undergoing primary cervical spine decompression and fusion (CSDF). SUMMARY OF BACKGROUND DATA: Semaglutide, a GLP-1 receptor agonist, is gaining popularity as a weekly injectable medication for the treatment of T2DM and obesity. Existing research indicates that higher levels of HbA1c and obesity are linked to fewer positive results after undergoing spine surgery, particularly cervical decompression and fusion. Nevertheless, there is a scarcity of publications evaluating the influence of semaglutide therapy on surgical complications, including surgical site infection, wound complications, and reoperation within 6 months, which were aggregated into a composite measure. METHODS: The PearlDiver Database was queried from January 2010 to December 2021 for patients with a primary diagnosis of T2DM who underwent CSDF for degenerative pathology. Patients with semaglutide treatment within 6 months before index surgery were propensity score-matched to patients without the treatment, employing age, gender, and Charlson comorbidity index (CCI) as matching covariates. A multivariate regression model was used to investigate the impact of semaglutide treatment on postoperative surgical complications. RESULTS: The propensity score-matched cohort included 596 patients (semaglutide cohort: 298, control cohort: 298). There were no statistically significant differences between cohorts in the composite measure of postoperative surgical complications following index CSDF (OR 1.26, 95% CI 0.83-1.93, P=0.331). Similarly, both 30-day (OR 0.83, 95% CI 0.49-1.42, P=0.589) and 90-day readmission rate (OR 0.89, 95% CI 0.56-1.42, P=0.724) were similar between both cohorts. CONCLUSION: This study suggests that in patients with T2DM, semaglutide treatment is not associated with higher rates of short-term adverse events after CSDF. The effect of semaglutide use on long-term outcomes remains unknown.

Factors Associated with and Impact of Open Conversion in Laparoscopic and Robotic Minor Liver Resections: An International Multicenter Study of 10,541 Patients.

INTRODUCTION: Despite the increasing widespread adoption and experience in minimally invasive liver resections (MILR), open conversion occurs not uncommonly even with minor resections and as been reported to be associated with inferior outcomes. We aimed to identify risk factors for and outcomes of open conversion in patients undergoing minor hepatectomies. We also studied the impact of approach (laparoscopic or robotic) on outcomes. METHODS: This is a post-hoc analysis of 20,019 patients who underwent RLR and LLR across 50 international centers between 2004-2020. Risk factors for and perioperative outcomes of open conversion were analysed. Multivariate and propensity score-matched analysis were performed to control for confounding factors. RESULTS: Finally, 10,541 patients undergoing either laparoscopic (LLR; 89.1%) or robotic (RLR; 10.9%) minor liver resections (wedge resections, segmentectomies) were included. Multivariate analysis identified LLR, earlier period of MILR, malignant pathology, cirrhosis, portal hypertension, previous abdominal surgery, larger tumor size, and posterosuperior location as significant independent predictors of open conversion. The most common reason for conversion was technical issues (44.7%), followed by bleeding (27.2%), and oncological reasons (22.3%). After propensity score matching (PSM) of baseline characteristics, patients requiring open conversion had poorer outcomes compared with successful MILR cases as evidenced by longer operative times, more blood loss, higher requirement for perioperative transfusion, longer duration of hospitalization and higher morbidity, reoperation, and 90-day mortality rates. CONCLUSIONS: Multiple risk factors were associated with conversion of MILR even for minor hepatectomies, and open conversion was associated with significantly poorer perioperative outcomes.

A digital twin model incorporating generalized metabolic fluxes to identify and predict chronic kidney disease in type 2 diabetes mellitus.

