Systematic review and meta-analysis evaluating clinical outcomes in adult acute myeloid leukemia patients with central nervous system involvement.

Patients with acute myeloid leukemia (AML) may experience extramedullary involvement when disease is present outside of the blood and bone marrow. In particular, the presence of central nervous system (CNS) involvement has traditionally been thought of as a poor prognostic factor. In the presently available literature, there is a paucity of conclusive data surrounding CNS AML given its rarity and lack of unified screening practices. Thus, we performed a systematic review and meta-analysis in order to more definitively characterize survival outcomes in this patient population. In this meta-analysis, we evaluated survival outcomes and response rates from clinical studies on patients with AML stratified by the presence of CNS involvement. Twelve studies were included in the meta-analysis with a resulting hazard ratio (HR) for overall survival (OS) of 1.34 with a 95 % CI of 1.14 to 1.58. These findings suggest that CNS involvement in adult patients with AML is associated with an increased hazard of mortality compared to those patients without CNS involvement. As such, CNS involvement should be viewed as negative prognostic marker, and attention should be made to ensure prompt identification and treatment of patients who experience this complication.

Exclusion of Acute Myeloid Leukemia Patients with Central Nervous System Involvement from Clinical Trials: An Analysis of the National Institutes of Health Clinical Trials Registry from 2012-2022.

INTRODUCTION: Central nervous system (CNS) involvement in acute myeloid leukemia (AML) can be successfully treated with intrathecal chemotherapy and carries debatable prognostic impact. However, patients with CNS involvement are commonly excluded from clinical trials at an unknown rate. We systematically evaluated exclusion criteria of AML clinical trials based on CNS involvement and determined associations with clinical trial characteristics. METHODS: The National Institutes of Health Clinical Trials Registry was searched for interventional adult AML trials between 2012-2022 that were phase I, II, or III and relevant trial characteristics were extracted. RESULTS: 1270 trials were included in the analysis with 790 trials (62.1%) explicitly excluding CNS involvement. There was no significant change in rates of CNS exclusion over the past decade. CNS exclusion was higher in trials that included the non-transplant population compared to trials exclusive to the transplant population (66.9% vs. 43.8%, p<0.01). Non-transplant trials were also more likely to exclude patients with a history of or ambiguous timing of CNS involvement (p<0.01). Phase III trials were associated with more liberal definitions of CNS exclusion (history or ambiguous timing) as compared to phase I and II trials that had higher rates of excluding patients with only active CNS involvement (P<0.01). CONCLUSION: A majority of AML clinical trials, particularly in the non-transplant setting, exclude patients with CNS involvement. Many of these trials, most notably phase 3 trials, exclude patients not only with active, but any history of CNS involvement. Further research is needed to determine optimal management of these patients in order to increase representation in large clinical trials.

Multi-institutional analysis of outcomes in acute myeloid leukemia patients with central nervous system involvement.

We evaluated outcomes of AML patients with central nervous system (CNS) involvement at two academic institutions. Fifty-two adult patients were identified. Neurologic symptoms were reported in 69% of patients, with headache the most common (33%). 84% (n = 42) of patients cleared their cerebrospinal fluid (CSF), with a median number of one dose of intrathecal (IT) chemotherapy. Of these patients, 21% (n = 9) had a CSF relapse, with 67% (n = 6) of those experiencing CSF relapse also having concurrent bone marrow relapse. Of the 36 patients with baseline neurologic symptoms, 69% had improvement in symptoms post-IT therapy. The median overall survival was 9.3 months and 3.5 months for patients with CNS involvement diagnosed before/during induction and at relapse, respectively. In this study, IT therapy was rapidly effective in clearing CSF blasts and improving neurologic symptoms in most patients. Few patients experienced CSF relapse, which predominantly occurred in the setting of concomitant bone marrow relapse.

Emerging Treatment Options for Myelofibrosis: Focus on Anemia.

