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BACKGROUND AND OBJECTIVES: Schwannomas are benign, slow-growing peripheral nerve sheath tumors. Approximately 8% of intracranial schwannomas originate from the trigeminal nerve. No consensus exists regarding superiority of outcomes after resection vs stereotactic radiosurgery (SRS) in the treatment of trigeminal schwannomas (TS). The aim of this study was to compare the efficacy and outcomes of resection vs SRS for TS management. METHODS: Embase, PubMed, and SCOPUS databases were queried from the date of inception to July 2023 for primary data reporting TS treatment outcomes after SRS or resection. Risk of bias was reported under Newcastle-Ottawa Scale. RESULTS: Overall, 29 retrospective observational studies comprising 949 patients were included in the analysis. A total of 13 studies (n = 589) reported outcomes after SRS, and 16 studies (n = 360) reported outcomes after surgical resection, and 182 patients in the SRS group had previous resection. To ensure statistical validity of comparing the cohorts, 3 checkpoints were assessed: the median age (SRS: 48 vs surgery: 40 years old, P < .01), tumor volume (5.2 vs 8.9 cm 3 , P = .06), and median follow-up (53.9 vs 48.5 months, P = .59), which reflected the choice of treatment. Compared with surgical resection, the SRS group demonstrated significantly higher rates of facial hypesthesia improvement (44% vs 12%, P < .01) and lower rates of new onset (4% vs 15%, P = .051) at last follow-up. Facial pain was less likely to improve (58% vs 81%, P = .024) after SRS compared with surgery. However, worsened (5% vs 1%, P = .71) and new facial pain (2% vs 1%, P = .55) were comparable between cohorts. CONCLUSION: SRS seems to offer improvement in rates of hypesthesia and trigeminal motor deficits compared with surgical resection for TS. However, facial pain improvement was more favorable after surgery. These findings highlight the importance of individualized treatment decisions based on patient characteristics, tumor profile, and pretreatment symptoms.

This article highlights the important role of speech-language pathologists (SLPs) in palliative care (PC), emphasizing their contribution to supporting people with eating, drinking, and swallowing difficulties during serious illnesses and at the end of life. The recommendations underscore the necessity of interdisciplinary collaboration among SLPs and other PC team members, the importance of patient and caregiver education, and the application of patient-centered, comfort-focused approaches to dysphagia intervention. Drawing on current research and expert insights, this article explores the use of SLP services in PC, as well as the challenges in supporting people with eating and drinking difficulties in advanced stages of illness, embedded with practical tips for clinicians.

Background Novel treatment options are required in patients with platinum-resistant ovarian cancer (PROC). Myeloid-derived suppressor cells promote a hostile tumor microenvironment and are associated with worse clinical outcomes in PROC. We evaluated the safety and preliminary efficacy of PY159, an agonist antibody to Triggering receptor expressed on myeloid cells-1 (TREM1) that reprograms immunosuppressive intratumoral myeloid cells, and PY314, an antagonist antibody to Triggering receptor expressed on myeloid cells-2 (TREM2) that depletes tumor-associated macrophages, as single agents and in combination with pembrolizumab in subjects with PROC. Methods PY159 and PY314 were individually evaluated in patients with PROC. Patients were treated with monotherapy (PY159 3 mg/kg or PY314 10 mg/kg), based on the recommended dose for expansion derived from the phase 1a studies. At the time of first progression, patients could continue study drug and crossover to combination therapy with pembrolizumab (200 mg) every 3 weeks at the discretion of the investigator. Disease assessment by Response Evaluation Criteria in Solid Tumor version 1.1 was performed every 6 weeks. Results 17 patients were enrolled in the PY159 study (median age 67, range 22–77; median prior therapies 6, range 2–18) and 16 patients in PY314 (median age 65.5, range 49–81; median prior therapies 4, range 2–10). 7 patients in PY159 and 8 patients in PY314 crossed over to combination therapy. Safety events included the following: treatment-related adverse events occurred in 15 patients (88.2%) in PY159 and 9 patients (56.3%) in PY314. Infusion-related reactions occurred in 6 patients (35.3%) in PY159 and 3 patients (18.8%) in PY314. Immune-related adverse events occurred in 13 patients (76.5%) in PY159 (arthralgias) and 1 patient (6.3%) in PY314 (diarrhea). Serious adverse events occurred in 6 patients (36.3%) in PY159 (1 related) and 12 patients (75%) in PY314 (all unrelated). The best radiographic response in PY159 was stable disease in 8/16 patients (50%; median 16 weeks, range 9–33), and in PY314, it was stable disease in 8/16 patients (50%; median 12 weeks, range 6–36). Median PFS was 2.76 months and 2.69 months in PY159 and PY314, respectively. There were no responses in the crossover arm. Conclusions Both PY159 and PY314 were well tolerated, with an acceptable safety profile, as both single agents and in combination with pembrolizumab. Both agents warrant further investigation in heavily pretreated PROC.

