Intravenous Methadone versus Intrathecal Morphine as Part of an Enhanced Recovery After Cardiac Surgery Protocol on Postoperative Pain and Outcomes: A Retrospective Cohort Study.

OBJECTIVES: Evaluate the effect of intravenous (IV) methadone versus intrathecal morphine (ITM) within an Enhanced Recovery After Cardiac Surgery (ERACS) pathway on postoperative pain and outcomes (length of hospital stay and postoperative complications) after cardiac surgery. DESIGN: Retrospective cohort study. SETTING: Two tertiary academic medical institutions within the same health system. PARTICIPANTS: Eligible 289 adult patients undergoing elective cardiac surgery with an enhanced recovery pathway from January 2020 through July 2021. INTERVENTIONS: Patients were administered ITM (0.25 mg) or IV methadone (0.1 mg/kg) if ITM was contraindicated. All patients were enrolled in an ERACS pathway using current Enhanced Recovery After Surgery society guidelines. MEASUREMENTS AND MAIN RESULTS: Primary outcome measures included postoperative pain scores and opioid consumption measured as oral morphine equivalents. We analyzed patient demographics, procedural factors, intraoperative medications, and outcomes. Adjusted linear mixed models were fit to analyze associations between intervention and pain outcomes. ITM was associated with decrease in pain scores on postoperative day 0 after adjusting for clinical variables (average marginal effect, 0.49; 95% confidence interval, 0.002-0.977; p = 0.049). No difference in opioid consumption could be demonstrated between groups after adjusting for postoperative day and other variables of interest. CONCLUSIONS: ITM when compared with IV methadone was associated with a decrease in pain scores without any difference in opioid consumption after elective cardiac surgery. Methadone can be considered as a safe and effective alternative to ITM for ERACS protocols. Future large prospective studies are needed to validate this finding and further improve analgesia and safety.

Intrathecal Tigecycline in the Treatment of Hospital-Acquired Meningitis: A Review of Four Cases.

Objectives: Carbapenem-resistant A. baumannii is a common cause of nosocomial meningitis, and it presents a challenge in terms of treatment because of limited therapeutic options. Intravenous tigecycline has been considered a potential salvage therapy against multi-drug-resistant Acinetobacter baumannii. However, its effectiveness is limited by its poor ability to cross the blood-brain barrier. As an alternative treatment option, intrathecal tigecycline has shown promise with its minimal side effects and high concentration in cerebrospinal fluid. Methods: In this report, we present a series of four cases infected with multi-drug-resistant A. baumannii following neurosurgery and treated with intrathecal tigecycline, including antimicrobial therapy. Results: The rate of successful microbiological response was 2 out of 3 cases (66%) in whom microbiological response could be tested anytime during the intrathecal therapy, whereas the 30-day survival rate after treatment completion was » (25%). Conclusion: Although intrathecal tigecycline treatment has shown relative efficacy in achieving microbiological response, its impact on overall survival is still uncertain. Further studies involving larger groups of patients are necessary to evaluate the outcomes of intrathecal tigecycline therapy.

Drug delivery in leptomeningeal disease: Navigating barriers and beyond.

Leptomeningeal disease (LMD) refers to the infiltration of cancer cells into the leptomeningeal compartment. Leptomeninges are the two membranous layers, called the arachnoid membrane and pia mater. The diffuse nature of LMD poses a challenge to its effective diagnosis and successful management. Furthermore, the predominant phenotype; solid masses or freely floating cells, has altering implications on the effectiveness of drug delivery systems. The standard of care is the intrathecal delivery of chemotherapy drugs but it is associated with increased instances of treatment-related complications, low patient compliance, and suboptimal drug distribution. An alternative involves administering the drugs systemically, after which they must traverse fluid barriers to arrive at their destination within the leptomeningeal space. However, this route is known to cause off-target effects as well as produce subtherapeutic drug concentrations at the target site within the central nervous system. The development of new drug delivery systems such as liposomal cytarabine has improved drug delivery in leptomeningeal metastatic disease, but much still needs to be done to effectively target this challenging condition. In this review, we discuss about the anatomy of leptomeninges relevant for drug penetration, the conventional and advanced drug delivery methods for LMD. We also discuss the future directions being set by different clinical trials.