Myelofibrosis (MF) is a hematologic malignancy characterized by abnormal proliferation of myeloid cells and the release of pro-inflammatory cytokines, leading to progressive bone marrow dysfunction. The introduction of ruxolitinib just over a decade ago marked a significant advancement in MF therapy, with JAK inhibitors now being the first-line treatment for reducing spleen size and managing symptoms. However, early JAK inhibitors (ruxolitinib and fedratinib) are often associated with cytopenias, particularly thrombocytopenia and anemia, which limit their tolerability. To address these complications, pacritinib has been developed and recently approved for patients with thrombocytopenia, while momelotinib is in development for those with anemia. Although JAK inhibitors have significantly improved the quality of life of MF patients, they have not demonstrated the ability to reduce leukemic transformation and their impact on survival is debated. Numerous drugs are currently being developed and investigated in clinical trials, both as standalone therapy and in combination with JAK inhibitors, with promising results enhancing the benefits of JAK inhibitors. In the near future, MF treatment strategies will involve selecting the most suitable JAK inhibitor based on individual patient characteristics and prior therapy. Ongoing and future clinical trials are crucial for advancing the field and expanding therapeutic options for MF patients.

Thrombocytopenia in Patients With Myelofibrosis: Pathogenesis, Prevalence, Prognostic Impact, and Treatment.

Myelofibrosis (MF) is a clonal hematopoietic stem cell neoplasm, characterized by pathologic myeloproliferation associated with inflammatory and pro-angiogenic cytokine release, that results in functional compromise of the bone marrow. Thrombocytopenia is a disease-related feature of MF, which portends a poor prognosis impacting overall survival (OS) and leukemia free survival. Thrombocytopenia in MF has multiple causes including ineffective hematopoiesis, splenic sequestration, and treatment-related effects. Presently, allogeneic hematopoietic stem cell transplantation (HSCT) remains the only curable treatment for MF, which, unfortunately, is only a viable option for a minority of patients. All other currently available therapies are either focused on improving cytopenias or the alleviating systemic symptoms and burdensome splenomegaly. While JAK2 inhibitors have moved to the forefront of MF therapy, available JAK inhibitors are advised against in patients with severe thrombocytopenia (platelets < 50 × 109/L). In this review, we describe the pathogenesis, prevalence, and prognostic significance of thrombocytopenia in MF. We also explore the value and limitations of treatments directed at addressing cytopenias, splenomegaly and symptom burden, and those with potential disease modification. We conclude by proposing a treatment algorithm for patients with MF and severe thrombocytopenia.

Intraoperative haemodynamics and postoperative intensive care unit admission in older patients with cancer.

PURPOSE: Research on the impact of various intraoperative haemodynamic variables on the incidence of postoperative ICU admission among older patients with cancer is limited. In this study, the relationship between intraoperative haemodynamic status and postoperative intensive care unit admission among older patients with cancer is explored. METHODS: Patients aged ≥75 who underwent elective oncologic surgery lasting ≥120min were analysed. Chi-squared and t-tests were used to assess the associations between intraoperative variables with postoperative intensive care unit admission. Multivariable regressions were used to analyse potential predict risk factors for postoperative intensive care unit admission. RESULTS: Out of 994 patients, 48 (4.8%) were admitted to the intensive care unit within 30 days following surgery. Intensive care unit admission was associated with the presence of ≥4 comorbid conditions, intraoperative blood loss ≥100mL, and intraoperative tachycardia and hypertensive urgency. On multivariable analysis, operation time ≥240min (Odds Ratio [OR] = 2.29, p = 0.01), and each minute spent with intraoperative hypertensive urgency (OR = 1.06, p = 0.01) or tachycardia (OR = 1.01, p = 0.002) were associated with postoperative intensive care unit admission. CONCLUSION: Intraoperative hypertensive urgency and tachycardia were associated with postoperative intensive care unit admission in older patients undergoing cancer surgery.

Bispecific Antibodies in Multiple Myeloma: Present and Future.

