Potential perioperative cardiovascular outcomes in cannabis/cannabinoid users. A call for caution.

Background: Cannabis is one of the most widely used psychoactive substances. Its components act through several pathways, producing a myriad of side effects, of which cardiovascular events are the most life-threatening. However, only a limited number of studies address cannabis's perioperative impact on patients during noncardiac surgery. Methods: Studies were identified by searching the PubMed, Medline, EMBASE, and Google Scholar databases using relevant keyword combinations pertinent to the topic. Results: Current evidence shows that cannabis use may cause several cardiovascular events, including abnormalities in cardiac rhythm, myocardial infarction, heart failure, and cerebrovascular events. Additionally, cannabis interacts with anticoagulants and antiplatelet agents, decreasing their efficacy. Finally, the interplay of cannabis with inhalational and intravenous anesthetic agents may lead to adverse perioperative cardiovascular outcomes. Conclusions: The use of cannabis can trigger cardiovascular events that may depend on factors such as the duration of consumption, the route of administration of the drug, and the dose consumed, which places these patients at risk of drug-drug interactions with anesthetic agents. However, large prospective randomized clinical trials are needed to further elucidate gaps in the body of knowledge regarding which patient population has a greater risk of perioperative complications after cannabis consumption.

American Society of Pain and Neuroscience Best Practice (ASPN) Guideline for the Treatment of Sacroiliac Disorders.

Clinical management of sacroiliac disease has proven challenging from both diagnostic and therapeutic perspectives. Although it is widely regarded as a common source of low back pain, little consensus exists on the appropriate clinical management of sacroiliac joint pain and dysfunction. Understanding the biomechanics, innervation, and function of this complex load bearing joint is critical to formulating appropriate treatment algorithms for SI joint disorders. ASPN has developed this comprehensive practice guideline to serve as a foundational reference on the appropriate management of SI joint disorders utilizing the best available evidence and serve as a foundational guide for the treatment of adult patients in the United States and globally.

The analgesic effectiveness of perioperative lidocaine infusions for acute and chronic persistent postsurgical pain in patients undergoing breast cancer surgery: a systematic review and meta-analysis.

BACKGROUND: Breast cancer is the most common cancer among women and tumour resection carries a high prevalence of chronic persistent postsurgical pain (CPSP). Perioperative i.v. lidocaine infusion has been proposed as protective against CPSP; however, evidence of its benefits is conflicting. This review evaluates the effectiveness of perioperative lidocaine infusions for breast cancer surgery. METHODS: Randomised trials comparing perioperative lidocaine infusions with parenteral analgesia in breast cancer surgery patients were sought. The two co-primary outcomes were the odds of CPSP at 3 and 6 months after operation. Secondary outcomes included rest pain at 1, 6, 12, and 24 h; analgesic consumption at 0-24 and 25-48 h; quality of recovery; opioid-related side-effects; and lidocaine infusion side-effects. Hartung-Knapp-Sidik-Jonkman (HKSJ) random effects modelling was used. RESULTS: Thirteen trials (1039 patients; lidocaine: 518, control: 521) were included. Compared with control, perioperative lidocaine infusion did not decrease the odds of developing CPSP at 3 and 6 months. Lidocaine infusion improved postoperative pain at 1 h by a mean difference (95% confidence interval) of -0.65 cm (-0.73 to -0.57 cm) (P<0.0001); however, this difference was not clinically important (1.1 cm threshold). Similarly, lidocaine infusion reduced oral morphine consumption by 7.06 mg (-13.19 to -0.93) (P=0.029) over the first 24 h only; however, this difference was not clinically important (30 mg threshold). The groups were not different for any of the remaining outcomes. CONCLUSIONS: Our results provide moderate-quality evidence that perioperative lidocaine infusion does not reduce CPSP in patients undergoing breast cancer surgery. Routine use of lidocaine infusions for perioperative analgesia and CPSP prevention is not supported in this population. SYSTEMATIC REVIEW PROTOCOL: PROSPERO CRD42023420888.

Tuning valence tautomerism in a family of dinuclear cobalt complexes incorporating a conjugated bridging bis(dioxolene) ligand with weak communication.

