Citations

ABSTRACT As the treatment paradigm for Waldenström macroglobulinemia (WM) continues to evolve, the debate surrounding the prioritization of depth of response versus disease control as therapeutic goals gains significant relevance. However, the impact of depth of response from fixed‐duration therapy on overall survival (OS) was unclear. This multicenter study evaluated the prognostic impact of depth of response using a landmark survival analysis. A total of 440 patients with WM treated with frontline fixed‐duration regimens were included. Attaining a major response (MaR) was associated with superior outcomes, including significantly longer OS. The estimated 5‐year PFS rates for patients with MaR at 6 months versus not were 50% versus 32%, respectively, p < 0.001, and the estimated 5‐year OS rates for patients with MaR at 6 months versus not were 89% versus 70%, respectively, p < 0.001. In a multivariable analysis, MaR at 6 months was independently associated with superior PFS (HR 0.66, p = 0.007) and OS (HR 0.28, p < 0.001). Similar results were seen when considering deeper responses (CR + VGPR vs. PR). Depth of response at 6 months is an important prognostic marker in WM and an independent predictor of PFS and OS. These results support its utilization as a suitable endpoint in clinical studies in WM.

ABSTRACT Anemia in myeloid neoplasms is multifaceted, with heterogeneous pathogenetic mechanisms that include ineffective erythropoiesis, hepcidin‐induced iron‐restricted erythropoiesis, and abnormal inflammatory cytokine production. Current management of anemia is challenged by limited approved drugs that specifically treat anemia in myelofibrosis (MF) and myelodysplastic syndrome (MDS). Newer therapies target the transforming growth factor beta (TGF‐β)‐bone morphogenic protein/sons of mothers against decapentaplegic (BMP‐SMAD) signaling pathway, which plays a significant role in ineffective erythropoiesis (SMAD 2/3) and abnormal hepcidin production (SMAD 1/5/8). These include TGF‐β ligand traps (luspatercept, elritercept), activin A receptor type 1 (ACVR1)/activin receptor‐like kinase 2 (ALK2) inhibitors (momelotinib, zilurgisertib), and anti‐hemojuvelin antibody‐based therapies (DISC‐0974). Luspatercept and momelotinib are approved for anemia related to lower‐risk MDS and MF, respectively, and represent an important addition to the treatment armamentarium, along with imetelstat, a telomerase inhibitor, recently ratified for anemia in lower‐risk MDS. A promising strategy to overcome the limitations of existing anemia‐directed therapies includes the use of drug combinations with complementary mechanisms (luspatercept + erythropoiesis stimulating agents, luspatercept + momelotinib, DISC‐0974 + momelotinib), and harnessing the erythropoietic potential of sodium‐glucose co‐transporter‐2 inhibitors (SGLT‐2I). Future research should address the complex pathophysiology of anemia, standardize definitions for anemia with gender‐specified cutoffs, implement uniform erythroid response criteria, and consider early therapeutic intervention in clinical trials for anemia‐directed therapies.

ABSTRACTIntroductionStudies demonstrate an overlap of constipation with gastroparesis and functional dyspepsia, but the impact of treatments that target constipation on improving upper gastrointestinal (UGI) symptoms is unexplored. We quantified the effects of constipation medication therapies on UGI and constipation symptom severity in subjects presenting with symptoms of gastroparesis.MethodsFifty‐six subjects with symptoms of gastroparesis underwent concurrent wireless motility capsule and gastric emptying scintigraphy and were recommended to receive either a new medication therapy for constipation or a change in constipation therapy based on investigator interpretation of test results. Gastroparesis Cardinal Symptom Index (GCSI), upper abdominal pain, and constipation scores were compared between baseline and 6 months. Data were compared between delayed or non‐delayed gastric emptying and the presence or absence of slow colonic transit.Key ResultsSubjects with slow colonic transit had improvements in GCSI (p = 0.007) and constipation scores (p = 0.004) after treatment with a new or changed constipation medication, with the delayed emptying subgroup driving GCSI improvements (p = 0.004). Reductions in nausea/vomiting (p = 0.02) and early satiety/fullness subscores (p = 0.002) with trends to improved bloating/distention subscores (p = 0.06) were observed in this subgroup, but upper abdominal pain was unchanged. Subjects with normal colonic transit showed no improvement in GCSI scores regardless of gastric emptying status (p > 0.05).Conclusions and InferencesIdentifying and treating delayed colonic transit in gastroparetic (delayed gastric emptying) subjects improves global UGI symptoms as well as selected individual symptoms. Evaluation of whole gut motility as well as recognizing and managing extragastric delay may promote improved outcomes in these patients.Trial RegistrationClinicalTrials.gov: NCT02022826