We have developed a digital twin-based CKD identification and prediction model that leverages generalized metabolic fluxes (GMF) for patients with Type 2 Diabetes Mellitus (T2DM). GMF digital twins utilized basic clinical and physiological biomarkers as inputs for identification and prediction of CKD. We employed four diverse multi-ethnic cohorts (n = 7072): a Singaporean cohort (EVAS, n = 289) and a North American cohort (NHANES, n = 1044) for baseline CKD identification, and two multi-center Singaporean cohorts (CDMD, n = 2119 and SDR, n = 3627) for 3-year CKD prediction and risk stratification. We subsequently conducted a comprehensive study utilizing a single dataset to evaluate the clinical utility of GMF for CKD prediction. The GMF-based identification model performed strongly, achieving an AUC between 0.80 and 0.82. In prediction, the GMF generated with complete parameters attained high performance with an AUC of 0.86, while with incomplete parameters, it achieved an AUC of 0.75. The GMF-based prediction model utilizing complete inputs is the standard implementation of our algorithm: HealthVector Diabetes®. We have established the GMF digital twin-based model as a robust clinical tool capable of predicting and stratifying the risk of future CKD within a 3-year time horizon. We report the correlation of GMF with basic input parameters, their ability to differentiate between future health states and medication status at baseline, and their capability to quantify CKD progression rates. This holistic methodology provides insights into patients' health states and CKD progression rates based on GMF metabolic profile differences, enabling personalized care plans.

Impact of neoadjuvant chemotherapy on short-term outcomes after simple and complex minimally invasive minor hepatectomy for colorectal liver metastases: A propensity-score matched and coarsened exact matched study.

BACKGROUND: In the last three decades, minimally invasive liver resection has been replacing conventional open approach in liver surgery. More recently, developments in neoadjuvant chemotherapy have led to increased multidisciplinary management of colorectal liver metastases with both medical and surgical treatment modalities. However, the impact of neoadjuvant chemotherapy on the surgical outcomes of minimally invasive liver resections remains poorly understood. METHODS: A multicenter, international, database of 4998 minimally invasive minor hepatectomy for colorectal liver metastases was used to compare surgical outcomes in patients who received neoadjuvant chemotherapy with surgery alone. To correct for baseline imbalance, propensity score matching, coarsened exact matching and inverse probability treatment weighting were performed. RESULTS: 2546 patients met the inclusion criteria. After propensity score matching there were 759 patients in both groups and 383 patients in both groups after coarsened exact matching. Baseline characteristics were equal after both matching strategies. Neoadjuvant chemotherapy was not associated with statistically significant worse surgical outcomes of minimally invasive minor hepatectomy. CONCLUSION: Neoadjuvant chemotherapy had no statistically significant impact on short-term surgical outcomes after simple and complex minimally invasive minor hepatectomy for colorectal liver metastases.

New type of tin(IV) complex based turn-on fluorescent chemosensor for fluoride ion recognition: elucidating the effect of molecular structure on sensing property.

A novel type of chemosensor based on tin(IV) complexes incorporating hydroxyquinoline derivatives has been designed and investigated for selectively detecting fluoride ions. Sn(meq)2Cl2 (meq = 2-methyl-8-quinolinol) (complex 1) exhibits a significant enhancement in luminescence upon the introduction of fluoride ions. This enhancement greatly surpasses that observed with Snq2Cl2 and Sn(dmqo)2Cl2 (q = 8-hydroxyquinnoline; dmqo = 5,7-dimethyl-8-quinolinol). Furthermore, complex 1 displays excellent sensitivity and selectivity for fluoride detection in comparison to halides and other anions. As a result, complex 1 serves as an outstanding turn-on fluorescent chemosensor, effectively sensing fluoride ions. The Benesi-Hilderbrand method and Job's plot confirmed that complex 1 associates with F- in a 1 : 2 binding stoichiometry. Also, complex 1 exhibited a large binding constant (pKb = 10.4 M-2) and a low detection limit (100 nM). To gain a deeper insight into the photophysical properties and the underlying mechanism governing the formation of the tin(IV) fluoride complex via halide exchange, we successfully synthesized partially fluorinated Sn(meq)2F0.67Cl1.33 (2) and fully fluorinated Sn(meq)2F2 (3), all of which were characterized through computational studies, thereby elucidating their photophysical properties. DFT studies reveal that converting Sn(meq)2Cl2 to Sn(meq)2F2, an endergonic process, leads to greater stability due to reducing steric hindrance about the metal center. Furthermore, the fluorinated complex significantly increases dipole moment, resulting in high affinity toward the F- ion.

Clinical Insights into Structure, Regulation, and Targeting of ABL Kinases in Human Leukemia.