Valence tautomerism (VT) involves the stimulated reversible intramolecular electron transfer between a redox-active metal and ligand. Dinuclear cobalt complexes bridged by bis(dioxolene) ligands can undergo thermally-induced VT with access to {CoIII-cat-cat-CoIII}, {CoIII-cat-SQ-CoII} and {CoII-SQ-SQ-CoII} states (cat2- = catecholate, SQ˙- = semiquinonate, CoIII refers to low spin CoIII, CoII refers to high spin CoII). The resulting potential for two-step VT interconversions offers increased functionality over mononuclear examples. In this study, the bis(dioxolene) ligand 3,3',4,4'-tetrahydroxy-5,5'-dimethoxy-benzaldazine (thMH4) was paired with Mentpa (tpa = tris(2-pyridylmethyl)amine, n = 0-3 corresponds to methylation at 6-position of the pyridine rings) to afford [{Co(Mentpa)}2(thM)](PF6)2 (1a, n = 0; 2a, n = 2; 3a, n = 3). Structural, magnetic susceptibility and spectroscopic data show that 1a and 3a remain in the temperature invariant {CoIII-cat-cat-CoIII} and {CoII-SQ-SQ-CoII} forms in the solid state, respectively. In contrast, 2a exhibits incomplete thermally-induced VT between these two tautomeric forms via the mixed {CoIII-cat-SQ-CoII} tautomer. In solution, room temperature electronic absorption spectra are consistent with the assignments from the solid-state, with VT observed only for 2a. From electrochemistry, the proximity of the two 1e--processes for the thMn- ligand indicates weak electronic communication between the two dioxolene units, supporting the potential for a two-step VT interconversion in thMn- containing complexes. Comparison of the redox potentials of the Co and thMn- processes suggests that only 2a has these processes in sufficient proximity to afford the thermally-induced VT observed experimentally. Density functional theory calculations are consistent with the prerequisite energy ordering for a two-step transition for 2a, and temperature invariant {CoIII-cat-cat-CoIII} and {CoII-SQ-SQ-CoII} states for 1a and 3a, respectively. This work presents the third example, and the first formally conjugated example, of a bridging bis(dioxolene) ligand that can afford two-step VT in a Co complex, suggesting new possibilities towards applications based on multistep switching.

Chimeric Antigen Receptor T-Cell Therapy in the Outpatient Setting: An Expert Panel Opinion from the American Society for Transplantation and Cellular Therapy.

The first series of chimeric antigen receptor T (CAR-T) cell therapy products were approved in 2017 to 2019 and have shown remarkable efficacy in both clinical trials and the real-world setting, but at the cost of prolonged patient hospitalization. As the toxicity management protocols were refined, the concept of cellular therapy administered in the outpatient setting gained steam, and single institutions began to perform certain aspects of CAR-T monitoring in the outpatient setting for select patients. However, there are many considerations for a successful outpatient program. In anticipation of increasing use of CAR-T-cell therapy in the outpatient setting as a mechanism to overcome frequent hospital bed shortages and high cost of inpatient care, the American Society for Transplantation and Cellular Therapy convened a group of experts in hematology, oncology, and cellular therapy to provide a comprehensive review of the existing publications on outpatient CAR-T cell therapy, discuss selected ongoing clinical trials of outpatient CAR-T, and describe strategies to optimize safety without compromising efficacy for patients treated and monitored in the outpatient setting.

The Effect of Smoking on the Activated Clotting Time and the Incidence of Complications in Noncardiac Arterial Procedures.

