Citations

Summary Peroral endoscopic myotomy (POEM) in patients with achalasia who are status post bariatric surgery may be technically challenging due to postsurgical scarring and altered anatomy. The aim of the study was to assess the efficacy and safety of POEM for achalasia in patients with prior bariatric surgery. A review of prospectively maintained databases at three tertiary referral centers from January 2015 to January 2021 was performed. The primary outcome of interest was clinical success, defined as a post-treatment Eckardt score ≤ 3 or improvement in Eckardt score by ≥ 1 when the baseline score was <3, and improvement of symptoms. Secondary outcomes were adverse event rates and symptom recurrence. Sixteen patients status post Roux-en-Y gastric bypass (n = 14) and sleeve gastrectomy (n = 2) met inclusion criteria. Indications for POEM were achalasia type I (n = 2), type II (n = 9), and type III (n = 5). POEM was performed either by anterior or posterior approach. The pre-POEM mean integrated relaxation pressure was 26.2 ± 7.6 mm Hg. The mean total myotomy length was 10.2 ± 2.7 cm. The mean length of hospitalization was 1.4 ± 0.7 days. Pre- and postprocedure Eckardt scores were 6.1 ± 2.1 and 1.7 ± 1.8, respectively. The overall clinical success rate was 93.8% (15/16) with mean follow-up duration of 15.5 months. One patient had esophageal leak on postprocedure esophagram and managed endoscopically. Dysphagia recurred in two patients, which was successfully managed with pneumatic dilation with or without botulinum toxin injection. POEM appears to be safe and effective in the management of patients with achalasia who have undergone prior bariatric surgery.

Personalized treatment of genetically stratified subgroups has the potential to improve outcomes in many malignant tumors. This study distills clinically meaningful prognostic/predictive genomic marker for cervical adenocarcinoma using signature genomic aberrations and single-point nonsynonymous mutation-specific droplet digital PCR (ddPCR). Mutations in PIK3CA E542K, E545K, or H1047R were detected in 41.7% of tumors. PIK3CA mutation detected in the patient’s circulating DNA collected before treatment or during follow-up was significantly associated with decreased progression-free survival or overall survival. PIK3CA mutation in the circulating DNA during follow-up after treatment predicted recurrence with 100% sensitivity and 64.29% specificity. It is the first indication of the predictive power of PIK3CA mutations in cervical adenocarcinoma. The work contributes to the development of liquid biopsies for follow up surveillance and a possibility of tailoring management of this particular women’s cancer.

PURPOSEStandard cytotoxic induction chemotherapy for acute myeloid leukemia (AML) results in prolonged neutropenia and risk of infection. Romyelocel-L is a universal, allogeneic myeloid progenitor cell product being studied to reduce infection during induction chemotherapy.PATIENTS AND METHODSOne hundred sixty-three patients with de novo AML (age ≥ 55 years) receiving induction chemotherapy were randomly assigned on day 0 (d0), of whom 120 were evaluable. Subjects received either romyelocel-L infusion on d9 with granulocyte colony-stimulating factor (G-CSF) starting daily d14 (treatment group) or G-CSF daily alone on d14 (control) until absolute neutrophil count recovery to 500/µL. End points included days in febrile episode, microbiologically defined infections, clinically diagnosed infection, and days in hospital.RESULTSMean days in febrile episode was shorter in the treatment arm from d15 through d28 (2.36 v 3.90; P = .02). Similarly, a trend toward decreased microbiologically defined infections and clinically diagnosed infection in the treatment arm was observed from d9 to d28 (35.6% v 47.5%; P = .09), reaching a statistically significant difference from d15 to d28 (6.8% v 27.9%; P = .002). Because of this, antibacterial or antifungal use for treatment of an infection was significantly less in the treatment group (d9-d28: 44.1% v 63.9%; P = .01). Significantly fewer patients in the treatment arm received empiric antifungals from d9 tod28 (42.4% v 63.9%; P = .02) and d15-d28 (42.4% v 62.3%; P = .02). Patients in the treatment arm also had 3.2 fewer hospital days compared with control (25.5 v 28.7; P = .001). Remission rates and days to absolute neutrophil count recovery were similar in the two groups. No patients in the romyelocel-L plus G-CSF group died because of infection compared with two patients in the control arm. No graft-versus-host disease was observed.CONCLUSIONSubjects receiving romyelocel-L showed a decreased incidence of infections, antimicrobial use, and hospitalization, suggesting that romyelocel-L may provide a new option to reduce infections in patients with AML undergoing induction therapy.