Fecal incontinence (FI) is the involuntary and recurrent loss of stool. FI significantly affects both physical and social well-being, while imposing a substantial economic burden. The global prevalence of FI is approximately 8%. Risk factors include advanced age, diarrhea, anal sphincter damage from obstetric trauma or anorectal surgery, pelvic floor abnormalities (such as rectal prolapse), inflammatory bowel disease, and neurological conditions. Despite greater understanding of the impact of FI and advances in diagnostic techniques and treatment options, management remains inconsistent, likely because of limited awareness of available therapies. Patients often benefit from conservative treatments, including dietary modifications, fiber supplementation, antidiarrheal agents, and physical therapy, especially when these are tailored to specific symptoms and rigorously applied. Next level options include anorectal biofeedback therapy, the perianal injectable bulking agent dextranomer, or anal/vaginal barrier devices, which can be effective for patients if tolerated. Transanal irrigation may be considered for patients with neurogenic bowel and fecal retention to aid in rectal cleansing and prevent FI. Sacral neuromodulation is the preferred surgical treatment of FI. Noninvasive anal electrical and percutaneous tibial nerve stimulation are not superior to placebo in controlled trials. Translumbosacral magnetic stimulation was beneficial in an uncontrolled trial; sham-controlled trials are necessary. Owing to limited long-term efficacy, anal sphincteroplasty is typically reserved for younger patients with obstetric anal sphincter defects. Colostomy is considered a last resort. Injection of autologous muscle cells into the external anal sphincter has shown promise in small uncontrolled trials, although it has not yielded significant results in most controlled trials.

Study Design: Single-center retrospective analysis. Objective: To establish an empirically derived threshold to define both coronal and sagittal malalignment (CM & SM) based on preoperative patient-reported outcomes (PROs). Summary of Background Data: Currently, no radiographic alignment threshold defines preoperative CM in adult spinal deformity (ASD) patients based on disability. In a cohort of ASD patients undergoing corrective surgery, we sought to establish a threshold to define both CM and SM based on PRO and assess the clinical impact of CM and combined with SM. Methods: ASD patients with ≥6 level fusions were included. CVA and SVA were measured. PROs included preoperative ODI and SRS-22r scores. CVA and SVA thresholds were derived to accurately differentiate patients with ODI >40 and SRS-pain+function <5. Patients were then separated into 4 groups: (1) neutral alignment (NA); (2) CM; (3) SM; and (4) combined coronal and sagittal malalignment (CCSM). Results: Totally, 368 patients were included. Thresholds to distinguish patients with ODI ≥40 and SRS-pain/function <5 were: (1) CVA=3.96 cm (ODI) and 3.17 cm (SRS); (2) SVA=4.97 cm (ODI) and 7.52 cm (SRS). The lower numbers were chosen to define each threshold: CVA=3 cm and SVA=5 cm. Alignment breakdown was: NA=179 (48.6%), CM=66 (17.9%), SM=65 (17.7%), and CCSM=58 (15.8%). Both SM=( P =0.006) and CCSM ( P <0.001) patients had significantly worse ODI scores than NA patients, and CCSM patients were significantly worse than SM alone ( P =0.010). On the basis of preoperative total SRS-22r scores, only CCSM ( P =0.003) patients were significantly worse than the NA group. CVA significantly correlated with 4/7 (57.1%) preoperative PROs (ODI/SRS-total/function/image), while SVA correlated with 5/7 (71.4%) preoperative PROs (ODI/SRS-total/function/image/pain). A linear relationship was seen between increasing CVA and worsening ODI (β=0.92, 95% CI: 0.37–1.48, P =0.001). A significant and slightly stronger relationship was seen between increasing SVA and worsening ODI (β=1.28, 95% CI: 1.00–1.56, P <0.001). Conclusions: CM and SM thresholds that accurately distinguished ASD patients with severe pain and disability preoperatively were 3 cm for CVA and 5 cm for SVA, respectively. Preoperative CM was significantly associated with worse ODI, SRS-22r total/function/image scores. CCSM led to more disability than SM alone.