PURPOSE: Smoking is a well-known risk factor for developing arterial diseases and for an increase of complications during and after vascular procedures. Although smoking has a proven effect on hemostasis, no literature is available on the effect of smoking on the activated clotting time (ACT), which is used to monitor the effect of heparin during noncardiac arterial procedures (NCAP). The aim of this study was to examine the effect of smoking on ACT values and the incidence of complications during the same admission or 30 day follow-up of NCAP. MATERIALS AND METHODS: A post hoc analysis of a prospective multicenter cohort study was performed. Patients older than 18 years, who underwent NCAP between December 2016 and April 2021, were enrolled. Patients were divided into 2 groups based on smoking status: never/former smokers and current smokers. Two heparin dosing protocols were used: an initial bolus of 5000 IU or 100 IU/kg bodyweight. RESULTS: In total, 773 patients met the inclusion criteria. Five minutes after administration of 5000 IU of heparin, mean ACT values were 190 and 196 seconds for nonsmokers and smokers, respectively (p=0.078). After 100 IU/kg of heparin, mean ACT values were 229 and 226 seconds for nonsmokers and smokers, respectively (p=0.37). Incidence of complications in the whole study cohort was not significantly different for nonsmokers compared with smokers (arterial thrombo-embolic complication [ATEC] 4.7% vs 5.7% p=0.55; hemorrhagic complications 15% vs 18% p=0.29). In subgroup-analysis, a significant difference between smoking groups was found for hemorrhagic complications after open aneurysm repair (p=0.024). However, after adjusting for confounders, the difference between the smoking groups annulled. CONCLUSION: The results of this study suggest that smoking does not have a significant effect on ACT values or on the incidence of complications in NCAP. Large-scale studies are required to further analyze potential factors having an effect on the ACT and perioperative and postoperative complications, which could help individualize heparinization strategy. CLINICAL IMPACT: There is high variance between patients in their response on administration of heparin, this is not yet fully understood. This study investigated the effect of smoking in a large prospective multicentre cohort. The results suggests that active smoking does not have an effect on the activated clotting time after administration of heparin. Also no significant effect of smoking could be found on the incidence of all registered complications. Monitoring of the effect of heparin remains important to provide patients with safe anticoagulation during vascular procedures.

Neuromodulation for Peripheral Nerve Regeneration: Systematic Review of Mechanisms and In Vivo Highlights.

While denervation can occur with aging, peripheral nerve injuries are debilitating and often leads to a loss of function and neuropathic pain. Although injured peripheral nerves can regenerate and reinnervate their targets, this process is slow and directionless. There is some evidence supporting the use of neuromodulation to enhance the regeneration of peripheral nerves. This systematic review reported on the underlying mechanisms that allow neuromodulation to aid peripheral nerve regeneration and highlighted important in vivo studies that demonstrate its efficacy. Studies were identified from PubMed (inception through September 2022) and the results were synthesized qualitatively. Included studies were required to contain content related to peripheral nerve regeneration and some form of neuromodulation. Studies reporting in vivo highlights were subject to a risk of bias assessment using the Cochrane Risk of Bias tool. The results of 52 studies indicate that neuromodulation enhances natural peripheral nerve regeneration processes, but still requires other interventions (e.g., conduits) to control the direction of reinnervation. Additional human studies are warranted to verify the applicability of animal studies and to determine how neuromodulation can be optimized for the greatest functional restoration.

Cognitive dissonance increases spine loading in the neck and low back.

Cognitive dissonance refers to a state where two psychologically inconsistent thoughts, behaviours, or attitudes are held at the same time. The objective of this study was to explore the potential role of cognitive dissonance in biomechanical loading in the low back and neck. Seventeen participants underwent a laboratory experiment involving a precision lowering task. To establish a cognitive dissonance state (CDS), study participants were provided negative feedback on their performance running counter to a pre-established expectation that their performance was excellent. Dependent measures of interest were spinal loads in the cervical and lumbar spines, calculated via two electromyography-driven models. The CDS was associated with increases to peak spinal loads in the neck (11.1%, p < .05) and low back (2.2%, p < .05). A greater CDS magnitude was also associated with a greater spinal loading increase. Therefore, cognitive dissonance may represent a risk factor for low back/neck pain that has not been previously identified.Practitioner summary: Upon establishing a cognitive dissonance state in a group of participants, spinal loading in the cervical and lumbar spines were increased proportional to the magnitude of the cognitive dissonance reported. Therefore, cognitive dissonance may represent a risk factor for low back and neck pain that has not been previously identified.