Intrathecal dexamethasone-bupivacaine combination with bupivacaine alone in spinal anesthesia for cesarean delivery.

Background: Postoperative pain management can be achieved by adjuvant medications during the analgesia procedure. The study investigated the effect of intrathecal dexamethasone-bupivacaine combination with bupivacaine alone in spinal anesthesia for cesarean delivery. Methods: This randomized, double-blind clinical examination included 50 females who had previously experienced a cesarean section. The participants were assigned randomly into two categories: the intervention group, received intrathecal bupivacaine-dexamethasone, and the control group, received intrathecal bupivacaine-normal saline. Levels of pain were evaluated using a 10 cm visual analog scale (VAS) at intervals of 30 minutes, 1 hour, 2 hours after the operation. The span of the sensory block and postoperative analgesia were assessed. Results: The inclusion of intrathecal dexamethasone with bupivacaine resulted in a significant enhancement in the duration of pain relief during the intervention, lasting for an average of 473.4 ± 39.95 minutes (p<0.001). The duration of sensory and motor block analgesia in the intervention group was more than the control group (128.32 ± 7.30 vs. 92.84 ± 7.84) and (155.6±12.34 vs. 126.16±11.89), respectively (p<0.001). Pain score on the VAS scale at 30, 60, and 120 minutes was significantly lower in the intervention group (p<0.001). There was no difference in side effects and onset time between the study groups. Conclusion: The inclusion of intrathecal dexamethasone alongside bupivacaine has demonstrated enhancement in the duration of sensory block during spinal anesthesia. This improvement was observed without any alterations in the time it takes for the anesthesia to take effect and without any adverse effects during the postoperative period.

Survival and treatment outcomes in patients with leptomeningeal disease from metastatic melanoma.

Background: Melanoma leptomeningeal disease (LMD) has a poor prognosis. However, the management of patients with advanced melanoma has evolved with time, including those with LMD. We reviewed a large cohort of melanoma LMD patients to assess factors associated with survival. Methods: Retrospective clinical data was collected on patients diagnosed with LMD at MD Anderson Cancer Center from 2015 to 2020. Overall survival (OS) was determined from LMD diagnosis to date of death or last follow-up. The Kaplan-Meier method and log-rank test were used to estimate OS and to assess univariate group differences, respectively. Multivariable associations of survival with variables of interest were determined using Cox proportional hazards regression models. Results: A total of 172 patients were identified. The median age at LMD diagnosis was 53 (range 20-79) years, and all patients had radiographic evidence of LMD on magnetic resonance imaging of either brain or spine. In total 143 patients previously received systemic therapy (83%), with a median of 2 prior treatments (range 0-5). 81 patients (47%) had concurrent uncontrolled systemic disease and 80 patients (53%) had elevated serum LDH at the time of diagnosis. With a median follow-up of 4.0 months (range 0.1-65.3 months), median OS for all patients from LMD diagnosis was 4.9 months. Patients (n = 45) who received intrathecal therapy or systemic immunotherapy for LMD had a median OS of 8.0 months and 10.2 months, respectively. On multivariable analysis, decreased performance status, positive CSF cytology, elevated LDH, and whole brain radiation were associated with worse OS. Conclusions: Despite many advances in therapeutic options, the outcomes of melanoma patients with LMD remains poor. However, a subset of patients appears to derive benefit from LMD-directed treatment.

Implications of monoclonal gammopathy and isoelectric focusing pattern 5 on the free light chain kappa diagnostics in cerebrospinal fluid.