AbstractObjectiveThe objective of this study is to determine if a history of traumatic brain injury (TBI) degrades postoperative the audiological performance of patients with cochlear implantation (CI).Study DesignRetrospective review.SettingDepartment of Defense‐wide database.MethodsInternational Classification of Diseases, Ninth Revision (ICD‐9) and ICD‐10 codes were used to identify patients that were diagnosed with TBI prior to CI between 2005 and 2023. They were matched 2:1 with controls without TBI based on age and sex. Preoperative and postoperative pure tone average (PTA) thresholds and AzBio scores were compared.ResultsNineteen TBI patients representing 20 implanted ears were identified and matched with 39 patients without TBI representing 40 implanted ears. Thirteen ears carried a diagnosis of mild TBI, and seven were diagnosed with moderate to severe TBI. The average follow‐up period was 44 months. The TBI group attained mean postoperative PTA and AzBio scores of 37 dB (SD 24) and 67% (SD 28). The non‐TBI group attained scores of 31 dB (SD 12) and 69% (SD 26). P‐values for the PTA and AzBio intergroup comparisons were .93 and .88, respectively. All TBI ears attained at least sound awareness after implantation, with 79% achieving open‐set speech perception compared to 82% of non‐TBI ears.ConclusionCI after TBI of any severity provides hearing rehabilitation comparable to patients without a prior diagnosis of TBI.

AbstractObjectiveTo assess relations between Ménière's disease and suicidality, measured by suicidal ideation, suicidal behaviors, and death by suicide.Data SourcesCINAHL, Cochrane Library, PubMed, PsycINFO, and SCOPUS databases were searched from inception through July 2, 2024.Review MethodsObservational studies related to suicidality in patients with Ménière's disease were included. Non‐English language papers, editorials, and studies on vestibular disorders not specified as Ménière's disease were excluded. The Risk Of Bias In Nonrandomized Studies‐of Exposure tool was used for cohort and qualitative studies, and the Joanna Briggs Institute critical appraisal checklist was used for case‐control studies.ResultsFour studies (n = 168,566) were included in our review. Two cohort studies found significantly increased adjusted hazard ratios of 2.1 (95% CI: 2.0‐2.2) for death by suicide and 7.6 (95% CI: 4.4‐13.3) for suicidal behaviors, respectively, in patients with Ménière's disease compared to the control population after their diagnosis. However, a case‐control study found no significant difference in the prevalence of suicidal ideation or behaviors prior to the date of diagnosis in patients with Ménière's disease compared to the control population (0.9% vs 0.8%; P = .44). In addition, one patient with Ménière's disease expressed suicidal ideation in the qualitative study.ConclusionPatients may experience variable responses to Ménière's disease. Thus, otolaryngologists should be mindful of the potential for suicidality in patients with Ménière's disease.

Abstract Biliary strictures are a complicated entity that requires careful thought and dedicated workup to define, understand, and plan the proper management pathway. From a surgical standpoint, it can be a mixed bag at the time of presentation. Even then, the information may not be fully diagnostic and often requires multiple interventions to assess the pathology and extent of the disease. In most cases, there is concern for malignancy with no effective screening tools and small surgical windows for cure. Therefore, a dedicated multidisciplinary team of surgeons, interventional radiologists, advanced endoscopists, hepatologists, and oncologists is always necessary to work together efficiently to gather information, diagnose, prevent secondary complications, and create an effective treatment plan with aligned goals of care.

ABSTRACTThe goal of the present study was to investigate the effect of positioning a soft flexible tube‐based actuator parallel or orthogonal to the principle muscle fibre direction, on measurements of the stiffness of upper trapezius (UT) muscle obtained using magnetic resonance elastography (MRE). The effects of using three different vibration frequencies (60 Hz, 80 Hz and 100 Hz) and studying left and right sides of the body were also investigated. The relevant MRE datasets were acquired on a 1.5 T MRI system using a 2D gradient‐echo (GRE) MRE sequence, and corresponding wave images produced using multimodel direct inversion (MMDI) were analysed by two observers using the manual caliper technique. Except for two of the 108 individual datasets, when the agreement was moderate, there was substantial to perfect agreement between wave quality scores obtained by the two observers, with an identical mean value. Similarly, and again with only two exceptions, there was good to excellent agreement between the measurements of UT stiffness obtained by the two observers. UT stiffness values obtained when the acoustic waves were propagating along the principle muscle fibre direction were significantly higher than when the waves were propagating orthogonal to the principle muscle fibre direction at all vibration frequencies (p < 0.005), and only for the former was a significant dispersion effect observed whereby stiffness increased as frequency increased (p < 0.05). No significant asymmetry was observed in measurements of UT stiffness obtained for the left and right sides of the body (p = 0.29). In conclusion, the new soft and flexible tube‐based actuator is comfortable and produced very good wave propagation in UT when positioned in either orientation. However, it is recommended for wave propagation to be induced in the principle fibre direction and there was found to be no advantage in using a vibration frequency above 60 Hz.