Immune Effector Cell-Associated Hemophagocytic Lymphohistiocytosis-Like Syndrome.

T cell-mediated hyperinflammatory responses, such as cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS), are now well-established toxicities of chimeric antigen receptor (CAR) T cell therapy. As the field of CAR T cells advances, however, there is increasing recognition that hemophagocytic lymphohistiocytosis (HLH)-like toxicities following CAR T cell infusion are occurring broadly across patient populations and CAR T cell constructs. Importantly, these HLH-like toxicities are often not as directly associated with CRS and/or its severity as initially described. This emergent toxicity, however ill-defined, is associated with life-threatening complications, creating an urgent need for improved identification and optimal management. With the goal of improving patient outcomes and formulating a framework to characterize and study this HLH-like syndrome, we established an American Society for Transplantation and Cellular Therapy panel composed of experts in primary and secondary HLH, pediatric and adult HLH, infectious disease, rheumatology and hematology, oncology, and cellular therapy. Through this effort, we provide an overview of the underlying biology of classical primary and secondary HLH, explore its relationship with similar manifestations following CAR T cell infusions, and propose the term "immune effector cell-associated HLH-like syndrome (IEC-HS)" to describe this emergent toxicity. We also delineate a framework for identifying IEC-HS and put forward a grading schema that can be used to assess severity and facilitate cross-trial comparisons. Additionally, given the critical need to optimize outcomes for patients experiencing IEC-HS, we provide insight into potential treatment approaches and strategies to optimize supportive care and delineate alternate etiologies that should be considered in a patient presenting with IEC-HS. By collectively defining IEC-HS as a hyperinflammatory toxicity, we can now embark on further study of the pathophysiology underlying this toxicity profile and make strides toward a more comprehensive assessment and treatment approach.

Effect of Autograft CD34+ Dose on Outcome in Pediatric Patients Undergoing Autologous Hematopoietic Stem Cell Transplant for Central Nervous System Tumors.

Consolidation with autologous hematopoietic stem cell transplantation (HSCT) has improved survival for patients with central nervous system tumors (CNSTs). The impact of the autologous graft CD34+ dose on patient outcomes is unknown. We wanted to analyze the relationship between CD34+ dose, total nucleated cell (TNC) dose, and clinical outcomes, including overall survival (OS), progression-free survival (PFS), relapse, non-relapse mortality (NRM), endothelial-injury complications (EIC), and time to neutrophil engraftment in children undergoing autologous HSCT for CNSTs. A retrospective analysis of the CIBMTR database was performed. Children aged <10 years who underwent autologous HSCT between 2008 to 2018 for an indication of CNST were included. An optimal cut point was identified for patient age, CD34+ cell dose, and TNC, using the maximum likelihood method and PFS as an endpoint. Univariable analysis for PFS, OS, and relapse was described using the Kaplan-Meier estimator. Cox models were fitted for PFS and OS outcomes. Cause-specific hazards models were fitted for relapse and NRM. One hundred fifteen patients met the inclusion criteria. A statistically significant association was identified between autograft CD34+ content and clinical outcomes. Children receiving >3.6×106/kg CD34+ cells experienced superior PFS (p = .04) and OS (p = .04) compared to children receiving ≤3.6 × 106/kg. Relapse rates were lower in patients receiving >3.6 × 106/kg CD34+ cells (p = .05). Higher CD34+ doses were not associated with increased NRM (p = .59). Stratification of CD34+ dose by quartile did not reveal any statistically significant differences between quartiles for 3-year PFS (p = .66), OS (p = .29), risk of relapse (p = .57), or EIC (p = .87). There were no significant differences in patient outcomes based on TNC, and those receiving a TNC >4.4 × 108/kg did not experience superior PFS (p = .26), superior OS (p = .14), reduced risk of relapse (p = .37), or reduced NRM (p = .25). Children with medulloblastoma had superior PFS (p < .001), OS (p = .01), and relapse rates (p = .001) compared to those with other CNS tumor types. Median time to neutrophil engraftment was 10 days versus 12 days in the highest and lowest infused CD34+ quartiles, respectively. For children undergoing autologous HSCT for CNSTs, increasing CD34+ cell dose was associated with significantly improved OS and PFS, and lower relapse rates, without increased NRM or EICs.