OBJECTIVES: Oligoclonal bands (OCB) analysis is the reference standard for detecting an intrathecal IgG synthesis. Alongside OCB, free light chains kappa (FLCκ) are considered an additional sensitive biomarker for determining patterns 2 or 3, indicating intrathecal Ig synthesis. However, kFLC IF is not suitable for detecting a monoclonal pattern 5. The primary aim of this study was to evaluate the impact of incorporating FLCκ analysis into routine cerebrospinal fluid (CSF) diagnostics instead of OCB testing on the rate of missed monoclonal IgG detection. METHODS: A two-center retrospective biomarker study was conducted. OCB were identified using isoelectric focusing in polyacrylamide gels followed by silver staining or in agarose gels followed by immunofixation. FLCκ were quantified using nephelometry and FLCκ assay (Siemens). RESULTS: Out of a combined total of 17,755 OCB analyses conducted between 2011 and 2021, a subset of 269 cases (1.5 %) exhibited pattern 5. 98 samples (36 %), which included 18 samples with intrathecal inflammation as determined by additional OCB pattern 2 were included in the FLCκ analysis. Of those, 16 (89 %) had intrathecal FLCκ synthesis. CONCLUSIONS: While FLCκ offers a promising avenue for detecting an intrathecal inflammation, the pattern 5, though rare, remains a valuable additional finding of OCB analysis. A combined approach of FLCκ and OCB analysis is recommended for a comprehensive assessment of the humoral intrathecal immune response.

Efficacy and Safety of Intrathecal Morphine for Cesarean Delivery: A Narrative Review.

PURPOSE OF REVIEW: Pain management is a critical aspect of care during and following a cesarean delivery. Without proper control of pain, individuals can experience poor mobility, increased thromboembolic events, and difficulty caring for the neonate in the postpartum period. There have been multiple methods for pain management for cesarean delivery and intrathecal morphine (ITM) has emerged as a prominent option for post-operative analgesia due to its efficacy, safety, and potential benefits over other treatments. This review analyzes data on efficacy, side effects, and safety of ITM and the pain control alternatives. RECENT FINDINGS: A comprehensive literature review was conducted to compare ITM with other analgesic techniques in post-cesarean patients. ITM was found to be as effective or better than other analgesic options, including bilateral quadratus lumborum block (QLB), opioid-free epidural analgesia (CSEA-EDA), and intravenous fentanyl. One study found that both ITM and oral analgesia were effective in pain control and that ITM caused fewer breakthrough pain events but had a longer duration and a greater rate of side effects than oral opioid analgesia. Commonly observed side effects of intrathecal opioids include nausea, vomiting, pruritus, and urinary retention, and it is thought that the adverse effects from intrathecal administration of opioids are short-lived. ITM may provide a decreased risk of DVT and coagulation by decreasing lower extremity weakness and numbness, thereby decreasing recovery time and increasing mobility. ITM is a safe and effective option for post-cesarean analgesia, with comparable pain relief to alternative forms of pain control, and side effects that are generally manageable. Further research is warranted to explore beneficial combinations with other methods of pain management and optimal dosing strategies.

Severe CSF immune cell alterations in cryptococcal meningitis gradually resolve during antifungal therapy.

Cryptococcal meningitis (CM) is a severe fungal disease in immunocompromised patients affecting the central nervous system (CNS). Host response and immunological alterations in the cerebrospinal fluid (CSF) after invasion of Cryptococcus neoformans to the central nervous system have been investigated before but rigorous and comprehensive studies examining cellular changes in the CSF of patients with cryptococccal meningitis are still rare. We retrospectively collected CSF analysis and flow cytometry data of CSF and blood in patients with CM (n = 7) and compared them to HIV positive patients without meningitis (n = 13) and HIV negative healthy controls (n = 7). Within the group of patients with CM we compared those with HIV infection (n = 3) or other immunocompromised conditions (n = 4). Flow cytometry analysis revealed an elevation of natural killer cells and natural killer T cells in the CSF and blood of HIV negative patients with CM, pointing to innate immune activation in early stages after fungal invasion. HIV positive patients with CM exhibited stronger blood-CSF-barrier disruption. Follow-up CSF analysis over up to 150 days showed heterogeneous cellular courses in CM patients with slow normalization of CSF after induction of antifungal therapy.