Despite many recent advances in therapy, there is still no plateau in overall survival curves in multiple myeloma. Bispecific antibodies are a novel immunotherapeutic approach designed to bind antigens on malignant plasma cells and cytotoxic immune effector cells. Early-phase clinical trials targeting B-cell maturation antigen (BCMA), GPRC5D, and FcRH5 have demonstrated a favorable safety profile, with mainly low-grade cytokine release syndrome, cytopenias, and infections. Although dose escalation is ongoing in several studies, early efficacy data show response rates in the most active dose cohorts between 61% and 83% with many deep responses; however, durability remains to be established. Further clinical trial data are eagerly anticipated. SIGNIFICANCE: Overall survival of triple-class refractory multiple myeloma remains poor. Bispecific antibodies are a novel immunotherapeutic modality with a favorable safety profile and impressive preliminary efficacy in heavily treated patients. Although more data are needed, bispecifics will likely become an integral part of the multiple myeloma treatment paradigm in the near future. Studies in earlier lines of therapy and in combination with other active anti-multiple myeloma agents will help further define the role of bispecifics in multiple myeloma.

A Sleep Hygiene Intervention to Improve Sleep Quality for Hospitalized Patients.

INTRODUCTION: Poor sleep is a pervasive problem for hospitalized patients and can contribute to adverse health outcomes. METHODS: We aimed to improve self-reported sleep for patients on a general medicine ward as measured by the Richards-Campbell Sleep Questionnaire (RCSQ) as well as the Hospital Consumer Assessment of Healthcare Providers and Systems (HCAHPS) question addressing quietness at night. We utilized a non-pharmacologic sleep hygiene bundle composed of a short script with sleep hygiene prompts, such as whether patients would like the shades closed or the lights turned off, as well as a sleep package including an eye mask, earplugs, lavender scent pad, and non-caffeinated tea. Relaxing music was played at bedtime and signs promoting the importance of quietness at night were placed around the unit. Front-line champions were identified to aid with implementation. RESULTS: A total of 931 patients received the intervention. In a sample of surveyed patients, we observed an increase in the RCSQ global score from 6.0 (IQR 3.0-7.0) to 6.2 (IQR 4.0-7.8) from the pre- to post- intervention periods (p = 0.041), as well as increases in three of the five individual survey components. Additionally, HCAHPS "quietness at night" score increased on the unit from 34.1% pre-intervention to 42.5% post-intervention. CONCLUSION: A nonpharmacologic sleep hygiene protocol paired with provider education and use of champions was associated with modest improvements in patients' perceived sleep and unit HCAHPS scores.

The Disparity of Care and Outcomes for Medicaid Patients Undergoing Colectomy.

BACKGROUND: Colectomies are one of the most common surgeries in the United States with about 275,000 performed annually. Studies have shown that insurance status is an independent risk factor for worse surgical outcomes. This study aims to analyze the effect of insurance on health outcomes of patients undergoing colectomy procedures. METHODS: We examined hospital discharge data from the State Inpatient Database, Healthcare Cost and Utilization Project, Agency for Healthcare Research and Quality, from 2009 to 2014 in California, Florida, New York, Maryland, and Kentucky. The primary outcome was in-hospital mortality. Secondary outcomes included complications, length of stay (LOS), total hospital charges, and 30- and 90-d readmissions. RESULTS: A total of 444,877 patients were included in the analysis. Bivariate analysis showed that open surgeries were more common in Medicaid patients (50.5%), whereas robotic and laparoscopic surgeries were more common in private insurance holders (50.4% and 21.7%, respectively). In the adjusted multivariate models, when compared with private insurance patients, Medicaid patients had the highest odds ratio (OR) for mortality (OR, 1.96; 95% confidence interval [CI], 1.78-2.15), complication rates (OR, 1.43; 95% CI, 1.38-1.49), 30-d readmission (OR, 1.47; 95% CI, 1.40-1.55), 90-d readmission (OR, 1.44; 95% CI, 1.37-1.51), longer LOS (coefficient, 1.26; 95% CI, 1.24-1.28), and higher total hospital charges (coefficient, 1.15; 95% CI, 1.13-1.17). CONCLUSIONS: We identified Medicaid insurance status as a predictor of open colectomies and of higher mortality, LOS, complications, readmission rates, and charges after colectomy. Further research and initiatives are necessary to meet the specific needs of patients with different payer types.