Identifying Predictors for Early Percutaneous Spinal Cord Stimulator Explant at One and Two Years: A Retrospective Database Analysis.

OBJECTIVES: Placement of percutaneous spinal cord stimulator (SCS) implant has become a therapeutic option for various chronic pain conditions; however, early surgical explant still occurs. Unfortunately, evidence regarding the incidence of early surgical explant, and patient-specific factors and comorbidities associated with such, is limited and mixed. The objective of this retrospective analysis was to elucidate the incidence and predictors of percutaneous SCS explant within the first two years of device placement. MATERIALS AND METHODS: The PearlDiver-Mariner Patient Record Database of all payer claims was used to identify patients who underwent percutaneous lead SCS implant (leads and generator) with subsequent explant within two years of initial device implant. The primary outcome was to determine the incidence of SCS explant within the first two years of device placement. Secondary outcomes included evaluating the effects of several patient-specific comorbidities on explant rates using univariate regression analysis. RESULTS: Across the database, a total of 52,070 patients who underwent percutaneous lead SCS implant were included, of whom 3104 (5.96%) had SCS explant within the first two years. Most explants occurred within the first-year time interval at 72.8% (2260 patients), whereas only 27.2% (844 patients) had SCS explant between years one and two. At the one-year time interval, covariates associated with an increased odds ratio (OR) (95% CI) of SCS explant were 1) depression (1.39 [1.26, 1.52]), 2) chronic preoperative (1.27 [1.16, 1.39]) or postoperative (1.23 [1,13, 1.36]) opioid use, 3) cannabis abuse (1.58 [1.20, 2.02]), 4) tobacco use (1.13 [1.04, 1.23]), and 5) coagulopathy (1.22 [1.07, 1.38]). In contrast, the OR of explant was lower in patients who were older, men, or had diabetes (complicated or uncomplicated). All associated covariates became nonsignificant after the first year of SCS implant (ie, between the first and second years), and only depression and tobacco use remained as associated factors for device explant. CONCLUSIONS: Our retrospective analysis highlights that the rate of percutaneous SCS explant appears to considerably decrease after the first year of device implant. Furthermore, this analysis sheds additional insights into patients who may be at risk of early percutaneous SCS explant, especially within the first year of device placement, and underscores the importance of a continued multidimensional/biopsychologic assessment in patients with chronic pain.

Ecological Importance of Viral Lysis as a Loss Factor of Phytoplankton in the Amundsen Sea.

Whether phytoplankton mortality is caused by grazing or viral lysis has important implications for phytoplankton dynamics and biogeochemical cycling. The ecological relevance of viral lysis for Antarctic phytoplankton is still under-studied. The Amundsen Sea is highly productive in spring and summer, especially in the Amundsen Sea Polynya (ASP), and very sensitive to global warming-induced ice-melt. This study reports on the importance of the viral lysis, compared to grazing, of pico- and nanophytoplankton, using the modified dilution method (based on apparent growth rates) in combination with flow cytometry and size fractionation. Considerable viral lysis was shown for all phytoplankton populations, independent of sampling location and cell size. In contrast, the average grazing rate was 116% higher for the larger nanophytoplankton, and grazing was also higher in the ASP (0.45 d-1 vs. 0.30 d-1 outside). Despite average specific viral lysis rates being lower than grazing rates (0.17 d-1 vs. 0.29 d-1), the average amount of phytoplankton carbon lost was similar (0.6 µg C L-1 d-1 each). The viral lysis of the larger-sized phytoplankton populations (including diatoms) and the high lysis rates of the abundant P. antarctica contributed substantially to the carbon lost. Our results demonstrate that viral lysis is a principal loss factor to consider for Southern Ocean phytoplankton communities and ecosystem production.

The Potential Relationship Between a Cognitive Dissonance State and Musculoskeletal Injury: A Systematic Review.