Management of Cerebrospinal Fluid Leak After Intrathecal Baclofen Pump Procedures in Adolescents With Cerebral Palsy: A Retrospective Study.

STUDY OBJECTIVE:  Epidural blood patches (EBPs) are frequently performed in children with cerebral palsy (CP) to manage post-dural puncture headache (PDPH) due to cerebrospinal fluid (CSF) leak after intrathecal baclofen pump (ITBP) placement or replacement procedures. The purpose of our study was to review the incidence and management of CSF leak following ITBP placement or replacement procedures in children with CP. The study was a retrospective review of 245 patients representing 310 surgical cases of baclofen pump insertion (n=141) or reinsertion (n=169) conducted at a 125-bed children's hospital with prominent specialty orthopedics surgical cases. MEASUREMENTS:  Demographic and clinical information was obtained from the anesthesia pain service database on all new ITBP placement and subsequent replacements over an eight-year period. MAIN RESULTS:  The overall incidence of CSF leak in our population was 16% (50 of 310) and 18% (25 of 141) with a new ITBP placement. Children with diplegia were associated with a threefold risk of developing CSF leak. Of patients who developed CSF leak (n=50), 68% (n=34) were successfully treated conservatively, while 32% (n=16) required EBPs. EBPs were successful in 87.5% (14 of 16) of patients at relieving PDPH on the first attempt.  Conclusions: CSF leak is a known problem after ITBP placement and replacement. Most patients were successfully treated with conservative management and EBPs were successful in patients failing conservative therapy. Diagnosing PDPH in non-verbal patients can be challenging.

Unveiling the adverse events of Nusinersen in spinal muscular atrophy management based on FAERS database.

This study aims to collect and analyze adverse event (AE) reports related to Nusinersen from the FAERS database. The study employed a combination of signal quantification techniques, including the Reporting Odds Ratio (ROR), Proportional Reporting Ratio (PRR), Bayesian Confidence Propagation Neural Network (BCPNN), and Multi-item Gamma Poisson Shrinker (MGPS), to enhance the accuracy of signal detection and reduce the risk of false positives or negatives. Between the first quarter of 2017 and the third quarter of 2023, the FAERS database collected a total of 11,485,105 drug AE reports, of which 5772 were related to Nusinersen. Through signal mining analysis, 218 preferred term (PT) signals involving 27 system organ classes (SOCs) were identified. The study discovered AEs related to metabolism and nutrition disorders, psychiatric disorders, and cardiac disorders SOCs, which were not mentioned in the product information. Additionally, complications directly related to the intrathecal administration of Nusinersen, such as increased CSF pressure, positive CSF red blood cell count, and AEs related to the method of drug use, such as neuromuscular scoliosis and cerebrospinal fluid reservoir placement, were highlighted. Notably, AEs related to renal function abnormalities, such as abnormal Urine protein/creatinine ratio and protein urine presence, showed higher frequency and signal strength. The findings of this study emphasize the importance of comprehensive safety monitoring in the clinical application of Nusinersen. These results are significant for guiding future clinical practices, improving disease management strategies, and developing safer treatment protocols.

Comparing reactive versus empiric cerebrospinal fluid drainage strategies for spinal perfusion pressure optimization in patients with acute traumatic spinal cord injuries.