Background: Midlife vascular risk factors (MVRF) are associated with incident dementia. Similarly, amyloid β(Aβ) and neurodegeneration (e.g.brain volumes), as parts of the Alzheimer’s Disease (AD) ATN framework, are associated with cognition. Whether vascular and AD-associated factors contribute to dementia independently or interact synergistically to reduce cognitive ability is not well understood. Methods: Recruited from 3 U.S. communities, ARIC-PET participants were followed from 1987-89 (45-64 yo) through 2016-17 (74-94 yo). Cognition was evaluated in 2011-13 (ages 69-88), and twice more, every 2-3 years. In 2011-13, nondemented ARIC-PET participants had a brain MRI, with measurement of white matter hyperintensities (WMH) and brain volumes, with florbetapir (Aβ) PET scans in 2012-14; global cortical standardized uptake value ratio (SUVR) was log-transformed and standardized. Dementia was classified by expert review, as well as phone and medical record surveillance. The relative contributions of vascular risk (MVRF, WMH volume) and AD pathology (elevated Aβ SUVR, smaller AD signature region volumes) to incident dementia were evaluated with Cox proportional hazards regression. Results: In 298 individuals, 36 developed dementia. In models with key MVRF, demographics, and Aβ SUVR, hypertension and Aβ each independently predicted dementia risk (per SD of Aβ SUVR: HR 2.57, 95% CI 1.72-3.84; hypertension: HR 2.57, 95% CI 1.16-5.67), but didn’t interact on dementia risk. WMH (per SD: HR 1.51, 95% CI 1.03-2.20) and Aβ SUVR (per SD: HR 2.52, 95% CI 1.83-3.47) each contributed to incident dementia but WMH lost significance when MVRF were added to the model. Smaller AD signature regions were associated with incident dementia, independent of Aβ SUVR, and remained significant after adjustment for MVRF (HR per SD 2.18, 95% CI 1.18-4.01). Conclusions: Midlife hypertension and late-life Aβ independently contribute to dementia risk, but don’t synergize on a multiplicative scale. Neurodegeneration (e.g.smaller AD signature region volume) is also associated with incident dementia, independent of Aβ and MVRF. Multiple pathways leading to dementia should be considered when evaluating risk factors and interventions to reduce the burden of dementia.

Objective: The aim of this study was to investigate the midterm outcomes of fenestrated and branched endovascular aortic repair (FB-EVAR) of pararenal (PRA) and thoracoabdominal aortic aneurysms (TAAAs). Summary Background Data: FB-EVAR has been associated with decreased morbidity compared to open repair, but there is limited midterm data. Methods: A total of 430 patients (302 males, mean age 74 ± 8 years) treated by FB-EVAR were enrolled in a prospective, nonrandomized investigational device exemption study. Endpoints included 30-day mortality and major adverse events (MAEs), freedom from all cause and aortic-related mortality, target vessel patency, and freedom from secondary intervention and target vessel instability. Results: There were 133 PRAs and 297 TAAAs with 1673 renal-mesenteric arteries incorporated by fenestrations or directional branches (3.9 ± 0.5 vessels/patient). At 30 days or within the hospital stay if longer than 30 days, there were 4 (0.9%) deaths. MAEs included new-onset dialysis in 8 patients (2%), permanent paraplegia or stroke in 10 patients each (2%), and respiratory failure requiring tracheostomy in 2 patients (0.5%). After a mean follow-up of 26 ± 20 months, there were 3 (0.7%) aortic-related deaths from SMA stent occlusion, gastrointestinal hemorrhage, or complications of open arch repair. At 5 years, freedom from all-cause and aortic-related mortality were 57% ± 5% and 98% ± 1%, respectively. Freedom from secondary intervention was 64% ± 4%, primary target vessel patency was 94% ± 1%, and freedom from target vessel instability was 89% ± 2% at same interval. One patient (0.2%) had nonfatal aneurysm treated using endovascular repair. Conclusion: FB-EVAR is safe and effective for treatment of PRA and TAAAs with low rate of aortic-related mortality and aneurysm rupture on midterm follow-up.