Chronic myeloid leukemia is a multistep, multi-lineage myeloproliferative disease that originates from a translocation event between chromosome 9 and chromosome 22 within the hematopoietic stem cell compartment. The resultant fusion protein BCR::ABL1 is a constitutively active tyrosine kinase that can phosphorylate multiple downstream signaling molecules to promote cellular survival and inhibit apoptosis. Currently, tyrosine kinase inhibitors (TKIs), which impair ABL1 kinase activity by preventing ATP entry, are widely used as a successful therapeutic in CML treatment. However, disease relapses and the emergence of resistant clones have become a critical issue for CML therapeutics. Two main reasons behind the persisting obstacles to treatment are the acquired mutations in the ABL1 kinase domain and the presence of quiescent CML leukemia stem cells (LSCs) in the bone marrow, both of which can confer resistance to TKI therapy. In this article, we systemically review the structural and molecular properties of the critical domains of BCR::ABL1 and how understanding the essential role of BCR::ABL1 kinase activity has provided a solid foundation for the successful development of molecularly targeted therapy in CML. Comparison of responses and resistance to multiple BCR::ABL1 TKIs in clinical studies and current combination treatment strategies are also extensively discussed in this article.

The novel LESS (low-cost entrainment syringe system) O2 blender for use in modified bubble CPAP circuits: a clinical study of safety.

Background: Bubble continuous positive airway pressure (bCPAP) is used in resource-limited settings for children with respiratory distress. Low-cost modifications of bCPAP use 100% oxygen and may cause morbidity from oxygen toxicity. We sought to test a novel constructible low-cost entrainment syringe system (LESS) oxygen blender with low-cost modified bCPAP in a relevant clinical setting. Methods: We conducted a clinical trial evaluating safety of the LESS O2 blender among hospitalized children under five years old in rural Cambodia evaluating the rate of clinical failure within one hour of initiation of the LESS O2 blender and monitoring for any other blender-related complications. Findings: Thirty-two patients were included. The primary outcome (clinical failure) occurred in one patient (3.1%, 95% CI = 0.1-16.2%). Clinical failure was defined as intubation, death, transfer to another hospital, or two of the following: oxygen saturation <85% after 30 min of treatment; new signs of respiratory distress; or partial pressure of carbon dioxide ≥60 mmHg and pH <7.2 on a capillary blood gas. Secondary outcomes included average generated FiO2's with blender use, which were 59% and 52% when a 5 mm entrainment was used vs. a 10 mm entrainment port with 5-7 cm H2O of CPAP and 1-7 L/min (LPM) of flow; and adverse events including loss of CPAP bubbling (64% of all adverse events), frequency of repair or adjustment (44%), replacement (25%), and median time of respiratory support (44 h). Interpretation: Overall the LESS O2 blender was safe for clinical use. The design could be modified for improved performance including less repair needs and improved nasal interface, which requires modification for the blender to function more consistently.

Mechanistic Modeling of Intrathecal Chemotherapy Pharmacokinetics in the Human Central Nervous System.

PURPOSE: The pharmacokinetics of intrathecally administered antibody or small-molecule drugs in the human central nervous system (CNS) remains poorly understood. This study aimed to provide mechanistic and quantitative perspectives on the CNS pharmacokinetics of intrathecal chemotherapy, by using a physiologically based pharmacokinetic (PBPK) modeling approach. EXPERIMENTAL DESIGN: A novel CNS PBPK model platform was developed and verified, which accounted for the human CNS general anatomy and physiologic processes governing drug distribution and disposition. The model was used to predict CNS pharmacokinetics of antibody (trastuzumab) and small-molecule drugs (methotrexate, abemaciclib, tucatinib) following intraventricular injection or intraventricular 24-hour infusion, and to assess the key determinants of drug penetration into the deep brain parenchyma. RESULTS: Intraventricularly administered antibody and small-molecule drugs exhibited distinct temporal and spatial distribution and disposition in human CNS. Both antibody and small-molecule drugs achieved supratherapeutic or therapeutic concentrations in the cerebrospinal fluid (CSF) compartments and adjacent brain tissue. While intrathecal small-molecule drugs penetrated the deep brain parenchyma to a negligible extent, intrathecal antibodies may achieve therapeutic concentrations in the deep brain parenchyma. Intraventricular 24-hour infusion enabled prolonged CNS exposure to therapeutically relevant concentrations while avoiding excessively high and potentially neurotoxic drug concentrations. CONCLUSIONS: CNS PBPK modeling, in line with available clinical efficacy data, confirms the therapeutic value of intrathecal chemotherapy with antibody or small-molecule drugs for treating neoplastic meningitis and warrants further clinical investigation of intrathecal antibody drugs to treat brain parenchyma tumors. Compared with intraventricular injection, intraventricular 24-hour infusion may mitigate neurotoxicity while retaining potential efficacy.