BACKGROUND: Spinal cord hypoperfusion undermines clinical recovery in acute traumatic spinal cord injuries. New guidelines suggest cerebrospinal fluid (CSF) drainage is an important strategy for preventing spinal cord hypoperfusion in the acute post-injury phase. METHODS: This study included participants presenting to a single level 1 trauma center between 2018 and 2022 with cervical or thoracic traumatic spinal cord injury severity grade A-C, as evaluated by the American spinal injury association impairment scale (AIS). The primary objective of this study was to compare the efficacy of two CSF drainage protocols in preventing spinal cord hypoperfusion; 1) draining CSF only when spinal cord perfusion pressure (SCPP) drops below 65 mmHg (i.e. reactive) versus 2) empiric CSF drainage of 5-10 mL every hour. Intrathecal pressure, spinal cord perfusion pressure (SCPP), mean arterial pressure (MAP), and vasopressor utilization were compared using univariate T-test statistical analysis. RESULTS: While there was no difference in the incidence of sub-optimal SCPP (<65 mmHg; p = 0.1658), reactively drained participants were more likely to exhibit critical hypoperfusion (<50 mmHg; p = 0.0030) despite also having lower average intrathecal pressures (p < 0.001). There were no differences in average SCPP, mean arterial pressure (MAP), or vasopressor utilization between the two groups (p > 0.05). CONCLUSIONS: Empiric (vs reactive) CSF drainage resulted in fewer incidences of critical spinal cord hypoperfusion for patients with acute traumatic spinal cord injuries.

Assessment of three criteria to establish borrelial infection in suspected lyme neuroborreliosis.

PURPOSE: Diagnosis of (European) Lyme neuroborreliosis has been based on clinical presentation, cerebrospinal fluid (CSF) pleocytosis and demonstration of intrathecal borrelial antibody synthesis (ITBAS) to document Borrelia burgdorferi s. l. INFECTION: It is not known if other criteria to document Borrelia infection may contribute to the diagnosis. METHODS: We compared the sensitivity of three individual criteria (ITBAS, CSF Borrelia culture, and the presence of erythema migrans [EM]) to confirm the diagnosis of early Lyme neuroborreliosis in 280 patients ≥ 15 years of age evaluated at a Lyme borreliosis outpatient clinic in Slovenia. The patients had either radicular pain of new onset or involvement of a cranial nerve but without radicular pain, each in conjunction with CSF pleocytosis. Evaluation was of patients who had each of the three confirmatory criteria assessed, and for whom at least one criterion was positive. RESULTS: Analysis of 280 patients, 120 women and 160 men, median age 57 (range 15-84) years, revealed that ITBAS was the most frequently observed positive criterion (85.4%), followed by EM (52.9%), and by a positive CSF Borrelia culture (9.6%). Of the 280 patients, 154 (55%) met only one criterion (43.2% ITBAS only, 10.7% EM only, and 1.1% positive CSF culture only), whereas 42.1% met two criteria. Only 2.9% of patients were positive by all three criteria. CONCLUSION: Although ITBAS was the most frequent criterion for confirmation for Borrelia infection, the presence of EM alone confirmed an additional 10.7% of patients and a positive CSF Borrelia culture alone added another 1.1%.

Comparison of intrathecal morphine versus erector spinae block for postoperative analgesia in patients with end-stage kidney disease undergoing kidney transplantation: A randomised clinical study.

Background and Aims: Intrathecal morphine (ITM) or erector spinae plane (ESP) block reduces postsurgical pain in patients who underwent kidney transplantation surgeries. We aimed to compare the effectiveness of both modalities in terms of duration and quality of postoperative analgesia along with postoperative fentanyl consumption. Methods: We conducted a randomised study and analysed 60 patients posted for elective live-related kidney transplantation surgery. They were randomised into two groups. Group M patients received ITM, whereas Group E patients received ESP block. We standardised the postoperative analgesia for both groups with intravenous fentanyl-based patient-controlled analgesia. The primary outcome was to compare the quality of analgesia using the numerical rating scale score between the groups. The secondary outcome was to observe the effect of both modalities on the duration of analgesia, postoperative fentanyl consumption, rescue analgesics requirement, catheter-related bladder discomfort and any complications. Results: We found significantly lower pain scores at rest and while coughing in Group M at all time intervals, except at 24 h while coughing. The mean time to first analgesia requirement was significantly longer in Group M than in Group E (P = 0.002). No significant difference was found in postoperative consumption of total fentanyl (P = 0.065) and rescue analgesia in both groups. In Group M, there was significantly more nausea, vomiting and pruritus (P = 0.001). Conclusions: ITM provides long-lasting postoperative analgesia at the cost of higher side effects than ESP block.

