Citations

Abstract As patients with relapsed/refractory multiple myeloma (RRMM) continue to live longer, they might get exposed to most available drugs and drug classes during the disease course. For such late line RRMM or among patients without access to novel therapies, retreatment with a drug that the disease had previously been refractory to might be one option. In this retrospective study, we describe 315 patients with RRMM at our institution who were retreated with a drug that the disease had been previously refractory to. We found an overall response rate of 56.2% and a median progression-free survival (PFS) of 11 months with retreatment. Patients with a longer time on initial therapy with the index drug (>28.4 months) had a superior PFS with retreatment (median PFS, 16.9 vs 8.1 months; P < .001). Similarly, patients with a longer time gap between the initial line of therapy with index drug and retreatment with index drug (>46.1 months) had better PFS with retreatment (28.2 vs 8.9 months; P = .016). In conclusion, retreatment with a previously refractory drug is a viable therapeutic option for RRMM, with the most significant benefit derived in disease demonstrating sensitivity to initial drug exposure and among those with a longer gap between initial drug exposure and retreatment.

Abstract Accumulating evidence suggests dysregulated immune checkpoint (IC) signaling can exacerbate COVID-19 severity, but the role of these molecules in the pathogenesis of fatal COVID-19-related diffuse alveolar damage (DAD) remains elusive. Understanding how IC proteins influence acute lung injury due to COVID-19 can provide insights into potential therapeutic strategies to modulate immune responses and improve patient outcomes. Here, in a single-center autopsy cohort, we determined the cellular localization of ICs in lung tissue from cases of fatal COVID-19, DAD-comparators, and non-fibrotic controls by using immunohistochemistry, and investigated their association with clinical outcomes. We expanded our findings by performing analyses of publicly available single-cell RNA sequencing datasets from patients with fatal COVID-19 and non-fibrotic controls. We demonstrated the presence of protein-protein interaction networks of ICs in the lung cellular niche by performing transcriptomic profiling of lung tissue-derived RNA counts from patients with fatal COVID-19. Further, we leveraged data from the largest international, multi-center COVID-19 autopsy cohort and validated that, among patients with fatal COVID-19, those with higher PD-L1/CD274 expression in lung endothelial cells had more rapid clinical deterioration. Lastly, in a cohort of individuals with early COVID-19, IC plasma protein levels were elevated in those with persistent SARS-CoV-2 RNAemia and adverse clinical outcomes. Collectively, our data provide unique pathological insights into the role of IC dysregulation and differential disease severity in COVID-19.

AbstractBackgroundIrritable bowel syndrome (IBS) is a disorder of gut–brain interaction characterized by abdominal pain and altered bowel habits, with patient‐perceived dissatisfaction of treatment symptom control. We assessed disease burden, satisfaction with medication use, and impact on activities, in participants with IBS with constipation (IBS‐C) and diarrhea (IBS‐D).MethodsThis study assessed data from a large, United States survey of adults querying demographics, comorbid conditions, quality of life, medication use, satisfaction with symptom control, and work productivity. Participants were grouped into the IBS‐C or IBS‐D cohort if they met Rome IV criteria, with controls matched 1:1 according to age, sex, race, region, and Charlson Comorbidity Index score. All data were self‐reported.Key ResultsNine hundred and ten participants with IBS‐C and 669 with IBS‐D were matched to controls. The most reported symptoms were abdominal discomfort for IBS‐C and abdominal pain and abdominal discomfort for IBS‐D. Among the IBS‐C and IBS‐D cohorts, 74.2% and 65.9%, respectively, took prescription and/or over‐the‐counter medication for their symptoms. Respondents were more dissatisfied than satisfied with control of their symptoms. Respondents taking prescription medication(s) with or without over‐the‐counter medication(s) reported better symptom control than respondents only taking over‐the‐counter medications (p < 0.001). There was significantly higher mean presenteeism, work productivity loss, and daily activity impairment (p < 0.001 for all) in respondents with IBS compared with controls.Conclusions and InferencesThis study provides insight into respondents' experiences of IBS symptoms, including the impact on daily activity, as well as satisfaction with control of symptoms and prescription and over‐the‐counter medications.