Synthetic Interbody Devices and Traditional Bone Graft Are Associated With a Similar Rate of Surgical Complications After 1-2 Level Anterior Cervical Discectomy and Fusions.

STUDY DESIGN: Retrospective cohort. OBJECTIVE: To compare the rates of all-cause surgical complications of synthetic interbody devices versus allograft or autograft in patients undergoing 1-2 levels anterior cervical discectomy and fusion (ACDF) procedures. SUMMARY OF BACKGROUND DATA: Cervical degenerative disorders affect up to 60% of older adults in the United States. Both traditional allograft or autograft and synthetic interbody devices (polyetheretherketone or titanium) are used for decompression and arthrodesis, with increasing utilization of the latter. However, the differences in their postsurgical complication profiles are not well-characterized. PATIENTS AND METHODS: Patients who underwent 1-2 level ACDFs for cervical radiculopathy or myelopathy between 2010 and 2022 were identified using the PearlDiver Mariner all-claims insurance database. Patients undergoing surgery for nondegenerative pathologies, such as tumors, trauma, or infection, were excluded. 1:1 exact matching was performed based on factors that were significant predictors of all-cause surgical complications in a linear regression model. The primary outcome measure was the development of all-cause surgical complications after 1-2 level ACDFs. The secondary outcome was all-cause medical complications. RESULTS: 1:1 exact matching resulted in two equal groups of 11,430 patients who received treatment with synthetic interbody devices or allograft/autograft. No statistically significant difference in all-cause surgical complications was found between the synthetic cohort and the allograft or autograft cohort after 1-2 level ACDFs (Relative Risk: 0.86, 95% confidence interval: 0.730-1.014, P = 0.079). No significant differences were observed regarding any specific surgical complications except for pseudoarthrosis (Relative Risk: 0.73, 95% confidence interval: 0.554-0.974, P = 0.037), which was higher in the allograft/autograft cohort. CONCLUSION: After 1:1 exact matching to control for confounding variables, the findings of this study suggest that all-cause surgical complications are similar in patients undergoing ACDFs with synthetic interbody devices or allograft/autographs. However, the rate of pseudarthrosis appears to be higher in patients with allograft/autographs. Future prospective studies are needed to corroborate these findings.

Impact of liver cirrhosis, severity of cirrhosis and portal hypertension on the difficulty of laparoscopic and robotic minor liver resections for primary liver malignancies in the anterolateral segments.

INTRODUCTION: We performed this study in order to investigate the impact of liver cirrhosis (LC) on the difficulty of minimally invasive liver resection (MILR), focusing on minor resections in anterolateral (AL) segments for primary liver malignancies. METHODS: This was an international multicenter retrospective study of 3675 patients who underwent MILR across 60 centers from 2004 to 2021. RESULTS: 1312 (35.7%) patients had no cirrhosis, 2118 (57.9%) had Child A cirrhosis and 245 (6.7%) had Child B cirrhosis. After propensity score matching (PSM), patients in Child A cirrhosis group had higher rates of open conversion (p = 0.024), blood loss >500 mls (p = 0.001), blood transfusion (p < 0.001), postoperative morbidity (p = 0.004), and in-hospital mortality (p = 0.041). After coarsened exact matching (CEM), Child A cirrhotic patients had higher open conversion rate (p = 0.05), greater median blood loss (p = 0.014) and increased postoperative morbidity (p = 0.001). Compared to Child A cirrhosis, Child B cirrhosis group had longer postoperative stay (p = 0.001) and greater major morbidity (p = 0.012) after PSM, and higher blood transfusion rates (p = 0.002), longer postoperative stay (p < 0.001), and greater major morbidity (p = 0.006) after CEM. After PSM, patients with portal hypertension experienced higher rates of blood loss >500 mls (p = 0.003) and intraoperative blood transfusion (p = 0.025). CONCLUSION: The presence and severity of LC affect and compound the difficulty of MILR for minor resections in the AL segments. These factors should be considered for inclusion into future difficulty scoring systems for MILR.