The Disparities of Coronary Artery Bypass Grafting Surgery Outcomes by Insurance Status: A Retrospective Cohort Study, 2007-2014.

BACKGROUND: Coronary artery bypass grafting (CABG) surgery is the gold standard treatment for complex coronary artery disease. Social determinants of health, including primary payer status, are disproportionately associated with adverse outcomes following surgical operations. We sought to examine associations between insurance status, in particular having Medicaid public insurance, and postoperative outcomes following isolated CABG surgeries. METHODS: A retrospective review was performed using Florida, California, New York, Maryland, and Kentucky State Inpatient Databases (2007-2014) for isolated CABG patients ≥ 18 years. Multivariate regression for postsurgical inpatient mortality, postsurgical complications, 30- and 90-day readmission rates, total charges, and length of stay yielded adjusted odds ratios (ORs) reported for outcomes by insurance status. RESULTS: Among 312,018 individuals, patients with Medicaid insurance and those designated as Uninsured incurred increased adjusted ORs of postsurgical inpatient mortality (56 and 64%, respectively) compared to Private Insurance. Additionally, Medicaid had the highest adjusted OR for 30-day readmission (OR 1.52, 95% CI 1.45-1.59), 90-day readmission (OR 1.53, 95% CI 1.47-1.59), postsurgical complications (OR 1.10, 95% CI 1.07-1.14) including pulmonary and infectious complications, postoperative length of stay, and total hospital charges (2016 dollars). CONCLUSIONS: Medicaid insurance, compared to Private Insurance, is significantly associated with worse outcomes after isolated CABG. Our results demonstrate that Medicaid as a patient's primary insurance payer is an independent predictor of perioperative risks. Further research may help explain the reasons for the differences in payer groups.

Readmission Rates and Diagnoses Following Total Hip Replacement in Relation to Insurance Payer Status, Race and Ethnicity, and Income Status.

BACKGROUND: Total hip replacements (THRs) are the sixth most common surgical procedure performed in the USA. Readmission rates are estimated at between 4.0 and 10.9%, and mean costs are between $10,000 and $19,000. Readmissions are influenced by the quality of care received. We sought to examine differences in readmissions by insurance payer, race and ethnicity, and income status. METHODS: We analyzed all THRs from 2007 to 2011 in California, Florida, and New York from the State Inpatient Databases, Healthcare Cost and Utilization Project, Agency for Healthcare Research and Quality. Primary outcomes were readmission at 30 and 90 days after THR. Descriptive statistics were calculated, and multivariate logistic regression analysis was used to estimate adjusted odds ratio (OR) for readmissions. Statistical significance was evaluated at the < 0.05 alpha level. RESULTS: A total of 274,851 patients were included in the analyses. At 30 days (90 days), 5.6% (10.2%) patients had been readmitted. Multivariate logistic regression analysis showed that patients insured by Medicaid (OR 1.23, 95%CI 1.17-1.29) and Medicare (OR 1.58, 95%CI 1.44-1.73) had increased odds of 30-day readmission, as did patients living in areas with lower incomes, Black patients, and patients treated at lower volume hospitals. Ninety-day readmissions showed similar significant results. CONCLUSIONS: The present study has shown that patients on public insurance, Black patients, and patients who live in areas with lower median incomes have higher odds of readmission. Future research should focus on further identifying racial and socioeconomic disparities in readmission after THR with an eye towards implementing strategies to ameliorate these differences.