AbstractBackgroundChronic idiopathic constipation (CIC) is a disorder of gut–brain interaction characterized by a variety of bowel movement‐related and abdominal symptoms. A greater understanding of medication use and satisfaction with symptom control may provide insights to optimize patient care. Therefore, we explored these aspects of the disorder in adults with CIC.MethodsThis study assessed data collected from a large nationwide survey of adult participants in the United States, querying demographics, clinical characteristics, and comorbid conditions, as well as medication use, care‐seeking behaviors, and satisfaction with symptom control. Participants were grouped into the CIC cohort if they met Rome IV criteria, with controls matched 1:1 according to age, sex, race, region, and Charlson Comorbidity Index score. All data were self‐reported.Key ResultsTwo thousand five hundred and thirty‐three participants with CIC were matched 1:1 to controls. In the CIC cohort, abdominal pain was the most reported symptom leading to medication use: 15.9% of respondents were receiving a prescription medication in addition to an over‐the‐counter medication, while 26.3% were taking neither. In addition, only one‐third were satisfied with the control of their symptoms; however, satisfaction was significantly higher in respondents taking a prescription medication (p < 0.001). The proportion of reported comorbidities was significantly higher in the CIC cohort versus the control cohort, with chronic pain, anxiety, and depression among the highest (p < 0.001 for all).Conclusions and InferencesThis study emphasizes the need for better communication regarding prescription medications and their benefits, with the goal of further improving CIC patients' overall symptoms.

AbstractBackgroundGastric sensorimotor disorders (functional dyspepsia [FD] and gastroparesis [GP]) are prevalent and burdensome. Prolonged ambulatory recording using a wireless patch may provide novel information in these patients.MethodsConsecutive adult patients (age ≥ 18 years) referred for gastric emptying scintigraphy (GES) were eligible for study inclusion. Patients were excluded if they had prior foregut surgery; were taking opioids or other medications known to affect gastric emptying; had a HgbA1C > 10; or were recently hospitalized. Three wireless motility patches were applied to the skin prior to GES. Patients wore the patches for 6 days while recording meals, symptoms, and bowel movements using an iPhone app.Key ResultsTwenty‐three consecutive adults (87% women; mean age = 43.9 years; mean BMI = 26.7 kg/m2) were enrolled. A gastric histogram revealed three levels of gastric myoelectric activity: weak, moderate, and strong. Patients with delayed gastric emptying at 4 h had weak gastric myoelectrical activity. Patients with nausea and vomiting had strong intestinal activity. Those with FD had weak gastric and intestinal myoelectric activity, and a weak meal response in the stomach, intestine, and colon compared to those with nausea alone or vomiting alone.Conclusions and InferencesPatients with FD, and those with delayed gastric emptying, had unique gastrointestinal myoelectrical activity patterns. Reduced postprandial pan‐intestinal myoelectric activity may explain the symptoms of FD in some patients. Recording gastrointestinal activity over a prolonged period in the outpatient setting has the potential to identify unique pathophysiologic patterns and meal‐related activity that distinguishes patients with distinct gastric sensorimotor disease states.

Purpose of review Functional dyspepsia is a common gastrointestinal disease that is under-recognized and under-diagnosed. It is a complex disorder of gut–brain interaction with no FDA-approved treatment options. The purpose of this review is to highlight updates in the proposed pathophysiology and present new data regarding potential therapies for functional dyspepsia. Recent findings Alterations in the intestinal microbiome and integrity of the intestinal membrane may play a crucial role in the pathogenesis of functional dyspepsia. The low FODMAP diet, in addition to modulating the microbiome with antibiotics and probiotics, are targets for large future studies. Novel methods of delivery of gut–brain therapies have shown promising results, especially virtual reality. Summary The pathophysiology and management of functional dyspepsia is complex and there is still much unknown; however, continued research is identifying new targets for treatment. New and more targeted treatment options provide clinicians a variety of tools to offer patients with functional dyspepsia.