Ehlers-Danlos Syndrome is Associated with Increased Rates of Adjacent Segment Disease Following TLIF: A Propensity Matched Study.

BACKGROUND: Ehlers-Danlos syndrome (EDS) is a collection of connective tissue disorders which are often associated with tissue laxity and disc degeneration. However, the implications of EDS on the risk of adjacent segment disease (ASD) after transforaminal lumbar interbody fusion (TLIF) are not well described. The objective of this study is to compare the rates of ASD among patients with EDS and those without EDS. METHODS: Patients who underwent 1-3 level TLIF for degenerative disc disease between 2010-2022 were identified using the PearlDiver Mariner all-claims insurance database. Patients with all types of EDS were included. Patients undergoing surgery for tumors, trauma, or infection were excluded. 1:1 propensity matching was performed using demographic factors, medical comorbidities, and surgical factors which were significantly associated with ASD in a linear regression model. The primary outcome measure was the development of ASD. The secondary outcomes were the development of pseudoarthrosis, medical complications, and surgical complications. RESULTS: Propensity matching resulted in 2 equal groups of 85 patients who did or did not have EDS and underwent 1-3 level TLIF. Patients without EDS were less likely to experience ASD (RR 0.18, 95% CI 0.09-0.35, P < 0.001). There was no significant difference between the 2 patient groups with regards to a diagnosis of pseudoarthrosis, and there was no significant difference for all-cause medical and surgical complications between the 2 patient groups. CONCLUSIONS: After propensity matching to control for confounding variables, the findings of this study suggest that EDS may be associated with an increased risk of ASD following TLIF. Future studies are needed to corroborate these findings.

One node among many: sevoflurane-induced hypnosis and the challenge of an integrative network-level view of anaesthetic action.

Building on their known ability to influence sleep and arousal, Li and colleagues show that modulating the activity of glutamatergic pedunculopontine tegmental neurones also alters sevoflurane-induced hypnosis. This finding adds support for the shared sleep-anaesthesia circuit hypothesis. However, the expanding recognition of many neuronal clusters capable of modulating anaesthetic hypnosis raises the question of how disparate and anatomically distant sites ultimately interact to coordinate global changes in the state of the brain. Understanding how these individual sites work in concert to disrupt cognition and behaviour is the next challenge for anaesthetic mechanisms research.

Cannabis Use is Associated With Higher Rates of Pseudarthrosis Following TLIF: A Multi-Institutional Matched-Cohort Study.

STUDY DESIGN: This was a retrospective cohort study. OBJECTIVE: To compare the rates of pseudarthrosis in patients undergoing 1 to 3 level transforaminal lumbar interbody fusion (TLIF) procedures between cannabis users and noncannabis users. SUMMARY OF BACKGROUND DATA: Recreational use of cannabis is common, though it remains poorly studied and legally ambiguous in the United States. Patients with back pain may turn to adjunctive use of cannabis to manage their pain. However, the implications of cannabis use on the achievement of bony fusion are not well-characterized. METHODS: Patients who underwent 1 to 3 level TLIF for degenerative disc disease or degenerative spondylolisthesis between 2010 and 2022 were identified using the PearlDiver Mariner all-claims insurance database. Cannabis users were identified with ICD 10 code F12.90. Patients undergoing surgery for nondegenerative pathologies such as tumors, trauma, or infection were excluded. 1:1 exact matching was performed using demographic factors, medical comorbidities, and surgical factors which were significantly associated with pseudarthrosis in a linear regression model. The primary outcome measure was development of pseudarthrosis within 24 months after 1 to 3 level TLIF. The secondary outcomes were the development of all-cause surgical complications as well as all-cause medical complications. RESULTS: A 1:1 exact matching resulted in two equal groups of 1593 patients who did or did not use cannabis and underwent 1 to 3 level TLIF. Patients who used cannabis were 80% more likely to experience pseudarthrosis compared with patients who do not [relative risk (RR): 1.816, 95% CI: 1.291-2.556, P <0.001]. Similarly, cannabis use was associated with significantly higher rates of all-cause surgical complications (RR: 2.350, 95% CI: 1.399-3.947, P =0.001) and all-cause medical complications (RR: 1.934, 95% CI: 1.516-2.467, P <0.001). CONCLUSION: After 1:1 exact matching to control for confounding variables, the findings of this study suggest that cannabis use is associated with higher rates of pseudarthrosis, as well as higher rates of all-cause surgical and all-cause medical complications. Further studies are needed to corroborate our findings.