OBJECTIVE: The objective of this systematic review was to investigate the potential link between cognitive dissonance or its related constructs (emotional dissonance, emotional labor) and musculoskeletal disorders. BACKGROUND: The etiology of musculoskeletal disorders is complex, as pain arises from complex interactions among physical, social, and psychological stressors. It is possible that the psychological factor of cognitive dissonance may contribute to the etiology and/or maintenance of musculoskeletal disorders. METHOD: MEDLINE, APA PsycInfo, and CINAHL Plus databases were searched for studies investigating cognitive dissonance or its related constructs as exposure(s) of interest and outcomes related to physical health (including, but not limited to, musculoskeletal pain). Risk of bias was assessed using the Appraisal tool for Cross-Sectional Studies (AXIS) tool. RESULTS: The literature search yielded 7 studies eligible for inclusion. None of the included studies investigated cognitive dissonance directly but instead investigated dissonance-related constructs of emotional dissonance and emotional labor, in which a mismatch between required and felt emotions might elicit a psychological response consistent with the cognitive dissonance state. Moderate effect sizes between dissonance-related constructs and musculoskeletal disorders were noted (OR 1.25-2.22). CONCLUSION: There is likely a relationship between the two factors studied. However, as the included studies were cross-sectional in nature, a causal relationship between cognitive dissonance-related constructs and musculoskeletal disorders cannot be inferred. Therefore, future study proposing and validating a causal pathway between these variables is warranted. APPLICATION: Cognitive dissonance and its related constructs may serve as risk factors for musculoskeletal disorders that have not been considered previously.

Efficacy of PECS block in addition to multimodal analgesia for postoperative pain management in patients undergoing outpatient elective breast surgery: A retrospective study.

Background: Pectoralis nerve blocks (PECS) have been shown in numerous studies to be a safe and effective method to treat postoperative pain and reduce postoperative opioid consumption after breast surgery. However, there are few publications evaluating the PECS block effectiveness in conjunction with multimodal analgesia (MMA) in outpatient breast surgery. This retrospective study aims to evaluate the efficacy of PECS's blocks on perioperative pain management and opioid consumption. Methods: We conducted a retrospective study to assess the efficacy of preoperative PECS block in addition to preoperative MMA (oral acetaminophen and/or gabapentin) in reducing opioid consumption in adult female subjects undergoing outpatient elective breast surgery between 2015 and 2020. A total of 228 subjects were included in the study and divided in two groups: PECS block group (received PECS block + MMA) and control Group (received only MMA). The primary outcome was to compare postoperative opioid consumption between both groups. The secondary outcome was intergroup comparisons of the following: postoperative nausea and vomiting (PONV), incidence of rescue antiemetic medication, PACU non-opioid analgesic medication required, length of PACU stay and the incidence of 30-day postoperative complications between both groups. Results: Two hundred and twenty-eight subjects (n = 228) were included in the study. A total of 174 subjects were allocated in the control group and 54 subjects were allocated in the PECS block group. Breast reduction and mastectomy/lumpectomy surgeries were the most commonly performed procedures (48% and 28%, respectively). The total amount of perioperative (intraoperative and PACU) MME was 27 [19, 38] in the control group and 28.5 [22, 38] in the PECS groups (p = 0.21). PACU opioid consumption was 14.3 [7, 24.5] MME for the control group and 17 [8, 23] MME (p = 0.732) for the PECS group. Lastly, the mean overall incidence of postsurgical complications at 30 days was 3% (N = 5), being wound infection, the only complication observed in the PECS groups (N = 2), and hematoma (N = 2) and wound dehiscence (N = 1) in the control group. Conclusion: PECS block combined with MMA may not reduce intraoperative and/or PACU opioid consumption in patients undergoing outpatient elective breast surgery.

Incidence and Predictors of Inadvertent Dural Puncture After Percutaneous Spinal Cord Stimulation: A Retrospective Database Analysis.