Aim Cognitive and behavioral phenomena define behavioral variant frontotemporal dementia (bvFTD), but neuropsychiatric symptoms (NPS) outside the core criteria are common throughout the illness. Identifying how NPS cluster in bvFTD may guide development of future therapies. Methods Participants ( n = 354) with sporadic and genetic bvFTD were enrolled in the ARTFL LEFFTDS Longitudinal Frontotemporal Lobar Degeneration Consortium. Dementia stage was defined as early (CDR® plus NACC FTLD ≤1) or advanced (CDR® plus NACC FTLD ≥1). Baseline and annual follow‐up visit data were analyzed to compare NPS across stages of bvFTD. Psychiatric states were captured using the Neuropsychiatric Inventory‐Questionnaire and Clinician Judgment of Symptoms. Polychoric cluster analysis was used to describe NPS clusters. Results NPS were highly prevalent (≥90%) in early and late bvFTD. Four NPS clusters were identified based on magnitude of factor loadings: affective, disinhibited, compulsive, and psychosis. Neuropsychiatric symptoms fluctuated across visits. In the affective cluster, depression showed the least visit‐to‐visit stability. In the disinhibited cluster, elation showed the least stability. Symptoms in the psychosis and compulsive clusters (hallucinations, delusions, obsessions/compulsions, and hyperorality) were largely stable, persisting from visit‐to‐visit in more than 50% of cases. Symptoms in the affective and disinhibited cluster were associated with the highest caregiver burden, while symptoms in the obsessive cluster were associated with the most functional impairment. Conclusion NPS in bvFTD are frequent and cluster into four discrete groups. The fluctuating nature of some NPS in bvFTD suggests that they may not be reliable markers of disease progression or stage.

Background: Nonoperative and operative management techniques after anterior cruciate ligament (ACL) injury are both appropriate treatment options for selected patients. However, the subsequent development of posttraumatic knee osteoarthritis (PTOA) remains an area of active study. Purpose: To compare the risk of PTOA between patients treated without surgery and with ACL reconstruction (ACLR) after primary ACL disruption using a machine learning causal inference model. Study Design: Cohort study; Level of evidence, 3. Methods: A geographic database identified patients undergoing ACLR between 1990 and 2016 with minimum 7.5-year follow-up. Variables collected include age, sex, body mass index, activity level, occupation, relevant comorbid diagnoses, radiographic findings, injury characteristics, and clinical course. Treatment effects of ACLR on the development of PTOA and progression to total knee arthroplasty (TKA) were analyzed with machine learning models (MLMs) in a causal inference estimator (targeted maximum likelihood estimation, TMLE), while controlling for confounders. Results: The study included 1194 patients with a minimum follow-up of 7.5 years, among whom 974 underwent primary reconstruction and 220 underwent nonoperative treatment. A total of 215 (22%) patients developed symptomatic PTOA in the ACLR group compared with 140 (64%) in the nonoperative treatment group ( P < .001), whereas 25 (3%) patients underwent TKA in the ACLR group compared with 50 (23%) in the nonoperative treatment group ( P < .001). Patients in the ACLR group had delayed TKA compared with patients in the nonoperative treatment group (193.4 vs 166.0 months, respectively; P = .02). TMLE evaluation revealed that reconstruction decreased the risk of PTOA by 11% (95% CI, 8%-13%; P < .001) compared with nonoperative treatment but did not demonstrate a significant effect on the rate of progression to TKA. Survival analysis with random forest algorithm demonstrated significant delay to the onset of PTOA as well as time to progression of TKA in patients undergoing ACLR. Additional risk factors for the development of PTOA, irrespective of treatment, included older age at injury, greater body mass index, total number of arthroscopic knee surgeries, and residual laxity at follow-up. Conclusion: MLMs in a causal inference estimator found ACLR to exert a significant treatment effect in reducing the rate of development of PTOA by 11% compared with nonoperative treatment. ACLR also delayed the onset of PTOA and progression to TKA.