CT myelography by intrathecal injection of contrast medium though percutaneous administration route visualizes compressed cervical spinal cord in a mouse.

BACKGROUND: Chronic compressive myelopathy (CCM) is a major cause of spinal cord disorders in the elderly, in which the spinal cord is compressed by bony or soft tissue structures. Although computed tomography myelography (CTM) has been clinically used for the diagnosis of CCM, a method of CTM in rodents remains to be developed. NEW METHOD: A 50 µl Hamilton syringe attached to a disposable needle was percutaneously inserted into the subarachnoid space (cisterna magna) between the occipital bone and C1 lamina in an anesthetized adult mouse, followed by the injection of contrast medium and CT imaging. RESULTS: CTM clearly visualized the shape of the spinal cord of intact mice and tiptoe-walking Yoshimura (Twy) mice without any health issues. COMPARISON WITH EXISTING METHOD(S): Unlike histology, the current method functions in live mice, directly depicts the compressed spinal cord, and provides clinically related image information. Furthermore, the intrathecal administration of contrast medium through the percutaneous route makes CTM less invasive and takes less time than a conventional intrathecal injection method. CONCLUSIONS: The CTM method used in the present study enables clear visualization of the shape of the dural sac and spinal cord and is useful when conducting experiments on CCM and other spinal diseases in rodents.

Central Nervous System Prophylaxis Utilization in Patients With Newly Diagnosed Diffuse Large B-Cell Lymphoma Within a Large Community Health System.

Purpose: The impact of central nervous system (CNS) prophylaxis in diffuse large B-cell lymphoma (DLBCL) is contentious. The CNS International Prognostic Index (IPI) calculator offers prognostic guidance in identifying those patients who may be at highest risk of disease progression or relapse to the CNS. However, it is unclear whether this tool has guided clinician decision-making in a real-world setting. Studies have suggested that CNS prophylaxis may not offer clinically significant benefit in terms of preventing CNS disease progression. Given this, we investigated the utilization of CNS prophylaxis within our own population and documentation of the CNS-IPI score. Methods: We retrospectively evaluated patients with newly diagnosed DLBCL between January 1, 2014, and December 31, 2017. Patients were assessed for receipt of CNS prophylaxis in the form of intrathecal (IT) chemotherapy and/or high-dose intravenous (IV) methotrexate. CNS-IPI scores were calculated for all patients who received CNS prophylaxis or those who experienced CNS disease. Long-term outcomes at five years from diagnosis included CNS progression/relapse and survival. Results: Of 234 patients who met criteria, 20 (8.6%) received either IV methotrexate or IT chemotherapy; most received IT methotrexate. No patients in the IT prophylaxis group developed CNS disease, while two of eight IV methotrexate patients experienced CNS disease involvement. The incidence of CNS progression was 3.7% in the no prophylaxis group and 10% in those who received prophylaxis. Conclusions: This study revealed low utilization of CNS prophylaxis and CNS-IPI documentation in a community hospital system. Given large differences between groups, claims of CNS prophylaxis efficacy are unable to be made. CNS relapse rates were consistent with existing literature and promote continued evaluation of the utility of current CNS prophylaxis approaches in DLBCL. New unambiguously effective therapeutic approaches are needed and may encourage a higher rate of standardized use.

Postoperative Cesarean Section Pain Management Using Transversus Abdominis Plane Block Versus Intrathecal Morphine: A Systematic Review and Meta-analysis.