OBJECTIVES: Inadvertent dural puncture (IDP) is a known complication associated with traditional neuraxial procedures; however, its characterization after percutaneous spinal cord stimulation (SCS) lead placement has yet to be clearly established in large population studies. This retrospective analysis aims to understand the incidence and associated characteristics of patients with IDP after percutaneous SCS lead placement. MATERIALS AND METHODS: The PearlDiver Mariner database of national all-payer claims was used to identify patients who received percutaneous SCS leads and had a claim for IDP (intraoperative IDP or postdural puncture headache [PDPH] claim) within 45 days. The primary outcome was to determine the overall incidence of IDP. Secondary outcomes included an evaluation of associated risk factors for IDP and treatments used in symptomatic management. RESULTS: A total of 90,952 patients who underwent percutaneous lead SCS placement were included. The incidence of IDP was 0.48% (436/90,952 patients). Older age (odds ratio [OR]: 0.96; 95% CI: 0.95-0.97; p < 0.0001) and male sex (OR: 0.66; 95% CI: 0.53-0.81; p < 0.001) had a lower odds of having a claim for IDP, whereas a history of IDP was associated with a higher OR (95% CI) by 13.72 times (10.72-17.58) (p < 0.0001). Of the IDP patients, 64% (277/436 patients) had a claim for a therapeutic blood patch. Discrepancy in type of claim for IDP was observed, with most being for PDPH. CONCLUSIONS: Our findings suggest that IDP after percutaneous SCS lead placement is an uncommon event; however, certain factors are associated with its development. Overall, early recognition of IDP after percutaneous SCS lead placement is imperative to facilitate the delivery of targeted treatments and prevent further harmful consequences to the patient.

All Pedicle Screw versus Hybrid Hook-Screw Instrumentation in the Treatment of Thoracic Adolescent Idiopathic Scoliosis (AIS): A Prospective Comparative Cohort Study.

Background: Posterior spinal correction and fusion remains the most common surgical treatment in AIS. Surgeons currently favour all pedicle screw (AS) correction techniques with alternative implants being less utilised. The purpose of this study was to assess whether a hybrid hook−screw (HS) construct could achieve similar outcomes. Methods: A single centre, prospective cohort study was conducted. Patients with moderate and severe thoracic AIS (Lenke 1) were included. Clinical and radiological results of a standardised hybrid HS technique were compared with those obtained with an AS construct. All patients had a minimum 2-year follow-up. Results: 160 patients were included in this series (80 patients/group). The HS group had significantly reduced surgical time, blood loss and implant density. Both techniques achieved ≥75% scoliosis correction. The HS group was superior in restoring thoracic kyphosis and global sagittal balance with an average 31% increase in kyphosis compared to 10% with the AS group (p < 0.001). There was significant improvement in SRS-22 scores at 2 years postoperative (p < 0.001) in both groups. There were no neurological or visceral complications related to instrumentation, no detected non-union and no reoperations. The HS implant cost was significantly lower than that of AS, with a mean instrumentation saving of almost £2000/patient. Conclusion: A standardised hybrid HS technique achieved excellent correction of thoracic scoliosis, high patient satisfaction and low complication rates in patients with thoracic AIS. These results were comparable to the AS group. The HS technique achieved better correction of thoracic kyphosis and sagittal balance than the AS technique, together with reduced surgical time, blood loss and implant cost.

"FLipping" the Story: FLT3-Mutated Acute Myeloid Leukemia and the Evolving Role of FLT3 Inhibitors.

The treatment of many types of cancers, including acute myeloid leukemia (AML), has been revolutionized by the development of therapeutics targeted at crucial molecular drivers of oncogenesis. In contrast to broad, relatively indiscriminate conventional chemotherapy, these targeted agents precisely disrupt key pathways within cancer cells. FMS-like tyrosine kinase 3 (FLT3)-encoding a critical regulator of hematopoiesis-is the most frequently mutated gene in patients with AML, and these mutations herald reduced survival and increased relapse in these patients. Approximately 30% of newly diagnosed AML carries an FLT3 mutation; of these, approximately three-quarters are internal tandem duplication (ITD) mutations, and the remainder are tyrosine kinase domain (TKD) mutations. In contrast to its usual, tightly controlled expression, FLT3-ITD mutants allow constitutive, "run-away" activation of a large number of key downstream pathways which promote cellular proliferation and survival. Targeted inhibition of FLT3 is, therefore, a promising therapeutic avenue. In April 2017, midostaurin became both the first FLT3 inhibitor and the first targeted therapy of any kind in AML to be approved by the US FDA. The use of FLT3 inhibitors has continued to grow as clinical trials continue to demonstrate the efficacy of this class of agents, with an expanding number available for use as both experimental standard-of-care usage. This review examines the biology of FLT3 and its downstream pathways, the mechanism of FLT3 inhibition, the development of the FLT3 inhibitors as a class and uses of the agents currently available clinically, and the mechanisms by which resistance to FLT3 inhibition may both develop and be overcome.