ABSTRACTA total of 142 patients with myeloproliferative neoplasms (MPNs) or acute myeloid leukemia (AML) associated with multihit TP53 mutations (mTP53 MUT) were accessed from the Mayo Clinic database and included (i) chronic phase MPN (MPN‐CP; N = 19), (ii) accelerated phase MPN (MPN‐AP; N = 14), (iii) blast phase MPN (MPN‐BP; N = 28), and (iv) AML (N = 81). Concurrent ASXL1 MUT, EZH2 MUT, IDH1,MUT and IDH2 MUT were more common in MPN‐MUTBP‐mTP53 compared to AML‐mTP53 MUT. At median of 11.6 months follow‐up, 124 (87%) deaths and 19 (13%) allogeneic stem cell transplantations (ASCT) were documented. Overall survival (OS), calculated from the time of mTP53 MUT detection, was similar between MPN‐BP‐mTP53 MUT (median 4.6 months) and MPN‐AP‐mTP53 MUT (5.6 months; p = 0.5) but both were inferior to MPN‐CP‐mTP53 MUT (11.6 months, p < 0.01). OS in MPN‐CP‐mTP53 MUT was similar to that of AML‐mTP53 MUT (median 7.4 months, p = 0.07). In multivariable analysis, OS was favorably affected by ASCT (HR 0.4, p = 0.03) and disease stage (i.e., chronic phase disease) or achieving response to pre‐transplant chemotherapy (HR 0.2, p < 0.01) and unfavorably by the presence of concurrent TET2 MUT or DNMT3A MUT (HR 2.7, p < 0.01). Based on these risk factors, a 3‐tiered risk model was constructed: low (no risk factors; N = 18; median OS 23.8 months); intermediate (one risk factor; N = 44; 11.1 months); and high (two or more risk factors; N = 80; 4 months; p < 0.01). The current study highlights the equally detrimental impact of mTP53 MUT on long‐term survival in MPN and AML and identifies predictors of short‐term survival.

Abstract Objective: To better understand clinicians’ rationale for ordering testing for C. difficile infection (CDI) for patients receiving laxatives and the impact of the implementation of a clinical decision support (CDS) intervention. Design: A mixed-methods, case series was performed from March 2, 2017 to December 31, 2018. Setting: Yale New Haven Hospital, a 1,541 bed tertiary academic medical center. Participants: Hospitalized patients ≥ 18 years old, and clinicians who were alerted by the CDS. Intervention: CDS was triggered in real-time when a clinician sought to order testing for CDI for a patient who received one or more doses of laxatives within the preceding 24 hours. Results: A total of 3,376 CDS alerts were triggered during the 21-month study period from 2,567 unique clinician interactions. Clinicians bypassed the CDS alert 74.5% of the time, more frequent among residents (48.3% bypass vs. 39.9% accept) and advanced practice providers (APPs) (34.9% bypass vs. 30.6% accept) than attendings (11.3% bypass vs. 22.5% accept). Ordering clinicians noted increased stool frequency/output (48%), current antibiotic exposure (34%), and instructions by an attending physician to test (28%) were among the most common reasons for overriding the alert and proceeding with testing for CDI. Conclusions: Testing for CDI despite patient laxative use was associated with an increased clinician concern for CDI, patient risk for CDI, and attending physician instruction for testing. Attendings frequently accepted CDS guidance while residents and APPs often reinstated CDI test orders, suggesting a need for greater empowerment and discretion when ordering tests.