PURPOSE: Compare and evaluate the effectiveness of transversus abdominis plane (TAP) block versus intrathecal morphine (ITM) on elective postcesarean section pain, opioid consumption, and related side effects. DESIGN: Systematic review and meta-analysis. METHODS: A search for evidence was conducted in PubMed, Google Scholar, CINAHL, Cochrane Collaboration Database, UpToDate, Health Source, and gray literature. Only randomized controlled trials (RCTs) were included in the study. The methodological quality of evidence assessment was conducted using the Risk of Bias and Grades of Recommendation, Assessment, Development, and Evaluation system. The meta-analysis used Review Manager (RevMan 5.4, The Cochrane Collaboration). FINDINGS: A total of 11 RCTs involving 1,129 patients were analyzed. Compared to ITM, TAP has a similar effect on static (mean difference [MD]; 0.37; 95% confidence interval [CI], -0.04 to 0.79; P = .08) and dynamic pain scores (MD, 0.43; 95% CI, -0.06 to 0.92; P = .09) within the first 48 hours after surgery. Additionally, the TAP block had a lower incidence of postoperative nausea and vomiting (risk ratio, 0.45; 95% CI, 0.31 to 0.66; P < .0001) and increased opioid consumption (MD, 6.78; 95% CI, 3.79 to 9.77; P < .00001). Overall, TAP block and ITM did not differ in the time to first to rescue analgesia, incidence of sedation, and pruritus. CONCLUSIONS: Evidence suggests that TAP blocks are equivalent to ITM in pain scores and more effective at lowering the incidence of postoperative nausea and vomiting, yet ITM has been shown to be more effective in reducing postoperative opioid consumption.

Intrathecal topotecan with systemic checkpoint inhibitor therapy for gastroesophageal cancer with leptomeningeal involvement: two case reports and review of the literature.

Background: Leptomeningeal metastases (LM) in gastroesophageal (GE) malignancies are exceedingly rare. Historically, treatment for LM has included steroids, radiation, chemotherapy, and intrathecal (IT) chemotherapy. However, the outcomes in GE malignancies with LM remain poor. Unfortunately, clinical trials in GE malignancies have traditionally excluded those with LM, limiting advances in therapeutic strategies. Given that LM poses potentially devastating neurologic and psychologic sequelae, there is an urgent need for more effective treatments. Case Description: Patient 1 is a 44-year-old woman with localized esophageal adenocarcinoma who undergoes neoadjuvant chemoradiation followed by esophagectomy. Seven months following surgery, she develops ataxia, weakness, and nausea/vomiting. Magnetic resonance imaging (MRI) reveals intracranial disease that is subsequently successfully resected and then treated with gamma knife (GK) radiation. Pathology confirms metastases. Three months later she is found to have LM. She receives palliative whole brain radiation therapy as well as focal radiation to the spine. Following this she transitioned to concurrent IT topotecan plus intravenous (IV) ipilumumab/nivolumab with durable response beyond 14 months. Patient 2 is a 71-year-old man with de novo metastatic esophageal adenocarcinoma with durable response to 5-fluorouracil plus irinotecan. Asymptomatic intracranial metastases are detected on surveillance scans 2 years after initial diagnosis for which he receives GK. Follow up MRI identifies new LM. As such, to treat the LM, he was transitioned to IT topotecan and IV pembrolizumab with good response for 6 months until death from a gastrointestinal bleed. Conclusions: We present two cases of LM in patients with GE adenocarcinoma who had longer survival than what has been reported. They were treated with combination IT topotecan and IV checkpoint inhibition. Further studies evaluating the central nervous system tumor immune-microenvironment can help expand our understanding of how this combination has worked well in our patients and how to care for others with similar scenarios.

[A case of massive intrathecal hematoma of the rectus abdominis secondary to acute severe carbon monoxide poisoning].

Acute carbon monoxide poisoning can cause hypoxic injury to multiple organs. Neurological impairment and cardiac dysfunction are common manifestations of severe poisoning patients, but hemorrhagic complications are rare in clinic. The clinical diagnosis and treatment of a case of massive intrathecal hematoma of the rectus abdominis secondary to acute severe carbon monoxide poisoning was reported. The pathophysiological mechanism and treatment strategy of rectus sheath hematoma secondary to acute severe carbon monoxide poisoning was analyzed, in order to improve the understanding of hemorrhagic complications of carbon monoxide poisoning. This case suggests that for patients with a history of cardiovascular disease and taking anticoagulants, clinicians should be alert for the risk of bleeding when making medical decisions.