Malignant Peripheral Nerve Sheath Tumors-A Comprehensive Review of Pathophysiology, Diagnosis, and Multidisciplinary Management.

Malignant peripheral nerve sheath tumors (MPNSTs) are aggressive soft tissue sarcomas (STS) with nerve sheath differentiation and a tendency to metastasize. Although occurring at an incidence of 0.001% in the general population, they are relatively common in individuals with neurofibromatosis type 1 (NF1), for whom the lifetime risk approaches 10%. The staging of MPNSTs is complicated and requires close multi-disciplinary collaboration. Their primary management is most often surgical in nature, with non-surgical modalities playing a supportive, necessary role, particularly in metastatic, invasive, or widespread disease. We, therefore, sought to provide a comprehensive review of the relevant literature describing the characteristics of these tumors, their pathophysiology and risk factors, their diagnosis, and their multi-disciplinary treatment. A close partnership between surgical and medical oncologists is therefore necessary. Advances in the molecular characterization of these tumors have also begun to allow the integration of targeted RAS/RAF/MEK/ERK pathway inhibitors into MPNST management.

Perioperative subcutaneous methylnaltrexone does not enhance gastrointestinal recovery after posterior short-segment spinal arthrodesis surgery: a randomized controlled trial.

BACKGROUND CONTEXT: Postoperative ileus is a major barrier to gastrointestinal recovery following surgery. Opioid analgesics likely play an important causative role, particularly in spinal or orthopedic surgeries not involving bowel manipulation. Methylnaltrexone, a peripherally-acting µ-opioid receptor antagonist, is a potential prophylactic treatment. PURPOSE: To assess the influence of perioperative subcutaneous methylnaltrexone administration on gastrointestinal recovery following short-segment lumbar arthrodesis surgeries. DESIGN: This is a randomized, double-blind, controlled trial. PATIENT SAMPLE: Eligible patients undergoing posterior short-segment lumbar arthrodesis surgeries at a single institution between February 2019 and April 2021 were enrolled in this study. OUTCOME MEASURES: The primary outcome measure was time-to-first bowel movement. Secondary outcome measures included time-to-discharge/discharge eligibility. Exploratory outcome measures included daily postoperative opioid consumption and pain scores. METHODS: In this study, eligible patients were enrolled to receive either methylnaltrexone or placebo perioperatively. Time-to-bowel movement, time-to-discharge/discharge eligibility, intra and postoperative analgesic administration, and pain scores were recorded and compared. RESULTS: Eighty two patients in total were enrolled; 41 to the methylnaltrexone and 41 to the placebo group. Both groups were similar in their baseline characteristics. There was no difference in median (range) time-to-bowel movement between the 2 groups [61.8 hours (35.7-93.6) versus 50.7 hours (17.8-110.8), p = .391]. There was also no difference in time-to-discharge/discharge eligibility [105.0 hours (81.0 - 201.3) versus 90.7 (77.5 - 184.5), p=.784]. Finally, there were no differences in either postoperative opioid consumption or numeric rating scores for back, leg, or abdominal pain on postoperative days 0 to 4 (p>.05). CONCLUSIONS: Methylnaltrexone did not accelerate gastrointestinal recovery and did not affect opioid consumption or pain scores following short-segment spinal surgery as compared to placebo. Additional studies will be needed to identify effective opioid receptor antagonist dosing regimens for patients undergoing either short- or long-segment spinal arthrodesis procedures.