Medicaid insurance as primary payer predicts increased mortality after total hip replacement in the state inpatient databases of California, Florida and New York.

STUDY OBJECTIVE: To confirm the relationship between primary payer status as a predictor of increased perioperative risks and post-operative outcomes after total hip replacements. DESIGN: Retrospective cohort study. SETTING: Administrative database study using 2007-2011 data from California, Florida, and New York from the State Inpatient Databases (SID), Healthcare Cost and Utilization Project, Agency for Healthcare Research and Quality. PATIENTS: 295,572 patients age≥18years old who underwent total hip replacement with non-missing insurance data were collected, using International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) diagnoses and procedures code (ICD-9-CM code 81.51). INTERVENTIONS: Patients underwent total hip replacement. MEASUREMENTS: Patients were cohorted by insurance type as either Medicare, Medicaid, Uninsured, Other, and Private Insurance. Demographic characteristics and comorbidities were compared. Unadjusted rates of in-hospital mortality, postoperative complications, LOS, 30-day, and 90-day readmission status were compared. Adjusted odds ratios were calculated for our outcomes using multivariate linear and logistic regression models fitted to our data. MAIN RESULTS: Medicaid patients incurred a 125% increase in the odds of in-hospital mortality compared to those with Private Insurance (OR 2.25, 99% CI 1.01-5.01). Medicaid payer status was associated with the highest statistically significant adjusted odds of mortality, any complication (OR, 1.26), cardiovascular complications (OR, 1.37), and infectious complications (OR, 1.66) when compared with Private Insurance. Medicaid patients had the highest statistically significant adjusted odds of 30-day (OR, 1.63) and 90-day readmission (OR, 1.58) and the longest adjusted LOS. CONCLUSIONS: We found higher unadjusted rates and risk adjusted odds ratios of postoperative mortality, morbidity, LOS, and readmissions for patients with Medicaid insurance as compared to patients with Private Insurance. Our study shows that primary payer status serves as a predictor of perioperative risks and that primary payer status should be viewed as a peri-operative risk factor.

Anesthesia for the patient undergoing total knee replacement: current status and future prospects.

Total knee arthroplasty (TKA) has become one of the most common orthopedic surgical procedures performed nationally. As the population and surgical techniques for TKAs have evolved over time, so have the anesthesia and analgesia used for these procedures. General anesthesia has been the dominant form of anesthesia utilized for TKA in the past, but regional anesthetic techniques are on the rise. Multiple studies have shown the potential for regional anesthesia to improve patient outcomes, such as a decrease in intraoperative blood loss, length of stay, and patient mortality. Anesthesiologists are also moving toward multimodal analgesia, which includes peripheral nerve blockade, periarticular injection, and preemptive analgesia. The goal of multimodal analgesia is to improve perioperative pain control while minimizing systemic narcotic consumption. With improved postoperative pain management and rapid patient rehabilitation, new clinical pathways have been engineered to fast track patient recovery after orthopedic procedures. The aim of these clinical pathways was to improve quality of care, minimize unnecessary variations in care, and reduce cost by using streamlined procedures and protocols. The future of TKA care will be formalized clinical pathways and tracks to better optimize perioperative algorithms with regard to pain control and perioperative rehabilitation.

Crystallization of lysozyme with (R)-, (S)- and (RS)-2-methyl-2,4-pentanediol.

Chiral control of crystallization has ample precedent in the small-molecule world, but relatively little is known about the role of chirality in protein crystallization. In this study, lysozyme was crystallized in the presence of the chiral additive 2-methyl-2,4-pentanediol (MPD) separately using the R and S enantiomers as well as with a racemic RS mixture. Crystals grown with (R)-MPD had the most order and produced the highest resolution protein structures. This result is consistent with the observation that in the crystals grown with (R)-MPD and (RS)-MPD the crystal contacts are made by (R)-MPD, demonstrating that there is preferential interaction between lysozyme and this enantiomer. These findings suggest that chiral interactions are important in protein crystallization.