A Prospective, Multicenter, Observational Study of Surgical vs Nonsurgical Management for Pituitary Apoplexy.

CONTEXT: Pituitary apoplexy (PA) has been traditionally considered a neurosurgical emergency, yet retrospective single-institution studies suggest similar outcomes among patients managed medically. OBJECTIVE: We established a multicenter, international prospective registry to compare presentation and outcomes in PA patients treated with surgery or medical management alone. METHODS: A centralized database captured demographics, comorbidities, clinical presentation, visual findings, hormonal status, and imaging features at admission. Treatment was determined independently by each site. Key outcomes included visual, oculomotor, and hormonal recovery, complications, and hospital length of stay. Outcomes were also compared based on time from symptom onset to surgery, and from admission or transfer to the treating center. Statistical testing compared treatment groups based on 2-sided hypotheses and P less than .05. RESULTS: A total of 100 consecutive PA patients from 12 hospitals were enrolled, and 97 (67 surgical and 30 medical) were evaluable. Demographics, clinical features, presenting symptoms, hormonal deficits, and imaging findings were similar between groups. Severe temporal visual field deficit was more common in surgical patients. At 3 and 6 months, hormonal, visual, and oculomotor outcomes were similar. Stratifying based on severity of visual fields demonstrated no difference in any outcome at 3 months. Timing of surgery did not affect outcomes. CONCLUSION: We found that medical and surgical management of PA yield similar 3-month outcomes. Although patients undergoing surgery had more severe visual field deficits, we could not clearly demonstrate that surgery led to better outcomes. Even without surgery, apoplectic tumor volumes regress substantially within 2 to 3 months, indicating that surgery is not always needed to reduce mass effect.

Glioma immunotherapy enhancement and CD8-specific sialic acid cleavage by isocitrate dehydrogenase (IDH)-1.

The promise of adaptive cancer immunotherapy in treating highly malignant tumors such as glioblastoma multiforme (GBM) can only be realized through expanding its benefits to more patients. Alleviating various modes of immune suppression has so far failed to achieve such expansion, but exploiting endogenous immune enhancers among mutated cancer genes could represent a more direct approach to immunotherapy improvement. We found that Isocitrate Dehydrogenase-1 (IDH1), which is commonly mutated in gliomas, enhances glioma vaccine efficacy in mice and discerns long from short survivors after vaccine therapy in GBM patients. Extracellular IDH1 directly enhanced T cell responses to multiple tumor antigens, and prolonged experimental glioma cell lysis. Moreover, IDH1 specifically bound to and exhibited sialidase activity against CD8. By contrast, mutant IDH1R132H lacked sialidase activity, delayed killing in glioma cells, and decreased host survival after immunotherapy. Overall, our findings identify IDH1 as an immunotherapeutic enhancer that mediates the known T cell-enhancing reaction of CD8 desialylation. This uncovers a new axis for immunotherapeutic improvement in GBM and other cancers, reveals novel physiological and molecular functions of IDH1, and hints at an unexpectedly direct link between lytic T cell function and metabolic activity in target cells.

Pilot randomized controlled trial of a hospital-based substance use treatment and recovery team (START) to improve initiation of medication for alcohol or opioid use disorder and linkage to follow-up care.

OBJECTIVES: We conducted a pilot randomized controlled trial (RCT) to explore whether a hospital inpatient addiction consult team (Substance Use Treatment and Recovery Team [START]) based on collaborative care was feasible, acceptable to patients, and whether it could improve uptake of medication in the hospital and linkage to care after discharge, as well as reduce substance use and hospital readmission. The START consisted of an addiction medicine specialist and care manager who implemented a motivational and discharge planning intervention. METHODS: We randomized inpatients age ≥ 18 with a probable alcohol or opioid use disorder to receive START or usual care. We assessed feasibility and acceptability of START and the RCT, and we conducted an intent-to-treat analysis on data from the electronic medical record and patient interviews at baseline and 1-month postdischarge. The study compared RCT outcomes (medication for alcohol or opioid use disorder, linkage to follow-up care after discharge, substance use, hospital readmission) between arms by fitting logistic and linear regression models. FINDINGS: Of 38 START patients, 97 % met with the addiction medicine specialist and care manager; 89 % received ≥8 of 10 intervention components. All patients receiving START found it to be somewhat or very acceptable. START patients had higher odds of initiating medication during the inpatient stay (OR 6.26, 95 % CI = 2.38-16.48, p < .001) and being linked to follow-up care (OR 5.76, 95 % CI = 1.86-17.86, p < .01) compared to usual care patients (N = 50). The study found no significant differences between groups in drinking or opioid use; patients in both groups reported using fewer substances at the 1-month follow-up. CONCLUSIONS: Pilot data suggest START and RCT implementation are feasible and acceptable and that START may facilitate medication initiation and linkage to follow-up for inpatients with an alcohol or opioid use disorder. A larger trial should assess effectiveness, covariates, and moderators of intervention effects.

The Substance Use Treatment and Recovery Team (START) study: protocol for a multi-site randomized controlled trial evaluating an intervention to improve initiation of medication and linkage to post-discharge care for hospitalized patients with opioid use disorder.

BACKGROUND: People with opioid use disorder experience high burden of disease from medical comorbidities and are increasingly hospitalized with medical complications. Medications for opioid use disorder are an effective, life-saving treatment, but patients with an opioid use disorder admitted to the hospital seldom initiate medication for their disorder while in the hospital, nor are they linked with outpatient treatment after discharge. The inpatient stay, when patients may be more receptive to improving their health and reducing substance use, offers an opportunity to discuss opioid use disorder and facilitate medication initiation and linkage to treatment after discharge. An addiction-focus consultative team that uses evidence-based tools and resources could address barriers, such as the need for the primary medical team to focus on the primary health problem and lack of time and expertise, that prevent primary medical teams from addressing substance use. METHODS: This study is a pragmatic randomized controlled trial that will evaluate whether a consultative team, called the Substance Use Treatment and Recovery Team (START), increases initiation of any US Food and Drug Administration approved medication for opioid use disorder (buprenorphine, methadone, naltrexone) during the hospital stay and increases linkage to treatment after discharge compared to patients receiving usual care. The study is being conducted at three geographically distinct academic hospitals. Patients are randomly assigned within each hospital to receive the START intervention or usual care. Primary study outcomes are initiation of medication for opioid use disorder in the hospital and linkage to medication or other opioid use disorder treatment after discharge. Outcomes are assessed through participant interviews at baseline and 1 month after discharge and data from hospital and outpatient medical records. DISCUSSION: The START intervention offers a compelling model to improve care for hospitalized patients with opioid use disorder. The study could also advance translational science by identifying an effective and generalizable approach to treating not only opioid use disorder, but also other substance use disorders and behavioral health conditions. TRIAL REGISTRATION: Clinicaltrials.gov: NCT05086796, Registered on 10/21/2021. https://www. CLINICALTRIALS: gov/ct2/results?recrs=ab&cond=&term=NCT05086796&cntry=&state=&city=&dist = .