Correlation Between Rod Fracture and Shear Stress: A Novel Parameter.

BACKGROUND: We sought to assess the accuracy of a novel parameter proportional to the rod shear stress (RSS) in identifying patients at risk of rod fracture (RF) after surgery for correction of adult spinal deformity. METHODS: We performed a retrospective medical record review of patients aged ≥18 years treated for adult spinal deformity between 2004 and 2014 with ≥24 months of follow-up. The primary outcome was RFs identified radiographically. Patient weight (w), number of instrumented levels (N), and minimum rod diameter (d) were recorded and used to calculate the RSS parameter (RSS=Nwd2). Receiver operating characteristic curves were produced and the area under the curve (AUC ± 95% confidence interval [CI]) was calculated to compare this parameter's discriminative accuracy to that of its constituent variables. The sensitivity, specificity, and likelihood ratios (LRs) were calculated. RESULTS: A total of 28 RF-positive and 154 RF-negative patients were included. The average age was 59.2 ± 9.6 years, and 93.4% were women. The RSS parameter produced the greatest AUC (0.73 ± 0.11). At an RSS cutoff of 30.1, it achieved a sensitivity of 71.4% and specificity of 71.4% (LR, 2.5; 95% CI, 1.8-3.5). The number of instrumented levels produced the next-greatest AUC (0.65 ± 0.12), with a sensitivity of 78.6% and specificity of 50.0% at a cutoff of 15 (LR, 1.6; 95% CI, 1.2-2.0). CONCLUSIONS: The RSS is calculated using easily obtainable information and shows potential as a tool for predicting patient-specific risk of RF after spinal fusion. The number of instrumented levels also correlates strongly with the occurrence of RFs and is not significantly less accurate than the RSS. A larger sample size and prospective validation would be useful in determining with greater confidence which parameter is superior for predicting RFs after spinal fusion.

Impact of Liver Cirrhosis, Severity of Cirrhosis, and Portal Hypertension on the Difficulty and Outcomes of Laparoscopic and Robotic Major Liver Resections for Primary Liver Malignancies.

BACKGROUND: Minimally invasive liver resections (MILR) offer potential benefits such as reduced blood loss and morbidity compared with open liver resections. Several studies have suggested that the impact of cirrhosis differs according to the extent and complexity of resection. Our aim was to investigate the impact of cirrhosis on the difficulty and outcomes of MILR, focusing on major hepatectomies. METHODS: A total of 2534 patients undergoing minimally invasive major hepatectomies (MIMH) for primary malignancies across 58 centers worldwide were retrospectively reviewed. Propensity score (PSM) and coarsened exact matching (CEM) were used to compare patients with and without cirrhosis. RESULTS: A total of 1353 patients (53%) had no cirrhosis, 1065 (42%) had Child-Pugh A and 116 (4%) had Child-Pugh B cirrhosis. Matched comparison between non-cirrhotics vs Child-Pugh A cirrhosis demonstrated comparable blood loss. However, after PSM, postoperative morbidity and length of hospitalization was significantly greater in Child-Pugh A cirrhosis, but these were not statistically significant with CEM. Comparison between Child-Pugh A and Child-Pugh B cirrhosis demonstrated the latter had significantly higher transfusion rates and longer hospitalization after PSM, but not after CEM. Comparison of patients with cirrhosis of all grades with and without portal hypertension demonstrated no significant difference in all major perioperative outcomes after PSM and CEM. CONCLUSIONS: The presence and severity of cirrhosis affected the difficulty and impacted the outcomes of MIMH, resulting in higher blood transfusion rates, increased postoperative morbidity, and longer hospitalization in patients with more advanced cirrhosis. As such, future difficulty scoring systems for MIMH should incorporate liver cirrhosis and its severity as variables.